Surgery

Surgery, either by itself or used in combination with pre- and post-operative adjuvant therapies, has proved disappointing. A pleurectomy/decortication is the most common surgery, in which the lining of the chest is removed. Less common is an extrapleural pneumonectomy (EPP), in which the lung, lining of the inside of the chest, the hemi-diaphragm and the pericardium are removed. It is not possible to remove the entire mesothelium without killing the patient.

Treatment

Treatment of malignant mesothelioma using conventional therapies has not proved successful and patients have a median survival time of 6 - 12 months after presentation^{[citation needed]}. The clinical behaviour of the malignancy is affected by several factors including the continuous mesothelial surface of the pleural cavity which favours local metastasis via exfoliated cells, invasion to underlying tissue and other organs within the pleural cavity, and the extremely long latency period between asbestos exposure and development of the disease.

Staging

Mesothelioma is described as localized if the cancer is found only on the membrane surface where it originated. It is classified as advanced if it has spread beyond the original membrane surface to other parts of the body, such as the lymph nodes, lungs, chest wall, or abdominal organs

Screening

There is no universally agreed protocol for screening people who have been exposed to asbestos. Screening tests might diagnose mesothelioma earlier than conventional methods thus improving the survival prospects for patients. The serum osteopontin level might be useful in screening asbestos-exposed people for mesothelioma. The level of soluble mesothelin-related protein is elevated in the serum of about 75% of patients at diagnosis and it has been suggested that it may be useful for screening.^[2] Doctors have begun testing the Mesomark assay which measures levels of soluble mesothelin-related proteins (SMRPs) released by diseased mesothelioma cells.[3

Diagnosis

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 opening 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.

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 chest cavity), but it may also occur in the peritoneum (the lining of the abdominal cavity) or the pericardium (a sac that surrounds the heart).

Most people who develop mesothelioma have worked on jobs where they inhaled asbestos particles, or they have been exposed to asbestos dust and fibre in other ways, such as by washing the clothes of a family member who worked with asbestos. Unlike lung cancer, there is no association between mesothelioma and smoking.^[1] 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 can be made with chest X-rays and a CT scan, and 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.

Contents

[hide]

• 1 Signs and symptoms
• 2 Diagnosis
• 3 Screening
• 4 Staging
• 5 Pathophysiology
• 6 Epidemiology
  • 6.1 Incidence
  • 6.2 Risk factors
  • 6.3 Exposure
    • 6.3.1 Occupational
    • 6.3.2 Paraoccupational Secondary Exposure
    • 6.3.3 Asbestos in buildings
    • 6.3.4 Environmental exposures
• 7 Treatment
  • 7.1 Surgery
  • 7.2 Radiation
  • 7.3 Chemotherapy
  • 7.4 Immunotherapy
  • 7.5 Heated Intraoperative Intraperitoneal Chemotherapy
• 8 Notable people who died from mesothelioma
• 9 Notable people that have lived for some time with mesothelioma
• 10 Legal issues
• 11 Legal History
• 12 References
• 13 Footnotes
• 14 See also
• 15 External links

Pathology and The Role of Pathologists in the Diagnostic Process

Pathology, or the scientific study of cells, tissue, or fluid taken from the body is an integral part of a mesothelioma diagnosis. Most hospitals have their own pathology labs staffed by board-certified pathologists and licensed technologists. The importance of pathological diagnosis can not be underestimated, since the course of treatment is dependent upon an accurate diagnosis.

To make a diagnosis, pathologists examine tissue under a microscope, and based on established criteria, make a determination of benign vs. malignant cells. (More on biopsy tissue processing.) Subsequently, the type of cancer is determined. Although most pathologists have a general expertise of various diseases, a small number acquire training in a subspecialty, such as mesothelioma. These are physicians who have received world-wide recognition as premier experts, and have achieved high acclaim for their research, published articles and abstracts, and teaching. For a list of expert pathologists in the field of mesothelioma diagnosis, please call the MW toll free at 1-877-367-6376 or fill in the form at the bottom of this page specifying your request.

Knowing the stage is a factor in helping the doctor form a treatment plan. Mesothelioma is considered localized if the cancer is confined to the pleura, or advanced if it has spread beyond the pleura to other parts of the body such as the lungs, chest wall, abdominal cavity, or lymph nodes.

Immunohistochemical Markers for Mesothelioma

A diagnosis of any specific type of cancer often means ruling out other cancers in the process. This is true in the case of mesothelioma, where the most common “differential diagnosis” is that of adenocarcinoma versus mesothelioma.

During the biopsy procedure, the surgeon removes tissue samples to be sent to the laboratory. In the lab, slides are produced and then viewed and analyzed by a pathologist. These tissue specimens arrive at the lab with a request form that details patient information and history along with a description of the site in the body from which the specimen was obtained. Each individual specimen is numbered for each patient.

The pathologist then does a “gross examination” which consists of describing the tissue, and then placing it in a plastic cassette. The cassettes are then placed in a fixative that preserves the tissue permanently. Once the tissue has been fixed, it is processed into a paraffin block that will allow the pathologist to slice off thin microscopic sections that will then be stained to determine the patient’s diagnosis.

Immunohistochemistry is defined as “a method of analyzing and identifying cell types based on the binding of antibodies to specific components of the cell”. It is this process that helps diagnose mesothelioma versus adenocarcinoma (or other types of cancer).

Early on, the “markers” which helped distinguish mesothelioma from adenocarcinoma were “negative markers”; those expressed in adenocarcinomas, but not in mesotheliomas. This made it more difficult to confirm a diagnosis, because pathologists were dealing with the absence of, rather than the presence of certain markers. Some of these markers, which are normally “positive” in an adenocarcinoma diagnosis and “negative” in a mesothelioma diagnosis, are carcinoembryonic antigen (CEA), CD 15 (LeuM1), epithelial glycoprotein (Bg8), tumor glycoprotein (BerEp4) and tumor glycoprotein (MOC-31).

In more recent years, “positive markers” expressed by mesotheliomas have come to the forefront. Some of the markers which are normally “positive” in mesotheliomas and “negative” in adenocarcincomas are calretinin, cytokeratin 5, HBME-1, mesothelin, N-cadherin, thrombomodulin, vimentin and Wilm’s tumor gene product (WT-1).

It is important to remember that while the above markers are commonly used to help diagnose the epithelial sub-type of mesothelioma, that they may also be expressed in other types of cancer, and may not necessarily apply to the bi-phasic or sarcomatoid sub-types of mesothelioma. Your doctor can always contact a more specialized lab if he/she feels your diagnosis is in any way inconclusive.

MESOTHELIOMA DIAGNOSIS

How is mesothelioma diagnosed?

A diagnosis of mesothelioma is most often obtained with careful assessment of clinical and radiological findings in addition to a confirming tissue biopsy. (Learn about typical mesothelioma symptoms.) A review of the patient's medical history, including history of asbestos exposure is taken, followed by a complete physical examination, x-rays of the chest or abdomen, and lung function tests. A CT scan or MRI may also be done at this time. If any of these preliminary tests prove suspicious for mesothelioma; a biopsy is necessary to confirm this diagnosis.

About Mesothelioma

Mesothelioma is a rare form of cancer that develops in the mesothelial cells. These cells are tissue that surround or line the lungs, heart, and stomach. The mesothelial cells protect these organs by producing a lubricating fluid that allows these organs to move smoothly.

There are 2 types of tumors of the mesothelium, “benign” and “malignant”. A benign tumor is non-cancerous, which means it does not cause any damage or will not harm you. A malignant tumor of the mesothelial cells is called a malignant mesothelioma. Because tumors of the mesothelium are usually cancerous, malignant mesothelioma is usually just called “mesothelioma”.

Malignant mesotheliomas arise from the cells that line the surface of the pleura or the peritoneum. Eighty percent of these tumors are pleural in origin. Malignant mesotheliomas are rare, with an incidence of one to three cases per 1 million persons per year in the general population.

The relationship between asbestos exposure and malignant mesothelioma was established in 1960. The latency period between exposure and tumor development has usually been 30 years or more.

The incidence of malignant mesothelioma has been highest in persons with heavy occupational exposure to asbestos, such as shipyard workers. However, malignant mesothelioma can occur in the absence of any known asbestos exposure. No history of such exposure has been noted in about one-third of cases, and the etiology of these cases is unknown. Cigarette smoking is not considered a risk factor for malignant mesothelioma.

The patient with malignant mesothelioma of the pleura may have symptoms of dyspnea and pleuritic chest pain, with malaise and weight loss. A large pleural effusion is often seen on the radiograph. This effusion is frequently bloody, and the hyaluronic acid level may be elevated. Associated parenchymal fibrosis (asbestosis) is rare in pleural mesothelioma but appears to be more common in, peritoneal mesothelioma.

Malignant mesothelioma can be very difficult to diagnose; open biopsy is usually necessary, because needle biopsy of the pleura often yields an inadequate specimen.

There is no effective treatment for malignant mesothelioma. Surgical resection is not possible. The tumor encases the lung in a bulky, lobulated mass that invades the fissures and, eventually, the diaphragm and the chest wall. Average survival is less than two years. Except in rare cases, chemotherapy and radiation therapy have not been useful.

Mesothelioma Data, Statistics, & Information

Mesothelioma is fairly rare. There are an estimated 2,000 to 3,000 new cases of mesothelioma each year in the United States. The incidence of mesotheliomas in the United States increased from 1970 to 1990 and then stabilized. It may now be decreasing. Most of the past increase in cases, as well as the recent decrease in cases, has been in men. The rate, although lower, has been fairly steady for women. In European countries and world wide, the rate of mesotheliomas is still increasing.

Mesothelioma is rare in people under age 55. Its incidence increases with age. Three-fourths of people with mesothelioma are over 65 years old. The disease affects men 5 times more often than women. Mesothelioma is less common in African Americans than in white Americans.

Mesothelioma is a serious disease. The only known cause of mesothelioma is asbestos. By the time the symptoms appear and cancer is diagnosed, the disease is often advanced. The average survival time is about 1 year. The 5-year relative survival rate is around 10%, but this rate has been slowly improving.

The 5-year survival rate refers to the percentage of patients who live at least 5 years after their cancer is diagnosed. Many of these patients live much longer than 5 years after diagnosis, and 5-year rates are used to produce a standard way of discussing prognosis. Five-year relative survival rates do not include patients dying of other diseases and are considered to be a more accurate way to describe the prognosis for patients with a particular type and stage of cancer. That means that relative survival only talks about deaths from mesothelioma. Of course, 5-year survival rates are based on patients diagnosed and initially treated more than 5 years ago. They may no longer be accurate. Improvements in treatment result in a more favorable outlook for recently diagnosed patients.

• Each year 2,500 to 4,000 patients in the U.S. are diagnosed with mesothelioma and asbestos-related diseases.
  
• Mesothelioma has a long latency (inactive) period of anywhere between 15 – 50 years.
  
• Experts predict that mesothelioma diagnoses will continue to increase in the United States for at least another 10 to 20 years.
  
• While many countries have banned certain forms of asbestos, an estimated 5,000 asbestos-containing products exist today.
  
• As many as 8 million people in the U.S. have already been exposed to asbestos and it continues to pose a serious threat to workers in certain occupations.
  
• One study of asbestos insulation workers reported a mesothelioma death rate up to 344 times higher than the general population.
  
• Most mesothelioma victims die within 18 months of diagnosis. Mortality is swift not because the cancer is fast-growing but because it usually is far advanced by the time it is detected.
  
• Poor prognostic variables include: nonepithelial histology, older age (greater than 75 years), pleural primary, chest pain at presentation, poor performance status, and elevated platelet count (greater than 400,000/mcL).
  
• By the year 2030 there are estimates that asbestos will have caused 60,000 instances of mesothelioma and around 250,000 other cancers that result in death.
• Over half a million asbestos and mesothelioma injury claims have been filed to date. Over 50,000 were filed in 1998 alone.
• Every year, more than 10,000 people worldwide (3,000 in the U.S. alone) are diagnosed with mesothelioma or other asbestos-related conditions.
• More than 110,000 schools in the U.S. still contain some form of asbestos.
• 8 million Americans have been exposed to dangerous levels of asbestos.
• Asbestos insulation workers have a mesothelioma death rate 344 times higher than that of the general population.
• More than 7,500 Americans died from mesothelioma between 1999 and 2001.
• The industries with the highest mesothelioma mortality rates are ship building and ship repairing.
• People working around industrial chemicals had the second-highest rate, and those in the construction industry were third.
• 85% of mesothelioma deaths are male; this has more to do with asbestos exposure than with gender.
• There is also a high rate of mesothelioma deaths among schoolteachers, many of whom are female.
• The average age of people diagnosed with mesothelioma is between 50 and 70, but the number of people diagnosed with mesothelioma between the ages of 30 and 40 is increasing.
• Asbestos is used to make more than 5,000 products worldwide.
• Even when mesothelioma treatment is possible, it is very expensive, sometimes costing between $400,000 and $800,000 for oxygen, drugs, pain medicine and other forms of treatment