Faculty Bibliography

BACKGROUND:Few studies have investigated the relationship between anemia, smoking, drinking and survival in esophageal squamous cell carcinoma (ESCC) with primary radiotherapy. This study had the aim of evaluating the prognostic value of anemia, smoking and drinking in patients receiving primary radiotherapy for ESCC. METHODS:A total of 79 patients who underwent radiotherapy during initial treatment for ESCC were included in this study. The 2-year overall survival (OS) and disease-free survival (DFS) were analyzed between the anemic and non-anemic groups, non-smokers and smokers, and non-drinkers and drinkers using the Kaplan-Meier method and the Cox proportional hazards model. RESULTS:There were 79 patients (10 male) of median age 63 (range 38 to 84) years. The 2-year OS and DFS were 36% and 25%, respectively, in the non-anemic group, and 17% and 13%, respectively, in the anemic group (P = 0.019 for OS; P = 0.029 for DFS) using the Kaplan-Meier method. Survival analysis using the Kaplan-Meier method showed that the 2-year OS and DFS had no statistical difference between smoking, drinking and survival. In a univariate analysis, anemia was identified as a significant prognostic factor for 2-year OS (hazard ratio (HR) = 1.897; P = 0.024) and 2-year DFS (HR = 1.776; P = 0.036), independent of tumor, lymph node, metastasis (TNM) stage. In a multivariate analysis, anemia was identified as a highly significant prognostic factor for 2-year OS (HR = 2.125; P = 0.011) and 2-year DFS (HR = 1.898; P = 0.025), independent of TNM stage and initial treatment. We found no statistical difference in the 2-year OS and DFS associated with smoking (P > 0.2) and drinking (P > 0.6) using univariate and multivariate analysis. CONCLUSIONS:Smoking and drinking were not prognostic for 2-year OS or DFS. Anemia before radiotherapy was associated with poor prognosis and an increased risk of relapse, which may serve as a new prognostic characteristic in ESCC treated with primary radiotherapy. Hemoglobin is a routine examination and anemia is therefore simple and quick to determine.

Patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) develop more rapid fibrosis than those infected with HCV only. In HIV/HCV-coinfected patients, fibrosis progression correlates with HIV RNA levels, suggesting a direct role of HIV in liver fibrogenesis. Chemokine (C-C motif) receptor 5 (CCR5) and cysteine-X-cysteine receptor 4 (CXCR4), the two major coreceptors required for HIV entry into cells, are expressed on activated hepatic stellate cells (HSCs), the principle fibrogenic cell type in the liver. We therefore examined whether HIV can infect HSCs, explored the potential mechanisms of viral entry, and assessed the impact of infection as reflected by the ability of HSCs to transfer virus to T lymphocytes and elicit a proinflammatory and profibrogenic response. We report that the laboratory-adapted viruses HIV-IIIB (CXCR4-tropic or X4) and HIV-BaL (CCR5-tropic or R5) and primary HIV isolates can infect both a human stellate cell line, LX-2, and primary human HSCs. HIV entry and gene expression in HSCs was confirmed using HIV-green fluorescent protein (GFP) expression viral constructs in the presence or absence of the reverse-transcriptase inhibitor azidothymidine. CD4 expression on a subset of primary HSCs was demonstrated using fluorescence-activated cell sorting and immunofluorescence staining. Blocking experiments in the presence of anti-CD4, anti-CXCR4, and anti-CCR5 revealed that HIV entry into HSCs is predominantly CD4/chemokine coreceptor-independent. HIV infection promoted HSC collagen I expression and secretion of the proinflammatory cytokine monocyte chemoattractant protein-1. Furthermore, infected LX-2 cells were capable of transferring GFP-expressing virus to T lymphocytes in a coculture system. Conclusion: Taken together, our results suggest a potential role of HIV in liver fibrosis/inflammation mediated through effects on HSCs. The role of early highly active antiretroviral therapy initiation in patients with HIV/HCV coinfection warrants further investigation