MESOTHELIOMA
Mesothelioma
is a tough cancer
that is usually caused by some exposure to asbestos.
In this disease, malignant (cancerous) cells form in the mesothelium,
a protective lining that covers a lot of the body's internal organs.
Its most common area is the pleura (outer lining of the lungs and chest
cavity), but it may also occur in the peritoneum (the lining of the
abdominal cavity) or the pericardium (a
sac that envelopes the heart).
Most people
who get mesothelioma have
worked on jobs where they breathed in asbestos
particles, or have been exposed to asbestos
dust and fibre in other ways, such as by washing the clothes of a family
member who handled asbestos,
or by home renovation using asbestos
cement products. There isn't any association between mesothelioma and smoking.
SIGNS
AND SYMPTOMS OF MEOTHELIOMA
Symptoms of mesothelioma
may not appear until 20 to 50 years after exposure to
asbestos.
Shortness of breath, cough, and pain in the chest due to an accumulation
of fluid in the pleural space 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:
* chest
wall pain
* pleural effusion, or fluid surrounding the lung
* shortness of breath
* wheezing, hoarseness, or cough
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:
* abdominal
pain
* ascites, 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 thrombophlebitis
* disseminated intravascular coagulation, a disorder causing severe
bleeding in many body organs
* jaundice, or yellowing of the eyes and skin
* low blood sugar level
* pleural effusion
* pulmonary emboli, or blood clots in the arteries of the lungs
* severe ascites
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.
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 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 cytology if this fluid is aspirated with a
syringe. For pleural fluid this is done by a pleural tap or chest drain,
in ascites with an paracentesis or ascitic drain and in a 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).
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If cytology
is positive or a plaque is regarded as suspicious, a biopsy is needed
to confirm a diagnosis of mesothelioma . A doctor removes a sample of
tissue for examination under a microscope by a histopathologist. 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.
If the cancer
is in the abdomen, the doctor may perform a laparoscopy. To obtain tissue
for examination, the doctor makes a small opening 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.
Typical immunohistochemistry resultsPositive Negative
EMA (epithelial membrane antigen) CEA (carcinoembryonic antigen)
WT1 (Wilms' tumour 1) B72.3
Calretinin MOC-3 1
Mesothelin-1 CD15
Cytokeratin 5/6 Ber-EP4
HBME-1 (human mesothelial cell 1) TTF-1 (thyroid transcription factor-1)
Screening
There is no universally agreed protocol for screening people
who have been exposed to asbestos.
However some research indicates that the serum 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[3].
Staging
Once the
diagnosis is confirmed, the doctor may need to assess the stage to help
plan treatment.
mesothelioma
is described as localized if the cancer is found only on the membrane
surface where it originated. It is classified as advanced if it has
spread beyond the original membrane surface to other parts of the body,
such as the lymph nodes, lungs, chest wall, or abdominal organs.
Pathophysiology
The mesothelium
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 fibres in the parenchyma
of the lung may result in the penetration of the visceral pleura from
where the fibre 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
fibres from the lung are transported to the abdomen and associated organs
via the lymphatic system. Additionally, asbestos fibres may be deposited
in the gut after ingestion of sputum contaminated with asbestos
fibres.
Pleural
contamination with asbestos
or other mineral fibres has been shown to cause cancer. Long thin asbestos fibers (blue asbestos, amphibole fibers) are
more potent carcinogens than "feathery fibers" (chrysotile
or white asbestos
fibers)[4]. However, there is now evidence that smaller particles may
be more dangerous than the larger fibers.[5][6] 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.
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Mesothelioma
development in rats has been demonstrated following intra-pleural inoculation
of phosphorylated chrysotile fibres. It has been suggested that in humans,
transport of fibres to the pleura is critical to the pathogenesis of
mesothelioma . This is supported by the observed recruitment of significant
numbers of macrophages and other cells of the immune system to localised
lesions of accumulated asbestos
fibres 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 tumour. 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
fibres remain unclear despite the demonstration of its oncogenic capabilities.
However, complete in vitro transformation of normal human mesothelial
cells to malignant phenotype following exposure to asbestos fibres has not yet been
achieved. In general, asbestos
fibres 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
fibres and DNA has shown that phagocytosed fibres are able to
make contact with chromosomes, often adhering to the chromatin fibres
or becoming entangled within the chromosome. This contact between the
asbestos fibre 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 genes:
* Neurofibromatosis
type 2 at 22q12
* P16INK4A
* P14ARF
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 oncogenes
* Activation of proto-oncogenes due to incorporation of foreign DNA containing a promoter region
* Activation of DNA repair enzymes, which may be prone to error
* Activation of telomerase
* Prevention of apoptosis
asbestos fibres 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
may also 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 (LAK) 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-ß (TGF-ß) which
in turn, may induce the chronic stimulation and proliferation of mesothelial
cells after injury by asbestos
fibres.
Epidemiology
Incidence
Although
reported incidence rates have increased in the past 20 years, mesothelioma is still a relatively
rare cancer. The incidence is approximately one per 1,000,000. For comparison,
populations with high levels of smoking can have a lung cancer incidence
of over 1,000 per 1,000,000. Incidence of malignant mesothelioma currently ranges from
about 7 to 40 per 1,000,000 in industrialized Western nations, depending
on the amount of asbestos
exposure of the populations during the past several decades[8]. 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 mesothelioma s are peritoneal.
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Between
1940 and 1979, approximately 27.5 million people were occupationally
exposed to asbestos in the United States.[9]
Between 1973 and 1984, there has been a three-fold increase in the diagnosis
of pleural mesothelioma in
caucasion males. From 1980 to the late
1990s, the rate of deaths from mesothelioma increased from 2,000 to 3,000 a year.
in the late 1990se in annual deaths from mesotheiliom, 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 .
Risk factors
Working
with asbestos is the major risk factor
for mesothelioma . A history of asbestos
exposure exists in almost all cases. However, mesothelioma has been reported in some individuals
without any known exposure to asbestos.
In rare cases, mesothelioma
has also been associated with irradiation, intrapleural
thorium dioxide (Thorotrast), and inhalation of other fibrous silicates,
such as erionite.
asbestos is the name of a group of minerals that occur naturally
as masses of strong, flexible fibers that can be separated into thin
threads and woven. asbestos has been widely used in many industrial products, including cement, brake
linings, roof shingles, flooring products, textiles, and insulation.
If tiny asbestos
particles float in the air, especially during the manufacturing process,
they may be inhaled or swallowed, and can cause serious health problems.
In addition to mesothelioma , exposure to asbestos
increases the risk of lung cancer, asbestosis
(a noncancerous, chronic lung ailment), and other cancers, such as those
of the larynx and kidney.
The combination
of smoking and asbestos
exposure significantly increases a person's risk of developing cancer
of the airways (lung cancer, bronchial carcinoma). The Kent brand of cigarettes used asbestos in its filters for the
first few years of production in the 1950s and some cases of mesothelioma have resulted. Smoking
current cigarettes does not appear to increase the risk of mesothelioma
.
Some studies
suggest that simian virus 40 (SV40) may act as a cofactor in the development
of mesothelioma [11].
Exposure
asbestos has been mined and used commercially since the
late 1800s. Its use greatly increased during World War II. Since the
early 1940s, millions of American workers have been exposed to asbestos dust. Initially, the risks
associated with asbestos
exposure were not 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 U.S. Occupational Safety and Health Administration (OSHA) sets limits
for acceptable levels of asbestos
exposure in the workplace, and created guidelines for engineering controls
and respirators, protective clothing, exposure monitoring, hygiene facilities
and practices, warning signs, labeling, recordkeeping, and medical exams.
By contrast, the British Government's Health and Safety Executive (HSE) states formally that any threshold for mesothelioma must be at a very
low level and it is widely agreed that if any such threshold does exists
at all, then it cannot currently be quantified. For practical purposes,
therefore, HSE does not assume that any such threshold exists.
People who work
with asbestos
wear personal protective equipment to lower their risk of exposure.
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mesothelioma |
Exposure
to asbestos fibres has been recognised
as an occupational health hazard since the early 1900s. Several epidemiological
studies have associated exposure to asbestos with the development of
lesions such as asbestos
bodies in the sputum, pleural plaques, diffuse pleural thickening, asbestosis, carcinoma of the lung
and larynx, gastrointestinal tumours, and diffuse mesothelioma of the pleura and
peritoneum.
The documented
presence of asbestos
fibres in water supplies and food products has fostered concerns about
the possible impact of long-term and, as yet, unknown exposure of the
general population to these fibres. Although many authorities consider
brief or transient exposure to asbestos
fibres as inconsequential and an unlikely risk factor, some epidemiologists
claim that there is no risk threshold. Cases of mesothelioma have been found in
people whose only exposure was breathing the air through ventilation
systems. Other cases had very minimal (3 months or less) direct exposure.
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.
It is predicted that the number of cases within this study group will
reach in excess of 700 by the year 2020. By 1994, 539 reported deaths
due to mesothelioma had been reported
in Western Australia.
Family members
and others living with asbestos workers have
an increased risk of developing mesothelioma , and possibly other asbestos related diseases. This risk may be the result of
exposure to asbestos dust brought home on the clothing and hair of asbestos workers.
To reduce the chance of exposing family members to asbestos fibres, asbestos workers are usually required
to shower and change their clothing before leaving the workplace.
Treatment
Treatment
of MM using conventional therapies has not proved successful and patients
have a median survival time of 6 - 12 months after presentation. The
clinical behaviour of the malignancy is affected by several factors
including the continuous mesothelial surface of the pleural cavity which
favours local metastasis via exfoliated cells, invasion to underlying
tissue and other organs within the pleural cavity, and the extremely
long latency period between asbestos
exposure and development of the disease.
Surgery
Surgery,
either by itself or used in combination with pre- and post-operative
adjuvant therapies has proved disappointing with a 5 year survival rate
of less than 10%. 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.
Radiation
Although
the tumor is highly resistant to radiotherapy, these regimens are sometimes
used to relieve symptoms arising from tumor growth, such as obstruction
of a major blood vessel.
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Radiotherapy
is commonly applied to the sites of chest drain insertion, in order
to prevent growth of the tumor along the track in the chest wall.
Chemotherapy
In February
2004, the Food and Drug Administration approved pemetrexed (brand name
Alimta) for treatment of malignant pleural mesothelioma .
Immunotherapy
Treatment
regimens involving immunotherapy have yielded variable results. For
example, intrapleural inoculation of Bacillus Calmette-Guérin (BCG)
in an attempt to boost the immune response, was found to be of no benefit
to the patient (while it may benefit patients with bladder cancer).
mesothelioma cells proved susceptible to in vitro lysis by LAK cells
following activation by interleukin-2 (IL-2), but patients undergoing
this particular therapy experienced major side effects. Indeed, this
trial was suspended in view of the unacceptably high levels of IL-2
toxicity and the severity of side effects such as fever and cachexia.
Nonetheless, other trials involving interferon alpha have proved more
encouraging with 20% of patients experiencing a greater than 50% reduction
in tumor mass combined with minimal side effects.
Heated Intraoperative
Intraperitoneal Chemotherapy
A procedure
known as heated intraoperative intraperitoneal chemotherapy was developed
by Paul Sugarbaker at the Washington Cancer Institute[12]. 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.
Prevention
& Expectations
What can
be done to prevent the disease? Since the 1970s, the Environmental Protection
Agency and the Occupational Safety and Health Administration have regulated
the asbestos industry in the U.S. In the past, asbestos was used as a fire retardant and an insulator.
Other products are now used in its place. The controversy involving
exposure to different forms of asbestos continues.
There are two major types
of asbestos
called chrysotile and amphibole.
It is thought that the amphibole form of asbestos
is to blame for causing mesothelioma . However, asbestos is still being removed
even if it is the chrysotile variety. Removal is taking place in schools
and other public buildings throughout the U.S. The hope is that these measures will greatly reduce
the occurrence of this cancer.
What are
the long-term effects of the disease? A
mesothelioma is a highly aggressive tumor that is generally
deadly. Current treatment of malignant
mesothelioma is designed to make the person with cancer
comfortable. Long-term survival cannot usually be expected.
What are
the risks to others? mesothelioma is not contagious and cannot be passed
from one person to another. The exposure to the asbestos
that caused the cancer occurred many years to several decades before
the disease appeared. People who live with asbestos
workers have a higher risk of getting this cancer.
Legal issues
Main article:
asbestos and the law
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 link 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, and government attempts at
resolution of existing and future cases.
History
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Cancer. |
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. It was not until 1960 that an article published by Wagner et
al in 1960 first officially established
mesothelioma as a disease arising from exposure to crocidolite
asbestos[13]. The article referred
to over 30 case studies of people who had suffered from mesothelioma in South Africa. Some exposures were transient and some were mine
workers. In 1962 Dr McNulty reported the first diagnosed case of malignant
mesothelioma in an Australian asbestos
worker[14]. The worker had worked in the mill at the asbestos mine in Wittenoom from
1948 to 1950.
In the town
of Wittenoom, asbestos-containing
mine waste was used to cover schoolyards and playgrounds. In 1965 an
article in the British Journal of Industrial Medicine established that
people who lived in the neighbourhoods of asbestos
factories and mines, but did not work in them, had contracted mesothelioma
.
Despite
proof that the dust associated with asbestos
mining and milling causes asbestos
related disease, mining began at Wittenoom in 1943 and continued until
1966. It is difficult to understand why the mine and mill was allowed
to initially open and operate without adequate risk control measures;
and why nothing was done to force the owner (CSR) to clean them up,
adopt safer work practices or close down their operations.
In 1974 the first public warnings
of the dangers of blue asbestos were published
in a cover story called "Is this Killer in Your Home?"
in Australia's Bulletin magazine. In 1978 the Western Australian
Government decided to phase out the town of Wittenoom, following the publication of a Health Dept. booklet,
"The Health Hazard at Wittenoom", containing the results of
air sampling and an appraisal of worldwide medical information.
By 1979
the first writs for negligence related to Wittenoom were issued against
CSR and its subsidiary ABA, and the asbestos
Diseases Society was formed to represent the Wittenoom victims.
External
links
* mesothelioma
: Questions and Answers from the National Cancer Institute
* American Cancer Society
* asbestos
Newspaper Archive Free archive of 50,000 newspaper pages dedicated to
asbestos
* Cancer.gov: Malignant mesothelioma
* CancerBACUP: mesothelioma Information Centre
* Medlineplus: mesothelioma
* Worksafe, Western Australia
* US Nat'l Institute for Occupational Safety and Health
Sources
The first
version of this article was adapted from a public domain U.S. National
Cancer Institute fact sheet at http://www.cancer.gov/cancertopics/factsheet/Sites-Types/
mesothelioma
Tumors (and related structures), Cancer, and Oncology
Benign - Premalignant - Carcinoma in situ - Malignant
Topography:
Anus - Bladder - Bone - Brain - Breast - Cervix - Colon/rectum - Duodenum
- Endometrium - Esophagus - Eye - Gallbladder - Head/Neck - Liver -
Larynx - Lung - Mouth - Pancreas - Penis - Prostate - Kidney - Ovaries
- Skin - Stomach - Testicles - Thyroid
Morphology:
Papilloma/carcinoma - Adenoma/adenocarcinoma - Soft tissue sarcoma -
Melanoma - Fibroma/fibrosarcoma - Lipoma/liposarcoma - Leiomyoma/leiomyosarcoma
- Rhabdomyoma/rhabdomyosarcoma - mesothelioma - Angioma/angiosarcoma
- Osteoma/osteosarcoma - Chondroma/chondrosarcoma - Glioma - Lymphoma/leukemia
Treatment:
Chemotherapy - Radiation therapy - Immunotherapy - Experimental cancer
treatment
Related
structures: Cyst - Dysplasia - Hamartoma - Neoplasia - Nodule - Polyp
- Pseudocyst
Misc: Tumor
suppressor genes/oncogenes - Staging/grading - Carcinogenesis/metastasis
- Carcinogen - Research - Paraneoplastic phenomenon - ICD-O - List of
oncology-related terms
Retrieved from "http://en.wikipedia.org/wiki/ mesothelioma "
Categories:
Oncology | Pulmonology | Types of cancer
This article
is licensed under the GNU Free Documentation License. It uses material
from the Wikipedia article " mesothelioma ".
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mesothelioma peritoneal Asbestos |
asbestos (a misapplication of Latin: asbestos "quicklime" from
Greek ?sßest??: a, "not" and sbestos, "extinguishable")
describes any of a group of minerals that can be fibrous, many of which
are metamorphic and are hydrous magnesium silicates. These minerals,
together with their occurrences, uses, and associated hazards, have
been discussed in detail by Guthrie and Mossman (1993).
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