Spectrum of somatic EGFR, KRAS, BRAF, PTEN mutations and TTF-1 expression in Brazilian lung cancer patients.

Lung cancer is the leading global cause of cancer-related mortality. Inter-individual variability in treatment response and prognosis has been associated with genetic polymorphisms in specific genes: EGFR, KRAS, BRAF, PTEN and TTF-1. Somatic mutations in EGFR and KRAS genes are reported at rates of 15-40% in non-small cell lung cancer (NSCLC) in ethnically diverse populations. BRAF and PTEN are commonly mutated genes in various cancer types, including NSCLC, with PTEN mutations exerting an effect on the therapeutic response of EGFR/AKT/PI3K pathway inhibitors. TTF-1 is expressed in approximately 80% of lung adenocarcinomas and its positivity correlates with higher prevalence of EGFR mutation in this cancer type. To determine molecular markers for lung cancer in Brazilian patients, the rate of the predominant EGFR, KRAS, BRAF and PTEN mutations, as well as TTF-1 expression, was assessed in 88 Brazilian NSCLC patients. EGFR exon 19 deletions (del746-750) were detected in 3/88 (3·4%) patients. Activating KRAS mutations in codons 12 and 61 were noted in five (5·7%) and two (2·3%) patients, respectively. None of the common somatic mutations were detected in either the BRAF or PTEN genes. TTF-1 was overexpressed in 40·7% of squamous-cell carcinoma (SCC). Our findings add to a growing body of data that highlights the genetic heterogeneity of the abnormal EGFR pathway in lung cancer among ethnically diverse populations.

Cavernostomy x resection for pulmonary aspergilloma: a 32-year history.

BACKGROUND: The most adequate surgical technique for the treatment of pulmonary aspergilloma is still controversial. This study compared two groups of patients submitted to cavernostomy and pulmonary parenchyma resection. METHODS: Cases of pulmonary aspergilloma operated upon between 1979 and 2010 were analyzed retrospectively. Group 1 consisted of patients submitted to cavernostomy and group 2 of patients submitted to pulmonary parenchyma resection. The following variables were compared between groups: gender, age, number of hospitalizations, pre- and postoperative length of hospital stay, time of follow-up, location and type of aspergilloma, preoperative symptoms, underlying disease, type of fungus, preoperative pulmonary function, postoperative complications, patient progression, and associated diseases. RESULTS: A total of 208 patients with pulmonary aspergilloma were studied (111 in group 1 and 97 in group 2). Group 1 was older than group 2. The number of hospitalizations, length of hospital stay and time of follow-up were higher in group 1. Hemoptysis was the most frequent preoperative symptom in group 1. Preoperative respiratory malfunction was more severe in group 1. Hemorrhagic complications and recurrence were more frequent in group 1 and infectious complications and residual pleural space were more common in group 2. Postoperative dyspnea was more frequent in group 2. Patient progression was similar in the two groups. No difference in the other factors was observed between groups. CONCLUSIONS: Older patients with severe preoperative respiratory malfunction and peripheral pulmonary aspergilloma should be submitted to cavernostomy. The remaining patients can be treated by pulmonary resection.

Impacto do 18F-FDG PET/CT no estadiamento de pacientes com câncer de pulmão: chave para melhorar o tratamento / The impact of 18F-FDG PET/CT in staging of non-small cell lung cancer patients: the key to improve patient treatment strategy

O câncer de pulmão lidera a causa de mortes relacionadas ao câncer em homens e mulheres em todo o mundo. O mais comum é o câncer do pulmão de células não pequenas (NSCLC), sendo essencial o seu estadiamento preciso para a escolha do tratamento. A tomografia por emissão de pósitrons (PET) com 18F-fluorodeoxiglicose (18F-FDG) pode fornecer informações molecular e metabólica que, quando adquiridas simultaneamente com tomografia computadorizada (TC), constituemse instrumento muito útil no diagnóstico e no estadiamento do câncer. O estadiamento do câncer de pulmão é importante para evitar cirurgias desnecessárias, e reduzir a morbidade e os custos do tratamento. Este estudo objetivou analisar o impacto da 18F-FDG PET/TC na avaliação de pacientes com NSCLC na realidade brasileira. Foram incluídos 26 pacientes com diagnóstico histopatológico de NSCLC que foram submetidos a estadiamento em dois momentos com: 1. Imagens morfológicas (raios-x e TC); 2. 18F-FDG PET/CT. A 18F-FDG PET/CT mudou 30% o estadiamento linfonodal classificado como operável com alta sensibilidade e valor preditivo negativo. Em relação ao estádio de metástase, a 18F-FDG PET/CT aumentou em 11,5% a detecção de metástases não detectadas. A 18F-FDG PET/CT reduziu significativamente o número de pacientes classificados como operáveis, evitando a realização de toracotomia desnecessária em 19,2% dos casos. A informação metabólica obtida pela 18F-FDG PET/CT demonstrou melhor precisão quando comparada com métodos anatômicos na detecção de linfonodos e metástases à distância. Assim, demonstra impacto importante na estratégia e nos custos relacionados com o tratamento.

Lung cancer leads the cause of cancer-related deaths in men and women around the world. The most common is non-small cell lung cancer (NSCLC). Fast and accurate staging is essential for choosing treatment for NSCLC. The positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG) can provide molecular and metabolic information, which acquired simultaneously with computed tomography (CT), has proved to be a very useful tool in the cancer diagnosis and staging. Identifying the stage of lung cancer is important to avoid unnecessary surgeries, reducing morbidity and treatment costs. This study aims to examine the impact of 18F-FDG PET/CT in the initial evaluation of patients with NSCLC in the Brazilian reality. Twenty-six patients with histopathologic diagnosis of NSCLC were included. They underwent staging in two separated moments: first with morphological images (x-ray and computed tomography scan) and after with 18F-FDG PET/CT. The performance of 18F-FDG PET/CT changed lymph node staging in around 30% of the patients initially classified as potentially operable, with high sensitivity and negative predictive values. Regarding the stage of metastasis, 18F-FDG PET/CT increased by 11.5% the detection of metastasis not previously detected. About the clinical staging, using the 18F-FDG PET/CT significantly reduced the number of patients classified as potentially operable in the early stages, avoiding the use of unnecessary thoracotomies in 19.2% of patients. The metabolic information obtained by 18F-FDG PET/CT demonstrated better accuracy when comparated to anatomic methods in the detection of lymph node and distant metastases. Thus, having important impact on therapeutic strategy and treatment cost related.

Intimal sarcoma of the pulmonary artery: a differential diagnosis of chronic pulmonary thromboembolism.

Intimal sarcoma of the pulmonary artery is a rare and potentially lethal tumor, the diagnosis of which is difficult and therefore frequently delayed. The clinical signs and symptoms are nonspecific, often mimicking chronic pulmonary thromboembolism (CPTE). We report the case of a 45-year-old male under treatment for CPTE associated with pulmonary arterial hypertension and chronic cor pulmonale. There was no response to treatment with anticoagulants and sildenafil. We emphasize the difficulties in diagnosing intimal sarcoma of the pulmonary artery, the need to investigate this neoplasm in the differential diagnosis of CPTE and the systematic use of criteria for the appropriate prescription of new medications for pulmonary artery hypertension.

Sarcoma intimal de artéria pulmonar: um diagnóstico diferencial do tromboembolismo pulmonar crônico / Intimal sarcoma of the pulmonary artery: a differential diagnosis of chronic pulmonary thromboembolism

O sarcoma intimal de artéria pulmonar é um tumor raro e potencialmente letal, de diagnóstico difícil e, muitas vezes, tardio. Os sinais e sintomas clínicos são inespecíficos, simulando com frequência o tromboembolismo pulmonar crônico (TEPC). Apresentamos o caso de um homem de 45 anos em tratamento de TEPC associado com hipertensão arterial pulmonar e cor pulmonale crônico, sem resposta ao uso de anticoagulantes e sildenafil. Ressaltamos as dificuldades para o diagnóstico do sarcoma intimal de artéria pulmonar, a necessidade de se pesquisar essa neoplasia no diagnóstico diferencial do TEPC e a utilização sistemática de critérios para a adequada indicação dos novos medicamentos para a hipertensão arterial pulmonar.

Intimal sarcoma of the pulmonary artery is a rare and potentially lethal tumor, the diagnosis of which is difficult and therefore frequently delayed. The clinical signs and symptoms are nonspecific, often mimicking chronic pulmonary thromboembolism (CPTE). We report the case of a 45-year-old male under treatment for CPTE associated with pulmonary arterial hypertension and chronic cor pulmonale. There was no response to treatment with anticoagulants and sildenafil. We emphasize the difficulties in diagnosing intimal sarcoma of the pulmonary artery, the need to investigate this neoplasm in the differential diagnosis of CPTE and the systematic use of criteria for the appropriate prescription of new medications for pulmonary artery hypertension.