Fumihiko Toyoshima

The G-Protein β3 subunit 825 TT genotype is associated with epigastric pain syndrome-like dyspepsia

BackgroundAlthough familial clustering of functional dyspepsia (FD) has been reported, the role of genetics in the susceptibility to FD is still not well understood. Several reports indicate an association between FD and G-protein β3 (GNB3) subunit gene polymorphism (C825T); however, these studies had small sample sizes and the findings are inconclusive. In the present study we clarified the association between GNB3 gene polymorphism and dyspepsia in a large population of Japanese subjects who visited a hospital for annual health check-up.MethodsSubjects with significant upper gastrointestinal findings were excluded. Subjects with dyspeptic symptoms were divided into either a postprandial distress syndrome (PDS) group or an epigastric pain syndrome (EPS) group according to the Rome III criteria. The presence of the GNB3 C825T polymorphism was then evaluated and logistic regression analysis was used to test all variables.ResultsThe GNB3 genotype distribution in subjects without dyspepsia was 191 CC (25.1%), 368 TC (48.4%), and 202 TT (26.5%) and 17 CC (25.0%), 29 TC (42.6%), and 22 TT (32.4%) in subjects with dyspepsia. No significant correlation was found between the GNB3 825TT genotype and dyspepsia. However, the TT genotype was significantly associated with subjects with EPS-like symptoms (odds ratio (OR) = 2.00, 95% confidence interval (CI); 1.07-3.76) compared to the CT/CC genotype adjusted for gender and age. No significant correlation was found between GNB3 polymorphism and PDS-like symptoms (OR = 0.68, 95% CI; 0.31-1.51). With the exclusion of subjects with both EPS- and PDS-like symptoms, only the TT genotype was significantly associated with EPS-like symptoms (OR = 2.73, 95% CI; 1.23-5.91).ConclusionThe homozygous GNB3 825T allele influences the susceptibility to EPS-like dyspepsia.

Generation of dyspeptic symptoms by direct acid and water infusion into the stomachs of functional dyspepsia patients and healthy subjects.

Aliment Pharmacol Ther 2012; 35: 175–182

Serotonin transporter gene polymorphism may be associated with functional dyspepsia in a Japanese population

BackgroundAlthough familial clustering of functional dyspepsia (FD) has been reported, the role of genetics in the susceptibility to FD is still not well understood. In the present study, the association between serotonin transporter (SERT) gene (SLC6A4) polymorphism and FD was explored.MethodsSubjects were divided into either a postprandial distress syndrome (PDS) group or an epigastric pain syndrome (EPS) group according to the Rome III criteria. The healthy controls were those who had visited a hospital for an annual health check-up. The presence of the SLC6A4 promoter polymorphism, 5-hydroxytryptamin transporter gene linked polymorphic region (5-HTTLPR), was then evaluated, and logistic regression analysis was used to test all variables.ResultsThe 5-HTTLPR genotype distribution was 448 SS, 174 SL, and 24 LL in controls and 30 SS, 20 SL, and 3 LL in FD subjects. No significant correlation was found between the 5-HTTLPR genotype and FD. When the genotypes and subtypes of FD were exploratory evaluated, the SL genotype was significantly associated with PDS [odds ratio (OR) = 2.24, 95% confidence interval (CI); 1.16-4.32, P = 0.034 after Bonferroni correction] compared to the SS genotype adjusted for sex and age. Comparison of the SS genotype with the SL/LL genotype also showed a significant association of genotype with PDS (OR = 2.32, 95% CI; 1.23-4.37, P = 0.009).ConclusionThe present results suggest that 5-HTTLPR L allele may influence the susceptibility to PDS.

Genetic factors for functional dyspepsia.

Background:  Although familial clustering of functional dyspepsia (FD) has been reported, the role of genetics in the susceptibility to FD is still not well established. Several reports indicate the associations between FD and gene polymorphisms, however the data are inconsistent. This review summarized the evidence of genetics in FD based on genetic epidemiology.

Prospective randomized controlled trial to compare the effects of omeprazole and famotidine in preventing delayed bleeding and promoting ulcer healing after endoscopic submucosal dissection.

Background and Aims:  Proton pump inhibitors (PPIs) are generally used to prevent delayed bleeding after endoscopic submucosal dissection (ESD) and to heal the artificial ulcers. However, it remains controversial whether PPIs or histamine‐2 receptor antagonists (H2RAs) are more effective in preventing delayed bleeding after ESD. We prospectively compared the effects of omeprazole and famotidine in preventing delayed bleeding and promoting artificial ulcer healing after ESD.

Do endoscopic features suggesting eosinophilic esophagitis represent histological eosinophilia

Esophageal linear furrows, corrugated rings, and/or white exudates are often seen in patients with eosinophilic esophagitis (EoE); however, whether these are specific to EoE remains unclear. Endoscopic surveillance of these features was conducted to determine whether these represent esophageal eosinophilia, which is essential for the diagnosis of EoE.

Prevalence and Self-recognition of Chronic Constipation: Results of an Internet Survey

Background/Aims Although chronic constipation is a common symptom, to date no international consensus has been reached regarding its definition. The aims of this study were (1) to investigate defecation habits and (2) to examine the prevalence of constipation using the Japanese Society of Internal Medicine (JSIM) and the Rome III criteria using an online survey. Methods An online questionnaire composed of items on the frequency, interval, form of defecation, the management, and self-recognition of constipation (reference standard of constipation) was created. A total of 5155 valid responses were received. In addition, constipation symptoms were evaluated through a survey using the JSIM and the Rome III criteria. Results In the internet survey, 28.4% of the respondents considered themselves to be constipated. Stratified by sex, significantly more females (37.5%) than males (19.1%) considered themselves to be constipated (P < 0.001). The prevalence of constipation among the respondents was 28.0% using the Rome III, but only 10.1% using the JSIM. The diagnostic accuracy was 73.2% for the Rome III and 78.1% for the JSIM, while the diagnostic specificity was 81.1% for the Rome III and 97.5% for the JSIM. However, the diagnostic sensitivities for both measures were low, at 52.2% and 29.2% for the Rome III and the JSIM, respectively. Conclusions The online survey developed for this study was able to provide clarification regarding defecation patterns. The results also suggest a discrepancy between the self-recognized prevalence of constipation in Japan and prevalence of constipation based on the JSIM criteria.

Effects of Helicobacter pylori eradication on the development of metachronous gastric cancer after endoscopic treatment: analysis of molecular alterations by a randomised controlled trial

Background:Whether Helicobacter pylori eradication actually suppresses the development of metachronous gastric cancer (MGC) after endoscopic resection (ER) remains controversial. The aims of this study were to clarify (1) the molecular markers related to carcinogenesis in intestinal metaplasia (IM) by a cross-sectional study, and (2) the changes of those markers by an open-label, randomised controlled trial (RCT) of H. pylori treatment.Methods:First, we evaluated microsatellite instability (MSI), the methylation status at hMLH1, CDKN2A and APC genes, and immunoreactivity using the monoclonal antibody (mAb) Das-1 in IM in the background mucosa of 131 patients who underwent ER for gastric neoplasia and 22 chronic gastritis cases (control). Next, we performed an RCT to evaluate the changes of MSI between the H. pylori-eradicated (n=19) and non-eradicated patients (n=17) at 1 year among the H. pylori-positive patients.Results:Microsatellite instability and mAb Das-1 reactivity showed significantly higher incidences in both the H. pylori-positive and -negative patients compared with the control group, thus suggesting that MSI and mAb Das-1 reactivity are associated with gastric neoplasia (OR=5.06 for MSI; OR=2.51 for mAb Das-1 reactivity). The RCT showed that H. pylori eradication did not provide significant reversals of any molecular alterations including MSI (the primary end point) and other methylation statuses and mAb Das-1 reactivity (secondary end points).Conclusions:H. pylori eradication did not produce significant changes in the molecular alterations related to carcinogenesis, suggesting that H. pylori treatment may not prevent the development of MGC in background mucosa with IM.

Use of scintigraphy to evaluate gastric accommodation and emptying: Comparison with barostat

Scintigraphy is a useful noninvasive technique for assessment of gastric motility, especially emptying, but there is little knowledge of use of the technique to assess gastric accommodation. Therefore, to clarify the usefulness of scintigraphy as a technique for assessing gastric accommodation, we compared scintigraphy with barostat, the gold standard modality.

A case of Cronkhite-Canada syndrome complicated by McKittrick-Wheelock syndrome associated with advanced villous adenocarcinoma

F w Cronkhite-Canada syndrome (CCS) is a rare noninherited disease characterized by hyperplastic GI polyposis with various GI symptoms, alopecia, and onychodystrophy.1 Although the etiology remains unclear, a significant umber of CCS patients with GI malignancy, especially olorectal adenoma and/or cancer, have been reported.2,3 McKittrick-Wheelock syndrome (MWS) is an infrequent disorder that has the clinical features of depletion syndrome characterized by dehydration, watery diarrhea, and various symptoms caused by hyponatremia and hypokalemia4 as well as CCS. The most frequently reported leions causing MWS are villous adenomas situated primarly in the rectum and sigmoid colon.4,5 We report an extremely rare case of a patient with CCS complicated by MWS, presumably caused by a large villous adenocarcinoma of the rectum.