Malignant Mesothelioma

Malignant mesothelioma is a lethal cancer that affects the lining of the lung, chest cavity, or abdominal cavity. The only known cause for mesothelioma, malignant and benign, is exposure to asbestos. It is the presence of microscopic asbestos fibers within the body that cause mesothelioma. The disease develops in the mesothelium, membrane found throughout the body that serves as a covering and protective surface for several of the body's internal organs, as well as lining for the chest cavity and the abdominal cavity. Cancer that develops in the mesothelium is called mesothelioma. Benign mesothelioma is usually a soft tumor that develops on either the membrane lining the chest cavity wall or on the abdominal cavity wall. It does not develop as a diffuse cancer, like malignant mesothelioma often does, and is relatively rare. Benign mesothelioma accounts for about 10% of all diagnosed mesothelioma cases.

Three Types of Malignant Mesothelioma

Pleural Mesothelioma develops in the section of the mesothelium that provides the outer lining of the lungs and that lines the chest cavity wall. This section of the mesothelium is called the pleura; the area between the two membranes is called the pleural space or pleural cavity. This form of the disease is by far the most common, constituting seventy percent or more of all diagnosed cases of malignant mesothelioma. The reason this form of the disease is predominant is that the asbestos fibers that cause it most often are internalized by breathing. They are tough microscopic fibers that can be inhaled unknowingly in any location where an old or torn asbestos product may release them; they are invisible and light enough to float on a cloud of dust.

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Peritoneal Mesothelioma is located in the membrane that lines the wall of the abdominal cavity. This form of the disease accounts for fifteen to twenty percent of all diagnoses. It begins by thickening and inflaming the peritoneal mesothelium, or peritoneum, which often causes the development of excess fluid in the area. Pressure develops on the intestines and other nearby organs, resulting in a number of symptoms that are often read as intestinal blockage, kidney problems, or liver disease.

Pericardial Mesothelioma is the most unusual diagnosis, occurring in five percent or less of all malignant mesothelioma cases. This portion of the mesothelium forms a sac around the heart. When the disease becomes active it causes the membrane – known as the pericardium – to thicken, harden and put pressure on the heart. The result is often heart palpitations, arrhythmia, chest pain that is commonly associated with heart disease, and if the pericardium becomes too thick, heart failure.

Cell Types of Malignant Mesothelioma

Mesothelioma is also broken down into cell types; there are two distinct types of cancer cells that may be part of this malignancy. Epithelioid mesothelioma is caused by epithelial cells; about 50% to 60% of mesothelioma cancers are of this type. It tends to have a better prognosis than the other types. Sarcomatoid or fibrous cells cause 10% to 20% of malignant mesotheliomas. These cases are much more difficult to treat effectively. The third possibility is biphasic mesothelioma, which includes both types of cells. They make up about 30% to 40% of all cases.

Malignant Mesothelioma Risk

The most common cause of malignant mesothelioma is asbestos exposure. Workers in the steel, mining, plumbing, milling, insulation, and power generation industries, among hundreds of others who handle or manufacture asbestos products, are at the highest risk of developing malignant mesothelioma. Asbestos exposure in the workplace has resulted in tens of thousands of mesothelioma cases over the past half century, as asbestos was a widely used component of industrial, manufacturing and construction products.

While the risks of the disease increase depending on the frequency and intensity of asbestos exposure, there have been a number of malignant mesothelioma cases among people who have had only one or two months of exposure. One of the unusual aspects of the disease is the extraordinarily long period of latency that usually accompanies it. Mesothelioma symptoms generally begin to manifest themselves twenty to fifty years after the hazardous asbestos exposure has occurred. That means the average mesothelioma patient is well over fifty years old and in many cases retired. And, in too many cases, mesothelioma victims are also inflicted with some of the medical frailties that accompany old age, making diagnosis of this rare disease more difficult.

Asbestos fibers are sharp and easily cling to various surfaces such as hair, skin, clothes, and shoes of workers who may track the toxic fibers into their homes subjecting innocent family members to serious illnesses and disease. They may be contained in dust collected on clothing during the course of a workday. Family members of those who are regularly exposed asbestos brought into the home also are at risk of developing malignant mesothelioma.

Symptoms of Malignant Mesothelioma

Pleural mesothelioma being the most common form of the disease, the symptoms most often seen involve the chest. Those may include chest pain, a dry cough, shortness of breath and difficulty with physical exertion. Beyond these physical symptoms are the medical causes. Pleural effusion, a condition that causes the accumulation of fluid in the pleural space, is seen in a majority of pleural mesothelioma cases. Thickening of the pleura is brought on by inflammation and the development of small tumors across the membrane's surface.

Peritoneal mesothelioma is characterized by a swollen abdomen and abdominal pain, usually caused by a buildup of fluid. Bowel obstruction, edema in the legs, and thrombosis in the legs are also seen with this version of malignant mesothelioma. Anemia and loss of appetite may occur.

Pericardial mesothelioma causes chest pain similar to that felt with cardiovascular disease. It can also cause thrombosis in the veins and arteries around the heart, as well as the palpitations and arrhythmia mentioned above. Like pleural mesothelioma it will cause shortness of breath and lack of physical stamina. For all of these forms of malignant mesothelioma, fatigue, sweating, weight loss and difficulty sleeping may also become physical difficulties.

Malignant Mesothelioma Treatment

The nature of the treatment received by mesothelioma patients is directed by the degree to which the disease has advanced. That question is analyzed by medical personnel through the process of staging, a formal protocol that provides a series of benchmarks for the malignancy, the degree to which it has spread, its location(s) within the body and the types of malignant cells that make up the tumor development.

The key question for mesothelioma treatment is whether or not there is a surgical option to remove some or all of the malignant tissue. If the staging diagnosis determines that surgery is feasible, a resection procedure will remove the malignant portion of the mesothelium, or as much as can be removed, and often adjacent tissue that is diseased or threatened as well. With pleural mesothelioma, for example surgical intervention often involves a partial pneumonectomy, which means removing a portion of the lung next to the malignant mesothelium tissue. Surgery to remove portions of the peritoneum in the case of peritoneal mesothelioma may also involve removing portions of the stomach.

In cases where surgical intervention is warranted and performed, a program of chemotherapy combined with radiotherapy usually follows. Depending on the location of the malignancy and whether or not malignant tissue remains in the body, the chemotherapy may be administered via the standard intravenous method or may be applied directly to the targeted tissue during surgery. The two drugs that the FDA has approved for the treatment of mesothelioma are pemetrexed and cisplatin, usually used in combination because they attack different weaknesses in cancer cells.

Techniques have been developed to minimize the damage that radiation therapy does to healthy cells near the malignant areas being targeted, but limiting healthy cell damage remains an issue for both chemotherapy treatment and radiation. Sometimes radiotherapy is used during the course of surgery so that physicians can target precisely the diseased tissue remaining in the body while it is still exposed on the operating table.

Photodynamic therapy has been developed to allow for the targeting of radiological cancer treatment as well. Still in experimental stages, photodynamic therapy essentially uses photosensitive medications that are injected into the patient and activated by light when they reach the appropriate area to be treated. This promising technique is under study in several clinical trials, as is immunotherapy – another method of attacking cancer cells with specific molecules.

Mesothelioma Staging

There are three or more sets of guidelines for the staging of malignant mesothelioma cases. The most common is the TNM system, an acronym that references tumors, nodes and metastases. TNM is used to stage lung cancer, ovarian cancer and other types of the disease, and has been approved as a standard by the American Joint Committee on Cancer, an organization that counts the National Cancer Institute among its founding members.

Currently pleural mesothelioma is the only form of the disease that has a formal staging structure. It is the most common form of a relatively rare disease; accordingly physicians assess the spread of cancer in peritoneal mesothelioma or pericardial mesothelioma based on less form analyses of the presence of malignancy.

Briefly, the four TNM stages are as follows:

Stage I: Mesothelioma is present in the pleura covering either the right or left lung. It may have spread to the pericardium or the diaphragm or lung on the same side of the body. There is no evidence of cancer in the lymph nodes.

Stage II: Mesothelioma meets all of the conditions of stage I with the additional spread to lymph nodes near the malignant tissue in the pleura and on the same side of the body.

Stage III: Mesothelioma has advanced into the chest wall, the heart, the esophagus or possibly the ribs on the same side of the body as the original pleural malignancy. There may or may not be lymph node involvement.

Stage IV: Mesothelioma has moved to the opposite side of the body, impacting the pleura on the other lung as well as the opposite lung itself, and possibly extending to organs in the abdominal cavity. Metastases have occurred in several areas.

Malignant Mesothelioma Prognosis

Surgery to resect malignant tissue is generally a viable choice with stages one and two, and often with stage three. In the latter case, it depends on the location of the extended malignancy. In stage two and stage three cases, the surgery may involve only a partial removal of malignant tissue, a process referred to as "debulking." In all cases, a regimen of chemotherapy and usually radiotherapy follows the surgical procedure.

In cases where surgery has been performed and an aggressive chemotherapy program undertaken, the prognosis for mesothelioma patients who are otherwise healthy patients may extend to eighteen months or beyond. If the cancer was at stage one or stage two, the outlook for a reasonable survival period can be encouraging. Unfortunately, the median survival period for mesothelioma patients in general hovers at around one year. Some studies have shown the figure to be thirteen months; others closer to eleven months or less. But the value of a surgical intervention followed by chemotherapy seems to be well established; while most gains are in months some are in years.

Mesothelioma Clinical Trials

There is an excellent database of current clinical trials underway for mesothelioma treatment at the National Institutes of Health (NIH) website ClinicalTrials.gov. Most of them evolve around the use of various chemotherapy drugs in combination with one another. The two drugs that have proven to impact mesothelioma tumors with some success are pemetrexed and cisplatin; these are the only two approved by the FDA for mesothelioma treatment.

The drugs are effective against some forms of mesothelioma malignant cells and less so against others; effective with pleural mesothelioma, perhaps, but ineffective with the pericardium. The point is that these two drugs have proven the ability to successfully kill some of the cancer cells some of the time and so many of the clinical trials involve using other cancer chemotherapy drugs in conjunction with pemetrexed, cisplatin, or both.

All of the chemotherapy drugs used in mesothelioma clinical trials such as these have been approved for treatment of other types of tumors. For example some drugs such as Bortezomib act by stopping blood flow to a tumor, and by killing certain enzymes that allow malignant cells to proliferate. There is currently a clinical study using this drug in conjunction with cisplatin to test the success with malignant mesothelioma tumors.

Onconase is a drug that impacts the RNA in some cancer cells, causing them to die. Clinical trials using this chemotherapy drug in conjunction with other drugs that starve tumors by choking off blood supply or that somehow suppress the ability of malignant cells to multiply are underway in several locations. Some of these trials are sponsored by the National Cancer Institute, some are generated in foreign medical centers, and some are undertaken by cancer centers in the U.S. with the assistance of grants from the NIH.

There are also trials underway attempting to establish effective methods of using photodynamic therapy to target diseased cells, along with other methods that are meant to protect the healthy cells surrounding tumors. Destroying healthy cells has always been an issue with chemotherapy and radiotherapy; today researchers are using new technology and molecular knowledge to try and find healthier ways to treat post-operative malignant mesothelioma.

Sources:

  1. Localized Benign Pleural Mesothelioma, Altin, et al, Zonguldak Karaelmas University, Department of Pulmonology, Turkey, 2003
  2. Detailed Guide: Malignant Mesothelioma, American Cancer Society, http://www.cancer.org/docroot/CRI/content/CRI_2_4_1X_What_is_malignant_mesothelioma_29.asp?sitearea=
  3. Malignant Mesothelioma Diagnosis, American Cancer Society, http://www.cancer.org/docroot/CRI/content/CRI_2_4_3X_How_is_malignant_mesothelioma_diagnosed_29.asp?sitearea=
  4. Malignant Pleural Mesothelioma, Boutin et al, European Respiratory Journal, p. 5, 1998
  5. What's New in Malignant Mesothelioma Research and Treatment, American Cancer Society, http://www.cancer.org/docroot/CRI/content/CRI_2_4_6X_Whats_new_in_malignant_mesothelioma_research_and_treatment_29.asp?sitearea=

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