Tsuneya Wada

Fatty liver predicts impaired fasting glucose and type 2 diabetes mellitus in Japanese undergoing a health checkup

Background and Aim:  The question of whether fatty liver might predict impaired fasting glucose or type 2 diabetes mellitus in a longitudinal manner was assessed in Japanese subjects undergoing a health checkup.

Efficacy of rabeprazole on heartburn symptom resolution in patients with non‐erosive and erosive gastro‐oesophageal reflux disease: a multicenter study from Japan

Background  Few studies have compared the efficacy of proton pump inhibitors in resolving the symptoms of non‐erosive reflux disease (NERD) and of erosive gastro‐oesophageal reflux disease (GERD) in Japan.

Advantages of endoscopic submucosal dissection over conventional endoscopic mucosal resection

Background:  Endoscopic mucosal resection is an established method for treating intramucosal gastric neoplasms. Conventional endoscopic mucosal resection has predominantly been performed using strip biopsy, but local recurrence sometimes occurs due to such piecemeal resection. Endoscopic submucosal dissection has recently been performed in Japan using new devices such as an insulation‐tip diathermic knife. The efficacy and problems associated with endoscopic submucosal dissection were evaluated by comparison with conventional endoscopic mucosal resection.

Validity of endoscopic classification of nonerosive reflux disease

BackgroundMinimal changes, such as erythema without sharp demarcation or whitish turbidity of the lower esophageal mucosa, have recently been used for endoscopic classification of nonerosive reflux disease (NERD) in Japan. This study examined the usefulness of such changes in characterizing the pathophysiology of NERD.MethodsPhysicians specializing in esophageal endoscopy performed endoscopy on 115 patients with NERD. Based on the presence or absence of minimal changes, patients were categorized as displaying NERD with minimal changes (grade M, n = 49) or with no minimal changes or mucosal breaks (grade N, n = 66). Clinical features, quality of life (QOL) scores, and ambulatory 24-h esophageal pH values were compared between groups. Ambulatory 24-h esophageal pH values were monitored in 31 patients (14 grade M and 17 grade N patients) who gave consent out of 115 patients.ResultsIn ambulatory 24-h esophageal pH monitoring, 57.1% (8/14) of grade M patients had pH < 4 more than 4% of the time (abnormal acid reflux) compared with 11.8% (2/17) in the grade N group, a significant difference (P = 0.018). QOL scores did not differ significantly between grades and were significantly lower in both groups compared with the general Japanese population. No significant differences were observed in patient background between the grade M and grade N groups.ConclusionsFrequency of abnormal acid reflux with NERD is higher in patients with minimal changes than in patients without such changes. Minimal changes are most likely attributable to gastric acid reflux.

Randomised clinical trial: efficacy of the addition of a prokinetic, mosapride citrate, to omeprazole in the treatment of patients with non‐erosive reflux disease – a double‐blind, placebo‐controlled study

Aliment Pharmacol Ther 2011; 33: 323–332

Impaired gastric motility and its relationship to reflux symptoms in patients with nonerosive gastroesophageal reflux disease

BackgroundMore than half of patients with refluxrelated symptoms have no endoscopic evidence of mucosal breaks. These patients are considered to have nonerosive gastroesophageal reflux disease (NERD). The pathogenesis of NERD may be multifactorial, but the role played by gastric motility in symptom generation in patients with NERD has not been examined. In this study, we elucidate gastric motility in patients with NERD and the efficacy of a prokinetic agent in the treatment of NERD.MethodsGastric motility was evaluated with electrogastrography (EGG) and by measurement of gastric emptying using the acetaminophen method in 26 patients with NERD and in 11 matched healthy controls. NERD patients were treated with a prokinetic agent (mosapride 15 mg, orally three times daily) for a period of 4 weeks, after which gastric motility was measured again.ResultsCompared with the healthy controls, the NERD patients showed a significantly lower percentage of normogastria, a lower power ratio in EGG, and delayed gastric emptying. Ten patients had normal gastric motor function (group A), and 16 showed abnormalities of either gastric myoelectrical activity or gastric emptying (group B). After treatment with mosapride, gastric motility improved significantly in both groups of patients compared with pretreatment values. The subjective assessment by the patient after the treatment was improved in 20.0% of group A versus 62.5% of group B patients (P < 0.05).ConclusionsGastric hypomotility appears to be an important factor in reflux symptom generation in some NERD patients.

Blockage of angiotensin II type 1 receptor regulates TNF-α-induced MAdCAM-1 expression via inhibition of NF-κB translocation to the nucleus and ameliorates colitis

Mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1) is an important target in the treatment of inflammatory bowel disease (IBD). Recently, treatment of IBD with an antibody to alpha4beta7-integrin, a ligand for MAdCAM-1, has been an intense focus of research. Our aim was to clarify the mechanism by which MAdCAM-1 is regulated via angiotensin II type 1 receptor (AT1R), and to verify if AT1R might be a novel target for IBD treatment. The role of AT1R in the expression of MAdCAM-1 in SVEC (a murine high endothelial venule cell) and MJC-1 (a mouse colonic endothelial cell) was examined following cytokine stimulation. We further evaluated the effect of AT1R on the pathogenesis of immune-mediated colitis using AT1R-deficient (AT1R-/-) mice and a selective AT1R blocker. AT1R blocker significantly suppressed MAdCAM-1 expression induced by TNF-alpha, but did not inhibit phosphorylation of p38 MAPK or of IkappaB that modulate MAdCAM-1 expression. However, NF-kappaB translocation into the nucleus was inhibited by these treatments. In a murine colitis model induced by dextran sulfate sodium, the degree of colitis, judged by body weight loss, histological damage, and the disease activity index, was much milder in AT1R-/- than in wild-type mice. The expression of MAdCAM-1 was also significantly lower in AT1R-/- than in wild-type mice. These results suggest that AT1R regulates the expression of MAdCAM-1 under colonic inflammatory conditions through regulation of the translocation of NF-kappaB into the nucleus. Furthermore, inhibition of AT1R ameliorates colitis in a mouse colitis model. Therefore, AT1R might be one of new therapeutic target of IBD via regulation of MAdCAM-1.

Elevated Serum Uric Acid Predicts Chronic Kidney Disease

Introduction:The question of whether elevated serum uric acid is an independent risk factor for chronic kidney disease in a longitudinal manner was assessed in Japanese subjects undergoing a health checkup. Methods:A total of 14,399 participants (8,161 men and 6,238 women) without medication for hyperuremia in both 2000 and 2005 were included. After exclusion of participants taking treatments influencing serum uric acid and having chronic kidney disease defined as estimated glomerular filtration rate <60 mL/min/1.73m2, in 2000, multiple logistic regression analyses were performed for 6,887 men (48.4 ± 9.9 years) and 5,340 women (49.9 ± 9.0 years) to identify independent factors for newly diagnosed chronic kidney disease in 2005. Adjustment was made for age, body mass index, elevated blood pressure or hypertension, hypertriglyceridemia, impaired fasting glucose, either urinary protein or occult blood, alcohol drinking and smoking. Results:The prevalence of chronic kidney disease and the values of body mass index, systolic and diastolic blood pressure and triglyceride were significantly higher in the participants with elevated serum uric acid quartiles. Chronic kidney disease was newly diagnosed in 4.1% of men and 3.7% of women, within the 5-year period. In multivariate models, the higher quartiles of serum uric acid were associated with increased risk of chronic kidney disease in both sexes. The odds ratio and 95% confidence interval for 1 increment of serum uric acid were 1.42 and 1.28 to 1.58 in men and 1.32 and 1.12 to 1.56 in women, respectively. Conclusions:Elevated serum uric acid predicts chronic kidney disease in subjects undergoing a health checkup.

Gastroesophageal and laryngopharyngeal reflux symptoms correlate with histopathologic inflammation of the upper and lower esophagus.

Background The presence of laryngopharyngeal reflux disease is controversial when abnormal sensation of the laryngopharynx is felt without heartburn. Goals The aims of this study were to investigate the relationship between abnormal sensation of the laryngopharynx and gastroesophageal reflux, and to elucidate the pathology of laryngopharyngeal reflux disease by investigating histopathologic findings of the upper and lower esophagus. Study Upper and lower esophageal tissues were biopsied by endoscopy in 300 consenting patients, excluding those with serious diseases. Results Fifty-seven patients (19.0%) reported reflux symptoms alone (reflux symptom group), 48 patients (16.0%) reported abnormal sensation of the laryngopharynx alone (abnormal laryngopharyngeal sensation group), and 74 patients (24.7%) reported both reflux symptoms and abnormal sensation of the laryngopharynx (complication group), whereas 121 patients (40.3%) did not report subjective reflux symptoms and abnormal sensation of the laryngopharynx (control group). Histopathologic inflammation of the upper esophagus was significantly greater in the complication and abnormal laryngopharyngeal sensation groups compared with the control group. Histologic inflammation of the lower esophagus was significantly higher in the complication and reflux symptom groups compared with the control group. Conclusions The histopathologic findings of the upper and lower esophagus elucidated an association between gastroesophageal reflux and abnormal sensation of the laryngopharynx.

Efficacy of famotidine and omeprazole in healing symptoms of non-erosive gastro-oesophageal reflux disease: randomized-controlled study of gastro-oesophageal reflux disease

Background : The epidemiology and pathophysiology of non‐erosive gastro‐oesophageal reflux disease differs from erosive gastro‐oesophageal reflux disease. There is a possibility that non‐erosive gastro‐oesophageal reflux disease treatment requires a different regimen/approach but it is not yet acknowledged.