A common secretomic signature across epithelial cancers metastatic to the pleura supports IL-6 axis therapeutic targeting.

Background: Many cancers metastasize to the pleura, resulting in effusions that cause dyspnea and discomfort. Regardless of the tissue of origin, pleural malignancies are aggressive and uniformly fatal, with no treatment shown to prolong life. The pleural mesothelial monolayer is joined by tight junctions forming a contained bioreactor-like space, concentrating cytokines and chemokines secreted by the mesothelium, tumor, and infiltrating immune cells. This space represents a unique environment that profoundly influences tumor and immune cell behavior. Defining the pleural secretome is an important step in the rational development localized intrapleural immunotherapy. Method: We measured cytokine/chemokine content of 252 malignant pleural effusion (MPE) samples across multiple cancers using a 40-analyte panel and Luminex multiplexing technology. Results: Eleven analytes were consistently present in concentrations ≥ 10.0 pM: CXCL10/IP10 (geometric mean = 672.3 pM), CCL2/MCP1 (562.9 pM), sIL-6Rα (403.1 pM), IL-6 (137.6 pM), CXCL1/GRO (80.3 pM), TGFß1 (76.8 pM), CCL22/MDC (54.8 pM), CXCL8/IL-8 (29.2 pM), CCL11/Eotaxin (12.6 pM), IL-10 (11.3 pM), and G-CSF (11.0 pM). All are capable of mediating chemotaxis, promotion of epithelial to mesenchymal transition, or immunosuppression, and many of are reportedly downstream of a pro-inflammatory cytokine cascade mediated by cytokine IL-6 and its soluble receptor. Conclusion: The data indicate high concentrations of several cytokines and chemokines across epithelial cancers metastatic to the pleura and support the contention that the pleural environment is the major factor responsible for the clinical course of MPE across cancer types. A sIL-6Rα to IL-6 molar ratio of 2.7 ensures that virtually all epithelial, immune and vascular endothelial cells in the pleural environment are affected by IL-6 signaling. The central role likely played by IL-6 in the pathogenesis of MPE argues in favor of a therapeutic approach targeting the IL-6/IL-6R axis.

Characterizing soluble immune checkpoint molecules and TGF-ß1,2,3 in pleural effusion of malignant pleural mesothelioma.

The clinical impact of soluble molecules in pleural effusion (PE) is unclear in patients with malignant pleural mesothelioma (MPM). In this single-center, retrospective, observational study, we assessed soluble forms of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), and PD-1 ligand 1 (PD-L1) using enzyme-linked immunosorbent assays; three TGF-ß isoforms were measured via multiplex assay in PE of patients with fibrinous pleuritis (FP) or MPM, to assess relationships between the levels of six molecules, clinicopathological characteristics, and efficacy of immune checkpoint inhibitors. Soluble forms of CTLA-4, PD-L1, PD-1, TGF-ß1, TGF-ß2, and TGF-ß3 were variably produced in PE of FP (n = 34) and MPM (n = 79); we found significant relationships between the six molecules and clinicopathological features. Although none of the three soluble immune checkpoint molecules showed diagnostic or prognostic effects in patients with MPM, TGF-ß2 level in PE is a useful differential diagnostic marker between FP and MPM. Both TGF-ß1 and TGF-ß3 levels are promising prognostic markers for MPM. Moreover, we found that higher baseline levels of PD-1 soluble forms predicted the response to anti-PD1 monotherapy. Our findings identify novel diagnostic, prognostic, and predictive biomarkers for anti-PD1 therapy in patients with MPM.

Identification of Potential Biomarkers of EGFR Mutation in Pleural Effusion of Non-Small Cell Lung Cancer Patients Based on Metabolomics.

BACKGROUND: Malignant pleural effusion (MPE) is a common complication of non-small cell lung cancer (NSCLC). Patients with NSCLC exhibit a high rate of epidermal growth factor receptor (EGFR) mutations. The detection of EGFR mutations is usually time-consuming and costly. This study aimed at identifying potential biomarkers of EGFR mutations in MPE of NSCLC patients by metabolomics. METHODS: In total, 58 MPE samples from 30 EGFR mutant and from 28 wild-type NSCLC patients were collected and analyzed by using hydrogen nuclear magnetic resonance (1H NMR) based metabolomics and UPLC-MS/MS based amino acid analysis. RESULTS: Our 1H NMR study showed a significant increase in the lysine levels but a significant decrease in the alanine levels in MPE of NSCLC patients with EGFR-mutant. Twelve amino acids in MPE were further determined by UPLC-MS/MS. It showed that alanine in MPE (6.34 ± 1.88 vs. 8.73 ± 3.68) were significantly decreased and leucine (3.13 ± 0.57 vs. 2.22 ± 0.13), lysine (2.19 ± 0.50 vs. 1.53 ± 0.40), and tyrosine (2.69 ± 0.71 vs. 1.89 ± 0.46) were increased in the EGFR mutation group; leucine (2.19 ± 0.50 vs. 1.53 ± 0.40), methionine (2.19 ± 0.50 vs. 1.53 ± 0.40), and threonine (2.19 ± 0.50 vs. 1.53 ± 0.40) in MPE were significantly lower in the EGRF 19 mutation compared with 21 mutation patients. The area under the receiver operating characteristic curve of 0.851 and 0.931 would be achieved by the logistic model for classification of EGFR-mutant patients from the wild-type controls or the exon 19 from exon 21 mutant patients. CONCLUSIONS: Amino acids in MPE are significantly altered and helpful in the diagnosis of EGFR-mutant patients from the wild-type controls or the exon 19 from exon 21 mutant patients with high accuracy, which is worthy of further study.

Interleukin-8/CXCR1 Signaling Contributes to the Progression of Pulmonary Adenocarcinoma Resulting in Malignant Pleural Effusion.

Pulmonary adenocarcinoma (PADC) treatment limited efficacy in preventing tumor progression, often resulting in malignant pleural effusion (MPE). MPE is filled with various mediators, especially interleukin-8 (IL-8). However, the role of IL-8 and its signaling mechanism within the fluid microenvironment (FME) implicated in tumor progression warrants further investigation. Primary cultured cells from samples of patients with MPE from PADC, along with a commonly utilized lung cancer cell line, were employed to examine the role of IL-8 and its receptor, CXCR1, through comparative analysis. Our study primarily assessed migration and invasion capabilities, epithelial-mesenchymal transition (EMT), and cancer stem cell (CSC) properties. Additionally, IL-8 levels in MPE fluid versus serum, along with immunohistochemical expression of IL-8/CXCR1 signaling in tumor tissue and cell blocks were analyzed. IL-8/CXCR1 overexpression enhanced EMT and CSC properties. Furthermore, the immunocytochemical examination of 17 cell blocks from patients with PADC and MPE corroborated the significant correlation between upregulated IL-8 and CXCR1 expression and the co-expression of IL-8 and CXCR1 in MPE with distant metastasis. In summary, the IL-8/ CXCR1 axis in FME is pivotal to tumor promotion via paracrine and autocrine signaling. Our study provides a therapeutic avenue for improving the prognosis of PADC patients with MPE.

Quantitative proteomics revealed protein biomarkers to distinguish malignant pleural effusion from benign pleural effusion.

To identify protein biomarkers capable of early prediction regarding the distinguishing malignant pleural effusion (MPE) from benign pleural effusion (BPE) in patients with lung disease. A four-dimensional data independent acquisition (4D-DIA) proteomic was performed to determine the differentially expressed proteins in samples from 20 lung adenocarcinoma MPE and 30 BPE. The significantly differential expressed proteins were selected for Gene Ontology (GO) enrichment and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis. Protein biomarkers with high capability to discriminate MPE from BPE patients were identified by Random Forest (RF) algorithm prediction model, whose diagnostic and prognostic efficacy in primary tumors were further explored in public datasets, and were validated by ELISA experiment. 50 important proteins (30 up-regulated and 20 down-regulated) were selected out as potential markers to distinguish the MPE from BPE group. GO analysis revealed that those proteins involving the most important cell component is extracellular space. KEGG analysis identified the involvement of cellular adhesion molecules pathway. Furthermore, the Area Under Curve (AUC) of these proteins were ranged from 0.717 to 1.000，with excellent diagnostic properties to distinguish the MPE. Finally, significant survival and gene and protein expression analysis demonstrated BPIFB1, DPP4, HPRT1 and ABI3BP had high discriminating values. SIGNIFICANCE: We performed a 4D-DIA proteomics to determine the differentially expressed proteins in pleural effusion samples from MPE and BPE. Some potential protein biomarkers were identified to distinguish the MPE from BPE patients., which may provide helpful diagnostic and therapeutic insights for lung cancer. This is significant because the median survival time of patients with MPE is usually 4-12 months, thus, it is particularly important to diagnose MPE early to start treatments promptly. The most common causes of MPE are lung cancers, while pneumonia and tuberculosis are the main causes of BPE. If more diagnostic markers could be identified periodically, there would be an important significance to clinical diagnose and treatment with drugs in lung cancer patients.

Differences in 1HNMR Based Metabolomic Patterns of Malignant and Benign Pleural Effusions.

OBJECTIVE: Malignant pleural effusion (MPE) is a common complication of lung cancer with poor prognosis. Benign pleural effusion (BPE), such as tuberculous and pneumonic pleural effusion, usually has a good prognosis. Differential diagnosis between MPE and BPE remains a clinical challenge. METHODS: 52 MPE, 93 BPE, and their corresponding serum samples were analyzed by hydrogen nuclear magnetic resonance (1HNMR) based metabolomics. RESULTS: The 1HNMR study showed that some amino acids and betaine in MPE are significantly altered in pleural effusion and serum compared to BPE patients. Levels of serum glucose and glutamine have strong positive correlation with those in pleural effusion (r>0.6) for MPE patients. The area under the receiver operating characteristic curve (AUROC) values of metabolites in pleural effusion or serum were less than 0.805 in differentiating MPE from BPE. Improved an AUROC value of 0.901 was observed using pleural effusion-serum ratios of glutamic acid in differentiating MPE from BPE, which was further validated by 15 double-blind samples. CONCLUSIONS: Compared with BPE patients, amino acids and betaine in MPE are significantly altered in pleural effusion and serum. Pleural effusion-serum ratio of glutamic acid may contribute to the rapid diagnosis of MPE from BPE by 1HNMR analysis.

Single-cell transcriptomics reveal metastatic CLDN4+ cancer cells underlying the recurrence of malignant pleural effusion in patients with advanced non-small-cell lung cancer.

BACKGROUND: Recurrent malignant pleural effusion (MPE) resulting from non-small-cell lung cancer (NSCLC) is easily refractory to conventional therapeutics and lacks predictive markers. The cellular or genetic signatures of recurrent MPE still remain largely uncertain. METHODS: 16 NSCLC patients with pleural effusions were recruited, followed by corresponding treatments based on primary tumours. Non-recurrent or recurrent MPE was determined after 3-6 weeks of treatments. The status of MPE was verified by computer tomography (CT) and cytopathology, and the baseline pleural fluids were collected for single-cell RNA sequencing (scRNA-seq). Samples were then integrated and profiled. Cellular communications and trajectories were inferred by bioinformatic algorithms. Comparative analysis was conducted and the results were further validated by quantitative polymerase chain reaction (qPCR) in a larger MPE cohort from the authors' centre (n = 64). RESULTS: The scRNA-seq revealed that 33 590 cells were annotated as 7 major cell types and further characterized into 14 cell clusters precisely. The cell cluster C1, classified as Epithelial Cell Adhesion Molecule (EpCAM)+ metastatic cancer cell and correlated with activation of tight junction and adherence junction, was significantly enriched in the recurrent MPE group, in which Claudin-4 (CLDN4) was identified. The subset cell cluster C3 of C1, which was enriched in recurrent MPE and demonstrated a phenotype of ameboidal-type cell migration, also showed a markedly higher expression of CLDN4. Meanwhile, the expression of CLDN4 was positively correlated with E74 Like ETS Transcription Factor 3 (ELF3), EpCAM and Tumour Associated Calcium Signal Transducer 2 (TACSTD2), independent of driver-gene status. CLDN4 was also found to be associated with the expression of Hypoxia Inducible Factor 1 Subunit Alpha (HIF1A) and Vascular Endothelial Growth Factor A (VEGFA), and the cell cluster C1 was the major mediator in cellular communication of VEGFA signalling. In the extensive MPE cohort, a notably increased expression of CLDN4 in cells from pleural effusion among patients diagnosed with recurrent MPE was observed, compared with the non-recurrent group, which was also associated with a trend towards worse overall survival (OS). CONCLUSIONS: CLDN4 could be considered as a predictive marker of recurrent MPE among patients with advanced NSCLC. Further validation for its clinical value in cohorts with larger sample size and in-depth mechanism studies on its biological function are warranted. TRIAL REGISTRATION: Not applicable.

Consistency Analysis of Programmed Death Ligand 1 Expression in Non-Small Cell Lung Cancer Between Pleural Effusion and Matched Primary Lung Cancer Tissues by Immunohistochemical Double Staining.

In clinical practice, programmed death ligand 1 (PD-L1) detection is prone to nonspecific staining due to the complex cellular composition of pleural effusion smears. In this study, diaminobenzidine (DAB) and 3-amino-9-ethylcarbazole (AEC) immunohistochemistry double staining was performed to investigate PD-L1 expression in tumor cells from malignant pleural effusion (MPE). MPE was considered as a metastasis in non-small cell lung cancer patients; thus, the heterogeneity between metastatic and primary lung cancer was revealed as well. Ninety paired specimens of MPE cell blocks and matched primary lung cancer tissues from non-small cell lung cancer patients were subjected to PD-L1 and thyroid transcription factor-1(TTF-1)/p63 immunohistochemistry double staining. Two experienced pathologists independently evaluated PD-L1 expression using 3 cutoffs (1%, 10%, and 50%). PD-L1 expression in MPE was strongly correlated with that in matched primary lung cancer tissues (R = 0.813; P < .001). Using a 4-tier scale (cutoffs: 1%, 10%, and 50%), the concordance was 71.1% (Cohen's κ = .534). Using a 2-tier scale, the concordance was 75.6% (1%, Cohen's κ = 0.53), 78.9% (10%, Cohen's κ = 0.574), and 95.6% (50%, Cohen's κ = 0.754). The rates of PD-L1 positivity in MPE (56.7%) were higher than that in lung tissues (32.2%). All 27 discordant cases had higher scores in MPE. The double-staining method provided superior identification of PD-L1-positive tumor cells on a background with nonspecific staining. In conclusion, PD-L1 expression was moderately concordant between metastatic MPE cell blocks and matched primary lung carcinoma tissues, with variability related to tumor heterogeneity. MPE should be considered to detect PD-L1 when histological specimens are unattainable, especially when PD-L1 expression is >50%. PD-L1 positivity rates were higher in MPE. Double staining can improve PD-L1 detection by reducing false-negative/positive results.

Use of tumor markers in distinguishing lung adenocarcinoma-associated malignant pleural effusion from tuberculous pleural effusion.

BACKGROUND: The distinction between lung adenocarcinoma-associated malignant pleural effusion (MPE) and tuberculous pleural effusion (TPE) continues to pose a challenge. This study sought to assess the supplementary value of tumor markers in enabling a differential diagnosis. METHODS: Data concerning tumor markers, which included carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), cancer antigen 153 (CA153), cancer antigen 724 (CA724), neuron-specific enolase (NSE), cytokeratin19 fragment (Cyfra21-1), and squamous cell carcinoma antigen (SCCA), in both serum and pleural effusion samples, were retrospectively compiled from lung adenocarcinoma-associated MPE and TPE patients. A comparative analysis of tumor marker concentrations between the two groups was performed to assess diagnostic utility, followed by a multiple logistic regression to control for confounding variables. RESULTS: While gender, serum CA125 and SCCA, and pleural effusion SCCA manifested comparability between the groups, distinctions were noted in patient age and the concentration of other tumor markers in serum and pleural effusion, which were notably elevated in the MPE group. Multiple logistic regression demonstrated a positive association between the risk of lung adenocarcinoma-associated MPE and levels of CEA and CA153 in serum and pleural effusion, as well as Cyfra21-1 in serum (P < 0.05). The odds ratio for CEA surpassed that of CA153 and Cyfra21-1. CONCLUSIONS: CEA and CA153 in serum and pleural effusion, and Cyfra21-1 in serum emerge as biomarkers possessing supplementary diagnostic value in distinguishing lung adenocarcinoma-associated MPE from TPE. The diagnostic efficacy of CEA is superior to CA153 and Cyfra21-1. Conversely, the utility of CA125, CA724, NSE, and SCCA appears constrained.

Cell origins and significance of IL-17 in malignant pleural effusion

PURPOSE: T cells are dominant in the immune regulation of malignant pleural effusion (MPE). However, it is unclear about the role of IL-17+ T cells, particularly for IL-17+CD8+ Tc17 cells in antitumor immunity. This retrospective study is aimed at evaluating the prognostic significance of IL-17+ T cells in patients with MPE. METHODS: The frequency of IL-17+CD4+ Th17 and IL-17+CD8+ Tc17 cells in peripheral blood (PB), pleural fluids (PF), and tumor tissues in 24 patients undergoing thoracoscopy was determined by flow cytometry, immunohistochemistry, and ELISA. The association among the different measures was analyzed by Spearman's correlation tests. RESULTS: The percentages of PF Th17 and Tc17 cells were significantly higher than those in the PB of MPE patients and healthy controls (p < 0.01). Analysis of Th17 and Tc17 cells in the tumor tissues indicated that the percentages of Th17 and Tc17 cells in the invading tumor edge were significantly higher than those in the non-tumor tissues and intra-tumor regions (p < 0.05). More importantly, the percentages of IL-17+ T cells were associated with prolonged survival of patients with MPE. CONCLUSIONS: Both Th17 and Tc17 cells were involved in the tumor immunity against MPE. Increased frequency of Tc17 cells may serve as a biomarker for the prognosis of patients with MPE (AU)

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Proteomic analysis of pleural effusion from lung adenoncarcinoma patients by shotgun strategy

PURPOSE: To construct a protein catalogue of malignant pleural effusion from lung adenocarcinoma patients and to screen the potential candidates of biomarkers for diagnostic value in human lung adenocarcinoma. METHOD: Five malignant pleural effusion samples of lung adenocarcinoma patients were collected from January 2009 to September. A composite sample was analyzed using shotgun strategy. Pleural effusion samples were separated by means of SDS-PAGE. Proteomic analysis was performed by 1D-LC-MS/MS, and then the proteins were identified using SEQUEST software and protein database search. RESULTS: Among 230 unique proteins, 123 proteins were identified with higher confidence levels (at least two unique peptide sequences matched). Most of these proteins have been reported in plasma. However, there are 7 proteins, including JUP protein, suprabasin, annexin A2, transforming growth factor-beta-induced protein ig-h3 (βig-h3), V-set and immunoglobulin domain-containing protein 4 precursor, ifapsoriasin 2 and actin, cytoplasmic 1 have not been reported in serum. CONCLUSIONS: Seven proteins may represent potential candidates of biomarkers. Annexin A2 is of special interest since it may play a role in the regulation of intercellular adhesion and cell proliferation (AU)

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Apolipoproteína A1 y apolipoproteína B en los derrames pleurales / Apolipoprotein A1 and apoliprotein B in pleural effusions

Objetivo. Determinar los niveles de apolipoproteína A1 y apolipoproteína B en los derrames pleurales y analizar su posible valor diagnóstico. Pacientes y métodos. Se incluyeron 117 pacientes con derrame pleural (30 trasudados y 87 exudados). Las apolipoproteínas se determinaron mediante turbidimetría. Resultados. En el suero los valores de apolipoproteína B fueron ligeramente inferiores en trasudados que en exudados, y ambas apolipoproteínas tenían valores inferiores en pacientes con exudados benignos que en malignos. En el líquido pleural los niveles de apolipoproteínas fueron inferiores en trasudados que en exudados. Las razones líquido pleural/suero de ambas apolipoproteínas fueron significativamente inferiores en los derrames malignos comparados con los exudados benignos. No se encontró un valor de corte que permitiera diferenciar entre trasudados y exudados o entre exudados benignos y malignos con niveles de sensibilidad o especificidad que tuvieran interés clínico. Conclusiones. Los niveles de apolipoproteína A1 y apolipoproteína B en líquido pleural son diferentes en trasudados y exudados, y también lo son las razones líquido pleural/suero entre exudados benignos y malignos; no obstante, su determinación no aporta información clínica adicional

Objective. To determine the levels of apolipoprotein A1 and apolipoprotein B in pleural effusions and analyze their possible diagnostic value. Patients and methods. A total of 117 patients with pleural effusion (30 transudates and 87 exudates) were included. The apolipoproteins were measured by turbidimetry. Results. The apolipoprotein B values in serum were slightly lower in transudates than in exudates, and both apolipoproteins had lower values in patients with benign exudates than in malignant ones. The apolipoprotein levels in pleural fluid were lower in transudates than in exudates. The pleural/serum fluid ratios of both apolipoproteins were significantly lower in malignant effusions compared with benign exudates. No cutoff value was found that would make it possible to differentiate between transudates and exudates or between benign and malignant exudates with sensitivity or specificity levels that had clinical interest. Conclusions. Apolipoprotein A1 and apolipoprotein B levels in pleural fluid are different in transudates and exudates, and the pleural/serum fluid ratios are also different between benign and malignant exudates. However, their measurement does not supply additional clinical information

El factor de crecimiento endotelial vascular en los derrames pleurales benignos y malignos / Vascular endothelial growth factor in benign and malignant pleural effusions

Objetivo: El factor de crecimiento endotelial vascular (VEGF) es un potente inductor de la permeabilidad capilar y desempeña un papel clave como mediador en la formación del derrame pleural. Este estudio se ha realizado para evaluar la utilidad del VEGF en el diagnóstico de los derrames pleurales malignos y no malignos de diversas causas. Pacientes y métodos: Mediante la técnica de inmunoabsorción ligada a enzimas se determinaron las concentraciones de VEGF en los derrames pleurales correspondientes a 52 pacientes (20 con derrame pleural maligno, 12 con derrame de origen tuberculoso, 10 con derrame de tipo trasudado y 10 con derrame paraneumónico). Resultados: La concentración media del VEGF fue significativamente mayor (p = 0,001) en los derrames pleurales (10,16 pg/ml) de tipo exudado que en los derrames de tipo trasudado (3,82 pg/ml). Aunque los derrames pleurales malignos mostraron una tendencia a las concentraciones medianas y medias mayores de VEGF, en comparación con los derrames de origen tuberculoso, la diferencia no fue estadísticamente significativa. Tampoco fueron significativamente diferentes las concentraciones pleurales de VEGF en los distintos subtipos de cáncer pulmonar, y tampoco en los derrames malignos de distintos orígenes. Conclusiones: Aunque las concentraciones de VEGF son distintas en los derrames pleurales de orígenes diferentes, en nuestro estudio no han permitido discriminar los exudados de los trasudados. Son necesarios nuevos estudios de investigación sobre grupos más numerosos de pacientes con objeto de establecer el papel que puede desempeñar la concentración de VEGF en el diagnóstico de los derrames malignos, tuberculosos o ambos

Objective: Vascular endothelial growth factor (VEGF) is a potent inducer of capillary permeability and its role as a crucial mediator in pleural fluid formation has been established. This study was conducted to assess the usefulness of VEGF for diagnosing malignant and non-malignant pleural effusions of various causes. Patients and Methods: VEGF levels in pleural effusions collected from 52 patients (20 with malignant effusion, 12 with tuberculous effusion, 10 with transudative effusion, and 10 with parapneumonic effusion) were assessed by enzyme-linked immunosorbent assay. Results: The median level of VEGF was significantly higher (P=.001) in exudative effusions (10.16 pg/mL) than in the transudative effusions (3.82 pg/mL). Although malignant pleural fluids tended to have higher median and mean levels of VEGF compared to tuberculous effusions, the difference was not statistically significant. Pleural VEGF levels in subtypes of lung cancer and in malignant effusions of different origins were not significantly different. Conclusions: In conclusion, although VEGF levels in pleural effusions of different origins vary, they were only able to discriminate exudates from transudates significantly in this study. Further studies in larger groups of patients are needed to establish the role of VEGF in diagnosing malignant and/or tuberculous effusions

What is the Clinical Significance of Transudative Malignant Pleural Effusion?

BACKGROUND: A few reports of transudative malignant effusion on a small number of patients have suggested the need to perform routine cytologic examination in all cases of transudative pleural effusion, whether encountered for malignancy or not. The purpose of this study was to investigate whether cytologic examination should be performed in all cases of transudative pleural effusion for the diagnosis of malignancy. METHODS: We performed a retrospective study of 229 consecutive patients with malignant pleural effusion, proven either cytologically or with biopsy. In patients with transudative pleural effusion, we reviewed medical records, results of transthoracic echocardiography, fiberoptic bronchoscopy, chest X-ray, chest CT scan, and ultrasonogram of the abdomen. These data were examined with particular attention to identifying whether or not the malignancy was suggested on chest X-ray, examining the involvement of the superior vena cava, great vessels, and lymph nodes, determining the presence of pericardial effusion, and observing the endobronchial obstruction. RESULTS: Transudative malignant pleural effusion was observed in seven (3.1%) of the 229 patients, and was caused either by the malignancy itself (6 patients) or by coexisting cardiac diseases (1 patient). All the patients showed evidence suggesting the presence of malignancy at the time of initial thoracentesis, which facilitated the decision of most clinicians on whether to perform cytologic examination for the diagnosis of malignancy. CONCLUSION: Therefore, in all cases of transudative pleaural effusion, no clinical implications indicating malignancy were found on cytologic examination.

Vascular endothelial growth factor in malignant and tuberculous pleural effusions

The purpose of this study is to assess the usefulness of soluble vascular endothelial growth factor (VEGF) in the effusions of patients with malignant and tuberculous diseases. Using a sandwich enzyme-linked immunoadsorbent assay, VEGF concentration was measured in malignant (n=17) and tuberculous (n=11) pleural effusions. Pleural biopsy, cytology or microbiological methods were used to make final diagnoses. Adenosine deaminase (ADA) levels in tuberculous pleural effusions were significantly higher than those in malignant pleural effusions. The median level of VEGF in patients with malignant effusions (median, 2418 pg/mL; range, 97-62103 pg/mL) was significantly higher than tuberculous effusions (median, 994 pg/mL; range, 44-3552 pg/mL). There were no significant differences in pleural VEGF levels in patients with different histological types of lung cancer. The VEGF level was not correlated with ADA, lactate dehydrogenase and total protein levels of pleural fluid. In conclusion, pleural VEGF levels in patients with malignant effusions were significantly higher than tuberculous effusions, and the measurement of pleural VEGF is helpful in discriminating between malignant and tuberculous effusions. Further studies are needed to determine the clinical value of VEGF as a tumor marker and a prognostic factor.

Vascular endothelial growth factor in malignant and tuberculous pleural effusions

The purpose of this study is to assess the usefulness of soluble vascular endothelial growth factor (VEGF) in the effusions of patients with malignant and tuberculous diseases. Using a sandwich enzyme-linked immunoadsorbent assay, VEGF concentration was measured in malignant (n=17) and tuberculous (n=11) pleural effusions. Pleural biopsy, cytology or microbiological methods were used to make final diagnoses. Adenosine deaminase (ADA) levels in tuberculous pleural effusions were significantly higher than those in malignant pleural effusions. The median level of VEGF in patients with malignant effusions (median, 2418 pg/mL; range, 97-62103 pg/mL) was significantly higher than tuberculous effusions (median, 994 pg/mL; range, 44-3552 pg/mL). There were no significant differences in pleural VEGF levels in patients with different histological types of lung cancer. The VEGF level was not correlated with ADA, lactate dehydrogenase and total protein levels of pleural fluid. In conclusion, pleural VEGF levels in patients with malignant effusions were significantly higher than tuberculous effusions, and the measurement of pleural VEGF is helpful in discriminating between malignant and tuberculous effusions. Further studies are needed to determine the clinical value of VEGF as a tumor marker and a prognostic factor.