Objective: To determine the levels of the tumor markers carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21-1) and carbohydrate antigen 15-3 (CA 15-3) in the blood and pleural fluid of patients with benign or malignant pleural effusion, evaluating the sensitivity of each marker in these fluids. Methods: We prospectively evaluated 85 patients with pleural effusion. The study of the pleural fluid observed the criteria established in the literature. Levels of the markers were determined using electrochemiluminescence. The sensitivity was determined on the condition that the specificity was ≥ 90%. Results: Of the 85 cases, 36 (42.4%) were malignant, 30 (35.3%) were benign, and the results were inconclusive in 19 (22.3%). In the malignant cases, the CEA and CYFRA21-1 levels were higher in the pleural fluid than in the blood, which was not observed for CA 15-3. In the benign cases, the CYFRA21-1 levels were higher in the pleural fluid than in the blood, whereas the opposite was found for CEA and CA 15-3. There were significant differences between malignant and benign cases for all markers, in pleural fluid and blood. In the pleural fluid, the sensitivity of CEA, CYFRA21-1 and CA 15-3 was 69.4, 69.4 and 66.7%, respectively, and the combined sensitivity was 80.6%. In the blood, the sensitivity was 57.1%, 71.4% and 48.6% for CEA, CYFRA21-1 and CA 15-3, respectively, and the combined sensitivity was 77%. Conclusion: The results suggest that these markers might be useful in the differentiation between malignant and benign pleural effusion.

Keywords: Biological tumor marker; Cyfra 21.1; CEA; CA 15.3; Pleural effusion.

Objective: The objective of this study was to identify the clinical and pathological factors that can influence the prognosis of breast cancer patients with clinical symptoms of malignant pleural effusion. Methods: This was a clinical cohort study, in which we analyzed the medical charts of patients diagnosed with malignant pleural effusion between 2006 and 2010. By examining the charts, we identified the female patients with a history of breast cancer. For those patients, we collected pathology data related to the primary tumor and cytopathology data related to the pleural metastasis. Results: We evaluated 145 patients, 87 (60%) of whom had tested positive for malignant cells in the pleural fluid. Ductal histology was observed in 119 (82%). The triple-negative breast cancer phenotype was seen in 25 cases (17%). Those patients had the worst prognosis (with a sharp decline in the survival curve), and 20 of the 25 (80%) died during the follow-up period (through June of 2011). The mean survival after the identification of malignant pleural effusion was 6 months. Conclusions: In patients with triple-negative breast cancer who test positive for malignant cells in the pleural fluid, the prognosis is poor and survival is reduced.

Keywords: Pleural effusion, malignant/mortality; Breast neoplasms/mortality; Breast neoplasms/genetics.

Background: The decision to drain parapneumonic pleural effusion in children is still controversial. An indicative scoring system to assess the need for chest-tube drainage arose from a partnership between pediatricians and surgeons. Objective: To evaluate the utility of the score in indicating whether drainage should be performed in pediatric patients with parapneumonic effusion. Method: A cross-sectional study involving 250 inpatients with parapneumonic effusion, treated in a tertiary-care hospital between 1994 and 1999. The following variables were analyzed: clinical presentation, chest X-rays, pleural fluid culture and biochemical analysis of the pleural fluid, as well as the score and treatment. The score was based on four categories: general appearance of the pleural fluid, chest X-rays, laboratory findings, and the second thoracentesis. Drainage was recommended for patients scoring higher than 5.5. Results: Of 941 children with pneumonia, parapneumonic effusion occurred in 304 (32.2%), 250 of which were included in the study. Of those, 146 (58.4%) were male, with mean of age of 3 years (median, 2 years). The cutoff points (determined through receiver operating characteristic curve analysis) for suggesting pleural drainage were pH < 7.29 (89.2% sensitivity and 76.5% specificity), score > 5.0 (68.7% sensitivity and 81.7% specificity). These values were more strongly correlated with the need for drainage (p = 0.001), as were those reported in the literature (pH = 7.0 and glucose < 40). The lactate dehydrogenase did not prove to be a good parameter for indicating a need for drainage. Conclusion: In addition to the purulent aspect, pH = 7.29 and score were the best indicators of the need for chest-tube drainage in pediatric patients with parapneumonic effusion. However, we suggest that some score variables be readjusted to improve the usefulness of this particular scoring system.

Keywords: Empyema. Pleural effusion. Pneumonia.

The usefulness of serum tumor markers in lung cancer is not well defined. Objective: The aim of this study is to examine the correlation between serum tumor markers and tumor extension and its prognostic value. Patients and method: From February 1995 to September 1997, 103 patients with non-small cell lung carcinoma were evaluated at the Department of Thoracic Surgery. Serum levels of CEA, CYFRA21.1, CA15.3, CA19.9, CA72.4, and NSE were determined before treatment. Results: The serum level of CYFRA21.1 was the most frequent elevated tumor marker (55%). Patients with advanced tumor had higher mean serum level of CEA (90.8 ng/ml), CYFRA21.1 (20.3 ng/ml) and CA15.3 (56.5%) than those with localized carcinoma, respectively 10.2 ng/ml, 12.6 ng/ml and 22.2 ng/ml. Considering all serum tumor markers evaluated in this study, only patients with elevated CEA had greater chance (5.6) of presenting with advanced non-small lung carcinoma than patients with normal CEA. Overall survival was influenced by performance status (p = 0.001), tumor extension (p = 0.006), elevated serum level of CEA (p = 0.043), more than two elevated serum tumor markers (p < 0.001), and type of treatment (p < 0.001). The prognostic value of anatomical tumor extension reached the limit of significance (p = 0.052); however, two or more elevated serum tumor markers and type of treatment had independent prognostic value (respectively, p = 0.035 and p = 0.005). Conclusion: None of these serum tumor markers had clinical value in the management of NSCLC patients.

Keywords: biological tumor markers, neoplasm staging, non-small cell lung carcinoma, prognosis

Objective: To evaluate the role of intrapleural positioning of a pleural catheter in early lung expansion and pleurodesis success in patients with recurrent malignant pleural effusion (RMPE). Methods: This was a retrospective study nested into a larger prospective cohort study including patients with RMPE recruited from a tertiary university teaching hospital between June of 2009 and September of 2014. The patients underwent pleural catheter insertion followed by bedside pleurodesis. Chest CT scans were performed twice: immediately before pleurodesis (iCT) and 30 days after pleurodesis (CT30). Catheter positioning was categorized based on iCT scans as posterolateral, anterior, fissural, and subpulmonary. We used the pleural volume on iCT scans to estimate early lung expansion and the difference between the pleural volumes on CT30 and iCT scans to evaluate radiological success of pleurodesis. Clinical pleurodesis success was defined as no need for any other pleural procedure. Results: Of the 131 eligible patients from the original study, 85 were included in this nested study (64 women; mean age: 60.74 years). Catheter tip positioning was subpulmonary in 35 patients (41%), anterior in 23 (27%), posterolateral in 17 (20%), and fissural in 10 (12%). No significant differences were found among the groups regarding early lung expansion (median residual pleural cavity = 377 mL; interquartile range: 171-722 mL; p = 0.645), radiological success of pleurodesis (median volume = 33 mL; interquartile range: −225 to 257 mL; p = 0.923), and clinical success of pleurodesis (85.8%; p = 0.676). Conclusions: Our results suggest that the position of the tip of the pleural catheter influences neither early lung expansion nor bedside pleurodesis success in patients with RMPE.

Keywords: Pleurodesis; Pleural effusion, malignant; Tomography; Catheters.

Our objective was to determine the levels of lactate dehydrogenase, IL-6, IL-8, and VEGF, as well as the total and differential cell counts, in the pleural fluid of lung transplant recipients, correlating those levels with the occurrence and severity of rejection. We analyzed pleural fluid samples collected from 18 patients at various time points (up to postoperative day 4). The levels of IL-6, IL-8, and VEGF tended to elevate in parallel with increases in the severity of rejection. Our results suggest that these levels are markers of acute graft rejection in lung transplant recipients.

Keywords: Lung transplantation; Pleural effusion; Cytokines; Graft rejection.

Objective: Previous studies have demonstrated that closed pleural biopsy (CPB) has a sensitivity of less than 60% for diagnosing malignancy. Therefore, controversy has recently emerged regarding the value of CPB as a diagnostic test. Our objective was to assess the accuracy of CPB in diagnosing malignancy in patients with pleural effusion. Methods: This was a prospective 8-year study of individuals who underwent CPB to establish the etiology of pleural effusion. Information on each patient was obtained from anatomopathological reports and medical records. When CPB findings showed malignancy or tuberculosis, the biopsy was considered diagnostic, and that was the definitive diagnosis. In cases in which biopsy histopathological findings were nonspecific, a definitive diagnosis was established on the basis of other diagnostic procedures, such as thoracoscopy, thoracotomy, fiberoptic bronchoscopy, biochemical and cellular measurements in pleural fluid, and/or microbiological tests. The accuracy of CPB was determined with 2 × 2 contingency tables. Results: A total of 1034 biopsies from patients with pleural effusion were studied. Of those, 171 (16.54%) were excluded from the accuracy analysis either because of inadequate samples or insufficient information. The results of the accuracy analysis were as follows: sensitivity, 77%; specificity, 98%; positive predictive value, 99%; negative predictive value, 66%; positive likelihood ratio, 38.5; negative likelihood ratio, 0.23; pre-test probability, 2.13; and post-test probability, 82. Conclusions: CPB is useful in clinical practice as a diagnostic test, because there is an important change from pre-test to post-test probability.

Keywords: Biopsy; Pleural effusion, malignant/diagnosis; Pleural effusion, malignant/epidemiology.

Objective: Assess the relationship between adherence to long-term oxygen therapy (LTOT) with mortality in patients with chronic obstructive pulmonary disease (COPD) and chronic respiratory failure and their clinical features. Methods: Longitudinal retrospective analysis of 254 patients with COPD and chronic respiratory failure from 2008 to 2016. At baseline, we evaluated the diagnosis, spirometry values, arterial blood gas analysis, blood count, pulse oximetry, body composition and health questionnaires (dyspnea, quality of life, anxiety and depression). For referred adherence analysis to LTOT we included 199 patients, divided according to prescription of oxygen: 12h/day (G1), 15h/day (G2) and 24h/day (G3). The cause of death and dates were studied over the five-year period. Results: In five years we identified 124 deaths (62.3%). No significant difference was found in mortality between the adherence groups (p=0.75) nor did we find differences in the clinical parameters evaluated. LTOT prescription was not associated with mortality (p=0.07). In Cox regression analysis, there was no association between mortality and non-adherence to LTOT (HR: 0.75; IC95%: 0.21-2.70). The risk of mortality was increased in G3 compared with G1 (HR: 7.16; IC 95%: 1.44-35.38) and in those with a higher depression score (HR: 1.35; IC: 1.14-1.59). Conclusion: No association was found between LTOT adherence and mortality in patients with COPD and respiratory failure. There were no clinical differences between the adherence groups.

Keywords: Chronic obstructive pulmonary disease; Oxygen therapy; Cooperation and treatment adherence; Morbidity and mortality indicators.

A significant percentage of pleural effusions remains without a diagnostic explanation. In such circumstances, the anatomical-pathological result of nonspecific chronic pleuritis should be revised. This is an important issue, not only for the pathologist, but mainly for the pneumologist, who usually makes the clinical-pathological correlation during the routine practice. Although the existence of established criteria is accepted, they are certainly subjective and make the communication by means of a common language difficult, mainly among pathologists. The authors recently studied 311 pleural biopsies with histo-pathological diagnoses of chronic nonspecific pleuritis. All specimens were reviewed and the histo-pathological parameters quantified by stereology. The patients were stratified according to the final diagnosis of their disease, including cases of chronic renal failure, vasculitis, pancreatitis, tuberculosis, cancer, and congestive cardiac failure, in this case considering the pleura as normal. This procedure allowed us to obtain a discriminating model, whose morphological subcriteria classified almost 90% of the nonspecific chronic pleuritis biopsies, according to their final clinical diagnoses, which included true nonspecific chronic pleuritis or tuberculosis pleuritis, paraneoplastic pleuritis, or even normal pleura. By adding to this model the biochemistry or differential cytology of the pleural liquid, its classificatory power reaches 99% of correctness. This study represents the result of the experience acquired over several years in the histo-pathological interpretation of pleural biopsies, based on the correlation between morphology and biochemistry and cytology of the pleural fluid.

Keywords: Biopsy, needle. Pleura/pathology. Pleura/cytology. Pleural effusion.

Objective: To evaluate the safety and feasibility of the use of indwelling pleural catheters (IPCs) in patients with malignant pleural effusion (MPE). Methods: We prospectively collected data from patients with MPE undergoing IPC placement between January of 2014 and July of 2015. All patients submitted to IPC placement had a life expectancy > 30 days, in accordance with the MPE treatment guidelines established by the British Thoracic Society. The data collected included gender, age, body mass index, primary cancer site, duration of IPC drainage, IPC-related complications, length of hospital stay, pleural effusion recurrence, and occurrence of spontaneous pleurodesis. Results: A total of 19 patients underwent IPC placement during the study period. Median overall survival after IPC insertion was 145 days. The median follow-up among the surviving patients was 125 days (range, 53-485 days), and the median time between catheter insertion and removal was 31 days (range, 2-126 days). There were IPC-related complications in 5 patients (26.2%), and spontaneous pleurodesis was achieved in 8 (42.0%). Among those 8 patients, the IPC was removed between days 30 and 126 in 4, and spontaneous pleurodesis occurred within the first 30 days in 4. Conclusions: The use of IPCs seems to be feasible and safe in patients with MPE.

Keywords: Pleural effusion, malignant; Survival; Palliative care.

Objective: To investigate the diagnostic value of α-enolase (ENO1) and serum ENO1 autoantibody levels in lung cancer. Methods: Immunohistochemistry staining and ELISA were performed to detect ENO1 expression in lung tissue and serum ENO1 autoantibody levels, respectively. Results: The expression of ENO1 was higher in lung cancer tissues than in benign lung disease tissues (p < 0.001). The proportion of lung cancer samples expressing ENO1 was not significantly different among the various pathological classification groups. The proportion of samples expressing ENO1 was higher in lung cancer patients in stages I/II than in those in stages III/IV (χ2 = 5.445; p = 0.018). The expression of ENO1 in lung cancer tissues was not associated with age, gender, or smoking history. Serum ENO1 antibody levels were significantly higher in the lung cancer group than in the benign lung disease and control groups (p < 0.001). The differences among the pathological classification groups were not statistically significant. Serum ENO1 antibody levels were also in lung cancer patients in stages I/II than in those in stages III/IV (p < 0.01). Serum ENO1 antibody levels were not associated with age, gender, or smoking history in lung cancer patients. The ROC curve representing the diagnosis of lung cancer based on ENO1 antibody levels had an area under the curve of 0.806. Conclusions: Our results suggest that high levels of ENO1 are associated with the clinical stage of lung cancer and that ENO1 expression and its serum autoantibody levels show diagnostic value in lung cancer.

Keywords: Phosphopyruvate hydratase/analysis; Enzyme-linked immunosorbent assay; Immunohistochemistry; Lung neoplasms.

Objective: To evaluate the pattern of pro-inflammatory cytokines, anti-inflammatory cytokines and the acute phase response (APR) as markers of the response to treatment of pulmonary tuberculosis. Methods: Twenty-eight patients with pulmonary tuberculosis were evaluated at three time points: pretreatment (T0), treatment month 3 (T3) and treatment month 6 (T6). Levels of interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), interleukine-10 (IL-10) and transforming growth factor-beta (TGF-β) were determined using ELISA in the supernatant of peripheral blood mononuclear cell and monocyte culture. Levels of total protein, albumin, globulins, C-reactive protein (CRP), alpha-1-acid glycoprotein (AAG) and erythrocyte sedimentation rate (ESR) were also determined. All of these parameters were also evaluated, only once, in a group of healthy controls. Results: In relation to controls, patients presented cytokine levels and APR that were higher at T0, lower at T3 and either lower (TNF-α, IL-10, TGF-β, AAG and ESR) or normal (IFN-γ and CRP) at T6. Conclusions: For individuals with negative smear sputum microscopy, CRP, AAG and ESR are potential markers of pulmonary tuberculosis and of the need for treatment; CRP (T0 > T3 > T6 = reference) can also be a marker of treatment response. In the patients, the Th0 profile (IFN-γ, IL-10, TNF-α and TGF-β), inducer of and protector against inflammation, predominated at T0, whereas the Th2 profile (IL-10, TNF-α and TGF-β), protecting against the harmful pro-inflammatory effect of the remaining TNF-α, predominated at T6. The behavior of IFN-γ (T0 > T3 > T6 = controls) suggests its use as a marker of treatment response.

Keywords: Acute-phase proteins; Cytokines; Mycobacterium tuberculosis; Tuberculosis/therapy.

Objective: To determine whether serum total IgE levels and total eosinophil counts have any relationship with the response to routine pharmacological treatment in patients with acute asthma. Methods: A cross-sectional study involving 162 patients with acute asthma. Serum total IgE levels, peripheral blood cell counts and eosinophil counts were determined. The treatment was adjusted for each patient according to the severity of asthma. Spirometry was performed at baseline and two weeks after the treatment. The patients were divided into two groups: high IgE (≥100 IU/mL) and low IgE (<100 IU/mL). We compared the two groups in terms of the relationships between baseline values and final values (percentage change) for the following parameters: FEV1, FVC, FEF25-75%, peripheral white blood cell counts and eosinophil counts. Results: There were no significant differences between the groups regarding the percentage changes of the studied parameters. Nor were there significant differences between the groups regarding FEV1, FVC, and FEF25-75% (% of the predicted values) at baseline. Conclusions: On the basis of these findings, we conclude that serum total IgE levels, peripheral white blood cell counts and eosinophil counts cannot predict the response to the pharmacological treatment of patients with acute asthma.

Keywords: Asthma/drug therapy; Eosinophils; Immunoglobulin E

Objective: To evaluate the results of thoracoscopy for the treatment of pleural empyema in pediatric patients. Methods: A retrospective study of 117 patients who underwent mediastinoscopy or video-assisted thoracoscopy for pleural empyema treatment. General anesthesia and single-lumen oral intubation were used. Surgery was indicated when there was pleural effusion and no clinical and radiological response to clinical treatment (antibiotics, physiotherapy and thoracocentesis) or severe sepsis, together with loculated pleural effusion (confirmed through ultrasound or computed tomography of the chest). Results: Between February of 1983 and July of 2006, 117 thoracoscopies were performed in patients ranging in age from 5 months to 17 years (mean, 4 years). Mean time for thoracic drainage was 9 days (range, 2-33 days), and mean period of hospitalization was 16.4 days (range, 4 to 49 days). One patient (0.8%) died after surgery, and persistent fistula was observed in 33 patients (28%). In 7 cases (6%), open thoracotomy with pulmonary decortication was performed due to the disposition of the empyema. Conclusions: Management of pleural empyema in this age bracket is still controversial, and surgical indication is often delayed, particularly when there are multiple loculations or severe sepsis. Early thoracoscopy yields a better clinical outcome for pediatric patients with pleural empyema, with apparent decreased morbidity and mortality, earlier chest tube removal, earlier hospital discharge and improved response to antibiotic therapy.

Keywords: Empyema, pleural; Pediatrics/instrumentation; Thoracoscopy; Thoracic surgery, video-assisted.

Objective: To evaluate Brazilian studies by summarizing the accuracy of adenosine deaminase in the diagnosis of the pleural tuberculosis, with the objective of lending support to the movement to make the test part of the routine in the investigation of pleural effusions. Methods: A search for Brazilian studies related to the determination of adenosine deaminase levels in the pleural liquid was carried out. These studies were evaluated and included in this study. The data were analyzed using summary receiver operating characteristic (SROC) curves, which enabled the studies to be collected and evaluated regarding the accuracy of the diagnosis. As for the global values of sensitivity and specificity, the Bayes' theorem was applied to calculate the post-test probabilities in different prevalences of the disease. Results: Twenty-five studies dating from 1987 to 2005 and including enough information to be used in the meta-analysis were identified. After evaluation, nine studies were included, totaling 1674 patients. According to the SROC curve, a sensitivity of 91.8% (95% CI: 89.8‑93.6%) and a specificity of 88.4% (95% CI: 86.0-90.5%) were found, with an area of 0.969 below the curve. The overall odds ratio was 112.0 (95% CI: 51.6-243.2). Considering a prevalence of tuberculosis of 50% (considered neutral), the post-test probability was 88.7% for a positive test and 91.5% for a negative test. Conclusion: Despite the differences found among studies, it is possible to conclude that the determination of adenosine deaminase levels has high accuracy in the diagnosis of the pleural tuberculosis and should be used as a routine test in its investigation.

Keywords: Pleural effusion; Tuberculosis; Diagnosis; Adenosine deaminase; Meta-analysis.