Study objectives: Patients with recurrent pleural effusions secondary to malignancy are subjected to pleurodesis if clinically indicated. Pleurodesis involves the introduction of a sclerosing agent into the pleural space. Talc is one of the most commonly used sclerosing agents in treating patients with recurrent, symptomatic malignant pleural effusions. However, the mechanisms whereby talc mediates pleural fibrosis remain unclear. We hypothesized that the intrapleural instillation of talc induces the pleural mesothelial production of basic fibroblast growth factor (bFGF), which is responsible for pleural fibrosis.
Methods: Samples of pleural fluid collected from 23 patients with malignant pleural effusions and 6 patients with congestive heart failure (control group) were included in this study. A tumor grading scale (1 to 9) was used to demonstrate the extent of the tumor. In vitro pleural mesothelial cells (PMCs) were activated with talc, and the conditioned medium was collected to evaluate bFGF levels by enzyme-linked immunosorbent assay. The bFGF-induced proliferation of fibroblasts was studied by [(3)H]thymidine incorporation. The messenger RNA expression of bFGF in talc-activated PMCs was determined by Northern analysis.
Results: In this study, we demonstrated that patients who have undergone successful pleurodesis following intrapleural talc insufflation have significantly higher levels of bFGF in their pleural fluid compared to those who do not respond to pleurodesis. In addition, we found a significant negative correlation between bFGF levels and tumor size. Talc-activated PMCs produce significantly higher levels of bFGF compared to control, which correlates with bFGF messenger RNA expression in PMCs stimulated with talc. The neutralization of pleural fluids and conditioned medium from talc-stimulated PMCs with bFGF antibodies significantly inhibits the bFGF-induced proliferation of pleural fibroblasts.
Conclusions: An important outcome of this study was the finding that patients with extensive tumor involvement of the pleural mesothelium have a significantly lower pleural fluid bFGF response to talc compared to those who have limited involvement. Patients with limited pleural disease and higher bFGF responses go on to have successful pleurodesis, demonstrating that the presence of a mesothelium that is free of tumor enhances the possibility of success. In vitro PMCs stimulated with talc release biologically active bFGF.