RESUMEN
Introdução: O câncer de pulmão é uma doença grave, sendo a segunda maior causa de morte em todo o mundo, entretanto, em alguns países desenvolvidos, tornou-se já a primeira causa de morte. Cerca de 90% dos casos de neoplasia pulmonares são causados pela inalação da fumaça do cigarro. Objetivo: Correlacionar a prevalência de tabagismo e morbimortalidade por câncer de pulmão nos estados brasileiros, além de demonstrar a associação destes com sexo e faixa etária. Métodos: Estudo de caráter ecológico acerca da prevalência de tabagismo e morbimortalidade por câncer de pulmão nos estados brasileiros, nos períodos de 2013 e 2019, dividida por sexo e faixa etária. Foram utilizados bancos de coleta de dados como o Tabnet e Pesquisa Nacional de Saúde. Resultados: As maiores taxas de mortalidade e internações hospitalares foram do público masculino, em 2013, com taxa de 2,7 e 10, respectivamente, e em 2019 com 3,3 e 11,9, respectivamente. Ademais, a maior prevalência de tabagismo foi encontrada nos homens; entretanto seu índice tem caído, enquanto a quantidade de mulheres tabagistas tem aumentado. A Região Sul demonstrou maiores números de mortalidade em ambos os períodos estudados, com taxas de 4,9 e 5,8 por 100 mil habitantes, e morbidade hospitalar com 19,9 e 23,5 por 100 mil habitantes. Já a Região Norte se configurou com as menores prevalências: em 2013 apresentou taxa de óbito por câncer de pulmão de 1,0 e morbidade hospitalar de 3,5/100 mil habitantes, em 2019 apresentou taxa de mortalidade de 4,6 e internações de 1,6/100 mil habitantes. Os coeficientes de correlação de morbidade hospitalar e prevalência de tabagismo foram R2=0,0628, r=0,251 e p=0,042, enquanto os de mortalidade e prevalência de tabagismo foram R2=0,0337, r=0,183 e p=0,140. Conclusões: Na presente pesquisa, pode-se inferir que houve associação positiva na comparação entre taxa de morbidade hospitalar e prevalência de tabagismo; em contrapartida, não foi possível observar associação positiva na correlação da taxa de mortalidade por câncer de pulmão e prevalência de tabagismo.
Introduction: Lung cancer is a serious disease, being the second leading cause of death worldwide. Moreover, in some developed countries, it has already become the leading cause of death. About 90% of lung cancer cases are caused by cigarette smoking. Objective: To correlate the prevalence of smoking and lung cancer morbidity and mortality in Brazilian states, and to demonstrate their association with sex and age group as well. Methods: An ecological study on the prevalence of smoking and lung cancer morbidity and mortality in Brazilian states between 2013 and 2019, divided by sex and age group. The data collection databases Tabnet and National Health Survey were used. Results: The highest rates of mortality and hospital admissions were among men, in 2013 with a rate of 2.7 and 10, respectively, and in 2019 with 3.3 and 11.9, respectively. In addition, the highest prevalence of smoking was found in men, but this rate has fallen, while the number of women smokers has increased. The South region showed higher mortality rates in both periods studied, with rates of 4.9 and 5.8 per 100,000 inhabitants, and hospital morbidity with 19.9 and 23.5 per 100,000 inhabitants. The North region had the lowest prevalence, where in 2013, it had a death rate from lung cancer of 1.0 and hospital morbidity of 3.5/100 thousand inhabitants, and where in 2019, it had a mortality rate of 4.6 and hospitalizations of 1.6/100 thousand inhabitants. The correlation coefficients for hospital morbidity and smoking prevalence were R2=0.0628, r=0.251 and p=0.042, while for mortality and smoking prevalence, these were R2=0.0337, r=0.183 and p=0.140. Conclusions: In the present study, it can be inferred that there was a positive association between hospital morbidity rate and prevalence of smoking, while it was not possible to observe a correlation between lung cancer mortality rate and prevalence of smoking.
Introducción: El cáncer de pulmón es una enfermedad grave, siendo la segunda causa de muerte en todo el mundo, sin embargo, en algunos países desarrollados, ya se ha convertido en la primera causa de muerte. Alrededor del 90% de los casos de neoplasias pulmonares están causados por la inhalación del humo del cigarrillo. Objetivo: Correlacionar la prevalencia de tabaquismo y la morbimortalidad por cáncer de pulmón en los estados brasileños, además de demostrar la asociación de estos con el género y el grupo de edad. Métodos: estudio ecológico sobre la prevalencia de tabaquismo y morbimortalidad por cáncer de pulmón en los estados brasileños, dentro de los períodos 2013 y 2019, divididos por sexo y grupo de edad. Se utilizaron bancos de recogida de datos como Tabnet y la Encuesta Nacional de Salud. Resultados: las mayores tasas de mortalidad e ingresos hospitalarios se dieron en el público masculino, en 2013 con una tasa de 2,7 y 10, respectivamente, y en 2019 con 3,3 y 11,9, respectivamente. Además, la mayor prevalencia del tabaquismo se encontró en los hombres, sin embargo, su tasa ha disminuido, mientras que la cantidad de mujeres fumadoras ha aumentado. La región Sur presentó cifras más altas de mortalidad en ambos periodos estudiados, con tasas de 4,9 y 5,8 por 100.000 habitantes, y de morbilidad hospitalaria con 19,9 y 23,5 por 100.000 habitantes. Mientras que la región Norte se configuró con las prevalencias más bajas, en 2013 presentó una tasa de mortalidad por cáncer de pulmón de 1,0 y una morbilidad hospitalaria de 3,5/100.000 habitantes, en 2019 presentó una tasa de mortalidad de 4,6 y hospitalizaciones de 1,6/100.000 habitantes. Los coeficientes de correlación para la morbilidad hospitalaria y la prevalencia del tabaquismo fueron R2=0,0628, r=0,251 y p=0,042, mientras que para la mortalidad y la prevalencia del tabaquismo fueron R2=0,0337, r=0,183 y p=0,140. Conclusiones: En la presente investigación se puede inferir que existe una asociación positiva en la comparación entre la tasa de morbilidad hospitalaria y la prevalencia de tabagismo, en contrapartida, no fue posible observar una asociación positiva en la correlación de la tasa de mortalidad por cáncer de pulmón y la prevalencia de tabagismo.
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Humanos , Tabaquismo , Carcinógenos , Productos de Tabaco , Neoplasias PulmonaresRESUMEN
BACKGROUND: Heterogeneous Black populations encounter significant obstacles in accessing cancer care, yet research on lung cancer treatment disparities remains limited. This study investigates whether the disparity in receiving curative-intent treatment (curative-intent surgery and/or stereotactic body radiation therapy [SBRT]) for early-stage non-small cell lung cancer (NSCLC) between non-Hispanic Whites (NHWs) and total Blacks extends to diverse Black populations, including US-born, Afro-Haitian, West Indian Black, and Hispanic Black individuals. METHODS: This cross-sectional study included all Florida cancer registry early-stage NSCLC cases 2005-2017, linked to individual-level discharge data containing comorbidity and specific treatment details (surgery and/or SBRT). Multivariable logistic regression assessed the association between race/ethnicity and the receipt of curative-intent treatment, while accounting for sociodemographic factors (poverty, age, insurance, and smoking status) and clinical variables. RESULTS: Among 55,655 early-stage NSCLC patients, 71.1% received curative-intent treatment: 72.1% NHW and 59.7% Black (non-Hispanic and Hispanic) individuals. Black patients had 35% lower odds (ORadj, 0.65; 95% CI, 0.59-0.70) of receiving curative-intent treatment compared to NHW patients. ORs varied from 0.57 (95% CI, 0.59-0.70) for Hispanic Black to 0.76 (95% CI, 0.56-1.02) for West Indian Black. Remarkably, Black-White disparities persisted despite the availability of curative treatment options (SBRT) for both high Charlson Comorbidity Index (CCI) observed among US-born Blacks and surgery for low CCI patients among all other Black subgroups. CONCLUSIONS: Pronounced disparities in accessing curative-intent treatments for early-stage NSCLC were evident across all Black subgroups, regardless of treatment availability and comorbidity profile. These findings underscore the need to address Black heterogeneity and prompt further research to rectify treatment disparities in early-stage NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas , Disparidades en Atención de Salud , Neoplasias Pulmonares , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Negro o Afroamericano , Carcinoma de Pulmón de Células no Pequeñas/terapia , Carcinoma de Pulmón de Células no Pequeñas/etnología , Carcinoma de Pulmón de Células no Pequeñas/patología , Estudios Transversales , Florida/epidemiología , Disparidades en Atención de Salud/etnología , Hispánicos o Latinos , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/etnología , Neoplasias Pulmonares/patología , Estadificación de Neoplasias , Pueblos CaribeñosRESUMEN
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.
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Secciones por Congelación , Neoplasias Pulmonares , Sensibilidad y Especificidad , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Estudios Prospectivos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Reproducibilidad de los Resultados , Periodo Intraoperatorio , Valor Predictivo de las Pruebas , Anciano de 80 o más Años , Invasividad Neoplásica , Adulto , Cuidados Intraoperatorios/métodos , Neumonectomía/métodosRESUMEN
OBJECTIVE: The purpose of this study was to assess performance in the Brazilian Lung Cancer Registry Database by using the parsimonious EuroLung risk models for morbidity and mortality. METHODS: The EuroLung1 and EuroLung2 models were tested and evaluated through calibration (calibration plot, Brier score, and the Hosmer-Lemeshow test) and discrimination (ROC AUCs), in a national multicenter registry of 1,031 patients undergoing anatomic lung resection. RESULTS: The evaluation of performance in Brazilian health care facilities utilizing risk-adjustment models, specifically EuroLung1 and EuroLung2, revealed substantial miscalibration, as evidenced by calibration plots and Hosmer-Lemeshow tests in both models. In terms of calibration, EuroLung1 exhibited a calibration plot with overlapping points, characterized by a slope of 1.11 and a Brier score of 0.15; the Hosmer-Lemeshow test yielded a statistically significant p-value of 0.015; and the corresponding ROC AUC was 0.678 (95% CI: 0.636-0.721). The EuroLung2 model displayed better calibration, featuring fewer overlapping points in the calibration plot, with a slope of 1.22, with acceptable discrimination, as indicated by a ROC AUC of 0.756 (95% CI: 0.670-0.842). Both models failed to accurately predict morbidity and mortality outcomes in this specific health care context. CONCLUSIONS: Discrepancies between the EuroLung model predictions and outcomes in Brazil underscore the need for model refinement and for a probe into inefficiencies in the Brazilian health care system.
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Neoplasias Pulmonares , Sistema de Registros , Humanos , Neoplasias Pulmonares/mortalidad , Brasil/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Medición de Riesgo/métodos , Factores de Riesgo , Reproducibilidad de los Resultados , CalibraciónRESUMEN
Brain metastasis is a significant clinical challenge for patients with advanced lung cancer, occurring in about 20-40% of cases. Brain metastasis causes severe neurological symptoms, leading to a poor prognosis and contributing significantly to lung cancer-related mortality. However, the underlying molecular mechanism behind brain metastasis remains largely unknown. MicroRNAs (miRNAs) are small, non-coding RNAs linked to several aspects of cancer progression, including metastasis. In the context of lung cancer, significant research has shown the involvement of miRNAs in regulating critical pathways related to metastatic spread to the brain. This review summarizes the scientific evidence regarding the regulatory roles of intra- and extracellular miRNAs, which specifically drive the spread of lung cancer cells to the brain. It also revises the known molecular mechanisms of brain metastasis, focusing on those from lung cancer as the primary tumor to better understand the complex mechanisms underlying this regulation. Understanding these complex regulatory mechanisms holds promise for developing novel diagnostic biomarkers and potential therapeutic strategies in brain metastasis.
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Neoplasias Encefálicas , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares , MicroARNs , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , AnimalesAsunto(s)
Neoplasias Pulmonares , Neoplasias Cutáneas , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/secundario , Masculino , Anciano , Adenocarcinoma/secundario , Adenocarcinoma/patología , Adenocarcinoma/diagnóstico por imagen , Persona de Mediana EdadRESUMEN
Breast cancer (BC) accounts for 24.2% of all women's malignant tumors, with rising survival rates due to advancements in chemotherapy and targeted treatments. However, second primary cancers, particularly lung cancer (LC), have become more prevalent, often emerging approximately 10 years after BC treatment. This study presents a case series of 9 women diagnosed with second primary LC following BC, treated at a high-complexity hospital in Colombia between 2014 and 2019. All initial BCs were ductal carcinomas, 7 were triple negative, 1 was human epidermal growth factor receptor 2 positive, and 1 was estrogen and progesterone positive. Each patient had undergone radiation therapy, and 7 had received chemotherapy, increasing their LC risk. The second primary LCs, all adenocarcinomas, were confirmed using immunohistochemical stains for thyroid transcription factor-1 (TTF-1), Napsin A, and estrogen receptor (ER) status. The interval between treatments and LC detection ranged from 1 to 17 years, with 4 cases identified after 10 years and 3 within 1 to 3 years, underscoring the need for prolonged surveillance. Seven LCs were ipsilateral to the BC and radiation site, while 2 were contralateral, highlighting the necessity of monitoring both sides for potential LC development. This case series enhances the local epidemiological understanding, showing that prior radiotherapy for BC and histological analysis are key in characterizing second primary LC patients. The study emphasizes the critical role of accurate histological diagnosis in guiding treatment approaches for lung lesions in BC survivors.
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Neoplasias de la Mama , Neoplasias Pulmonares , Neoplasias Primarias Secundarias , Humanos , Femenino , Neoplasias Pulmonares/patología , Neoplasias Primarias Secundarias/patología , Persona de Mediana Edad , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Anciano , Adulto , Adenocarcinoma/patología , Adenocarcinoma/terapia , Ácido Aspártico Endopeptidasas , ColombiaRESUMEN
This study presents an observational, cross-sectional analysis of 64 patients diagnosed with small cell lung cancer (SCLC) at a reference laboratory for thoracic pathology between 2022 and 2024. The primary objective was to evaluate the expression of Delta-like ligand 3 (DLL3) and other neuroendocrine markers such as Chromogranin, and Synaptophysin, utilizing both traditional immunohistochemistry and digital pathology tools. Patients were primarily older adults, with a median age of over 71, and most biopsies were obtained from lung parenchyma. Immunohistochemistry (IHC) was performed using specific monoclonal antibodies, with DLL3 showing variable expression across the samples. Notably, DLL3 was expressed in 72.3% of the cases, with varied intensities and a semi-quantitative H-score applied for more nuanced analysis. ASCL1 was expressed in 97% of cases, with the majority considered low-expressors. Only 11% had high expression. TTF-1, traditionally not a conventional marker for the diagnosis of SCLC, was positive in half of the cases, suggesting its potential as a biomarker. The study underscores the significant variability in the expression of neuroendocrine markers in SCLC, with implications for both diagnosis and potential therapeutic targeting. DLL3, particularly, shows promise as a therapeutic target due to its high expression rate in the cohort. The use of digital pathology software QuPath enhanced the accuracy and depth of analysis, allowing for detailed morphometric analysis and potentially informing more personalized treatment approaches. The findings emphasize the need for further research into the role of these markers in the management and treatment of SCLC, considering the poor prognosis and high mortality rate observed in the cohort.
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Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico , Biomarcadores de Tumor , Péptidos y Proteínas de Señalización Intracelular , Neoplasias Pulmonares , Proteínas de la Membrana , Medicina de Precisión , Carcinoma Pulmonar de Células Pequeñas , Factores de Transcripción , Humanos , Carcinoma Pulmonar de Células Pequeñas/metabolismo , Carcinoma Pulmonar de Células Pequeñas/patología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/mortalidad , Masculino , Femenino , Anciano , Persona de Mediana Edad , Biomarcadores de Tumor/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Medicina de Precisión/métodos , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Proteínas de la Membrana/metabolismo , Anciano de 80 o más Años , Factores de Transcripción/metabolismo , Estudios Transversales , Inmunohistoquímica , Proteínas de Unión al ADN/metabolismo , AdultoRESUMEN
BACKGROUND: Lymphangioleiomyomatosis (LAM) is a rare (twenty-one per million female inhabitants) neoplastic cystic lung disease that impairs health-related quality of life (HRQoL). However, the factors associated with impaired quality of life in patients with LAM are poorly understood. OBJECTIVE: To assess the clinical, psychosocial, and functional characteristics associated with impaired quality of life in patients with LAM. METHODS: This was a cross-sectional study performed on two nonconsecutive days. HRQoL (SF-36 and CRQ), lung function tests, anxiety and depression symptoms (HADS), maximal (CPET and ISWT), and submaximal exercise capacity (6MWT) were assessed. Linear associations among outcomes were assessed using Pearson's correlation and multivariate tests. RESULTS: Forty-five women with LAM (46 ± 10.years; FEV1,74%pred) were evaluated. The lowest SF-36 scores were observed for general health and vitality and the highest for the physical and social domains. The lowest CRQ scores were observed for dyspnea and fatigue, and the highest were for the emotional function and self-control domains. Sixteen (35%) women had anxiety, and 8 (17%) had depression symptoms. Most of the SF-36 and CRQ domains were associated with anxiety and depression symptoms (from r = 0.4 to r = 0.7; p < 0.05) and exercise capacity (from r = 0.3 to r = 0.5; p < 0.05). Lung function parameters were weakly or not associated with quality of life domains. After multiple linear regression, HRQoL was independently associated with depression symptoms and physical capacity but not with lung function. CONCLUSION: Our results show that aerobic capacity and depression symptoms are the main factors, rather than lung function, related to quality of life in patients with LAM.
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Ansiedad , Depresión , Tolerancia al Ejercicio , Linfangioleiomiomatosis , Calidad de Vida , Humanos , Linfangioleiomiomatosis/psicología , Linfangioleiomiomatosis/fisiopatología , Linfangioleiomiomatosis/complicaciones , Femenino , Estudios Transversales , Persona de Mediana Edad , Adulto , Depresión/psicología , Ansiedad/psicología , Pruebas de Función Respiratoria , Neoplasias Pulmonares/psicología , Neoplasias Pulmonares/fisiopatología , Fatiga/psicología , Fatiga/fisiopatología , Fatiga/etiología , Disnea/fisiopatología , Disnea/psicología , Volumen Espiratorio Forzado , Pulmón/fisiopatología , Estado de SaludRESUMEN
Despite treatment advances through immunotherapies, including anti-PD-1/PD-L1 therapies, the overall prognosis of non-small cell lung cancer (NSCLC) patients remains poor, underscoring the need for novel approaches that offer long-term clinical benefit. This review examined the literature on the subject over the past 20 years to provide an update on the evolving landscape of dendritic cell-based immunotherapy to treat NSCLC, highlighting the crucial role of dendritic cells (DCs) in immune response initiation and regulation. These cells encompass heterogeneous subsets like cDC1s, cDC2s, and pDCs, capable of shaping antigen presentation and influencing T cell activation through the balance between the Th1, Th2, and Th17 profiles and the activation of regulatory T lymphocytes (Treg). The intricate interaction between DC subsets and the high density of intratumoral mature DCs shapes tumor-specific immune responses and impacts therapeutic outcomes. DC-based immunotherapy shows promise in overcoming immune resistance in NSCLC treatment. This article review provides an update on key clinical trial results, forming the basis for future studies to characterize the role of different types of DCs in situ and in combination with different therapies, including DC vaccines.
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Carcinoma de Pulmón de Células no Pequeñas , Células Dendríticas , Neoplasias Pulmonares , Humanos , Células Dendríticas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/terapia , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/inmunología , Animales , Inmunoterapia/métodos , Vacunas contra el Cáncer/inmunología , Vacunas contra el Cáncer/uso terapéuticoRESUMEN
BACKGROUND: Lung cancer screening (LCS) using low-dose computed tomography (LDCT) is a strategy for early-stage diagnosis. The implementation of LDCT screening in countries with a high prevalence/incidence of tuberculosis (TB) is controversial. This systematic review and meta-analysis aim to identify whether LCS using LDCT increases early-stage diagnosis and decreases mortality, as well as the false-positive rate, in regions with a high prevalence of TB. METHODS/DESIGN: Studies were identified by searching BVS, PUBMED, EMBASE, and SCOPUS. RCT and cohort studies (CS) that show the effects of LDCT in LC screening on mortality and secondary outcomes were eligible. Two independent reviewers evaluated eligibility and a third judged disagreements. We used the Systematic Review Data Repository (SRDR+) to extract the metadata and record decisions. The analyses were stratified by study design and incidence of TB. We used the Cochrane "Risk of bias" assessment tool. RESULTS: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) were used. Thirty-seven papers were included, referring to 22 studies (10 RCTs and 12 cohorts). Few studies were from regions with a high incidence of TB (One RCT and four cohorts). Nonetheless, the evidence is compatible with European and USA studies. RCTs and CS also had consistent results. There is an increase in early-stage (I-II) diagnoses and reduced LC mortality in the LCDT arm compared to the control. Although false-positive rates varied, they stayed within the 20 to 30% range. DISCUSSION: This is the first meta-analysis of LDCT for LCS focused on its benefits in regions with an increased incidence/prevalence of TB. Although the specificity of Lung-RADS was higher in participants without TB sequelae than in those with TB sequelae, our findings point out that the difference does not invalidate implementing LDCT LCS in these regions. TRIAL REGISTRATION: Systematic review registration Systematic review registration PROSPERO CRD42022309581.
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Detección Precoz del Cáncer , Neoplasias Pulmonares , Tomografía Computarizada por Rayos X , Humanos , Detección Precoz del Cáncer/métodos , Detección Precoz del Cáncer/estadística & datos numéricos , Incidencia , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/epidemiología , Tamizaje Masivo/métodos , Tamizaje Masivo/organización & administración , Tamizaje Masivo/estadística & datos numéricos , Prevalencia , Tomografía Computarizada por Rayos X/métodos , Tomografía Computarizada por Rayos X/estadística & datos numéricos , Tuberculosis/diagnóstico por imagen , Tuberculosis/epidemiologíaRESUMEN
BACKGROUND: Epstein-Barr virus (EBV) is involved in the development of lymphomas, nasopharyngeal carcinomas (NPC), and a subgroup of gastric carcinomas (GC), and has also been detected in lung carcinomas, even though the role of the virus in this malignancy has not yet been established. BamH1-A Rightward Frame 1 (BARF1), a suggested exclusive epithelial EBV oncoprotein, is detected in both EBV-associated GCs (EBVaGC) and NPC. The expression and role of BARF1 in lung cancer is unknown. METHODS: A total of 158 lung carcinomas including 80 adenocarcinomas (AdCs) and 78 squamous cell carcinomas (SQCs) from Chilean patients were analyzed for EBV presence via polymerase chain reaction (PCR), Immunohistochemistry (IHC), or chromogenic in situ hybridization (CISH). The expression of BARF1 was evaluated using Reverse Transcription Real-Time PCR (RT-qPCR). Additionally, A549 and BEAS-2B lung epithelial cells were transfected with a construct for ectopic BARF1 expression. Cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) were evaluated. RESULTS: We found that EBV was present in 37 out of 158 (23%) lung carcinomas using PCR. Considering EBV-positive specimens using PCR, IHC for Epstein-Barr nuclear antigen 1 (EBNA1) detected EBV in 24 out of 30 (80%) cases, while EBERs were detected using CISH in 13 out of 16 (81%) cases. Overall, 13 out of 158 (8%) lung carcinomas were shown to be EBV-positive using PCR/IHC/CISH. BARF1 transcripts were detected in 6 out of 13 (46%) EBV-positive lung carcinomas using RT qPCR. Finally, lung cells ectopically expressing BARF1 showed increased migration, invasion, and EMT. CONCLUSIONS: EBV is frequently found in lung carcinomas from Chile with the expression of BARF1 in a significant subset of cases, suggesting that this viral protein may be involved in EBV-associated lung cancer progression.
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Progresión de la Enfermedad , Transición Epitelial-Mesenquimal , Herpesvirus Humano 4 , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/virología , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Herpesvirus Humano 4/genética , Transición Epitelial-Mesenquimal/genética , Femenino , Masculino , Persona de Mediana Edad , Proteínas Virales/metabolismo , Proteínas Virales/genética , Anciano , Proliferación Celular/genética , Línea Celular Tumoral , Movimiento Celular/genética , Infecciones por Virus de Epstein-Barr/virología , Infecciones por Virus de Epstein-Barr/genética , Infecciones por Virus de Epstein-Barr/complicaciones , Adulto , Células A549RESUMEN
Background: The diagnosis and treatment of lung, colon, and gastric cancer through the histologic characteristics and genomic biomarkers have not had a strong impact on the mortality rates of the top three global causes of death by cancer. Methods: Twenty-five transcriptomic analyses (10 lung cancer, 10 gastric cancer, and 5 colon cancer datasets) followed our own bioinformatic pipeline based on the utilization of specialized libraries from the R language and DAVID´s gene enrichment analyses to identify a regulatory metafirm network of transcription factors and target genes common in every type of cancer, with experimental evidence that supports its relationship with the unlocking of cell phenotypic plasticity for the acquisition of the hallmarks of cancer during the tumoral process. The network's regulatory functional and signaling pathways might depend on the constant crosstalk with the microbiome network established in the oral-gut-lung axis. Results: The global transcriptomic network analysis highlighted the impact of transcription factors (SOX4, TCF3, TEAD4, ETV4, and FOXM1) that might be related to stem cell programming and cancer progression through the regulation of the expression of genes, such as cancer-cell membrane receptors, that interact with several microorganisms, including human T-cell leukemia virus 1 (HTLV-1), the human papilloma virus (HPV), the Epstein-Barr virus (EBV), and SARS-CoV-2. These interactions can trigger the MAPK, non-canonical WNT, and IFN signaling pathways, which regulate key transcription factor overexpression during the establishment and progression of lung, colon, and gastric cancer, respectively, along with the formation of the microbiome network. Conclusion: The global transcriptomic network analysis highlights the important interaction between key transcription factors in lung, colon, and gastric cancer, which regulates the expression of cancer-cell membrane receptors for the interaction with the microbiome network during the tumorigenic process.
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Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Transcriptoma , Humanos , Neoplasias Pulmonares/microbiología , Neoplasias Pulmonares/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Biología Computacional , Pulmón/microbiología , Pulmón/patología , Boca/microbiología , Transducción de Señal , Microbioma Gastrointestinal/genética , Microbiota/genética , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/genética , Regulación Neoplásica de la Expresión GénicaRESUMEN
OBJECTIVE: Large cell neuroendocrine carcinoma of the lung is a rare type of lung cancer. There is a limited number of studies on clinical and histopathological characteristics that are effective in survival. The aim of this study was to investigate the relationship between histopathological and clinical characteristics, mainly Ki-67 proliferation index, and survival in patients diagnosed with large cell neuroendocrine carcinoma of the lung. METHODS: The data of 38 patients followed up with the diagnosis of large cell neuroendocrine carcinoma of the lung were evaluated. The mean Ki-67 value was determined to be 65.8% (±20.8). The patients' clinical characteristics and survival times were compared according to the cut-off value determined for Ki-67 index. RESULTS: When median overall survival times were compared, it was seen that overall survival was numerically lower in patients aged 65 years and over, in tumors located on the right side, in cases who were in the metastatic stage at diagnosis, whose Ki-67 index was 65% and above, who did not receive chemotherapy, who did not undergo curative surgery, and in patients with chronic diseases (p>0.05). In the Kaplan-Meier analysis, the median overall survival was determined to be 22.2 months (95%CI 21.7-22.7) in the patients with Ki-67<65%, while it was found to be 20.3 months (95%CI 4.5-36.2) in the patients with Ki-67≥65% (p=0.351). CONCLUSION: Our study identified subgroups with decreased survival in large cell neuroendocrine carcinoma of lung patients. Studies including a larger number of patients are needed to identify the prognostic importance of these clinical and histopathological characteristics.
Asunto(s)
Carcinoma de Células Grandes , Carcinoma Neuroendocrino , Antígeno Ki-67 , Neoplasias Pulmonares , Humanos , Antígeno Ki-67/análisis , Carcinoma Neuroendocrino/mortalidad , Carcinoma Neuroendocrino/patología , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/mortalidad , Masculino , Femenino , Anciano , Persona de Mediana Edad , Carcinoma de Células Grandes/mortalidad , Carcinoma de Células Grandes/patología , Proliferación Celular , Adulto , Estimación de Kaplan-Meier , Pronóstico , Anciano de 80 o más Años , Estadificación de NeoplasiasRESUMEN
PURPOSE: Lung cancer remains one of the leading causes of cancer-related mortality worldwide. It is the third cause of death among patients with cancer in Puerto Rico (PR) and non-small cell lung cancer (NSCLC) is the most prevalent. This study aims to describe the first-line treatment (1LT) and health care resource utilization (HCRU) among patients with NSCLC in PR. METHODS: A retrospective cohort study was conducted using the PR Central Cancer Registry Health Insurance Linkage Database to describe patients with NSCLC from 2012 to 2016. It describes sociodemographic and clinical characteristics on the basis of stage and histology and includes 1LT patterns and HCRU. RESULTS: A total of 1,011 patients met the inclusion criteria. Most were male (57.1%), married (54.1%), and had no comorbidities (55.8%). A significant proportion of patients (71.1%) were diagnosed at stages III and IV, with nonsquamous cell carcinoma being the most prevalent histology group (75.9%). About 61.7% received systemic therapy, 36.7% received radiotherapy, and 21.9% underwent surgery. Platinum (Pt)-based combinations were the most common 1LT (82.9%). On average, patients had 4.7 emergency room visits, nearly six hospitalizations, and 22.4 outpatient visits annually. The mean frequencies of positron emission tomography, ultrasounds, computerized tomography scans, and magnetic resonance imaging were 0.95, 0.11, 4.88, and 0.91, respectively. CONCLUSION: To our knowledge, this study provides the first description of 1LT patterns, HCRU, and sociodemographic information among patients with NSCLC in PR. A significant number of patients were diagnosed at stage III or higher and received Pt-based systemic therapy as their 1LT. More research is required to investigate treatment patterns beyond the 1LT and to gain a comprehensive understanding of optimal care interventions and factors associated with early NSCLC diagnosis.
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Carcinoma de Pulmón de Células no Pequeñas , Atención a la Salud , Recursos en Salud , Neoplasias Pulmonares , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/terapia , Puerto Rico , Recursos en Salud/estadística & datos numéricos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Atención a la Salud/normas , Atención a la Salud/estadística & datos numéricos , Estudios Retrospectivos , Estudios de Cohortes , Factores Sociodemográficos , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Anciano de 80 o más AñosRESUMEN
Emerging evidence demonstrates that curcumin has an inhibitory effect on non-small cell lung cancer (NSCLC), and its targets and mechanism of action need further exploration. The goal of this study was to explore the potential targets and mechanism of curcumin against NSCLC by network pharmacology, bioinformatics, and experimental validation, thereby providing more insight into combination treatment with curcumin for NSCLC in preclinical and clinical research. Curcumin targets against NSCLC were predicted based on HIT2.0, STD, CTD, and DisGeNET, and the core targets were analyzed via protein-protein interaction network construction (PPI), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and molecular docking. The gene expression levels of samples in A549 cells, NCI-H460, and curcumin treated groups were detected by real-time quantitative PCR. A total of 67 common targets between curcumin and NSCLC were collected by screening public databases. GO and KEGG analysis suggested that curcumin treatment of NSCLC mainly involves cancer-related pathways, such as PI3K-AKT signaling pathway, Foxo signaling pathway, microRNAs, MAPK signaling pathway, HIF-1 signaling pathway, etc. The targets with the highest degree were identified through the PPI network, namely CASP3, CTNNB1, JUN, IL6, MAPK3, HIF1A, STAT3, AKT1, TP53, CCND1, VEGFA, and EGFR. The results of the in vitro experiments showed that curcumin treatment of NSCLC down-regulated the gene expressions of CCND1, CASP3, HIF1A, IL-6, MAPK3, STAT3, AKT1, and TP53. Our findings revealed that curcumin functions as a potential therapeutic candidate for NSCLC by suppressing multiple signaling pathways and interacting with multiple gene targets.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Biología Computacional , Curcumina , Neoplasias Pulmonares , Simulación del Acoplamiento Molecular , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Humanos , Curcumina/farmacología , Curcumina/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Mapas de Interacción de Proteínas/efectos de los fármacos , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Transducción de Señal/efectos de los fármacos , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
BACKGROUND: CD155 is a transmembrane protein that inhibits antitumor immune response and represents a predictor of worse prognosis in non-small-cell lung cancer (NSCLC). However, it remains unexplored its association with clinical characteristics and genomic status of Latin American patients. This study characterizes the CD155 expression and its clinical implications in this population. METHODS: Tissue biopsies from 86 patients with locally-advanced or metastatic NSCLC were assessed for CD155 protein expression, ALK rearrangements and EGFR mutations. Cutoff values for high CD155 expression (CD155high) were determined from receiver operating characteristic (ROC) curves according to 2-year survival. It was evaluated its association with clinicopathological features, median progression-free survival (mPFS) and overall survival (mOS). RESULTS: the cutoff score for CD155high was 155 in the entire cohort and in patients without oncogenic alterations, and it was 110 in patients with oncogenic alterations. Eighty-four patients (97.7%) were CD155 positive, of which fifty-six (65.0%) had CD155high. EGFR L858R mutation related to lower CD155 IHC score than exon 19 deletion. Individuals with CD155high showed a shorter mOS (13.0 vs. 30.8 months; HR: 1.96 [95% CI, 1.15-3.35]; p = 0.014). Patients without oncogenic alterations having a CD155high displayed shorter mPFS (1.6 vs. 6.4 months, HR: 2.09 [95% CI, 1.06-4.20]; p = 0.034) and mOS (2.9 vs. 23.1 months; HR: 1.27 [95% CI, 1.07- 4.42]; p = 0.032). Patients with oncogenic alterations having CD155high only showed a trend to shorter mOS (26.3 vs. 52.0 months; HR: 2.39 [95% CI, 0.98-5.83]; p = 0.058). CONCLUSION: CD155high is a predictor of worse outcomes in patients with advanced NSCLC, predominantly among those without oncogenic alterations. CD155 could be a potential biomarker and a molecular target in patients with poor responses to current therapies.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Receptores Virales , Humanos , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Masculino , Femenino , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Persona de Mediana Edad , Pronóstico , Anciano , Receptores Virales/genética , Receptores Virales/metabolismo , Mutación/genética , Adulto , Receptores ErbB/metabolismo , Receptores ErbB/genética , Anciano de 80 o más Años , Curva ROCRESUMEN
NLRP1, the first identified inflammasome-forming sensor, is thought to be involved in cancer, yet its definite function in lung adenocarcinoma (LUAD) remains unclear. Herein, we explored the expression and function of NLRP1 in LUAD. Decreased NLRP1 expression was identified in LUAD, which was associated with a poor prognosis. Overexpression of NLRP1 inhibited tumor growth in vitro and in vivo. Mechanically, this effect was observed regardless of inflammasome activation. Further studies revealed that overexpression of NLRP1 downregulated the phosphorylation of DRP1 and promoted mitochondrial fusion, which was mediated by inhibition of NF-κB activity. NF-κB agonist could neutralize the effect of NLRP1 on mitochondrial dynamics. In addition, LUAD sensitivity to cisplatin was enhanced by decreased mitochondrial fission resulting from up-regulated NLRP1. In conclusion, our findings demonstrated an unexpected role of NLRP1 in LUAD by modulating mitochondrial activities, which provides strong evidence for its potential in LUAD treatment.
Asunto(s)
Adenocarcinoma del Pulmón , Inflamasomas , Neoplasias Pulmonares , Mitocondrias , Proteínas NLR , Humanos , Inflamasomas/metabolismo , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/metabolismo , Proteínas NLR/metabolismo , Animales , Mitocondrias/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Proteínas Reguladoras de la Apoptosis/metabolismo , Línea Celular Tumoral , Dinámicas Mitocondriales/efectos de los fármacos , Dinámicas Mitocondriales/fisiología , Ratones , Masculino , Proliferación Celular/efectos de los fármacos , FemeninoRESUMEN
El dolor es un síntoma frecuente de presentación en los casos de cáncer pulmonar y es un dolor refractario debido a la multiplicidad de generadores de dolor. Las presentaciones pueden ser una invasión pleural, metastasis costales, invasión mixta o síndrome costo-pleural, tumor de Pancoast, y metástasis vertebral con o sin invasion paravertebral. Se han desarrollado terapias intervencionales mínimamente invasivas para tratar el dolor, que en etapas tempranas en pacientes con dolor no controlado mejoran su condición de salud, mejoran su rendimiento para enfrentar la enfermedad y su tratamiento, y evitan o retrasan la escalada de opioides con sus efectos adversos asociados. Se requiere estandarizar las técnicas, mejorar la calidad de los ensayos clínicos y desarrollar guías de práctica clínica en un trabajo conjunto con oncología.
Pain is a frequent presenting symptom in cases of lung cancer and it is a refractory pain due to the multiplicity of pain generators. Clinical presentations may be pleural invasion, rib metastasis, mixed invasion or costo-pleural syndrome, Pancoast tumor, and vertebral metastasis with or without paravertebral invasion. Minimally invasive interventional therapies have been developed to treat pain, which in early stages in patients with uncontrolled pain improve their health condition, improve their performance in coping with the disease and its treatment, and prevent or delay the escalation of opioids with their associated side effects. It is necessary to standardize the techniques, improve the quality of clinical trials and develop clinical practice guidelines in a joint effort with oncology.
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Humanos , Dolor en el Pecho/terapia , Dolor en Cáncer/terapia , Neoplasias Pulmonares/complicaciones , Ondas de Radio/uso terapéutico , Toracotomía/efectos adversos , Neuropatías del Plexo Braquial/terapia , Desnervación , Mastectomía/efectos adversosRESUMEN
Lung cancer is one of the most commonly occurring malignant tumours worldwide. Although some reference methods such as X-ray, computed tomography or bronchoscope are widely used for clinical diagnosis of lung cancer, there is still a need to develop new methods for early detection of lung cancer. Especially needed are approaches that might be non-invasive and fast with high analytical precision and statistically reliable. Herein, we developed a swab "dip" test in saliva whereby swabs were analysed using attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy harnessed to principal component analysis-quadratic discriminant analysis (QDA) and variable selection techniques employing successive projections algorithm (SPA) and genetic algorithm (GA) for feature selection/extraction combined with QDA. A total of 1944 saliva samples (56 designated as lung-cancer positive and 1888 designed as controls) were obtained in a lung cancer-screening programme being undertaken in North-West England. GA-QDA models achieved, for the test set, sensitivity and specificity values of 100.0% and 99.1%, respectively. Three wavenumbers (1422 cm-1, 1546 cm-1 and 1578 cm-1) were identified using the GA-QDA model to distinguish between lung cancer and controls, including ring C-C stretching, CîN adenine, Amide II [δ(NH), ν(CN)] and νs(COO-) (polysaccharides, pectin). These findings highlight the potential of using biospectroscopy associated with multivariate classification algorithms to discriminate between benign saliva samples and those with underlying lung cancer.