Ventilator-induced Lung Injury Promotes Inflammation within the Pleural Cavity.

Mechanical ventilation contributes to the morbidity and mortality of patients in intensive care, likely through the exacerbation and dissemination of inflammation. Despite the proximity of the pleural cavity to the lungs and exposure to physical forces, little attention has been paid to its potential as an inflammatory source during ventilation. Here, we investigate the pleural cavity as a novel site of inflammation during ventilator-induced lung injury. Mice were subjected to low or high tidal volume ventilation strategies for up to 3 hours. Ventilation with a high tidal volume significantly increased cytokine and total protein levels in BAL and pleural lavage fluid. In contrast, acid aspiration, explored as an alternative model of injury, only promoted intraalveolar inflammation, with no effect on the pleural space. Resident pleural macrophages demonstrated enhanced activation after injurious ventilation, including upregulated ICAM-1 and IL-1ß expression, and the release of extracellular vesicles. In vivo ventilation and in vitro stretch of pleural mesothelial cells promoted ATP secretion, whereas purinergic receptor inhibition substantially attenuated extracellular vesicles and cytokine levels in the pleural space. Finally, labeled protein rapidly translocated from the pleural cavity into the circulation during high tidal volume ventilation, to a significantly greater extent than that of protein translocation from the alveolar space. Overall, we conclude that injurious ventilation induces pleural cavity inflammation mediated through purinergic pathway signaling and likely enhances the dissemination of mediators into the vasculature. This previously unidentified consequence of mechanical ventilation potentially implicates the pleural space as a focus of research and novel avenue for intervention in critical care.

Liposarcoma of the pleural cavity.

Liposarcoma rarely occurs in the pleura or thoracic cavity, and few reports appear in the literature. We hypothesized that combining clinicopathologic, immunohistochemical, and fluorescence in situ hybridization methods would allow definite diagnoses. Using formalin-fixed, paraffin-embedded blocks, we examined 6 atypical lipomatous tumor/well-differentiated liposarcomas (ALT/WDLPS), 5 dedifferentiated liposarcomas (DDLPSs), 2 pleomorphic liposarcomas, and 1 myxoid liposarcoma (MLPS). We used the Kaplan-Meier method and the Wilcoxon test for survival analysis for prognostic factor evaluation. Histologically, ALT/WDLPS was composed of a relatively mature adipocytic proliferation, accompanied by some lipoblasts. DDLPS exhibited round-to-oval tumor cells with a high nucleus-to-cytoplasm ratio that had proliferated in nests, accompanied in case 10 by some giant cells but no fatty cells. The pleomorphic type contained a varying proportion of pleomorphic lipoblasts. MLPS displayed uniform round- to oval-shaped cells and small signet-ring lipoblasts in a myxoid stroma. Immunohistochemically, 11 (79%), 11 (79%), and 10 (71%) of 14 cases were positive for S-100, p16, and CDK4, respectively. Six of the 14 cases (43%) were positive for MDM2 and adipophilin. One case of ALT/WDLPS and 3 cases of DDLPS exhibited MDM2 amplification by fluorescence in situ hybridization (Vysis LSI MDM2 SpectrumGreen Probe plus Vysis CEP 12 SpectrumOrange probe). ALT/WDLPS was the most favorable type for survival, while adipophilin tended to be a negative prognostic factor for pleural liposarcoma. For a firm diagnosis of liposarcoma in the pleura, immunohistochemistry for CDK4, MDM2, and adipophilin together with MDM2 gene amplification by fluorescence in situ hybridization may be an important diagnostic tool.

Cytokine/Chemokine/Growth Factor Levels in Malignant Pleural Effusion of Non-small Cell Lung Cancer.

OBJECTIVE: Malignant pleural effusions (MPEs) deteriorate the quality of life in patients with advanced stages of cancer. Although vascular endothelial growth factor (VEGF) is known to be a key factor for MPE formation, it is not fully clarified whether there are other components related to its appearance. METHODS: Pleural effusion and serum samples were collected from patients with MPEs of non-small cell lung cancer. Cellular analysis of pleural effusion was performed using fluorescence flow cytometry. The concentrations of 12 cytokines, chemokines, and growth factors in MPEs and serum samples were analyzed using the cytometric bead array method. RESULTS: Fifteen patients (median age: 70 years, 11 males) with non-small cell lung cancer (13 adenocarcinoma, 2 squamous cell carcinoma) were enrolled in this study. Concentrations of VEGF, interleukin (IL)-5, IL-6, IL-8, IL-12/IL-23p40, and C-C motif chemokine ligand (CCL) 2 were significantly higher in MPE than in serum. Pleural IL-5 levels correlated with malignant cell numbers in MPE. There was no factor related to the total amount of drained effusion or period of chest tube insertion. CONCLUSIONS: Production of six molecules were increased in the pleural cavity with MPE of non-small cell lung cancer. Complex interactions among these molecules may regulate MPE formation.

Auxiliary diagnostic value of tumor biomarkers in pleural fluid for lung cancer-associated malignant pleural effusion.

BACKGROUND: Pleural effusion (PE) can be divided into benign pleural effusion (BPE) and malignant pleural effusion (MPE). There is no consensus on the identification of lung cancer-associated MPE using the optimal cut-off levels from five common tumor biomarkers (CEA, CYFRA 21-1, CA125, SCC-Ag, and NSE). Therefore, we aimed to find indicators for the auxiliary diagnosis of lung cancer-associated MPE by analyzing and then validating the optimal threshold levels of these biomarkers in pleural fluid (PF) and serum, as well as the PF/serum ratio. PATIENTS AND METHOD: The study has two sets of patients, i.e. the training set and the test set. In the training set, 348 patients with PE, between January 1, 2016 and December 31, 2017, were divided into BPE and MPE based on the cytological diagnosis. Subsequently, the optimal cut-off levels of tumor biomarkers were analyzed. In the test set, the diagnostic compliance rate was verified with 271 patients with PE from January 1, 2018 to July 31, 2019 to evaluate the auxiliary diagnostic value of the aforementioned indicators. RESULT: In the training set, PF CEA at the cut-off value of 5.23 ng/ml was the most effective indicator for MPE compared with other tumor biomarkers (all p < 0.001). In the test set, PF CEA at the cut-off value of 5.23 ng/ml showed the highest sensitivity, specificity and accuracy, positive and negative predictive value among other tumor biomarkers, which were 99.0%, 69.1%, 91.6%, 90.7%, and 95.9%, respectively. CONCLUSION: PF CEA at the cut-off level of 5.23 ng/ml was the most effective indicator for identifying lung cancer-associated MPE among the five common tumor biomarkers.

Cyclic AMP Regulates Key Features of Macrophages via PKA: Recruitment, Reprogramming and Efferocytosis.

Macrophages are central to inflammation resolution, an active process aimed at restoring tissue homeostasis following an inflammatory response. Here, the effects of db-cAMP on macrophage phenotype and function were investigated. Injection of db-cAMP into the pleural cavity of mice induced monocytes recruitment in a manner dependent on PKA and CCR2/CCL2 pathways. Furthermore, db-cAMP promoted reprogramming of bone-marrow-derived macrophages to a M2 phenotype as seen by increased Arg-1/CD206/Ym-1 expression and IL-10 levels (M2 markers). Db-cAMP also showed a synergistic effect with IL-4 in inducing STAT-3 phosphorylation and Arg-1 expression. Importantly, db-cAMP prevented IFN-γ/LPS-induced macrophage polarization to M1-like as shown by increased Arg-1 associated to lower levels of M1 cytokines (TNF-α/IL-6) and p-STAT1. In vivo, db-cAMP reduced the number of M1 macrophages induced by LPS injection without changes in M2 and Mres numbers. Moreover, db-cAMP enhanced efferocytosis of apoptotic neutrophils in a PKA-dependent manner and increased the expression of Annexin A1 and CD36, two molecules associated with efferocytosis. Finally, inhibition of endogenous PKA during LPS-induced pleurisy impaired the physiological resolution of inflammation. Taken together, the results suggest that cAMP is involved in the major functions of macrophages, such as nonphlogistic recruitment, reprogramming and efferocytosis, all key processes for inflammation resolution.

A Predictive Model for the Identification of Cardiac Effusions Misclassified by Light's Criteria.

OBJECTIVES: The application of Light's criteria misidentifies approximately 30% of transudates as exudates, particularly in patients on diuretics with cardiac effusions. The purpose of this study was to establish a predictive model to effectively identify cardiac effusions misclassified by Light's criteria. METHODS: We retrospectively studied 675 consecutive patients with pleural effusion diagnosed by Light's criteria as exudates, of which 43 were heart failure patients. A multivariate logistic model was developed to predict cardiac effusions. The performance of the predictive model was assessed by receiver operating characteristic (ROC) curves, as well as by examining the calibration. RESULTS: It was found that protein gradient of >23 g/L, pleural fluid lactate dehydrogenase (PF-LDH) levels, ratio of pleural fluid LDH to serum LDH level (P/S LDH), pleural fluid adenosine deaminase (PF-ADA) levels, and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) levels had a significant impact on the identification of cardiac effusions, and those were simultaneously analyzed by multivariate regression analysis. The area under the curve (AUC) value of the model was 0.953. The model also had higher discriminatory properties than protein gradients (AUC, 0.760) and NT-pro-BNP (AUC, 0.906), all at a P value of <.01. CONCLUSION: In cases of suspected cardiac effusion, or where clinicians cannot identify the cause of an exudative effusion, this model may assist in the correct identification of exudative effusions as cardiac effusions.

Prolonged retention of liposomes in the pleural cavity of normal mice and high tumor distribution in mice with malignant pleural effusion, after intrapleural injection.

Background: Intrapleural administration of compounds is a lung targeted, innovative therapeutic strategy for mesothelioma, which can be refined as a route for drug delivery that minimizes the potential for systemic toxicity. However, little is currently known about the retention of liposomal drugs at the site, after such topical administration. Purpose: To evaluate the retention of liposomes in lungs following intrapleural injection, and how this might be modulated by liposome properties and disease progression. Methods: DiR-incorporating liposomes with various lipid compositions and sizes were prepared, characterized (for size distribution and zeta potential) and injected intrapleurally in normal mice and mice with malignant pleural effusion (MPE). DiR retention in pleural cavity was followed by biofluorescence imaging. Results: Experimental results demonstrate that liposome size and PEG-coating, have a significant effect on residence time in the pleural cavity; negative surface charge does not. More than 20% liposomal-DiR is retained 24 d post-injection (in some cases), indicating the high potential towards localized diseases. Ex-vivo liposomal-DiR signal in tumors of MPE mice was similar to signal in liver, suggesting high tumor targeting potential of intrapleurally injected liposomes. Finally, no difference was noticed in liposomal-DiR retention between tumor-inoculated (MPE) and healthy mice, indicating the stability of liposomes in the presence of effusion (in MPE mice). Conclusion: The current study provides novel insights for using liposomes by intrapleural administration for the treatment of lung diseases.

A novel diagnostic method for distinguishing parapneumonic effusion and empyema from other diseases by using the pleural lactate dehydrogenase to adenosine deaminase ratio and carcinoembryonic antigen levels.

Pleural effusions are a common medical problem not only for pulmonologists but also for general physicians, often needing thoracentesis for a definite diagnosis. However, thoracentesis cannot always reveal malignant cells or microbiological evidence.In this context, we prospectively enrolled a total of 289 patients with pleural effusions due to diverse etiologies: parapneumonic effusion (PPE) (63), empyema (22), tuberculous pleural effusion (TBPE) (54), malignant pleural effusion (MPE) (140), or chronic renal failure (CRF)/congestive heart failure (CHF) (10). The MPE group consisted of lung cancer (adenocarcinoma, n = 90; squamous cell carcinoma, n = 5; small cell carcinoma, n = 4), malignant lymphoma (n = 17), malignant mesothelioma (n = 11), malignant melanoma (n = 3), and metastasis from other organs (n = 10).This study demonstrated that the pleural lactate dehydrogenase (LDH)to adenosine deaminase (ADA) ratios differed significantly between patients with CHF/CRF, MPE, TBPE, empyema, and PPE. We discovered a simple method to differentiate pleural diseases based on the pleural LDH to ADA ratio and carcinoembryonic antigen (CEA). A pleural LDH to ADA ratio greater than 15.5 and a pleural CEA level of less than 5 ng/mL is indicative of PPE or empyema rather than TBPE, MPE, or transudative pleural effusion (CRF, CHF).This method has a sensitivity of 62.0%, a specificity of 91.0%, and an area under the receiver operating characteristic curve of 0.765 (95% confidence interval [CI]: 0678-0.852, P < .001), odds ratio of 16.6 (95% CI: 7.28-37.8, P < .001), a positive likelihood ratio (LR) of 6.8, and a negative LR of 0.02.

Pulmonary extranodal marginal zone lymphoma that presented with macroglobulinemia and marked plasmacytic cell proliferation carrying the t(14;18)(q32;q21)/MALT1-immunoglobulin heavy-chain fusion gene in pleural fluid.

An 80-year-old man presented with the accumulation of pleural fluid in the right thoracic cavity. Serum electrophoresis revealed an M-component and immunofixation confirmed IgM/λ. The level of IgM was 1,526 mg/dL. Imaging studies showed an infiltrative condition of the ipsilateral lung parenchyma. The fluid contained abundant neoplastic cells with the morphological and immunophenotypic features of plasma cells, which expressed IgM/λ monoclonal immunoglobulins on the cell surface and in the cytoplasm. The karyotype was 48,XY,+3,add(9)(p13),+12,add(14)(q32),del(16)(q22),-18,+mar, and a series of fluorescence in situ hybridization studies demonstrated that the add(14) chromosome represented der(14)t(14;18)(q32;q21), at which the MALT1-immunoglobulin heavy-chain (IGH) fusion gene was localized. A long-distance polymerase chain reaction amplified the fragment encompassing the two genes, showing that the junction occurred at the J6 segment of IGH and 3.7-kb upstream of the MALT1 breakpoint cluster. We propose that this case represents an extreme form of the plasmacytic differentiation of extranodal marginal zone lymphoma that developed in the lung.

Pleural cavity cytokine release syndrome in CD19-directed chimeric antigen receptor-modified T cell therapy: A case report.

RATIONALE: Cytokine release syndrome (CRS) is a common and potentially fatal complication of CAR-T cell therapy. However, compartment CRS is relatively rare in hematological malignancies, as well as in solid tumors. The pathogenesis and prognosis of compartment CRS are unclear and there is no standardized treatment yet. In this case report, we will introduce a patient developing pleural cavity CRS after CART19s infusion. PATIENT CONCERNS: A 28-year-old woman was admitted for evaluation of mediastinal mass. Her relevant examinations were comoleted. DIAGNOSES: She was diagnosed as diffuse large B cell lymphoma (DLBCL, non-GCB type). INTERVENTIONS: She received chemotherapies including 1 cycle of R-DAEPORCH, 1 cycle of R-CHOPE, 2 cycles of R-CHOP, and 4 cycles of R-GDP during the disease course. OUTCOMES: The cytokine levels of hydrothorax were considerably high when serum cytokines were within normal range, with IL-6 at 1212.45 versus 5.69 pg/mL. qPCR analysis for CAR constructs showed 1,119,696 copies/µg DNA in hydrothorax and 522,227 copies/µg DNA in blood. LESSONS: The results indicated that CART19 cells trafficked to the pleural cavity and interacted with the CD19-positive lymphoma cells directly, causing cytokine release in situ.

Anti-inflammatory Evaluation and Toxicological Analysis of Campomanesia xanthocarpa Berg.

Campomanesia xanthocarpa (Myrtaceae) is used in Brazilian traditional medicine against fever, diabetes, hypercholesteremic, obesity, and urinary diseases. In the present study, the compounds 2',6'-dihydroxy-3'-methyl-4'-metoxychalcone and 2',4'-dihydroxy-3',5'-dimethyl-6'-methoxychalcone were identified for the first time in leaves of the C. xanthocarpa. These compounds and the hydroethanolic extract (HECX) significantly inhibited paw edema and reduced both leukocyte migration and the leakage of protein into the pleural cavity. No toxicity was detected by HECX in an acute toxicity test.

Contraste radiológico oral en la cavidad pleural / Oral radiological contrast in the pleural cavity

No disponible

In Vivo Models to Study Chemokine Biology.

Chemokines are essential mediators of leukocyte movement in vivo. In vitro assays of leukocyte migration cannot mimic the complex interactions with other cell types and matrix needed for cells to extravasate and migrate into tissues. Therefore, in vivo strategies to study the effects and potential relevance of chemokines for the migration of particular leukocyte subsets are necessary. Here, we describe methods to study the effects and endogenous role of chemokine in mice. Advantages and pitfalls of particular models are discussed and we focus on description in model's joint and pleural cavity inflammation and the effects and relevance of CXCR2 and CCR2 ligands on cell migration.

Diagnostic accuracy of epithelial membrane antigen for malignant effusions: a meta-analysis.

BACKGROUND AND OBJECTIVES: Body cavity fluid examination sometimes presents a diagnostic challenge in cytology practice. This meta-analysis was undertaken to comprehensively assess the diagnostic potential of epithelial membrane antigen (EMA) in malignant effusions. MATERIALS AND METHODS: All relevant original articles about EMA in the diagnosis of malignant effusions published up to July 1, 2014 were retrieved. The overall sensitivity, specificity, positive and negative likelihood ratio, diagnostic odds ratio, and summary receiver operating characteristic (SROC) curve were pooled to evaluate the diagnostic value of EMA for malignant effusions using the Meta-Disc 1.4 and STATA 12.0 statistical software. RESULTS: Eleven studies met the inclusion criteria for the meta-analysis and the summary estimates for EMA in the diagnosis of malignant effusions were as follows: sensitivity 0.9 (95% CI 0.83-0.87), specificity 0.87 (95% CI 0.96-0.99), positive likelihood ratio 5.8 (95% CI 15.59-36.37), negative likelihood ratio 0.15 (95% CI 0.07-0.20) and diagnostic odds ratio 52.63 (95% CI 20.91-132.49). The SROC curve indicated that the maximum joint sensitivity and specificity (Q-value) was 0.88; the area under the curve was 0.94. CONCLUSION: The present meta-analysis indicated that EMA may be a useful diagnostic tool with good sensitivity and specificity for differentiating malignant effusions from benign effusions.

Assessment of asbestos body formation by high resolution FEG-SEM after exposure of Sprague-Dawley rats to chrysotile, crocidolite, or erionite.

This work presents a comparative FEG-SEM study of the morphological and chemical characteristics of both asbestos bodies and fibres found in the tissues of Sprague-Dawley rats subjected to intraperitoneal or intrapleural injection of UICC chrysotile, UICC crocidolite and erionite from Jersey, Nevada (USA), with monitoring up to 3 years after exposure. Due to unequal dosing based on number of fibres per mass for chrysotile with respect to crocidolite and erionite, excessive fibre burden and fibre aggregation during injection that especially for chrysotile would likely not represent what humans would be exposed to, caution must be taken in extrapolating our results based on instillation in experimental animals to human inhalation. Notwithstanding, the results of this study may help to better understand the mechanism of formation of asbestos bodies. For chrysotile and crocidolite, asbestos bodies are systematically formed on long asbestos fibres. The number of coated fibres is only 3.3% in chrysotile inoculated tissues. In UICC crocidolite, Mg, Si, and Fe are associated with the fibres whereas Fe, P and Ca are associated with the coating. Even for crocidolite, most of the observed fibres are uncoated as coated fibres are about 5.7%. Asbestos bodies do not form on erionite fibres. The crystal habit, crystallinity and chemistry of all fibre species do not change with contact time, with the exception of chrysotile which shows signs of leaching of Mg. A model for the formation of asbestos bodies from mineral fibres is postulated. Because the three fibre species show limited signs of dissolution in the tissue, they cannot act as source of elements (primarily Fe, P and Ca) promoting nucleation and growth of asbestos bodies. Hence, the limited number of coated fibres should be due to the lack of nutrients or organic nature.

[Therapeutical effects of pleural injecting recombinant human endostain to 
malignant pleural effusion nude mice model].

BACKGROUND AND OBJECTIVE: The prognosis of malignant pleural effusion (MPE) was poor, injecting anti-angiogenesis agents in pleural cavity might be to reducing the volume of pleural effusion. The aim of this study is to investigate the therapeutical effect of pleural injection of recombinant human endostain, cisplatin and recombinant human endostain combined with cisplatin to MPE nude mice. METHODS: MPE model was built by intrpleural injection of Lewis lung cancer cells (LCC) into BALB/c nude mice. Intrpleural injection of recombinant human endostain (E), cisplatin (P) and recombinant human endostain combined with cisplatin (EP) was performed, MPE volume was measured, immunohistochemistry of CD31 was carried out to calculate micro vessel density (MVD), angiogenesis and apoptosis gene expression was detected. RESULTS: MPE volume was reduced by intrapleiral injection of recombinant human endostain and recombinant human endostain combined with cisplatin, MPE volume was positive correlated with MVD. Vescular epidermal growth factor-α (VEGF-α) expression reduced simultaneously with expression of hypoxia induced factor-1 (HIF1-α) elevated at the same time. CONCLUSIONS: MPE model could be made by intrapleural injection of LLC. Intrapleural injection of recombinant human endostain could reduce MPE volume of nude mice. The potential molecular mechanism of the therapeutical effects of intapleural injection of recombiant endostatin might be related to the downregulation of VEGF-α expression and neovascularization.
.

Mast cells mediate malignant pleural effusion formation.

Mast cells (MCs) have been identified in various tumors; however, the role of these cells in tumorigenesis remains controversial. Here, we quantified MCs in human and murine malignant pleural effusions (MPEs) and evaluated the fate and function of these cells in MPE development. Evaluation of murine MPE-competent lung and colon adenocarcinomas revealed that these tumors actively attract and subsequently degranulate MCs in the pleural space by elaborating CCL2 and osteopontin. MCs were required for effusion development, as MPEs did not form in mice lacking MCs, and pleural infusion of MCs with MPE-incompetent cells promoted MPE formation. Once homed to the pleural space, MCs released tryptase AB1 and IL-1ß, which in turn induced pleural vasculature leakiness and triggered NF-κB activation in pleural tumor cells, thereby fostering pleural fluid accumulation and tumor growth. Evaluation of human effusions revealed that MCs are elevated in MPEs compared with benign effusions. Moreover, MC abundance correlated with MPE formation in a human cancer cell-induced effusion model. Treatment of mice with the c-KIT inhibitor imatinib mesylate limited effusion precipitation by mouse and human adenocarcinoma cells. Together, the results of this study indicate that MCs are required for MPE formation and suggest that MC-dependent effusion formation is therapeutically addressable.

In-depth proteomic analysis of six types of exudative pleural effusions for nonsmall cell lung cancer biomarker discovery.

Pleural effusion (PE), a tumor-proximal body fluid, may be a promising source for biomarker discovery in human cancers. Because a variety of pathological conditions can lead to PE, characterization of the relative PE proteomic profiles from different types of PEs would accelerate discovery of potential PE biomarkers specifically used to diagnose pulmonary disorders. Using quantitative proteomic approaches, we identified 772 nonredundant proteins from six types of exudative PEs, including three malignant PEs (MPE, from lung, breast, and gastric cancers), one lung cancer paramalignant PE, and two benign diseases (tuberculosis and pneumonia). Spectral counting was utilized to semiquantify PE protein levels. Principal component analysis, hierarchical clustering, and Gene Ontology of cellular process analyses revealed differential levels and functional profiling of proteins in each type of PE. We identified 30 candidate proteins with twofold higher levels (q<0.05) in lung cancer MPEs than in the two benign PEs. Three potential markers, MET, DPP4, and PTPRF, were further verified by ELISA using 345 PE samples. The protein levels of these potential biomarkers were significantly higher in lung cancer MPE than in benign diseases or lung cancer paramalignant PE. The area under the receiver-operator characteristic curve for three combined biomarkers in discriminating lung cancer MPE from benign diseases was 0.903. We also observed that the PE protein levels were more clearly discriminated in effusions in which the cytological examination was positive and that they would be useful in rescuing the false negative of cytological examination in diagnosis of nonsmall cell lung cancer-MPE. Western blotting analysis further demonstrated that MET overexpression in lung cancer cells would contribute to the elevation of soluble MET in MPE. Our results collectively demonstrate the utility of label-free quantitative proteomic approaches in establishing differential PE proteomes and provide a new database of proteins that can be used to facilitate identification of pulmonary disorder-related biomarkers.

Biodegradable drug-eluting pellets provide steady and sustainable cisplatin release in the intrapleural cavity: in vivo and in vitro studies.

The purpose of this study is to develop biodegradable drug-eluting pellets to provide a sustainable delivery of cisplatin intrapleurally. Poly(d,l)-lactide-co-glycolide (PLGA) (LA:GA=50:50) copolymer and cisplatin were mixed, compressed, and sintered to construct biodegradable pellets and placed in phosphate-buffered saline to test the characteristics of in vitro release. In vivo, equal amounts of cisplatin (10mg/kg) were introduced into rabbit pleural cavities either by free form (Gr1) or pellets form (Gr2). Cisplatin concentrations in the collected pleural effusion and blood were measured and compared by repeated measurement ANOVA. In vitro, approximately 5% of the cisplatin was released in the first day while the rest was gradually released in the following 50 days. In vivo, the cisplatin level in the pleural fluid was equally high during the first 2 days but dropped quickly in Gr1 while remaining high in Gr2 for 18 days, the difference was statistically significant (P<0.001) In contrast, the plasma cisplatin level was 10 times significantly higher in Gr1 than in Gr2 (P<0.001), which resulted in two early deaths of rabbits. Thus we concluded that our biodegradable pellets could achieve high and steady cisplatin release in the pleural cavity. This novel drug delivery system may have the potential to serve as an adjuvant treatment for malignant pleural lesion.