Three types of Malignant Mesothelioma

Treatment options are the same for all 3 types.

• epithelioid (50% to 70% are of this type) -- this type has the best outlook for survival (prognosis)
• sarcomatoid (7% to 20% are of this type)
• mixed/biphasic (20% to 35% are of this type)

About 75% of mesotheliomas start in the chest cavity. They are known as pleural mesotheliomas. Another 10% to 20% begin in the abdomen. These are called peritoneal mesotheliomas. Pericardial mesotheliomas start in the cavity around the heart and are very rare. The covering layer of the testicles is actually an outpouching of peritoneum into the scrotum. Mesotheliomas that affect this covering of the testicles can occur but are quite rare.

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

A type of benign tumor that used to be called benign fibrous mesothelioma can form in the pleura surrounding the lungs. Doctors now know that this tumor actually starts from tissue under the mesothelium and not from mesothelial cells. For this reason, the new name of this tumor is solitary fibrous tumor of the pleura. This disease is usually not cancerous, but cancerous forms can occur. A similar disease starting in the peritoneum is called solitary fibrous tumor of the peritoneum. The tumors described in this paragraph are usually removed by surgery, and there is no need for additional treatment. Only malignant mesothelioma will be discussed further in this document.

What is malignant Mesothelioma??

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

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

Tumors of the mesothelium can be non-cancerous (benign) or cancerous (malignant). A malignant tumor of the mesothelium is called a malignant mesothelioma; however, malignant mesothelioma is often simply called mesothelioma.

Two types of Mesothelioma

• Pleural mesothelioma
• Peritoneal mesothelioma

The pleural type grows in the tissues covering the lungs. The peritoneal type grows in the tissue lining the inside of the abdomen (tummy). Pleural mesothelioma is much more common than peritoneal mesothelioma.

Between 70% - 80% of cases are pleural mesothelioma. Peritoneal mesothelioma is much less common, making up between 10% - 20%.

Cell types
Mesothelioma is also grouped according to how the cells look under a microscope. When mesothelioma is grouped this way, there are 3 types
• Epitheloid
• Sarcomatoid or fibrous
• Mixed type (also called Biphasic type)
Between 50%-70% of mesothelioma diagnosed are the epitheloid type.

Between 7% – 20% of mesothelioma diagnosed are sarcomatoid type.

Between 20% – 35% of mesothelioma diagnosed are mixed and have both epitheloid and sarcomatoid cells.

These types of mesothelioma cells can further divide into other types of cancerous cells called
• Clear cell
• Small cell
• Acinar cell
• Tubopapillary cell

With so many different types of cells capable of developing into mesothelioma, it makes it very difficult to diagnose this disease.

Sysmptoms of Mesothelioma

Mesothelioma does not have many symptoms in the earlier stages. The symptoms can caused by the cancer growing and pressing on a nerve or other body organ when they do develop.

The symptoms of the 2 main types of mesothelioma are different.

The symptoms of pleural mesothelioma are
• Pain in the lower back or the side of the chest
• A persistent cough
• Shortness of breath
• A hoarse or husky voice
• Losing more than 10% of your weight when not dieting
• Sweating and fevers
• Difficulty swallowing

The symptoms of peritoneal mesothelioma are
• Pain in the abdomen (tummy)
• Swelling in the abdomen
• Feeling or being sick
• Poor appetite
• Losing more than 10% of your weight when not dieting
• Diarrhoea or constipation

These symptoms are all more likely to be caused by some other illness, rather than by mesothelioma. But if you have these symptoms, see

Testing for Mesothelioma

At the time of writing, there is no screening programme for mesothelioma in the UK. Before screening for any type of cancer can be carried out, doctors must have an accurate test to use. The test must be reliable in picking up cancers that are there. And it must not give a positive result in people who do not have cancer.

If screening were to be introduced for mesothelioma, the test would have to be simple, quick and not too expensive. Diagnosing mesothelioma can be difficult. The usual tests for lung diseases often appear to be negative with mesothelioma.

As only about 2,000 cases are diagnosed each year, it is not sensible to screen everyone in the country for such a rare disease.

It would be more cost effective to screen people who are thought to be at a higher risk of mesothelioma. But to do that, we have to be able to identify all those who are at higher risk.

Benefits of purchasing long term-care Insurance

If the need for long-term care arises and you don't have insurance, the associated costs may have to be paid out of personal savings or financed by loved ones. If you are unable to afford the cost of hiring care providers, family members may be required to assist you, which means they may have to take unpaid leave from work. By purchasing long-term care insurance, you help to ensure that any costs associated with your care are covered, thereby lessening the financial burden on yourself and your family. It may be beneficial to purchase your long-term care insurance at an early age, as the premiums are usually lower for younger individuals. However, remember that long-term care insurance is not for everyone and is usually purchased by younger individuals only when they have a history of family illness that are covered under these policies. Bear in mind that coverage may be denied if the potential insured is already at a stage that requires long-term care. For example, if someone already has Alzheimer's disease, he or she may no longer be eligible for long-term care insurance. Finally, remember that paying premiums is less costly than paying long-term expenses out of your pocket. Before purchasing a policy, be sure to compare rates, features and benefits offered by different insurance companies, independent brokers and so on. More importantly, consult with your estate or financial planner and/or attorney about the choices that are appropriate for you and your family.

Cost of long term Care Insurance

The cost of long-term care insurance is usually determined by factors such as the type of policy, the age of the insured and the time period the policy covers. Naturally, policies that provide coverage for an unlimited period will cost more than policies that provide coverage for a limited period. Policies purchased at an early age are less costly than policies purchased later, because a younger person is more likely to pay premiums for a longer time. The cost of the policy may also be affected by the preferred location of the service - whether in-home, at a nursing home or at some other facility providing professional care - and whether the coverage is comprehensive or basic, as defined by the policy.

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Long term- care Insurance

Long-term care is typically needed by the elderly, but it is also required by anyone with a debilitating illness or injury who needs assistance to perform what we consider everyday functions, such as feeding oneself, bathing and getting dressed. In fact, in 1995, 43% of individuals needing long-term care were children and working adults (as reported in Long Term Care: Diverse, Growing Population Includes Millions of Americans of All Ages by the U.S. General Accounting Office in 1995.)

Like other services covered by insurance, long-term care insurance must be purchased before the insured requires the services covered under the policy. This means that many individuals will purchase the policy and never benefit from it. The likelihood of this happening is greater among younger individuals, whose chances of requiring long-term care are lower. Consequently, some financial professionals recommend that only individuals closer to ages 50 to 65 purchase long-term care insurance, as these individuals are more likely to benefit from the purchase of a policy.

If you are employed, you may want to check with your employer regarding coverage, as most employers provide long-term care insurance for their employees, and some will even extend coverage to parents of their employees. If you are already covered under an employer-sponsored policy, then you may not need to purchase a separate policy until after you retire.

Doctrine of adhesion

The doctrine of adhesion states that you must accept the entire insurance contract and all of its terms and conditions without bargaining. Because the insured has no opportunity to change the terms, any ambiguities in the contract will be interpreted in favor of the insured.

When purchasing insurance, most of us rely on our insurance advisor for everything - from choosing a policy for us to filling in the insurance application forms. Most people try to stay away from the boring legal terms of insurance contracts, but it is always handy to be familiar with these words and phrases and to become familiar with the terms of the policy you are paying for.

Doctrine of utmost good faith

All insurance contracts are based on the concept of "uberrima fidei", or the doctrine of utmost good faith. This doctrine emphasizes the presence of mutual faith between the insured and the insurer. In simple terms, while applying for life insurance, it becomes your duty to disclose your past illnesses to the insurer. Likewise, the insurer cannot hide information about the insurance coverage that is being sold.

Principle of Subrogation

Subrogation allows an insurer to sue a third party that has caused a loss to the insured and pursue all methods of getting back some of the money that it has paid to the insured as a result of the loss.

For example, if you are injured in a road accident that is caused by the reckless driving of another party, you will be compensated by your insurer. However, your insurance company may also sue the reckless driver in an attempt to recover that money.

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Insurable Interest

It is your legal right to insure any type of property or any event that may cause financial loss or create a legal liability to you. This is called insurable interest.

Suppose you are living in your uncle's house, and you apply for homeowners' insurance because you believe that you may inherit the house later. Insurers will decline your offer because you are not the owner of the house and, therefore, you do not stand to suffer financially in the event of a loss.

This example demonstrates that when it comes to insurance, it is not the house, car or machinery that is insured. Rather, it is the monetary interest in that house, car or machinery to which your policy applies.

It is also the principle of insurable interest that allows married couples to take out insurance policies on the lives of their spouses - they may suffer financially if the spouse dies. Insurable interest also exists in some business arrangements, as seen between a creditor and debtor, between business partners or between employers and employees.

Additional Factors of Insurance contract

• Under-Insurance: Often, in order to save on premiums, you may insure your house at $80,000 when the total value of the house actually comes to $100,000. At the time of partial loss, your insurer will pay only a proportion of $80,000 while you have to dig into your savings to cover the remaining portion of the loss. This is called under-insurance, and you should try to avoid it as much as possible.
  
• Excess: To avoid trivial claims, the insurers have introduced provisions like excess. For example, you have auto insurance with the applicable excess of $5,000. Unfortunately, your car had an accident with the loss amounting to $7,000. Your insurer will pay you the $7,000 because the loss has exceeded the specified limit of $5,000. But, if the loss comes to $3,000 then the insurance company will not pay a single penny and you have to bear the loss expenses yourself. In short, the insurers will not entertain claims unless and until your losses exceed a minimum amount set by the insurer.

Not all insurance contracts are indemnity contracts. Life insurance contracts and most personal accident insurance contracts are non-indemnity contracts. You may purchase a life insurance policy of $1 million, but that does not imply that your life's value is equal to this dollar amount. Because you can't calculate your life's net worth and fix a price on it, an indemnity contract does not apply. (For more information on non-indemnity contracts, read Buying Life Insurance: Term Versus Permanent, Long-Term Care Insurance: Who Needs It? and Shifting Life Insurance Ownership.)

Find the value in the Indemnity contracts

Most insurance contracts are indemnity contracts. Indemnity contracts apply to insurances where the loss suffered can be measured in terms of money.

Principle of Indemnity: This states that insurers pay no more than the actual loss suffered. The purpose of an insurance contract is to leave you in the same financial position you were in immediately prior to the incident leading to an insurance claim. When your old Chevy Cavalier is stolen, you can't expect your insurer to replace it with a brand new Mercedes-Benz. In other words, you will be remunerated according to the total sum you have assured for the car. (To read more on indemnity contracts, see Shopping For Car Insurance and How does the 80% rule for home insurance work?)

Essentials of a valid Insurance contract

• Offer and Acceptance: When applying for insurance, the first thing you do is get the proposal form of a particular insurance company. After filling in the requested details, you send the form to the company (sometimes with a premium check). This is your offer. If the insurance company accepts your offer and agrees to insure you, this is called an acceptance. In some cases, your insurer may agree to accept your offer after making some changes to your proposed terms (for example, charging you a double premium for your chain-smoking habit).
  
• Consideration: This is the premium or the future premiums that you have pay to your insurance company. For insurers, consideration also refers to the money paid out to you should you file an insurance claim. This means that each party to the contract must provide some value to the relationship.
  
• Legal Capacity: You need to be legally competent to enter into an agreement with your insurer. If you are a minor or are mentally ill, for example, then you may not be qualified to make contracts. Similarly, insurers are considered to be competent if they are licensed under the prevailing regulations that govern them.
  
• Legal Purpose: If the purpose of your contract is to encourage illegal activities, it is invalid.

What is Insurance contract??

Almost all of us have insurance. When your insurer gives you the policy document, generally, all you do is glance over the decorated words in the policy and pile it up with the other bunch of financial papers on your desk, right? If you spend thousands of dollars each year on insurance, don't you think that you should know all about it? Your insurance advisor is always there for you to help you understand the tricky terms in the insurance forms, but you should also know for yourself what your contract says. In this article, we'll make reading your insurance contract easy. Read on to take a look at the basic principles of insurance contracts and how they are put to use in daily life.

Life insurance specific features

• Incontestibility - in the United States, life insurance contracts may not be contested by the insurer at any point after the contract has been in force for two years. The insurer has the burden to investigate fully anything they wish to make sure the insured is an acceptable risk within those two years. Any material mistatements on the insurance application (which generally forms a part of the contract) cannot be used as a reason for the insurer not to pay the death benefit, as long as it does not constitute fraud on the part of the insured. The insurer's only recourse if there is no fraud is they can adjust the death benefit to correct for the correct age or sex of the insured if they are different from what the application noted.

Parts of an Insurance contract

• Definitions - define important terms used in the policy language.
• Insuring Agreement - describes the covered perils, or risks assumed, or nature of coverage, or makes some reference to the contractual agreement between insurer and insured. It summarizes the major promises of the insurance company, as well as stating what is covered.
• Declarations - identifies who is an insured, the insured's address, the insuring company, what risks or property are covered, the policy limits (amount of insurance), any applicable deductibles, the policy period and premium amount.
• Exclusions - take coverage away from the Insuring Agreement by describing property, perils, hazards or losses arising from specific causes which are not covered by the policy.
• Conditions - provisions, rules of conduct, duties and obligations required for coverage. If policy conditions are not met, the insurer can deny the claim.

General Features

The insurance contract is a contract whereby the insurer will pay the insured (the person whom benefits would be paid to, or on the behalf of), if certain defined events occur. Subject to the "fortuity principle", the event must be uncertain. The uncertainty can be either as to when the event will happen (i.e. in a life insurance policy, the time of the insured's death is uncertain) or as to if it will happen at all (i.e. a fire insurance policy).

• Insurance contracts are generally considered contracts of adhesion because the insurer draws up the contract and the insured has little or no ability to make material changes to it. This is interpreted to mean that the insurer bears the burden if there is any ambiguity in any terms of the contract.

• Insurance contracts are aleatory in that the amounts exchanged by the insured and insurer are unequal and depend upon uncertain future events.

• Insurance contracts are unilateral, meaning that only the insurer makes legally enforceable promises in the contract. The insured is not required to pay the premiums, but the insurer is required to pay the benefits under the contract if the insured has paid the premiums and met certain other basic provisions.

• Insurance contracts are governed by the principle of utmost good faith (uberrima fides) which requires both parties of the insurance contact to deal in good faith and in particular it imparts on the insured a duty to disclose all material facts which relate to the risk to be covered. This contrasts with the legal doctrine that covers most other types of contracts, caveat emptor (let the buyer beware).

Insurance contract

An Insurance contract determines the legal framework under which the features of an insurance policy are enforced. Insurance contracts are designed to meet very specific needs and thus have many features not found in many other types of contracts. Many features are similar across a wide variety of different types of insurance policies.

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. 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. 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.

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). The liability resulting from the sheer number of lawsuits and people affected has reached billions of dollars.^{[citation needed]} The amounts and method of allocating compensation have been the source of many court cases, and government attempts at resolution of existing and future cases.

Notable people that have lived for sometime 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 Messag.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.

Author Paul Kraus was diagnosed with mesothelioma in June 1997 following an umbilical hernia operation. His prognosis was "a few months." He continues to survive using a variety of integrative and complimentary modalities and has written a book about his experience.

Notable people that died from 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 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 Mr 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-elect Kevin Rudd mentioned Mr 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 US Marines as a young adult—asbestos was then commonly used to insulate ships' piping—or because of its use as an insulating material in car racing suits.It is also reported that he worked in a shipyard during World War II, where he might have been exposed to asbestos.

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. His mesothelioma has been attributed to his younger years spent working on building sites in London.

Bob Miner, one of the founders of Software Development Labs, the forerunner of Oracle Corporation died of mesothelioma in 1994.

Preventions and Expectation of Mesothelioma

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. In the past, asbestos was used as a fire retardant and an insulator. Other products are now used in its place. The controversy involving exposure to different forms of asbestos continues.

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.

Removal is taking place in schools and other public buildings throughout the U.S. The hope is that these measures will greatly reduce the occurrence of this cancer.

What are the long-term effects of the disease? A mesothelioma is a highly aggressive tumor that is generally deadly. Current treatment of malignant mesothelioma is designed to make the person with cancer comfortable. Although long-term survival cannot usually be expected, the case of famed paleontologist Stephen Jay Gould is a noted exception.

What are the risks to others? Mesothelioma is not contagious and cannot be passed from one person to another. The exposure to the asbestos that caused the cancer occurred many years to several decades before the disease appeared. People who live with asbestos workers have a higher risk of getting this cancer.

What happens once treatment is over? Although mesothelioma is very unpleasant it's still important for person after treatment is over to keep up all follow-up appointments and that's vital because further testing is always needed to check whether cancer is coming back or to examine possible side effects that could be rather unpleasant and what's even worse permanent.

Treatment of Mesothelioma

Treatment of MM 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.

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.

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.^[8] 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

In February 2004, the United States 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.

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. 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.

Exposure of Mesothelioma

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.

Occupational

Exposure to asbestos fibres has been recognised 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. 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.

Environmental Exposure

Incidence of mesothelioma had been found to be higher in populations living near Naturally Occurring Asbestos (NOA).

Risk Factors of Mesothelioma

Working with asbestos is the major risk factor for mesothelioma. 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.

Epidemiology

Incidence

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.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 . 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.

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).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.

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 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 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.

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. However some research indicates that 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.

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.

Doctors have begun testing the Mesomark assay which measures levels of soluble mesothelin-related proteins (SMRPs) released by diseased mesothelioma cells. The procedure could diagnose mesothelioma earlier than conventional methods thus improving the survival prospects for patients.^[3]

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)

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

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 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, or by home renovation using asbestos cement products. Unlike lung cancer, there is no association between mesothelioma and smoking.