Exploring Inflammatory Asthma Phenotypes: Proteomic Signatures in Serum and Induced Sputum.

Asthma drug responses may differ due to inflammatory mechanisms triggered by the immune cells in the pulmonary microenvironment. Thus, asthma phenotyping based on the local inflammatory profile may aid in treatment definition and the identification of new therapeutic targets. Here, we investigated protein profiles of induced sputum and serum from asthma patients classified into eosinophilic, neutrophilic, mixed granulocytic, and paucigranulocytic asthma, according to inflammatory phenotypes. Proteomic analyses were performed using an ultra-performance liquid chromatography (ultra-HPLC) system coupled to the Q Exactive Hybrid Quadrupole Orbitrap Mass Spectrometer. Fifty-two (52) proteins showed significant differences in induced sputum among the groups, while only 12 were altered in patients' sera. Five proteins in the induced sputum were able to discriminate all phenotypic groups, while four proteins in the serum could differentiate all except the neutrophilic from the paucigranulocytic inflammatory pattern. This is the first report on comparative proteomics of inflammatory asthma phenotypes in both sputum and serum samples. We have identified a potential five-biomarker panel that may be able to discriminate all four inflammatory phenotypes in sputum. These findings not only provide insights into potential therapeutic targets but also emphasize the potential for personalized treatment approaches in asthma management.

Bronchodilator response as a hallmark of uncontrolled asthma: a randomised clinical trial.

INTRODUCTION: The goal of this study is to determine whether bronchodilator (BD) response can be used as a reliable measure of asthma control by analyzing the effects of a short course of oral corticosteroids (OC) or placebo (P) on spirometry, sputum cytology and BD response in controlled asthma patients scoring less than 1.5 on the ACQ5. METHODS: Seventy patients with moderate to severe asthma who were undergoing combination therapy and were considered to be controlled based on ACQ5 scores, but who exhibited persistent positive BD response, were randomly assigned to two groups, one receiving OC and the other P. Patients were evaluated before and after 2 weeks of treatment. Intervention response (comparison of FEV(1) before and after OC or P treatment) was used as a measure of intervention efficacy, with values equal to or greater than 200 mL considered positive. RESULTS: Patients who received OC showed significant improvement in FEV(1), and no longer exhibited a positive BD response. Those in the P group showed no change. In addition, sputum eosinophil counts significantly decreased in the OC group. CONCLUSIONS: BD response can be used as a reliable measure of asthma control. This study suggests that ACQ5 scores alone are not sufficient to fully assess asthma control, and that BD response should be included as an essential measurement in any algorithm of asthma control evaluation.

Lung cancer screening in Brazil: recommendations from the Brazilian Society of Thoracic Surgery, Brazilian Thoracic Association, and Brazilian College of Radiology and Diagnostic Imaging.

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.

Preoperative 6-min walking distance does not predict pulmonary complications in upper abdominal surgery.

BACKGROUND AND OBJECTIVE: Field exercise tests have been increasingly used for pulmonary risk assessment. The 6-min walking distance (6MWD) is a field test commonly employed in clinical practice; however, there is limited evidence supporting its use as a risk assessment method in abdominal surgery. The aim was to assess if the 6MWD can predict the development of post-operative pulmonary complications (PPCs) in patients having upper abdominal surgery (UAS). METHODS: This prospective cohort study included 137 consecutive subjects undergoing elective UAS. Subjects performed the 6MWD on the day prior to surgery, and their performance were compared with predicted values of 6MWD (p6MWD) using a previously validated formula. PPCs (including pneumonia, tracheobronchitis, atelectasis with clinical repercussions, bronchospasm and acute respiratory failure) were assessed daily by a pulmonologist blinded to the 6MWD results. 6MWD and p6MWD were compared between subjects who developed PPC (PPC group) and those who did not (no PPC group) using Student's t-test. RESULTS: Ten subjects experienced PPC (7.2%) and no significant difference was observed between the 6MWD obtained in the PPC group and no PPC group (466.0 ± 97.0 m vs. 485.3 ± 107.1 m; P = 0.57, respectively). There was also no significant difference observed between groups for the p6MWD (100.7 ± 29.1% vs. 90.6 ± 20.9%; P > 0.05). CONCLUSIONS: The results of the present study suggest that the 6-min walking test is not a useful tool to identify subjects with increased risk of developing PPC following UAS.

Quality of life and physical limitations in primary brain tumor patients.

OBJECTIVE: To correlate quality of life (QoL) and physical limitations in histological proven primary brain tumor patients using a battery of generic, disease-specific and symptom questionnaires. METHODS: Thirty patients with primary brain tumors were selected from a neuro-oncology outpatient clinic. The FACT-Br Functional Assessment of Cancer Therapy-Brain (specific quality of life questionnaire for patients with brain tumors), SF-36 (generic quality of life questionnaire), HADS (anxiety and depression), and Barthel Index (functionality scale) were answered by the patients at the same interview. RESULTS: The Barthel index did not demonstrate correlation with any subscale of the FACT-Br questionnaire. The HADS had a negative correlation with all FACT-Br subscales and its total score. The SF-36 had a significant weak to moderate correlation with the FACT-Br questionnaire. CONCLUSION: Considering that the FACT-Br is a quick specific questionnaire, it can be a valuable and simple option in evaluating QoL in brain tumor patients with good functional capacity.

Role that anorexia and weight loss play in patients with stage IV lung cancer.

OBJECTIVE: To evaluate the prevalence of anorexia and weight loss at diagnosis (pre-treatment), to identify the factors associated with pre-treatment weight loss, and to determine the prognostic role of anorexia and weight loss in the overall survival of patients with stage IV lung cancer. METHODS: This was a retrospective observational cohort study. The patients were stratified by the presence/absence of anorexia and of pre-treatment weight loss, which generated a measure composed of four categories, which were the independent variables. RESULTS: Among the 552 patients included in the study, anorexia and pre-treatment weight loss were present in 39.1% and 70.1%, respectively. After adjusting for age, male gender, and Karnofsky performance status, we found that anorexia and tumor size were significantly associated with pre-treatment weight loss. In a Cox multivariate analysis, adjusted for age, male gender and low Karnofsky performance status were found to be independent predictors of worse survival, as was concomitance of anorexia and weight loss. CONCLUSIONS: Anorexia and pre-treatment weight loss appear to be relevant problems in the follow-up of patients with advanced (stage IV) lung cancer Specific interventions are of crucial importance in individualized treatment plans, even within the context of palliative care.

Lung cancer screening in Brazil: recommendations from the Brazilian Society of Thoracic Surgery, Brazilian Thoracic Association, and Brazilian College of Radiology and Diagnostic Imaging / Recomendações da Sociedade Brasileira de Cirurgia Torácica, Sociedade Brasileira de Pneumologia e Tisiologia e Colégio Brasileiro de Radiologia e Diagnóstico por Imagem para o rastreamento do câncer de pulmão no Brasil

ABSTRACT 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.

RESUMO O câncer de pulmão (CP) é uma das neoplasias mais comuns e letais no Brasil, e apenas 15% dos pacientes são diagnosticados nos estágios iniciais. O tabagismo persiste como o responsável por mais de 85% de todos os casos. O rastreamento do CP (RCP) por meio da TC de baixa dosagem de radiação (TCBD) reduz a mortalidade do CP em 20%, e, quando combinado com a cessação do tabagismo, essa redução chega a 38%. Na última década, diversos países adotaram o RCP como recomendação de saúde populacional. No Brasil, embora ainda incipiente, a discussão sobre o tema é cada vez mais ampla e necessária. Com o intuito de aumentar o conhecimento e estimular o debate sobre o RCP, a Sociedade Brasileira de Cirurgia Torácica, a Sociedade Brasileira de Pneumologia e Tisiologia e o Colégio Brasileiro de Radiologia e Diagnóstico por Imagem constituíram um painel de especialistas para elaborar as recomendações para o RCP. As recomendações aqui apresentadas foram baseadas em revisão narrativa da literatura, com ênfase em grandes estudos populacionais, em revisões sistemáticas e em recomendações de diretrizes internacionais, sendo construídas após ampla discussão pelo grupo de especialistas. Os temas revisados foram os seguintes: porque rastrear, considerações gerais sobre tabagismo, epidemiologia do CP, critérios de elegibilidade, achados incidentais, lesões granulomatosas, modelos probabilísticos, requisitos mínimos da TCBD, aquisições volumétricas, riscos do rastreamento, estrutura mínima e papel da equipe multidisciplinar, conduta segundo o Lung CT Screening Reporting and Data System (Lung-RADS), custos vs. benefícios e perspectivas do rastreamento.

Time required to achieve asthma control in not previously inhaled corticosteroid treated adult patients.

BACKGROUND: To achieve the best health possible, asthma patients require targeted education to understand the disease and how it may affect them, and what they need to do to keep it controlled. AIM: To measure the length of time needed in a structured educational training program to achieve well-controlled asthma status. METHODS: This 5-month clinical trial enrolled previously untreated adult asthma patients at the Asthma Center of the President Dutra Public Hospital/Federal University of Maranhao-Brazil. At the first visit, patients were stratified according to their pre-bronchodilator peak expiratory flow rate (PEFR) measurements: Class I was defined as PEFR > 80% of the predicted value; Class II as PEFR 50-80% of predicted value, and Class III as PEFR < 50% of predicted value. At enrollment and each follow-up visit patients were assessed for asthma symptoms and health care utilization. In the educational program, sessions covered signs and symptoms of asthma exacerbation, triggering factors, environmental control, and asthma drug effects. The time required to achieve well-controlled status and the total time free of asthma symptoms were evaluated by Kaplan-Meier curves. The log-rank test was used to compare PEFR classes, with significance being measured as p-values < or = 0.05. RESULTS: A total of 121 patients met the eligibility criteria and underwent the 6-month follow-up. The first six-month Kaplan-Meier curve demonstrated that Class I patients had a significantly better probability of achieving well-controlled asthma than the other classes (log rang = 6.78, p = 0.03), The second 6-month Kaplan-Meier curve analyzed the total time free of asthma symptoms according to PEFR class (log rank = 11, 22 p = 0.003). The time required to reach a well-controlled status was 2 or 3 months, depending on the baseline level of airway obstruction: patients in PEFR classes I and II achieved good control earlier than patients in PEFR Class III. Education and targeted training remain a key element of doctor-patient interactions and success of asthma control efforts.

Management of lung nodules in Brazil-assessment of realities, beliefs and attitudes: a study by the Brazilian Society of Thoracic Surgery (SBCT), the Brazilian Thoracic Society (SBPT) and the Brazilian College of Radiology (CBR).

BACKGROUND: Pulmonary nodules are common; some are inconsequential while others are malignant. Management of solitary pulmonary nodule (SPN) in Brazil appears to be highly variable, potentially leading to suboptimal outcomes. Assessment of the variability and the association with the degree of availability of resources can provide a foundation for development of clinical guidelines for management of SPN specific for the Brazilian setting. METHODS: A web-based survey was developed by thoracic surgeons, pulmonologists and radiologists to evaluate SPN perception and management. This survey was sent to their respective national societies members and answers collected between August and December 2016. That included multiple choice questions regarding age, specialty, SPN management, accessibility to exams and interventional procedures characterizing public (SUS) and supplementary private working settings. RESULTS: A total of 461 questionnaires were answered. More than half of participants live in cities with over one million people. Specialties were reasonable equilibrated with 43.5% radiologists, 33.5% thoracic surgeons, 20.3% pulmonologists and 2.6% others. Most of the respondents work in both public and private sector (72.7%). Private has a similar reality compared to well-developed nations regarding exams accessibility and interventions. SUS setting has a significant variability access according to the participants. CT is only easily available in 31.9% of cases, PET-CT is easily available in 24.4%, bronchoscopy is easily available for 42.8%, transthoracic needle biopsy is only easily available in 13.9% and video-assisted thoracoscopic surgery (VATS) biopsy is not available in 19.5%. When there is a probability of malignancy of 50% or higher, 46.5% of participants would be comfortable recommending surgical biopsy. When the probability is higher than 10%, only 36.9% would be comfortable following up radiologically. CONCLUSIONS: Brazil has a very different setting for public and private patients regarding exams accessibility and management options. That might explain why participants have a higher tendency to choose interventional diagnosis and explains why current guidelines may not be applicable to developing countries reality.

Survival in a cohort of patients with lung cancer: the role of age and gender in prognosis.

OBJECTIVE: To determine the demographic and clinical characteristics of patients with non-small cell lung cancer (NSCLC), as well as their disease course, by age group and gender. METHODS: This was a retrospective cohort study of patients diagnosed with NSCLC from 2000 to 2012 and followed until July 2015 in a tertiary referral hospital in the city of São Paulo, Brazil. Based on the 25th and 75th percentiles of the age distribution, patients were stratified into three age groups: < 55 years; ≥ 55 and < 72 years; and ≥ 72 years. Survival time was evaluated during the follow-up period of the study. Functions of overall and gender-specific survival stratified by age groups (event: all-cause mortality) were calculated using the Kaplan-Meier method. Differences among survival curves were assessed via the log-rank test. RESULTS: We included 790 patients with the following age distribution: < 55 years, 165 patients; ≥ 55 and < 72 years, 423; and ≥ 72 years, 202. In the entire sample, there were 493 men (62.4%). Adenocarcinoma was the most common histological pattern in the < 72-year age groups; 575 patients (73%) presented with advanced disease (stages IIIB-IV). The median 5-year survival was 12 months (95% CI: 4-46 months), with no significant differences among the age groups studied. CONCLUSIONS: NSCLC remains more common in men, although we found an increase in the proportion of the disease in women in the < 55-year age group. Adenocarcinoma predominated in women. In men, squamous cell carcinoma predominated in the ≥ 72-year age group. Most patients presented with advanced-stage disease at diagnosis. There were no statistical differences in survival between genders or among age groups.

Family caregiver burden: the burden of caring for lung cancer patients according to the cancer stage and patient quality of life.

OBJECTIVE:: Patients with lung cancer experience different feelings and reactions, based on their family, social, cultural, and religious backgrounds, which are a source of great distress, not only for the patients but also for their family caregivers. This study aimed to evaluate the impact that lung cancer stage and quality of life (QoL) of lung cancer patients have on caregiver burden. METHODS:: This was a prospective cross-sectional study. Consecutive patient-caregiver dyads were selected and asked to complete the Hospital Anxiety and Depression Scale and the Medical Outcomes Study 36-item ShortForm Health Survey (SF-36). Family caregivers also completed the Caregiver Burden Scale. Group-based modeling was used in order to identify patients with early- or advanced-stage cancer (IA to IIIA vs. IIIB to IV) plus non-impaired or impaired QoL (SF36 total score > 50 vs. ≤ 50). Patient-caregiver dyads were stratified into four groups: early-stage cancer+non-impaired QoL; advanced-stage cancer+non-impaired QoL; early-stage cancer+impaired QoL; and advanced-stage cancer+impaired QoL. RESULTS:: We included 91 patient-caregiver dyads. The majority of the patients were male and heavy smokers. Family caregivers were younger and predominantly female. The burden, QoL, level of anxiety, and level of depression of caregivers were more affected by the QoL of the patients than by their lung cancer stage. The family caregivers of the patients with impaired QoL showed a higher median burden than did those of the patients with non-impaired QoL, regardless of disease stage. CONCLUSIONS:: Caregiver burden is more affected by patient QoL than by lung cancer stage. OBJETIVO:: Pacientes com câncer de pulmão vivenciam diferentes sentimentos e reações, dependendo de sua formação familiar, social, cultural e religiosa, que são fonte de grande sofrimento, não só para os pacientes mas também para seus cuidadores familiares. Este estudo objetivou avaliar o impacto do estágio do câncer de pulmão e da qualidade de vida (QV) dos pacientes com câncer de pulmão na sobrecarga do cuidador. MÉTODOS:: Estudo prospectivo transversal. Díades paciente-cuidador foram selecionadas consecutivamente e solicitadas a preencher a Hospital Anxiety and Depression Scale e o Medical Outcomes Study 36-item Short-Form Health Survey (SF-36). Os cuidadores familiares também preencheram a Caregiver Burden Scale. Utilizou-se a modelagem de grupos para identificar pacientes com câncer em estágio inicial ou avançado (IA a IIIA vs. IIIB a IV) mais QV não comprometida ou comprometida (pontuação total no SF36 > 50 vs. ≤ 50). As díades paciente-cuidador foram estratificadas em quatro grupos: câncer em estágio inicial+QV não comprometida; câncer em estágio avançado+QV não comprometida; câncer em estágio inicial+QV comprometida; e câncer em estágio avançado+QV comprometida. RESULTADOS:: Foram incluídas 91 díades paciente-cuidador. A maioria dos pacientes era do sexo masculino e grande fumante. Os cuidadores familiares eram mais jovens e predominantemente do sexo feminino. A sobrecarga, QV, nível de ansiedade e nível de depressão dos cuidadores foram mais afetados pela QV dos pacientes do que pelo estágio do câncer de pulmão. Os cuidadores familiares dos pacientes com QV comprometida apresentaram maior mediana de sobrecarga do que os dos pacientes com QV não comprometida, independentemente do estágio da doença. CONCLUSÕES:: A sobrecarga do cuidador é mais afetada pela QV do paciente do que pelo estágio do câncer de pulmão.

Systemic effects of chronic obstructive pulmonary disease in young-old adults' life-space mobility.

PURPOSE: The objective was to assess whether dyspnea, peripheral muscle strength and the level of physical activity are correlated with life-space mobility of older adults with COPD. PATIENTS AND METHODS: Sixty patients over 60 years of age (40 in the COPD group and 20 in the control group) were included. All patients were evaluated for lung function (spirometry), life-space mobility (University of Alabama at Birmingham Study of Aging Life-Space Assessment), dyspnea severity (Modified Dyspnea Index), peripheral muscle strength (handgrip dynamometer), level of physical activity and number of daily steps (accelerometry). Groups were compared using unpaired t-test. Pearson's correlation was used to test the association between variables. RESULTS: Life-space mobility (60.41±16.93 vs 71.07±16.28 points), dyspnea (8 [7-9] vs 11 [10-11] points), peripheral muscle strength (75.16±14.89 vs 75.50±15.13 mmHg), number of daily steps (4,865.4±2,193.3 vs 6,146.8±2,376.4 steps), and time spent in moderate to vigorous activity (197.27±146.47 vs 280.05±168.95 minutes) were lower among COPD group compared to control group (p<0.05). The difference was associated with the lower mobility of COPD group in the neighborhood. CONCLUSION: Life-space mobility is decreased in young-old adults with COPD, especially at the neighborhood level. This impairment is associated to higher dyspnea, peripheral muscle weakness and the reduced level of physical activity.

Survival rates and tolerability of platinum-based chemotherapy regimens for elderly patients with non-small-cell lung cancer (NSCLC).

BACKGROUND: The combination therapy for non-small-cell lung cancer (NSCLC) with platinum-based treatment is well known, but its utility in elderly has not been explored systematically. AIM: To examine whether aging compromises survival or exacerbates toxicity in patients with advanced lung cancer receiving platinum-based treatment. METHODS: We performed a nested case-control study in a cohort of chemotherapy naïve patients enrolled January 1998-December 2003. Cases were consecutive patients over 70 at diagnosis with stage III or IV NSCLC. Controls were a subset of patients under 70 years matched by stage and year in which they had been treated. All patients received Cisplatin (80 mg/m2) or Carboplatin (4-6 AUC), every 4 weeks, followed by Vinorelbine (30 mg/m2) for a maximum of six courses. The medical history, physical examination and tumor imaging evaluation were performed at baseline and then monthly. Survival was calculated by Kaplan-Meier method and log-rank test was used for survival comparisons. Chi-squared test was used to compare side effects in the two groups. RESULTS: A total of 419 patients were identified for the case-control study (205 elderly/214 young) with 3.6 cycles per patient, on average. The 2- and 3-year survival rates were 20.5% and 6.8% for elderly patients and 9.8% and 2.3% for younger patients (p=0.017 and 0.014, respectively for 2 and 3 years). The proportion of patients with adverse effects, either grade 3 or 4, was the same in both groups at 2 years (43.9% versus 43.9%; p=0.99). CONCLUSIONS: Although elderly patients may self-select or be selected to be healthier, our findings suggest that elderly patients currently undergoing chemotherapy for lung cancer do as well or better than younger patients. Elderly age alone should not preclude patients from receiving platinum-based chemotherapy, since it seems well tolerated and effective in non-small-cell lung cancer among elderly patients.

Who Needs to Be Allocated in ICU after Thoracic Surgery? An Observational Study.

Background. The effective use of ICU care after lung resections has not been completely studied. The aims of this study were to identify predictive factors for effective use of ICU admission after lung resection and to develop a risk composite measure to predict its effective use. Methods. 120 adult patients undergoing elective lung resection were enrolled in an observational prospective cohort study. Preoperative evaluation and intraoperative assessment were recorded. In the postoperative period, patients were stratified into two groups according to the effective and ineffective use of ICU. The use of ICU care was considered effective if a patient experienced one or more of the following: maintenance of controlled ventilation or reintubation; acute respiratory failure; hemodynamic instability or shock; and presence of intraoperative or postanesthesia complications. Results. Thirty patients met the criteria for effective use of ICU care. Logistic regression analysis identified three independent predictors of effective use of ICU care: surgery for bronchiectasis, pneumonectomy, and age ≥ 57 years. In the absence of any predictors the risk of effective need of ICU care was 6%. Risk increased to 25-30%, 66-71%, and 93% with the presence of one, two, or three predictors, respectively. Conclusion. ICU care is not routinely necessary for all patients undergoing lung resection.

The role of PD-L1 expression as a predictive biomarker in advanced non-small-cell lung cancer: a network meta-analysis.

BACKGROUND: Tumor programmed death ligand one (PD-L1) expression has been studied in several trials in non-small-cell lung cancer. METHODS: We assessed the potential role of PD-L1 expression according to Cochrane Collaboration's Guidelines. RESULTS: 13 studies with 1979 patients were included. Among 915 PD-L1 negative patients this rate was 13% (RR 2.08; 95% CI: 1.49-2.91; p < 0.01). The response rate has increased concurrent to the PD-L1 expression (Pearson's correlation, r = 0.43). PD-L1 expression was also related to better 24-weeks progression-free rate (RR 0.79; 95% CI: 0.71-0.89) and a trend toward better 1-year overall survival rate (RR 0.96; 95% CI: 0.87-1.06). CONCLUSION: Taking this data in account, PD-L1 overexpression could not be currently considered a robust biomarker to tailor the immune checkpoint inhibitors treatment.

A pooled analysis of nivolumab for the treatment of advanced non-small-cell lung cancer and the role of PD-L1 as a predictive biomarker.

BACKGROUND: Recent studies with nivolumab (a monoclonal antibody against programmed cell death 1 [PD-1] receptor) have shown promise non-small-cell lung cancer (NSCLC) treatment. METHODS: To review available clinical trials data in order to assess nivolumab efficacy and the role of tumoral PDL-1 expression as a biomarker. RESULTS: Nine eligible studies included 2102 patients. In the second line setting, nivolumab achieved a 1-year survival rate of 41%; and in the first line, a 1-year survival rate of 76%. For those with PD-L1 expression <1%, nivolumab showed a trend for improved survival compared with docetaxel. CONCLUSIONS: The available data reinforce nivolumab activity against NSCLC in first-line or subsequent lines. Although PD-L1 expression is related to greater response, PD-L1 negative patients had also some benefit.

Role that anorexia and weight loss play in patients with stage IV lung cancer / Papel do binômio anorexia e perda de peso em pacientes com câncer de pulmão em estádio IV

ABSTRACT Objective: To evaluate the prevalence of anorexia and weight loss at diagnosis (pre-treatment), to identify the factors associated with pre-treatment weight loss, and to determine the prognostic role of anorexia and weight loss in the overall survival of patients with stage IV lung cancer. Methods: This was a retrospective observational cohort study. The patients were stratified by the presence/absence of anorexia and of pre-treatment weight loss, which generated a measure composed of four categories, which were the independent variables. Results: Among the 552 patients included in the study, anorexia and pre-treatment weight loss were present in 39.1% and 70.1%, respectively. After adjusting for age, male gender, and Karnofsky performance status, we found that anorexia and tumor size were significantly associated with pre-treatment weight loss. In a Cox multivariate analysis, adjusted for age, male gender and low Karnofsky performance status were found to be independent predictors of worse survival, as was concomitance of anorexia and weight loss. Conclusions: Anorexia and pre-treatment weight loss appear to be relevant problems in the follow-up of patients with advanced (stage IV) lung cancer Specific interventions are of crucial importance in individualized treatment plans, even within the context of palliative care.

RESUMO Objetivo: Avaliar a prevalência de anorexia e perda de peso ao diagnóstico (pré-tratamento), os fatores associados à perda de peso pré-tratamento e o papel prognóstico da anorexia e da perda de peso na sobrevida global de pacientes com câncer de pulmão em estádio IV. Métodos: Estudo de coorte retrospectivo observacional. Os pacientes foram estratificados, dependendo da presença/ausência de anorexia e da presença/ausência de perda de peso pré-tratamento, o que gerou uma medida composta de anorexia e perda de peso de quatro níveis, que foi a variável independente. Resultados: Entre os 552 pacientes incluídos no estudo, as prevalências de anorexia e de perda de peso pré-tratamento foram de 39,1% e 70,1%, respectivamente. Após ajustar para idade, sexo masculino e índice de Karnofsky, a presença de anorexia e o tamanho do tumor foram significativamente associados à perda de peso pré-tratamento. Na análise multivariada de Cox, após ajustar para a idade, as variáveis sexo masculino, presença concomitante de anorexia e perda de peso e índice de Karnofsky reduzido foram preditores independentes de pior probabilidade de sobrevida. Conclusões: O presente estudo demonstrou que a presença de anorexia e de perda de peso pré-tratamento são problemas relevantes no seguimento de pacientes com câncer de pulmão avançado (estádio IV). Intervenções específicas são de crucial importância no plano de assistência individualizada, mesmo dentro da proposta de cuidados paliativos.

Gastroesophageal reflux disease and non-esophageal cancer.

The association of gastroesophageal reflux disease (GERD) and esophageal cancer is well known. The carcinogenic properties of the gastroduodenal contents may also lead to cancer in target organs for GERD especially considering that they do not have intrinsic protective mechanisms as found in the esophagus. This review focuses on the putative relation between GERD and non-esophageal cancer. Most of the papers reviewed are far from ideal to prove the relationship of extra-esophageal cancer and GERD since a small number of patients is presented, most do not control cases based on tobacco usage and obesity, and the diagnosis of GERD is variable, not always from an objective measurement such as pH monitoring but relying on symptoms in most reports. Nevertheless, head and neck and lung cancer have a growing incidence parallel to GERD and a shift towards non-smoking, female gender and adenocarcinoma (compared to squamous cell carcinoma) is arising, similar to the example of esophageal cancer with the exception of the female gender.

Evaluation of lung volumes, vital capacity and respiratory muscle strength after cervical, thoracic and lumbar spinal surgery.

CONTEXT AND OBJECTIVE: Studies have shown that physiopathological changes to the respiratory system can occur following thoracic and abdominal surgery. Laminectomy is considered to be a peripheral surgical procedure, but it is possible that thoracic spinal surgery exerts a greater influence on lung function. The aim of this study was to evaluate the pulmonary volumes and maximum respiratory pressures of patients undergoing cervical, thoracic or lumbar spinal surgery. DESIGN AND SETTING: Prospective study in a tertiary-level university hospital. METHODS: Sixty-three patients undergoing laminectomy due to diagnoses of tumors or herniated discs were evaluated. Vital capacity, tidal volume, minute ventilation and maximum respiratory pressures were evaluated preoperatively and on the first and second postoperative days. Possible associations between the respiratory variables and the duration of the operation, surgical diagnosis and smoking status were investigated. RESULTS: Vital capacity and maximum inspiratory pressure presented reductions on the first postoperative day (20.9% and 91.6%, respectively) for thoracic surgery (P = 0.01), and maximum expiratory pressure showed reductions on the first postoperative day in cervical surgery patients (15.3%; P = 0.004). The incidence of pulmonary complications was 3.6%. CONCLUSIONS: There were reductions in vital capacity and maximum respiratory pressures during the postoperative period in patients undergoing laminectomy. Surgery in the thoracic region was associated with greater reductions in vital capacity and maximum inspiratory pressure, compared with cervical and lumbar surgery. Thus, surgical manipulation of the thoracic region appears to have more influence on pulmonary function and respiratory muscle action.