Silvia Bielsa

Diagnostic performance of adenosine deaminase activity in pleural fluid: a single-center experience with over 2100 consecutive patients.

OBJECTIVE To determine the diagnostic utility of adenosine deaminase (ADA) in a large series of pleural effusions of different etiologies. METHODS A retrospective study of 2104 consecutive patients presenting with pleural effusion was carried out at a Spanish university hospital. ADA levels in pleural fluid were determined using a non-Giusti automatic kinetic assay, and a receiver operating characteristics curve analysis was applied to estimate their discriminative properties. RESULTS Pleural tuberculosis (TB) accounted for 221 (10.5%) effusions. Pleural fluid ADA >35U/L yielded 93% sensitivity, 90% specificity, a positive likelihood ratio (LR) of 10.05 and a negative LR of 0.07 for the diagnosis of TB among lymphocytic exudates. The ADA activity was significantly higher in neutrophil- (111.6U/L) than in lymphocyte-rich (62.4U/L; p=0.002) TB effusions. Overall, more than 40% of parapneumonics and half of lymphomatous effusions exceeded the cutoff set for TB. These were the only causes of ADA activity above 250U/L. When the prevalence of TB as a cause of exudative effusions is low (e.g., 1%), the estimated positive predictive value of the ADA test may be as low as 7%, although the negative predictive value remains high (99.9%). CONCLUSION Where available, pleural ADA should be routinely used to rule TB in or out in areas with moderate to high or low TB prevalence, respectively. A high ADA level is a characteristic not only of lymphocytic, but also of neutrophilic TB effusions. An extremely high ADA activity should raise suspicion of empyema or lymphoma.

Biomarkers of infection for the differential diagnosis of pleural effusions

We aimed to investigate whether pleural fluid concentrations of biomarkers for bacterial infection, namely triggering receptor expressed on myeloid cells (sTREM-1), procalcitonin (PCT), lipopolysaccharide-binding protein (LBP) and C-reactive protein (CRP), might identify infectious effusions and discriminate between complicated (CPPEs) and uncomplicated parapneumonic effusions (UPPEs). Stored pleural fluid samples from 308 patients with different causes of pleural effusion were used to measure the four biomarkers. Receiver-operating characteristic analysis determined the accuracy of the new tests. Median pleural fluid levels of CRP, sTREM-1 and LBP were significantly higher in CPPE compared with those in other aetiologies. The area under the curve for distinguishing infectious (parapneumonics and tuberculosis) from noninfectious effusions was 0.87 for CRP, 0.86 for sTREM-1, 0.57 for PCT and 0.87 for LBP. Regarding the discrimination of nonpurulent CPPE versus UPPE, a multivariate analysis found that pleural fluid glucose ≤60 mg·dL−1, LBP ≥17 μg·mL−1 and CRP ≥80 mg·L−1 were the best parameters. Individually, none of the new biomarkers achieved better performance characteristics than pH, glucose or lactate dehydrogenase in labelling CPPE. In conclusion, elevated pleural fluid levels of CRP, sTREM and LBP identify patients with infectious effusions, particularly those with CPPE. PCT has no value for the differential diagnosis of pleural effusions.

Etiología del derrame pleural: análisis de más de 3.000 toracocentesis consecutivas

OBJECTIVE To investigate the etiology of pleural effusions (PE) in adults and the accuracy of pleural fluid (PF) cytology and cultures in malignant and infectious PE, respectively. PATIENTS AND METHODS Retrospective analysis of all consecutive patients with PE undergoing diagnostic thoracentesis during the last 19 years in a university hospital. RESULTS The leading causes of PE among the 3,077 patients were: cancer (27%), heart failure (21%), pneumonia (19%), tuberculosis (9%), abdominal surgery (4%), pericardial diseases (4%) and cirrhosis (3%). Tuberculosis was the most common etiology in patients <34 years of age (52%), whereas heart failure predominated in octogenarians (45%). The most common primary tumors in malignant PE were lung (37%) and breast (16%). The overall accuracy of PF cytology was 59%, although it was significantly lower in mesotheliomas (27%) and squamous cell lung cancer (25%). In infectious PE, only 30% of cultures yielded positive results, a percentage which increased two-fold (66%) in purulent fluids (empyemas). Viridans streptococci were the most commonly isolated pathogens (25.5%). The sensitivity of solid media cultures of PF for Mycobacterium tuberculosis was low (18.5%). CONCLUSIONS Three-quarters of patients with PE in whom a diagnostic thoracentesis was indicated had cancer, heart failure, pneumonia or tuberculosis. PF cytology and cultures give false negative results in a significant number of cases.

Prognostic significance of pleural fluid data in patients with malignant effusion.

BACKGROUND To determine the effects of the biochemical and cytological properties of the pleural fluid (PF) on the survival of patients with malignant pleural effusion (MPE). METHODS A retrospective study of 284 patients with MPE was performed, which measured overall survival, survival of patients with different types of primary tumors, and survival as a function of PF biochemical variables transformed into quartiles. RESULTS Median overall survival of MPE patients was 5.4 months following diagnosis. Survival varied significantly depending on the type of the primary tumor: 17.4 months for mesothelioma, 13.2 months for breast cancer, 7 months for lymphoma and 2.6 months for lung cancer. A multivariate analysis of PF biochemical parameters showed that survival was lower as the concentration of lactate dehydrogenase (LDH) increased (11.3 months if LDH was between 140 U/L and 358 U/L vs 2.8 months if LDH was between 1027 U/L and 10,110 U/L) or the concentration of pleural proteins decreased (9.4 months if proteins were between 4.92 g/dL and 7.94 g/dL vs 2.2 months if proteins were between 0.97 g/dL and 3.85 g/dL). We also found that when mesotheliomas were excluded from the analysis, survival was lower in patients with a PF pH lower than 7.3 (2.4 months vs 6.8 months, p=0.03). CONCLUSIONS Tumor type as well as some biochemical features of the pleural fluid, such as pH and concentrations of proteins and LDH, influence survival in patients with MPE.

Solving the Light's criteria misclassification rate of cardiac and hepatic transudates

Background and objective:  Pleural transudates are most commonly due to heart failure (HF) or hepatic hydrothorax (HH), but a number of these effusions are misclassified as exudates by standard (Lights) criteria. The aim of this study was to determine the prevalence of mislabelled transudates and to establish simple alternative parameters to correctly identify them.

Pleural fluid C-reactive protein contributes to the diagnosis and assessment of severity of parapneumonic effusions

BACKGROUND AND AIMS Prompt identification of parapneumonic effusions has immediate therapeutic benefits. We aimed to assess whether C-reactive protein (CRP) and routine biochemistries in pleural fluid are accurate markers of parapneumonic effusions, and to evaluate their properties as indicators for drainage (complicated parapneumonic effusion). METHODS A retrospective review of 340 non-purulent parapneumonic effusions and 1,659 non-parapneumonic exudates from a single center was performed and the discriminative properties of pleural fluid routine biochemistries and, when available, CRP were evaluated. CRP, along with classical fluid parameters, was also applied to classify patients as having complicated or uncomplicated parapneumonic effusions. ROC analysis established the threshold of CRP for discriminating between groups. RESULTS Pleural fluids with neutrophilic predominance and CRP levels >45 mg/dL were most likely to be parapneumonic in origin (likelihood ratio=7.7). When attempting to differentiate non-purulent complicated from uncomplicated effusions, a CRP >100mg/L had the same performance characteristics (area under the curve=0.81) as the widely accepted biochemistries pH and glucose. Combinations of CRP with pH or glucose resulted in incrementally discriminating values, pertaining to either sensitivity (75-80%) or specificity (97%), for complicated effusions. CONCLUSION Pleural fluid CRP may be a useful adjunctive test in pleural effusions, both as a marker of parapneumonics and, particularly, as a differentiator between complicated and uncomplicated effusions.

Diagnostic and Prognostic Implications of Pleural Adhesions in Malignant Effusions

Background and objective: We aimed to examine the frequency of pleural adhesions and to determine their relationship with pleural tumor burden, pleural fluid (PF) biochemistries, PF cytologic yield, and survival in patients with malignant pleural effusion (MPE). Methods: We performed retrospective analysis of 540 consecutive patients with MPE who underwent medical thoracoscopy. Pleural lesion rating and grade of pleural adhesions based on a thoracoscopic score model were recorded. Results: Sixty percent of patients with MPE were found to have adhesions in the pleural space. The sensitivity of PF cytology was 71% if there were no pleural adhesions, and 20% if the maximum adhesion score was reached (p < 0.01). The extent of pleural adhesions correlated positively with the pleural tumor burden, and inversely with PF pH. The median survival of patients with minimal or no adhesions in the pleural space was 9 months as compared with patients with the highest grade of adhesions, whose median survival was 5 months (p < 0.01). Conclusion: MPE are often loculated. The higher the grade of pleural adhesions, the greater the tumor burden exists, and paradoxically the lower the PF cytologic yield. The presence of pleural adhesions in MPE implies a poor prognosis.

Accuracy of Fluorodeoxyglucose-PET Imaging for Differentiating Benign From Malignant Pleural Effusions: A Meta-analysis

BACKGROUND The role of fluorodeoxyglucose (FDG)-PET imaging for diagnosing malignant pleural effusions is not well defined. The aim of this study was to summarize the evidence for its use in ruling in or out the malignant origin of a pleural effusion or thickening. METHODS A meta-analysis was conducted of diagnostic accuracy studies published in the Cochrane Library, PubMed, and Embase (inception to June 2013) without language restrictions. Two investigators selected studies that had evaluated the performance of FDG-PET imaging in patients with pleural effusions or thickening, using pleural cytopathology or histopathology as the reference standard for malignancy. Subgroup analyses were conducted according to FDG-PET imaging interpretation (qualitative or semiquantitative), PET imaging equipment (PET vs integrated PET-CT imaging), and/or target population (known lung cancer or malignant pleural mesothelioma). Study quality was assessed using Quality Assessment of Diagnostic Accuracy Studies-2. We used a bivariate random-effects model for the analysis and pooling of diagnostic performance measures across studies. RESULTS Fourteen non-high risk of bias studies, comprising 407 patients with malignant and 232 with benign pleural conditions, met the inclusion criteria. Semiquantitative PET imaging readings had a significantly lower sensitivity for diagnosing malignant effusions than visual assessments (82% vs 91%; P = .026). The pooled test characteristics of integrated PET-CT imaging systems using semiquantitative interpretations for identifying malignant effusions were: sensitivity, 81%; specificity, 74%; positive likelihood ratio (LR), 3.22; negative LR, 0.26; and area under the curve, 0.838. Resultant data were heterogeneous, and spectrum bias should be considered when appraising FDG-PET imaging operating characteristics. CONCLUSIONS The moderate accuracy of PET-CT imaging using semiquantitative readings precludes its routine recommendation for discriminating malignant from benign pleural effusions.

Original Research: Disorders of the PleuraAccuracy of Fluorodeoxyglucose-PET Imaging for Differentiating Benign From Malignant Pleural Effusions: A Meta-analysis

BACKGROUND The role of fluorodeoxyglucose (FDG)-PET imaging for diagnosing malignant pleural effusions is not well defined. The aim of this study was to summarize the evidence for its use in ruling in or out the malignant origin of a pleural effusion or thickening. METHODS A meta-analysis was conducted of diagnostic accuracy studies published in the Cochrane Library, PubMed, and Embase (inception to June 2013) without language restrictions. Two investigators selected studies that had evaluated the performance of FDG-PET imaging in patients with pleural effusions or thickening, using pleural cytopathology or histopathology as the reference standard for malignancy. Subgroup analyses were conducted according to FDG-PET imaging interpretation (qualitative or semiquantitative), PET imaging equipment (PET vs integrated PET-CT imaging), and/or target population (known lung cancer or malignant pleural mesothelioma). Study quality was assessed using Quality Assessment of Diagnostic Accuracy Studies-2. We used a bivariate random-effects model for the analysis and pooling of diagnostic performance measures across studies. RESULTS Fourteen non-high risk of bias studies, comprising 407 patients with malignant and 232 with benign pleural conditions, met the inclusion criteria. Semiquantitative PET imaging readings had a significantly lower sensitivity for diagnosing malignant effusions than visual assessments (82% vs 91%; P = .026). The pooled test characteristics of integrated PET-CT imaging systems using semiquantitative interpretations for identifying malignant effusions were: sensitivity, 81%; specificity, 74%; positive likelihood ratio (LR), 3.22; negative LR, 0.26; and area under the curve, 0.838. Resultant data were heterogeneous, and spectrum bias should be considered when appraising FDG-PET imaging operating characteristics. CONCLUSIONS The moderate accuracy of PET-CT imaging using semiquantitative readings precludes its routine recommendation for discriminating malignant from benign pleural effusions.

High levels of tumor markers in pleural fluid correlate with poor survival in patients with adenocarcinomatous or squamous malignant effusions

BACKGROUND The aim of this study was to determine whether several pleural fluid (PF) tumor markers, either alone or in combination, could be used to predict survival time of patients with malignant pleural effusion secondary to adenocarcinoma or squamous cell carcinoma. METHODS A total of 224 patients with confirmed metastatic pleural malignancies due to adenocarcinoma or squamous cell carcinoma were enrolled. PF tumor markers were determined either by electrochemiluminescence immunoassay (CEA, CA 15-3, CYFRA 21-1) or microparticle enzyme immunoassay (CA 125) technologies. Cutoff points that predicted death during the first month after diagnoses, with a specificity of 60%, were selected for each marker, using receiver operating characteristic analysis. RESULTS In patients with adenocarcinomatous or squamous malignant effusion, the combination of PF CA 125>or=1000 U/mL and CYFRA 21-1>or=100 ng/mL predicted a lower survival (4 vs. 11.7 months, p=0.03; and 0.3 vs. 8.4 months, p=0.003 respectively). This tumor marker combination remained as an independent predictor of poor outcome when adjusted for age and tumor type. CONCLUSION High PF tumor marker levels identify a subgroup of patients with a shorter median survival.