Mesothelioma
Encyclopedia
Mesothelioma, more precisely malignant mesothelioma, is a rare form of cancer
that develops from the protective lining that covers many of the body's internal organs, the mesothelium
. It is usually caused by exposure to asbestos
.
Its most common site is the pleura (outer lining of the lung
s and internal chest wall), but it may also occur in the peritoneum
(the lining of the abdominal cavity), the pericardium
(a sac that surrounds the heart
), or the tunica vaginalis
(a sac that surrounds the testis).
Most people who develop mesothelioma have worked on jobs where they inhaled asbestos, or they have been exposed to asbestos dust and fiber in other ways. It has also been suggested that washing the clothes of a family member who worked with asbestos can put a person at risk for developing mesothelioma. Unlike lung cancer, there is no association between mesothelioma and smoking
, but smoking greatly increases the risk of other asbestos-induced cancers. Those who have been exposed to asbestos have collected damages for asbestos-related disease, including mesothelioma. Compensation via asbestos funds or lawsuits is an important issue in law practices regarding mesothelioma (see asbestos and the law
).
The symptoms of mesothelioma include shortness of breath due to pleural effusion
(fluid between the lung and the chest wall) or chest wall pain
, and general symptoms such as weight loss
. The diagnosis may be suspected with chest X-ray
and CT scan, and is confirmed with a biopsy
(tissue sample) and microscopic
examination. A thoracoscopy
(inserting a tube with a camera into the chest) can be used to take biopsies. It allows the introduction of substances such as talc
to obliterate the pleural space (called pleurodesis
), which prevents more fluid from accumulating and pressing on the lung. Despite treatment with chemotherapy
, radiation therapy
or sometimes surgery
, the disease carries a poor prognosis
. Research about screening tests for the early detection of mesothelioma is ongoing.
) are often symptoms of pleural mesothelioma.
Symptoms of peritoneal
mesothelioma include weight loss and cachexia
, abdominal swelling and pain due to ascites
(a buildup of fluid in the abdominal cavity). Other symptoms of Peritoneal Mesothelioma
may include bowel obstruction, blood clotting abnormalities, anemia
, and fever
. 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.
These symptoms may be caused by mesothelioma or by other, less serious conditions.
Mesothelioma that affects the pleura can cause these signs and symptoms:
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.
Tumors that affect the abdominal cavity often do not cause symptoms until they are at a late stage. Symptoms include:
In severe cases of the disease, the following signs and symptoms may be present:
A mesothelioma does not usually spread to the bone, brain, or adrenal glands. Pleural tumors are usually found only on one side of the lungs.
is the major risk factor for mesothelioma. In the United States, asbestos is the major cause of malignant mesothelioma and has been considered "indisputably" 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. A history of asbestos exposure exists in most cases. However, mesothelioma has been reported in some individuals without any known exposure to asbestos. In rare cases, mesothelioma has also been associated with irradiation, intrapleural thorium dioxide (Thorotrast
), and inhalation of other fibrous silicates, such as erionite
. Some studies suggest that simian virus
40 (SV40
) may act as a cofactor
in the development of mesothelioma.
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 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, they are not adequate to prevent or protect against asbestos-related cancers such as mesothelioma. Likewise, 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 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. There appears to be a linear, dose-response relationship, with increasing dose producing increasing disease. Nevertheless, mesothelioma may be related to brief, low level or indirect exposures to asbestos. The dose necessary for effect appears to be lower for asbestos-induced mesothelioma than for pulmonary asbestosis or lung cancer. Again, there is no known safe level of exposure to asbestos as it relates to increased risk of mesothelioma.
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. People who work with asbestos wear personal protective equipment to lower their risk of exposure.
Latency, the time from first exposure to manifestation of disease, is prolonged in the case of mesothelioma. It is virtually never less than fifteen years and peaks at 30–40 years. In a review of occupationally related mesothelioma cases, the median latency was 32 years. Based upon the data from Peto et al., the risk of mesothelioma appears to increase to the third or fourth power from first exposure.
, Turkey, mesothelioma was causing 50% of all deaths in three small villages — Tuzköy, Karain and Sarıhıdır. Initially, this was attributed to erionite
, a zeolite mineral with similar properties to asbestos
. Recently, however, detailed epidemiological investigation showed that erionite causes mesothelioma mostly in families with a genetic predisposition.
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.
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 mesothelioma had occurred by 1985. By 1994, 539 reported deaths due to mesothelioma had been reported in Western Australia.
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
was banned in the UK around 1985. Buildings built or renovated prior to these dates may contain asbestos materials.
Diagnosing mesothelioma is often difficult, because the symptoms are similar to those of a number of other conditions. Diagnosis begins with a review of the patient's medical history. A history of exposure to asbestos may increase clinical suspicion for mesothelioma. A physical examination is performed, followed by chest X-ray
and often lung function tests
. The X-ray may reveal pleural thickening commonly seen after asbestos exposure and increases suspicion of mesothelioma. A CT
(or CAT) scan or an MRI is usually performed. If a large amount of fluid is present, abnormal cells may be detected by cytopathology
if this fluid is aspirated
with a syringe. For pleural fluid, this is done by thoracentesis
or tube thoracostomy (chest tube
); for ascites, with paracentesis
or ascitic drain; and for pericardial effusion with pericardiocentesis
. While absence of malignant cells on cytology does not completely exclude mesothelioma, it makes it much more unlikely, especially if an alternative diagnosis can be made (e.g. tuberculosis
, heart failure). Unfortunately, the diagnosis of malignant mesothelioma by cytology alone is difficult, even with expert pathologists.
Generally, a biopsy
is needed to confirm a diagnosis of malignant mesothelioma. A doctor removes a sample of tissue for examination under a microscope by a pathologist
. A biopsy may be done in different ways, depending on where the abnormal area is located. If the cancer is in the chest, the doctor may perform a thoracoscopy
. In this procedure, the doctor makes a small cut through the chest wall and puts a thin, lighted tube called a thoracoscope into the chest between two ribs. Thoracoscopy allows the doctor to look inside the chest and obtain tissue samples. Alternatively, the chest surgeon might directly open the chest (thoracotomy
). If the cancer is in the abdomen, the doctor may perform a laparoscopy
. To obtain tissue for examination, the doctor makes a small incision in the abdomen and inserts a special instrument into the abdominal cavity. If these procedures do not yield enough tissue, more extensive diagnostic surgery may be necessary.
Immunohistochemical studies play an important role for the pathologist in differentiating malignant mesothelioma from neoplastic mimics. There are numerous tests and panels available. No single test is perfect for distinguishing mesothelioma from carcinoma or even benign versus malignant.
There are three histological types of malignant mesothelioma: (1) Epithelioid; (2) Sarcomatoid; and (3) Biphasic (Mixed). Epithelioid comprises about 50-60% of malignant mesothelioma cases and generally holds a better prognosis than the Sarcomatoid or Biphasic subtypes.
of mesothelioma is based on the recommendation by the International Mesothelioma Interest Group. TNM classification of the primary tumor, lymph node
involvement, and distant metastasis
is performed. Mesothelioma is staged Ia–IV (one-A to four) based on the TNM status.
osteopontin
level might be useful in screening asbestos-exposed people for mesothelioma. The level of soluble mesothelin-related protein is elevated in the serum of about 75% of patients at diagnosis and it has been suggested that it may be useful for screening. Doctors have begun testing the Mesomark assay
which measures levels of soluble mesothelin
-related proteins (SMRPs) released by diseased mesothelioma cells.
consists of a single layer of flattened to cuboidal cells forming the epithelial
lining of the serous cavities of the body including the peritoneal
, pericardial
and pleural cavities. Deposition of asbestos fibers in the parenchyma
of the lung may result in the penetration of the visceral pleura from where the fiber can then be carried to the pleural surface, thus leading to the development of malignant mesothelial plaques. The processes leading to the development of peritoneal mesothelioma
remain unresolved, although it has been proposed that asbestos fibers from the lung are transported to the abdomen and associated organs via the lymphatic system
. Additionally, asbestos fibers may be deposited in the gut after ingestion of sputum contaminated with asbestos fibers.
Pleural contamination with asbestos or other mineral fibers has been shown to cause cancer. Long thin asbestos fibers (blue asbestos, amphibole
fibers) are more potent carcinogen
s than "feathery fibers" (chrysotile
or white asbestos fibers). However, there is now evidence that smaller particles may be more dangerous than the larger fibers. They remain suspended in the air where they can be inhaled, and may penetrate more easily and deeper into the lungs. "We probably will find out a lot more about the health aspects of asbestos from [the World Trade Center attack], unfortunately," said Dr. Alan Fein, chief of pulmonary and critical-care medicine at North Shore-Long Island Jewish Health System. Dr. Fein has treated several patients for "World Trade Center syndrome" or respiratory ailments from brief exposures of only a day or two near the collapsed buildings.
Mesothelioma development in rats has been demonstrated following intra-pleural inoculation of phosphorylated chrysotile fibers. It has been suggested that in humans, transport of fibers to the pleura is critical to the pathogenesis of mesothelioma. This is supported by the observed recruitment of significant numbers of macrophage
s and other cells of the immune system
to localized lesions of accumulated asbestos fibers in the pleural and peritoneal cavities of rats. These lesions continued to attract and accumulate macrophages as the disease progressed, and cellular changes within the lesion culminated in a morphologically malignant tumor.
Experimental evidence suggests that asbestos acts as a complete carcinogen with the development of mesothelioma occurring in sequential stages of initiation and promotion. The molecular mechanisms underlying the malignant transformation of normal mesothelial cells by asbestos fibers remain unclear despite the demonstration of its oncogenic capabilities (see next-but-one paragraph). However, complete in vitro transformation of normal human mesothelial cells to malignant phenotype
following exposure to asbestos fibers has not yet been achieved. In general, asbestos fibers are thought to act through direct physical interactions with the cells of the mesothelium in conjunction with indirect effects following interaction with inflammatory cells such as macrophages.
Analysis of the interactions between asbestos fibers and DNA
has shown that phagocytosed fibers are able to make contact with chromosome
s, often adhering to the chromatin
fibers or becoming entangled within the chromosome. This contact between the asbestos fiber and the chromosomes or structural proteins of the spindle apparatus can induce complex abnormalities. The most common abnormality is monosomy
of chromosome 22. Other frequent abnormalities include structural rearrangement of 1p, 3p, 9p and 6q chromosome arms.
Common gene abnormalities in mesothelioma cell lines include deletion of the tumor suppressor gene
s:
Asbestos has also been shown to mediate the entry of foreign DNA into target cells. Incorporation of this foreign DNA may lead to mutations and oncogenesis by several possible mechanisms:
Asbestos fibers have been shown to alter the function and secretory properties of macrophages, ultimately creating conditions which favour the development of mesothelioma. Following asbestos phagocytosis, macrophages generate increased amounts of hydroxyl radicals
, which are normal by-products of cellular anaerobic metabolism. However, these free radicals are also known clastogenic
and membrane-active agents thought to promote asbestos carcinogenicity. These oxidants can participate in the oncogenic process by directly and indirectly interacting with DNA, modifying membrane-associated cellular events, including oncogene activation and perturbation of cellular antioxidant defences.
Asbestos also may possess immunosuppressive
properties. For example, chrysotile fibres have been shown to depress the in vitro proliferation of phytohemagglutinin-stimulated peripheral blood lymphocytes, suppress natural killer cell lysis and significantly reduce lymphokine-activated killer cell
viability and recovery. Furthermore, genetic alterations in asbestos-activated macrophages may result in the release of potent mesothelial cell mitogens such as platelet-derived growth factor
(PDGF) and transforming growth factor
-β (TGF-β) which in turn, may induce the chronic stimulation and proliferation of mesothelial cells after injury by asbestos fibres.
) was only 11.7 months. However, research indicates varied success when used in combination with radiation and chemotherapy (Duke, 2008). (For more information on multimodality therapy with surgery, see below). A pleurectomy/decortication is the most common surgery, in which the lining of the chest is removed. Less common is an extrapleural pneumonectomy (EPP), in which the lung, lining of the inside of the chest, the hemi-diaphragm
and the pericardium
are removed.
Although mesothelioma is generally resistant to curative treatment with radiotherapy alone, palliative treatment regimens are sometimes used to relieve symptoms arising from tumor growth, such as obstruction of a major blood vessel. Radiation therapy when given alone with curative intent has never been shown to improve survival from mesothelioma. The necessary radiation dose to treat mesothelioma that has not been surgically removed would be very toxic.
chemotherapy alone with a combination of cisplatin and pemetrexed
(brand name Alimta) chemotherapy in patients who had not received chemotherapy for malignant pleural mesothelioma previously and were not candidates for more aggressive "curative" surgery. This trial was the first to report a survival advantage from chemotherapy in malignant pleural mesothelioma, showing a statistically significant improvement in median
survival from 10 months in the patients treated with cisplatin alone to 13.3 months in the group of patients treated with cisplatin in the combination with pemetrexed and who also received supplementation with folate and vitamin B12. Vitamin supplementation was given to most patients in the trial and pemetrexed related side effects were significantly less in patients receiving pemetrexed when they also received daily oral folate 500mcg and intramuscular vitamin B12 1000mcg every 9 weeks compared with patients receiving pemetrexed without vitamin supplementation. The objective response rate increased from 20% in the cisplatin group to 46% in the combination pemetrexed group. Some side effects such as nausea and vomiting, stomatitis
, and diarrhoea were more common in the combination pemetrexed group but only affected a minority of patients and overall the combination of pemetrexed and cisplatin was well tolerated when patients received vitamin supplementation; both quality of life
and lung function tests improved in the combination pemetrexed group. In February 2004, the United States Food and Drug Administration
approved pemetrexed for treatment of malignant pleural mesothelioma. However, there are still unanswered questions about the optimal use of chemotherapy, including when to start treatment, and the optimal number of cycles to give.
Cisplatin in combination with raltitrexed
has shown an improvement in survival similar to that reported for pemetrexed in combination with cisplatin, but raltitrexed is no longer commercially available for this indication. For patients unable to tolerate pemetrexed, cisplatin in combination with gemcitabine or vinorelbine is an alternative, or vinorelbine on its own, although a survival benefit has not been shown for these drugs. For patients in whom cisplatin cannot be used, carboplatin can be substituted but non-randomised data have shown lower response rates and high rates of haematological toxicity for carboplatin-based combinations, albeit with similar survival figures to patients receiving cisplatin.
In January 2009, the United States FDA approved using conventional therapies such as surgery in combination with radiation and or chemotherapy on stage I or II Mesothelioma after research conducted by a nationwide study by Duke University concluded an almost 50 point increase in remission rates.
(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.
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.
This technique is also used in patients with malignant pleural mesothelioma.
Between 1940 and 1979, approximately 27.5 million people were occupationally exposed to asbestos in the United States. Between 1973 and 1984, the incidence of pleural mesothelioma among Caucasian males increased 300%. From 1980 to the late 1990s, the death rate from mesothelioma in the USA increased from 2,000 per year to 3,000, with men four times more likely to acquire it than women. These rates may not be accurate, since it is possible that many cases of mesothelioma are misdiagnosed as adenocarcinoma of the lung, which is difficult to differentiate from mesothelioma.
was diagnosed with peritoneal mesothelioma
. After his diagnosis, Gould wrote "The Median Isn't the Message" for Discover magazine, in which he argued that statistics such as median survival are just useful abstractions, not destiny. Gould lived for another 20 years, eventually succumbing to metastatic adenocarcinoma of the lung, not mesothelioma. Author Paul Kraus
was diagnosed with peritoneal mesothelioma
in July 1997. He was given a prognosis of less than a year to live and used a variety of complementary modalities. He continued to outlive his prognosis and wrote a book about his experience "Surviving Mesothelioma and Other Cancers: A Patient's Guide" in which he presented his philosophy about healing and the decision making that led him to use integrative medicine
.
History
The first lawsuit against asbestos manufacturers was brought in 1929. The parties settled that lawsuit, and as part of the agreement, the attorneys agreed not to pursue further cases. In 1960, an article published by Wagner et al. was seminal in establishing mesothelioma as a disease arising from exposure to 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. Prior to the use of advanced microscopy techniques, malignant mesothelioma was often diagnosed as a variant form of lung cancer. In 1962 McNulty reported the first diagnosed case of malignant mesothelioma in an Australia
n 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. 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 Australia
n 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.
In Leeds
, England the Armley asbestos disaster involved several court cases against Turner & Newall
where local residents who contracted mesothelioma claimed compensation because of the asbestos pollution from the company's factory. One notable case was that of June Hancock, who contracted the disease in 1993 and died in 1997.
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
that develops from the protective lining that covers many of the body's internal organs, the mesothelium
Mesothelium
The mesothelium is a membrane that forms the lining of several body cavities: the pleura , peritoneum and pericardium . Mesothelial tissue also surrounds the male internal reproductive organs and covers the internal reproductive organs of women...
. It is usually caused by exposure to asbestos
Asbestos
Asbestos is a set of six naturally occurring silicate minerals used commercially for their desirable physical properties. They all have in common their eponymous, asbestiform habit: long, thin fibrous crystals...
.
Its most common site is the pleura (outer lining of the lung
Lung
The lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...
s and internal chest wall), but it may also occur in the peritoneum
Peritoneum
The peritoneum is the serous membrane that forms the lining of the abdominal cavity or the coelom — it covers most of the intra-abdominal organs — in amniotes and some invertebrates...
(the lining of the abdominal cavity), the pericardium
Pericardium
The pericardium is a double-walled sac that contains the heart and the roots of the great vessels.-Layers:...
(a sac that surrounds the heart
Heart
The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...
), or the tunica vaginalis
Tunica vaginalis
The tunica vaginalis is the serous covering of the testis.It is a pouch of serous membrane, derived from the processus vaginalis of the peritoneum, which in the fetus preceded the descent of the testis from the abdomen into the scrotum....
(a sac that surrounds the testis).
Most people who develop mesothelioma have worked on jobs where they inhaled asbestos, or they have been exposed to asbestos dust and fiber in other ways. It has also been suggested that washing the clothes of a family member who worked with asbestos can put a person at risk for developing mesothelioma. Unlike lung cancer, there is no association between mesothelioma and smoking
Smoking
Smoking is a practice in which a substance, most commonly tobacco or cannabis, is burned and the smoke is tasted or inhaled. This is primarily practised as a route of administration for recreational drug use, as combustion releases the active substances in drugs such as nicotine and makes them...
, but smoking greatly increases the risk of other asbestos-induced cancers. Those who have been exposed to asbestos have collected damages for asbestos-related disease, including mesothelioma. Compensation via asbestos funds or lawsuits is an important issue in law practices regarding mesothelioma (see asbestos and the law
Asbestos and the law
This article concerns asbestos-related legal and regulatory issues. Litigation related to asbestos injuries and property damages has been claimed to be the longest-running mass tort in U.S. history...
).
The symptoms of mesothelioma include shortness of breath due to pleural effusion
Pleural effusion
Pleural effusion is excess fluid that accumulates between the two pleural layers, the fluid-filled space that surrounds the lungs. Excessive amounts of such fluid can impair breathing by limiting the expansion of the lungs during ventilation.-Pathophysiology:...
(fluid between the lung and the chest wall) or chest wall pain
Pain
Pain is an unpleasant sensation often caused by intense or damaging stimuli such as stubbing a toe, burning a finger, putting iodine on a cut, and bumping the "funny bone."...
, and general symptoms such as weight loss
Weight loss
Weight loss, in the context of medicine, health or physical fitness, is a reduction of the total body mass, due to a mean loss of fluid, body fat or adipose tissue and/or lean mass, namely bone mineral deposits, muscle, tendon and other connective tissue...
. The diagnosis may be suspected with chest X-ray
Chest X-ray
In medicine, a chest radiograph, commonly called a chest X-ray , is a projection radiograph of the chest used to diagnose conditions affecting the chest, its contents, and nearby structures...
and CT scan, and is confirmed with a biopsy
Biopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
(tissue sample) and microscopic
Histopathology
Histopathology refers to the microscopic examination of tissue in order to study the manifestations of disease...
examination. A thoracoscopy
Thoracoscopy
Thoracoscopy is a medical procedure involving internal examination, biopsy, and/or resection of disease or masses within the pleural cavity and thoracic cavity...
(inserting a tube with a camera into the chest) can be used to take biopsies. It allows the introduction of substances such as talc
Talc
Talc is a mineral composed of hydrated magnesium silicate with the chemical formula H2Mg34 or Mg3Si4O102. In loose form, it is the widely-used substance known as talcum powder. It occurs as foliated to fibrous masses, its crystals being so rare as to be almost unknown...
to obliterate the pleural space (called pleurodesis
Pleurodesis
Pleurodesis is a medical procedure in which the pleural space is artificially obliterated. It involves the adhesion of the two pleura.- Uses :Pleurodesis is done to prevent recurrence of pneumothorax or recurrent pleural effusion...
), which prevents more fluid from accumulating and pressing on the lung. Despite treatment with chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
, radiation therapy
Radiation therapy
Radiation therapy , radiation oncology, or radiotherapy , sometimes abbreviated to XRT or DXT, is the medical use of ionizing radiation, generally as part of cancer treatment to control malignant cells.Radiation therapy is commonly applied to the cancerous tumor because of its ability to control...
or sometimes surgery
Surgery
Surgery is an ancient medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, or to help improve bodily function or appearance.An act of performing surgery may be called a surgical...
, the disease carries a poor prognosis
Prognosis
Prognosis is a medical term to describe the likely outcome of an illness.When applied to large statistical populations, prognostic estimates can be very accurate: for example the statement "45% of patients with severe septic shock will die within 28 days" can be made with some confidence, because...
. Research about screening tests for the early detection of mesothelioma is ongoing.
Signs and symptoms
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 effusionPleural effusion
Pleural effusion is excess fluid that accumulates between the two pleural layers, the fluid-filled space that surrounds the lungs. Excessive amounts of such fluid can impair breathing by limiting the expansion of the lungs during ventilation.-Pathophysiology:...
) are often symptoms of pleural mesothelioma.
Symptoms of peritoneal
Peritoneum
The peritoneum is the serous membrane that forms the lining of the abdominal cavity or the coelom — it covers most of the intra-abdominal organs — in amniotes and some invertebrates...
mesothelioma include weight loss and cachexia
Cachexia
Cachexia or wasting syndrome is loss of weight, muscle atrophy, fatigue, weakness, and significant loss of appetite in someone who is not actively trying to lose weight...
, abdominal swelling and pain due to ascites
Ascites
Ascites is a gastroenterological term for an accumulation of fluid in the peritoneal cavity.The medical condition is also known as peritoneal cavity fluid, peritoneal fluid excess, hydroperitoneum or more archaically as abdominal dropsy. Although most commonly due to cirrhosis and severe liver...
(a buildup of fluid in the abdominal cavity). Other symptoms of Peritoneal Mesothelioma
Peritoneal mesothelioma
Peritoneal mesothelioma is the name given to the cancer that attacks the lining of the abdomen. This type of cancer affects the lining that protects the contents of the abdomen and which also provides a lubricating fluid to enable the organs to move and work properly.The peritoneum is made of two...
may include bowel obstruction, blood clotting abnormalities, anemia
Anemia
Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
, and fever
Fever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
. 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.
These symptoms may be caused by mesothelioma or by other, less serious conditions.
Mesothelioma that affects the pleura can cause these signs and symptoms:
- Chest wall pain
- Pleural effusion, or fluid surrounding the lung
- Shortness of breath
- Fatigue or anemia
- Wheezing, hoarseness, or cough
- Blood in the sputumSputumSputum is mucus that is coughed up from the lower airways. It is usually used for microbiological investigations of respiratory infections....
(fluid) coughed up (hemoptysisHemoptysisHemoptysis or haemoptysis is the expectoration of blood or of blood-stained sputum from the bronchi, larynx, trachea, or lungs Hemoptysis or haemoptysis is the expectoration (coughing up) of blood or of blood-stained sputum from the bronchi, larynx, trachea, or lungs Hemoptysis or haemoptysis ...
)
In severe cases, the person may have many tumor
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...
masses. The individual may develop a pneumothorax
Pneumothorax
Pneumothorax is a collection of air or gas in the pleural cavity of the chest between the lung and the chest wall. It may occur spontaneously in people without chronic lung conditions as well as in those with lung disease , and many pneumothoraces occur after physical trauma to the chest, blast...
, or collapse of the lung
Lung
The lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...
. The disease may metastasize, or spread, to other parts of the body.
Tumors that affect the abdominal cavity often do not cause symptoms until they are at a late stage. Symptoms include:
- Abdominal pain
- AscitesAscitesAscites is a gastroenterological term for an accumulation of fluid in the peritoneal cavity.The medical condition is also known as peritoneal cavity fluid, peritoneal fluid excess, hydroperitoneum or more archaically as abdominal dropsy. Although most commonly due to cirrhosis and severe liver...
, or an abnormal buildup of fluid in the abdomen - A mass in the abdomen
- Problems with bowel function
- Weight loss
In severe cases of the disease, the following signs and symptoms may be present:
- Blood clots in the veins, which may cause thrombophlebitisThrombophlebitisThrombophlebitis is phlebitis related to a thrombus . When it occurs repeatedly in different locations, it is known as "Thrombophlebitis migrans" or "migrating thrombophlebitis".-Signs and symptoms:...
- Disseminated intravascular coagulationDisseminated intravascular coagulationDisseminated intravascular coagulation , also known as disseminated intravascular coagulopathy or consumptive coagulopathy, is a pathological activation of coagulation mechanisms that happens in response to a variety of diseases. DIC leads to the formation of small blood clots inside the blood...
, a disorder causing severe bleeding in many body organs - JaundiceJaundiceJaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...
, 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
A mesothelioma does not usually spread to the bone, brain, or adrenal glands. Pleural tumors are usually found only on one side of the lungs.
Cause
Working with asbestosAsbestos
Asbestos is a set of six naturally occurring silicate minerals used commercially for their desirable physical properties. They all have in common their eponymous, asbestiform habit: long, thin fibrous crystals...
is the major risk factor for mesothelioma. In the United States, asbestos is the major cause of malignant mesothelioma and has been considered "indisputably" 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. A history of asbestos exposure exists in most cases. However, mesothelioma has been reported in some individuals without any known exposure to asbestos. In rare cases, mesothelioma has also been associated with irradiation, intrapleural thorium dioxide (Thorotrast
Thorotrast
Thorotrast is a suspension containing particles of the radioactive compound thorium dioxide, ThO2, used as a contrast medium in X-ray diagnostics in the 1930s and 40s ....
), and inhalation of other fibrous silicates, such as erionite
Erionite
Erionite is a naturally occurring fibrous mineral that belongs to a group of minerals called zeolites. It usually is found in volcanic ash that has been altered by weathering and ground water. Erionite forms brittle, wool-like fibrous masses in the hollows of rock formations and has an internal...
. Some studies suggest that simian virus
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
40 (SV40
SV40
SV40 is an abbreviation for Simian vacuolating virus 40 or Simian virus 40, a polyomavirus that is found in both monkeys and humans...
) may act as a cofactor
Cofactor (biochemistry)
A cofactor is a non-protein chemical compound that is bound to a protein and is required for the protein's biological activity. These proteins are commonly enzymes, and cofactors can be considered "helper molecules" that assist in biochemical transformations....
in the development of mesothelioma.
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
World War II
World War II, or the Second World War , was a global conflict lasting from 1939 to 1945, involving most of the world's nations—including all of the great powers—eventually forming two opposing military alliances: the Allies and the Axis...
. 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 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
Occupational Safety and Health Administration
The United States Occupational Safety and Health Administration is an agency of the United States Department of Labor. It was created by Congress of the United States under the Occupational Safety and Health Act, signed by President Richard M. Nixon, on December 29, 1970...
(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, they are not adequate to prevent or protect against asbestos-related cancers such as mesothelioma. Likewise, the British Government's Health and Safety Executive
Health and Safety Executive
The Health and Safety Executive is a non-departmental public body in the United Kingdom. It is the body responsible for the encouragement, regulation and enforcement of workplace health, safety and welfare, and for research into occupational risks in England and Wales and Scotland...
(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 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. There appears to be a linear, dose-response relationship, with increasing dose producing increasing disease. Nevertheless, mesothelioma may be related to brief, low level or indirect exposures to asbestos. The dose necessary for effect appears to be lower for asbestos-induced mesothelioma than for pulmonary asbestosis or lung cancer. Again, there is no known safe level of exposure to asbestos as it relates to increased risk of mesothelioma.
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. People who work with asbestos wear personal protective equipment to lower their risk of exposure.
Latency, the time from first exposure to manifestation of disease, is prolonged in the case of mesothelioma. It is virtually never less than fifteen years and peaks at 30–40 years. In a review of occupationally related mesothelioma cases, the median latency was 32 years. Based upon the data from Peto et al., the risk of mesothelioma appears to increase to the third or fourth power from first exposure.
Environmental exposures
Incidence of mesothelioma had been found to be higher in populations living near naturally occurring asbestos. For example, in central CappadociaCappadocia
Cappadocia is a historical region in Central Anatolia, largely in Nevşehir Province.In the time of Herodotus, the Cappadocians were reported as occupying the whole region from Mount Taurus to the vicinity of the Euxine...
, Turkey, mesothelioma was causing 50% of all deaths in three small villages — Tuzköy, Karain and Sarıhıdır. Initially, this was attributed to erionite
Erionite
Erionite is a naturally occurring fibrous mineral that belongs to a group of minerals called zeolites. It usually is found in volcanic ash that has been altered by weathering and ground water. Erionite forms brittle, wool-like fibrous masses in the hollows of rock formations and has an internal...
, a zeolite mineral with similar properties to asbestos
Asbestos
Asbestos is a set of six naturally occurring silicate minerals used commercially for their desirable physical properties. They all have in common their eponymous, asbestiform habit: long, thin fibrous crystals...
. Recently, however, detailed epidemiological investigation showed that erionite causes mesothelioma mostly in families with a genetic predisposition.
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.
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.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 mesothelioma had occurred by 1985. By 1994, 539 reported deaths due to mesothelioma had been reported in Western Australia.
Paraoccupational secondary exposure
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 fibres, asbestos workers are usually required to shower and change their clothing before leaving the workplace.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 DIYDo it yourself
Do it yourself is a term used to describe building, modifying, or repairing of something without the aid of experts or professionals...
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
Riebeckite
Riebeckite is a sodium-rich member of the amphibole group of silicate minerals, chemical formula [][Na2][32][2|Si8O22]. It forms a series with magnesioriebeckite. It crystallizes in the monoclinic system, usually as long prismatic crystals showing a diamond-shaped cross section, but also in...
was banned in the UK around 1985. Buildings built or renovated prior to these dates may contain asbestos materials.
Diagnosis
Diagnosing mesothelioma is often difficult, because the symptoms are similar to those of a number of other conditions. Diagnosis begins with a review of the patient's medical history. A history of exposure to asbestos may increase clinical suspicion for mesothelioma. A physical examination is performed, followed by chest X-ray
Chest X-ray
In medicine, a chest radiograph, commonly called a chest X-ray , is a projection radiograph of the chest used to diagnose conditions affecting the chest, its contents, and nearby structures...
and often lung function tests
Spirometry
Spirometry is the most common of the pulmonary function tests , measuring lung function, specifically the measurement of the amount and/or speed of air that can be inhaled and exhaled...
. The X-ray may reveal pleural thickening commonly seen after asbestos exposure and increases suspicion of mesothelioma. A CT
Computed tomography
X-ray computed tomography or Computer tomography , is a medical imaging method employing tomography created by computer processing...
(or CAT) scan or an MRI is usually performed. If a large amount of fluid is present, abnormal cells may be detected by cytopathology
Cytopathology
Cytopathology is a branch of pathology that studies and diagnoses diseases on the cellular level. The discipline was founded by Rudolf Virchow in 1858. A common application of cytopathology is the Pap smear, used as a screening tool, to detect precancerous cervical lesions and prevent cervical...
if this fluid is aspirated
Needle aspiration biopsy
Needle aspiration biopsy , may refer to fine needle aspiration cytology , fine needle aspiration biopsy and fine needle aspiration , is a diagnostic procedure sometimes used to investigate superficial lumps or masses...
with a syringe. For pleural fluid, this is done by thoracentesis
Thoracentesis
Thoracentesis , also known as thoracocentesis or pleural tap, is an invasive procedure to remove fluid or air from the pleural space for diagnostic or therapeutic purposes. A cannula, or hollow needle, is carefully introduced into the thorax, generally after administration of local anesthesia...
or tube thoracostomy (chest tube
Chest tube
A chest tube is a flexible plastic tube that is inserted through the side of the chest into the pleural space. It is used to remove air or fluid , or pus from the intrathoracic space...
); for ascites, with paracentesis
Paracentesis
Paracentesis is a medical procedure involving needle drainage of fluid from a body cavity, most commonly the peritoneal cavity in the abdomen.A related procedure is thoracocentesis, which is needle drainage of the chest cavity...
or ascitic drain; and for pericardial effusion with pericardiocentesis
Pericardiocentesis
In medicine, pericardiocentesis is a procedure where fluid is aspirated from the pericardium .-Position:The patient undergoing pericardiocentesis is positioned supine with the head of the bed raised to a 30- to 60-degree angle.This places the heart in proximity to the chest wall for easier...
. While absence of malignant cells on cytology does not completely exclude mesothelioma, it makes it much more unlikely, especially if an alternative diagnosis can be made (e.g. tuberculosis
Tuberculosis
Tuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body...
, heart failure). Unfortunately, the diagnosis of malignant mesothelioma by cytology alone is difficult, even with expert pathologists.
Generally, a biopsy
Biopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
is needed to confirm a diagnosis of malignant mesothelioma. A doctor removes a sample of tissue for examination under a microscope by a pathologist
Histopathology
Histopathology refers to the microscopic examination of tissue in order to study the manifestations of disease...
. A biopsy may be done in different ways, depending on where the abnormal area is located. If the cancer is in the chest, the doctor may perform a thoracoscopy
Thoracoscopy
Thoracoscopy is a medical procedure involving internal examination, biopsy, and/or resection of disease or masses within the pleural cavity and thoracic cavity...
. In this procedure, the doctor makes a small cut through the chest wall and puts a thin, lighted tube called a thoracoscope into the chest between two ribs. Thoracoscopy allows the doctor to look inside the chest and obtain tissue samples. Alternatively, the chest surgeon might directly open the chest (thoracotomy
Thoracotomy
Thoracotomy is an incision into the pleural space of the chest. It is performed by a surgeon, and, rarely, by emergency physicians, to gain access to the thoracic organs, most commonly the heart, the lungs, the esophagus or thoracic aorta, or for access to the anterior spine such as is necessary...
). If the cancer is in the abdomen, the doctor may perform a laparoscopy
Laparoscopy
Laparoscopy is an operation performed in the abdomen or pelvis through small incisions with the aid of a camera...
. To obtain tissue for examination, the doctor makes a small incision in the abdomen and inserts a special instrument into the abdominal cavity. If these procedures do not yield enough tissue, more extensive diagnostic surgery may be necessary.
Immunohistochemical studies play an important role for the pathologist in differentiating malignant mesothelioma from neoplastic mimics. There are numerous tests and panels available. No single test is perfect for distinguishing mesothelioma from carcinoma or even benign versus malignant.
| Positive | Negative |
| EMA (epithelial membrane antigen) in a membranous distribution | CEA (carcinoembryonic antigen Carcinoembryonic antigen Carcinoembryonic antigen is a glycoprotein involved in cell adhesion. It is normally produced during fetal development, but the production of CEA stops before birth. Therefore, it is not usually present in the blood of healthy adults, although levels are raised in heavy smokers... ) |
| WT1 WT1 Wilms tumor protein is a protein that in humans is encoded by the WT1 gene.- Function :This gene encodes a transcription factor that contains four zinc finger motifs at the C-terminus and a proline / glutamine-rich DNA-binding domain at the N-terminus... (Wilms' tumour 1) |
B72.3 |
| Calretinin Calretinin Calretinin also known as 29 kDa calbindin is a vitamin D-dependent calcium-binding protein involved in calcium signaling. In humans, the calretinin protein is encoded by the CALB2 gene.- Function :... |
MOC-3 1 |
| Mesothelin-1 | CD15 CD15 CD15 is a cluster of differentiation antigen - an immunologically significant molecule. CD15 is a carbohydrate adhesion molecule that can be expressed on glycoproteins, glycolipids and proteoglycans.- Function :... |
| Cytokeratin Cytokeratin Cytokeratins are proteins of keratin-containing intermediate filaments found in the intracytoplasmic cytoskeleton of epithelial tissue. The term "cytokeratin" began to be used in the late 1970s when the protein subunits of keratin intermediate filaments inside cells were first being identified and... 5/6 |
Ber-EP4 |
| HBME-1 (human mesothelial cell 1) | TTF-1 (thyroid transcription factor-1) |
There are three histological types of malignant mesothelioma: (1) Epithelioid; (2) Sarcomatoid; and (3) Biphasic (Mixed). Epithelioid comprises about 50-60% of malignant mesothelioma cases and generally holds a better prognosis than the Sarcomatoid or Biphasic subtypes.
Staging
StagingCancer staging
The stage of a cancer is a description of the extent the cancer has spread. The stage often takes into account the size of a tumor, how deeply it has penetrated, whether it has invaded adjacent organs, how many lymph nodes it has metastasized to , and whether it has spread to distant organs...
of mesothelioma is based on the recommendation by the International Mesothelioma Interest Group. TNM classification of the primary tumor, lymph node
Lymph node
A lymph node is a small ball or an oval-shaped organ of the immune system, distributed widely throughout the body including the armpit and stomach/gut and linked by lymphatic vessels. Lymph nodes are garrisons of B, T, and other immune cells. Lymph nodes are found all through the body, and act as...
involvement, and distant metastasis
Metastasis
Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...
is performed. Mesothelioma is staged Ia–IV (one-A to four) based on the TNM status.
Screening
There is no universally agreed protocol for screening people who have been exposed to asbestos. Screening tests might diagnose mesothelioma earlier than conventional methods thus improving the survival prospects for patients. The serumBlood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
osteopontin
Osteopontin
Osteopontin , also known as bone sialoprotein I , early T-lymphocyte activation , secreted phosphoprotein 1 , 2ar and Rickettsia resistance , is a human gene product, which is also conserved in other species...
level might be useful in screening asbestos-exposed people for mesothelioma. The level of soluble mesothelin-related protein is elevated in the serum of about 75% of patients at diagnosis and it has been suggested that it may be useful for screening. Doctors have begun testing the Mesomark assay
Mesomark assay
The Mesomark Assay is an in vitro test to monitor and possibly diagnose Pleural Mesothelioma and Peritoneal Mesothelioma.Developed by Fujirebio Diagnostics and approved in late January 2007 by the U.S. Food and Drug Administration , it works by measuring levels of soluble mesothelin-related...
which measures levels of soluble mesothelin
Mesothelin
Mesothelin also known as MSLN is a protein that in humans is encoded by the MSLN gene.- Function :Mesothelin is a 40kDa protein present on normal mesothelial cells and overexpressed in several human tumors, including mesothelioma and ovarian and pancreatic adenocarcinoma. The protein was first...
-related proteins (SMRPs) released by diseased mesothelioma cells.
Pathophysiology
The mesotheliumMesothelium
The mesothelium is a membrane that forms the lining of several body cavities: the pleura , peritoneum and pericardium . Mesothelial tissue also surrounds the male internal reproductive organs and covers the internal reproductive organs of women...
consists of a single layer of flattened to cuboidal cells forming the epithelial
Epithelium
Epithelium is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. Epithelial tissues line the cavities and surfaces of structures throughout the body, and also form many glands. Functions of epithelial cells include secretion, selective...
lining of the serous cavities of the body including the peritoneal
Peritoneum
The peritoneum is the serous membrane that forms the lining of the abdominal cavity or the coelom — it covers most of the intra-abdominal organs — in amniotes and some invertebrates...
, pericardial
Pericardium
The pericardium is a double-walled sac that contains the heart and the roots of the great vessels.-Layers:...
and pleural cavities. Deposition of asbestos fibers in the parenchyma
Parenchyma
Parenchyma is a term used to describe a bulk of a substance. It is used in different ways in animals and in plants.The term is New Latin, f. Greek παρέγχυμα - parenkhuma, "visceral flesh", f. παρεγχεῖν - parenkhein, "to pour in" f. para-, "beside" + en-, "in" + khein, "to pour"...
of the lung may result in the penetration of the visceral pleura from where the fiber can then be carried to the pleural surface, thus leading to the development of malignant mesothelial plaques. The processes leading to the development of peritoneal mesothelioma
Peritoneal mesothelioma
Peritoneal mesothelioma is the name given to the cancer that attacks the lining of the abdomen. This type of cancer affects the lining that protects the contents of the abdomen and which also provides a lubricating fluid to enable the organs to move and work properly.The peritoneum is made of two...
remain unresolved, although it has been proposed that asbestos fibers from the lung are transported to the abdomen and associated organs via the lymphatic system
Lymphatic system
The lymphoid system is the part of the immune system comprising a network of conduits called lymphatic vessels that carry a clear fluid called lymph unidirectionally toward the heart. Lymphoid tissue is found in many organs, particularly the lymph nodes, and in the lymphoid follicles associated...
. Additionally, asbestos fibers may be deposited in the gut after ingestion of sputum contaminated with asbestos fibers.
Pleural contamination with asbestos or other mineral fibers has been shown to cause cancer. Long thin asbestos fibers (blue asbestos, amphibole
Amphibole
Amphibole is the name of an important group of generally dark-colored rock-forming inosilicate minerals, composed of double chain tetrahedra, linked at the vertices and generally containing ions of iron and/or magnesium in their structures.-Mineralogy:...
fibers) are more potent carcinogen
Carcinogen
A carcinogen is any substance, radionuclide, or radiation that is an agent directly involved in causing cancer. This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes...
s than "feathery fibers" (chrysotile
Chrysotile
Chrysotile or white asbestos is the most commonly encountered form of asbestos, accounting for approximately 95% of the asbestos in place in the United States and a similar proportion in other countries. It is a soft, fibrous silicate mineral in the serpentine group of phyllosilicates; as such, it...
or white asbestos fibers). However, there is now evidence that smaller particles may be more dangerous than the larger fibers. They remain suspended in the air where they can be inhaled, and may penetrate more easily and deeper into the lungs. "We probably will find out a lot more about the health aspects of asbestos from [the World Trade Center attack], unfortunately," said Dr. Alan Fein, chief of pulmonary and critical-care medicine at North Shore-Long Island Jewish Health System. Dr. Fein has treated several patients for "World Trade Center syndrome" or respiratory ailments from brief exposures of only a day or two near the collapsed buildings.
Mesothelioma development in rats has been demonstrated following intra-pleural inoculation of phosphorylated chrysotile fibers. It has been suggested that in humans, transport of fibers to the pleura is critical to the pathogenesis of mesothelioma. This is supported by the observed recruitment of significant numbers of macrophage
Macrophage
Macrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...
s and other cells of the immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
to localized lesions of accumulated asbestos fibers in the pleural and peritoneal cavities of rats. These lesions continued to attract and accumulate macrophages as the disease progressed, and cellular changes within the lesion culminated in a morphologically malignant tumor.
Experimental evidence suggests that asbestos acts as a complete carcinogen with the development of mesothelioma occurring in sequential stages of initiation and promotion. The molecular mechanisms underlying the malignant transformation of normal mesothelial cells by asbestos fibers remain unclear despite the demonstration of its oncogenic capabilities (see next-but-one paragraph). However, complete in vitro transformation of normal human mesothelial cells to malignant phenotype
Phenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...
following exposure to asbestos fibers has not yet been achieved. In general, asbestos fibers are thought to act through direct physical interactions with the cells of the mesothelium in conjunction with indirect effects following interaction with inflammatory cells such as macrophages.
Analysis of the interactions between asbestos fibers and DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
has shown that phagocytosed fibers are able to make contact with chromosome
Chromosome
A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...
s, often adhering to the chromatin
Chromatin
Chromatin is the combination of DNA and proteins that make up the contents of the nucleus of a cell. The primary functions of chromatin are; to package DNA into a smaller volume to fit in the cell, to strengthen the DNA to allow mitosis and meiosis and prevent DNA damage, and to control gene...
fibers or becoming entangled within the chromosome. This contact between the asbestos fiber and the chromosomes or structural proteins of the spindle apparatus can induce complex abnormalities. The most common abnormality is monosomy
Monosomy
Monosomy is a form of aneuploidy with the presence of only one chromosome from a pair. Partial monosomy occurs when only a portion of the chromosome has one copy, while the rest has two copies.-Human monosomy:...
of chromosome 22. Other frequent abnormalities include structural rearrangement of 1p, 3p, 9p and 6q chromosome arms.
Common gene abnormalities in mesothelioma cell lines include deletion of the tumor suppressor gene
Tumor suppressor gene
A tumor suppressor gene, or anti-oncogene, is a gene that protects a cell from one step on the path to cancer. When this gene is mutated to cause a loss or reduction in its function, the cell can progress to cancer, usually in combination with other genetic changes.-Two-hit hypothesis:Unlike...
s:
- NeurofibromatosisNeurofibromatosisNeurofibromatosis is a genetically-inherited disorder in which the nerve tissue grows tumors that may be benign or may cause serious damage by compressing nerves and other tissues...
type 2 at 22q12 - P16INK4AP16 (gene)Cyclin-dependent kinase inhibitor 2A, also known as multiple tumor suppressor 1 , is a tumor suppressor protein, that in humans is encoded by the CDKN2A gene...
- P14ARFP14arfp14ARF is an alternate reading frame product of the CDKN2A locus. Both p16INK4a and p14ARF are involved in cell cycle regulation. p14ARF inhibits mdm2, thus promoting p53, which promotes p21 activation, which then binds and inactivates certain cyclin-CDK complexes, which would otherwise promote...
Asbestos has also been shown to mediate the entry of foreign DNA into target cells. Incorporation of this foreign DNA may lead to mutations and oncogenesis by several possible mechanisms:
- Inactivation of tumor suppressor genes
- Activation of oncogeneOncogeneAn oncogene is a gene that has the potential to cause cancer. In tumor cells, they are often mutated or expressed at high levels.An oncogene is a gene found in the chromosomes of tumor cells whose activation is associated with the initial and continuing conversion of normal cells into cancer...
s - Activation of proto-oncogenes due to incorporation of foreign DNA containing a promoter region
- Activation of DNA repairDNA repairDNA repair refers to a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as UV light and radiation can cause DNA damage, resulting in as many as 1...
enzymes, which may be prone to error - Activation of telomeraseTelomeraseTelomerase is an enzyme that adds DNA sequence repeats to the 3' end of DNA strands in the telomere regions, which are found at the ends of eukaryotic chromosomes. This region of repeated nucleotide called telomeres contains non-coding DNA material and prevents constant loss of important DNA from...
- Prevention of apoptosisApoptosisApoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
Asbestos fibers have been shown to alter the function and secretory properties of macrophages, ultimately creating conditions which favour the development of mesothelioma. Following asbestos phagocytosis, macrophages generate increased amounts of hydroxyl radicals
Radical (chemistry)
Radicals are atoms, molecules, or ions with unpaired electrons on an open shell configuration. Free radicals may have positive, negative, or zero charge...
, which are normal by-products of cellular anaerobic metabolism. However, these free radicals are also known clastogenic
Clastogenic
Clastogenic is an adjective that describes the ability of an agent or process to act as a clastogen—an agent or process giving rise to or inducing disruption or breakages of chromosomes.-Biology:...
and membrane-active agents thought to promote asbestos carcinogenicity. These oxidants can participate in the oncogenic process by directly and indirectly interacting with DNA, modifying membrane-associated cellular events, including oncogene activation and perturbation of cellular antioxidant defences.
Asbestos also may possess immunosuppressive
Immunosuppressant
An immunosuppressant is any substance that performs immunosuppression of the immune system. They may be either exogenous, as immunosuppressive drugs, or endogenous, as ,e. g., testosterone...
properties. For example, chrysotile fibres have been shown to depress the in vitro proliferation of phytohemagglutinin-stimulated peripheral blood lymphocytes, suppress natural killer cell lysis and significantly reduce lymphokine-activated killer cell
Lymphokine-activated killer cell
In cell biology, a lymphokine-activated killer cell is a white blood cell that has been stimulated to kill tumour cells...
viability and recovery. Furthermore, genetic alterations in asbestos-activated macrophages may result in the release of potent mesothelial cell mitogens such as platelet-derived growth factor
Platelet-derived growth factor
In molecular biology, platelet-derived growth factor is one of the numerous growth factors, or proteins that regulate cell growth and division. In particular, it plays a significant role in blood vessel formation , the growth of blood vessels from already-existing blood vessel tissue. Uncontrolled...
(PDGF) and transforming growth factor
Transforming growth factor
Transforming growth factor is used to describe two classes of polypeptide growth factors, TGFα and TGFβ....
-β (TGF-β) which in turn, may induce the chronic stimulation and proliferation of mesothelial cells after injury by asbestos fibres.
Treatment
The prognosis for malignant mesothelioma remains disappointing, although there have been some modest improvements in prognosis from newer chemotherapies and multimodality treatments. Treatment of malignant mesothelioma at earlier stages has a better prognosis, but cures are exceedingly rare. Clinical behavior of the malignancy is affected by several factors including the continuous mesothelial surface of the pleural cavity which favors 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. The histological subtype and the patient's age and health status also help predict prognosis. The epithelioid histology responds better to treatment and has a survival advantage over sarcomatoid histology.Surgery
Surgery, by itself, has proved disappointing. In one large series, the median survival with surgery (including extrapleural pneumonectomyPneumonectomy
A pneumonectomy is a surgical procedure to remove a lung. Removal of just one lobe of the lung is specifically referred to as a lobectomy, and that of a segment of the lung as a wedge resection .-Indications:...
) was only 11.7 months. However, research indicates varied success when used in combination with radiation and chemotherapy (Duke, 2008). (For more information on multimodality therapy with surgery, see below). A pleurectomy/decortication is the most common surgery, in which the lining of the chest is removed. Less common is an extrapleural pneumonectomy (EPP), in which the lung, lining of the inside of the chest, the hemi-diaphragm
Thoracic diaphragm
In the anatomy of mammals, the thoracic diaphragm, or simply the diaphragm , is a sheet of internal skeletal muscle that extends across the bottom of the rib cage. The diaphragm separates the thoracic cavity from the abdominal cavity and performs an important function in respiration...
and the pericardium
Pericardium
The pericardium is a double-walled sac that contains the heart and the roots of the great vessels.-Layers:...
are removed.
Radiation
For patients with localized disease, and who can tolerate a radical surgery, radiation is often given post-operatively as a consolidative treatment. The entire hemi-thorax is treated with radiation therapy, often given simultaneously with chemotherapy. Delivering radiation and chemotherapy after a radical surgery has led to extended life expectancy in selected patient populations with some patients surviving more than 5 years. As part of a curative approach to mesothelioma, radiotherapy is also commonly applied to the sites of chest drain insertion, in order to prevent growth of the tumor along the track in the chest wall.Although mesothelioma is generally resistant to curative treatment with radiotherapy alone, palliative treatment regimens are sometimes used to relieve symptoms arising from tumor growth, such as obstruction of a major blood vessel. Radiation therapy when given alone with curative intent has never been shown to improve survival from mesothelioma. The necessary radiation dose to treat mesothelioma that has not been surgically removed would be very toxic.
Chemotherapy
Chemotherapy is the only treatment for mesothelioma that has been proven to improve survival in randomised and controlled trials. The landmark study published in 2003 by Vogelzang and colleagues compared cisplatinCisplatin
Cisplatin, cisplatinum, or cis-diamminedichloroplatinum is a chemotherapy drug. It is used to treat various types of cancers, including sarcomas, some carcinomas , lymphomas, and germ cell tumors...
chemotherapy alone with a combination of cisplatin and pemetrexed
Pemetrexed
Pemetrexed is a chemotherapy drug manufactured and marketed by Eli Lilly and Company. Its indications are the treatment of Pleural Mesothelioma as well as non-small cell lung cancer.-History:...
(brand name Alimta) chemotherapy in patients who had not received chemotherapy for malignant pleural mesothelioma previously and were not candidates for more aggressive "curative" surgery. This trial was the first to report a survival advantage from chemotherapy in malignant pleural mesothelioma, showing a statistically significant improvement in median
Median
In probability theory and statistics, a median is described as the numerical value separating the higher half of a sample, a population, or a probability distribution, from the lower half. The median of a finite list of numbers can be found by arranging all the observations from lowest value to...
survival from 10 months in the patients treated with cisplatin alone to 13.3 months in the group of patients treated with cisplatin in the combination with pemetrexed and who also received supplementation with folate and vitamin B12. Vitamin supplementation was given to most patients in the trial and pemetrexed related side effects were significantly less in patients receiving pemetrexed when they also received daily oral folate 500mcg and intramuscular vitamin B12 1000mcg every 9 weeks compared with patients receiving pemetrexed without vitamin supplementation. The objective response rate increased from 20% in the cisplatin group to 46% in the combination pemetrexed group. Some side effects such as nausea and vomiting, stomatitis
Stomatitis
Stomatitis is an inflammation of the mucous lining of any of the structures in the mouth, which may involve the cheeks, gums, tongue, lips, throat, and roof or floor of the mouth...
, and diarrhoea were more common in the combination pemetrexed group but only affected a minority of patients and overall the combination of pemetrexed and cisplatin was well tolerated when patients received vitamin supplementation; both quality of life
Quality of life
The term quality of life is used to evaluate the general well-being of individuals and societies. The term is used in a wide range of contexts, including the fields of international development, healthcare, and politics. Quality of life should not be confused with the concept of standard of...
and lung function tests improved in the combination pemetrexed group. In February 2004, the United States Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
approved pemetrexed for treatment of malignant pleural mesothelioma. However, there are still unanswered questions about the optimal use of chemotherapy, including when to start treatment, and the optimal number of cycles to give.
Cisplatin in combination with raltitrexed
Raltitrexed
Raltitrexed is an antimetabolite drug used in cancer chemotherapy. It is an inhibitor of thymidylate synthase, and is manufactured by AstraZeneca.-Mechanism of action:...
has shown an improvement in survival similar to that reported for pemetrexed in combination with cisplatin, but raltitrexed is no longer commercially available for this indication. For patients unable to tolerate pemetrexed, cisplatin in combination with gemcitabine or vinorelbine is an alternative, or vinorelbine on its own, although a survival benefit has not been shown for these drugs. For patients in whom cisplatin cannot be used, carboplatin can be substituted but non-randomised data have shown lower response rates and high rates of haematological toxicity for carboplatin-based combinations, albeit with similar survival figures to patients receiving cisplatin.
In January 2009, the United States FDA approved using conventional therapies such as surgery in combination with radiation and or chemotherapy on stage I or II Mesothelioma after research conducted by a nationwide study by Duke University concluded an almost 50 point increase in remission rates.
Immunotherapy
Treatment regimens involving immunotherapy have yielded variable results. For example, intrapleural inoculation of Bacillus Calmette-GuérinBacillus Calmette-Guérin
Bacillus Calmette-Guérin is a vaccine against tuberculosis that is prepared from a strain of the attenuated live bovine tuberculosis bacillus, Mycobacterium bovis, that has lost its virulence in humans by being specially subcultured in an artificial medium for 13 years, and also prepared from...
(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
Bladder cancer
Bladder cancer is any of several types of malignant growths of the urinary bladder. It is a disease in which abnormal cells multiply without control in the bladder. The bladder is a hollow, muscular organ that stores urine; it is located in the pelvis...
). 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.
This technique is also used in patients with malignant pleural mesothelioma.
Multimodality Therapy
All of the standard approaches to treating solid tumors—radiation, chemotherapy, and surgery—have been investigated in patients with malignant pleural mesothelioma. Although surgery, by itself, is not very effective, surgery combined with adjuvant chemotherapy and radiation (trimodality therapy) has produced significant survival extension (3–14 years) among patients with favorable prognostic factors. However, other large series of examining multimodality treatment have only demonstrated modest improvement in survival (median survival 14.5 months and only 29.6% surviving 2 years). Reducing the bulk of the tumor with cytoreductive surgery is key to extending survival. Two surgeries have been developed: extrapleural pneumonectomy and pleurectomy/decortication. The indications for performing these operations are unique. The choice of operation depends on the size of the patient's tumor. This is an important consideration because tumor volume has been identified as a prognostic factor in mesothelioma. Pleurectomy/decortication spares the underlying lung and is performed in patients with early stage disease when the intention is to remove all gross visible tumor (macroscopic complete resection), not simply palliation. Extrapleural pneumonectomy is a more extensive operation that involves resection of the parietal and visceral pleurae, underlying lung, ipsilateral diaphragm, and ipsilateral pericardium. This operation is indicated for a subset of patients with more advanced tumors, who can tolerate a pneumonectomy.Epidemiology
Although reported incidence rates have increased in the past 20 years, mesothelioma is still a relatively rare cancer. The incidence rate varies from one country to another, from a low rate of less than 1 per 1,000,000 in Tunisia and Morocco, to the highest rate in Britain, Australia and Belgium: 30 per 1,000,000 per year. 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.Between 1940 and 1979, approximately 27.5 million people were occupationally exposed to asbestos in the United States. Between 1973 and 1984, the incidence of pleural mesothelioma among Caucasian males increased 300%. From 1980 to the late 1990s, the death rate from mesothelioma in the USA increased from 2,000 per year to 3,000, with men four times more likely to acquire it than women. These rates may not be accurate, since it is possible that many cases of mesothelioma are misdiagnosed as adenocarcinoma of the lung, which is difficult to differentiate from mesothelioma.
Notable cases
Mesothelioma, though rare, has had a number of notable patients.- Malcolm McLarenMalcolm McLarenMalcolm Robert Andrew McLaren was an English performer, impresario, self-publicist and manager of the Sex Pistols and the New York Dolls...
, former manager of New York DollsNew York DollsThe New York Dolls is an American rock band, formed in New York in 1971. The band's protopunk sound prefigured much of what was to come in the punk rock era; their visual style influenced the look of many new wave and 1980s-era glam metal groups, and they began the local New York scene that later...
and Sex PistolsSex PistolsThe Sex Pistols were an English punk rock band that formed in London in 1975. They were responsible for initiating the punk movement in the United Kingdom and inspiring many later punk and alternative rock musicians...
, died on 8 April 2010.
- Billy VaughnBilly VaughnRichard "Billy" Vaughn was an American singer, multi-instrumentalist, orchestra leader, and A&R man for Dot Records....
, American bandleader, died in 1991.
- Hamilton JordanHamilton JordanWilliam Hamilton McWhorter Jordan was Chief of Staff to President of the United States Jimmy Carter.-Early life:...
, Chief of Staff for U.S. President Jimmy Carter and lifelong cancer activist, died in 2008.
- Richard J. Herrnstein, psychologist and co-author of The Bell CurveThe Bell CurveThe Bell Curve is a best-selling and controversial 1994 book by the Harvard psychologist Richard J. Herrnstein and political scientist Charles Murray...
, died in 1994.
- Australian anti-racism activist Bob BellearBob BellearBob Bellear was the first Indigenous Australian judge.Bob was born in the far north-east of New South Wales, and grew up near the town of Mullumbimby...
died in 2005.
- British science fiction writer Michael G. ConeyMichael G. ConeyMichael Greatrex Coney was a British science fiction writer who spent the later half of his life in Canada. Born in Birmingham, England on September 28, 1932, he moved to Victoria, British Columbia in 1972...
, responsible for nearly 100 works, also died in 2005.
- American film and television actor Paul GleasonPaul GleasonPaul Xavier Gleason was an American film and television actor, known for his roles on TV series such as All My Children and films such as The Breakfast Club, Trading Places and Die Hard.-Early life:...
, perhaps best known for his portrayal of Principal Richard Vernon in the 1985 film The Breakfast ClubThe Breakfast ClubThe Breakfast Club is a 1985 American teen drama film written and directed by John Hughes. The storyline follows five teenagers as they spend a Saturday in detention together and come to realize that they are all deeper than their respective stereotypes.-Plot:The plot follows five students at...
, died in 2006.
- Mickie MostMickie MostMickie Most was an English record producer, with a string of hit singles with acts such as The Animals, Arrows, Herman's Hermits, Donovan, Suzi Quatro and the Jeff Beck Group often issued on his own RAK Records label....
, an English record producer, died of mesothelioma in 2003.
- Paul RudolphPaul Rudolph (architect)Paul Marvin Rudolph was an American architect and the dean of the Yale School of Architecture for six years, known for use of concrete and highly complex floor plans...
, American architect, died in 1997.
- Bernie BantonBernie BantonBernard Douglas Banton AM was an Australian social justice campaigner. He was the widely-recognised face of the legal and political campaign to achieve compensation for the many sufferers of asbestos-related conditions, which they contracted after working for the company James Hardie.Banton...
, an Australian workers' rights activist, fought a long battle for compensation from James HardieJames HardieJames Hardie Industries Ltd. is an industrial building materials company headquartered in Ireland and listed on the Australian Securities Exchange which specialises in fibre cement products. James Hardie manufactures and develops technologies, materials and processes for the production of building...
after he contracted mesothelioma after working for that company. He claimed James Hardie knew of the dangers of asbestos before he began work with the substance making insulation for power stations. Mesothelioma eventually took his life along with his brothers and hundreds of James Hardie workers. James Hardie made an undisclosed settlement with Banton only when his mesothelioma had reached its final stages and he was expected to have no more than 48 hours to live. Australian Prime Minister Kevin RuddKevin RuddKevin Michael Rudd is an Australian politician who was the 26th Prime Minister of Australia from 2007 to 2010. He has been Minister for Foreign Affairs since 2010...
mentioned Banton's extended struggle in his acceptance speech after winning the 2007 Australian federal election.
- Actor Steve McQueen was diagnosed with peritoneal mesotheliomaPeritoneal mesotheliomaPeritoneal mesothelioma is the name given to the cancer that attacks the lining of the abdomen. This type of cancer affects the lining that protects the contents of the abdomen and which also provides a lubricating fluid to enable the organs to move and work properly.The peritoneum is made of two...
on December 22, 1979. He was not offered surgery or chemotherapy because doctors felt the cancer was too advanced. McQueen subsequently sought alternative treatments at clinics in Mexico. He died of a heart attack on November 7, 1980, in Juárez, MexicoCiudad JuárezCiudad Juárez , officially known today as Heroica Ciudad Juárez, but abbreviated Juárez and formerly known as El Paso del Norte, is a city and seat of the municipality of Juárez in the Mexican state of Chihuahua. Juárez's estimated population is 1.5 million people. The city lies on the Rio Grande...
, following cancer surgery. He may have been exposed to asbestos while serving with the U.S. Marines as a young adult—asbestos was then commonly used to insulate ships' piping—or from its use as an insulating material in automobile racing suits (McQueen was an avid racing driver and fan).
- United States Congressman Bruce VentoBruce VentoBruce Frank Vento was an American politician, a Democratic-Farmer-Labor member of the United States House of Representatives from 1977 until his death in 2000...
died of mesothelioma in 2000. The Bruce Vento Hopebuilder award is given yearly by his wife at the MARFMesothelioma Applied Research FoundationThe Mesothelioma Applied Research Foundation is a non-profit organization that funds mesothelioma research, provides services to patients, educates the public, and advocates in Washington, DC for governmental funding for mesothelioma research...
Symposium to persons or organizations who have done the most to support mesothelioma research and advocacy.
- Rock and roll musician and songwriter Warren ZevonWarren ZevonWarren William Zevon was an American rock singer-songwriter and musician noted for including his sometimes sardonic opinions of life in his musical lyrics, composing songs that were sometimes humorous and often had political or historical themes.Zevon's work has often been praised by well-known...
, after a long period of untreated illness and pain, was diagnosed with inoperable mesothelioma in the fall of 2002. Refusing treatments that he believed might incapacitate him, Zevon focused his energies on recording his final album The WindThe Wind (album)The Wind is the last studio album by American singer/songwriter Warren Zevon, released in 2003. Zevon began recording the album shortly after he was diagnosed with inoperable pleural mesothelioma , and it was released just two weeks before his death on September 7, 2003 .The album was awarded the...
, including the song "Keep Me in Your Heart," which speaks of his failing breath. Zevon died at his home in Los Angeles, California, on September 7, 2003.
- Christie HennessyChristie HennessyChristie Hennessy was an Irish folk singer-songwriter.-Early life:...
, the influential Irish singer-songwriter, died of mesothelioma in 2007, and had stridently refused to accept the prognosis in the weeks before his death. Hennessy's mesothelioma has been attributed to his younger years spent working on building sites in LondonLondonLondon is the capital city of :England and the :United Kingdom, the largest metropolitan area in the United Kingdom, and the largest urban zone in the European Union by most measures. Located on the River Thames, London has been a major settlement for two millennia, its history going back to its...
.
- Bob MinerBob MinerRobert Nimrod "Bob" Miner was a co-founder of Oracle Corporation and architect of Oracle's relational database management system....
, one of the founders of Software Development Labs, the forerunner of Oracle CorporationOracle CorporationOracle Corporation is an American multinational computer technology corporation that specializes in developing and marketing hardware systems and enterprise software products – particularly database management systems...
, died of mesothelioma in 1994.
- Scottish Labour MP John William MacDougall died of mesothelioma on August 13, 2008, after fighting the disease for two years.
- Australian journalist and news presenter Peter LeonardPeter LeonardPeter Antony Leonard was an Australian journalist and newsreader. He was born in Yass, New South Wales, the son of a Greek immigrant father who died when Peter was 17. He was educated at Yass Primary School then at Canberra Grammar School as a boarder...
of CanberraCanberraCanberra is the capital city of Australia. With a population of over 345,000, it is Australia's largest inland city and the eighth-largest city overall. The city is located at the northern end of the Australian Capital Territory , south-west of Sydney, and north-east of Melbourne...
succumbed to the condition on September 23, 2008.
- Terrence McCannTerrence McCannTerrence John McCann , commonly known as Terry McCann, was an American wrestler who won the Gold Medal in the bantamweight division of freestyle wrestling at the 1960 Summer Olympics in Rome, and later helped found the United States Wrestling Federation...
, Olympic gold medalist and longtime Executive Director of Toastmasters, died of mesothelioma on June 7, 2006, at his home in Dana Point, California.
- Merlin OlsenMerlin OlsenMerlin Jay Olsen was an American football player in the National Football League, NFL commentator, and actor. He played his entire 15-year career with the Los Angeles Rams and was elected to the Pro Bowl in 14 of those seasons, a current record shared with Bruce Matthews...
, Pro Football Hall of Famer and television actor, died on March 10, 2010, from mesothelioma that had been diagnosed in 2009.
Notable people who have lived for some time with mesothelioma
Although life expectancy with this disease is typically limited, there are notable survivors. In July 1982, Stephen Jay GouldStephen Jay Gould
Stephen Jay Gould was an American paleontologist, evolutionary biologist, and historian of science. He was also one of the most influential and widely read writers of popular science of his generation....
was diagnosed with peritoneal mesothelioma
Peritoneal mesothelioma
Peritoneal mesothelioma is the name given to the cancer that attacks the lining of the abdomen. This type of cancer affects the lining that protects the contents of the abdomen and which also provides a lubricating fluid to enable the organs to move and work properly.The peritoneum is made of two...
. After his diagnosis, Gould wrote "The Median Isn't the Message" for Discover magazine, in which he argued that statistics such as median survival are just useful abstractions, not destiny. Gould lived for another 20 years, eventually succumbing to metastatic adenocarcinoma of the lung, not mesothelioma. Author Paul Kraus
Paul Kraus
Paul Kraus is an Australian author who was born in a Nazi forced labour camp in Viehofen, near St. Poelten, Austria in 1944 and migrated with his parents to Australia as a young child. In the 1960s Paul worked near a factory where asbestos sheets were sawn into smaller pieces...
was diagnosed with peritoneal mesothelioma
Peritoneal mesothelioma
Peritoneal mesothelioma is the name given to the cancer that attacks the lining of the abdomen. This type of cancer affects the lining that protects the contents of the abdomen and which also provides a lubricating fluid to enable the organs to move and work properly.The peritoneum is made of two...
in July 1997. He was given a prognosis of less than a year to live and used a variety of complementary modalities. He continued to outlive his prognosis and wrote a book about his experience "Surviving Mesothelioma and Other Cancers: A Patient's Guide" in which he presented his philosophy about healing and the decision making that led him to use integrative medicine
Integrative medicine
Integrative medicine or integrative health is the combination of the practices and methods of alternative medicine with conventional medicine. The term is relatively recent, and is mainly promoted by proponents of alternative therapies in the west...
.
Legal issues
The first lawsuits against asbestos manufacturers were in 1929. Since then, many lawsuits have been filed against asbestos manufacturers and employers, for neglecting to implement safety measures after the links between asbestos, asbestosis, and mesothelioma became known (some reports seem to place this as early as 1898). The liability resulting from the sheer number of lawsuits and people affected has reached billions of dollars. The amounts and method of allocating compensation have been the source of many court cases, reaching up to the United States Supreme Court, and government attempts at resolution of existing and future cases. However, to date, the US Congress has not stepped in and there are no federal laws governing asbestos compensation.History
The first lawsuit against asbestos manufacturers was brought in 1929. The parties settled that lawsuit, and as part of the agreement, the attorneys agreed not to pursue further cases. In 1960, an article published by Wagner et al. was seminal in establishing mesothelioma as a disease arising from exposure to 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. Prior to the use of advanced microscopy techniques, malignant mesothelioma was often diagnosed as a variant form of lung cancer. In 1962 McNulty reported the first diagnosed case of malignant mesothelioma in an Australia
Australia
Australia , officially the Commonwealth of Australia, is a country in the Southern Hemisphere comprising the mainland of the Australian continent, the island of Tasmania, and numerous smaller islands in the Indian and Pacific Oceans. It is the world's sixth-largest country by total area...
n asbestos worker. The worker had worked in the mill at the asbestos mine in Wittenoom
Wittenoom, Western Australia
Wittenoom is a ghost town located 1,106 kilometres north-northeast of Perth in the Hamersley Range in the Pilbara region of Western Australia. It is the site of Australia's greatest industrial disaster....
from 1948 to 1950.
In the town of Wittenoom
Wittenoom, Western Australia
Wittenoom is a ghost town located 1,106 kilometres north-northeast of Perth in the Hamersley Range in the Pilbara region of Western Australia. It is the site of Australia's greatest industrial disaster....
, 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. 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 Australia
Western Australia
Western Australia is a state of Australia, occupying the entire western third of the Australian continent. It is bounded by the Indian Ocean to the north and west, the Great Australian Bight and Indian Ocean to the south, the Northern Territory to the north-east and South Australia to the south-east...
n 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.
In Leeds
Leeds
Leeds is a city and metropolitan borough in West Yorkshire, England. In 2001 Leeds' main urban subdivision had a population of 443,247, while the entire city has a population of 798,800 , making it the 30th-most populous city in the European Union.Leeds is the cultural, financial and commercial...
, England the Armley asbestos disaster involved several court cases against Turner & Newall
Turner & Newall
Turner & Newall was a leading manufacturing business based in Manchester, United Kingdom. At its peak, it was a constituent of the FT30 index of leading companies on the London Stock Exchange.-1871-1920:...
where local residents who contracted mesothelioma claimed compensation because of the asbestos pollution from the company's factory. One notable case was that of June Hancock, who contracted the disease in 1993 and died in 1997.
See also
- Mesothelioma Applied Research FoundationMesothelioma Applied Research FoundationThe Mesothelioma Applied Research Foundation is a non-profit organization that funds mesothelioma research, provides services to patients, educates the public, and advocates in Washington, DC for governmental funding for mesothelioma research...
- AsbestosisAsbestosisAsbestosis is a chronic inflammatory and fibrotic medical condition affecting the parenchymal tissue of the lungs caused by the inhalation and retention of asbestos fibers...
- Peritoneal MesotheliomaPeritoneal mesotheliomaPeritoneal mesothelioma is the name given to the cancer that attacks the lining of the abdomen. This type of cancer affects the lining that protects the contents of the abdomen and which also provides a lubricating fluid to enable the organs to move and work properly.The peritoneum is made of two...
- Serous carcinomaSerous carcinomaIn pathology, serous carcinoma is an epithelial malignancy that arises from the lining of a cavity that produces a serum-like fluid .Serous lined cavities include the peritoneum, pericardium and pleural space and tunica vaginalis....
External links
- ATSDR — Case Studies in Environmental Medicine: Asbestos Toxicity U.S. Department of Health and Human Service (public domain)
- Mesothelioma: Questions and Answers from the U.S. National Cancer InstituteNational Cancer InstituteThe National Cancer Institute is part of the National Institutes of Health , which is one of 11 agencies that are part of the U.S. Department of Health and Human Services. The NCI coordinates the U.S...
- Cancer.gov: Malignant Mesothelioma from the U.S. National Cancer InstituteNational Cancer InstituteThe National Cancer Institute is part of the National Institutes of Health , which is one of 11 agencies that are part of the U.S. Department of Health and Human Services. The NCI coordinates the U.S...
- Mesothelioma from the American Cancer SocietyAmerican Cancer SocietyThe American Cancer Society is the "nationwide community-based voluntary health organization" dedicated, in their own words, "to eliminating cancer as a major health problem by preventing cancer, saving lives, and diminishing suffering from cancer, through research, education, advocacy, and...
- Malignant Mesothelioma review article from the American Cancer SocietyAmerican Cancer SocietyThe American Cancer Society is the "nationwide community-based voluntary health organization" dedicated, in their own words, "to eliminating cancer as a major health problem by preventing cancer, saving lives, and diminishing suffering from cancer, through research, education, advocacy, and...
- Medlineplus: Mesothelioma from MEDLINEMEDLINEMEDLINE is a bibliographic database of life sciences and biomedical information. It includes bibliographic information for articles from academic journals covering medicine, nursing, pharmacy, dentistry, veterinary medicine, and health care...
, part of the United States National Library of MedicineUnited States National Library of MedicineThe United States National Library of Medicine , operated by the United States federal government, is the world's largest medical library. Located in Bethesda, Maryland, the NLM is a division of the National Institutes of Health... - Worksafe, Western Australia, from Western Australia's Department of Consumer and Employment ProtectionDepartment of Consumer and Employment ProtectionThe Department of Consumer and Employment Protection was a department of the Government of Western Australia. As of 1 January 2009, it became the Department of Commerce.-External links:* *...
- US Nat'l Institute for Occupational Safety and Health, from the Centers for Disease Control
- Australian Mesothelioma Register
- What is Mesothelioma? Research and advocacy from the Mesothelioma Applied Research FoundationMesothelioma Applied Research FoundationThe Mesothelioma Applied Research Foundation is a non-profit organization that funds mesothelioma research, provides services to patients, educates the public, and advocates in Washington, DC for governmental funding for mesothelioma research...
- Radiology of mesotheliomas, with additional examples from Radiopaedia.org
- Clinically reviewed mesothelioma information from Cancer Research UKCancer Research UKCancer Research UK is a cancer research and awareness charity in the United Kingdom, formed on 4 February 2002 by the merger of The Cancer Research Campaign and the Imperial Cancer Research Fund. Its aim is to reduce the number of deaths from cancer. As the world's largest independent cancer...
- UK mesothelioma statistics from Cancer Research UKCancer Research UKCancer Research UK is a cancer research and awareness charity in the United Kingdom, formed on 4 February 2002 by the merger of The Cancer Research Campaign and the Imperial Cancer Research Fund. Its aim is to reduce the number of deaths from cancer. As the world's largest independent cancer...
- Malignant Pleural Mesothelioma NCCN Patient Guidelines for Malignant Pleural Mesothelioma National Comprehensive Cancer NetworkNational Comprehensive Cancer NetworkNational Comprehensive Cancer Network is an alliance of twenty-one cancer centers in the United States, most of which are designated by the National Cancer Institute as comprehensive cancer centers...