Sunday, July 19, 2009

Chronic Cough

Some common causes of chronic cough include asthma, allergic rhinitis, sinus problems (for example sinus infection), and esophageal reflux of stomach contents. In rare occasions, chronic cough may be the result of aspiration of foreign objects into the lungs (usually in children). It is very important to obtain a chest x-ray if a chronic cough is present. The following pertains to patients who have a normal chest x-ray.
Cigarette smoking is the most common cause of chronic cough.
Asthma is a disease of airways, resulting in difficulty breathing or wheezing often characterized by abnormal breathing tests. Some asthma sufferers have chronic cough as their only symptom. They may even have normal lung functions tests. This is often referred to as cough-variant asthma. Asthma symptoms can be aggravated by cold air, exposure to air pollutants or pollen, smoke, or perfumes. For further reading, please read the Asthma article.
Gastroesophageal reflux disease (GERD) refers to reflux, or backward flow, of stomach acid and other contents into the esophagus. If stomach acid moves backward up the esophagus, reflexes result in spasm of the airways that can cause shortness of breath and coughing. In some instances, reflux can be so severe that substances can be aspirated into the lungs and cause similar symptoms as well as damage to lung tissue. In some individuals, no sensation of heartburn is felt and their only symptom may be cough.
Sinus problems and postnasal drip can also cause chronic cough. This condition can be difficult to detect. Sometimes CT scan of the sinuses is necessary for diagnosis. Patients often complain of a "tickle in their throat" and frequent throat clearing. For further reading, please read the Sinus Infection article.
Infections such as bronchitis or pneumonia can cause coughing. These infections can be caused by virus, bacteria or fungus. Viral infections do not respond to antibiotics. In patients with asthma, viral upper respiratory infections often result in a protracted cough even after the infection has cleared.
Certain medications, notably ace inhibitors [enalapril (Vasotec), captopril (Capoten) etc.] used in treating high blood pressure, can cause chronic cough.
Less common causes can also include tumors, sarcoidosis or other lung disease.

Lung Cancer

What is cancer of the lung?
Cancer of the lung, like all cancers, results from an abnormality in the body's basic unit of life, the cell. Normally, the body maintains a system of checks and balances on cell growth so that cells divide to produce new cells only when needed. Disruption of this system of checks and balances on cell growth results in an uncontrolled division and proliferation of cells that eventually forms a mass known as a tumor.
Tumors can be benign or malignant; when we speak of "cancer," we refer to those tumors that are considered malignant. Benign tumors can usually be removed and do not spread to other parts of the body. Malignant tumors, on the other hand, grow aggressively and invade other tissues of the body, allowing entry of tumor cells into the bloodstream or lymphatic system and then to other sites in the body. This process of spread is termed metastasis; the areas of tumor growth at these distant sites are called metastases. Since lung cancer tends to spread or metastasize very early in its course, it is a very life-threatening cancer and one of the most difficult cancers to treat. While lung cancer can spread to any organ in the body, certain organs -- particularly the adrenal glands, liver, brain, and bone -- are the most common sites for lung-cancer metastasis.

Health Tip: Don't Abuse Alcohol

HealthDay News) -- An occasional glass of beer or wine may help you relax, but excessive alcohol consumption is dangerous.
The U.S. Centers for Disease Control and Prevention says drinking too much increases the risk of:
Accident and injury, including car accidents, drowning and falling.
Miscarriage and stillbirth.
Physical and mental birth defects for your baby.
Alcohol poisoning.
Neurologic problems and dementia.
Cardiovascular issues, including heart attack and high blood pressure.
Anxiety and depression.
Cancer.
Liver disease.
Gastrointestinal tract problems.

Neutropenia

Neutropenia" is a condition in which the number of neutrophils in the bloodstream is decreased. Neutrophils are a type of white blood cell also known as polymorphonuclear leukocytes or PMNs. Neutropenia affects the body's ability to fight off infections.
White blood cells are also known as leukocytes. There are five major types of white blood cells:

Sexually Transmitted Diseases

Sexually transmitted diseases (STDs) are infections that can be transferred from one person to another through any type of sexual contact. STDs are sometimes referred to as sexually transmitted infections (STIs) since they involve the transmission of a disease-causing organism from one person to another during sexual activity. It is important to realize that sexual contact includes more than just sexual intercourse (vaginal and anal). Sexual contact includes kissing, oral-genital contact, and the use of sexual "toys," such as vibrators. STDs probably have been around for thousands of years, but the most dangerous of these conditions, the acquired immunodeficiency syndrome (AIDS), has only been recognized since 1984.
Many STDs are treatable, but effective cures are lacking for others, such as HIV, HPV, and hepatitis B and C. Even gonorrhea, once easily cured, has become resistant to many of the older traditional antibiotics. Many STDs can be present in, and spread by, people who do not have any symptoms of the condition and have not yet been diagnosed with an STD. Therefore, public awareness and education about these infections and the methods of preventing them is important.
There really is no such thing as "safe" sex. The only truly effective way to prevent STDs is abstinence. Sex in the context of a monogamous relationship wherein neither party is infected with a STD also is considered "safe." Most people think that kissing is a safe activity. Unfortunately, syphilis, herpes, and other infections can be contracted through this relatively simple and apparently harmless act. All other forms of sexual contact carry some risk. Condoms are commonly thought to protect against STDs. Condoms are useful in decreasing the spread of certain infections, such as chlamydia and gonorrhea; however, they do not fully protect against other infections such as genital herpes, genital warts, syphilis, and AIDS. Prevention of the spread of STDs is dependent upon the counseling of at-risk individuals and the early diagnosis and treatment of infections

Cervical Cancer

The cervix is part of a woman's reproductive system. It is the lower, narrow part of the uterus (womb). The uterus is a hollow, pear-shaped organ in the lower abdomen. The cervix connects the uterus to the vagina. The vagina leads to the outside of the body.
The cervical canal is a passageway. Blood flows from the uterus through the canal into the vagina during a woman's menstrual period. The cervix also produces mucus. The mucus helps sperm move from the vagina into the uterus. During pregnancy, the cervix is tightly closed to help keep the baby inside the uterus. During childbirth, the cervix dilates (opens) to allow the baby to pass through the vagina.

Breast Cancer

Your mammogram is suspicious for breast cancer." "Your biopsy was positive for breast cancer." These are among the most terrifying words a woman can hear from her doctor. Breast cancer elicits so many fears, including those relating to surgery, death, loss of body image and loss of sexuality. Managing these fears can be facilitated by information and knowledge so that each woman can make the best decisions concerning her care. Optimally, these issues are best discussed with the patient's doctor on an individual basis. What follows is a review of information on breast cancer intended to aid patients and their families in their navigation through the vast ocean of breast cancer issues.

Exams For Both Men And Women

Skin - The doctor should examine your skin during regular checkups for signs of skin cancer. You should also check regularly for new growths, sores that do not heal, changes in the size, shape, or color of any moles, or any other changes on the skin. Warning signs like these should be reported to the doctor right away.
Colon and Rectum - Beginning at age 50, you should have a yearly fecal occult blood test. This test is a check for hidden (occult) blood in the stool. A small amount of stool is placed on a plastic slide or on special paper. It may be tested in the doctor's office or sent to a lab. This test is done because cancer of the colon and rectum can cause bleeding. However, noncancerous conditions can also cause bleeding, so having blood in the stool does not necessarily mean a person has cancer. If blood is found, the doctor orders more tests to help make a diagnosis.
To check for cancer of the rectum, the doctor inserts a gloved finger into the rectum and feels for any bumps or abnormal areas. A digital rectal exam should be done during regular checkups.
Every 3 to 5 years after age 50, an individual should have sigmoidoscopy. In this exam, the doctor uses a thin, flexible tube with a light to look inside the rectum and colon for abnormal areas.
Mouth - Your doctor and dentist should examine your mouth at regular visits. Also, by looking in a mirror, you can check inside your mouth for changes in the color of the lips, gums, tongue, or inner cheeks, and for scabs, cracks, sores, white patches, swelling, or bleeding. It is often possible to see or feel changes in the mouth that might be cancer or a condition that might lead to cancer. Any symptoms in your mouth should be checked by a doctor or dentist. Oral exams are especially important for people who use alcohol or tobacco products and for anyone over age 50.
Exams For MenProstate - Men over age 40 should have a yearly digital rectal exam to check the prostate gland for hard or lumpy areas. The doctor feels the prostate through the wall of the rectum.

How can cancer be detected early?

In many cases, the sooner cancer is diagnosed and treated, the better a person's chance for a full recovery. If you develop cancer, you can improve the chance that it will be detected early if you have regular medical checkups and do certain self-exams. Often a doctor can find early cancer during a physical exam or with routine tests, even if a person has no symptoms. Some important medical exams, tests, and self- exams are discussed on the next pages. The doctor may suggest other exams for people who are at increased risk for cancer.
Ask your doctor about your cancer risk, problems to watch for, and a schedule of regular checkups. The doctor's advice will be based on your age, medical history, and other risk factors. The doctor also can help you learn about self-exams. (More information and free booklets about self-exams are available from the Cancer Information Service).
Many local health departments have information about cancer screening or early detection programs. The Cancer Information Service also can tell you about such programs.

What is the brain

The brain is a soft, spongy mass of tissue. It is protected by the bones of the skull and three thin membranes called meninges. Watery fluid called cerebrospinal fluid cushions the brain. This fluid flows through spaces between the meninges and through spaces within the brain called ventricles.
A network of nerves carries messages back and forth between the brain and the rest of the body. Some nerves go directly from the brain to the eyes, ears, and other parts of the head. Other nerves run through the spinal cord to connect the brain with the other parts of the body. Within the brain and spinal cord, glial cells surround nerve cells and hold them in place.
The brain directs the things we choose to do (like walking and talking) and the things our body does without thinking (like breathing). The brain is also in charge of our senses (sight, hearing, touch, taste, and smell), memory, emotions, and personality.
The three major parts of the brain control different activities:
Cerebrum - The cerebrum is the largest part of the brain. It is at the top of the brain. It uses information from our senses to tell us what is going on around us and tells our body how to respond. It controls reading, thinking, learning, speech, and emotions.
The cerebrum is divided into the left and right cerebral hemispheres, which control separate activities. The right hemisphere controls the muscles on the left side of the body. The left hemisphere controls the muscles on the right side of the body.
Cerebellum - The cerebellum is under the cerebrum at the back of the brain. The cerebellum controls balance and complex actions like walking and talking.
Brain Stem - The brain stem connects the brain with the spinal cord. It controls hunger and thirst. It also controls breathing, body temperature, blood pressure, and other basic body functions.

Risk factors

Doctors often cannot explain why one person develops cancer and another does not. But research shows that certain risk factors increase the chance that a person will develop cancer. These are the most common risk factors for cancer:
Growing older
Tobacco
Sunlight
Ionizing radiation
Certain chemicals and other substances
Some viruses and bacteria
Certain hormones
Family history of cancer
Alcohol
Poor diet, lack of physical activity, or being overweight
Many of these risk factors can be avoided. Others, such as family history, cannot be avoided. People can help protect themselves by staying away from known risk factors whenever possible.
If you think you may be at risk for cancer, you should discuss this concern with your doctor. You may want to ask about reducing your risk and about a schedule for checkups.
Over time, several factors may act together to cause normal cells to become cancerous.

Saturday, July 18, 2009

Fever:

fever is a very non-specific symptom of many mild to severe conditions, including cancer. In relation to cancer, a fever that is persistent or one that comes and goes frequently can signal stress on the immune system. Fevers are commonly associated with types of cancer that affects the blood, like leukemia and lymphoma, but are also common in people whose cancer

Pain

Typically, pain is not an early symptom of cancer, except in some cancer types like those that spread to the bone. Pain generally occurs when cancer spreads and begins to affect other organs and ner

Unintentional Weight Loss

welcome surprise to lose weight without trying, it can be a red flag for many illnesses, including cancer. Losing 10 pounds or more unintentionally definitely warrants a visit to the doctor. This type of weight loss can occur with or without loss of appetite. Remember, weight loss can be a symptom of cancer, but is also a symptom of many other illnesses, too.

cancer types

Anemia is commonly the culprit -- a condition that is associated with many types of cancer, especially types affecting the bowel. Fatigue is a symptom of both malignant and non-malignant conditions and should be evaluated by a physician.

Symptoms of Cancer

Cancer is a broad term that encompasses over one hundred different types of cancer. Although each type has its own set of characteristics, there are some cancer symptoms that occur in many types of cancer.
It is important to note that some types of cancer do not present any symptoms until they are in advanced stages. This is why cancer screening and risk assessment are vital for cancer prevention and early detection.

Wednesday, July 15, 2009

about MESOTHELIOMA

For those diagnosed with mesothelioma, an asbestos-related cancer of the

lining

of the lung (pleura) or the lining of the abdominal cavity (peritoneum), finding a

credible source of information about the disease itself and the medical options

available, is of the highest priority. After years of research and synthesis of

information, we have assembled a web site and packet for patients and their

loved ones. We hope you find this web site helpful.


A mesothelioma diagnosis can be overwhelming, and we are here to answer any

questions you might have, and to help you take the steps necessary to find the

options that are best suited to your individual needs.


Our staff is experienced and knowledgeable in dealing with mesothelioma

patients and their family members, and the service we provide is always with

appreciation for the difficult time you are facing. Although you have found us on

the Internet, rest assured there are real people here to help. Please feel free to

contact us at any time at 1-877-FOR-MESO (367-6376)

Mesothelioma: Questions and Answers

Mesothelioma is a rare form of cancer in which malignant (cancerous) cells are found in the mesothelium, a protective sac that covers most of the body's internal organs. Most people who develop mesothelioma have worked on jobs where they inhaled asbestos particles.

  1. What is the mesothelium?
  2. 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.

  3. What is mesothelioma?
  4. 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.

  5. How common is mesothelioma?
  6. 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.

  7. What are the risk factors for mesothelioma?
  8. 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 thelarynx 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.

  9. Who is at increased risk for developing mesothelioma?
  10. 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.

  11. What are the symptoms of mesothelioma?
  12. 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.

  13. How is mesothelioma diagnosed?
  14. 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 MRImay 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 medicaloncologist (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.

  15. How is mesothelioma treated?
  16. 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.

  17. Are new treatments for mesothelioma being studied?
  18. 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

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 pericardiumare removed.

[edit]Radiation

For patients with localized disease, and who can tolerate a radical surgery, radiation is often given post-operatively as a consolidative treatment. The entire hemi-thorax is treated with radiation therapy, often given simultaneously with chemotherapy. This approach of using surgery followed by radiation with chemotherapy has been pioneered by the thoracic oncology team at Brigham & Women's Hospital in Boston.[16] Delivering radiation and chemotherapy after a radical surgery has led to extended life expectancy in selected patient populations with some patients surviving more than 5 years. As part of a curative approach to mesothelioma, radiotherapy is also commonly applied to the sites of chest drain insertion, in order to prevent growth of the tumor along the track in the chest wall.

Although mesothelioma is generally resistant to curative treatment with radiotherapy alone, palliative treatment regimens are sometimes used to relieve symptoms arising from tumor growth, such as obstruction of a major blood vessel. Radiation therapy when given alone with curative intent has never been shown to improve survival from mesothelioma. The necessary radiation dose to treat mesothelioma that has not been surgically removed would be very toxic.

[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 andpemetrexed (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.

[edit]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.

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 centralCappadocia, 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 withchromosomes, 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 ismonosomy 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.