>> What Treatment Options Will I Be Offered?

Treatment options may vary according to the age and over-all health of the patient, and the extent of the disease. It is important to be informed of all available options for your particular case, so that you can make decision on the option you feel most comfortable with. Surgery, chemotherapy, and clinical trials, as well as new approaches such as photodynamic therapy, immunotherapy, and gene therapy may be offered. Speak openly with your doctor regarding suggested procedures. Questions may include:

• Why is this procedure best for me?
• What does the procedure entail?
• What are the advantages/disadvantages of this treatment (i.e, will this procedure limit my eligibility for other treatments)?
• What are the possible risks or adverse side effects?
• What are the response, survival, and mortality rates associated with this procedure?

>> Mesathelioma Stages

Treatment options are often determined by the stage of mesothelioma a patient is in. There are three staging systems currently in use for pleural mesothelioma and each one measures somewhat different variables; peritoneal mesothelioma is not staged.

Staging is the term used to describe the extent of a patient's cancer, based on the primary tumor and its spread in the body. It can help the medical team plan treatment, estimate prognosis and identify clinical trials for which the patient may be eligible.

Staging is based on a knowledge of how the cancer develops, from the primary tumor, to the invasion of nearby organs and tissues, to distant spread or metastasis. Staging systems have evolved over time, and they continue to change as scientists learn more about cancer. Some staging systems cover many different types of cancer, while others focus on more specific cancers. The TNM (primary tumor, regional lymph nodes, distant metastasis) is the most common staging system for mesothelioma.

Some elements common to most staging systems are:

• Location of the primary tumor.
• Size and number of the tumors.
• Lymph node involvement.
• Cell type and tumor grade.
• Metastasis.

Many cancer registries, such as the National Cancer Institute's Surveillance, Epidemiology, and End Results Program (SEER) use summary staging, a system used for all types of cancer. Summary staging groups cancer into five main categories:

• In situ - cancer that is present only in the layer of cells in which it began.
• Localized - cancer that is limited to the organ in which it began with no evidence of spread.
• Regional - cancer that has spread from the primary site to nearby lymph nodes or organs.
• Distant - cancer that has spread from the primary site to distant lymph nodes or organs.
• Unknown - cases where not enough information exists to indicate stage.

Several types of testing may be used to help doctors determine stage, and to formulate a treatment plan.

• Physical examinations. The doctor examines the body by looking, feeling and listening to anything out of the ordinary.
• Imaging techniques. Procedures such as x-rays, CT scans, MRIs and PET scans may show the location, size of the tumor and whether the cancer has spread.
• Laboratory tests. Studies of blood, urine, fluid and tissue can provide information about the cancer. Tumor markers, sometime elevated when cancer is present, may provide information.
• Pathology reports. Results of the examination of tissue samples can include information about the size of the tumor(s), extension into adjacent structures, type of cells and grade of the tumor. Results of the examination of cells in fluid, such as that from a mesothelioma-related pleural effusion, may also provide information.
• Surgical reports. Observations about the size and appearance of the tumor(s), lymph nodes and nearby organs.

Staging information should be provided to the patient by his doctor so that potential treatment plans can be discussed. Stage of the mesothelioma, as well as consideration of other factors such as age, health status and the patient's wishes may dictate different treatment options.

The oldest staging system and the one most often used is the Butchart System which is based mainly on the extent of primary tumor mass and divides mesotheliomas into four stages. The more recent TNM system considers variables of tumor in mass and spread, lymph node involvement, and metastasis. The Brigham System is the latest system and stages mesothelioma according to resectability (the ability to surgically remove) and lymph node involvement.

Butchart System – extent of primary tumor mass

• Stage I: Mesothelioma is present in the right or left pleura and may also involve the diaphragm on the same side.
• Stage II: Mesothelioma invades the chest wall or involves the esophagus, heart, or pleura on both sides. Lymph nodes in the chest may also be involved.
• Stage III: Mesothelioma has penetrated through the diaphragm into the lining of the abdominal cavity or peritoneum. Lymph nodes beyond those in the chest may also be involved.
• Stage IV: There is evidence of metastasis or spread through the bloodstream to other organs.

TNM System -- variables of T (tumor), N (lymph nodes), M (metastasis)

• Stage I: Mesothelioma involves right or left pleura and may also have spread to the lung, pericardium, or diaphragm on the same side. Lymph nodes are not involved.
• Stage II: Mesothelioma has spread from the pleura on one side to nearby 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 is now in the chest wall, muscle, ribs, heart, esophagus, or other organs in the chest on the same side with or without spread to lymph nodes on the same side as the primary tumor.
• Stage IV: Mesothelioma has spread into the lymph nodes in the chest on the side opposite the primary tumor, or extends to the pleura or lung on the opposite side, or directly extends into organs in the abdominal cavity or neck. Any distant metastases is included in this stage.

Brigham System: (variables of tumor resectability and nodal status)

• Stage I: Resectable mesothelioma and no lymph node involvement
• Stage II: Resectable mesothelioma but with lymph node involvement
• Stage III: Unresectable mesothelioma extending into chest wall, heart, or through diaphragm, peritoneum; with or without extrathoracic lymph node involvement
• Stage IV: Distant metastatic disease

>> Who Gets Mesothelioma?

Statistics show that, because of their work history, the disease most often affects men between the ages of 50 and 70 who were employed in an asbestos-laden environment before asbestos warnings and bans were in place in the 1970s. Though women still have a much lower frequency of the disease, cases of second-hand exposure to asbestos has prompted more diagnoses among women, especially those whose male family members worked with asbestos. The occupations most associated with mesothelioma are shipyard workers, electricians, plumbers, construction industry workers, pipefitters, boilermakers, and anyone subject to heavy exposure to dangerous asbestos and airborne asbestos fibers.

An abundance of cases have also demonstrated that mesothelioma can develop among people who lived in communities where asbestos factories or mines were located. In some instances, entire towns have been adversely affected by the presence of asbestos fibers in the air. For example, in Libby, Montana - site of a former vermiculite asbestos mine - hundreds have already died of mesothelioma.

Though still significantly rarer than other cancers, an estimated 2,000 to 3,000 new cases of mesothelioma are diagnosed each year in the United States. Other countries, notably the United Kingdom and Australia, report a much higher incidence of the disease. Nevertheless, the United States - like many other countries - has seen an increase in asbestos-caused cancer as men who worked in U.S. shipyards in the 1940s and 1950s, at the height of production, are now being diagnosed with mesothelioma.

>> Effects of the Disease

The invasion of the mesothelium by cancer cells makes it very difficult for the patient to breathe, resulting in the need for oxygen, especially as the disease progresses. Those with the pleural form of mesothelioma may also suffer from pleural effusions. These effusions prevent the smooth movement of the lungs and other organs in the chest. Peritoneal mesothelioma also affects the stomach area and abdominal cavity, causing nausea, vomiting, or loss of appetite, which can result in dangerous weight loss. In addition to breathing difficulties and loss of appetite, mesothelioma victims also complain of excessive coughing, sleeping difficulties, persistent chest pain, fever, and pain in the lower back.

Mesothelioma, in general, is a very painful disease and because it is usually not diagnosed until it's in an advanced stage. For this reason, the symptoms are typically quite serious. Late diagnosis also means that the cancer is more likely to have metastasized, or spread, making successful mesothelioma treatment even more difficult.

>> Mesothelioma Treatment - A Patient's Options

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 questions 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.

>> Risk factors

Working with asbestos is the major risk factor for mesothelioma.^[9] Mesothelioma is now known to occur in those who are genetically pre-disposed to it. 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.

>> Pathophysiology

lining of the serous cavities of the body including the The mesothelium consists of a single layer of flattened to cuboidal cells forming the epithelialperitoneal, 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.[1][2] 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.[3]

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
• P16^INK4A
• P14^ARF

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.

>> Diagnosis

CT scan of a patient with mesothelioma, coronal section (the section follows the plane the divides the body in a front and a back half). The mesothelioma is indicated by yellow arrows, the central pleural effusion (fluid collection) is marked with a yellow star. Red numbers: (1) right lung, (2) spine, (3) left lung, (4) ribs, (5) descending part of the aorta, (6) spleen, (7) left kidney, (8) right kidney, (9) liver.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.

>> 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.

>> What is Mesothelioma

Mesothelioma is a form of cancer that is almost always caused by previous 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. Washing the clothes of a family member who worked with asbestos can also put a person at risk for developing mesothelioma. Unlike lung cancer, there is no association between mesothelioma and smoking. 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.