The Western Australian Mesothelioma Registry: Analysis of 60 years of cases.

BACKGROUND AND OBJECTIVE: Australia introduced a partial ban on asbestos consumption in 1984. There is continuing concern about exposure to asbestos in the built environment and non-occupational exposures. The aim of this study was to describe epidemiological trends of mesothelioma in Western Australia (WA) over the 60 years since the first case was recorded. METHODS: Every case of mesothelioma notified to the WA Cancer Registry is reviewed by an expert panel. Data include demographic and clinical variables including principal mode of asbestos exposure and age at first exposure. Trends over time for survival, latency and pathological subtype of mesothelioma where analysed. Incidence rates for cases exposed during home renovation where calculated. RESULTS: Two thousand seven hundred ninety-six cases of mesothelioma were identified with males comprising the majority (n = 2368, 84.7%). The median (IQR) age at diagnosis was 70 (62-78) years, and median latency of 47 (38-55) years. Pleural mesothelioma was recorded in 2620 (93.7%) cases with the epithelioid subtype most prevalent (n = 1730, 61.9%). Overall, median survival was 298 (128-585) days and latency 46 (37-54) years, both effectively doubling over the study period. Non-occupational exposures were proportionally higher in females (52.6%), compared with males (9.5%). Home renovation was the primary exposure in 227 (8.1%) cases, with number of cases and incidence rate ratio peaking in 2005/09 but subsequently decreasing. CONCLUSION: The annual number of cases of mesothelioma in WA may have hit a plateau. The majority of females have non-occupational exposures and incidence rates from home renovation exposure may have peaked, suggesting the ban on asbestos has been effective.

Lung cancer screening an asbestos exposed population: Existing lung cancer risk criteria are not sufficient.

BACKGROUND AND OBJECTIVE: Asbestos is a major risk factor for lung cancer, with or without tobacco smoke exposure. Low dose computed tomography (LDCT) screening for early lung cancer is effective but only when targeting high risk populations. This study aimed to analyse the effectiveness of LDCT screening in an asbestos exposed population and to compare lung cancer screening program (LCSP) eligibility criteria. METHODS: Participants in an asbestos health surveillance program, the Western Australia Asbestos Review Program, underwent at least one LDCT scan and lung function assessment as part of annual review between 2012 and 2017. Lung cancer cases were confirmed through linkage to the WA cancer registry. Theoretical eligibility for different screening programs was calculated. RESULTS: Five thousand seven hundred and two LDCT scans were performed on 1743 individuals. The median age was 69.8 years, 1481 (85.0%) were male and 1147 (65.8%) were ever-smokers (median pack-year exposure of 20.0). Overall, 26 lung cancers were detected (1.5% of the population; 3.5 cases per 1000 person-years of observation). Lung cancer was early stage in 86.4% and four (15.4%) cases were never smokers. Based on current lung screening program criteria, 1299 (74.5%) of this population, including the majority (17, 65.4%) of lung cancer cases, would not have been eligible for any LCSP. CONCLUSION: This population is at raised risk despite modest tobacco exposure. LDCT screening is effective at identifying early-stage lung cancer in this population and existing lung cancer risk criteria do not capture this population adequately.

Correlation of lung function with ultra-low-dose CT-detected lung parenchymal abnormalities: a cohort study of 1344 asbestos exposed individuals.

INTRODUCTION: Deliberate exposure to medical ionising radiation should be as low as reasonably practicable but the reduction of radiation from CT should be balanced against diagnostic image quality. The ability of ultra-low-dose CT (uLDCT: similar radiation to chest X-ray) to demonstrate low contrast abnormalities (emphysema and interstitial lung abnormality (ILA)) is unclear.The aim of this cross-sectional study was to analyse the lung parenchymal findings from uLDCT scans against physiological measures of respiratory function. METHODS: WA Asbestos Review Programme participants were eligible if they had an uLDCT scan and lung function assessment between Janary and December 2018. All scans were performed using a single CT machine and reported using a standardised, semiquantitative synoptic report which includes emphysema and linear fibrosis (ILA) scores. RESULTS: Of 1344 participants, median (IQR) age was 72.0 (65.0-78.0) years, the majority were males (84.9%) with mixed occupational asbestos exposure (68.1%). There were 721 (53.6%) with no abnormality, 158 (11.8%) with emphysema, 465 (34.6%) with ILA. Mean radiation dose was 0.12 mSv. There was statistically significant between group differences for all physiological parameters of lung function compared with controls. For instance, the emphysema score significantly correlated with obstructive forced expiratory volume in 1 s (FEV1)/forced vital capacity ratio (r=0.512), per cent predicted FEV1 (r=0.24) and lower diffusion of carbon monoxide (DLCO) (r=0.337). Multivariate modelling demonstrated that increasing age, emphysema and fibrosis scores predicted reduced DLCO (adjusted R2=0.30). DISCUSSION: uLDCT-detected parenchymal lung abnormalities correlate strongly with significant changes on lung function testing suggesting the observed CT abnormalities are of physiological and clinical significance.

Rapid Assessment of Oxidative Damage Potential: A Comparative Study of Engineered Stone Dusts Using a Deoxyguanosine Assay.

The popularity of engineered stone (ES) has been associated with a global increase in occupational lung disease in workers exposed to respirable dust during the fabrication of benchtops and other ES products. In this study, the reactivity and subsequent oxidative reduction potential of freshly generated ES dusts were evaluated by (i) comparing different engineered and natural stones, (ii) comparing settled and respirable stone dust fractions and (iii) assessing the effect of ageing on the reactivity of freshly generated stone dust. An established cell-free deoxyguanosine hydroxylation assay was used to assess the potential for oxidative DNA damage. ES dust exhibited a higher relative reactivity than two of the three natural stones tested. Respirable dust fractions were found to be significantly more reactive than their corresponding settled fraction (ANOVA, p < 0.05) across all stone types and samples. However, settled dust still displayed high relative reactivity. The lower reactivity of the settled dust was not due to decay in reactivity of the respirable dust when it settled but rather a result of the admixture of larger nonrespirable particles. No significant change in respirable dust reactivity was observed for three ES samples over a 21-day time period, whereas a significant decrease in reactivity was observed in the natural stone studied. This study has practical implications for dust control and housekeeping in industry, risk assessment and hazard management.

Mapping Research on miRNAs in Cancer: A Global Data Analysis and Bibliometric Profiling Analysis.

miRNAs biomarkers are emerging as an essential part of clinical oncology. Their oncogenic and tumour suppressor properties playing a role in malignancy has generated interest in their potential for use in disease prognosis. While several studies on miRNA have been carried out across the globe, evaluating the clinical implications of miRNAs in cancer diagnosis and prognosis research has currently not been attempted. A study delineating the area of miRNA research, including the topics presently being focused on, the seminal papers in this field, and the direction of research interest, does not exist. This study aims to conduct a large-scale, global data analysis and bibliometric profiling analysis of studies to evaluate the research output of clinical implications of miRNAs in cancer diagnosis and prognosis listed in the SCOPUS database. A systematic search strategy was followed to identify and extract all relevant studies, subsequently analysed to generate a bibliometric map. SPSS software (version 27) was used to calculate bibliometric indicators or parameters for analysis, such as year and country of affiliation with leading authors, journals, and institutions. It is also used to analyse annual research outputs, including total citations and the number of times it has been cited with productive nations and H-index. The number of global research articles retrieved for miRNA-Cancer research over the study period 2003 to 2019 was 18,636. Between 2012 and 2019, the growth rate of global publications is six times (n = 15,959; 90.71 percent articles) that of 2003 to 2011. (2704; 9.29 per cent articles). China published the most publications in the field of miRNA in cancer (n = 7782; 41%), while the United States had the most citations (n = 327,538; 48%) during the time span. Of these journals, Oncotarget has the highest percentage of article publications. The journal Cancer Research had the most citations (n = 41,876), with 6.20 per cent (n = 41,876). This study revealed a wide variety of journals in which miRNA-Cancer research are published; these bibliometric parameters exhibit crucial clinical information on performance assessment of research productivity and quality of research output. Therefore, this study provides a helpful reference for clinical oncologists, cancer scientists, policy decision-makers and clinical data researchers.

What Do Safety Data Sheets for Artificial Stone Products Tell Us About Composition? A Comparative Analysis with Physicochemical Data.

Artificial stone (AS) is a composite material that has seen widespread use in construction, particularly for kitchen benchtops. However, fabrication processes with AS have been associated with serious lung disease. Safety data sheets (SDSs) aim to provide important information pertaining to composition and health risks. In the case of a complex mixture, SDSs may be problematic in terms of specific information on overall health risks. To assess this issue, we compared empirically determined mineral, metallic, and organic resin content of 25 individual AS products across six suppliers, with the corresponding SDS information. X-ray diffraction was used to quantitate the mineralogical components of AS samples, and X-ray fluorescence was used to estimate the metallic components. Organic material (resin content) was estimated using weight loss during calcination. Although the resin content for all AS samples was within the SDS-reported ranges, there was considerable variability in the crystalline silica content when comparing with supplier's SDS. Potentially toxicologically relevant metallic and mineral constituents were not reported. Some supplier SDSs were found to provide more information than others. Only one of the six suppliers provided crystalline mineral content other than silica, and only two suppliers provided any information about metals. There remains a limited understanding of lung pathogenesis from AS, and this study highlights the need for more comprehensive and standardized SDS information for risk assessment and management.

Hospital-based multidisciplinary lung cancer care in Australia: a survey of the landscape in 2021.

INTRODUCTION: Lung cancer is the leading cause of cancer death in Australia and has the highest cancer burden. Numerous reports describe variations in lung cancer care and outcomes across Australia. There are no data assessing compliance with treatment guidelines and little is known about lung cancer multidisciplinary team (MDT) infrastructure around Australia. METHODS: Clinicians from institutions treating lung cancer were invited to complete an online survey regarding the local infrastructure for lung cancer care and contemporary issues affecting lung cancer. RESULTS: Responses from 79 separate institutions were obtained representing 72% of all known institutions treating lung cancer in Australia. Most (93.6%) held a regular MDT meeting although recommended core membership was only achieved for 42/73 (57.5%) sites. There was no thoracic surgery representation in 17/73 (23.3%) of MDTs and surgery was less represented in regional and low case volume centres. Specialist nurses were present in just 37/79 (46.8%) of all sites. Access to diagnostic and treatment facilities was limited for some institutions. IT infrastructure was variable and most sites (69%) do not perform regular audits against guidelines. The COVID-19 pandemic has driven most sites to incorporate virtual MDT meetings, with variable impact around the country. Clinician support for a national data-driven approach to improving lung cancer care was unanimous. DISCUSSION: This survey demonstrates variations in infrastructure support, provision and membership of lung cancer MDTs, in particular thoracic surgery and specialist lung cancer nurses. This heterogeneity may contribute to some of the well-documented variations in lung cancer outcomes in Australia.

Clinical Theragnostic Relationship between Chemotherapeutic Resistance, and Sensitivity and miRNA Expressions in Head and Neck Cancers: A Systematic Review and Meta-Analysis Protocol.

Background: The microRNAs (miRNAs) are small noncoding single-stranded RNAs typically 19-25 nucleotides long and regulated by cellular and epigenetic factors. These miRNAs plays important part in several pathways necessary for cancer development, an altered miRNA expression can be oncogenic or tumor-suppressive. Recent experimental results on miRNA have illuminated a different perspective of the molecular pathogenesis of head and neck cancers. Regulation of miRNA can have a detrimental effect on the efficacy of chemotherapeutic drugs in both neoadjuvant and adjuvant settings. This miRNA-induced chemoresistance can influence the prognosis and survival rate. The focus of the study is on how regulations of various miRNA levels contribute to chemoresistance in head and neck cancer (HNC). Recent findings suggest that up or down-regulation of miRNAs may lead to resistance towards various chemotherapeutic drugs, which may influence the prognosis. Methods: Studies on miRNA-specific chemoresistance in HNC were collected through literary (bibliographic) databases, including SCOPUS, PubMed, Nature, Elsevier, etc., and were systematically reviewed following PRISMA-P guidelines (Preferred Reporting Items for Systematic Review and Meta-analysis Protocol). We evaluated various miRNAs, their up and downregulation, the effect of altered regulation on the patient's prognosis, resistant cell lines, etc. The data evaluated will be represented in the form of a review and meta-analysis. Discussion: This meta-analysis aims to explore the miRNA-induced chemoresistance in HNC and thus to aid further researches on this topic. PROSPERO registration: CRD42018104657.

Prognostic Utility of Platelet-Lymphocyte Ratio, Neutrophil-Lymphocyte Ratio and Monocyte-Lymphocyte Ratio in Head and Neck Cancers: A Detailed PRISMA Compliant Systematic Review and Meta-Analysis.

Inflammation plays a major role in cancer development and progression and has the potential to be used as a prognostic marker in cancer. Previous studies have attempted to evaluate Platelet-to-lymphocyte ratio (PLR), neutrophil-lymphocyte ratio (NLR) or monocyte-lymphocyte ratio (MLR) as indicators of inflammation/prognostic markers in cancer, but there is no common consensus on their application in clinical practice. The aim of this systematic review and meta-analysis is to (a) assess the prognostic efficacy of all three prognostic markers in comparison to each other and (b) investigate the prognostic potential of these three markers in HNC. The study followed PRISMA guidelines, with the literature being collated from multiple bibliographic databases. Preliminary and secondary screening were carried out using stringent inclusion/exclusion criteria. Meta-analysis was carried out on selected studies using CMA software and HR as the pooled effect size metric. A total of 49 studies were included in the study. The pooled HR values of PLR, NLR and MLR indicated that they were significantly correlated with poorer OS. The pooled effect estimates for PLR, NLR and MLR were 1.461 (95% CI 1.329-1.674), 1.639 (95% CI 1.429-1.880) and 1.002 (95% CI 0.720-1.396), respectively. Significant between-study heterogeneity was observed in the meta-analysis of all three. The results of this study suggest that PLR, NLR and MLR ratios can be powerful prognostic markers in head and neck cancers that can guide treatment. Further evidence from large-scale clinical studies on patient cohorts are required before they can be incorporated as a part of the clinical method. PROSPERO Registration ID: CRD42019121008.

Prognostic Value of MicroRNAs in Stage II Colorectal Cancer Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: We performed a systematic review and meta-analysis to identify and underline multiple microRNAs (miRNAs) as biomarkers of disease prognosis in stage II colorectal cancer (CRC) patients. METHODS AND ANALYSIS: This systematic review and meta-analysis study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The required articles were collected from online bibliographic databases from January 2011 to November 2019 with multiple permutation keywords. Quantitative data synthesis was based on a meta-analysis with pooled data to observe and analyse the outcome measures and effect estimates by using the random effect model. The subgroup analysis was performed from demographic characteristics and the available data. RESULTS: Eighteen articles were included in this study, 16 of which were incorporated for meta-analysis to examine the stage II CRC prognosis with up- and downregulated miRNA expressions. The pooled hazard ratio (HR) for death in stage II CRC patients was 1.90 (95% confidence interval 1.63-2.211), with a significant p value. A subgroup analysis based on up- or downregulated miRNA expression individually and any deregulated miRNA was also associated with a worse prognosis. The subgroup analysis included parameters such as age, gender, stage II and III combined patients' survival and the repetitive miRNAs (miR21, miR215, miR143-5p, miR106a and miR145) individually. CONCLUSION: MicroRNAs play a significant role in determining prognosis in stage II CRC patients, with upregulation of miR21, miR215, miR143-5p and miR106a, in particular, portending a worse prognosis. These miRNAs could be considered for further evaluation as biomarkers of prognosis and to guide the decision to administer adjuvant chemotherapy.

The Significance of miRNAs as a Prognostic Biomarker for Survival Outcome in T Cell - Acute Lymphoblastic Leukemia Patients: A Systematic Review and Meta-Analysis.

PURPOSE: T-cell acute lymphoblastic leukemia (T-ALL) affects lymphoid cells. Previous studies have reported that miRNAs play a significant role in T-ALL prognosis and have the potential to function as biomarkers in T-ALL. Therefore, this systematic review and meta-analysis study was designed to evaluate the overall prognostic impact of miRNAs in T-ALL patients. METHODS: Eligible studies published between Jan 2010 and April 2018 were retrieved from online bibliographic databases based on multiple keywords to generate search strings. Meta-analysis was performed using the outcome measure, Hazard Ratio (HR). A survival analysis of all studies was conducted and a subsequent forest plot was generated to evaluate the pooled effect size, across all T-ALL patients. Subgroup analysis was conducted based on demographic characteristics and commonly represented miRNAs among the included studies. RESULTS: A total of 17 studies were included for systematic review, among which 16 studies were eligible for meta-analysis, which, in total discussed 32 different miRNAs. The mean effect size of HR value was 0.929 (CI 0.878-0984), which indicates a decrease in risk of death by 7.1%. The analysis was based on the random effects model with the heterogeneity measure index (I2) being 84.92%. The pooled effect size (HR) of upregulated and downregulated miRNA expressions on survival outcome in the T-ALL patient was 0.787 (CI 0.732-0.845) and 1.225 (CI 1.110-1.344) respectively. The subgroup analysis was performed based on demographic characteristics (age, gender, lactate dehydrogenase, WBC count) and expression of miR221 and miR46a. CONCLUSION: Our systematic review and meta-analysis findings suggest that the overall miRNA expression is potentially associated with a decreased likelihood of death in T-ALL patients. Although our findings are inconclusive, the results point toward miRNA expression allowing for prognostic evaluation of T-ALL patients.

Clinical Theragnostic Relationship between Drug-Resistance Specific miRNA Expressions, Chemotherapeutic Resistance, and Sensitivity in Breast Cancer: A Systematic Review and Meta-Analysis.

Awareness of breast cancer has been increasing due to early detection, but the advanced disease has limited treatment options. There has been growing evidence on the role of miRNAs involved in regulating the resistance in several cancers. We performed a comprehensive systematic review and meta-analysis on the role of miRNAs in influencing the chemoresistance and sensitivity of breast cancer. A bibliographic search was performed in PubMed and Science Direct based on the search strategy, and studies published until December 2018 were retrieved. The eligible studies were included based on the selection criteria, and a detailed systematic review and meta-analysis were performed based on PRISMA guidelines. A random-effects model was utilised to evaluate the combined effect size of the obtained hazard ratio and 95% confidence intervals from the eligible studies. Publication bias was assessed with Cochran's Q test, I2 statistic, Orwin and Classic fail-safe N test, Begg and Mazumdar rank correlation test, Duval and Tweedie trim and fill calculation and the Egger's bias indicator. A total of 4584 potential studies were screened. Of these, 85 articles were eligible for our systematic review and meta-analysis. In the 85 studies, 188 different miRNAs were studied, of which 96 were upregulated, 87 were downregulated and 5 were not involved in regulation. Overall, 24 drugs were used for treatment, with doxorubicin being prominently reported in 15 studies followed by Paclitaxel in 11 studies, and 5 drugs were used in combinations. We found only two significant HR values from the studies (miR-125b and miR-4443) and our meta-analysis results yielded a combined HR value of 0.748 with a 95% confidence interval of 0.508-1.100; p-value of 0.140. In conclusion, our results suggest there are different miRNAs involved in the regulation of chemoresistance through diverse drug genetic targets. These biomarkers play a crucial role in guiding the effective diagnostic and prognostic efficiency of breast cancer. The screening of miRNAs as a theragnostic biomarker must be brought into regular practice for all diseases. We anticipate that our study serves as a reference in framing future studies and clinical trials for utilising miRNAs and their respective drug targets.