Endoscopy plays a significant role in the diagnosis, management, and surveillance of colorectal cancer (CRC) and inflammatory bowel diseases (IBDs). Moreover, magnifying endoscopy and image-enhanced endoscopy has a crucial role in the clinical setting. Recently, a super-magnifying endoscope has been developed, and two devices, confocal laser endomicroscopy (CLE) and an endocytoscopy system (ECS), which allow in vivo microscopic inspection of the microstructural mucosal features of the gastrointestinal tract, are currently available. Studies on the use of ECS in CRC were reported by a Japanese group. Additionally, a few studies on the use of ECS in IBD have been reported. CLE has been shown to be reliable in assessing the activity of the disease in IBDs in both ulcerative colitis and Crohn's disease. Various published studies evaluated the use of CLE during colonoscopy to distinguish colorectal polyp pathology and neoplasia. However, these studies are heterogeneous, and further evidence is necessary to confirm the efficacy of CLE.
Asian Continental Ancestry Group ; Colitis, Ulcerative ; Colonoscopy ; Colorectal Neoplasms ; Crohn Disease ; Diagnosis ; Endoscopes ; Endoscopy* ; Gastrointestinal Tract ; Humans ; Inflammatory Bowel Diseases ; Pathology ; Polyps

Colon capsule endoscopy was initially introduced in 2006. Since the results of a prospective study to evaluate first-generation colon capsule endoscopy efficacy for the detection of colonic neoplasia were unsatisfactory, second-generation colon capsule endoscopy was developed and reported in 2009. In this review article, we provide an overview of the current state of colon capsule endoscopy for evaluation of inflammatory bowel disease in a clinical setting and describe our clinical experience with this technology and its application. Among the various types of inflammatory bowel diseases, ulcerative colitis is the primary target for application of colon capsule endoscopy. Nevertheless, the initial results of studies using first-generation colon capsule endoscopy to evaluate inflammation were unclear. More recently, second-generation colon capsule endoscopy has provided higher accuracy for assessment of inflammation in patients with ulcerative colitis. Colon capsule endoscopy enables noninvasive observation (with reduced volume preparation) of mucosal inflammation severity in patients with ulcerative colitis.

Background/Aims: Adalimumab has been shown to induce and maintain clinical remission in patients with moderate to severe ulcerative colitis (UC). However, no large-scale population-based studies have been performed in Japan. This study was conducted to evaluate the safety and effectiveness of adalimumab in clinical practice in Japanese patients with UC. Methods: In this 52-week, prospective, multicenter, single-cohort, noninterventional, observational, postmarketing surveillance study, patients with moderate to severe UC received an initial subcutaneous injection of adalimumab 160 mg, followed by 80 mg at 2 weeks, and then 40 mg every other week. Safety assessments were the incidence of adverse drug reactions (ADRs) and serious ADRs. Effectiveness assessments were clinical remission, corticosteroid-free remission, mucosal healing, and change in C-reactive protein (CRP) levels from baseline. Results: Of 1,593 registered patients, 1,523 (male, 57.6%; mean age, 41.8 years) and 1,241 patients were included in the safety and effectiveness populations, respectively. ADRs were reported in 18.1% and serious ADRs in 4.9% of patients. Clinical remission was achieved in 49.7% of patients at week 4, increasing to 74.4% at week 52. Corticosteroid-free remission rates increased over time, from 10.4% at week 4 to 53.1% at week 52. More than 60% of patients demonstrated mucosal healing at weeks 24 and 52. Mean CRP levels (mg/dL) decreased from 1.2 at baseline to 0.6 at week 4 and 0.3 at week 52. Conclusions This large real-world study confirmed the safety and effectiveness of adalimumab in patients with UC in Japan. No new safety concerns were identified.

BACKGROUND/AIMS: This study assessed the efficacy and safety of high-dose multimatrix mesalazine once-daily (QD) compared to another form of high-dose mesalazine. METHODS: In this multicenter, randomized, double-blind study, 280 patients with mildly to moderately active ulcerative colitis (UC) received multimatrix mesalazine 4.8 g/day QD or pH-dependent-release mesalazine 3.6 g/day three times daily for 8 weeks. The primary endpoint was the change in the UC-Disease Activity Index (UC-DAI) at the end of the treatment period. RESULTS: The change in the UC-DAI (mean±standard deviation) in the per-protocol set was −2.6±2.47 in the multimatrix mesalazine 4.8 g/day group (n=134) and −1.8±2.64 in the pH-dependent-release mesalazine 3.6 g/day group (n=129). The difference in the mean change between the 2 groups was −0.7 (two-sided 95% confidence interval, −1.3 to −0.1). The noninferiority of multimatrix mesalazine 4.8 g/day to pH-dependent-release mesalazine 3.6 g/day was verified within the noninferiority margin (1.1). The superiority of multimatrix mesalazine 4.8 g/day to pH-dependent-release mesalazine 3.6 g/day was also investigated and confirmed in the full analysis set, according to the study protocol. In subgroup analyses, the effectiveness of multimatrix mesalazine 4.8 g/day was consistent in all subgroups. There was no difference in safety between the 2 treatment groups. CONCLUSIONS: Multimatrix mesalazine 4.8 g/day has higher efficacy and shows no difference in safety in mildly to moderately active UC, in comparison with pH-dependent-release mesalazine 3.6 g/day.
Colitis, Ulcerative* ; Double-Blind Method* ; Humans ; Mesalamine* ; Ulcer*

BACKGROUND/AIMS: In capsule endoscopy (CE), the capsule does not always reach the cecum within its battery life, which may reduce its diagnostic yield. We evaluated the effect of mosapride citrate, a 5-hydroxytryptamine-4 agonist that increases gastrointestinal motility, on CE completion. METHODS: In a retrospective study, we performed univariate and multivariate analyses for 232 CE procedures performed at our hospital. To identify factors that affect CE completion, the following data were systematically collected: gender, age, gastric transit time (GTT), nonsteroidal anti-inflammatory drug administration, previous abdominal surgery, hospitalization, use of a polyethylene glycol solution, use of mosapride citrate (10 mg), body mass index (BMI), and total recording time. RESULTS: The univariate analysis showed that oral mosapride citrate, GTT, and BMI were associated with improved CE completion. Multivariate analyses showed that oral mosapride citrate (odds ratio [OR], 1.99; 95% confidence interval [CI], 1.01 to 3.91) and GTT (OR, 2.34; 95% CI, 1.13 to 4.87) were significant factors for improving the CE completion. Oral mosapride citrate significantly shortened the GTT and small bowel transit time (SBTT). CONCLUSIONS: Oral mosapride citrate reduced the GTT and SBTT during CE and improved the CE completion rate.
Administration, Oral ; Benzamides ; Body Mass Index ; Capsule Endoscopy ; Cecum ; Citric Acid ; Gastrointestinal Motility ; Hospitalization ; Morpholines ; Multivariate Analysis ; Polyethylene Glycols ; Retrospective Studies

BACKGROUND/AIMS: This study compared the efficacy of once-daily administration of multimatrix mesalazine 2.4 g/day with multiple-dose mesalazine for the maintenance of remission. METHODS: In this multicenter, randomized, double-blind study, 203 patients with ulcerative colitis in remission received multimatrix mesalazine 2.4 g/day once-daily or time-dependent (controlled-release) mesalazine 2.25 g/day 3 times-daily for 48 weeks. The primary efficacy endpoint was the proportion of patients without rectal bleeding. RESULTS: The proportion of patients without rectal bleeding during the 48-week treatment period in the per protocol set was 84.8% (84/99) in the multimatrix mesalazine 2.4 g/day group and 78.0% (78/100) in the controlled-release mesalazine 2.25 g/day group. The difference between the 2 treatment groups was 6.8% (two-sided 95% confidence interval, −3.9% to 17.6%). The noninferiority margin of −10% was met in the comparison of multimatrix mesalazine 2.4 g/day once-daily with controlled-release mesalazine 2.25 g/day. Multimatrix mesalazine 2.4 g/day once-daily demonstrated consistent efficacy in all subgroups. There was no difference between the 2 treatment groups with regard to safety. CONCLUSIONS: A once-daily dose of 2 multimatrix mesalazine tablets (2.4 g) was not inferior to controlled-release mesalazine 2.25 g/day 3 times-daily in maintaining absence of rectal bleeding in ulcerative colitis.
Colitis, Ulcerative* ; Double-Blind Method* ; Hemorrhage ; Humans ; Mesalamine* ; Tablets ; Ulcer*

Although ileocolonoscopy is the gold standard for diagnosis of inflammatory bowel disease and is useful for assessing the disease severity in the colon and terminal ileum, several alternative diagnostic techniques have been developed recently. For ulcerative colitis (UC), magnification colonoscopy, endocytoscopy, and confocal laser endomicroscopy enable assessment of histological inflammation without the need for biopsy. Capsule endoscopy is useful for detection of small intestinal and colonic lesions in both female and male patients. For UC, capsule endoscopy may be useful for evaluating colonic inflammation in patients with a previous poor colonoscopy experience, while it should be used only in Crohn's disease (CD) patients with unexplained symptoms when other examinations are negative. Magnetic resonance enterography (MRE) is particularly useful for detecting transmural inflammation, stenosis, and extraintestinal lesions, including abscesses and fistulas. MRE is also useful when evaluating small and large intestinal lesions, even in cases with severe strictures in which full evaluation of the small bowel would be virtually impossible using other devices. Therefore, the appropriate diagnostic devices for detecting CD lesions in the small and large intestine should be used.
Colitis, Ulcerative/*diagnosis ; Crohn Disease/*diagnosis ; Cytodiagnosis/trends ; Diagnostic Imaging/*trends ; Endoscopy, Gastrointestinal/*trends ; Humans ; Magnetic Resonance Imaging/trends ; Microscopy, Confocal/trends ; Predictive Value of Tests ; Prognosis ; Severity of Illness Index

BACKGROUND/AIMS: This study compared the efficacy of multimatrix mesalazine 2.4 g/day and 4.8 g/day with controlled-release mesalazine 2.25 g/day. METHODS: In this multicenter, randomized, double-blind study, 251 patients with mildly to moderately active ulcerative colitis received multimatrix mesalazine 2.4 g/day once daily (Multimatrix-2.4), 4.8 g/day once daily (Multimatrix-4.8), or controlled-release (time-dependent) mesalazine 2.25 g/day 3 times daily (Time-2.25) for 8 weeks. The primary efficacy endpoint was the change in the ulcerative colitis-disease activity index (UC-DAI) score. RESULTS: The mean change in the UC-DAI score and standard deviation in the per protocol set was −1.9±2.5 for Multimatrix-2.4 and −2.4±2.8 for Time-2.25. The difference between Multimatrix-2.4 and Time-2.25 was 0.3 (two-sided 95% confidence interval [CI], −0.5 to 1.1), thus non-inferiority was not demonstrated based on the pre-defined non-inferiority margin (1.0). In the full analysis set, the difference between Multimatrix-4.8 and Time-2.25 was −1.2 (two-sided 95% CI, −2.0 to −0.5), and the mean change in UC-DAI score in the FAS was −3.3 (two-sided 95% CI, −3.9 to −2.8) for Multimatrix-4.8 and −1.9 (two-sided 95% CI, −2.5 to −1.3) for Multimatrix-2.4, indicating that Multimatrix-4.8 was more effective than Time-2.25 and Multimatrix-2.4. There was no difference among the treatment groups in terms of safety. CONCLUSIONS: This study showed that the efficacy of multimatrix mesalazine 2.4 g/day was comparable to controlled release mesalazine 2.25 g/day, although non-inferiority was not demonstrated. Importantly, this was the first study to indicate that multimatrix mesalazine 4.8 g/day was more effective than 2.4g/day with no associated safety concerns.
Colitis, Ulcerative* ; Double-Blind Method* ; Humans ; Mesalamine* ; Ulcer*

Background/Aims: Crohn’s disease is a chronic disorder; therefore, it is essential to investigate long-term safety and efficacy of treatments. This study assessed the safety and effectiveness of adalimumab for up to 3 years in Japanese patients with Crohn’s disease in real-world settings. Methods: This was a multicenter, single-cohort, observational study of patients with Crohn’s disease. Safety assessments included incidence of adverse drug reactions. Effectiveness assessments included clinical remission, mucosal healing, and Work Productivity and Activity Impairment (WPAI). Results: The safety and effectiveness analysis populations comprised 389 and 310 patients, respectively. Mean (standard deviation) exposure to adalimumab in the safety analysis population was 793.4 (402.8) days, with a 58.1% retention rate. A total of 105 patients (27.0%) and 43 patients (11.1%) experienced adverse drug reactions and serious adverse drug reactions, respectively, with no patient reporting tuberculosis or hepatitis B. Infections and serious infections were reported in 37 patients (9.5%) and 17 patients (4.4%), respectively. Malignancy was reported as an adverse drug reaction in 2 patients (0.5%). Remission rate increased from 37.8% (98/259) at baseline to 73.9% (167/226) at week 4 and remained > 70% over 3 years. Proportion of patients without mucosal ulcerations increased from 2.7% (2/73) at baseline to 42.3% (11/26) between years > 2 to ≤ 3. WPAI improvement started at 4 weeks, with the overall work impairment score improving from 42.7 (n = 102) at baseline to 26.9 (n = 84) at 4 weeks. Conclusions Results from this study confirm the long-term safety and effectiveness of adalimumab treatment in Japanese patients with Crohn’s disease in the real-world setting.

BACKGROUND/AIMS: A flexible spectral imaging color enhancement system was installed in new capsule software for video capsule endoscopy. Contrast image capsule endoscopy (CICE) is a novel technology using light-emitting diodes selected for the main absorption range of hemoglobin. We assessed the feasibility and diagnostic effi cacy for small bowel surveillance in patients with polyposis syndromes. METHODS: Six patients with polyposis syndromes, four with familial adenomatous polyposis and one each with Cowden syndrome (CS) and Cronkhite-Canada syndrome (CCS) were examined using CICE. We conducted three evaluations to assess the effect on the numbers of the detected polyps; compare polyp diagnostic rates between adenoma and hamartoma; and assess polyp visibility. RESULTS: The numbers of detected polyps and diagnostic accuracy did not differ signifi cantly between pre-contrast and contrast images. However, 50% of the adenomatous polyps displayed enhanced visibility on contrast images. CICE contrast images exhibited clearly demarcated lesions and improved the visibility of minute structures of adenomatous polyps. Hamartomatous polyp micro-structures in patients with CS and CCS were more clearly visualized on contrast than pre-contrast images. CONCLUSIONS: CICE is an effective tool for enhancing the visibility of polyps in patients with polyposis syndrome.
Absorption ; Adenoma ; Adenomatous Polyposis Coli ; Adenomatous Polyps ; Capsule Endoscopes ; Capsule Endoscopy ; Hamartoma Syndrome, Multiple ; Hemoglobins ; Humans ; Intestinal Polyposis ; Polyps