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Objectives: To estimate total direct health care costs associated to diagnosis and treatment of women with breast cancer in Italy, and to investigate their distribution by service type according to the disease pathway and patient characteristics., Methods: Data on patients provided by population-based Cancer Registries are linked at individual level with data on health-care services and corresponding claims from administrative databases. A combination of cross-sectional approach and a threephase of care decomposition model with initial, continuing and final phases-of-care defined according to time occurred since diagnosis and disease outcome is adopted. Direct estimation of cancer-related costs is obtained., Results: Study cohort included 49,272 patients, 15.2% were in the initial phase absorbing 42% of resources, 79.7% in the continuing phase absorbing 44% of resources and 5.1% in the final phase absorbing 14% of resources. Hospitalization was the most important cost driver, accounting for over 55% of the total costs., Conclusions: This paper represents the first attempt in Italy to estimate the economic burden of cancer at population level taking into account the entire disease pathway and using multiple current health care databases. The evidence produced by the study can be used to better plan resources allocation. The model proposed is replicable to countries with individual health care information on services and claims.

Objective: To evaluate the frequency of neoadjuvant therapy (NT) in women with stage I-III breast cancer in Italy and whether it is influenced by biological characteristics, screening history, and geographic area., Methods: Data from the High Resolution Study conducted in 7 Italian cancer registries were used; they are a representative sample of incident cancers in the study period (2009-2013). Included were 3546 women aged <85 years (groups <50, 50-69, 70-64, and 75+) with stage I-III breast cancer at diagnosis who underwent surgery. Women were classified as receiving NT if they received chemotherapy, target therapy, and/or hormone therapy before the first surgical treatment. Logistic models were built to test the association with biological and contextual variables., Results: Only 8.2% of women (290 cases) underwent NT; the treatment decreases with increasing age (14.5% in age <50 and 2.2% in age 75+), is more frequent in women with negative receptors (14.8%), HER2-positive (15.7%), and triple-negative (15.6%). The multivariable analysis showed the probability of receiving NT is higher in stage III (odds ratio [OR] 3.83; 95% confidence interval [CI] 2.83-5.18), luminal B (OR 1.87; 95% CI 1.27-2.76), triple-negatives (OR 1.88; 95% CI 1.15-3.08), and in symptomatic cancers (OR 1.98; 95% CI 1.13-3.48). Use of NT varied among geographic areas: Reggio Emilia had the highest rates (OR 2.29; 95% CI 1.37-3.82) while Palermo had the lowest (OR 0.41; 95% CI 0.24-0.68)., Conclusions: The use of NT in Italy is limited and variable. There are no signs of greater use in hospitals with more advanced care.

Virus cell-to-cell spread has been reported for many different viruses and may contribute to pathogenesis of viral disease. The role played by cell-to-cell contact in hepatitis C virus (HCV) transmission was studied in vitro by cell co-cultivation experiments. A human lymphoblastoid B-cell line, infected persistently with HCV in vitro (TO.FE(HCV)), was used as HCV donor [Serafino et al., 2003]; recipient cells were the human hepatoma HepG2 cell line. Both cell types were co-cultured for 48 hr to allow the cell-to-cell contacts. The hepatoma HepG2 cells are not permissive to free-virus infection, but they were infected successfully using TO.FE(HCV) cells as source of virus. The kinetics of viral RNA synthesis and the percentage of infected cells were compared in cell-mediated-and cell-free-viral infection. After co-cultivation, a consistent proportion of hepatoma cells replicated HCV and stably expressed viral antigens. Virus produced was infectious as demonstrated by the ability to reinfect fresh B-cells. This cell model shows that permissiveness to HCV infection can be achieved in vitro in non-permissive hepatoma cells by direct cell-to-cell contacts with infected human B-cells. This mechanism of virus spread may also play a pathogenic role in vivo., (Copyright 2005 Wiley-Liss, Inc.)

It has been suggested that an atypical course of primary infection by EBV and the reactivation of EBV infection in transplanted patients may induce hepatitis. We explored the possibility to dissect the infectious activity from the ability to promote B lymphocyte proliferation in vivo by injecting in nu/nu mice a low number (2 x 10(6)-0.05 x 10(6)) of cells from CE a normal human bone marrow-derived B cell line. This line carries an endogenous EBV in episomal and linear forms. Twenty nu/nu mice were inoculated subcutaneously with the B cell line CE and a matched group with the cell line RAG obtained by EBV in vitro infection of normal human peripheral blood. The mice injected with the CE line did not develop a lymphoproliferative disease, but 5 of them displayed typical histopathological lesions of chronic hepatitis without involvement of other organs. Similar results were obtained in 2 out of 20 animals in the RAG group. A close association between liver lesions and a previous EBV infection, by putative circulating B lymphoblastoid cells releasing their EBV, was established by PCR and by in situ hybridization with BamHI "W" DNA probe. This latter probe detected the presence of about 15% of positive cells only in affected livers. In addition, the rare detection in some hepatocytes of "A" type Cowdry bodies would suggest the occurrence of continuous EBV replication although at a very low level. These data show that we succeeded in dissecting the infectious from the proliferative activity of the endogenous EBV carrier CE cell line. This provides in addition a promising model for chronic EBV-associated hepatitis., (Copyright 2002 Wiley-Liss, Inc.)