Carolyn Vachani, MSN, RN, AOCN and Charles B. Simone II, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: May 20, 2013
The mesothelium is a protective sac that covers and protects most internal organs in the body. It is composed of two layers, one layer covers the organ and the second layer forms a sac around it. The mesothelium produces a lubricating fluid that is released between these layers, allowing moving organs (such as the lungs) to move easily. The area between the two layers is often called the pleural space. Mesothelial tissue is found lining the abdominal cavity organs, lungs, testes and heart.
Mesothelioma occurs when the mesothelial cells grow out of control. These cells also lose the ability to stop producing the lubricating fluid when there is enough. This results in the unwanted encasement of organs within a thick rind of tumor tissue and excess fluid buildup, ultimately causing symptoms. These cells can grow and invade other organs, or spread to other areas of the body. When the cells spread to other areas of the body, it is called metastasis.
The majority of mesotheliomas are found in the lining of the lung (approximately 70%). About 20-30% percent of cases are found in the abdominal cavity lining, and even more rarely, mesothelioma is found in the lining of the heart (1-2%) or testicles.
Mesothelioma is a rare cancer, with approximately 2, 500 cases diagnosed each year in the United States. It is five times more common in men, which is due in most part to work-related exposure to asbestos. Risk also increases with age. The biggest risk factor for developing the disease is exposure to asbestos, accounting for 50 to 80 percent of all cases. Asbestos has been used in many products, including cement, brake linings, roof shingles, flooring products, textiles, and insulation. Particles can be released from these products, particularly during the manufacturing process, and inhaled. Prior to knowing the dangers, asbestos miners and other workers exposed to asbestos worked without wearing any protection. Since the 1970's, the U.S. Occupational Safety and Health Administration (OSHA) has set limits for acceptable levels of asbestos exposure and requires protective equipment in the workplace. Family members of people who worked with asbestos were also exposed to the toxin when it was carried home on clothing and hair, putting them at increased risk for mesothelioma.
While up to 80% of cases of pleural mesothelioma occur in individuals who have had known asbestos exposure, only 10% of people with a history of heavy exposure develop the disease. This suggests that additional exposures or factors are involved to actually develop the disease. Even more puzzling is the fact that only 50% of people with peritoneal mesothelioma have a history of asbestos exposure.
It takes 20 to 50 years from the time of asbestos exposure until mesothelioma is detected. Although most individuals who develop mesothelioma had a repeated exposure to asbestos over many years or longer, some develop the cancer with as little as one or two months of asbestos exposure. The incidence of mesothelioma varies in different areas of the world, depending on when asbestos was widely used in that area. Rates are higher in the United Kingdom, where about 1800 cases per year are diagnosed. The incidence takes into consideration the number of cases and the size of the population. This is because asbestos use in Western Europe remained high until 1980, whereas maximum exposure in the U.S. was from the 1930s to 1960s. Australia was one of the world's largest producers of asbestos, leading to the country having the highest rates worldwide (based on the size of the population). Rates in the U.S. are beginning to decline, whereas rates in Europe and Australia are expected to plateau in the next 10-15 years before declining.
Following the ban of asbestos in many countries, asbestos producers started to promote the sale of their product to developing countries, such as Asia and Latin America. Experts fear that the peak rates in these areas are yet to come, and will mimic what has been seen in the U.S. and Europe. As asbestos is widely available, even today, in China and India, rates in those countries are projected to increase significantly over the next two decades.
Other risk factors include prior radiation therapy to the chest, exposure to erionite fibers (mineral in gravel roads), collapsotherapy (for the treatment of tuberculosis), and potentially even exposure to the DNA tumor simian virus SV40. Smoking does not seem to increase the risk of developing the disease.
By decreasing exposure to asbestos, the risk of mesothelioma is decreased. Workers who are exposed to asbestos on the job should wear protective clothing and masks. These workers should change their clothing before leaving the work site to avoid carrying any particles home. OSHA has set standards regulating these procedures.
There is no good screening test for mesothelioma. Radiologic studies (x-ray, CT scan) are not sensitive enough to detect tumors before symptoms occur. Currently, researchers are investigating the use of several blood markers in an attempt to detect mesothelioma earlier than conventional methods for people with a history of asbestos exposure. These tests include measurements of serum osteoporin, levels of the soluble mesothelin-related protein, and the Mesomark assay that evaluates the levels of soluble mesothelin-related proteins released by mesothelioma cells. Presently, however, all of these tests are considered experimental.
The symptoms of mesothelioma are often caused by a build-up of tumor tissue surrounding the lung and accumulation of fluid in the pleural space that prevents the lung from expanding fully. This causes pressure on the lung, leading to pain and shortness of breath. As the disease progresses, patients may lose weight and have a dry, hacking cough. Mesothelioma originating in the pleura can directly spread into the abdomen, or mesothelioma can originate in the peritoneum of the abdomen. Symptoms most commonly associated with abdominal disease includes abdominal swelling, pain and weight loss.
Patients who present with symptoms worrisome for mesothelioma often initially have a chest x-ray done that shows a build-up of fluid in the lining of the lung. These patients then undergo a CT scan of the chest to further evaluate the cancer. In the case of abdominal mesothelioma, a CT scan is obtained to visualize the anatomy in the abdomen.
The fluid in the lining of the lung is often drained to improve symptoms. A diagnosis of mesothelioma can sometimes be made by looking at the cells of this fluid under the microscope. If a diagnosis is not possible with the fluid alone, patients would then undergo a biopsy to have the diagnosis confirmed. In the lung, a thoracoscope is used to go through the chest wall, between the ribs, to obtain a sample of the tissue. A peritoneoscope or abdominal laparoscopy are used to enter the abdomen to obtain a tissue sample to diagnose abdominal mesothelioma.
Staging refers to determining the extent of the disease, and the stage dictates the treatment. Physicians use the TNM system (also called tumor - node - metastasis system). This describes the size and locally invasiveness of the tumor (T), which if any lymph nodes are involved (N), and if it has spread to other more distant areas of the body (M). This is then interpreted as a stage somewhere from I (one) denoting more limited disease to IV (four) denoting more advanced disease. Patients with earlier stage tumors tend to live longer and respond better to available treatments.
Treatment is dependent on the stage of the disease, the location of the tumor, the patient's age, and his or her state of health and performance status. Younger, healthy patients with early-stage malignant pleural mesothelioma may be candidates for surgery that removes the mesothelial tissue around the tumor. Although surgery to either remove the entire lung with the tumor (termed extrapleural pneumonectomy) or lung-sparing surgery that removes only the tumor and the lining of the lung (termed extended or radical pleurectomy) is the most standard option for these patients, Similar comprehensive surgery is often considered in patients with peritoneal mesothelioma. All of these definitive thoracic or peritoneal surgeries are extensive, many patients are not able to undergo surgery due to having advanced disease at diagnosis or not being able to medically tolerate the surgery, and there currently is limited randomized data showing a survival benefit with extensive surgery compared with non-surgical treatments.
For patients that have surgery that removes the entire lung, postoperative radiation therapy is commonly given to treat that side of the chest to attempt to kill any remaining cancer cells not removed by surgery. Postoperative radiation therapy after lung-sparing surgery, however, is not routinely administered since the radiation damage to the healthy lung tissue in the process of treating any remaining cancer cells may result in toxicity that outweighs any benefit of radiotherapy. Radiation therapy is also commonly delivered to surgical incision sites to prevent the cancer from recurring locally at those sites. In patients who do not undergo surgery, radiation therapy is generally only given, as needed, to treat problem spots to relieve symptoms like pain or trouble breathing.
Chemotherapy is the most standard treatment for mesothelioma and can provide significant relief of symptoms and also improve surgery. Agents that are used, either alone or in combination, include cisplatin, carboplatin, pemetrexed, gemcitabine, and vinorelbine. These medications achieve responses in 10 to 30 percent of patients.
In a key trial that randomized patients to receive either cisplatin alone or cisplatin in combination with pemetrexed (Alimta), patients who received the combination of drugs had increased response rates, survived longer, and had fewer side effects. In addition, researchers found that giving folic acid and vitamin B12 along with the combination resulted in less toxicity and no decrease in the therapy's effectiveness. The combination of cisplatin (can be substituted with carboplatin if clinically appropriate) and pemetrexed is now considered standard of care for mesothelioma and can be given alone or before or after surgery.
Because the current therapies have limited effectiveness, researchers are continuing to look for new ways to treat mesothelioma. Some of the treatments being investigated include immunotherapy, gene therapy (a method that attempts to correct the abnormal gene that causes the cancer to grow out of control), chemotherapy administered directly into the pleural space, and intraoperative Photodynamic Therapy (PDT- a treatment that uses a laser to activate a photosensitizing drug during the surgical removal of the cancer in an attempt to kill any remaining cancer cells not removed by surgery). Patients should talk with their physicians about current clinical trials for mesothelioma.
One problem that patients may encounter is the recurring build-up of fluid in the pleural space. This fluid can be removed with a chest tube (a tube that is put into the chest wall and left in for a period of time to allow drainage) or a procedure called thoracentesis (a small needle is put through the chest wall into the pleural space, the fluid is drained, and the needle is removed). In many cases, this will be followed by a procedure called pleurodesis, in which a medication (talc, bleomycin) is injected into the lung to create scar tissue in the hopes of decreasing future fluid from developing. In the abdomen, the procedure to remove fluid is called paracentesis. In this procedure, a needle is inserted through the abdomen into the fluid filled space, and the fluid is drained. If this is a chronic problem, patients may have a catheter placed semi-permanently, allowing them to drain the fluid themselves at home as needed. Removal of the fluid alleviates the difficulty in breathing and the pain that is caused by the fluid build-up.
The physician will follow the patient with physical examinations and surveillance imaging.
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Vogelzang, N et al., Phase III Study of Pemetrexed in Combination With Cisplatin Versus Cisplatin Alone in Patients With Malignant Pleural Mesothelioma, Journal of Clinical Oncology, 21: 2636-2644 (2003)
National Cancer Institute. Mesothelioma: Questions & Answers
The Mesothelioma Applied Research Foundation: This nonprofit organization's website is a great resource for patients, families & healthcare professionals.