Mechanism Of Pleural Injection Bleomycin In The Treatment Of Malignant Pleural Effusions

Objective:Malignant pleural effusion (MPE) may becaused by a pleural metastases tumor or primary malignant tumor arising from the pleural. The appearance of MPE often means that the tumor has spread, and patients have lost the chance of operation. The objective of treatment is to increase efficiency, reduce adverse reaction, improving quality of life.Small-bore drainage tube of pleural effusion, and pleural injection mediated pleurodesis have become the mainstream method for the treatment of MPE. Although bleomycin has became a widely effective drug, that specific mechanisms of that method are still need to be elucidated. In this study, we try to investigate the mechanisms of BLM through the ways of inflammatory response, fibrinolytic functionchanges, direct anti-tumor effect and immune regulationto.Methods:Since January2011to February2012,35patients of the fifth thoracic surgery wards in the fourth hospital affiliated to Hebei Medical University with MPE were recruited for the study. Patients shoud meet the following criterions:1. confirmed by pathology or cytology;2. the initial treatment of cases;3. Imaging confirmed a unilateral moderate amount pleural effusion or above;4. quality of life score(KPS)≥60,expected survival time>3month;5.without lung and pleural infection;6.signing an informed consent. Central venouscatheter was placed in the pleural to drain pleural effusion after the local anesthesia, when the flow amount was less than150ml/d or the lung was reexpansion,60mg BLM with50ml saline was injected into the pleural cavity, the catheter was closed for24hours, and was unpluged after the flow amount was less than150ml/d. The patients were given chemotherapy after72h. The efficacy was evaluated one month later 30ml pleural effusion and2ml peripheral blood before and after intrapleural BLM injection72hours would be collected. T lymphocyte subsets were measured by flow cytometry; the IL-8,PAI-1levels were detected by ELISA, the CEA,CYFRA211,NSE,CA-50levels were detected by CLIA respectively.Results:1. One month after BLM injection, our data demonstrate that:CR:11cases, PR:14cases, the rate of MPE control was71.43%. Short-term major adverse reactions are:fever, gastrointestinal reactions, chest pain. No catheter-related infection, bone marrow suppression or liver and kidney injury occured.2. No correlation was found between the effective and void group clinical factors like age, gender, weight and KPS, fever (P>0.05)3. The levels of IL-8and PAI-1after treatment were higher than those before treatment(P<0.05). In effective group, the levels of IL-8and PAI-1were all higher, in void group, the IL-8level was higher after treatment, but the PAI-1level remains stable.After the injection of BLM, the levels of PAI-1was higher in effective group than in void group.4. The levels of CEA and CY21after treatment were lower than those before treatment,and they were all lower in effective and void group (P<0.05).No changes were found in NSE and CA50between before and after treatment, and no differences were deteoted in effective and void group (P>0.05). Before treatment the levels of CEA was higher in void group than effective group, after treatment its higher in void group than effective group(P<0.05).5. The levels of CD3and CD4/CD8in pleural effusion were higher after treatment than those before treatment, and the level of CD8was lower (P<0.05), the level of CD4was stabced (P>0.05). In effective group the levels of CD3and CD4/CD8were higher after treatment than those before treatment, while the levelof CD8was lower(P<0.05) and the level of CD4was remained stabce (P>0.05). In effective group no differences of the levels of CD3,CD4,CD8, CD4/CD8were found (P>0.05). After treatment, the levels of CD4/CD8was higher in effective group than in void group (P<0.05).6. NO chanes of the levels of CD3, CD4, CD8,CD4/CD8in peripheral blood were detected before and after treatment (P>0.05). similarly the levels of CD3, CD4, CD8,CD4/CD8were also stabced between the different groups at the same time(P>0.05).Conclusions:1. Pleural injection of bleomycin is an effective and safe treatment option for MPE. Adverse reactions were mild, the ommon adverse reactions are:fever, gastrointestinal reactions and chest pain.2. There was no correlation between the treatment efficacy and clinical factors like age, gender, weight, KPS, fever in the two groups.3. The levels of IL-8increased after pleural injection of bleomycin, and the level of IL-8is higher in the effective group than void group which confirmed that the induced pleural inflammation reaction is one of the mechanisms of bleomycin treatment for MPE. the inflammatory reaction is more intense, the better treatment effect.4. The level of PAI-1in pleural effusion increased after pleural injection of bleomycin, but in the void group the level of PAI-1did not change, which confirmed that inhibition of local fibrinolysis is one of the mechanisms of bleomycin treatment for MPE.5. The levels of CEA、CY21in pleural effusion reduced after pleural injection of bleomycin, the level of CEA is higher in the void group before pleural injection of bleomycin which confirmed that direct anti-tumor effect of bleomycin is one of the mechanisms of the treatment of MPE, the level of carcinoembryonic antigen (CEA) before treatment is one methods that can predict the effects of bleomycin treatment of MPE, patients with high tumor burden often get poor efficacy. 6. The level of CD4/CD8in pleural effusion increased after treatment, but in the void group the immune parameters did not change, which confirmed that bleomycin take part in changing the immune microenvironment of pleural cavity.7. the immune parameters did not change in peripheral blood after treatment mean that bleomycin can not improve the body’s immune function.