Mesothelioma

Overview

Mesothelioma is a type of cancer that occurs in the mesothelium, or the thin membrane lining the body's internal organs. The most common site of mesothelioma is within the pleura, a thin membrane which surrounds the lungs and chest wall. Mesothelioma also occurs in the peritoneum, which surrounds the abdominal cavity, as well as within the pericardium, which envelops the heart.¹

Mesothelioma is associated with asbestos exposure. Most individuals diagnosed with mesothelioma have worked with or within proximity of airborne asbestos particles or asbestos dust. Asbestos is a naturally occurring mineral that has been used as an insulation material dating back to the early Greco-Roman eras. Industrial use of the mineral, however, is the culprit for the majority of exposures. While symptoms are similar, mesothelioma is not lung cancer and there is no known nexus between smoking and the development of mesothelioma.²

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1. Chahinian, A. Philippe; Pass, Harvey I. "Malignant Mesothelioma".
2. National Cancer Institute. "General Information about Malignant Mesothelioma." 2006.

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Symptoms and Warning Signs

There is a great deal of latency between exposure to asbestos and the onset of mesothelioma symptoms. In many patients, first signs of the disease will not occur for 30 to 50 years after exposure.³ Pleural mesothelioma, which is the most common form of the disease, is associated with the following symptoms:

• Pain within the chest wall
• Shortness of breath (due to the accumulation of fluid in the pleural space, also known as pleural effusion)
• Excessive fatigue
• Chronic cough
• Blood in the respiratory tract fluid (sputum)

Symptoms of abdominal disease, like peritoneal mesothelioma, will not typically manifest until the cancer is in its later stages. These symptoms include abdominal pain, buildup of fluid in the peritoneal space, a visible mass in the abdominal region, and problems with bowel function. Symptoms of pericardial mesothelioma include chest pain, heart palpitations, and shortness of breath. Symptoms of later-stage or metastasized disease include extreme pleural effusion, blood clotting, diminished blood sugar levels, and severe fluid build-up in the peritoneal space.⁴

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3. National Cancer Institute. "Asbestos Exposure: Questions and Answers." 2007
4. American Cancer Society. "Detailed Guide: Malignant Mesothelioma".

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Diagnosis of Mesothelioma

Physicians have difficulty conclusively diagnosing mesothelioma in the early stages of their evaluation because the symptoms of the disease so closely mimic those of other malignancies and illnesses, such as lung cancer. In most cases the first step is a thorough physical exam and review of a patient's medical history. If a patient has a known asbestos-exposure history, suspicion of mesothelioma will likely be enhanced.⁵

Imaging

A chest X-ray will likely be used to determine if there is visible growth in the pleural, pericardial, or peritoneal space. These early-stage imaging exams can reveal a thickening in the pleural space, which is common among those who worked with asbestos. A magnetic resonance image (MRI) or computer topography (CT) scan is then performed, which can indicate the buildup of fluid in the pleural space or elsewhere. If there is a substantial fluid buildup, a cytological exam will likely be necessary to examine the fluid. A pleural tap or chest drain procedure is then used to extract fluid.

Biopsy

If cytology confirms the presence of malignant cells, a biopsy will likely be used to examine surrounding tissue for the presence of malignant growth. Depending on where the cancer occurs, biopsy procedures will differ. A thoracoscopy will likely be used to examine malignant cells in the chest, while a laparoscopy would be used to extract cells from the abdominal region.⁶

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5. Pass, I., Vogelzang, N., Carbone, M. Malignant Mesothelioma: Advances in Pathogenesis, Diagnosis, and Transitional Therapies. Springer: New York. 2005.
6. American Cancer Society. "How is Malignant Mesothelioma Diagnosed?" Detailed Guide: Malignant Mesothelioma. 19 Oct 2006.

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Screening: Asbestos Risk and Assessment

There has yet to be developed a universal method of screening those who are believed to be at high risk of mesothelioma, which are those people who have known asbestos exposure history. As mesothelioma is often not diagnosed until it is in its later stages, physicians are working on methods of identifying early-stage diagnosis or risk assessment platforms. Early diagnosis of the disease dramatically improves prognosis and expands a patient's treatment options.⁷ Chemically, there is no conclusive test for early stage mesothelioma, though identifying serum osteopontin and mesothelin-related protein levels has shown potential to be the first identified chemical indicators of mesothelioma.⁸

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7. Robinson BW, Creaney J, Lake R, et al (July 2005). "Soluble mesothelin-related protein--a blood test for mesothelioma". Lung Cancer 49 Suppl 1: S109:11.
8. Dodson, R. and Hammar, S. Asbestos: Risk Assessment, Epidemiology, and Health Effects. Taylor & Francis: Boca Raton. 2006.

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Pathophysiology

The relationship between pleural mesothelioma and asbestos exposure is clearer than the relationship between asbestos and pericardial mesothelioma and peritoneal mesothelioma. Asbestos has six different varieties. Amphibole asbestos fibers are those which are more commonly associated with asbestos exposure. Amphibole fibers are microscopic with a long, thin composition. Inhaled asbestos fibers will lodge within the outer portion of the lung, eventually penetrating the visceral surface lining of the mesothelium and potentially forming a malignancy. Physicians surmise, though have not confirmed, that peritoneal mesothelioma is caused by ingested asbestos fibers which penetrate the abdominal cavity's mesothelial lining through contaminated sputum. In addition, there is a common belief among physicians and cancer researchers that peritoneal mesothelioma may be caused by asbestos fibers transported through the lymphatic system.

Some of the most current theories concerning the pathogenesis of the disease are now centered around the genetic mutations of patient DNA. Cell membranes can envelop microscopic fibers, which may react with chromosomal structures.

Over time, asbestos fibers within the mesothelium cause a sustained inflammation of the surrounding tissue. Fibers will collide with and irritate mesothelial cells, causing the development of scar tissue and malignant plaques on the surface of the membrane.⁹

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9. Roggli VL, Sharma A, Butnor KJ, Sporn T, Vollmer RT (2002). "Malignant mesothelioma and occupational exposure to asbestos: a clinicopathological correlation of 1445 cases". Ultrastruct Pathol 26 (2): 55:65.

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Incidence

Mesothelioma is a rare cancer, affecting between 2,500 and 3,000 people in the United States each year. Higher rates of incidence are found in the United Kingdom and Australia, due mostly to similar levels of industrialized asbestos use as those in the United States. Mesothelioma is much more likely to occur in males than it is females, largely because of occupational exposures to asbestos in male-dominated industries.¹⁰

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10. Bianchi, C; Bianchi T (June 2007). "Malignant mesothelioma: global incidence and relationship with asbestos". Industrial Health 45 (3): 379:387.

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Risk Factors

Those who worked with asbestos are most at risk of mesothelioma. There have been some cases of mesothelioma in patients with no known or suspected asbestos history, though these are extremely uncommon and are considered medical anomalies. Asbestos was used in many industries and exposure was possible in a number of jobsites. Shipyards, power plants, and boiler constructions are commonly associated with asbestos use, and incidence of mesothelioma is likewise high in former workers of these industries. Asbestos use is not limited to these industries, however. Asbestos was used in a number of construction compounds including tiling, siding, insulation, drywall, and cements. Those who worked with these materials for a sustained period of time prior to 1980 may also be at elevated mesothelioma risk.

Occupational Exposure

Industrial asbestos use climaxed in the middle of the twentieth century but has been used for centuries. Those who engaged with loose asbestos materials, such as insulation and asbestos dust, or unstable asbestos compounds, are most at-risk of exposure.¹¹

Secondary Exposure

Family members of those who worked with asbestos are also at elevated risk of mesothelioma, due to their contact with the person or clothing of the person working with asbestos.¹²

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11. Muscat JE, Wynder EL (May 1991). "Cigarette smoking, asbestos exposure, and malignant mesothelioma". Cancer Res. 51 (9): 2263:7.
12. Eastbourne Today. "Woman's death from asbestos"

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Mesothelioma Treatment

Surgery

Mesothelioma is often diagnosed in its later stages, meaning most tumors are inoperable at that point. However, surgeons have had some degree of success with early stage tumors using a number of different procedures. Surgery has, when used alone, proven disappointing in preventing notable remission.¹³ Typically surgical procedures will be performed in conjunction with chemotherapy or radiation therapy. Some of the more common procedures are:

Pneumonectomy

Pneumonectomy is a surgical procedure in which an affected lung or portion of an affected lung is resected. Pneumonectomy is more commonly used to remove lung cancer tumors but is sometimes used to resect early stage tumors of mesothelioma so that they do not spread further around the lungs.¹⁴

Extrapleural Pneumonectomy

Extrapleural pneumonectomy is now considered the most advanced surgery for the treatment of malignant mesothelioma. During the surgery, a thoracic surgeon will remove the entire affected lung, a portion of the pericardium, the diaphragm, and parietal pleura. The diaphragm will then be replaced by a prosthetic lining to sustain lung function.

Extrapleural pneumonectomy is a comprehensive procedure and is typically only possible for patients in good health. This procedure, however, represents the forefront of advancement in resectable mesothelioma tumors and has thus improved survival periods dramatically.¹⁵

Thoracentesis

Thoracentesis is a palliative procedure designed to eliminate pain and patient discomfort and is common in patients of malignant mesothelioma. Thoracentesis involves the alleviation of pleural effusion (fluid buildup in the pleural space). This procedure is often performed in conjunction with pleurodesis, in which talc is injected into the chest wall to prevent further fluid proliferation.¹⁶

Radiation/Immunotherapy

Radiation has likewise been disappointing when used by itself. The necessary dosage of radiation to kill the malignant cells has been considered too toxic to employ in the treatment of mesothelioma. Radiation has however been used with varying levels of success in conjunction with chemotherapeutic drugs and post-operatively following surgical procedures, including resection.

Immunotherapy, which employs localized radiation through the intra-pleural injection of interferon or interleukin-2 has also shown mixed results, but has shown enough positive patient response that further tests are ongoing to determine its effectiveness as a whole.¹⁷

Chemotherapy

Chemotherapy is currently the only treatment for malignant mesothelioma clinically proven to improve patient survival rates.¹⁸ The most common treatment regimen involves the use Alimta® (pemetrexed) in combination with the alkalizing agent, Cisplatin. A 2003 study of the pemetrexed/Cisplatin combination was the first to positive response among in both randomized and controlled trials, showing statistically significant improvement in patient survival. Alimta® is now the only drug approved by the Food and Drug Administration for the treatment of malignant pleural mesothelioma.¹⁹

There are a number of ongoing trials of other drugs and cocktails for the treatment of malignant mesothelioma. Among those in various stages of trial include GEMzar®(gemcitabine), Navelbine®(vinorelbine), and Onconase®(ranpirnase).²⁰

Chemotherapy can be utilized both unilaterally in the treatment of malignant mesothelioma or post-operatively and in conjunction with radiation therapy.

Heated Intraoperative-Intracavitary Chemotherapy

Heated intracavitary chemotherapy is an intra-operative procedure which is performed after surgeons have removed the critical mass of malignant cells from the chest or abdominal cavity. A chemotherapy agent, heated to between 40 and 48 degrees Celsius, is applied to the affected area and surrounding tissue. Chemotherapy treatment of this nature would typically not be possible, as these temperatures and high concentrations of cytoactive drugs would be considered too toxic using traditional systemic injection. The chemotherapeutic agent is left throughout the affected area for one to two hours and then drained.