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Behçet's disease (BD) is an intractable systemic inflammatory disease characterized by four main symptoms: oral and genital ulcers and ocular and cutaneous involvement. The Japanese diagnostic criteria of BD classify intestinal BD as a specific disease type. Volcano-shaped ulcers in the ileocecum are a typical finding of intestinal BD, and punched-out ulcers can be observed in the intestine or esophagus. Tumor necrosis factor inhibitors were first approved for the treatment of intestinal BD in Japan and have been used as standard therapy. In 2007 and 2014, the Japan consensus statement for the diagnosis and management of intestinal BD was established. Recently, evidence-based JSBD (Japanese Society for BD) Clinical Practice Guidelines for BD (Japanese edition) were published, and the section on intestinal BD was planned to be published in English. Twenty-eight important clinical questions (CQs) for diagnosis (CQs 1–6), prognosis (CQ 7), monitoring and treatment goals (CQs 8–11), medical management and general statement (CQs 12–13), medical treatment (CQs 14–22), and surgical treatment (CQs 23–25) of BD and some specific situations (CQs 26–28) were selected as unified consensus by the members of committee. The statements and comments were made following a search of published scientific evidence. Subsequently, the levels of recommendation were evaluated based on clinical practice guidelines in the Medical Information Network Distribution Service. The degree of agreement was calculated using anonymous voting. We also determined algorithms for diagnostic and therapeutic approaches for intestinal BD. The present guidelines will facilitate decision making in clinical practice.

Patients with longstanding inflammatory bowel disease are at high risk of developing intestinal cancers. In this study, we aimed to elucidate the differences between intestinal cancers associated with ulcerative colitis and Crohn's disease.Intestinal cancers in ulcerative colitis and Crohn's disease patients treated between 1983 and 2020 at 43 Japanese institutions were retrospectively analyzed..A total of 1505 intestinal cancers in 1189 ulcerative colitis and 316 Crohn's disease patients were studied. Almost all of ulcerative colitis-associated cancers (99%) were in the colon and rectum, whereas half of Crohn's disease-associated cancers (44%) were in the anus, with 11% in the small intestine. Ulcerative colitis-associated cancers were diagnosed more frequently by surveillance (67% vs. 25%, P 0.0001) and at earlier stages (stages 0-1, 71% vs. 27%, P 0.0001) compared with Crohn's disease-associated cancers. Colorectal cancers associated with Crohn's disease showed a significantly worse 5-year overall survival rate than those associated with ulcerative colitis (stage 2, 76% vs. 89%, P = 0.01, stage 3, 18% vs. 68%, P = 0.0009, and stage 4, 0% vs. 13%, P = 0.04). Surveillance correlated with earlier diagnoses for ulcerative colitis- and Crohn's disease-associated intestinal cancers, whereas shorter intervals between endoscopic examinations correlated with an earlier cancer diagnosis in ulcerative colitis patients but not in Crohn's disease patients.The clinical and oncological features of ulcerative colitis- and Crohn's disease-associated cancers were very different. Crohn's disease-associated cancers were diagnosed at more advanced stages and were detected less frequently by surveillance. Additionally, they showed a significantly poorer prognosis.

Japan has the largest aging society, where many elderly people have intractable diseases including ulcerative colitis (UC). Along with the increasing total number of UC patients, the number of elderly UC patients has also been increasing and will continue to do so in the future. Although the clinical features and natural history of UC in the elderly have many similarities with UC in the non-elderly population, age-specific concerns including comorbidities, immunological dysfunction, and polypharmacy make the diagnosis and management of elderly UC challenging compared to UC in non-elderly patients. Based on increasing data related to elderly UC patients from Japan, as well as other countries, we reviewed the epidemiology, clinical course, differential diagnosis, management of comorbidities, surveillance, medical therapy, and surgery of UC in the elderly.

Inflammatory bowel disease (IBD) is a general term for chronic or remitting/relapsing inflammatory diseases of the intestinal tract and generally refers to ulcerative colitis (UC) and Crohn’s disease (CD). Since 1950, the number of patients with IBD in Japan has been increasing. The etiology of IBD remains unclear; however, recent research data indicate that the pathophysiology of IBD involves abnormalities in disease susceptibility genes, environmental factors and intestinal bacteria. The elucidation of the mechanism of IBD has facilitated therapeutic development. UC and CD display heterogeneity in inflammatory and symptomatic burden between patients and within individuals over time. Optimal management depends on the understanding and tailoring of evidence-based interventions by physicians. In 2020, seventeen IBD experts of the Japanese Society of Gastroenterology revised the previous guidelines for IBD management published in 2016. This English version was produced and modified based on the existing updated guidelines in Japanese. The Clinical Questions (CQs) of the previous guidelines were completely revised and categorized as follows: Background Questions (BQs), CQs, and Future Research Questions (FRQs). The guideline was composed of a total of 69 questions: 39 BQs, 15 CQs, and 15 FRQs. The overall quality of the evidence for each CQ was determined by assessing it with reference to the Grading of Recommendations Assessment, Development and Evaluation approach, and the strength of the recommendation was determined by the Delphi consensus process. Comprehensive up-to-date guidance for on-site physicians is provided regarding indications for proceeding with the diagnosis and treatment.

Japan has the largest aging society, where many elderly people have intractable diseases including ulcerative colitis (UC). Along with the increasing total number of UC patients, the number of elderly UC patients has also been increasing and will continue to do so in the future. Although the clinical features and natural history of UC in the elderly have many similarities with UC in the non-elderly population, age-specific concerns including comorbidities, immunological dysfunction, and polypharmacy make the diagnosis and management of elderly UC challenging compared to UC in non-elderly patients. Based on increasing data related to elderly UC patients from Japan, as well as other countries, we reviewed the epidemiology, clinical course, differential diagnosis, management of comorbidities, surveillance, medical therapy, and surgery of UC in the elderly.

Although several complications capable of causing pouch failure may develop after restorative proctocolectomy (RPC) for ulcerative colitis (UC), the incidences and causes are conflicting and vary according to country, race and institution. To avoid pouch failure, this study aimed to evaluate the rate of pouch failure and its risk factors in UC patients over the past decade via a nationwide cohort study. We conducted a retrospective, observational, multicenter study that included 13 institutions in Japan. Patients who underwent RPC between January 2005 and December 2014 were included. The characteristics and backgrounds of the patients before and during surgery and their postoperative courses and complications were reviewed. A total of 2376 patients were evaluated over 6.7 ± 3.5 years of follow-up. Twenty-seven non-functional pouches were observed, and the functional pouch rate was 98.9% after RPC. Anastomotic leakage (odds ratio, 9.1) was selected as a risk factor for a non-functional pouch. The cumulative pouch failure rate was 4.2%/10 years. A change in diagnosis to Crohn’s disease/indeterminate colitis (hazard ratio, 13.2) was identified as an independent risk factor for pouch failure. The significant risk factor for a non-functional pouch was anastomotic leakage. The optimal staged surgical procedure should be selected according to a patient’s condition to avoid anastomotic failure during RPC. Changes in diagnosis after RPC confer a substantial risk of pouch failure. Additional cohort studies are needed to obtain an understanding of the long-standing clinical course of and proper treatment for pouch failure.

Muscarinic acetylcholine receptors (mAChRs) are major regulators of gut epithelial functions. However, the precise subtype composition has not been clarified.We characterized the pharmacological profile of mAChRs on mouse colonic crypts, employing [(3)H]-N-methyl scopolamine chloride as a radioligand and several subtype-selective chemicals, and the functional aspect by measuring short-circuit current (I sc) in Ussing chambers and by evaluating MAP kinase phosphorylation in mouse colonic mucosal sheets.The mAChRs were detected on the crypts (K d = 163.2 ± 32.3 pM, B max = 47.3 ± 2.6 fmol/mg of total cell protein). Muscarinic toxin 7 (MT-7, M1 subtype selective) gave a displacement curve with high affinity, but there was a part insensitive to MT-7 (18.8 ± 0.4 % of the total specific binding). The MT-7-insensitive component was displaced completely by darifenacin (M3 selective) with high affinity. ACh induced an increase in I sc, which was significantly enhanced by MT-7 but was completely inhibited by darifenacin or atropine. Colitis induction resulted in a significant decrease in the density of mAChRs, which occurred mainly in the MT-7-sensitive component (M1 subtype). Immunological experiments exhibited a reduction of M1 but not of M3 signal after colitis induction. Muscarinic stimulation induced an increase in MAP kinase phosphorylation, which was completely suppressed by MT-7 and was attenuated by inflammation, in mouse colonic epithelium.These results suggest that mAChRs in mouse colonic epithelial cells consist of two subtypes, M1 (80 %) and M3 (20 %). The major M1 subtype was likely to regulate epithelial chloride secretion negatively and was susceptible to inflammation and may be relevant to inflammatory gut dysfunction.

Ulcerative colitis (UC) is regarded as confined to the colorectum; however, there are several case reports showing upper gastrointestinal involvement. The aim of this study was to examine the prevalence and characteristics of gastroduodenitis associated with UC (GDUC). Esophagogastroduodenoscopy with biopsies was prospectively performed on 250 UC patients (134 men, 116 women; mean age, 42 years; 162 with colectomy, 163 with pancolitis). Criteria for GDUC were created on the basis of endoscopic and histological comparisons with non-UC controls, and the prevalence and characteristics were statistically analyzed. GDUC was defined endoscopically as friable mucosa (erosive or ulcerative mucosa with contact or spontaneous bleeding), granular mucosa (multiple white spots almost without a red halo), or, conditionally, multiple aphthae (multiple white spots surrounded by a red halo, clinically excluding other disorders such as Crohn’s disease). The prevalence of GDUC was 19/250 (7.6%). The clinical characteristics included more extensive colitis, lower dose of prednisolone, higher prevalence of pouchitis, and longer postoperative period. In our population, the presence of pancolitis and a lower dose of prednisolone were significant risk factors for developing GDUC in multivariate analysis. The high prevalence of GDUC suggests that the gut inflammatory reaction in UC may not be restricted to the large intestine. Administered steroids might conceal GDUC, and more aggressive UC such as active pancolitis may be related to the development of GDUC.