Asbestos Exposure Research Articles

DHEA-S, Androstenedione, 17-β-estradiol signature as novel biomarkers for early prediction of risk of malignant pleural mesothelioma linked to asbestos-exposure: A preliminary investigation

17-β-estradiol, involved in mesothelioma pathogenesis, and its precursors were explored as potential biomarkers for the early diagnosis of mesothelioma. Using enzyme-linked immunosorbent assay(ELISA) for 17-β-estradiol and ultra-high performance liquid chromatography/tandem mass spectrometry(UHPLC-MS/MS) for 19 17-β-estradiol precursors, a comprehensive analysis of 20steroid hormones was conducted in the serum of mesothelioma patients(n=67), asbestos-exposed healthy subjects(n=39), and non-asbestos-exposed healthy subjects(n=35). Bioinformatics analysis explored three potential serum biomarkers: 17-β-estradiol, DHEA-S, and androstenedione. The results revealed significant differences in 17-β-estradiol levels between mesothelioma patients and both non-asbestos-exposed and asbestos-exposed healthy subjects. No significant variations in serum 17-β-estradiol levels were observed among mesothelioma patients at different stages, suggesting its potential as an early diagnostic marker. 17-β-estradiol levels were similar in mesothelioma patients with environmental and occupational asbestos exposure, while males with occupational asbestos exposure exhibited significantly higher levels of 17-β-estradiol compared to females. Significant reduction in androstenedione and an increase in DHEA-S were observed in asbestos-exposed individuals compared to non-asbestos-exposed individuals. The analysis of DHEA-S-androstenedione-17-β-estradiol signature score showed an increase in asbestos-exposed individuals and mesothelioma patients compared to non-asbestos-exposed individuals, and this score effectively distinguished between the groups. The Cancer Genome Atlas data was utilized to analyze the expression of 5-α-reductase1 and hydroxysteroid-17β-dehydrogenase2 genes. The findings indicated that mesothelioma patients with elevated gene values for 5-α-reductase1 and hydroxysteroid-17β-dehydrogenase2 have a worse or better prognosis on overall survival, respectively. In conclusion, this study suggests 17-β-estradiol, DHEA-S, and androstenedione as biomarkers for mesothelioma risk and early diagnosis of mesothelioma in asbestos-exposed individuals, aiding timely intervention and improved care.

Asbestos ban policies and mesothelioma mortality in Greece

BackgroundMalignant mesothelioma is a rare form of cancer that mostly affects the pleura and has a strong link to asbestos exposure. Greece banned the use of asbestos in 2005, however, the public was already aware of this substance in the 1980s. This research aims to present an overview of Greece’s mesothelioma age-standardized mortality rates (ASMR) from 1983 to 2019 by age, gender, and geographic region and to determine whether the actions to ban asbestos impacted these rates.MethodsData were retrieved by the Hellenic Statistical Authority (HSA) from death certificates that mentioned mesothelioma as the cause of death from 1983 to 2019 with details on the residence, gender, and age. Statistical analysis was performed using PRISM 6.0 software, a two-way ANOVA test, Trend analysis was conducted using Joinpoint Regression Program 5.0 software. The linear and non-linear model was used to calculate the age-standardized rates of annual percentage change (APC) and its 95% confidential interval (95% CI).ResultsFrom 1983 to 2019, 850 total mesothelioma deaths were recorded, the majority of whom were males (634). A rate of 74.6% accounts for males and 25.4% for females, and the ratio of Males: Females was 3:1. Males’ ASMR and the whole population’s ASMR reached their highest levels in 2011 (0.93/100000person-years and 0.53/100000person-years, respectively). To look for potential changes between the first two decades of the 21st century, we compared the mean ASMR of each geographic region in Greece between two different 10-year subperiods (2000–2009 and 2010–2019). Except for Epirus, all regions of Greece had elevated regional ASMRs, particularly in those with the highest asbestos deposits. Notably, the ASMR in Epirus decreased from 0.54/100000person-years (2000–2009) to 0.31/100000person-years (2010–2019). After 2011, the ASMR for men and the general population stabilized. This stability is important since mesothelioma in men is associated with occupational asbestos exposure. The intriguing discovery of a lower ASMR in Epirus emphasizes the need to raise awareness of the condition and implement effective public health measures.ConclusionsIn Greece, the annual ASMR for males and the whole population reached its highest level in 2011, which is positive and encouraging and may be a sign that the rate will stabilize during the following years. Moreover, this study showed that the actions made in the 1980s regarding public awareness and surveillance directly impacted the decrease in Epirus rates. Future research, continual awareness, information, and recording are needed to monitor the mesothelioma epidemic. The possible benefit of a mesothelioma registry and the epidemiological surveillance of asbestos-related diseases, particularly mesothelioma mortality, need to be addressed.Trial registrationNot applicable.

Asbestos: detection and characterization in tissue

When asbestos fibers are inhaled, asbestos bodies can form in the lungs with the involvement of macrophages. It can take decades from the last exposure to the onset of an asbestos-related disease. The aim of this review is to present methods to detect asbestos bodies in lung tissue, the development of diagnostic criteria and to discuss pros and cons of different methods. Observations and evaluations from the German Mesothelioma Register, along with relevant literature review and expert recommendations in guidelines are presented. Assessing asbestos-related diseases requires recognition of the person's occupational history, the asbestos fiber burden in the lungs, and determining fiber types. Various methods have been developed and validated, including light microscopy techniques such as bright-field microscopy, phase-contrast microscopy, polarization microscopy, and differential interference microscopy, as well as electron microscopy techniques like field-emission-scanning electron microscopy (e.g., FE-SEM) and transmission electron microscopy (TEM). The use of asbestos has been heavily restricted worldwide, even completely banned in Europe. Thus, patients' exposure to asbestos is decreasing. However, asbestos exposure during renovations, demolitions, or through unconscious handling of asbestos-containing materials remains aconcern.

Diffuse Pleural Mesotheliomas with Genomic Near-Haploidization: A Newly Recognized Subset with Distinct Clinical, Histologic, and Molecular Features.

Diffuse pleural mesotheliomas (DPM) with genomic near-haploidization (GNH) represent a novel subtype first recognized by The Cancer Genome Atlas project; however, its clinicopathologic and molecular features remain poorly defined. We analyzed clinical genomic profiling data from 290 patients with DPM using the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) assay. Allele-specific copy number analysis was performed using the Fraction and Allele-Specific Copy Number Estimates from Tumor Sequencing (FACETS) algorithm. A total of 210 patients were evaluable for loss of heterozygosity (LOH) analysis using FACETS from MSK-IMPACT tumor:normal sequencing data. In this cohort, GNH, defined as LOH across >80% of the genome, was detected in 10 cases (4.8%). Compared with non-GNH tumors, GNH DPMs were associated with younger age and less frequent self-reported history of occupational asbestos exposure. Histologically, GNH DPMs were enriched in biphasic subtype (80% vs. 14.5%) and showed abundant tumor-infiltrating lymphocytes (TILs). Genomic analysis revealed a higher frequency of TP53 alterations, whereas SETDB1 mutations were present in nearly all and only in this subset. The clinicopathologic and molecular findings were further validated in a separate cohort. Despite the younger age, patients with GNH DPMs had a shorter overall survival (10.9 vs. 25.4 months, P = 0.004); the poor prognostic impact of GNH remained significant after controlling for biphasic histology. Of three patients with GNH DPMs who received immune checkpoint blockade, two achieved a clinician-assessed partial response. GNH defines an aggressive subtype of mainly biphasic DPMs in younger patients with recurrent alterations in SETDB1 and TP53. The enrichment in biphasic histology and TILs, together with our preliminary immune checkpoint blockade response data and anecdotal clinical trial data, suggests that further evaluation of immunotherapy may be warranted in this subset.

Development of Patient and Caregiver Conceptual Models Investigating the Health-Related Quality of Life Impacts of Malignant Pleural Mesothelioma.

Malignant pleural mesothelioma (MPM) is a rare and usually fatal malignancy frequently linked to occupational asbestos exposures and associated with poor prognosis and considerable humanistic burden. The study aimed to develop conceptual models of the health-related quality of life (HRQoL) impact on patients with and receiving treatment for MPM, and the burden on their caregivers. This multi-country study (Australia and United Kingdom) adopted a qualitative methodology to conduct semi-structured, independent interviews with people with MPM (n = 26), current caregivers (n = 20), and caregivers of people who had recently died because of MPM (n = 4). Participants were recruited using a purposive sampling approach and interviews conducted via telephone between January 2021 and January 2022. Transcripts were analysed using thematic analysis and used to construct conceptual models. Patient analysis yielded four overarching themes: (1) debilitating burden of breathlessness and fatigue; (2) physical mesothelioma symptoms experienced by patients; (3) distress of MPM on the self and family; and (4) treatment is worth 'having a go' despite the potential impact on symptoms. Caregiver analysis yielded five core themes: (1) daily life limited by caregiving duties; (2) emotional well-being and the need for support; (3) the relational role shift to caregiver; (4) time spent providing care negatively impacts work and productivity; and (5) positive aspects and outcomes of caregiving. This study highlights the substantial daily and emotional HRQoL impact that MPM symptoms have on patients and caregivers. Both groups reduced work, productivity, and social and leisure activities. There was evidence of positive HRQoL impacts as a result of immunotherapy and radiotherapy, but less for chemotherapy. Caregiver impacts were intensified during the end-of-life period and persisted following patient death. Evident is a need for increased psychological support, information, and advice for caregivers, increased during the end-of-life period.

The asbestos-asbestosis exposure-response relationship: a cohort study of the general working population.

The association between asbestos exposure and asbestosis in high-exposed industrial cohorts is well-known, but there is a lack of knowledge about the exposure-response relationship for asbestosis in a general working population setting. We examined the exposure-response relationship between occupational asbestos exposure and asbestosis in asbestos-exposed workers of the Danish general working population. We followed all asbestos-exposed workers from 1979 to 2015 and identified incident cases of asbestosis using the Danish National Patient Register. Individual asbestos exposure was estimated with a quantitative job exposure matrix (SYN-JEM) from 1976 onwards and back-extrapolated to age 16 for those exposed in 1976. Exposure-response relations for cumulative exposure and other exposure metrics were analyzed using a discrete time hazard model and adjusted for potential confounders. The range of cumulative exposure in the population was 0.001 to 18 fibers per milliliter-year (f/ml-year). We found increasing incidence rate ratios (IRR) of asbestosis with increasing cumulative asbestos exposure with a fully adjusted IRR per 1 f/ml-years of 1.18 [95% confidence interval (CI) 1.15- -1.22]. The IRR was 1.94 (95% CI 1.53-2.47) in the highest compared to the lowest exposure tertile. We similarly observed increasing risk with increasing cumulative exposure in the inception population. This study found exposure-response relations between cumulative asbestos exposure and incident asbestosis in the Danish general working population with mainly low-level exposed occupations, but there is some uncertainty regarding the exposure levels.

Prolonged survival and novel prognostic factors in women with pleural mesothelioma treated with extended pleurectomy decortication.

Pleural mesothelioma (PM) is an uncommon and extremely aggressive malignancy associated with past exposure to asbestos. The low representation of women among PM patients is likely due to differences in occupational asbestos exposure. Due to the controversial role of female sex as a prognostic factor in PM, the study aims to evaluate the survival of females treated with lung-sparing surgery. We present a cohort of 114 consecutive female patients with PM who underwent intended extended pleurectomy decortication (ePD) over 11 years in a high-volume single institution. All women from 2007-2017 who underwent intended ePD were enrolled in the study. Data on clinical, operative, and outcome were collected. Kaplan-Meier estimators and log-rank tests were employed to assess the overall survival, and Cox regression models were utilized to analyze prognostic factors. During the study period, 454 patients underwent thoracotomy with intended ePD in a single institution. There were 114 females (25%), and macroscopic complete resection (MCR) was achieved in 97 (85.1%). The median age was 65 years, histology was epithelioid in 81 (71.0%), biphasic in 31 (27.2%), and sarcomatoid in 2 (1.8%). The 30- and 90-day mortality were 3.5% and 6.1%, respectively. Median survival in females was 38 months, and 5-year survival was 28.2%. The median survival and 5-year survival rate for patients with epithelioid histology and MCR were 44.4 months and 36.4%, respectively. In a univariate analysis, several factors were found to be associated with patient overall survival including MCR [hazard ratio (HR): 0.3, P<0.001], early T status (HR: 1.6, P=0.03), adjuvant therapy (HR: 0.5, P=0.006), intraoperative heated chemotherapy (IOHC) (HR: 0.8, P=0.03), age (HR: 1.02, P=0.03) and epithelioid histology (HR: 0.5, P=0.009). For women with epithelioid PM undergoing intended ePD within a multimodal setting, prolonged survival is anticipated.

Abstract 7545: Epigenetic plasticity in rewiring DNMT1/UHRF1-RB1- NFkB signaling circuit regulates asbestos-induced mesothelial malignant transformation

Abstract The exact mechanisms underlying the causal relationship between asbestos exposure and malignant mesothelioma (MM) have yet to be elucidated. Widespread genomic and epigenomic alterations are being implicated in rewiring of oncogenic signaling networks which may contribute to initiation and progression of MM. In the present study, we examined the molecular profiles of mesothelial cells exposed to asbestos in-vitro and found that asbestos-induced activation of DNMT1/UHRF1 mediated epigenetic repression of RB1 in normal mesothelial cells as well as mesothelioma cells via promoter-specific methylation mechanisms. RB1, as a noncanonical transcription factor, was capable of also negatively modulating the transcriptional activities of DNMT1/UHRF1 mesothelium and mesothelioma. Functioning as one of the downstream effectors of RB1, NFkB was also involved in the transcriptional regulation of DNMT1/UHRF1 directly in a promoter-selective manner and played a pivotal role in the acute as well as chronic functional and phenotypic changes of mesothelial cells following asbestos exposure. Pharmacological interference of the dysregulated RB1-DNMT1/UHRF1- RB1-NFkB signaling circuit constitutively arrested the invasive growth of MPM cells. In-vivo studies using FVB genetic background wild-type and Bap1+/- mice further revealed involvement of epigenetically dysregulation of the RB1-DNMT1/UHRF1- RB1-NFkB signaling circuit during asbestos-induced malignant transformation of mesothelial cells. Taken together, our data are the first to describe that asbestos epigenetically rewires the RB1-DNMT1/UHRF1- RB1-NFkB signaling circuit during mesothelioma development and suggest potential novel strategies to reverse these epigenetic perturbations for MPM treatment in the clinic. Citation Format: Sichuan Xi, Xinwei Wu, David M Straughan, Eden C Payabyab, Haitao Wang, Ruihong Wang, Mary Zhang, Shamus R. Carr, Chuong D. Hoang, David S. Schrump. Epigenetic plasticity in rewiring DNMT1/UHRF1-RB1- NFkB signaling circuit regulates asbestos-induced mesothelial malignant transformation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7545.

Abstract 4716: First-in-class peroxiredoxin 3 (PRX3) inhibitor RSO-021 triggers mesenchymal-to-epithelial transition in mesothelioma

Abstract Mesothelioma, a lethal cancer associated with asbestos exposure, lacks effective drug therapy particularly in the relapsed treatment setting. Epithelial-to-mesenchymal transition (EMT) confers an aggressive sarcomatoid phenotype capable of invasion, metastasis, and drug resistance. Pharmacological targeting of EMT could favorably alter the progression and treatment of mesothelioma. We identified a geospatial transcriptomic gradient between adjacent epithelioid and sarcomatoid regions in patient-derived biphasic mesotheliomas involving hypoxia tolerance, TGF-β, mitochondrial oxidative phosphorylation, and EMT. Mesothelioma cells rely on buffering of mitochondrial oxidative stress through the expression and activity of mitochondrial peroxiredoxin 3 (PRX3), which is covalently inactivated by the first-in-class inhibitor RSO-021, now under investigation in the phase 1/2 MITOPE clinical trial (NCT05278975). To better understand the pharmacodynamics of RSO-021, transcriptomic profiles of drug sensitive and resistant biphasic mesothelioma cell lines were generated. Differential analysis revealed that RSO-021 induced up-regulation of ROS response and apoptosis signaling, while down-regulating TGF-β and EMT markers, WNT signaling, and TEAD target genes. Additionally, we observed altered expression of the mesothelioma specific EMT genes Col5A2, mesothelin and VISTA. Resistance to RSO-021 conferred significant proliferative defects and was reversible upon RSO-021 removal, however the down-regulation of EMT genes was conserved, suggesting an irreversible mesenchymal-to-epithelial transition. In summary PRX3 is a clinically actionable drug target, inhibition of which correlates with EMT modulation. This activity suggests a mechanism to alter mesothelioma progression and prevent the emergence of the most aggressive mesothelioma phenotype. Citation Format: Terri Messier, Victoria Gibson, David J. Seward, Essa Y. Baitei, Peter Wells Jordan, Charlotte Poile, Joanna Dzialo, Aleksandra Bzura, Kudzayi Kutywayo, Apostolos Nakas, George N. Naumov, Dean A. Fennell, Brian Cunniff. First-in-class peroxiredoxin 3 (PRX3) inhibitor RSO-021 triggers mesenchymal-to-epithelial transition in mesothelioma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4716.

Abstract 4085: The anti-VISTA x MSLN bispecific antibody-interferon beta mutein fusion protein: A trispecific immunocytokine with potent therapeutic efficacy against malignant pleural mesothelioma

Abstract Background Malignant pleural mesothelioma (MPM) is a rare and highly fatal cancer primarily induced by asbestos exposure. The 5-year overall survival rate for MPM patients is less than 20%. Before the FDA approval of the combination of immune checkpoint inhibitors (Nivolumab + Ipilimumab, CHECKMATE-743), chemotherapy was the only systemic therapy for MPM. However, the predominant histological type of MPM, epithelioid MPM, comprising approximately 70% of cases, showed limited clinical benefits from immune checkpoint inhibitors when compared to non-epithelioid histology. Consequently, there is an unmet medical need to develop a new anti-cancer drug specifically for the treatment of epithelioid MPM. In this study, we discovered that V-domain Ig suppressor of T cell activation (VISTA), an immune checkpoint protein, and Mesothelin (MSLN), a tumor differentiation antigen, are co-expressed in epithelioid MPM. Subsequently, we developed a biomarker-based anti-VISTA x MSLN bispecific antibody (BsAb) and anti-VISTA x MSLN BsAb-IFN-β mutein fusion protein (trispecific immunocytokine) for the treatment of epithelioid MPM. Method We designed and screened various structures of the anti-VISTA x MSLN BsAb. To produce the trispecific immunocytokine, we fused IFN-β mutein (R27T/C17S), which exhibits improved stability, productivity, and pharmacokinetic properties compare to recombinant IFN-β. The in vitro efficacy of the trispecific immunocytokine was tested in human MPM cell lines, and its in vivo efficacy was evaluated in a human MPM xenograft mouse model and a human IFNAR1/2 Knock-in (KI) mouse model. Results We demonstrated a strong positive correlation between the expression levels of VISTA and MSLN in epithelioid MPM. The Anti-VISTA x MSLN BsAb showed improved binding affinity and antibody-dependent cell cytotoxicity (ADCC) activity. The trispecific immunocytokine displays analogous biological activities to both Anti-VISTA x MSLN BsAb and IFN-β mutein. The trispecific immunocytokine exhibited potent in vivo and in vitro anti-cancer activities against epithelioid MPM preclinical models, operating through both direct cytotoxicity and indirect activation of immune cells. Conclusion The trispecific immunocytokine demonstrated robust in vitro and in vivo anti-cancer efficacy in the epithelioid MPM model. Our findings suggest that the trispecific immunocytoine is a promising drug candidate for epithelioid MPM. Citation Format: Hee Geon Park, Hyeon Ju Kim, Myeung Ryun Seo, Ji Eun Park, Tae Won Kim, Jeung Hoo Choi, Jay Park, Kyoung Song, Chan Gyu Lee, Hae Min Jeong, Jun Young Choi, Yeong Jeong Jeon, Yoon La Choi, Sung Youl Hong, Young Kee Shin. The anti-VISTA x MSLN bispecific antibody-interferon beta mutein fusion protein: A trispecific immunocytokine with potent therapeutic efficacy against malignant pleural mesothelioma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4085.

Abstract 3424: Assessing a DNA methylation-based telomere length estimator in individuals with a heavy smoking history

Abstract Telomere length (TL) and DNA methylation are associated with age and smoking exposure, as well as aging-related outcomes including lung cancer and mortality. A DNA methylation-based TL score (DNAmTL) was developed to estimate TL using DNA methylation array data, both in blood. DNAmTL effectively estimates telomere-related aging using 140 CpGs that are moderately enriched in sub-telomeric regions and not included in existing epigenetic clocks. We examined DNAmTL in individuals with a heavy smoking history (mean 56 pack years, range 11-185) in a nested lung cancer case-control study of 350 cases and 350 controls from the β-Carotene and Retinol Efficacy Trial identified through 2005. Twenty-two controls became cases with additional follow-up through 2013, so 328 controls and 372 cases were considered for these analyses. Leukocyte TL was measured using quantitative polymerase chain reaction (T/S ratio, log2-transformed), and DNA methylation was assayed on the Illumina EPIC array, in blood samples obtained on average 4.9 years prior to diagnosis in cases. We observed weak positive Pearson correlations between DNAmTL and TL in cases (r=0.19, p=0.0003) and controls (r=0.14, p=0.009) that persisted after age-adjustment: r=0.16, p=0.002 and r=0.14, p=0.014, respectively. Age-adjusted DNAmTL, but not TL, was longer for female compared to male cases (T=3.6, p=0.0004) and controls (T=2.2, p=0.03), and for those in the placebo compared to the intervention arm in cases (T=2.1, p=0.03) and controls (T=2.3, p=0.02). Linear regression models of TL and DNAmTL adjusted for age, sex, and race and ethnicity were not statistically significant for smoking variables at blood draw (pack years, current vs former smoking status, cigarettes smoked per day during smoking history, years smoked, years since quit), nor asbestos exposure in either cases or controls. Longer age-adjusted DNAmTL was associated with a lower hazard ratio (HR) for time to lung cancer death (0.60, 95% Confidence Interval (CI): 0.37-0.97) among cases (n=313 lung cancer-specific mortality events) in Cox proportional hazards models adjusted for age, sex, race and ethnicity, and time from blood draw to diagnosis with stage as a stratification variable (early I/II, advanced III/IV, unknown). Analogous age-adjusted TL model showed a similar direction but did not reach statistical significance (HR 0.86, CI: 0.71-1.05). Further adjustment of these models by DNA methylation-estimated leukocyte proportions of granulocytes, monocytes, natural killer, CD8+T, and CD4+T (excluding B cells) yielded similar results for age-adjusted DNAmTL (HR 0.54, CI: 0.31-0.92) and age-adjusted TL (HR 0.87, CI: 0.71-1.05). Our results illustrate that while DNAmTL may not be closely associated with smoking exposure among heavily exposed individuals, shorter DNAmTL may be more strongly associated with lung cancer mortality than TL in individuals with a heavy smoking history. Citation Format: Laurie Grieshober, Stefan Graw, Matt J. Barnett, Gary E. Goodman, Chu Chen, Devin C. Koestler, Carmen J. Marsit, Jennifer A. Doherty. Assessing a DNA methylation-based telomere length estimator in individuals with a heavy smoking history [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3424.

Global, regional, and national burden of non-communicable diseases attributable to occupational asbestos exposure 1990–2019 and prediction to 2035: worsening or improving?

Understanding the burden associated with occupational asbestos exposure on a global and regional scale is necessary to implement coordinated prevention and control strategies. By the GBD Study 2019, we conducted a comprehensive assessment of the non-communicable diseases burden attributable to occupational asbestos exposure. In 2019, 239,330 deaths and 4,189,000 disability-adjusted life years (DALYs) worldwide due to occupational asbestos exposure occurred. 1990–2019, deaths and DALYs attributed to occupational asbestos exposure increased by 65.65% and 43.66%, respectively. Age-standardized mortality rate (ASMR) and age-standardized DALYs rate (ASDR) decreased, with the most rapid declines in high Socio-Demographic Index (SDI) regions, with average annual percent change (AAPC) of − 1.05(95%CI: −1.2, −0.89) and −1.53(95%CI: −1.71, −1.36), respectively. Lung cancer, mesothelioma and ovarian cancer were the top three contributors to the increase in deaths and DALYs, accounting for more than 96%. AAPCs of ASMR and ASDR were positively associated with SDI. Global deaths from occupational asbestos exposure were predicted to increase and ASMR to decrease by 2035, mostly in males. Due consideration should be given to the susceptibility of the elderly, the lag of asbestos onset, and the regional differences, and constantly improve the prevention and control measures of occupational asbestos exposure and related diseases.

A functional regression model for the retrospective assessment of asbestos exposure among Venetian dock workers

A functional regression model for the retrospective assessment of asbestos exposure among Venetian dock workers

Survival analysis under imperfect record linkage using historic census data

BackgroundAdvancements in linking publicly available census records with vital and administrative records have enabled novel investigations in epidemiology and social history. However, in the absence of unique identifiers, the linkage of the records may be uncertain or only be successful for a subset of the census cohort, resulting in missing data. For survival analysis, differential ascertainment of event times can impact inference on risk associations and median survival.MethodsWe modify some existing approaches that are commonly used to handle missing survival times to accommodate this imperfect linkage situation including complete case analysis, censoring, weighting, and several multiple imputation methods. We then conduct simulation studies to compare the performance of the proposed approaches in estimating the associations of a risk factor or exposure in terms of hazard ratio (HR) and median survival times in the presence of missing survival times. The effects of different missing data mechanisms and exposure-survival associations on their performance are also explored. The approaches are applied to a historic cohort of residents in Ambler, PA, established using the 1930 US census, from which only 2,440 out of 4,514 individuals (54%) had death records retrievable from publicly available data sources and death certificates. Using this cohort, we examine the effects of occupational and paraoccupational asbestos exposure on survival and disparities in mortality by race and gender.ResultsWe show that imputation based on conditional survival results in less bias and greater efficiency relative to a complete case analysis when estimating log-hazard ratios and median survival times. When the approaches are applied to the Ambler cohort, we find a significant association between occupational exposure and mortality, particularly among black individuals and males, but not between paraoccupational exposure and mortality.DiscussionThis investigation illustrates the strengths and weaknesses of different imputation methods for missing survival times due to imperfect linkage of the administrative or registry data. The performance of the methods may depend on the missingness process as well as the parameter being estimated and models of interest, and such factors should be considered when choosing the methods to address the missing event times.

Bi-level Analysis of Computed Tomography Images of Malignant Pleural Mesothelioma: Deep Learning-Based Classification and Subsequent Three-Dimensional Reconstruction

Abstract A bi-level analysis of computed tomography (CT) images of malignant pleural mesothelioma (MPM) is presented in this paper, starting with a deep learning-based system for classification, followed by a three-dimensional (3D) reconstruction method. MPM is a highly aggressive cancer caused by asbestos exposure, and accurate diagnosis and determination of the tumor’s volume are crucial for effective treatment. The proposed system employs a bi-level approach, utilizing machine learning and deep learning techniques to classify CT lung images and subsequently calculate the tumor’s volume. The study addresses challenges related to deep neural networks, such as the requirement for large and diverse datasets, hyperparameter optimization, and potential data bias. To evaluate performance, two convolutional neural network (CNN) architectures, Inception-v3 and ResNet-50, were compared in terms of their features and performance. Based on CT images, the second stage incorporates 3D volume reconstruction. The process is carried out by cropping, registering, filtering, and segmenting images. This study demonstrated the efficacy of the developed system by combining CNN optimizations with 3D image reconstruction. It is intended to improve the accuracy of MPM diagnosis and to assist in the determination of chemotherapy doses, both of which may result in improved outcomes for patients.

Analysis of mesothelioma cases and National Cancer Registry data to assess asbestos exposure in India

&lt;sec&gt;&lt;title&gt;SETTING&lt;/title&gt;Asbestos exposure can cause mesothelioma, a form of cancer which should be recorded by cancer registries. However, such registries currently cover only a small fraction (16%) of the population in India. Because India still uses asbestos, it is important to understand its health impact, especially the number of mesothelioma cases.&lt;/sec&gt;&lt;sec&gt;&lt;title&gt;OBJECTIVE&lt;/title&gt;To assess the number of mesothelioma cases in India and compare these to the number reported to the National Cancer Registry.&lt;/sec&gt;&lt;sec&gt;&lt;title&gt;DESIGN&lt;/title&gt;We used the Right to Information Act 2005 to gather data for 83 hospitals across India from 2012 to 2022-2023.&lt;/sec&gt;&lt;sec&gt;&lt;title&gt;RESULTS&lt;/title&gt;From a total of 83 hospitals, there were 2,213 cases of mesothelioma from 2012 onwards. During the 2012–2016 period, the number of reported cases in the Cancer Registry was 54, whereas 1,126 cases were reported by these hospitals for this period. Only 21 (25%) of the hospitals assessed in this study were part of the population-based national cancer registry programme. Overall, cases of mesothelioma occur far more frequently than are reported in cancer registries.&lt;/sec&gt;&lt;sec&gt;&lt;title&gt;CONCLUSION&lt;/title&gt;National record-keeping is inadequate and the system needs to be expanded and improved across all of India. This will provide more effective reporting and help to highlight the risk of exposure to asbestos.&lt;/sec&gt;

Testicular mesothelioma disguised as hydrocele: a case report

BackgroundTesticular tumors have many different manifestations. The majority of these cases are presented as an incidental finding during hydrocelectomy. Malignant mesotheliomas are uncommon tumours that can arise from the coelomic epithelium of the pleura, peritoneum, pericardium, and tunica vaginalis.Case presentationWe present a 51-year-old South Asian (Indian) male patient with a rare case of mesothelioma, presenting with right hydrocele, to whom a right hydrocelectomy was performed. Any history of trauma or asbestos exposure was not present. Histopathological and immunohistochemistry reports revealed a malignant mesothelioma of tunica vaginalis. There was no invasion of the tumour to the epididymis and spermatic cord. Imaging studies showed no signs of metastasis. 1 month later, a high inguinal orchidectomy was performed. The patient underwent adjuvant chemotherapy thereafter and is still on follow-up.ConclusionAlthough hydrocele is common, detailed evaluation is mandatory to rule out certain rare tumours-testicular and paratesticular variants.

The lncRNAs Gas5, MALAT1 and SNHG8 as diagnostic biomarkers for epithelial malignant pleural mesothelioma in Egyptian patients

Long noncoding RNAs have been shown to be involved in a myriad of physiological and pathological pathways. To date, malignant pleural mesothelioma (MPM) is considered an extremely aggressive cancer. One reason for this is the late diagnosis of the disease, which can occur within 30–40 years of asbestos exposure. There is an immense need for the development of new, sensitive, inexpensive and easy methods for the early detection of this disease other than invasive methods such as biopsy. The aim of this study was to determine the expression of circulating lncRNAs in mesothelioma patient plasma to identify potential biomarkers. Ten previously identified lncRNAs that were shown to be aberrantly expressed in mesothelioma tissues were selected as candidates for subsequent validation. The expression of the ten selected candidate lncRNAs was verified via quantitative PCR (qPCR) in human plasma samples from mesothelioma patients versus healthy controls. The expression levels of circulating GAS5, SNHG8 and MALAT1 were significantly greater in plasma samples from patients than in those from controls. The ROC analysis of both MALAT1 and SNHG8 revealed 88.89% sensitivity and 66.67% specificity. The sensitivity of these markers was greater than that of GAS5 (sensitivity 72.22% and specificity 66.67%). The regression model for GAS5 was statistically significant, while that for SNHG8 and MALAT1 was not significant due to the small sample size. The area under the curve (AUC) of the three ROC curves was acceptable and significant: 0.7519 for GAS5, 0.7352 for SNHG8 and 0.7185 for MALAT1. This finding confirmed their ability to be used as markers. The three lncRNAs were not affected by age, sex or smoking status. The three lncRNAs showed great potential as independent predictive diagnostic biomarkers. Although the prediction model for MALAT1 did not significantly differ, MALAT1 was significantly expressed in patients more than in controls (p = 0.0266), and the recorded sensitivity and specificity were greater than those of GAS5.

Multi-temporal change detection of asbestos roofing: A hybrid object-based deep learning framework with post-classification structure

The detection of changes in asbestos roofing is vital due to the significant health risks associated with asbestos exposure. Utilising remote sensing for this task is promising, yet it encounters challenges like misregistration and variations in illumination within temporal images. This study presents a novel object-based deep learning framework with a post-classification structure designed specifically to detect changes in asbestos roofing. The method employs a hybrid deep learning model that utilises DenseNet121 to extract spatial features and integrates with either LSTM (DenseNet-LSTM) or conv1D (DenseNet-Conv1D) to capture temporal features. Using VHR aerial imagery, image patch sequences were generated for each roofing object across seven temporal points. After training the model, labels were assigned to each image patch in the sequence through binary classification. In post-processing, sequence alignment based on Hamming distance was used to enhance label assignments by aligning them with a pre-determined set of valid label sequences. Finally, the temporal change map was generated by comparing label transitions across temporal points. The results highlighted the model's robust capability to address inconsistencies across temporal points without relying on preprocessing techniques to manage such temporal discrepancies. The DenseNet-LSTM and DenseNet-Conv1D models demonstrated comparable classification performance in asbestos roofing detection, achieving average overall accuracies of 95.8% and 96.0%, respectively. Furthermore, the model's generalisability was underscored by a test on an independent dataset, which produced up to 94% detection accuracy for asbestos class. While the framework has limitation in detecting painted asbestos roofing and partial changes, it offers a reproducible approach for change detection tasks that target a specific roofing type, rather than detecting changes in all roofing types within remote sensing imagery.

Sarcomatoid Malignant Pleural Mesothelioma: A Case Report

Mesothelioma is a rare neoplasm and found 1 case/ million / year. It develops mainly in individuals over 60 year of age. Main risk factor is asbestos exposure. Other risk factors include: - Simian virus 40, ERIONITE fibre exposure, radiation induced. This is a case report of a 70-year-old female diagnosed with Mesothelioma of Sarcomatoid type by IHC markers.