What are the types of Mesothelioma

Pleural Mesothelioma - Mesothelioma of Pleura

Pleural mesothelioma is a type of cancer that affects the pleural sac that surrounds the lungs, and is caused by exposure to asbestos. Pleural mesothelioma is the most common form of mesothelioma with estimated 75% of all mesothelioma cases being of this form.

Description of the Pleura:

The pleura is a sac which contains the lungs and also a thin membrane called the mesothelium which secretes a fluid that enables the lungs to expand and contract during breathing. Inhaling asbestos causes a build-up of fibers inside the lungs, and due to the microscopic size and sharpness of the fibers it is possible for them to penetrate the walls of the lung and enter the pleural cavity. As they migrate from the lung into the pleural cavity, the sharp strands shred and mutilate the mesothelium, destroying it and potentially causing cancer.

Thickening of the Pleural Fluid and Cancerous Tumors.

Once asbestos fibers invade the pleural cavity, cancerous tumors may develop which thicken the pleural fluid and inhibit proper lung movement. Tumors can also constrict the lungs and press on the ribcage or other organs resulting in agonizing pain. Also, because the lungs are responsible for re-oxygenating blood, should the cancer advance directly into the lungs it is possible for the cancerous cells to spread into other parts of the body through the bloodstream.

Pleural mesothelioma is often confused with less serious or deadly diseases such as:

• Pneumonia
• Common Cold
• Whooping cough
• The Flu
• Laryngitis
• Bruised/Broken Ribs due to chest pain
• Sometimes there are no symptoms at all

Mesothelium Mutatation and Asbestos.

Scientists and doctors are do not know why asbestos fibers cause the mesothelium to mutate into cancer, but as more asbestos cases are reported, doctors are learning more and more about this devastating condition. It is believed that even one single fiber can begin the cascade of events that cause mesothelioma.

Diagnosis of Pleural Mesothelioma.

Although there is no cure for mesothelioma, early diagnosis provides doctors the opportunity to relieve a great deal of suffering, and prolong and improve many patients’ lives. These avenues of treatment depend on the extent of the condition and the progession of the disease.

Development of Pleural Mesothelioma:

Because the time it takes for the asbestos particle to turn cancerous is very great - sometimes between 30 to 40 years - it can be difficult to spot. Most cases of pleural mesothelioma develop in the sac that contains the lungs.

Common treatments for Pleural Mesothelioma include:

• Surgery: Surgeons can remove all or part of the lung to excise tumors or prevent their spread. In some occasions fluid needs to be drained from the lungs, or in extreme cases the entire lung needs to be removed.
• Radiation: Cancer is often treated with high doses of radiation. This treatment uses high energy waves to kill cancerous cells, but unfortunately it also kills healthy cells and causes a number of peripheral health problems.
• Chemotherapy: Strong anti-cancer drugs are pumped directly into the tumors or taken orally can inhibit their growth and spread, but these drugs can also cause severe health problems in other bodily systems.

Affects of Pleural Mesothelioma:

Make sure that if you or someone you love has developed pleural mesothelioma, you owe it to yourself to take action. The asbestos industry allegedly knew of the dangers of their product, but rather than take action to prevent serious harm they hid this information from their workers and the public until the damage had been done. Now, thousands of people hurt by this deception are coming forward to collect compensation for their pain and suffering, and you could be the next person to receive restitution for their condition. Let us help you. Contactus today.

Peritoneal Mesothelioma

Peritoneal mesothelioma is a cancer that affects the thin cell membrane called the peritoneum. This collection of cells surrounds the gastrointestinal tract and provides lubrication for the stomach and intestines to move so that they may function properly. These organs must be able to move properly in order to properly digest and process food, and a failure in the peritoneum can result in severe and debilitating consequences. Unfortunately, the symptoms of peritoneal mesothelioma can be so subtle that it can be confused with other, less dangerous diseases, and this aspect of the disease significantly contributes to its already staggering mortality rate.

Common symptoms of peritoneal mesothelioma:

• Stomach pain
• Lower abdominal pain
• Difficulty with bowel movements
• Weight lost
• Nausea
• Loss of appetite
• Weakness
• Abdominal swelling

When asbestos is ingested, minute fibers enter the stomach and penetrate the stomach lining. As more and more fibers penetrate this delicate organ, the cells on the exterior lining begin to mutate into cancerous mesothelioma cells. These cells accumulate into tumors, and eventually overwhelm the peritoneum, killing off healthy stomach cells in the process. Furthermore, these tumors prevent the peritoneum from making the protective lining that aids the stomach in movement. In less drastic instances, the tumors on the stomach lining grow and exert increasing pressure on surrounding organs causing agonizing pain.

There is no cure for any type of mesothelioma, but certain conditions can aid in treatment. Age, type of cell affected, size and stage of the tumor, and whether or not the tumor responds to treatment greatly affect what course of action doctors can take.

Common treatments for peritoneal mesothelioma:

• Chemotherapy: Strong drugs are used to shrink the size and kill tumors, but these drugs are extremely potent and often cause significant damage to other healthy cells. These drugs can be taken orally, or in some cases the drugs are directly introduced into the tumors if they are resistant to other treatment
• Radiation therapy: Radiation is one of the ways to treat peritoneal mesothelioma. Powerful X-rays can kill diseased cells, but they also can kill healthy cells, and many people undergoing radiation treatment for peritoneal mesothelioma often suffer hair loss and other side effects.
• Surgery: This most drastic option often involves the removal of the tumor or cancerous tissue in the abdomen or gastrointestinal tract. The necessity of surgery is generally based on the extent and progression of the cancer.

Vigorous treatment and early diagnosis are often the keys to long term survival. Unfortunately, mesothelioma lies dormant for years, so most victims do not experience any side effects until the cancer is extremely advanced. After the cancer has overwhelmed the stomach, it is rare for patients to survive longer than five years.

Victims of peritoneal mesothelioma

Many victims of mesothelioma take comfort in knowing that the asbestos industry will no longer injure innocent people through deception and blatant lies. Another source of comfort many victims discover is through the law. Thousands of people are taking action against the asbestos industry in order to recover financial restitution for their pain and suffering, and you could be next. Let our dedicated and experienced peritoneal mesothelioma attorneys help you get the compensation you may deserve. Contact us today.

Pericardial Mesothelioma

Pericardial mesothelioma is the rarest type of the three main malignant forms of the disease. The heart, as with any organ that requires constant movement to work properly, requires constant lubrication. Lubrication comes in the form of a thin layer of mucous, and in normal systems the heart beats on as normal.

Effects on the Pericardium

Pericardial mesothelioma affects the pericardium, the protective sac that covers the heart and provides lubrication so that it can beat properly. Asbestos exposure is the most common culprit of this debilitating form of cancer, a type that usually comprises 5% of all mesothelioma cases.

Pericardium Mutations

Inhaled asbestos fibers can pierce and shred the pericardium and cause mutations that can result in mesothelioma. Once the cancer begins to spread, it can cause chronic coughing, chest pain, shortness of breath, and heart palpitations. Like the other forms of the cancer, decades pass without incident as pericardial mesothelioma slowly destroys the tissues around the heart. Unfortunately, by the time symptoms appear it is usually far too late to treat pericardial mesothelioma with conventional drugs or therapies.

Common symptoms of pericardial mesothelioma include:

• Shortness of breath
• Different degrees of chest pain
• Heart palpitations
• Irregular heart beat
• Coughing

Treatments for pericardial mesothelioma.

There are a few marginally effective treatments for victims of pericardial mesothelioma. Radiation treatments are usually the preferred course of action to help slow the spread of the cancer, and chemotherapy can provide help in bolstering the effects of the radiation. Another type of treatment involves “fine needle aspiration” to draw out excess fluid that collects in the pericardium, which can help relieve some symptoms. In rare cases, doctors perform surgery to remove the pericardium, although this is usually a treatment of last resort. This course of action usually only slows the growth of pericardial mesothelioma, for no amount of surgery, chemotherapy, or radiation will fully eliminate the cancer.

If you or a loved one developed pericardial mesothelioma as a consequence of asbestos exposure, you deserve a voice and you may have the right to seek financial compensation for your pain and suffering. Let a dedicated and compassionate mesothelioma lawyer help you get the restitution you deserve. You must act quickly, for the statute of limitations in your state could end your case before it has a chance to begin. Don’t wait - contact someone who understands your fear and frustration today.

Mesothelioma Cancer Cell Types

To understand mesothelioma is to understand cancer. Cancer is essentially uncontrolled cellular growth. Under normal circumstances, body cells in the hair, bone, organs, or blood grow to a certain point, die off, and are replaced by newer, healthier cells. Unfortunately, most cancer cells are damaged to some degree, and as the body reproduces them they begin to take over for healthy cells, leading to eventual system failure.

Mesothelioma cells are divided into three main categories: epithelioid, sarcomatoid cells, and a mix of the two types called biphasic mesothelioma.

Cancers like mesothelioma can affect virtually any type of cells in the body, often radically affecting the prognosis and treatment options for patients. The tragedy of mesothelioma is that it takes decades before most symptoms appear, and by the time the cancer is discovered it is too entrenched in the system to treat.

Epithelioid Mesothelioma

The most common and relatively treatable form of the cancer is Epithelioid mesothelioma. Under a microscope this type of the disease is seen as a papillary or tubular growth and generally affects membranes and tissues that cover organs and other internal bodily surfaces. Between 50-70% of mesothelioma cases fall into this category, and this type is most likely to respond to treatment

Sarcomatoid Mesothelioma

Sarcomatoid mesothelioma is the most serious form of the disease, as it rarely responds to any treatment whatsoever. Fortunately it is also the rarest, as it only strikes 10-20% of patients with mesothelioma. It appears as spindle-shaped pattern of cells that overlap one another, and generally arises from support tissues such as bone, cartilage, muscle, and fat. Death usually occurs within six months of diagnosis of sarcomatoid mesothelioma.

Biphasic Mesothelioma

Biphasic mesothelioma is not a condition unto itself, but rather it is a combination of the other two types. It can take on both the good and bad aspects of sarcomatoid and epithelioid mesotheliomas and 20-35% of all mesothelioma cases are mixed or biphasic.

Mesothelioma is truly the deadly scourge of the 21st century. Because it takes decades before the first symptoms appear, many health professionals believe that there will be a mesothelioma epidemic in the decades to come. If you or someone you love was the victim of this deadly disease, you must consult one of our dedicated and experienced mesothelioma attorneys today. You may be entitled to compensation for your pain and suffering. Don’t delay. Call now.

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Peoples Views About Heart Lung Machine

heart-lung machine effects?

by Mariette Geest, Oct 16, 1999 12:00AM

Tags: Heart, Bypass Surgery, Cancer, cognitive, neurological, Heart surgery

Dear Doctors

I would like to know if there are any side effectts on the use of a heart-lung machine during a heart surgery. I read somewhere that there is an increased risk for cancer. Is this true? Are there any other side effects?

Thanks very much for your reply

Mariette

Doctor's Answer

by CCF CARDIO MD - DLB, Oct 16, 1999 12:00AM

There is no increased risk of cancer. The majorMajor tears
Major-con risk appears to be neurological problems, especially subtle changes in cognitiveMental status tests function.

Questions for your doctor

Questions for your doctor

Preparing questions in advance can help patients to have more meaningful discussions with their physicians regarding their treatment options. The following questions related to the heart-lung machine may be helpful: Will a heart-lung machine be used during my surgery? How common is the use of a heart-lung machine with my type of surgery? What are my risks with the heart-lung machine? How long will I be on the heart-lung machine? What will happen if my heart does not function when they remove me from the bypass machine? What specialists will be used during my surgery? Are there any other alternatives available to me? Will by recovery be any more or less difficult if a heart-lung machine is used? Do I need any special preparations for surgery using a heart-lung machine? Will I need to change my medications prior to my surgery? How long will it take me to recover from the surgery? Could a heart-lung machine affect my pregnancy in any way?

What are the Risks of Using Heart Lung Machine

Potential risks of heart-lung machines

Since its first use in humans in 1955, the heart-lung machine has been used in millions of open-heart surgeries. Nevertheless, there are risks associated with use of the machine. The complication rate is between 1 and 4 percent, depending on the kind of surgery. The major risks associated with the heart-lung machine include: Blood clots. These may form as the machine processes blood and in extreme cases may cause stroke, heart attack or kidney failure upon return to the body’s bloodstream. Postpericardiotomy syndrome. A severe inflammatory response that may damage many of the body’s systems and organs. The reintroduction of fat and debris from the surgical field through the use of suction. Cardiac arrest. Problems with temporary confusion or memory loss have also been reported in some cases. To avoid these risks, new surgical techniques called beating heart (or off-pump) surgeries have been developed, in which the heart beats throughout the operation and the heart-lung machine is not used. Some types of beating heart surgery are minimally invasive, requiring only small incisions. Other versions involve opening the chest. Today, about 25 percent of coronary artery bypass surgeries are performed without use of the heart-lung machine.

How Heart Lung Machine works

Summary

During an open-heart surgery (such as valve or bypass surgery), the heart-lung machine is used to take over the functions of the heart and lungs. Also known as a cardiopulmonary bypass machine, it allows the surgeon to carefully stop the heart while the vital organs continue to receive blood and oxygen. When patients are on the heart-lung machine, very delicate work can be performed by surgeons without interference from bleeding or the heart’s pumping motion. When first used successfully in humans in 1955, the machine was a revolutionary piece of equipment. Today, the heart-lung machine is used in about 1 million cardiac surgeries every year, including surgeries to the coronary arteries, heart valves and other structures of the heart. The heart-lung machine has a very low complication rate, approaching 1 percent for certain surgeries. Newer medical technology is being developed that may someday replace the heart-lung machine in some circumstances. These technologies include systems that allow surgeons to operate on a beating heart, without use of the heart-lung machine. Known as off-pump surgery, this is used when surgeons are operating on the coronary arteries.

About heart-lung machines

During an open-heart surgery (such as valve or bypass surgery), the heart-lung machine takes over the functions of the heart and lungs. Also known as a cardiopulmonary bypass machine, it allows the heart to can be carefully stopped and drained of blood. Surgeons can then operate in a blood-free, quiet surgical field. The heart-lung machine allows surgeons to perform complicated surgeries without the interference of a beating heart. The heart-lung machine basically consists of a pump (to replace the heart) and a bubble oxygenator (to replace the lungs). Acting as a mechanical heart and lungs, it keeps oxygen-rich blood flowing throughout the body after the patient’s heart has been carefully stopped. In a process called perfusion, the machine receives the patient’s blood, removes the carbon dioxide and other waste products, adds oxygen, warms (or cools) the blood and pumps it back through the body. Cooling the blood lowers body temperature. This helps protect the body's organs while the heart-lung machine is in use. After the surgery is completed, the heart is restarted, the heart-lung machine is stopped and the machine is disconnected from the patient. The heart-lung machine can perform other tasks. For example, it can directly deliver medications into the recirculated blood. It can also minimize blood loss by vacuuming up and recirculating any blood that may get into the surgical field. The first step in using a heart-lung machine during open-heart surgery is to give the patient a drug called heparin, which is a powerful anticoagulant. Heparin reduces the blood’s ability to clot, reducing the risk of clots forming in the heart-lung machine and within the tubes placed in the heart. Once the medication has taken effect, a tube (cannula) from the heart-lung machine is placed in the upper-right chamber of the heart (the right atrium), which receives oxygen-poor blood from the body. Another cannula is placed in the aorta, a large artery that carries oxygen-rich blood from the heart to the rest of the body. By setting up the machine in this way, oxygen-poor blood drains into the machine, receives fresh oxygen and is returned to the aorta to be carried to the rest of the body.

Once the machine is functioning, the surgeon can carefully stop the heart with medications in order to perform the necessary surgery. A patient may remain on the heart-lung machine for several hours, though surgeons typically try to limit the amount of time patients are on bypass. When the surgery is complete, the surgeon will restart the heart. Once the surgical team is satisfied that the heart is beating strongly again, the tubes are removed from the right atrium and the aorta. To reverse the effects of the heparin given at the beginning of the process, the patient will be administered another medication called protamine.

Throughout this process, the heart-lung machine is operated by a perfusionist, one of several medical specialists on hand in the operating room during open-heart surgery. While the heart is stopped and the machine is working, the perfusionist continually monitors blood pressure, blood oxygen levels, carbon dioxide levels, blood temperature and breathing.

What is Heart Lung Machine

1. a pump to maintain circulation during heart surgery; diverts blood from the heart and oxygenates it and then pumps it through the body
2. Cardiopulmonary bypass (CPB) is a technique that temporarily takes over the function of the heart and lungs during surgery, maintaining the circulation of blood and the oxygen content of the body. The CPB pump itself is often referred to as a Heart-Lung Machine or the Pump.
3. a machine that pumps blood during open heart surgery.
4. Another term for machine which provides extracorporeal circulation (ECC)

References

The first version of this article was adapted from a public domain U.S. National Cancer Institute fact sheet at http://www.cancer.gov/cancertopics/factsheet/Sites-Types/mesothelioma

Legal History

The first lawsuit against asbestos manufacturers was brought in 1929. The parties settled that lawsuit, and as part of the agreement, the attorneys agreed not to pursue further cases. It was not until 1960 that an article published by Wagner et al. first officially established mesothelioma as a disease arising from exposure to crocidolite asbestos.[28] The article referred to over 30 case studies of people who had suffered from mesothelioma in South Africa. Some exposures were transient and some were mine workers. In 1962 McNulty reported the first diagnosed case of malignant mesothelioma in an Australian asbestos worker.[29] The worker had worked in the mill at the asbestos mine in Wittenoom from 1948 to 1950. In the town of Wittenoom, asbestos-containing mine waste was used to cover schoolyards and playgrounds. In 1965 an article in the British Journal of Industrial Medicine established that people who lived in the neighbourhoods of asbestos factories and mines, but did not work in them, had contracted mesothelioma. Despite proof that the dust associated with asbestos mining and milling causes asbestos related disease, mining began at Wittenoom in 1943 and continued until 1966. In 1974 the first public warnings of the dangers of blue asbestos were published in a cover story called "Is this Killer in Your Home?" in Australia's Bulletin magazine. In 1978 the Western Australian Government decided to phase out the town of Wittenoom, following the publication of a Health Dept. booklet, "The Health Hazard at Wittenoom", containing the results of air sampling and an appraisal of worldwide medical information. By 1979 the first writs for negligence related to Wittenoom were issued against CSR and its subsidiary ABA, and the Asbestos Diseases Society was formed to represent the Wittenoom victims. In Armley, Leeds, England the J W Roberts asbestos incident involved several court cases against Turner & Newall where local residents who contracted mesothelioma claimed compensation because of the asbestos pollution from the company's factory. One notable case was that of June Hancock, who contracted the disease in 1993 and died in 1997.

Legal issues

The first lawsuits against asbestos manufacturers were in 1929. Since then, many lawsuits have been filed against asbestos manufacturers and employers, for neglecting to implement safety measures after the links between asbestos, asbestosis, and mesothelioma became known (some reports seem to place this as early as 1898). Today, you may see a commercial stating something like, "Mesothelioma is a rare type of cancer caused by asbestos particles. Asbestos particles can be found in lumberyards, shipyards or any of the heating or automotive industries." The liability resulting from the sheer number of lawsuits and people affected has reached billions of dollars.[26] The amounts and method of allocating compensation have been the source of many court cases, reaching up to the United States Supreme Court, and government attempts at resolution of existing and future cases. However, to date, Congress has not stepped in and there are no federal laws governing asbestos compensation

Notable people who have lived for some time with mesothelioma

Although life expectancy with this disease is typically limited, there are notable survivors. In July 1982, Stephen Jay Gould was diagnosed with peritoneal mesothelioma. After his diagnosis, Gould wrote the "The Median Isn't the Message"[25] for Discover magazine, in which he argued that statistics such as median survival are just useful abstractions, not destiny. Gould lived for another twenty years eventually succumbing to metastatic adenocarcinoma of the lung, not mesothelioma.

Notable people who died from mesothelioma

Mesothelioma, though rare, has had a number of notable patients. Hamilton Jordan, Chief of Staff for President Jimmy Carter and life long cancer activist, died in 2008. Australian anti-racism activist Bob Bellear died in 2005. British science fiction writer Michael G. Coney, responsible for nearly 100 works also 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. Bernie Banton was an Australian workers' rights activist, who fought a long battle for compensation from James Hardie after he contracted mesothelioma after working for that company. He claimed James Hardie knew of the dangers of asbestos before he began work with the substance making insulation for power stations. Mesothelioma eventually took his life along with his brothers and hundreds of James Hardie workers. James Hardie made an undisclosed settlement with Banton only when his mesothelioma had reached its final stages and he was expected to have no more than 48hrs to live. Australian Prime Minister Kevin Rudd mentioned Banton's extended struggle in his acceptance speech after winning the 2007 Australian Federal Election. Steve McQueen was diagnosed with peritoneal mesothelioma on December 22, 1979. He was not offered surgery or chemotherapy because doctors felt the cancer was too advanced. McQueen sought alternative treatments from clinics in Mexico. He died of a heart attack on November 7, 1980, in Juárez, Mexico, following cancer surgery. He may have been exposed to asbestos while serving with the U.S. Marines as a young adult—asbestos was then commonly used to insulate ships' piping—or from its use as an insulating material in car racing suits.[20] (It is also reported that he worked in a shipyard during World War II, where he might have been exposed to asbestos.[citation needed]) 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, rock and roll musician and songwriter Warren Zevon was diagnosed with inoperable mesothelioma in the fall of 2002. Refusing treatments he believed might incapacitate him, Zevon focused his energies on recording his final album The Wind including the song "Keep Me in Your Heart," which speaks of his failing breath. Zevon died at his home in Los Angeles, California, on September 7, 2003. Christie Hennessy, the influential Irish singer-songwriter, died of mesothelioma in 2007, and had stridently refused to accept the prognosis in the weeks before his death.[21] His mesothelioma has been attributed to his younger years spent working on building sites in London.[22][23] Bob Miner, one of the founders of Software Development Labs, the forerunner of Oracle Corporation died of mesothelioma in 1994. Scottish Labour MP John William MacDougall died of mesothelioma on August 13, 2008, after fighting the disease for two years.[24] Canberra journalist and news presenter, Peter Leonard also succumbed to the condition on 23 September 2008. Terrence McCann Olympic gold medalist and longtime Executive Director of Toastmasters, died of mesothelioma on June 7, 2006 at his home in Dana Point, California.

Treatment

Treatment of malignant mesothelioma using conventional therapies in combination with radiation and or chemotherapy on stage I or II Mesothelioma have proved on average 74.6 percent successful in extending the patients life span by five years or more [commonly known as remission][this percentage may increase or decrease depending on date of discovery / stage of malignant development] (Oncology Today, 2009). Treatment course is primarily determined by the staging or development. This is unlike traditional treatment such as surgery by itself which has proved only be 16.3 percent likely to extend a patient's life span by five years or more [commonly known as remission]. Clinical behavior of the malignancy is affected by several factors including the continuous mesothelial surface of the pleural cavity which favors 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. Surgery Surgery, by itself, has proved disappointing. However, research indicates varied success when used in combination with radiation and chemotherapy (Duke, 2008) 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. 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, often 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.[16] Delivering radiation and chemotherapy after a radical surgery has led to extended life expectancy in selected patient populations with some patients surviving more than 5 years. As part of a curative approach to mesothelioma, radiotherapy is also commonly applied to the sites of chest drain insertion, in order to prevent growth of the tumor along the track in the chest wall. Although mesothelioma is generally resistant to curative treatment with radiotherapy alone, palliative treatment regimens are sometimes used to relieve symptoms arising from tumor growth, such as obstruction of a major blood vessel. Radiation therapy when given alone with curative intent has never been shown to improve survival from mesothelioma. The necessary radiation dose to treat mesothelioma that has not been surgically removed would be very toxic. Chemotherapy Chemotherapy is the only treatment for mesothelioma that has been proven to improve survival in randomised and controlled trials. The landmark study published in 2003 by Vogelzang and colleagues compared cisplatin chemotherapy alone with a combination of cisplatin and pemetrexed (brand name Alimta) chemotherapy) in patients who had not received chemotherapy for malignant pleural mesothelioma previously and were not candidates for more aggressive "curative" surgery.[17] This trial was the first to report a survival advantage from chemotherapy in malignant pleural mesothelioma, showing a statistically significant improvement in median survival from 10 months in the patients treated with cisplatin alone to 13.3 months in the combination pemetrexed group in patients who received supplementation with folate and vitamin B12. Vitamin supplementation was given to most patients in the trial and pemetrexed related side effects were significantly less in patients receiving pemetrexed when they also received daily oral folate 500mcg and intramuscular vitamin B12 1000mcg every 9 weeks compared with patients receiving pemetrexed without vitamin supplementation. The objective response rate increased from 20% in the cisplatin group to 46% in the combination pemetrexed group. Some side effects such as nausea and vomiting, stomatitis, and diarrhoea were more common in the combination pemetrexed group but only affected a minority of patients and overall the combination of pemetrexed and cisplatin was well tolerated when patients received vitamin supplementation; both quality of life and lung function tests improved in the combination pemetrexed group. In February 2004, the United States Food and Drug Administration approved pemetrexed for treatment of malignant pleural mesothelioma. However, there are still unanswered questions about the optimal use of chemotherapy, including when to start treatment, and the optimal number of cycles to give. Cisplatin in combination with raltitrexed has shown an improvement in survival similar to that reported for pemetrexed in combination with cisplatin, but raltitrexed is no longer commercially available for this indication. For patients unable to tolerate pemetrexed, cisplatin in combination with gemcitabine or vinorelbine is an alternative, or vinorelbine on its own, although a survival benefit has not been shown for these drugs. For patients in whom cisplatin cannot be used, carboplatin can be substituted but non-randomised data have shown lower response rates and high rates of haematological toxicity for carboplatin-based combinations, albeit with similar survival figures to patients receiving cisplatin.[18] In January 2009, the United States FDA approved using conventional therapies such as surgery in combination with radiation and or chemotherapy on stage I or II Mesothelioma after research conducted by a nationwide study by Duke University concluded an almost 50 point increase in remission rates. 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. Indeed, this trial was suspended in view of the unacceptably high levels of IL-2 toxicity and the severity of side effects such as fever and cachexia. Nonetheless, other trials involving interferon alpha have proved more encouraging with 20% of patients experiencing a greater than 50% reduction in tumor mass combined with minimal side effects. Heated Intraoperative Intraperitoneal Chemotherapy A procedure known as heated intraoperative intraperitoneal chemotherapy was developed by Paul Sugarbaker at the Washington Cancer Institute.[19] The surgeon removes as much of the tumor as possible followed by the direct administration of a chemotherapy agent, heated to between 40 and 48°C, in the abdomen. The fluid is perfused for 60 to 120 minutes and then drained. This technique permits the administration of high concentrations of selected drugs into the abdominal and pelvic surfaces. Heating the chemotherapy treatment increases the penetration of the drugs into tissues. Also, heating itself damages the malignant cells more than the normal cells.

Epidemiology

Incidence Although reported incidence rates have increased in the past 20 years, mesothelioma is still a relatively rare cancer. The incidence rate is approximately one per 1,000,000. The highest incidence is found in Britain, Australia and Belgium: 30 per 1,000,000 per year.[8] 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.[9] It has been estimated that incidence may have peaked at 15 per 1,000,000 in the United States in 2004. Incidence is expected to continue increasing in other parts of the world. Mesothelioma occurs more often in men than in women and risk increases with age, but this disease can appear in either men or women at any age. Approximately one fifth to one third of all mesotheliomas are peritoneal. Between 1940 and 1979, approximately 27.5 million people were occupationally exposed to asbestos in the United States.[10] Between 1973 and 1984, there has been a threefold increase in the diagnosis of pleural mesothelioma in Caucasian males. From 1980 to the late 1990s, the death rate from mesothelioma in the USA increased from 2,000 per year to 3,000, with men four times more likely to acquire it than women. These rates may not be accurate, since it is possible that many cases of mesothelioma are misdiagnosed as adenocarcinoma of the lung, which is difficult to differentiate from mesothelioma. Risk factors Working with asbestos is the major risk factor for mesothelioma.[11] A history of asbestos exposure exists in almost all cases. However, mesothelioma has been reported in some individuals without any known exposure to asbestos. In rare cases, mesothelioma has also been associated with irradiation, intrapleural thorium dioxide (Thorotrast), and inhalation of other fibrous silicates, such as erionite. 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. If tiny asbestos particles float in the air, especially during the manufacturing process, they may be inhaled or swallowed, and can cause serious health problems. In addition to mesothelioma, exposure to asbestos increases the risk of lung cancer, asbestosis (a noncancerous, chronic lung ailment), and other cancers, such as those of the larynx and kidney. The combination of smoking and asbestos exposure significantly increases a person's risk of developing cancer of the airways (lung cancer, bronchial carcinoma). The Kent brand of cigarettes used asbestos in its filters for the first few years of production in the 1950s and some cases of mesothelioma have resulted. Smoking modern cigarettes does not appear to increase the risk of mesothelioma. Some studies suggest that simian virus 40 (SV40) may act as a cofactor in the development of mesothelioma.[12] Exposure Asbestos was known in antiquity, but it wasn't mined and widely used commercially until 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 known. However, an increased risk of developing mesothelioma was later found among shipyard workers, people who work in asbestos mines and mills, producers of asbestos products, workers in the heating and construction industries, and other tradespeople. Today, the U.S. Occupational Safety and Health Administration (OSHA) sets limits for acceptable levels of asbestos exposure in the workplace, and created guidelines for engineering controls and respirators, protective clothing, exposure monitoring, hygiene facilities and practices, warning signs, labeling, recordkeeping, and medical exams. By contrast, the British Government's Health and Safety Executive (HSE) states formally that any threshold for mesothelioma must be at a very low level and it is widely agreed that if any such threshold does exist at all, then it cannot currently be quantified. For practical purposes, therefore, HSE does not assume that any such threshold exists. People who work with asbestos wear personal protective equipment to lower their risk of exposure. Environmental exposures Incidence of mesothelioma had been found to be higher in populations living near naturally occurring asbestos. For example, in central Cappadocia, Turkey, mesothelioma was causing 50% of all deaths in three small villages — Tuzköy, Karain and Sarıhıdır. Initially, this was attributed to erionite, a zeolite mineral with similar properties to asbestos, however, recently, detailed epidemiological investigation showed that erionite causes mesothelioma mostly in families with a genetic predisposition.[13][14] Occupational Exposure to asbestos fibres has been recognized as an occupational health hazard since the early 1900s. Several epidemiological studies have associated exposure to asbestos with the development of lesions such as asbestos bodies in the sputum, pleural plaques, diffuse pleural thickening, asbestosis, carcinoma of the lung and larynx, gastrointestinal tumours, and diffuse mesothelioma of the pleura and peritoneum. The documented presence of asbestos fibres in water supplies and food products has fostered concerns about the possible impact of long-term and, as yet, unknown exposure of the general population to these fibres. Although many authorities consider brief or transient exposure to asbestos fibres as inconsequential and an unlikely risk factor, some epidemiologists claim that there is no risk threshold. Cases of mesothelioma have been found in people whose only exposure was breathing the air through ventilation systems. Other cases had very minimal (3 months or less) direct exposure. Commercial asbestos mining at Wittenoom, Western Australia, occurred between 1945 and 1966. A cohort study of miners employed at the mine reported that while no deaths occurred within the first 10 years after crocidolite exposure, 85 deaths attributable to mesothelioma had occurred by 1985. By 1994, 539 reported deaths due to mesothelioma had been reported in Western Australia. Paraoccupational secondary exposure Family members and others living with asbestos workers have an increased risk of developing mesothelioma, and possibly other asbestos related diseases.[15] This risk may be the result of exposure to asbestos dust brought home on the clothing and hair of asbestos workers. To reduce the chance of exposing family members to asbestos fibres, asbestos workers are usually required to shower and change their clothing before leaving the workplace. Asbestos in buildings Many building materials used in both public and domestic premises prior to the banning of asbestos may contain asbestos. Those performing renovation works or DIY activities may expose themselves to asbestos dust. In the UK use of Chrysotile asbestos was banned at the end of 1999. Brown and blue asbestos was banned in the UK around 1985. Buildings built or renovated prior to these dates may contain asbestos materials.

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 cavities. Deposition of asbestos fibres in the parenchyma of the lung may result in the penetration of the visceral pleura from where the fibre can then be carried to the pleural surface, thus leading to the development of malignant mesothelial plaques. The 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. Additionally, asbestos fibres may be deposited in the gut after ingestion of sputum contaminated with asbestos fibres.

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).[6] However, there is now evidence that smaller particles may be more dangerous than the larger fibers. They remain suspended in the air where they can be inhaled, and may penetrate more easily and deeper into the lungs. "We probably will find out a lot more about the health aspects of asbestos from [the World Trade Center attack], unfortunately," said Dr. Alan Fein, chief of pulmonary and critical-care medicine at North Shore-Long Island Jewish Health System. Dr. Fein has treated several patients for "World Trade Center syndrome" or respiratory ailments from brief exposures of only a day or two near the collapsed buildings.[7] Mesothelioma development in rats has been demonstrated following intra-pleural inoculation of phosphorylated chrysotile fibres. It has been suggested that in humans, transport of fibres to the pleura is critical to the pathogenesis of mesothelioma. This is supported by the observed recruitment of significant numbers of macrophages and other cells of the immune system to localised lesions of accumulated asbestos fibres in the pleural and peritoneal cavities of rats. These lesions continued to attract and accumulate macrophages as the disease progressed, and cellular changes within the lesion culminated in a morphologically malignant tumour. Experimental evidence suggests that asbestos acts as a complete carcinogen with the development of mesothelioma occurring in sequential stages of initiation and promotion. The molecular mechanisms underlying the malignant transformation of normal mesothelial cells by asbestos fibres remain unclear despite the demonstration of its oncogenic capabilities. However, complete in vitro transformation of normal human mesothelial cells to malignant phenotype following exposure to asbestos fibres has not yet been achieved. In general, asbestos fibres are thought to act through direct physical interactions with the cells of the mesothelium in conjunction with indirect effects following interaction with inflammatory cells such as macrophages. Analysis 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. This contact between the asbestos fibre and the chromosomes or structural proteins of the spindle apparatus can induce complex abnormalities. The most common abnormality is monosomy of chromosome 22. Other frequent abnormalities include structural rearrangement of 1p, 3p, 9p and 6q chromosome arms. Common gene abnormalities in mesothelioma cell lines include deletion of the tumor suppressor genes:

• Neurofibromatosis type 2 at 22q12
• P16^INK4A
• P14^ARF

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 o
f oncogenesActivation of proto-oncogenes due to incorporation of foreign DNA containing a promoter regionActivation of DNA repair enzymes, which may be prone to errorActivation of telomerasePrevention of apoptosi
• s

Asbestos fibers have been shown to alter the function 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. However, these free radicals are also known clastogenic and membrane-active agents thought to promote asbestos carcinogenicity. These oxidants can participate in the oncogenic process by directly and indirectly interacting with DNA, modifying membrane-associated cellular events, including oncogene activation and perturbation of cellular antioxidant defences. 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.

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.[4] Doctors have begun testing the Mesomark assay which measures levels of soluble mesothelin-related proteins (SMRPs) released by diseased mesothelioma cells.[5]

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 incision 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.

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 transcription factor-1)

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)

I

n 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.

Introduction

Mesothelioma is a form of cancer that is almost always caused by 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 internal chest wall), but it may also occur in the peritoneum (the lining of the abdominal cavity), the heart,[1] the pericardium (a sac that surrounds the heart) or tunica vaginalis. Most people who develop mesothelioma have worked on jobs where they inhaled asbestos particles, or they have been exposed to asbestos dust and fiber in other ways. It has also been suggested that washing the clothes of a family member who worked with asbestos can put a person at risk for developing mesothelioma.[2] Unlike lung cancer, there is no association between mesothelioma and smoking, but smoking greatly increases risk of other asbestos-induced cancer.[3] 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 may be suspected with chest X-ray and CT scan, and is 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.