Nobuhide Oshitani

Evaluation of Deep Small Bowel Involvement by Double-Balloon Enteroscopy in Crohn's Disease

OBJECTIVES:Double-balloon enteroscopy (DBE) enables inspection of deep small bowel, and total small bowel examination can be performed by either antegrade or retrograde DBE. The aim of this study was to evaluate ileal involvement, which cannot be achieved using conventional colonoscopy, by DBE in patients with Crohns disease.METHODS:From December 2003 to September 2005, a total of 44 patients with Crohns disease underwent 53 examinations using DBE.RESULTS:Forty patients with Crohns disease, seven women and 33 men, underwent DBE, and the ileum was investigated in 38 patients. There were 25 cases of ileitis, 2 of colitis, and 13 of ileocolitis. Jejunal lesions were found in two and ileal lesions proximal to the terminal ileum were found in 24 patients with Crohns disease. DBE was superior to radiological study to detect aphthae, erosions, and small ulcers in the ileum. Small bowel stricture was demonstrated in six and nine patients with DBE and small bowel barium study (SBBS), respectively. An additional mucosal finding was demonstrated in one of the eight patients who underwent wireless capsule endoscopy, and one patient had a capsule removed by DBE that had become lodged because of an ileal stricture. One ileal perforation because of overtube balloon pressure occurred in 53 examinations of patients with Crohns disease (1.9%).CONCLUSION:DBE is useful to evaluate small bowel lesions in patients with Crohns disease; however, special attention should be paid to mesenteric longitudinal ulcers during insertion and the overtube balloon should not be inflated if a clear intestinal view is not possible.

Small Bowel Injury by Low-Dose Enteric-Coated Aspirin and Treatment With Misoprostol: A Pilot Study

BACKGROUND & AIMS With capsule endoscopy, the ulcerogenic effect of low-dose enteric-coated aspirin on the small bowel and the therapeutic effect of misoprostol on intestinal injury were evaluated. METHODS Eleven patients who developed gastric ulcers while undergoing low-dose enteric-coated aspirin therapy were enrolled. They continued aspirin therapy while taking proton pump inhibitors (PPIs) for 8 weeks to heal the gastric ulcers. Then misoprostol 200 microg 4 times a day was administered instead of PPIs for 8 weeks. When the patients could not tolerate misoprostol as a result of side effects, they received another 8 weeks of PPI therapy. RESULTS Capsule endoscopy performed after 8 weeks of PPI treatment identified red spots and mucosal breaks in 100% (11/11) and 90.9% (10/11) of patients, respectively. In 7 patients who completed the study protocol, misoprostol significantly decreased the median number of red spots and mucosal breaks, with complete disappearance of mucosal breaks in 4 patients. Intestinal lesions tended not to heal in 3 patients who discontinued misoprostol. CONCLUSIONS Low-dose enteric-coated aspirin frequently damages the small intestine, and misoprostol is effective in the treatment of aspirin-induced enteropathy.

Exogenous administration of mesenchymal stem cells ameliorates dextran sulfate sodium-induced colitis via anti-inflammatory action in damaged tissue in rats.

AIMS Mesenchymal stem cells (MSCs) may modulate inflammatory responses resulting in improvement in inflammatory diseases, as well as tissue regeneration via cellular differentiation. We examined the therapeutic effects of exogenously administered MSCs in dextran sulfate sodium (DSS)-induced colitis in rats. MAIN METHODS Experimental colitis was produced in inbred male Lewis rats by administration of 4% DSS in drinking water for 7 days. MSCs (5x10(6) cells) which were isolated from whole marrow cells and cultured in an optimal medium for MSC outgrowth were administered to the treated rats via the tail vein on days 0, 2, and 4. On day 7, we evaluated colon length, histological changes, and colonic various mRNA expressions by RT-PCR. Localization of MSCs was evaluated using a green-fluorescent cell linker dye. To evaluate the anti-inflammatory action of MSCs, we assayed LPS-induced TNF-alpha secretion in a co-culture of MSCs and monocytes (THP-1 cells) using ELISA. KEY FINDINGS MSCs reduced in bloody stools, weight loss, colon shortening, and microscopic injuries. In the rectum of MSCs-treated rats, mRNA expression of TNF-alpha, IL-1beta, and COX-2 decreased to 40, 15, and 15% of their respective control levels. MSCs significantly suppressed mRNA expression of VEGF, HGF, and b-FGF to 40, 25, and 25% of their respective control levels. Green-fluorescent-labeled MSCs were found only within the lamina propria in inflamed regions. LPS-induced TNF-alpha secretion by THP-1 cells was significantly suppressed by co-culture with MSCs dose-dependently. SIGNIFICANCE We conclude that exogenous MSCs accumulated in inflamed tissues and ameliorated DSS-induced colitis via a local anti-inflammatory action.

Prevalence of gastroesophageal reflux disease and gastroesophageal reflux disease symptoms in Japan.

Background and Aim:  Epidemiological studies have shown that 10–48% of people in developed countries have gastroesophageal reflux disease (GERD) symptoms such as heartburn and acid regurgitation. The present study aimed to examine the prevalence of GERD symptoms and GERD in Japanese subjects.

A prospective, single-blind trial comparing wireless capsule endoscopy and double-balloon enteroscopy in patients with obscure gastrointestinal bleeding

BackgroundWireless capsule endoscopy (CE) and double-balloon enteroscopy (DBE) are new methods enabling diagnostic endoscopy of the entire small intestine. However, which of the two is superior is unclear. We therefore prospectively compared the clinical efficacy of CE and DBE.MethodsWe prospectively examined 32 patients with obscure gastrointestinal bleeding. CE preceded DBE by 1–7 days, and all patients underwent DBE twice, by antegrade and retrograde approaches, to evaluate the entire small intestine. Physicians evaluating the results of CE and DBE were blind to the results of the other method. We evaluated diagnosis, diagnostic yield of the two methods, and clinical outcomes.ResultsCE revealed abnormal findings in 29 (90.6%) of 32 patients. CE definitively or probably detected the sources of bleeding in 23 (71.9%) of the 32 patients, including angioectasias (eight), erosions (seven), ulcers (five), tumor (one), and hemorrhagic polyps (two). DBE definitely or probably detected the sources of bleeding in 21 (65.6%) of the 32 patients, including angioectasias (seven), erosions (four), ulcers (five), tumor (one), hemorrhagic polyps (two) and diverticula (two). CE yielded more abnormal findings than DBE (CE 90.6%, DBE 65.6%) (P = 0.032), although there were no significant differences in diagnostic yield between the methods. We were able to perform additional treatment or biopsy with DBE in 13 patients, including coagulation therapy (ten), endoscopic mucosal resection (one), biopsy (seven), and extraction of retained CE (two).ConclusionsOur results demonstrate the superiority of CE in detecting abnormal lesions, and the superiority of DBE in endoscopic management.

Differences in clinical characteristics between patients with endoscopy-negative reflux disease and erosive esophagitis in Japan

OBJECTIVE:Helicobacter pylori infection and atrophic gastritis are inversely related to erosive esophagitis. Whether these factors affect the pathogenesis of endoscopy-negative reflux disease is not clear. We aimed to elucidate the differences in clinical characteristics between endoscopy-negative erosive disease and erosive esophagitis.METHODS:253 subjects (89 with endoscopy-negative reflux disease and 164 with erosive esophagitis) were studied. Gastric atrophy was assessed by measurement of serum pepsinogen. Logistic regression was used to calculate the odds ratio (OR) and 95% confidence intervals (CI) of endoscopy-negative reflux disease compared with erosive esophagitis.RESULTS:Among GERD patients, female gender (OR = 2.27, 95% CI, 1.25–4.10), smoking (OR = 0.45, 95% CI, 0.22–0.91), and the presence of hiatal hernia (OR = 0.30, 95% CI, 0.17–0.56) were significantly associated with endoscopy-negative reflux disease compared with male gender, not smoking, and absence of hiatal hernia, respectively. Body mass index (BMI) was also significantly associated with a decreased OR for endoscopy-negative reflux disease. Although H. pylori infection and gastric atrophy were significantly more common in patients with endoscopy-negative reflux disease, these associations did not persist in a multiple-adjustment model. After adjustment for gender, BMI, smoking, and hiatal hernia, a decrease in serum pepsinogen I/II ratio was significantly associated with an increased OR for endoscopy-negative reflux disease (p for trend = 0.018).CONCLUSIONS:Female gender, low BMI, not smoking, absence of hiatal hernia, and severity of gastric atrophy were positively associated with endoscopy-negative reflux disease compared with erosive esophagitis among Japanese patients.

Cigarette Smoking and Alcohol Consumption Associated with Gastro-Oesophageal Reflux Disease in Japanese Men

Background: Associations between lifestyle factors and gastro-oesophageal reflux disease (GORD) have been conflicting. We aimed to examine these associations in Japanese men. Methods: We performed a cross-sectional study of Japanese male workers who visit a clinic for a routine health check-up and asked them to fill out a self-report questionnaire. Logistic regression was used to calculate odds ratios (OR) with 95% confidence intervals (CI) for GORD, defined as heartburn and/or acid regurgitation at least twice weekly. Results: Of the 4095 eligible subjects, 276 (6.7%) were diagnosed as having GORD. Current smoking was significantly associated with GORD compared with non-smoking (OR r = r 1.35, 95% CI, 1.01-1.82). Moderate drinking (16-37 r mL/day) and heavy drinking ( S 38 r mL/day) were also associated with GORD, while age and body mass index were not. After adjustment for age, daily alcohol consumption and body mass index, an increase in number of pack-years of cigarette smoking was significantly associated with an increased OR of GORD ( P for trend r = r 0.034), and the OR for persons whose number of pack-years of cigarette smoking was more than 20.1 was 1.45 (CI 1.04-2.04) compared with non-smokers. Conclusion: Cigarette smoking and alcohol consumption are associated with an increased odds ratio for GORD in Japanese men.BACKGROUND Associations between lifestyle factors and gastro-oesophageal reflux disease (GORD) have been conflicting. We aimed to examine these associations in Japanese men. METHODS We performed a cross-sectional study of Japanese male workers who visit a clinic for a routine health check-up and asked them to fill out a self-report questionnaire. Logistic regression was used to calculate odds ratios (OR) with 95% confidence intervals (CI) for GORD, defined as heartburn and/or acid regurgitation at least twice weekly. RESULTS Of the 4095 eligible subjects, 276 (6.7%) were diagnosed as having GORD. Current smoking was significantly associated with CORD compared with non-smoking (OR = 1.35, 95% CI, 1.01-1.82). Moderate drinking (16-37 mL/day) and heavy drinking (> or = 38 mL/day) were also associated with GORD, while age and body mass index were not. After adjustment for age, daily alcohol consumption and body mass index, an increase in number of pack-years of cigarette smoking was significantly associated with an increased OR of GORD (P for trend = 0.034), and the OR for persons whose number of pack-years of cigarette smoking was more than 20.1 was 1.45 (CI 1.04-2.04) compared with non-smokers. CONCLUSION Cigarette smoking and alcohol consumption are associated with an increased odds ratio for GORD in Japanese men.

Dietary fat attenuates the benefits of an elemental diet in active Crohn's disease: a randomized, controlled trial.

Objectives Although an elemental diet has been established as the primary treatment for patients with Crohns disease, the influence of dietary fat on the elemental diet remains unclear. We have designed the first randomized, controlled trial for elemental diets containing different fat percentages in patients with active Crohns disease. Methods Each patient was randomized to receive one of three dose levels of fat in an elemental diet (Elental) for 4 weeks: 10 patients received low fat (3.06 g/day), 10 patients received medium fat (16.56 g/day) and eight patients received high fat (30.06 g/day). The additional fat was composed of long-chain fatty acids. All patients were evaluated using the International Organization of Inflammatory Bowel Disease rating, plus C-reactive protein level and erythrocyte sedimentation rate, which were measured at weekly intervals. Results Although the International Organization of Inflammatory Bowel Disease rating, C-reactive protein level and erythrocyte sedimentation rate in the low-fat group decreased, the values in the medium- and high-fat groups fluctuated during the study. The remission rate after 4 weeks in each group was 80%, 40% and 25% for patients in the low-, medium- and high-fat groups, respectively. Conclusions When the fat consisted of long-chain triglycerides, a high amount of this fat in the elemental diet formula decreased its therapeutic effect against active Crohns disease.

Association Between Dinner-to-Bed Time and Gastro-Esophageal Reflux Disease

OBJECTIVE:It is generally recommended that patients with gastro-esophageal reflux disease (GERD) refrain from eating within 3 h of going to sleep. In addition to a remarkable lack of supporting clinical evidence, whether GERD patients have shorter dinner-to-bed time is unknown. This study was designed to determine a possible association between dinner-to-bed time and GERD, compared with healthy adults.METHODS:In a matched case-control study, we enrolled 147 GERD patients, and age- and sex-matched 294 controls without GERD symptoms such as heartburn and acid regurgitation during the previous year. Dinner-to-bed time, defined as the time intervals until going to bed after finishing eating dinner, was examined by a self-report questionnaire. Logistic regression was used to calculate odds ratio (OR) and 95% confidence intervals (CI) for GERD.RESULTS:After adjustment for smoking habits, drinking habits, and body mass index, shorter dinner-to-bed time was significantly associated with an increased OR of GERD (p < 0.0001) and the OR for patients whose dinner-to-bed time was less than 3 h was 7.45 (95% CI 3.38–16.4) compared with patients whose dinner-to-bed time was 4 h or more. These observations were consistent in both patients with nonerosive GERD and erosive esophagitis, and there was no significant difference in dinner-to-bed time intervals between nonerosive GERD and erosive esophagitis.CONCLUSION:In this matched case-control study, shorter dinner-to-bed time was significantly associated with an increased OR for GERD.

Type 1 T helper cell predominance in granulomas of Crohn's disease

OBJECTIVE:The pathogenesis of Crohns disease (CD) is thought to be associated with production of several cytokines, especially type-1 cytokines. To elucidate the in situ cytokine profiles in CD, cytokine-containing cells were localized by immunohistochemistry, with special attention to noncaseating granulomas. The results were compared with those from studies of ulcerative colitis (UC).METHODS:We adopted the biotin-streptavidin-peroxidase method on frozen sections obtained at surgery from patients with CD or UC, and we immunohistochemically examined the expression of several cytokines (interferon-gamma, interleukin-2, -4, -10, and -12).RESULTS:In normal colonic tissue, expression of these cytokines was rare except for interleukin-4. In actively inflamed areas of CD, increased expression of all cytokines by mononuclear cells was observed. In contrast, granulomas in CD involved interferon-gamma+ lymphocytes and interleukin-12+ macrophage-lineage cells (epithelioid cells and multinucleated giant cells) but few interleukin-4+ or -10+ cells. Actively inflamed areas of UC also showed an increase in the number of cytokine-containing cells; however, quantitative analysis revealed that there was more expression of interferon-gamma and interleukin-12, and less of interleukin-10, in CD than in UC, indicating the presence of more type 1 T-helper cells in CD tissue than in UC.CONCLUSIONS:The findings of the present study suggest that granulomas of CD are coupled with type 1 T-helper responses; these responses may contribute to the pathogenesis of this disease.