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Background: Although intestinal Behçet's disease has been treated anecdotally with various therapeutic modalities, clinical evidence regarding management of intestinal Behçet's disease is lacking. The objective of this study was to develop consensus-based practice guidelines for diagnosis and treatment of intestinal Behçet's disease by using a modified Delphi approach.Methods: Three groups of Japanese gastroenterology specialists were involved in the study: moderators, an expert panel, and a professional group. Clinical statements for ratings were extracted from relevant literature, a survey of the professional group, and by discussion among the expert panel. The expert panel rated the clinical statements according to a nine point scale. After the first round of ratings, a panelist meeting was held to discuss areas of disagreement and to clarify areas of uncertainty. The list of clinical statements was revised after the panelist meeting, and a second round of rating was conducted.Results: Thirty-two relevant articles were selected in a literature search, and 35 clinical statements were extracted. An additional 209 clinical statements were developed from the survey and discussion among gastroenterology specialists. In the first and second rounds, 56% and 60% of statements, respectively, received median scores > or =7. The range of scores decreased considerably from the first to the second round.Conclusions: 5-Aminosalycylic acid, corticosteroids, immunosuppressants, enteral nutrition, total parenteral nutrition, and surgical therapy were considered standard therapy for intestinal Behçet's disease. Infliximab, colchicines, thalidomide, other pharmacological therapy, endoscopic therapy, and leukocytapheresis were deemed experimental therapy. Based on a two-round modified Delphi approach, practice guidelines for diagnosis and treatment of intestinal Behçet's disease were developed. [ABSTRACT FROM AUTHOR]

BACKGROUND: The purpose of this study was to clarify the long-term course of Crohn's disease (CD) and predictors of its prognosis in Japan. METHODS: This was a historical cohort study of 276 patients with CD who had been diagnosed between 1965 and 1998. The clinical course was evaluated by the course of the CD score (CCDS) according to the required treatments. The predictive factors were examined by stepwise regression test. The cumulative rates of operation and survival were calculated by the Kaplan-Meier method. RESULTS: Patients with colitis-type CD had significantly lower annual and cumulative operation rates than those with other types, and showed significantly better progress, estimated by the CCDS, than patients with ileocolitis type. Reliable predictors for the 2- to 5-year clinical course after starting treatment were the CCDS, the presence of laparotomy during the initial year, and onset at age 30 years or more. The predictors for the 6- to 10-year clinical course were the duration of symptoms at diagnosis and onset at age 16 years or less. The predictors for the 11- to 15-year clinical course were the CCDS, the maximum International Organization of the Study of Inflammatory Bowel Disease (IOIBD) assessment score during the first year after starting treatment, and the effectiveness of the initial treatment. Relative survival rates at 5, 10, 15, and 20 years after the onset were 98.9%, 98.1%, 97.7%, and 94.9%, respectively. CONCLUSIONS: CD patients with colitis type showed a better clinical course and had significantly different clinical features compared with the patients with ileitis and ileocolitis type. Prediction of the longterm course of CD is possible by using clinical factors during the first year after starting treatment. The relative survival rates in Japanese patients with CD are not different from those seen in Western countries. The purpose of this study was to clarify the long-term course of Crohn's disease (CD) and predictors of its prognosis in Japan. [ABSTRACT FROM AUTHOR]

Telomere length in human somatic cells gradually decreases with the number of cell divisions and is regarded as a marker of somatic cell turnover. Mucosal cells of the affected colon show rapid turnover in individuals with active ulcerative colitis (UC). Telomere length was determined by Southern blot analysis of terminal restriction fragments (TRFs) from the colonic mucosa of 17 patients with UC in remission, two of whom showed dysplasia, and 17 control subjects without colitis. For each individual, mean TRF length was compared between rectal mucosa and unaffected cecal mucosa. The mean TRF length of the rectal mucosa was significantly less than that of cecal mucosa in UC patients (7.87 +/- 0.36kb versus 8.77 +/- 0.21 kb; P = 0.0015, Wilcoxon signed rank test), whereas no significant difference was detected in the control subjects. The extent of telomere shortening was 10.6 +/- 3.35% in UC patients, compared with 0.8 +/- 0.64% in noncolitis controls (P = 0.0024, Mann-Whitney U-test). Four UC patients, two of whom had dysplasia, showed telomere shortening of more than 20% in the rectal mucosa. These observations suggest that telomere shortening in the colonic mucosa of individuals with UC may represent the history of mucosal inflammation during disease of long duration, and that it may contribute to aneuploidy in UC. [ABSTRACT FROM AUTHOR]

Background: Recently in Japan, the morbidity of colorectal polyp has been increasing. As a result, a large number of cases of colorectal polyps that are diagnosed and treated using colonoscopy has now increased, and clinical guidelines are needed for endoscopic management and surveillance after treatment., Methods: Three committees [the professional committee for making clinical questions (CQs) and statements by Japanese specialists, the expert panelist committee for rating statements by the modified Delphi method, and the evaluating committee by moderators] were organized. Ten specialists for colorectal polyp management extracted the specific clinical statements from articles published between 1983 and September 2011 obtained from PubMed and a secondary database, and developed the CQs and statements. Basically, statements were made according to the GRADE system. The expert panel individually rated the clinical statements using a modified Delphi approach, in which a clinical statement receiving a median score greater than seven on a nine-point scale from the panel was regarded as valid., Results: The professional committee created 91CQs and statements for the current concept and diagnosis/treatment of various colorectal polyps including epidemiology, screening, pathophysiology, definition and classification, diagnosis, treatment/management, practical treatment, complications and surveillance after treatment, and other colorectal lesions (submucosal tumors, nonneoplastic polyps, polyposis, hereditary tumors, ulcerative colitis-associated tumor/carcinoma)., Conclusions: After evaluation by the moderators, evidence-based clinical guidelines for management of colorectal polyps have been proposed for 2014.

Background and Aims: Oral mesalazine formulations are effective in the treatment of active ulcerative colitis (UC). It is not clear what induction dose of mesalazine is optimal for treating patients with active UC. We aimed to evaluate the efficacy and safety of 4 versus 2.25 g/day for selected patients with active UC., Methods: A multicenter, randomized, double-blind, parallel-group clinical study in 39 Japanese medical institutions. A total of 123 patients with moderately active UC received 4 g/day (two divided doses) versus 2.25 g/day (three divided doses) for 8 weeks. Primary endpoint was the ulcerative colitis-disease activity index (UC-DAI) score before and after 8 weeks of treatment. The improvement of each individual UC-DAI variable, remission, and efficacy rates were secondary endpoints. Safety was determined by laboratory data, vital signs, subjective symptoms, and objective findings., Results: Patients receiving 4 g/day achieved a change in UC-DAI score significantly superior to those receiving 2.25 g/day [-3.0 (95% confidence intervals (CI) -3.8 to -2.3) vs. -0.8 (95% CI -1.8 to 0.1), respectively]. There were significant differences in all UC-DAI variables between the groups. Remission rates were 22.0% (4 g/day) and 15.3% (2.25 g/day). The efficacy rate was significantly better with 4 versus 2.25 g/day [76.3 vs. 45.8%, respectively (95% CI 13.8-47.2); P = 0.001]. No difference was seen in adverse events or adverse drug reactions., Conclusions: A dose of 4 g/day was significantly superior to 2.25 g/day in terms of UC-DAI score for patients with moderately active UC. Safety profiles were similar for both doses.

Background. A major longterm risk for patients with ulcerative colitis (UC) is the development of colorectal dysplasia and cancer. Microsatellite instability (MI) has now been reported not only in colitic cancers but also in dysplasias, and even in nondysplastic inflamed mucosa. With the conventional microdissection technique, however, contamination by nonepithelial cells cannot be prevented and this could produce less reliable results than other methods. Therefore, we examined the condition of MI and loss of heterozygosity (LOH) of UC epithelium using a crypt isolation technique. Methods. One hundred and twenty-nine biopsy samples from 21 patients with UC were investigated for histology and microsatellite status, using nine microsatellite markers. A total of 1031 polymenase chain reaction (PCR) products were evaluated. Results. We found that no microsatellite markers displayed instability, but LOH at the 3p locus was detected in the nondysplastic epithelium of one patient with longstanding UC. Conclusions. Our study strongly suggests that MI does not contribute to the progression of the colitis-dysplasia sequence.

To evaluate the effect of a controlled-release mesalazine tablet, in patients with ulcerative colitis (UC), a multicenter double-blind study was carried out, using sulfasalazine (500 mg tablet) as the control drug. The mesalazine tablet contained 250 mg of ethyl cellulose-coated mesalazine granules. The patients were assigned to two groups, one to receive mesalazine tablets (1500 mg/day) and a sulfasalazine placebo (group M) and the other to receive sulfasalazine tablets (3000 mg/day) and a mesalazine placebo (group S). The test medications were administered orally for 4 consecutive weeks. The study subjects were selected from among patients with mild to moderate active UC, and 118 patients were enrolled. Concomitant use of steroids and immunosuppressors was prohibited during the study period. Of the 118 patients, 9 dropped out. A total of 109 complete records were thus obtained, 52 in group M and 57 in group S. There was no difference in the improvement of clinical symptoms and endoscopic findings between the two groups. The overall safety, based on adverse reactions and laboratory data, was higher, at 86.5%, for group M (n = 52), compared to 66.7% for group S (n = 57). The general usefulness, based on the improvement and safety, was higher, at 65.3%, for group M (n = 49), compared to 45.6% for group S (n = 57). The controlled-release mesalazine tablet thus appears to be useful in the treatment of mild to moderate active UC.

Many of the in vivo activities of interferon (IFN)-gamma match the changes found in inflammatory bowel disease, but its importance is controversial. Interferon (IFN)-gamma induces the expression of B7-2 costimulatory molecules on monocytes. We measured levels of IFN-gamma production in intestinal mucosa and isolated lamina propria mononuclear cells (LPMC) in patients with Crohn's disease (CD) and ulcerative colitis (UC). We also investigated the induction of B7-2 on the LPMC by flow cytometry. Mucosal IFN-gamma production was higher than the control level in patients with CD, but this was not the case in UC. IFN-gamma production and B7-2 expression in the LPMC of CD were higher than in the LPMC of UC and controls, and high levels of B7-2 expression were observed on the LPMC of CD after incubation with endotoxin. The induction of B7-2 on the LPMC of CD may provide a mechanism for the amplification of T cell proliferation and lymphokine production by IFN-gamma-activated LPMC.

Crohn's disease (CD) often flares up and requires frequent hospitalization and/or surgery. Cyclic home elemental enteral alimentation (C-HEEA) was developed to prevent flare-up of CD and to minimize patient hospitalization. However, its therapeutic efficacy has not been studied in a large patient population. Therefore, questionnaires were sent to members of the Inflammatory Bowel Disease (IBD) Research Group of Japan to evaluate the therapeutic efficacy of C-HEEA and to define the factors that may affect the efficacy of the treatment. Data for 410 patients (C-HEEA-treated n = 322; drug-treated n = 88) were collected from 29 institutions and analysis showed the following results. The cumulative remission and non-hospitalization rates of the C-HEEA treated group were significantly higher than the rates of the drug-treated group in all patients and in those with ileitis and ileo-colitis (P < 0.0001, P < 0.001, and P < 0.01, respectively), but no significant difference was noted in patients with colitis. Cumulative remission and non-hospitalization rates were also influenced by the daily calorie content of the elemental diet (ED); more than 1200 kcal of the ED per day was found to be more effective than lower amounts to maintain remission and to prevent hospitalization. The therapeutic efficacy of C-HEEA was shown to be superior to that of drug treatment in patients with CD with ileal involvement, and it is suggested that more than 1200kcal per day should be supplied by the ED to enhance its therapeutic efficacy.

To clarify the long-term prognosis of Japanese patients with ulcerative colitis, we investigated the cumulative colectomy rate and the survival rate, and compared the results with reports from Western countries. The subjects were 778 patients who had visited 8 hospitals from 1973 to 1990. A total of 114 of the 778 patients (14.7%) had required colectomy and 21 (2.7%) had died. These rates were higher in the patients who had total colitis, and in those who had acute fulminant type of severe type. There were no significant differences in these rates according to age of onset (under 29 years, 30-49 years, and more than 50 years). The cumulative colectomy rate increased rapidly within 2 years after onset. Thereafter, the rate increased gradually, by 1%-2% per year. In patients with total colitis, 14.1% required colectomy within 2 years. The age at onset had no effect on this rate. The cumulative survival rate decreased gradually throughout the first 10 years, the rate being 96.2% in the 10th year. No deaths occurred in the 11-18th years after onset. Despite our inclusion of more patients with total or severe colitis, our results were similar to or slightly superior to those reported from Western countries; this may be attributed to a temporal bias.