Ryuta Masui

G protein-coupled receptor 43 moderates gut inflammation through cytokine regulation from mononuclear cells.

Background: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. Methods:Colitis was induced by adding dextran sulfate sodium to the drinking water of GPR43 knockout (−/−) and wild-type mice. Results: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. Conclusions:SCFA–GPR43 interactions modulate colitis by regulating inflammatory cytokine production in mononuclear cells.

Predictive Factors for Intractability to Endoscopic Hemostasis in the Treatment of Bleeding Gastroduodenal Peptic Ulcers in Japanese Patients

Background/Aims Despite improvements in endoscopic hemostasis and pharmacological therapies, upper gastrointestinal (UGI) ulcers repeatedly bleed in 10% to 20% of patients, and those without early endoscopic reintervention or definitive surgery might be at a high risk for mortality. This study aimed to identify the risk factors for intractability to initial endoscopic hemostasis. Methods We analyzed intractability among 428 patients who underwent emergency endoscopy for bleeding UGI ulcers within 24 hours of arrival at the hospital. Results Durable hemostasis was achieved in 354 patients by using initial endoscopic procedures. Sixty-nine patients with Forrest types Ia, Ib, IIa, and IIb at the second-look endoscopy were considered intractable to the initial endoscopic hemostasis. Multivariate analysis indicated that age ≥70 years (odds ratio [OR], 2.06; 95% confidence interval [CI], 1.07 to 4.03), shock on admission (OR, 5.26; 95% CI, 2.43 to 11.6), hemoglobin <8.0 mg/dL (OR, 2.80; 95% CI, 1.39 to 5.91), serum albumin <3.3 g/dL (OR, 2.23; 95% CI, 1.07 to 4.89), exposed vessels with a diameter of ≥2 mm on the bottom of ulcers (OR, 4.38; 95% CI, 1.25 to 7.01), and Forrest type Ia and Ib (OR, 2.21; 95% CI, 1.33 to 3.00) predicted intractable endoscopic hemostasis. Conclusions Various factors contribute to intractable endoscopic hemostasis. Careful observation after endoscopic hemostasis is important for patients at a high risk for incomplete hemostasis.

ENDOSCOPIC SUBMUCOSAL DISSECTION WITH SHEATH-ASSISTED COUNTER TRACTION FOR EARLY GASTRIC CANCERS

Aim:  Endoscopic submucosal dissection (ESD) is associated with frequent complications, such as bleeding and perforation. The procedure is technically difficult, requires considerable skill and is longer than conventional endoscopic mucosal resection (EMR). Thus, non‐invasive tools and methods are needed to facilitate direct visualization of the submucosal layer during ESD.

Nonsteroidal anti-inflammatory drug-induced visible and invisible small intestinal injury

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.

Usefulness of a Slow Nutrient Drinking Test for Evaluating Gastric Perception and Accommodation

Background/Aim: An implication of the drinking test for gastric function is controversial. We evaluated the usefulness of a nutrient drinking test for examining gastric function by comparing it with a gastric barostat study. Methods: We investigated perceived pressure of an intragastric bag with stepwise distension and postprandial peak gastric volume (accommodation volume) with a consistent pressure after drinking a liquid meal (200 ml, 300 kcal) in 18 volunteers. Drinking a similar liquid meal on a different day at a continual rate of 15 ml/min was performed to score satiety and bloated sensations at 5-min intervals. An additional 10 volunteers performed the drinking test before and after administration of mosapride citrate or a placebo in a double-blind crossover study. Results: Pressure to induce severe discomfort correlated positively with maximum satiety volume in the drinking test (r = 0.60, p = 0.02). Accommodation volume in the barostat study showed a significant correlation (r = 0.59, p = 0.03) with threshold volume to induce bloating in the drinking test. Mosapride tended to increase the volume inducing the first bloated sensation as compared to the placebo. Conclusion: The present drinking test may be useful for evaluating the threshold to induce severe discomfort and accommodation volume.

Long-term survival and improved quality of life after chemoradiotherapy to treat esophageal small cell carcinoma: a report of two cases.

In case 1, endoscopy revealed a submucosal tumor with central ulceration in the esophagus of a 54- year-old man. A biopsy specimen revealed small cell carcinoma without metastasis and the stage of the cancer was stage I (T2N0M0). Two cycles of concurrent cisplatin, etoposide and radiotherapy resulted in an incomplete response/stable disease. The tumor recurred and had metastasized to the brain, lung, liver, lymph nodes of the mediastinum, abdomen and bones after six cycles. Two cycles of irinotecan and cisplatin then elicited a complete response in the primary esophageal lesion. However, progressive disease was identified in the metastatic bone tumors. Despite two further cycles of therapy, he died 447 days after the initial course. In case 2, a biopsy specimen of a tumor with central ulceration in the esophagus of a 77-year old man with swallowing difficulty indicated small cell carcinoma. The stage of the cancer was diagnosed as stage II (T3N0M0). Two cycles of irinotecan, cisplatin and concurrent radiotherapy elicited a complete response. However, the tumor metastasized to the brain and the liver 644 days after starting treatment. Two cycles of carboplastin plus irinotecan elicited a partial response in the metastatic tumors, but he died 988 days after starting chemotherapy.

Effect of aspirin cessation before endoscopy in Japanese patients with low-dose-aspirin-associated gastroduodenal mucosal injury

Background The incidence of upper gastrointestinal injury by low-dose aspirin (LDA) has increased. Objective We aimed to clarify the risk factors and prevention strategies associated with LDA-induced gastroduodenal ulcer in Japanese patients. Methods 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. Results 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). Conclusions 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.

Endoscopic submucosal dissection with sheath-assisted counter traction using a novel sheath for early gastric cancers.

BACKGROUND/AIMS Endoscopic submucosal dissection (ESD) is technically demanding and requires considerable skill. We previously described sheath-assisted counter traction ESD that uses simple materials and methods to improve cutting line visualization. We recently improved counter-traction of the submucosal layer using a novel chemically treated sheath that reduces slippage and maintains traction, and investigated the utility of the novel sheath for ESD. METHODOLOGY Forty-three and 25 consecutive patients with early gastric carcinomas were treated by standard ESD and traction ESD assisted with novel sheaths, respectively. The mean duration of procedures relative to tumor size and location, as well as complications after ESD between the two groups were compared. RESULTS The mean duration of ESD procedures for lesions =20mm in diameter was significantly reduced using the novel sheath. The mean duration of procedures for all locations of resected tumors in the stomach was significantly reduced using the novel sheath. However, no perforation and delayed bleeding developed after treatment with the novel sheath. CONCLUSIONS Sheath-assisted counter traction ESD by the novel sheath was technically simpler and thus less time-consuming regardless of the location of lesions, especially when =20mm in diameter. The traction ESD with the novel sheath is safe and not invasive, and it can be universally applied to standard ESD.

Tu1622 Evaluation of Relationship Between Gastroesophageal Reflux Disease (GERD) and Laryngopharyngeal Reflux Disease (LPRD)

Evaluation of Relationship Between Gastroesophageal Reflux Disease (GERD) and Laryngopharyngeal Reflux Disease (LPRD) Yoshihiro Kondo*, Makoto Sasaki, Naotaka Ogasawara, Yasushi Funaki, Mari Mizuno, Akihito Iida, Naohiko Kawamura, Kentaro Tokudome, Yasutaka Hijikata, Shinya Izawa, Ryuta Masui, Yoshitsugi Ito, Yasuhiro Tamura, Hisatsugu Noda, Kunio Kasugai Gastroenterology, Aichi Medical University, Nagakute, Japan Introduction: Gastroesophageal reflux disease (GERD) is defined as a condition that develops when reflux of the stomach contents involving gastric acid juice causes troublesome symptoms. GERD typically presents heartburn and regurgitation, but it can also present atypically as chronic cough, throat pain, and asthma. Atypical symptoms such as chronic cough, throat pain, and asthma are considered to be associated with laryngopharyngeal reflux disease (LPRD). Currently, LPRD is associated with laryngeal irritation such as laryngitis caused by reflux of the gastric acid juice. However, the accurate relationship between GERD, especially endoscopic positive esophagitis (EE) and LPRD is still unknown. In this study, we examined the grades of EE and the larynx findings using esophago-gastroendoscopy, and investigated the relationship between GERD and LPRD. Methods: Four hundred two patients except gastrointestinal malignant tumors, gastrointestinal ulcer, esophageal varices, and usage of proton pump inhibitor or H2-blocker underwent esophago-gastroendoscopy for examining the findings of gastro-esophageal junction, cardiac position of the stomach, and larynx at the Department of Gastroenterology, Aichi Medical University School of Medicine between January 2007 and December 2008. Three otorhinolaryngologists and three gastroendoscopists blindly evaluated the findings of laryngopharyngeal area (edema of inferior position of larynx, redness of aryepiglottic fold, thickness of interarytenoid mucosa, and presence of vocal fold granuloma) and gastro-esophageal junction, respectively. Independent and significant predictive factors of EE (background of patients, symptoms, the laryngopharyngeal findings, presence of esophageal hernia) were determined by multivariate analysis. Results: Thirty patients (7.5%) were diagnosed as EE. Of all patients, 114 (28.4%), 230 (57.2%), 271 (67.4%), and 7 (1.7%) patients harbored edema of inferior position of larynx, reddness of aryepiglottic fold, thickness of interarytenoid mucosa, and granuloma of vocal fold, respectively. One hundred fifteen patients (28.6%) complained of laryngopharyngeal reflux symptoms, but there was no relationship between laryngopharyngeal reflux symptoms, the grades of EE, and the findings of larynx. However, esophageal hernia [odds ratio (OR), 2.6], and thickness of interarytenoid mucosa (OR, 4.9), were independent predictive factors of EE. Conclusion: Although laryngopharyngeal reflux symptoms possessed no statistical relation to the findings of both EE and laryngitis, the thickness of interarytenoid mucosa which might be initially affected by the reflux of stomach contents involving gastric acid juice was exceedingly related to EE.

Sa2052 Putative IBD Prophylaxis in Addition to Metabolic Syndrome by Oligosaccharide Synthesize Enzyme

Introduction: Obesity and metabolic disorders are linked to inflammation via gut flora and/ or gut permeability. Gut derived endotoxin triggers inflammation leading to metabolic syndrome (MetS) and contributing to oxidative stress. Aim: To investigate the effect of Lactobacillus casei Shirota on gut permeability, presence of endotoxin and neutrophil function in MetS. Patients and Methods: Patients with MetS were randomized to receive 3 x 6.5x109 CFU Lactobacillus casei Shirota (probiotic group) or not for 3 months. Gut permeability was assessed by a differential sugar absorption method, endotoxin by an adapted limulus amoebocyte lysate assay, neutrophil function and toll-like receptor (TLR) expression by flow cytometry and ELISA was used to detect lipopolysaccharide binding protein (LBP) and sCD14 levels. Results: Twenty-eight patients and 10 healthy controls were included. Gut permeability was significantly increased in MetS compared to controls but did not differ between patient groups. None of the patients were positive for endotoxin. LBP and sCD14 levels were not significantly different from healthy controls. C-reactive protein and LBP levels slightly but significantly increased after 3 months within the probiotics group. Neutrophil function and TLR expression did not differ from healthy controls or within the patient groups. Discussion: Gut permeability of MetS patients was increased before markers of low grade inflammation were measurable, most likely because only a minority of patients had morbid obesity normally leading to inflammation. Lactobacillus casei Shirota did not have any influence on any parameter tested possibly due to too short study duration or underdosing of Lactobacillus casei Shirota.