Mesothelioma is a form of cancer that is almost always caused by exposure to asbestos. In this disease, malignant cells develop in the mesothelium, a protective lining that covers most of the body's internal organs. Its most common site is the pleura (outer lining of the lungs and internal chest wall), but it may also occur in the peritoneum (the lining of the abdominal cavity), the heart,the pericardium (a sac that surrounds the heart) or tunica vaginalis.
Most people who develop mesothelioma have worked on jobs where they inhaled asbestos particles, 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 risk of other asbestos-induced cancer.Compensation via asbestos funds or lawsuits is an important issue in 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.
Wednesday, July 29, 2009
MESOTHELIOMA TREATMENT OPTIONS
The treatment program for mesothelioma depends on many factors, including: the stage of the cancer, where the cancer is, how far the cancer has spread, how the cancer cells look under the microscope and the patient’s age and desires.
TIME MATTERS
People diagnosed with this disease are often told the expected survival rate is only eight to twelve months. However, specialists in treating malignant mesothelioma at the leading cancer centers often have better statistics.
For instance, the five-year survival rate has approached 40% for selected patients of Dr. David Sugarbaker at Brigham and Women’s Center in Boston. To qualify for Dr. Sugarbaker’s treatment you must meet certain criteria. One of them is being in the early stages of the disease, so time is of the essence.
TRADITIONAL CARE
There are three traditional kinds of treatment for patients with malignant mesothelioma:
Surgery (taking out the cancer)
Chemotherapy (using drugs to fight the cancer)
Radiation Therapy (using high-dose x-rays or other high-energy rays to kill cancer cells)
MESOMARK BLOOD TEST
n January 2007, the Food and Drug Administration (FDA) approved the MESOMARK assay to help monitor response to treatment in epithelial and bi-phasic malignant mesothelioma patients. A specific protein, or biomarker, called Soluble Mesothelin-Related Peptide (SMRP), may be released into the blood by mesothelioma cancer cells. By measuring the amount of SMRP in a blood sample, doctors may be able to better monitor a patient's progress. Based on the limited amount of data currently available, use of this test may be beneficial, but effectiveness has not been determined at this time. The MESOMARK blood test has NOT yet been approved for the early diagnosis of mesothelioma.
This test has been approved as a Humanitarian Use Device (HUD), meaning that physicians must follow certain procedures to qualify their patients for testing. Once the physician is certified, informational brochures will be sent to be distributed to each applicable patient.
Those wishing to take part in
MESOMARK testing will be asked to provide one or more samples of blood. The blood samples will then be sent to a national reference laboratory for testing. In conjunction with other clinical and laboratory data obtained by your doctor, decisions regarding your treatment and care may be simplified. You may discontinue testing at any time.
The costs associated with the MESOMARK blood test may not be covered under health insurance, therefore, you may be required to pay all or part of the costs out of pocket. It is recommended that you check with your insurance carrier to determine whether coverage is available under your policy.
TIME MATTERS
People diagnosed with this disease are often told the expected survival rate is only eight to twelve months. However, specialists in treating malignant mesothelioma at the leading cancer centers often have better statistics.
For instance, the five-year survival rate has approached 40% for selected patients of Dr. David Sugarbaker at Brigham and Women’s Center in Boston. To qualify for Dr. Sugarbaker’s treatment you must meet certain criteria. One of them is being in the early stages of the disease, so time is of the essence.
TRADITIONAL CARE
There are three traditional kinds of treatment for patients with malignant mesothelioma:
Surgery (taking out the cancer)
Chemotherapy (using drugs to fight the cancer)
Radiation Therapy (using high-dose x-rays or other high-energy rays to kill cancer cells)
MESOMARK BLOOD TEST
n January 2007, the Food and Drug Administration (FDA) approved the MESOMARK assay to help monitor response to treatment in epithelial and bi-phasic malignant mesothelioma patients. A specific protein, or biomarker, called Soluble Mesothelin-Related Peptide (SMRP), may be released into the blood by mesothelioma cancer cells. By measuring the amount of SMRP in a blood sample, doctors may be able to better monitor a patient's progress. Based on the limited amount of data currently available, use of this test may be beneficial, but effectiveness has not been determined at this time. The MESOMARK blood test has NOT yet been approved for the early diagnosis of mesothelioma.
This test has been approved as a Humanitarian Use Device (HUD), meaning that physicians must follow certain procedures to qualify their patients for testing. Once the physician is certified, informational brochures will be sent to be distributed to each applicable patient.
Those wishing to take part in
MESOMARK testing will be asked to provide one or more samples of blood. The blood samples will then be sent to a national reference laboratory for testing. In conjunction with other clinical and laboratory data obtained by your doctor, decisions regarding your treatment and care may be simplified. You may discontinue testing at any time.
The costs associated with the MESOMARK blood test may not be covered under health insurance, therefore, you may be required to pay all or part of the costs out of pocket. It is recommended that you check with your insurance carrier to determine whether coverage is available under your policy.
MESOTHELIOMA'S CAUSE - ASBESTOS EXPOSURE
At some point in our lives, nearly all of us have been exposed to asbestos in the air we breathe and the water we drink; from natural deposits in the earth, and from the deterioration of asbestos products around us. Most of us, however, do not become ill as a result of our exposure. More commonly, those who at some point are diagnosed with asbestos disease, have worked in jobs where more substantial exposure occurred over longer periods of time. Nevertheless, cases of mesothelioma have been documented as the result of lesser exposure, affecting family members of workers who came into contact with asbestos and brought it home on their clothing, skin or hair, or affecting those who lived in close proximity to asbestos manufacturing facilities. Symptoms of asbestos disease usually are not be apparent until decades after exposure.
Asbestos was used commercially in North America as early as the late 1800s, but its use increased dramatically during the World War II era when shipyards produced massive numbers of ships for the war effort. Since that time, asbestos-containing products were used by the construction and building trades, the automotive industry and the manufacturing industry. All told, more than 5,000 products contained asbestos.
For more than 50 years, products containing asbestos remained unregulated, and the manufacturers of those products continued to prosper, knowing full well that many of the millions of workers who came into contact with their products would ultimately suffer as the result of their actions. Finally, in the late 1970s, the Consumer Products Safety Commission banned the use of asbestos in wallboard patching compounds and artificial ash for gas fireplaces because the fiber could easily be released during use. In 1989, the Environmental Protection Agency banned all new use of asbestos, but uses established prior to that time were still allowed. Although awareness of the dangers of asbestos and public concern over the issue have led to a decline in domestic consumption over the years, a total ban on asbestos has not come to fruition. Asbestos is still imported, still used and still dangerous.
Although it is suggested that the number of mesothelioma cases in the U.S. has reached its peak and has begun to drop, a forecast released by the National Cancer Institute's Surveillance, Epidemiology, and End Results Program (SEER), in April, 2003, projected the total number of American male mesothelioma cases from 2003-2054 to be approximately 71,000. This number, however, does not take into consideration events such as the World Trade Center disaster on September 11, 2001, when millions of New Yorkers were potentially exposed to air filled with carcinogenic asbestos particles. The incidence of mesothelioma cases by state and county are shown in these tables. When the latency period for asbestos disease is factored in, cases of mesothelioma will continue to be diagnosed for years to come.
Asbestos was used commercially in North America as early as the late 1800s, but its use increased dramatically during the World War II era when shipyards produced massive numbers of ships for the war effort. Since that time, asbestos-containing products were used by the construction and building trades, the automotive industry and the manufacturing industry. All told, more than 5,000 products contained asbestos.
For more than 50 years, products containing asbestos remained unregulated, and the manufacturers of those products continued to prosper, knowing full well that many of the millions of workers who came into contact with their products would ultimately suffer as the result of their actions. Finally, in the late 1970s, the Consumer Products Safety Commission banned the use of asbestos in wallboard patching compounds and artificial ash for gas fireplaces because the fiber could easily be released during use. In 1989, the Environmental Protection Agency banned all new use of asbestos, but uses established prior to that time were still allowed. Although awareness of the dangers of asbestos and public concern over the issue have led to a decline in domestic consumption over the years, a total ban on asbestos has not come to fruition. Asbestos is still imported, still used and still dangerous.
Although it is suggested that the number of mesothelioma cases in the U.S. has reached its peak and has begun to drop, a forecast released by the National Cancer Institute's Surveillance, Epidemiology, and End Results Program (SEER), in April, 2003, projected the total number of American male mesothelioma cases from 2003-2054 to be approximately 71,000. This number, however, does not take into consideration events such as the World Trade Center disaster on September 11, 2001, when millions of New Yorkers were potentially exposed to air filled with carcinogenic asbestos particles. The incidence of mesothelioma cases by state and county are shown in these tables. When the latency period for asbestos disease is factored in, cases of mesothelioma will continue to be diagnosed for years to come.
How do you get malignant mesothelioma?
Mesothelioma is caused by asbestos exposure. Asbestos, once regarded as a miracle mineral, was popular due its lightweight but tough characteristics as well as for its heat-resistant properties. This naturally occurring mineral was used in many commercial and consumer products, from construction materials such as cement, roofing shingles and insulation, to consumer and industrial applications such as hair dryers, automobile brake pads and pipe insulation
Most people with malignant mesothelioma worked on jobs where they breathed asbestos. Others were exposed to asbestos in a household environment, often without knowing it.
Most people with malignant mesothelioma worked on jobs where they breathed asbestos. Others were exposed to asbestos in a household environment, often without knowing it.
Signs and symptoms
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
Fatigue or anemia
Wheezing, hoarseness, or cough
Blood in the sputum (fluid) coughed up (hemoptysis)
In severe cases, the person may have many tumor masses. The individual may develop a pneumothorax, or collapse of the lung. The disease may metastasize, or spread, to other parts of the body.
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.
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
Fatigue or anemia
Wheezing, hoarseness, or cough
Blood in the sputum (fluid) coughed up (hemoptysis)
In severe cases, the person may have many tumor masses. The individual may develop a pneumothorax, or collapse of the lung. The disease may metastasize, or spread, to other parts of the body.
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).
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 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.
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.
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 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.
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.
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). 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 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 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.
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). 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 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 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.
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