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Asbestos
Diseases
Mesothelioma
 What
is mesothelioma?
Malignant
mesothelioma is an uncommon, but no longer
rare, cancer that is difficult to diagnose
and poorly responsive to therapy.
Malignant mesothelioma is the most serious
of all asbestos-related diseases.
A
layer of specialized cells called
mesothelial cells lines the chest cavity,
abdominal cavity, and the cavity around
the heart. These cells also cover the
outer surface of most internal organs. The
tissue formed by these cells is called
mesothelium.
The
mesothelium helps protect the organs by
producing a special lubricating fluid that
allows organs to move around. For example,
this fluid makes it easier for the lungs
to move inside the chest during breathing.
The mesothelium of the chest is called the
pleura and the mesothelium of the abdomen
is known as the peritoneum. The
mesothelium of the pericardial cavity (the
"sac-like" space around the heart) is
called the pericardium.
Tumors
of the mesothelium can be benign
(noncancerous) or malignant (cancerous). A
malignant tumor of the mesothelium is
called a malignant mesothelioma. Because
most mesothelial tumors are cancerous,
malignant mesothelioma is often simply
called mesothelioma.
Mesothelioma
was recognized as a tumor of the pleura,
peritoneum and pericardium in the late
1700's. However it was not until much
later, in 1960, that this particular type
of tumor was described in more detail and
even more importantly, its association
with asbestos exposure was recognized. The
first report linking mesothelioma to
asbestos exposure was written by
J.C.Wagner, and described 32 cases of
workers in the "Asbestos Hills" in South
Africa. Since than the relationship
between mesothelioma and asbestos exposure
has been confirmed in studies around the
world.
The
incidence of mesothelioma in the United
States remains very low, with 14 cases
occurring per million people per year.
Despite these numbers the noticed
threefold increase in mesothelioma in
males between 1970 and 1984, is directly
associated with environmental and
occupational exposure to asbestos, mostly
in areas of asbestos product plants and
shipbuilding facilities.
Although
the disease is much more commonly seen in
60-year old men, it has been described in
women and early childhood as well. The
cause of the disease is not so well
understood in these latter two groups, but
there is some evidence of possible
asbestos exposure for some of these cases
as well.
Malignant
mesotheliomas are divided into three main
types. About 50% to 70% of mesotheliomas
are the epithelioid type. This type has
the best prognosis (outlook for survival).
The other two types are the sarcomatoid
type (7%-20%), and the mixed/biphasic type
(20%-35%). Treatment options for all three
types are the same.
About
three-fourths of mesotheliomas start in
the chest cavity. They are known as
pleural mesotheliomas. Another 10% to 20%
begin in the abdomen. These are called
peritoneal mesotheliomas. Pericardial
mesotheliomas, those starting in the
cavity around the heart, are very rare.
The covering layer of the testicles is
actually an outpouching of peritoneum into
the scrotum. Mesotheliomas that affect
this covering of the testicles are quite
rare.
What
are the key statistics about
mesothelioma?
Mesothelioma
is fairly rare. There are an estimated
2,000 to 3,000 new cases per year of
mesothelioma in the United States, but
this figure appears to be
increasing.
The
average age at diagnosis is 50 to 70 years
old. The disease affects men 3 to 5 times
more often than women. Mesothelioma is
less common in African Americans than in
white Americans.
Mesothelioma
is a serious disease. By the time the
symptoms appear and cancer is diagnosed,
the disease is often advanced. The average
survival time is about one year. However,
if the cancer is found early and treated
aggressively, almost half of the patients
whose cancer is found early reach the
two-year mark, and about 20% survive five
years.
The
5-year survival rate refers to the percent
of patients who live at least 5 years
after their cancer is diagnosed. Many of
these patients live much longer than 5
years after diagnosis, and 5-year rates
are used to produce a standard way of
discussing prognosis. Five-year relative
survival rates exclude from the
calculations patients dying of other
diseases, and are considered to be a more
accurate way to describe the prognosis for
patients with a particular type and stage
of cancer. Of course, 5-year survival
rates are based on patients diagnosed and
initially treated more than 5 years ago.
Improvements in treatment often result in
a more favorable outlook for recently
diagnosed patients.
What
are the different types of
mesothelioma?
Pleural
Mesothelioma
Pleural
mesothelioma spreads within the chest
cavity, sometimes involving the lung.
Metastases can occur in any organ,
including the brain, and are much more
common than previously thought.
The
onset of mesothelioma is usually very
slow, the most common presenting symptom
is persistent pain localized in the chest.
Sometimes the pain is accompanied by
severe difficulty breathing, due to an
accumulation of fluid in the pleural space
known as pleural effusion. Cough, weight
loss and fever are not uncommon. The most
valuable single test to show the extent of
the disease is a computed chest tomograph
(CT-scan).
There
are currently no serum markers available
for the diagnosis of mesothelioma. The
detection of elevated serum levels of
hyaluronic acid may be useful in
differentiating mesotheliomas from other
tumors, or to follow the effect of
treatment.
The
median survival is about 17 months from
the beginning of symptoms. The 3-year
survival is 10% the 5-year survival is
approximately 5% ( if 100 patients are
diagnosed with mesothelioma at a specific
point in time, that means that 10 patients
will still be alive at the end of 3 years
and 5 patients will only be alive at the
end of 5 years).
Peritoneal
Mesothelioma
Peritoneal
mesothelioma involves the abdominal
cavity, infiltrating the liver, spleen or
the bowel. As with pleural mesothelioma
pain is the most common presenting
complaint. In addition, due to fluid
accumulation in the abdominal cavity
(ascites), the abdomen appears enlarged.
The patients experience nausea, vomiting,
swelling of their feet, fever and
difficulty in moving their bowels.
The
prognosis is poorer than for pleural
mesothelioma with a median survival time
of about 10 months from the onset of
symptoms.
Benign
Mesothelioma:
A
rare form of mesothelioma is the cycstic
mesothelioma of the peritoneum. Its
prognosis is benign. Its occurrence has
been described primarily in young women.
However the diagnosis presents
difficulties, requiring extensive electron
miscroscopy and immunohistochemical
studies.
Rare
Sites:
Mesothelioma
of the pericardium, is a very seldom seen
cardiac cancer. The mass is usually
detected at a late stage by
echocardiography, the prognosis is very
poor , with or without therapy.
Mesothelioma of the ovaries and the
scrotum have also been reported in the
literature. The management differs based
on the stage of the disease, the prognosis
is also very poor. The etiology of the few
cases of mesothelioma described in
children remains unclear and is not
believed to be asbestos-related, the
therapy and prognosis differ on an
individual basis.
What
are the risk factors for malignant
mesothelioma?
A
risk factor is anything that increases a
person's chance of getting a disease such
as cancer. Different cancers have
different risk factors. For example,
unprotected exposure to strong sunlight is
a risk factor for skin cancer and smoking
is a risk factor for lung cancer as well
as other types of cancer. Scientists have
found several risk factors that make a
person more likely to develop
mesothelioma.
Asbestos:
The main risk factor for developing
mesothelioma is exposure to asbestos.
Asbestos refers to a family of
magnesium-silicate mineral fibers. In the
past, asbestos was used widely for
insulation because it does not conduct
heat well and it is resistant to melting
or burning. As the link between asbestos
and mesothelioma has become well known,
the use of this material has decreased.
However, up to 8 million Americans may
already have been exposed to
asbestos.
According
to the United States Environmental
Protection Agency, as many as 733,000
schools and public buildings in the
country today contain asbestos insulation.
As many as 10% to 15% of schools in the
United States may contain asbestos
insulation. People who may be at risk for
occupational asbestos exposure include
some miners, factory workers, insulation
manufacturers, railroad workers, ship
builders, gas mask manufacturers, and
construction workers, particularly those
involved with installing insulation.
Several studies have shown that family
members of people exposed to asbestos at
work have an increased risk of developing
mesothelioma, because asbestos fibers are
carried home on the clothes of the
workers.
There
are two main forms of asbestos --
serpentine and amphiboles. Serpentine
fibers are curly and pliable. Chrysotile
is the only type of serpentine fiber and
it is the most widely used form of
asbestos. Amphiboles are thin, rod-like
fibers of which there are 5 main
types-crocidolite, amosite, anthrophylite,
tremolite, and actinolyte. Amphiboles
(particularly crocidolite) are considered
to be the most carcinogenic
(cancer-causing). However, even the more
commonly used chrysotile fibers have been
associated with malignant (cancerous)
mesotheliomas and should be considered
dangerous as well.
It
may be that asbestos causes cancer by
physically irritating cells rather than by
a chemical effect. When fibers are
inhaled, most are cleared in the nose,
throat, trachea (windpipe), or bronchi
(large breathing tubes of the lungs).
Fibers are cleared by sticking to mucus
inside the air passages and being coughed
up or swallowed. The long, thin, fibers
are less readily cleared, and they may
reach the ends of the small airways and
penetrate into the pleural lining of the
lung and chest wall. These fibers may then
directly injure mesothelial cells of the
pleura, and eventually cause
mesothelioma.
Asbestos
fibers can also damage cells of the lung
and result in asbestosis (formation of
scar tissue in the lung), and/or lung
cancer. The risk of lung cancer among
people exposed to asbestos is increased by
7 times, compared with the general
population. Indeed, asbestosis,
mesothelioma, and lung cancer are the
three most frequent causes of death and
disease among people with heavy asbestos
exposure. Peritoneal mesothelioma, which
forms in the abdomen, may result from
coughing up and swallowing inhaled
asbestos fibers. Cancers of the larynx,
pancreas, esophagus, colon, and kidney
have also been linked to asbestos
exposure, but the increased risk is not as
great as with lung cancer.
The
risk of developing a mesothelioma is
related to how much asbestos a person was
exposed to and how long this exposure
lasted. People exposed at an early age,
for a long period of time, and at higher
levels are most likely to develop this
cancer. Mesotheliomas take a long time to
develop. The time between exposure to
asbestos and diagnosis of mesothelioma is
usually between 20 and 40 years.
Although
the risk of developing mesothelioma rises
with the amount of asbestos exposure, it
is clear that genetic factors also play a
role in determining who develops the
disease. This explains why not all persons
exposed to high levels of asbestos dust
develop mesothelioma.
Radiation:
There have been a few published reports of
pleural and peritoneal mesotheliomas that
developed following exposure to thorium
dioxide (Thorotrast). This material was
used in the past by doctors for certain
x-ray tests. Because Thorotrast was found
to cause cancers, it has not been used for
many years.
Zeolite:
This is a silicate mineral, chemically
related to asbestos, common in the soil of
the Anatoli region of Turkey. A few cases
of mesothelioma have been described in
this region and may have been caused by
this mineral.
Simian
Virus 40 (SV40):
This virus has recently been identified by
researchers in human mesothelioma cells,
and has been shown to induce mesothelioma
in the animal model. Polio vaccines
administered as a primary prevention
measure during 1955 - 1961 have been shown
to be contaminated with SV40. However the
implications of these facts are not
totally understood and further research
will be needed to clarify the link between
malignant mesothelioma and a viral
etiology.
Tobacco:
Although tobacco smoking has not been
associated with the development of
mesotheliomas, the combination of smoking
and asbestos exposure greatly increases
the risk of lung cancer. Asbestos workers
who also smoke have a lung cancer risk 50
to 90 times greater than that of the
general population. More asbestos workers
die of lung cancer than of
mesothelioma.
What
causes mesothelioma?
Asbestos
exposure is the main cause of
mesothelioma. After these fibers are
breathed in, they travel to the ends of
small air passages and reach the pleura
where they cause physical damage to
mesothelial cells that may result in
cancer. In addition, they also cause
injury to lung cells that can result in
lung cancer and/or asbestosis (replacement
of lung tissue by scar tissue). If
swallowed, these fibers can reach the
abdominal cavity where they have a role in
causing peritoneal mesothelioma.
Exposure
to asbestos, though mostly occupational,
can also be environmental, or familial by
household contamination, through the work
clothes of an asbestos worker for
instance.
Beginning
15 years after the onset of exposure,
about 6% of asbestos workers die of
mesothelioma. In one study of asbestos
insulation workers, the death rate from
mesothelioma was 344 times higher than in
the general population. (Selifoff IJ et
al. Relation between exposure to asbestos
and mesothelioma. NEJM)
What
are the signs and symptoms of
mesothelioma?
Early
symptoms of mesotheliomas are not specific
to the disease. People often ignore them
or mistake them for common, minor
ailments. Most people with mesothelioma
have symptoms for only 2 to 3 months
before they are diagnosed. About
one-fourth have symptoms for at least six
months prior to their diagnosis.
Over
half of patients with pleural mesothelioma
have pain in the lower back or at the side
of the chest. Many report shortness of
breath. A smaller percentage have trouble
swallowing, cough, fever, sweating,
fatigue, and weight loss. Other symptoms
include hoarseness, coughing up blood,
swelling of the face and arms, muscle
weakness, and sensory loss.
Symptoms
of peritoneal mesothelioma include
abdominal (belly) pain, weight loss,
nausea, and vomiting. There may also be a
hernia, fluid in the abdominal cavity or a
mass in the abdomen.
A
person with any of these symptoms who has
been exposed to asbestos should see a
doctor right away.
How
is mesothelioma diagnosed?
If
there is a reason to suspect you may have
a mesothelioma, the doctor will use one or
more methods to find out if the disease is
really present.
Medical
history and physical
examination:
A
complete medical history (interview) is
taken to check for risk factors and
symptoms. This will include questions to
determine if you have been exposed to
asbestos.
A
physical exam will provide information
about signs of mesothelioma and other
health problems. Patients with pleural
mesotheliomas (mesotheliomas of the chest)
often have pleural effusion (fluid in
their chest cavity) caused by the cancer.
Ascites (fluid in the abdominal cavity) in
cases of peritoneal mesothelioma, and
pericardial effusion (fluid in the
pericardium) in cases of pericardial
mesothelioma can also be detected during a
physical exam.
Imaging
tests:
A
chest x-ray may show irregular thickening
of the pleura, pleural calcifications
(mineral deposits), lowering of the lung
fissures (spaces between the lobes of the
lungs), and fluid in the pleural space.
These findings suggest asbestos exposure
leading to the development of a
mesothelioma.
Imaging
studies such as x-rays, computed
tomography (CT) scans, and magnetic
resonance imaging (MRI) scans will help
determine the location, size, and extent
of the cancer. The CT scan uses a rotating
x-ray beam to create a series of pictures
of the body from many angles. A computer
combines these pictures to produce
detailed cross-sectional images of a
selected part of the body. To highlight
details on the CT scan, you may be asked
for permission to have a harmless dye
injected into a vein. MRI uses magnetic
fields instead of x-rays to create images
of selected areas of the body. As with the
CT scan, a computer generates a detailed
cross-sectional image.
Tests
of fluid and tissue samples:
In
patients with a pleural effusion, a sample
of this fluid can be removed by inserting
a needle into the chest cavity. A similar
technique can be used to obtain abdominal
fluid and pericardial fluid. The fluid is
then tested to show its chemical make up
and viewed under a microscope to determine
whether cancer cells are present.
A
tissue sample of a pleural or pericardial
tumor can be obtained using a relatively
new technique called thoracoscopy. A
thoracoscope (telescope-like instrument
connected to a video camera) is inserted
through a small incision into the chest.
The doctor can see the tumor through the
thoracoscope, and can use special forceps
to take a tissue biopsy. Similarly,
laparoscopy can be used to see and obtain
a biopsy of a peritoneal tumor. In this
procedure, a flexible tube attached to a
video camera is inserted into the
abdominal cavity through small incisions
on the front of the abdomen. Fluid can
also be collected during thoracoscopy or
laparoscopy.
Surgery,
either a thoracotomy (which opens the
chest cavity) or a laparotomy (which opens
the abdominal cavity), allows the surgeon
to remove a larger sample of tumor or,
sometimes, to remove the entire
tumor.
For
patients who might have pleural
mesothelioma, the doctor may also do a
bronchoscopy. In this procedure a flexible
lighted tube is inserted through the
mouth, down the trachea, and into the
bronchi to see if there are other masses
in the airway. Small samples of
abnormal-appearing tissue can be removed
for testing.
The
patient may also have a mediastinoscopy. A
lighted tube is inserted under the sternum
(chest bone) at the level of the neck and
moved down into the chest. Mediastinoscopy
allows the surgeon to view the lymph nodes
in this area and remove samples to check
for cancer. Lymph nodes are bean-sized
collections of immune system cells that
help the body fight infections and
cancers. Cancers arising in the lung often
spread to lymph nodes, but mesotheliomas
rarely do this. Tests of lymph nodes can
give the doctor information on whether a
cancer is still localized or if it has
started to spread, and can help
distinguish lung cancer from
mesothelioma.
It
is often hard to diagnose mesothelioma by
looking at the cells from the fluid around
the lungs, abdomen or heart. It is even
hard to diagnose mesothelioma with tissue
from biopsies. Under the microscope,
mesothelioma can look like several other
types of cancer. For example, pleural
mesothelioma may resemble some types of
lung cancer and peritoneal mesothelioma
may resemble some cancers of the ovaries.
For this reason, special laboratory tests
are often done to help distinguish
mesothelioma from some other cancers.
These tests often use special techniques
to recognize certain markers (types of
chemicals) known to be contained in
mesotheliomas. Different markers are
present in cancer of the lung or ovary.
The electron microscope can sometimes be
helpful in diagnosing mesothelioma. This
microscope can magnify samples more than
100 times greater than the light
microscope which is generally used in
cancer diagnosis. This stronger microscope
makes it possible to see small parts of
the cancer cells that distinguish
mesothelioma from other types of
cancer.
The
diagnosis of mesothelioma presents
problems primarily initially in the
distinction between mesothelioma and other
forms of cancer such as adenocarcinoma or
benign, noncancerous pleural inflammation.
The best diagnostic tools at the moment
remain the open pleural biopsy performed
during thoracoscopy. This procedure also
allows for direct visualization of the
inside of the chest, and information of
involvment of other organs and extension
of disease. Other procedures with lower
yields are CT guided pleural biopsy, or
blind pleural biopsy. In addition to the
gross appearance of the tumor,
pathologists often rely on a panel of
histochemical and immunohistochemical
stains to diagnose or exclude
meosothelioma. Currently markers linked to
prognosis of mesothelioma are under study,
but have not been validated for the
general use.
How
is mesothelioma staged?
Staging
is the process of finding out how far the
cancer has spread. Staging of mesothelioma
is based on imaging studies such as
x-rays, CT scans, and MRI scans. The
treatment and outlook for patients with
mesothelioma largely depends on the stage
(extent of spread) of their cancer. Since
pleural mesothelioma occurs most
frequently and has been studied the most,
it is the only mesothelioma for which a
staging classification exists.
The
staging system most often used for
mesothelioma is the Butchart system. This
system is based mainly on the extent of
the primary tumor mass, and divides
mesotheliomas into stages I through
IV.
Butchart
Staging System
Stage
I:
Mesothelioma is present within the
right or left pleura, and may also
involve the lung, pericardium, or
diaphragm (the muscle separating the
chest from the abdomen) on the same
side.
Stage
II:
Mesothelioma invades the chest wall or
involves the esophagus (food passage
connecting the throat to the stomach),
heart, or pleura on both sides. The
lymph nodes in the chest may also be
involved.
Stage
III:
Mesothelioma has penetrated through the
diaphragm into the peritoneum (lining
of the abdominal cavity). Lymph nodes
beyond those in the chest may also be
involved.
Stage
IV:
There is evidence of distant metastases
(spread through the bloodstream to
other organs).
Another
staging system has recently been developed
by the American Joint Committee on Cancer
(AJCC). This is a TNM system, similar to
staging systems used for most other
cancers. T stands for tumor (its size and
how far it has spread to nearby organs), N
stands for spread to lymph nodes and M is
for metastasis (spread to distant organs).
In TNM staging, information about the
tumor, lymph nodes, and metastasis is
combined in a process called stage
grouping to assign a stage described by
Roman numerals from I to IV. Minor
differences exist between the AJCC TNM
staging system and the Butchart staging
system.
TNM
Staging System
Stage
I:
Mesothelioma involves the right or left
pleura. It may also have spread into
the lung, pericardium, or diaphragm on
the same side. It has not yet spread to
the lymph nodes.
Stage
II:
Mesothelioma has spread from the pleura
on one side to the nearby peribronchial
and/or hilar lymph nodes next to the
lung on the same side. It may also have
spread into the lung, pericardium, or
diaphragm on the same side.
Stage
III:
Mesothelioma has spread into the chest
wall muscle, ribs, heart, esophagus, or
other organs in the chest on the same
side as the primary tumor, with or
without spread to subcarinal and/or
mediastinal lymph nodes on the same
side as the main tumor. Subcarinal
nodes are located at the point where
the windpipe branches to the left and
right lungs. Mediastinal lymph nodes
are located in the space behind the
chest bone in front of the heart.
Mesotheliomas with the same extent of
local spread as in stage II that have
also spread to subcarinal and/or
mediastinal lymph nodes on the same
side are also included in stage
III.
Stage
IV:
Mesothelioma has spread into the lymph
nodes in the chest on the side opposite
that of the primary tumor, or directly
extends to the pleura or lung on the
opposite side, or directly extends into
the peritoneum, or directly extends
into organs in the abdominal cavity or
neck. Any mesothelioma with evidence of
distant metastases (spread to other
organs through the bloodstream) or
spread to organs beyond the chest or
abdomen is included in this
stage.
Although
the recently developed TNM classification
is the most detailed and precise, the
original Butchart staging system is still
used most often to describe the spread of
pleural mesotheliomas. Understanding these
staging systems for mesothelioma is
important both for estimating and better
understanding prognosis, and also for
assessing therapeutic options.
Prognostic
Factors:
Because
pleural mesothelioma has been better
studied than peritoneal mesothelioma we
know more about factors associated with
prognosis for pleural mesothelioma.
Younger age at diagnosis, performance
status (functional status) and absence of
weight loss are associated with a more
favorable prognosis.
Mesotheliomas
are usually of three different cell types
(histological analysis): 1) epithelial
cell type - has the most favorable
prognosis; 2) fibrosarcomatous cell type -
carries the worst prognosis and 3) mixed
cell type - has an intermediate
prognosis.
What
treatments are available for
Mesothelioma?
 Conventional
Treatments
Experimental
Treatments
Clinical
Trials
Mesothelioma
Treatment by Stage
Questions
to ask your Doctor
Leading
Cancer Centers
Leading
Mesothelioma
Physicians
Articles
and Abstracts
Other
Sources for
Information
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