Successful drainage of complex haemoserous malignant pleural effusion with a single modified low-dose intrapleural alteplase and dornase alfa.

Patients with symptomatic complex malignant pleural effusion (MPE) are frequently unfit for decortication and have a poorer prognosis. Septations can develop in MPE, which may lead to failure of complete drainage and pleural infection. Intrapleural fibrinolytic therapy (IPFT) is an alternative treatment. The use of IPFT in patients with anaemia and high risk for intrapleural bleeding is not well established. We report a successful drainage of complex haemoserous MPE with a single modified low-dose of intrapleural 5 mg of alteplase and 5 mg of dornase alfa in a patient with pre-existing anaemia with no significant risk of intrapleural bleeding.

Microbiome profile associated with malignant pleural effusion.

INTRODUCTION: There is ongoing research into the development of novel molecular markers that may complement fluid cytology malignant pleural effusion (MPE) diagnosis. In this exploratory pilot study, we hypothesized that there are distinct differences in the pleural fluid microbiome profile of malignant and non-malignant pleural diseases. METHOD: From a prospectively enrolled pleural fluid biorepository, samples of MPE were included. Non-MPE effusion were included as comparators. 16S rRNA gene V4 region amplicon sequencing was performed. Exact Sequence Variants (ESVs) were used for diversity analyses. The Shannon and Richness indices of alpha diversity and UniFrac beta diversity measures were tested for significance using permutational multivariate analysis of variance. Analyses of Composition of Microbiome was used to identify differentially abundant bacterial ESVs between the groups controlled for multiple hypothesis testing. RESULTS: 38 patients with MPE and 9 with non-MPE were included. A subgroup of patients with metastatic adenocarcinoma histology were identified among MPE group (adenocarcinoma of lung origin (LA-MPE) = 11, breast origin (BA-MPE) = 11). MPE presented with significantly greater alpha diversity compared to non-MPE group. Within the MPE group, BA-MPE was more diverse compared to LA-MPE group. In multivariable analysis, ESVs belonging to family S24-7 and genera Allobaculum, Stenotrophomonas, and Epulopiscium were significantly enriched in the malignant group compared to the non-malignant group. CONCLUSION: Our results are the first to demonstrate a microbiome signature according to MPE and non-MPE. The role of microbiome in pleural effusion pathogenesis needs further exploration.

Routine Microbiologic Studies of Pleural Fluid Specimens in Cancer Patients.

BACKGROUND: Patients who have pleural effusions typically undergo thoracentesis with examination of pleural fluid in their initial assessment. However, limited data are available on the diagnostic yield of pleural fluid bacterial cultures and fungal and acid-fast bacilli (AFB) smear and cultures in patients with cancer. METHODS: We performed a retrospective cohort study of consecutive patients who had new onset pleural effusions and underwent an initial thoracentesis. The primary outcome was diagnostic yield of pleural fluid bacterial cultures and fungal and AFB smear and cultures. RESULTS: Of 1637 patients, 1547 (94%) had evidence of active malignancy and 1359 (83%) had evidence of metastatic disease. Of the 1637 patients, 542 (33%) had high clinical suspicion of pneumonia within 14 days prior to thoracentesis. Only 14 patients (1.1%) had positive pleural fluid bacterial cultures, and only 6 of these positive cultures met the criteria for true pleural space infection. CONCLUSIONS: The incidence of positive results from pleural fluid bacterial, fungal, and AFB in cancer populations is very low. Unless there is a suspicion for infection, microbiological analysis should be ordered selectively.

Tunneled pleural catheter use for pleural palliation does not increase infection rate in patients with treatment-related immunosuppression.

PURPOSE: Concerns for infections resulting from antineoplastic therapy-associated immunosuppression may deter referral for symptom palliation with a tunneled pleural catheter (TPC) in patients with malignant/para-malignant pleural effusions (MPE/PMPE). While rates of TPC-related infections range from 1 to 21%, those in patients receiving antineoplastic therapy with correlation to immune status has not been established. We aimed to assess TPC-related infection rates in patients on antineoplastic therapy, determine relation to immune system competency, and assess impact on the patient. METHODS: Patients with a MPE/PMPE undergoing TPC management associated with antineoplastic therapy, from 2008 to 2016, were reviewed and categorized into those with an immunocompromised versus immunocompetent immune status. RESULTS: Of the 150 patients, a TPC-related infection developed in 13 (9%): pleural space in 11 (7%) and superficial in 2 (1%). Ninety-three percent (139/150) were identified to be immunocompromised during their antineoplastic therapy. No difference in TPC-related infections was seen in patients with an immunocompromised (9%, 12/139) versus immunocompetent status (9%, 1/11); p = 0.614. The presence of a catheter-related infection did not negatively impact overall survival over a median follow-up of 144 days (interquartile range 41-341); p = 0.740. CONCLUSIONS: These results suggest that antineoplastic therapy may not significantly increase the overall risk of TPC-related infections, as the rate remains low and comparable to rates in patients not undergoing antineoplastic therapy. Regardless of immune status, the presence of a catheter-related infection did not negatively impact overall survival. These results should reassure clinicians that the need to initiate antineoplastic therapy should not delay definitive pleural palliation with a TPC.

Vitamin D nutritional status and vitamin D regulated antimicrobial peptides in serum and pleural fluid of patients with infectious and noninfectious pleural effusions.

BACKGROUND: Vitamin D and vitamin D dependent antimicrobial peptides such as Cathelicidin (LL-37) and ß-defensin 2 have an important role in innate and adaptative immunity, but their role in pleural effusions has not been studied before. METHODS: Serum and pleural fluid samples from 152 patients with pleural effusion were collected, corresponding to 45 transudates and 107 exudates, 51 infectious effusions (14 complicated and 37 non-complicated), 44 congestive heart failure effusions and 38 malignant effusions. The levels of 25 OH-vitamin D, 1,25-(OH)2-vitamin D, Vitamin D Binding Protein (VDBP), LL-37 and ß-defensin 2, both in serum and pleural fluid were evaluated in this prospective study. Differences between groups were analysed using unpaired t tests or Mann-Whitney tests. Correlations between data sets were examined using Pearson correlation coefficient or Spearman rank correlation coefficient. Diagnostic accuracy was estimated using ROC curve analysis. RESULTS: Low serum 25 OH vitamin D levels were found in all groups. Infectious effusions (IE) had higher serum and pleural fluid LL-37 levels compared to congestive heart failure or malignant effusions. Among IE, complicated had higher serum and pleural fluid LL-37 levels, and lower serum ß-defensin-2 levels. Positive correlations were found between serum 25 OH-vitamin D levels and serum or pleural 1,25-(OH)2-vitamin D levels, and between 1,25-(OH)2-vitamin D and LL-37 serum. Diagnostic accuracy of the different molecules was moderate at best. CONCLUSIONS: Hypovitaminosis D is highly prevalent in pleural effusions. LL-37 is produced intrapleurally in IE. This production is higher in complicated IE. No evidence of pleural production of ß-defensin 2 was found in any of the groups. Diagnostic accuracy of the different molecules is at the best moderate for discriminating different types of effusions.

[Simultaneous detection of tumor cells and the positive result of genetic test for Mycobacterium tuberculosis in pleural effusion]. / Jednoczesne wykrycie komórek nowotworowych i materialu genetycznego pratków gruzlicy w plynie oplucnowym.

Pleural effusion is a frequently observed lesion in the course of respiratory diseases such as inflammatory process and cancer metastasis. Its cause may be either tuberculosis (the most common extrapulmonary location is the pleura) and malignant disease of the pleura. Confirmation of tuberculosis is often troublesome. The primary site of cancer may be also difficult to find despite the application of difficult diagnostic methods. Below we present history of 79-year-old female in whom carcinomatous cells and positive result of PCR for Mycobacterium tuberculosis in pleural fluid were discovered simultaneously suggesting the tuberculosis and cancer of unknown primary origin.

Limitations of detection of malignancy in pleural effusions using ELISA-based TRAP assay: comparison with cytological examination.

OBJECTIVE: Telomerase is active in almost all cancers from various organs but is not detectable in most normal cells. Thus, telomerase activity might be a universal and specific marker for diagnosing malignancy. The aim was to evaluate the potential use of the ELISA-based TRAP assay to detect malignancy in pleural effusion, and to compare it with conventional cytological examination. METHODS: Using the ELISA-based TRAP assay, telomerase activity was examined in 94 consecutive pleural effusions submitted for cytological examination. RESULTS: According to the results of cytology, the 94 samples were divided into two groups: group I, 79 non-malignant pleural effusions, including group IA, no association with a malignant tumour, a control group (n = 63), and group IB, associated with a malignant tumour (n = 16); and group II, 15 malignant pleural effusions. Telomerase activity was detected in five of 63 samples in group IA (7.9%), four of 16 samples in group IB (25%), and six of 15 samples in group II (40%). All five false-positive effusions were from patients with tuberculosis. Comparing group II with group IA, the TRAP assay showed 40% sensitivity, 92.1% specificity, 54.5% positive and 86.6% negative predictive value, and 82.1% accuracy. However, the detection rate of the TRAP assay (88.9%) was higher than that of the cytological examination (66.7%) in lung cancer-inflicted pleural effusions. CONCLUSION: The ELISA-based TRAP assay is relatively insensitive; therefore, it is unsuitable as a routine diagnostic tool for pleural effusion. False-positive telomerase activity due to lymphocytic contamination may weaken its diagnostic value for malignant effusions in a tuberculosis-endemic area.

[Apolipoprotein A1 and apolipoprotein B in pleural effusions]. / Apolipoproteína A1 y apolipoproteína B en los derrames pleurales.

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.

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

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

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.

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

A malignant pleural effusion infected with Salmonella enteritidis.

A patient is described with a unilateral pleural effusion persistently infected with Salmonella enteritidis. The infection was eventually eradicated with ciprofloxacin. A computed tomographic scan and mediastinal lymph node biopsy demonstrated an underlying small cell bronchogenic carcinoma.

Detection of human cytomegalovirus in pleural fluid of lymphoblastic lymphoma T-cell type.

We report a case of T-lymphoblastic lymphoma in which lymphoma cells infected with cytomegalovirus were found in the pleural fluid. A 16-year-old boy with an anterior mediastinal mass developed pleural fluid accumulation. Immunoperoxidase staining of pathologic cells in the pleural fluid revealed them to be CD4+/-, CD7+, CD8-, CD34+, CD20- and HLA-DR+. The diagnosis of lymphoblastic lymphoma T-cell type was made. Electron microscopic examination revealed virus particles with an electron-dense core and capsid, late structures of virus, in the pleural fluid cells. Polymerase chain reaction (PCR) amplification was used to detect human cytomegalovirus (HCMV) DNA in pleural fluid cells. A pair of synthetic oligonucleotide primers from the CMV phosphoprotein 71, an early structural protein, coding region (HindIII fragments L, c and b of the Ad 169 strain) could amplify DNA from the pleural fluid cells from the patient. Immunoperoxidase staining of the pleural fluid cells with anti-HCMV positive sera also revealed a positive reaction. These findings suggest the entry of HCMV into lymphoma cells with positive PCR amplification of DNA encoding an early structural protein, and replication from the presence of late structures of virus, electron-dense core and capsid. Replication of lymphoid cell lines of B and T origin were reported in the literature but replication of HCMV in lymphoma cells in vivo has not been reported.

[Cytological, biochemical and immunologic parameters of pleural effusions. Presentation of differences in relation to the nature of the effusion]. / Parametry cytologiczne, biochemiczne i immunologiczne plynów oplucnowych. II. Wystepowanie róznic w zaleznosci od rodzaju wysieku.

In 96 patients with pleural exudates of known origin the authors assessed different cytological, biochemical and immunological parameters in the fluid and serum. In 44 patients the pleural effusions were malignant, in 26 tuberculosis, in 17 bacterial and 9 of viral nature. Statistical analysis was carried on mean values of studied parameters. The results indicate that only bacterial effusions differ significantly from the other pleural effusions. In effusions of malignant, tuberculous and viral nature the studied parameters did not differ significantly and cannot be used as differentiating criteria.