Doppler ultrasound findings correlate with tissue vascularity and inflammation in surgical pathology specimens from patients with small intestinal Crohn’s disease

BACKGROUND: Crohn’s disease (CD) is routinely evaluated using clinical symptoms, laboratory variables, and the CD activity index (CDAI). However, clinical parameters are often nonspecific and do not precisely reflect the actual activity of CD small-intestinal lesions. The purposes of this prospective study were to compare color Doppler ultrasound (US) findings with histological findings from surgically resected specimens and confirm the hypothesis that color Doppler US can distinguish tissue inflammation and fibrosis. METHODS: Among 1764 consecutive patients who underwent color Doppler US examinations, 10 patients with CD (12 small-intestinal CD lesions) who underwent US examinations before elective small-intestine resection were evaluated in the present study. Areas of thickened intestinal walls were evaluated in terms of blood flow using color Doppler US imaging. The blood flow was semiquantitatively classified as “hyper-flow” and “hypo-flow” according to the Limberg score. Resected lesions were macroscopically and histopathologically processed. Inflammatory cell infiltration, fibrosis and vascularity were evaluated by myeloperoxidase (granulocytes), CD163 (macrophages), CD79a (B cells), CD3 (T cells), Masson’s trichrome (fibrosis), and factor VIII staining (vascular walls). All histopathological images were entered into virtual slide equipment and quantified using a quantitative microscopy integrated system (TissueMorph™). RESULTS: There were no significant differences in disease features or laboratory findings between “hypo-flow” lesions (n = 4) and “hyper-flow” lesions (n = 8). Histopathologically, “hyper-flow” lesions showed significantly greater bowel wall vascularity (factor VIII) (p = 0.047) and inflammatory cell infiltration, including CD163 macrophages (p = 0.008), CD3 T cells, and CD79a B cells (p = 0.043), than did “hypo-flow” lesions. There was no apparent association between the blood flow and CDAI. CONCLUSIONS: In this study, active CD lesions were macroscopically visible in surgical specimens of patients with increased blood flow on preoperative color Doppler US imaging. Additionally, these CD lesions exhibited significantly greater vascularity and numbers of inflammatory leukocytes microscopically. Color Doppler US may predict tissue inflammation and fibrosis in small-intenstinal CD lesions

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

Pregnancy outcome in women with inflammatory bowel disease treated with anti-tumor necrosis factor and/or thiopurine therapy: a multicenter study from Japan

Background/AimsAnti-tumor necrosis factor drugs (anti-TNF) and thiopurines are important treatment options in patients with inflammatory bowel disease (IBD), including during pregnancy. However, there are limited data on the benefit/risk profile of anti-TNF and thiopurines during pregnancy in Asia. The aim of this study was to analyze pregnancy outcomes of female Japanese IBD patients treated with anti-TNF and/or thiopurines.MethodsThis cross-sectional study assessed pregnancy outcomes in 72 women with IBD. Pregnancy outcomes were compared among 31 pregnancies without exposure to infliximab (IFX), adalimumab (ADA), or thiopurines; 24 pregnancies with exposure to anti-TNF treatment (23 IFX, 1 ADA); 7 pregnancies with exposure to thiopurines alone; and 10 pregnancies with exposure to both IFX and thiopurines.ResultsThirty-five of the 41 pregnancies (85.3%) that were exposed to anti-TNF treatment and/or thiopurines resulted in live births after a median gestational period of 38 weeks. Of the 35 live births, 3 involved premature deliveries; 7, low birth weight; and 1, a congenital abnormality. There were 6 spontaneous abortions in pregnancies that were exposed to anti-TNF treatment (17.7%). Pregnancy outcomes among the 4 groups were similar, except for the rate of spontaneous abortions (P =0.037).ConclusionsExposure to anti-TNF treatment or thiopurines during pregnancy was not related to a higher incidence of adverse pregnancy outcomes in Japanese IBD patients except for spontaneous abortion

Mice lacking a transcriptional corepressor Tob are predisposed to cancer

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 wild-type 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