Meet in the middle: Could cell mediated-immunity assays be the answer for ideal Cytomegalovirus prophylaxis after lung transplantation? Observational study from a single center with intermittent antiviral prophylaxis.

BACKGROUND: Cytomegalovirus (CMV) can cause tissue-invasive disease and indirect effects after lung transplantation (LTx) such as acute rejection episodes and chronic lung allograft dysfunction. Monitoring CMV-specific cell immune recovery (CMV-CIR) after LTx can individualize CMV risks and establish better antiviral approach. This study evaluated the dynamics of CMV-CIR, using QuantiFERON-CMV assay (Qiagen Group), in the first year after LTx. METHODS: Prospective observational cohort study included lung transplant recipients from December/2015 to December/2016. Universal antiviral prophylaxis with intravenous ganciclovir 5 mg/kg/day 3 days/week for 3 months was given for CMV-seropositive recipients (R+) and only CMV-seropositive donor and negative recipient (D+/R-) received a 6-month-prophylaxis with ganciclovir and valganciclovir, on alternate days, in the first 3 months and then, 3 more months of valganciclovir. QuantiFERON-CMV was measured at the same time points of surveillance bronchoscopies. CMV infection was defined as any DNAemia detected and CMV disease with proven biopsy or antigenemia pp65 above 10 cells/300.000 neutrophils. RESULTS: Thirty-eight patients were included. On days 45, 90, and 365 days post-LTx, 60%, 72%, and 81% QuantiFERON-CMV were reactive, respectively. Eleven patients (28.9%) presented CMV-disease and 27 DNAemia/CMV infections. Reactive tests were able to predict CMV disease only at 90 days after LTx (p = .027) but failed on DNAemia/CMV infection (p = .148). Daily prophylaxis, for D+/R- patients (13.2%), remained as an independently associated factor for not achieving reactive QuantiFERON-CMV (adjusted OR .27, 95%CI .12-.60, p = .02). CONCLUSION: QuantiFERON-CMV may be another diagnostic tool to help stratify CMV-disease risk and individualized antiviral prophylaxis after LTx.

Shear stress-exposed pulmonary artery endothelial cells fail to upregulate HSP70 in chronic thromboembolic pulmonary hypertension.

The pathophysiological mechanisms underlying chronic thromboembolic pulmonary hypertension (CTEPH) are still unclear. Endothelial cell (EC) remodeling is believed to contribute to this pulmonary disease triggered by thrombus and hemodynamic forces disbalance. Recently, we showed that HSP70 levels decrease by proatherogenic shear stress. Molecular chaperones play a major role in proteostasis in neurological, cancer and inflammatory/ infectious diseases. To shed light on microvascular responses in CTEPH, we characterized the expression of molecular chaperones and annexin A2, a component of the fibrinolytic system. There is no animal model that reproduces microvascular changes in CTEPH, and this fact led us to isolated endothelial cells from patients with CTEPH undergoing pulmonary endarterectomy (PEA). We exposed CTEPH-EC and control human pulmonary endothelial cells (HPAEC) to high- (15 dynes/cm2) or low- (5 dynes/cm2) shear stress. After high-magnitude shear stress HPAEC upregulated heat shock protein 70kDa (HSP70) and the HSP ER paralogs 78 and 94kDa glucose-regulated protein (GRP78 and 94), whereas CTEPH-ECs failed to exhibit this response. At static conditions, both HSP70 and HSP90 families in CTEPH-EC are decreased. Importantly, immunohistochemistry analysis showed that HSP70 expression was downregulated in vivo, and annexin A2 was upregulated. Interestingly, wound healing and angiogenesis assays revealed that HSP70 inhibition with VER-155008 further impaired CTEPH-EC migratory responses. These results implicate HSP70 as a novel master regulator of endothelial dysfunction in type 4 PH. Overall, we first show that global failure of HSP upregulation is a hallmark of CTEPH pathogenesis and propose HSP70 as a potential biomarker of this condition.

Evaluation of cellular alterations and inflammatory profile of mesothelial cells and/or neoplastic cells exposed to talc used for pleurodesis.

Introdution: To determine the role of Pleural Mesothelial Cells (PMC) and/or Neoplasic Cells (NC) in the initiation and regulation of acute inflammatory response after exposure to talc for evaluating inflammatory mediators and cellular alterations. MATERIALS AND METHODS: PMC cultures, human lung (A549) and breast (MCF7) adenocarcinoma cells were divided in 5 groups: 100% PMC, 100% NC, 25% PMC + 75% NC, 50% of each type and 75% PMC + 25% NC. All groups were exposed to talc and measured IL-6, IL-1ß, IL-10, TNF-α, TNFRI, pH, LDH, apoptosis and necrosis. STATISTICAL ANALYSIS: One-way Anova. RESULTS: High IL-6, IL-1ß and TNFRI levels were found in PMC and NC exposed to talc. IL-6 was higher at the points of more confluence of PMC. The highest levels of IL-1ß and TNFRI were found in mixed cultures. In pure cultures TNFRI was higher in A549 followed by PMC and MCF7. LDH was higher in A549 than PMC. The lowest pH was found in 100% NC. All cell line exposed to talc reduced viability and increased necrosis. Apoptotic cells exposed to talc were higher in pure cultures of NC than in PMC. Mixed cultures of PMC and A549 showed lower levels of apoptosis in cultures with more NC. CONCLUSIONS: PMC after talc exposure participates in the inflammatory process contributing to production of molecular mediators, necessary for effective pleurodesis. Talc acted in NC causing higher rates of apoptosis, contributing in a modest way to tumoral decrease. Different types of tumor cells may respond differently to exposure to talc.

Influence of the progression of pleural neoplasia on the outcome of pleurodesis in mice.

PURPOSE: Experimental study aimed at evaluating whether pleural neoplastic disease is associated with the degree of pleural fibrosis over time caused by talc pleurodesis. The study describes changes in levels of inflammatory mediators and determines whether the course of time involved in progression of neoplastic pleural disease is the factor that influences safety of talc pleurodesis usage in mice. MATERIALS AND METHODS: Animals were randomized into two groups: Cancer group (CG) that received intrapleural injection of Lewis cells or Saline group (SG) that received saline injection. After, the animals were subdivided into Early (pleurodesis 3 days after pleural injection) and Late (pleurodesis 7 days after pleural injection) groups. Half of the animals in each group were euthanized 24 hours after pleurodesis (to obtain the inflammatory data); the remaining animals were killed after 8 days (to obtain the scores of pleural fibrosis). RESULTS: CGs had lower fibrosis scores than SGs comparing early phases to late phases. Inflammation scores were lower in CGs, particularly in Late group. In SGs the inflammation was intense in 100% of the animals. In Late CG group pleural adhesions had the lowest scores; we found intense fibrosis only in SGs. VEGF and LDH levels had increased in animals with cancer, particularly in Late group. Systemic distribution of talc occurred only in Late CG. CONCLUSIONS: The time for pleural neoplasia to evolve is inversely proportional to the degree of pleural fibrosis. Earlier pleurodesis yielded the best results related to fibrosis, with less systemic inflammation and is safer in mice.

Analysis of Quality of Life after Pleurodesis in Patients with Malignant Pleural Effusion.

BACKGROUND: Malignant pleural effusion is one of the most important complications of metastatic cancer, and recurrent pleural effusions do not only have an impact on survival but also cause a huge repercussion on a patient's quality of life. OBJECTIVES: The main objective was to describe quality of life status before and after pleurodesis in patients with malignant pleural effusion. Secondary, we aimed to find predictors of quality of life improvement in such a population. METHODS: Retrospective analysis of a database collected prospectively. We included patients who underwent pleurodesis from June 2004 to July 2014. Quality of life was evaluated through the WHOQOL-BREF questionnaire and applied before and 30 days after pleurodesis. We used a paired t test and the Wilcoxon rank-sum to compare pre-/post-pleurodesis results, Kaplan-Meier curves for survival analysis, and multiple linear regressions to find predictors of quality of life improvement. RESULTS: 183 patients were included (145 were women). Mean age was 58.3 ± 12.3 years, the most numerous primary tumor was breast cancer. Median survival time was 9 months. Dyspnea was the most prevalent symptom. Baseline results showed that patients had low quality of life scores. After pleurodesis, there was a significant improvement in respiratory symptoms, physical domain, and general health. Linear regression showed an improvement in physical domain with the sclerosing agent nitrate (p = 0.005). Male gender (p = 0.002) and a higher lymphocyte count (p = 0.01) were inversely associated with improvement in physical domain. CONCLUSIONS: Pleurodesis improved symptoms and quality of life in patients with malignant pleural effusion. Gender, lymphocyte count, and sclerosing agent might interfere with quality of life improvement.

Preanalytical conditions can interfere with M. tuberculosis detection by PCR in respiratory samples

OBJECTIVES: Tuberculosis is one of the most prevalent infections in humans. Although culture is the reference for diagnosis, its sensitivity is compromised, especially in paucibacillary samples. Because polymerase chain reaction (PCR) amplifies mycobacterial DNA, it is more sensitive than culture for the diagnosis of Mycobacterium tuberculosis (Mtb). However, its performance can be affected by intrinsic sample inhibitors and by the extraction/detection techniques used. METHODS: We evaluated the influence of preanalytical conditions on Mtb detection in samples of sputum (SPU), bronchoalveolar lavage (BAL), and pleural fluid (PF) using combinations of extraction/detection methods. Respiratory samples were prepared to contain different concentrations of red blood cells and nucleated cells to which increasing amounts of Mtb colonies were inoculated and submitted to PCR. RESULTS: Up to 102 CFU/ml of Mtb were detected in the SPU in all methods, except for the Roche extraction/detection method, regardless of the preanalytical sample condition. In BAL samples, medium and high concentrations of cells and high concentrations of red blood cells contributed to a lower Mtb detection, regardless of the extraction method used. In PF, red blood cells were the variable that most interfered with Mtb detection, with better recovery (102 CFU/ml) observed with the Qiagen/Nanogen combination. CONCLUSION: The choice of Mtb extraction and detection method is of fundamental importance for PCR analytical sensitivity, especially when paucibacillary samples and/or samples containing potential PCR inhibitors are analyzed.

Intrapleural targeted therapies (anti-VEGF and anti-EGFR) in the model of malignant pleural effusion.

RATIONALE: Malignant pleural effusion has few options of treatment and drugs administrated by different routes can lead to a less permissive microenvironment for the development of malignant pleural disease. OBJECTIVES: To analyze therapies administered intrapleurally in malignant pleural disease and to study EGFR and KRAS mutations in adenocarcinoma. METHODS: Mice received LLC cells and were treated intrapleurally with anti-VEGF, anti-EGFR, anti-VEGF+anti-EGFR or saline. Animal survival, weight and mobility, volume, biochemistry and immunology of fluid, gene expression, KRAS and EGFR mutation were evaluated. RESULTS: All animals developed malignant effusion and presented progressive weight loss without difference between groups; however, groups treated with anti-EGFR were more active. No difference in mortality was observed. Temporal increase of volume and inflammatory markers was observed mainly in the untreated group. Gene expression in tumors was overexpressed in VEGF, EGFR and KRAS compared with normal tissue. Mutation in exon 2 of the KRAS gene was observed. CONCLUSIONS: Intrapleural Anti-VEGF and/or anti-EGFR reduced volume and inflammatory mediators in pleural fluid. Anti-EGFR and anti-VEGF+anti-EGFR decreased morbidity although without impact on survival. LLC tumors presented KRAS mutation, this could have influenced the action of these therapies.

Profile of Metalloproteinases and Their Association with Inflammatory Markers in Pleural Effusions.

BACKGROUND: Matrix metalloproteinases (MMPs) are responsible for the breakdown of the extracellular matrix and play an important role in the inflammatory processes of pleural exudates. The imbalance between MMPs and their inhibitors (TIMPs) is present in various pathological processes. OBJECTIVE: To evaluate the profile of MMPs and TIMPs in pleural effusions of different etiologies correlated with inflammatory markers. METHODS: The patients with pleural effusion due to tuberculosis (TB), cancer (CA) or transudate were prospectively evaluated. Pleural fluid was submitted to cytological, biochemical, cytokines, MMP, and TIMP analysis. Statistical analysis was performed using ANOVA and Spearman's correlation, and p < 0.05 was considered significant. RESULTS: One hundred and fourteen patients were enrolled, 80 exudates (41 TB and 39 CA) and 34 transudates. The levels of MMP-8 and MMP-9 were higher in exudates compared to transudates. The level of MMP-8 was significantly higher in TB than in CA. TIMP-1 levels were higher in exudates. IL-6, VEGF, and TGF-ß1 showed differences between exudates and transudates. However, IL-6 level was higher in TB than in CA. We found a significant correlation between MMPs and TIMPs with inflammation markers. MMP-1 was correlated with LDH levels. MMP-8 was correlated with LDH, total cell count, neutrophils, and ADA as well as MMP-1 levels. MMP-9 was correlated with IL-6, TGF-ß1, and VEGF. TIMP-1 was correlated with MMP-9 and IL-6. CONCLUSIONS: MMPs and TIMPs are expressed in pleural fluid of different etiologies and correlate with inflammatory mediators. MMPs may be useful in determining the cause of fluid, but more studies are needed to determine the spectrum of diseases associated with the various isoforms of MMPS and TIMPs.

Pleural Fluid Adenosine Deaminase (ADA) Predicts Survival in Patients with Malignant Pleural Effusion.

PURPOSE: Systemic and local inflammations have been described as relevant prognostic factors in patients with cancer. However, parameters that stand for immune activity in the pleural space have not been tested as predictors of survival in patients with malignant pleural effusion. The objective of this study was to evaluate pleural lymphocytes and Adenosine Deaminase (ADA) as predictors of survival in patients with recurrent malignant pleural effusion. METHODS: Retrospective cohort study includes patients who underwent pleurodesis for malignant pleural effusion in a tertiary center. Pleural fluid protein concentration, lactate dehydrogenase, glucose, oncotic cytology, cell count, and ADA were collected before pleurodesis and analyzed. Survival analysis was performed considering pleurodesis as time origin, and death as the event. Backwards stepwise Cox regression was used to find predictors of survival. RESULTS: 156 patients (out of 196 potentially eligible) were included in this study. Most were female (72 %) and breast cancer was the most common underlying malignancy (53 %). Pleural fluid ADA level was stratified as low (<15 U/L), normal (15 ≤ ADA < 40), and high (≥40). Low and high ADA levels were associated with worse survival when compared to normal ADA (logrank: 0.0024). In multivariable analysis, abnormal ADA (<15 or ADA ≥ 40) and underlying malignancies different from lymphoma, lung, or breast cancer were associated with worse survival. Pleural fluid cell count and lymphocytes number and percentage did not correlate with survival. CONCLUSIONS: Pleural fluid Adenosine Deaminase levels (<15 or ≥40 U/L) and neoplasms other than lung, breast, or lymphoma are independent predictors of worse survival in patients with malignant pleural effusion who undergo pleurodesis.

Diagnóstico e tratamento dos derrames pleurais malignos / Diagnosis and treatment of malignant pleural effusions

Carcinomas brônquicos, com maior frequência os adenocarcinomas, linfomas e carcinoma de mama, constituem 75% das causas de derrame pleural maligno (DPM). Para utilização das diversas opções terapêuticas paliativas disponíveis deve ser considerada uma avaliação multidisciplinar do estado do paciente, em conjunto com a experiência do profissional médico assistente, a capacidade técnica da instituição onde o tratamento será realizado e o custo-benefício AU.

Lung cancer, more often adenocarcinomas, lymphomas and breast carcinoma, are 75.0% of the causes of malignant pleural effusion. Palliative therapeutic options should be considered a multidisciplinary assessment of the patient's condition, together with the experience of the physician assistant professional, technical capacity of the institution where the treatment will be carried out and cost-effective AU.

A modified experimental model of malignant pleural disease induced by lung Lewis carcinoma (LLC) cells.

BACKGROUND: Malignant pleural effusion resulting mainly from pleural metastases of lung adenocarcinoma has clinical relevance, being a sign of poor prognosis and low life expectancy. Experimental models can mimic the human condition, contributing to advances in current understanding of the mechanisms patients' pleural fluid accumulation and possible therapeutic strategies. The objective of this study is to evaluate the role of different concentrations of Lewis lung carcinoma cells (LLC cells) at the time of induction of experimental MPE and the main effects on survival of animals. METHODS: C57BL/6 mice received intrapleural injection of 0.1, 0.5 or 1.5 × 10(5) LLC cells and survival curve, biochemical and pathological analyses of pleural fluid and tissue were analyzed. RESULTS: Evaluation of weight loss, mobility and survival showed that animals that received 0.5 × 10(5) cells maintained more stable condition up to day 14 and a gain of 6 days survival over mice that received the highest concentration. CONCLUSION: This study may allow a better understanding the mechanisms involved in the development of malignant pleural effusion and it may be promising in evaluating therapy to avoid recurrence, as the best time to indicate pleurodesis or target therapies.

Inflammatory Cytokines Contribute to Asbestos-Induced Injury of Mesothelial Cells.

BACKGROUND: Several diseases have been related to asbestos exposure, including the pleural tumor mesothelioma. The mechanism of pleural injury by asbestos fibers is not yet fully understood. The inflammatory response with release of mediators leading to a dysregulation of apoptosis may play a pivotal role in the pathophysiology of asbestos-induced pleural disease. OBJECTIVE: To determine whether pro-inflammatory cytokines produced by asbestos-exposed pleural mesothelial cells modify the injury induced by the asbestos. METHODS: Mouse pleural mesothelial cells (PMC) were exposed to crocidolite or chrysotile asbestos fibers (3.0 µg/cm(2)) for 4, 24, or 48 h and assessed for viability, necrosis and apoptosis, and the production of cytokines IL-1ß, IL-6 and macrophage inflammatory protein-2 (MIP-2). Cells exposed to fibers were also treated with antibodies anti-IL-1ß, anti-IL-6, anti- IL-1ß+anti-IL-6 or anti-MIP-2 or their irrelevant isotypes, and assessed for apoptosis and necrosis. Non-exposed cells and cells treated with wollastonite, an inert particle, were used as controls. RESULTS: Mesothelial cells exposed to either crocidolite or chrysotile underwent both apoptosis and necrosis and released cytokines IL-1ß, IL-6 and MIP-2. In the crocidolite group, apoptosis and the levels of all cytokines were higher than in the chrysotile group, at comparable concentrations. Neutralization of IL-1ß andIL-6, but not MIP-2, inhibited apoptosis and necrosis, especially in the cells exposed to crocidolite fibers. CONCLUSIONS: Both crocidolite and chrysotile asbestos fibers induced apoptosis and produced an acute inflammatory response characterized by elevated levels of IL-1ß, IL-6 and MIP-2 in cultured mouse PMC. IL-1ß and IL-6, but not MIP-2, were shown to contribute to asbestos-induced injury, especially in the crocidolite group.

Safety and systemic consequences of pleurodesis with three different doses of silver nitrate in patients with malignant pleural effusion.

BACKGROUND: Silver nitrate (SN) is an alternative to talc pleurodesis in patients with malignant pleural effusion (MPE). Nevertheless, SN complications have not been thoroughly investigated so far. OBJECTIVE: To evaluate frequent adverse events (AE) of SN treatment at three different doses for pleurodesis in patients with MPE. The secondary objective was to evaluate systemic inflammation, efficacy and quality of life in these patients. METHODS: A double-blind, randomized, clinical trial was conducted in patients with recurrent MPE at a tertiary university hospital. The study patients underwent pleural catheter insertion and were randomly assigned to one of the three pleurodesis groups treated with 30 ml 0.3%, 30 ml 0.5% or 60 ml 0.3% SN. Patients were discharged 3 days after the procedure, and returned to follow-up visits on days 10 and 30. During follow-up, AE, inflammatory markers, quality of life and CT scans were systematically assessed and documented. RESULTS: Sixty patients (11 males and 49 females, median age 62.13 years) were included. Overall, 199 AE were observed, including 23 serious AE. Grade 1/2 metabolic AE, such as increases in creatinine and liver enzymes, were the most frequent. Grade 3/4 hypoxia was observed in 13 patients. Four patients died, 3 due to disease progression and in 1 patient death was possibly related to pleurodesis. C-reactive protein levels increased in a dose-dependent manner and peaked 48 h after pleurodesis. No significant difference was observed among groups regarding quality of life or clinical/radiological recurrence. CONCLUSION: Hypoxia was the most significant AE following SN pleurodesis; mild metabolic events were very common. SN instillation causes substantial dose-dependent systemic inflammatory responses.

Differentiating between tuberculosis-related and lymphoma-related lymphocytic pleural effusions by measuring clinical and laboratory variables: is it possible?

OBJECTIVE: To describe clinical and laboratory characteristics in patients with tuberculosis-related or lymphoma-related lymphocytic pleural effusions, in order to identify the variables that might contribute to differentiating between these diseases. METHODS: This was a retrospective study involving 159 adult HIV-negative patients with tuberculosis-related or lymphoma-related lymphocytic effusions (130 and 29 patients, respectively), treated between October of 2008 and March of 2010 at the Pleural Diseases Outpatient Clinic of the University of São Paulo School of Medicine Hospital das Clínicas Heart Institute, in the city of São Paulo, Brazil. RESULTS: Mean age and the mean duration of symptoms were lower in the tuberculosis group than in the lymphoma group. The levels of proteins, albumin, cholesterol, amylase, and adenosine deaminase (ADA) in pleural fluid, as well as the serum levels of proteins, albumin, and amylase, were higher in the tuberculosis group, whereas serum cholesterol and triglycerides were higher in the lymphoma group. Pleural fluid leukocyte and lymphocyte counts were higher in the tuberculosis group. Of the tuberculosis group patients, none showed malignant cells; however, 4 showed atypical lymphocytes. Among the lymphoma group patients, cytology for neoplastic cells was positive, suspicious, and negative in 51.8%, 24.1%, and 24.1%, respectively. Immunophenotyping of pleural fluid was conclusive in most of the lymphoma patients. CONCLUSIONS: Our results demonstrate clinical and laboratory similarities among the patients with tuberculosis or lymphoma. Although protein and ADA levels in pleural fluid tended to be higher in the tuberculosis group than in the lymphoma group, even these variables showed an overlap. However, none of the tuberculosis group patients had pleural fluid ADA levels below the 40-U/L cut-off point.

É possível diferenciar derrames pleurais linfocíticos secundários a tuberculose ou linfoma através de variáveis clínicas e laboratoriais? / Differentiating between tuberculosis-related and lymphoma-related lymphocytic pleural effusions by measuring clinical and laboratory variables: Is it possible?

OBJETIVO: Descrever características clínicas e laboratoriais em pacientes com derrames pleurais linfocíticos secundários a tuberculose ou linfoma, a fim de identificar as variáveis que possam contribuir no diagnóstico diferencial dessas doenças. MÉTODOS: Estudo retrospectivo com 159 pacientes adultos HIV negativos com derrame pleural linfocítico secundário a tuberculose ou linfoma (130 e 29 pacientes, respectivamente) tratados no Ambulatório da Pleura, Instituto do Coração, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo (SP), entre outubro de 2008 e março de 2010. RESULTADOS: A média de idade e de duração dos sintomas foi menor no grupo tuberculose que no grupo linfoma. Os níveis pleurais de proteínas, albumina, colesterol, amilase e adenosina desaminase (ADA), assim como os níveis séricos de proteínas, albumina e amilase, foram maiores no grupo tuberculose, enquanto os níveis séricos de colesterol e triglicérides foram maiores no grupo linfoma. As contagens de leucócitos e linfócitos no líquido pleural foram maiores no grupo tuberculose. Células malignas estavam ausentes no grupo tuberculose, entretanto, linfócitos atípicos foram observados em 4 desses pacientes. No grupo linfoma, a citologia para células neoplásicas foi positiva, suspeita e negativa em 51,8%, 24,1% e 24,1% dos pacientes, respectivamente. A imunofenotipagem do líquido pleural foi conclusiva na maioria dos pacientes com linfoma. CONCLUSÕES: Nossos resultados demonstram semelhanças clínicas e laboratoriais entre os pacientes com tuberculose ou linfoma. Embora os níveis de proteínas e ADA no líquido pleural tendam a ser mais elevados no grupo tuberculose que no grupo linfoma, mesmo essas variáveis mostraram uma sobreposição. Entretanto, nenhum paciente com tuberculose apresentou níveis de ADA no líquido pleural inferiores ao ponto de corte (40 U/L).

OBJECTIVE: To describe clinical and laboratory characteristics in patients with tuberculosis-related or lymphoma-related lymphocytic pleural effusions, in order to identify the variables that might contribute to differentiating between these diseases. METHODS: This was a retrospective study involving 159 adult HIV-negative patients with tuberculosis-related or lymphoma-related lymphocytic effusions (130 and 29 patients, respectively), treated between October of 2008 and March of 2010 at the Pleural Diseases Outpatient Clinic of the University of São Paulo School of Medicine Hospital das Clínicas Heart Institute, in the city of São Paulo, Brazil. RESULTS: Mean age and the mean duration of symptoms were lower in the tuberculosis group than in the lymphoma group. The levels of proteins, albumin, cholesterol, amylase, and adenosine deaminase (ADA) in pleural fluid, as well as the serum levels of proteins, albumin, and amylase, were higher in the tuberculosis group, whereas serum cholesterol and triglycerides were higher in the lymphoma group. Pleural fluid leukocyte and lymphocyte counts were higher in the tuberculosis group. Of the tuberculosis group patients, none showed malignant cells; however, 4 showed atypical lymphocytes. Among the lymphoma group patients, cytology for neoplastic cells was positive, suspicious, and negative in 51.8%, 24.1%, and 24.1%, respectively. Immunophenotyping of pleural fluid was conclusive in most of the lymphoma patients. CONCLUSIONS: Our results demonstrate clinical and laboratory similarities among the patients with tuberculosis or lymphoma. Although protein and ADA levels in pleural fluid tended to be higher in the tuberculosis group than in the lymphoma group, even these variables showed an overlap. However, none of the tuberculosis group patients had pleural fluid ADA levels below the 40-U/L cut-off point.

Effectiveness and safety of outpatient pleurodesis in patients with recurrent malignant pleural effusion and low performance status.

OBJECTIVES: To evaluate the effectiveness and safety of pleurodesis carried out entirely on an outpatient basis in patients with recurrent malignant pleural effusions and Karnofsky Performance Status scores <70. METHODS: This study was a prospective trial comprising patients with symptomatic recurrent malignant pleural effusion and Karnofsky Performance Status scores <70 but >30. All selected patients underwent pleural catheter placement (14 Fr) in an outpatient facility. When chest radiography revealed post-drainage lung expansion of >90%, pleurodesis (3 g of talc) was performed. Catheters were maintained until the daily output was ,100 mL/day. The patients were evaluated in the first month and every three months thereafter for fluid recurrence, the need for additional procedures, and complications. RESULTS: During the study period (January 2005 to July 2007), 64 patients (24 men, 40 women), with an average age of 61.4 years, underwent elective chest tube drainage. Primary sites of the underlying malignancy were breast (27), lung (22), and others (15). Sixty-six pleural catheters were placed (bilaterally in 2 patients), and 52 talc pleurodesis procedures were performed. Fourteen patients had a trapped lung and were excluded from the trial. No complications were observed during catheter placement or pleurodesis. Post-pleurodesis complications included catheter obstruction (4 patients) and empyema (1). The average drainage time was 9.9 days. The recurrence rate observed in patients that were alive 30 days after pleurodesis was 13.9% (5/36 patients). Six patients required additional procedures after the pleurodesis. The average survival time was 101 days. CONCLUSION: In this study, talc pleurodesis was safely performed in an outpatient setting with good efficacy and a reasonable complication rate, thereby avoiding hospital admission.

Is silver nitrate pleurodesis for patients with malignant pleural effusion feasible and safe when performed in an outpatient setting?

BACKGROUND: The purpose of this study was to analyze the effectiveness and safety of silver nitrate pleurodesis (SNP) in patients with recurrent malignant pleural effusion (RMPE) when performed in an outpatient setting. MATERIALS AND METHODS: Prospective study including patients with RMPE recruited in a tertiary university-based hospital from February 2008 to June 2009. Elected patients underwent pleural catheter insertion (Day 1) followed by 0.5% SNP (Day 2), and on 7th day the drain was removed. All procedures were performed in an outpatient facility. Pleurodesis was considered successful when no additional pleural procedure was necessary by the 30th day. Complications were registered and graded according to the CTCAE3.0. Quality of life was evaluated before and 30 days after SNP. RESULTS: A total of 68 patients (54 female, 14 male, mean age: 57.3 years) were included. In addition, 7 had bilateral pleural effusions; therefore, 75 hemithoraces were drained. Also, 5 were excluded, and 70 hemithoraces (63 patients) underwent SNP. During the period of 30 days postpleurodesis, 8 deaths not related to the procedure occurred, and we lost contact with 10 patients who were followed elsewhere. At the 30th day, 48 hemithoraces (45 patients) were reevaluated, and 2 recurrences observed. The most frequent complication was pain--graded as 3 or more in 7 patients; infection occurred in 2 patients. Physical and environmental aspects of quality of life improved significantly after pleurodesis. CONCLUSIONS: In this study, SNP could be performed safely in an outpatient setting, with pain the most frequent complication. Recurrences occurred in 4% of the patients.