Mesothelioma

Cancer of the pleura is most often metastatic, usually adenocarcinoma from the breast or lung.

Primary malignant neoplasms of the pleura are relatively rare. Pleural neoplasms frequently produce a malignant pleural effusion, making cytology a useful tool in their detection.

Thoracoscopy is also very useful tool for obtaining tissue samples for diagnosis because it allows the direct visualization of the pleural surfaces.

Prognosis in this disease is difficult to assess consistently because there is great variability in the time before diagnosis and the rate of disease progression.

Various surgical procedures may be possible in selected patients, providing long-term survival without cure. In large retrospective series of pleural mesothelioma patients, important prognostic factors were found to be stage, age, performance status, and histology.

For patients treated with aggressive surgical approaches, factors associated with improved long-term survival include epithelial histology, negative lymph nodes, and negative surgical margins.

For those patients treated with aggressive surgical approaches, nodal status is an important prognostic factorMedian survival for malignant local pleural disease has been reported as 16 months, and extensive disease as 5 months. In some instances the tumor grows through the diaphragm making site of origin difficult to assess. Cautious interpretation of treatment results in this disease is imperative because of the selection differences among series.

Effusions, both pleural and peritoneal, represent major symptomatic problems for at least two thirds of the patients. A history of asbestos exposure is reported in about 70%-80% of all cases of mesothelioma

Mesotheliomas are the most common primary malignant tumors of the pleura.

Other rare primary tumors of the pleura include fibrosarcoma, angiosarcoma, and other sarcomas

. Mesotheliomas arise from pleura in about 80% of cases and from the peritoneum in the remaining 20%.

In the chest, the tumors can arise from either the visceral or parietal pleura. Approximately 75% of these tumors are diffuse and malignant. The rest are localized and usually benign. Mesotheliomas are more common in men, who represent about 75% of all cases.

The benign mesothelioma, also known as a fibroma, is usually a small (1-2 cm) localized growth which may enlarge.

These tumors always remain confined to the surface of the lung and do not normally produce a pleural effusion. Generally they become symptomatic when their growth impinges on adjacent structures within the chest. They are sometimes associated with hypoglycemia, and they are not associated with asbestos exposure. Histologically they are composed of whorls of reticulin and collagen fibers amongst cytologically benign spindled cells resembling fibroblasts.

The more common malignant pleural mesotheliomas, however, are strongly associated with asbestos exposure. In the normal population, mesotheliomas are rare tumors with an incidence of 2 to 17 cases per 1,000,000 people; however, in asbestos workers the relative risk is over 1000 times greater. The risk of bronchogenic carcinoma is increased only 5 fold in asbestos workers, but the risk is 55 times greater in asbestos workers who smoked.

It should be stressed that there is no increased risk of mesothelioma in smokers who have asbestos exposure, which is in direct contrast to the association between asbestos exposure and bronchogenic carcinoma, where the risk is markedly increased.

Common occupational sources for asbestos exposure include the mining, milling, manufacturing processes. A history of shipyard work or replacement of automobile brake lining in the past places a patient at risk for mesothelioma. Epidemiologic studies have determined that 70% to 90% of cases have identifiable asbestos exposure.

The suggested pathogenesis for the development of mesothelioma from asbestos exposure begins with the inhalation of the asbestos fibers.

The carcinogenic effects of the fibers is believed to be related to their size and shape rather than chemical composition, based on the fact the certain fiber shapes are more carcinogenic.

The inhaled fibers are not easily cleared from the upper airway and diffuse out to the distal endothelium, where they can then penetrate the interstitial tissues and visceral pleura. When the fibers are ingested by macrophages, they damage the macrophages, causing them to release cytokines, free radicals, and enzymes.

These compounds mediate the ensuing inflammatory and fibrotic reactions.

Asbestos fibers may also carry absorbed carcinogens, which may further contribute to the carcinogenesis and explain the strong association between asbestos exposure, smoking and subsequent elevated risk of bronchogenic carcinoma.

The average age of onset for malignant mesothelioma is 60 years.

There is a long latent period of 20-40 years between exposure and disease expression.

Common symptoms include the gradual onset of shortness of breath and nonpleuritic chest pain. The chest pain can be severe and unremitting.

A pleural effusion is often the first physical and radiographic finding.

Physical signs include dullness to percussion and decreased breath sounds on the involved side. Other radiologic signs include nodular, irregular pleural thickening.

Open pleural biopsy is often required to obtain an adequate amount of specimen to make a histological diagnosis.

Malignant mesotheliomas spread rapidly along the pleural surface, and can rapidly involve the pericardium and contralateral pleura.

The tumor may later extend to involve the abdominal lymph nodes and organs.

The average survival time from the onset of symptoms ranges from 5 months in cases of extensive disease to 16 months in localized cases. Histologic type also correlates with survival time, epithelioid variants show a longer mean and 5 year survival rates. However, approximately 75% of patients die within one year of diagnosis. Treatment has generally been unsuccessful.

Malignant Mesothelioma Diagnosed?

If there is a reason to suspect you may have a mesothelioma, such as any of the symptoms discussed in the section "Can Mesothelioma Be Found Early," the doctor will use one or more methods to find out if the disease is really present.

Medical History and Physical Examination

A complete medical history (interview) is taken to check for risk factors and symptoms. This will include questions to determine if you have been exposed to asbestos.

A physical exam will provide information about signs of mesothelioma and other health problems. Patients with pleural mesotheliomas (mesotheliomas of the chest) often have pleural effusion (fluid in their chest cavity) caused by the cancer. Ascites (fluid in the abdominal cavity) in cases of peritoneal mesothelioma, and pericardial effusion (fluid in the pericardium) in cases of pericardial mesothelioma can also be detected during a physical exam.

Imaging Tests

A chest x-ray may show irregular thickening of the pleura, pleural calcifications (mineral deposits), lowering of the lung fissures (spaces between the lobes of the lungs), and fluid in the pleural space. These findings suggest asbestos exposure leading to the development of a mesothelioma.

Imaging studies such as x-rays, computed tomography (CT) scans, and magnetic resonance imaging (MRI) scans will help determine the location, size, and extent of the cancer. The CT scan uses a rotating x-ray beam to create a series of pictures of the body from many angles. A computer combines these pictures to produce detailed cross-sectional images of a selected part of the body. To highlight details on the CT scan, you may be asked for permission to have a harmless dye injected into a vein. MRI uses magnetic fields instead of x-rays to create images of selected areas of the body. As with the CT scan, a computer generates a detailed cross-sectional image.

Tests of Fluid and Tissue Samples

In patients with a pleural effusion, a sample of this fluid can be removed by inserting a needle into the chest cavity. A similar technique can be used to obtain abdominal fluid and pericardial fluid. The fluid is then tested to show its chemical make up and viewed under a microscope to determine whether cancer cells are present.

A tissue sample of a pleural or pericardial tumor can be obtained using a relatively new technique called thoracoscopy. A thoracoscope (telescope-like instrument connected to a video camera) is inserted through a small incision into the chest. The doctor can see the tumor through the thoracoscope, and can use special forceps to take a tissue biopsy. Similarly, laparoscopy can be used to see and obtain a biopsy of a peritoneal tumor. In this procedure, a flexible tube attached to a video camera is inserted into the abdominal cavity through small incisions on the front of the abdomen. Fluid can also be collected during thoracoscopy or laparoscopy.

Surgery, either a thoracotomy (which opens the chest cavity) or a laparotomy (which opens the abdominal cavity), allows the surgeon to remove a larger sample of tumor or, sometimes, to remove the entire tumor.

For patients who might have pleural mesothelioma, the doctor may also do a bronchoscopy. In this procedure a flexible lighted tube is inserted through the mouth, down the trachea, and into the bronchi to see if there are other masses in the airway. Small samples of abnormal-appearing tissue can be removed for testing.

The patient may also have a mediastinoscopy. A lighted tube is inserted under the sternum (chest bone) at the level of the neck and moved down into the chest. Mediastinoscopy allows the surgeon to view the lymph nodes in this area and remove samples to check for cancer. Lymph nodes are bean-sized collections of immune system cells that help the body fight infections and cancers. Cancers arising in the lung often spread to lymph nodes, but mesotheliomas rarely do this. Tests of lymph nodes can give the doctor information on whether a cancer is still localized or if it has started to spread, and can help distinguish lung cancer from mesothelioma.

It is often hard to diagnose mesothelioma by looking at the cells from the fluid around the lungs, abdomen or heart. It is even hard to diagnose mesothelioma with tissue from biopsies. Under the microscope, mesothelioma can look like several other types of cancer. For example, pleural mesothelioma may resemble some types of lung cancer and peritoneal mesothelioma may resemble some cancers of the ovaries. For this reason, special laboratory tests are often done to help distinguish mesothelioma from some other cancers. These tests often use special techniques to recognize certain markers (types of chemicals) known to be contained in mesotheliomas. Different markers are present in cancer of the lung or ovary. The electron microscope can sometimes be helpful in diagnosing mesothelioma. This microscope can magnify samples more than 100 times greater than the light microscope which is generally used in cancer diagnosis. This stronger microscope makes it possible to see small parts of the cancer cells that distinguish mesothelioma from other types of cancer.

Gross Appearance

In their early stages, malignant mesotheliomas appear as multiple small nodules on the parietal or visceral pleura.

With time, the nodules grow and may coalesce to form large plaques involving both layers of the pleura, encasing the lungs, and obliterating the pleural space.

In the late stages of the disease there may be involvement of the chest wall, mediastinum, and diaphragm.

The tumor itself is usually firm and white-yellow. Rarely does the tumor penetrate the lung parenchyma to a depth greater than 1 cm.

Microscopic Features

Mesotheliomas display a wide range of histologic features.

The malignant cells may appear epithelial or mesenchymal, or show features of intermediate differentiation (biphasic).

The architectural and cellular features may range from well differentiated to anaplastic.

The well differentiated tumors can be recognized by their light microscopic appearance, while more poorly differentiated tumors necessitate immunohistochemical and ultrastructural studies to reveal their identity.

Mesotheliomas are also separated into four histologic categories:

epithelial (50%),

sarcomatous (15-20%),

biphasic (15-20%),

and poorly differentiated or undifferentiated (15-20%).

Malignant Mesothelioma

A layer of specialized cells called mesothelial cells lines the chest cavity, abdominal cavity, and the cavity around the heart. These cells also cover the outer surface of most internal organs. The tissue formed by these cells is called mesothelium.

The mesothelium helps protect the organs by producing a special lubricating fluid that allows organs to move around. For example, this fluid makes it easier for the lungs to move inside the chest during breathing. The mesothelium of the chest is called the pleura and the mesothelium of the abdomen is known as the peritoneum. The mesothelium of the pericardial cavity (the "sac-like" space around the heart) is called the pericardium.

Tumors of the mesothelium can be benign (noncancerous) or malignant (cancerous). A malignant tumor of the mesothelium is called a malignant mesothelioma. Because most mesothelial tumors are cancerous, malignant mesothelioma is often simply called mesothelioma.

It is important not to confuse malignant mesothelioma with benign tumors that also start in the mesothelium. The mesothelium of certain female and male reproductive organs may develop a type of benign tumor called an adenomatoid tumor. In men, this noncancerous tumor often starts in the epididymis (a small collection of ducts that carry sperm cells out of the testicle). In women this tumor may begin in the fallopian tubes (tubes that carry eggs from the ovaries to the uterus or womb). Another noncancerous tumor that may begin in mesothelium near female reproductive organs is called benign cystic mesothelioma.

A type of benign tumor that used to be called benign fibrous mesothelioma can form in the pleura surrounding the lungs. Doctors now know that this tumor actually starts from tissue under the mesothelium and not from mesothelial cells. For this reason, the new name of this tumor is solitary fibrous tumor of the pleura. This disease is usually not cancerous, but cancerous forms can occur. A similar disease starting in the peritoneum is called solitary fibrous tumor of peritoneum. The tumors described in this paragraph are usually removed surgically, and the patient does not receive any additional treatment. Only malignant mesothelioma will be discussed further in this document.

Malignant mesotheliomas are divided into three main types. About 50% to 70% of mesotheliomas are the epithelioid type. This type has the best prognosis (the outlook for chances of survival). The other two types are the sarcomatoid type (7%-20%), and the mixed/biphasic type (20%-35%). Treatment options for all three types are the same.

About three-fourths of mesotheliomas start in the chest cavity. They are known as pleural mesotheliomas. Another 10% to 20% begin in the abdomen. These are called peritoneal mesotheliomas. Pericardial mesotheliomas, those starting in the cavity around the heart, are very rare. The covering layer of the testicles is actually an outpouching of peritoneum into the scrotum. Mesotheliomas that affect this covering of the testicles are quite rare.

Epitheloid

The epitheloid subtype is recognized by its papillary and tubular growth patterns, although poorly differentiated forms have a more solid growth pattern.

The tumor cells are usually cuboidal, but can range from squamoid to columnar.

More well differentiated epitheloid tumors may have dome shaped cells at their apical edge.

Another feature of the well differentiated tumor is cytoplasmic vacuoles which are round with sharp borders and appear empty.

The vacuoles represent intracytoplasmic lumina.

They are lined by microvilli, which is a useful ultrastructural finding, and is a distinguishing feature from adenocarinoma.

Fibrous/sarcomatous

The fibrous variant of mesothelioma is composed of malignant-appearing spindle cells which grown in fasicles within various amounts of fibrous stroma. There may be areas of storiforming growth and multinucleated atypical cells. The cells of the well differentiated forms often resemble reactive fibroblasts and resemble fibromatoses. However, they differ from fibromatoses by their cytokine expression.

Mixed/biphastic

The mixed variant is the easiest to recognize, being composed of a mixture of epitheloid and sarcomatous elements. It is also the least common of the three subtypes of mesothelioma. Rare adenocarcinomas may present with biphastic growth patterns, thus immunohistochemistry is useful in separating the two.

Mesotheliomas may also mimick a wide variety of tumors including malgnant fibrous histiocytoma, hemangiopericytoma, schwannoma, small cell carcinoma, and other sarcomas. Although some mesotheliomas may be differentiated by light microscopy alone, the majority require many additional studies including special stains, immunohistochemistry, and electron microscopy.

Asbestos bodies are a marker of exposure to asbestos, and increased numbers are found in the lungs of patients with mesotheliomas. Under light microscopy, asbestos bodies are golden-brown, fusiform (beaded) rods with a translucent center. They consist of a core of asbestos fibers coated by ferritin, presumably from the macrophages. Because of their iron coating, they are also known as ferruginous bodies.

The epithelial variant consists of papillary or tubular formations of flat or cuboidal cells with vesicular nuclei and prominent nucleoli. Well differentiated forms may show a resemblance to hyperplastic mesothelium or adenocarcinoma. Psammoma bodies may be present in forms with papillary architecture, and cause further diagnostic confusion with metastatic adenocarcinoma. Sarcomatoid variants are composed of spindled neoplastic mesenchymal cells present in a variety of architectural patterns. Biphasic forms contain epithelial and mesenchymal elements. Poorly and undifferentiated tumors are composed of sheets of round and polygonal cells with a high degree of pleomorphism.

Special stains are very useful in identifying mesotheliomas. The mucicarmine and periodic acid-Schiff (PAS) stains are useful in characterizing the contents of cytoplasmic mucin vacuoles and thus differentiating mesotheliomas from metastatic adenocarcinoma. Adenocarcinomas contain cytoplasmic vacuoles which stain with mucicarmine and PAS. The latter is unaffected by pretreatment with diastase. Mesotheliomas do not produce mucin and are therefore negative for mucicarmine and PASD.

The presence of cytoplasmic hyaluronic acid is considered a diagnostic feature of mesotheliomas and can be detected with colloidal iron or Alcian blue stains. A positive test can be confirmed when staining is lost or decreased by pretreating the samples with hyaluronidase.

Immunohistochemical stains can also be useful diagnostic tools. When there is a question of mesothelioma versus metastatic adenocarcinoma, detection of the markers carcinoembryonic antigen (CEA), Leu M1, B72.3, and Ber-EP4 is indicative of metastatic adenocarcinoma. Immunoreactivity for any one of the latter markers excludes mesothelioma as a diagnostic consideration. Unfortunately, there is no immunohistochemical marker currently available which is positive in mesothelioma and negative in carcinoma. Thus, the immunohistochemical diagnosis of mesothelioma is always an exclusionary one.

Ultrastructural Features

Electron microscopy can be useful in differentiating mesothelioma from metastatic adenocarcinoma.

Ultrastructurally, mesothelioma cells possess numerous long, slender, branching microvilli sometimes from all cell surfaces, and abundant tonofilaments, while lacking lamellar bodies and microvillous rootlets.

These features coupled with the proper clinical context is virtually diagnostic of mesothelioma.

However, there have been mesotheliomas which possess short straight microvilli present on luminal surfaces, like adenocarcinoma, and making it impossible to differentiate the two carcinomas.

As tumors lose their differentiation, it becomes increasingly difficult to diagnose mesothelioma based upon ultrastructural features because the cells lose their unique structures. More often than not, the eventual diagnosis of mesothelioma requires the combination of histochemical stains (mucicarmine, PASD. alcian blue), immunohistochemical stains (CEA, Leumi, B72.3), and ultrastructural analysis.

CELLULAR CLASSIFICATION

Histologically, these tumors are composed of fibrous or epithelial elements or both.

The epithelial form occasionally causes confusion with peripheral anaplastic lung carcinomas or metastatic carcinomas.

Attempts at diagnosis by cytology or needle biopsy of the pleura are often noncontributory. It can be especially difficult to differentiate mesothelioma from carcinoma on small tissue specimens.

Thoracoscopy can be valuable in obtaining adequate tissue specimens for diagnostic purposes.

Examination of the gross tumor at surgery and use of special stains or electron microscopy can often help.

The special stains reported to be most useful include

periodic acid-Schiff diastase,

hyaluronic acid,

mucicarmine,

CEA,

and Leu M1.

Histologic appearance appears to be of prognostic value, with most clinical studies showing that epithelial mesotheliomas have a better prognosis than fibrous or sarcomatous mesotheliomas

STAGE INFORMATION

Butchart Staging System

Stage I: Mesothelioma is present within the right or left pleura, and may also involve the lung, pericardium, or diaphragm (the muscle separating the chest from the abdomen) on the same side.

Stage II: Mesothelioma invades the chest wall or involves the esophagus (food passage connecting the throat to the stomach), heart, or pleura on both sides. The lymph nodes in the chest may also be involved.

Stage III: Mesothelioma has penetrated through the diaphragm into the peritoneum (lining of the abdominal cavity). Lymph nodes beyond those in the chest may also be involved.

Stage IV: There is evidence of distant metastases (spread through the bloodstream to other organs

TNM Staging System

Stage I: Mesothelioma involves the right or left pleura. It may also have spread into the lung, pericardium, or diaphragm on the same side. It has not yet spread to the lymph nodes.

Stage II: Mesothelioma has spread from the pleura on one side to the nearby peribronchial and/or hilar 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 has spread into the chest wall muscle, ribs, heart, esophagus, or other organs in the chest on the same side as the primary tumor, with or without spread to subcarinal and/or mediastinal lymph nodes on the same side as the main tumor. Subcarinal nodes are located at the point where the windpipe branches to the left and right lungs. Mediastinal lymph nodes are located in the space behind the chest bone in front of the heart. Mesotheliomas with the same extent of local spread as in stage II that have also spread to subcarinal and/or mediastinal lymph nodes on the same side are also included in stage III.

Stage IV: Mesothelioma has spread into the lymph nodes in the chest on the side opposite that of the primary tumor, or directly extends to the pleura or lung on the opposite side, or directly extends into the peritoneum, or directly extends into organs in the abdominal cavity or neck. Any mesothelioma with evidence of distant metastases (spread to other organs through the bloodstream) or spread to organs beyond the chest or abdomen is included in this stage.

below more classification more easy to undersytand if you did not understand these 2 types

Patients with stage I disease have a significantly better prognosis than those with more advanced stages. However, because of the relative rarity of this disease, exact survival information based upon stage is limited.A proposed staging system based upon thoracic surgery principles and clinical data is shown below. It is a modification of the older system proposed by Butchart et al.[3] Other staging systems that have been employed, including a proposed new international TNM staging system, are summarized by the International Mesothelioma Interest Group.[4]

Stage I: Disease confined within the capsule of the parietal pleura: ipsilateral pleura, lung, pericardium, and diaphragm

Stage II: All of stage I with positive intrathoracic (N1 or N2) lymph nodes

Stage III: Local extension of disease into the following: chest wall or mediastinum; heart or through the diaphragm, peritoneum; with or without extrathoracic or contralateral (N3) lymph node involvement

Stage IV: Distant metastatic disease

Localized malignant mesothelioma

See description of stage I above.

Advanced malignant mesothelioma

See descriptions of stages II, III, and IV above.

For the purposes of the discussion of treatment in this statement, the disease is categorized as either localized or advanced.

The staging system most often used for mesothelioma is the Butchart system. This system is based mainly on the extent of the primary tumor mass, and divides mesotheliomas into stages I through IV.

Stage I: Mesothelioma is present within the right or left pleura, and may also involve the lung, pericardium, or diaphragm (the muscle separating the chest from the abdomen) on the same side.

Stage II: Mesothelioma invades the chest wall or involves the esophagus (food passage connecting the throat to the stomach), heart, or pleura on both sides. The lymph nodes in the chest may also be involved.

Stage III: Mesothelioma has penetrated through the diaphragm into the peritoneum (lining of the abdominal cavity). Lymph nodes beyond those in the chest may also be involved.

Stage IV: There is evidence of distant metastases (spread through the bloodstream to other organs).

Another staging system has recently been developed by the American Joint Committee on Cancer (AJCC). This is a TNM system, similar to staging systems used for most other cancers. T stands for tumor (its size and how far it has spread to nearby organs), N stands for spread to lymph nodes and M is for metastasis (spread to distant organs). In TNM staging, information about the tumor, lymph nodes, and metastasis is combined in a process called stage grouping to assign a stage described by Roman numerals from I to IV. Minor differences exist between the AJCC TNM staging system and the Butchart staging.

Stage I: Mesothelioma involves the right or left pleura. It may also have spread into the lung, pericardium, or diaphragm on the same side. It has not yet spread to the lymph nodes.

Stage II: Mesothelioma has spread from the pleura on one side to the nearby peribronchial and/or hilar 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 has spread into the chest wall muscle, ribs, heart, esophagus, or other organs in the chest on the same side as the primary tumor, with or without spread to subcarinal and/or mediastinal lymph nodes on the same side as the main tumor. Subcarinal nodes are located at the point where the windpipe branches to the left and right lungs. Mediastinal lymph nodes are located in the space behind the chest bone in front of the heart. Mesotheliomas with the same extent of local spread as in stage II that have also spread to subcarinal and/or mediastinal lymph nodes on the same side are also included in stage III.

Stage IV: Mesothelioma has spread into the lymph nodes in the chest on the side opposite that of the primary tumor, or directly extends to the pleura or lung on the opposite side, or directly extends into the peritoneum, or directly extends into organs in the abdominal cavity or neck. Any mesothelioma with evidence of distant metastases (spread to other organs through the bloodstream) or spread to organs beyond the chest or abdomen is included in this stage.

The Signs of Mesothelioma

The signs of asbestos-related cancer can remain undetectable for up to forty years after the initial exposure.

These decades of latency become marked by progressively worsening inflammation of the lungs. Initial symptoms include:

Difficulty breathing

Shortness of breath

Coughing

Fatigue

Weight loss

Loss of appetite

Chest or abdominal pain

Lower back pains

Over time, symptoms become more severe and may include:

Increasing breathing problems

Short of breath (even while inactive)

Difficulty and pain in swallowing

Coughing up blood

Severe pain in the chest

Fever

Chills

Weakness

Fatigue

Nausea

Vomiting

Pleural effusion (an accumulation of fluid in the pleura)

Constant raspy voice

Abdominal swelling

If you or someone that you care about has experienced any of these symptoms and think you may have been exposed to asbestos fibers, consult a physician immediately.

Symptoms of peritoneal mesothelioma include:

Weight loss

Abdominal pain and swelling (due to a buildup of fluid in the abdomen)

Bowel obstruction

Blood clotting abnormalities

Anemia

Fever

Diagnosing Mesothelioma

This can often be a difficult process due to the fact that many symptoms of mesothelioma resemble those of other conditions.

During a doctor's visit, a patient will undergo a thorough exam, with particular emphasis given to symptoms and problems commonly associated with asbestos exposure.

Diagnosing the disease involves taking a chest and abdominal X-ray.

look for a build up of fluid in the lungs (pleural effusion) or the abdomen. If tests show high levels of CEA (carcinoembryonic antigen), it may indicate lung cancer instead of mesothelioma.

The first step towards detecting a dangerous growth involve a CT scan, (a detailed picture of specific regions within the body) which visually indicates the degree to which the tumor has spread to other parts of the body.

Another method involves using an MRI (a powerful magnet that also creates pictures of specific regions within the body) that can indicate the presence of mesothelioma.

Often, however, these steps do not provide enough information to give a definitive diagnosis.

In these cases, the doctor may make a very small incision between the ribs and abdomen, and insert a scope into the chest cavity or abdomen (depending on the affected area). Using these scopes can help a physician to view the surface of the mesothelium and to withdraw appropriate samples that are then examined at a lab.

Prognosis of Mesothelioma

Prognosis depends on numerous factors, including:

Location of cancer

Size of the cancer

Stage of cancer (localized or advanced)

How cancer responds to treatment

Age of patient

General health condition

(Smoking does not appear to increase the risk of mesothelioma. However, smoking in conjunction to asbestos exposure greatly heightens the risk of lung cancer.)

How is Mesothelioma Treated?

There is no cure for mesothelioma of the lungs, chest, or abdomen. However, the scientific and healthcare community is constantly searching for better and move effective treatment options. While there are many different approaches to prolonging or treating mesothelioma, the typical course of action involves traditional approaches such as anti-cancer medicine, radical surgery to remove the cancerous growth, and other approaches such as radiation or immunotherapy. This multimodal approach is often used when the cancer has spread to different parts of the body. (Certain drugs have been used is anti-agents, but none has achieve great results.)

EPPs and pleurectomy/decortications are complex surgeries that are used to rid the body of malignant mesothelioma. These surgeries are only performed at certain centers by physicians who specialize in these types of cancers.

If malignant mesothelioma has advanced extensively, treatment may be limited to relieving the pain of the symptoms through such options as oxygen and prescription painkillers.

The three most popular approaches (used in conjunction with surgery) include:

1. Chemotherapy: uses specific and usually very toxic drugs to try and kill the cancer. Chemotherapy may be administered by pill, or it may be put into the body by a needle in the vein or muscle. Chemotherapeutic agents can be administered either systemically (through the blood stream) or intrapleurally (in the pleural cavity). When it is administered intrapleurally, the treatment is localized at the site of the tumor.

2. Radiation therapy: uses high-energy X-rays to kill cancer cells and shrink tumors.

Radiation may come from a machine outside the body (external radiation therapy) or by putting materials that produce radiation through thin plastic tubes into the cancerous region of the body.

3. Photodynamic therapy: the patient is given special medicines that make the cancerous cells very sensitive to light. During a surgery, the surgeon uses a laser that creates a chemical reaction that can then kill the cancer.

The Photodynamic therapy is still under investigation for treatment of malignant mesothelioma.

There are several new experimental treatments that attempt to strengthen the immune system's ability to combat malignant mesothelioma. These include gene therapy and the use of cytokine proteins such as interferons and interleukins.

These treatments are being tested in combination with chemotherapy and other treatments (L-NDDP, onconase).

Immunotherapy (or biological therapy) is based on the theory that it is possible to mobilize the body's own immune defenses against cancerous cells.

Gene therapy, which is still in clinical trials, uses an adenovirus for delivery a "suicide gene" that is inserted directly into the tumor. This gene makes the cells sensitive to a normally ineffective drug, such as glanciclovir. Treatment with the drug then destroys the cancer cells, thereby leaving the healthy cells unharmed.

Surgery

Depending on the stage of a mesothelioma, surgery may be used to remove the cancer and some of the surrounding tissue. Often, however, an operation is not appropriate and the patient may have only minimally invasive procedures to relieve symptoms. A thoracentesis, where fluid in the chest is removed by placing a needle into the chest cavity, may be done to make a patient more comfortable. Sometimes talc or an antibiotic may be injected into the chest cavity to try to prevent the fluid from returning. These techniques are successful in controlling the fluid, at least temporarily, in as many as 90% of patients. Because pleural fluid can compress the lung and cause shortness of breath, these procedures can help patients breathe more easily, however, they do not cure the cancer. In the case of peritoneal mesothelioma, a needle may be inserted into the abdomen to drain the fluid. Similarly, a needle inserted into the pericardium (sac around the heart) can drain pericardial fluid and help relieve circulatory problems. However, draining this fluid may result in complications. Sometimes the cancer cells spread along the needle path, and a tumor nodule may form under the skin of that area.

Surgery for mesothelioma may be performed for one of two reasons: for palliation (to relieve pain and discomfort caused by the tumor), or to cure. Palliative surgery is typically done in cases where the tumor has already spread beyond the mesothelium and is difficult to completely remove, or in cases where the patient is too ill to tolerate a more extensive operation. Curative surgery is offered when the patient is in otherwise good health and the tumor is thought to be localized and can be completely removed. Unfortunately, microscopic spread of cancer cells into the chest wall and diaphragm are common even when such spread cannot be detected by routine tests. Therefore, given the extent of these operations and their very limited success, the exact role of surgery in treating mesothelioma is often debated.

There are two types of operations that may be offered to patients with pleural mesothelioma: pleurectomy/decortication and extrapleural pneumonectomy. Pleurectomy/decortication is usually a palliative (relieves symptoms without curing the cancer) operation in cases where the entire tumor cannot be removed. It involves removal of the pleura, where the majority of the tumor is located. It is effective in controlling effusions (fluid accumulation) and decreasing the pain caused by the cancer.

Extrapleural pneumonectomy is a far more extensive operation and most often used in cases of localized mesothelioma. The operation is technically difficult and performed only by surgeons in large specialized medical centers. It involves removing the pleura, diaphragm, pericardium, and the whole lung on the side of the tumor. The patient must be in overall good health with no other serious illnesses in order to tolerate the large operation. This operation is intended to remove all or most of the cancer and some surrounding tissues as well.

Surgical treatment of peritoneal mesothelioma is often performed either to help relieve symptoms or to attempt to remove the tumor from the wall of the abdomen and other digestive organs. As with pleural mesothelioma, these tumors are often too extensive to remove completely. Similar operations can be performed to remove a mesothelioma from the pericardium (the sac around the heart).

Chemotherapy

Chemotherapy is the use of drugs for treating cancer. The drugs can be swallowed in pill form or they can be injected by a needle into a vein or muscle. Chemotherapy is systemic therapy. This means that the drug enters the bloodstream and circulates throughout the body (through the whole system) to reach and destroy the cancer cells.

In treating mesothelioma, these drugs may also be given intrapleurally (directly into the chest cavity), or intraperitoneally (into the abdominal cavity). Depending on the type and stage of mesothelioma, chemotherapy may be given as the primary (main) treatment or as an adjuvant (addition) to surgery.

Several anticancer drugs have been used to treat mesothelioma. The drug most effective when given alone is doxorubicin (Adriamycin). Other drugs that may be given alone include cisplatin and methotrexate. These anticancer drugs are often given in combination to try to increase their effectiveness. Combinations of drugs used in the treatment of mesothelioma include methotrexate and vincristine; cisplatin, vinblastine and mitomycin; cisplatin and doxorubicin; and doxorubicin, cyclophosphamide (or ifosfamide) and cisplatin. Other drugs such as paclitaxel and irinotecan are currently being studied to determine their effectiveness in treating mesothelioma.

Chemotherapy drugs kill cancer cells but also damage some normal cells. Therefore, careful attention must be given to avoiding or minimizing side effects, which depend on the specific drugs, the amount taken, and the length of treatment. Temporary side effects might include nausea and vomiting, loss of appetite, loss of hair, and mouth sores. Because chemotherapy can damage the blood-producing cells of the bone marrow, patients may have low blood cell counts. This can result in an increased risk of infection (due to a shortage of white blood cells), bleeding or bruising after minor cuts or injuries (due to a shortage of blood platelets), and fatigue or shortness of breath (due to low red blood cell counts).

Most side effects disappear once treatment is stopped. There are remedies for many of the temporary side effects of chemotherapy. For example, antiemetic drugs can be given to prevent or reduce nausea and vomiting. If you experience any side effects, be sure to talk with your doctor.

Radiation Therapy

Radiation therapy uses high-energy x-rays to kill cancer cells. External beam radiation therapy uses radiation delivered from outside the body that is focused on the cancer. This type of radiation therapy is often used to treat mesothelioma. These treatments are much like getting a diagnostic x-ray except for a longer time. Brachytherapy involves radioactive material being placed directly into the chest or the abdomen at the site of the mesothelioma. Radiation therapy is sometimes used as the main treatment of mesothelioma in some patients, especially those whose general health is too poor to undergo surgery. Adjuvant radiation therapy can be used in addition to surgery to kill small deposits of cancer that cannot be seen and removed during surgery. Palliative radiation therapy can also be used to ease symptoms of mesothelioma such as shortness of breath, pain, bleeding, and difficulty swallowing.

Side effects of radiation therapy may include fatigue and mild skin changes that resemble a sunburn. Often these side effects are temporary. Radiation may also make the side effects of chemotherapy worse. Chest radiation therapy may cause lung damage and lead to difficulty breathing and shortness of breath. Abdominal radiation therapy may cause nausea, vomiting and diarrhea. If you are having any of these side effects of radiation therapy, talk with your doctor since there are ways to help control these symptoms.

The Risk Factors For Malignant Mesothelioma

A risk factor is anything that increases a person's chance of getting a disease such as cancer. Different cancers have different risk factors. For example, unprotected exposure to strong sunlight is a risk factor for skin cancer and smoking is a risk factor for lung cancer as well as other types of cancer. Scientists have found several risk factors that make a person more likely to develop mesothelioma.

Asbestos: The main risk factor for developing mesothelioma is exposure to asbestos. Asbestos refers to a family of magnesium-silicate mineral fibers. In the past, asbestos was used widely for insulation because it does not conduct heat well and it is resistant to melting or burning. As the link between asbestos and mesothelioma has become well known, the use of this material has decreased. However, up to 8 million Americans may already have been exposed to asbestos.

According to the United States Environmental Protection Agency, as many as 733,000 schools and public buildings in the country today contain asbestos insulation. As many as 10% to 15% of schools in the United States may contain asbestos insulation. People who may be at risk for occupational asbestos exposure include some miners, factory workers, insulation manufacturers, railroad workers, ship builders, gas mask manufacturers, and construction workers, particularly those involved with installing insulation. Several studies have shown that family members of people exposed to asbestos at work have an increased risk of developing mesothelioma, because asbestos fibers are carried home on the clothes of the workers.

There are two main forms of asbestos -- serpentine and amphiboles. Serpentine fibers are curly and pliable. Chrysotile is the only type of serpentine fiber and it is the most widely used form of asbestos. Amphiboles are thin, rod-like fibers of which there are 5 main types-crocidolite, amosite, anthrophylite, tremolite, and actinolyte. Amphiboles (particularly crocidolite) are considered to be the most carcinogenic (cancer-causing). However, even the more commonly used chrysotile fibers have been associated with malignant (cancerous) mesotheliomas and should be considered dangerous as well.

It may be that asbestos causes cancer by physically irritating cells rather than by a chemical effect. When fibers are inhaled, most are cleared in the nose, throat, trachea (windpipe), or bronchi (large breathing tubes of the lungs). Fibers are cleared by sticking to mucus inside the air passages and being coughed up or swallowed. The long, thin, fibers are less readily cleared, and they may reach the ends of the small airways and penetrate into the pleural lining of the lung and chest wall. These fibers may then directly injure mesothelial cells of the pleura, and eventually cause mesothelioma.

Asbestos fibers can also damage cells of the lung and result in asbestosis (formation of scar tissue in the lung), and/or lung cancer. The risk of lung cancer among people exposed to asbestos is increased by 7 times, compared with the general population. Indeed, asbestosis, mesothelioma, and lung cancer are the three most frequent causes of death and disease among people with heavy asbestos exposure. Peritoneal mesothelioma, which forms in the abdomen, may result from coughing up and swallowing inhaled asbestos fibers. Cancers of the larynx, pancreas, esophagus, colon, and kidney have also been linked to asbestos exposure, but the increased risk is not as great as with lung cancer.

The risk of developing a mesothelioma is related to how much asbestos a person was exposed to and how long this exposure lasted. People exposed at an early age, for a long period of time, and at higher levels are most likely to develop this cancer. Mesotheliomas take a long time to develop. The time between exposure to asbestos and diagnosis of mesothelioma is usually between 20 and 40 years.

Radiation: There have been a few published reports of pleural and peritoneal mesotheliomas that developed following exposure to thorium dioxide (Thorotrast). This material was used in the past by doctors for certain x-ray tests. Because Thorotrast was found to cause cancers, it has not been used for many years.

Zeolite: This is a silicate mineral, chemically related to asbestos, common in the soil of the Anatoli region of Turkey. A few cases of mesothelioma have been described in this region and may have been caused by this mineral.

Tobacco: Although tobacco smoking has not been associated with the development of mesotheliomas, the combination of smoking and asbestos exposure greatly increases the risk of lung cancer. Asbestos workers who also smoke have a lung cancer risk 50 to 90 times greater than that of the general population. More asbestos workers die of lung cancer than of mesothelioma.