Baumann F, Maurizot P, Mangeas M, Ambrosi JP, Douwes J, Robineau B.

University of New Caledonia.

Abstract

Background: High incidences of malignant mesothelioma (MM) have been observed in New Caledonia. Previous work showed an association between MM and soil containing serpentinite.

Objectives: To study the spatial and temporal variation of MM and its association with environmental factors.

Methods: All 109 MM cases recorded in the Cancer Registry of New Caledonia between 1984 and 2008 were investigated. Spatial, temporal and space-time cluster analyses were performed. We conducted an ecological analysis involving 100 tribes over a large area including those with the highest incidence rates. Associations with environmental factors were assessed using logistic and Poisson regression analyses.

Results: The highest incidence was observed in the Houaïlou area with a world age standardised rate of 128.7 per 100,000 person-years; 95%CI: 70.41–137.84. A significant spatial cluster grouped 18 tribes (31 observed cases vs 8.12 expected cases, p=0.001), but no significant temporal clusters were identified. The ecological analyses identified serpentinite on roads as the greatest environmental risk factor: odds ratio = 495.0, 95%CI: 46.2–4679.7; multivariate incidence rate ratio = 13.0, 95%CI: 10.2-16.6. The risk increased with serpentinite surface, proximity to serpentinite quarries and distance to the peridotite massif. The association with serpentines was stronger than for amphiboles. Living on a slope and close to dense vegetation appeared protective. The use of whitewash, previously suggested to be a risk factor, was not associated with MM incidence.

Conclusions: Presence of serpentinite on roads is a major environmental risk factor for mesothelioma in New Caledonia.

Archimandriti DT, Dalavanga YA, Cianti R, Bianchi L, Manda-Stachouli C, Armini A, Koukkou AI, Rottoli P, Constantopoulos SH, Bini L.

Department of Pneumonology, Medical School, University of Ioannina, Ioannina, Greece.

Abstract

Inhabitants of Metsovo, NW Greece, have been exposed to an asbestos whitewash, resulting in malignant pleural mesothelioma (MPM) and pleural calcifications (PCs). Interestingly, those with PCs (PC⁺) are less prone to MPM. They also have lymphocytic alveolitis, and differences in bronchoalveolar lavage (BAL) proteins, compared with those without pleural calcifications (PC^-). This may mean a different response to the fiber leading to different susceptibility to neoplasia. To further evaluate this, a proteomic analysis of BAL proteins was performed. Proteomic analysis (2D-electrophoresis/Mass Spectrometry) of BAL in Metsovites nonoccupationally exposed to asbestos revealed increased albumin fragments, alpha1-antitrypsin, S100-A9 and HSP27, suggesting ongoing inflammation. In those without pleural calcifications, increased expression of acid ceramidase, glutathione-S-transferase and presence of calcyphosin, all involved in cell cycle regulation and death as well as in the detoxification of mutagenic and toxic agents, lend further support to our thesis of possible “protection against neoplasia” in Metsovites with pleural calcifications.

Moore AJ, Parker RJ, Wiggins J.

Department of Respiratory Medicine, Wexham Park Hospital, Wexham, Slough, Berkshire, UK. a.moore@ic.ac.uk

Abstract

Malignant mesothelioma is a fatal asbestos-associated malignancy originating from the lining cells (mesothelium) of the pleural and peritoneal cavities, as well as the pericardium and the tunica vaginalis. The exact prevalence is unknown but it is estimated that mesotheliomas represent less than 1% of all cancers. Its incidence is increasing, with an expected peak in the next 10-20 years. Pleural malignant mesothelioma is the most common form of mesothelioma. Typical presenting features are those of chest pain and dyspnoea. Breathlessness due to a pleural effusion without chest pain is reported in about 30% of patients. A chest wall mass, weight loss, sweating, abdominal pain and ascites (due to peritoneal involvement) are less common presentations. Mesothelioma is directly attributable to occupational asbestos exposure with a history of exposure in over 90% of cases. There is also evidence that mesothelioma may result from both para-occupational exposure and non-occupational “environmental” exposure. Idiopathic or spontaneous mesothelioma can also occur in the absence of any exposure to asbestos, with a spontaneous rate in humans of around one per million. A combination of accurate exposure history, along with examination radiology and pathology are essential to make the diagnosis. Distinguishing malignant from benign pleural disease can be challenging. The most helpful CT findings suggesting malignant pleural disease are 1) a circumferential pleural rind, 2) nodular pleural thickening, 3) pleural thickening of > 1 cm and 4) mediastinal pleural involvement. Involvement of a multidisciplinary team is recommended to ensure prompt and appropriate management, using a framework of radiotherapy, chemotherapy, surgery and symptom palliation with end of life care. Compensation issues must also be considered. Life expectancy in malignant mesothelioma is poor, with a median survival of about one year following diagnosis.

Schneider F, Sporn TA, Roggli VL.

Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710, USA. frank.schneider@duke.edu

Abstract

This study reports changes in the frequency of detection of various asbestos fiber types between 1982 and 2005. Crocidolite is increasingly detected in U.S. mesothelioma patients. The percentage of crocidolite fibers detected in lung tissue has risen from 4 to 10%, and the percentage of cases in which crocidolite was detected increased from 19 to 37%. Meanwhile, the frequency of detection of amosite and chrysotile has decreased. The authors performed a detailed analysis of cases in which crocidolite was identified in the absence of amosite. Most of such cases were identified in recent years, a finding of concern since crocidolite is considered the most potent fiber type with respect to the pathogenesis of mesothelioma.

Keywords: amosite; amphiboles; asbestos; crocidolite; mesothelioma

Reid A, Heyworth J, de Klerk N, Musk AW.

Occupational Respiratory Epidemiology, School of Population Health, M431, University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, Australia. Alison.Reid@uwa.edu.au

Abstract

Objectives: Knowledge of mortality patterns following exposure to asbestos has been determined mostly from cohort studies of men who were exposed to asbestos in their workplace. Women are more likely to have obtained their asbestos exposure domestically or from their environment.

Methods: 2552 women and girls are documented to have lived in the blue asbestos mining and milling township of Wittenoom between 1943 and 1992 and were not involved in asbestos mining or milling. Quantitative asbestos exposure measurements were derived from periodic dust surveys undertaken in the industry and around the township. Death records were obtained for the period 1950–2004. Standardised mortality ratios (SMRs) were calculated to compare the Wittenoom women’s mortality with that of the Western Australian female population.

Results: There were 425 deaths, including 30 from malignant mesothelioma. There was excess mortality for all causes of death (SMR = 1.13), all neoplasms (SMR = 1.42), symptoms, signs and ill defined conditions (SMR = 6.35), lung cancer (SMR = 2.15) and pneumoconiosis (SMR = 11.8). Mortality from cancer of the ovary (SMR = 1.52), upper aerodigestive cancers (SMR = 2.70) and tuberculosis (SMR = 5.38) was increased but not significantly. The risk of death from mesothelioma was increased, but not significantly, in residents known to have lived with or washed the clothes of an Australian Blue Asbestos Company asbestos worker (HR = 2.67, 95% CI 0.77 to 9.21; HR = 2.61, 95% CI 0.85 to 7.99, respectively).

Conclusion: Women who were former residents of Wittenoom, exposed to asbestos in their environment or in their home, have excess cancer mortality, including mesothelioma, compared with the Western Australian female population.

Okuda M, Kashio M, Tanaka N, Masuno T, Kamei J, Tsuyuguchi I.

Osaka Hospital, Anti-Tuberculosis Association, Osaka Branch.

Abstract

We report a case of non-tuberculous mycobacteriosis (NTM) with pleurisy in a 75-year-old man. The patient was admitted with a diagnosis of pneumonia. Chest radiography and CT scans revealed a tumorous shadow that increased rapidly in size despite treatment with antibiotics. Bronchoalveolar lavage fluid (BALF) disclosed numerous asbestos bodies, suggesting dense exposure and pulmonary silicosis. The tumorous chest shadow remained undiagnosed. Repeated microscopic examination of sputum and BALF revealed no acidophilic-bacilli. Diagnostic pneumonectomy was performed to further explore the nature of the tumorous shadow on chest radiography. Ziehl-Neelsen staining of excised lung tissue disclosed no acid-bacilli; however, the washed fluid of the tissue specimen showed acid-fast bacilli that were subsequently verified as M. avium by in vitro culture. The X-ray findings in our case were not consistent with NTM or specific for disease due to asbestos inhalation. A final diagnosis of NTM was confirmed via open biopsy of the lung. Our case suggests that in addition to tuberculosis, NTM should be taken into consideration as a complication of silicosis.

Musti M, Pollice A, Cavone D, Dragonieri S, Bilancia M.

Department of Internal Medicine and Public Medicine, Section of Occupational Medicine "Ramazzini", University of Bari, National Register of Mesothelioma, Regional Operative Centre (C.O.R.), Apulia, Italy.

Abstract

Objectives: To estimate the mesothelioma risk and environmental asbestos exposure (EAE) due to an asbestos-cement plant.

Methods: A spatial case–control study including 48 malignant mesothelioma (MM) cases occurred in the period 1993–2003 selected from the regional mesothelioma register (RMR) and 273 controls. The disease risk was estimated by means of a logistic-regression model, in which the probability of disease-occurrence is expressed as a function of the classes of distances. A non-parametric method was applied to estimate the full relative risk surface.

Results: Significant MM odds ratio of 5.29 (95 CI: 1.18–23.74) was found for people living within a range up to 500 m centered on the plant. The non-parametric estimation of relative risk surface unveiled a marked peak near the plant not paralleled by the spatial distribution of controls.

Conclusion: Evidence of an association between mesothelioma risk and EAE is highlighted. The role played by the RMR in increasing the public health local authorities awareness is stressed.

Keywords Asbestos-cement plant – Environmental-neighborhood exposure – Mesothelioma register – Spatial case–control study – Public health – Italy

Reid A, Berry G, Heyworth JS, de Klerk N, Musk AB.

University of Western Australia, Australia

Abstract

Introduction: Nearly 3,000 women and girls were documented to have lived at the blue asbestos mining and milling town of Wittenoom, in Western Australia between 1943 and 1992. Eight percent of deaths among these women to the end of 2004 have been from malignant mesothelioma of the pleura. AIM: To predict future mortality from mesothelioma to 2030 in this cohort.

Methods: Mesothelioma mortality rates incorporating parameters for cumulative exposure, a power of time since first exposure and annual rates of fibre clearance from the lung were calculated from maximum likelihood estimates. These rates plus age specific mortality rates for Western Australian females incorporating an excess lung cancer risk were then applied to all the Wittenoom cohort women surviving to the end of 2004, in yearly increments, to predict the future numbers of cases of mesothelioma to 2030.

Results: There were 40 deaths from mesothelioma among the Wittenoom women to the end of 2004. Using a range of models that incorporate time since first exposure, competing risks from other diseases, latency periods and clearance of mesothelioma from the lungs we predict 66 (lowest estimate) to 87 (highest estimate) deaths from mesothelioma until 2030. This represents one and a half to two and a half times the number of deaths that have already occurred to the end of 2004.

Conclusion: The high toll from mesothelioma in this cohort of women and girls will continue well into the future.

Weiner SJ, Neragi-Miandoab S.

Cleveland Clinic Lerner College of Medicine, 9500 Euclid Avenue, Cleveland, OH, USA.

Abstract

Background: Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor for which no effective therapy exists despite the discovery of many possible molecular and genetic targets. The late stage of MPM diagnosis and the long latency that exist between some exposures and diagnosis have made it difficult to comprehensively evaluate the role of risk factors and their downstream molecular effects.

Methods: This manuscript is a review of current literature about the pathogenesis of malignant mesothelioma. In this overview, current published studies concerning pathogenesis of malignant mesothelioma are reviewed, with insights into its etiology and pathogenesis. We searched pubmed using the following subjects: mesothelioma, radiation, genetics, pediatric malignant mesothelioma, SV40 virus, and growth factors. We selected 350 valuable articles of which 152 sources were used to complete this review.

Conclusion: Many risk factors for MPM development have been recognized including environmental exposures, genetic susceptibility, viral contamination, and radiation. In this review, we discuss the current molecular and genetic contributors to MPM pathogenesis and the risk factors associated with these carcinogenic processes.

Keywords: Radiation – Genetics – Pediatric malignant mesothelioma – SV40 virus – Growth factors

Miles SE, Sandrini A, Johnson AR, Yates DH.

Dust Diseases Board Research & Education Unit, Sydney, NSW, Australia. Deborahy88@hotmail.com.

Abstract

Asbestos-related diffuse pleural thickening (DPT), or extensive fibrosis of the visceral pleura secondary to asbestos exposure, is increasingly common due to the large number of workers previously exposed to asbestos. It may coexist with asbestos related pleural plaques but has a distinctly different pathology. The pathogenesis of this condition as distinct from pleural plaques is gradually becoming understood. Generation of reactive oxygen and nitrogen species, profibrotic cytokines and growth factors in response to asbestos is likely to play a role in the formation of a fibrinous intrapleural matrix. Benign asbestos related pleural effusions commonly antedate the development of diffuse pleural thickening. Environmental as well as occupational exposure to asbestos may also result in pleural fibrosis, particularly in geographic areas with naturally occurring asbestiform soil minerals. Pleural disorders may also occur after household exposure. High resolution computed tomography (CT) is more sensitive and specific than chest radiography for the diagnosis of diffuse pleural thickening, and several classification systems for asbestos-related disorders have been devised. Magnetic resonance imaging and fluorodeoxyglucose positron emission tomography (PET) scanning may be useful in distinguishing between DPT and malignant mesothelioma. DPT may be associated with symptoms such as dyspnoea and chest pain. It causes a restrictive defect on lung function and may rarely result in respiratory failure and death. Treatment is primarily supportive.