Mesothelioma

Mesothelioma is a type of cancer that develops from the thin layer of tissue that covers many of the internal organs (known as the mesothelium).[9] The most common area affected is the lining of the lungs and chest wall.[1][3] Less commonly the lining of the abdomen and rarely the sac surrounding the heart,[10] or the sac surrounding the testis may be affected.[1][11] Signs and symptoms of mesothelioma may include shortness of breath due to fluid around the lung, a swollen abdomen, chest wall pain, cough, feeling tired, and weight loss.[1] These symptoms typically come on slowly.[2]

More than 80% of mesothelioma cases are caused by exposure to asbestos.[3] The greater the exposure the greater the risk.[3] As of 2013 about 125 million people have been exposed to asbestos at work.[12] High rates of disease occur in people who mine asbestos, produce products from asbestos, work with asbestos products, live with asbestos workers, or work in buildings containing asbestos.[3] Asbestos exposure and the onset of cancer are generally separated by about 40 years.[3] Washing the clothing of someone who worked with asbestos also increases the risk.[12] Other risk factors include genetics and infection with the simian virus 40.[3] The diagnosis may be suspected based on chest X-ray and CT scan findings, and is confirmed by either examining fluid produced by the cancer or by a tissue biopsy of the cancer.[2]

Prevention centers around reducing exposure to asbestos.[4] Treatment often includes surgery, radiation therapy, and chemotherapy.[5] A procedure known as pleurodesis, which involves using substances such as talc to scar together the pleura, may be used to prevent more fluid from building up around the lungs.[5] Chemotherapy often includes the medications cisplatin and pemetrexed.[2] The percentage of people that survive five years following diagnosis is on average 8% in the United States.[6]

In 2015 about 60,800 people had mesothelioma and 32,000 died from the disease.[7][8] Rates of mesothelioma vary in different areas of the world.[3] Rates are higher in Australia, the United Kingdom, and lower in Japan.[3] It occurs in about 3,000 people per year in the United States.[13] It occurs more often in males than females.[3] Rates of disease have increased since the 1950s.[3] Diagnosis typically occurs after the age of 65 and most deaths occur around 70 years old.[3] The disease was rare before the commercial use of asbestos.[3]

Signs and symptoms

Pleural mesothelioma

Symptoms or signs of mesothelioma may not appear until 20 to 50 years (or more) after exposure to asbestos. Shortness of breath, cough, and pain in the chest due to an accumulation of fluid in the pleural space (pleural effusion) are often symptoms of pleural mesothelioma.[14]

Mesothelioma that affects the pleura can cause these signs and symptoms:[14]

  • Chest wall pain
  • Pleural effusion, or fluid surrounding the lung
  • Shortness of breath
  • Fatigue or anemia
  • Wheezing, hoarseness, or a cough
  • Blood in the sputum (fluid) coughed up (hemoptysis)

In severe cases, the person may have many tumor masses. The individual may develop a pneumothorax, or collapse of the lung. The disease may metastasize, or spread to other parts of the body.

Peritoneal mesothelioma

The most common symptoms of peritoneal mesothelioma are abdominal swelling and pain due to ascites (a buildup of fluid in the abdominal cavity). Other features may include weight loss, fevernight sweats, poor appetite, vomiting, constipation, and umbilical hernia.[15] If the cancer has spread beyond the mesothelium to other parts of the body, symptoms may include pain, trouble swallowing, or swelling of the neck or face.[citation needed] These symptoms may be caused by mesothelioma or by other, less serious conditions.

Tumors that affect the abdominal cavity often do not cause symptoms until they are at a late stage. Symptoms include:[citation needed]

  • Abdominal pain
  • Ascites, or an abnormal buildup of fluid in the abdomen
  • A mass in the abdomen
  • Problems with bowel function
  • Weight loss

Pericardial mesothelioma

Pericardial mesothelioma is not well characterized, but observed cases have included cardiac symptoms, specifically constrictive pericarditisheart failurepulmonary embolism, and cardiac tamponade. They have also included nonspecific symptoms, including substernal chest pain, orthopnea(shortness of breath when lying flat), and cough. These symptoms are caused by the tumor encasing or infiltrating the heart.[10]

End stage mesothelioma

In severe cases of the disease, the following signs and symptoms may be present:[citation needed]

  • Blood clots in the veins, which may cause thrombophlebitis
  • Disseminated intravascular coagulation, a disorder causing severe bleeding in many body organs
  • Jaundice, or yellowing of the eyes and skin
  • Low blood sugar level
  • Pleural effusion
  • Pulmonary emboli, or blood clots in the arteries of the lungs
  • Severe ascites
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If a mesothelioma forms metastases, these most commonly involve the liveradrenal glandkidney, or other lung.[16]

Causes

Working with asbestos is the most common risk factor for mesothelioma.[17] However, mesothelioma has been reported in some individuals without any known exposure to asbestos. Tentative evidence also raises concern about carbon-fibre nanotubes.[18][19]

Asbestos

The incidence of mesothelioma has been found to be higher in populations living near naturally occurring asbestos. People can be exposed to naturally occurring asbestos in areas where mining or road construction is occurring, or when the asbestos-containing rock is naturally weathered. Another common route of exposure is through asbestos-containing soil, which is used to whitewash, plaster, and roof houses in Greece.[12] In central Cappadocia, Turkey, mesothelioma was causing 50% of all deaths in three small villages—Tuzköy, Karain, and Sarıhıdır. Initially, this was attributed to erionite. Environmental exposure to asbestos has caused mesothelioma in places other than Turkey, including Corsica, Greece, Cyprus, China, and California.[12][20][21] In the northern Greek mountain town of Metsovo, this exposure had resulted in mesothelioma incidence around 300 times more than expected in asbestos-free populations, and was associated with very frequent pleural calcification known as “Metsovo Lung“.[22][23]

The documented presence of asbestos fibers 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 fibers.[citation needed]

Exposure to talc is also a risk factor for mesothelioma; exposure can affect those who live near talc mines, work in talc mines, or work in talc mills.[24]

In the United States, asbestos is considered the major cause of malignant mesothelioma[25] and has been considered “indisputably”[26] associated with the development of mesothelioma. Indeed, the relationship between asbestos and mesothelioma is so strong that many consider mesothelioma a “signal” or “sentinel” tumor.[27][28][29][30] A history of asbestos exposure exists in most cases.

Pericardial mesothelioma may not be associated with asbestos exposure.[10]

Asbestos was known in antiquity, but it was not mined and widely used commercially until the late 19th century. 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 publicly known. However, an increased risk of developing mesothelioma was later found among naval personnel (e.g., Navy, Marine Corps, and Coast Guard), 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 official position of the U.S. Occupational Safety and Health Administration (OSHA) and the U.S. EPA is that protections and “permissible exposure limits” required by U.S. regulations, while adequate to prevent most asbestos-related non-malignant disease, are not adequate to prevent or protect against asbestos-related cancers such as mesothelioma.[31]Likewise, the British Government’s Health and Safety Executive (HSE) states formally that any threshold for exposure to asbestos must be at a very low level and it is widely agreed that if any such threshold does exist at all, then it cannot currently be quantified. For practical purposes, therefore, HSE assumes that no such “safe” threshold exists. Others have noted as well that there is no evidence of a threshold level below which there is no risk of mesothelioma.[32] There appears to be a linear, dose-response relationship, with increasing dose producing increasing risk of disease.[33] Nevertheless, mesothelioma may be related to brief, low level or indirect exposures to asbestos.[26] The dose necessary for effect appears to be lower for asbestos-induced mesothelioma than for pulmonary asbestosis or lung cancer.[26] Again, there is no known safe level of exposure to asbestos as it relates to increased risk of mesothelioma.

The time from first exposure to onset of the disease, is between 25 and 70 years.[34] It is virtually never less than fifteen years and peaks at 30–40 years.[26][35] The duration of exposure to asbestos causing mesothelioma can be short. For example, cases of mesothelioma have been documented with only 1–3 months of exposure.[36][37]

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Occupational

Exposure to asbestos fibers has been recognized as an occupational health hazard since the early 20th century. Numerous epidemiological studies have associated occupational exposure to asbestos with the development of pleural plaques, diffuse pleural thickening, asbestosis, carcinoma of the lung and larynx, gastrointestinal tumors, and diffuse malignant mesothelioma of the pleura and peritoneum. Asbestos has been widely used in many industrial products, including cement, brake linings, gaskets, roof shingles, flooring products, textiles, and insulation.[38]

Commercial asbestos mining at Wittenoom, Western Australia, took place from 1937 to 1966. The first case of mesothelioma in the town occurred in 1960. The second case was in 1969, and new cases began to appear more frequently thereafter. The lag time between initial exposure to asbestos and the development of mesothelioma varied from 12 years 9 months up to 58 years.[39] A cohort study of miners employed at the mine reported that 85 deaths attributable to mesothelioma had occurred by 1985. By 1994, 539 reported deaths due to mesothelioma had been reported in Western Australia.[citation needed]

Occupational exposure to asbestos in the United States mainly occurs when people are maintaining buildings that already have asbestos. Approximately 1.3 million US workers are exposed to asbestos annually; in 2002, an estimated 44,000 miners were potentially exposed to asbestos.[24]

Paraoccupational secondary exposure

Family members and others living with asbestos workers have an increased risk of developing mesothelioma, and possibly other asbestos-related diseases.[11][40][41] This risk may be the result of exposure to asbestos dust brought home on the clothing and hair of asbestos workers via washing a worker’s clothes or coming into contact with asbestos-contaminated work clothing.[12][24] To reduce the chance of exposing family members to asbestos fibres, asbestos workers are usually required to shower and change their clothing before leaving the workplace.[citation needed]

Asbestos in buildings

Many building materials used in both public and domestic premises prior to the banning of asbestos may contain asbestos. Those performing renovation works or DIY activities may expose themselves to asbestos dust. In the UK, use of chrysotile asbestos was banned at the end of 1999. Brown and blue asbestos were banned in the UK around 1985. Buildings built or renovated prior to these dates may contain asbestos materials.[citation needed]

Genetic disposition

In a recent research carried on white American population in 2012, it was found that people with a germline mutation in their BAP1 gene are at higher risk of developing mesothelioma and uveal melanoma.[42]

Erionite

Erionite is a zeolite mineral with similar properties to asbestos and is known to cause mesothelioma.[11]Detailed epidemiological investigation has shown that erionite causes mesothelioma mostly in families with a genetic predisposition.[12][20][21] Erionite is found in deposits in the Western United States, where it is used in gravel for road surfacing, and in Turkey, where it is used to construct homes. In Turkey, the United States, and Mexico, erionite has been associated with mesothelioma and has thus been designated a “known human carcinogen” by the US National Toxicology Program.[21]

Other

In rare cases, mesothelioma has also been associated with irradiation of the chest or abdomen, intrapleural thorium dioxide (thorotrast) as a contrast medium, and inhalation of other fibrous silicates, such as erionite or talc.[11][24] Some studies suggest that simian virus 40 (SV40) may act as a cofactor in the development of mesothelioma.[24] This has been confirmed in animal studies,[43][44] but studies in humans are inconclusive.[43][45][46]