Malignant mesothelioma in a cohort of asbestos insulation workers: clinical presentation, diagnosis, and causes of death

Malignant mesothelioma has been rare in the general population. In recent decades its incidence has risen dramatically, parallel to the increasing use of asbestos in industry since 1930. Altogether 17,800 asbestos insulation workers, members of the International Association of Heat and Frost Insulators and Asbestos Workers (AFL-CIO-CLC) in the United States and Canada, were enrolled for prospective study on 1 January 1967 and followed up to the present. Every death that occurs is investigated by our laboratory. One hundred and seventy five deaths from mesothelioma occurred among the 2221 men who died in 1967-76 and 181 more such deaths in the next eight years. Altogether, 356 workers had died of malignant mesothelioma (pleural or peritoneal) by 1984. Diagnosis of mesothelioma was accepted only after all available clinical, radiological, and pathological material was reviewed by our laboratory and histopathological confirmation by the pathology unit made in each case. One hundred and thirty four workers died of pleural and 222 of peritoneal mesothelioma. Age at onset of exposure, age at onset of the disease, and age at death were similar in both groups of patients. Significant difference was noted only in the time elapsed from onset of exposure to the development of first symptoms, which was longer in the group with peritoneal mesothelioma. Shortness of breath, either new or recently increased, and chest pain were the most frequent presenting symptoms in the group with pleural mesothelioma; abdominal pain and distension were frequent in the patients with peritoneal mesothelioma. Pleural effusion or ascites were found in most patients. The most effective approach to the diagnosis of malignant pleural mesothelioma in these cases was by open lung biopsy; exploratory laparotomy was best for diagnosing peritoneal mesothelioma. Patients with pleural mesothelioma died principally from pulmonary insufficiency whereas those with peritoneal mesothelioma succumbed after a period of pronounced wasting.     

Survival of asbestos insulation workers with mesothelioma.

Malignant mesothelioma is a lethal disease. It is rare in the general population; however, workers exposed to asbestos suffer significant burdens of the neoplasm. The survival time of 457 consecutive fatal cases of pleural and peritoneal mesothelioma that occurred among 17,800 asbestos insulation workers observed prospectively from 1 January 1967 to 1 January 1987 was studied. Mean survival time from initial presentation of the disease to death was 11.4 months for the pleural mesothelioma patients compared with 7.4 months for the peritoneal group. This difference was statistically significant. Mean survival time from diagnosis to death was shorter for both groups of patients: 8.4 months for pleural mesothelioma v 5.8 months for the peritoneal cases. In conclusion, survival time in mesothelioma patients is short; most die within a year from the onset of the initial symptoms. No effective therapy is yet available.     

Influence of age at death on accuracy of death certificate disease diagnosis: findings in 475 consecutive deaths of mesothelioma among asbestos insulation workers and asbestos factory workers.

Age at death had no appreciable influence on accuracy of death certificate diagnoses of 475 consecutive deaths of mesothelioma among asbestos insulation and asbestos factory workers, until age 75 or older.     

Amosite mesothelioma in a cohort of asbestos workers

A cohort of 820 asbestos workers with a short duration of exposure to amosite between 1941 and 1945 was followed. These men were alive five years after starting work and were observed until 1988. Seventeen cases of malignant mesothelioma (eight pleural, nine peritoneal) were found. The mean age at the onset of exposure was 33 years for men with pleural mesothelioma and 30 years for those with peritoneal mesothelioma. Chest pain was the main symptom in pleural mesothelioma and abdominal pain in peritoneal mesothelioma. Open lung biopsy was the most useful diagnostic approach for pleural mesothelioma, whereas for peritoneal mesothelioma it was exploratory laparotomy. Pleural patients died of pulmonary insufficiency, and peritoneal patients of wasting and inanition. In both groups the death certificate diagnosis was less accurate than the clinical diagnosis at death. The mean survival was 12.5 months from first symptom to death for the pleural group and 5.4 months for the peritoneal group.     

Non-malignant chest x ray changes in patients with mesothelioma in a large cohort of asbestos insulation workers.

To assess the prevalence of non-malignant chest x ray abnormalities in cases of mesothelioma 184 cases of mesothelioma (72 pleural and 112 peritoneal) which had occurred in a cohort of asbestos insulation workers followed up since 1967 were studied. Chest x ray films of satisfactory quality, on which the presence or absence of non-malignant radiological changes indicating interstitial pulmonary fibrosis or pleural fibrosis or both, could be assessed with a high degree of certainty were available. In some cases (20% for pleural mesothelioma, 11.6% for peritoneal mesothelioma) non-malignant radiological changes were not radiologically detectable. Parenchymal interstitial fibrosis (small irregular opacities) only was found in a proportion of cases (25.4% of pleural mesotheliomas, 12.5% of peritoneal mesotheliomas). Pleural fibrosis only was detected in 17% of cases of pleural mesothelioma and 27% of cases of peritoneal mesothelioma. Most patients had both parenchymal and pleural fibrosis. Although these results tend to indicate that in peritoneal mesothelioma the proportion of pleural fibrosis is significantly higher, these findings might have been due to the fact that in most cases of pleural mesothelioma non-malignant changes were interpreted in one hemithorax only. In 46 cases (21 pleural, 25 peritoneal) in which sufficient lung tissue was available histopathology of lung parenchyma indicated the presence of interstitial fibrosis; in 20 (43.5%) of these the chest x ray film had been read as negative. Thus the absence of radiologically detectable small opacities on the chest x ray film does not exclude the existence of interstitial pulmonary fibrosis in cases of mesothelioma among insulation workers. With lower levels of exposure (such as in family contacts of asbestos workers) it is conceivable that mesothelioma might occur in the absence of interstitial pulmonary fibrosis.     

Non-malignant chest x ray changes in patients with mesothelioma in a large cohort of asbestos insulation workers

To assess the prevalence of non-malignant chest x ray abnormalities in cases of mesothelioma 184 cases of mesothelioma (72 pleural and 112 peritoneal) which had occurred in a cohort of asbestos insulation workers followed up since 1967 were studied. Chest x ray films of satisfactory quality, on which the presence or absence of non-malignant radiological changes indicating interstitial pulmonary fibrosis or pleural fibrosis or both, could be assessed with a high degree of certainty were available. In some cases (20% for pleural mesothelioma, 11.6% for peritoneal mesothelioma) non-malignant radiological changes were not radiologically detectable. Parenchymal interstitial fibrosis (small irregular opacities) only was found in a proportion of cases (25.4% of pleural mesotheliomas, 12.5% of peritoneal mesotheliomas). Pleural fibrosis only was detected in 17% of cases of pleural mesothelioma and 27% of cases of peritoneal mesothelioma. Most patients had both parenchymal and pleural fibrosis. Although these results tend to indicate that in peritoneal mesothelioma the proportion of pleural fibrosis is significantly higher, these findings might have been due to the fact that in most cases of pleural mesothelioma non-malignant changes were interpreted in one hemithorax only. In 46 cases (21 pleural, 25 peritoneal) in which sufficient lung tissue was available histopathology of lung parenchyma indicated the presence of interstitial fibrosis; in 20 (43.5%) of these the chest x ray film had been read as negative. Thus the absence of radiologically detectable small opacities on the chest x ray film does not exclude the existence of interstitial pulmonary fibrosis in cases of mesothelioma among insulation workers. With lower levels of exposure (such as in family contacts of asbestos workers) it is conceivable that mesothelioma might occur in the absence of interstitial pulmonary fibrosis.     

Prediction of mesothelioma and lung cancer in a cohort of asbestos exposed workers

BACKGROUND: Several papers have reported state-wide projections of mesothelioma deaths, but few have computed these predictions in selected exposed groups. OBJECTIVE: To predict the future deaths attributable to asbestos in a cohort of railway rolling stock workers. METHODS: The future mortality of the 1,146 living workers has been computed in term of individual probability of dying for three different risks: baseline mortality, lung cancer excess, mesothelioma mortality. Lung cancer mortality attributable to asbestos was calculated assuming the excess risk as stable or with a decrease after a period of time since first exposure. Mesothelioma mortality was based on cumulative exposure and time since first exposure, with the inclusion of a term for clearance of asbestos fibres from the lung. RESULTS: The most likely range of the number of deaths attributable to asbestos in the period 2005-2050 was 15-30 for excess of lung cancer, and 23-35 for mesothelioma. CONCLUSION: This study provides predictions of asbestos-related mortality even in a selected cohort of exposed subjects, using previous knowledge about exposure-response relationship. The inclusion of individual information in the projection model helps reduce misclassification and improves the results. The method could be extended in other selected cohorts.     

Malignant mesothelioma: attributable risk of asbestos exposure.

OBJECTIVES--To evaluate a case-control study of malignant mesothelioma through patterns of exposure to asbestos based upon information from telephone interviews with next of kin. METHODS--Potential cases, identified from medical files and death certificates, included all people diagnosed with malignant mesothelioma and registered during 1975-1980 by the Los Angeles County Cancer Surveillance Program, the New York State Cancer Registry (excluding New York City), and 39 large Veterans Administration hospitals. Cases whose diagnosis was confirmed in a special pathology review as definite or probable mesothelioma (n = 208) were included in the analysis. Controls (n = 533) had died of other causes, excluding cancer, respiratory disease, suicide, or violence. Direct exposure to asbestos was determined from responses to three types of questions: specific queries as to any exposure to asbestos; occupational or non-vocational participation in any of nine specific activities thought to entail exposure to asbestos; and analysis of life-time work histories. Indirect exposures were assessed through residential histories and reported contact with family members exposed to asbestos. RESULTS--Among men with pleural mesothelioma the attributable risk (AR) for exposure to asbestos was 88% (95% confidence interval (95% CI) 76-95%). For men, the AR of peritoneal cancer was 58% (95% CI 20-89%). For women (both sites combined), the AR was 23% (95% CI 3-72%). The large differences in AR by sex are compatible with the explanations: a lower background incidence rate in women, lower exposure to asbestos, and greater misclassification among women. CONCLUSIONS--Most of the pleural and peritoneal mesotheliomas in the men studied were attributable to exposure to asbestos. The situation in women was less definitive.     

Malignant mesothelioma: incidence, asbestos exposure, and reclassification of histopathology.

The Los Angeles County Cancer Surveillance Program abstracts records on almost all cases of cancer occurring in the county. In a study of those cases of pleural and peritoneal malignant mesothelioma (MM) that occurred from 1972 to 1979 occupational histories were obtained during interviews, and histopathology of the tumours was reviewed and classified by a member of a mesothelioma reference panel who was unaware of the exposure histories. About half the cases reviewed had likely exposure to asbestos at work. The greatest proportion of cases designated as MM by the pathologist occurred among individuals likely to have had the heaviest exposure of asbestos (42%). No upward trend of incidence over time was apparent among cases designated as MM. The age adjusted incidence rates for designated MM were lower than in other studies. The well recognised interobserver variability in diagnosing MM apparently produces raised estimates of incidence and an overestimate of trends of incidence. The interobserver variability may result from different awareness of MM occurrence, a lack of precise histopathological criteria for the diagnosis, or the influence of a history of exposure to asbestos on the interpretation. A history of exposure to asbestos may bias interpretation of histopathology and should not be used to make the histological diagnosis.     

Malignant mesothelioma in Emilia-Romagna: incidence and asbestos exposure

This paper describes the activity, the sources of informations, methods and results of the "Emilia-Romagna Mesothelioma Registry" (ReM). The Registry started in 1996 and collects all cases of Malignant Mesothelioma (MM) occurring in Emilia-Romagna. 323 new cases (225 males and 98 females) have been detected during the period 1996-2001. Most cases (n = 286) concerned pleura. Other observed localizations were: peritoneum (n = 30), tunica vaginalis testis (n = 4) and pericardium (n = 3). Most of the cases were reported by the Institutes of Pathology and Occupational Health and by the Safety Services (respectively the 62% and the 18%). 87% of all the cases were histologically, 8% TC, 4% radiologically and only 1% clinically confirmed. The regional incidence rate (for 10(5) person-years, age standardized on the 1991 Italian population), has been estimated to be 1.98 in males and 0.88 in females. The highest rates were registered in Piacenza and Reggio Emilia province among men and Reggio Emilia and Ravenna province among women. 72% of cases have been classified as exposed to asbestos (64% occupationally and 8% as domestic/environmentally exposed).     

Cancer mortality and incidence of mesothelioma in a cohort of wives of asbestos workers in Casale Monferrato, Italy

BACKGROUND: Family members of asbestos workers are at increased risk of malignant mesothelioma (MM). Although the hazard is established, the magnitude of the risk is uncertain, and it is unclear whether risk is also increased for other cancers. Few cohort studies have been reported. OBJECTIVE: The "Eternit" factory of Casale Monferrato (Italy), active from 1907 to 1986, was among the most important Italian plants producing asbestos-cement (AC) goods. In this article we present updated results on mortality and MM incidence in the wives of workers at the factory. METHODS: We studied a cohort of 1,780 women, each married to an AC worker during his employment at the factory but not personally occupationally exposed to asbestos. Cohort membership was defined starting from the marital status of each worker, which was ascertained in 1988 from the Registrar's Office in the town where workers lived. At the end of follow-up (April 2003), 67% of women were alive, 32.3% dead, and 0.7% lost to follow-up. Duration of exposure was computed from the husband's period of employment. Latency was the interval from first exposure to the end of follow-up. RESULTS: The standardized mortality ratio (SMR) for pleural cancer [21 observed vs. 1.2 expected; SMR = 18.00; 95% confidence interval (CI), 11.14-27.52] was significantly increased. Mortality for lung cancer was not increased (12 observed vs. 10.3 expected; SMR = 1.17; 95% CI, 0.60-2.04). Eleven incident cases of pleural MM were observed (standardized incidence ratio = 25.19; 95% CI, 12.57-45.07). CONCLUSIONS: Household exposure, as experienced by these AC workers' wives, increases risk for pleural MM but not for lung cancer.     

Malignant mesothelioma: clustering in a family producing asbestos cement in their home.

In a family with a remarkable aggregation of malignant mesothelioma the father, mother, and a son all died of the condition, whereas two other sons and a daughter were unaffected. From 1944 to 1961 the family produced a material that was used to fix screws in drilled holes and consisted of amosite, gypsum, and sand. It was produced in the basement of their villa and was described as being a dusty job. The father died in 1984 aged 74, the son in 1985 aged 45, and the mother in 1987 aged 79. It is concluded that there is a high risk of malignant mesothelioma after massive exposure to amosite and the risk and latency period are independent of age during the exposure.     

Malignant mesothelioma: global incidence and relationship with asbestos

Mesothelioma incidence varies markedly from one country to another. The highest annual crude incidence rates (about 30 cases per million) are observed in Australia, Belgium, and Great Britain. A lot of data indicate a relationship between mesothelioma and asbestos. The hot areas for mesothelioma exactly correspond to the sites of industries with high asbestos use, such as shipbuilding and asbestos-cement industry. However, in many countries with high asbestos consumption, mesothelioma incidence is low. The reasons for this fact are not clear. The latency periods elapsing between first exposure to asbestos and development of mesothelioma are mostly longer than 40 yr. An inverse relationship exists between intensity of asbestos exposure and length of the latency period. Mesothelioma generally develops after long-time exposures to asbestos. Some recent studies show that the risk increases with the duration of exposure. Possible co-factors in the pathogenesis of asbestos-related mesothelioma include genetic predisposition, diets poor in fruit and vegetables, viruses, immune impairment, recurrent serosal inflammation. The study of co-morbidity in mesothelioma could give an insight into the pathogenesis of the tumor. While a levelling-off in mesothelioma incidence has been registered in some countries, a worsening of the epidemic is predictable in large parts of the world.     

Asbestosis: interstitial pulmonary fibrosis and pleural fibrosis in a cohort of asbestos insulation workers: influence of cigarette smoking

A cohort of 1,117 asbestos insulation workers was established in 1963 and has been prospectively followed since then. Chest X-ray abnormalities detected at the initial medical examination, and interpreted according to the International Labour Office Classification of Radiographs of Pneumoconioses are reported in this paper. The prevalence of all radiographic abnormalities (pleural and pulmonary) increased with duration from onset of asbestos exposure. A positive smoking history was associated with a significantly higher prevalence of small irregular opacities indicating interstitial pulmonary fibrosis. Such an association was not found for pleural fibrosis. The possible mechanisms which underlie the effect of smoking on asbestos-induced interstitial fibrosis seem to be of much less importance in the development of pleural fibrosis. Progression of radiographic changes over the 20-year interval 1963-1983 will be separately reported as will the predictive significance of these changes.     

Prediction of mesothelioma, lung cancer, and asbestosis in former Wittenoom asbestos workers.

Projections have been made of the number of mesotheliomas, lung cancers, and cases of asbestosis that might occur over the period 1987 to 2020 in former workers at the Wittenoom crocidolite asbestos mine in Western Australia. Predictions were based on the observed mortality to the end of 1986 and modelling of the mesothelioma rate. Elimination of crocidolite from the lungs was included in the model. Between the years 1987 and 2020 it is predicted that between 250 and 680 deaths will occur due to mesothelioma. This wide range is due to uncertainty on the functional form of the relation between mesothelioma rate and time, and insufficient data to estimate the elimination rate of crocidolite from the lungs. The most likely range is the lower half of this total range--that is, between 250 and 500. It is predicted that between 340 and 465 deaths will occur due to lung cancer. About 45% of these deaths would be attributable to exposure to asbestos. It is estimated that currently there are up to 200 cases of undiagnosed asbestosis. Of these about 50 will die of lung cancer or mesothelioma and are therefore also included in the figures above. Up to 60 former workers may develop the first signs of asbestosis in the future but any such cases are likely to progress to more serious disease at a much slower rate than the cases that have already been identified.     

Prediction of mesothelioma, lung cancer, and asbestosis in former Wittenoom asbestos workers.

Projections have been made of the number of mesotheliomas, lung cancers, and cases of asbestosis that might occur over the period 1987 to 2020 in former workers at the Wittenoom crocidolite asbestos mine in Western Australia. Predictions were based on the observed mortality to the end of 1986 and modelling of the mesothelioma rate. Elimination of crocidolite from the lungs was included in the model. Between the years 1987 and 2020 it is predicted that between 250 and 680 deaths will occur due to mesothelioma. This wide range is due to uncertainty on the functional form of the relation between mesothelioma rate and time, and insufficient data to estimate the elimination rate of crocidolite from the lungs. The most likely range is the lower half of this total range--that is, between 250 and 500. It is predicted that between 340 and 465 deaths will occur due to lung cancer. About 45% of these deaths would be attributable to exposure to asbestos. It is estimated that currently there are up to 200 cases of undiagnosed asbestosis. Of these about 50 will die of lung cancer or mesothelioma and are therefore also included in the figures above. Up to 60 former workers may develop the first signs of asbestosis in the future but any such cases are likely to progress to more serious disease at a much slower rate than the cases that have already been identified.