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: 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.

We report the case of a 56-year-old patient who underwent left single lung transplantation for idiopathic pulmonary fibrosis (IPF). Despite the high level of immunosuppression after the surgery, there was rapid progression to IPF in the native (right) lung as demonstrated by thoracoscopic lung biopsy. After 104 days on mechanical ventilation, the patient underwent right lung transplant and was discharged from the hospital on postoperative day 26.

Keywords: Idiopathic pulmonary fibrosis; Lung transplantation; Case reports [publication type].

Abstract Objective: The incidence of tuberculosis worldwide has emphasized the need for better assays designed to diagnose the disease, principally the extrapulmonary form. The objective of the present study was to validate the performance of an automated method for the determination of adenosine deaminase (ADA) activity in pleural fluid (PF) and cerebrospinal fluid (CSF), comparing it with a conventional method (the modified Giusti method). Methods: In total, 134 samples were selected from among those tested in our laboratory: 94 PF samples and 40 CSF samples. The ADA activity was determined using the two methods. Inter- and intra-assay precision was determined, linear regression analysis was performed, simple concordance tests were conducted, and the means of the differences were calculated. Results: The correlation coefficients for PF and CSF samples were, respectively, 0.96 and 0.95. Inter-assay precision was determined using 21 replicates at 3 different activity levels: low, medium and high. The percentage coefficient of variation (%CV) was, respectively, 5.9, 8.1 and 5.8 for PF samples, compared with 21.9, 18.6 and 13.8 for CSF samples. Intra-assay precision in %CV was 1.3 and 11.7, respectively, for PF and CSF samples. The concordance between the methods in PF and CRF samples was, respectively, 96.8% and 100%, considering the reference values for the diagnosis of TB to be 40 U/L (conventional) and 30 U/L (automated) in PF samples, versus 9 U/L (for both methods) in CSF samples. Conclusions: The results validate the use of the automated method of determining ADA activity in PF and CSF samples as an alternative to the conventional method.

Keywords: Adenosine deaminase; Tuberculosis/diagnosis; Pleural effusion; Cerebrospinal fluid.

Biological markers are cellular, structural and biochemical components that can define cellular as well as molecular changes in both normal and neoplastic cells. There are two types of biological markers: 1) intermediate markers that evaluate cellular and molecular alterations before malignancy occurs; and 2) diagnostic markers, present in association with malignancy. The identification and validation of biological markers for clinical use are performed in stages: initial identification in cell cultures of the tumor;
testing of the marker in tissues obtained in biopsies of patients with an established diagnosis of the tumor;
testing of biopsies of normal tissues and tissues with an inflammatory process;
sputum, blood or urine tests for validation as a non-invasive test that can be used in high-risk populations. Sorologic and histopathologic biological markers are cellular, structural and biochemical components found in both normal and neoplastic cells that can be quantitatively assessed by biochemical, immunological and molecular methods in the body fluids or tissues, respectively, and may be associated with malignancies and, possibly, with the neoplastic organ. Biological markers are studied in diverse primary neoplasms. However, few of them proved to be clinically valuable. The role of biological markers in lung cancer patients remains unclear because only a small number of markers has been properly identifiassessed. The aim of this paper is to understand the role of sorologic and histologic biological markers in the prognosis and survival of lung cancer patients based on our previous works. Furthermore, we present a future perspective of the early detection of lung cancer on the basis of the role of intermediate biological markers.

Keywords: Biologic markers. Lung cancer. Prognosis. Survival. Morphometric method.

Lung transplantation is the most effective modality for the treatment of patients with end-stage lung diseases. Unfortunately, many people cannot benefit from this therapy due to insufficient donor availability. In this review and update article, we discuss donation after circulatory death (DCD), which is undoubtedly essential among the strategies developed to increase the donor pool. However, there are ethical and legislative considerations in the DCD process that are different from those of donation after brain death (DBD). Among others, the critical aspects of DCD are the concept of the end of life, cessation of futile treatments, and withdrawal of life-sustaining therapy. In addition, this review describes a rationale for using lungs from DCD donors and provides some important definitions, highlighting the key differences between DCD and DBD, including physiological aspects pertinent to each category. The unique ability of lungs to maintain cell viability without circulation, assuming that oxygen is supplied to the alveoli-an essential aspect of DCD-is also discussed. Furthermore, an updated review of the clinical experience with DCD for lung transplantation across international centers, recent advances in DCD, and some ethical dilemmas that deserve attention are also reported.

Keywords: Tissue and organ procurement; Brain death; Lung transplantation; Respiratory insufficiency.

Although the incidence of bronchial anastomosis as a complication of lung transplantation has decreased in recent years, it remains a significant cause of morbidity and mortality in these patients. Treatment options include balloon dilatation, laser photocoagulation, placement of a stent (silicone or metal), and performing a second operation. We report the case of a patient who presented bronchial stenosis after left lung transplantation and was treated with a self-expanding metal alloy (nitinol) stent (UltraflexÒ). Despite the fact that this was the first case of stenosis treated in this fashion in Brazil, the positive clinical response, in agreement with results reported in the literature, indicates that this treatment is a viable alternative in such cases.

Keywords: Lung transplantation. Tracheal stenosis. Prosthesis and implants. Stents. Postoperative complications.

Objective: To evaluate whether methylene blue (MB) could minimize the effects of ischemia-reperfusion injury in the nonischemic lung on a lung transplantation rodent model. Methods: Forty female Sprague-Dawley rats were divided into 20 donors and 20 recipients. The 20 recipient rats were divided into two groups (n = 10) according to the treatment (0.9% saline vs. 1% MB solutions). All animals underwent unilateral lung transplantation. Recipients received 2 mL of saline or MB intraperitoneally prior to transplantation. After 2 h of reperfusion, the animals were euthanized and histopathological and immunohistochemical analyses were performed in the nonischemic lung. Results: There was a significant decrease in inflammation-neutrophil count and intercellular adhesion molecule-1 (ICAM-1) expression in lung parenchyma were higher in the saline group in comparison with the MB group-and in apoptosis-caspase-3 expression was higher in the saline group and Bcl-2 expression was higher in MB group. Conclusions: MB is an effective drug for the protection of nonischemic lungs against inflammation and apoptosis following unilateral lung transplantation in rats.

Keywords: Reperfusion injury; Methylene blue; Lung transplantation; Apoptosis; Inflammation.

Background: The diagnosis of pleural tuberculosis continues to be a challenge due to the low sensitivity of traditional diagnostic methods. Histopathological examination of pleural tissue is the most accurate method, with a sensitivity of up to 80%. Determination of adenosine deaminase levels is a recently introduced method, although its usefulness in the diagnosis of pleural tuberculosis in Brazil has yet to better elucidated. Objective: To verify the sensitivity and specificity of an experimental method of measuring adenosine deaminase activity in pleural fluid in a series of patients with pleural effusion patients evaluated between August 1998 and November 2002 in Rio de Janeiro (RJ). Results: Out of 137 cases, 111 pleural fluid samples were available. Of those, 83 were from pleural tuberculosis patients. Among the 67 pleural tuberculosis patients tested, 10 (14.9%) presented human immunodeficiency virus. The adenosine deaminase cutoff value of 35U/L was determined by a receiver operator characteristic curve. The sensitivity, specificity and likelihood ratios (positive and negative) were 92.8%, 93.3%, 25.8 and 13.9, respectively. Mean adenosine deaminase in the pleural tuberculosis group was 84.7 ± 43.1 U/L, versus 15.9 ± 11.1 U/L in the group with other diseases. There was no significant difference in adenosine deaminase activity between patients with and without human immunodeficiency virus co-infection. Conclusions: Adenosine deaminase measurement in pleural fluid is a sensitive and specific method for the diagnosis of pleural tuberculosis and its use can preclude the need for pleural biopsy in the initial workup of pleural effusion patients. An adenosine deaminase cutoff value of 35U/L is recommended.

Keywords: Pleural fluid. Adenosine deaminase. Diagnosis. Tuberculosis. HIV

The objective of this study was to review the literature on bronchoalveolar lavage fluid cell profiles in healthy children and adolescents, as well as on the use of BAL as a diagnostic and follow-up tool for lung disease patients in this age bracket. To that end, we used the Medline database, compiling studies published between 1989 and 2009 employing the following MeSH descriptors (with Boolean operators) as search terms: bronchoalveolar lavage AND cytology OR cell AND child. In healthy children, the cell profile includes alveolar macrophages (> 80%), lymphocytes (approximately 10%), neutrophils (approximately 2%) and eosinophils (< 1%). The profile varies depending on the disease under study. The number of neutrophils is greater in wheezing children, especially in non-atopic children, as well as in those with pulmonary infectious and inflammatory profiles, including cystic fibrosis and interstitial lung disease. Eosinophil counts are elevated in children/adolescents with asthma and can reach high levels in those with allergic bronchopulmonary aspergillosis or eosinophilic syndromes. In a heterogenous group of diseases, the number of lymphocytes can increase. Evaluation of the BAL fluid cell profile, when used in conjunction with clinical and imaging findings, has proven to be an essential tool in the investigation of various lung diseases. Less invasive than transbronchial and open lung biopsies, BAL has great clinical value. Further studies adopting standard international protocols should be carried out. Such studies should involve various age groups and settings in order to obtain reference values for BAL fluid cell profiles, which are necessary for a more accurate interpretation of findings in children and adolescents with lung diseases.

Keywords: Bronchoalveolar lavage; Bronchoalveolar lavage fluid/cytology; Child; Adolescent.

Despite preventive measures, lung hyperinflation is a relatively common complication following single lung transplantation to treat pulmonary emphysema. The progressive compression of the graft can cause mediastinal shift and respiratory failure. In addition to therapeutic strategies such as independent ventilation, the treatment consists of the reduction of native lung volume by means of lobectomy or lung volume reduction surgery. We report two cases of native lung hyperinflation after single lung transplantation. Both cases were treated by means of lobectomy or lung volume reduction surgery.

Keywords: Lung transplantation; Postoperative complications; Pulmonary emphysema; Pneumonectomy.

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

The increasing demand in transplantation research requires efficient and less expensive animal models in order to obtain reliable results that are reproducible in larger animal models and, ultimately, applied clinically. The model of unilateral left lung transplantation in rats has proven to be a useful alternative for those purposes. We demonstrate a technical modification of this model, which consists of the isolation and ligation of the contralateral (right) pulmonary artery, allowing blood circulation exclusively in the transplanted lung. This model is feasible and reproducible. However, the short survival time restricts the assessment of the transplanted lung to a maximum period of three hours.

Objectives: Pleural tuberculosis (PlTB) diagnosis is a challenge due to its paucibacillary nature and to the need of invasive procedures. This study aimed to identify easily available variables and build a predictive model for PlTB diagnosis which may allow earlier and affordable alternative strategy to be used in basic health care units. Methods: An observational cross-sectional study compared PlTB and non-TB patients followed at a tertiary Brazilian hospital between 2010 and 2018. Unconditional logistic regression analysis was performed and a Decision Tree Classifier (DTC) model was validated and applied in additional PlTB patients with empiric diagnosis. The accuracy (Acc), sensitivity (Se), specificity (Sp), positive and negative predictive values were calculated. Results: From 1,135 TB patients, 160 were considered for analysis (111 confirmed PlTB and 49 unconfirmed PlTB). Indeed, 58 non-TB patients were enrolled as controls. Hyporexia [adjusted odds ratio (aOR) 27.39 (95% CI 6.26 - 119.89)] and cellular/biochemical characteristics on pleural fluid (PF) (polimorphonuclear in two categories: 3-14% aOR 26.22, 95% CI 7.11 - 96.68 and < 3% aOR 28.67, 95% CI 5.51 - 149.25; and protein = 5g/dL aOR 7.24, 95% CI 3.07 - 17.11) were associated with higher risk for TB. The DTC constructed using these variables showed Acc=87.6%, Se=89.2%, Sp=84.5% for PlTB diagnosis and was successfully applied in unconfirmed PlTB patients. Conclusion: The DTC model showed an excellent performance for PlTB diagnosis and can be considered as an alternative diagnostic strategy by using clinical patterns in association with PF cellular/biochemical characteristics, which were affordable and easily performed in basic health care units.

Keywords: Pleural tuberculosis; Diagnosis; Decision tree classifier.