Mesothelioma of the Lung

Mesothelioma of the Lung



Mesothelioma is a form of cancer that is almost always caused by previous exposure to asbestos.[1] 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).

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Signs and symptoms

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

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 ********

· 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.

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Diagnosing mesothelioma

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 ******** 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).

Typical immunohistochemistry results

Typical immunohistochemistry results

Positive .............................................................................Negative

EMA (epithelial membrane antigen) in a
membranous distribution ....................................................CEA (carcinoembryonic antigen)

WT1 (Wilms' tumour 1) ........................................................B72.3

Calretinin .................................................................................MOC-3 1

Mesothelin-1 ...........................................................................CD15

Cytokeratin 5/6 ......................................................................Ber-EP4

HBME-1 (human mesothelial cell 1) ....................................TTF-1 (thyroid tran******ion factor-1)

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Screening

There is no universally agreed protocol for screening people who have been exposed to asbestos. However some research indicates that the serum osteopontin level might be useful in screening asbestos-exposed people for mesothelioma.

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Staging

Mesothelioma is described as localized if the cancer is found only on the membrane surface where it originated.

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Pathophysiology

The mesothelium consists of a single layer of flattened to cuboidal cells forming the epithelial lining of the serous cavities of the body including the peritoneal, pericardial and pleural cavitiesThe processes leading to the development of peritoneal mesothelioma remain unresolved, although it has been proposed that asbestos fibres from the lung are transported to the abdomen and associated organs via the lymphatic system. Pleural contamination with asbestos or other mineral fibres has been shown to cause cancer. Long thin asbestos fibers (blue asbestos, amphibole fibers) are more potent carcinogens than "feathery fibers" (chrysotile or white asbestos fibers).[4] However, there is now evidence that smaller particles may be more dangerous than the larger fibers.[1][2] Mesothelioma development in rats has been demonstrated following intra-pleural inoculation of phosphorylated chrysotile fibresAnalysis of the interactions between asbestos fibres and DNA has shown that phagocytosed fibres are able to make contact with chromosomes, often adhering to the chromatin fibres or becoming entangled within the chromosome. Common gene abnormalities in mesothelioma cell lines include deletion of the tumor suppressor genes: · Neurofibromatosis type 2 at 22q12 · P16INK4A · P14ARF Asbestos has also been shown to mediate the entry of foreign DNA into target cells. Incorporation of this foreign DNA may lead to mutations and oncogenesis by several possible mechanisms: · Inactivation of tumor suppressor genes · Activation of oncogenes · Activation of proto-oncogenes due to incorporation of foreign DNA containing a promoter region · Activation of DNA repair enzymes, which may be prone to error · Activation of telomerase · Prevention of apoptosis Asbestos fibres have been shown to alter the ******** and secretory properties of macrophages, ultimately creating conditions which favour the development of mesothelioma. Following asbestos phagocytosis, macrophages generate increased amounts of hydroxyl radicals, which are normal by-products of cellular anaerobic metabolism. Asbestos also may possess immunosuppressive properties. For example, chrysotile fibres have been shown to depress the in vitro proliferation of phytohemagglutinin-stimulated peripheral blood lymphocytes, suppress natural killer cell lysis and significantly reduce lymphokine-activated killer cell viability and recovery. Furthermore, genetic alterations in asbestos-activated macrophages may result in the release of potent mesothelial cell mitogens such as platelet-derived growth factor (PDGF) and transforming growth factor-β (TGF-β) which in turn, may induce the chronic stimulation and proliferation of mesothelial cells after injury by asbestos fibres.

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Epidemiology

Although reported incidence rates have increased in the past 20 years, mesothelioma is still a relatively rare cancer. The incidence is approximately one per 1,000,000. For comparison, populations with high levels of smoking can have a lung cancer incidence of over 1,000 per 1,000,000. Incidence of malignant mesothelioma currently ranges from about 7 to 40 per 1,000,000 in industrialized Western nations, depending on the amount of asbestos exposure of the populations during the past several decades

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Risk factors

Working with asbestos is the major risk factor for mesothelioma. A history of asbestos exposure exists in almost all cases. Asbestos is the name of a group of minerals that occur naturally as masses of strong, flexible fibers that can be separated into thin threads and woven. Asbestos has been widely used in many industrial products, including cement, brake linings, roof shingles, flooring products, textiles, and insulation.

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Exposure

Asbestos has been mined and used commercially since the late 1800s. Its use greatly increased during World War II. Since the early 1940s, millions of American workers have been exposed to asbestos dust. Initially, the risks associated with asbestos exposure were not publicly knownExposure to asbestos fibres has been recognised as an occupational health hazard since the early 1900s.

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Treatment

Treatment of MM using conventional therapies has not proved successful and patients have a median survival time of 6 - 12 months after presentation

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Surgery

Surgery, either by itself or used in combination with pre- and post-operative adjuvant therapies has proved disappointing with a 5 year survival rate of less than 10%. 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.

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Radiation

For patients with localized disease, and who can tolerate a radical surgery, radiation is often given post-operatively as a consolidative treatment. The entire hemi-thorax is treated with radiation therapy and is often times given simultaneously with chemotherapy. This approach of using surgery followed by radiation with chemotherapy has been pioneered by the thoracic oncology team at Brigham & Women's Hospital in Boston.

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Immunotherapy

Treatment regimens involving immunotherapy have yielded variable results. For example, intrapleural inoculation of Bacillus Calmette-Guérin (BCG) in an attempt to boost the immune response, was found to be of no benefit to the patient (while it may benefit patients with bladder cancer). Mesothelioma cells proved susceptible to in vitro lysis by LAK cells following activation by interleukin-2 (IL-2), but patients undergoing this particular therapy experienced major side effects.

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Chemotherapy

In February 2004, the Food and Drug Administration approved pemetrexed (brand name Alimta) for treatment of malignant pleural mesothelioma. Pemetrexed is given in combination with cisplatin. Folic acid is also used to reduce the side-effects of pemetrexed.

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Heated Intraoperative Intraperitoneal Chemotherapy

A procedure known as heated intraoperative intraperitoneal chemotherapy was developed by Paul Sugarbaker at the Washington Cancer Institute

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Prevention & Expectations

What can be done to prevent the disease? Since the 1970s, the Environmental Protection Agency and the Occupational Safety and Health Administration have regulated the asbestos industry in the U.S. There are two major types of asbestos: chrysotile and amphibole. It is thought that exposure to the amphibole form is more likely to cause mesothelioma. However, chrysotile has been used more frequently, hence many mesotheliomas are caused by chrysotile.

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Traditional Mesothelioma Treatment

There are three types of malignant mesothelioma. The most common is pleural mesothelioma, then peritoneal mesothelioma and lastly pericardial mesothelioma. Pleural mesothelioma is found in the lining of the lungs. Peritoneal mesothelioma is found in the abdominal cavity and pericardial mesothelioma is found around the lining of the heart. The traditional treatments for malignant mesothelioma include:

Surgery (removing the mesothelioma).

Surgery could be diagnostic, palliative, or potentially curative. The method of surgery used most commonly in mesothelioma treatments are: * A pleurectomy/decortication is the removal of the pleura (lining of the lung) without removing the underlying lung. Instead of removing the lung, the tumor is instead stripped away from the lung, diaphragm and vessels. In cases of peritoneal mesothelioma, cytoreductive surgery (debulking) can be performed. The surgeon will look for signs of cancer in the abdominal cavity and removes as much of the tumor as necessary. This will help make it more likely that chemotherapy/radiation can kill the cancer cells that are left over. * An extrapleural pneumonectomy (which is a radical procedure) involves removing the lung, lung lining (pleura) and the pericardium which surrounds the heart, along with part of the diaphragm. Surgery is typically perceived as the first option for eligible mesothelioma treatment patients and all evaluations should come from a physician which specializes in these surgical techniques.

Mesothelioma Chemotherapy (using drugs to fight the mesothelioma).

Mesothelioma Chemotherapy is actual "chemical therapy" where chemicals are injected into the area in order to destroy the cancer cells. Anticancer drugs help to prevent cancer cells from multiplying and spreading. A majority of patients receive some form of mesothelioma chemotherapy. Several different chemicals are used and some are used either alone or in combination with other drugs. Most drugs used for mesothelioma treatment are accopmlished by injection into a vein or muscle (some do come in pill form). In some cases, specialists can administer chemotherapy directly into the pleural or peritoneal cavity. In doing so, they hope to target the mesothelioma tumor more effectively. The most obvious reason for using of chemotherapy is to control the cancer and stopping it from spread or slowing it's growth include: * Neoadjuvant mesothelioma chemotherapy is used to shrink tumors prior to other treatments, such as surgery.
* Adjuvant mesothelioma chemotherapy is used to destroy microscopic disease which may remain after surgery. * Palliative mesothelioma chemotherapy is used to relieve symptoms, such as pain.

Chemotherapy drugs may have undesirable side effects. Doctors monitor the effects of these treatments. It is important to discuss with your doctor the chemotherapy options you are offered, including the expectations of success and possible side effects.

Radiation Therapy (high dose x-rays or other high-energy rays to eradocate the mesothelioma).

In many cases, two or more of these mesothelium treatments will be combined. Although these are clasified as "traditional" treatments, exciting treatment options are being developed currently.

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Mesothelioma Lawyers and Attorneys

Medical Reports confirming the diagnosis of mesothelioma

It's best to include one (or more) of the following reports:

Pathology report: Laboratory report on tests performed on tumor tissue taken from your biopsy. It is typically just a few pages in length. This is the report that often confirms a mesothelioma diagnosis.

Cytology report: Laboratory report on tests performed on liquid drained from your lung or abdominal cavity. You might have this instead of a pathology report.

Surgical Report: This provides your doctor an assessment of the surgery, and may also include pathology or cytology results. If you haven't had a biopsy or a fluid sample taken, a copy of a CAT scan or PET scan report would be helpful to your mesothelioma attorney or lawyer.

Additional important information for your mesothelioma lawyer:

1) Information about your history of asbestos exposure with any documentation you may have to help support your claim.

2) Names of witnesses (with information on how to contact them) confirming your asbestos exposure. This may include names of co-workers at jobs where you were exposed to asbestos, or family members who may have worked with or around asbestos and brought it home on their clothing.

3) Your current will. Your mesothelioma attorney will need a copy of your will (in the event you pass away before your case is resolved). This will allow them in to identify the executor of your estate.

4) Family members pursuing a claim for a deceased mesothelioma victim: a copy of the death certificate (with autopsy report if available).

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What is mesothelioma?

Mesothelioma is a cancer of the mesothelium. The mesothelium is a thin membrane that lines the chest and abdomen and surrounds the organs in these areas. The lining around the lungs is called the pleura and in the abdomen it is known as the peritoneum. About 2000 people in the UK are diagnosed with mesothelioma each year. Mesothelioma of the lining of the lungs, known as pleural mesothelioma, is much more common than mesothelioma in the peritoneum. For every one person with peritoneal mesothelioma, there will be about 12 people who have pleural mesothelioma.
Pleural mesothelioma
Peritoneal mesothelioma

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What are the risk factors for mesothelioma?

The main risk factor for mesothelioma is contact with asbestos. In the past, asbestos was used for insulation because it does not conduct heat well and doesn’t easily melt or burn. It was also used in other products such as floor tiles, door gaskets, roofing, and patching compounds.
If asbestos fibers are breathed in, they travel to the ends of the small air passages and reach the lining of the lungs. There they can damage the mesothelial cells or the lining of the lung cells. If swallowed, these fibers can also reach the lining of the abdominal cavity where they play a part in causing a cancer called peritoneal mesothelioma. As the link between asbestos and cancer has become well known, use of this material has decreased. All use stopped after 1989.

The following may increase chances of developing mesothelioma:

Radiation - There have been a few published reports of pleural and peritoneal mesotheliomas that developed following exposure to thorium dioxide (Thorotrast).

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

Tobacco Smoking - the combination of smoking and asbestos exposure also greatly increases the risk of lung cancer.

SV40 Virus - Some recent studies have raised the possibility that infection with simian virus 40 (SV40) might increase a person's risk of developing mesothelioma.

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What are some ways to try to prevent mesothelioma?

· Avoid exposure to asbestos
· Eat Healthy
· Exercise

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What are some ways to detect mesothelioma?

· Chest X-Ray
· CT Scan
· MRI
· Thoracoscopy - A thoracoscope (telescope-like instrument connected to a video camera) is inserted through a small incision into the chest. Your doctor can see the tumor through the thoracoscope, and can use special forceps to take a tissue biopsy
· Bronchoscopy - In this procedure a flexible lighted tube is inserted through your 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.
· Mediastinoscopy - A lighted tube is inserted under the sternum (chest bone) at the level of the neck and moved down into the chest allowing the surgeon to view the lymph nodes in this area and remove samples to check for cancer.

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Notable people with mesothelioma

Mesothelioma, though rare, has had a number of notable patients. Australian anti-racism activist Bob Bellear died in 2005. British science fiction writer Michael G. Coney, responsible for nearly 100 works died in 2005. American film and television actor Paul Gleason, perhaps best known for his portrayal of Principal Richard Vernon in the 1985 film The Breakfast Club, died in 2006. Mickie Most, an English record producer, died of mesothelioma in 2003. Paul Rudolph, an American architect known for his cubist building designs, died in 1997.

United States Congressman Bruce Vento died of mesothelioma in 2000. The Bruce Vento Hopebuilder is awarded yearly by his wife at the MARF symposium to persons or organizations who have done the most to support mesothelioma research and advocacy.

After a long period of untreated illness and pain, roc

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Pleural mesothelioma

The pleura has two layers: the inner (visceral) layer, which is next to the lung; and the outer (parietal) layer, which lines the chest wall. The two layers of the pleura are usually in contact and slide over each other as we breathe. The membranes produce fluid, which allows them to slide over each other easily.

When mesothelioma develops in the pleura (pleural mesothelioma), the delicate membranes thicken and may press inwards on the lung. Fluid may also collect between the two layers of the pleura: this is known as a pleural effusion.

Structure of the lungs and pleura

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Peritoneal mesothelioma

The lining of the abdomen is known as the peritoneum. It also has two layers: the inner (visceral) layer, which is next to the abdominal organs, and the outer (parietal) layer, which lines the abdominal wall.

If the mesothelioma is in the peritoneum it is called peritoneal mesothelioma and causes thickening of the membranes surrounding the abdominal organs and a collection of fluid in the abdomen. The collection of fluid is called ascites and causes swelling of the abdomen.

Side view of the abdomen. The peritoneum is shown as the thick line surrounding the abdominal organs.

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