Pleural Fluid Mesothelin as an Adjunct to the Diagnosis of Pleural Malignant Mesothelioma

Rationale:. The diagnosis of pleural malignant mesothelioma (MM) by effusion cytology may be difficult and is currently controversial. Effusion mesothelin levels are increased in patients with MM but the clinical role of this test is uncertain. Objectives:. To determine the clinical value of measuring mesothelin levels in pleural effusion supernatant to aid diagnosis of MM. Methods and Measurements. Pleural effusion samples were collected prospectively from 1331 consecutive patients. Mesothelin levels were determined by commercial ELISA in effusions and their relationship to concurrent pathology reporting and final clinical diagnosis was determined. Results:. 2156 pleural effusion samples from 1331 individuals were analysed. The final clinical diagnosis was 183 MM, 436 non-MM malignancy, and 712 nonmalignant effusions. Effusion mesothelin had a sensitivity of 67% for MM at 95% specificity. Mesothelin was elevated in over 47% of MM cases in effusions obtained before definitive diagnosis of MM was established. In the setting of inconclusive effusion cytology, effusion mesothelin had a positive predictive value of 79% for MM and 94% for malignancy. Conclusions:. A mesothelin-positive pleural effusion, irrespective of the identification of malignant cells, indicates the likely presence of malignancy and adds weight to the clinical rationale for further investigation to establish a malignant diagnosis

Serum mesothelin for early detection of asbestos-induced cancer malignant mesothelioma

Background: Malignant mesothelioma is an aggressive, almost uniformly fatal tumor, primarily caused by exposure to asbestos. Since the recent discovery that serum mesothelin is a sensitive and highly specific biomarker for mesothelioma, one of the key issues raised is whether mesothelin levels represent a useful screening test for asbestos-exposed at-risk individuals. In this study, soluble mesothelin was determined in sequential serum samples collected from asbestos-exposed individuals before the development of mesothelioma. Methods: Archival serum samples from 106 individuals who developed mesothelioma, 99 asbestosexposed individuals from the Wittenoom Cancer Surveillance Program, and 109 non-asbestos-exposed individuals from the Busselton Health Survey were identified. Serum mesothelin concentrations were determined using the MESOMARK assay. Results: Longitudinal mesothelin levels determined in healthy asbestos-exposed individuals over a period of 4 years were stable (Pearson's r = 0.96; P < 0.0001). There was no correlation between mesothelin concentration and cumulative asbestos exposure. Mesothelin concentrations were greater than the threshold value of 2.5 nmol/L in the penultimate serum sample before the diagnosis of mesothelioma in 17 of 106 people. Using an increase above the 95% confidence interval of the mean of a given individual's longitudinal mesothelin results, 33 of 82 individuals had increasing mesothelin levels before diagnosis. Conclusion: In a population with a high pretest probability of developing mesothelioma, the serum biomarker mesothelin is elevated in absolute terms in 15% and in relative terms in 40% of the group. Impact: Future studies examining a combination of biomarkers could improve sensitivity of screening. ©2010 AACR

Plasma retinol and total carotenes and fracture risk after long-term supplementation with high doses of retinol

Observational studies suggest that moderate intakes of retinol and increased circulating retinol levels may increase fracture risk. Easy access to supplements, combined with an aging population, makes this a potentially important association. The aim of this study was to investigate plasma retinol and total carotene concentrations in relation to fracture risk after long-term supplementation with retinol and/or beta-carotene in 998 adults between 1990 and 2007. Methods: Participants were 663 men and 335 women in a cancer prevention program who were initially randomized to a retinol (7.5 mg RE/d) or beta-carotene (30 mg/d) supplement between 1990 and 1996. After 1996, all participants received the retinol supplement only. Plasma retinol and total carotene, medication use and various lifestyle factors were measured at annual clinic visits. Fractures were identified by self-report in 2007. The risk for any fracture or osteoporotic fracture was modeled using Cox proportional hazard models.Results: Over a median follow-up of 7.8 y, 123 participants with plasma samples reported an incident fracture. Although plasma retinol concentrations were markedly higher than those reported in observational studies, no association was observed between plasma retinol and risk for any fracture (hazard ratio [HR], 0.86 μmol/L; 95% confidence interval [CI], 0.65–1.14) or osteoporotic fracture (HR, 0.97 μmol/L; 95% CI, 0.66–1.43). A lower risk for any fracture was suggested with increasing plasma total carotenes (HR, 0.85 μmol/L; 95% CI, 0.71–1.01). Conclusions: This study does not support earlier reports of an increased fracture risk associated with increased plasma retinol concentration. The potential for carotenes to prevent fractures deserves further investigation

The mental health of asbestos-exposed subjects with pleural abnormalities

Purpose: To examine the effect of knowledge of radiographic abnormalities on the mental health of asbestos-exposed people with and without pleural abnormalities. Methods: Subjects were former asbestos mine and mill workers and residents of the mining town who had participated in an annual health review program. Pleural abnormalities (pleural plaques, diffuse pleural thickening and asbestosis) were determined from plain chest X-rays. All Participants completed a questionnaire on mental health status (SF-12) and locus of control (LOC). Results: There were no significant differences between asbestos-exposed people with and without radiographic abnormalities for either the SF-12 mental health score or LOC. However, the asbestos-exposed cohorts had lower mental health scores compared with a random sample of the local population. Conclusion: The presence of pleural abnormalities did not further affect the mental health of asbestos-exposed people beyond a decrement associated with exposure per se