Long-term course of Crohn's disease in Japan: Incidence of complications, cumulative rate of initial surgery, and risk factors at diagnosis for initial surgery.

BACKGROUND AND AIMS: Intestinal complications of stenosis or fistula may occur during the course of Crohn's disease (CD), and surgery is performed in a fair number of patients. The risk factors for initial surgery in a Japanese hospital-based cohort of CD patients were evaluated. METHODS: This study was a single-center, retrospective, cohort study. The subjects were 520 patients who underwent inpatient and outpatient treatment at our hospital, had a definitive diagnosis of CD, and no previous surgery. Three parameters were investigated: (i) cumulative incidence of stenosis and fistula; (ii) cumulative rate of initial surgery for each disease type; and (iii) risk factors at diagnosis for initial surgery. RESULTS: (i) Stenosis and fistula increased with time, with stenosis or fistula appearing in about half of the patients after 5 years. (ii) The cumulative rate of initial surgery was about 50% after 10 years. (iii) The patient factors at diagnosis of current smoker, upper gastrointestinal disease, stricturing, penetrating, moderate to severe stenosis of the jejunum, moderate to severe stenosis of the ileum, and moderate to severe stenosis of the terminal ileum were risk factors for initial surgery. CONCLUSIONS: Stenosis or fistula appeared in about half of the patients after 5 years from diagnosis. When upper gastrointestinal disease or complicated small intestinal lesions are seen at the time of diagnosis, the cumulative rate of initial surgery is significantly higher.

Mucosal healing of ileal lesions is associated with long-term clinical remission after infliximab maintenance treatment in patients with Crohn's disease.

BACKGROUND AND AIM: The aim of the present study was to endoscopically evaluate ileal mucosal healing during maintenance therapy with infliximab in order to investigate the clinical significance of endoscopic examination of ileal lesions in Crohn's disease patients. METHODS: This study retrospectively analyzed 54 patients who mainly had active ulcers of the ileum on endoscopy at baseline who were responsive to infliximab induction and who received infliximab maintenance therapy. Mucosal healing was defined as no ulcer or only ulcer scar. At the time of follow-up endoscopy after starting infliximab, endoscopic score, mucosal healing, and clinical remission were evaluated. On long-term follow up, correlations between mucosal healing and long-term clinical remission, and between mucosal healing and the need for major abdominal surgery, were also evaluated. RESULTS: Ileal mucosal healing and complete mucosal healing were significantly correlated with clinical remission (P = 0.046, P = 0.0001, respectively). The rate of long-term clinical remission was significantly higher in patients with complete mucosal healing (P = 0.025). The rate of major abdominal surgery for strictures was significantly lower in patients with complete mucosal healing (P = 0.044). CONCLUSIONS: Complete mucosal healing after 1-2 years was a predictive factor for long-term clinical remission up to 4 years after starting infliximab. A lack of complete mucosal healing was a predictive factor for major abdominal surgery for strictures. The present study suggests that endoscopic evaluation of ileal lesions is useful for long-term prognosis of Crohn's disease patients.

Can we accurately diagnose minute gastric cancers (≤5 mm)? Chromoendoscopy (CE) vs magnifying endoscopy with narrow band imaging (M-NBI).

BACKGROUND: Chromoendoscopy (CE) is relatively ineffective at identifying the cancer-specific morphological characteristics of minute gastric cancers less than or equal to 5 mm in diameter, and on its own is insufficient to make an accurate diagnosis. The aim of this study is to assess the diagnostic performance of magnifying endoscopy with narrow band imaging (M-NBI) for minute gastric cancers. METHODS: The minute cancer group comprised consecutive endoscopic submucosal dissection-resected minute gastric cancers histologically measured as no larger than 5 mm in diameter. The non-cancer group comprised consecutive non-cancer lesions no larger than 5 mm in diameter. The two groups were subject to retrospective analysis to evaluate the diagnostic ability (sensitivity, specificity, and diagnostic accuracy) and reproducibility of CE and M-NBI. RESULTS: The results for CE versus M-NBI were as follows: sensitivity 43.7 % (95 % CI, 26.5-61.0 %) versus 78.0 % (95 % CI, 64.0-92.0 %); specificity 81.6 % (95 % CI, 72.6-90.6 %) versus 92.9 % (95 % CI, 87.0-98.9 %); and diagnostic accuracy 69.9 % (95 % CI, 61.0-78.6 %) versus 88.3 % (95 % CI, 82.0-94.5 %). The sensitivity and diagnostic accuracy were, therefore, significantly higher for M-NBI than for CE. The inter-observer variability was κ = 0.08 for CE and κ = 0.56 for M-NBI, while the intra-observer variability was κ = 0.38 and κ = 0.65, respectively. CONCLUSIONS: M-NBI has greater sensitivity and reproducibility than CE for the diagnosis of minute gastric cancers.

Second peak in the distribution of age at onset of ulcerative colitis in relation to smoking cessation.

BACKGROUND AND AIM: The prevalence of ulcerative colitis (UC) is increasing steadily in Japan. In Western countries, a bimodal distribution, with UC onset peaks in youth and middle age, is observed, and smoking cessation is reported as a risk factor for UC. However, there are few reports on a bimodal distribution of onset age among Japanese patients. Therefore, the distribution of onset age and factors related to late onset (i.e. onset at 50 years old or later) were investigated in UC patients in Japan. METHODS: A questionnaire survey of UC patients was conducted to investigate the distribution of the age of onset and factors that may be related to UC onset in a Japanese university hospital. RESULTS: Among 465 UC patients, 343 patients responded. In the distribution of onset age, a large peak was seen in patients aged 10-20s, and small peaks were seen at age 40-44 years and then in 50-60s. In addition, the onset age was older in the UC patients diagnosed in 2001 or later than in those diagnosed in 2000 or earlier. Late onset was more common among the UC patients diagnosed in 2001 or later (vs 2000 or earlier: interaction odds ratio = 4.98, 95% CI: 2.21-11.25, P < 0.01) and among former smokers (vs never-smokers: interaction odds ratio = 2.93, 95% CI: 1.40-6.14, P < 0.01) on multivariate analysis. CONCLUSIONS: Similar to UC patients in Western countries, a bimodal distribution of onset age was also observed in Japanese UC patients, and smoking cessation may partly contribute to the increase in late-onset UC patients in recent years in Japan.

Impact of CYP3A5 genetic polymorphisms on the pharmacokinetics and short-term remission in patients with ulcerative colitis treated with tacrolimus.

BACKGROUND AND AIM: The pharmacokinetics of tacrolimus (Tac) differ among individuals, and genetic polymorphisms of cytochrome P-450 (CYP) 3A4, CYP3A5, and ABCB1 are thought to be involved. The aim of this study was to clarify whether these genetic polymorphisms affect the pharmacokinetics of Tac in patients with ulcerative colitis. METHODS: The subjects in this study were 45 patients with moderate-to-severe ulcerative colitis who were resistant to other therapies and were treated with Tac. The subjects were tested for genetic polymorphisms of CYP3A4, CYP3A5, and ABCB1, and the relationship between Tac pharmacokinetics and the remission rate was investigated. RESULTS: Of the 45 subjects, 24 (53.3%) were CYP3A5 expressers (Exp), and 21 (46.7%) were non-expressers (Non-Exp). The trough level and the dose-adjusted trough level on days 2-5 were significantly higher in the Non-Exp group than in the Exp group (10.16 ± 5.84 vs 4.47 ± 2.50 ng/mL, P < 0.0001, 139.36 ± 77.43 vs 61.37 ± 41.55 ng/mL per mg/kg/day, P < 0.0001). The percentage of patients achieving the optimal trough level on days 2-5 was significantly higher in the Non-Exp group than in the Exp group (40.0% vs 4.3%, P = 0.01). This trend was also observed on days 7-10. On multivariate analysis, factors associated with achievement of the optimal trough level were food non-intake and Non-Exp of CYP3A5. The remission rate was significantly higher in the Non-Exp group than in the Exp group (47.6% vs 16.7%, P = 0.046). CONCLUSIONS: CYP3A5 genetic polymorphisms affected the pharmacokinetics of Tac, so that the short-term clinical remission rate was different between Exp and Non-Exp of CYP3A5.

Incidence, clinical characteristics, long-term course, and comparison of progressive and nonprogressive cases of aphthous-type Crohn's disease: a single-center cohort study.

BACKGROUND/AIMS: In Japan, aphthous-type Crohn's disease (type A CD) is thought to represent an early phase of Crohn's disease (CD), and diagnosis of type A CD is possible in the diagnostic criteria for CD in Japan. However, the details of type A CD are not well understood. METHODS: Subjects comprised 649 CD patients diagnosed between 1985 and 2011. The incidence of type A CD over time was clarified in two periods (1985-2004 and 2005-2011). The course of type A CD was also investigated, and cases that did and did not progress to typical CD were compared. RESULTS: No significant difference was seen in the incidence of type A CD between the two periods (5.2 vs. 8.5%, p = 0.125). Type A CD patients followed at our hospital progressed to typical CD at a rate of 59.3%. In comparing progressive and nonprogressive cases, the frequency of large, densely distributed aphthous lesions in the small intestine was higher among progressive cases (p = 0.018). CONCLUSION: Type A CD is an early phase of CD, and CD diagnostic criteria including early cases are valid in Japan.

Cancer risk in Japanese Crohn's disease patients: investigation of the standardized incidence ratio.

BACKGROUND AND AIM: There have been very few reported investigations on the standardized incidence ratio (SIR) of intestinal cancer and all cancers other than intestinal cancer with Crohn's disease (CD) by organ in Japan. This study examined the risk of developing cancer (i.e. SIR) that occurs in association with CD. METHODS: The subjects were 770 CD patients managed at our hospital department, which specializes in inflammatory bowel disease, during the approximately 25 years from July 1985 to August 2010. The number of expected cancer patients in a healthy population matched for sex and age with the CD patients in our hospital was then calculated. The relative risk, or SIR, was also calculated. RESULTS: The total observation period was 10,552 person-years, during which 19 cases (2.5%) of cancer were discovered in 770 subjects. The cancer cases included nine cases of colorectal cancer (CRC), one case of small bowel cancer, one case of stomach cancer, three cases of acute myeloid leukemia, two cases of endometrial cancer, one case of lung cancer, one case of skin cancer, and one case of thyroid cancer. The SIR for cancers in Japan in 2003 was 0.87 (95% confidence interval [CI] 0.52-1.35) for all cancers, 2.79 (95% CI 1.28-5.29) for CRC, and 6.94 (95% CI 1.43-20.3) for leukemia. CONCLUSIONS: Among the cancers in CD patients in our hospital, no significant difference was seen in the risk for all cancers in comparison with the standard population. However, the risks for CRC and leukemia were significantly higher than in the standard population.