Modelo experimental de doença pleural maligna induzida por células LLC (Lewis Lung Carcinoma)

Derrame pleural maligno (DPM) é um fator de mau prognóstico em pacientes com câncer de pulmão avançado. Sua patogênese ainda é pouco compreendida e as opções terapêuticas são limitadas. Modelos animais de DPM podem demonstrar novos aspectos fisiopatológicos desta doença. Stathopoulos et al. em 2006 (Am J Respir Cell Mol Biol. 2006;34:142-50) descreveram um modelo de DPM com 1,5 x105 células de LLC injetadas diretamente no espaço pleural de camundongos. Os autores relataram carcinomatose com derrame pleural, tumores pleurais e 100% de mortalidade após 17 dias. [...

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 &gt;30. All selected patients underwent pleural catheter placement (14 Fr) in an outpatient facility. When chest radiography revealed post-drainage lung expansion of &gt;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

Does the Evaluation of Coagulation Factors Contribute to Etiological Diagnosis of Pleural Effusions?

OBJECTIVE: The aim of this study was to identify the participation of the coagulation system in the differential diagnosis of pleural effusions. INTRODUCTION: Imbalance between immunologic and metabolic factors triggers a sequence of events resulting in pleural reactions and accumulation of fluid. The coagulation system, which is fundamental for the maintenance of homeostasis, contributes to the inflammatory process responsible for pleural effusions, and participates in cellular proliferation and migration as well as in the synthesis of inflammatory mediators. METHODS: We evaluated the laboratory profile of coagulation and fibrinolysis in 54 pleural fluids (15 transudates and 39 exudates). RESULTS: The coagulation system acts according to the pathophysiologic mechanisms involved in the development of pleural effusions. In inflammatory effusions (exudates), there is activation of coagulation with increased levels of fragment 1+2 and thrombin-antithrombin complex in addition to reduction of fibrinogen levels due to fibrinolysis and fibrin tissue incorporation. As a consequence, there is activation of the fibrinolytic system with increased levels of fibrin degradation products, including the D-dimer. These changes are not sufficient for differentiation of different subgroups of exudates. In transudates, these events were observed to a lesser degree. CONCLUSION: The coagulation system plays an important role in the development of pleural diseases. Coagulation tests show differences between transudates and exudates but not among exudate subgroups. Understanding the physiopathological mechanisms of pleural disorders may help to define new diagnostic and therapeutic approaches

Anti-EGFR reduces malignant pleural effusion and morbidity in experimental model of adenocarcinoma

Introduction: A lot patients with lung cancer develop pleural effusion in an advanced stage of the disease, with high&nbsp;morbidity and mortality. The pathogenesis of the malignant pleural effusion is not well known and the therapeutic options&nbsp;are limited. Currently target therapy, like the antibody anti-EGFR, is been used more often in the treatment of the lung&nbsp;cancer. The EGFR is a tyrosine-kinase receptor considered oncogenic and responsible for the growing, the survival, the&nbsp;proliferation and the differentiation of loads of cell types. The use of antibodies anti-EGFR may entail positive effects in&nbsp;the fight against the tumor and the effects of the malignant pleural effusion.&nbsp;Goals: To evaluate the effects of intrapleural therapy with anti-EGFR in experimental model of malignant pleural effusion.&nbsp;Material e Methods: This study received the approval of the Comitê de Ética no Uso de Animais (CEUA) from HCFMUSP.&nbsp;Sixty C57BL/6 mice received intrapleural injection of 0,5x105 Lewis Lung Carcinoma (LLC) cells. The animals were&nbsp;divided in two groups that received the intrapleural injection with anti-EGFR or PBS (No treatment/Control) after 3, 7, 10&nbsp;and 14 days from the induction of the pleural neoplasia. Ten animals from each group were observed until their death to&nbsp;evaluate a survival graphic curve. Forty animals were submitted to euthanasia after 7, 10, 14 or 21 days. We evaluated the&nbsp;weight gain or loss in grams (g), the mobility (score 0-3), the volume of recovered pleural effusion in milliliters (mL), and&nbsp;the presence of tumor in in the pleura, the pericardium, the inflammatory cells of the lungs and the histological changes&nbsp;in the kidneys, liver and spleen. Tumor apoptosis (TUNEL) and proliferation (PCNA) were evaluated by scores (0-4).&nbsp;Statistical analysis: One Way ANOVA, Kaplan-Meier, p &lt;0,05.&nbsp;Results: On the survival analysis we did not observe any statistical difference between the groups. The mice weight loss&nbsp;was observed in all the groups after 21 days. It was observed a better mobility in the groups that receives the anti-EGFR&nbsp;&nbsp;treatment. The pleural effusion volume was higher in the control group during all the study. The presence of pleural tumor&nbsp;implants was higher in the control group in comparison to the group that received treatment after 14 days. Pulmonary&nbsp;inflammation was discreet in all groups. The histological evaluation of the pericardium and the cardiac muscle showed&nbsp;tumor implants in the control group after 21 days. Hepatic and renal steatosis were more evident after 14 days in the&nbsp;control group. White flesh hyperplasia of the spleen was observed in all the periods of the study, especially in the 21st day&nbsp;in the control group. Higher levels of apoptosis and lower levels of tumor proliferation were observed in the groups that&nbsp;received treatment with anti-EGFR.&nbsp;Conclusions: In this experimental model, although it did not showed any benefic change in the animals survival, the target&nbsp;therapy with anti-EGFR reduced the pleural effusion volume, the morbidity and showed good histological parameters

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)