Predicting significant fibrosis in hepatitis C patients in Luxembourg using serological markers.

OBJECTIVE: The aim of our study was to assess the diagnostic performance of various serological markers and scores for predicting significant fibrosis retrospectively in a population of patients referring to our hospital for liver biopsy and chronic hepatitis C. MATERIALS AND METHODS: Stored serum obtained from 186 patients were tested for a number of biological markers putatively associated with liver fibrosis. Fibrotest and Forns scores were compared with liver fibrosis pathology scored according to the METAVIR system by multiple logistic regression. RESULTS: The prevalence of significant fibrosis was 44%. Aspartate amino transferase (AST) and gamma-glutamyltransferase (GGT) were most correlated with METAVIR staging, followed by platelet counts and alpha2-macroglobulin. The negative predictive value was 77% and 83% and the positive predictive value was 100% and 84% for the Forns score and the Fibrotest, respectively. In multivariate analysis AST, GGT and alpha2-macroglobulin had independent predictive power. CONCLUSIONS: The accuracy of serological markers in predicting significant fibrosis is limited, because approximately two thirds of patients lie into an indeterminate "grey zone". Serological markers might be useful for patients reluctant to undergo liver biopsy but current predictive scoring systems are too inaccurate to replace biopsies in a routine manner.

Atypical glandular cells in conventional cervical smears: incidence and follow-up.

BACKGROUND: Atypical glandular cells on cervical smears are often associated with clinically significant uterine lesions. The frequency and accuracy of AGC-NOS (i.e. atypical glandular cells, not otherwise specified) diagnoses, regardless of the gland cell type or the degree of suspicion, and their outcome were investigated. METHODS: From January 1, 1990 to December 31, 1999 a total of 261 patients had an AGC-NOS diagnosis made by conventional cervical Papanicolaou smear interpretation representing 0.05% of all Pap-smears analyzed at the national level. 191 (73.2%) patients had a subsequent histological examination, 8 samples were not representative by origin and were excluded. RESULTS: Out of 183 AGC-NOS diagnosed, 56.3% (103/183) were associated with tissue-proven precancerous and/or cancerous lesions, 44% being of endocervical and 56% of endometrial origin. 75% of all AGC-patients were asymptomatic. 66.7% (6/9) of the patients with subsequent invasive endocervical adenocarcinoma (AC) and 56% (28/50) of those patients with invasive endometrial AC were without clinical symptoms. 3 patients out of 9 with an invasive endocervical AC were 35 years of age or less. 10.1% and 12.3% of all 'new' tissue-proven invasive endocervical or endometrial AC respectively recorded by the national Morphologic Tumour Registry (MTR) were first identified by a cytological AGC-NOS diagnosis. CONCLUSION: Our findings emphasize the importance of the cytological AGC-category even in the absence of a precise origin or cell type specification. 56% of the AGC-diagnoses being associated with significant cancerous or precancerous conditions, a complete and careful evaluation is required.

Bronchial airway gene expression in smokers with lung or head and neck cancer.

Cigarette smoking is the major cause of cancers of the respiratory tract, including non-small cell lung cancer (NSCLC) and head and neck cancer (HNC). In order to better understand carcinogenesis of the lung and upper airways, we have compared the gene expression profiles of tumor-distant, histologically normal bronchial biopsy specimens obtained from current smokers with NSCLC or HNC (SC, considered as a single group), as well as nonsmokers (NS) and smokers without cancer (SNC). RNA from a total of 97 biopsies was used for gene expression profiling (Affymetrix HG-U133 Plus 2.0 array). Differentially expressed genes were used to compare NS, SNC, and SC, and functional analysis was carried out using Ingenuity Pathway Analysis (IPA). Smoking-related cancer of the respiratory tract was found to affect the expression of genes encoding xenobiotic biotransformation proteins, as well as proteins associated with crucial inflammation/immunity pathways and other processes that protect the airway from the chemicals in cigarette smoke or contribute to carcinogenesis. Finally, we used the prediction analysis for microarray (PAM) method to identify gene signatures of cigarette smoking and cancer, and uncovered a 15-gene signature that distinguished between SNC and SC with an accuracy of 83%. Thus, gene profiling of histologically normal bronchial biopsy specimens provided insight into cigarette-induced carcinogenesis of the respiratory tract and gene signatures of cancer in smokers.