Once a rare disease, lung cancer has become the most common type of lethal cancer throughout the world. This change has occurred since the 1920s , when it was observed both in Europe and in North America that the number of the cases began to increase. Although mentioned sporadically in the medical literature in the first half of the century, it was in 1950 that several well-performed case-controlled studies first suggested tobacco smoking as the overwhelming cause of lung cancer. It took even more years before results of large prospective studies, like the pioneering work of Doll and Hill, convinced both the public and the governments that smoking is the most important cause of the disease. Histologically, lung cancer is divided into four major subgroups: squamous-, adeno-, small cell, and large cell carcinomas. In a substantial number of cases, however, accurate histological diagnosis may be difficult, due to both intrinsic tumor heterogeneity and to inter-observer variability. Kreyberg suggested that only squamous and small cell carcinomas were caused by tobacco smoking, but most of the more recent studies indicate that the majority of adenocarcinomas is also caused by tobacco smoking. In all studies the proportion of adenocarcinoma is much higher in females than in males and secular trends during 1980s and 1990s have shown an increase in the occurrence of adenocarcinoma. Most occupational carcinogens, with the exception of chloromethyl ethers and radiation (radon), which have a higher tendency to promote small cell lung cancer, give rise to tumors with a histological distribution that is similar to tumors caused by tobacco smoke.

Keywords: Lung cancer. Epidemiology.

Objective: To estimate and compare the frequency of CYP1A1*2A gene polymorphisms in a Brazilian population and determine the possible contribution of these genetic variations to lung cancer risk. Methods: The study population included 200 patients with lung cancer, and the control group consisted of 264 blood donors. Genomic DNA was obtained from peripheral blood samples. The PCR-RFLP method was used for analysis of the CYP1A1*2A gene. Results: There was no statistically significant difference between the lung cancer patients and the controls in terms of the distribution of CYP1A1*2A polymorphisms (p = 0.49). A multivariate logistic regression model analysis by ethnic group revealed that, within the lung cancer group, the CYP1A1*2A genotype CC plus TC was more common among the African-Brazilian patients than among the White patients (adjusted OR = 3.19; 95% CI: 1.53‑6.65). Conclusions: The CYP1A1*2A gene cannot be linked with lung cancer risk in Brazilian patients at this time. Larger epidemiologic studies are needed in order to establish whether the CC plus TC polymorphism increases the risk of lung cancer in African-Brazilians.

Keywords: Lung neoplasms; Polymorphism, genetic; Metabolism.

Although lung cancer (LC) is one of the most common and lethal tumors, only 15% of patients are diagnosed at an early stage. Smoking is still responsible for more than 85% of cases. Lung cancer screening (LCS) with low-dose CT (LDCT) reduces LC-related mortality by 20%, and that reduction reaches 38% when LCS by LDCT is combined with smoking cessation. In the last decade, a number of countries have adopted population-based LCS as a public health recommendation. Albeit still incipient, discussion on this topic in Brazil is becoming increasingly broad and necessary. With the aim of increasing knowledge and stimulating debate on LCS, the Brazilian Society of Thoracic Surgery, the Brazilian Thoracic Association, and the Brazilian College of Radiology and Diagnostic Imaging convened a panel of experts to prepare recommendations for LCS in Brazil. The recommendations presented here were based on a narrative review of the literature, with an emphasis on large population-based studies, systematic reviews, and the recommendations of international guidelines, and were developed after extensive discussion by the panel of experts. The following topics were reviewed: reasons for screening; general considerations about smoking; epidemiology of LC; eligibility criteria; incidental findings; granulomatous lesions; probabilistic models; minimum requirements for LDCT; volumetric acquisition; risks of screening; minimum structure and role of the multidisciplinary team; practice according to the Lung CT Screening Reporting and Data System; costs versus benefits of screening; and future perspectives for LCS.

Keywords: Lung neoplasms; Early detection of cancer; Tomography, X-ray computed; Tobacco use disorder.

Objective: To evaluate the efficacy of stereotactic body radiotherapy (SBRT) versus surgery for early-stage non-small cell lung cancer (NSCLC) by means of a meta-analysis of comparative studies. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analysis of Observational Studies in Epidemiology guidelines, searches were performed on PubMed, MEDLINE, Embase, and Cochrane Library for eligible studies. The meta-analysis compared the hazard ratios (HR) for overall survival (OS), cancer-specific survival (CSS), and local control (LC). Subgroup and meta-regression analyses evaluated the association of extent of surgical resection, study publication year, tumor staging, propensity score matching, proportion of chemotherapy use, and proportion of pathological lymph node involvement with CSS and OS. Results: Thirty studies involving 29,511 patients were included (surgery group: 17,146 patients and SBRT group: 12,365 patients). There was a significant difference in favor of surgery vs. SBRT in the 3-year OS (HR = 1.35; 95% CI: 1.22-1.44; I2 = 66%) and 3-year CSS (HR = 1.23; 95% CI: 1.09-1.37; I2 = 17%), but not in the 3-year LC (HR = 0.97; 95% CI: 0.93-1.08; I2 = 19%). In the subgroup analysis for OS, no significant difference between surgery and SBRT groups was observed in the T1N0M0 subgroup (HR = 1.26; 95% CI: 0.95-1.68; I2 = 0%). In subgroup analysis for CSS, no significant difference was detected between the sublobar resection subgroup and the SBRT group (HR = 1.21; 95% CI: 0.96-1.53; I2 = 16%). Conclusions: Surgery generally resulted in better 3-year OS and CSS than did SBRT; however, publication bias and heterogeneity may have influenced these findings. In contrast, SBRT produced LC results similar to those of surgery regardless of the extent of surgical resection. These findings may have important clinical implications for patients with comorbidities, advanced age, poor pulmonary reserve, and other factors that may contraindicate surgery.

Keywords: Carcinoma, Non-Small-Cell Lung/surgery; Radiosurgery; Meta-analysis.

The evaluation of patients with lung cancer involves not only the detection of enlarged mediastinal lymph nodes and the delineation of the relationship between the primary lesion with the mediastinal structures but also the determination of extra thoracic metastases. This article reviews the major imaging techniques that are currently used to stage bronchogenic carcinoma. Radiologic studies have made an important impact on the evaluation of the solitary pulmonary nodule. Mediastinal staging coupled with imaging methods is not accurate. CT and MR imaging of the chest and abdomen are often used to stage a known or suspected lung carcinoma. Despite their limitations, CT and MR prevent unnecessary thoracotomies and invasive procedures. MR can be helpful in the evaluation of parts of the chest not well shown on CT. PET-FDG imaging complements chest CT in the noninvasive evaluation of lung cancer and strategies for its use merit further investigation.

Keywords: Radiology. Bronchogenic carcinoma. Lung neoplasms. Diagnostic imaging. Emission-computed tomography. Nuclear magnetic resonance.

Lung cancer is a multifactorial disease. Hereditary, genetic, and environmental factors interact in its genesis. The principal risk factor for lung cancer is smoking. However, the workplace provides an environment in which there is a risk of exposure to carcinogens. The International Agency for Research on Cancer currently lists 19 substances/work situations/occupations that have been proven to be associated with lung cancer (group 1). Thorough occupational history taking is not widely practiced in patients with lung cancer, which has a negative impact on the investigation of causality and, consequently, on the identification of cases of occupational cancer. The objectives of this review were to list the agents that are recognized as causes of lung cancer, to discuss the contribution of occupation to the development of the disease, to cite national studies on the subject, and to propose a list of procedures that are essential to the appropriate investigation of causality between lung cancer and occupation.

Keywords: Lung neoplasms; Occupational diseases; Occupations; Carcinogens.

A review of the role of radiotherapy in lung cancer is presented, with the most recent innovations. Indications for postoperative irradiation and chemo-radiotherapy in non-small cell lung cancer are discussed. Recommendations are made for prophylactic cranium irradiation and perspectives of thoracic radiotherapy for small cell lung cancer. Recent techniques and results of the "Brazilian Consensus on Lung Cancer - Radiotherapy" are also presented.

The relationship between cancer and coagulopathy was suggested by Trousseau nearly 150 years ago. Later, it became more evident that oncologic patients are at a higher risk of experiencing thromboembolic events. This can be due to activation of the coagulation system either by neoplastic cells or by prescribed therapies (chemotherapy or surgical procedures). In fact, these events can constitute the first manifestation of cancer, and their recurrence, despite efficient anticoagulation, has been described. The coagulation system is normally activated in order to provide healing. In the presence of neoplasms, this complex system is activated as a response to multiple stimuli and seems to contribute to cancer progression. Activation of the coagulation system has a greater effect on metastatic foci than on the primary tumor. However, most cancer victims die from complications caused by metastasis, which underscores the importance of this theme. In this area, various mechanisms have been described, creating promising perspectives for future treatments. The current success in using low-molecular-weight heparins against small cell lung cancer is encouraging. Although the knowledge of those mechanisms is relatively incipient, many basic research and clinical studies are underway.

Keywords: Lung neoplasms; Thrombophilia.

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.

Keywords: Lung neoplasms/epidemiology; Lung neoplasms/therapy; Lung neoplasms/diagnosis; Biomarkers; Brazil.

Objective: To describe the trends in tumor histology, gender and age among patients with non-small cell lung cancer (NSCLC) treated with lung resection. The histology of lung cancer has changed in developed countries, and there is still little information available on the topic for developing countries. Methods: This was a retrospective study of 1,030 patients with NSCLC treated with lung resection between 1986 and 2015 at a university hospital in southern Brazil. Differences in histology, stage, and type of surgery were analyzed by gender and for three periods (1986-1995, 1996-2005, and 2006-2015). Results: Most (64.5%) of the patients were males, and the main histological types were squamous cell carcinoma (in 40.6%) and adenocarcinoma (in 44.5%). The mean age at surgery during the first period was 56.4 years for women and 58.9 years for men, compared with 62.2 for women and 64.6 for men in the third period (p < 0.001). The proportion of females increased from 26.6% in the first period to 44.1% in the third. From the first to the third period, the proportion of patients with squamous cell carcinoma decreased from 49.6% to 34.8% overall (p < 0.001), decreasing to an even greater degree (from 38.9% to 23.2%) among men. Among the NSCLC patients in our sample, females with adenocarcinoma accounted for 11.9% in the first period and 24.0% in the third period (p < 0.001). Conclusions: As has been seen in developed countries, the rates of lung cancer in females in southern Brazil have been rising over the last three decades, although they have yet to surpass those observed for males in the region. The incidence of squamous cell carcinoma has decreased in males, approaching adenocarcinoma rates, whereas adenocarcinoma has significantly increased among women.

Keywords: Lung neoplasms; Epidemiology; Histology; Adenocarcinoma; Carcinoma, non-small-cell lung; Carcinoma, squamous cell.

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.

Keywords: Lung neoplasms/surgery; Lung neoplasms/epidemiology; Lung neoplasms/therapy; Survival analysis; Thoracic surgery; Thoracic surgery, video-assisted.

Objective: Although EBUS-TBNA combined with EUS-FNA or EUS-B-FNA stands as the primary approach for mediastinal staging in lung cancer, guidelines recommend mediastinoscopy confirmation if a lymph node identified on chest CT or showing increased PET scan uptake yields negativity on these techniques. This study aimed to assess the staging precision of EBUS/EUS. Methods: We conducted a retrospective study comparing the clinical staging of non-small cell lung cancer patients undergoing EBUS/EUS with their post-surgery pathological staging. We analyzed the influence of histology, location, tumor size, and the time lapse between EBUS and surgery. Patients with N0/N1 staging on EBUS/EUS, undergoing surgery, and with at least one station approached in both procedures were selected. Post-surgery, patients were categorized into N0/N1 and N2 groups. Results: Among the included patients (n = 47), pathological upstaging to N2 occurred in 6 (12.8%). Of these, 4 (66.7%) had a single N2 station, and 2 (33.3%) had multiple N2 stations. The adenopathy most frequently associated with upstaging was station 7. None of the analyzed variables demonstrated a statistically significant difference in the occurrence of upstaging. PET scan indicated increased uptake in only one of these adenopathies, and only one was visualized on chest CT. Conclusions: Upstaging proved independent of the studied variables, and only 2 patients with negative EBUS/EUS would warrant referral for mediastinoscopy. Exploring other noninvasive methods with even greater sensitivity for detecting micrometastatic lymph node disease is crucial.

Keywords: Carcinoma, non-small cell lung; Neoplasm staging; Endoscopic ultrasound-guided fine needle aspiration.

Epidemiological studies have demonstrated a causal relationship between smoking and lung cancer. Although most lung cancer cases are linked to smoking, only a minority of heavy smokers develop lung cancer, leading to the notion that genetic factors affect individual susceptibility. The principal molecular changes in lung cancer are seen in tumor suppressor genes, proto-oncogenes, growth factors, telomerase activity, and methylation status of promoters. Well-known agents include angiogenesis-stimulating factors (such as vascular endothelial growth factor), as well as factors related to tumor cell proliferation and apoptosis (epidermal growth factor receptor, p53, K-ras, retinoblastoma and BCL-2). Several of these genetic factors have already been investigated, but no single parameter has yet presented sufficient selectivity regarding prognostic value or therapeutic efficacy. Treatment strategies to cure lung cancer should focus on these early genetic lesions in order to promote their repair or to eliminate these lung cancer cells.

Keywords: Smoking; Lung neoplasms; Genetic markers; Prognosis

Silicosis, the most prevalent of the pneumoconioses, is caused by inhalation of crystalline silica particles. Silica-exposed workers, with or without silicosis, are at increased risk for tuberculosis and nontuberculous mycobacteria-related diseases. The risk of a patient with silicosis developing tuberculosis is higher (2.8 to 39 times higher, depending on the severity of the silicosis) than that found for healthy controls. Various regimens for tuberculosis chemoprophylaxis in patients with silicosis have been studied, all of which present similar efficacy and overall risk reduction to about one half of that obtained with placebo. Long-term regimens have potential side effects (particularly hepatotoxicity). In addition, the use of such regimens can jeopardize adherence to treatment. The current guidelines recommend that tuberculin skin tests be performed, and, if positive, that chemoprophylaxis be instituted. There are several possible regimens, varying in terms of the drugs prescribed, as well as in terms of treatment duration. We recommend the use of isoniazid at 300 mg/day (or 10 mg/kg/day) for six months for patients with silicosis, as well as for healthy patients with periods of exposure to silica longer than 10 years and strongly positive tuberculin skin test results (induration ≥ 10 mm). Nevertheless, further studies are necessary so that indications, drugs, doses and duration of chemoprophylaxis regimens can be more properly defined.

Keywords: Silicosis; Tuberculosis; Diagnostic techniques and procedures; Chemoprevention.

A 79 year-old man sought treatment in the emergency room complaining of persistent fever, chest pain, and general fatigue. A chest X-ray showed a giant infectious bulla (24 cm in diameter) in the left lung. The patient had no history of abnormalities on X-rays, and his latest medical check-up, conducted in the preceding year, had produced no abnormal findings. Diagnostic procedures, including bronchoscopy, revealed lung cancer (large cell carcinoma) in the left lower bronchus. The tumor obstructed the airway. Although there have been various reports of giant bullae, their etiology remains unknown. We suggest that an obstruction, such as that caused by the tumor in this case, can lead to air trapping, resulting in the formation of a bulla. In the case of a giant bulla that rapidly increases in size, lung cancer should be included in the differential diagnosis.

Keywords: Lung neoplasms/complications; Infection; Drainage.

The presence of mediastinal lymph node metastasis in lung cancer has a great influence on treatment selection and prognosis, and the diagnosis of lymphatic metastasis must be accurate. CT chest scans and mediastinoscopy are the diagnostic tools available to detect mediastinal lymph node metastases and to establish preoperative staging. Lymph node size evaluated by CT scans is not an acceptable criterion in the patients studied here. The aim of this study was to find out a representative pattern of size to indicate the possibility of neoplastic invasion in the population studied. Fifty consecutive patients were operated on and were submitted to pulmonary resection and mediastinal dissection to treat lung cancer. Seventy-four percent of the lymph nodes with transverse section of more than 3 cm had no neoplastic invasion. CT scans and mediastinoscopy have similar sensitivity (close to 65%), but mediastinoscopy has higher specificity (100%). This means that the authors must have histologic confirmation of any suspected lymph node to achieve a correct staging.

Keywords: Carcinoma, non-small cell. Lung neoplasias. Lymph nodes. Lymphatic metastasis. Mediatinoscopy. Neoplasm, staging. CT scanning.

The authors analyze the nutritional status of patients with lung cancer. 131 patients, 96 (73.3%) male and 35 (26.7%) female, were classified into three groups: I - malnourished patients; II - eutrophic patients and III - obese patients. Most of the malnourished had anorexia (59.7%), which was not seen in the eutrophic (25%) and obese patients (26.1%). More than 70% of patients reported some degree of previous weight loss at the initial evaluation, weight loss being higher among malnourished patients. Weight loss was observed in more than 60% of the patients during the follow-up period of 3 months after the first evaluation. Patients with squamous carcinoma neoplasms prevailed in the malnourished group whereas adenocarcinoma was more prevalent in the other two groups. Most patients had advanced stages of the disease.

Keywords: Lung cancer. Nutritional status.

Silica is one of the main occupational agents associated with lung cancer. It is classified by the International Agency for Research on Cancer (IARC) as a Group 1 substance, i.e., carcinogenic for humans, since 1996. The objective of this paper is to report two cases of workers previously exposed to silica who developed lung cancer, seen in an out-patient clinic, focusing on important points of the current literature on the subject.