Inflammatory bowel disease (IBD) is a chronic disorder involving mainly the intestinal tract, but possibly other gastrointestinal and extraintestinal organs. Although etiology is still uncertain, recent knowledge in pathogenesis has accumulated, and novel diagnostic and therapeutic modalities have become available for clinical use. Therefore, the previous guidelines were urged to be updated. In 2016, the Japanese Society of Gastroenterology revised the previous versions of evidence-based clinical practice guidelines for ulcerative colitis (UC) and Crohn’s disease (CD) in Japanese. A total of 59 clinical questions for 9 categories (1. clinical features of IBD; 2. diagnosis; 3. general consideration in treatment; 4. therapeutic interventions for IBD; 5. treatment of UC; 6. treatment of CD; 7. extraintestinal complications; 8. cancer surveillance; 9. IBD in special situation) were selected, and a literature search was performed for the clinical questions with use of the MEDLINE, Cochrane, and Igaku Chuo Zasshi databases. The guidelines were developed with the basic concept of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Recommendations were made using Delphi rounds. This English version was produced and edited based on the existing updated guidelines in Japanese.

This article has an accompanying continuing medical education activity, also eligible for MOC credit, on page e23. Learning Objective: Upon completion of this evaluation, successful learners will be able to manage patients with ulcerative colitis who are at high risk for the development of colorectal cancer.

BackgroundClinical evidence regarding intestinal Behçet’s disease (BD) management is lacking and intestinal lesions are a poor prognostic factor. In 2007, the Japan consensus statement for diagnosis and management of intestinal BD was developed. Recently, the efficacy of anti-tumor necrosis factor (TNF)α monoclonal antibodies (mAbs), and infliximab (IFX) was reported and adalimumab (ADA) was approved for intestinal BD in Japan. This study renewed consensus-based practice guidelines for diagnosis and treatment of intestinal BD focusing on the indication of anti-TNFα mAbs.MethodsAn expert panel of Japanese gastroenterology and rheumatology specialists was involved. Clinical statements for ratings were extracted from the literature, a professional group survey, and by an expert panel discussion, which rated clinical statements on a nine-point scale. After the first round of ratings, a panelist meeting discussed areas of disagreement and clarified areas of uncertainty. The list of clinical statements was revised after the panelist meeting and a second round of ratings was conducted.ResultsFifteen relevant articles were selected. Based on the first edition consensus statement, improved clinical statements regarding indications for anti-TNFα mAbs use were developed. After a two-round modified Delphi approach, the second edition of consensus statements was finalized.ConclusionsIn addition to standard therapies in the first edition, anti-TNFα mAbs (ADA and IFX) should be considered as a standard therapy for intestinal BD. Colchicines, thalidomide, other pharmacological therapy, endoscopic therapy, and leukocytapheresis were deemed experimental therapies.

Intensive GMA in patients with active UC seems to be more efficacious than weekly treatment, and significantly reduced the patients' morbidity time without increasing the incidence of side effects.

tob is a member of antiproliferative family genes. Mice lacking tob are prone to spontaneous formation of tumors. The occurrence rate of diethylnitrosamine-induced liver tumors is higher in tob −/− mice than in wildtype mice. tob −/− p53 −/− mice show accelerated tumor formation in comparison with single null mice. Expression of cyclin D1 mRNA is increased in the absence of Tob and is reduced by Tob. Tob acts as a transcriptional corepressor and suppresses the cyclin D1 promoter activity through an interaction with histone deacetylase. Levels of tob mRNA are often decreased in human cancers, implicating tob in cancer development.Supplemental material is available at http://www.genesdev.org. There is accumulating evidence that genes involved in the negative control of cell growth can function as tumor suppressors. In humans, tob, tob2, ana, pc3b, btg1, and btg2 comprise a family (tob family) of antiproliferative genes (Bradbury et al. 1991;Fletcher et al. 1991;Rouault et al. 1992;Matsuda et al. 1996;Guehenneux et al. 1997;Yoshida et al. 1998;Ikematsu et al. 1999;Buanne et al. 2000). Exogenous expression of Tob family proteins suppresses growth of NIH-3T3 cells by inhibiting G1 progression of the cell cycle (Yoshida et al. 1998;Ikematsu et al. 1999;Guardavaccaro et al. 2000;Maekawa et al. 2002;Suzuki et al. 2002). We showed previously that Tob is a substrate of Erk MAPK, and unphosphorylated Tob suppresses cell-cycle entry of quiescent cells. Erk phosphorylation of Tob blocks the antiproliferative activity (Maekawa et al. 2002;Suzuki et al. 2002), which, at least in part, describes the importance of Erk activation in the cells stimulated by growth factors. When Tob is depleted, Cyclin D1 continues to be expressed and readily progress into S phase during serum starvation (Suzuki et al. 2002). In addition, the antiproliferative activity of Tob is impaired in the presence of exogenously coexpressed Cyclin D1 (Suzuki et al. 2002). These data suggest that tob functions as a tumor suppressor. However, possible involvement of Tob in tumorigenesis and roles of Tob in the control of cyclin D1 expression are unclear.Tob family proteins associate with transcription factors. Virtually all of the Tob family members interact with Caf1 (Rouault et al. 1998;Ikematsu et al. 1999;Yoshida et al. 2001), whose yeast homolog is a component of the CCR4-NOT transcriptional complex (Albert et al. 2000). The CCR4-NOT complex participates in the control of specific sets of genes such as those involved in the late mitotic phase of the cell cycle (Liu et al. 1997). Both BTG1 and BTG2 associate with HoxB9 and estrogen receptor ␣, and modulate their transcription activity (Prevot et al. 2000(Prevot et al. , 2001. Tob associates with Smads transcription complex and affects Smad-mediated gene expression (Yoshida et al. 2000;Tzachanis et al. 2001). This suggests that Tob family proteins are regulators of gene transcription, functioning as either coactivators or corepressors.Here, we report that mice lacking tob are prone to spontaneous formation o...