Comparison of Targeted vs Random Biopsies for Surveillance of Ulcerative Colitis-Associated Colorectal Cancer

Background & AimsA random biopsy is recommended for surveillance of ulcerative colitis (UC)-associated colorectal cancer. However, a targeted biopsy might be more effective. We conducted a randomized controlled trial to compare rates of neoplasia detection by targeted vs random biopsies in patients with UC.MethodsWe performed a study of 246 patients with UC for 7 years or more, seen at 52 institutions in Japan from October 1, 2008 through December 31, 2010. Patients were randomly assigned to the random group (4 random biopsies collected every 10 cm in addition to targeted biopsies, n = 122) or the target group (biopsies collected from locations of suspected neoplasia, n = 124). The primary end point was the number of neoplastic lesions detected in a single surveillance colonoscopy. We estimated the ratio and difference in the mean number of neoplastic lesions between the groups. We also evaluated the non-inferiority between the groups as an exploratory study. A non-inferiority margin of 0.65 (0.13 of 0.20) was considered for the ratio of the mean number of neoplastic lesions between groups.ResultsThe mean number of biopsies found to contain neoplastic tissue per colonoscopy was 0.211 (24 of 114) in the target group and 0.168 (18 of 107) in the random group (ratio of 1.251; 95% confidence interval, 0.679–2.306). The lower limit was above the non-inferiority margin of 0.65. Neoplasias were detected in 11.4% of patients in the target group and 9.3% of patients in the random group (P = .617). Larger numbers of biopsy samples per colonoscopy were collected in the random group (34.8 vs 3.1 in the target group; P < .001), and the total examination time was longer (41.7 vs 26.6 minutes in the target group; P < .001). In the random group, all neoplastic tissues found in random biopsies were collected from areas of the mucosa with a history or presence of inflammation.ConclusionsIn a randomized controlled trial, we found that targeted and random biopsies detect similar proportions of neoplasias. However, a targeted biopsy appears to be a more cost-effective method. Random biopsies from areas without any signs of present or past inflammation were not found to contain neoplastic tissues. Clinical Trial Registry: UMIN000001608

Development and Improvement of Simple Colonic Mucosal Ulcer during Treatment of Severe Ulcerative Colitis with Tacrolimus

Diarrhea, melena, and lower abdominal pain developed in a male in his 20s and colonoscopy showed pancolitis-type severe ulcerative colitis (UC). Treatment was initiated with 4,000 mg of 5-aminosalicylic acid and 60 mg/day of prednisolone, but the symptoms and inflammatory reaction worsened with prednisolone dose reduction. Tacrolimus was added to the treatment, which subsequently induced remission. Serial colonoscopies during the treatment showed improvement in ulcer and mucosal edema throughout the entire large intestine, but a new solitary round ulcer appeared at the end of the ileum. Since no signs of Behçet’s disease were noted, it was considered as a simple ulcer, a complication of UC. Tacrolimus treatment was continued based on continued improvement in clinical features and colonic mucosa, excluding the end of the ileum. Colonoscopy at 6 months after initiation of tacrolimus showed healing of the large intestinal mucosa, although mild congestion was still noted. The solitary round ulcer at the end of the ileum improved to a small erosion. We report the improvement of a simple ulcer that developed during tacrolimus treatment

Adalimumab for the Treatment of Japanese Patients With Intestinal Behçet’s Disease

Behçet’s disease is a chronic, relapsing inflammatory disease that can involve the mouth, skin, eyes, genitals, and intestines. Active intestinal Behçet’s disease can be complicated by gastrointestinal (GI) bleeding and perforation. We performed a multicenter, open-label, uncontrolled study to evaluate the efficacy and safety of adalimumab, a fully human monoclonal antibody against tumor necrosis factor α, in patients with intestinal Behçet’s disease who were refractory to corticosteroid and/or immunomodulator therapies. The study was conducted at 12 sites in Japan, from November 2010 through October 2012. Twenty patients were given 160 mg adalimumab at the start of the study and 80 mg 2 weeks later, followed by 40 mg every other week for 52 weeks; for some patients, the dose was increased to 80 mg every other week. A composite efficacy index, combining GI symptom and endoscopic assessments, was used to evaluate efficacy. The primary efficacy end point was the percentage of patients with scores of 1 or lower for GI symptom and endoscopic assessments at week 24. Secondary end points included complete remission and resolution of non-GI Behçet’s-related symptoms. Nine patients (45%) had GI symptom and endoscopic assessment scores of 1 or lower at week 24 of treatment, and 12 patients (60%) had these scores by week 52. Four patients (20%) achieved complete remission at weeks 24 and 52. Individual global GI symptom and endoscopic scores improved for most patients at weeks 24 and 52. Two thirds of patients with oral aphthous ulcers, skin symptoms, and genital ulcers, and 88% of patients with erythema nodosum had complete resolution of these conditions at week 52. A total of 9 of 13 patients (69%) taking steroids at baseline were able to taper (n = 1) or completely discontinue steroids (n = 8) during the study. No new safety signals were observed. Adalimumab is a potentially effective treatment for intestinal Behçet’s disease in Japanese patients who are refractory to conventional treatments. ClinicalTrials.gov number: NCT01243671