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| Adenocarcinoma is the most common non-small cell cancer of the lung; it is often seen in nonsmokers and women. You probably will not have any symptoms when the cancer is found on a chest x-ray. |
| Squamous cell carcinoma is the type of lung cancer that smokers tend to get. It sometimes located near or in a major airway, so the cancer can cause symptoms earlier in its growth. Coughing, producing bloody phlegm (sputum), shortness of breath, or pneumonia are common symptoms. It usually does not spread to distant sites in the body. It is more likely than other types of lung cancers to be cured with surgery. |
| Large cell carcinomas represent about 10% of non-small cell cancers of the lung. It grows and spreads quickly, often spreading to other parts of the body including the brain. Large cell carcinoma does not have the specific features (such as cell shape or location of growth) of any of the other lung cancer cell types mentioned. Frequently it will turn out to be one of the subtypes if further tissue is obtained. |
Small cell carcinomas are almost always found in patients who are smokers. They are the most aggressive types of lung cancers. Small cell cancer (sometimes called oat cell cancer) accounts for 15% to 25% of the lung cancer cases diagnosed annually. Symptoms don't usually develop until the cancer has progressed significantly.
Small cell cancers rapidly grow and spread (metastasize) to distant sites, and often have spread by time of discovery. Although both types of lung cancer are dangerous, prognosis for small cell cancer is usually worse than prognosis for non-small cell cancer.
Symptoms
Symptoms of lung cancer vary according to what type of lung cancer you have and where it is located in the lungs. Some symptoms of lung cancer, when and if they occur, are persistent coughing, shortness of breath, blood in the sputum and wheezing.
Symptoms of lung cancer don't usually occur until the disease has become significantly worse. Symptoms may be noticed once the cancerous mass of cells, called a tumor (carcinoma) has increased in size, invaded surrounding tissue, or spread to other parts of the body. Persistent coughing, shortness of breath, blood in the sputum, and wheezing are possible symptoms. Recurring pneumonia may be a sign of cancer, and deserves further investigation. If the cancer has spread to surrounding tissue, you may also experience chest or shoulder pain, hoarseness, and difficulty swallowing. If it has reached other parts of the body, weight loss, fatigue, bone pain, yellowing of the skin, lumps under the skin, weakness in the arms and legs, headaches, seizures, and other symptoms may occur, depending on where the tumor has metastasized.
You may experience different symptoms depending on the disease's progression and what type of lung cancer you have.
Table 2. Potential Symptoms of Lung Cancer According to Stage
| Local (small area of lung) | Cancer has spread within the lung | Cancer has spread to other body systems |
|---|---|---|
| Shortness of breath | Shortness of breath | Weight loss, often dramatic, leading to sunken eyes and hollow cheeks |
| Spitting up blood | Cough | Fatigue |
| Chest pain | Spitting up blood | Bone pain |
| Pneumonia | Pneumonia | Yellowing of the skin caused by a liver malfunction (jaundice). |
| Chest pain | Pain in the liver | |
| Inflammation of the tissue that surrounds the lungs (pleurisy) | Skin lesions | |
| Shoulder pain | Headache |
Risk Factors
Smoking cigarettes contributes to more cases of lung cancer than any other cause. Long-term smokers face a lung cancer risk 20 times greater than nonsmokers. The odds increase for heavier smokers. Changing to low-tar cigarettes, cigars, or pipes does not decrease the danger. Your risk decreases significantly five years after smoking your last cigarette, and after 10 to 15 years, you begin to get close to the level of a nonsmoker. Stopping smoking, even later in life, benefits your health, although the earlier you quit the better.
Women exposed to the same amount of smoke as men are more likely to develop lung cancer. Exposure to asbestos or other industrial chemicals increases your odds of developing lung cancer. If you have worked as a ship builder, as a miner, or you manufacture or repair brakes, you may have been exposed to large amounts of harmful toxins, which increases your risk three to fourfold. If you work with harsh toxins and you smoke, your chance of getting lung cancer is even higher.
Family members of people with lung cancer are at greater risk for the disease. Siblings and offspring of lung cancer patients have a slightly higher chance of developing the disease, which could be due to genetics. If the lung cancer patient is a smoker, the increased risk may be due to secondhand smoke. If you are a smoker, you put your family members at greater risk by exposing them to your cigarette smoke.
Your risk for lung cancer increases with age. A previous diagnosis of cancer and scarring of the lungs after pneumonia or tuberculosis also increases your risk.
Most cases of lung cancer are diagnosed in people between the ages of 55 and 65. It is not often seen in younger people, although it has happened. If you have had cancer before, you are at greater risk of developing it again than someone who has never had it. This is true of all cancers. Having chronic obstructive lung diseases, such as emphysema or chronic bronchitis puts you at greater risk for lung cancer. Both of these diseases are linked to heavy cigarette smoking.
Secondhand smoke increases your chances for developing lung cancer, putting spouses and those working in smoke-filled environments at greater risk. Air pollution and vitamin deficiencies also may contribute to the disease.
Diagnosis
Lung cancer is often diagnosed by having a chest x-ray as part of a routine screening or preceding a surgical procedure. If there is a spot or a mass on the x-ray of you lungs, your doctor will identify it as a lesion and will want to investigate further. If you are a smoker, your doctor will probably want to have regularly scheduled chest x-rays in hopes of detecting cancer as early as possible.
If you have symptoms, or if a suspicious lesion shows up on an x-ray, you will receive a complete physical exam, diagnostic tests, and a biopsy to determine if the problem is caused by cancer. A very accurate picture of suspected cancerous tissue can be taken in order to get a better look at a lesion. Using a computed tomography scan (CT scan), x- ray photographs are taken from different angles. A computer then combines the pictures into one complete picture. CT scans can help determine size, position, features, and lymph node involvement. Doctors may use computed tomography to guide a needle into the lung to remove a tissue specimen from the tumor. This process is called a biopsy, and is used to test the tissue for the presence of cancer cells.
Bronchoscopy is another method used for diagnosis. Your doctor can look into your lungs through a special fiber-optic tube (bronchoscope) inserted through your nose or mouth and down the windpipe. This test can help your doctor determine what state the tumor is in. A local anesthesia is used to relax the nostril and throat muscles, so you may feel fluid running down the back of the throat and need to cough or gag until the anesthetic begins working. You may be required to stay in the hospital overnight. After the test, your throat may hurt or feel scratchy, but you will be able eat and drink normally after about two hours.
Bone scans and other diagnostic procedures may be ordered to determine how advanced the cancer has become. Brain and abdominal CT scans are often performed, to check for cancer that has spread.
Once you have been diagnosed, your doctor will categorize your cancer into a stage in order to determine treatment options and prognosis. Staging is a method of classifying the tumor by size, location, and the extent to which the cancer has spread (metastasis).
There are four stages for non-small cell lung cancer. The five-year survival rates assigned to each stage are averages. You should remember that everyone responds differently to cancer and its treatment and that survival rates always vary. For non-small cell cancers, most practitioners follow a system that is used worldwide. The system takes into account size and location of the tumor, the lymph node involvement and whether or not the tumor has spread (metastasis). Depending on the stage, removing the tumor may or may not be possible.
Stage 0 non-small cell lung cancer is also called carcinoma in situ (in place, or “localized” cancer). This cancer is limited to a few layers of cells in one area of the lung. It has not penetrated the lining of the lung, or the lung tissue. The cancer can be cured with surgery alone.
Stage I non-small cell lung cancer is limited to the lung only. Surgery is the preferred method of treatment for this stage, which is further divided in to IA and IB.
- Stage IA About 13% of all non-small cell lung cancers are diagnosed at this stage. The tumor is small, and there is no lymph node involvement, nor has it spread to other locations. The five year survival rate is 67%.
- Stage IB about 23% of non-small cell lung cancers are diagnosed at this stage. The tumor is slightly larger than at state IA, but it still has not spread to other tissues, nor is there lymph node involvement. The five year survival rate is 57%.
Stage II non-small cell lung cancer has spread to nearby lymph nodes. Surgery is still the primary method used to treat it.
- Stage IIA is when the tumor is still small, there is some lymph node involvement, but it has not spread. It has a survival rate of 55%
- Stage IIB is when the tumor is a bit larger, there is either some or no lymph node involvement and it has not spread. It has a survival rate of 39%.
Stage III non-small cell lung cancer has spread to the chest wall, the diaphragm, or to the lymph nodes in the space between the chest bone and in front of the heart (mediastinum), on the other side of the chest, or near the lungs. This stage is further divided into two stages:
- Stage IIIa: may be removed with surgery in some cases. Chemotherapy and radiation may be used. The average five-year survival is from 15% to 35%.
- Stage IIIb: cannot be removed by surgery. Chemotherapy and radiation combinations are commonly used to prolong survival. The average five-year survival is 5%.
Stage IV non-small cell lung cancer has spread to distant sites in the body. The average five-year survival is less than 5%.
There are two stages for small cell cancer: limited and extensive. Small cell lung cancer is usually found in people who smoke or who used to smoke cigarettes.
Limited stage small cell lung cancer is limited to one side of the chest (one lung and in nearby lymph nodes). About 40% of small cell lung cancer patients fall into the limited stage. Average survival is 14 to 21 months with current treatments, with most people surviving 16 to 18 months. Two- year survival for limited disease is about 20%.
Extensive stage small cell lung cancer has spread beyond one lung to other parts of the body. Average survival for extensive stage disease is 6 to 12 months with current treatments. Two-year survival for limited stage disease is less than 4%.
Figure 2. Lung needle biopsy
Using an ultrasound machine or CT scan, a needle will be guided into your lung to remove a small amount of the suspicious tissue for testing. Before the doctor inserts the needs, you will receive a local injection of anesthetic. You will feel pressure and brief sharp pain when the needle touches the lung. You will be monitored for a few hours after the procedure and then sent home. The lab results should be available within a few days.
Prevention and Screening
Not smoking and avoiding contact with secondhand smoke offers the most effective means of preventing lung cancer. Giving up the habit significantly lowers but does not completely eliminate the risk. No one can completely eliminate the risk of lung cancer, but not smoking is the best step you can take to protect yourself.
Some doctors advise regular screening for smokers and former smokers. There are several different ways of screening for lung cancer. Sputum cytology, a method used to analyze cells the patient coughs up, can determine the presence of malignant cells, but not the location of the tumor. Sputum cytology followed by a bronchoscopy or CT scan offers the best prospect for picking up lesions before they spread. Spiral CT, a type of noninvasive diagnostic scan, has picked up malignancies in patients without symptoms and may be used for screening. The test takes about 15 to 20 seconds. The one drawback of the test is that the scans may indicate nonmalignant abnormalities, which would prompt the doctor to order a biopsy. A biopsy of the lung is invasive, involving the insertion of a needle through the chest wall into the lung.
Treatment
Urgent Care
Lung tumors can press on a major blood vessel, the superior vena cava, creating a medical emergency. Symptoms of this condition include swelling in the neck and face, difficulty breathing, and coughing. Bending forward or lying down may make symptoms worse.
Lung cancer that has spread to other organs can create medical emergencies, for example, by compressing the spinal cord or blocking the bowels. Symptoms of spinal cord compression include back pain and tenderness that feels worse when lying on the back and a tingling sensation in the back or legs. If you experience abdominal pain and vomiting, you could be experiencing the side effects of chemotherapy, or you could have a bowel obstruction. Consult your doctor or go to the emergency room for any of these problems.
Get prompt medical attention if you have a change in cough or breathing, or if your cough produces blood.
Self Care
Stop smoking and seek medical attention. Lung cancer is not something you can manage without medical care. Early diagnosis improves prognosis. You should stop smoking to decrease risk of additional cancers, to improve your general health, and to increase the effectiveness of treatment.
Drug Therapy
Your doctor is the best source of information on the drug treatment choices available to you.
Other Therapies
Radiation is often used to control symptoms produced by the lung tumor, such as pain, bleeding, and difficulty swallowing. It is also used to shrink the tumor itself. Radiation uses beams of high-energy rays. Doctors may order radiation before surgery to shrink the tumor or after surgery in hopes of killing any cells not visible that could have been missed. Its use is routine in patients with small cell lung cancer, as it prolongs survival. Radiation can produce skin irritation, nausea, and vomiting, a sore throat, and fatigue. Notify the doctor of any difficulties, and discuss methods of managing side effects with members of the healthcare team.
Photodynamic therapy (PDT) uses lasers to treat very small tumors and relieve symptoms. Doctors inject a special light-sensitive chemical that is absorbed by cells throughout the entire body. However, the chemical remains in the cancer cells for a longer period of time than normal cells. A laser light then activates the special chemical to kill the cancer cells. The skin and eyes may become sensitive to light for six or more weeks following therapy, so you will be advised to avoid bright lights and sunshine, and to wear protective clothing and sunglasses.
Drug, radiation, and surgical treatments may be used in combination. You may also opt to participate in a clinical trial. Clinical trials compare the safety and effectiveness of new treatments and combinations of treatments with the current standard of care.
Surgery
Surgery is almost completely restricted to those who have non-small cell lung cancer. Certain kinds of lung cancer that are small, that are found early, and are isolated to one part of the lung can be removed by having surgery.
Surgically removing the tumor offers the only real opportunity for a cure or long-term survival. This is usually only an option for early stage lung cancer.
During surgery, a small part of the lung may be cut away, a procedure called a wedge or segmental resection; an entire section (lobe) of the lung may be removed during a lobectomy; or an entire lung may be removed during a pheumonectomy. You have two sponge-like lungs, left and right, but you can live with just one.
Fewer than 30% of lung cancers can be surgically removed. While surgery offers the best hope for survival of non-small cell cancer, other medical conditions may rule out the possibility. If you have poor lung function or heart problems, you may not be a good candidate. Your risk of death during surgery or not recovering from the surgery is significantly increased, and your doctor may not want to take the chance.
Alternative Medicine
Alternative medicine can be helpful in dealing with a diagnosis of cancer for some patients. Meditation, visualization and support groups help patients cope with the disease as well as the strenuous treatments.
Prognosis
Only 14% of patients survive for five years. By the time doctors diagnose most lung cancers, the disease has progressed to become incurable. Only 15% of lung cancers are found in the early stages. Some experts predict that early diagnosis, recognition of risk factors, screening, and timely intervention could increase survival rate. If lung cancer is caught before it spreads, the five-year survival rate increases to between 42% and 48%.
Follow-up
Your doctor will want to see you on a regular basis to check for recurrences. The earlier a cancer is detected, the better your prognosis. In addition to a physical exam, a chest x-ray, blood tests, and other diagnostic procedures may be ordered at set intervals. Immediately report any new or recurring symptoms to the doctor. Do not wait until your next scheduled appointment.
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This massive collection of information about Mesothelioma comes to us from www.wikipedia.org
Signs and symptoms
Symptoms of mesothelioma may not appear until 20 to 50 years after exposure to asbestos. Shortness of breath, cough, and pain in the chest due to an accumulation of fluid in the pleural space are often symptoms of pleural mesothelioma.
Symptoms of peritoneal mesothelioma include weight loss and cachexia, abdominal swelling and pain due to ascites (a buildup of fluid in the abdominal cavity). Other symptoms of peritoneal mesothelioma may include bowel obstruction, blood clotting abnormalities, anemia, and fever. If the cancer has spread beyond the mesothelium to other parts of the body, symptoms may include pain, trouble swallowing, or swelling of the neck or face.
These symptoms may be caused by mesothelioma or by other, less serious conditions.
Mesothelioma that affects the pleura can cause these signs and symptoms:
- chest wall pain
- pleural effusion, or fluid surrounding the lung
- shortness of breath
- fatigue or anemia
- wheezing, hoarseness, or cough
- blood in the sputum (fluid) coughed up
In severe cases, the person may have many tumor masses. The individual may develop a pneumothorax, or collapse of the lung. The disease may metastasize, or spread, to other parts of the body.
Tumors that affect the abdominal cavity often do not cause symptoms until they are at a late stage. Symptoms include:
- abdominal pain
- ascites, or an abnormal buildup of fluid in the abdomen
- a mass in the abdomen
- problems with bowel function
- weight loss
In severe cases of the disease, the following signs and symptoms may be present:
- blood clots in the veins, which may cause thrombophlebitis
- disseminated intravascular coagulation, a disorder causing severe bleeding in many body organs
- jaundice, or yellowing of the eyes and skin
- low blood sugar level
- pleural effusion
- pulmonary emboli, or blood clots in the arteries of the lungs
- severe ascites
A mesothelioma does not usually spread to the bone, brain, or adrenal glands. Pleural tumors are usually found only on one side of the lungs.
Diagnosis
Diagnosing mesothelioma is often difficult, because the symptoms are similar to those of a number of other conditions. Diagnosis begins with a review of the patient's medical history. A history of exposure to asbestos may increase clinical suspicion for mesothelioma. A physical examination is performed, followed by chest X- ray and often lung function tests. The X-ray may reveal pleural thickening commonly seen after asbestos exposure and increases suspicion of mesothelioma. A CT (or CAT) scan or an MRI is usually performed. If a large amount of fluid is present, abnormal cells may be detected by cytology if this fluid is aspirated with a syringe. For pleural fluid this is done by a pleural tap or chest drain, in ascites with an paracentesis or ascitic drain and in a pericardial effusion with pericardiocentesis. While absence of malignant cells on cytology does not completely exclude mesothelioma, it makes it much more unlikely, especially if an alternative diagnosis can be made (e.g. tuberculosis, heart failure).
If cytology is positive or a plaque is regarded as suspicious, a biopsy is needed to confirm a diagnosis of mesothelioma. A doctor removes a sample of tissue for examination under a microscope by a pathologist. A biopsy may be done in different ways, depending on where the abnormal area is located. If the cancer is in the chest, the doctor may perform a thoracoscopy. In this procedure, the doctor makes a small cut through the chest wall and puts a thin, lighted tube called a thoracoscope into the chest between two ribs. Thoracoscopy allows the doctor to look inside the chest and obtain tissue samples.
If the cancer is in the abdomen, the doctor may perform a laparoscopy. To obtain tissue for examination, the doctor makes a small opening in the abdomen and inserts a special instrument into the abdominal cavity. If these procedures do not yield enough tissue, more extensive diagnostic surgery may be necessary.
| 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) |
Screening
There is no universally agreed protocol for screening people who have been exposed to asbestos. However some research indicates that the serum osteopontin level might be useful in screening asbestos-exposed people for mesothelioma. The level of soluble mesothelin-related protein is elevated in the serum of about 75% of patients at diagnosis and it has been suggested that it may be useful for screening.
Staging
Mesothelioma is described as localized if the cancer is found only on the membrane surface where it originated. It is classified as advanced if it has spread beyond the original membrane surface to other parts of the body, such as the lymph nodes, lungs, chest wall, or abdominal organs.
Pathophysiology
The mesothelium consists of a single layer of flattened to cuboidal cells forming the epithelial lining of the serous cavities of the body including the peritoneal, pericardial and pleural cavities. Deposition of asbestos fibres in the parenchyma of the lung may result in the penetration of the visceral pleura from where the fibre can then be carried to the pleural surface, thus leading to the development of malignant mesothelial plaques. The processes leading to the development of peritoneal mesothelioma remain unresolved, although it has been proposed that asbestos fibres from the lung are transported to the abdomen and associated organs via the lymphatic system. Additionally, asbestos fibres may be deposited in the gut after ingestion of sputum contaminated with asbestos fibres.
Pleural contamination with asbestos or other mineral fibres has been shown to cause cancer. Long thin asbestos fibers (blue asbestos, amphibole fibers) are more potent carcinogens than "feathery fibers" (chrysotile or white asbestos fibers). However, there is now evidence that smaller particles may be more dangerous than the larger fibers. They remain suspended in the air where they can be inhaled, and may penetrate more easily and deeper into the lungs. "We probably will find out a lot more about the health aspects of asbestos from [the World Trade Center attack], unfortunately," said Dr. Alan Fein, chief of pulmonary and critical-care medicine at North Shore-Long Island Jewish Health System. Dr. Fein has treated several patients for "World Trade Center syndrome" or respiratory ailments from brief exposures of only a day or two near the collapsed buildings.
Mesothelioma development in rats has been demonstrated following intra- pleural inoculation of phosphorylated chrysotile fibres. It has been suggested that in humans, transport of fibres to the pleura is critical to the pathogenesis of mesothelioma. This is supported by the observed recruitment of significant numbers of macrophages and other cells of the immune system to localised lesions of accumulated asbestos fibres in the pleural and peritoneal cavities of rats. These lesions continued to attract and accumulate macrophages as the disease progressed, and cellular changes within the lesion culminated in a morphologically malignant tumour.
Experimental evidence suggests that asbestos acts as a complete carcinogen with the development of mesothelioma occurring in sequential stages of initiation and promotion. The molecular mechanisms underlying the malignant transformation of normal mesothelial cells by asbestos fibres remain unclear despite the demonstration of its oncogenic capabilities. However, complete in vitro transformation of normal human mesothelial cells to malignant phenotype following exposure to asbestos fibres has not yet been achieved. In general, asbestos fibres are thought to act through direct physical interactions with the cells of the mesothelium in conjunction with indirect effects following interaction with inflammatory cells such as macrophages.
Analysis of the interactions between asbestos fibres and DNA has shown that phagocytosed fibres are able to make contact with chromosomes, often adhering to the chromatin fibres or becoming entangled within the chromosome. This contact between the asbestos fibre and the chromosomes or structural proteins of the spindle apparatus can induce complex abnormalities. The most common abnormality is monosomy of chromosome 22. Other frequent abnormalities include structural rearrangement of 1p, 3p, 9p and 6q chromosome arms.
Common gene abnormalities in mesothelioma cell lines include deletion of the tumor suppressor genes:
- Neurofibromatosis type 2 at 22q12
- P16INK4A
- P14ARF
Asbestos has also been shown to mediate the entry of foreign DNA into target cells. Incorporation of this foreign DNA may lead to mutations and oncogenesis by several possible mechanisms:
- Inactivation of tumor suppressor genes
- Activation of oncogenes
- Activation of proto-oncogenes due to incorporation of foreign DNA containing a promoter region
- Activation of DNA repair enzymes, which may be prone to error
- Activation of telomerase
- Prevention of apoptosis
Asbestos fibres have been shown to alter the 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.
Epidemiology
Incidence
Although reported incidence rates have increased in the past 20 years, mesothelioma is still a relatively rare cancer. The incidence is approximately one per 1,000,000. For comparison, populations with high levels of smoking can have a lung cancer incidence of over 1,000 per 1,000,000. Incidence of malignant mesothelioma currently ranges from about 7 to 40 per 1,000,000 in industrialized Western nations, depending on the amount of asbestos exposure of the populations during the past several decades. It has been estimated that incidence may have peaked at 15 per 1,000,000 in the United States in 2004. Incidence is expected to continue increasing in other parts of the world. Mesothelioma occurs more often in men than in women and risk increases with age, but this disease can appear in either men or women at any age. Approximately one fifth to one third of all mesotheliomas are peritoneal.
Between 1940 and 1979, approximately 27.5 million people were occupationally exposed to asbestos in the United States. Between 1973 and 1984, there has been a threefold increase in the diagnosis of pleural mesothelioma in Caucasian males. From 1980 to the late 1990s, the death rate from mesothelioma in the USA increased from 2,000 per year to 3,000, with men four times more likely to acquire it than women. These rates may not be accurate, since it is possible that many cases of mesothelioma are misdiagnosed as adenocarcinoma of the lung, which is difficult to differentiate from mesothelioma.
Risk factors
Working with asbestos is the major risk factor for mesothelioma. A history of asbestos exposure exists in almost all cases. However, mesothelioma has been reported in some individuals without any known exposure to asbestos. In rare cases, mesothelioma has also been associated with irradiation, intrapleural thorium dioxide (Thorotrast), and inhalation of other fibrous silicates, such as erionite.
Asbestos is the name of a group of minerals that occur naturally as masses of strong, flexible fibers that can be separated into thin threads and woven. Asbestos has been widely used in many industrial products, including cement, brake linings, roof shingles, flooring products, textiles, and insulation. If tiny asbestos particles float in the air, especially during the manufacturing process, they may be inhaled or swallowed, and can cause serious health problems. In addition to mesothelioma, exposure to asbestos increases the risk of lung cancer, asbestosis (a noncancerous, chronic lung ailment), and other cancers, such as those of the larynx and kidney.
The combination of smoking and asbestos exposure significantly increases a person's risk of developing cancer of the airways (lung cancer, bronchial carcinoma). The Kent brand of cigarettes used asbestos in its filters for the first few years of production in the 1950s and some cases of mesothelioma have resulted. Smoking modern cigarettes does not appear to increase the risk of mesothelioma.
Some studies suggest that simian virus 40 (SV40) may act as a cofactor in the development of mesothelioma.
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.
Occupational
Exposure to asbestos fibres has been recognised as an occupational health hazard since the early 1900s. Several epidemiological studies have associated exposure to asbestos with the development of lesions such as asbestos bodies in the sputum, pleural plaques, diffuse pleural thickening, asbestosis, carcinoma of the lung and larynx, gastrointestinal tumours, and diffuse mesothelioma of the pleura and peritoneum.
The documented presence of asbestos fibres in water supplies and food products has fostered concerns about the possible impact of long-term and, as yet, unknown exposure of the general population to these fibres. Although many authorities consider brief or transient exposure to asbestos fibres as inconsequential and an unlikely risk factor, some epidemiologists claim that there is no risk threshold. Cases of mesothelioma have been found in people whose only exposure was breathing the air through ventilation systems. Other cases had very minimal (3 months or less) direct exposure.
Commercial asbestos mining at Wittenoom, Western Australia, occurred between 1945 and 1966. A cohort study of miners employed at the mine reported that while no deaths occurred within the first 10 years after crocidolite exposure, 85 deaths attributable to mesothelioma had occurred by 1985. By 1994, 539 reported deaths due to mesothelioma had been reported in Western Australia.
Paraoccupational Secondary Exposure
Family members and others living with asbestos workers have an increased risk of developing mesothelioma, and possibly other asbestos related diseases. This risk may be the result of exposure to asbestos dust brought home on the clothing and hair of asbestos workers. To reduce the chance of exposing family members to asbestos fibres, asbestos workers are usually required to shower and change their clothing before leaving the workplace.
Asbestos in buildings
Many building materials used in both public and domestic premises prior to the banning of asbestos may contain asbestos. Those performing renovation works or diy activities may expose themselves to asbestos dust. In the UK use of Chrysotile asbestos was banned at the end of 1999. Brown and blue asbestos was banned in the UK around 1985. Buildings built or renovated prior to these dates may contain asbestos materials.
Environmental Exposure
Incidence of mesothelioma had been found to be higher in populations living near Naturally Occuring Asbestos (NOA)
Treatment
Treatment of MM using conventional therapies has not proved successful and patients have a median survival time of 6 - 12 months after presentation. The clinical behaviour of the malignancy is affected by several factors including the continuous mesothelial surface of the pleural cavity which favours local metastasis via exfoliated cells, invasion to underlying tissue and other organs within the pleural cavity, and the extremely long latency period between asbestos exposure and development of the disease.
Surgery
Surgery, either by itself or used in combination with pre- and post- operative adjuvant therapies has proved disappointing. A pleurectomy/decortication is the most common surgery, in which the lining of the chest is removed. Less common is an extrapleural pneumonectomy (EPP), in which the lung, lining of the inside of the chest, the hemi-diaphragm and the pericardium are removed. It is not possible to remove the entire mesothelium without killing the patient.
Radiation
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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. Delivering radiation and chemotherapy after a radical surgery has led to extended life expectancy in selected patient populations with some patients surviving more than 5 years. As part of a curative approach to mesothelioma, radiotherapy is also commonly applied to the sites of chest drain insertion, in order to prevent growth of the tumor along the track in the chest wall.
Although mesothelioma is generally resistant to curative treatment with radiotherapy alone, palliative treatment regimens are sometimes used to relieve symptoms arising from tumor growth, such as obstruction of a major blood vessel. Radiation therapy when given alone with curative intent has never been shown to improve survival from mesothelioma. The necessary radiation dose to treat mesothelioma that has not been surgically removed would be very toxic.
Chemotherapy
In February 2004, the United States Food and Drug Administration approved pemetrexed (brand name Alimta) for treatment of malignant pleural mesothelioma. Pemetrexed is given in combination with cisplatin. Folic acid is also used to reduce the side-effects of pemetrexed.
Immunotherapy
Treatment regimens involving immunotherapy have yielded variable results. For example, intrapleural inoculation of Bacillus Calmette-Guérin (BCG) in an attempt to boost the immune response, was found to be of no benefit to the patient (while it may benefit patients with bladder cancer). Mesothelioma cells proved susceptible to in vitro lysis by LAK cells following activation by interleukin- 2 (IL-2), but patients undergoing this particular therapy experienced major side effects. Indeed, this trial was suspended in view of the unacceptably high levels of IL-2 toxicity and the severity of side effects such as fever and cachexia. Nonetheless, other trials involving interferon alpha have proved more encouraging with 20% of patients experiencing a greater than 50% reduction in tumor mass combined with minimal side effects.
Heated Intraoperative Intraperitoneal Chemotherapy
A procedure known as heated intraoperative intraperitoneal chemotherapy was developed by Paul Sugarbaker at the Washington Cancer Institute.The surgeon removes as much of the tumor as possible followed by the direct administration of a chemotherapy agent, heated to between 40 and 48°C, in the abdomen. The fluid is perfused for 60 to 120 minutes and then drained.
This technique permits the administration of high concentrations of selected drugs into the abdominal and pelvic surfaces. Heating the chemotherapy treatment increases the penetration of the drugs into tissues. Also, heating itself damages the malignant cells more than the normal cells.
Prevention & Expectations
What can be done to prevent the disease? Since the 1970s, the Environmental Protection Agency and the Occupational Safety and Health Administration have regulated the asbestos industry in the U.S. In the past, asbestos was used as a fire retardant and an insulator. Other products are now used in its place. The controversy involving exposure to different forms of asbestos continues.
There are two major types of asbestos: chrysotile and amphibole. It is thought that exposure to the amphibole form is more likely to cause mesothelioma. However, chrysotile has been used more frequently, hence many mesotheliomas are caused by chrysotile.
Removal is taking place in schools and other public buildings throughout the U.S. The hope is that these measures will greatly reduce the occurrence of this cancer.
What are the long-term effects of the disease? A mesothelioma is a highly aggressive tumor that is generally deadly. Current treatment of malignant mesothelioma is designed to make the person with cancer comfortable. Although long-term survival cannot usually be expected, the case of famed paleontologist Stephen Jay Gould is a noted exception.
What are the risks to others? Mesothelioma is not contagious and cannot be passed from one person to another. The exposure to the asbestos that caused the cancer occurred many years to several decades before the disease appeared. People who live with asbestos workers have a higher risk of getting this cancer.
Notable people with mesothelioma
Mesothelioma, though rare, has had a number of notable patients. Australian anti-racism activist Bob Bellear died in 2005. British science fiction writer Michael G. Coney, responsible for nearly 100 works 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.
Steve McQueen was diagnosed with peritoneal mesothelioma on December 22, 1979. He was not offered surgery or chemotherapy because doctors felt the cancer was too advanced. McQueen sought alternative treatments from clinics in Mexico. He died of a heart attack on November 7, 1980, in Juárez, Mexico, following cancer surgery. He may have been exposed to asbestos while serving with the US Marines as a young adult—asbestos was then commonly used to insulate ships' piping—or because of its use as an insulating material in car racing suits. (It is also reported that he worked in a shipyard during World War II, where he might have been exposed to asbestos.
United States Congressman Bruce Vento died of mesothelioma in 2000. The Bruce Vento Hopebuilder is awarded yearly by his wife at the MARF symposium to persons or organizations who have done the most to support mesothelioma research and advocacy.
After a long period of untreated illness and pain, rock and roll musician and songwriter Warren Zevon was diagnosed with inoperable mesothelioma in the fall of 2002. Refusing treatments he believed might incapacitate him, Zevon focused his energies on recording his final album The Wind including the song Keep me in your heart which speaks of his failing breath. Zevon died at his home in Los Angeles, California, on September 7, 2003.
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" for Discover magazine, in which he argued that statistics such as median survival are just useful abstractions, not destiny. Gould lived for another twenty years eventually succumbing to metastatic adenocarcinoma of the lung, not mesothelioma.
Author Paul Kraus was diagnosed with mesothelioma in June 1997 following an umbilical hernia operation. His prognosis was "a few months." He continues to survive using a variety of integrative and complimentary modalities and has written a book about his experience.
Legal issues
The first lawsuits against asbestos manufacturers were in 1929. Since then, many lawsuits have been filed against asbestos manufacturers and employers, for neglecting to implement safety measures after the links between asbestos, asbestosis, and mesothelioma became known (some reports seem to place this as early as 1898). The liability resulting from the sheer number of lawsuits and people affected has reached billions of dollars. The amounts and method of allocating compensation have been the source of many court cases, and government attempts at resolution of existing and future cases.
History
The first lawsuit against asbestos manufacturers was brought in 1929. The parties settled that lawsuit, and as part of the agreement, the attorneys agreed not to pursue further cases. It was not until 1960 that an article published by Wagner et al first officially established mesothelioma as a disease arising from exposure to crocidolite asbestos. The article referred to over 30 case studies of people who had suffered from mesothelioma in South Africa. Some exposures were transient and some were mine workers. In 1962 McNulty reported the first diagnosed case of malignant mesothelioma in an Australian asbestos worker. The worker had worked in the mill at the asbestos mine in Wittenoom from 1948 to 1950.
In the town of Wittenoom, asbestos-containing mine waste was used to cover schoolyards and playgrounds. In 1965 an article in the British Journal of Industrial Medicine established that people who lived in the neighbourhoods of asbestos factories and mines, but did not work in them, had contracted mesothelioma.
Despite proof that the dust associated with asbestos mining and milling causes asbestos related disease, mining began at Wittenoom in 1943 and continued until 1966. In 1974 the first public warnings of the dangers of blue asbestos were published in a cover story called "Is this Killer in Your Home?" in Australia's Bulletin magazine. In 1978 the Western Australian Government decided to phase out the town of Wittenoom, following the publication of a Health Dept. booklet, "The Health Hazard at Wittenoom", containing the results of air sampling and an appraisal of worldwide medical information.
By 1979 the first writs for negligence related to Wittenoom were issued against CSR and its subsidiary ABA, and the Asbestos Diseases Society was formed to represent the Wittenoom victims.
References
- ^ United States Department of Health and Human Services.
- ^ "Cigarette smoking, asbestos exposure, and malignant mesothelioma" by Muscat JE, Wynder EL in Cancer Research (1991) volume 51 pages 2263-7 Entrez PubMed 2015590
- ^ "Soluble mesothelin-related protein--a blood test for mesothelioma" by B. W. Robinson, J. Creaney, R. Lake, A. Nowak, A. W. Musk, N. de Klerk, P. Winzell, K. E. Hellstrom and I. Hellstrom in Lung Cancer (2005) volume 49, pages S109- S111 Entrez PubMed 15950789.
- ^ "Malignant mesothelioma and occupational exposure to asbestos: a clinicopathological correlation of 1445 cases" by V. L. Roggli, A. Sharma, K. J. Butnor, T. Sporn and R. T. Vollmer in Ultrastruct Pathol (2002) volume 26 pages 55-65 Entrez PubMed 12036093.
- ^ "Advances in Malignant Mesothelioma" by Bruce W. S. Robinson and Richard A. Lake in The New England Journal of Medicine (2005) volume 353 pages 1591-1603 Entrez PubMed 16221782.
- ^ "SV40 in human tumors: new documents shed light on the apparent controversy" by D. S. MacLachlan in Anticancer Res (2002) volume 22, pages 3495-3499 Entrez PubMed 12552945.
- ^ a b "Resection margins, extrapleural nodal status, and cell type determine postoperative long-term survival in trimodality therapy of malignant pleural mesothelioma: results in 183 patients." by D. Sugarbaker in J Thorac Cardiovasc Surg (1999) volume 117, pages 54-63 Entrez PubMed 9869758.
- ^ McQueen's Legacy of Laetrile. (2005- 11-15).
- ^ Gould, Stephen Jay. The Median Isn't the Message.
- ^ "Diffuse pleural mesothelioma and asbestos exposure in the North Western Cape Province" by J. C. Wagner, C. A. Sleggs and P. Marchand in Br J Ind Med. (1960) volume 17, pages 260-271 Entrez PubMed 13782506.
- ^ "Malignant pleural mesothelioma in an asbestos worker" by J. C. McNulty in Med J Aust (1962) volume 49, pages 953-954 Entrez PubMed 13932248.
External links
- Mesothelioma: Questions and Answers from the U.S. National Cancer Institute
- Cancer.gov: Malignant Mesothelioma from the U.S. National Cancer Institute
- American Cancer Society from the American Cancer Society
- Malignant Mesothelioma review article from the American Cancer Society
- CancerBACUP: Mesothelioma Information Centre
- Medlineplus: Mesothelioma from MEDLINE, part of the United States National Library of Medicine
- Worksafe, Western Australia, from Western Australia's Department of Consumer and Employment Protection
- US Nat'l Institute for Occupational Safety and Health, from the Occupational Safety and Health Administration
Sources
The first version of this article was adapted from a public domain U.S. National Cancer Institute fact sheet at http://www.cancer.gov/cancertopics/factsheet/Sites- Types/mesothelioma
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