Development and validation of a scoring system for the identification of pleural exudates of cardiac origin.

BACKGROUND: Light's criteria misclassify about 30% of cardiac effusions as exudates, possibly leading to unnecessary testing. Our purpose was to derive and validate a scoring model to effectively identify these falsely categorized cardiac effusions, in the setting of natriuretic peptide lacking data. METHODS: We retrospectively analyzed data from 3182 patients with exudative pleural effusions based on Light's criteria, of whom 276 had heart failure (derivation set). A scoring model was generated with those variables identified as independent predictors of cardiac effusions in a logistic regression analysis, and further evaluated in an independent population of 1165 patients. RESULTS: The score consisted of age ≥75years (3 points), albumin gradient >1.2g/dL (3 points), pleural fluid lactate dehydrogenase <250U/L (2 points), bilateral effusions on chest radiograph (2 points), and protein gradient >2.5g/dL (1 point). At the best cutoff of ≥7 points, the score yielded 92% diagnostic accuracy, a likelihood ratio positive of 12.7 and a likelihood ratio negative of 0.39 for labeling cardiac effusions in the derivation sample. The respective figures in the validation sample were 87%, 6.5 and 0.33. Notably, the score had higher discriminatory properties than protein and albumin gradients in both the derivation (respective area under the curve - AUC - of 0.925, 0.825, and 0.801) and validation (respective AUC of 0.908 0.862 and 0.802; all p≤0.01) cohorts. CONCLUSIONS: A simple scoring system can assist clinicians in accurately identifying false cardiac exudates when natriuretic peptides are not available.

Utilidad de la medición de CEA y CA 15-3 en los exudados pleurales no purulentos para diagnosticar malignidad: experiencia de un único centro / Utility of CEA and CA 15-3 measurements in non-purulent pleural exudates in the diagnosis of malignancy: A single-center experience

Objetivo: Establecer la rentabilidad diagnóstica de la medición de CEA y CA 15-3 en el líquido pleural (LP) para identificar malignidad, así como el valor adicional de estos marcadores en pacientes con derrame pleural maligno (DPM) y citología pleural falsamente negativa. Método: Se determinaron las concentraciones de CEA o CA 15-3 en el LP de 1.575 pacientes con exudados no purulentos, de los que 549 tenían DPM demostrados, 284 derrames probablemente malignos y 742 derrames benignos. Se buscaron puntos de corte 100% específicos para dichos marcadores, de forma que no pudieran ser superados por ningún derrame benigno. Resultados: El 41, 40 y el 60% de los pacientes con DPM tenían concentraciones pleurales elevadas de CEA (>45 ng/mL), CA 15-3 (>77 UI/L), o de alguno de los anteriores, respectivamente. Estos porcentajes fueron del 30, 19 y 41% en los DPM con biopsia pleural positiva y estudios citológicos del LP negativos; y del 24, 13 y 35% en los derrames considerados clínicamente malignos, pero sin demostración citohistológica. Los marcadores tumorales no tuvieron utilidad en linfomas ni mesoteliomas. El área bajo la curva de eficacia diagnóstica (AUC) del CEA fue de 0,819 (IC 95%: 0,793-0,845) y la del CA 15-3 de 0,822 (IC 95%: 0,796-0,847). Globalmente, el uso adicional de los marcadores tumorales incrementó el diagnóstico de malignidad un 14% respecto a la citología pleural de forma aislada. Conclusiones: La determinación de CEA y CA 15-3 en LP puede complementar a la citología pleural en la identificación de los DPM (AU)

Objective: To establish the diagnostic accuracy of pleural fluid (PF) CEA and CA 15-3 in identifying malignancy, and to determine the additional value of these markers in patients with malignant pleural effusions (MPEs) with false negative results from cytological fluid examination. Methods: PF concentrations of CEA and/or CA 15-3 were determined in 1,575 patients with non-purulent exudates, 549 of whom had confirmed MPEs, 284 probable MPEs, and 742 benign effusions. Tumor marker cut-off points were set to ensure 100% specificity for malignant effusion. Results: The 41, 40 and 60% of MPE patients had high PF levels of CEA (>45 ng/mL), CA 15-3 (>77 UI/l) or both, respectively. These percentages were 30, 19 and 41% in MPEs with positive pleural biopsy and negative PF cytology; and 24, 13 and 35% in clinical MPEs without histocytological confirmation. Tumor markers were of no value in lymphomas and mesotheliomas. The area-under-the-curve for CEA was 0.819 (95% CI: 0,793-0,845) and for CA 15-3, it was 0.822 (95% CI: 0,796-0,847). The use of tumor markers compared to cytology alone, increased the diagnosis of malignancy by 14%. Conclusions: Measurements of PF CEA and CA 15-3 may complement pleural cytology in the identification of MPEs (AU)

Utility of CEA and CA 15-3 measurements in non-purulent pleural exudates in the diagnosis of malignancy: A single-center experience. / Utilidad de la medición de CEA y CA 15-3 en los exudados pleurales no purulentos para diagnosticar malignidad: experiencia de un único centro.

OBJECTIVE: To establish the diagnostic accuracy of pleural fluid (PF) CEA and CA 15-3 in identifying malignancy, and to determine the additional value of these markers in patients with malignant pleural effusions (MPEs) with false negative results from cytological fluid examination. METHODS: PF concentrations of CEA and/or CA 15-3 were determined in 1,575 patients with non-purulent exudates, 549 of whom had confirmed MPEs, 284 probable MPEs, and 742 benign effusions. Tumor marker cut-off points were set to ensure 100% specificity for malignant effusion. RESULTS: The 41, 40 and 60% of MPE patients had high PF levels of CEA (>45ng/mL), CA 15-3 (>77 UI/l) or both, respectively. These percentages were 30, 19 and 41% in MPEs with positive pleural biopsy and negative PF cytology; and 24, 13 and 35% in clinical MPEs without histocytological confirmation. Tumor markers were of no value in lymphomas and mesotheliomas. The area-under-the-curve for CEA was 0.819 (95% CI: 0,793-0,845) and for CA 15-3, it was 0.822 (95% CI: 0,796-0,847). The use of tumor markers compared to cytology alone, increased the diagnosis of malignancy by 14%. CONCLUSIONS: Measurements of PF CEA and CA 15-3 may complement pleural cytology in the identification of MPEs.

Clinical features and survival of lung cancer patients with pleural effusions.

BACKGROUND AND OBJECTIVE: The clinical relevance of pleural effusions in lung cancer has seldom been approached systematically. The aim of this study was to determine the prevalence, causes and natural history of lung cancer-associated pleural effusions, as well as their influence on survival. METHODS: Retrospective review of clinical records and imaging of 556 consecutive patients with a newly diagnosed lung cancer over a 4-year period at our institution. RESULTS: Lung cancer comprised 490 non-small cell and 66 small cell types. About 40% of patients with lung cancer developed pleural effusions at some time during the course of their disease. In half the patients, the effusions were too small to be tapped. These effusions did not progress to require a pleural intervention. Patients with minimal effusions had a worse prognosis compared to patients without pleural effusions (median survival of 7.49 vs 12.65 months, P < 0.001). Less than 20% of the 113 patients subjected to a diagnostic thoracentesis had benign causes for their effusions. Palliative pleural procedures (like therapeutic thoracenteses, pleurodesis or tunnelled pleural catheters) were conducted in 79 (84%) of the 94 malignant effusions. An effusion's size equal to or greater than half of the hemithorax was a strong predictor of the need for a palliative procedure. Overall survival of patients with malignant effusions was 5.49 months. CONCLUSIONS: Malignant pleural effusions are a poor prognostic factor in the setting of lung cancer, which includes minimal effusions not amenable to tapping.

Comparison of pleural N-terminal pro-B-type natriuretic peptide, midregion pro-atrial natriuretic peptide and mid-region pro-adrenomedullin for the diagnosis of pleural effusions associated with cardiac failure.

BACKGROUND AND OBJECTIVE: The purpose of this study was to compare the diagnostic utility of pleural fluid N-terminal pro-B-type natriuretic peptide (NT-proBNP), midregion pro-atrial natriuretic peptide (MR-proANP) and midregion pro-adrenomedullin (MR-proADM) for discriminating heart failure (HF)-associated effusions. METHODS: NT-proBNP, MR-proANP and MR-proADM were measured by commercially available methodologies in the pleural fluid of a retrospective cohort of 185 consecutive patients with pleural effusions, of whom 95 had acute decompensated HF. Receiver-operating characteristic and area under the curve (AUC) analyses allowed comparisons of the discriminative properties of these biomarkers to be made at their optimal cut-off points. RESULTS: The diagnostic accuracy of NT-proBNP and MR-proANP for HF as quantified by the AUC was 0.935 and 0.918, respectively, whereas MR-proADM was of limited value (AUC = 0.62). A pleural fluid MR-proANP >260 pmol/L or NT-proBNP >1700 pg/mL argues for HF (likelihood ratio (LR) positive >5), while levels below these cut-off values significantly decrease the probability of having the disease (respective LR negative 0.19 and 0.10). The optimal cut-off points for natriuretic peptides were influenced by age, renal function and body mass index. Finally, both NT-proBNP and the albumin gradient correctly identified more than 80% of those cardiac effusions misclassified as exudates by standard criteria. CONCLUSIONS: MR-proANP is as valuable a diagnostic tool as NT-proBNP for diagnosing or excluding HF as the cause of pleural effusion.