Asbestos exposure and differences in occurrence of peritoneal mesothelioma between men and women across countries

Objective

In several countries the incidence of peritoneal mesotheliomas among women closely mirrors the pattern among men. The aim was to investigate the role of asbestos exposure in the aetiology of peritoneal mesotheliomas in women and men.

Methods

All cases of peritoneal mesothelioma were selected from the Swedish and Netherlands Cancer Registers for the period 1989–2003. For both countries incidence rates were calculated and stratified by sex. A linear regression analysis was used to analyse the existence of a trend over time.

Results

Among men the incidence rate of peritoneal mesothelioma in the Netherlands (0.60 per 100 000 persons) was consistently higher than in Sweden with an average ratio of 1.8 (range 1.4–2.8). In both countries no trend over time was observed. During the 15-year period in the Netherlands the incidence rate among men was about 3.3-fold higher than among women. In Sweden the incidence rate among women was slightly higher than in men up to 1999, and thereafter about threefold higher among men. This sudden shift was statistically significant and seemed mainly caused by changes in classification of peritoneal tumours.

Conclusion

The absence of a time trend in the incidence rate of peritoneal mesothelioma in the Netherlands and Sweden in the past 15 years may point to a more limited role of occupational exposure to asbestos in the aetiology of peritoneal mesothelioma than for pleural mesothelioma, especially among women. The observed drop around 2000 in annual incidence of peritoneal mesothelioma among Swedish women indicates the presence in the past of a substantial misclassification with other tumours in the peritoneum.In many Western countries the pleural mesothelioma incidence among men has increased dramatically in the past 30 years.¹ In recent years in some countries a deceleration or leveling off of mesothelioma rates has been observed,^2,3,4 whereas in other countries the mesothelioma incidence is still expected to rise until 2020.^5,6,7 These trends have been attributed to occupational exposure to asbestos which has been substantial throughout the workforce from the 1930s up to the 1980s. It was estimated that among men with pleural mesothelioma the attributable risk was 88%.⁸ In some countries the pleural mesothelioma risk among women appears to be constant over time, suggesting that the incidence among women may be less dependent on occupational asbestos exposure.^2,5,8 It has also been suggested that the constant incidence among women implies that environmental exposure to asbestos is associated with a negligible risk⁵ or that the typical levels of environmental asbestos exposure will not exceed the threshold for mesothelioma risk.²Peritoneal mesothelioma is also linked to asbestos exposure, although with a much lower attributable risk than for pleural mesothelioma—that is, about 58% among men and less than 23% among women.⁸ Another study on elevated asbestos fibre contents in lung tissue concluded that 75% of peritoneal mesothelioma in men were most likely asbestos-related, whereas only 33% of the cases among women were attributed to asbestos exposure.⁹ It has been suggested that peritoneal mesotheliomas occur primarily among workers with higher cumulative exposures¹⁰ and that the risk increases more steeply at high exposures compared with pleural mesothelioma.^11,12 The participation of women in the industrial workforce was low, especially in occupations with high asbestos exposure such as insulators, miners and shipyard workers. Thus, a primary hypothesis would be that the peritoneal mesothelioma rates between men and women differ at least to the same extent as those for pleural mesothelioma.Trends in peritoneal mesothelioma among men and women are not as well described as trends for pleural mesothelioma. However, in the few countries with published data on trends, the annual incidence of peritoneal mesothelioma among women closely mirrors the pattern among men.^6,13,14 This surprising finding raises several important questions. First, is peritoneal mesothelioma in women the same disease as peritoneal mesothelioma among men? Second, do peritoneal mesothelioma and pleural mesothelioma differ between men and women with regard to asbestos exposure as a causal factor? The aims of this paper are to analyse differences in incidence rates of peritoneal mesothelioma in two countries and to evaluate time trends in incidence of peritoneal mesothelioma among men and women.     

Asbestos and mesothelioma in Scotland

Summary A retrospective study of the incidence of mesothelioma in Scotland and its association with asbestos is described. For the years 1950–1967, 80 cases were traced from pathological reports and biopsy material of malignant tumours invading the peritoneum and pleura. Detailed histories of residence, occupation and degree of exposure to asbestos were obtained from relatives or friends for these 80 cases and also for two sets of controls matched for age and sex. The incidence of mesothelioma in Scotland was confirmed to be associated with exposure to asbestos and its incidence was shown to be similar to that in other areas of Britain.     

Asbestos burden predicts survival in pleural mesothelioma

BACKGROUND: Malignant pleural mesothelioma (MPM) is a rapidly fatal asbestos-associated malignancy with a median survival time of <1 year following diagnosis. Treatment strategy is determined in part using known prognostic factors. OBJECTIVE: The aim of this study was to examine the relationship between asbestos exposure and survival outcome in MPM in an effort to advance the understanding of the contribution of asbestos exposure to MPM prognosis. METHODS: We studied incident cases of MPM patients enrolled through the International Mesothelioma Program at Brigham and Women's Hospital in Boston, Massachusetts, using survival follow-up, self-reported asbestos exposure (n=128), and a subset of cases (n=80) with quantitative asbestos fiber burden measures. RESULTS: Consistent with the established literature, we found independent, significant associations between male sex and reduced survival (p<0.04), as well as between nonepithelioid tumor histology and reduced survival (p<0.02). Although self-reported exposure to asbestos was not predictive of survival among our cases, stratifying quantitative asbestos fiber burden [number of asbestos bodies per gram of lung (wet weight)] into groups of low (0-99 asbestos bodies), moderate (100-1,099), and high fiber burden (>1,099), suggested a survival duration association among these groups (p=0.06). After adjusting for covariates in a Cox model, we found that patients with a low asbestos burden had a 3-fold elevated risk of death compared to patients with a moderate fiber burden [95% confidence interval (CI), 0.95-9.5; p=0.06], and patients with a high asbestos burden had a 4.8-fold elevated risk of death (95% CI, 1.5-15.0; p<0.01) versus those with moderate exposure. CONCLUSION: Our data suggest that patient survival is associated with asbestos fiber burden in MPM and is perhaps modified by susceptibility.     

Asbestos tissue burden study on human malignant mesothelioma

Asbestos fibers in the lung and mesothelial tissues (mesotheliomatous tissue and hyaline plaque) taken from 151 human malignant mesothelioma cases were identified and characterized by high resolution analytical electron microscopy. Asbestos fibers were present in almost all of the lung tissue as well as in the mesothelial tissue. The most common asbestos types seen in the lung were an admixture of chrysotile with amphiboles followed by amphiboles alone and chrysotile alone. The majority of asbestos types seen in the mesothelial tissues were chrysotile alone, followed by chrysotile plus amphibole and amphibole alone. A disproportion of asbestos types between the lung and mesothelial tissues was frequently observed. The most common pattern of the disproportion was chrysotile plus amphibole(s) in the lung and chrysotile only in the mesothelial tissues, followed by amphibole(s) in the lung and chrysotile only in the mesothelial tissues. Such a disproportion was considered to have been caused by chrysotile fiber's strong capacity to translocate from the lung to mesothelial tissues. The number of asbestos fibers in the lung was 456.4 x 10(6) fibers/dry gram in maximum, 0.08 x 106 fibers/dry gram in minimum and 105 x 10(6) fibers/dry gram on average; in the mesothelial tissues it was 240.0 x 106 fibers/dry gram in maximum, 0.03 x 106 fibers/dry gram in minimum and 49.84 x 106 fibers/dry gram on average. These numbers were greater than those seen in the general population. The majority of asbestos fibers detected in the lung and mesothelial tissues were shorter than 5 microm in length. Asbestos fibers fit to Stanton's hypothetical dimensions (> or =8.0 microm in length and < or =0.25 microm in diameter) were only 4.0%, since the majority of these fibers were shorter (<8 microm) and thinner (<0.25 microm) fibers. We concluded that such short, thin asbestos fibers should not be excluded from those contributing to the induction of human malignant mesothelioma. The present study supports that chrysotile asbestos can induce human malignant mesothelioma, since, in some of the mesothelioma cases, asbestos fibers detected in both the lung and mesothelial tissues, or lung tissue alone or mesothelial tissues alone were exclusively chrysotile fibers.     

Asbestos fiber analysis in 27 malignant mesothelioma cases.

The asbestos body counts per 5 gm wet lung tissue in 27 (23 pleural and 4 peritoneal) malignant mesothelioma cases derived from 19 autopsy and 8 surgical cases were, according to our own criteria, low level exposure in 13 cases (48.2%), moderate level exposure in 2 cases (7.4%), and high level exposure in 12 cases (44.4%). In our previous study on 235 consecutive autopsy cases, the low level exposure was considered to be environmental, the moderate level was secondary or blue collar, and the high level was occupational. In the present study, about half of the cases examined (44.4%, high level exposure) are closely related to some occupational asbestos exposure and the other half (48.2%) to environmental exposure. The type and size of asbestos fibers from the 12 cases of high level exposure were analyzed and the characteristics were compared with those of cases of low level exposure without lung cancer or mesothelioma. Most fibers analyzed (98%) were longer than 5 microns and thicker than 0.10 micron by our counting rules. In the control group, predominant fibers were tremolite or actinolite. In all the 11 pleural mesothelioma cases, the content of amosite fibers was significantly higher than in the controls. In one case of peritoneal mesothelioma, incipient asbestosis was found and the predominant fibers were crocidolite. It is suggested that the presence of amosite and crocidolite is linked to mesothelioma. The mean lengths of amosite and crocidolite, as detected by our resolution capabilities, were 36.0 and 20.9 microns, and the mean diameters were 0.51 and 0.27 micron, respectively. Both amosite and crocidolite fibers had high aspect ratios (94.2 and 115.4).     

Asbestos and Peritoneal Mesothelioma among College-educated Men

Abstract

The proportion of peritoneal mesotheliomas among all mesotheliomas has been decreasing, leading some to suggest that peritoneal mesothelioma occurs only after high levels of exposure to asbestos. To investigate the relationship between asbestos exposure and the development of peritoneal mesothelioma, a case–control study examined 40 cases of primary peritoneal mesothelioma from a single institution. This series differed from previous reports in that 75% of the cases and controls had attended college. Results show an odds ratio of 6.6 for asbestos exposure among this group of primary peritoneal mesothelioma cases with relatively slight asbestos exposures.     

腹膜恶性间皮瘤临床分析

目的提高对腹膜恶性间皮瘤的临床特征、诊断及治疗手段的认识。方法分析9例女性恶性腹膜间皮瘤的临床资料。结果确诊后的患者经过治疗,症状有缓解,延长了生存期。结论腹膜恶性间皮瘤是起源于腹膜间皮细胞的肿瘤,为罕见病,起病隐匿,临床表现常无特异性,在临床中最易出现误诊,因此对于腹膜恶性间皮瘤明确诊断与规范治疗至关重要。     

Incidence rates of malignant mesothelioma in Denmark and predicted future number of cases among men

OBJECTIVES: This study analyzed the incidence rates of malignant mesothelioma in Denmark in order to predict the future number of cases that will occur among Danish men. METHODS: The 1912 cases of malignant mesothelioma reported to the Danish Cancer registry in 1943-1993 were analyzed in order to describe current incidence rates. By a Poisson regression model the relative risks of synthetic birth cohorts were estimated and used in the prediction of the future number of cases that will occur among Danish men. RESULTS: The incidence rate increased to 1.33 per 100000 person-years in 1983-1987 among men and to 0.51 in 1973-1977 among women. From the Poisson regression model, the risk for birth cohorts of men, relative to the 1940-1944 cohort, peaked in the 1940-1944 cohort and decreased to 0.57 in the 1950-1954 cohort. The age-specific incidence rate peaked at 246 per 100000 person-years in the age group 80-84 years. The future annual number of mesothelioma cases is expected to peak around 2015 with 93 cases among men born before 1955. CONCLUSIONS: The fit of the models was not ideal, but with careful interpretation of the results, it was concluded that a further increase in the number of mesothelioma cases can be expected, and the effect of regulating the environmental exposure to asbestos cannot be expected within the next 10-15 years.     

Asbestos-induced peritoneal mesothelioma in a construction worker

Occupational and environmental asbestos exposure continues to represent a public health problem, despite increasingly restrictive laws adopted by most industrialized countries. Peritoneal mesothelioma is a rare and aggressive asbestos-related malignancy. We present the case of a 65-year-old man who developed recurrent ascites after having been exposed to asbestos in the building industry for > 40 years. Liver function and histology were normal. Abdominal computed tomography initially excluded the presence of expansive processes, and no abnormal cells were found in the ascitic fluid. Laparoscopy showed diffuse neoplastic infiltration of the peritoneum. Histopathology of bioptic samples revealed epithelioid neoplastic proliferation with a tubulopapillary pattern, falsely suggesting metastatic adenocarcinomatosis. In consideration of the occupational history, and after further diagnostic procedures had failed to identify the hypothetical primitive tumor, immunostaining of the neoplastic tissue was performed. Results were negative for carcinoembrionary antigen and the epithelial glycoprotein Ber-EP4, whereas results were positive for the mesothelial markers cytokeratins, calretinin, epithelial membrane antigen, and HBME-1, thus leading to the correct diagnosis of peritoneal epithelial mesothelioma. The Italian Workers' Compensation Authority recognized the occupational origin of the disease. Cytoreductive surgery associated with continuous hyperthermic peritoneal perfusion (cisplatin at 42 degrees C, for 1 hr) was performed. The disease relapsed after 4 months and was later complicated by a bowel obstruction requiring palliative ileostomy. The patient died 23 months after diagnosis. This case illustrates the insidious diagnostic problems posed by peritoneal mesothelioma, a tumor which often simulates other malignancies (e.g., metastatic carcinomas) at routine histopathological examination. Occupational history and immunohistochemistry are helpful for the correct diagnosis, which, in turn, is important in relation to prognosis and treatment (adoption of new integrated procedures that seem to promise prolonged survival and increased quality of life), and in relation to medicolegal issues and occupation-related compensation claims following asbestos exposure.