Patterns of drug resistance among patients with tuberculous pleural effusion in Greece.

SETTING: Data on the relationship between pleural tuberculosis (TB) and anti-tuberculosis drug resistance are scarce. OBJECTIVE: To determine the patterns of drug resistance among pleural Mycobacterium tuberculosis isolates in Greece and the incidence of tuberculous pleural effusion (TPE) among patients with multidrug-resistant (MDR) or extensively drug-resistant (XDR) pulmonary TB. DESIGN: Drug susceptibility testing (DST) results recorded in the database of the National Reference Centre for Tuberculosis in Athens, Greece, over a 9-year period (2003-2011) were reviewed. Chest X-rays from hospitalised patients with pulmonary MDR/XDR-TB during the same period were also reviewed for the presence of TPE. RESULTS: Resistance to at least one first-line drug was observed in 11% of the cases (MDR-TB 3%, XDR-TB 1%), while 29% of the patients with pulmonary MDR/XDR-TB presented with TPE during the course of their disease, the majority ipsilateral to the lung lesions, which responded to guided anti-tuberculosis treatment. CONCLUSION: The prevalence of drug resistance among pleural M. tuberculosis isolates in Greece highlights the importance of DST prior to treatment selection in TPE patients. In our study population, TPE that developed in one third of the patients with pulmonary MDR/XDR-TB usually resolved with DST-guided anti-tuberculosis treatment.

Secreted phosphoprotein-1 directly provokes vascular leakage to foster malignant pleural effusion.

Secreted phosphoprotein-1 (SPP1) promotes cancer cell survival and regulates tumor-associated angiogenesis and inflammation, both central to the pathogenesis of malignant pleural effusion (MPE). Here, we examined the impact of tumor- and host-derived SPP1 in MPE formation and explored the mechanisms by which the cytokine exerts its effects. We used a syngeneic murine model of lung adenocarcinoma-induced MPE. To dissect the effects of tumor- versus host-derived SPP1, we intrapleurally injected wild-type and SPP1-knockout C57/BL/6 mice with either wild-type or SPP1-deficient syngeneic lung cancer cells. We demonstrated that both tumor- and host-derived SPP1 promoted pleural fluid accumulation and tumor dissemination in a synergistic manner (P<0.001). SPP1 of host origin elicited macrophage recruitment into the cancer-affected pleural cavity and boosted tumor angiogenesis, whereas tumor-derived SPP1 curtailed cancer cell apoptosis in vivo. Moreover, the cytokine directly promoted vascular hyper-permeability independently of vascular endothelial growth factor. In addition, SPP1 of tumor and host origin differentially affected the expression of proinflammatory and angiogenic mediators in the tumor microenvironment. These results suggest that SPP1 of tumor and host origin impact distinct aspects of MPE pathobiology to synergistically promote pleural fluid formation and pleural tumor progression. SPP1 may present an attractive target of therapeutic interventions for patients with MPE.

Combined expression of p53, Bcl-2, and p21WAF-1 proteins in lung cancer and premalignant lesions: association with clinical characteristics.

We examined p53, p21WAF-1, and Bcl-2 protein expression in malignant and nonmalignant bronchial specimens obtained during bronchoscopy from 60 lung cancer patients. Twenty-six (43.3%), 36 (60%), and 20 (33.3%) of the tumors were p53, p21WAF-1, and Bcl-2 positive, respectively. High-level p53 and Bcl-2 expression characterized advanced preneoplastic lesions, while hyperplasias, squamous metaplasias, and mild dysplasias exhibited low levels of expression. There was no difference between early and advanced preneoplastic lesions in the level of p21WAF-1, expression. A history of heavy smoking was associated with p21WAF-1, expression in preneoplastic lesions (p = 0.022) and tumors (p = 0.032). p53(-)/p21WAF-1(++)/bcl-2(-) was the only significant independent predictor of lower clinical stage (OR: 0.88, p = 0.038). In univariate analysis, survival of NSCLC patients was affected by disease stage (p <0.001) and tumor histology (p = 0.018). While single-protein expression was not associated with prognosis, the combined immunophenotype p53(-)/p21WAF-1(++)/bcl-2(-) predicted longer survival (p = 0.03). In multivariate analysis, only the TNM stage was found to be a prognostic factor for NSCLC. We conclude that p53 and Bcl-2 alterations may happen early in bronchial carcinogenesis and that absence of these alterations in combination with p21WAF-1, overexpression may be associated with a less aggressive tumor behavior.