Role of the Microbiota in Lung Cancer: Insights on Prevention and Treatment.

The microbiota is increasingly recognized as a critical player in cancer onset and progression and response to cancer chemotherapy treatment. In recent years, several preclinical and clinical studies have evidenced the involvement of microbiota in lung cancer, one of the world's deadliest cancers. However, the mechanisms by which the microbiota can impact this type of cancer and patient survival and response to treatments remain poorly investigated. In this review, the peculiarities of the gut and lung microbial ecosystems have been highlighted, and recent findings illustrating the possible mechanisms underlying the microbiota-lung cancer interaction and the host immune response have been discussed. In addition, the mucosal immune system has been identified as a crucial communication frame to ease interactive dynamics between the immune system and the microbiota. Finally, the use of specific next-generation intestinal probiotic strains in counteracting airway diseases has been evaluated. We believe that restoring homeostasis and the balance of bacterial microflora should become part of the routine of integrated cancer interventions, using probiotics, prebiotics, and postbiotics, and promoting a healthy diet and lifestyle.

Evolution of the surgical treatment of lung cancer at a tertiary referral center in Brazil, 2011-2018 / Evolução do tratamento cirúrgico do câncer de pulmão em uma instituição terciária de referência no Brasil, 2011-2018

ABSTRACT Objective: To evaluate the evolution of clinical and epidemiological data, as well as data related to diagnosis, staging, treatment, and survival, among patients undergoing curative surgery for lung cancer at a tertiary referral center in the city of São Paulo, Brazil. Methods: This was a retrospective study of cases in the International Association for the Study of Lung Cancer database. We selected only cases of patients undergoing curative surgery between January of 2011 and April of 2018. We determined overall and disease-free survival at 36 months and compared the data between two periods (2011-2014 and 2015-2018). Results: Comparing the two periods (N = 437 cases), we observed trends toward increases in the number of female patients, as well as in the proportions of former smokers (44.09% vs. 53.59%), of patients diagnosed with adenocarcinoma (52.21% vs. 59.72%), and of patients diagnosed at an earlier pathological stage, together with a decrease in 30-day mortality (4.05% vs. 2.39%). There were significant increases in the proportions of cases diagnosed at an earlier clinical stage (p = 0.002) or incidentally (p = 0.003). Although lobectomy was the main surgical technique employed, there was a proportional increase in segmentectomies (2.67% vs. 7.11%; p = 0.026). Overall and disease-free survival rates were 79.4% (95% CI: 74.0-83.9%) and 75.1% (95% CI: 69.1-80.1%), respectively. The difference in overall survival between the periods lost statistical significance when adjusted for pathological stage, the only factor that affected survival (log-rank: p = 0.038 to p = 0.079). Conclusions: The clinical and epidemiological evolution presented in this study corroborates global trends. The decrease in 30-day mortality was probably due to better patient selection and improved surgical techniques.

RESUMO Objetivo: Avaliar a evolução de dados clínicos e epidemiológicos, assim como dados sobre diagnóstico, estadiamento, tratamento e sobrevida em pacientes submetidos a tratamento cirúrgico curativo de câncer de pulmão em uma instituição terciária na cidade de São Paulo (SP). Métodos: Estudo retrospectivo baseado nos casos inseridos no banco de dados da International Association for the Study of Lung Cancer submetidos à cirurgia curativa entre janeiro de 2011 e abril de 2018. Determinamos a sobrevida global e livre de doença em 36 meses e comparamos os dados em dois períodos (2011-2014 e 2015-2018). Resultados: Comparando-se os dois períodos (N = 437 casos), houve uma tendência de aumento no número de pacientes do sexo feminino, ex-tabagistas (44,09% vs. 53,59%), com diagnóstico de adenocarcinoma (52,21% vs. 59,72%) e em estádio patológico mais precoce, assim como queda da mortalidade em 30 dias (4,05% vs. 2,39%). Houve aumento significativo de casos em estádio clínico mais precoce (p = 0,002) e diagnosticados incidentalmente (p = 0,003). A lobectomia foi a principal técnica cirúrgica; entretanto, houve aumento de segmentectomias (2,67% vs. 7,11%; p = 0,026). As sobrevidas global e livre de doença foram de 79,4% (IC95%: 74,0-83,9%) e 75,1% (IC95%: 69,1-80,1%), respectivamente. Houve perda de significância estatística na sobrevida global entre os períodos quando ajustada por estadiamento patológico, o único fator a impactar a sobrevida (log-rank: p = 0,038 para p = 0,079). Conclusões: A evolução clínica e epidemiológica apresentada neste estudo corrobora tendências mundiais. A diminuição da mortalidade em 30 dias provavelmente ocorreu devido a melhor seleção de pacientes e melhora da técnica cirúrgica.

Tumor-node-metastasis staging and treatment patterns of 73, 167 patients with lung cancer in Brazil / Estadiamento tumor-nódulo-metástase e padrão de tratamento oncológico de 73. 167 pacientes com câncer de pulmão no Brasil

ABSTRACT Objective: To characterize the clinical and histological profile, as well as treatment patterns, of patients with early-stage, locally advanced (LA), or advanced/metastatic (AM) lung cancer, diagnosed between 2000 and 2014, in Brazil. Methods: This was an analytical cross-sectional epidemiological study employing data obtained for the 2000-2014 period from the hospital cancer registries of two institutions in Brazil: the José Alencar Gomes da Silva National Cancer Institute, in the city of Rio de Janeiro; and the São Paulo Cancer Center Foundation, in the city of São Paulo. Results: We reviewed the data related to 73,167 patients with lung cancer. The proportions of patients with early-stage, LA, and AM lung cancer were 13.3%, 33.2%, and 53.4%, respectively. The patients with early-stage lung cancer were older and were most likely to receive a histological diagnosis of adenocarcinoma; the proportion of patients with early-stage lung cancer remained stable throughout the study period. In those with LA lung cancer, squamous cell carcinoma predominated, and the proportion of patients with LA lung cancer decreased significantly over the period analyzed. Those with AM lung cancer were younger and were most likely to have adenocarcinoma; the proportion of patients with AM lung cancer increased significantly during the study period. Small cell carcinoma accounted for 9.2% of all cases. In our patient sample, the main treatment modality was chemotherapy. Conclusions: It is noteworthy that the frequency of AM lung cancer increased significantly during the study period, whereas that of LA lung cancer decreased significantly and that of early-stage lung cancer remained stable. Cancer treatment patterns, by stage, were in accordance with international guidelines.

RESUMO Objetivo: Caracterizar o perfil clínico e histológico, assim como o de tratamento oncológico, de pacientes com câncer de pulmão nos estádios precoce, localmente avançado (LA) e avançado/metastático (AM), diagnosticados entre 2000 e 2014 no Brasil. Métodos: Estudo epidemiológico transversal analítico com dados brasileiros obtidos de registros hospitalares de câncer do Instituto Nacional de Câncer José Alencar Gomes da Silva, localizado na cidade do Rio de Janeiro, e da Fundação Oncocentro de São Paulo, localizada na cidade de São Paulo, de 2000-2014. Resultados: Foram avaliados 73.167 pacientes com câncer de pulmão. As proporções de pacientes nos estádios precoce, LA e AM foram de 13,3%, 33,2% e 53,4%, respectivamente. Os pacientes em estádio precoce apresentavam idade mais avançada, adenocarcinoma como tipo histológico predominante e frequência estável ao longo do período do estudo; aqueles em estádio LA apresentaram mais frequentemente carcinoma de células escamosas, havendo uma redução significativa de sua frequência relativa no período do estudo; e aqueles em estádio AM tinham idade menor, predominância de adenocarcinoma, com um significativo aumento da sua frequência no período. O carcinoma de células pequenas correspondeu a 9,2% dos casos. A quimioterapia foi a principal modalidade de tratamento utilizada. Conclusões: A frequência do estádio AM mostrou estar em aumento durante o período de estudo, concomitantemente a uma expressiva redução na frequência do estádio LA e estabilidade do estádio precoce. O padrão de tratamento oncológico esteve em conformidade com as diretrizes internacionais de acordo com o estadiamento.

El cáncer del pulmón: algunas consideraciones epidemiológicas, del diagnóstico y el tratamiento / Lung cancer: some epidemiologic, diagnoses and treatment considerations

RESUMEN Fundamento: el cáncer es una de las causas principales de muerte alrededor del mundo. En el año 2012 hubo 14 millones de casos nuevos, así como 8,2 millones de muertes relacionadas. Dentro de todas las localizaciones del cáncer, es el pulmón el de mayor incidencia y mortalidad para el hombre y en el caso de la mujer ocupa el segundo lugar. Objetivos: realizar una actualización en aspectos epidemiológicos, del diagnóstico, así como del tratamiento del cáncer pulmonar a nivel global, regional y local. Métodos: se realizó una búsqueda en las bases de datos Pub Med, SciELO, Medline, Cochrane, Lilacs, mediante EndNote y Clinical Key, en un período desde el primero de septiembre al 15 de diciembre de 2017. Se emplearon las palabras claves: lung cancer, epidemiology, diagnostic, treatment, screening. Se realizó una revisión bibliográfica de un total 302 artículos de ellos se utilizaron 40 citas la mayoría de ellas de los últimos tres y cinco años. Se consideraron para la revisión, artículos originales, revisiones a texto completo, así como artículos de opinión. Desarrollo: se abordaron aspectos del cáncer pulmonar relacionados con estadísticas globales, regionales y locales, así como de los indicadores de impacto, aspectos relacionados con el diagnóstico precoz a través del tamizaje y elementos novedosos de ensayos clínicos relacionados con la aplicación de la vacuna CIMAvax-EGF. Conclusiones: con el elevado aporte del cáncer de pulmón a la morbilidad y mortalidad general en Cuba y en particular en la provincia de Camagüey, así como el consecuente impacto negativo en la duración y calidad de vida de la población, se considera pertinente y necesario el diseño de un programa integral asistencial organizacional para atender a pacientes con esta terrible y letal enfermedad.

ABSTRACT Background: cancer is one of the leading causes of death around the world. In 2012, there were 14 million of new cases, as well as 8.2 million related deaths. Within all cancer locations, the lung is the one with the highest incidence and mortality for men and in the case of women, it occupies the second place. Objectives: to carry out an update on epidemiological aspects of diagnosis, as well as the treatment of lung cancer at a global, regional and local level. Methods: a search on Pub Med, SciELO, Medline, Cochrane, Lilacs databases using EndNote and Clinical Key was carried out, from September 1 to December 15, 2017. The following keywords were used: lung cancer, epidemiology, diagnostic, treatment, screening. A bibliographic review of a total of 302 articles was made, of them 40 citations were used, most of them from the last three and five years. Original articles, full-text reviews, as well as opinion articles were considered for the review. Development: aspects of lung cancer, related to global, regional and local statistics, as well as impact indicators, aspects related to early diagnosis through screening and novel elements of clinical trials related to the application of the vaccine CIMAvax-EGF were addressed. Conclusions: with the high contribution of lung cancer to morbidity and general mortality in Cuba and in particular in Camagüey province, as well the negative consequent impact on the duration and quality of life of the population, it is considered necessary to design a comprehensive organizational assistance program to care for patients with this terrible and lethal disease.

Lung cancer in Brazil / Câncer de pulmão no Brasil

ABSTRACT Lung cancer is one of the most incident types of cancer and a leading cause of cancer mortality in Brazil. We reviewed the current status of lung cancer by searching relevant data on prevention, diagnosis, and treatment in the country. This review highlights several issues that need to be addressed, including smoking control, patient lack of awareness, late diagnosis, and disparities in the access to cancer health care facilities in Brazil. We propose strategies to help overcome these limitations and challenge health care providers, as well as the society and governmental representatives, to work together and to take a step forward in fighting lung cancer.

RESUMO O câncer de pulmão é um dos tipos de câncer com maior incidência e uma das principais causas de mortalidade por câncer no Brasil. Revisamos a situação atual do câncer de pulmão por meio de pesquisa de dados relevantes a respeito de prevenção, diagnóstico e tratamento no país. Esta revisão mostra várias questões que precisam de atenção, tais como controle do tabagismo, educação dos pacientes, desconhecimento por parte dos pacientes, diagnóstico tardio e desigualdade de acesso ao tratamento de câncer no Brasil. Propomos estratégias para ajudar a superar essas limitações e desafiamos os profissionais de saúde, a sociedade e os representantes do governo a trabalhar em conjunto e dar um passo à frente na luta contra o câncer de pulmão.

Anatomic pulmonary resection via video-assisted thoracic surgery: analysis of 117 cases at a referral center in Brazil / Ressecções pulmonares anatômicas por cirurgia torácica videoassistida: experiência de 117 casos em um centro de referência no Brasil

ABSTRACT Objective: To describe our experience with video-assisted thoracic surgery (VATS) for anatomic pulmonary resection at a referral center for thoracic surgery in Brazil. Methods: All patients who underwent anatomic pulmonary resection by VATS between 2010 and 2015 were included. Clinical and pathological data, as well as postoperative complications, were analyzed. Results: A total of 117 pulmonary resections by VATS were performed, of which 98 were lobectomies and 19 were anatomic segmentectomies. The mean age of the patients was 63.6 years (range, 15-86 years). Females predominated (n = 69; 59%). The mean time to chest tube removal was 2.47 days, and the mean length of ICU stay was 1.88 days. The mean length of hospital stay was 4.48 days. Bleeding ≥ 400 mL occurred in 15 patients. Conversion to thoracotomy was required in 4 patients. Conclusions: Our results are similar to those published in major international studies, indicating that VATS is an important strategy for pulmonary resection. They also show that VATS can be safely performed with adequate training. This technique should be used more often for the treatment of lung diseases in Brazil.

RESUMO Objetivo: Relatar a experiência com cirurgia torácica videoassistida (CTVA) para ressecções pulmonares anatômicas em um centro nacional de referência de cirurgia torácica no Brasil. Métodos: Foram incluídos todos os pacientes tratados com ressecções pulmonares anatômicas por CTVA entre 2010 e 2015 e analisados dados clínicos e patológicos, assim como complicações pós-operatórias. Resultados: Foram realizadas 117 ressecções pulmonares por CTVA, sendo 98 lobectomias e 19 segmentectomias anatômicas. A média de idade foi de 63,6 anos (variação, 15-86 anos), sendo a maioria mulheres (n = 69; 59%). A média de tempo de permanência com dreno foi de 2,47 dias e a de estada em UTI foi de 1,88 dias. A média de tempo de internação foi de 4,48 dias. Sangramento ≥ 400 ml ocorreu em 15 pacientes. Houve conversão para toracotomia em 4 pacientes. Conclusões: Nossos resultados vão ao encontro de publicações em grandes séries internacionais, corroborando que a CTVA é uma importante via de execução de ressecções pulmonares e que pode ser realizada com segurança quando há treinamento adequado, devendo ser mais utilizada no Brasil para o tratamento das doenças pulmonares.

Malignant Pure Pulmonary Ground-Glass Opacity Nodules: Prognostic Implications

OBJECTIVE: This study was designed to evaluate follow-up results in terms of patient prognosis for malignant pulmonary nodules depicted as pure ground-glass opacity (GGO) lesion observed at high-resolution CT (HRCT). MATERIALS AND METHODS: Surgical removal for malignant GGO nodules was accomplished in 58 patients (26 men, 32 women; mean age, 57 years; age range, 29-78 years). Patient prognoses were assessed by patient clinical status and the presence of changes in nodule size determined after a follow-up HRCT examination. Differences in patient prognoses were compared for nodule number, size, surgical method, change in size before surgical removal, and histopathological diagnosis by use of Fisher's exact test and Pearson's chi-squared test. RESULTS: Of the 58 patients, 40 patients (69%) were confirmed to have a bronchioloalveolar carcinoma (BAC) and 18 patients (31%) were confirmed to have an adenocarcinoma with a predominant BAC component. Irrespective of nodule size, number, treatment method, change in size before surgical removal and histopathological diagnosis, neither local recurrence nor a metastasis occurred in any of these patients as determined at a follow-up period of 24 months (range; 12-65 months). Of 14 patients with multiple GGO nodules, all of the nodules were resected without recurrence in six patients. In the remaining eight patients, the remaining nodules showed no change in size in seven cases and a decrease in size in one case as determined after a follow-up CT examination. CONCLUSION: Prognoses in patients with pure GGO malignant pulmonary nodules are excellent, and not significantly different in terms of nodule number, size, surgical method, presence of size change before surgical removal and histopathological diagnosis.

Percutaneous Radiofrequency Thermal Ablation of Lung VX2 Tumors in a Rabbit Model: Evaluation with Helical CT Findings for the Complete and Partal Ablation

PURPOSE: To evaluate the radiologic findings for complete and partial ablation after percutaneous CT-guided transthoracic radiofrequency ablation (RFA) of lung VX2 tumor implanted in rabbits. MATERIALS AND METHODS: Thirteen rabbits with successfully implanted lung VX2 were used. Three rabbits as controls did not receive RFA while the other ten rabbits underwent RFA; 5 complete and 5 partial. RFA was performed using an internally cooled, 17-gauge electrode (Radionics, Burlington, MA) with a 1-cm active tip under CT guidance. Postprocedural CT was performed within 3 days, and we analyzed the ablated size, enhancement pattern, shape, margin, and complications of the complete and partial ablation groups. Rabbits were sacrificed after postprocedural CT with an overdose of ketamine, and pathologic findings of the ablated groups were compared with those of the control group. RESULTS: The size of the ablated lesions and the enhancement pattern differed between the completely and partially ablated groups on chest CT. The size of the ablated lesions was increased by 47.1% in the completely ablated group and by 2.1% in the partially ablated group. In the completely ablated group, VX2 tumor showed absolutely no enhancement, whereas only ablated pulmonary parenchyma outside VX2 showed mild enhancement on enhanced CT. In the partial ablated group, a part of VX2 became strongly enhanced on enhanced CT. On microscopic examination, the completely ablated group demonstrated that a viable tumor cell was not visible. In the partially ablated group, however, a viable tumor cell within the surrounding fibrous capsule on the peripheral area of the VX2 was observed. CONCLUSION: The important CT findings for evaluation of complete and partial RFA are the ablated size and enhancement pattern of the ablated lesion.

Percutaneous Radiofrequency Ablation of Inoperable Primary Lung Cancer

PURPOSE: To present the initial experience of percutaneous radiofrequency ablation (RFA) of inoperable primary lung cancer, and to assess the technical feasibility and potential complications. MATERIALS AND METHODS: Twenty patients with inoperable lung cancer underwent percutaneous RFA. Nineteen of 20 patients had stage III or IV non-small cell lung cancer, and the remaining one had stage I lung cancer with pulmonary dysfunction. The mean tumor size was 4.6+/-0.4 cm (range, 1.8-8.4 cm). RFA was performed with a single (n=18) or cluster (n=2) cool-tip RF electrode and a generator under CT guidance using local anesthesia and conscious sedation. Twenty tumors were treated in 28 sessions. Patients were assessed by contrast-enhanced CT in all cases at 1 week, 1 month, and 3 months. Eleven patients received chemotherapy (n=10) or radiotherapy (n=1) after RFA. RESULTS: RFA was technically successful and well tolerated in all patients. Complete necrosis was attained in 7 lesions (35%), near complete (90-99%) necrosis in 10 lesions (50%), and partial (50-89%) necrosis in 3 lesions (15%). During the mean follow up of 202 days (21 to 481 days), tumor size was decreased in 13 patients, unchanged in 3, and increased in 4. In the latter four, additional RFA was performed. One patient underwent surgery three months after RFA and the histopathologic findings showed a large cavity with thin fibrotic wall suggestive of complete necrosis. During or after the procedure, pneumothorax (n=10), moderate pain (n=4), blood tinged sputum (n=2), and pneumonia (n=2) were developed. Chest tube drainage was required in only 1 patient due to severe pneumothorax. Other patients were managed conservatively. Seven patients died at 61 to 398 days (mean, 230 days) after RFA. The remaining 13 patients were alive 21 to 481 days (mean, 187 days) after RFA. CONCLUSION: RFA appears to be a technically feasible and relatively safe procedure for the cytoreductive treatment of inoperable, non-small cell lung cancer and warrants further investigation as a complementary treatment to chemotherapy or radiation therapy.