Chikako Tokoro

Metformin Suppresses Colorectal Aberrant Crypt Foci in a Short-term Clinical Trial

The biguanide metformin is widely used for treating diabetes mellitus. We previously showed the chemopreventive effect of metformin in two rodent models of colorectal carcinogenesis. However, besides epidemiologic studies, little is known about the effects of metformin on human colorectal carcinogenesis. The objective of this pilot study was to evaluate the chemopreventive effect of metformin on rectal aberrant crypt foci (ACF), which are an endoscopic surrogate marker of colorectal cancer. We prospectively randomized 26 nondiabetic patients with ACF to treatment with metformin (250 mg/d, n = 12) or no treatment (control, n = 14); 23 patients were evaluable for end point analyses (9 metformin and 14 control); the two groups were similar in ACF number and other baseline clinical characteristics. Magnifying colonoscopy determined the number of rectal ACF in each patient at baseline and after 1 month in a blinded fashion (as were all laboratory end point analyses). We also examined proliferative activity in colonic epithelium (via proliferating cell nuclear antigen labeling index) and apoptotic activity (via terminal deoxynucleotidyl transferase dUTP nick-end labeling). At 1 month, the metformin group had a significant decrease in the mean number of ACF per patient (8.78 ± 6.45 before treatment versus 5.11 ± 4.99 at 1 month, P = 0.007), whereas the mean ACF number did not change significantly in the control group (7.23 ± 6.65 versus 7.56 ± 6.75, P = 0.609). The proliferating cell nuclear antigen index was significantly decreased and the apoptotic cell index remained unaltered in normal rectal epithelium in metformin patients. This first reported trial of metformin for inhibiting colorectal carcinogenesis in humans provides preliminary evidence that metformin suppresses colonic epithelial proliferation and rectal ACF formation in humans, suggesting its promise for the chemoprevention of colorectal cancer. Cancer Prev Res; 3(9); 1077–83. ©2010 AACR.

Quantitive cytokine mRNA expression profiles in the colonic mucosa of patients with steroid naïve ulcerative colitis during active and quiescent disease

Background: Cytokines have validated roles in the immunopathogenesis of inflammatory bowel disease (IBD). This study was to investigate the expressions of tumor necrosis factor (TNF)‐&agr;, interleukin (IL)‐6, IL‐8, and IL‐10 mRNAs in the colonic mucosa of patients with ulcerative colitis (UC) during active and quiescent UC. Methods: At colonoscopy, biopsies were taken from inflamed and non‐inflamed mucosa of patients with steroid‐naive UC (n = 15), non‐IBD inflammatory colitis controls (ICC, n = 6), and non‐colitis controls (NCC, n = 14). The presence of extensive mononuclear cells and neutrophils infiltrate in the lamina propria, cryptitis, and epithelial damage defined an inflammatory lesion in the mucosa. Quantitative cytokine mRNA expressions in biopsies were measured by real‐time polymerase chain reaction (PCR). Results: Of 15 UC patients, 3 remitted with 5‐aminosalicylate and 11 received granulocytapheresis; of these, 10 remitted. At baseline, IL‐6, IL‐8, TNF‐&agr;, and IL‐10 mRNAs were high in inflamed mucosa compared with NCC (P < 0.01). In active UC, IL‐6, IL‐8 and IL‐10 mRNAs were high compared with non‐inflamed mucosa (P = 0.03, P = 0.03, P < 0.05, respectively). Both TNF‐&agr; mRNA (P = 0.03) and IL‐6 mRNA (P = 0.04) were higher in UC compared with ICC. Even in non‐inflamed mucosa, IL‐8 and TNF‐&agr; mRNA expressions were high compared with NCC. Both IL‐6 and IL‐8 mRNAs decreased to normal levels after granulocytapheresis. Conclusions: During active UC, all 4 cytokine mRNA levels were high; only IL‐6 and IL‐8 mRNAs decreased to normal levels during remission. IL‐8 mRNA was high even at sites of endoscopically quiescent UC during active disease. Steroid naïve patients respond well to granulocytapheresis.

Visceral obesity and the risk of Barrett's esophagus in Japanese patients with non-alcoholic fatty liver disease

BackgroundThe association between obesity and the risk of Barretts esophagus (BE) is unclear. Furthermore, the association between visceral obesity and the risk of BE is entirely unknown.MethodsWe conducted a retrospective study in 163 patients with non-alcoholic fatty liver disease (NAFLD) who underwent both endoscopy and abdominal CT at an interval of less than a year at our institution. BE was endoscopically diagnosed based on the Prague C & M Criteria. The surface areas of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were calculated from CT images at the level of the umbilicus. The correlations between the BMI, VAT, and SAT and the risk of BE were examined by univariate and multivariate analyses.ResultsSixty-nine of the 163 study participants (42.3%) were diagnosed to have endoscopic BE, which was classified as short-segment BE (SSBE) in almost all of the cases. There were no significant differences in the age or gender distribution between the groups with and without BE. According to the results of the univariate analysis, VAT was significantly associated with the risk of BE; the BMI tended to be higher in the group with BE than in the group without BE, but this relation did not reach statistical significance. VAT was independently associated with the risk of BE even after adjustment for the BMI.ConclusionIn Japanese patients with NAFLD, obesity tended to be associated with the risk of BE, and this risk appeared to be mediated for the most part by abdominal visceral adiposity.

Risk factors for colonic diverticular hemorrhage: Japanese multicenter study.

Background and Aim: Diverticular hemorrhage is the common cause of lower gastrointestinal bleeding, and its incidence has been increasing in Japan. However, the exact cause of diverticular hemorrhage is not well understood. We investigated the risk factors for diverticular hemorrhage. Methods: We selected 103 patients with diverticular hemorrhage as cases and patients with colonic diverticulosis without a history of bleeding were selected as control subjects, exactly matched for age and gender. We collected the data from the medical records of each of the patients, such as those related to the comorbidities, medications and findings of colonoscopy, and conducted a matched case-control study to analyze the risk factors for diverticular hemorrhage. Results: Both groups were composed of 75 men and 28 women. The median age of the patients in both groups was 72.0 years (47.0–87.0). The body weight (p = 0.0065), body mass index (p = 0.006), prevalence of hypertension (p = 0.0242), prevalence of ischemic heart disease (p = 0.0015), and frequency of use of low-dose aspirin (p = 0.042) were significantly different between the two groups. The percentage of patients with bilateral diverticula, that is, diverticula on both the right and left hemicolon, was significantly higher in the diverticular hemorrhage group (p = 0.0011). Multiple regression analysis identified only the diverticular location as being significantly associated with the risk of diverticular hemorrhage (p = 0.0021). Conclusions: Only the diverticular location (bilateral) was found to be an independent risk factor for diverticular hemorrhage.

Optimal Approach for Small Bowel Capsule Endoscopy Using Polyethylene Glycol and Metoclopramide with the Assistance of a Real-Time Viewer

Aim: Capsule endoscopy is limited by the poor image quality of the distal bowel and incomplete small bowel transit. The aim of this study was to establish an optimal medication protocol for capsule endoscopy performed using a real-time viewer. Methods: A total of 80 patients were prospectively recruited. The patients were randomized into two groups: the ‘conventional group’ (without any preparation) and the ‘real-time group’ (in which a real-time viewer was attached). At 60 min after swallowing the capsule, if the capsule hadreached the small bowel, 500 ml of polyethylene glycol was administered; if the capsule was still located in the stomach, 10 mg of metoclopramide was given intramuscularly, followed by 500 ml of polyethylene glycol solution. Results: The completion rate was significantly higher in the real-time group as compared with that in the conventional group (72.5 vs. 90.0%). Our protocol yielded a significantly improved image quality of the distal small bowel [image quality score = 1.6 vs. 3.0 (max 4.0)]. The detection rate of lesions in the distal small bowel was higher in the real-time group than in the conventional group. Conclusions: The present study clearly showed that our protocol yielded an improved completion rate and also improved image quality.

QUANTITATIVE ANALYSIS OF LOW-DOSE ASPIRIN-ASSOCIATED SMALL BOWEL INJURY USING A CAPSULE ENDOSCOPY SCORING INDEX

Aim:  The major limitation of capsule endoscopy (CE) has been the lack of a standardized and validated severity scale for mucosal injury. The aim of the present study was to verify the usefulness of quantifying small bowel mucosal changes associated with giving low‐dose aspirin (LDA) using a CE scoring index.

Effects of Histamine-2 Receptor Antagonists and Proton Pump Inhibitors on the Rate of Gastric Emptying: A Crossover Study Using a Continuous Real-Time C Breath Test (BreathID System).

Background/Aims The effects of Histamine-2 receptor antagonists and proton pump inhibitors on the gastrointestinal motility have not yet been sufficiently investigated. The aim of this study was to determine the effects of intravenous bolus administration of famotidine and omeprazole on the rate of gastric emptying using the continuous 13C breath test (BreathID system, Exalenz Bioscience Ltd, Israel). Methods Twelve healthy male volunteers participated in this randomized, 3-way crossover study. After fasting overnight, the subjects were randomly assigned to receive 20 mg of famotidine, 20 mg of omeprazole or 20 mL of saline alone by intravenous bolus injection before a test meal (200 kcal per 200 mL, containing 100 mg of 13C-acetate). Gastric emptying was monitored for 4 hours after the ingestion of test meal by the 13C-acetic acid breath test performed using the BreathID system. Results No significant differences in the calculated parameters, namely, the T1/2, Tlag, GEC, β and κ, were observed among the 3 test conditions. Conclusions The study revealed that intravenous administration of gastric acid suppressant drugs had no significant influence on the rate of gastric emptying in comparison with that of saline alone as a placebo. Our results indicating the absence of any effect of either famotidine or omeprazole on accelerating the rate of gastric emptying suggest that both medications can be administered safely to patients suffering from hemorrhagic peptic ulcers who need to be kept nil by mouth from the viewpoint of possible acceleration of gastrointestinal motility in the clinical setting.

Ulcerative Colitis with Multidrug-Resistant Pseudomonas aeruginosa Infection Successfully Treated with Bifidobacterium

A 71-year-old man was diagnosed with ulcerative colitis (UC) complicated by bacterial infections, and his active disease proved difficult to treat with steroid therapy or antibiotics. Although the patient’s UC failed to respond to several types of induction therapy, his condition finally improved when treated using Bifidobacterium. Probiotics could be one of the treatment agents for induction of remission in UC.

Change of gastric emptying with chewing gum: evaluation using a continuous real-time C breath test (BreathID system).

Background/Aims There are few reports on the correlation between chewing gum and the gastrointestinal functions. But previous report showed use of chewing gum to be an effective method for controlling gastrointestinal symptoms. The aim of this study was to determine the correlation between chewing gum and gastric emptying using the continuous real time 13C breath test (BreathID system). Methods Ten healthy male volunteers participated in this randomized, 2-way crossover study. The subjects fasted overnight and were randomly assigned to chewing gum (Xylish, 2-3/1 tablet) for an hour following intake of a test meal (200 kcal/200 mL) or intake of the test meal alone. Gastric emptying was monitored for 4 hours after administration of the test meal by the 13C-acetic acid breath test performed continually using the BreathID system. Results No significant differences in the calculated parameters, namely, T1/2 (median, 111.82 vs 109.26 minutes; P = 0.575), Tlag (median, 53.28 vs 56.53 minutes; P = 0.333), gastric emptying coefficient (median, 3.58 vs 3.65; P = 0.285), regression-estimated constant β (median, 1.85 vs 1.80; P = 0.575) and regression-estimated constant κ (median, 0.61 vs 0.62; P = 0.959) were observed between the test meal alone group and the test meal and chewing gum group. Conclusions This study showed that chewing gum had no effect on the rate of gastric emptying. Therefore, since chewing gum did not enhance the speed of gastric emptying, it may ameliorate gastrointestinal symptoms through other mechanisms, such as saliva and autonomic nervous system.

Capsule endoscopic evaluation of eosinophilic enteritis before and after treatment.

Dear Sir, A 41-year-old man presented with intermittent, colicky abdominal pain after meals for 6 months and water diarrhea for 1 month. Laboratory results showed profound eosinophilia [49.4% (reference range, 0–6%)]. Stool cultures and a parasitological examination were negative. The results of gastroscopy and a total colonoscopy were within the normal limits. However, a capsule endoscopy examination revealed multiple erythematous mucosal lePublished online: November 1, 2010