Modern insights into the pathophysiology and treatment of pseudoachalasia.

BACKGROUND: Secondary achalasia or pseudoachalasia is a clinical presentation undistinguishable from achalasia in terms of symptoms, manometric, and radiographic findings, but associated with different and identifiable underlying causes. METHODS: A literature review was conducted on the PubMed database restricting results to the English language. Key terms used were "achalasia-like" with 63 results, "secondary achalasia" with 69 results, and "pseudoachalasia" with 141 results. References of the retrieved papers were also manually reviewed. RESULTS: Etiology, diagnosis, and treatment were reviewed. CONCLUSIONS: Pseudoachalasia is a rare disease. Most available evidence regarding this condition is based on case reports or small retrospective series. There are different causes but all culminating in outflow obstruction. Clinical presentation and image and functional tests overlap with primary achalasia or are inaccurate, thus the identification of secondary achalasia can be delayed. Inadequate diagnosis leads to futile therapies and could worsen prognosis, especially in neoplastic disease. Routine screening is not justifiable; good clinical judgment still remains the best tool. Therapy should be aimed at etiology. Even though Heller's myotomy brings the best results in non-malignant cases, good clinical judgment still remains the best tool as well.

Integrative diagnostics of the gastro-intestinal tract - gastroesophageal reflux and constipation in practice.

Common disorders of the gastrointestinal (GI) tract, such as gastroesophageal reflux/disease (GER/D) and constipation, are frequent causes for seeking medical support in infants. Diagnostic workup must ensure that diagnosed diseases are responsible for such complaints, thus enabling appropriate therapy. In this context assessment consists of clinical examination, functional tests, and imaging, which should be done in a staged manner. Close cooperation between clinicians and clinical radiologists enables optimal diagnostics, thus forming the basis for appropriate therapy.

Predictors of Underlying Esophageal Motility Disorders in Patients Presenting with Esophageal Candidiasis.

OBJECTIVES: Esophageal motility disorders (EMDs) are a known risk factor for esophageal candidiasis (EC), but this relation has not been described particularly well. We sought to evaluate the predictors of underlying EMDs in patients presenting with EC. METHODS: Cases of EC at a single medical center between 2010 and 2021 were identified retrospectively based on the International Classification of Diseases, Ninth Revision code. Demographic, clinical, endoscopic, and manometric data were reviewed. The diagnosis of EC was based on typical endoscopic appearance. RESULTS: In total, 130 EC patients were identified (mean age 69.5 ± 14.6; 66.2% male). Of these, 12 (9.2%) had an underlying EMD (11 cases of achalasia; 1 case of esophagogastric junction outflow obstruction). Five (41.7%) of these patients had previously been diagnosed as having an EMD, whereas 7 were newly diagnosed only after their presentation with EC. No significant differences were noted between those with or without EMDs in terms of demographics, medical comorbidities, or medication use. Patients with an EMD, however, were more likely to complain of dysphagia (91.7% vs 30.5%, P < 0.001), and on endoscopy, they were more likely to have residual food in the esophagus, residual fluid in the esophagus, a dilated esophagus, and resistance to traversing the esophagogastric junction (all P < 0.001). Sixty-one (46.9%) patients with EC died during follow-up (mean 58 months). CONCLUSIONS: EMDs are present in approximately 10% of patients presenting with EC, with half being diagnosed only after presenting with EC. Similar to non-EC patients, patients with EC with dysphagia and the typical endoscopic findings of achalasia are more likely to have an EMD and warrant prompt manometric evaluation.

[Recurrent acute pancreatitis secondary to sphincter of oddi dysfunction: Case report]. / Pancreatitis aguda recurrente secundaria a disfunción del esfínter de oddi: Reporte de caso.

Sphincter of Oddi Dysfunction (SOD) is a rare pathology that should be considered in the differential diagnosis of patients with biliary pain episodes or recurrent acute pancreatitis and a background of cholecystectomy. Generally, these are patients with multiple consultations where this pathology has considerably affected their quality of life. Diagnosis is based on clinical findings, serological markers and supporting diagnostic tests requested according to the suspected sphincteric component. The most effective treatment is endoscopic sphincterotomy. The use of prosthesis is accepted but debated. We present the case of a male patient in his forties who consulted for multiple episodes of recurrent acute pancreatitis with etiology studies suspecting dysfunction of the pancreatic sphincter of Oddi and who was taken to endoscopic management with improvement of his clinical picture.

[State of the Art Diagnostics of the Esophagus]. / State of the Art Diagnostik des Ösophagus.

State of the Art Diagnostics of the Esophagus Abstract. Modern diagnostics of the esophagus is highly technical. It mainly includes endoscopic, radiological, nuclear medicine, functional and electrochemical examinations. Diagnostic tools for esophageal disorders involve esophagogastroduodenoscopies with chromoendoscopy, manometric and pH-impedance catheters as well as radiological techniques, such as CT, MRI or PET-CTs. The patient's history including the main clinical symptoms such as heartburn or dysphagia, and the physical examination will determine the choice and order of subsequent examinations. The esophagogastroduodenoscopy is one of the most important diagnostic tools and has a very low complication rate. During esophagogastroduodenoscopy biopsies, chromoendoscopy or therapeutic interventions can be performed. Endosonography is essential for the staging of esophageal cancer and accuracy can be improved by endosonographically guided biopsies. A CT scan completes the tumor staging and is essential to search for metastases. For motility disorders high resolution manometry is the gold standard which can be supplemented with esophagus barium swallow exams. pH-impedance catheters can be used for diagnosis of reflux. MRI swallow exams are predominantly applied in clinical studies but may be more frequently used in the future.

[Postpartum fecal incontinence. State of the problem]. / Poslerodovoe anal'noe nederzhanie. Sostoyanie problemy.

A review of the current national and foreign literature is devoted to epidemiology, risk factors, causes, diagnosis and modern treatment approaches for fecal incontinence (FI). Incidence of FI in early and delayed period after childbirth is 30% or more. At the same time, up to 87% of postpartum injuries of anal sphincter remain undiagnosed. Importantly, routine caesarean section does not reduce the risk of incontinence. In addition to typical complaints of spontaneous gas and stool, diagnosis of FI after childbirth includes transrectal ultrasound, MRI, anorectal manometry and pudendal nerve terminal motor latency testing. Survey of proctologists from different regions of Russia revealed a high demand from medical community for educational programs devoted to diagnosis, treatment and rehabilitation of patients with postpartum perineal injuries.

Anxiety Associated With High-resolution Anorectal Manometry in Pediatric Patients and Parents.

High-resolution anorectal manometry is an increasingly common procedure performed in pediatric patients to rule out Hirschsprung and assess anorectal function and sensation. The purpose of the present study was to evaluate anxiety of patients and their parents associated with high-resolution anorectal manometry. Preprocedural anxiety was assessed by standardized questionnaire in all parents and children older than 8 years and observed behavioral distress was recorded by the attending pediatric gastroenterologist. Thirty-five children (mean age = 7.2 years, ±2.8) and their parents completed the study. Patient anxiety was found to be markedly elevated. Observed behavioral distress was elevated compared to more invasive procedures. Self-reported parental anxiety was comparable to adults undergoing endoscopic procedures themselves. Despite the low risk of this procedure, healthcare providers should be aware of the high levels of anxiety and distress that occur in patients and their parents associated with anorectal manometry.

Effects of high-resolution esophageal manometry on oxygen saturation and hemodynamic function.

The effect of high-resolution esophageal manometry (HRM) on oxygen saturation (SaO2) and hemodynamic function has not been previously evaluated. This was a prospective study of consecutive patients referred for HRM. Demographic and clinical data were collected on all patients. The study variables included SaO2, heart rate (HR) and blood pressure (BP). SaO2 and HR were measured at baseline, during intubation, during and 5 min after HRM. BP was measured at baseline, during and after HRM. 158 (56% women) patients with a mean age of 56 (SD 15) years were included. Thirty-five (22%) were obese and 55 (35%) were overweight. Eighteen (12%) patients had a history of respiratory disease and 27 (17%) were smokers. Intubation was difficult in 22%. Exploration tolerance was poor in 17% or very poor in 6%. The average duration of the test was 9.9 (SD 2.8) minutes. Sixty-four (47%) and 59 (37%) patients had SaO2 below 95% during intubation and during HRM, respectively. Three patients had SaO2 ≤90%. Sixty-nine (44%) patients had tachycardia during intubation and 8 (5%) during HRM. The appearance of desaturation (SaO2 <95%) during intubation was associated with a lower basal SaO2; desaturation during HRM and 5 minutes after HRM was associated with a higher age, a higher BMI and a lower basal SaO2. HRM decreases SaO2 and increases heart rate primarily during the insertion of the probe, as part of the standard stress response and therefore HMR can be considered a safe procedure. However, in older and overweight patients, respiratory parameters should be monitored.

Estimated aortic blood pressure based on radial artery tonometry underestimates directly measured aortic blood pressure in patients with advancing chronic kidney disease staging and increasing arterial stiffness.

Central blood pressure (BP) can be assessed noninvasively based on radial tonometry and may potentially be a better predictor of clinical outcome than brachial BP. However, the validity of noninvasively obtained estimates has never been examined in patients with chronic kidney disease (CKD). Here we compared invasive aortic systolic BP (SBP) with estimated central SBP obtained by radial artery tonometry and examined the influence of renal function and arterial stiffness on this relationship. We evaluated 83 patients with stage 3 to 5 CKD (mean estimated glomerular filtration rate [eGFR] 30 ml/min/1.73 m(2)) and 41 controls without renal disease undergoing scheduled coronary angiography. BP in the ascending aorta was measured through the angiography catheter and simultaneously estimated using radial tonometry. The mean difference between estimated central and aortic SBP was -13.2 (95% confidence interval -14.9 to -11.4) mm Hg. Arterial stiffness was evaluated by carotid-femoral pulse wave velocity (cf-PWV) and was significantly increased in CKD patients compared with (versus) control patients (mean 10.7 vs. 9.3 m/s). The difference in BP significantly increased 1.0 mm Hg for every 10 ml/min decrease in eGFR and by 1.6 mm Hg per 1 m/s increase in cfPWV. Using multivariate regression analysis including both eGFR and cfPWV, the difference between estimated central and invasive aortic SBP was significantly increased by 0.7 mm Hg. For the entire cohort brachial SBP significantly better reflected invasive SBP than estimated SBP. Thus, tonometry-based estimates of central BP progressively underestimate invasive central SBP with decreasing renal function and increasing arterial stiffness in CKD patients.

High-Resolution Manometry Improves the Diagnosis of Esophageal Motility Disorders in Patients With Dysphagia: A Randomized Multicenter Study.

OBJECTIVES: High-resolution manometry (HRM) might be superior to conventional manometry (CM) to diagnose esophageal motility disorders. We aimed to compare the diagnosis performed with HRM and CM and confirmed at 6 months in a multicenter randomized trial. METHODS: Patients with unexplained dysphagia were randomized to undergo either CM or HRM. Motility disorders were diagnosed using the Castell and Spechler classification for CM and the Chicago classification for HRM. Diagnosis confirmation was based on clinical outcome and response to treatment after 6-month follow-up. The initial diagnosis and percentage of confirmed diagnoses were compared between the two arms (CM and HRM). RESULTS: In total, 247 patients were randomized and 245 analyzed: 122 in the CM arm and 123 in the HRM arm. A manometric diagnosis was more frequently initially achieved with HRM than with CM (97% vs. 84%; P<0.01). Achalasia was more frequent in the HRM arm (26% vs. 12% in the CM arm; P<0.01) while normal examinations were more frequent in the CM arm (52% vs. 28% in the HRM arm; P<0.05). After follow-up, the initial diagnosis was confirmed in 89% of patients in the HRM arm vs. 81% in the CM arm (P=0.07). Finally, overall procedure tolerance was better with CM than with HRM (P<0.01). CONCLUSIONS: This randomized trial demonstrated an improved diagnostic yield for achalasia with HRM compared with CM. Diagnoses tended to be more frequently confirmed in patients who underwent HRM, suggesting that esophageal motility disorders could be identified earlier with HRM than with CM (ClinicalTrial.gov, NCT01284894).

A complex case of dysphagia with dual aetiology.

A woman in her early 60s was referred with dysphagia and chest pain to a tertiary referral centre specialising in oesophageal disorders. Cardiac symptom origin and sinister oesophageal pathology had been excluded at her local hospital in NHS Scotland. Under multidisciplinary team oversight, reinvestigation of mucosal pathology and oesophageal motility ultimately uncovered both Type III achalasia and eosinophilic oesophagitis. This case demonstrates the benefit of including provocative testing during high-resolution manometry to reproduce relevant dysphagia and the importance of stopping proton-pump inhibitors long enough to uncover excessive eosinophils which could otherwise be masked. Ultimately, tailored management for both conditions separately was required to achieve symptoms resolution.

Colonic manometry and colonic scintigraphy as a diagnostic tool for children with severe constipation.

OBJECTIVE: In adults, colonic manometry and colonic scintigraphy are both valuable studies in discriminating normal and abnormal colonic motility. The objective of this study was to compare the diagnostic yield and tolerability of colonic manometry and colonic scintigraphy in children with severe constipation. METHODS: Twenty-six children (mean age 11.4 years, 77% boys) who had received colonic manometry and colonic scintigraphy as part of a colonic motility evaluation were included. Manometry was performed as per department protocol. After swallowing a methacrylate-coated capsule containing indium-111, images were taken at 4, 24, and 48 hours, and geometric centers were calculated. Results of both tests were categorized in 3 groups: normal, abnormal function in the distal part of the colon, and colonic inertia. Cohen κ was used for the level of agreement. Patients and parents completed a questionnaire regarding their experience. RESULTS: Colonic scintigraphy showed normal transit time in 20%, delay in the distal colon in 48%, and colonic inertia in 32% of patients. Colonic manometry was normal in 40%, abnormal in the distal colon in 40%, and colonic inertia was diagnosed in 20%. The κ score was 0.34. All 5 patients with colonic inertia during manometry had a similar result by scintigraphy. Eighty-eight percent of patients preferred scintigraphy over manometry and 28% of parents preferred colonic manometry over scintigraphy. CONCLUSIONS: Colonic manometry and colonic scintigraphy have a fair agreement regarding the categorization of constipation. Scintigraphy is well tolerated in pediatric patients and may be a useful tool in the evaluation of children with severe constipation.

Clinical efficacy and mechanism of transcutaneous neuromodulation on ineffective esophageal motility in patients with gastroesophageal reflux disease.

BACKGROUND: Esophageal motility disorder is one of the pathogenesis of gastroesophageal reflux disease (GERD). The clinical and functional relationship between the ineffective esophageal motility (IEM) and GERD have been found. PPI is a widely used drug of this diaease, but some patients have poor efficacy. The purpose of this study was to investigate the efficacy and possible mechanism of Transcutaneous Neuromodulation in these patients. METHODS: Fifty-six patients with GERD with IEM were enrolled and randomly divided into two groups, one group was TN ST-36 group, the other group was sham TN group. The GERD questionnaire (GerdQ), quality of life score, MOS item short from health survey (SF-36), Hospital Anxiety and Depression Scale (HADS) were used to assess the severity of symptoms. High-resolution esophageal manometry (HRM) test was performed to assess low esophageal sphincter (LES) pressure and distal contractile integral (DCI). The heart rate variability (HRV) test was performed to assess autonomic nervous function. KEY RESULTS: Compared with sham TN, chronic TN treatment decreased the GERD-Q score (p < 0.001). The anxiety score (p = 0.058) and depression score (p = 0.156) were decreased, but there were no statistical differences. Chronic TN treatment also significantly improved the quality of life of patients, mainly in physical function, physical pain, overall health, vitality, social function, emotional function, and mental health. Acute TN treatment increased the DCI (p < 0.001) and LES pressure (p < 0.001) significantly and decreased the combined percentage of failed and weak peristalsis (p < 0.001). Concurrently, acute TN enhanced vagal activity (p < 0.001). CONCLUSIONS AND INFERENCES: IEM is an important link in the pathogenesis of GERD. Chronic TN treatment can significantly improve the clinical symptoms of patients. Acute TN treatment can significantly increase LES pressure and DCI and reduce the frequency of esophageal lost peristalsis and weak peristalsis. The improvement of esophageal motility in GERD patients with IEM by TN treatment may be related to the regulation of autonomic nervous function.

The Transdiaphragmatic Pressure Gradient and the Lower Esophageal Sphincter in the Pathophysiology of Gastroesophageal Reflux Disease: an Analysis of 500 Esophageal Function Tests.

BACKGROUND: Gastroesophageal reflux disease (GERD) pathophysiology is multifactorial. Greater importance has been attributed to a defective lower esophageal sphincter (LES) in comparison to an altered transdiaphragmatic pressure gradient (TPG). This study aims to evaluate the role of the TPG and LES disfunction in GERD pathogenesis. METHODS: Five hundred consecutive esophageal function tests from patients with clinically suspected GERD were reviewed. Patients were classified according to the pH monitoring in GERD positive or GERD negative. Abdominal pressure, thoracic pressure, TPG (abdominal-thoracic pressures), LES resting pressure (mid-respiratory, expiratory, and EGJ-CI), and LES retention pressure (LES resting pressure-TPG) were determined. RESULTS: GERD was present in 296 (59%) individuals. GERD-positive patients were mostly males. LES resting pressure (by all parameters) and thoracic pressure were not different between groups. Abdominal pressure and TPG were higher in GERD-positive patients. LES retention pressure (by all parameters) was lower in GERD-positive patients. DeMeester score had a positive correlation with LES resting pressure, TPG, and LES retention pressure (by all parameters) but not with abdominal pressure and thoracic pressure. CONCLUSIONS: LES valvular competency as measured by absolute resting pressure was not reliable to predict GERD; however, it was associated with GERD severity. Relative LES pressure (LES retention pressure) predicted GERD presence and severity, but no parameter showed superiority. TPG plays an important role in the pathophysiology of GERD since it is related to GERD presence and severity; still TPG is altered mostly based on a higher abdominal pressure.

Relationship between pharyngeal or esophageal reconstruction and esophageal pressure after swallowing.

BACKGROUND: High-resolution manometry, which measures esophageal luminal pressure changes after swallowing, could shed more light on food-transport dynamics after pharyngeal/esophageal reconstruction. This prospective cohort study assessed the influence of two head-and-neck and esophageal tumor-resection and reconstruction approaches on esophageal pressure. METHODS: The cohort consisted of 17 patients who underwent esophageal/pharyngeal resection/reconstruction for cancer and then participated in postoperative high-resolution manometry. Five healthy controls also underwent manometry for comparison. RESULTS: Partial pharyngectomy with patch grafts associated with smooth and continuous esophageal/pharyngeal movement. By contrast, surgery that removed the thoracic esophagus led to complete loss of peristalsis and poor food transport. CONCLUSIONS: High-resolution manometry effectively characterized the changes in food-transport dynamics caused by pharyngeal/esophageal resection/reconstruction. These findings suggest that continuous and smooth movement of the pharynx and esophagus is important for swallowing and high resolution manometry could be useful in patients after pharyngeal/esophageal resection/reconstruction.

Defecatory disorders in patients with type 1 diabetes and chronic constipation.

BACKGROUND AND OBJECTIVES: Chronic constipation (CC) may be caused by defecatory disorders (DDs) and associated with reduced rectal sensation. Among patients with type 1 diabetes (T1D) and CC (T1DCC patients), the prevalence of DDs and reduced rectal sensation is unknown. We sought to compare complications of T1D, anorectal dysfunction, and CC symptoms, among T1DCC patients with versus without a DD. METHODS: Anorectal pressures at rest and during squeeze and evacuation, as well as rectal sensation and rectal balloon expulsion time (BET) were measured with high-resolution anorectal manometry in 114 consecutive T1DCC patients. RESULTS: Thirty-seven patients (32%) had prolonged BET, suggestive of a DD. Complications of T1D included peripheral neuropathy (n = 67, 59%), retinopathy (n = 42, 37%), and nephropathy (n = 26, 23%). Among these complications, only retinopathy was associated with, that is, more prevalent in patients with normal (45%) than prolonged BET (19%). Compared with patients with normal BET, patients with prolonged BET had a lower rectal pressure (mean [SD], 32 [23] mm Hg vs. 23 [19] mm Hg, p = 0.03), greater anal pressure (91 [23] mm Hg vs. 68 [36] mm Hg, p < 0.001), and lower rectoanal gradient (-67 [30] mm Hg vs. -36 [32] mm Hg, p < 0.0001) during evacuation. Anal resting pressure and anal squeeze increment were below normal in 14 (13%) and 32 (29%) of patients and one or more rectal sensory thresholds were above normal in 34 (30%) patients; these abnormalities affected similar proportions in the normal and prolonged BET cohorts. CONCLUSIONS: Among T1DCC patients, 37 (32%) had prolonged BET, which was associated with anorectal pressures indicative of a DD but was not associated with reduced rectal sensation, suggesting that DDs are more likely explained by abdomino-anal dyscoordination than visceral disturbance.

Rectal sensitivity and associated factors in patients with different subtypes of functional defecation disorder.

OBJECTIVE: To investigate rectal sensitivity and associated factors in patients with different subtypes of functional defecation disorder (FDD). METHODS: We segregated individuals diagnosed with FDD into two groups based on their defecation patterns: those with dyssynergic defecation and those with inadequate defecatory propulsion. We gathered general information through questionnaires and assessed rectal sensitivity using anorectal manometry. The rectal sensitivity performances of the two groups were compared; the factors related to rectal sensitivity were analyzed to determine the factors associated with rectal sensitivity, and the effect of biofeedback therapy on rectal sensitivity was clarified. RESULTS: Rectal sensitivity in different subtypes of FDD decreased, and the difference between the two groups was not statistically significant ( P  > 0.05). There were no statistically significant differences in the first constant sensation volume, defecatory desire volume, and maximum tolerable volume between the different subtypes of FDD ( P  > 0.05). Multi-factor binary logistic regression analysis showed that age, constipation symptom score, and diabetes were all independent risk factors for decreased rectal sensitivity ( P  < 0.05). There were no statistically significant differences between the prior- and post-biofeedback therapy in the first constant sensation volume, defecatory desire volume, and maximum tolerable volume ( P  > 0.05). CONCLUSION: Rectal sensitivity in different subtypes of FDD decreased. Age, constipation symptom score, and diabetes were independent risk factors for decreased rectal sensitivity. Short-term biofeedback therapy did not improve rectal hyposensitivity in patients with FDD.

Dysphagia.

Dysphagia is an important clinical symptom that increases in prevalence with age. Both oropharyngeal and esophageal processes can contribute to dysphagia, and these can be differentiated with a careful history. Neuromuscular processes are more prevalent than structural causes in oropharyngeal dysphagia, therefore, investigation should start with a modified barium swallow. In contrast, structural processes dominate in esophageal dysphagia, and endoscopy can offer biopsy and therapy by way of dilation. Manometry is performed for esophageal dysphagia when no structural etiology is found. Specific management of dysphagia is dependent on the etiology and mechanism of dysphagia.

The influence of supragastric belching severity on esophageal acid exposure and motility.

BACKGROUND: Supragastric belching (SGB) is a phenomenon where air is rapidly sucked from the pharynx into the esophagus and immediately expelled through abdominal straining. It is considered a behavior disorder and is increasingly recognized not only in patients with excessive belching, but also in those with reflux-like symptoms. Increased prevalence of esophageal hypomotility and increased acid exposure were previously reported in small cohorts of SGB patients. We aimed to clarify the impact of SGB on motility, reflux, and acid exposure in a large cohort of SGB patients. METHODS: In a single-center database study, we searched for patients with pathological SGB. MII-pH and Manometry tracings were manually re-evaluated in all patients. Demographic, clinical, motility, reflux, and SGB-related data were gathered. KEY RESULTS: Three hundred and forty-eight patients were included. Heartburn, belching, and regurgitation were the most common symptoms. Ineffective esophageal motility (IEM) was found in 27% of patients. SGB related to 47% of all reflux and to 53.6% of acid reflux events, and accounted for 27.3% of acid exposure time (AET). In those with severe SGB, 62% of acid reflux events and 46% of AET were SGB-related. CONCLUSIONS & INFERENCES: Supragastric belching is common, associated with higher incidence of IEM and is responsible for almost a third of esophageal acid burden. The impact of SGB is proportional to its severity. Diagnosis of SGB should be sought in patients with excessive belching and in patients with refractory reflux symptoms. Recognizing SGB and treating patients with behavioral therapy may alleviate acid exposure and improve quality of life.

Evaluating the efficacy and safety of acotiamide in patients with esophagogastric junction outflow obstruction: study protocol for an investigator-initiated, multi-center, randomized, double-blind, placebo-controlled phase II trial.

BACKGROUND: We have determined that the impaired accommodation of the lower esophageal sphincter (LES) underlies the pathogenesis of esophagogastric junction outflow obstruction (EGJOO). We have also found that acotiamide may treat EGJOO by improving impaired LES accommodation. The effects of acotiamide in patients with EGJOO need to be further confirmed in a prospective study. METHODS: This trial is a multicenter, randomized, double-blind, placebo-controlled study to compare the efficacy and safety of acotiamide (300 mg/day or 600 mg/day) with those of a placebo in the treatment of patients with EGJOO. The primary endpoint will be the proportion of patients who report an improvement in symptom of food sticking in the chest after 4 weeks of treatment period 1. The secondary endpoints will be the proportion of patients with normalized integrated relaxation pressure (IRP), the value of change from baseline in the distal contractile integral, basal LES pressure, EGJOO-quality of life score, Gastrointestinal Symptom Rating Scale, and the correlation between IRP and each symptom score. During the 2-year trial period, 42 patients from five institutions will be enrolled. DISCUSSION: This trial will provide evidence to clarify the efficacy and safety of acotiamide as a treatment for patients with EGJOO. Acotiamide might help improve the quality of life of patients with EGJOO and is expected to prevent the progression of EGJOO to achalasia. TRIAL REGISTRATION: This study was approved by the Institutional Review Board (IRB) of Kyushu University Hospital as well as the local IRBs of the participating sites for clinical trials and registered in the Japan Registry of Clinical Trials (jRCT: 2071210072). The registration date is on October 11, 2021.