High detection rate of adenomas in familial colorectal cancer.

BACKGROUND AND AIMS: Subjects with one first-degree relative (FDR) with colorectal cancer (CRC) <50 years old or two FDRs with CRC have an increased risk for CRC (RR 4-6). Current guidelines recommend colonoscopic surveillance of such families. However, information about the yield of surveillance is limited. The aim of the present study was to evaluate the outcome of surveillance and to identify risk factors for the development of adenomas. PATIENTS AND METHODS: Subjects were included if they fulfilled the following criteria: asymptomatic subjects aged between 45 and 65 years, with one FDR with CRC <50 years old (group A) or two FDRs with CRC diagnosed at any age (group B). Subjects with a personal history of inflammatory bowel disease or colorectal surgery were excluded. RESULTS: A total of 551 subjects (242 male) met the selection criteria. Ninety-five subjects with a previous colonoscopy were excluded. Two of 456 remaining subjects (0.4%) were found to have a colorectal tumour (one CRC and one carcinoid). Adenomas were detected in 85 (18.6%) and adenomas with advanced pathology in 37 subjects (8.1%). 30 subjects (6.6%) had multiple (>1) adenomas. Men were more often found to have an adenoma than women (24% vs 14.3%; p=0.01). Adenomas were more frequent in group B compared with group A (22.0% vs 15.6%; p=0.09). CONCLUSION: The yield of colonoscopic surveillance in familial CRC is substantially higher than the yield of screening reported for the general population.

Malabsorption syndrome in a patient of Mediterranean origin; immunoproliferative small intestinal disease.

We describe a 30-year-old woman of Turkish descent presenting with abdominal pain and signs of malabsorption. The cause of her complaints turned out to be immunoproliferative small intestinal disease which is a very uncommon disorder in our geographical region. We discuss the differential diagnosis of this disease and the therapeutical options.

CD4 antibody treatment in patients with active Crohn's disease: a phase 1 dose finding study.

BACKGROUND: T cells play an important part in Crohn's disease. Immunomodulating therapies that target T cell activation may have clinical effects in Crohn's disease. AIM: To investigate the toxicity and potential efficacy of anti-CD4 monoclonal antibody therapy in patients with Crohn's disease. PATIENTS AND METHODS: A dose escalating pilot study was conducted in three groups of four patients with intractable Crohn's disease, refractory to steroids. They received 70, 210, or 700 mg of cM-T412, a depleting anti-CD4 monoclonal antibody (mAb). RESULTS: The mean reduction in Crohn's disease activity index (CDAI) was respectively 25%, 24%, and 36% at four weeks, and 24% and 52% at 10 weeks in the 210 mg and 700 mg groups. There was only a minor effect on endoscopically evaluated disease activity. Side effects were mild to moderate fever with chills and headache. No signs of opportunistic infection were seen. There was a sustained decrease in CD4 count which lasted at least four weeks in the 70 mg group (76.3 (SD 40.6)% of the baseline value), and 10 weeks in both the 210 mg group (80.8 (SD 60.9)%) and the 700 mg group (24.8 (SD 15.4)%). The primary and secondary humoral immune response was not influenced by anti-CD4 mAb treatment. CONCLUSION: This study shows the moderate potential efficacy of treatment of patients with Crohn's disease using a depleting chimeric monoclonal anti-CD4 antibody.

Mediators of mucosal inflammation: implications for therapy.

Treatment of inflammatory bowel disease remains a challenge. The major shortcoming in the development of new therapeutic approaches is the fact that the cause of inflammatory bowel disease is still unknown. Recognition of the importance of the arachidonic acid cascade of inflammatory mediators presents the opportunity to specifically inhibit or antagonize leukotriene B4, thromboxane, platelet activating factor, or phospholipase. Interleukins and cytokines have more recently been defined as targets for specific therapy. The results of these specific immune modulating studies are not only important from a therapeutic point of view, but substantially contribute to our understanding of the pathogenic cascades in IBD. In this review, several targets for novel therapeutic intervention are discussed.

Effect of intestinal resection on serum antibodies to the mycobacterial 45/48 kilodalton doublet antigen in Crohn's disease.

Interest in the role of mycobacterial infection in Crohn's disease has been revived by the cultural detection of Mycobacterium paratuberculosis in patients with Crohn's disease. This hypothesis was examined serologically using assays with high specificity for Crohn's disease. The effect of intestinal resection on serum antibodies specific for Crohn's disease was investigated with an immunoblot assay and an enzyme linked immunosorbent assay using the 45/48 kilodalton doublet antigen of Mycobacterium tuberculosis. Antibodies were detected in 64.7% of patients with Crohn's disease (n = 17), 10% of patients with ulcerative colitis (n = 10), 5% of patients with carcinoma of the colon (n = 20), and none of 10 healthy subjects with the immunoblot assay. Statistical comparison of the Crohn's disease patients with each control group resulted in p = 0.0000236. Immunoglobulin G was essentially unchanged 75 days (mean) after surgery. After more than 180 days, however, the antibody response was reduced in all of five patients studied, and was no longer demonstrable in two of them (40%). Simultaneously, the Crohn's disease activity index (CDAI) decreased. Both the high specificity of this assay for Crohn's disease and the diminished antibody response after intestinal resection in parallel with decreased CDAI support a mycobacterial aetiology of Crohn's disease.

Anti-CD4 Therapy Decreases Epithelial Expression of HLA-DR Molecules in Patients with Crohn's Disease.

: Mucosal cells from patients with Crohn's disease regularly express HLA-class II antigens, which are thought to be induced by cytokines, in particular interferon gamma, that are secreted by activated T-cells. Abberant MHC-class II expression by epithelial cells may play a role in diseases characterized by T-cell activation. Activated CD4-positive T-cells are present in the lamina propria of patients with Crohn's disease. In this study we report the results of an open label, single center anti-CD4 ~ trial in patients with steroid refractory Crohn's disease. A rapid and near complete loss of HLA-DR expression by mucosal cells was observed in 10 out of 12 patients, following infusion of the chimeric anti-CD4 antibody M-T412. These results suggest that CD4-positive T-cells are necessary for epithelial class II expression in patients with Crohn's disease.

CD4 antibody treatment in Crohn's disease.

Immunologic changes may play a role in the pathogenesis of Crohn's disease. Whether these changes are the primary cause of the disease or secondary to the inflammatory response remains unknown. Activated T helper cells probably play a pivotal role in Crohn's disease, although no causative antigen has been identified. Possible targets for immunomodulating therapy should include neutralization of the antigens, deletion of reactive activated T cells or, less specifically, interference with the antigen-presenting process. New, humanized, monoclonal antibodies that interfere with the antigen-presenting process are now available for clinical investigation. In particular, CD4 antibody treatment seems of interest, in view of the predominant role of T cells in Crohn's disease. Finally, because tumor necrosis factor is necessary for granuloma formation, inhibition of this factor may be expected to improve disease activity in Crohn's disease.