Risk Factors.The number one risk factor for mesothelioma is working with asbestos. A history of asbestos exposure is present in nearly all cases. However, mesothelioma has been reported in some individuals without any known exposure to asbestos (rare).

Asbestos. Asbestos is the name of a group of metamorphic minerals that occur naturally as masses of strong, flexible fibers made up of hydrous magnesium silicate. The natural resistance to fire is the major reason why asbestos has been exploited for a variety to uses. Asbestos has been widely used in many industrial products, including cement mats and fabrics, brake shoes and gaskets, roof tars and shingles, flooring plasters and stuccos, adhesive textiles, and fireproofing insulation.

During the manufacturing process, tiny asbestos particles may be inhaled or swallowed, causing serious health problems. Exposure to asbestos increases the risk of lung cancer, asbestosis (noncancerous), mesothelioma and other cancers in the airway passage. Smoking does not appear to increase the risk of mesothelioma itself. However, the combination of smoking and asbestos exposure significantly increases the risk of developing cancer of the lungs.

Types of Asbestos. Asbestos is typically categorized into 2 subgroups. The serpentine group is derived from serpentine rocks that yield curled, corkscrewed fibers that are more soluble. The amphibole group is straight and needle-like.

• Serpentine Group. Chrysotile is the white asbestos that is most often used in the United States. Because chrysotile is less friable that other asbestos types, it is less likely to be inhaled. There is some controversy to whether chrysotile fibers, when inhaled, can cause mesothelioma. It is now thought that this form of white asbestos is indeed harmful but not to the level that amphiboles are hazardous.
• Amphibole Group. The amphibole group of asbestos fibers include amosite (brown asbestos), crocidolite (blue asbestos), tremolite, actinolite and anthophylite. These asbestos types are easily friable. For this reason, a single, large amphibole rock can easily break into millions of smaller needle-like fragments that are primed for inhalation. The crocidolite form from Africa and Australia is considered to be the most dangerous type of asbestos. Due to the deadly nature of these fibers, asbestos from the amphibole group was banned in the U.S. in the mid-1980s. However, due to the ready supply and cheaper cost, some unscrupulous companies continued to use amphiboles for construction pipes, casings for communications, and thermal insulations. This has lead to expansion of mesothelioma litigation in the United States

Some History. Since the late 1800s, asbestos has been mined and used commercially. With more industrialization, its use greatly increased (especially during World War II). Since the early 1940s, millions of American workers have been exposed to asbestos fibers when the risks associated with asbestos exposure were not known. Over time, an increased risk of developing mesothelioma was found among shipyard workers, people who worked in asbestos mines, producers of asbestos products, and workers in the heating and construction industries. Today, the U.S. Occupational Safety and Health Administration (OSHA) sets limits for acceptable levels of asbestos exposure in the workplace.

Epidemiology. Studies have associated exposure to asbestos with the development of lesions in the airway. Though not completely clear in all cases, it is thought that asbestos contributes as insoluable foreign bodies that the body forms a reaction to. The result is often a series of physical signs such as asbestos bodies in the sputum, pleural plaques, diffuse pleural fibrosis, asbestosis, carcinoma of the lung, gastrointestinal tumours and diffuse mesothelioma of the pleura and peritoneum.

The duration, the intensity and the reoccurance of exposure is thought to play a role in increasing the risk of developing mesothelioma. This is sometimes misleading, however, as there have been cases in which incidental, short-term exposure has resulted in mesothelioma. Likewise, not all people that have been exposed to asbestos have developed disease. This just goes to show that the development of mesothelioma may not necessarily have a risk threshold.

Evidence has shown that some family members (as well as other co-inhabitants) of asbestos workers have an increased risk of developing mesothelioma. It is thought that this increased 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.

How Asbestos Causes Disease


When inhaled, asbestos fibers in the amphibole group travel down the respiratory passage and embed themselves into the parenchyma of the lung. Because these fibers are not very soluble in the body, they often dig themselves in and can puncture into the deeper tissue.



This penetration of tissue usually starts off locally in the lower lungs and develops into noticeable plaques in the lung pleura. After the deposition of a plaque in the mesothelium, unresolved asbestos fibers can spread further than this primary site. Though the mechanism remains unclear, it is thought that these fibers travel through the lymphatic system (much like many other cancers) to disperse themselves in other areas and associated organs.

Once these asbestos fibers reach their target destinations, the actual conversion of healthy tissue into malignant tissue remains unclear. Several lab experiments and clinical trials that have introduced amphibole fibers to the pleura have yield mixed results. Further research is being done to see if there are other factors necessary for the essential transformation and progression step.

Histologically, the deposition of asbestos seems to mimic a foreign body reaction. Initially, polymorphonuclear neutrophils (PMNs) act as the “first responders” at the scene. These important immune system cells can further trigger response by recruiting other immune system cells to the region. Through a process using chemotaxis, large amounts of macrophages are recruited to the specific areas. These macrophages build up quickly in a matter of days. Over time, the unresolved asbestos lesions can continue to attract and accumulate larger groups of macrophages. Experimental evidence suggests that asbestos acts as a cancer causing agent with the development of mesothelioma occurring sequentially in stages of initiation and promotion. Specific molecular mechanisms underlying the malignant transformation of normal mesothelial cells by asbestos fibers is still not known. In general, asbestos fibers are thought to exert their carcinogenic effects via direct physical interactions with the cells of the mesothelium in a foreign body affect that elicits indirect interaction, recruitment and accumulation of inflammatory cells such as macrophages.

Of curious note, asbestos fibers that have been phagocytosed have shown an interesting interaction with the nucleus. Within the nucleus, there exists the vital information for the well-being of the cell. Specifically, the DNA within the cell seems to be affected by asbestos fibers. Normally, during replication, DNA is tightly wrapped around proteins called histones. On a larger scale, these wrapped DNA strands make up what we call chromosomes. It seems that asbestos fibers can interact with chromosomes and can cause losses, rearrangements and in some cases, unwanted duplications. At that level, small abnormalities can have devastating effects that are often irreparable. Some common gene abnormalities in mesothelioma cell lines include deletion of various tumor suppressor genes.

In a process called transformation used in molecular biology, asbestos has been shown to mediate the entry of foreign DNA into target cells. Successful incorporation of this foreign DNA in key regions and areas can lead to mutations and other changes that specifically promote cancer in a process referred to as oncogenesis. Some possible mechanisms include:

• Inactivation of tumor suppressor genes (eliminating genes that help suppress tumors)
• Activation of oncogenes (genes that can potentially cause cancer)
• Activation of proto-oncogenes due to incorporation of foreign DNA containing a promoter region (transformation)
• Activation of telomerase (an enzyme crucial for the length, stability and lifespan of DNA)
• Prevention of apoptosis (programmed cell death)

Compare laboratory tests and imaging modalities utilized in the diagnosis of Mesothelioma.

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Analyze the complications and prognosis for patients with Mesothelioma.

What is the incidence/prevalence of mesothelioma?

List and describe the four stages of mesothelioma, as described by the Butchart Staging System.