[Show abstract][Hide abstract] ABSTRACT: A 47-year-old man was found to have a 3-cm epiphrenic esophageal diverticulum on an upper gastrointestinal (UGI) barium study. He developed the symptoms of heartburn approximately 12 months later. UGI endoscopy indicated non-erosive gastroesophageal reflux disease (NERD) and an epiphrenic esophageal diverticulum. A proton pump inhibitor (PPI) did not relieve the symptoms. An UGI barium study at that time showed that the epiphrenic esophageal diverticulum had enlarged to 7 cm, and esophageal manometry showed findings of achalasia and diffuse esophageal spasm (DES), thus vigorous achalasia was diagnosed. Resection of the epiphrenic esophageal diverticulum, myotomy, and fundoplication (the Heller-Dor procedure) were successfully performed and no postoperative symptoms were encountered.
[Show abstract][Hide abstract] ABSTRACT: To investigate the pathophysiology of functional heartburn (FH) in Japanese patients.
A total of 111 patients with proton pump inhibitor (PPI)-refractory non-erosive gastroesophageal reflux disease underwent intraesophageal pressure testing and 24-h multichannel intraluminal impedance-pH (24MII-pH) testing. The patients also completed several questionnaires while they were receiving the PPI treatment, including the questionnaire for the diagnosis of reflux disease (QUEST), the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG), the gastrointestinal symptoms rating scale (GSRS), SF-36, and the Cornell Medical Index (CMI). The subjects were classified into FH and endoscopy-negative reflux disease (ENRD) groups based on the Rome III criteria.
Thirty-three patients with esophageal motility disorder were excluded from this study, while 22 patients with abnormal esophageal acid exposure time (pH-POS) and 34 with hypersensitive esophagus (HE) were included in the ENRD group. The FH group included 22 patients with no reflux involvement. Sex, age, and body mass index did not differ significantly between the groups. The mean SF-36 values were < 50 (normal) for all scales in these groups, with no significant differences. The GSRS scores in these groups were not different and showed overlap with other gastrointestinal symptoms. The QUEST and the FSSG scores did not differ significantly between the groups. Neuroticism was diagnosed using the CMI questionnaire in 17 of the 78 included subjects within the pH-POS (n = 4), HE (n = 8), and FH (n = 5) groups, with no significant differences.
Clinical characteristics of the FH and PPI-refractory ENRD groups were similar. Therefore, esophageal function should be examined via manometry and 24MII-pH testing to differentiate between them.
[Show abstract][Hide abstract] ABSTRACT: A 53-year-old man was admitted to our hospital with anterior chest pain and difficulty swallowing. Computed tomography revealed significant esophageal wall thickening. Esophageal intraluminal manometry revealed uncoordinated contraction and strong peristaltic pressure associated with the chest pain. The patient was subsequently diagnosed with diffuse esophageal spasm (DES). His serum immunoglobulin E level was high, and peripheral blood eosinophilia was observed. No eosinophilic infiltration was detected in the esophageal mucosa on endoscopic biopsy. It was presumed that this case of DES was induced by allergic disease. Treatment with 30 mg of oral prednisolone led to a prompt resolution of symptoms;the thickness of the esophageal wall decreased, and the simultaneous contractions disappeared. However, given the presence of a strong peristaltic wave, nutcracker esophagus (NE) was also suspected. This was a rare case of atypical DES induced by allergic disease and associated with NE.
Full-text · Article · Sep 2014 · Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology
[Show abstract][Hide abstract] ABSTRACT: Long-term administration of low-dose aspirin (LDA) is associated with a greater risk of adverse events, including gastroduodenal ulcers. The purpose of this study was to identify the risk factors for and assess the role of medication use in the development of peptic ulcer disease in Japanese patients with no history of peptic ulcers.
Consecutive outpatients receiving LDA (75 mg/day) who underwent esophagogastroduodenoscopy between January and December 2010 were enrolled. Clinical parameters, peptic ulcer history, concomitant drugs, the presence of Helicobacter pylori infection, reason for endoscopy, and endoscopic findings were analysed.
Of 226 total patients, 14 (6.2%) were endoscopically diagnosed with peptic ulcer. Age, sex, current smoking status, current alcohol consumption, endoscopic gastric mucosal atrophy, and abdominal symptoms were not significantly associated with peptic ulcers. Diabetes mellitus was more frequent (42.9% vs. 16.5%; P = 0.024) in patients with peptic ulcers than in those without peptic ulcers. Using multiple logistic regression analysis, co-treatment with anticoagulants or proton pump inhibitors (PPIs) was significantly associated with increased and decreased risk for peptic ulcer, respectively (odds ratio [OR], 5.88; 95% confidence interval [CI], 1.19 - 28.99; P = 0.03 and OR, 0.13; 95% CI, 0.02 - 0.73; P = 0.02, respectively). Co-treatment with additional antiplatelet agents, H2-receptor antagonists, angiotensin II Type 1 receptor blockers, angiotensin-converting enzyme inhibitor, 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor, or nonsteroidal anti-inflammatory drugs was not associated with peptic ulcer development.
The use of PPIs reduces the risk of developing gastric or duodenal ulcers in Japanese patients taking LDA without pre-existing gastroduodenal ulcers. However, this risk is significantly increased in both patients ingesting anticoagulants and patients with diabetes. These results may help identify patients who require intensive prophylaxis against aspirin-induced peptic ulcers.
Full-text · Article · Nov 2013 · BMC Research Notes
[Show abstract][Hide abstract] ABSTRACT: Short-chain fatty acids (SCFAs), which are produced by the fermentation of dietary fiber by intestinal microbiota, may positively influence immune responses and protect against gut inflammation. SCFAs bind to G protein-coupled receptor 43 (GPR43). Here, we show that SCFA-GPR43 interactions profoundly affect the gut inflammatory response.
Colitis was induced by adding dextran sulfate sodium to the drinking water of GPR43 knockout (-/-) and wild-type mice.
Dextran sulfate sodium-treated GPR43 mice exhibited weight loss, increased disease activity index (a combined measure of weight loss, rectal bleeding, and stool consistency), decreased hematocrit, and colon shortening, resulting in significantly worse colonic inflammation than in wild-type mice. Tumor necrosis factor alpha and interleukin 17 protein levels in the colonic mucosa of GPR43 mice were significantly higher than in wild-type mice. Treatment of wild-type mice with 150 mM acetate in their drinking water markedly improved these disease indices, with an increase in colon length and decrease in the disease activity index; however, it had no effect on GPR43 mice. Mononuclear cell production of tumor necrosis factor alpha after lipopolysaccharide stimulation was suppressed by acetate. This effect was inhibited by anti-GPR43 antibody.
SCFA-GPR43 interactions modulate colitis by regulating inflammatory cytokine production in mononuclear cells.
No preview · Article · Oct 2013 · Inflammatory Bowel Diseases
[Show abstract][Hide abstract] ABSTRACT: Background:
The incidence of upper gastrointestinal injury by low-dose aspirin (LDA) has increased.
We aimed to clarify the risk factors and prevention strategies associated with LDA-induced gastroduodenal ulcer in Japanese patients.
A retrospective study involving 284 LDA users who underwent oesophagogastroduodenoscopy between January and December 2010 were included. We investigated the patients' clinical characteristics and endoscopic findings.
Of 284 patients, 29 (10.2%) had gastro and/or duodenal ulcers. Male gender, peptic ulcer history, abdominal symptoms, half-dose proton pump inhibitors (PPIs), complete-dose PPIs, and nonsteroidal anti-inflammatory drugs were significantly associated with LDA-induced gastro and/or duodenal ulcers: odds ratio (95% confidence interval) 3.62 (1.06-12.27), 6.60 (1.84-23.62), 3.06 (1.12-8.40), 0.16 (0.03-0.94), 0.07 (0.01-0.61), and 9.68 (1.64-57.18), respectively. PPI significantly reduced gastric ulcers and/or duodenal ulcers (p = 0.03). The modified Lanza score for gastric mucosal lesion in the LDA cessation group was significantly lower than in the LDA noncessation group (0.53 vs. 1.02; p = 0.008).
Half-dose PPIs as well as complete-dose PPIs were effective for preventing LDA-induced gastric and/or duodenal ulcers. The cessation of LDA before endoscopy may lead to an underestimation of LDA-induced gastric injury.
Full-text · Article · Aug 2013 · United European Gastroenterology Journal
[Show abstract][Hide abstract] ABSTRACT: Permeation of the small intestinal mucosa is a key mechanism in the induction of enteropathy. We investigated the effect of rebamipide in healthy subjects with diclofenac-induced small intestinal damage and permeability. In this crossover study, each treatment period was 1 week with a 4-week washout period. Diclofenac (75 mg/day) and omeprazole (20 mg/day) plus rebamipide (300 mg/day) or placebo were administered. Capsule endoscopy and a sugar permeability test were performed on days 1 and 7 in each period. Ten healthy subjects were enrolled. Small intestinal injuries were observed on day 7 in 6 of 10 subjects in both groups. Urinary excretion of administered lactulose increased from 0.30% to 0.50% of the initial dose during the first treatment period in the placebo group, and from 0.13% to 0.33% in the rebamipide group. Despite recovery from small-intestinal mucosal damage, the increased permeability in both groups resulted in sustained high levels of lactulose (0.50% to 1.06% in the placebo group and 0.33% to 1.12% in the rebamipide group) through the 4-week washout period. Diclofenac administration induced enteropathy and hyperpermeability of the small intestine. The sustained hyperpermeability during the washout period may indicate the presence of invisible fragility.
Full-text · Article · Jul 2013 · Journal of Clinical Biochemistry and Nutrition
[Show abstract][Hide abstract] ABSTRACT: Recently, the relationship between gut microbiota and obesity has been highlighted. The present randomized, double-blind, placebo-controlled study aimed to evaluate the efficacy of transglucosidase (TGD) in modulating blood glucose levels and body weight gain in patients with type 2 diabetes mellitus (T2DM) and to clarify the underlying mechanism by analyzing the gut microbiota of T2DM patients.
This study included 60 patients who received placebo or TGD orally (300 or 900 mg/day) for 12 weeks, and blood and fecal samples were collected before and after 12 weeks. Comparisons of fecal bacterial communities were performed before and after the TGD treatment and were performed between T2DM patients and 10 healthy individuals, using the terminal-restriction fragment length polymorphism analysis.
The Clostridium cluster IV and subcluster XIVa components were significantly decreased, whereas the Lactobacillales and Bifidobacterium populations significantly increased in the T2DM patients compared with the healthy individuals. By dendrogram analysis, most of the healthy individuals (6/10) and T2DM patients (45/60) were classified into cluster I, indicating no significant difference in fecal bacterial communities between the healthy individuals and the T2DM patients. In the placebo and TGD groups, the bacterial communities were generally similar before and after the treatment. However, after 12 weeks of TGD therapy, the Bacteroidetes-to-Firmicutes ratio in the TGD groups significantly increased and was significantly higher compared with that in the placebo group, indicating that TGD improved the growth of the fecal bacterial communities in the T2DM patients.
Therefore, TGD treatment decreased blood glucose levels and prevented body weight gain in the T2DM patients by inducing the production of oligosaccharides in the alimentary tract and modulating gut microbiota composition.
Full-text · Article · May 2013 · BMC Gastroenterology
[Show abstract][Hide abstract] ABSTRACT: It is known that the pharmacokinetic profile of proton pump inhibitors (PPIs) after postprandial administration may differ among PPIs. The purpose of this study was to compare the inhibitory effects of gastric acid secretion by PPIs administered after a meal, based on a 24-hour intragastric pH monitoring.
Ten healthy men who provided written informed consent participated in the study. They were given a 20-mg omeprazole tablet and a 30-mg lansoprazole orally dispersing tablet in a two-way crossover manner. At baseline, the anti-HP-IgG antibody levels in blood and the pepsinogen (PG) I/II ratio were measured. Participants were given a standardized meal and 200 mL of water at 9:30 am, 13:30 pm, and 18.30 pm. Participants took the PPI after breakfast.
Two of the ten participants tested positive for Helicobacter pylori infection. The PG I/II ratio indicated negative gastric atrophy in all the participants. The percentage 24-hour intragastric pH > 4 holding times (median, range) with omeprazole and lansoprazole were 29.3, 19.3-50.0% and 27.8, 13.0-42.3%, respectively, which shows that with the administration of omeprazole, the pH was maintained at >4 for a longer period (p < 0.05). Each median intragastric pH value per hour at 3, 17, and 18 hours after a dose of omeprazole was significantly higher than that of lansoprazole (p < 0.05).
Compared with lansoprazole, a single postprandial dose of omeprazole showed a more rapid and sustained acid-inhibitory effect.
No preview · Article · Mar 2013 · Journal of the Chinese Medical Association
[Show abstract][Hide abstract] ABSTRACT: To evaluate the efficacy, safety, and long-term outcomes of endoluminal gastroplication (ELGP) in patients with proton pump inhibitor (PPI)-resistant, non-erosive reflux disease (NERD).
The subjects were NERD patients, diagnosed by upper endoscopy before PPI use, who had symptoms such as heartburn or reflux sensations two or more times a week even after 8 wk of full-dose PPI treatment. Prior to ELGP, while continuing full-dose PPI medication, patients' symptoms and quality of life (QOL) were assessed using the questionnaire for the diagnosis of reflux disease, the frequency scale for symptoms of gastro-esophageal reflux disease (FSSG), gastrointestinal symptoms rating scale, a 36-item short-form. In addition, 24-h esophageal pH monitoring or 24-h intraesophageal pH/impedance (MII-pH) monitoring was performed. The Bard EndoCinch(TM) was used for ELGP, and 2 or 3 plications were made. After ELGP, all acid reducers were temporarily discontinued, and medication was resumed depending on the development and severity of symptoms. Three mo after ELGP, symptoms, QOL, pH or MII-pH monitoring, number of plications, and PPI medication were evaluated. Further, symptoms, number of plications, and PPI medication were evaluated 12 mo after ELGP to investigate long-term effects.
The mean FSSG score decreased significantly from before ELGP to 3 and 12 mo after ELGP (19.1 ± 10.5 to 10.3 ± 7.4 and 9.3 ± 9.9, P < 0.05, respectively). The total number of plications decreased gradually at 3 and 12 mo after ELGP (2.4 ± 0.8 to 1.2 ± 0.8 and 0.8 ± 1.0, P < 0.05, respectively). The FSSG scores in cases with no remaining plications and in cases with one or more remaining plications were 4.4 and 2.7, respectively, after 3 mo, and 2.0 and 2.8, respectively, after 12 mo, showing no correlation to plication loss. On pH monitoring, there was no difference in the percent time pH < 4 from before ELGP to 3 mo after. Impedance monitoring revealed no changes in the number of reflux episodes or the symptom index for reflux events from before ELGP to 3 mo after, but the symptom sensitivity index decreased significantly 3 mo after ELGP (16.1 ± 12.9 to 3.9 ± 8.3, P < 0.01). At 3 mo after ELGP, 6 patients (31.6%) had reduced their PPI medication by 50% or more, and 11 patients (57.9%) were able to discontinue PPI medication altogether. After 12 mo, 3 patients (16.7%) were able to reduce the amount of PPI medication by 50% or more, and 12 patients (66.7%) were able to discontinue PPI medication altogether. A high percentage of cases with remaining plications had discontinued PPIs medication after 3 mo, but there was no difference after 12 mo. No serious complications were observed in this study.
ELGP was safe, resulted in significant improvement in subjective symptoms, and allowed less medication to be used over the long term in patients with PPI-refractory NERD.
Full-text · Article · Nov 2012 · World Journal of Gastroenterology
[Show abstract][Hide abstract] ABSTRACT: To evaluate the effects of omeprazole on gastric mechanosensitivity in humans.
A double lumen polyvinyl tube with a plastic bag was introduced into the stomach of healthy volunteers under fluorography and connected to a barostat device. Subjects were then positioned so they were sitting comfortably, and the minimal distending pressure (MDP) was determined after a 30-min adaptation period. Isobaric distensions were performed in stepwise increments of 2 mmHg (2 min each) starting from the MDP. Subjects were instructed to score feelings at the end of every step using a graphic rating scale: 0, no perception; 1, weak/vague; 2, weak but significant; 3, moderate/vague; 4, moderate but significant; 5, severe discomfort; and 6, unbearable pain. After this first test, subjects received omeprazole (20 mg, after dinner) once daily for 1 wk. A second test was performed on the last day of treatment.
No adverse effects were observed. Mean MDP before and after treatment was 6.3 ± 0.3 mmHg and 6.2 ± 0.5 mmHg, respectively. One subject before and 2 after treatment did not reach a score of 6 at the maximum bag volume of 750 mL. After omeprazole, there was a significant increase in the distension pressure required to reach scores of 1 (P = 0.019) and 2 (P = 0.017) as compared to baseline. There were no changes in pressure required to reach the other scores after treatment. Two subjects before and one after omeprazole rated their abdominal feeling < 1 at MDP, and mean (± SE) abdominal discomfort scores at MDP were 0.13 ± 0.09 and 0.04 ± 0.04, respectively. Mean scores induced by each MDP + 2, 4, 6, 8, 10, 12, 14, 16, 18 and 20 (mmHg) were 1.1 ± 0.3, 2.0 ± 0.4, 2.9 ± 0.5, 3.3 ± 0.4, 4.6 ± 0.3, 5.2 ± 0.3, 5.5 ± 0.2, 5.5 ± 0.3, 5.7 ± 0.3, and 5.4, respectively. After omeprazole, abdominal feeling scores for the same incremental pressures over MDP were 0.3 ± 0.1, 0.8 ± 0.1, 2.0 ± 0.4, 2.8 ± 0.4, 3.8 ± 0.4, 4.6 ± 0.4, 4.9 ± 0.3, 5.4 ± 0.4, 5.2 ± 0.6, and 5.0 ± 1.0, respectively. A significant decrease in feeling score was observed at intrabag pressures of MDP + 2 mmHg (P = 0.028) and + 4 mmHg (P = 0.013), respectively, after omeprazole. No significant score changes were observed at pressures ≥ MDP + 6 mmHg.
Although the precise mechanisms are undetermined, the present study demonstrated that omeprazole decreases mechanosensitivity to mild gastric distension.
Full-text · Article · Oct 2012 · World Journal of Gastroenterology
[Show abstract][Hide abstract] ABSTRACT: The gastric barostat study is the gold standard method for evaluating gastric perception and accommodation. This technique has serious drawbacks, such as expense and invasiveness. Several drinking tests have been developed as noninvasive methods. Such tests are easily performed without special instruments and are well tolerated. We have reported that (1) a threshold volume inducing mild bloating in the slow nutrient drinking test might be an alternative parameter of gastric accommodation volume as determined by the barostat method and (2) the maximum satiety volume in the drinking test correlated positively with the pressure to induce severe discomfort in healthy volunteers, indicating that the slow nutrient drinking test may be useful for evaluating accommodation volume and the threshold to induce severe discomfort. However, the correlation between the maximum satiety drinking volume and accommodation volume as measured by the barostat study has been controversial. Therefore, validation of a certain nutrient drink test for measuring gastroduodenal function might be recommended in each institution.
Full-text · Article · Jul 2012 · Journal of neurogastroenterology and motility