Mesothelioma Research

Mesothelioma is a cancer in which cells of the mesothelium (the tissue that lines parts of the body cavity) become abnormal and divide without control or order. It is almost always associated with asbestos exposure.

Most cases of mesothelioma begin in the pleura (the lining of the chest) or peritoneum (the lining of the abdomen). Rarely, they begin in the pericardium (the lining around the heart). There is no known cure for mesothelioma, and the vast majority of patients die within five years of diagnosis.

The first descriptions of cases likely to have been mesothelioma were written up in 1767. It was recognized as a distinct disease in 1870, but knowledge about mesothelioma appears to have remained at a standstill for the next 60 years; it wasn't until 1931 that the histological features of mesothelioma were described in detail, and it was not tracked as a separate cause of death in the U.S. until 1999.

The increased recognition of asbestos-related diseases over the past few decades has resulted in more attention to mesothelioma, but the body of research into its incidences, causes, and treatments is still smaller than for many other diseases.

Asbestos's Role in Mesothelioma

While it is now recognized that asbestos exposure is the primary cause of mesothelioma, that was not always the case. In 1947, a case record of pleural mesothelioma failed to recognize the link to asbestos, even though the write-up identified the patient as an asbestos worker and described his work cutting asbestos insulating board. A key study in 1960 finally identified asbestos as a causative factor in mesothelioma cases in South Africa. In 1992 researchers learned that DNA can adhere to asbestos fibers; when these fibers enter cells, they can transfer DNA from one cell to another, leading to mutations and cancer.

For many years it was believed that the chrysotile form of asbestos was relatively safe and did not cause mesothelioma. Several studies, however, suggest that no form of asbestos is safe. As far back as 1977, researchers found that tissues taken from mesothelioma patients often contained a mixture of chrysotile and amphiboles. The 1992 study about DNA and other cellular effects of asbestos also reported that mesothelial cells appear to be sensitive to all asbestos fiber types.

Researchers in 1994 examined the lung tissue of mesothelioma patients and found that amosite asbestos existed in 81% of the samples. Tremolite, actinolite, and anthophyllite were found in 55%, chrysotile in 21% and crocidolite in 16%. A separate study done in 1998 concluded that chrysotile asbestos is similar in potency to amphibole asbestos.

A study published in 2002 analyzed the type, number, and dimensions of asbestos fibers in lung and mesothelial tissues in mesothelioma patients. The researchers found that asbestos fibers were present in almost all of the lung and mesothelial tissues. The average number of asbestos fibers in both lung and mesothelial tissues was two orders of magnitude greater than the number found in the general population. The lung tissues of mesothelioma patients most often contained a combination of chrysotile with amphiboles, though some contained amphibole fibers alone and a smaller number contained chrysotile alone. In mesothelial tissues, chrysotile fibers were over 30 times more common than amphiboles. In some cases, the only asbestos fibers detected in either lung or mesothelial tissue were chrysotile fibers.

Therefore, while amphibole asbestos such as crocidolite and amosite have been most commonly linked to mesothelioma, exposure to chrysotile asbestos also puts people at risk. Since natural asbestos fibers are rarely pure but usually are mixtures of different types, all asbestos should considered dangerous, and exposure to any kind of asbestos should be cause for concern.

Risks of Developing Mesothelioma

Working with asbestos is considered the major risk factor for mesothelioma. Although asbestos has been mined and used commercially since the late 1800s, its use greatly increased during World War II, with an estimated 27.5 million workers in the U.S. exposed to asbestos as part of their jobs from 1940 through 1979. Current statistics indicate that between 70% and 90% of patients who develop mesothelioma have been exposed to asbestos, often through work, and cases tend to be clustered near shipyards and plants that produce asbestos products. In 1978, researchers found that beginning 15 years after first asbestos exposure, approximately six percent of asbestos workers 35 or older die of mesothelioma. They also noted that the mesothelioma death rate in asbestos insulation workers was over 340 times higher than in the general population.

Environmental and familial exposures have also been factors. A 1990 study found that half the people who develop mesothelioma by age 40 were exposed to asbestos in childhood, either because they lived near asbestos plants or naturally occurring asbestos, or because one or both of their parents worked with asbestos and inadvertently brought it home on their clothes, skin, or hair.

A study published in 1994 found that, among men with pleural mesothelioma the attributable risk for exposure to asbestos was 88%; in peritoneal cancer cases in men it was 58%. For women with either type of mesothelioma, the attributable risk for exposure to asbestos was 23% though the researchers questioned whether there was a greater misclassification among women due to incomplete understanding of non-occupational exposure to asbestos.

In a 1988 comparison of asbestos fibers found in the tissues of mesothelioma patients versus those found in people without the disease, people with pleural mesothelioma had seven times as much asbestos in their tissues as the control samples; those with peritoneal mesothelioma had 16 times as much asbestos as those in the control group. Another study in 2000 found that peritoneal mesothelioma risk appears to be proportional to the square of cumulative exposure, while pleural mesothelioma rises less than linearly with cumulative dose.

In 1998, researchers investigated the reported histories of cancer in first-degree relatives of mesothelioma patients. They found indications that people with a family history of cancer may have a greater chance of developing mesothelioma or at least may be more susceptible to mesothelioma given asbestos exposure. This may explain why some individuals with only brief exposures to asbestos develop mesothelioma.

Types of and Occurrence of Mesothelioma

Analysis done in 1997 found that 80% of mesothelioma cases involved the pleura, though some groups of asbestos workers developed peritoneal mesothelioma more frequently than pleural. The analysis also showed that pleural mesothelioma rose by nearly 300% in Caucasian males between 1973 and 1984, with the average age of patients approximately 60 years.

According to a paper presented in 2002, in the 1960s up to 30% of mesothelioma cases were peritoneal but by the first part of this century, the proportion had fallen to about 10%. This was due in part to pleural mesothelioma cases rising steadily during that period.

A European study also published in 2002 predicted that the number of men who die from mesothelioma in Western Europe each year would rise from 5000 in 1998 to about 9000 around 2018. Mesothelioma deaths are expected to decline after that, with a total over the next 30 years estimated at 250,000. The study predicted that about one in 150 Western European men born between 1945 and 1950 will die of mesothelioma.

Treatments

Because mesothelioma is often at an advanced stage by the time diagnosis is made and because the tumors are often large, surgery is seldom effective. Likewise, radiation treatment has not been successful in most cases.

Photodynamic therapy, in which light-sensitive chemicals are introduced into the body and then subjected to laser light via thoracotomy or thoracoscopy, showed some promising results in studies published in 1990 and 1991. Gene therapy is also being explored.

A 1993 study reported that chemotherapy with single or multiple agents was not generally successful; treatment with doxorubicin and cisplatin or mitomycin and cisplatin were found to be most active, producing measurable disease reduction in 25% of mesothelioma cases. Alimta, a relatively new drug approved by the U.S. FDA as a treatment for mesothelioma, works by inhibiting enzymes that contribute to rapid tumor growth. It is usually prescribed with cisplatin; clinical trials showed that patients who were treated with both drugs had a median survival of 12.1 months compared to 9.3 months for patients who only received cisplatin.

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