Sunday, July 12, 2009

Cigarette Smoking and Cancer: Questions and Answers

Tobacco use, particularly cigarette smoking, is the single most preventable cause of death in the United States. Cigarette smoking alone is directly responsible for approximately 30 percent of all cancer deaths annually in the United States (1). Cigarette smoking also causes chronic lung disease (emphysema and chronic bronchitis), cardiovascular disease, stroke, and cataracts. Smoking during pregnancy can cause stillbirth, low birthweight, Sudden Infant Death Syndrome (SIDS), and other serious pregnancy complications (2). Quitting smoking greatly reduces a person’s risk of developing the diseases mentioned, and can limit adverse health effects on the developing child.

1. What are the effects of cigarette smoking on cancer rates?

Cigarette smoking causes 87 percent of lung cancer deaths (1). Lung cancer is the leading cause of cancer death in both men and women (3). Smoking is also responsible for most cancers of the larynx, oral cavity and pharynx, esophagus, and bladder. In addition, it is a cause of kidney, pancreatic, cervical, and stomach cancers (2, 4), as well as acute myeloid leukemia (2).
2. Are there any health risks for nonsmokers?

The health risks caused by cigarette smoking are not limited to smokers. Exposure to secondhand smoke, or environmental tobacco smoke (ETS), significantly increases the risk of lung cancer and heart disease in nonsmokers, as well as several respiratory illnesses in young children (5). (Secondhand smoke is a combination of the smoke that is released from the end of a burning cigarette and the smoke exhaled from the lungs of smokers.) The U.S. Environmental Protection Agency (EPA), the National Institute of Environmental Health Science’s National Toxicology Program, and the World Health Organization’s International Agency for Research on Cancer (IARC) have all classified secondhand smoke as a known human carcinogen—a category reserved for agents for which there is sufficient scientific evidence that they cause cancer (5, 6, 7). The U.S. EPA has estimated that exposure to secondhand smoke causes about 3,000 lung cancer deaths among nonsmokers and is responsible for up to 300,000 cases of lower respiratory tract infections in children up to 18 months of age in the United States each year (5). For additional information on ETS, see the NCI fact sheet Environmental Tobacco Smoke, which can be found at http://www.cancer.gov/cancertopics/factsheet/Tobacco/ETS on the Internet.
3. What harmful chemicals are found in cigarette smoke?

Cigarette smoke contains about 4,000 chemical agents, including over 60 carcinogens (8). In addition, many of these substances, such as carbon monoxide, tar, arsenic, and lead, are poisonous and toxic to the human body. Nicotine is a drug that is naturally present in the tobacco plant and is primarily responsible for a person’s addiction to tobacco products, including cigarettes. During smoking, nicotine is absorbed quickly into the bloodstream and travels to the brain in a matter of seconds. Nicotine causes addiction to cigarettes and other tobacco products that is similar to the addiction produced by using heroin and cocaine (9).
4. How does exposure to tobacco smoke affect the cigarette smoker?

Smoking harms nearly every major organ of the body (2). The risk of developing smoking-related diseases, such as lung and other cancers, heart disease, stroke, and respiratory illnesses, increases with total lifetime exposure to cigarette smoke (7). This includes the number of cigarettes a person smokes each day, the intensity of smoking (i.e., the size and frequency of puffs), the age at which smoking began, the number of years a person has smoked, and a smoker’s secondhand smoke exposure.
5. How would quitting smoking affect the risk of developing cancer and other diseases?

Smoking cessation has major and immediate health benefits for men and women of all ages. Quitting smoking decreases the risk of lung and other cancers, heart attack, stroke, and chronic lung disease. The earlier a person quits, the greater the health benefit. For example, research has shown that people who quit before age 50 reduce their risk of dying in the next 15 years by half compared with those who continue to smoke (3). Smoking low-yield cigarettes, as compared to cigarettes with higher tar and nicotine, provides no clear benefit to health (2). For additional information on quitting smoking, see the NCI fact sheet Questions and Answers About Smoking Cessation, which can be found at http://www.cancer.gov/cancertopics/factsheet/Tobacco/cessation on the Internet.
6. What additional resources are available?

For additional information about cancer or tobacco use, call 1–800–4–CANCER or visit the NCI’s Web site about tobacco at http://www.cancer.gov/cancerinfo/tobacco on the Internet.

For help with quitting smoking, call NCI’s smoking cessation quitline at 1–877–44U–QUIT or visit NCI’s smoking cessation Web site at http://www.smokefree.gov on the Internet.

Information about the health risks of smoking is also available from Centers for Disease Control and Prevention’s Office on Smoking and Health (OSH) at 1–800–CDC–1311 (1–800–232–1311) or via their Web site at http://www.cdc.gov/tobacco on the Internet.

Prevention

1. What are antioxidants?

Antioxidants are substances that may protect cells from the damage caused by unstable molecules known as free radicals. Free radical damage may lead to cancer. Antioxidants interact with and stabilize free radicals and may prevent some of the damage free radicals might otherwise cause. Examples of antioxidants include beta-carotene, lycopene, vitamins C, E, and A, and other substances.
2. Can antioxidants prevent cancer?

Considerable laboratory evidence from chemical, cell culture, and animal studies indicates that antioxidants may slow or possibly prevent the development of cancer. However, information from recent clinical trials is less clear. In recent years, large-scale, randomized clinical trials reached inconsistent conclusions.
3. What was shown in previously published large-scale clinical trials?

Five large-scale clinical trials published in the 1990s reached differing conclusions about the effect of antioxidants on cancer. The studies examined the effect of beta-carotene and other antioxidants on cancer in different patient groups. However, beta-carotene appeared to have different effects depending upon the patient population. The conclusions of each study are summarized below.
* The first large randomized trial on antioxidants and cancer risk was the Chinese Cancer Prevention Study, published in 1993. This trial investigated the effect of a combination of beta-carotene, vitamin E, and selenium on cancer in healthy Chinese men and women at high risk for gastric cancer. The study showed a combination of beta-carotene, vitamin E, and selenium significantly reduced incidence of both gastric cancer and cancer overall (1).

* A 1994 cancer prevention study entitled the Alpha-Tocopherol (vitamin E)/ Beta-Carotene Cancer Prevention Study (ATBC) demonstrated that lung cancer rates of Finnish male smokers increased significantly with beta-carotene and were not affected by vitamin E (2).

* Another 1994 study, the Beta-Carotene and Retinol (vitamin A) Efficacy Trial (CARET), also demonstrated a possible increase in lung cancer associated with antioxidants (3).

* The 1996 Physicians’ Health Study I (PHS) found no change in cancer rates associated with beta-carotene and aspirin taken by U.S. male physicians (4).

* The 1999 Women's Health Study (WHS) tested effects of vitamin E and beta-carotene in the prevention of cancer and cardiovascular disease among women age 45 years or older. Among apparently healthy women, there was no benefit or harm from beta-carotene supplementation. Investigation of the effect of vitamin E is ongoing (5).

4. Are antioxidants under investigation in current large-scale clinical trials?

Three large-scale clinical trials continue to investigate the effect of antioxidants on cancer. The objective of each of these studies is described below. More information about clinical trials can be obtained using http://www.cancer.gov/clinicaltrials, http://www.clinicaltrials.gov, or the CRISP database at http://crisp.cit.nih.gov/ on the Internet.
* The Women’s Health Study (WHS) is currently evaluating the effect of vitamin E in the primary prevention of cancer among U.S. female health professionals age 45 and older. The WHS is expected to conclude in August 2004.

* The Selenium and Vitamin E Cancer Prevention Trial (SELECT) is taking place in the United States, Puerto Rico, and Canada. SELECT is trying to find out if taking selenium and/or vitamin E supplements can prevent prostate cancer in men age 50 or older. The SELECT trial is expected to stop recruiting patients in May 2006.

* The Physicians' Health Study II (PHS II) is a follow up to the earlier clinical trial by the same name. The study is investigating the effects of vitamin E, C, and multivitamins on prostate cancer and total cancer incidence. The PHS II is expected to conclude in August 2007.

5. Will the National Cancer Institute (NCI) continue to investigate the effect of beta-carotene on cancer?

Given the unexpected results of ATBC and CARET, and the finding of no effect of beta-carotene in the PHS and WHS, NCI will follow the people who participated in these studies and will examine the long-term health effects of beta-carotene supplements. Post-trial follow-up has already been funded by NCI for CARET, ATBC, the Chinese Cancer Prevention Study, and the two smaller trials of skin cancer and colon polyps. Post-trial follow-up results have been published for ATBC, and as of July 2004 are in press for CARET and are in progress for the Chinese Cancer Prevention Study.
6. How might antioxidants prevent cancer?

Antioxidants neutralize free radicals as the natural by-product of normal cell processes. Free radicals are molecules with incomplete electron shells which make them more chemically reactive than those with complete electron shells. Exposure to various environmental factors, including tobacco smoke and radiation, can also lead to free radical formation. In humans, the most common form of free radicals is oxygen. When an oxygen molecule (O2) becomes electrically charged or “radicalized” it tries to steal electrons from other molecules, causing damage to the DNA and other molecules. Over time, such damage may become irreversible and lead to disease including cancer. Antioxidants are often described as “mopping up” free radicals, meaning they neutralize the electrical charge and prevent the free radical from taking electrons from other molecules.
7. Which foods are rich in antioxidants?

Antioxidants are abundant in fruits and vegetables, as well as in other foods including nuts, grains, and some meats, poultry, and fish. The list below describes food sources of common antioxidants.
* Beta-carotene is found in many foods that are orange in color, including sweet potatoes, carrots, cantaloupe, squash, apricots, pumpkin, and mangos. Some green, leafy vegetables, including collard greens, spinach, and kale, are also rich in beta-carotene.

* Lutein, best known for its association with healthy eyes, is abundant in green, leafy vegetables such as collard greens, spinach, and kale.

* Lycopene is a potent antioxidant found in tomatoes, watermelon, guava, papaya, apricots, pink grapefruit, blood oranges, and other foods. Estimates suggest 85 percent of American dietary intake of lycopene comes from tomatoes and tomato products.

* Selenium is a mineral, not an antioxidant nutrient. However, it is a component of antioxidant enzymes. Plant foods like rice and wheat are the major dietary sources of selenium in most countries. The amount of selenium in soil, which varies by region, determines the amount of selenium in the foods grown in that soil. Animals that eat grains or plants grown in selenium-rich soil have higher levels of selenium in their muscle. In the United States, meats and bread are common sources of dietary selenium. Brazil nuts also contain large quantities of selenium.

* Vitamin A is found in three main forms: retinol (Vitamin A1), 3,4-didehydroretinol (Vitamin A2), and 3-hydroxy-retinol (Vitamin A3). Foods rich in vitamin A include liver, sweet potatoes, carrots, milk, egg yolks, and mozzarella cheese.

* Vitamin C is also called ascorbic acid, and can be found in high abundance in many fruits and vegetables and is also found in cereals, beef, poultry, and fish.

* Vitamin E, also known as alpha-tocopherol, is found in almonds, in many oils including wheat germ, safflower, corn, and soybean oils, and is also found in mangos, nuts, broccoli, and other foods.

Selected References

1. Blot WJ, Li JY, Taylor PR, et al. Nutrition intervention trials in Linxian, China: supplementation with specific vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general population. J Natl Cancer Inst 1993;85:1483–91.

2. The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. The effects of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N Engl J Med 1994;330:1029–35.

3. Omenn GS, Goodman G, Thomquist M, et al. The beta-carotene and retinol efficacy trial (CARET) for chemoprevention of lung cancer in high risk populations: smokers and asbestos-exposed workers. Cancer Res 1994;54(7 Suppl):2038s–43s.

4. Hennekens CH, Buring JE, Manson JE, Stampfer M, Rosner B, Cook NR, et al. Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease. N Engl J Med 1996;334:1145–9.

5. Lee IM, Cook NR, Manson JE. Beta-carotene supplementation and incidence of cancer and cardiovascular disease: Women’s Health Study. J Natl Cancer Inst 1999;91:2102–6.

Fact Sheets: Risk Factors and Possible Causes

Key Points

* Acrylamide is a chemical used primarily for industrial purposes (see Question 1).
* Acrylamide has been found in certain foods, with especially high levels in potato chips, French fries, and other food products produced by high-temperature cooking (see Question 2).
* Food and cigarette smoke are the major sources of exposure to acrylamide (see Question 6).
* Acrylamide is considered to be a mutagen and a probable human carcinogen, based mainly on studies in laboratory animals (see Question 7).
* Scientists do not yet know with any certainty whether the levels of acrylamide typically found in some foods pose a health risk for humans (see Questions 7 and 10).

1. What is acrylamide?

Acrylamide is a chemical used primarily as a building block in making polyacrylamide and acrylamide copolymers. Polyacrylamide and acrylamide copolymers are used in many industrial processes, such as the production of paper, dyes, and plastics, and in the treatment of drinking water and wastewater, including sewage. They are also found in consumer products, such as caulking, food packaging, and some adhesives. Trace amounts of acrylamide generally remain in these products.
2. Is there acrylamide in food?

Researchers in Europe and the United States have found acrylamide in certain foods that were heated to a temperature above 120 degrees Celsius (248 degrees Fahrenheit), but not in foods prepared below this temperature (1). Potato chips and French fries were found to contain higher levels of acrylamide compared with other foods (2). The World Health Organization (WHO) and the Food and Agriculture Organization (FAO) stated that the levels of acrylamide in foods pose a “major concern” and that more research is needed to determine the risk of dietary acrylamide exposure (2).
3. How does cooking produce acrylamide?

Asparagine is an amino acid (a building block of proteins) that is found in many vegetables, with higher concentrations in some varieties of potatoes. When heated to high temperatures in the presence of certain sugars, asparagine can form acrylamide. High-temperature cooking methods, such as frying, baking, or broiling, have been found to produce acrylamide (3), while boiling and microwaving appear less likely to do so. Longer cooking times can also increase acrylamide production when the cooking temperature is above 120 degrees Celsius (4, 5).
4. Is there anything in the cooking process that can be changed to lower dietary acrylamide exposure?

Decreasing cooking time, blanching potatoes before frying, and postdrying (drying in a hot air oven after frying) have been shown to decrease the acrylamide content of some foods (6, 7).
5. Should I change my diet?

Acrylamide levels in food vary widely depending on the manufacturer, the cooking time, and the method and temperature of the cooking process (8, 9). The best advice at this time is to follow established dietary guidelines and eat a healthy, balanced diet that is low in fat and rich in high-fiber grains, fruits, and vegetables.
6. Are there other ways humans are exposed to acrylamide?

Food and cigarette smoke are the major sources of acrylamide exposure (10). Exposure to acrylamide from other sources is likely to be significantly less than that from food or smoking, but scientists do not yet have a complete understanding of all sources of exposure. Acrylamide and polyacrylamide are used in some industrial and agricultural procedures, and regulations are in place to limit exposure in those settings.
7. Does acrylamide increase the risk of cancer?

Studies in rodent models have found that acrylamide exposure poses a risk for several types of cancer (11, 12, 13). However, the evidence from human studies is still incomplete. The National Toxicology Program (NTP) and the International Agency for Research on Cancer consider acrylamide to be a “probable human carcinogen,” based on studies in laboratory animals given acrylamide in drinking water. However, toxicology studies have shown differences in acrylamide absorption rates between humans and rodents (14).

A series of case-control studies have investigated the relationship between dietary intake of acrylamide and the risk of developing cancers of the oral cavity, pharynx, esophagus, larynx, large bowel, kidney, breast, and ovary. These studies generally found no excess of tumors associated with acrylamide intake (15, 16, 17, 18, 19). In the studies, however, not all acrylamide-containing foods were included in estimating exposures. In addition, information in case-control studies about exposures is often based on interviews (personal or through questionnaires) with the case and control subjects, and these groups may differ in the accuracy of their recall about exposures. One factor that might influence recall accuracy in cancer-related dietary studies is that diets are often altered after receiving a diagnosis of cancer.

To avoid such limitations in accurately determining acrylamide exposure, biomarkers of exposure were recently used in a Danish cohort study designed to evaluate the subsequent risk of breast cancer in postmenopausal women (20). Among women with higher levels of acrylamide bound to the hemoglobin in their blood, there was a statistically significant increase in risk of estrogen receptor-positive breast cancer. This finding suggests an endocrine hormone-related effect, which would be consistent with the results of a questionnaire-based cohort study in the Netherlands that found an excess of endometrial and ovarian cancer—but not of postmenopausal breast cancer—associated with higher levels of acrylamide exposure (21). Another cohort study from the Netherlands suggested a positive association between dietary acrylamide and the risk of renal cell cancer, but not of prostate or bladder cancer (22).
8. What are other health effects of acrylamide?

High levels of acrylamide in the workplace have been shown to cause neurological damage, e.g., among workers using acrylamide polymers to clarify water in coal preparation plants (23).
9. Are acrylamide levels regulated?

The U.S. Environmental Protection Agency (EPA) regulates acrylamide in drinking water. The EPA established an acceptable level of acrylamide exposure, set low enough to account for any uncertainty in the data relating acrylamide to cancer and neurotoxic effects. The U.S. Food and Drug Administration regulates the amount of residual acrylamide in a variety of materials that come in contact with food, but there are currently no guidelines governing the presence of acrylamide in food itself.
10. What research is needed?

Although studies in rodent models suggest that acrylamide is a potential carcinogen, additional epidemiological cohort studies are needed to help determine any effects of dietary acrylamide intake on human cancer risk. It is also important to determine how acrylamide is formed during the cooking process and whether acrylamide is present in foods other than those already tested. This information will enable more accurate and comprehensive estimates of dietary exposure. Biospecimen collections in cohort studies will provide an opportunity to avoid the limitations of interview-based dietary assessments by examining biomarkers of exposure to acrylamide and its metabolites in relation to the subsequent risk of cancer.

For information about acrylamide in food from the WHO and FAO, please visit the WHO Web site at http://www.who.int/foodsafety/chem/chemicals/acrylamide/en on the Internet.

For information about acrylamide from the NTP’s Eleventh Report on Carcinogens, please visit http://ntp.niehs.nih.gov/index.cfm?objectid=32BA9724-F1F6-975E-7FCE50709CB4C932 on the Internet.

Acute Lymphoblastic Leukemia in Children

Acute Lymphoblastic Leukemia in Children
Key Points
* Acute lymphoblastic leukemia (ALL) is a cancer of the white blood cells, the cells in the body that normally fight infections.
* In ALL, the abnormal cells may collect in the brain or spinal cord, also called the central nervous system (CNS).
* In cancers such as leukemia that appear throughout the body during their earliest stages, screening does not appear to be useful. Rather, children with any symptoms that suggest the possibility of ALL should be seen by their physician.
* Although leukemia cells from different children with ALL often look very similar under the microscope, there are actually many distinctive subtypes of ALL.
* With the exception of prenatal exposure to X-rays and specific genetic syndromes, such as Down syndrome, little is known about the causes of and risk factors for childhood ALL.

1. What is acute lymphoblastic leukemia (ALL)?

Acute lymphoblastic leukemia (ALL) is a cancer of the white blood cells, the cells in the body that normally fight infections. There are two main types of white blood cells-lymphoid cells and myeloid cells. ALL affects lymphoid cells.

Leukemia cells are abnormal cells that cannot do what normal blood cells do. The abnormal cells are immature white blood cells that cannot help the body fight infections. For this reason, children with ALL often get infections and have fevers.

ALL is also called acute lymphocytic leukemia. It is the most common leukemia in children.

2. What are the symptoms of ALL?

Like all blood cells, leukemia cells travel through the body. Depending on the number of abnormal cells and where these cells collect, patients with leukemia may have a number of symptoms. Children with ALL frequently have low amounts of healthy red blood cells and platelets. As a result, there are not enough red blood cells to carry oxygen through the body. With this condition, called anemia, patients may look pale and feel weak and tired. When there are not enough platelets, patients bleed and bruise easily.

Some of the common symptoms of ALL include:
• Fever;
• Fatigue;
• Frequent infections;
• Swollen or tender lymph nodes, liver, or spleen;
• Paleness or pallor;
• Easy bleeding or bruising;
• Tiny red spots (called petechiae) under the skin; and/or
• Bone or joint pain.

In ALL, the abnormal cells may collect in the brain or spinal cord, also called the central nervous system (CNS). The result may be headaches with or without vomiting, although most children with the disease do not have these symptoms. Leukemia cells also can collect in the testicles and cause swelling.

3. Is there a screening test for ALL?

No. Screening is a means of detecting disease in people who have no symptoms. As described in the National Cancer Institute's "Cancer Screening Overview (PDQ)," two requirements must be met for screening to be useful:

(1) There must be a test or procedure that will detect cancers earlier than if the cancer were detected as a result of the development of symptoms and,

(2) There must be evidence that treatment initiated earlier as a consequence of screening results in an improved outcome.

These two requirements have not been met for childhood ALL.

In cancers such as leukemia that appear throughout the body during their earliest stages, screening does not appear to be useful. Rather, children with any symptoms that suggest the possibility of ALL should be seen by their physician. The physician can then examine the child and determine if further testing is needed.

4. How is ALL diagnosed?

If a child has symptoms that suggest leukemia, the physician may first order blood tests. A sample of blood is examined to determine the number of normal blood cells, to see what the cells look like, and to find out if any leukemia cells are present in the blood. For a definitive diagnosis of ALL, a doctor who specializes in leukemia examines a sample of bone marrow under a microscope. The sample is obtained by a procedure called bone marrow aspiration. In this procedure, the doctor inserts a needle into a large bone, usually the hip, and removes a small amount of liquid bone marrow for examination.

If leukemia cells are found in the bone marrow sample, the patient's doctor orders other tests to find out the extent of the disease. For example, a spinal tap, which is also called a lumbar puncture, checks for leukemia cells in the cerebrospinal fluid-the fluid that fills the spaces in and around the brain and spinal cord.

5. Are there different types of ALL?

Although leukemia cells from different children with ALL often look very similar under the microscope, there are actually many distinctive subtypes of ALL. Most cases of leukemia are associated with changes in genes and chromosomes in the cancerous white blood cells. The various subtypes of ALL can be identified using special laboratory tests that look for specific changes in genes and chromosomes. It is increasingly important for doctors treating children with ALL to determine their patients' subtype of ALL, as some treatments work better for some subtypes than for others.

6. How common is ALL?

Cancer in children and adolescents is rare. But, ALL is the most common cancer in children, representing 23 percent of cancer diagnoses among children younger than 15 years of age. It occurs in about one of every 29,000 children in the United States each year.

7. What causes ALL?

With the exception of prenatal exposure to X-rays and specific genetic syndromes, such as Down syndrome, little is known about the causes of and risk factors for childhood ALL.

Scientists know that ALL in children occurs slightly more often in boys than in girls and in white children more often than in black children. However, they cannot explain why one person gets leukemia and another does not.

8. What treatments are available for the disease?

There are treatments for all children with ALL. The primary treatment for ALL is chemotherapy. The specific drugs used for chemotherapy are different for the various subtypes of ALL and are not the same for all patients.

Treatment for children with ALL is complex and involves multiple drugs given in precise schedules over a period of two to three years. Because of this, children with the disease should be treated by doctors with experience and expertise in the treatment of childhood leukemias.

Many children with ALL participate in clinical trials. These studies test a new drug or a new combination of drugs, often comparing them to the current standard treatment. A participant will usually be assigned to the standard group or the new group by chance, a process called randomization. It is not known at the start of the trial whether the new treatment is better than, the same as, or worse than the standard treatment. Clinical trials for children with ALL often enroll large numbers of children and are conducted at children's cancer centers nationwide. Much of the success in curing children with ALL is the result of better treatments that were identified in such clinical trials. Still, doctors are doing clinical trials to try to improve ALL treatments and reduce side effects.

9. What is the survival rate for children with ALL?

The improvement in survival for children with ALL over the past 35 years is one of the great success stories of cancer treatment. In the 1960s, less than 5 percent of children with ALL survived for more than five years. Today, about 85 percent of children with ALL live five years or more.

10. What factors determine successful treatment for children with ALL?

The chance of survival for children with ALL is dependent upon a number of factors. The most important factor is receiving optimal care at a center experienced in the treatment of children with ALL. Even with optimal care, some children with ALL are much more difficult to treat successfully than others.

In the past, factors such as age and white blood cell count at diagnosis were commonly used to predict outcome. For example, children 1 to 9 years old have higher survival rates than do infants or older children. However, factors such as age and white blood cell count at diagnosis are, at best, crude predictors of outcome.

It is now clear that the patient's subtype of ALL has a powerful impact on survival. For example, infants commonly have a subtype of ALL in which a specific gene is modified. This subtype of ALL is very hard to treat successfully and only a minority of infants with this subtype of ALL survive with current therapy. Other subtypes of ALL in which different genes are modified occur more commonly in older children and have a much more favorable outcome.

It is now common practice for the leukemia cells of children with ALL to be tested for the gene modifications. The type of treatment is then based on the particular change seen in the leukemia cells.

Mesothelioma: Questions and Answers

# What is the mesothelium?

The mesothelium is a membrane that covers and protects most of the internal organs of the body. It is composed of two layers of cells: One layer immediately surrounds the organ; the other forms a sac around it. The mesothelium produces a lubricating fluid that is released between these layers, allowing moving organs (such as the beating heart and the expanding and contracting lungs) to glide easily against adjacent structures.

The mesothelium has different names, depending on its location in the body. The peritoneum is the mesothelial tissue that covers most of the organs in the abdominal cavity. The pleura is the membrane that surrounds the lungs and lines the wall of the chest cavity. The pericardium covers and protects the heart. The mesothelial tissue surrounding the male internal reproductive organs is called the tunica vaginalis testis. The tunica serosa uteri covers the internal reproductive organs in women.

# What is mesothelioma?

Mesothelioma (cancer of the mesothelium) is a disease in which cells of the mesothelium become abnormal and divide without control or order. They can invade and damage nearby tissues and organs. Cancer cells can also metastasize (spread) from their original site to other parts of the body. Most cases of mesothelioma begin in the pleura or peritoneum.

# How common is mesothelioma?

Although reported incidence rates have increased in the past 20 years, mesothelioma is still a relatively rare cancer. About 2,000 new cases of mesothelioma are diagnosed in the United States each year. 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.

# What are the risk factors for mesothelioma?

Working with asbestos is the major risk factor for mesothelioma. A history of asbestos exposure at work is reported in about 70 percent to 80 percent of all cases. However, mesothelioma has been reported in some individuals without any known exposure to asbestos.

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.

Smoking does not appear to increase the risk of mesothelioma. However, the combination of smoking and asbestos exposure significantly increases a person's risk of developing cancer of the air passageways in the lung.

# Who is at increased risk for developing mesothelioma?

Asbestos has been mined and used commercially since the late 1800s. Its use greatly increased during World War II. Since the early 1940s, millions of American workers have been exposed to asbestos dust. Initially, the risks associated with asbestos exposure were not 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. People who work with asbestos wear personal protective equipment to lower their risk of exposure.

The risk of asbestos-related disease increases with heavier exposure to asbestos and longer exposure time. However, some individuals with only brief exposures have developed mesothelioma. On the other hand, not all workers who are heavily exposed develop asbestos-related diseases.

There is some evidence that 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 fibers, asbestos workers are usually required to shower and change their clothing before leaving the workplace.

# What are the symptoms of mesothelioma?

Symptoms of mesothelioma may not appear until 30 to 50 years after exposure to asbestos. Shortness of breath and pain in the chest due to an accumulation of fluid in the pleura are often symptoms of pleural mesothelioma. Symptoms of peritoneal mesothelioma include weight loss and abdominal pain and swelling due to a buildup of fluid in the abdomen. 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. It is important to see a doctor about any of these symptoms. Only a doctor can make a diagnosis.

# How is mesothelioma diagnosed?

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, including any history of asbestos exposure. A complete physical examination may be performed, including x-rays of the chest or abdomen and lung function tests. A CT (or CAT) scan or an MRI may also be useful. A CT scan is a series of detailed pictures of areas inside the body created by a computer linked to an x-ray machine. In an MRI, a powerful magnet linked to a computer is used to make detailed pictures of areas inside the body. These pictures are viewed on a monitor and can also be printed.

A biopsy is needed to confirm a diagnosis of mesothelioma. In a biopsy, a surgeon or a medical oncologist (a doctor who specializes in diagnosing and treating cancer) 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 peritoneoscopy. To obtain tissue for examination, the doctor makes a small opening in the abdomen and inserts a special instrument called a peritoneoscope into the abdominal cavity. If these procedures do not yield enough tissue, more extensive diagnostic surgery may be necessary.

If the diagnosis is mesothelioma, the doctor will want to learn the stage (or extent) of the disease. Staging involves more tests in a careful attempt to find out whether the cancer has spread and, if so, to which parts of the body. Knowing the stage of the disease helps the doctor plan treatment.

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.

# How is mesothelioma treated?

Treatment for mesothelioma depends on the location of the cancer, the stage of the disease, and the patient's age and general health. Standard treatment options include surgery, radiation therapy, and chemotherapy. Sometimes, these treatments are combined.

* Surgery is a common treatment for mesothelioma. The doctor may remove part of the lining of the chest or abdomen and some of the tissue around it. For cancer of the pleura (pleural mesothelioma), a lung may be removed in an operation called a pneumonectomy. Sometimes part of the diaphragm, the muscle below the lungs that helps with breathing, is also removed.

* Radiation therapy, also called radiotherapy, involves the use of high-energy rays to kill cancer cells and shrink tumors. Radiation therapy affects the cancer cells only in the treated area. The radiation may come from a machine (external radiation) or from putting materials that produce radiation through thin plastic tubes into the area where the cancer cells are found (internal radiation therapy).

* Chemotherapy is the use of anticancer drugs to kill cancer cells throughout the body. Most drugs used to treat mesothelioma are given by injection into a vein (intravenous, or IV). Doctors are also studying the effectiveness of putting chemotherapy directly into the chest or abdomen (intracavitary chemotherapy).

To relieve symptoms and control pain, the doctor may use a needle or a thin tube to drain fluid that has built up in the chest or abdomen. The procedure for removing fluid from the chest is called thoracentesis. Removal of fluid from the abdomen is called paracentesis. Drugs may be given through a tube in the chest to prevent more fluid from accumulating. Radiation therapy and surgery may also be helpful in relieving symptoms.

# Are new treatments for mesothelioma being studied?

Yes. Because mesothelioma is very hard to control, the National Cancer Institute (NCI) is sponsoring clinical trials (research studies with people) that are designed to find new treatments and better ways to use current treatments. Before any new treatment can be recommended for general use, doctors conduct clinical trials to find out whether the treatment is safe for patients and effective against the disease. Participation in clinical trials is an important treatment option for many patients with mesothelioma.

People interested in taking part in a clinical trial should talk with their doctor. Information about clinical trials is available from the Cancer Information Service (CIS) (see below) at 1–800–4–CANCER. Information specialists at the CIS use PDQ®, NCI's cancer information database, to identify and provide detailed information about specific ongoing clinical trials. Patients also have the option of searching for clinical trials on their own. The clinical trials page on the NCI's Cancer.gov Web site, located at http://www.cancer.gov/clinicaltrials on the Internet, provides general information about clinical trials and links to PDQ.

People considering clinical trials may be interested in the NCI booklet Taking Part in Cancer Treatment Research Studies. This booklet describes how research studies are carried out and explains their possible benefits and risks. The booklet is available by calling the CIS, or from the NCI Publications Locator Web site at http://www.cancer.gov/publications on the Internet.

Mesothelioma Research Charities

The Mick Knighton Mesothelioma Research Fund
c/o British Lung Foundation
Sir G B Hunter Memorial Hospital The Green
Wallsend
Tyne & Wear
NE28 7PB

Website: www.mickknightonmesorf.org
Email: c.knighton@mkmrf.org.uk
Telephone: 0191 2630276
Cheque payee: Mick Knighton Mesothelioma Research Fund

The June Hancock Mesothelioma Research Fund
c/o Adrian Budgen, Irwin Mitchell
Riverside East
2 Millsands
Sheffield
S3 8DT

Website: www.junehancockfund.org
Email: info@junehancockfund.org
Telephone: 0114 2744420
Cheque payee: June Hancock Mesothelioma Research Fund

Special Trustees of St Bartholomew's Hospital
Dr Jeremy Steele
Mesothelioma Group
Department of Medical Oncology
St Bartholomew's Hospital
London
EC1A 7BE

Website: www.mesothelioma.co.uk
Email: jeremy.steele@bartsandthelondon.nhs.uk
Cheque payee: Special Trustees of St Bartholomew's Hospital
(this will be forwarded to Bart's Mesothelioma Research Fund Account)

Symptom Control in Mesothelioma

This section describes symptoms that may be experienced by people with Mesothelioma. It will include how these symptoms can be managed, based on medical evidence wherever possible. With care, much can be done to lessen the impact of most symptoms. In complex cases this requires the involvement of a variety of professionals - the multidisciplinary approach - such as doctors from palliative medicine and pain specialists, oncologists (cancer specialists), specialist nurses, physiotherapists, complementary therapists, psychologists and others. UK trade names for medicines are placed in brackets when used.

This section does not contain an exhaustive list of symptoms that may occur in mesothelioma. If you are concerned about any symptoms do go and discuss them with your GP, Macmillan nurse or hospital consultant and ask for specialist referral if the problems persist.

All terms in bold in this section can be found in the Glossary.

Clinical Trials

Cancer trials are carried out to try to find new and better treatments for cancer. Trials that are carried out on patients are known as clinical trials.

Many drugs and treatments that have been tested in clinical trials are now in common use and without ongoing clinical trials it would not be possible to add to the current knowledge about effective treatments.

Clinical trials of a new treatment rarely stop when specialists agree that it works. There may be better ways of using it, such as giving it in different doses or combining it with other treatments.

The National Cancer Research Network (NCRN) provides the NHS with the infrastructure to support cancer clinical trials in England.

Listed below are the trials currently open or under development for mesothelioma. If you would like further information about clinical trials please speak with your doctor/nurse specialist.
MesoVATS Trial
A study to compare a surgical treatment with a medical treatment for patients with a pleural effusion due to mesothelioma.

For most patients with mesothelioma the first symptom is shortness of breath, which is caused by a build up of fluid around the lungs (pleural effusion). The most common method of controlling the collection of fluid is by inserting a chest drain in the space between the lung and the chest wall, which will drain away the fluid, followed by the insertion of talc to stick the lung up against the chest wall to prevent further collection of fluid (medical pleurodesis).

Over the past five years an alternative procedure has been available namely a video assisted thoracoscopic (VATS) surgical pleurectomy. This procedure appears to be very effective at controlling the build up of fluid around the lungs and may improve survival. However, it may possibly cause more complications because it involves surgery.

The Trial will compare the two procedures to see whether the (VATS) Surgical Pleurectomy offers any benefit over the medical pleurodesis in terms of control of symptoms, improving survival, preventing the fluid in the chest cavity from coming back and your quality of life.

Please follow this link to Cancer Research UK's information on this trial http://www.cancerhelp.org.uk/trials/trials/trial.asp?=&trialno=4855
Mesothelioma and Lung Cancer Study (MALCS)
This study is looking at the occupations of men and women and the development of mesothelioma and lung cancer in relation to occupation.

Please follow this link to Cancer Research UK's information on this trial http://www.cancerhelp.org.uk/trials/trials/trial.asp?=&trialno=2253

Mesothelioma UK

Mesothelioma UK provides impartial up-to-date information for patients diagnosed with Mesothelioma and their carers. The Centre supports the development of specialist nursing practice and research which promotes the highest possible standards of care. A Consultant Nurse is the lead for Mesothelioma UK.

There is a free phone helpline available which provides access to timely, accurate and relevant advice for patients, carers and health care professionals. Callers are able to access local information and support and be signposted to relevant websites.

Member of the Telephone Helplines Association - Mesothelioma UK is a member of the Telephone Helplines Association (THA). The THA is a member organisation supporting the development of professional standards for helpline provision in the UK voluntary and statutory sectors.
4th Mesothelioma UK Patient and Carer Day 2009
Date: Saturday 3rd October 2009
Venue: Life Conference Centre, Newcastle
This event is kindly supported by a grant from the Mick Knighton Mesothelioma Research Fund.

The objectives for the day are to give mesothelioma patients and carers the chance to meet and share experiences with others affected by the disease and to give up-to-date, unbiased information on treatment and care, clinical research, peritoneal mesothelioma, campaigning for mesothelioma, legal and compensation issues, complementary therapies and living with mesothelioma. The programme for the day is currently in development.

Places at the day are free of charge for mesothelioma patients, their carers, relatives and friends. A charge will be made to voluntary organisations, health professionals and related industry representatives who wish to attend.

Asbestosis

Asbestosis is a chronic inflammatory medical condition affecting the parenchymal tissue of the lungs. It occurs after long-term, heavy exposure to asbestos, e.g. in mining, and is therefore regarded as an occupational lung disease. Sufferers have severe dyspnea (shortness of breath) and are at an increased risk regarding several different types of lung cancer.

As clear explanations are not always stressed in non-technical literature, care should be taken to distinguish between several forms of relevant diseases. According to the World Health Organisation (WHO), these may be defined as; asbestosis (the subject of this article), lung cancer, and mesothelioma (generally a very rare form of cancer, but increasing in frequency as people exposed to asbestos age).

Mesothelioma Applied Research Foundation

The Mesothelioma Applied Research Foundation (Meso Foundation, formerly MARF) is a non-profit organization that funds mesothelioma research, provides services to patients, educates the public, and advocates in Washington, DC for governmental funding for mesothelioma research. The organization's mission is to eradicate mesothelioma as a life-ending disease.

Mesothelioma is a cancer caused by exposure to asbestos.

To date, the Foundation has funded over $5 million in clinical research and is the host of the annual International Symposium on Malignant Mesothelioma.

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.

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 complementary modalities and has written a book about his experience.

[edit] Legal issues
Main article: Asbestos and the law

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.[27]

[edit] 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.

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.

[edit] 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.

[edit] 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.

[edit] 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.

[edit] Radiation
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Radiation Oncology/Lung/Mesothelioma

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.

[edit] 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.

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.

[edit] 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]

[edit] 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.

[edit] 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]

[edit] 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.

[edit] 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.

[edit] 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
* P16INK4A
* P14ARF

Asbestos has also been shown to mediate the entry of foreign DNA into target cells. Incorporation of this foreign DNA may lead to mutations and oncogenesis by several possible mechanisms:

* Inactivation of tumor suppressor genes
* Activation of oncogenes
* Activation of proto-oncogenes due to incorporation of foreign DNA containing a promoter region
* Activation of DNA repair enzymes, which may be prone to error
* Activation of telomerase
* Prevention of apoptosis

Asbestos 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.

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)

[edit] 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]

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Mesothelioma Cancer Center

The link www.asbestos.com has been removed after being added, I wished to start a discussion about this and explain it is NOT a law firm, merely one of the sponsors IS a law firm.

I understand your linking policy and respect that you only want to include links that you feel are educational and are funded by individuals/organizations that are credible. However, asbestos exposure is an incredibly serious issue that directly causes life-threatening diseases such as mesothelioma cancer, asbestosis, and other forms of cancer. Asbestos.com is a completely separate entity from "the Peterson Firm", They merely provide most of the funding for the educational site [asbestos.com]. Asbestos.com is actually funded by a multiple number of organizations, all of which have the goal of educating the public about the dangers of asbestos exposure.

Just recently Asbestos.com has achieved HON code approval (Health On the Net (HON) Foundation is a not-for-profit foundation that works to preserve the accuracy and trustworthiness of Web-based medical information). They also at first denied our application for HON, until we explained to them the same thign I'm explaining to you, and they had a chance to look through the 2,000 pages of Doctor reviewed and edited material. Our site has employed a full staff of writers dedicated to research and writing about asbestos exposure and the diseases that result from exposure to the toxic mineral. In addition, our site has hired a medical adviser and editor, Dr. Mauricio Salazar,M.D., who has worked in the field of cancer treatment for years, has personally reviewed, edited, and approved all medical information on our site. Asbestos.com has a knowledgeable 24-year navy veteran on staff that helps any veteran who fills out a form or calls 1-800-asbestos with all VA claims. He has helped over 1,000 veterans file and complete VA claims since the Mesothelioma Cancer Center was founded. All of these services on the site, from the free books and informational packets to suffers, to the VA claim assistance, are completely Free. The only reason we are able to offer these services for free to the public is because of our funding from all of the organizations that support us (especially the peterson firm).

Again I’d like you to just consider us once more as a resource for your site because I believe we offer unique information and services that no other sites offer, Thank you again for taking time out of your day to talk to me about this, I hope to hear back from you regardless of your decision in the matter. Have a great day.

Timothy Cavanaugh —Preceding unsigned comment added by Elkyyy (talk • contribs) 17:08, 14 November 2008 (UTC)

Tim, the issue is the intent. The content on asbestos.com is well-written and pretty comprehensive but the reason that sites like asbestos.com, maacenter.org, mesotheliomaweb.org, mesothelioma.com, mesotheliomanews.com etc ... even exist is to recruit clients for one of the most profitable mass litigation industries.

Putting a link to asbestos.com would open up the floodgates and soon half of the content on the page would be links to law firms or sourced to pages on their sites, which in turn hurts the credibility of Wikipedia because it is an implicit endorsement. I'm sure there are links on a number of pages that go to law firm sites but the value of a link on wikipedia for mesothelioma would improve your competitive advantage in SEO (yes it's nofollowed but Google does have trust rank) and probably get you guys some more cases (avg settlement 200k at a near 70% success rate)which in turn means profiting over the credibility of wikipedia.

Right now I did a search for mesothelioma and asbestos.com occupied the third and fourth results positions. Isn't that good enough for you guys?

Also you weren't honest in the above section, you mentioned funding from multiple organizations, I didn't see anything on the site. Also with the money the site is making, why would there be a need for funding from multiple sources?

Also I did a Whois search and the contact info for asbestos.com was:

Asbestos & Mesothelioma Awareness Group (I'd like to see you prove this "group" exists in real life)
3208 E. Colonial Drive
Suite 180
Orlando, Florida 32803
United States

You claim that "Asbestos.com is a completely separate entity from "the Peterson Firm" yet visiting petersonfirm.com reveals that they are headquartered a mere 3 miles away at 20 N. Orange Ave (according to Google Maps).

I have a hard time believing that this "separate entity" is conveniently located 8 minutes from their sponsor.

Mesothelioma

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. Washing the clothes of a family member who worked with asbestos can also 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.