Epidemiology

Incidence
Although reported incidence rates have increased in the past 20 years, mesothelioma is still a relatively rare cancer. The incidence is approximately one per 1,000,000. For comparison, populations with high levels of smoking can have a lung cancer incidence of over 1,000 per 1,000,000. Incidence of malignant mesothelioma currently ranges from about 7 to 40 per 1,000,000 in industrialized Western nations, depending on the amount of asbestos exposure of the populations during the past several decades. It has been estimated that incidence may have peaked at 15 per 1,000,000 in the United States in 2004. Incidence is expected to continue increasing in other parts of the world. Mesothelioma occurs more often in men than in women and risk increases with age, but this disease can appear in either men or women at any age. Approximately one fifth to one third of all mesotheliomas are peritoneal.

Risk factors
Working with asbestos is the major risk factor for mesothelioma. A history of asbestos exposure exists in almost all cases. However, mesothelioma has been reported in some individuals without any known exposure to asbestos. Asbestos is the name of a group of minerals that occur naturally as masses of strong, flexible fibers that can be separated into thin threads and woven. Asbestos has been widely used in many industrial products, including cement, brake linings, roof shingles, flooring products, textiles, and insulation. If tiny asbestos particles float in the air, especially during the manufacturing process, they may be inhaled or swallowed, and can cause serious health problems. In addition to mesothelioma, exposure to asbestos increases the risk of lung cancer, asbestosis (a noncancerous, chronic lung ailment), and other cancers, such as those of the larynx and kidney. The combination of smoking and asbestos exposure significantly increases a person's risk of developing cancer of the airways (lung cancer, bronchial carcinoma). The Kent brand of cigarettes used asbestos in its filters for the first few years of production in the 1950s and some cases of mesothelioma have resulted. Smoking current cigarettes does not appear to increase the risk of mesothelioma. Some studies suggest that simian virus 40 (SV40) may act as a cofactor in the development of mesothelioma.

Exposure
Asbestos has been mined and used commercially since the late 1800s. Its use greatly increased during World War II. Since the early 1940s, millions of American workers have been exposed to asbestos dust. Initially, the risks associated with asbestos exposure were not known. However, an increased risk of developing mesothelioma was later found among shipyard workers, people who work in asbestos mines and mills, producers of asbestos products, workers in the heating and construction industries, and other tradespeople. Today, the U.S. Occupational Safety and Health Administration (OSHA) sets limits for acceptable levels of asbestos exposure in the workplace. By contrast, the British Government's Health and Safety Executive (HSE) states formally that any threshold for mesothelioma must be at a very low level and it is widely agreed that if any such threshold does exists at all, then it cannot currently be quantified. For practical purposes, therefore, HSE does not assume that any such threshold exists. People who work with asbestos wear personal protective equipment to lower their risk of exposure. Exposure to asbestos fibres has been recognised as an occupational health hazard since the 1900s. Several epidemiological studies have associated exposure to asbestos with the development of lesions such as asbestos bodies in the sputum, pleural plaques and diffuse pleural fibrosis, asbestosis, carcinoma of the lung and larynx, gastrointestinal tumours and diffuse mesothelioma of the pleura and peritoneum. The documented presence of asbestos fibres in water supplies and food products has fostered concerns about the possible impact of long-term and, as yet, unknown exposure of the general population to these fibres. Although many authorities consider brief or transient exposure to asbestos fibres as inconsequential and an unlikely risk factor, some epidemiologists claim that there is no risk threshold. Commercial asbestos mining at Wittenoom, Western Australia, occurred between 1945 and 1966. A cohort study of miners employed at the mine reported that while no deaths occurred within the first 10 years after crocidolite exposure, 85 deaths attributable to MM had occurred by 1985. It is predicted that the number of cases within this study group will reach in excess of 700 by the year 2020. By 1994, 539 reported deaths due to MM had been reported in western Australia. Family members and others living with asbestos workers have an increased risk of developing mesothelioma, and possibly other asbestos related diseases. This risk may be the result of exposure to asbestos dust brought home on the clothing and hair of asbestos workers. To reduce the chance of exposing family members to asbestos fibers, asbestos workers are usually required to shower and change their clothing before leaving the workplace.

Treatment

Treatment of Mesothelioma using conventional therapies has not proved successful and patients have a median survival time of 6 - 12 months after presentation. The clinical behaviour of the malignancy is affected by several factors including the continuous mesothelial surface of the pleural cavity which favours local metastasis via exfoliated cells, invasion to underlying tissue and other organs within the pleural cavity, and the extremely long latency period between asbestos exposure and development of the disease.

Surgery
Surgery, either by itself or used in combination with pre- and post-operative adjuvant therapies has proved disappointing with a 5 year survival rate of less than 10%. It is most useful for palliation.

Radiation
Although the tumor is highly resistant to radiotherapy and chemotherapy, these regimens are sometimes used to relieve symptoms arising from tumour metastases such as obstruction of a major blood vessel.

Chemotherapy
In February 2004, the Food and Drug Administration approved pemetrexed (brand name Alimta) for treatment of malignant pleural mesothelioma.

Immunotherapy
Treatment regimens involving immunotherapy have yielded variable results. For example, intrapleural inoculation of Bacillus Calmette-Guérin (BCG) in an attempt to boost the immune response, was found to be of no benefit to the patient (while it may benefit patients with bladder cancer). Mesothelioma cells proved susceptible to in vitro lysis by LAK cells following activation by interleukin-2 (IL-2), but patients undergoing this particular therapy experienced major side effects. Indeed, this trial was suspended in view of the unacceptably high levels of IL-2 toxicity and the severity of side effects such as fever and cachexia. Nonetheless, other trials involving interferon alpha have proved more encouraging with 20% of patients experiencing a greater than 50% reduction in tumor mass combined with minimal side effects.

Heated Intraoperative Intraperitoneal Chemotherapy
A procedure known as heated intraoperative intraperitoneal chemotherapy was developed by Paul Sugarbaker at the Washington Cancer Institute. The surgeon removes as much of the tumor as possible followed by the direct administration of a chemotherapy agent, heated to between 40 and 48°C, in the abdomen. The fluid is perfused for 60 to 120 minutes and then drained. This technique permits the administration of high concentrations of selected drugs into the abdominal and pelvic surfaces. Heating the chemotherapy treatment increases the penetration of the drugs into tissues. Also, heating itself damages the malignant cells more than the normal cells.

History

An article published by Wagner et al in 1960 first established mesothelioma as a disease arising from exposure to crocidolite asbestos. The article referred to over 30 case studies of people who had suffered from mesothelioma in South Africa. Some exposures were transient and some were mine workers. In 1962 Dr McNulty reported the first diagnosed case of malignant mesothelioma in an Australian asbestos worker. The worker had worked in the mill at the asbestos mine in Wittenoom from 1948 to 1950. In the town of Wittenoom, asbestos-containing mine waste was used to cover schoolyards and playgrounds. In 1965 an article in the British Journal of Industrial Medicine established that people who lived in the neighbourhoods of asbestos factories and mines, but did not work in them, had contracted mesothelioma. Despite proof that the dust associated with asbestos mining and milling causes asbestos related disease, mining began at Wittenoom in 1943 and continued until 1966. It is difficult to understand why the mine and mill was allowed to initially open and operate without adequate risk control measures; and why nothing was done to force the owner (CSR) to clean them up, adopt safer work practices or close down their operations. In 1974 the first public warnings of the dangers of blue asbestos were published in a cover story called "Is this Killer in Your Home?" in Australia's Bulletin magazine. In 1978 the Western Australian Government decided to phase out the town of Wittenoom, following the publication of a Health Dept. booklet, "The Health Hazard at Wittenoom", containing the results of air sampling and an appraisal of worldwide medical information. By 1979 the first writs for negligence related to Wittenoom were issued against CSR and its subsidiary ABA, and the Asbestos Diseases Society was formed to represent the Wittenoom victims.

Legal issues

In the United States, the average mesothelioma-related settlement was $1 million; for cases that go to trial awards averaged $6 million, according to a study by the RAND Corporation. Only a small fraction of the thousands of asbestos-related lawsuits in the United States every year are related to mesothelioma. In 2004, a bill in the United States Senate aimed an asbestos litigation reform failed to reach a floor vote. In January of 2005, Senate Judiciary Committee Chairman Arlen Specter announced he would again try to pass an asbestos litigation reform bill. A separate bill introduced on March 17, 2005, the Fairness in Asbestos Injury Resolution Act of 2005 (FAIR act of 2005), seeks to ensure a set amount of compensation dependent on the symptoms of the victim. The range is from Medical Monitoring for victims with Asbestosis or Pleural Disease to $35,000 for victims with Mixed Disease With Impairment all the way to over $1,000,000 for Mesothelioma victims and nonsmoking Lung Cancer victims.