Desmoplastic Malignant Mesothelioma

Desmoplastic malignant mesothelioma is the growth of fibrous or connective tissues around the tumor of the lining of the lung or chest cavity. The term .desmoplastic. refers to the growth of fibrous or connective tissue. "Desmo-" comes from the Greek "desmos" meaning "a fetter or band" and "-plastic" is also borrowed from the Greek, from "plassein" meaning "to form" = to form a band or fetter.

Pericardial Mesothelioma

Pericardial Mesothelioma is affects the thin lining of tissue that surrounds the heart, or the pericardium. This cancer can occur at any age, although the mean age of presentation is 46. Symptoms include chest pain, cough, dyspnea, and palpitations. As with the other forms of Mesothelioma, a strong link to asbestos exposure seems evident. Surgery and radiation therapy can provide some palliation, however the prognosis is extremely poor.

A common sign of pericardial mesothelioma is pericardial effusion, or a collection of fluid in the sac that surrounds the heart. If caused by cancer, this symptom can be caused by the direct spread of cancer, or the result of cancer metastasized from other parts of the body.

Peritoneal Mesothelioma

Peritoneal Mesothelioma affects the abdomincal cavity and organs, including the liver, spleen and bowels. Pain is the most common symptom in cases of Peritoneal Mesothelioma. However, the accumulation of fluid can often cause the abdominal region to appear enlarged. Other common symptoms include vomiting, nausea, foot swelling, increased body temperature or fever, and difficulty in moving bowels. The survival time is poorer than pleural mesothelioma, with most patients averaging 10 months from the first display of symptoms. Peritoneal Mesothelioma accounts for approx. 10 percent of mesothelioma cases.

Pleural Mesothelioma - Cancer of the Lung Lining

Pleural Mesothelioma affects the chest cavity, sometimes including the lungs. Metastates, or the spreading of the cancer, can occur in any other organs, and is much more common than originally thought. This form of mesothelioma usually has a slow onset, with the most common symptoms is localized chest pain. This can be accompanied by trouble breathing, caused by pleural effusion, or a buildup of liquid in the pleural space (chest cavity). Additional symptoms include cough, weight loss, and fever. The best test for determining the extent of Pleural Mesothelioma is a computed chest tomograph (CT-scan). Median survival time for this form of Mesothelioma is approximately 17 months from the onset of symptoms. This is the most common form of mesothelioma, accounting for 80-90% of cases.

The pleura are the tissues lining or covering surrounding the actual lungs. There are 2 pleural membranes, separated by the pleural space. These membranes are fibrous sheets, protecting the lungs by producing a lubricating fluid to assist in lung operation.

Types of Mesothelioma

There are five known types of mesothelioma. Four of these are malignant cancers, and one is a benign condition.

Once asbestos is inhaled it can effect many of the bodys different organs including the throat, lungs, stomach, heart and testicles.

Pleural Mesothelioma: This type of mesothelioma develops in the lining of the lungs, known as the pleura. It is the most common form of malignant mesothelioma, with around 70 percent of cases being pleural in origin.

Peritoneal Mesothelioma: This form of mesothelioma develops in the lining of the abdominal cavity, known as the peritoneal membrane. Approximately 25 percent of mesothelioma cases are of this type.

Pericardial Mesothelioma: This form of mesothelioma develops in the lining of the heart, known as the pericardium. About 5 percent of all mesothelioma cases are pericardial.

Testicular Mesothelioma: This is the rarest type of malignant mesothelioma; to date, there have been less than 100 recorded cases. Testicular mesothelioma develops in the tunica vaginalis of the testicles.

Benign Mesothelioma: The benign form of mesothelioma most commonly develops in the pleura. This is the only form of mesothelioma for which full cure and recovery is a probable outcome, though it may be a precursor of future asbestos-related problems

Mesothelioma Causes & Steps After a Diagnosis

Mesothelioma is a rare type of cancer that develops in the mesothelial cells that lines many organs and body cavities. The mesothelium (composed of mesothelial cells) is the membrane that lines three of the body's cavities, and depending on what cavity it lines it is given a specific name: the thoracic cavity (pleura), abdominal cavity (peritoneum), and the heart sac (pericardium).

Mesothelioma is a rare cancer that can develop in the mesothelium of the thoracic cavity in the lungs.

The mesothelium that covers the internal organs is called the visceral mesothelium, while the layer that covers the body wall is called parietal mesothelium.

Mesothelium tissue also surrounds the male internal reproductive organs and covers the internal reproductive organs in women.

Mesothelioma is an aggressive cancer of the mesothelium, in which cells of the mesothelium become abnormal and divide uncontrollably and without order. They can invade and damage nearby tissues and organs. Most cases of mesothelioma begin in the thoracic cavity (pleura) or the abdominal cavity (peritoneum).

Approximately 2,000 to 3,000 cases of mesothelioma are diagnosed each year in the United States, comprising around 3 percent of all cancer diagnoses. This cancer occurs about four times more frequently in men than in women. All forms of mesothelioma, except for benign mesothelioma, are invariably fatal. The prognosis for mesothelioma is almost always poor and most studies report a median survival of less than one year, but the prognosis really depends on how early the cancer is diagnosed and how aggressively it is treated.

After a mesothelioma patient learns of their diagnosis, the next step is often exploring applicable treatment options to create the best treatment plan possible. Treatment options range from surgery to chemotherapy and we offer information about the various types of treatment available to patients. To help you learn more about these options, we provide an informational packet to interested patients and their loved ones at the top, right of this page.

Veteran Support

Navy veterans who worked in navy shipyards and or served on our nation’s warships and submarine’s from WWII through the Vietnam War were exposed to high concentrations of deadly asbestos. Boiler rooms, engine rooms, sleeping quarters, and other areas of naval vessels were the most common areas where asbestos was present. As a result, Navy veterans are at a greater risk of developing mesothelioma. Veterans who were exposed should fill out the brief form on this page to receive a free mesothelioma and asbestos exposure information kit. Support systems are in place to make sure you receive the assistance you deserve.

Asbestos Exposure

Asbestos exposure is the single known cause of mesothelioma. Inhaled or ingested asbestos fibers may cause an inflammation of internal tissue and disrupt organ function which leads to the development of the disease. Asbestos products were used extensively throughout the 20th century in a wide variety of applications. Many of these products were responsible for asbestos exposure sustained by both the individuals who manufactured the products as well as those who used them at commercial and industrial jobsites including shipyards, refineries, power plants, steel plants and more. Several asbestos companies continued to produce these products even after they were known to be hazardous and harmful to workers and their families. Those who have become sick because of exposure to these products may now be eligible for financial compensation if they were wrongfully exposed.

Asbestos was also used at many New York jobsites including Ground Zero and the former World Trade Center site. Common asbestos exposure sites in New York include the Brooklyn Navy Yard, Todd Shipyard, and the Con Edison power plant in New York City.

Who is at risk for Mesothelioma?

The only recognized cause of mesothelioma is exposure to asbestos, though other factors such as smoking can make the disease more or less likely in some individuals. Industrial laborers were widely subjected to asbestos exposure on the job, as the material was widely used throughout the 20th century. Few of these workers knew they were being exposed to asbestos, however, despite the fact that many manufacturers were aware the material was hazardous. In most cases, mesothelioma symptoms will not appear in an individual exposed to asbestos until many years after the exposure has occurred. Those who believe they may have been exposed to asbestos should fill out our form to receive a free mesothelioma information packet, detailing treatment options, emerging therapies, and jobsite exposure information.

Mesothelioma Treatment

Once an individual has been diagnosed with mesothelioma, the next step is to discuss mesothelioma treatment options with his/her physician. Recent scientific research has produced significant breakthroughs with regard to treatment protocols for mesothelioma patients and more options are now available for managing the disease and supporting improved quality of life. Newly diagnosed patients always have many questions about the treatment options that would be most effective for them, including those about new treatment therapies like Alimta and Cisplatin and other chemotherapy drugs. In addition to these newer drugs that are being used to treat asbestos cancer, mesothelioma patients also have a number of "conventional" treatment options to consider, including chemotherapy, radiation therapy and surgery.

Clinical trials and experimental treatments are still other options that some mesothelioma patients may be eligible to participate in. Our site features a comprehensive mesothelioma cancer treatment section that includes important information for patients and families. We've included resources on top mesothelioma doctors such as Dr. Sugarbaker, as well as a comprehensive list of questions that you may wish to discuss with your personal physician when preparing a treatment plan. We are always providing new and informative resources regarding mesothelioma treatment including: Clinical Trials, conventional treatments, experimental therapies, and more. Check back often for the most recent advances in mesothelioma treatments.

Are new treatments for mesothelioma being studied?

Yes. Because mesothelioma is very hard to control, the National Cancer Institute (NCI) is sponsoring clinical trials (research studies with people) that are designed to find new treatments and better ways to use current treatments. Before any new treatment can be recommended for general use, doctors conduct clinical trials to find out whether the treatment is safe for patients and effective against the disease. Participation in clinical trials is an important treatment option for many patients with mesothelioma.
People interested in taking part in a clinical trial should talk with their doctor. Information about clinical trials is available from the Cancer Information Service (CIS) (see below) at 1–800–4–CANCER. Information specialists at the CIS use PDQ®, NCI's cancer information database, to identify and provide detailed information about specific ongoing clinical trials. Patients also have the option of searching for clinical trials on their own. The clinical trials page on the NCI's Cancer.gov Web site, located at http://www.cancer.gov/clinicaltrials on the Internet, provides general information about clinical trials and links to PDQ.
People considering clinical trials may be interested in the NCI booklet Taking Part in Cancer Treatment Research Studies. This booklet describes how research studies are carried out and explains their possible benefits and risks. The booklet is available by calling the CIS, or from the NCI Publications Locator Web site at http://www.cancer.gov/publications on the Internet.

How is mesothelioma treated?

Treatment for mesothelioma depends on the location of the cancer, the stage of the disease, and the patient's age and general health. Standard treatment options include surgery, radiation therapy, and chemotherapy. Sometimes, these treatments are combined.
Surgery is a common treatment for mesothelioma. The doctor may remove part of the lining of the chest or abdomen and some of the tissue around it. For cancer of the pleura (pleural mesothelioma), a lung may be removed in an operation called a pneumonectomy. Sometimes part of the diaphragm, the muscle below the lungs that helps with breathing, is also removed.
Radiation therapy, also called radiotherapy, involves the use of high-energy rays to kill cancer cells and shrink tumors. Radiation therapy affects the cancer cells only in the treated area. The radiation may come from a machine (external radiation) or from putting materials that produce radiation through thin plastic tubes into the area where the cancer cells are found (internal radiation therapy).
Chemotherapy is the use of anticancer drugs to kill cancer cells throughout the body. Most drugs used to treat mesothelioma are given by injection into a vein (intravenous, or IV). Doctors are also studying the effectiveness of putting chemotherapy directly into the chest or abdomen (intracavitary chemotherapy).
To relieve symptoms and control pain, the doctor may use a needle or a thin tube to drain fluid that has built up in the chest or abdomen. The procedure for removing fluid from the chest is called thoracentesis. Removal of fluid from the abdomen is called paracentesis. Drugs may be given through a tube in the chest to prevent more fluid from accumulating. Radiation therapy and surgery may also be helpful in relieving symptoms.

Doctor Explains Mesothelioma Symptoms, Diagnosis & Treatment

Risks of Mesothelioma

Risks of Mesothelioma

What is Mesothelioma?

Mesothelioma is a cancer of the mesothelium. The mesothelium is a thin membrane that lines the chest and abdomen and surrounds the organs in these areas. The lining around the lungs is called the pleura and in the abdomen it is known as the peritoneum.
About 2000 people in the UK are diagnosed with mesothelioma each year.
Mesothelioma of the lining of the lungs, known as pleural mesothelioma, is much more common than mesothelioma in the peritoneum. For every one person with peritoneal mesothelioma, there will be about 12 people who have pleural mesothelioma.

Pleural mesothelioma

The pleura has two layers: the inner (visceral) layer, which is next to the lung; and the outer (parietal) layer, which lines the chest wall. The two layers of the pleura are usually in contact and slide over each other as we breathe. The membranes produce fluid, which allows them to slide over each other easily.
When mesothelioma develops in the pleura (pleural mesothelioma), the delicate membranes thicken and may press inwards on the lung. Fluid may also collect between the two layers of the pleura: this is known as a pleural effusion.

Structure of the lungs and pleura

Peritoneal mesothelioma

The lining of the abdomen is known as the peritoneum. It also has two layers: the inner (visceral) layer, which is next to the abdominal organs, and the outer (parietal) layer, which lines the abdominal wall.
If the mesothelioma is in the peritoneum it is called peritoneal mesothelioma and causes thickening of the membranes surrounding the abdominal organs and a collection of fluid in the abdomen. The collection of fluid is called ascites and causes swelling of the abdomen.
Side view of the abdomen. The peritoneum is shown as the thick line surrounding the abdominal organs.

Surgery for mesothelioma

In the uncommon situation where the cancer is only in one area of the pleura (localised), surgery can be used to treat mesothelioma. It may involve removing part, or all, of the pleura and the lung tissue close to it. This is known as pleurectomy. Sometimes the pleura, diaphragm, and the whole lung on the affected side are removed as well as the tumour. This operation is known as extra-pleural pneumonectomy.
At present it is not clear whether surgery can give better control of symptoms or can help people to live for longer than just using active symptom control. A research trial is currently looking at whether extra-pleural pneumonectomy can give a better quality and length of life for people with localised pleural mesothelioma. This trial is called the MARS trial. You may be invited to take part if your doctor thinks that surgery could possibly be helpful for you.
It is not usually possible to surgically remove abdominal (peritoneal) mesothelioma. If surgery is possible, it is carried out by surgeons with specialist expertise in treating mesothelioma. However, the operation is not likely to cure the mesothelioma.
It is important that you discuss any operation fully with your doctor beforehand so that you understand what it involves. Remember, no operation or procedure will be done without your consent.
Surgery may sometimes be combined with radiotherapy or chemotherapy.

Drips and drains

A drip (intravenous infusion) will be used to give you fluids for a couple of days, until you are able to eat and drink normally again. You will also have drainage tubes in your wound. These are usually removed about 2–7 days after your operation depending on your recovery. X-rays will be taken regularly to make sure your lung is working properly.

Pain

It is normal to have some pain or discomfort after your operation. This can usually be controlled using painkilling drugs. Let your doctor or one of the nurses know if you have any pain so they can treat it as soon as possible. Mild discomfort or pain in your chest can last for several weeks and you will be given some painkilling tablets to take home with you.

Going home

You can usually go home after about seven days after a pleurectomy. If you have an extra-pleural pneumonectomy it will probably be about 14 days before you are ready to go home. If you think you might have problems when you go home – for example, if you live alone or have several flights of stairs to climb – let one of the nurses or the hospital social worker know when you are admitted to the ward, so that help can be arranged.
When you go home, it is important to exercise gently, to build up your strength and fitness. Walking and swimming are suitable for most people after surgery to the lung area. But it is a good idea to check with your doctor or physiotherapist which kind of exercise would be suitable for you

Mesothelioma

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,[1] 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. Washing the clothes of a family member who worked with asbestos can also put a person at risk for developing mesothelioma.[2] Unlike lung cancer, there is no association between mesothelioma and smoking, but smoking greatly increases risk of other asbestos induced cancer.[3] 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.

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 painpleural effusion, or fluid surrounding the lungshortness of breathfatigue or anemiawheezing, hoarseness, or coughblood 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 painascites, or an abnormal buildup of fluid in the abdomena mass in the abdomenproblems with bowel functionweight loss In severe cases of the disease, the following signs and symptoms may be present: blood clots in the veins, which may cause thrombophlebitisdisseminated intravascular coagulation, a disorder causing severe bleeding in many body organsjaundice, or yellowing of the eyes and skinlow blood sugar levelpleural effusionpulmonary emboli, or blood clots in the arteries of the lungssevere 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. Typical immunohistochemistry results Positive Negative EMA (epithelial membrane antigen) in a membranous distribution 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. Screening tests might diagnose mesothelioma earlier than conventional methods thus improving the survival prospects for patients. 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.[4] Doctors have begun testing the Mesomark assay which measures levels of soluble mesothelin-related proteins (SMRPs) released by diseased mesothelioma cells.

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).[6] 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.[7] 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 22q12P16INK4AP14ARF 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 genesActivation of oncogenesActivation of proto-oncogenes due to incorporation of foreign DNA containing a promoter regionActivation of DNA repair enzymes, which may be prone to errorActivation of telomerasePrevention 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.

Epidemiology

Incidence

cidence Although reported incidence rates have increased in the past 20 years, mesothelioma is still a relatively rare cancer. The incidence rate is approximately one per 1,000,000. The highest incidence is found in Britain, Australia and Belgium: 30 per 1,000,000 per year.[8] 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.[9] 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.[10] Between 1973 and 1984, there has been a threefold increase in the diagnosis of pleural mesothelioma in Caucasian males. 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. Risk factors Working with asbestos is the major risk factor for mesothelioma.[11] 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 modern 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.[12] Exposure Asbestos was known in antiquity, but it wasn't mined and widely used commercially until 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 exist 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. Recent findings have shown that a mineral called erionite has been known to cause genetically pre-dispositioned individuals to have malignant mesothelioma rates much higher than those not pre-dispositioned genetically. A study in Cappadocia, Turkey has shown that 3 villiages in Turkey have death rates of 51% attributed to erionite related mesothelioma. Occupational 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. 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 DIY activities may expose themselves to asbestos dust. In the UK use of Chrysotile asbestos was banned at the end of 1999. Brown and blue asbestos was banned in the UK around 1985. Buildings built or renovated prior to these dates may contain asbestos materials. Environmental exposures Incidence of mesothelioma had been found to be higher in populations living near naturally occurring asbestos. For example, in Cappadocia, Turkey, an unprecedented mesothelioma epidemic caused 50% of all deaths in three small villages. Initially, this was attributed to erionite, however, recently, it has been shown that erionite causes mesothelioma mostly in families with a genetic predisposition.[13]

Treatment

Treatment of malignant mesothelioma using conventional therapies in combination with radiation and or chemotherapy on stage I or II Mesothelioma have proved on average 74.6 percent successful in extending the patients life span by five years or more [commonly known as remission][this percentage may increase or decrease depending on date of discovery / stage of malignant development] (Oncology Today, 2009). Treatment course is primarily determined by the staging or development. This is unlike traditional treatment such as surgery by itself which has proved only be 16.3 percent likely to extend a patient's life span by five years or more [commonly known as remission]. 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. Surgery Surgery, by itself, has proved disappointing. However, research indicates varied success when used in combination with radiation and chemotherapy (Duke, 2008) 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. RadiationFor 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. This approach of using surgery followed by radiation with chemotherapy has been pioneered by the thoracic oncology team at Brigham & Women's Hospital in Boston.[14] 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 cisplatin 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.[15] 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 combination pemetrexed group in patients who 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, 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.[16] 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-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.[17] 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.

Notable people who died from mesothelioma

Mesothelioma, though rare, has had a number of notable patients. Hamilton Jordan, Chief of Staff for President Jimmy Carter and life long cancer activist, died in 2008. Australian anti-racism activist Bob Bellear died in 2005. British science fiction writer Michael G. Coney, responsible for nearly 100 works also died in 2005. American film and television actor Paul Gleason, perhaps best known for his portrayal of Principal Richard Vernon in the 1985 film The Breakfast Club, died in 2006. Mickie Most, an English record producer, died of mesothelioma in 2003. Paul Rudolph, an American architect known for his cubist building designs, died in 1997. Bernie Banton was an Australian workers' rights activist, who fought a long battle for compensation from James Hardie 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 48hrs to live. Australian Prime Minister Kevin Rudd mentioned Banton's extended struggle in his acceptance speech after winning the 2007 Australian Federal Election. Steve McQueen was diagnosed with peritoneal mesothelioma on December 22, 1979. He was not offered surgery or chemotherapy because doctors felt the cancer was too advanced. McQueen sought alternative treatments from clinics in Mexico. He died of a heart attack on November 7, 1980, in Juárez, Mexico, 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 car racing suits.[18] (It is also reported that he worked in a shipyard during World War II, where he might have been exposed to asbestos.[citation needed]) United States Congressman Bruce Vento died of mesothelioma in 2000. The Bruce Vento Hopebuilder is awarded yearly by his wife at the MARF Symposium to persons or organizations who have done the most to support mesothelioma research and advocacy. After a long period of untreated illness and pain, rock and roll musician and songwriter Warren Zevon was diagnosed with inoperable mesothelioma in the fall of 2002. Refusing treatments he believed might incapacitate him, Zevon focused his energies on recording his final album The Wind 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 Hennessy, the influential Irish singer-songwriter, died of mesothelioma in 2007, and had stridently refused to accept the prognosis in the weeks before his death.[19] His mesothelioma has been attributed to his younger years spent working on building sites in London.[20][21] Bob Miner, one of the founders of Software Development Labs, the forerunner of Oracle Corporation 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.[22] Canberra journalist and news presenter, Peter Leonard also succumbed to the condition on 23 September 2008. Terrence McCann Olympic gold medalist and longtime Executive Director of Toastmasters, died of mesothelioma on June 7, 2006 at his home in Dana Point, California.

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 Gould was diagnosed with peritoneal mesothelioma. After his diagnosis, Gould wrote the "The Median Isn't the Message"[23] for Discover magazine, in which he argued that statistics such as median survival are just useful abstractions, not destiny. Gould lived for another twenty years eventually succumbing to metastatic adenocarcinoma of the lung, not mesothelioma. Author Paul Kraus was diagnosed with mesothelioma in June 1997 following an umbilical hernia operation. His prognosis was "a few months." He continues to survive using a variety of integrative and complementary modalities and has written a book about his experience.

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). Today, you may see a commercial stating something like, "Mesothelioma is a rare type of cancer caused by asbestos particles. Asbestos particles can be found in lumberyards, shipyards or any of the heating or automotive industries." The liability resulting from the sheer number of lawsuits and people affected has reached billions of dollars.[24] 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, Congress has failed to enact significant asbestos reforms.

Legal 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. It was not until 1960 that an article published by Wagner et al. first officially established mesothelioma as a disease arising from exposu

re to crocidolite asbestos.[26] 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 McNulty reported the first diagnosed case of malignant mesothelioma in an Australian asbestos worker.[27] 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 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.