Fibulin-3 levels in malignant pleural mesothelioma are associated with prognosis but not diagnosis.

BACKGROUND: Fibulin-3 (FBLN3) was recently presented as a promising novel biomarker for malignant pleural mesothelioma (MPM), warranting independent validation studies. METHODS: ELISA was used to measure cellular and secreted FBLN3 in cell lines, in plasma of xenograft tumour-bearing mice, in plasma from two independent series of MPM and non-MPM patients and in pleural fluid from a third series. Diagnostic and prognostic potential of FBLN3 was assessed by receiver operating characteristics curve analysis and Kaplan-Meier method, respectively. RESULTS: FBLN3 was expressed in all MPM and benign mesothelial cell lines tested, and a correlation was observed between cellular protein expression and secreted levels. Human FBLN3 was detectable in plasma of tumour-bearing mice, suggesting that MPM cells contribute to levels of circulating FBLN3. Plasma FBLN3 was significantly elevated in MPM patients from the Sydney cohort, but not the Vienna cohort, but the diagnostic accuracy was low (63%, (95% CI: 50.1-76.4) and 56% (95% CI: 41.5-71.0), respectively). Although FBLN3 levels in pleural effusions were not significantly different between cases and controls, FBLN3 levels in pleural effusion fluid were found to be independently associated with prognosis (hazard ratio of 9.92 (95% CI: 2.14-45.93)). CONCLUSIONS: These data confirm the potential prognostic value of pleural effusion FBLN3, but question the diagnostic value of this protein in MPM patients.

Asbestos exposure during home renovation in New South Wales.

OBJECTIVE: Asbestos exposure is causally associated with the development of malignant mesothelioma (MM), which is increasingly being reported after exposure to asbestos fibro sheeting in Australia. In this study, we investigate self-reported non-occupational asbestos exposure during home renovation in New South Wales. DESIGN AND SETTING: Cross-sectional mailed questionnaire examining renovation activity, tasks undertaken during renovation and self-reported exposure to asbestos among respondents and their family members in NSW between January and June 2008. PARTICIPANTS: 10 000 adults aged 18-99 years, randomly selected from the NSW electoral roll. We received 3612 responses, while 365 questionnaires did not reach addressees, giving an overall response rate of 37.5%. MAIN OUTCOME MEASURES: Differences in self-reported asbestos exposure between do-it-yourself (DIY) and non-DIY renovators. RESULTS: 1597 participants (44.2%) had renovated their home and among these, 858 participants (53.7%) self-reported as DIY renovators. Of these, 527 (61.4%) reported asbestos exposure during home renovations, 337 (39.3%) reported that their partner had been exposed to asbestos during renovations, and 196 (22.8%) reported that their children had been exposed. More than 20% of renovators planned to further renovate their current homes within the next 5 years. CONCLUSIONS: Self-reported asbestos exposure during home renovation is common. This preventable exposure could place adults and children at risk of MM many years into the future. Although such exposure is self-reported and ideally should be verified, this study identifies a potentially important problem in NSW.

Asbestos-related lung cancer: Clinical characteristics and survival outcomes in an Australian cohort seeking workers compensation.

BACKGROUND AND OBJECTIVES: Due to difficulties in identifying sufficient-sized cohorts there remains uncertainty about prognostic and clinical differences that may be unique to asbestos-related lung cancer (ARLC). In this study, we use the Helsinki Criteria to define a group of ex-workers with lung cancer attributable to asbestos exposure and investigate differences that may exist. METHODS: A total of 529 patients seeking workers' compensation for their lung cancer were assigned to either ARLC or the non-ARLC based on parameters defined in the Helsinki Criteria. Clinical and survival details were collected and analyzed. RESULTS: In our study population, ARLC patients were on average older (72.1 ± 7.8) than non-ARLC patients (66.5 ± 10.2, P < 0.001) and were more likely to be diagnosed as a result of incidental findings or screening program (P < 0.001). The groups were similar in terms of clinical characteristics with the only difference being that plaques were more prevalent among ARLC patients (P < 0.001). Differences were observed for median overall survival (OS), ARLC (9 months) and non-ARLC (13 months, P = 0.005), as well for treatment (P = 0.01). After adjusting for age, however, these differences disappeared. CONCLUSIONS: Age at diagnosis, pleural plaques, and asymptomatic presentation were the attributes that we identified as significantly different between asbestos-related cancer and other lung cancers. In this cohort, ARLC patients were older diagnosis and with worse overall survival.

Occupational exposure to asbestos in New South Wales, Australia (1970-1989): development of an asbestos task exposure matrix.

OBJECTIVES: To design and construct a standardised tool to provide exposure information associated with commonly used asbestos products and their related tasks in New South Wales (NSW), Australia. METHODS: Asbestos dust exposure measurements taken during workplace inspections in the 1970s and 1980s were collected and stored in an exposure database. Measurements were assigned to specific asbestos product and task groups and divided into two sampling periods 1970-1979 and 1980-1989. RESULTS: A total of 1578 asbestos air measurements collected from WorkCover and Dust Diseases Board company records were entered into a custom built exposure database. An asbestos-specific exposure matrix (ASTEM) was constructed in Microsoft Excel 2000, consisting of 3 axes incorporating 12 tasks, 8 asbestos products and the 2 time periods based on 872 individual measurements extracted from the exposure database. Each matrix cell contains the mean asbestos exposure levels measured in fibres/ml, 5th and 95th percentiles and number of data points in the set. CONCLUSION: An ASTEM has been developed which provides exposure levels for different task/product combinations. When used in conjunction with a detailed occupational history, it will improve exposure estimates of a worker's cumulative asbestos exposure.

Prediction modelling using routine clinical parameters to stratify survival in Malignant Pleural Mesothelioma patients undergoing cytoreductive surgery.

INTRODUCTION: Malignant pleural mesothelioma (MPM) is an uncommon cancer with a poor prognosis and heterogeneous survival. Surgery for MPM is offered in some specialist centers to highly selected patients. A previously described classification and regression tree (CART) model stratified survival in unselected MPM patients using routinely collected clinical data. This study aimed to examine the performance of this CART model on a highly selected surgical population. METHODS: Data were collected from subjects undergoing cytoreductive surgery for MPM from specialist centers in Hyõgo, Japan, and Sydney, Australia, between 1991 and 2016. The CART model was applied using the combination of clinical variables to stratify subjects into risk groups (1 through 4); survival characteristics were then compared. RESULTS: Two hundred eighty-nine cases were included (205 from Australia, 84 from Japan). Overall median survival was 34.6 (interquartile range: 17.5-56.1) months; median age was 63.0 (interquartile range: 57.0-67.8) years, and 83.0% (n = 240) were male. There were no clinically meaningful differences between the two cohorts. Survival across the four risk groups was significantly different (p < 0.0001); the model stratified survival well with a Harrell's concordance statistic of 0.62 (95% confidence interval: 0.57-0.66) at 36 months. The group with the longest survival (median, 82.5 months) had: no weight loss, hemoglobin > 153 g/L and serum albumin > 43 g/L at time of referral to the surgical center. CONCLUSIONS: Using routinely available clinical variables, the CART model was able to stratify surgical patients into risk groups with statistically different survival characteristics with fair to good performance. Presence of weight loss, anemia, and low albumin should confer caution when considering surgical therapy for MPM.

Effect of Trimetazidine Dihydrochloride Therapy on Exercise Capacity in Patients With Nonobstructive Hypertrophic Cardiomyopathy: A Randomized Clinical Trial.

Importance: Hypertrophic cardiomyopathy causes limiting symptoms in patients, mediated partly through inefficient myocardial energy use. There is conflicting evidence for therapy with inhibitors of myocardial fatty acid metabolism in patients with nonobstructive hypertrophic cardiomyopathy. Objective: To determine the effect of oral therapy with trimetazidine, a direct inhibitor of fatty acid ß-oxidation, on exercise capacity in patients with symptomatic nonobstructive hypertrophic cardiomyopathy. Design, Setting, and Participants: This randomized, placebo-controlled, double-blind clinical trial at The Heart Hospital, University College London Hospitals, London, United Kingdom was performed between May 31, 2012, and September 8, 2014. The trial included 51 drug-refractory symptomatic (New York Heart Association class ≥2) patients aged 24 to 74 years with a maximum left ventricular outflow tract gradient 50 mm Hg or lower and a peak oxygen consumption during exercise of 80% or less predicted value for age and sex. Statistical analysis was performed from March 1, 2016 through July 4, 2018. Interventions: Participants were randomly assigned to trimetazidine, 20 mg, 3 times daily (n = 27) or placebo (n = 24) for 3 months. Main Outcomes and Measures: The primary end point was peak oxygen consumption during upright bicycle ergometry. Secondary end points were 6-minute walk distance, quality of life (Minnesota Living with Heart Failure questionnaire), frequency of ventricular ectopic beats, diastolic function, serum N-terminal pro-brain natriuretic peptide level, and troponin T level. Results: Of 49 participants who received trimetazidine (n = 26) or placebo (n = 23) and completed the study, 34 (70%) were male; the mean (SD) age was 50 (13) years. Trimetazidine therapy did not improve exercise capacity, with patients in the trimetazidine group walking 38.4 m (95% CI, 5.13 to 71.70 m) less than patients in the placebo group at 3 months after adjustment for their baseline walking distance measurements. After adjustment for baseline values, peak oxygen consumption was 1.35 mL/kg per minute lower (95% CI, -2.58 to -0.11 mL/kg per minute; P = .03) in the intervention group after 3 months. Conclusions and Relevance: In symptomatic patients with nonobstructive hypertrophic cardiomyopathy, trimetazidine therapy does not improve exercise capacity. Pharmacologic therapy for this disease remains limited. Trial Registration: ClinicalTrials.gov identifier: NCT01696370.

Incidence trends and gender differences in malignant mesothelioma in New South Wales, Australia.

OBJECTIVES: Features of malignant mesothelioma reportedly differ between men and women, including occupational asbestos exposure, histological subtype, and median survival. In this study, incidence trends and clinical features for malignant mesothelioma were compared between genders in New South Wales (NSW), where notification of malignant mesothelioma to the Central Cancer Registry is a statutory requirement. METHODS: Notifications to the Central Cancer Registry were compared with those to the registry of the NSW Workers' Compensation (Dust Diseases) Board. The latter includes occupational and clinical data. RESULTS: Of the 3090 cases of malignant mesothelioma reported to the Central Cancer Registry between 1972 and 2004, 456 (15%) were female. Altogether 1995 malignant mesotheliomas were compensated between 1969 and 2004, of which 105 (5%) occurred among women. The incidence increased for both genders by approximately 15-fold. Median survival was similar for the men and women for all of the cases (7 versus 6 months), but was better among the women who received compensation (8.5 versus 10.4 months, P<0.0001). The mean disease latency (42.8 years) increased over the study period (P<0.001). CONCLUSIONS: In New South Wales over the last 30 years, the total number of malignant mesotheliomas and the number of compensated cases of malignant mesothelioma have risen for both genders. The mean latency is increasing, and increasing numbers of "nonoccupational" cases are being reported. Survival remains poor.

Asbestos-related occupational lung diseases in NSW, Australia and potential exposure of the general population.

Asbestos is a fibrous silicate which is recognized as causing a variety of lung disorders including malignant mesothelioma of the pleura, lung cancer and asbestosis. Asbestos use has been banned in most developed countries but exposure still occurs under strict regulation in occupational settings and also occasionally in domestic settings. Although the hazards of asbestos are well known in developed countries, awareness of its adverse health effects is less in other parts of the world, particularly when exposure occurs in non-occupational settings. Experience of asbestos use and its adverse heath effects in developed countries such as Australia have resulted in development of expertise in the diagnosis and treatment of asbestos-related diseases as well as in screening and this can be used to help developing countries facing the issue of asbestos exposure.