Mesothelioma

Bruce W S Robinson, A Philippe Chahinian, Bruce W S Robinson, A Philippe Chahinian

• Editore: CRC Press
• Anno: 2002
• ISBN:
  9781135285968
• Edizione: 1
• Argomento: Medicina
• Categoria: Teoria, pratica e riferimenti medici

Mesothelioma used to be a rare disease, but because of the widespread use of asbestos it has now been described as an epidemic around the world. The disease has proven exceptionally resistant to common forms of treatment (chemotherapy, radiotherapy and surgery). Mesothelioma has a very aggressive natural history with a median survival of around 9 m

1
The North American Experience with Malignant Mesothelioma

Alissa K. Greenberg, Theodore C. Lee and William N. Rom

Incidence

In the United States

In 1890 Biggs¹ reported a case of ‘endothelioma’ of the pleura. This report may have been the first recognised case of malignant mesothelioma in North America. Since then the incidence of mesothelioma in North America and the world has steadily climbed.

Studies of the incidence of mesothelioma in North America have been hampered by a paucity of data. Before 1988, the United States did not even have a specific code for mesothelioma, so many cases were misclassified on death certificates as lung cancers or abdominal cancers. In the United States, the best estimates of mesothelioma incidence are derived from the Surveillance, Epidemiology and End Results (SEER) Program of the National Cancer Institute. The SEER database² includes about 9.5 per cent of the United States population. It covers 10 regional areas, in five states (Connecticut, Iowa, New Mexico, Utah and Hawaii), and five major urban areas – San Francisco–Oakland, New Orleans, Seattle, Atlanta, and Detroit. Although the SEER regions are reasonably representative of the United States population in terms of demographic and epidemiological factors, the programme may not accurately reflect the country as a whole. It includes some shipbuilding areas, but large urban areas where asbestos was used in manufacturing and construction are underrepresented. The database is organised by case; each case is identified by age, sex, race, date of diagnosis and cancer type. The data for mesothelioma are published only intermittently. However, this database provides the most comprehensive national incidence data available for this disease.

In 1997 Price³ analysed the SEER data for mesothelioma. He divided the data into five-year age groups in each diagnosis year. He found a consistently higher rate of mesothelioma in men than in women. The rate for women remained relatively constant over the years. On the other hand, the rate for men increased until 1992, when it peaked at 1.9 per 100 000 people. Since then the incidence rate in men has been slowly decreasing (Fig. 1.1).2 This trend is presumably due to occupational asbestos exposure, which was highest during the years 1930–60. The highest lifetime risk was for the 1925–30 birth cohort – a group that would have been at work in shipyards, manufacturing and construction during the years 1930–60. In recent years in the United States, the incidence has been approximately 2000–3000 cases per year, or 11.4 cases per million men and 2.8 cases per million women.⁴ The mortality rate in people with prolonged heavy exposure to asbestos varies from 2 to 10 per cent in different studies, and the latency period between initial exposure and manifestation of disease is usually 20–50 years. From 1987 to 1996 an average of 520 people died per year in the United States of malignant mesothelioma.

Figure 1.1. Age-adjusted mesothelioma incidence in the United States. Source: SEER data. Values for 1998 estimated.

Data from the United States Department of Health and Human Services⁵ show that states with the highest incidence of mesothelioma are all coastal or Great Lakes States. Florida has displaced New York as the State with the highest number of deaths per year from mesothelioma. In 1996, 78 people died of mesothelioma in Florida. The states with the highest age-adjusted mortality rates were Washington and Oregon, probably due to the presence of shipyards. The most frequently recorded occupation on death certificates of people with mesothelioma in the United States was homemaker (10.6 per cent of all deaths), followed by managers and administrators, plumbers, pipefitters and steamfitters, production supervisors, labourers, electricians, farmers, carpenters and machinists. The most common industry was construction, followed by ship building and railroads. Other areas with significant mesothelioma incidence were schools and government.

In Canada

In Canada several large epidemiological studies have provided data for estimates of the incidence of mesothelioma. Morrison and colleagues in 1984⁶ looked at all cases of pleural mesothelioma diagnosed in British Columbia from 1973 through 1980 and reported to the National Cancer Incidence Reporting System (NCIRS) of Statistics Canada. They identified 64 cases (54 men and 10 women). Almost all cases were clustered in Cowichan Valley, Capital and Greater Vancouver counties. They noted an overall increasing incidence with age. Among men, but not women, they found an increasing incidence over time, and correlated this with a relatively high level of shipbuilding and ship repair activity in Vancouver and Victoria thirty to forty years before the study. Similar increased rates of mesothelioma have been observed in shipbuilding centers in the United States and Great Britain. The authors also compared the incidence of mesothelioma obtained from NCIRS data to that obtained by looking at death records. They found that only 60 percent of the cases were identified by looking at mortality data – so death records are therefore a poor substitute for incidence records, since mesothelioma is often not recorded as the cause of death.

In 1985 Churg and colleagues⁷ surveyed all pathologists in British Columbia, in an attempt to identify all cases of mesothelioma diagnosed in 1982. Occupational histories were obtained when possible, the pathology slides were reviewed, and when tissue was available the lung was analysed for asbestos content. They identified 19 cases (17 men and 2 women) of confirmed mesothelioma; obtained occupational histories for 16, and analysed lung tissue fibre content in 7. The calculated incidence per year based on their data was 17 cases per million men and 1.9 cases per million women over age 15. Compared with data from 1966–1975, this was a marked increase in the incidence rate for men, but no obvious increase for women – similar to the observations by Price in the United States. Fourteen of fifteen men had a history of occupational asbestos exposure, mostly in shipyards, or in construction or insulation work. In the six men whose lung tissue was analysed, the pulmonary content of chrysotile asbestos was within the range of the general population, but the values for amosite and crocidolite were elevated on average 300-fold compared to a reference population. No commercial amphibole was found in the lungs of the one woman analysed. They concluded that the cases in women may not have been associated with asbestos, and may represent the background nonasbestos associated mesothelioma rate in the general population.

Since the end of 1967, all pathologists in Canada (over 400) have been surveyed periodically to identify all cases of fatal mesothelioma diagnosed at autopsy or biopsy. In 1972 the survey was extended for one year to all pathologists (almost 7000) throughout the United States.⁸ On each occasion, nearly all responded. The investigators visited the pathologists and collected material for panel review. They selected a control from the same pathology file with metastatic lung disease from a primary tumor outside the chest, matched for date, sex and age. They also interviewed relatives to obtain detailed residential and occupation histories. As of 1972, there were 344 male cases of mesothelioma; 188 cases compared with 78 controls fell into one of five defined exposure groups. Insulation work showed the highest relative risk at 46.1. Asbestos production and manufacture was next at 6.1. Occupational exposure to asbestos was recorded in only two of 162 female cases, and in no controls. In eight cases and two controls, exposure had been in the home, likely from the clothing of an asbestos worker.

Based on this study, the annual incidence in Canada for 1960 to 1966 was one case per million persons – 1.5 in men and 0.8 in women. For the period 1966–1972 the incidence in Canada was 2.9 per million men and 1.4 per million women; in the United States in 1972 the rates were 2.7 and 0.8 per million. The authors also investigated the effect of neighbourhood exposure. They compared the number of cases and controls who had lived within 20 miles of asbestos mines in Canada and California. They found no increased risk associated with living near chrysotile mines. They also looked at neighbourhoods with asbestos factories. By applying age and sex specific rates found in Canada, the number of mesotheliomas expected was compared with the number observed in various areas. The highest ratio of expected to observed cases was found in the Manville–Somerville area of New Jersey (to be discussed below) where the ratio of observed to expected was 26.5.⁹

Causes of malignant mesothelioma

Asbestos

The adverse effects of asbestos were first observed in the early 1900s and the relationship to mesothelioma was suggested in the 1940s. One of the earliest reports linking mesothelioma to occupational asbestos exposure came out of the medical clinic at an asbestos mine in Canada. At a scientific meeting in 1952 Cartier,¹⁰ then in charge of the industrial medical clinic at Thetford Mines, Quebec, reported eight cases of respiratory cancer, two of which he described as pleural tumors. He declared that two such rare cancers in a small series of only eight cases suggested an occupational origin. By 1960 the scientific community generally recognised asbestos as a cause of mesothelioma.

However, the issue was far from settled. In a national survey of mesothelioma in Canada from 1960 to 1968, McDonald and colleagues¹¹ found a history of asbestos contact in a relatively small proportion of cases – mostly in insulation and allied trades rather than in the asbestos-producing industry. They surveyed pathologists across the country to find all cases of mesothelioma after 1959. They found 165 cases (111 pleural, 47 peritoneal, 3 both and 4 pericardial). Updates in subsequent years showed a slightly increased association with asbestos exposure, but still lower than expected. When pathologists reviewed the cases¹² the diagnosis was confirmed in only about 50 per cent of the cases, among whom the incidence of asbestos exposure was also higher. A follow-up analysis added a chrysotile mining industry cohort and two small groups of employees in gas mask factories to the survey data. They found 254 fatal cases of mesothelioma (181 men, 73 women) in Quebec from 1960 to 1978. They were able to obtain occupational and residential histories for the majority, and found that only about 40 per cent of the male cases and 5.4 per cent of the female cases were attributable to occupational asbestos exposure (asbestos manufacture, production, insulation, heating trades, shipyards, and construction). Six people probably had household exposure. The intervals between first employment and death from mesothelioma were longer for miners and millers than for manufacturing workers. All the miners and millers had pleural mesothelioma, while the factory workers included 8 with peritoneal mesothelioma. The incidence did not clearly increase over this time period.

Subsequent studies showed an increased percentage of cases attributable to asbestos exposure. Ruffie and colleagues conducted a retrospective study of 332 patients diagnosed with pleural mesothelioma at several teaching hospitals in Ontario and Quebec between 1965 and 1984.¹³ They found 396 patients with mesothelioma, including 332 of the pleura. Of the patients with pleural mesothelioma, 262 were men and 70 were women. Ages ranged from 22 to 85 years. About 60 per cent of those with history available had identifiable asbestos exposure. Only 3 were known to have had household exposure and 68 per cent of men and 17 per cent of women had identifiable occupational exposure. With more detailed occupational histories, more exposures may have been found. In Sherbrooke and Quebec City, almost all of the exposed patients came from the asbestos mining areas of Asbestos and Thetford Mines – most working in asbestos processing, as opposed to mining. In Ontario, an important source of exposure was from asbestos-cement factories, where 21 cases were observed in a cohort of 535.¹⁴ Twenty-five per cent of patients with mesothelioma in Ontario were immigrants who had asbestos exposure in their country of origin.

In 1994 Spirtas and colleagues¹⁵ published a study aimed at defining the attributable risk of asbestos exposure in the United States. They used the Los Angeles County Cancer Surveillance Program, the New York State Cancer Registry (excluding New York City), and 39 large Veterans Administration hospitals to identify people diagnosed with mesothelioma from 1975 to 1980. They identified 208 cases of pathologically confirmed mesothelioma. Controls were 533 people who had died of other causes. They interviewed immediate family members to obtain asbestos exposure history. Among men the attributable risk for asbestos exposure was 88 per cent, among women it was 23 per cent (although the confidence interval was very wide at 3–72%). The increasing incidence of mesothelioma in the United States is primarily due to the increased incidence among men, thus probably reflecting more occupational exposure.

Most patients with mesothelioma do have a history of exposure to asbestos, although it may have been brief and remote in time. The variability in percentages of cases with identifiable asbestos exposure may be related to several factors: incomplete history taking, unknown or hidden occupational exposures, or environmental exposure.

Other possible causes

Although it is clear that asbestos causes mesothelioma, other factors also play a role. It is not clear why only a relatively small proportion of people exposed to asbestos develop mesothelioma, or why anywhere from 20 to 60 per cent of people with mesothelioma in different studies lack a known history of as...

Indice dei contenuti

• Cover Page
• Title Page
• Copyright Page
• Contributors
• Introduction
• 1: The North American Experience with Malignant Mesothelioma
• 2: History and Experience of Mesothelioma in Europe
• 3: The History of Mesothelioma in Australia 1945–2001
• 4: Mesothelioma and Exposure to Asbestos in South Africa: 1956–62
• 5: Mesothelioma and Exposure to Asbestos in South Africa: 1962–2000
• 6: Clinical and Palliative Care Aspects of Malignant Mesothelioma
• 7: Pleuroscopy in the Management of Malignant Pleural Mesothelioma
• 8: Pathology of Mesothelioma
• 9: Surgery and Staging of Malignant Mesothelioma
• 10: Imaging in Mesothelioma
• 11: Treatment of Malignant Mesothelioma: Radiotherapy and Chemotherapy
• 12: Gene Therapy for Malignant Mesothelioma – ‘Suicide Gene’ and Immunological Approaches
• 13: Photodynamic Therapy (PDT) and Pleural Mesothelioma
• 14: Doctors in the Courtroom: Medico-Legal Aspects of Mesothelioma in Australia
• 15: Asbestos Fibres and their Interaction with Mesothelial Cells in vitro and in vivo
• 16: Novel Molecular, Epidemiological, and Therapeutic Issues in Mesothelioma: The Role of SV40
• 17: The Molecular Pathogenesis of Mesothelioma
• 18: Immunotherapy of Malignant Mesothelioma
• 19: Epidemiology of Mesothelioma
• 20: Mesothelioma in Japan