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1.
J Clin Oncol ; 41(12): 2125-2133, 2023 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-37068377

RESUMO

PURPOSE: Patients with malignant pleural mesothelioma, a rapidly progressing malignancy with a median survival time of 6 to 9 months, have previously responded poorly to chemotherapy. We conducted a phase III trial to determine whether treatment with pemetrexed and cisplatin results in survival time superior to that achieved with cisplatin alone. PATIENTS AND METHODS: Chemotherapy-naive patients who were not eligible for curative surgery were randomly assigned to receive pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 on day 1, or cisplatin 75 mg/m2 on day 1. Both regimens were given intravenously every 21 days. RESULTS: A total of 456 patients were assigned: 226 received pemetrexed and cisplatin, 222 received cisplatin alone, and eight never received therapy. Median survival time in the pemetrexed/cisplatin arm was 12.1 months versus 9.3 months in the control arm (P = .020, two-sided log-rank test). The hazard ratio for death of patients in the pemetrexed/cisplatin arm versus those in the control arm was 0.77. Median time to progression was significantly longer in the pemetrexed/cisplatin arm: 5.7 months versus 3.9 months (P = .001). Response rates were 41.3% in the pemetrexed/cisplatin arm versus 16.7% in the control arm (P < .0001). After 117 patients had enrolled, folic acid and vitamin B12 were added to reduce toxicity, resulting in a significant reduction in toxicities in the pemetrexed/cisplatin arm. CONCLUSION: Treatment with pemetrexed plus cisplatin and vitamin supplementation resulted in superior survival time, time to progression, and response rates compared with treatment with cisplatin alone in patients with malignant pleural mesothelioma. Addition of folic acid and vitamin B12 significantly reduced toxicity without adversely affecting survival time.

2.
Biochim Biophys Acta Mol Basis Dis ; 1868(10): 166473, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35753541

RESUMO

Malignant pleural mesothelioma (MPM), an aggressive cancer associated with exposure to fibrous minerals, can only be diagnosed in the advanced stage because its early symptoms are also connected with other respiratory diseases. Hence, understanding the molecular mechanism and the discrimination of MPM from other lung diseases at an early stage is important to apply effective treatment strategies and for the increase in survival rate. This study aims to develop a new approach for characterization and diagnosis of MPM among lung diseases from serum by Fourier transform infrared spectroscopy (FTIR) coupled with multivariate analysis. The detailed spectral characterization studies indicated the changes in lipid biosynthesis and nucleic acids levels in the malignant serum samples. Furthermore, the results showed that healthy, benign exudative effusion, lung cancer, and MPM groups were successfully separated from each other by applying principal component analysis (PCA), support vector machine (SVM), and especially linear discriminant analysis (LDA) to infrared spectra.


Assuntos
Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurais , Biomarcadores Tumorais , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Mesotelioma/diagnóstico , Mesotelioma/patologia , Neoplasias Pleurais/diagnóstico , Neoplasias Pleurais/patologia , Soro
3.
J Thorac Oncol ; 17(7): 873-889, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35462085

RESUMO

The most common malignancies that develop in carriers of BAP1 germline mutations include diffuse malignant mesothelioma, uveal and cutaneous melanoma, renal cell carcinoma, and less frequently, breast cancer, several types of skin carcinomas, and other tumor types. Mesotheliomas in these patients are significantly less aggressive, and patients require a multidisciplinary approach that involves genetic counseling, medical genetics, pathology, surgical, medical, and radiation oncology expertise. Some BAP1 carriers have asymptomatic mesothelioma that can be followed by close clinical observation without apparent adverse outcomes: they may survive many years without therapy. Others may grow aggressively but very often respond to therapy. Detecting BAP1 germline mutations has, therefore, substantial medical, social, and economic impact. Close monitoring of these patients and their relatives is expected to result in prolonged life expectancy, improved quality of life, and being cost-effective. The co-authors of this paper are those who have published the vast majority of cases of mesothelioma occurring in patients carrying inactivating germline BAP1 mutations and who have studied the families affected by the BAP1 cancer syndrome for many years. This paper reports our experience. It is intended to be a source of information for all physicians who care for patients carrying germline BAP1 mutations. We discuss the clinical presentation, diagnostic and treatment challenges, and our recommendations of how to best care for these patients and their family members, including the potential economic and psychosocial impact.


Assuntos
Neoplasias Pulmonares , Melanoma , Mesotelioma Maligno , Mesotelioma , Neoplasias Cutâneas , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirurgia , Melanoma/genética , Mesotelioma/diagnóstico , Mesotelioma/genética , Mesotelioma/cirurgia , Qualidade de Vida , Neoplasias Cutâneas/genética , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Ubiquitina Tiolesterase/genética , Ubiquitina Tiolesterase/metabolismo
5.
Front Genet ; 13: 812715, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35222535

RESUMO

Objective: To investigate the effects of genetic polymorphisms of human nicotinic acetylcholine receptor subunits α3, α4 and α5, which are encoded by CHRNA3, CHRNA4 CHRNA5 genes, respectively, on nicotine addiction and outcomes of pharmacological treatments for smoking cessation. Methods: A total of 143 smokers and 130 non-smokers were included. Genotyping for CHRNA3 rs578776, CHRNA4 rs1044396-rs1044397, CNRNA5 rs16969968 polymorphisms was performed by PCR, flowed by RFLP. Clinical outcomes and success rates of pharmacological treatments for smoking cessation with nicotine replacement therapy (NRT), bupropion or varenicline were determined at the 12th week of the treatment. Results: Overall, 52 out of 143 (36.4%) smokers who received pharmacotherapy were able to quit smoking. Success rates for smoking cessation were similar for female (30.3%) and male (41.6%) subjects (p = 0.16). The success rate for smoking cessation treatment with varenicline (58.5%) was significantly higher as compared to other treatments with NRT (20.0%), bupropion (32.3%) or bupropion + NRT (40.0%) (chi-square test, p = 0.001). Smoker vs. non-smoker status and the clinical outcomes of drugs used for smoking cessation were found similar in subjects carrying wild-type and variant alleles of human nicotinic acetylcholine receptor α subunits. Conclusion: In this study, smoking cessation treatment with varenicline was significantly more effective than treatments with nicotine replacement or bupropion in a cohort of Turkish subjects. Smoker/non-smoker status and the clinical outcomes of treatment with pharmacological agents were similar in subjects with wild-type or variant alleles for human nicotinic acetylcholine receptor subunits α3 (CHRNA3), α4 (CHRNA4) and α5 (CHRNA5).

6.
Anatol J Cardiol ; 25(8): 544-554, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34369882

RESUMO

OBJECTIVE: In this study, we aimed to evaluate the accuracy of the original and simplified pulmonary embolism (PE) severity index (PESI) to predict all-cause mortality after 30 days of acute PE diagnosis up to five years within consecutive sub-periods. METHODS: Adult patients diagnosed with acute PE between January 1, 2003, and June 30, 2013, were retrospectively included. Data on baseline characteristics and mortality during a five-year follow-up were collected. RESULTS: The study included 414 patients (Male/Female=192/222). The median age at diagnosis was 61.5 (minimum-maximum, 18-93) years. Mortality rates were 13.3% at 30 days, 21.8% at 90 days, 32.6% at one year, and 51.0% at five years. Both stratification into risk classes according to the original PESI and low vs. high-risk classification of original and simplified PESI were significantly correlated with the 30-day, 31-90-day, 91-day-one-year, and one-five-year mortality. Significant PESI predictors for mortality were history of cancer [hazard ratio (HR): 3.31, 95% confidence interval (CI): 1.64-6.68; p=0.001] and heart failure (HR: 2.35, 95% CI: 1.04-5.32, p=0.041) at 31-90-day, history of cancer (HR: 5.45, 95% CI: 2.86-10.40, p<0.001) at 91-day-one-year, advancing age (HR: 1.04, 95% CI: 1.02-1.06, p<0.001) and history of cancer (HR: 5.53, 95% CI: 3.41-8.98, p<0.001) at one-five-year after acute PE diagnosis. CONCLUSION: All-cause long-term mortality in high-risk patients with acute PE according to original or simplified PESI significantly increased up to five years of follow-up. This survival disadvantage was mainly related to cancer and comorbidities rather than acute clinical manifestations. Future prospective studies are needed to demonstrate the effect of various comorbidities on long-term mortality in these patients.


Assuntos
Embolia Pulmonar , Doença Aguda , Adulto , Feminino , Humanos , Masculino , Prognóstico , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença
7.
Front Genet ; 11: 571997, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33329709

RESUMO

OBJECTIVES: To determine the effects of genetic polymorphisms of ABCB1 (MDR1), CYP2A6, CYP2B6 on smoking status, and clinical outcomes of smoking cessation therapies in a Turkish population. METHODS: 130 smokers and 130 non-smokers were recruited. Individuals who never smoked were described as non-smokers. 130 smokers were treated with nicotine replacement therapy (NRT) (n = 40), bupropion (n = 47), bupropion + NRT (n = 15), and varenicline (n = 28). Smokers were checked by phone after 12 weeks of treatment whether they were able to quit smoking or not. Genotyping and phenotyping were performed. RESULTS: Cessation rates were as follows; 20.0% for NRT, 29.8% for bupropion, 40.0% for bupropion + NRT, 57.1% for varenicline (p = 0.013). The frequency of ABCB1 1236TT-2677TT-3435TT haplotype was significantly higher in non-smokers as compared to smokers (21.5% vs. 10.8, respectively; p = 0.018). Neither smoking status nor smoking cessation rates were associated with genetic variants of CYP2A6 (p = 0.652, p = 0.328, respectively), or variants of CYP2B6 (p = 0.514, p = 0.779, respectively). CONCLUSION: Genetic variants of the drug transporter ABCB1 and the 1236TT-2677TT-3435TT haplotype was significantly associated with non-smoking status. Neither ABCB1 nor CYP2A6, CYP2B6 genetic variants were associated with smoking cessation rates at the 12th week of drug treatment.

8.
Turk J Med Sci ; 50(4): 945-952, 2020 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-32394679

RESUMO

Background/Aim: The patients with cystic fibrosis (CF) are living longer compared to the past, but respiratory failure is still the most common cause of mortality. The aim of this study is to investigate factors associated with severe lung disease in a cohort of adult patients with CF. Materials and methods: Demographic data, clinical and laboratory findings of the patients aged 18 years and more were collected and the patients were grouped according to forced expiratory volume in 1 s (FEV1) as severe group: <40% and nonsevere ≥40%. Associations were investigated between groups and clinical outcomes. Results: A total of 76 patients were enrolled in the study. The mean age was 24.5 ± 5.25 years and 36 (47.4%) patients were female. In the severe group; the mean age was higher (27.1 ± 6.0 vs 23.6 ± 4.7, P = 0.013), the median Chrispin-Norman score of severe lung disease group was higher (14 (6­22) vs 5.5 (0­20), P < 0.001), hospitalization at least once in a year for intravenous antibiotic was more common (12/18 (66%) vs 19/58 (32%), P = 0.014). There was a positive correlation between body mass index (BMI) and lung function, indicating that lower nutritional status was related to lower FEV1, r2 = 0.21, P < 0.001. The median FEV1% was lower in patients with CF-related diabetes (38 (14­95) vs 66 (13­121), P = 0.042). Dornase alpha use and physiotherapy rate were higher in severe lung disease group (P = 0.008 and P < 0.001, respectively). Conclusion: Lower BMI, older age, presence of CF-related diabetes, higher radiologic scores, use of dornase alpha and physiotherapy and higher hospitalization rate for intravenous antibiotic therapy are significantly associated with severe lung disease.


Assuntos
Fibrose Cística/fisiopatologia , Adolescente , Adulto , Fatores Etários , Antibacterianos/administração & dosagem , Índice de Massa Corporal , Fibrose Cística/mortalidade , Desoxirribonuclease I/administração & dosagem , Complicações do Diabetes/fisiopatologia , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Modalidades de Fisioterapia , Proteínas Recombinantes/administração & dosagem , Testes de Função Respiratória , Fatores de Risco , Índice de Gravidade de Doença
9.
Cytopathology ; 30(6): 592-600, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31165505

RESUMO

OBJECTIVE: The aim of this study was to investigate the utility of BRCA1-associated protein-1 (BAP1), glucose transporter (GLUT)-1 and desmin expression by immunohistochemistry in the discrimination between reactive and malignant mesothelial proliferations. METHODS: A total of 88 biopsies and 30 effusions from mesothelioma cases were studied. Control groups were composed of 35 tissues and 30 cell blocks. The 88 mesothelioma cases were from 43 males and 45 females (mean age 56 years). Tumours were mostly localised to pleura (66/88, 75%) and of epithelioid histology (75/88, 85%). Cytology samples were from 17 males and 13 females (mean age 58 years), and 16 pleural and 14 peritoneal effusions. Twenty cytology cases had corresponding tissue biopsies. RESULTS: BAP1 loss was detected in 61/88 (69%) tissues and in 20/30 (67%) cytology samples from mesothelioma with a specificity of 100% for both sampling methods. BAP1 loss was observed more frequently in pleural and biphasic tumours. GLUT-1 immunoreactivity was identified in 54/81 (67%) and 23/25 (92%) malignant tissues and effusions, and in 6/33 (18%) and 6/30 (20%) benign tissues and effusions, respectively. Desmin loss was observed in 74/80 (92%) malignant biopsy samples, 16/21 (76%) malignant effusions and 10/34 (29%) of benign tissues, but in none of the reactive effusions. Concordance rate of results between biopsy and cytology was as follows: BAP1 20/20 (100%); GLUT-1 13/18 (72%); and desmin 10/14 (71%). CONCLUSIONS: BAP1, GLUT-1 and desmin are useful markers in the discrimination between reactive and malignant mesothelial proliferations. BAP1 loss seems to be diagnostic for mesotheliomas both in biopsy and cytology samples.


Assuntos
Desmina/genética , Transportador de Glucose Tipo 1/genética , Neoplasias Pulmonares/diagnóstico , Mesotelioma/diagnóstico , Neoplasias Mesoteliais/diagnóstico , Proteínas Supressoras de Tumor/genética , Ubiquitina Tiolesterase/genética , Biomarcadores Tumorais/genética , Proliferação de Células/genética , Citodiagnóstico , Diagnóstico Diferencial , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Imuno-Histoquímica/métodos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Mesotelioma/genética , Mesotelioma/patologia , Mesotelioma Maligno , Pessoa de Meia-Idade , Neoplasias Mesoteliais/genética , Neoplasias Mesoteliais/patologia , Derrame Pleural Maligno
10.
J Biomed Opt ; 23(10): 1-14, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30317725

RESUMO

This study was conducted to differentiate malignant pleural mesothelioma (MPM) from lung cancer (LC) and benign pleural effusion (BPE) from pleural fluids using the diagnostic power of Fourier transform-infrared spectroscopy with attenuated total reflectance mode coupled with chemometrics. Infrared spectra of MPM (n = 24), LC (n = 20), and BPE (n = 25) were collected, and hierarchical cluster analysis (HCA) and principal component analysis (PCA) were applied to their spectra. HCA results indicated that MPM was differentiated from LC with 100% sensitivity and 100% specificity and from BPE, with 100% sensitivity and 88% specificity, which were also confirmed by PCA score plots. PCA loading plots indicated that these separations originated mainly from lipids, proteins, and nucleic acids-related spectral bands. There was significantly higher lipid, protein, nucleic acid, and glucose contents in the MPM and LC. However, the significant changes in triglyceride and cholesterol ester content, protein and nucleic acid structure, a lower membrane fluidity, and higher membrane order were only observed in the MPM. To check the classification success of some test samples/each group, soft independent modeling of class analogies was performed and 96.2% overall classification success was obtained. This approach can provide a rapid and inexpensive methodology for the efficient differentiation of MPM from other pleural effusions.


Assuntos
Neoplasias Pulmonares , Mesotelioma , Derrame Pleural , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Idoso , Análise por Conglomerados , Feminino , Humanos , Neoplasias Pulmonares/química , Neoplasias Pulmonares/diagnóstico , Masculino , Mesotelioma/química , Mesotelioma/diagnóstico , Mesotelioma Maligno , Pessoa de Meia-Idade , Derrame Pleural/classificação , Derrame Pleural/diagnóstico , Derrame Pleural/metabolismo , Análise de Componente Principal/métodos , Sensibilidade e Especificidade
11.
Clin Biochem ; 58: 15-19, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29729229

RESUMO

BACKGROUND AND AIM: Early diagnosis and histological subtyping are important issues in the management of patients with lung cancer (LC). The aim of this study is to investigate the diagnostic value of a panel of serum tumor markers in newly diagnosed patients with LC. METHODS: Venous blood samples were collected from 99 patients with LC (42 adenocarcinoma, 35 squamous, and 22 small cell carcinoma) and 30 patients with benign lung disease. Progastrin releasing peptide (ProGRP), squamous cell carcinoma antigen (SCCAg), cytokeratin 19-fragments (CYFRA 21.1), human epididymis protein 4 (HE4), Chromogranin A (CgA) and neuron specific enolase (NSE) levels were measured. The diagnostic value of the biomarkers was assessed with ROC curve analyses; the area under the curve (AUC) was calculated. RESULTS: Serum CYFRA 21.1, ProGRP, SCCAg, NSE levels were significantly higher in LC patients. While ProGRP levels were higher (p = 0.009) in SCLC; CYFRA 21.1 and SCCAg levels were higher in NSCLC (p = 0.019 and p = 0.001, respectively). The sensitivity and specificity of tumor markers were 72%, 83% for CYFRA 21.1; 70%, 57% for HE4; 18%, 93% for ProGRP; 43%, 77% for SCCAg; 54%, 53% for CgA; 73%, 50% for NSE. CYFRA 21.1 (p < 0.001, r = 0.394), HE4 (p = 0.014, r = 0.279) and CgA (p = 0.023, r = 0.259) levels were positively correlated with tumor stage in NSCLC. CgA levels were significantly higher in extensive stage SCLC (p = 0.004). CYFRA 21.1 had the highest diagnostic value for LC (AUC = 0.865). When it is combined with HE4, diagnostic value increased (AUC = 0.899). ProGRP had the highest diagnostic value (AUC = 0.875, p < 0.001) for discriminating SCLC from NSCLC. CONCLUSION: A panel of three tumor markers CYFRA 21.1, HE4 and ProGRP may play a role for discriminating LC from benign lung disease and subtyping as SCLC.


Assuntos
Antígenos de Neoplasias/sangue , Biomarcadores Tumorais/sangue , Queratina-19/sangue , Neoplasias Pulmonares , Proteínas de Neoplasias/sangue , Fragmentos de Peptídeos/sangue , Proteínas/metabolismo , Carcinoma de Pequenas Células do Pulmão , Adulto , Idoso , Feminino , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/classificação , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Proteínas Recombinantes/sangue , Carcinoma de Pequenas Células do Pulmão/sangue , Carcinoma de Pequenas Células do Pulmão/classificação , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Carcinoma de Pequenas Células do Pulmão/patologia , Proteína 2 do Domínio Central WAP de Quatro Dissulfetos
12.
Eur Geriatr Med ; 9(2): 263-267, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34654262

RESUMO

BACKGROUND: In older patients, diagnosis and initial treatment should be considered as soon as possible because of high disease burden and complications. Conventional transbronchial needle aspiration (C-TBNA) is an important and safe method for the diagnosis of mediastinal lesions and staging lung cancer in the general population. We aimed to evaluate the diagnostic utility and complications of C-TBNA procedure in older patients aged ≥ 65 years. METHOD: We retrospectively evaluated C-TBNA results consecutively. Demographic data, clinical, radiological and flexible bronchoscopy (FB) findings, complications during C-TBNA and incidence of diagnostic C-TBNA with the presence of abundant lymphoid cells of polymorphous appearance both in patients aged ≥ 65 years and in younger patients were determined. RESULTS: C-TBNA was performed to a total of 317 patients, including 109 older and 208 younger patients attended to our clinic between 2012 and 2016. The mean ages of older and younger patients were 70.3 ± 4.6 and 52.5 ± 10 years, respectively (p < 0.001). Overall, 75.2% of older and 80.3% of younger patients had diagnostic C-TBNA. The diagnostic utility of C-TBNA did not differ significantly between older and younger patients (p = 0.297). During C-TBNA, one older patient had a complication of bronchospasm, and four younger patients had complications such as bleeding (n = 1) and bronchospasm (n = 3). There was no statistically significant difference between older and younger patients in terms of complications during C-TBNA procedure (p = 0.49). CONCLUSION: C-TBNA is a safe procedure with similar diagnostic yield in older patients.

13.
Sarcoidosis Vasc Diffuse Lung Dis ; 35(2): 143-149, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-32476894

RESUMO

Background and objectives: Sarcoidosis is a systemic inflammatory disease of unknown etiology that involves any part of the body, mainly the lungs and thoracic lymph nodes. The clinical presentation is heterogeneous based on the degree and extent of organ involvement. The existence of variable clinical presentations and treatment responses suggest an important role of genetic predisposition. In genetic studies, sarcoidosis was found to be associated with several genes, but the strongest link was with HLA region. The aim of this study was to investigate the association of HLA class II alleles with the extent and course of disease in Turkish patients with sarcoidosis. Methods: The study included 103 patients with sarcoidosis and 100 unrelated healthy controls. HLA-DRB1 and HLA-DQB1 typing was performed by using Polymerase Chain Reaction-Sequence Specific Priming (PCR-SSP) method at low resolution level. Results: HLA-DRB1* and -DQB1* analysis revealed that while the frequency of HLA-DRB1*01 was significantly higher in the control group, HLA-DRB1*13 and -DQB1*06 alleles were more frequent in the sarcoidosis patients. When the patients were grouped based on clinical outcome as remitters and non-remitters, HLA-DRB1*10 allele was only detected in the remitters, whereas the frequency of HLA-DQB1*06 allele was significantly higher in non-remitters. Conclusions: This study supported the association of HLA alleles with sarcoidosis. In a considerably high number of patients with Turkish origin, the frequency of HLA-DRB1*13, -DRB1*10 and HLA-DQB1*06 alleles was significantly associated with increased risk and clinical outcome. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 143-149).

14.
Ann Transl Med ; 5(11): 239, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28706907

RESUMO

The epidemic of mesothelioma in Cappadocia, Turkey, is unprecedented in medical history. In three Cappadocian villages, Karain, Tuzkoy and "old" Sarihidir, about 50% of all deaths (including neonatal deaths and traffic fatalities) have been caused by mesothelioma. No other epidemic in medical history has caused such a high incidence of death. This is even more unusual when considering that (I) epidemics are caused by infectious agents, not cancer, and (II) mesothelioma is a rare cancer. World-wide mesothelioma incidence varies between 1/106 in areas with no asbestos industry to about 10-30/106 in areas with asbestos industry. This article reviews how the mesothelioma epidemic was discovered in Cappadocia by Dr. Baris (my mentor), how we initially linked the epidemic to erionite exposure, and later (with Dr. Carbone) to the interaction between genetic predisposition and environmental exposure. Our team's work had an important positive impact on the lives of those living in Cappadocia and also in many genetically predisposed families living around the world. I will discuss how the work that started in three remote Cappadocian villages led to the award of a NCI P01 grant to support our studies. Our studies proved that genetics modulates mineral fiber carcinogenesis and led to the discovery that carriers of germline BAP1 mutations have a very high risk of developing mesothelioma and other malignancies. A new, very active field of research developed following our discoveries to elucidate the mechanism by which BAP1 modulates mineral fiber carcinogenesis as well as to identify additional genes that when mutated increase the risk of mesothelioma and other environmentally related cancers. I am the only surviving member of this research team who saw all the phases of this research and I believe it is important to provide an accurate report, which hopefully will inspire others.

16.
Tuberk Toraks ; 64(2): 137-43, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27481080

RESUMO

INTRODUCTION: Conventional transbronchial needle aspiration biopsy (C-TBNA) is a technique in evaluating mediastinal/hilar lymph nodes (LN). We aimed to investigate diagnostic yield (DY) and safety of C-TBNAs performed in a single university clinic. PATIENTS AND METHODS: We retrospectively reviewed 363 consecutive C-TBNA procedures in 219 patients. The DY and its relationship with location, shortest diameter, SUVmax of LN, and number of sampled stations were evaluated. RESULT: Procedures were diagnostic in 257 (71%) LNs. The most common diagnoses were malignancy (n= 109.30%) and granulomatous inflammation (n= 68, 18.7%).The ratio of patients with at least one diagnostic cytology result was 77% (n= 168). DY was significantly increased with the increased number of sampled LNs (p= 0.033) and larger LN diameter (p< 0.001). Sensitivity, specificity, positive, and negative predictive values were 83.3%, 43.2%, 79.6%, and 49.3% respectively for cut-off LN diameter of 11.5 mm. There was nearly a significant relationship between DY and SUVmax (p= 0.05, cut-off= 4.8). The highest DY was in subcarinal LN (77.4%). No major complications were recorded. CONCLUSIONS: The DY of C-TBNA was 71%. The ratio of the patients with at least one diagnostic cytology result was 77%. The most common diagnoses were malignancy and granulomatous inflammation. The DY of C-TBNA was increased with the increased number of sampled LNs, larger LN diameter, and increased SUVmax. C-TBNA is a safe procedure.


Assuntos
Biópsia por Agulha Fina/métodos , Broncoscopia/métodos , Neoplasias Pulmonares/patologia , Linfonodos/patologia , Adulto , Feminino , Humanos , Pulmão/patologia , Masculino , Doenças do Mediastino/patologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade
17.
Acta Clin Belg ; 71(6): 441-443, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27112770

RESUMO

OBJECTIVE AND IMPORTANCE: Sarcoidosis is a multisystem inflammatory disorder of unknown etiology. It is characterized by the presence of noncaseating granulomas and an inflammatory process in which T lymphocytes, especially type-1 helper T (Th1) cells, macrophages and different cytokines are involved. Different studies have shown the importance of genetic background in addition to environmental exposure in explaining different clinical phenotypes and disease outcome. In addition, potential auto antigens that might lead to the disease have been identified. CLINICAL PRESENTATION: Here, we present a 53-year-old female patient presenting with subcutaneous nodules and mediastinal hilar lymphadenopathies refractory for corticosteroid treatment. Computed tomography of the thorax revealed a soft-tissue lesion in the thymus location. INTERVENTION: The lesions due to sarcoidosis resolved after thymectomy. CONCLUSION: The remission of skin and pulmonary sarcoidosis only after thymectomy does potentially indicate the critical role that the thymus might play in the pathogenesis of this disease in a certain group of patients.


Assuntos
Pneumopatias/complicações , Pulmão/diagnóstico por imagem , Recuperação de Função Fisiológica , Sarcoidose/complicações , Dermatopatias/complicações , Pele/diagnóstico por imagem , Timectomia/métodos , Hiperplasia do Timo/cirurgia , Feminino , Humanos , Pulmão/fisiopatologia , Pneumopatias/diagnóstico , Pessoa de Meia-Idade , Sarcoidose/diagnóstico , Dermatopatias/diagnóstico , Hiperplasia do Timo/complicações , Tomografia Computadorizada por Raios X
19.
Int J Occup Med Environ Health ; 29(1): 55-68, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26489943

RESUMO

OBJECTIVES: Prior studies have been performed on cotton textile plants throughout the world. This study was planned to identify the rate of byssinosis and chronic obstructive pulmonary disease (COPD) in hemp and jute workers and those who worked with both of them. MATERIAL AND METHODS: The study was realized in a factory which consecutively processed hemp and jute. The study enrollment included 266 people, 164 of whom were active workers and 102 were retired. A questionnaire, plain chest X-rays, physical examination and pulmonary function tests were performed. Dust levels were measured in various sections of the factory during 8 h work shifts. Endotoxin levels of various quality hemp fibers and dusts were measured. RESULTS: The rate of byssinosis (28.2%) was higher among the workers that who exposed to both jute and hemp dust. The frequency of chronic bronchitis in retired workers who previously smoked was higher (20%) as compared to currently smoking workers (17%). High dust levels were measured in some parts of the factory (mean (M) = 2.69 mg/m3). Working in dense dust areas, active smoking, being older than 40 years of age, being an ex-smoker, and working in the factory for a period exceeding 15 years were significantly associated with bronchitis and emphysema development. High endotoxin levels were determined for fine hemp dust (605 EU/mg), coarse hemp dust (336 EU/mg) and poor quality hemp fibers (114 EU/mg), whereas in fresh hemp stalks the level of endotoxin was determined to be lower (0.27 EU/mg). CONCLUSIONS: Because of high exposures to jute and hemp dusts that are associated with high byssinosis rates, personal protection and environmental hygiene is crucial to prevention of byssinosis.


Assuntos
Bissinose/epidemiologia , Cannabis/efeitos adversos , Corchorus/efeitos adversos , Doenças Profissionais/epidemiologia , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Indústria Têxtil/estatística & dados numéricos , Adulto , Bronquite/epidemiologia , Bronquite/etiologia , Bissinose/etiologia , Poeira , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/etiologia , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/estatística & dados numéricos , Doença Pulmonar Obstrutiva Crônica/etiologia
20.
Asian Cardiovasc Thorac Ann ; 24(1): 98-100, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26207004

RESUMO

Rhabdomyosarcoma is an aggressive malignant tumor of childhood, originating from immature cells that are destinated to form striated skeletal muscle. It usually arises in the head and neck or the extremities. Primary diffuse pleural rhabdomyosarcoma is exceptionally rare. Herein we report a case of primary diffuse pleural rhabdomyosarcoma in a 48-year-old man. The diagnosis was confirmed by percutaneous pleural biopsy. Chemotherapy (cisplatin, ifosfamide, adriamycin, vincristine) was initiated due to the large volume of the tumor. After 3 months, computed tomography of the thorax showed stable radiological findings.


Assuntos
Neoplasias Pleurais/patologia , Rabdomiossarcoma/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/administração & dosagem , Doxorrubicina/administração & dosagem , Evolução Fatal , Humanos , Ifosfamida/administração & dosagem , Masculino , Pessoa de Meia-Idade , Derrame Pleural/etiologia , Neoplasias Pleurais/complicações , Neoplasias Pleurais/tratamento farmacológico , Rabdomiossarcoma/complicações , Rabdomiossarcoma/tratamento farmacológico , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Carga Tumoral , Vincristina/administração & dosagem
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