Objective: EBUS-TBNA cytological sampling is routinely performed for pathological diagnosis, mediastinal staging, and molecular testing in lung cancer patients. EBUS-TBNA samples are not formally accepted for testing programmed death-ligand 1 (PD-L1) expression. The objective of the study was to compare the feasibility, reproducibility, and accuracy of PD-L1 expression assessment in cytological specimens and histological samples. Methods: We prospectively collected histological (transbronchial forceps biopsy) and cytological (EBUS-TBNA) samples from peribronchial neoplastic lesions during an endoscopic procedure at the same target lesion for the pathological diagnosis and molecular assessment of stage IV non-small cell lung cancer (NSCLC). Results: Fifteen patients underwent the procedure. Adequate cytological samples (at least 100 neoplastic cells) were obtained in 12 cases (92.3%). Assessment of PD-L1 expression was similar between histological and cytological samples (agreement rate = 92%). Sensitivity and diagnostic accuracy of EBUS-TBNA cytological specimens were 88.9% and 100%, respectively. Conclusions: The evaluation of PD-L1 expression in EBUS-TBNA cytological specimens is feasible and presents good reproducibility when compared with routine histological samples. EBUS-TBNA cytological samples could be used for the assessment of PD-L1 expression in patients with NSCLC as a minimally invasive approach in stage IV NSCLC cancer patients.

Keywords: Ultrasonography; Biopsy, needle; Lung neoplasms; Molecular targeted therapy.

Objective: To evaluate the efficacy of the joint use of cervical mediastinoscopy and video-assisted thoracoscopy for the sampling of mediastinal lymph nodes in patients with non-small cell lung cancer (NSCLC) and candidates for pulmonary resection. Methods: Sixty-two patients diagnosed with NSCLC were submitted to cervical mediastinoscopy and video-assisted thoracoscopy. The samples obtained (from paratracheal chains, anterior and posterior subcarinal chains, paraesophageal chains and pulmonary ligament) were submitted to frozen section analysis. The following variables were also evaluated: age; gender; weight loss; diagnostic method; tomographic findings; histological type; staging; and location and size of the primary tumor. Results: In 11 patients, mediastinoscopy showed no involvement of the subcarinal chain, whereas such involvement was identified when video-assisted thoracoscopy was used: positive predictive value = 88.89% (95% CI: 51.75-99.72); negative predictive value = 94.34% (95% CI: 84.34-98.82); prevalence = 17.74% (95% CI: 9.2-29.53); sensitivity = 72.73% (95% CI: 39.03-93.98); and specificity = 98.77% (95% CI: 93.31-99.97). In 60% of the patients with involvement of the posterior subcarinal chain, the primary tumor was in the right inferior lobe. (p = 0.029) Conclusions: The joint use of cervical mediastinoscopy and video-assisted thoracoscopy for the evaluation of posterior mediastinal lymph nodes proved to be an efficacious method. When there is no access to posterior chains by means of ultrasound with transbronchial or transesophageal biopsy, which dispenses with general anesthesia, this should be the method of choice for the correct evaluation of mediastinal lymph nodes in patients with NSCLC.

Keywords: Neoplasm staging; Mediastinoscopy; Biopsy; Lymphatic metastasis.

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.

Objective: To investigate the diagnostic value of α-enolase (ENO1) and serum ENO1 autoantibody levels in lung cancer. Methods: Immunohistochemistry staining and ELISA were performed to detect ENO1 expression in lung tissue and serum ENO1 autoantibody levels, respectively. Results: The expression of ENO1 was higher in lung cancer tissues than in benign lung disease tissues (p < 0.001). The proportion of lung cancer samples expressing ENO1 was not significantly different among the various pathological classification groups. The proportion of samples expressing ENO1 was higher in lung cancer patients in stages I/II than in those in stages III/IV (χ2 = 5.445; p = 0.018). The expression of ENO1 in lung cancer tissues was not associated with age, gender, or smoking history. Serum ENO1 antibody levels were significantly higher in the lung cancer group than in the benign lung disease and control groups (p < 0.001). The differences among the pathological classification groups were not statistically significant. Serum ENO1 antibody levels were also in lung cancer patients in stages I/II than in those in stages III/IV (p < 0.01). Serum ENO1 antibody levels were not associated with age, gender, or smoking history in lung cancer patients. The ROC curve representing the diagnosis of lung cancer based on ENO1 antibody levels had an area under the curve of 0.806. Conclusions: Our results suggest that high levels of ENO1 are associated with the clinical stage of lung cancer and that ENO1 expression and its serum autoantibody levels show diagnostic value in lung cancer.

Keywords: Phosphopyruvate hydratase/analysis; Enzyme-linked immunosorbent assay; Immunohistochemistry; Lung neoplasms.

Surgical resection is the primary treatment option for early-stage non-small cell lung cancer, lobectomy being considered the standard of care. In elderly patients, physiological characteristics can limit the suitability for surgery and the extent of resection. Sublobar resection (SLR) can be offered as an alternative. The aim of this real-world analysis was to compare lobectomy and SLR in terms of recurrence and survival rates in patients over 70 years of age.

Keywords: Carcinoma, non-small-cell lung/mortality; Carcinoma, non-small-cell lung/surgery; Recurrence; Aged; Aged, 80 and over.

Objective: Adjuvant chemotherapy (AC) improves survival of patients with resected non-small cell lung cancer (NSCLC). However, the cisplatin-vinorelbine regimen has been associated with a significant risk of clinically relevant toxicity. We sought to evaluate the effectiveness, safety, and feasibility of AC for NSCLC patients in a real-world setting. Methods: This was a single-center, retrospective cohort study of patients with stage I-III NSCLC undergoing surgery with curative intent between 2009 and 2018. AC was administered at the discretion of physicians. The patients were divided into two groups: AC group and no AC (control) group. Study outcomes included overall survival (OS) and recurrence-free survival (RFS), as well as the safety profile and feasibility of the cisplatin-vinorelbine regimen in a real-world setting. Results: The study involved 231 patients, 80 of whom received AC. Of those, 55 patients received the cisplatin-vinorelbine regimen. Survival analyses stratified by tumor stage showed that patients with stage II NSCLC in the AC group had better RFS (p = 0.036) and OS (p = 0.017) than did those in the no AC group. Among patients with stage III NSCLC in the AC group, RFS was better (p < 0.001) and there was a trend toward improved OS (p = 0.060) in comparison with controls. Of those who received the cisplatin-vinorelbine regimen, 29% had grade 3-4 febrile neutropenia, and 9% died of toxicity. Conclusions: These results support the benefit of AC for NSCLC patients in a real-world setting. However, because the cisplatin-vinorelbine regimen was associated with alarming rates of toxicity, more effective and less toxic alternatives should be investigated.

Keywords: Lung neoplasms; Chemotherapy, adjuvant; Cisplatin/toxicity; Vinorelbine/toxicity.

Objectives: To determine the effect that the treatment of GERD has on the clinical management, as well as the respiratory function, of patients with asthma and to evaluate the clinical characteristics of this group of patients. Methods: Patients with asthma and concomitant GERD, documented using 24 h pH-metry, were evaluated by means of quality of life questionnaires, as well as questionnaires related to respiratory and digestive symptoms. In addition, esophageal manometry, spirometry and the determination of peak expiratory flow were also performed prior to and after the study. Forty-nine individuals who were diagnosed with GERD by means of 24 h esophageal pH-metry were selected and participated in a clinical randomized double-blind placebo-controlled study, involving the administration of 40 mg/day of pantoprazol for 12 consecutive weeks. Results: Forty-four individuals completed the study (n = 22 per group). There was significant improvement in the scores for respiratory symptoms and quality of life only in the group that received pantoprazol (p = 0.01 and p = 0.001, respectively). No respiratory function parameters changed in either group. Conclusions: In this study, the effective treatment of GERD improved patient quality of life, and the symptoms of asthma significantly decreased in the group that received the medication. There were no changes in pulmonary function parameters.

Keywords: Asthma; Gastroesophageal reflux/treatment; Diagnosis; Antacids.

Objective: To determine the role of prophylactic cranial irradiation (PCI) in patients with small cell lung cancer (SCLC). Methods: We searched various databases, selecting randomized clinical trials published in journals or conference proceedings within the last 30 years and investigating the role of PCI in the mortality of patients with SCLC, submitted to PCI or not. Results: Sixteen randomized clinical trials, collectively involving 1,983 patients, were considered eligible for inclusion. Of those 1,983 patients, 1,021 were submitted to PCI and 962 were not. Overall mortality was 4.4% lower in the patients submitted to PCI than in those who were not (OR = 0.73; 95% CI: 0.57-0.97; p = 0.01), especially among the patients showing a complete response after induction chemotherapy (OR = 0.68; 95% CI: 0.50-0.93; p = 0.02) and in those submitted to PCI after that treatment (OR = 0.68; 95% CI: 0.49-0.94; p = 0.03). That decrease did not correlate with the stage of the disease: limited disease (OR = 0.73; 95% CI: 0.55-0.97; p = 0.03); and extensive disease (OR = 0.48; 95% CI: 0.26-0.87; p = 0.02). Conclusions: Our findings suggest that PCI decreases mortality in patients with SCLC, especially in those showing a complete response after induction chemotherapy and in those submitted to PCI after that treatment, regardless of the stage of the disease.

Keywords: Small cell lung carcinoma; Radiotherapy; Survival analysis.

Objective: Because SARS-CoV-2 infection can severely affect the lungs and persistent functional changes can occur after severe disease, we aimed to determine lung function parameters of COVID-19 patients at 45 days after hospital discharge and compare changes according to the severity of the disease. Methods: This was a prospective descriptive analytical multicenter study. The participants were allocated into three groups: ward admission (WA) group; ICU admission not on mechanical ventilation (ICU/MV-) group; and ICU admission on MV (ICU/MV+) group. Lung volumes, DLco, MIP, MEP, and six-minute walk distance (6MWD) were measured 45 days after discharge. Results: The sample comprised 242 patients (mean age = 59.4 ± 14.8 years; 52.1% of males), and 232 (96%) had altered lung function. In the total cohort, restrictive disorder was observed in 96%, as well as reductions in DLco (in 21.2% of the patients), FEV1/FVC (in 39.7%), and PEmax (in 95.8%), with no differences between the groups. Comparing the groups, the ICU/MV+ group had reduced DLco in 50% of the patients (p < 0.001) and a lower mean 6MWD % of the predicted value (p = 0.013). Oxygen desaturation in the six-minute walk test was observed in 32.3% of the cohort and was less frequent in the IE group. Conclusions: This is the first South American study involving severe COVID-19 survivors whose lung function was assessed 45 days after hospital discharge. Changes were frequent, especially in those on MV, which highlights the importance of lung function evaluation after severe COVID-19.

Keywords: COVID-19; Respiratory function tests; Pulmonary diffusing capacity; Virus disease; SARS-CoV-2.

Objective: The present study aimed to assess the functional status of children diagnosed with COVID-19 at the time of hospitalization and the associations with clinical features. Methods: This prospective cohort study was carried out with children diagnosed with COVID-19 admitted to a tertiary hospital. The patients' functioning was assessed using the pediatric Functional Status Scale (FSS). Results: A total of 62 children with a median age of 3 years old were included in the study, and 70% had some comorbidity prior to the diagnosis of COVID-19. The median length of stay was nine days, during which period five patients died. The FSS assessment of the sample showed that approximately 55% had some functional alteration. The group of patients with the highest FSS scores presented a lengthier hospital stay (p = 0.016), required more oxygen therapy (p < 0.001), mechanical ventilation (p = 0.001), and intensive care unit admissions (p = 0.019), and had more cardiac (p = 0.007), neurological (p = 0.003), and respiratory (p = 0.013) comorbidities. In the multivariate analysis, there was an association between the dependent variable length of stay and the total FSS score (b = 0.349, p = 0.004) and the presence of comorbidities (b = 0.357, p = 0.004). Conclusions: We observed that more than half of the children hospitalized due to COVID-19 had some level of functional change. Greater alterations in functional status were associated with the presence of previous comorbidities, a greater need for ventilatory support, and longer hospital stays.

Keywords: COVID-19, coronavirus, pediatrics, physical functional performance, functional status.

Objective: To compare a once-daily long-acting β2 agonist (indacaterol 150 µg) with a once-daily long-acting anticholinergic (tiotropium 5 µg) in terms of their effects on exercise endurance (limit of tolerance, Tlim) in patients with moderate COPD. Secondary endpoints were their effects on lung hyperinflation, exercise-related dyspnea, and daily-life dyspnea. Methods: This was a randomized, single-blind, crossover pilot study involving 20 patients (mean age, 60.9 ± 10.0 years; mean FEV1, 69 ± 7% of predicted). Spirometric parameters, Transition Dyspnea Index scores, Tlim, and exertional dyspnea were compared after three weeks of each treatment (with a one-week washout period between treatments). Results: Nineteen patients completed the study (one having been excluded because of COPD exacerbation). Improvement in Tlim from baseline tended to be greater after treatment with tiotropium than after treatment with indacaterol (96 ± 163 s vs. 8 ± 82 s; p = 0.06). Tlim significantly improved from baseline after treatment with tiotropium (having increased from 396 ± 319 s to 493 ± 347 s; p = 0.010) but not after treatment with indacaterol (having increased from 393 ± 246 to 401 ± 254 s; p = 0.678). There were no differences between the two treatments regarding improvements in Borg dyspnea scores and lung hyperinflation at "isotime" and peak exercise. There were also no significant differences between treatments regarding Transition Dyspnea Index scores (1.5 ± 2.1 vs. 0.9 ± 2.3; p = 0.39). Conclusions: In patients with moderate COPD, tiotropium tends to improve Tlim in comparison with indacaterol. No significant differences were observed between the two treatments regarding their effects on lung hyperinflation, exercise-related dyspnea, and daily-life dyspnea. Future studies, including a larger number of patients, are required in order to confirm our findings and explore mechanistic explanations. (ClinicalTrials.gov identifier: NCT01693003 [http://www.clinicaltrials.gov/])

Keywords: Pulmonary disease, chronic obstructive; Exercise; Bronchodilator agents.

Objective: Lung cancer is a global public health problem and is associated with high mortality. Lung cancer could be largely avoided by reducing the prevalence of smoking. The objective of this study was to analyze the effects of social, behavioral, and clinical factors on the survival time of patients with non-small cell lung cancer treated at Cancer Hospital I of the José Alencar Gomes da Silva National Cancer Institute, located in the city of Rio de Janeiro, Brazil, between 2000 and 2003. Methods: This was a retrospective hospital cohort study involving 1,194 patients. The 60-month disease-specific survival probabilities were calculated with the Kaplan-Meier method for three stage groups. The importance of the studied factors was assessed with a hierarchical theoretical model after adjustment by Cox multiple regression. Results: The estimated 60-month specific-disease lethality rate was 86.0%. The 60-month disease-specific survival probability ranged from 25.0% (stages I/II) to 2.5% (stage IV). The performance status, the intention to treat, and the initial treatment modality were the major prognostic factors identified in the study population. Conclusions: In this cohort of patients, the disease-specific survival probabilities were extremely low. We identified no factors that could be modified after the diagnosis in order to improve survival. Primary prevention, such as reducing the prevalence of smoking, is still the best method to reduce the number of people who will suffer the consequences of lung cancer.

Keywords: Lung neoplasms/epidemiology; Carcinoma, non-small-cell lung; Survival analysis.

Objective: To establish the accuracy of frozen section examination in identifying tumor spread through air spaces (STAS), as well as to propose a reproducible technical methodology for frozen section analysis. We also aim to propose a method to be incorporated into the decision making about the need for conversion to lobectomy during sublobar resection. Methods: This was a nonrandomized prospective study of 38 patients with lung cancer who underwent surgical resection. The findings regarding STAS in the frozen section were compared with the definitive histopathological study of paraffin-embedded sections. We calculated a confusion matrix to obtain the positive predictive value (PPV), negative predictive value (NPV), sensitivity, specificity and accuracy. Results: The intraoperative frozen section analysis identified 7 STAS-positive cases that were also positive in the histopathological examination, as well as 3 STAS-negative cases that were positive in the in the histopathological examination. Therefore, frozen section analysis was determined to have a sensitivity of 70%, specificity of 100%, PPV of 100%, NPV of 90.3%, and accuracy of 92% for identifying STAS. Conclusions: Frozen section analysis is capable of identifying STAS during resection in patients with lung cancer. The PPV, NPV, sensitivity, and specificity showed that the technique proposed could be incorporated at other centers and would allow advances directly linked to prognosis. In addition, given the high accuracy of the technique, it could inform intraoperative decisions regarding sublobar versus lobar resection.

Keywords: Neoplasm invasiveness; Frozen sections; Lung neoplasms/pathology; Lung neoplasms/surgery.

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.

Objective: To evaluate cognitive learning, ability to perform and interpret lung ultrasound exams, and self-perception of learning among medical students after a short pedagogical intervention at a medical school in Brazil. Methods: An experimental pilot study was conducted with medical students at different stages of their education (basic cycle, clinical cycle, and medical internship). The participants underwent a cognitive test before and after the intervention, a practical test, a test to recognize lung ultrasound pathologies, and a qualitative evaluation test at the end of the intervention. Statistical analysis was performed using a significance level of p < 0.05. Results: A total of 42 students were included in the study, with a median age of 23 years and a predominance of males. The mean score of the pre-intervention cognitive test was 2.97 ± 0.87, and that of the post-intervention test was 6.57 ± 1.41, showing significant improvement (p < 0.001). The score of the practical test and that of the recognition of pathologies test also showed significant improvement after the intervention. There was no significant difference in execution time between the groups. Students in the clinical cycle had a better self-perception of learning. Conclusions: Theoretical teaching and practical training of lung ultrasound in a short pedagogical intervention can improve cognitive performance, practical skills, and interpretation of the exam. The level of learning achievement was higher among more advanced students in medical education. Additionally, the students in the clinical cycle had a better perception of their learning.

Keywords: Ultrasonography; Lung; Students, medical; education, medical.