Predictive cytogenetic biomarkers for colorectal neoplasia in medium risk patients.

RATIONALE: DNA damage and chromosomal alterations in peripheral lymphocytes parallels DNA mutations in tumor tissues. OBJECTIVE: The aim of our study was to predict the presence of neoplastic colorectal lesions by specific biomarkers in "medium risk" individuals (age 50 to 75, with no personal or family of any colorectal neoplasia). METHODS AND RESULTS: We designed a prospective cohort observational study including patients undergoing diagnostic or opportunistic screening colonoscopy. Specific biomarkers were analyzed for each patient in peripheral lymphocytes - presence of micronuclei (MN), nucleoplasmic bridges (NPB) and the Nuclear Division Index (NDI) by the cytokinesis-blocked micronucleus assay (CBMN). Of 98 patients included, 57 were "medium risk" individuals. MN frequency and NPB presence were not significantly different in patients with neoplastic lesions compared to controls. In "medium risk" individuals, mean NDI was significantly lower for patients with any neoplastic lesions (adenomas and adenocarcinomas, AUROC 0.668, p 00.5), for patients with advanced neoplasia (advanced adenoma and adenocarcinoma, AUROC 0.636 p 0.029) as well as for patients with adenocarcinoma (AUROC 0.650, p 0.048), for each comparison with the rest of the population. For a cut-off of 1.8, in "medium risk" individuals, an NDI inferior to that value may predict any neoplastic lesion with a sensitivity of 97.7%, an advanced neoplastic lesion with a sensitivity of 97% and adenocarcinoma with a sensitivity of 94.4%. DISCUSSION: NDI score may have a role as a colorectal cancer-screening test in "medium risk" individuals. ABBREVIATIONS: DNA = deoxyribonucleic acid; CRC = colorectal cancer; EU = European Union; WHO = World Health Organization; FOBT = fecal occult blood test; CBMN = cytokinesis-blocked micronucleus assay; MN = micronuclei; NPB = nucleoplasmic bridges; NDI = Nuclear Division Index; FAP = familial adenomatous polyposis; HNPCC = hereditary non-polypoid colorectal cancer; IBD = inflammatory bowel diseases; ROC = receiver operating characteristics; AUROC = area under the receiver operating characteristics curve.

Double blind clinical trial in a series of 115 patients with seborrheic dermatitis: prevention of relapses using a topical modulator of Toll like receptor 2.

AIM: Seborrheic dermatitis is a chronic inflammatory disease aggravated by Malassezia species. Toll-like receptors (TLR) are part of innate immune system that can be activated by yeasts. Previous studies showed that an association of Umbelliferae extract with a lipid (TLR2-Regul™) decreases the IL-8 expression in human skin in contact with M. furfur. The aim of this study was to assess the activity of a topical formulated with TLR2-Regul™ in the prevention of seborrheic dermatitis (SD) relapses. METHODS: Immune-competent SD adult patients were treated for SD (topical imidazoles or steroids). Cleared patients were randomized and received a topical containing TLR2-Regul™ (A) or its vehicle (B). Erythema, scales and pruritus were assessed during two months. RESULTS: The study included 115 patients, mean age 43.4, sex ratio m/f 1.5. At week 4 the relapse rate was 26% (N.=15) in group A and 43% (N.=25) in group B. At W8 the relapse rate was 21% (N.=12) in group A and 40% (N.=23) (P=0.0309). CONCLUSION: In this series of 115 adults with seborrheic dermatitis, patients treated with a topical containing TLR-Regul™ showed a significantly less relapse rate compared with the excipient group (P<0.05). TLR modulation could represent a new therapeutic approach in the prevention of seborrheic dermatitis relapses.

Oral mucosa lesions in hypereosinophilic syndrome--an update.

Hypereosinophilic syndrome (HES) is a rare disorder characterized by persistent and marked eosinophilia. Some HES forms have a poor prognosis, either because of end-organ damage (particularly endomyocardial fibrosis), or because of associated myeloid leukemia or malignant T-cell lymphoma. Oral mucosa ulcerations can be early clinical signs in severe forms. They are discrete, round or oval, sometimes confluent ulcers or erosions, located on non-keratinized, unattached oral mucosa. In the last 15 years a better understanding of eosinophil biology has led to a new clinical classification of HES. The lymphocytic form is characterized by T-lymphocyte clonality, IL-5 production, and a possible progression to T-cell lymphoma. Oral lesions are more frequently associated with the myeloproliferative form, characterized by an increased risk of developing myeloid malignancies and a good response to a recent anti-tyrosine kinase therapy (imatinib mesylate). The target of imatinib is a novel kinase resulting from an 800-kb deletion on chromosome 4. Recently, the resulting FIP1L1-PDGFRalpha fusion gene was characterized as a marker of response to imatinib. Exclusion of other erosive ulcerative oral disease and early recognition of HES in patients with oral ulcerations, and precise characterization of the lymphocytic or myeloproliferative form are therefore important to rapidly initiate an effective therapy.