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Background: Nonanastomotic biliary strictures (NAS) are a serious complication after orthotopic liver transplantation (OLT). Matrix metalloproteinases (MMPs) are involved in connective tissue remodelling in chronic liver disease and complications after OLT. Aim: To evaluate the relationship between MMP-2 and MMP-9 gene polymorphisms and NAS. Methods: MMP-2 (-1306 C/T) and MMP-9 (-1562 C/T) gene promoter polymorphisms were analysed in 314 recipient-donor combinations. Serum levels of these MMPs were determined in subgroups of patients as well. NAS were identified with various radiological imaging studies performed within 4 years after OLT and defined as any stricture, dilation or irregularity of the intra-or extrahepatic bile ducts of the liver graft followed by an intervention, after exclusion of hepatic artery thrombosis and anastomotic strictures. Results: The average incidence of NAS was 15%. The major clinical risk factor for the development of NAS was PSC in the recipient. The presence of the MMP-2 CT genotype in donor and/or recipient was associated with a significantly higher incidence of NAS, up to 29% when both donor and recipient had the MMP-2 CT genotype (P = 0.003). In the multivariate analyses, pre-OLT PSC (hazard ratio 2.1, P = 0.02) and MMP-2 CT genotype (hazard ratio 3.5, P = 0.003) were found to be independent risk factors for the development of NAS after OLT. No obvious association was found between NAS and the MMP-9 genotype and serum levels of the MMPs. Conclusion: MMP-2 CT genotype of donor and recipient is an independent risk factor, in addition to PSC, for the development of NAS after OLT.

Transforming growth factor-β1 (TGF-β1), a cytokine involved in various stages of cancer, is produced as a latent complex and requires processing to become active. We have determined total and active TGF-β1 levels in homogenates of colorectal neoplasia. In contrast to total TGF-β levels, showing a stepwise increase in the mucosa-adenoma-carcinoma sequence, active TGF-β1 levels are increased only in carcinomas but not in premalignant adenomas. Furthermore, solely active TGF-β1 levels are associated with the stage of the carcinomas and worse patient prognosis. Active TGF-β1 levels correlated significantly with plasminogen activator inhibitor (PAI)-1, α-smooth muscle actin (SMA) and several matrix-remodeling proteinases. Interestingly, SMA levels are also significantly increased in colorectal carcinomas but not in adenomas, suggesting that despite the enhanced total TGF-β1 levels, myofibroblast accumulation is not (yet) occurring in these premalignant neoplasias. The correlation between active TGF-β1 and SMA expression in tumors indicates that tumor-promoting myofibroblasts might arise as a result of increased TGF-β1 activation. These data underline the significance of the interaction between malignant cells and (myo)-fibroblasts in the tumor microenvironment, modulating the biologic behavior of colorectal cancer. © 2009 Japanese Cancer Association.

Background Fish oil supplements, which are rich in n-3 fatty acids, may reduce inflammation, decrease the need for anti-inflammatory drugs, and promote normal weight gain in people with ulcerative colitis. Objectives This review evaluates the efficacy of fish oil for induction of remission in ulcerative colitis using all available randomised controlled trials. Search methods The Cochrane Central Register of Controlled Trials (CENTRAL), PUBMED, EMBASE, CINAHL, the database of ongoing trials and the reference lists of all publications of included or excluded trials were searched. Selection criteria Randomised controlled trials and quasi-randomised controlled trials with active ulcerative colitis patients who were treated with fish oil. Data collection and analysis The reviewers performed study selection, assessment of methodological quality by using different approaches: including Cochrane assessment of allocation concealment and Jadad quality assessment score. Data extraction forms were used by the two reviewers to extract the data independently. Authors were contacted for additional information. Main results Six studies were included. Three were of cross-over design and three were of parallel design. No data were pooled for analysis due to differences in outcomes and methodology among the included studies. One small study shows a positive benefit for induction of remission (RR 19.00; 95% CI 1.27 to 284.24). Some of the other included studies show some positive benefits for secondary outcomes. However, these results need to be interpreted with caution due to small study size and poor study quality. Authors' conclusions The current data does not allow for a definitive conclusion regarding the efficacy of fish oil. There is no adequate information to make recommendations for clinical practice. More research is required.