Journal of Neurogastroenterology and Motility最新文献

Background/aims: Gastroesophageal reflux disease (GERD) is a common chronic gastrointestinal disorder that typically requires long-term maintenance therapy. However, little is known about patient preferences and satisfaction and real-world prescription patterns regarding maintenance therapy for GERD.

Methods: This observational, cross-sectional, multicenter study involved patients from 18 referral hospitals in Korea. We surveyed patients who had been prescribed proton pump inhibitors (PPIs) for GERD for at least 90 days with a minimum follow-up duration of 1 year. The main outcome was overall patient satisfaction with different maintenance therapy modalities.

Results: A total of 197 patients were enrolled. Overall patient satisfaction, patient preferences, and GERD health-related quality of life scores did not significantly differ among the maintenance therapy modality groups. However, the on-demand therapy group experienced a significantly longer disease duration than the continuous therapy group. The continuous therapy group demonstrated a lower level of awareness of potential adverse effects associated with PPIs than the on-demand therapy group but received higher doses of PPIs than the on-demand therapy group. The prescribed doses of PPIs also varied based on the phenotype of GERD, with higher doses prescribed for non-erosive reflux disease than erosive reflux disease.

Conclusion: Although overall patient satisfaction did not significantly differ among the different PPI maintenance therapy modality groups, awareness of potential adverse effects was significantly different between the on-demand and continuous therapy groups.

Background/aims: Irritable bowel syndrome (IBS) is accepted as a disorder of gut-brain interactions. Berberine and rifaximin are non-absorbed antibiotics and have been confirmed effective for IBS treatment, but there is still lack of direct comparison of their effects. This study aims to compare the effect of the 2 drugs on the alteration of gut-brain axis caused by gut microbiota from IBS patients.

Methods: Germ-free rats received fecal microbiota transplantation from screened IBS patients and healthy controls. After 14 days' colonization, rats were administrated orally with berberine, rifaximin or vehicle respectively for the next 14 days. The visceral sensitivity was evaluated, fecal microbiota profiled and microbial short chain fatty acids were determined. Immunofluorescence staining and morphological analysis were performed to evaluate microglial activation.

Results: Visceral hypersensitivity induced by IBS-fecal microbiota transplantation was relieved by berberine and rifaximin, and berberine increased sucrose preference rate. Microbial α-diversity were reduced by both drugs. Compared with rifaximin, berberine significantly changed microbial structure and enriched Lachnoclostridium. Furthermore, berberine but not rifaximin significantly increased fecal concentrations of acetate and propionate acids. Berberine restored the morphological alterations of microglia induced by dysbiosis, which may be associated with its effect on the expression of microbial gene pathways involved in peptidoglycan biosynthesis. Rifaximin affected neither the numbers of activated microglial cells nor the microglial morphological alterations.

Conclusions: Berberine enriched Lachnoclostridium, reduced the expression of peptidoglycan biosynthesis genes and increased acetate and propionate. The absence of these actions of rifaximin may explain the different effects of the drugs on microbiota-gut-brain axis.

Background/aims: Previous studies reveal that immune-mediated neuroinflammation plays a key role in the etiology of esophageal achalasia. However, the understanding of leucocyte phenotype and proportion is limited. This study aim to evaluate the phenotypes of leukocytes and peripheral blood mononuclear cells transcriptomes in esophageal achalasia.

Methods: We performed high-dimensional flow cytometry to identified subsets of peripheral leukocytes, and further validated in lower esophageal sphincter histologically. RNA sequencing was applied to investigate the transcriptional changes in peripheral blood mononuclear cells of patients with achalasia. Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) was used for estimating the immune cell types. A differential gene expression analysis was performed and the differential expressed genes were subjected to gene ontology, Kyoto Encyclopedia of Genes and Genomes network, protein-protein interaction network construction.

Results: An imbalance between innate and adaptive immune cells occurred in achalasia. Specifically, neutrophils and CD8+ T cells increased both in peripheral blood and lower esophageal sphincter in achalasia. Eosinophils decreased in peripheral blood but massively infiltrated in lower esophageal sphincter. CIBERSORT analysis of peripheral blood mononuclear cells RNA sequencing displayed an increased prevalence of CD8+ T cells. 170 dysregulated genes were identified in achalasia, which were enriched in immune cells migration, immune response, etc. Proton pump inhibitor analysis revealed the intersections and gained 7 hub genes in achalasia, which were IL-6, Toll-like receptor 2, IL-1β, tumor necrosis factor, complement C3, and complement C1q A chain.

Conclusion: Patients with achalasia exhibited an imbalance of systematic innate and adaptive immunity, which may play an important role in the development of achalasia.

Background/aims: Achalasia and hiatal hernia are rarely associated. The aim of the current study is to explore the clinical and manometric findings in patients with achalasia and hiatal hernia, and to determine if the presence of a hiatal hernia should influence therapeutic management in patients with achalasia.

Methods: This retrospective single center analysis included a group of patients with achalasia and hiatal hernia (study group) and a group of matched patients with achalasia but no hiatal hernia (control group). We recorded demographic, clinical, endoscopic, and manometric parameters and compared initial presentation and treatment outcomes between the groups.

Results: Between 2015 and 2022, achalasia was diagnosed in 294/1513 (19.4%) patients. Concomitant hiatal hernia was identified in 13/294 (4.4%) patients. Compared to patients with achalasia and no hiatal hernia, patients in the study group had lower Eckardt scores at baseline (5.4 ± 2.0 vs 7.8 ± 2.4; P = 0.005) but similar integrated relaxation pressure. Following treatment, patients in the study and control group had similar clinical success and prevalence of gastroesophageal reflux symptoms.

Conclusions: Hiatal hernia is rarely associated with achalasia. The presence of a hiatal hernia should not influence treatment decisions in patients with achalasia.

Achalasia is a major esophageal motor disorder featured by the altered relaxation of the esophagogastric junction in the absence of effective peristaltic activity. As a consequence of the esophageal outflow obstruction, achalasia patients present with clinical symptoms of dysphagia, chest pain, weight loss, and regurgitation of indigested food. Other less specific symptoms can also present including heartburn, chronic cough, and aspiration pneumonia. The delay in diagnosis, particularly when the presenting symptoms mimic those of gastroesophageal reflux disease, may be as long as several years. The widespread use of high-resolution manometry has permitted earlier detection and uncovered achalasia phenotypes which can have prognostic and therapeutic implications. Other tools have also emerged to help define achalasia severity and which can be used as objective measures of response to therapy including the timed barium esophagogram and the functional lumen imaging probe. Such diagnostic innovations, along with the increased awareness by clinicians and patients due to the availability of alternative therapeutic approaches (laparoscopic and robotic Heller myotomy, and peroral endoscopic myotomy) have radically changed the natural history of the disorder. Herein, we report the most recent advances in the diagnosis, classification, and management of esophageal achalasia and underline the still-grey areas that needs to be addressed by future research to reach the goal of personalizing treatment.

Background/aims: Non-cardiac chest pain (NCCP) is defined as recurring angina-like retrosternal chest pain of non-cardiac origin. Information about the epidemiology of NCCP in Japan is lacking. We aim to determine the prevalence and characteristics of NCCP in the Japanese general population.

Methods: Two internet-based surveys were conducted among the general population in March 2017. Questions investigated the characteristics of symptoms associated with chest pain and consultation behavior. Quality of life, anxiety, depression, and gastroesophageal reflux disease were analyzed.

Results: Five percent of the survey respondents reported chest pain. Subjects with chest pain showed higher frequencies of anxiety and depression and lower quality of life. Among subjects with chest pain, approximately 30% had sought medical attention for their symptoms. Among all consulters, 70% were diagnosed with NCCP. Females were less likely to seek consultations for chest pain than males. Further, severity and frequency of chest pain, lower physical health component summary score, and more frequent gastroesophageal reflux disease were associated with consultation behavior. Subjects with NCCP and cardiac chest pain experienced similar impacts on quality of life, anxiety, and depression. Among subjects with NCCP, 82% visited a primary-care physician and 15% were diagnosed with reflux esophagitis.

Conclusions: The prevalence of chest pain in this sample of a Japanese general population was 5%. Among all subjects with chest pain, less than one-third consulted physicians, approximately 70% of whom were diagnosed with NCCP. Sex and both the severity and frequency of chest pain were associated with consultation behavior.

Background/aims: Multiple sclerosis (MS) is an inflammatory disease characterized by the demyelination of primarily the central nervous system. Diffuse esophageal spasm (DES) and achalasia are both disorders of esophageal peristalsis which cause clinical symptoms of dysphagia. Mechanisms involving dysfunction of the pre- and post-ganglionic nerve fibers of the myenteric plexus have been proposed. We sought to determine whether MS confers an increased risk of developing achalasia or DES.

Methods: Cohort analysis was done using the Explorys database. Univariate logistic regression was performed to determine the odds MS confers to each motility disorder studied. Comparison of proportions of dysautonomia comorbidities was performed among the cohorts. Patients with a prior diagnosis of diabetes mellitus, chronic Chagas' disease, opioid use, or CREST syndrome were excluded from the study.

Results: Odds of MS patients developing achalasia or DES were (OR, 2.09; 95% CI, 1.73-2.52; P < 0.001) and (OR, 3.15; 95% CI, 2.89-3.42; P < 0.001), respectively. In the MS/achalasia cohort, 27.27%, 18.18%, 9.09%, and 45.45% patients had urinary incontinence, gastroparesis, impotence, and insomnia, respectively. In the MS/DES cohort, 35.19%, 11.11%, 3.70%, and 55.56% had these symptoms. In MS patients without motility disorders, 12.64%, 0.79%, 2.21%, and 21.85% had these symptoms.

Conclusions: Patients with MS have higher odds of developing achalasia or DES compared to patients without MS. MS patients with achalasia or DES have higher rates of dysautonomia comorbidities. This suggests that these patients have a more severe disease phenotype in regards to the extent of neuronal degradation and demyelination causing the autonomic dysfunction.

Background/aims: The evidence suggests that a shorter esophageal length (EL) in gastroesophageal reflux disease (GERD) patients is associated with the presence of hiatal hernia (HH). However, there are no reports of this association in patients with achalasia. The aim is to (1) determine the prevalence of hiatal hernia in achalasia patients, (2) compare achalasia EL with GERD patients and healthy volunteers (HV), (3) measure achalasia manometric esophageal length to height (MELH) ratio, and (4) determine if there are differences in symptoms between patients with and without hiatal hernia.

Methods: This retrospective and cross-sectional study consist of 87 pre-surgical achalasia patients, 22 GERD patients, and 30 HV. High-resolution manometry (HRM), barium swallow, and upper endoscopy were performed to diagnose HH. The EL and MELH ratio were measured by HRM. Symptoms were assessed with Eckardt, Eating Assessment Tool, and GERD-health-related quality of life questionnaires.

Results: The HH in GERD's prevalence was 73% vs 3% in achalasia patients (P < 0.001). Achalasia patients had a longer esophagus and a higher MELH ratio than HV and GERD patients (P < 0.001). GERD patients had a lower MELH ratio than HV (P < 0.05). EAT-10 (P < 0.0001) and Eckardt (P < 0.05) scores were higher in achalasia without HH vs HH.

Conclusions: The prevalence of HH in achalasia is significantly lower than in GERD. The longer EL and the higher MELH ratio in achalasia could explain the lower prevalence of HH. Despite the low prevalence of HH in achalasia patients, the surgeon should be encouraged not to rule out HH since the risk of postoperative reflux may increase if this condition is not identified and corrected.

Background/aims: It remains unclear which maintenance treatment modality is most appropriate for mild gastroesophageal reflux disease (GERD). We aimed to compare on-demand treatment with continuous treatment using a proton pump inhibitor (PPI) in the maintenance treatment for patients with non-erosive GERD or mild erosive esophagitis.

Methods: Patients whose GERD symptoms improved after 4 weeks of standard dose PPI treatment were prospectively enrolled at 25 hospitals. Subsequently, the enrolled patients were randomly assigned to either an on-demand or a continuous maintenance treatment group, and followed in an 8-week interval for up to 24 weeks.

Results: A total of 304 patients were randomized to maintenance treatment (continuous, n = 151 vs on-demand, n = 153). The primary outcome, the overall proportion of unwillingness to continue the assigned maintenance treatment modality, failed to confirm the non-inferiority of on-demand treatment (45.9%) compared to continuous treatment (36.1%). Compared with the on-demand group, the GERD symptom and health-related quality of life scores significantly more improved and the overall satisfaction score was significantly higher in the continuous treatment group, particularly at week 8 and week 16 of maintenance treatment. Work impairment scores were not different in the 2 groups, but the prescription cost was less in the on-demand group. Serum gastrin levels significantly elevated in the continuous treatment group, but not in the on-demand group.

Conclusions: Continuous treatment seems to be more appropriate for the initial maintenance treatment of non-erosive GERD or mild erosive esophagitis than on-demand treatment. Stepping down to on-demand treatment needs to be considered after a sufficient period of continuous treatment.