OBJECTIVES: The aim of this study is to evaluate the access of patients with lung cancer in a densely populated area of São Paulo to the Brazilian Public Health System, focusing on the time spent from symptom onset or initial diagnosis until the beginning of treatment. METHODS: We retrospectively reviewed 509 patients with malignant lung neoplasms who were admitted to a single reference oncology center of the public health system between July 2008 and December 2014. Patients were considered eligible for this study if they were older than 18 years and had not undergone any previous oncology treatment when they were admitted to the institution. The following data were collected from all patients: age, gender, smoking status, tumor staging, time from the when the first symptoms were experienced by the patient to when the patient was diagnosed with cancer, time from the first appointment to cancer diagnosis, and time from when the patient was diagnosed with cancer to the initiation of treatment. RESULTS: The median time from symptom onset to diagnosis was three months. From the first appointment to diagnosis, the median time interval was one month; however, 79% of patients were diagnosed in up to two months. The median time from diagnosis to the start of treatment was one month, but most patients (82.5%) started treatment in up to two months. CONCLUSION: In our highly populated region with preferential access to the public health system, patients are required to wait a relatively long time to effectively begin treatment for lung cancer. This type of study is important to alert medical societies and government health agencies.

ABSTRACT Laetia suaveolens (Poepp.) Benth., Salicaceae, popularly known as "casinga-cheirosa", "caferana", or "laranjinha", is native to Brazil but not endemic to this country. A crude organic extract was obtained from the leaves and stem and intraperitoneally administered in male Balb-c mice. Its behavioral effects were evaluated in the open field and elevated plus maze in a two-stage experiment that assessed ten different parameters related to behavior as locomotion, emotionality, and anxiety. In the first stage of the experiment, intraperitoneal the crude organic extract administration dose-dependently impaired locomotion and emotionality 30–120 min after administration. A significant decrease in defecation was observed, which was related to emotionality. No alterations in the elevated plus maze were found; thus, this apparatus was not used in the next stage of the experiment. In the second stage, the previously determined non-lethal dose of 0.1563 g/kg was intraperitoneally administered, which impaired locomotion and rearing frequency and increased immobility time. Necropsy revealed smooth intestine hemorrhage. Rutin, leucoside, nicotiflorin, guaijaverin, and astragalin were isolated from the crude organic extract. This is the first time that these compounds have been identified in L. suaveolens. In conclusion, the crude organic extract impaired locomotion and emotionality and caused hemorrhage in male Balb-c mice, indicating that its consumption can be harmful to humans and animals. The present results provide a basis for further studies on the pharmacology, toxicology, and natural product chemistry of the crude organic extract.

The organic extract EB689, obtained from the stem of Abarema auriculata (Benth.) Barneby & J.W.Grimes, Fabaceae, commonly known as "saboeiro-ferro", was chemically studied, as well as its influence over behavioral effects such as locomotion, emotionality and anxiety, after intra-peritonial administration were assessed. The open-field and elevated-plus maze were used in experiments divided into two stages. The first stage aimed for the identification of the main effects over behavior using a reduced number of animals against half-fold diluted doses of EB689. The same variables were also tested in a second stage of the experiment using the non-lethal intra-peritoneal dose of 4.8 mg/kg in a larger number of animals. It was observed that EB689 clearly decreased locomotion, which was probably caused by internal hemorrhage causing hypovolemic shock. Although it is the first time lupeol and eucryphin are described in A. auriculata, it is still not clear if they are involved in the toxicology of A. auriculata. The undesirable effects of EB689 are better understood, the basis for further pharmacological assays aiming antitumor activity are supported.

RESUMO Os sarcomas primários do pulmão são raros e representam aproximadamente 0,5% de todas as neoplasias pulmonares. Havia aproximadamente 300 casos descritos na literatura até 2006. Todos os tipos histológicos foram relatados, sendo que os sarcomas intratorácicos mais comuns são o angiossarcoma, leiomiossarcoma, fibrossarcoma, hemangiopericitoma e rabdomiossarcoma. Devido à sua baixa frequência, o comportamento biológico desses tumores não é bem conhecido. O leiomiossarcoma é um dos subtipos mais encontrados no pulmão, e normalmente ocorre na sexta década de vida com predominância nos homens. Embora a frequência de doença metastática não esteja relacionada ao tamanho do tumor, o prognóstico é pior nos tumores de alto grau. Quando comparados a outros sarcomas, a sobrevida após a ressecção completa dos leiomiossarcomas de pulmão é mais prolongada. Relatamos o caso de um paciente com leiomiossarcoma primário de pulmão de origem brônquica tratado com ressecção completa e seguimento de longo prazo.

ABSTRACT Primary sarcomas of the lung are rare and account for 0.5% of all primary lung tumors. There were approximately 300 cases described in the literature as of 2006. All histologic types of sarcoma were described, and the most common intrathoracic types reported were angiosarcoma, leiomyosarcoma, fibrosarcoma, hemangiopericytoma, and rhabdomyosarcoma. The biological behavior of these tumors is not well-known due to their low frequency. Leiomyosarcomas represent one of the most common subtypes encountered in the lungs, and usually occur during the sixth decade, with male predominance. Although the frequency of metastatic disease is not related to tumor size, prognosis was reported to be poorer in high-grade tumors. In comparison with other sarcomas, survival after complete resection of pulmonary leiomyosarcoma was reported as longer. We report on a patient with primary leiomyosarcoma originating from the bronchus with complete resection and long-term follow-up.

OBJETIVO: A quimioterapia dupla com base em platina consiste no tratamento padrão para o câncer de pulmão não pequenas células (CPNPC) avançado. Contudo, o prognóstico dos pacientes com doença recorrente ou em progressão após a quimioterapia de primeira linha é ruim. Quimioterapia de manutenção, de segunda linha e até de terceira linha são tratamentos válidos para pacientes com CPNPC de estádio avançado. Infelizmente, poucos pacientes são candidatos para o tratamento quimioterápico além daquele de primeira linha. O presente estudo avalia as características de pacientes com CPNPC e os resultados do tratamento da doença metastática, com ênfase na quimioterapia de segunda e de terceira linha. MÉTODOS: Este é um estudo observacional e retrospectivo de 2.673 pacientes com CPNPC metastático, estádio IV, admitidos para tratamento em duas instituições de São Paulo, SP. A quimioterapia de primeira linha foi definida como a primeira abordagem quimioterápica administrada ao paciente. Quimioterapias de segunda e de terceira linha foram definidas como tratamento sistêmico administrado após a interrupção da quimioterapia de primeira linha, seja por intolerância ou por doença em progressão ou recorrente. RESULTADOS: A maioria dos pacientes (57,9%) foi submetida à quimioterapia de primeira linha; aproximadamente 23,4% receberam quimioterapia de segunda linha e 8% de terceira. Apenas 2,5% foram submetidos ao regime de quarta linha. A sobrevida global mediana (OS) foi de 8 meses (IC 95%: 8-9 meses). Na análise univariada, sexo (p < 0,05), histologia, quimioterapia de primeira linha, resposta imparcial à quimioterapia de primeira linha e quimioterapia de segunda linha (p < 0,01) foram fatores prognósticos relacionados com a sobrevida global. Na análise multivariada, status de performance (p = 0,04), submissão do paciente a qualquer tipo de quimioterapia de segunda linha (p < 0,01) e resposta à quimioterapia de primeira linha (p < 0,01) foram os únicos fatores independentes preditivos de maior sobrevida. CONCLUSÃO: A quimioterapia de segunda linha é uma estratégia terapêutica a ser considerada em seletos grupos de pacientes. O status de performance e a resposta à quimioterapia de primeira linha poderiam ser alguns dos fatores determinantes durante o processo de seleção dos pacientes que deverão ser submetidos a regimes quimioterápicos além da primeira linha.

OBJECTIVE: Platinum-based doublet chemotherapy is considered the standard of care for advanced non-small cell lung cancer (NSCLC). However, prognosis after recurrent or progressive disease following first-line chemotherapy is usually poor. Maintenance chemotherapy, second line treatment and even third line chemotherapy are available for patients with advanced NSCLC. Unfortunately, few patients are candidates for chemotherapy beyond first line. The present study evaluated characteristics of patients with NSCLC and outcomes of the treatment of their metastatic disease, with emphasis on second and third-line chemotherapy. METHODS: This was a retrospective observational study of 2,673 patients with metastatic, stage IV, non-small cell lung cancer admitted for treatment in two São Paulo institutions. First-line chemotherapy was defined as the first chemotherapeutic approach administered to the patient. Second and third-line chemotherapy were defined as the systemic treatment administered after discontinuing first-line chemotherapy, either for intolerance or for progressive or recurrent disease. RESULTS: Most patients (57.9%) received first-line chemotherapy, and approximately 23.4% received second-line and 8% third-line regimens. Only 2.5% received fourth-line chemotherapy. Median overall survival (OS) was 8 months (95% CI: 8-9 months). At univariate analyses, gender (p < 0.05), histology, first-line chemotherapy, objective response to first-line chemotherapy and second-line chemotherapy (p < 0.01) were prognostic factors related to overall survival. At multivariate analysis, only performance status (p = 0.04), receiving any second-line chemotherapy (p < 0.01) and response to first-line chemotherapy (p < 0.01) were independent predictors of overall survival. CONCLUSION: Second-line chemotherapy is a therapeutic strategy that should be considered for a selected group of patients. Performance status and response to first-line chemotherapy could be determinant characteristics to select patients who might be treated beyond first-line chemotherapy.

A traqueostomia percutânea tem substituído a traqueostomia convencional em muitas Unidades de Terapia Intensiva, devido à facilidade e segurança do método realizado à beira do leito, dispensando o transporte do paciente da Unidade de Terapia Intensiva para o Centro Cirúrgico. Alguns autores sugerem que a dissecção limitada resulta em menor dano tecidual, diminui o risco de sangramento e infecção de ferida operatória. Esta revisão visa analisar e sintetizar estudos prospectivos e randomizados, revisões sistemáticas e meta-análises, comparando a traqueostomia percutânea e traqueostomia convencional em pacientes adultos em Unidades de Terapia Intensiva.

OBJECTIVES: The percutaneous dilatational tracheostomy has become the technique of choice in the Intensive Care Unit, due safety and facilities to be performed at bedside, wich may overcome the risks associated with transport of critically ill patients to the Operating Room. Proponents of percutaneous dilatational tracheostomy suggest that the limited dissection results in less tissue damage, lowers the risk of bleeding and wound infection. The aim of this study is to review the techniques of percutaneous dilatational tracheostomy through a critical analysis of it's indications, contra-indications and complications, as well to compare percutaneous dilatational tracheostomy to surgical tracheostomy. This manuscript analysis and synthesizes randomized prospective studies, meta-analysis and systematic reviews, comparing both techniques in adult critically ill patients in the Intensive Care Unit.

INTRODUCTION: The antibacterial effect of ozone (O3) has been described in the extant literature, but the role of O3 therapy in the treatment of certain types of infection remains controversial. OBJECTIVES: To evaluate the effect of intraperitoneal (i.p.) O3 application in a cecal ligation/puncture rat model on interleukins (IL-6, IL-10) and cytokine-induced neutrophil chemoattractant (CINC)-1 serum levels, acute lung injury and survival rates. METHODS: Four animal groups were used for the study: a) the SHAM group underwent laparotomy; b) the cecal ligation/puncture group underwent cecal ligation/puncture procedures; and c) the CLP+O2 and CLP+O3 groups underwent CLP+ corresponding gas mixture infusions (i.p.) throughout the observation period. IL-6, CINC-1 and IL-10 concentrations were determined by enzyme-linked immunosorbent assay (ELISA). Acute lung injury was evaluated with the Evans blue dye lung leakage method and by lung histology. P<0.05 was considered significant. RESULTS: CINC-1 was at the lowest level in the SHAM group and was lower for the CLP+O3 group vs. the CLP+O2 group and the cecal ligation/puncture group. IL-10 was lower for the SHAM group vs. the other three groups, which were similar compared to each other. IL-6 was lower for the SHAM group vs. all other groups, was lower for the CLP+O3 or CLP+O2 group vs. the cecal ligation/puncture group, and was similar for the CLP+O3 group vs. the CLP+O2 group. The lung histology score was lower for the SHAM group vs. the other groups. The Evans blue dye result was lower for the CLP+O3 group vs. the CLP+O2 group and the cecal ligation/puncture group but similar to that of the SHAM group. The survival rate for the CLP+O3 group was lower than for the SHAM group and similar to that for the other 2 groups (CLP and CLP+O2). CONCLUSION: Ozone therapy modulated the inflammatory response and acute lung injury in the cecal ligation/puncture infection model in rats, although there was no improvement on survival rates.

INTRODUCTION: Isolated pulmonary metastases from soft tissue sarcomas occur in 20-50% of these(the issue is about metastases, not lung cancer )patients, and 70% of these patients will present disease limited only to the lungs. Surgical resection is well accepted as a standard approach to treat metastases from soft tissue sarcomas isolated in the lungs, and many studies investigating this technique have reported an overall 5-year survival ranging from 30-40%. The most consistent predictor of survival in these patients is complete resection. The aim of the present study was to determine the demographics and clinical treatment-related variables associated with long-term (90-month) overall survival in patients with lung metastases undergoing pulmonary metastasectomy from soft tissue sarcomas. METHODS: We performed a retrospective review of patients admitted in the Thoracic Surgery Department with lung metastases who underwent thoracotomy for resection following treatment of the primary tumor. Data regarding primary tumor features, demographics, treatment, and outcome were collected. RESULTS: One hundred twenty-two thoracotomies and 273 nodules were resected from 77 patients with previously treated soft tissue sarcomas. The median follow-up time of all patients was 36.7 months (range: 10-138 months). The postoperative complication rate was 9.1%, and the 30-day mortality rate was 0%. The 90-month overall survival rate for all patients was 34.7%. Multivariate analysis identified the following independent prognostic factors for overall survival: the number of metastases resected, the disease-free interval, and the number of complete resections. CONCLUSION: These results confirm that lung metastasectomy is a safe and potentially curative procedure for patients with treated primary tumors. A select group of patients can achieve long-term survival after lung resection.

OBJETIVO: O objetivo do presente estudo foi avaliar a eficácia do estadiamento clínico pré-operatório com tomografia computadorizada com o estadiamento patológico. MÉTODOS: Entre 1990 e 2005, foram revisados retrospectivamente os prontuários dos pacientes com câncer de pulmão não-pequenas células (CPNPC). O estágio clínico foi baseado em exames pré-operatórios de imagem. Tomografia por emissão de pósitrons não foi incluída na rotina de exames pré-operatórios. Lesões suspeitas, que contra-indicassem a ressecção cirúrgica curativa, foram confirmadas patologicamente. O estágio patológico foi considerado aquele baseado na análise patológica pós-operatória ou em biópsia de lesão suspeita. Foi gerada uma tabela de correlação entre estágio clínico e patológico. Foram calculados o índice kappa de Cohen, a sensibilidade, a especificidade, o valor preditivo positivo e negativo, e a acurácia. RESULTADOS: 291 prontuários de pacientes foram revisados. Os estágios Ia, Ib, IIa, IIb, IIIa, IIIb e IV foram encontrados em 8,9%, 31,9%, 0,3%, 18,6%, 25,4%, 11% e 3,8%, respectivamente. Estágio patológico foi diferente do estágio clínico em 33% dos pacientes (15% foram sobre-estadiados e 18% sub-estadiados). Sensibilidade, especificidade, valor preditivo positivo e negativo, e acurácia foram 78%, 69%, 82%, 64% e 67%, respectivamente. O índice kappa de Cohen foi de 0,574 (P < 0,001). CONCLUSÃO: O estadiamento clínico pré-operatório apresenta eficácia limitada no estadiamento dos pacientes com CPNPC.

OBJECTIVE: The objective of this study was to evaluate the accuracy of preoperative clinical staging with computed tomography in predicting the correct pathological stage. METHODS: Medical records of non-small cell lung cancer (NSCLC) patients treated, from 1990 to 2005 were reviewed. Clinical stage was based on routine preoperative clinical and imaging evaluation. Positron emission tomography was not routinely performed. Suspected lesions, that would preclude a surgical resection, were pathologically confirmed. The pathological stage was based on final postoperative or biopsy pathological assessment. A correlation table between clinical and pathological stages was generated. Cohen's kappa index, sensitivity, specificity, positive and negative predictive values and accuracy were calculated. RESULTS: Records of 291 patients were reviewed. Clinical stages Ia, Ib, IIa, IIb, IIIa, IIIb and IV were found respectively in 8.9%, 31.9%, 0.3%, 18.6%, 25.4%, 11% and 3.8%. Pathological staging was different from clinical staging in 33% (15% were upstaged and 18% downstaged). Sensitivity, specificity, positive and negative predictive values and accuracy for clinical staging were 78%, 69%, 82%, 64% and 67%, respectively. Cohen's kappa index was 0.574 (P < 0.001). CONCLUSION: Preoperative clinical staging presents limited efficacy for the correct staging of NSCLC patients from this sample of Brazilian population.

O objetivo deste estudo é revisar a literatura acerca da eficácia, segurança e viabilidade da cirurgia redutora de volume pulmonar (CRVP) em pacientes com enfisema pulmonar avançado. Estudos de CRVP de janeiro de 1995 a dezembro de 2009 foram incluídos através de pesquisa na Pubmed (MEDLINE) e Cochrane Library, na literatura inglesa. Palavras de busca tais como lung volume reduction surgery ou lung reduction surgery, pneumoplasty ou reduction pneumoplasty, COPD ou chronic obstructive pulmonary disease e surgery foram utilizadas. Também realizamos comparação entre terapia médica e cirúrgica. Os estudos analisados consistiram de randomizados controlados, estudos clínicos controlados, (randomizados e não randomizados), revisões e séries de casos. As questões acerca da validade através dos relatos iniciais, seguimentos incompletos, critérios de seleção indefinidos e análises de sobrevida confundiram a interpretação dos dados clínicos provenientes da CRVP. Pacientes com enfisema de predomínio em lobos superiores, inferiores e difuso, foram incluídos; também analisamos pontos chave, tais como morbidade e mortalidade peri-operatórias, assim como a medida da função pulmonar através do VEF 1. Enfisema do tipo bolhoso foi excluído desta revisão. Foram incluídas para análise também vias de acesso cirúrgico como esternotomia mediana, toracotomias unilateral ou bilateral e videotoracoscopia unilateral ou bilateral com grampeamento ou ablação por laser. Os resultados dos estudos prospectivos randomizados entre o tratamento clínico e a CRVP são essenciais para que alguma conclusão possa ser definitiva.

This study intends to review the literature on the efficacy, safety and feasibility of lung volume reduction surgery (LVRS) in patients with advanced emphysema. Studies on LVRS from January 1995 to December 2009 were included by using Pubmed (MEDLINE) and Cochrane Library literature in English. Search words such as lung volume reduction surgery or lung reduction surgery, pneumoplasty or reduction pneumoplasty, COPD or chronic obstructive pulmonary disease and surgery, were used. We also compared medical therapy and surgical technique. Studies consisting of randomized controlled trials, controlled clinical trials (randomized and nonrandomized), reviews and case series were analyzed. Questions regarding validity of the early clinical reports, incomplete follow-up bias, selection criteria and survival, confounded the interpretation of clinical data on LVRS. Patients with upper, lower and diffuse distribution of emphysema were included; we also analyzed as key points perioperative morbidity and mortality and lung function measurement as FEV1. Bullous emphysema was excluded from this review. Surgical approach included median sternotomy, unilateral or bilateral thoracotomy, and videothoracoscopy with stapled or laser ablation. Results of prospective randomized trials between medical management and LVRS are essential before final assessment can be established.

Problemas dermatológicos relacionados com a pigmentação resultam em hiperpigmentações ou hipopigmentação cutâneas. Produtos cosméticos e farmacêuticos com atividade despigmentante são utilizados para o tratamento de pacientes que apresentam distúrbios de hiperpigmentação, tais como melasma ou cloasma, hiperpigmentação pós-inflamatória, lentigem senil e efélides. Os despigmentantes atualmente utilizados não são totalmente eficazes ou seguros, razão pela qual há intensa pesquisa, principalmente em países asiáticos, com a finalidade de se obter novos agentes com esta ação, em especial inibidores de enzimas envolvidas na melanogênese, como a tirosinase. Considerando-se que algumas substâncias obtidas de plantas apresentam essa atividade, a flora brasileira constitui-se uma fonte potencial de obtenção de novos despigmentantes. Por essa razão, 25 extratos aquosos e 24 orgânicos obtidos de 19 plantas da Floresta Amazônica e Mata Atlântica, provenientes de 11 diferentes famílias, foram avaliados quanto à atividade de inibição da tirosinase. Do total de 49 extratos testados, 9 mostraram atividade. Os valores de concentração da atividade inibitória 50% (AI 50%), foram calculados e o mais ativo foi o extrato orgânico das folhas e caule de Ruprechtia sp. (AI50 33,76 mg.mL-1) seguido do extrato orgânico dos órgãos aéreos de Rapanea parviflora (AI50 64,19 mg.mL-1).

Dermatological disorders related to pigmentation result in tenuous hyper or hypopigmentation Cosmetic and pharmaceutical products containing depigmenting substances are used in the treatment of patients who have high pigmentation disorders, such as melasma or chloasma, post-inflammatory hyperpigmentation, senile lentigo and ephelides. Skin lightening agents are not yet totally effective or safe and therefore intensive research for the discovery of new agents is continuous. Enzyme inhibitors involved in melanogenesis, such as tyrosinase, have been discovered in Asian countries, including those isolated from plant extracts. The Brazilian flora has the highest species diversity in the world, and the chemical, pharmacological and cosmetic potential for the discovery of new skin whitening agents is in proportion with this biodiversity. For these reasons, 25 aqueous and 24 organic extracts obtained from 19 plants native to the Amazon rain forest and to the Atlantic forest, belonging to 11 different families, were evaluated as tyrosinase inhibitors. Nine out of 49 extracts showed inhibitory activity in the screening process. The 50% inhibitory activity (IA50) was calculated, revealing that the most active extracts were the organic extracts from the leaves and stem of Ruprechtia sp. (IA50 33.76 mg.mL-1) and the organic extract from the aerial organs of Rapanea parviflora (IA50 64.19 mg.mL-1).