Female Lung Research Articles

A Review on Targeted Cell Therapy for Breast Cancer, Colon Cancer and Lung Cancer

Cancer mainly defined as a group of diseases lead to growth of abnormal cells anywhere in the body. Anything that potentially leads to the growth of abnormal cells in the body is called cancer. Cancer cells grow with potential to invade or spread in any parts of the body. Cancer can be caused by various agents and factors depending upon the type of cancer developed in the particular region. Chemical and toxic substance exposure, ionizing agents and genetic factors are majorly responsible for developing cancer cells in the body state or degree of disease is determined by medical uses such as biopsy which helps in diagnosis of cancer and determining its types and extent of cancer cells spread throughout the body. The molecular targets such as VEGF, oestrogen, protease activated receptor, BRAF has become major innovations towards drug discovery both naturally and chemically.Symptoms of cancer varies according to the types and extent of disease developed in body symptoms like fatigue, weight loss, change in bowel and bladder function, cough and skin tone are some of the early signs of developing cancerous cells in the body. In this study, we focussed the targets of leading cancers among male and female like breast cancer, lung cancer and colon cancer in drug discovery and development.

Oestrogen-mediated upregulation of the Mas receptor contributes to sex differences in acute lung injury and lung vascular barrier regulation.

Epidemiological data from the SARS-CoV-2 outbreak suggest sex differences in mortality and vulnerability; however, sex-dependent incidence of acute respiratory distress syndrome (ARDS) remains controversial and the sex-dependent mechanisms of endothelial barrier regulation are unknown. In premenopausal women, increased signalling of angiotensin (Ang)(1-7) via the Mas receptor has been linked to lower cardiovascular risk. Since stimulation of the Ang(1-7)/Mas axis protects the endothelial barrier in acute lung injury (ALI), we hypothesised that increased Ang(1-7)/Mas signalling may protect females over males in ALI/ARDS.Clinical data were collected from Charité inpatients (Berlin) and sex differences in ALI were assessed in wild-type (WT) and Mas-receptor deficient (Mas-/- ) mice. Endothelial permeability was assessed as weight change in isolated lungs and as transendothelial electrical resistance (TEER) in vitroIn 734 090 Charité inpatients (2005-2016), ARDS had a higher incidence in men as compared to women. In murine ALI, male WT mice had more lung oedema, protein leaks and histological evidence of injury than female WT mice. Lung weight change in response to platelet-activating factor (PAF) was more pronounced in male WT and female Mas-/- mice than in female WT mice, whereas Mas-receptor expression was higher in female WT lungs. Ovariectomy attenuated protection in female WT mice and reduced Mas-receptor expression. Oestrogen increased Mas-receptor expression and attenuated endothelial leakage in response to thrombin in vitro This effect was alleviated by Mas-receptor blockade.Improved lung endothelial barrier function protects female mice from ALI-induced lung oedema. This effect is partially mediated via enhanced Ang(1-7)/Mas signalling as a result of oestrogen-dependent Mas expression.

Multidimensional penalized splines for incidence and mortality-trend analyses and validation of national cancer-incidence estimates.

Cancer-incidence and mortality-trend analyses require appropriate statistical modelling. In countries without a nationwide cancer registry, an additional issue is estimating national incidence from local-registry data. The objectives of this study were to (i) promote the use of multidimensional penalized splines (MPS) for trend analyses; (ii) estimate the national cancer-incidence trends, using MPS, from only local-registry data; and (iii) propose a validation process of these estimates. We used an MPS model of age and year for trend analyses in France over 1990-2015 with a projection up to 2018. Validation was performed for 22 cancer sites and relied essentially on comparison with reference estimates that used the incidence/health-care ratio over the period 2011-2015. Alternative estimates that used the incidence/mortality ratio were also used to validate the trends. In the validation assessment, the relative differences of the incidence estimates (2011-2015) with the reference estimates were <5% except for testis cancer in men and < 7% except for larynx cancer in women. Trends could be correctly derived since 1990 despite incomplete histories in some registries. The proposed method was applied to estimate the incidence and mortality trends of female lung cancer and prostate cancer in France. The validation process confirmed the validity of the national French estimates; it may be applied in other countries to help in choosing the most appropriate national estimation method according to country-specific contexts. MPS form a powerful statistical tool for trend analyses; they allow trends to vary smoothly with age and are suitable for modelling simple as well as complex trends thanks to penalization. Detailed trend analyses of lung and prostate cancers illustrated the suitability of MPS and the epidemiological interest of such analyses.

Lung cancer in women in 21th century.

Lung cancer is the first cause of death from malignant disease. The distressing epidemiological data show the increasing female to male incidence ratio for this tumor. A high incidence of lung cancer in never smokers with importance of environmental agents makes a problem among women. Adenocarcinoma (ADC) is noted in women with increasing rate and ethnic background impacts female lung cancer with differences in the incidence of genetic aberrations. The conception of different hormonal status is taken into consideration as potential explanation of variant cancer biology and clinical manifestation in women and men. The impact of 17-β-estradiol, estrogen receptors, aromatase expression, pituitary sex hormones receptors in carcinogenesis with relation between estrogens and genetic aberrations are investigated. The response to newest therapies among female is also different than in men. This overview summarizes currently available evidence on the specificity of female lung cancer and presents the direction of necessary studies.

Abstract MP172: Y-chromosome Gene, Uty, Confers Male Protection Against Pulmonary Hypertension by Mediating Pro-inflammatory Chemokine Effects

Background: Idiopathic pulmonary arterial hypertension (PAH) is a terminal vascular lung disease characterized by increased PA pressure resulting in right ventricular (RV) failure and death. For reasons largely unknown, PAH is up to 4x more prevalent in females. We published that the Y-Chromosome (Chrm) is protective against hypoxia (Hx)-induced pulmonary hypertension (PH) in mice and identified four Y-Chrm genes expressed in the lung. Here, we identify the protective Y-Chrm gene, investigate its mechanism and demonstrate a novel therapeutic approach. Methods and Results: To test the effect of Y-Chrm candidate genes on PH development, we knocked down (KD) each Y-Chrm gene via sequential intratracheal instillation of siRNA in the lungs of male mice exposed to Hx. KD of Y-Chrm gene Uty, but none of the other genes, resulted in more severe PH measured by increased RV systolic pressure (RVSP) and decreased pulmonary arterial acceleration time (PAAT) compared to control (n=4/group; RVSP: Uty-KD= 48.93mmHg, Control= 37.33mmHg, p=0.04; PAAT: Uty-KD= 11.88ms, Control= 14.43ms, p=0.01). RNAseq analysis (Uty-KD vs Control) revealed an increase in pro-inflammatory cytokines Cxcl9 (Log2FC: 1.3, p-adjusted=0.05) and Cxcl10 (Log2FC: 0.9, p-adjusted=0.002). We found Cxcl9/10 significantly upregulated in human PAH lungs vs healthy and female PAH lungs vs male (RT-qPCR). Fluorescent in-situ hybridization revealed Uty and Cxcl9/10 expression co-localized in CD68 + macrophages within the lung. Treatment of human pulmonary artery endothelial cells (PAEC) with Cxcl9/10 resulted in significantly increased apoptosis. We inhibited Cxcl9/10 activity in female rats 14 days post monocrotaline (MCT) injection by treating them with a small molecular inhibitor. Treated rats (n=6) had less severe PH than vehicle-treated controls (n=5) when measured 28-days post MCT (RVSP: Treated= 36.75mmHg, Vehicle=43.62 mmHg, p=0.03; PAAT: Treated= 26.7ms, Vehicle=20 ms, p=0.01; RV hypertrophy index (RV/(LV+IVS)): Treated= 0.48, Vehicle= 0.35, p=0.01). Conclusion: Y-Chrm gene, Uty, is protective against PH. Uty inhibition increases pro-inflammatory cytokines Cxcl9/10 which contribute to PAEC death. Inhibition of Cxcl9/10 activity may provide a novel therapy for the treatment of PH.

Sarcoma epidemiology and cancer-related hospitalisation in Western Australia from 1982 to 2016: a descriptive study using linked administrative data

BackgroundSarcomas are a heterogeneous group of malignancies arising from mesenchymal cells. Epidemiological studies on sarcoma from Australia are lacking, as previous studies have focused on a sarcoma type (e.g. soft tissue) or anatomical sites.MethodsLinked cancer registry, hospital morbidity and death registration data were available for Western Australia (WA) from 1982 to 2016. All new sarcoma cases among WA residents were included to estimate incidence, prevalence, relative survival and cancer-related hospitalisation, using the Information Network on Rare Cancers (RARECARENet) definitions. To provide a reference point, comparisons were made with female breast, colorectal, prostate and lung cancers.ResultsFor 2012–16, the combined sarcoma crude annual incidence was 7.3 per 100,000, with the majority of these soft tissue sarcoma (STS, incidence of 5.9 per 100,000). The age-standardised incidence and prevalence of STS increased over time, while bone sarcoma remained more stable. Five-year relative survival for the period 2012–16 for STS was 65% for STS (higher than lung cancer, but lower than prostate, female breast and colorectal cancers), while five-year relative survival was 71% for bone sarcoma. Cancer-related hospitalisations cost an estimated $(Australian) 29.1 million over the study period.ConclusionsSTS incidence has increased over time in WA, with an increasing proportion of people diagnosed aged ≥65 years. The analysis of health service use showed sarcoma had a lower mean episode of cancer-related hospitalisation compared to the reference cancers in 2016, but the mean cost per prevalent person was higher for sarcoma than for female breast, colorectal and prostate cancers.

Profile of Female Lung Cancer at a Tertiary Care Hospital in Kashmir Valley

Profile of Female Lung Cancer at a Tertiary Care Hospital in Kashmir Valley

Abstract C015: Cardiovascular disease and health-related quality of life among African American and white cancer survivors

Abstract Background: Cardiovascular disease (CVD) is common among cancer survivors and is a leading cause of death among survivors of several forms of cancer. Race disparities exist in the prevalence of several forms of CVD, and these may have implications for the health-related quality of life (HRQOL) of cancer survivors. The current study estimates the association between several forms of CVD and HRQOL among a diverse cohort of cancer survivors. Methods: This analysis was conducted using data from 979 participants (574 African American, 405 white) with female breast, colorectal, lung, or prostate cancer in the Detroit Research On Cancer Survivors (ROCS) pilot study who were diagnosed and/or treated at the Karmanos Cancer Center in Detroit, Michigan. The analyses were conducted using linear regression with binary measurements of five different forms of CVD included in the ROCS pilot survey (self-reported history of congestive heart failure (CHF), myocardial infarction (MI), hypertension, peripheral vascular disease (PVD), and stroke) as predictors of HRQOL measured using the Functional Assessment of Cancer Therapy – General (FACT-G), controlling for demographic, socioeconomic, and cancer-related characteristics. We also tested for effect modification by race. Results: FACT-G scores were 2.2 (95% CI: -4.3, 0.0) points lower among cancer survivors who were diagnosed with any type of CVD compared to those who were not. This association did not differ by race (Pinteraction=0.25). FACT-G scores were somewhat lower among survivors diagnosed with hypertension [-1.9; 95% confidence interval (CI): -4.1, 0.1], MI (-4.1; 95% CI: -8.4, 0.2), CHF (-3.7; 95% CI: -8.2, 0.9), or stroke (-4.0; 95% CI: -8.5, 0.5); however, the magnitude of these differences was not clinically meaningful and the findings did not reach statistical significance. History of MI was associated with clinically meaningful differences in HRQOL among African American (-6.1; 95% CI: -11.3, -0.8) but not white survivors (-0.4, 95% CI: -7.9, 7.2; Pinteraction=0.15). Conclusions: Overall, any type of CVD was not associated with meaningful differences in HRQOL among cancer survivors. Our finding that history of MI was associated with clinically meaningful differences in HRQOL among African American survivors, but not white, could represent an opportunity for future efforts to improve survivors’ HRQOL. Citation Format: Jaclyn M. Kyko, Jennifer L. Beebe-Dimmer, Tara E. Baird, Ann G. Schwartz, Theresa A. Hastert. Cardiovascular disease and health-related quality of life among African American and white cancer survivors [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr C015.

Abstract D074: Variations in genomic testing across cancer sites and by demographic characteristics

Abstract Study Objective: Genomic testing is essential to identify the best treatment modalities for certain cancers; yet, its uptake has been relatively low, especially among disadvantaged subgroups of the population. The aim of this study is to identify demographic and clinical factors associated with receipt of genomic testing in Ohioans diagnosed with either incident female breast, kidney, bladder, prostate, colorectal, or lung cancer. Methods: We used data from the 2009 linked Ohio Cancer Incidence Surveillance System and Medicare files, and identified genomic testing using the appropriate procedure codes in claims data. Our study population included 10,945 patients. Independent variables examined were age at diagnosis (&amp;lt; 65, 65-74, 75+), sex, race (White or All Other), dual enrollment in the Medicare and Medicaid program (or ‘dual’) as a marker for low income and heightened vulnerability, and advanced stage at diagnosis (Regional/Distant versus Local stage). We conducted multivariable logistic regression analysis to identify correlates of genomic testing by cancer site. Results: For all cancer sites combined, 11.1% were younger than 65, and 40.6% were older than 75 years of age. Eighty eight percent were White, 47.0% were women, 13.9% were duals, and one third were diagnosed with advanced-stage cancer. Overall, only 19.5% underwent genomic testing, ranging from a low of 6.7% in prostate cancer patients, to a high of 39.3% in breast cancer patients. In addition, we observed considerable variation in genomic testing by age, race, sex, dual status, and cancer stage across cancer sites. Adjusting for the independent variables listed above, being 75 years of age or older was significantly and positively associated with increased likelihood of undergoing genomic testing in breast (adjusted odds ratio: 1.17, 95% confidence interval: 1.04, 1.32), kidney and bladder combined (1.29 (1.09, 1.53)), and prostate cancer patients (1.45 (1.12, 1.89)). Advanced-stage disease was associated with increased likelihood of genomic testing in breast and colorectal cancer patients (1.40 (1.17, 1.67) and 3.07 (2.30, 4.11), respectively), but with decreased likelihood in kidney and bladder cancer patients (0.66 (0.48, 0.91)). Finally, we note that White patients with lung cancer were significantly more likely than others to undergo genomic testing (2.49 (1.29, 4.78)). Conclusion: Our data from 2009 provide baseline statistics on genomic testing uptake in Ohio. Data for subsequent years will help us to assess trends in providing personalized medicine. Citation Format: Siran Koroukian, Weichuan Dong, Johnie Rose, Fredrick Schumacher, Sarah Markt. Variations in genomic testing across cancer sites and by demographic characteristics [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr D074.

Abstract PR07: Lung cancer incidence and risk factors in never-smoking Asian American, Native Hawaiian, and Pacific Islander women: A multilevel dataset of electronic health record, cancer registry, and environmental data

Abstract Background: For Asian American, Native Hawaiian, and Pacific Islander (AANHPI) females, lung cancer is one of the most common cancers and the leading cause of cancer death. More than half of AANHPI female lung cancers occur in never-smokers, and contributing risk factors among never-smokers remain largely unknown. Until now, there was no single sufficiently large data source to document lung cancer incidence rates by smoking status and sex among specific AANHPI ethnic groups, which is central to understanding and reducing the burden of this disease in this population. We assembled a large-scale cohort to quantify the burden of lung cancer by smoking status among single- and multiethnic AANHPI groups, with an emphasis on identifying the underlying factors driving lung cancer risk among never-smoking AANHPI females. Methods: Assembly of the cohort involved (1) harmonizing and pooling electronic health record (EHR) data on known and putative lung cancer risk factors from two large health systems (i.e., Northern California Sutter Health system and Kaiser Permanente Hawaii (KPH)), (2) linking EHR data from Sutter and KPH with tumor and diagnosis data from the California Cancer Registry and Hawaii Tumor Registry, respectively, (3) geocoding and linking the Sutter portion of the cohort to regional air pollutant data and data on specific neighborhood contextual factors from the California Neighborhoods Data System, and (4) developing neighborhood contextual variables to enhance the geocoded data for KPH cohort members. Incidence rates stratified by sex, detailed race/ethnicity, smoking status, and lung cancer histology have been calculated; as well as incidence rate ratios by race/ethnicity. Results: The cohort comprises over 2.3 million individuals (250,000 AANHPI females) followed up to 15 years for incident lung cancer. It includes over 6,000 incident lung cancer cases, of which 558 are AANHPI females. Among AANHPI female groups, proportions of lung cancers among never-smokers range from 31% among Native Hawaiian to 88% among Chinese females. Incidence rates of never-smoking lung cancer are highest among Native Hawaiian females (AAIR, 28.7) and Asian females reporting multiple races/ethnicities (AAIR, 27.8). Conclusions: We have assembled a large, integrated dataset well suited to study multilevel risk of lung cancer that will serve as a critical evidence base to inform screening, research, and public health priorities, especially among AANHPI females. Ongoing work will include longitudinal analyses of lung cancer risk among never-smoking AANHPI females, including absolute risk modeling, examining six exposure domains representing known and putative lung cancer risk factors. This abstract is also being presented as Poster A104. Citation Format: Mindy C. DeRouen, Caroline Thompson, Alison J. Canchola, Anqi Jin, Siaxing Nie, Jennifer Jain, Salma Shariff-Marco, Daphne Y. Lichetensztajn, Yihe Daida, Carmen Wong, Yuqing Li, Manali I. Patel, Heather A. Wakelee, Su-Ying Liang, Beth E. Waitzfelder, Iona Cheng, Scarlett L. Gomez. Lung cancer incidence and risk factors in never-smoking Asian American, Native Hawaiian, and Pacific Islander women: A multilevel dataset of electronic health record, cancer registry, and environmental data [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr PR07.

Abstract IA37: Lung cancer incidence and risk factors in never-smoking Asian American, Native Hawaiian, and Pacific Islander women: The development of a multilevel integrated dataset of EHR, cancer registry, and environmental data

Abstract Background: For Asian American, Native Hawaiian, and Pacific Islander (AANHPI) females, lung cancer is one of the most common cancers and the leading cause of cancer death. More than half of AANHPI female lung cancers occur in never-smokers, and contributing risk factors among never-smokers remain largely unknown. Until now, there was no single sufficiently-large data source to document lung cancer incidence rates by smoking status and sex among specific AANHPI ethnic groups, which is central to understanding and reducing the burden of this disease in this population. We assembled a large-scale cohort to quantify the burden of lung cancer by smoking status among single- and multiethnic AANHPI groups, with an emphasis on identifying the underlying factors driving lung cancer risk among never-smoking AANHPI females. Methods: Assembly of the cohort involved (1) harmonizing and pooling electronic health record (EHR) data on known and putative lung cancer risk factors from two large health systems (i.e., Northern California Sutter Health system and Kaiser Permanente Hawaii [KPH]); (2) linking EHR data from Sutter and KPH with tumor and diagnosis data from the California Cancer Registry and Hawaii Tumor Registry, respectively; (3) geocoding and linking the Sutter portion of the cohort to regional air pollutant data and data on specific neighborhood contextual factors from the California Neighborhoods Data System; and (4) developing neighborhood contextual variables to enhance the geocoded data for KPH cohort members. Incidence rates stratified by sex, detailed race/ethnicity, and smoking status were calculated. Results: The cohort comprises 1.8 million individuals, including 750,000 females of whom 190,000 are AANHPI females, with up to 15 years' follow-up for incident lung cancer. It includes over 24,000 incident lung cancer cases, of which 10,595 are females and over 1,500 are single- and multiethnic AANHPI females. The cohort has high representation of Asian Indian, Chinese, Japanese, Filipino, Korean, and Pacific Islander never-smoking females in addition to multiple multiethnic AANHPI ethnic groups. Ongoing analyses, including overall and histologic cell-type specific incidence rates of lung cancer by sex, race/ethnicity, and smoking status will be presented. Conclusions: We have assembled a large, integrated dataset well suited to study multilevel risk of lung cancer that will serve as a critical evidence base to inform screening, research, and public health priorities, especially among AANHPI females. Future work will include longitudinal analyses of lung cancer risk among never-smoking AANHPI females, including absolute risk modeling, examining six exposure domains representing putative lung cancer risk factors: second-hand smoke, previous lung diseases, infections, reproductive history and hormone exposure, body size, and neighborhood environmental factors, including measures of particulate matter, traffic density, neighborhood socioeconomic status, and ethnic enclave. Citation Format: Mindy C. DeRouen, Salma Shariff-Marco, Daphne Lichtensztajn, Anqi Jin, Yihe G. Daida, Alison J. Canchola, Yuqing Li, Jennifer Jain, Laura Allen, Sixiang Nie, Carmen Wong, Robert Haile, Manali Patel, Peggy Reynolds, Heather Wakelee, Hal Luft, Caroline Thompson, Su-Ying Liang, Beth E. Waitzfelder, Iona Cheng, Scarlett L. Gomez. Lung cancer incidence and risk factors in never-smoking Asian American, Native Hawaiian, and Pacific Islander women: The development of a multilevel integrated dataset of EHR, cancer registry, and environmental data [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr IA37.

IMPACT OF SMOKING AND DECREASED LUNG FUNCTION ON THE PROGNOSIS OF FEMALE LUNG CANCER: ANALYSIS OF THE KOREAN ASSOCIATION OF LUNG CANCER REGISTRY

TYPE: Abstract Publication TOPIC: Lung Cancer PURPOSE: The clinical characteristics of smokers were reported to be less favorable than those in the never-smoker population of women with lung cancer. However, the accumulation and analysis of more real-life data are necessary. The present study evaluated Korean women with lung cancer and compared the clinical characteristics of ever-smoker and never-smoker groups using the National Lung Cancer Registry. METHODS: In affiliation with the Korean Central Cancer Registry (KCCR), the Korean Association for Lung Cancer (KALC) constructed a registry (KALC-R) into which 10% of the lung cancer cases from all Korean nationals were registered after the survey. Female lung cancer patients with valid smoking history were evaluated. RESULTS: A total of 735 female lung cancer patients were selected and evaluated. There were 643 (87.5%) never-smokers and 92 (12.5%) smokers. The median survival was significantly longer in the never-smoker group. Among 683 patients with non-small cell lung cancer (NSCLC), the never-smoker group showed significantly longer median survival and a higher proportion of stage I cancer. Among 481 patients who underwent epidermal growth factor receptor (EGFR) tests, 248 (51.6%) were EGFR wild-type and 233 (48.4%) were EGFR mutation-positive. Survival analysis of the NSCLC patients showed that smoking status, receiving only supportive care for treatment, EGFR mutation status, lung cancer stage, and forced vital capacity (FVC) (%) were significantly associated with mortality in the multivariate analysis. CONCLUSIONS: In Korean women with NSCLC, smoking experience and poor lung function were independent predictors of shorter overall survival. CLINICAL IMPLICATIONS: Never-smoker female lung cancer has different clinical implication compared with ever-smoker lung cancer. DISCLOSURE: No significant relationships. KEYWORDS: lung cancer, female, Korea

SARS-CoV-2 and Norovirus Co-Infection after Lung Transplantation

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is spreading as a pandemic in 2020. Few reports on infections in thoracic transplantation have been published so far. We present a case of COVID-19 in a 55-year old female lung transplant recipient infected 5 months posttransplant, who additionally was co-infected with a Norovirus. Respiratory and gastrointestinal symptoms were observed without need of therapeutic escalation except for antibiotic therapy. We observed a moderate disease evolution likely due to triple immunosuppression.

Management of bronchopulmonary carcinoid: NCDB database analysis.

e21007 Background: There is a lack of data to guide the management of resectable bronchopulmonary carcinoid tumors (BCTs). Methods: The NCDB database was retrospectively reviewed to analyze the roles of surgery, chemotherapy and radiation. Patients with a diagnosis of clinically staged T1-2/N0-1 typical carcinoid (TC) and atypical carcinoid (AC) between 2004-2012 were included. Kaplan-Meier methods and multivariable analysis were performed. Results: A total of 2148 patients (TC 1874 &amp; AC 274; T1/1648 &amp; T2/500) were identified. The median age was 59 (range 18-89). There was a female (69.7%) and right lung (56.9%) predominance. Fifty-three patients received pneumonectomy, 68 chemotherapy, and 84 radiation therapy. The impact of age, histology (TC vs. AC), medical comorbidities (Charlson/Deyo score 0 vs. ≥1) and type of surgery [sublobar resection (SR) vs. lobectomy vs. lobectomy with mediastinal lymph node dissection (L/MLND)] were subsequently examined. AC, older age, and comorbidities were associated with shorter overall survival (OS) by both univariate and multivariable analysis. Patients who underwent lobectomy had longer OS (119 months) than those with SR (109 months) or L/MLND (115 months). However, this association was not significant by multivariable analysis with age incorporated as either a categorical ( &lt; 60 vs. ≥60) or a continuous variable (Table). In the subgroup analysis of patients with T1, T2, TC and AC respectively, type of surgical resection was not significantly associated with OS by multivariable analysis. Conclusions: Patients with resectable BCTs have excellent OS. Atypical histology, older age, and comorbidities predicted inferior OS. There were insufficient data to support the use of perioperative chemotherapy or radiation therapy. Lobectomy was associated with prolonged OS by univariate analysis but this was not significant in the multivariable model, suggesting that SR is a reasonable approach for patients who cannot tolerate lobectomy. MLND did not seem to provide additional survival benefits. [Table: see text]

Polyneoplasia associated with gastrointestinal stromal tumor: literature review and case report

The purpose of the study was to demonstrate a rare clinical case of polyneoplasia associated with GIST, combining three malignant neoplasms of different nosological affiliation and different tissue origin. Scientific interest is caused by the need to study polyneoplasia associated with Gist, which can be explained by the concept of Rodriquenz M.G. et al. (2016), suggesting the special role of a solitary GisT in the potential development of polyneoplasia. Material and Methods . The search for relevant sources was carried out in the Medline, Cochrane Library, Elibrary systems, includibg publications from January 2009 to October 2019. Of the 507 studies, 21 were used to write a systematic review. Results. In the vast majority of cases, polyneoplasia is represented by two malignant neoplasms in a single patient. Primary multiple metachronous and primary multiple synchronous tumors with three or more tumors are observed very rarely. Among all multiple primary tumors, our attention was drawn to polyneoplasia containing GisT. A neoplasm associated with a GisT is localized mainly in the gastrointestinal tract, and also occurs in the organs of the urinary system, female genital system, thyroid gland, breast, lungs, and testicles. Conclusion. This clinical case is a rather rare phenomenon of polyneoplasia associated with GisT of rectum, which combines three malignant neoplasms. It should be noted that primary Gist in the rectum occurs in 4% of cases.

Meta-analysis for the effect of hormone replacement therapy on survival rate in female with lung cancer.

The effects of hormone replacement therapy on the survival rate of female lung cancer patients are still controversial. The Meta-analysis aims to systematically evaluate the effect of hormone replacement therapy on the survival rate of female lung cancer patients. Retrospective studies regarding the effect of hormone replacement therapy on female lung cancer patients' survival rate were searched from the database of Embase, Cochrane, Pubmed, CNKI, Wanfang, and Weipu. The Meta-analysis was conducted with Stata 12.0 software. I2 test was used to analyze the heterogeneity among included studies. The analysis was conducted by randomized model. Egger's test and Begg's test were used to assess the publication bias. Five retrospective studies were included, involving 2 582 female patients with lung cancer. There were 1 054 cases of female lung cancer with hormone replacement therapy and 1 528 cases of female lung cancer without hormone replacement therapy. No publication bias was observed among these studies. The sensitivity analysis result showed that the overall results were stable. Meta-analysis showed that compared with patients without hormone replacement therapy, patients with hormone replacement therapy had an increased survival time for 5 years (ES=0.346; 95% CI 0.216 to 0.476; P<0.001). Hormone replacement therapy improves 5-year survival in female lung cancer patients. Female lung cancer patients with menopausal syndrome can use hormone replacement therapy properly under their doctors' suggestion.

Health related quality of life in adult primary Ciliary dyskinesia patients in Cyprus: development and validation of the Greek version of the QOL-PCD questionnaire

BackgroundThe QOL-PCD questionnaire is a recently developed Health Related Quality of Life (HRQoL) instrument for Primary Ciliary Dyskinesia. The aim of this study was to translate the adult QOL-PCD questionnaire into Greek language and to conduct psychometric validation to assess its performance.MethodsForward translations to Greek and backward translation to English were performed, followed by cognitive interviews in 12 adult PCD patients. The finalized translated version was administered to a consecutive sample of 31 adult, Greek speaking PCD patients in Cyprus for psychometric validation, which included assessment of internal consistency, test-retest reliability, construct and convergent validity. Internal consistency was assessed by Cronbach’s alpha test in terms of the overall and sub-scales. Test-retest reliability was assessed by repeat administration of the questionnaire within 2 weeks and calculation of the intra-class correlation (ICC). Construct validity was assessed by comparing different groups of patients based on a-priori hypotheses and convergent validity was evaluated by examining associations between the QOL-PCD and SF-36 questionnaires.ResultsModerate to good internal consistency was observed (Cronbach’s α: 0.46–0.88 across sub-scales) and test-retest reliability assessment demonstrated good repeatability for most scales (ICC: 0.67–0.91 across subscales). Patients of female gender, older age and lower lung function exhibited lower QOL-PCD scores in general, while high correlations for most QOL-PCD scales with corresponding SF-36 scales were observed, in particular for physical functioning (r = 0.78, p < 0.05).ConclusionThe adult version of QoL-PCD questionnaire has been translated according to international guidelines resulting to a cross-culturally validated Greek version which exhibited moderate to good metric properties in terms of internal consistency, stability, known-group and convergent validity.

Incidence of second malignancies in individuals diagnosed with malignant peripheral nerve sheath tumors.

The incidence of malignant peripheral nerve sheath tumors (MPNSTs) is low in the general population, although individuals with Neurofibromatosis Type I (NF1) are particularly susceptible. These tumors generally have a high probability of metastasis. The rate and types of second malignancies (SMNs) after a primary diagnosis of MPNST are not well characterized. We aimed to quantify the rate of SMNs among individuals with a first primary MPNST using population-based data. We estimated age-standardized incidence rates (SIRs) for SMNs among 1,579 primary MPNST cases between ages 0-85+ using SEER 18 (2000-2015). We estimated incidence rate ratios (IRRs) and 95% confidence intervals (95% CI) for SMNs in MPNST cases compared with general population rates. We conducted sex-stratified and age-restricted analyses (< 30years at diagnosis). Seven percent (108/1579) of MPNST cases developed a SMN (SIR of 4635 cases/million). Compared to the general population, MPNST cases were more likely to develop SMNs (IRR: 29.3; 95% CI 23.8-34.8) and had a much higher rate of second MPNSTs (IRR: 15,992.9; 95% CI 9594.5-22,391.3). Aside from a second MPNST, second cancers were frequently diagnosed in the breast, lung, skin, and soft tissue in females and were myeloid and skin malignancies in males. When restricted to < 30years of age, second MPNSTs were the most common cancers diagnosed. The rate of SMNs among MPNST cases is tremendously higher than that observed among individuals with other cancers, particularly for second MPNSTs. These findings suggest rates of SMNs may also be higher in NF1 individuals.

Y‐Chromosome Gene, Uty, Protects Against Pulmonary Hypertension by Reducing Lung Pro‐Inflammatory Cytokines

RATIONALEIdiopathic pulmonary arterial hypertension (PAH) is a terminal vascular lung disease up to 4x more common in females. We published that the Y‐Chromosome (Chrm) is protective against hypoxia (Hx)‐induced pulmonary hypertension (PH) in mice and identified four Y‐Chrm genes expressed in the lung. Here, we identify Uty as the protective Y‐Chrm gene and investigate its mechanism of protection against PH to illuminate novel therapeutic targets.METHODS AND RESULTSTo test the effect of Y‐Chrm candidate genes on PH development, each of the four candidate YChrm genes were independently knocked‐down in the lungs of male mice exposed to Hxinduced PH via sequential intratracheal instillation of siRNA. Knockdown of Y‐Chrm gene Uty, but none of the other genes, resulted in more severe PH measured by increased right ventricular systolic pressure (RVSP) and decreased pulmonary arterial acceleration time (PAAT) when compared to experimental controls (n=4/group; RVSP: Uty‐KD= 48.93 mmHg, Control= 37.33 mmHg, p=0.04; PAAT: Uty‐KD= 11.88 ms, Control= 14.43 ms, p= 0.01). Pathway enrichment analysis of RNAseq data (Uty‐Knockdown vs Control) revealed an induction of proinflammatory cytokines including Cxcl9 (Log2FC: 1.3, p‐adjusted= 0.05) and Cxcl10 (Log2FC: 0.9, p‐adjusted=0.002). We found Cxcl9 and Cxcl10 were also significantly up‐regulated in human PAH lungs vs healthy (RT‐qPCR) and female PAH lungs vs male (GSE15197). Fluorescent in‐situ hybridization revealed Uty expression co‐localized with CD68+ macrophages, Cxcl9 and Cxcl10 in the lung. Upon stimulation, macrophages derived from bone marrow of male Uty‐knockout mice displayed increased expression of Cxcl9 and Cxcl10 compared to wildtype mice. Human pulmonary artery endothelial cells treated with Cxcl9 and Cxcl10 in‐vitro exhibited significantly increased cell death compared to those treated with vehicle.CONCLUSIONY‐Chrm gene, Uty, is protective against PH development and may explain Y‐Chrm protection in PH. Since Uty inhibition (both in‐vitro and in‐vivo) results in an increase in pro‐inflammatory cytokines, we hypothesize that a reduction or absence of Uty in the lungs of PAH patients or females results in an increase in lung pro‐inflammatory cytokines which contributes to vascular endothelial dysfunction and more severe PH.Support or Funding InformationAmerican Heart Association grant 17PRE33420159 (C.M.C.), Iris Cantor‐UCLA Women’s Health Center Executive Advisory Board NCATS UCLA CTSI Grant Number UL1TR001881 (C.M.C.), and NIH grants R01HL129051 (M.E.), R01HL131182 (M.E. and A.P.A.).

Lung Cancer Prognosis using Machine Learning

The paper calls attention to investigation of Lung Cancer in the light of regulated AI classifiers. The parameters incorporate age, smokes, passive smoking, alcohol and gender. Curve fitting has likewise been applied in request to break down the Lung Cancer. These days, around 33%of grown-ups are known to be smokers, and smoking rates are expanding among the female population. Tobacco use has been accounted for to be the fundamental driver of 90% of male and 79% of female lung malignancies. 90% of passing from lung malignancy are evaluated to be because of smoking.