Mediastinal abscess after endobronchial ultrasound with transbronchial needle aspiration: a case report

Endobronchial ultrasound (EBUS) with transbronchial needle aspiration is now becoming widely accepted as a preferred staging technique. It has been perceived as a non-invasive and well tolerated procedure with minimal complications. We report the development and treatment of a severe complication that developed 2 weeks after the initial procedure in the form of a complex mediastinal abscess. EBUS although useful in its non-invasive application for diagnosing mediastinal or hilar disease, must be regarded with caution since the potential exists to develop severe complications

CYP1A1, mEH, and GSTM1 Polymophisms and Risk of Oral and Pharyngeal Cancer: A Spanish Case-Control Study

Background. Genetic polymorphisms of drug metabolizing enzymes involved in the detoxification pathways of carcinogenic substances may influence cancer risk. Methods. Case-control study that investigates the relationship between CYP1A1 Ile/Val, exon 4 mEH, and GSTM1 null genetic polymorphism and the risk of oral and pharyngeal cancer examining the interaction between these genes, tobacco, and alcohol. 92 incident cases and 130 consecutive hospital-based controls have been included. Results. No significant associations were found for any of the genotypes assessed. The estimated risk was slightly elevated in subjects with the wild type of the mEH gene and the null GSTM1 genotype. For exon 4 mEH heterozygous polymorphism, the risk was slightly lower for heavy smokers than for light smokers. The inverse association was observed for the GSTM1 null genotype. Conclusions. The results suggest that exon 4 mEH and GSTM1 null polymorphisms might influence oral and pharyngeal cancer

Smoking-attributable mortality in Portugal and its regions in 2019

Funding Information: This research was supported by the Instituto de Salud Carlos III (ISCIII) through the project “ PI19/00288 ″ and co-funded by the European Union . Publisher Copyright: © 2023 Sociedade Portuguesa de PneumologiaIntroduction and objectives: Timely regional-specific estimates of smoking-attributable mortality (SAM) are crucial for healthcare planning and tobacco control advocacy. Currently, this information is lacking in Portugal. The aim of this study was to estimate SAM by region in 2019 among the Portuguese population aged ≥35 years. Methods: SAM was estimated using an independent-prevalence method. Observed mortality was obtained from Portugal Statistics; lung cancer mortality rates in smokers and never-smokers from the Cancer Prevention Study I-II and updated relative risks from five contemporary US cohort studies. SAM was estimated for each NUTS-II region by sex, age, and cause of death. Crude SAM rates, sex and age-specific rates, and age-adjusted rates were calculated using the direct method. Results: In 2019, tobacco consumption caused 13,847 deaths, representing 12.3% of total mortality among the Portuguese population aged ≥35 years. Of the total SAM, 71.2% occurred in men and 22.2% in those under 65 years; 42.5% was due to cancer, 35.4% to cardiovascular and metabolic diseases, and 22.2% to respiratory diseases. SAM greatly varied among regions from 2.1% in Madeira to 36.2% in the North region. In men, cancer was the leading cause of death in all regions, while in women it was cardiovascular and metabolic diseases. Conclusion: In Portugal, tobacco-mortality burden is high and varies significantly by region, sex and age. Therefore, estimates disaggregated by sociodemographic data and region may better support decision-makers while tailoring and implementing tobacco control policies addressing health population needs. The apparent lower tobacco burden among women and in some Portuguese regions may dramatically rise in the near future. This and the high SAM in Portugal, particularly in some regions, highlights the need to accelerate tobacco control both at national and regional levels.publishersversioninpres

How should performance in EBUS mediastinal staging in lung cancer be measured?

There has been a paradigm shift in mediastinal staging algorithms in non-small cell lung cancer over the last decade in the United Kingdom (UK). This has seen endoscopic nodal staging (predominantly endobronchial ultrasound, EBUS) almost replace surgical staging (predominantly mediastinoscopy) as the pathological staging procedure of first choic

Functional compensation of glutathione S-transferase M1 (GSTM1) null by another GST superfamily member,GSTM2

The gene for glutathione-S-transferase (GST) M1 (GSTM1), a member of the GST-superfamily, is widely studied in cancer risk with regard to the homozygous deletion of the gene (GSTM1 null), leading to a lack of corresponding enzymatic activity. Many of these studies have reported inconsistent findings regarding its association with cancer risk. Therefore, we employed in silico, in vitro, and in vivo approaches to investigate whether the absence of a functional GSTM1 enzyme in a null variant can be compensated for by other family members. Through the in silico approach, we identified maximum structural homology between GSTM1 and GSTM2. Total plasma GST enzymatic activity was similar in recruited individuals, irrespective of their GSTM1 genotype (positive/null). Furthermore, expression profiling using real-time PCR, western blotting, and GSTM2 overexpression following transient knockdown of GSTM1 in HeLa cells confirmed that the absence of GSTM1 activity can be compensated for by the overexpression of GSTM

Diagnostic value of endobronchial ultrasound-guided transbronchial needle aspiration in various lung diseases

Objective: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a new method for the diagnosis and staging of lung disease, and its use is increasing worldwide. It has been used as a means of diagnosing lung cancer in its initial stages, and there are data supporting its use for the diagnosis of benign lung disease. The aim of this study was to share our experience with EBUS-TBNA and discuss its diagnostic value. Methods: We retrospectively analyzed the results related to 159 patients who underwent EBUS-TBNA at our pulmonary medicine clinic between 2010 and 2013. We recorded the location and size of lymph nodes seen during EBUS. Lymph nodes that appeared to be affected on EBUS were sampled at least twice. We recorded the diagnostic results of EBUS-TBNA and (for cases in which EBUS-TBNA yielded an inconclusive diagnosis) the final diagnoses after further investigation and follow-up. Results: We evaluated 159 patients, of whom 89 (56%) were male and 70 (44%) were female. The mean age was 54.6 ± 14.2 years among the male patients and 51.9 ± 11.3 years among the female patients. Of the 159 patients evaluated, 115 (84%) were correctly diagnosed by EBUS. The diagnostic accuracy of EBUS-TBNA was 83% for benign granulomatous diseases and 77% for malignant diseases. Conclusions: The diagnostic value of EBUS-TBNA is also high for benign pathologies, such as sarcoidosis and tuberculosis. In patients with mediastinal disorders, the use of EBUS-TBNA should be encouraged, primarily because it markedly reduces the need for mediastinoscopy

Validity and reliability of transbronchial needle aspiration for diagnosing mediastinal adenopathies

<p>Abstract</p> <p>Background</p> <p>The aim is to assess the validity and reliability of transbronchial needle aspiration (TBNA) of mediastinal and hilar adenopathies and to evaluate factors predictive of TBNA outcome.</p> <p>Methods</p> <p>We performed an analysis of prospectively collected data of patients (n = 580) who underwent TBNA (n = 685) from January 1998 to December 2007 in our center. Validity and reliability were evaluated for the overall sample and according to specific pathology. Factors predicting the successful acquisition of diagnostic samples were analyzed by multivariate analysis.</p> <p>Results</p> <p>Overall sensitivity, specificity, accuracy, and positive and negative predictive (NPV) values for TBNA were 68%, 100%, 68.8%, 100%, and 10%, respectively. The most sensitive and accurate TBNAs were obtained for patients with small cell lung carcinoma and the worst results were for patients with lymphomas. NPV were similar for all pathologies. The most predictive factors of outcome were adenopathy size and the presence of indirect signs at the puncture site.</p> <p>Conclusion</p> <p>The sensitivity and accuracy of TBNA are high in small cell lung cancer, followed by other types of carcinoma, sarcoidosis, and tuberculosis, and low for lymphoproliferative diseases. The NPV of TBNA for all individual pathologies is low. The size of the adenopathy and the presence of indirect signs at the puncture site predict the achievement of diagnostic samples.</p

A review of the epidemiology of oral and pharyngeal carcinoma: update

Oral and pharyngeal cancers are the sixth most common cancers internationally. In the United States, there are about 30,000 new cases of oral and pharyngeal cancers diagnosed each year. Furthermore, survival rates for oral and pharyngeal cancers have not significantly improved over the last three decades. This review examines the scientific literature surrounding the epidemiology of oral and pharyngeal cancers, including but not limited to risk factors, disparities, preventative factors, and the epidemiology in countries outside the United States. The literature review revealed that much of the research in this field has been focused on alcohol, tobacco, and their combined effects on oral and pharyngeal cancers. The literature on oral and pharyngeal cancer disparities among racial groups also appears to be growing. However, less literature is available on the influence of dietary factors on these cancers. Finally, effective interventions for the reduction of oral and pharyngeal cancers are discussed

Validation of <i>N</i>-myristoyltransferase as Potential Chemotherapeutic Target in Mammal-Dwelling Stages of <i>Trypanosoma cruzi</i>

BACKGROUND:Trypanosoma cruzi causes Chagas disease, an endemic and debilitating illness in Latin America. Lately, owing to extensive population movements, this neglected tropical disease has become a global health concern. The two clinically available drugs for the chemotherapy of Chagas disease have rather high toxicity and limited efficacy in the chronic phase of the disease, and may induce parasite resistance. The development of new anti-T. cruzi agents is therefore imperative. The enzyme N-myristoyltransferase (NMT) has recently been biochemically characterized, shown to be essential in Leishmania major, Trypanosoma brucei, and T. cruzi¸ and proposed as promising chemotherapeutic target in these trypanosomatids. METHODOLOGY/PRINCIPAL FINDINGS:Here, using high-content imaging we assayed eight known trypanosomatid NMT inhibitors, against mammal-dwelling intracellular amastigote and trypomastigote stages and demonstrated that three of them (compounds 1, 5, and 8) have potent anti-proliferative effect at submicromolar concentrations against T. cruzi, with very low toxicity against human epithelial cells. Moreover, metabolic labeling using myristic acid, azide showed a considerable decrease in the myristoylation of proteins in parasites treated with NMT inhibitors, providing evidence of the on-target activity of the inhibitors. CONCLUSIONS/SIGNIFICANCE:Taken together, our data point out to the potential use of NMT inhibitors as anti-T. cruzi chemotherapy

Prospective Observational Study of Pazopanib in Patients with Advanced Renal Cell Carcinoma (PRINCIPAL Study)

Background: Real-world data are essential to accurately assessing efficacy and toxicity of approved agents in everyday practice. PRINCIPAL, a prospective, observational study, was designed to confirm the real-world safety and efficacy of pazopanib in patients with advanced renal cell carcinoma (RCC). Subjects, Materials, and Methods: Patients with clear cell advanced/metastatic RCC and a clinical decision to initiate pazopanib treatment within 30 days of enrollment were eligible. Primary objectives included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), relative dose intensity (RDI) and its effect on treatment outcomes, change in health-related quality of life (HRQoL), and safety. We also compared characteristics and outcomes of clinical-trial-eligible (CTE) patients, defined using COMPARZ trial eligibility criteria, with those of non-clinical-trial-eligible (NCTE) patients. Secondary study objectives were to evaluate clinical efficacy, safety, and RDI in patient subgroups. Results: Six hundred fifty-seven patients were enrolled and received ≥1 dose of pazopanib. Median PFS and OS were 10.3 months (95% confidence interval [CI], 9.2–12.0) and 29.9 months (95% CI, 24.7 to not reached), respectively, and the ORR was 30.3%. HRQoL showed no or little deterioration over time. Treatment-related serious adverse events (AEs) and AEs of special interest occurred in 64 (9.7%), and 399 (60.7%) patients, respectively. More patients were classified NCTE than CTE (85.2% vs. 14.8%). Efficacy of pazopanib was similar between the two groups. Conclusion: PRINCIPAL confirms the efficacy and safety of pazopanib in patients with advanced/metastatic RCC in a real-world clinical setting. Implications for Practice: PRINCIPAL is the largest (n = 657) prospective, observational study of pazopanib in patients with advanced/metastatic renal cell carcinoma, to the authors’ knowledge. Consistent with clinical trial results that often contain specific patient types, the PRINCIPAL study demonstrated that the effectiveness and safety of pazopanib is similarly safe and effective in patients with advanced kidney cancer in a real-world clinical setting. The PRINCIPAL study showed that patients with advanced kidney cancer who are treated with first-line pazopanib generally do not show disease progression for approximately 10 months and generally survive for nearly 30 months