Objective: To evaluate the effect of repeated thoracenteses on the fluid characteristics and the levels of various cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-5, IL-6, and IL-8, and of plasminogen activator inhibitor type 1 (PAI-1) and tissue type plasminogen activator in malignant pleural effusion and its clinical significance. Design: A prospective study. Patients and methods: Twenty-six patients with symptomatic and a large amount of free-flow malignant pleural effusions were studied. Thoracentesis with drainage of 500 mL of pleural fluid per day was performed for 3 continuous days (days 1 to 3). The effusion samples were collected to evaluate the changes of fluid characteristics, cytokine levels, and fibrinolytic activity. Chest ultrasonography was done on day 6 to observe the presence of fibrin strands. The result of pleurodesis was evaluated in the patients classified into groups based on chest ultrasonographic findings. Results: The values of TNF-α, PAI-1, IL-8, and neutrophil count in pleural fluid increased significantly during repeated thoracenteses in 26 patients studied. A positive correlation was found between the concentrations of TNF-α and PAI-1 and between the values of IL-8 and neutrophils. On day 6, fibrin strands were observed in the pleural effusion on chest ultrasonography in 11 patients (42%, fibrinous group) but were absent in the remaining 15 patients (nonfibrinous group). During repeated thoracenteses, a significant increase of effusion PAI-1 and TNF-α was observed in the fibrinous group but not in the nonfibrinous group. In addition, the levels of effusion PAI-1 and TNF-α obtained from day 2 and day 3 were significantly higher in the fibrinous group than in the nonfibrinous group. The success rate of pleurodesis was significantly higher in the fibrinous group (11 of 11 patients, 100%) than in the nonfibrinous group (8 of 12 patients, 67%). Conclusions: Repeated thoracenteses may cause pleural inflammation and induce local release of proinflammatory cytokine as TNF-α, which may subsequently enhance the release of PAI-1 and lead to fibrin formation in malignant effusion. The presence of fibrin strands after repeated thoracenteses may be of considerable value in predicting the success of subsequent pleurodesis in patients with malignant pleural effusions.
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