Abstract Manganese superoxide dismutase (MnSOD) is an important intracellular antioxidant enzyme, which has been suggested to play a role in tumour biology. In the present study, the expression and possible role of MnSOD in malignant pleural mesothelioma was investigated. Mesothelial cells in healthy visceral pleural tissue showed no MnSOD immunoreactivity in five out of six cases, whereas moderate or high immunoreactivity for MnSOD was detected in 30 out of 42 (71%) cases of mesothelioma. Only two of the 21 cases with metastatic adenocarcinoma of the pleura showed moderate MnSOD immunoreactivity, the remaining 19 (90.5%) showing negative or weak reactivity (p < 0.001, by Fisher's exact test compared to mesothelioma). The immunostaining of catalase, a hydrogen peroxide scavenging antioxidant enzyme, was detectable in 27 of the 35 (77%) mesothelioma cases studied, whereas all the five samples of healthy pleural mesothelium were negative. Reactive mesothelium showed positive immunoreactivity for MnSOD and catalase, suggesting that induction of these enzymes is not specific for mesothelioma. Two continuous human mesothelioma cell lines showed higher MnSOD activity, immunoreactive protein and mRNA levels than non-malignant mesothelial cells. In addition, mesothelioma cells expressing the highest MnSOD levels had the highest levels of catalase and copper-zinc superoxide dismutase. The mitochondria of these cells expressed higher MnSOD and lower superoxide levels than non-malignant mesothelial cells. The mesothelioma cells with the highest antioxidant enzyme levels were most resistant to oxidant- and drug-induced injury and to drug-induced apoptosis compared to non-malignant mesothelial cells and mesothelioma cells with lower MnSOD and catalase levels. The extent of cell proliferation and apoptosis of mesothelioma tissue were 14.1±13.2% and 1.1±1.2%, respectively. MnSOD expression was inversely associated with cell proliferation (p = 0.02 by t-test), and a tendency for a better prognosis among patients with moderate or strong MnSOD expression was demonstrated. Patients displaying a tumour with enhanced proliferation or apoptosis had a poorer prognosis (p < 0.001 by Log Rank test). In conclusion, the MnSOD level is usually high in pleural mesothelioma, which may affect the proliferation and drug-resistance of mesothelioma cells. MnSOD immunostaining can thus possibly be used to distinguish mesothelioma from metastatic adenocarcinoma but not from reactive mesothelium.

Die Talkumpleurodese stellt ein effektives Verfahren zur Behandlung von rezidivierenden malignen Pleuraergüssen dar. Sie ist ein rein palliatives Verfahren. Das Auftreten des malignen Pleuraergusses stellt den Beginn des letzten Lebensabschnittes eines Tumorpatienten dar. Es ist verbunden mit dem Kardinalsymptom Dyspnoe. Um diese zu lindern, wird im blinden Aktionismus die operative Pleurodese angeboten. Dieses führt zu einer hohen perioperativen Mortalität. In 36 Monaten (1997-1999) wurden in unserer Klinik 115 operative Talkum-Pleurodesen durchgeführt. Die perioperative Letalität lag bei 7,8 %. Die häufigsten Primärtumoren waren Mammakarzinom (MÜL 12,4 Monate), Bronchialkarzinm (MÜL 6,2 Monate), CUP (MÜL 10,7 Monate) Ovarialkarzinom (MÜL 2,2 Monate) und Mesotheliom (MÜL 10,9 Monate). Die Patienten mit Mammakarzinom, Bronchialkarzinom und Ovarialkarzinom litten postoperativ deutlich gehäufter unter erneuter Luftnot. Es ist daher nötig, Standards festzulegen, um ein geeignetes Patientengut zu behandeln. In der Literatur finden sich eindeutige Zusammenhänge zum Karnofsky-Index des Patienten sowie zu den Laborparametern pH (kritisch / Talc pleurodesis is the most effective treatment für malignant pleural effusions. It is a palliative procedure. The appearance of a malignant pleural effusions marks the beginning of the last part of life of a patient with cancer. The cardinal symptom is dyspnoea. To allay, we offer surgical pleurodesis, offen in blind action. This is causing high mortality. We performed 115 thoracoscopic talc pudrages between 1997 and 1999 (36 month). The inpatient mortality was 7,8%. The most offen origins of metastatic carcinoma were Breast cancer (MS 12,4 month), Lung cancer (MS 6,2 month), Carcinoma of unknown primary (MS 10,7 month), Malignant mesothelioma (MS 10,9 month) and Ovarian cancer (MS 2,2 month). The patients with Breast-, Lung- and Ovarian cancer suffered the must from dyspnoea after pleurodesis. That''s why it is necessary, to find standards to choose suitable patients, which profit. In literature there are definite connection between Karnofsky Performance Scale of a patient, pleural fluid pH (critically

Introduction: Waldenström's macroglobulinemia is a hematological neoplasm belonging to the group of monoclonal gammopathies, which includes systemic symptoms and those related to an increase in M paraprotein. Objective: To describe a case of cardiac amyloidosis associated with macroglobulinemia. Clinical case: Male patient who was admitted for asthenia, dysphonia, and who, during his evolution, developed progressive dyspnea, heart failure and pleural effusion. Additionally, echocardiography showed myocardial granular pattern, while pleural biopsy was positive for Congo red staining. Subsequently, he received treatment with bortezomib, dexamethasone and rituximab, with favorable evolution. Conclusions: In this disease, early diagnosis is an important advantage for survival. Therefore, its management is palliative of cardiac manifestations. The present case shows a diagnostic challenge, in which the less frequent etiologies of heart failure must be taken into account. / Revisión por pares

Thesis (PhD (Medicine. Internal medicine))--University of Stellenbosch, 2007. / 1.1. Background Tumors arising from the lung, pleura, or chest wall are a frequent problem in clinical pulmonary medicine. Most lesions are either infectious, neoplastic or granulomatous in nature, but a variety of other differential diagnoses must be considered. An accurate diagnosis is important because the available treatments differ substantially, and because any delay will impair the prognosis in potentially curable patients with lung carcinoma. The investigations involve the disciplines of radiology, pulmonology, surgery, microbiology, and anatomical pathology and consume a respectable amount of resources. The aim of the work covered in this thesis was to optimize the available diagnostic methods for the routine use in a health care setting with limited resources. 1.2. Methods The general idea of this work was to identify conventional sampling methods that could be developed further to become more useful for the diagnosis of chest tumors in a low resource health care setting. The key method was research performed: a) to revise and expand the indication for a sampling method, b) to technically improve the sampling process, and c) to optimize sample transport, preparation and analysis in collaboration with the analytical laboratory. 1.3. Results A list of invasive diagnostic procedures, imaging methods and analytical processes were developed, evaluated and integrated into clinical practice. A) transbronchial needle aspiration, B) transthoracic cutting needle biopsy, C) transthoracic fine needle aspiration, D) transthoracic ultrasound, and E) rapid on-site evaluation of needle aspirates by a cytopathologist. Five studies pertaining to this thesis were published in international peerreviewed journals: â ¢ Safety and yield of ultrasound-assisted transthoracic biopsy performed by pulmonologists (Respiration 2004;71:519-22) This paper established that ultrasound-assisted transthoracic biopsy performed by pulmonologists is feasible, safe, practical, low-cost and has a high yield. â ¢ Utility of rapid on-site evaluation of transbronchial needle aspirates (Respiration 2005;72:182-8) This paper demonstrated the economical advantages of on-site evaluation of transbronchial specimens in a low-resource setting. â ¢ Transbronchial needle aspirates: comparison of two preparation methods (Chest 2005;127:2015-8) This paper demonstrated that preparing smears on-site has a far better yield than pooling samples into a vial. This means that the yield is improved over the current standard at no additional cost. â ¢ Transbronchial needle aspirates: how many passes per target site? (European Respiratory Journal 2007;29:112-6) This paper investigated the most economical and effective approach to serial sampling with transbronchial needle aspiration during flexible bronchoscopy. â ¢ Ultrasound assisted transthoracic biopsy: fine needle aspiration or cutting needle biopsy? (European Respiratory Journal 2007;29:357-62) This paper compared two common methods of sampling and demonstrates that the less expensive method is sufficient in the majority of cases. 1.4. Conclusion This work has impacted on current practice in multiple ways. Conventional methods have been optimized by improving technical factors and with the integration of interdisciplinary collaboration. The initiated research is ongoing with the aim to achieve continued technical and economical improvements in the diagnosis of chest tumors.

INTRODUÇÃO: O primeiro passo na presença de derrame pleural maligno é a aspiração terapêutica do líquido para alívio dos sintomas e avaliar indicação de pleurodese. Infelizmente, em seres humanos a re-aeração e re- ventilação pulmonar após a retirada de líquido pleural foi avaliada apenas indiretamente. A tomografia de impedância elétrica (TIE) é uma técnica precisa que já foi extensivamente validada para quantificar aeração e ventilação pulmonar em tempo real e à beira-leito. O conhecimento das alterações em aeração e ventilação pulmonar após a retirada do líquido pleural é essencial para a compreensão da evolução clínica, objetivando novos esquemas de pleurodese e novos indicadores de reexpansão pulmonar. OBJETIVOS: Avaliar a aeração, ventilação e sincronia ventilatória antes e durante a primeira hora após a aspiração de um derrame pleural maligno. Objetivos secundários: correlacionar a re-aeração com variáveis que pudessem influenciá-la. Métodos: Critérios de inclusão: derrame pleural unilateral com necessidade de aspiração terapêutica e superior a 500 mL. Os sinais e imagens da TIE foram adquiridos em seis períodos diferentes: antes da aspiração pleural, imediatamente, 15, 30, 45 e 60 minutos após a aspiração. A re-aeração foi avaliada pela variação no valor da impedância (Z) ao final de uma expiração relaxada, enquanto a re-ventilação foi avaliada através da variação da impedância no volume corrente. Também medimos a sincronia entre os pulmões usando o ângulo de fase. Finalmente, correlacionamos à re-aeração final com o volume retirado, ângulo de fase inicial e elastância pleural. O pulmão afetado pelo derrame foi nomeado como ipsilateral e o não afetado como contralateral. RESULTADOS: Foram incluídos 22 pacientes. O volume médio aspirado foi 1438 ml. No pulmão ipsilateral, a média no final da expiração valor Z aumentou para 173,5 ± 122,3, imediatamente após a aspiração pleural (p <0,001), e a análise individual revelou que todos os pacientes ganharam re-aeracão pulmonar imediatamente, sem mais re-aerações após. O mesmo comportamento, mas com uma menor magnitude foi encontrado no pulmão contralateral. Na avaliação da re-ventilação, os pulmões ipsilateral e contralateral mostraram resultados heterogêneos, alguns aumentaram a ventilação, outros diminuíram ou mantiveram-na inalterada. Antes da aspiração pleural, a média do ângulo de fase foi de 93 ± 71 graus e diminuiu para 20 ± 30 graus, imediatamente após a aspiração pleural (p <0,001), sem outras alterações após. A re-aeração final correlacionou-se apenas com o volume de derrame aspirado (R2 = 0,49, p <0,01). CONCLUSÃO: Após a aspiração de derrame pleural unilateral neoplásico em pulmões não encarcerados, a re-aeração pulmonar ocorre imediatamente nos pulmões ipisilateral e contralateral, sem mais re-aeração durante a hora seguinte. As mudanças na re-ventilação mostram altas variações individuais. Há uma assincronia ventilatória entre os pulmões, que é imediatamente revertida pela aspiração pleural. A única variável correlacionada com a re-aeração do pulmão afetado é o volume de derrame drenado / INTRODUCTION: The first procedure in the management of a malignant pleural effusion is a therapeutic pleural aspiration to relieve symptoms and assess pleurodesis indication. Unfortunately, in humans the pulmonary re- aeration and re-ventilation after a pleural aspiration was evaluated only indirectly. Electrical impedance tomography (EIT) is an accurate, non- invasive and bedside method that has been extensively validated to quantify lung ventilation and aeration. The knowledge of changes in lung aeration and ventilation after a therapeutic pleural aspiration is essential to understand the clinical course, to propose new lung reexpansion predictors and pleurodesis schemas. OBJECTIVE: To measure the lung re-aeration, re-ventilation and ventilatory synchrony before and over the first hour after a therapeutic pleural aspiration for a malignant pleural effusion. As secondary objectives we correlate the lung re-aeration with variables that could influence them. METHODS: The inclusion criteria were the need of a therapeutic pleural aspiration of a unilateral effusion over 500 mL. EIT signals and images were acquired in six different periods: before the pleural aspiration, immediately and 15, 30, 45 and 60 minutes after the aspiration. The re-aeration was evaluated through the change in the end-expiratory lung impedance (Z), while the re-ventilation was evaluated through the change in tidal impedance. We also measure the ventilator synchrony between lungs using the phase angle. Finally we correlated the final re-aeration with the effusion volume drained, pleural elastances and baseline phase angle. The lung affected by the effusion was nominated as ipsilateral and the non-affected as contralateral. RESULTS: We included 22 patients. The mean volume of aspirated effusion was 1438 ml. In the ipsilateral lung, the mean end- expiratory Z value increased to 173.5 ± 122.3 immediately after the pleural aspiration (p < 0.001) and the individual analysis revealed that all patients re- aerated the lung immediately without further re-aeration thereafter. The same behavior but with a lower magnitude was found in the contralateral lung. The ipsilateral and contralateral lung re-ventilation showed heterogeneous results with patients increasing the ventilation, while others decreased or kept the ventilation unchanged. Before the pleural aspiration, the mean phase angle was 93 ± 71 degrees and decreased to 20 ± 30 degrees immediately after the pleural aspiration (p < 0.001), without further changes thereafter. The final re-aeration only correlated to the volume of effusion aspirated (R2 = 0.49; p < 0.01). CONCLUSION: In untrapped lungs, a pleural aspiration of a unilateral malignant pleural effusion causes an immediate re-aeration of the lung affected by the effusion and even of the contralateral lung, without further re-aeration over the next hour. The changes in ventilations show high individual variations. There is a ventilatory asynchrony between lungs that is immediately reversed by the aspiration. The only variable correlated to re- aeration of the affected lung is the effusion volume drained

INTRODUÇÃO: O câncer de pulmão é a principal causa de morte por câncer em todo o mundo e muitos pacientes apresentam derrame pleural em um estágio avançado da doença, com alta morbidade e mortalidade. Entretanto, a patogênese do derrame maligno é ainda pouco compreendida e as opções terapêuticas são limitadas. OBJETIVO: 1) Estudar a fisiopatologia do derrame pleural maligno em modelo animal com células de Lewis em diferentes concentrações; 2) Avaliar os efeitos da terapia intrapleural com anti-VEGF e anti-EGFR e a frequência de mutações de EGFR e KRAS neste modelo. MÉTODOS: Foi utilizado modelo de neoplasia pleural com camundongos C57BL/6 e células de Lewis (LLC) dividido em duas etapas: estudo com diferentes concentrações de células LLC (0,1, 0,5 e 1,5x105) e avaliação de terapias-alvo. Após a padronização do modelo, quatro grupos de camundongos receberam tratamento intrapleural com anti-VEGF, anti-EGFR, anti-VEGF+anti-EGFR ou solução fisiológica (não tratados) 3, 7, 10 e 14 dias após a indução da neoplasia pleural com 0,5x105 células LLC. Em vinte animais de cada grupo foi avaliada a curva de sobrevida. 160 animais foram submetidos à eutanásia 7, 10, 14 ou 21 dias após e avaliados peso, mobilidade, volume de líquido pleural, marcadores inflamatórios, imunológicos e bioquímicos no líquido, presença de tumores e alterações histológicas em pleura, pulmão, rim, fígado e baço. Através de imunohistoquimica avaliou-se apoptose, proliferação tumoral, VEGF e EGFR. Analisou-se a expressão gênica do EGFR, VEGF, KRAS e ALK e a frequência de mutações do EGFR e KRAS. Análise estatística: One Way ANOVA, Kaplan-Meier, p < 0,05. RESULTADOS: Na etapa de padronização do modelo observamos que a concentração que manteve os parâmetros de neoplasia pleural com maior sobrevida foi de 0,5x105 células LLC. Na segunda etapa do estudo, a carcinomatose pleural foi letal com sobrevida máxima de 25 dias, sem diferença entre os grupos. Redução de peso foi observada em todos os grupos após 21 dias. A mobilidade foi melhor nos grupos que receberam anti-EGFR. O volume de líquido pleural foi maior no grupo não tratado durante todo o estudo. Parâmetros imunológicos e bioquímicos aumentaram temporalmente sendo mais evidentes no grupo sem tratamento. Implantes tumorais na pleura foram mais evidentes no grupo não tratado após 14 dias. A inflamação pulmonar foi mínima em todos os grupos. No grupo não tratado observou-se implantes tumorais no pericárdio e músculo cardíaco após 21 dias, esteatose hepática e renal após 14 dias e hiperplasia de polpa branca do baço no 21º dia. Altos índices de apoptose e menores índices de proliferação tumoral foram observados nos grupos que receberam tratamento com anti-EGFR e anti-VEGF+anti-EGFR. Houve mutação do gene KRAS e superexpressão gênica tumoral do EGFR e do KRAS. CONCLUSÃO: As terapias-alvo reduziram significativamente o derrame pleural, morbidade e parâmetros histológicos, embora sem impacto na sobrevida dos animais neste modelo experimental. Nossos dados indicam que a linhagem tumoral LLC possui um fenótipo tumoral agressivo demonstrado através da mutação do KRAS e superexpressão do EGFR, o que pode estar associado ao pior prognóstico e menor resposta aos inibidores do EGFR / INTRODUCTION: Lung cancer is the leading cause of death by cancer in the world. Many patients have pleural effusion in an advanced stage of the disease, with high morbidity and mortality. However, the pathogenesis of malignant pleural effusion is still poorly understood and the treatment options are limited. OBJECTIVE: 1) To study the pathophysiology of malignant pleural effusion in animal model with Lewis cells in different concentrations; 2) Evaluate the effects of the intrapleural therapy with anti-VEGF and anti-EGFR and the frequency of EGFR and KRAS mutations in this model. METHODS: We used pleural neoplasm experimental model with mice C57BL/6 and Lewis cells (LLC) divided into two steps: study with different concentrations of LLC cells (0.1, 0.5 and 1.5x105) and evaluation of targeted therapies. After the standardization of the model, four groups of mice received intrapleural treatment with anti-VEGF, anti-EGFR, anti-VEGF+anti-EGFR or saline (untreated) 3, 7, 10 and 14 days after induction of pleural neoplasm with injection of 0.5x105 LLC cells. In 20 animals of each group was evaluated the survival curve. 160 animals underwent euthanasia 7, 10, 14 or 21 days after and assessed weight, mobility, volume of pleural fluid, inflammatory, immunological and biochemical markers in the liquid, presence of tumor and histological changes in pleura, lung, kidney, liver and spleen. It was evaluated, through immunohistochemistry, tumor apoptosis and proliferation, VEGF and EGFR. Gene expression of EGFR, VEGF, KRAS and ALK and frequency of mutations of EGFR and KRAS were also evaluated. Statistical analysis: One Way ANOVA, Kaplan-Meier, p < 0.05. RESULTS: In the standardization of the model we observed that the concentration that kept parameters of pleural neoplasm with higher survival rate was 0.5x105 LLC cells. In the second stage, target-therapies, pleural carcinomatosis was lethal with maximum survival of 25 days, with no difference between the groups. Weight decrease was observed in all groups after 21 days. Mobility was better in groups that receiving anti-EGFR. Pleural fluid volume was greater in the untreated group throughout the study. Immunological and biochemical parameters have increased temporarily being most evident in the untreated group. Tumor implants in pleura were more apparent in the untreated group after 14 days. The lung inflammation was minimal in all groups. The untreated group showed tumor implants in the pericardium and heart muscle after 21 days, hepatic and renal steatosis after 14 days and spleen white pulp hyperplasia in 21 day. High rates of apoptosis and smaller tumor proliferation indices were observed in groups that received treatment with anti-VEGF and anti-EGFR+anti-EGFR. We also found gene KRAS mutation and tumoral gene overexpression of EGFR and KRAS. CONCLUSION: Targeted therapies reduced significantly the pleural effusion, morbidity and histological parameters, although without an impact on survival rate in this experimental model. Our data indicate that the tumor lineage LLC has an aggressive tumor phenotype shown by KRAS mutation and overexpression of EGFR, which can be associated with a worse prognosis and a lower response to EGFR inhibitors

INTRODUÇÃO: O primeiro passo na presença de derrame pleural maligno é a aspiração terapêutica do líquido para alívio dos sintomas e avaliar indicação de pleurodese. Infelizmente, em seres humanos a re-aeração e re- ventilação pulmonar após a retirada de líquido pleural foi avaliada apenas indiretamente. A tomografia de impedância elétrica (TIE) é uma técnica precisa que já foi extensivamente validada para quantificar aeração e ventilação pulmonar em tempo real e à beira-leito. O conhecimento das alterações em aeração e ventilação pulmonar após a retirada do líquido pleural é essencial para a compreensão da evolução clínica, objetivando novos esquemas de pleurodese e novos indicadores de reexpansão pulmonar. OBJETIVOS: Avaliar a aeração, ventilação e sincronia ventilatória antes e durante a primeira hora após a aspiração de um derrame pleural maligno. Objetivos secundários: correlacionar a re-aeração com variáveis que pudessem influenciá-la. Métodos: Critérios de inclusão: derrame pleural unilateral com necessidade de aspiração terapêutica e superior a 500 mL. Os sinais e imagens da TIE foram adquiridos em seis períodos diferentes: antes da aspiração pleural, imediatamente, 15, 30, 45 e 60 minutos após a aspiração. A re-aeração foi avaliada pela variação no valor da impedância (Z) ao final de uma expiração relaxada, enquanto a re-ventilação foi avaliada através da variação da impedância no volume corrente. Também medimos a sincronia entre os pulmões usando o ângulo de fase. Finalmente, correlacionamos à re-aeração final com o volume retirado, ângulo de fase inicial e elastância pleural. O pulmão afetado pelo derrame foi nomeado como ipsilateral e o não afetado como contralateral. RESULTADOS: Foram incluídos 22 pacientes. O volume médio aspirado foi 1438 ml. No pulmão ipsilateral, a média no final da expiração valor Z aumentou para 173,5 ± 122,3, imediatamente após a aspiração pleural (p <0,001), e a análise individual revelou que todos os pacientes ganharam re-aeracão pulmonar imediatamente, sem mais re-aerações após. O mesmo comportamento, mas com uma menor magnitude foi encontrado no pulmão contralateral. Na avaliação da re-ventilação, os pulmões ipsilateral e contralateral mostraram resultados heterogêneos, alguns aumentaram a ventilação, outros diminuíram ou mantiveram-na inalterada. Antes da aspiração pleural, a média do ângulo de fase foi de 93 ± 71 graus e diminuiu para 20 ± 30 graus, imediatamente após a aspiração pleural (p <0,001), sem outras alterações após. A re-aeração final correlacionou-se apenas com o volume de derrame aspirado (R2 = 0,49, p <0,01). CONCLUSÃO: Após a aspiração de derrame pleural unilateral neoplásico em pulmões não encarcerados, a re-aeração pulmonar ocorre imediatamente nos pulmões ipisilateral e contralateral, sem mais re-aeração durante a hora seguinte. As mudanças na re-ventilação mostram altas variações individuais. Há uma assincronia ventilatória entre os pulmões, que é imediatamente revertida pela aspiração pleural. A única variável correlacionada com a re-aeração do pulmão afetado é o volume de derrame drenado / INTRODUCTION: The first procedure in the management of a malignant pleural effusion is a therapeutic pleural aspiration to relieve symptoms and assess pleurodesis indication. Unfortunately, in humans the pulmonary re- aeration and re-ventilation after a pleural aspiration was evaluated only indirectly. Electrical impedance tomography (EIT) is an accurate, non- invasive and bedside method that has been extensively validated to quantify lung ventilation and aeration. The knowledge of changes in lung aeration and ventilation after a therapeutic pleural aspiration is essential to understand the clinical course, to propose new lung reexpansion predictors and pleurodesis schemas. OBJECTIVE: To measure the lung re-aeration, re-ventilation and ventilatory synchrony before and over the first hour after a therapeutic pleural aspiration for a malignant pleural effusion. As secondary objectives we correlate the lung re-aeration with variables that could influence them. METHODS: The inclusion criteria were the need of a therapeutic pleural aspiration of a unilateral effusion over 500 mL. EIT signals and images were acquired in six different periods: before the pleural aspiration, immediately and 15, 30, 45 and 60 minutes after the aspiration. The re-aeration was evaluated through the change in the end-expiratory lung impedance (Z), while the re-ventilation was evaluated through the change in tidal impedance. We also measure the ventilator synchrony between lungs using the phase angle. Finally we correlated the final re-aeration with the effusion volume drained, pleural elastances and baseline phase angle. The lung affected by the effusion was nominated as ipsilateral and the non-affected as contralateral. RESULTS: We included 22 patients. The mean volume of aspirated effusion was 1438 ml. In the ipsilateral lung, the mean end- expiratory Z value increased to 173.5 ± 122.3 immediately after the pleural aspiration (p < 0.001) and the individual analysis revealed that all patients re- aerated the lung immediately without further re-aeration thereafter. The same behavior but with a lower magnitude was found in the contralateral lung. The ipsilateral and contralateral lung re-ventilation showed heterogeneous results with patients increasing the ventilation, while others decreased or kept the ventilation unchanged. Before the pleural aspiration, the mean phase angle was 93 ± 71 degrees and decreased to 20 ± 30 degrees immediately after the pleural aspiration (p < 0.001), without further changes thereafter. The final re-aeration only correlated to the volume of effusion aspirated (R2 = 0.49; p < 0.01). CONCLUSION: In untrapped lungs, a pleural aspiration of a unilateral malignant pleural effusion causes an immediate re-aeration of the lung affected by the effusion and even of the contralateral lung, without further re-aeration over the next hour. The changes in ventilations show high individual variations. There is a ventilatory asynchrony between lungs that is immediately reversed by the aspiration. The only variable correlated to re- aeration of the affected lung is the effusion volume drained

INTRODUÇÃO: O câncer de pulmão é a principal causa de morte por câncer em todo o mundo e muitos pacientes apresentam derrame pleural em um estágio avançado da doença, com alta morbidade e mortalidade. Entretanto, a patogênese do derrame maligno é ainda pouco compreendida e as opções terapêuticas são limitadas. OBJETIVO: 1) Estudar a fisiopatologia do derrame pleural maligno em modelo animal com células de Lewis em diferentes concentrações; 2) Avaliar os efeitos da terapia intrapleural com anti-VEGF e anti-EGFR e a frequência de mutações de EGFR e KRAS neste modelo. MÉTODOS: Foi utilizado modelo de neoplasia pleural com camundongos C57BL/6 e células de Lewis (LLC) dividido em duas etapas: estudo com diferentes concentrações de células LLC (0,1, 0,5 e 1,5x105) e avaliação de terapias-alvo. Após a padronização do modelo, quatro grupos de camundongos receberam tratamento intrapleural com anti-VEGF, anti-EGFR, anti-VEGF+anti-EGFR ou solução fisiológica (não tratados) 3, 7, 10 e 14 dias após a indução da neoplasia pleural com 0,5x105 células LLC. Em vinte animais de cada grupo foi avaliada a curva de sobrevida. 160 animais foram submetidos à eutanásia 7, 10, 14 ou 21 dias após e avaliados peso, mobilidade, volume de líquido pleural, marcadores inflamatórios, imunológicos e bioquímicos no líquido, presença de tumores e alterações histológicas em pleura, pulmão, rim, fígado e baço. Através de imunohistoquimica avaliou-se apoptose, proliferação tumoral, VEGF e EGFR. Analisou-se a expressão gênica do EGFR, VEGF, KRAS e ALK e a frequência de mutações do EGFR e KRAS. Análise estatística: One Way ANOVA, Kaplan-Meier, p < 0,05. RESULTADOS: Na etapa de padronização do modelo observamos que a concentração que manteve os parâmetros de neoplasia pleural com maior sobrevida foi de 0,5x105 células LLC. Na segunda etapa do estudo, a carcinomatose pleural foi letal com sobrevida máxima de 25 dias, sem diferença entre os grupos. Redução de peso foi observada em todos os grupos após 21 dias. A mobilidade foi melhor nos grupos que receberam anti-EGFR. O volume de líquido pleural foi maior no grupo não tratado durante todo o estudo. Parâmetros imunológicos e bioquímicos aumentaram temporalmente sendo mais evidentes no grupo sem tratamento. Implantes tumorais na pleura foram mais evidentes no grupo não tratado após 14 dias. A inflamação pulmonar foi mínima em todos os grupos. No grupo não tratado observou-se implantes tumorais no pericárdio e músculo cardíaco após 21 dias, esteatose hepática e renal após 14 dias e hiperplasia de polpa branca do baço no 21º dia. Altos índices de apoptose e menores índices de proliferação tumoral foram observados nos grupos que receberam tratamento com anti-EGFR e anti-VEGF+anti-EGFR. Houve mutação do gene KRAS e superexpressão gênica tumoral do EGFR e do KRAS. CONCLUSÃO: As terapias-alvo reduziram significativamente o derrame pleural, morbidade e parâmetros histológicos, embora sem impacto na sobrevida dos animais neste modelo experimental. Nossos dados indicam que a linhagem tumoral LLC possui um fenótipo tumoral agressivo demonstrado através da mutação do KRAS e superexpressão do EGFR, o que pode estar associado ao pior prognóstico e menor resposta aos inibidores do EGFR / INTRODUCTION: Lung cancer is the leading cause of death by cancer in the world. Many patients have pleural effusion in an advanced stage of the disease, with high morbidity and mortality. However, the pathogenesis of malignant pleural effusion is still poorly understood and the treatment options are limited. OBJECTIVE: 1) To study the pathophysiology of malignant pleural effusion in animal model with Lewis cells in different concentrations; 2) Evaluate the effects of the intrapleural therapy with anti-VEGF and anti-EGFR and the frequency of EGFR and KRAS mutations in this model. METHODS: We used pleural neoplasm experimental model with mice C57BL/6 and Lewis cells (LLC) divided into two steps: study with different concentrations of LLC cells (0.1, 0.5 and 1.5x105) and evaluation of targeted therapies. After the standardization of the model, four groups of mice received intrapleural treatment with anti-VEGF, anti-EGFR, anti-VEGF+anti-EGFR or saline (untreated) 3, 7, 10 and 14 days after induction of pleural neoplasm with injection of 0.5x105 LLC cells. In 20 animals of each group was evaluated the survival curve. 160 animals underwent euthanasia 7, 10, 14 or 21 days after and assessed weight, mobility, volume of pleural fluid, inflammatory, immunological and biochemical markers in the liquid, presence of tumor and histological changes in pleura, lung, kidney, liver and spleen. It was evaluated, through immunohistochemistry, tumor apoptosis and proliferation, VEGF and EGFR. Gene expression of EGFR, VEGF, KRAS and ALK and frequency of mutations of EGFR and KRAS were also evaluated. Statistical analysis: One Way ANOVA, Kaplan-Meier, p < 0.05. RESULTS: In the standardization of the model we observed that the concentration that kept parameters of pleural neoplasm with higher survival rate was 0.5x105 LLC cells. In the second stage, target-therapies, pleural carcinomatosis was lethal with maximum survival of 25 days, with no difference between the groups. Weight decrease was observed in all groups after 21 days. Mobility was better in groups that receiving anti-EGFR. Pleural fluid volume was greater in the untreated group throughout the study. Immunological and biochemical parameters have increased temporarily being most evident in the untreated group. Tumor implants in pleura were more apparent in the untreated group after 14 days. The lung inflammation was minimal in all groups. The untreated group showed tumor implants in the pericardium and heart muscle after 21 days, hepatic and renal steatosis after 14 days and spleen white pulp hyperplasia in 21 day. High rates of apoptosis and smaller tumor proliferation indices were observed in groups that received treatment with anti-VEGF and anti-EGFR+anti-EGFR. We also found gene KRAS mutation and tumoral gene overexpression of EGFR and KRAS. CONCLUSION: Targeted therapies reduced significantly the pleural effusion, morbidity and histological parameters, although without an impact on survival rate in this experimental model. Our data indicate that the tumor lineage LLC has an aggressive tumor phenotype shown by KRAS mutation and overexpression of EGFR, which can be associated with a worse prognosis and a lower response to EGFR inhibitors

<p>UVOD: Drenaža grudnog ko&scaron;a nakon resekcija pluća je osnovni grudno hirur&scaron;ki postupak, koji omogućuje pro&scaron;irenje (reekspanziju) pluća iz kolabiranog stanja, evakuaciju vazduha, krvi i izliva iz pleuralnog prostora i potpomognuta je primenom aspiracije na drenove (sukciona ili aspiraciona drenaža). Iako je drenaža&nbsp; svakodnevna grudno hirur&scaron;ka procedura, postupak sa drenovima je zasnovan prvenstveno na iskustvu, a manje na osnovu naučnih studija. Pri mirnom disanju inspiratorni pritisak u pleuralnom prostoru je prosečno - 8 cm H2O, a ekspiratorni - 4 cm H2O. Pri forsiranom disanju pritisci mogu dostići - 50 cm H2O i +70 cm H2O. Na osnovu tih fiziolo&scaron;kih podataka, većina hirurga primenjuje aspiraciju od - 10 do - 40 cm H2O. Koncepta pleuralnog deficita - disproporcije volumena preostalog plućnog tkiva i zapremine grudnog ko&scaron;a doveo je do razvoja tehničkih postupaka za postizanje nove fiziolo&scaron;ke ravnoteže u pleuralnom prostoru i razmatranja rutinske primene podvodne (pasivne) drenaže nakon resekcija pluća. Pritisak na zdravstvenu službu za smanjenje tro&scaron;kova i skraćenje postoperativne hospitalizacije uz mogućnost rane mobilizacije pacijenta čine podvodnu drenažu zanimljivom alternativom tradicionalno prihvaćenoj aktivnoj aspiraciji na drenove.&nbsp; CILJ: Da se utvrdi da li aplikacija aktivne aspiracije na drenove nakon lobektomije pluća u poređenju da podvodnom drenažom ima povoljno terapijsko dejstvo na postizanje i održavanje reekspanzije pluća; Da se kvantitativno uporede različiti modovi aktivne aspiracije preko drenova; Da se uporedi dužina hospitalizacije i pojava hirur&scaron;kih i nehirur&scaron;kih komplikacija između grupa ispitanika kod kojih se primenjuje podvodna (pasivna) drenaža i aspiracija preko drenova. METODOLOGIJA: Prospektivna studija bez randomizacije obuhvatila je 301 ispitanika kojima je načinjena lobektomija pluća zbog karcinoma pluća na Klinici za grudnu hirurgiju Instituta za plućne bolesti Vojvodine u Sremskoj Kamenici u periodu od 01.01.2008. - 28.02.2010. godine. Beleženi su i analizirani podaci o preoperativnom stanju: plućnoj funkciji, prethodno primljenoj neoadjuvantnoj hemioterapiji i pridruženim bolestima. Analizirani su hirur&scaron;ki operativni podaci o postojanju buloznog emfizema, adhezija u pleuralnom prostoru, anatomskoj vrsti lobektomije, dodatnim hirur&scaron;kim procedurama i postojanju gubitka vazduha na kraju operacije. Analizirani su postoperativni podaci o secernaciji na drenove tokom prva 24 h i ukupno, trajanju gubitka vazduha na drenove u danima, ukupnom trajanju drenaže, ukupnom trajanju hospitalizacije, pojavi produženog gubitka vazduha na dren definisanog kao gubitak duže od 7 dana, potrebi za redrenažom grudnog ko&scaron;a (broj drenova upotrebljenih za redrenažu), kompletnost reekspanzije pluća pre vađenja drenova, pojavi drugih hirur&scaron;kih komplikacija, pojavi op&scaron;tih medicinskih komplikacija i pojavi kasnih komplikacija &ndash; vi&scaron;e od 30 dana nakon operacije ili nakon otpusta. Prvu grupu ispitanika sačinjavaju pacijenti kojima je načinjena lobektomija pluća, nakon čega je aplikovana aspiracija od -20 cm vodenog stuba do klemovanja i vađenja drenova. Drugu grupu ispitanika sačinjavaju pacijenti kojima je aplikovana aspiracija od -20 cm vodenog stuba na dan operacije i zatim -10 cm vodenog stuba do klemovanja i vađenja drenova. Treću grupu ispitanika sačinjavaju pacijenti kojima je načinjena lobektomija pluća, nakon čega je aplikovana aspiracija od -20 cm vodenog stuba na dan operacije i zatim podvodna drenaža do klemovanja i vađenja drenova. Četvrtu grupu ispitanika sačinjavaju pacijenti kojima je načinjena lobektomija pluća, nakon čega je aplikovana aspiracija od -20 cm vodenog stuba na dan operacije i zatim dnevna procena i modifikacija na sledeći način: aspiracija od -20 cm vodenog stuba do postizanja reekspanzije pluća, zatim postepeno smanjenje aspiracije po nahođenju operatera do klemovanja i vađenja drenova. REZULTATI: Između grupa ispitanika ne postoji statistički značajna razlika po starosti (p=0,77),&nbsp; parametrima plućne funkcije: vrednost FEV1 (p=0,6316), vrednost ITGV (p=0,6202), vrednost TLC (p=0,6922) i za vrednost RV ne postoji razlika (p=0,6552). Razlika ne postoji između grupa ni u učestalosti pridruženih bolesti (p=0,4522). Grupe su međusobno homogene po preoperativnim parametrima. Snižen FEV1 u ukupnoj populaciji pacijenata nije uticao na pojavu produženog gubitka vazduha (P=0,571), kao ni povi&scaron;enje ITGV (P=0,22), RV (p=0,912), niti vrednost TLC (0,521). Upoređene su međusobno osnovne vrste lobektomija: desna gornja, leva gornja, desna donja, leva donja, srednja lobektomija, kao i donja i gornja bilobektomija desno. Kako je učestalost svake pojedinačne lobektomije u 4 grupe ispitanika mali da bi se uporedile iste lobektomije između grupa, poređenje je moguće samo između anatomski različitih lobektomija kumulativno u svim grupama. Razlika u pojavi produženog gubitka vazduha između različitih lobektomija postoji, ali nije dostigla statističku značajnost (p=0,061). Međutim, kada se analizira svaka lobektomija pojedinačno, uočava se da desna donja bilobektomija ima značajno veću učestalost produženog gubitka vazduha u odnosu na sve ostale lobektomije zajedno (P=0,009). Razlika u dužini drenaže kod&nbsp; različitih lobektomija je dostigla statistički značaj (p=0,0356), kao i u ukupnoj dužini hospitalizacije (p=0,0007). Dodatak resekcije perikarda, grudnog zida ili dijafragme, klinasta resekcija susednog režnja ili sleeve resekcija bronha kao dodatne procedure nisu uticali na pojavu produženog gubitka vazduha (p=0,58). Podaci o učestalosti adhezija u ispitivanoj populaciji pacijenata i njihovom uticaju na pojavu produženog gubitka vazduha daju granične vrednosti. I ovde je broj pacijenata u svakoj pojedinačnoj kategoriji adhezija (postojanje adhezija na skali od 0-3) mali da bi testiranje povezanosti sa produženim gubitkom vazduha moglo dostići statističku značajnost - razlika postoji, ali nije značajna (p=0,065). Radi povećanja statističke snage je izvedeno testiranje za podelu ima ili nema adhezija. Razlika postoji, ali ni ovim testiranjem nije dostignuta statistički značajna razlika (p=0,057). Postojanje buloznog emfizema takođe dovodi do povećanja učestalosti produženog gubitka vazduha, ali ni ovde razlika nije značajna (p=0,063).&nbsp; Primena hemoterapije pre operacije nije dovela do statistički značajne razlike u pojavi produženog gubitka vazduha (p=0,0623) i ukupnoj stopi komplikacija (p=0,088), kao ni dužine hospitalizacije (p=0,2), iako razlika postoji i paradoksalno rezultat je bolji kod pacijenata koji su primili hemioterapiju, &scaron;to može ukazivati na uticaj selekcije pacijenata za operaciju. Između 4 grupe ispitanika nije uočena razlika u potrebi za redrenažom grudnog ko&scaron;a (p=0,101), potrebi za povećanjem nivoa aktivne aspiracije (p=0,326), ukupnoj pojavi komplikacija (p=0,087) i pojavi produženog gubitka vazduha (P=0,323). Razlika postoji i visoko je značajna u dužini trajanja drenaže (p=0,001) i dužini hospitalizacije (P=0,000). Broj drenova (1 ili 2 drena postavljena intraoperativno) nije uticao na pojavu produženog gubitka vazduha (p=0,279), ali je značajno kraća hospitalizacija kod pacijenata sa jednim drenom (p=0,0001). Logistička regresiona analiza je pokazala da je samo donja bilobektomija značajno uticala na pojavu produženog gubitka vazduha na dren, dok nije nađen uticaj aktivne aspiracije na drenove, prisustva adhezija, buloznog emfizema, sniženih vrednosti FEV1, primene redukcije pleuralnog prostora (space reducing), broja drenova i dodatne operacije (resekcije). ZAKLJUČAK: Sprovedenim istraživanjem utvrđeno je da primena aktivne aspiracije na drenove ne pokazuje razliku u odnosu na podvodnu drenažu u postizanju i održavanju reekspanzije pluća nakon lobektomije. Aktivna aspiracija ne utiče na pojavu produženog gubitka vazduha na drenove definisanog kao gubitak vazduha duže od 7 dana, ali utiče na produženje ukupnog trajanja drenaže i hospitalizacije. Nivo aktivne aspiracije ili primena dnevnih modifikacija nivoa aspiracije ne utiče na rezultate lečenja.&nbsp; U ovom istraživanju preoperativna plućna funkcija, kao ni preoperativna hemoterapija ne utiču na pojavu produženog gubitka vazduha na drenove. Desna donja bilobektomija u odnosu na sve druge lobektomije dovodi do če&scaron;će pojave produženog gubitka vazduha, produžene drenaže i hospitalizacije. Dodatne resekcije okolnih tkiva u sklopu lobektomije ili primena redukcije pleuralnog prostora ne utiču na pojavu produženog gubitka vazduha. Intraoperativni nalaz adhezija u pleuri i buloznog emfizema pluća povećavaju rizik produženog gubitka vazduha, ali je taj uticaj na granici statističke značajnosti. Primena jednog drena nakon lobektomije umesto dva ne utiče na pojavu produženog gubitka vazduha, ali utiče na skraćenje drenaže i hospitalizacije. U multivarijatnoj analizi samo je donja bilobektomija značajno uticala na pojavu produženog gubitka vazduha na dren, dok nije nađen uticaj aktivne aspiracije na drenove, prisustva adhezija, buloznog emfizema, sniženih vrednosti FEV1, primene redukcije pleuralnog, broja drenova i dodatne resekcije okolnih tkiva.</p> / <p>INTRODUCTION: The drainage of the thorax after pulmonary resection is a basic thoracic surgery procedure which enables reexpansion after lung collapse and the evacuation of air, blood and effusion from the pleural cavity. It is supported by the use of drainage aspiration (suction or aspiration drainage). Although drainage is an everyday procedure in thoracic surgery, the use of drains is based mainly on specialist experience and less on scientific research. During calm breathing the inspiratory pressure in the pleural cavity is &ndash; 8cm H2O on average, while the expiratory pressure is &ndash; 4cm H2O. During forced breathing the pressures can reach up to &ndash; 50 cm H2O and + 70 cm H2O. Based on this physiological data, most surgeons apply the aspiration from &ndash; 10 to &ndash; 40 cm H2O. The concept of pleural deficit (the disproportion of the volume of the remaining pulmonary tissue and the volume of the thorax) has attributed to development of new technical procedures in order to achieve a new physiological balance in the pleural cavity. It has also brought upon the consideration of routine underwater seal drainage after pulmonary resection. Underwater seal drainage represents an interesting alternative to the traditional active drainage aspiration, especially considering the need to reduce medical expenses and shorten the postoperative hospitalization period. AIM: To determine whether active drainage aspiration after pulmonary lobectomy has a favorable therapeutic effect on achieving and maintaining pulmonary reexpansion in comparison with underwater seal drainage; to quantitatively compare the different modes of active drainage aspiration; to compare hospitalization duration and surgical and non-surgical complication with groups of patients on whom either underwater seal drainage or aspiration drainage was applied. METHODOLOGY: The prospective study without randomization has covered 301 patients on whom pulmonary lobectomy was performed due to lung carcinoma at the Thoracic Surgery Clinic of the Institute of Pulmonary Diseases of Vojvodina from 1st January 2008 to 28th February 2010. The data collected in the pre-operative state included: pulmonary function, previous neoadjuvant chemotherapy and comorbidities. In the research, surgical operative data and postoperative data were analyzed. Surgical operative data included information about the bullous emphysema, adhesion in the pleural cavity, anatomic type of lobectomy, additional surgical procedures and air leak after surgery. Postoperative data involved information about amount of fluid on drainage during the first 24 hours and in total, air leak duration in days, total drainage period, overall hospitalization period, prolonged air leak defined as leak longer than 7 days, the need for redrainage of thorax (number of tubes used for redrainage), completeness of pulmonary reexpansion before the end of drainage, other surgical complications, comorbidities and late complications (after more than 30 days following the surgery or release). The first group consists of patients on whom pulmonary lobectomy was performed, after which an aspiration of &ndash; 20 cm H2O was applied before clamping and tube extraction. The second group consists of patients on whom pulmonary lobectomy was performed, after which an aspiration of &ndash; 20 cm H2O was applied on surgery day and again &ndash; 10 cm H2O before clamping and tube extraction. The third group consists of patients on whom pulmonary lobectomy was performed, after which an aspiration of &ndash; 20 cm H2O was applied on surgery day and underwater seal drainage was applied before clamping and tube extraction. The fourth group consists of patients on whom pulmonary lobectomy was performed, after which an aspiration of &ndash; 20 cm H2O was applied on surgery day, and then daily monitored and modified in such a way that an aspiration of &ndash; 20 cm H2O was applied until pulmonary reexpansion and then gradually lowered according to individual surgery experience before clamping and tube extraction. RESULTS: There is no significant statistical difference between groups of patients in: age (p=0.77), FEV1 (p=0.6316), ITGV (p=0.6202), TLC (p=0.6922) and RV (p=0.6552) and comorbidities (p=0.4522). The groups are homogenous in pre-operative parameters. Lowered FEV1 among all patients did not affect prolonged air leak (p=0.571), nor the increase in values of ITGV (p=0.22), RV (p=0.912) and TLC (p=0.5211). The lobectomies that were compared were: upper right, upper left, lower right, lower left, middle, as well as upper and lower right bilobectomy. The comparison was implemented only on anatomically different lobectomies cumulatively among groups, due to the low occurrence of each type of lobectomy in groups. The difference in prolonged air leak does exist, but is not statistically significant (p=0.061). Prolonged air leak has a significantly higher occurrence in lower right bilobectomies (p=0.009). Drainage duration and hospitalization period variations in different kinds of lobectomy are statistically significant (p=0.0356 and p=0.0007, respectively). Additional pericardial, thoracic or diaphragm resection, wedge resection of the neighboring lobe, or sleeve bronchial resection did not affect prolonged air leak (p=0.58). The research has established that the occurrence of adhesion (on a scale 0-3) in patients and bulous emphysema attribute to prolonged air leak (p=0.065 and p=0.063, respectively).&nbsp; Comparison between patients with and without adhesions revealed similar result. Difference exists, but it is not statistically significant (p=0,057).&nbsp; Pre-operative chemotherapy had no statistical significance on prolonged air leak (p=0.0623), total rate of complications (p=0.088), nor hospitalization period (p=0.2). Paradoxically, the treatment was in favor of those patients who had taken pre-operative chemotherapy, which could be due to the selection of patients for surgery.&nbsp; Among the four groups, there was no difference in need for thoracic redrainage (p=0.101), need for increase in level of active aspiration (p=0.326), overall complication occurrence (p=0.087) and prolonged air leak occurrence (p=0.323). There is a statistically significant difference in drainage duration (p=0.001) and hospitalization period (p=0.000). The number of tubes (1 or 2 tubes set intraoperatively) did not affect prolonged air leak occurrence (p=0.279). The hospitalization period in patients with one tube set intraoperatively is significantly shorter (p=0.0001). Logistic regression analysis has shown that only lower bilobectomy had a significant impact on prolonged air leak, unlike active drainage aspiration, the presence of adhesions, bullous emphysema or lowered FEV1 values, pleural cavity space reducing, number of tubes and resection. CONCLUSION: The research has shown: Active drainage aspiration has no difference in effect in achieving and maintaining pulmonary reexpansion after lobectomy when compared to underwater seal drainage; Active drainage aspiration does not affect prolonged air leak, defined as air leak longer than 7 days; Active drainage aspiration has an impact on the overall drainage duration and hospitalization period; The level of active drainage aspiration and daily modification of the mentioned do not affect treatment results; Preoperative pulmonary function does not affect prolonged air leak occurrence; Preoperative chemotherapy does not affect prolonged air leak occurrence; Prolonged air leak and drainage and hospitalization period occur most often in lower right bilobectomies; Nor additional resections nor pleural cavity reduction affect prolonged air leak occurrence; The presence of pleural adhesions and bullous emphysema rarely attribute to the increase of prolonged air leak occurrence; The number of tubes implemented intraoperatively does not affect prolonged air leak occurrence, but it shortens drainage and hospitalization periods; By multivariate analysis, that only lower bilobectomy has a significant impact on prolonged air leak, unlike active drainage aspiration, the presence of adhesions, bulous emphysema or lowered FEV1 values, pleural cavity space reducing, number of tubes and resection.</p>

Evalúa los resultados del manejo del empiema con cirugía torácica videoasistida (VATS) en pacientes operados en hospitales y clínicas de la ciudad de Lima entre el periodo julio 2013 a diciembre del 2018. Se realiza un estudio no experimental, descriptivo y de ámbito retrospectivo y transversal. Se utilizó una ficha elaborada para recolectar la información de todos aquellos pacientes con empiema que fueron operados por cirugía torácica videoasistida en algunos hospitales y clínicas del país, 2013-2018; para analizar los datos en un programa estadístico (SPSS) y calcular las frecuencias y promedios de las variables. La población total fue de 20 pacientes presentando una mortalidad de 10% posterior a la cirugía, la tasa de conversión a cirugía abierta fue del 10%, el 65% de los pacientes presentaron complicaciones luego de la intervención, de las cuales las principales fueron de origen torácico (65%) siendo la neumonía intrahospitalaria la más frecuente de todas (28.5%), la resolución completa del empiema alcanzó el 95% del total de cirugías y la técnica más utilizada de la VATS fue el uso de un solo puerto (80%). La conclusión es que se evidenció baja tasa de mortalidad, bajo porcentaje de complicaciones postoperatorias, alta tasa de resolución del empiema y bajo porcentaje de conversión quirúrgica con el uso de esta técnica mínimamente invasiva. / Tesis