Cancer (medical term: malignant neoplasm) is a class of diseases in which a group of cells display uncontrolled growth (division beyond the normal limits), invasion (intrusion on and destruction of adjacent tissues), and sometimes metastasis (spread to other locations in the body via lymph or blood). These three malignant properties of cancers differentiate them from benign tumors, which are self-limited, and do not invade or metastasize. Most cancers form a tumor but some, like leukemia, do not. The branch of medicine concerned with the study, diagnosis, treatment, and prevention of cancer is oncology.
Cancer may affect people at all ages, even fetuses, but the risk for most varieties increases with age.[1] Cancer causes about 13% of all human deaths.[2] According to the American Cancer Society, 7.6 million people died from cancer in the world during 2007.[3] Cancers can affect all animals.
Nearly all cancers are caused by abnormalities in the genetic material of the transformed cells.[4] These abnormalities may be due to the effects of carcinogens, such as tobacco smoke, radiation, chemicals, or infectious agents. Other cancer-promoting genetic abnormalities may be randomly acquired through errors in DNA replication, or are inherited, and thus present in all cells from birth. The heritability of cancers are usually affected by complex interactions between carcinogens and the host's genome. New aspects of the genetics of cancer pathogenesis, such as DNA methylation, and microRNAs are increasingly recognized as important.
Genetic abnormalities found in cancer typically affect two general classes of genes. Cancer-promoting oncogenes are typically activated in cancer cells, giving those cells new properties, such as hyperactive growth and division, protection against programmed cell death, loss of respect for normal tissue boundaries, and the ability to become established in diverse tissue environments. Tumor suppressor genes are then inactivated in cancer cells, resulting in the loss of normal functions in those cells, such as accurate DNA replication, control over the cell cycle, orientation and adhesion within tissues, and interaction with protective cells of the immune system.
Diagnosis usually requires the histologic examination of a tissue biopsy specimen by a pathologist, although the initial indication of malignancy can be symptoms or radiographic imaging abnormalities. Most cancers can be treated and some cured, depending on the specific type, location, and stage. Once diagnosed, cancer is usually treated with a combination of surgery, chemotherapy and radiotherapy. As research develops, treatments are becoming more specific for different varieties of cancer. There has been significant progress in the development of targeted therapy drugs that act specifically on detectable molecular abnormalities in certain tumors, and which minimize damage to normal cells. The prognosis of cancer patients is most influenced by the type of cancer, as well as the stage, or extent of the disease. In addition, histologic grading and the presence of specific molecular markers can also be useful in establishing prognosis, as well as in determining individual treatments.
Tuesday, August 25, 2009
Monday, August 24, 2009
Consolidation
Why Debt Consolidation Can Work
For people seeking to consolidate debt, there are many options to choose from. Determining the right solution for each unique debt level can be intimidating. Understanding the differences between the various debt consolidation methods can help consumers choose more effectively for their situation. Below you will find a brief description of some common debt consolidation options:
■A debt settlement program involves a settlement company negotiating with creditors to lower the outstanding balance of a person’s debt. Monthly payments made under a debt settlement program are placed in a settlement fund or an escrow account in anticipation of reaching a settlement with creditors. Typically this option is not available if the total debt owed is less than $10,000. This option also carries a certain amount of risk as there are some creditors who will not accept the settlement terms and can pursue legal action against the consumer (See more: debt settlement).
■Debt consolidation can be available in the form of a loan. The loan is used to pay off multiple debts by securing a lower interest rate or a fixed interest rate with the convenience of a single monthly payment. Debt consolidation loans can be secured against an asset like a house, but unsecured loans are also available. This solution does have its risks. If the consumer takes out a loan against their home and are unable to maintain their loan payments, they risk foreclosure on their property (see more: debt consolidation loans).
■Credit counseling agencies provide debt consolidation without a loan. This type of debt consolidation is referred to as a debt management plan (DMP). Consolidating debt on a DMP can give consumers enough room in their monthly budgets to make progress on paying down their debt. The process involves consolidating multiple unsecured debts into one monthly payment. When consumers work with an accredited agency for credit counseling and debt consolidation, the agency may be able to negotiate better repayment terms based on their relationships with the creditors. The consolidated monthly payment is typically lower than what they were previously paying in total for all of their respective debts. It is important to note that these benefits vary widely from one creditor to another and some creditors do not extend any benefits at all
For people seeking to consolidate debt, there are many options to choose from. Determining the right solution for each unique debt level can be intimidating. Understanding the differences between the various debt consolidation methods can help consumers choose more effectively for their situation. Below you will find a brief description of some common debt consolidation options:
■A debt settlement program involves a settlement company negotiating with creditors to lower the outstanding balance of a person’s debt. Monthly payments made under a debt settlement program are placed in a settlement fund or an escrow account in anticipation of reaching a settlement with creditors. Typically this option is not available if the total debt owed is less than $10,000. This option also carries a certain amount of risk as there are some creditors who will not accept the settlement terms and can pursue legal action against the consumer (See more: debt settlement).
■Debt consolidation can be available in the form of a loan. The loan is used to pay off multiple debts by securing a lower interest rate or a fixed interest rate with the convenience of a single monthly payment. Debt consolidation loans can be secured against an asset like a house, but unsecured loans are also available. This solution does have its risks. If the consumer takes out a loan against their home and are unable to maintain their loan payments, they risk foreclosure on their property (see more: debt consolidation loans).
■Credit counseling agencies provide debt consolidation without a loan. This type of debt consolidation is referred to as a debt management plan (DMP). Consolidating debt on a DMP can give consumers enough room in their monthly budgets to make progress on paying down their debt. The process involves consolidating multiple unsecured debts into one monthly payment. When consumers work with an accredited agency for credit counseling and debt consolidation, the agency may be able to negotiate better repayment terms based on their relationships with the creditors. The consolidated monthly payment is typically lower than what they were previously paying in total for all of their respective debts. It is important to note that these benefits vary widely from one creditor to another and some creditors do not extend any benefits at all
Friday, August 14, 2009
Malignant mesothelioma
Malignant mesothelioma (me-zo-thee-le-O-muh) is a rare cancer that occurs in the thin layer of tissue that covers the majority of your internal organs (mesothelium).
Doctors divide mesothelioma into different types based on what part of the mesothelium is affected, including:
•Pleural malignant mesothelioma, which affects the tissue that surrounds the lungs and is the most common form of mesothelioma.
•Peritoneal mesothelioma, which occurs in the tissue in your abdomen.
•Pericardial mesothelioma, which affects the tissue surrounding the heart.
•Mesothelioma of the tunica vaginalis, which occurs in the lining around the testicles.
Between 2,000 and 3,000 people are diagnosed with mesothelioma in the United States each year, according to the American Cancer Society.
Signs and symptoms of mesothelioma vary depending on where the cancer occurs.
Pleural mesothelioma signs and symptoms may include:
Shortness of breath
Painful breathing (pleurisy)
Painful coughing
Chest pain under the rib cage
Unusual lumps of tissue under the skin on your chest
Unexplained weight loss
Dry (nonproductive) cough
Peritoneal mesothelioma signs and symptoms may include:
Abdominal pain
Abdominal swelling
A change in your bowel habits, such as more frequent diarrhea or constipation
Lumps of tissue in the abdomen
Unexplained weight loss
Other forms of mesothelioma
Signs and symptoms of pericardial mesothelioma and mesothelioma of the tunica vaginalis are unclear. These forms are so rare that not much information is available. Pericardial mesothelioma signs and symptoms may include difficulty breathing or chest pains. Mesothelioma of the tunica vaginalis may be first detected as a mass on a testicle.
When to see a doctor
See your doctor if you have signs and symptoms that may indicate mesothelioma. Signs and symptoms of mesothelioma aren't specific to this disease and, due to the rarity of mesothelioma, are more likely to be related to other conditions. If any persistent signs and symptoms seem unusual or bothersome to you, ask your doctor to evaluate them.
Doctors divide mesothelioma into different types based on what part of the mesothelium is affected, including:
•Pleural malignant mesothelioma, which affects the tissue that surrounds the lungs and is the most common form of mesothelioma.
•Peritoneal mesothelioma, which occurs in the tissue in your abdomen.
•Pericardial mesothelioma, which affects the tissue surrounding the heart.
•Mesothelioma of the tunica vaginalis, which occurs in the lining around the testicles.
Between 2,000 and 3,000 people are diagnosed with mesothelioma in the United States each year, according to the American Cancer Society.
Signs and symptoms of mesothelioma vary depending on where the cancer occurs.
Pleural mesothelioma signs and symptoms may include:
Shortness of breath
Painful breathing (pleurisy)
Painful coughing
Chest pain under the rib cage
Unusual lumps of tissue under the skin on your chest
Unexplained weight loss
Dry (nonproductive) cough
Peritoneal mesothelioma signs and symptoms may include:
Abdominal pain
Abdominal swelling
A change in your bowel habits, such as more frequent diarrhea or constipation
Lumps of tissue in the abdomen
Unexplained weight loss
Other forms of mesothelioma
Signs and symptoms of pericardial mesothelioma and mesothelioma of the tunica vaginalis are unclear. These forms are so rare that not much information is available. Pericardial mesothelioma signs and symptoms may include difficulty breathing or chest pains. Mesothelioma of the tunica vaginalis may be first detected as a mass on a testicle.
When to see a doctor
See your doctor if you have signs and symptoms that may indicate mesothelioma. Signs and symptoms of mesothelioma aren't specific to this disease and, due to the rarity of mesothelioma, are more likely to be related to other conditions. If any persistent signs and symptoms seem unusual or bothersome to you, ask your doctor to evaluate them.
Monday, August 10, 2009
Mesothelioma Diagnosis
Because mesothelioma's symptoms are not unique to it and the disease's relative rarity, cases of mesothelioma misdiagnosed are not uncommon. A review of the patient's medical history is an important part in assessing the risk of mesothelioma.
Mesothelioma: Diagnosis and Differentiation Journal Articles
12.02.08 - Monitoring of Chemotherapy Response in Malignant Pleural Mesothelioma Using Fluorodeoxyglucose Positron Emission Tomography
We report a 56-year-old man who underwent monitoring of the response to chemotherapy of malignant pleural mesothelioma (MPM). 8F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) and [...]
11.27.08 - The Role of Podoplanin in Tumor Progression and Metastasis
In the last decade, much data has been generated concerning the molecular mechanisms of lymphangiogenesis and its significance in pathological conditions. This was mainly due to the discovery of lymphatic endothelial cell (LEC)-specific [...]
11.27.08 - Clinicopathologic and prognostic significance of overexpression of her-2/neu and p53 oncoproteins in gastric carcinoma using tissue microarray
Background: The aim of the study was to verify the frequency of the immunohistochemical overexpression of her-2/neu and p53 in gastric carcinoma and their relation to the [...]
11.26.08 - Malignant pleural mesothelioma: biology and diagnosis
Malignant pleural mesothelioma (MPM) is a serious issue worldwide because of its increasing incidence and poor prognosis despite real recent improvements in the disease management. Most of the patients [...]
11.26.08 - Comparison of semiquantitative fluorescence imaging and PET tracer uptake in mesothelioma models as a monitoring system for growth and therapeutic effects
Introduction: Various techniques are available for in vivo imaging, and precise understanding of their characteristics is essential for effective use of the imaging results. We established human mesothelioma cell lines [...]As a first step in diagnosing the disease, the doctor may order an x-ray of the chest or abdomen or a CT (or CAT) scan or MRI may be performed. Although mesothelioma typically cannot be seen on an x-ray, the tumor often causes a pleural effusion, or fluid collection between the lung and chest wall. This abnormal finding is associated with shortness of breath and warrants clinical follow up. Lung function tests may also be completed.
The doctor may look inside the chest cavity with a special instrument called a thoracoscope. A cut will be made through the chest wall and the thoracoscope will be put into the chest between two ribs. This test, called thoracoscopy, is usually done in the hospital. Before the test, the patient will be given a local anesthetic (a drug that causes a loss of feeling for a short period of time). Some pressure may be felt, but usually there is no pain.
The doctor may also look inside the abdomen (peritoneoscopy) with a special tool called a peritoneoscope. The peritoneoscope is put into an opening made in the abdomen. This test is also usually done in the hospital. Before the test is done, a local anesthetic will be given.
If tissue that is not normal is found, the doctor will need to cut out a small piece and have it reviewed under a microscope to see if there are any cancer cells. This is called a biopsy. Biopsies are usually done during the thoracoscopy or peritoneoscopy.
Diagnosing mesothelioma is very difficult, and cases of mesothelioma misdiagnosed are unfortunately not uncommon. It is important to share your case history of work experience (especially in shipyards and at construction sites) and asbestos exposure potential with your physicians if you feel mesothelioma is a risk. Asbestos fibres can also be carried into the home on clothing, inadvertently exposing the deadly fibres, and the risk of mesothelioma, to family members.
A mesothelioma diagnosis is serious, but treatments are available. The chance of recovery (prognosis) depends on the size of the cancer, where the cancer is, how far the cancer has spread, how the cancer cells look under the microscope, how the cancer responds to treatment, and the patient's age. As with most types of cancer, early diagnosis is an excellent first step in fighting the disease.
Mesothelioma Symptoms
If you are wondering "do I have mesothelioma?" you should seek the guidance of your physician as early detection is a powerful asset during treatment. Malignant mesothelioma may not become apparent until 20 to 30 years after the first exposure to asbestos, but can be very aggressive once it takes hold. Because the symptoms of mesothelioma are not unique to the disease a mesothelioma diagnosis can be difficult to determine.
Symptoms of Pleural Mesothelioma
Symptoms of pleural mesothelioma (mesothelioma of the lining of the lung, known as the pleura) may include, but are not limited to, the following:
•shortness of breath (dyspnea) - hoarseness, difficulty swallowing, and/or coughing up of blood.
•pleural effusion - a build up of too much fluid between the pleura (linings of the lungs and chest); a pleural effusion may cause chest pain and difficulty breathing (dyspnea), however, many cause no symptoms and are first discovered during the physical examination or seen on a chest x-ray.
•pain in the chest - may sometimes be felt in upper abdomen, shoulder, or arm.
Patients diagnosed with diffuse pleural mesothelioma exhibited the following symptoms
(source: "Diffuse malignant mesothelioma of the pleura in Ontario and Quebec: a retrospective study of 332 patients." P Ruffie et al. Journal of Clinical Oncology Aug 1 1989: 1157-1168.) Symptom % exhibiting
Shortness of breath and/or chest pain 90%
Weight loss 29%
Cough, weakness, fever, loss of appetite 3%
Hemoptysis (coughing up blood), hoarseness, dysphagia (difficulty swallowing), Horner's syndrome less than 1%
Pleural Effusions 84%
Asymptomatic 3%
Symptoms of Peritoneal Mesothelioma
Symptoms of peritoneal mesothelioma (mesothelioma of the abdominal lining which is known as the peritoneum) may include, but are not limited to, the following:
•weight loss - but waist may increase in size.
•pain or swelling in the abdomen - fluid retention or tumor growth.
•bowel obstruction - blockage in the small or large intestine.
•anemia - a reduction in the number of red blood cells to below normal; this forces the heart and other organs to work harder to get oxygen where it's needed.
•fever
Patients diagnosed with peritoneal mesothelioma exhibited the following symptoms
(source: "Peritoneal Mesothelioma: A Review." Bridda A, Padoan I, Mencarelli R, Frego M. MedGenMed 2007 May 10;9(2):32.) Symptom % exhibiting
Abdominal pain 35%
Abdominal swelling 31%
anorexia, marked weight loss, and ascites percentage not given
less frequently night sweats and hypercoagulability percentage not given
Clinical presentation with fever of unknown origin, intestinal obstruction, or surgical emergency due o acute infalmmatory lesions have also been reported percentage not given
These symptoms can accompany many other, less serious medical conditions; if you are experiencing any of these symptoms, and have been exposed to asbestos, you should see a doctor immediately. Asbestos exposure may have taken place 20, 30, even 50 years prior to symptoms appearing, but is a major risk factor; exposure is reported in between 70-80% of all mesothelioma cases.
Very often, asbestos exposure was second hand through a family member. Clothes dirtied with asbestos dust have carried fibers into homes, affecting spouses and children. Workers handling asbestos are now required to change their clothing before leaving work. If you see your physician because you are experiencing any of the mesothelioma symptoms listed above, please make sure to make them aware for any prior exposure, either first- or second-hand.
Mesothelioma: Diagnosis and Differentiation Journal Articles
12.02.08 - Monitoring of Chemotherapy Response in Malignant Pleural Mesothelioma Using Fluorodeoxyglucose Positron Emission Tomography
We report a 56-year-old man who underwent monitoring of the response to chemotherapy of malignant pleural mesothelioma (MPM). 8F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) and [...]
11.27.08 - The Role of Podoplanin in Tumor Progression and Metastasis
In the last decade, much data has been generated concerning the molecular mechanisms of lymphangiogenesis and its significance in pathological conditions. This was mainly due to the discovery of lymphatic endothelial cell (LEC)-specific [...]
11.27.08 - Clinicopathologic and prognostic significance of overexpression of her-2/neu and p53 oncoproteins in gastric carcinoma using tissue microarray
Background: The aim of the study was to verify the frequency of the immunohistochemical overexpression of her-2/neu and p53 in gastric carcinoma and their relation to the [...]
11.26.08 - Malignant pleural mesothelioma: biology and diagnosis
Malignant pleural mesothelioma (MPM) is a serious issue worldwide because of its increasing incidence and poor prognosis despite real recent improvements in the disease management. Most of the patients [...]
11.26.08 - Comparison of semiquantitative fluorescence imaging and PET tracer uptake in mesothelioma models as a monitoring system for growth and therapeutic effects
Introduction: Various techniques are available for in vivo imaging, and precise understanding of their characteristics is essential for effective use of the imaging results. We established human mesothelioma cell lines [...]As a first step in diagnosing the disease, the doctor may order an x-ray of the chest or abdomen or a CT (or CAT) scan or MRI may be performed. Although mesothelioma typically cannot be seen on an x-ray, the tumor often causes a pleural effusion, or fluid collection between the lung and chest wall. This abnormal finding is associated with shortness of breath and warrants clinical follow up. Lung function tests may also be completed.
The doctor may look inside the chest cavity with a special instrument called a thoracoscope. A cut will be made through the chest wall and the thoracoscope will be put into the chest between two ribs. This test, called thoracoscopy, is usually done in the hospital. Before the test, the patient will be given a local anesthetic (a drug that causes a loss of feeling for a short period of time). Some pressure may be felt, but usually there is no pain.
The doctor may also look inside the abdomen (peritoneoscopy) with a special tool called a peritoneoscope. The peritoneoscope is put into an opening made in the abdomen. This test is also usually done in the hospital. Before the test is done, a local anesthetic will be given.
If tissue that is not normal is found, the doctor will need to cut out a small piece and have it reviewed under a microscope to see if there are any cancer cells. This is called a biopsy. Biopsies are usually done during the thoracoscopy or peritoneoscopy.
Diagnosing mesothelioma is very difficult, and cases of mesothelioma misdiagnosed are unfortunately not uncommon. It is important to share your case history of work experience (especially in shipyards and at construction sites) and asbestos exposure potential with your physicians if you feel mesothelioma is a risk. Asbestos fibres can also be carried into the home on clothing, inadvertently exposing the deadly fibres, and the risk of mesothelioma, to family members.
A mesothelioma diagnosis is serious, but treatments are available. The chance of recovery (prognosis) depends on the size of the cancer, where the cancer is, how far the cancer has spread, how the cancer cells look under the microscope, how the cancer responds to treatment, and the patient's age. As with most types of cancer, early diagnosis is an excellent first step in fighting the disease.
Mesothelioma Symptoms
If you are wondering "do I have mesothelioma?" you should seek the guidance of your physician as early detection is a powerful asset during treatment. Malignant mesothelioma may not become apparent until 20 to 30 years after the first exposure to asbestos, but can be very aggressive once it takes hold. Because the symptoms of mesothelioma are not unique to the disease a mesothelioma diagnosis can be difficult to determine.
Symptoms of Pleural Mesothelioma
Symptoms of pleural mesothelioma (mesothelioma of the lining of the lung, known as the pleura) may include, but are not limited to, the following:
•shortness of breath (dyspnea) - hoarseness, difficulty swallowing, and/or coughing up of blood.
•pleural effusion - a build up of too much fluid between the pleura (linings of the lungs and chest); a pleural effusion may cause chest pain and difficulty breathing (dyspnea), however, many cause no symptoms and are first discovered during the physical examination or seen on a chest x-ray.
•pain in the chest - may sometimes be felt in upper abdomen, shoulder, or arm.
Patients diagnosed with diffuse pleural mesothelioma exhibited the following symptoms
(source: "Diffuse malignant mesothelioma of the pleura in Ontario and Quebec: a retrospective study of 332 patients." P Ruffie et al. Journal of Clinical Oncology Aug 1 1989: 1157-1168.) Symptom % exhibiting
Shortness of breath and/or chest pain 90%
Weight loss 29%
Cough, weakness, fever, loss of appetite 3%
Hemoptysis (coughing up blood), hoarseness, dysphagia (difficulty swallowing), Horner's syndrome less than 1%
Pleural Effusions 84%
Asymptomatic 3%
Symptoms of Peritoneal Mesothelioma
Symptoms of peritoneal mesothelioma (mesothelioma of the abdominal lining which is known as the peritoneum) may include, but are not limited to, the following:
•weight loss - but waist may increase in size.
•pain or swelling in the abdomen - fluid retention or tumor growth.
•bowel obstruction - blockage in the small or large intestine.
•anemia - a reduction in the number of red blood cells to below normal; this forces the heart and other organs to work harder to get oxygen where it's needed.
•fever
Patients diagnosed with peritoneal mesothelioma exhibited the following symptoms
(source: "Peritoneal Mesothelioma: A Review." Bridda A, Padoan I, Mencarelli R, Frego M. MedGenMed 2007 May 10;9(2):32.) Symptom % exhibiting
Abdominal pain 35%
Abdominal swelling 31%
anorexia, marked weight loss, and ascites percentage not given
less frequently night sweats and hypercoagulability percentage not given
Clinical presentation with fever of unknown origin, intestinal obstruction, or surgical emergency due o acute infalmmatory lesions have also been reported percentage not given
These symptoms can accompany many other, less serious medical conditions; if you are experiencing any of these symptoms, and have been exposed to asbestos, you should see a doctor immediately. Asbestos exposure may have taken place 20, 30, even 50 years prior to symptoms appearing, but is a major risk factor; exposure is reported in between 70-80% of all mesothelioma cases.
Very often, asbestos exposure was second hand through a family member. Clothes dirtied with asbestos dust have carried fibers into homes, affecting spouses and children. Workers handling asbestos are now required to change their clothing before leaving work. If you see your physician because you are experiencing any of the mesothelioma symptoms listed above, please make sure to make them aware for any prior exposure, either first- or second-hand.
Saturday, August 8, 2009
Swine Flue : why is it infecting humans?
swine flu : The defination
The swine influenza A (H1N1) virus that has infected humans in the U.S. and Mexico is a novel influenza A virus that has not previously been identified in North America. This virus is resistant to the antiviral medications amantadine (Symmetrel) and rimantadine (Flumadine), but is sensitive to oseltamivir (Tamiflu) and zanamivir (Relenza). Investigations of these cases suggest that on-going human-to-human swine influenza A (H1N1) virus is occurring.
swine flu : Symptoms
Although uncomplicated influenza-like illness (fever, cough or sore throat) has been reported in many cases, mild respiratory illness (nasal congestion, rhinorrhea) without fever and occasional severe disease also has been reported. Other symptoms reported with swine influenza A virus infection include vomiting, diarrhea, myalgia, headache, chills, fatigue, and dyspnea. Conjunctivitis is rare, but has been reported. Severe disease (pneumonia, respiratory failure) and fatal outcomes have been reported with swine influenza A virus infection. The potential for exacerbation of underlying chronic medical conditions or invasive bacterial infection with swine influenza A virus infection should be considered.
Why is swine flu now infecting humans?
Many researchers now consider that two main series of events can lead to swine flu (and also avian or bird flu) becoming a major cause for influenza illness in humans.
First, the influenza viruses (types A, B, C) are enveloped RNA viruses with a segmented genome; this means the viral RNA genetic code is not a single strand of RNA but exists as eight different RNA segments in the influenza viruses. A human (or bird) influenza virus can infect a pig respiratory cell at the same time as a swine influenza virus; some of the replicating RNA strands from the human virus can get mistakenly enclosed inside the enveloped swine influenza virus. For example, one cell could contain eight swine flu and eight human flu RNA segments. The total number of RNA types in one cell would be 16; four swine and four human flu RNA segments could be incorporated into one particle, making a viable eight RNA segmented flu virus from the 16 available segment types. Various combinations of RNA segments can result in a new subtype of virus (known as antigenic shift) that may have the ability to preferentially infect humans but still show characteristics unique to the swine influenza virus (see Figure 1). It is even possible to include RNA strands from birds, swine, and human influenza viruses into one virus if a cell becomes infected with all three types of influenza (for example, two bird flu, three swine flu, and three human flu RNA segments to produce a viable eight-segment new type of flu viral genome). Formation of a new viral type is considered to be antigenic shift; small changes in an individual RNA segment in flu viruses are termed antigenic drift and result in minor changes in the virus. However, these can accumulate over time to produce enough minor changes that cumulatively change the virus' antigenic makeup over time (usually years).
Second, pigs can play a unique role as an intermediary host to new flu types because pig respiratory cells can be infected directly with bird, human, and other mammalian flu viruses. Consequently, pig respiratory cells are able to be infected with many types of flu and can function as a "mixing pot" for flu RNA segments (see Figure 1). Bird flu viruses, which usually infect the gastrointestinal cells of many bird species, are shed in bird feces. Pigs can pick these viruses up from the environment and seem to be the major way that bird flu virus RNA segments enter the mammalian flu virus population.
Infectious Period
Persons with swine influenza A (H1N1) virus infection should be considered potentially contagious for up to 7 days following illness onset. Persons who continue to be ill longer than 7 days after illness onset should be considered potentially contagious until symptoms have resolved. Children, especially younger children, might potentially be contagious for longer periods. The duration of infectiousness might vary by swine influenza A (H1N1) virus strain. Non-hospitalized ill persons who are a confirmed or suspected case of swine influenza A (H1N1) virus infection are recommended to stay at home (voluntary isolation) for at least the first 7 days after illness onset except to seek medical care.
Case definitions
A confirmed case of swine influenza A (H1N1) virus infection is defined as a person with an acute respiratory illness with laboratory confirmed swine influenza A (H1N1) virus infection at CDC by one or more of the following tests:
•real-time RT-PCR
•viral culture
•four-fold rise in swine influenza A (H1N1) virus-specific neutralizing antibodies
A suspected case of swine influenza A (H1N1) virus infection is defined as a person with acute febrile respiratory illness with onset within 7 days of close contact with a person who is a confirmed case of swine influenza A (H1N1) virus infection.
Close contact is defined as: within about 6 feet of an ill person who is a confirmed or suspected case of swine influenza A (H1N1) virus infection.
•Close contact is defined as: within about 6 feet of an ill person who is a confirmed case of swine influenza A virus infection
Acute respiratory illness is defined as recent onset of at least two of the following: rhinorrhea or nasal congestion, sore throat, cough (with or without fever or feverishness)
Recommendations for public health personnel
For interviews of healthy individuals (i.e. without a current respiratory illness), including close contacts of cases of confirmed swine influenza virus infection, no personal protective equipment or antiviral chemoprophylaxis is needed. See section on antiviral chemoprophylaxis for further guidance.
For interviews of an ill, suspected or confirmed swine influenza A virus case, the following is recommended:
•Keep a distance of at least 6 feet from the ill person; or
•Personal protective equipment: fit-tested N95 respirator [if unavailable, wear a medical (surgical mask)].
For collecting respiratory specimens from an ill confirmed or suspected swine influenza A virus case, the following is recommended:
•Personal protective equipment: fit-tested disposable N95 respirator [if unavailable, wear a medical (surgical mask)], disposable gloves, gown, and goggles.
•When completed, place all PPE in a biohazard bag for appropriate disposal.
•Wash hands thoroughly with soap and water or alcohol-based hand gel.
Infection Control
Recommended Infection Control for a non-hospitalized patient (ER, clinic or home visit):
1.Separation from others in single room if available until asymptomatic. If the ill person needs to move to another part of the house, they should wear a mask. The ill person should be encouraged to wash hand frequently and follow respiratory hygiene practices. Cups and other utensils used by the ill person should be thoroughly washed with soap and water before use by other persons.
Antiviral Treatment
Suspected Cases
Empiric antiviral treatment is recommended for any ill person suspected to have swine influenza A (H1N1) virus infection. Antiviral treatment with either zanamivir alone or with a combination of oseltamivir and either amantadine or rimantadine should be initiated as soon as possible after the onset of symptoms. Recommended duration of treatment is five days. Recommendations for use of antivirals may change as data on antiviral susceptibilities become available. Antiviral doses and schedules recommended for treatment of swine influenza A (H1N1) virus infection are the same as those recommended for seasonal influenza:
Confirmed Cases
For antiviral treatment of a confirmed case of swine influenza A (H1N1) virus infection, either oseltamivir (Tamiflu) or zanamivir (Relenza) may be administered. Recommended duration of treatment is five days. These same antivirals should be considered for treatment of cases that test positive for influenza A but test negative for seasonal influenza viruses H3 and H1 by PCR.
Pregnant Women
Oseltamivir, zanamivir, amantadine, and rimantadine are all "Pregnancy Category C" medications, indicating that no clinical studies have been conducted to assess the safety of these medications for pregnant women. Only two cases of amantadine use for severe influenza illness during the third trimester have been reported. However, both amantadine and rimantadine have been demonstrated in animal studies to be teratogenic and embryotoxic when administered at substantially high doses. Because of the unknown effects of influenza antiviral drugs on pregnant women and their fetuses, these four drugs should be used during pregnancy only if the potential benefit justifies the potential risk to the embryo or fetus; the manufacturers' package inserts should be consulted. However, no adverse effects have been reported among women who received oseltamivir or zanamivir during pregnancy or among infants born to such women.
Antiviral Chemoprophylaxis
For antiviral chemoprophylaxis of swine influenza A (H1N1) virus infection, either oseltamivir or zanamivir are recommended. Duration of antiviral chemoprophylaxis is 7 days after the last known exposure to an ill confirmed case of swine influenza A (H1N1) virus infection. Antiviral dosing and schedules recommended for chemoprophylaxis of swine influenza A (H1N1) virus infection are the same as those recommended for seasonal influenza:
Antiviral chemoprophylaxis (pre-exposure or post-exposure) with either oseltamivir or zanamivir is recommended for the following individuals:
1.Household close contacts who are at high-risk for complications of influenza (persons with certain chronic medical conditions, elderly) of a confirmed or suspected case.
2.School children who are at high-risk for complications of influenza (persons with certain chronic medical conditions) who had close contact (face-to-face) with a confirmed or suspected case.
3.Travelers to Mexico who are at high-risk for complications of influenza (persons with certain chronic medical conditions, elderly).
4.Border workers (Mexico) who are at high-risk for complications of influenza (persons with certain chronic medical conditions, elderly).
5.Health care workers or public health workers who had unprotected close contact with an ill confirmed case of swine influenza A (H1N1) virus infection during the case's infectious period.
Antiviral chemoprophylaxis (pre-exposure or post-exposure) with either oseltamivir or zanamivir can be considered for the following:
•Any health care worker who is at high-risk for complications of influenza (persons with certain chronic medical conditions, elderly) who is working in an area with confirmed swine influenza A (H1N1) cases, and who is caring for patients with any acute febrile respiratory illness.
•Non-high risk persons who are travelers to Mexico, first responders, or border workers who are working in areas with confirmed cases of swine influenza A (H1N1) virus infection.
Will a face mask protect me from getting the swine flu, and are there differences in face masks?
Information on the effectiveness of facemasks and respirators for the control of influenza in community settings is extremely limited. Thus, it is difficult to assess their potential effectiveness in controlling swine influenza A (H1N1) virus transmission in these settings. In the absence of clear scientific data, the interim recommendations below have been developed on the basis of public health judgment and the historical use of facemasks and respirators in other settings.
In areas with confirmed human cases of swine influenza A (H1N1) virus infection, the risk for infection can be reduced through a combination of actions. No single action will provide complete protection, but an approach combining the following steps can help decrease the likelihood of transmission. These actions include frequent handwashing, covering coughs, and having ill persons stay home, except to seek medical care, and minimize contact with others in the household. Additional measures that can limit transmission of a new influenza strain include voluntary home quarantine of members of households with confirmed or probable swine influenza cases, reduction of unnecessary social contacts, and avoidance whenever possible of crowded settings.
When it is absolutely necessary to enter a crowded setting or to have close contact3 with persons who might be ill, the time spent in that setting should be as short as possible. If used correctly, facemasks and respirators may help reduce the risk of getting influenza, but they should be used along with other preventive measures, such as avoiding close contact and maintaining good hand hygiene. A respirator that fits snugly on your face can filter out small particles that can be inhaled around the edges of a facemask, but compared with a facemask it is harder to breathe through a respirator for long periods of time.
When crowded settings or close contact with others cannot be avoided, the use of facemasks or respirators in areas where transmission of swine influenza A (H1N1) virus has been confirmed should be considered as follows:
1.Whenever possible, rather than relying on the use of facemasks or respirators, close contact with people who might be ill and being in crowded settings should be avoided.
2.Facemasks should be considered for use by individuals who enter crowded settings, both to protect their nose and mouth from other people's coughs and to reduce the wearers' likelihood of coughing on others; the time spent in crowded settings should be as short as possible.
3.Respirators should be considered for use by individuals for whom close contact with an infectious person is unavoidable. This can include selected individuals who must care for a sick person (e.g., family member with a respiratory infection) at home.
These interim recommendations will be revised as new information about the use of facemasks and respirators in the current setting becomes available.
What are the types of face masks and respirators?
•Unless otherwise specified, the term "facemasks" refers to disposable masks cleared by the U.S. Food and Drug Administration (FDA) for use as medical devices. This includes facemasks labeled as surgical, dental, medical procedure, isolation, or laser masks. Such facemasks have several designs. One type is affixed to the head with two ties, conforms to the face with the aid of a flexible adjustment for the nose bridge, and may be flat/pleated or duck-billed in shape. Another type of facemask is pre-molded, adheres to the head with a single elastic band, and has a flexible adjustment for the nose bridge. A third type is flat/pleated and affixes to the head with ear loops. Facemasks cleared by the FDA for use as medical devices have been determined to have specific levels of protection from penetration of blood and body fluids.
•Unless otherwise specified, "respirator" refers to an N95 or higher filtering facepiece respirator certified by the U.S. National Institute for Occupational Safety and Health (NIOSH).
•Three feet has often been used by infection control professionals to define close contact and is based on studies of respiratory infections; however, for practical purposes, this distance may range up to 6 feet. The World Health Organization uses "approximately 1 meter"; the U.S. Occupational Safety and Health Administration uses "within 6 feet." For consistency with these estimates, this document defines close contact as a distance of up to 6 feet.
The swine influenza A (H1N1) virus that has infected humans in the U.S. and Mexico is a novel influenza A virus that has not previously been identified in North America. This virus is resistant to the antiviral medications amantadine (Symmetrel) and rimantadine (Flumadine), but is sensitive to oseltamivir (Tamiflu) and zanamivir (Relenza). Investigations of these cases suggest that on-going human-to-human swine influenza A (H1N1) virus is occurring.
swine flu : Symptoms
Although uncomplicated influenza-like illness (fever, cough or sore throat) has been reported in many cases, mild respiratory illness (nasal congestion, rhinorrhea) without fever and occasional severe disease also has been reported. Other symptoms reported with swine influenza A virus infection include vomiting, diarrhea, myalgia, headache, chills, fatigue, and dyspnea. Conjunctivitis is rare, but has been reported. Severe disease (pneumonia, respiratory failure) and fatal outcomes have been reported with swine influenza A virus infection. The potential for exacerbation of underlying chronic medical conditions or invasive bacterial infection with swine influenza A virus infection should be considered.
Why is swine flu now infecting humans?
Many researchers now consider that two main series of events can lead to swine flu (and also avian or bird flu) becoming a major cause for influenza illness in humans.
First, the influenza viruses (types A, B, C) are enveloped RNA viruses with a segmented genome; this means the viral RNA genetic code is not a single strand of RNA but exists as eight different RNA segments in the influenza viruses. A human (or bird) influenza virus can infect a pig respiratory cell at the same time as a swine influenza virus; some of the replicating RNA strands from the human virus can get mistakenly enclosed inside the enveloped swine influenza virus. For example, one cell could contain eight swine flu and eight human flu RNA segments. The total number of RNA types in one cell would be 16; four swine and four human flu RNA segments could be incorporated into one particle, making a viable eight RNA segmented flu virus from the 16 available segment types. Various combinations of RNA segments can result in a new subtype of virus (known as antigenic shift) that may have the ability to preferentially infect humans but still show characteristics unique to the swine influenza virus (see Figure 1). It is even possible to include RNA strands from birds, swine, and human influenza viruses into one virus if a cell becomes infected with all three types of influenza (for example, two bird flu, three swine flu, and three human flu RNA segments to produce a viable eight-segment new type of flu viral genome). Formation of a new viral type is considered to be antigenic shift; small changes in an individual RNA segment in flu viruses are termed antigenic drift and result in minor changes in the virus. However, these can accumulate over time to produce enough minor changes that cumulatively change the virus' antigenic makeup over time (usually years).
Second, pigs can play a unique role as an intermediary host to new flu types because pig respiratory cells can be infected directly with bird, human, and other mammalian flu viruses. Consequently, pig respiratory cells are able to be infected with many types of flu and can function as a "mixing pot" for flu RNA segments (see Figure 1). Bird flu viruses, which usually infect the gastrointestinal cells of many bird species, are shed in bird feces. Pigs can pick these viruses up from the environment and seem to be the major way that bird flu virus RNA segments enter the mammalian flu virus population.
Infectious Period
Persons with swine influenza A (H1N1) virus infection should be considered potentially contagious for up to 7 days following illness onset. Persons who continue to be ill longer than 7 days after illness onset should be considered potentially contagious until symptoms have resolved. Children, especially younger children, might potentially be contagious for longer periods. The duration of infectiousness might vary by swine influenza A (H1N1) virus strain. Non-hospitalized ill persons who are a confirmed or suspected case of swine influenza A (H1N1) virus infection are recommended to stay at home (voluntary isolation) for at least the first 7 days after illness onset except to seek medical care.
Case definitions
A confirmed case of swine influenza A (H1N1) virus infection is defined as a person with an acute respiratory illness with laboratory confirmed swine influenza A (H1N1) virus infection at CDC by one or more of the following tests:
•real-time RT-PCR
•viral culture
•four-fold rise in swine influenza A (H1N1) virus-specific neutralizing antibodies
A suspected case of swine influenza A (H1N1) virus infection is defined as a person with acute febrile respiratory illness with onset within 7 days of close contact with a person who is a confirmed case of swine influenza A (H1N1) virus infection.
Close contact is defined as: within about 6 feet of an ill person who is a confirmed or suspected case of swine influenza A (H1N1) virus infection.
•Close contact is defined as: within about 6 feet of an ill person who is a confirmed case of swine influenza A virus infection
Acute respiratory illness is defined as recent onset of at least two of the following: rhinorrhea or nasal congestion, sore throat, cough (with or without fever or feverishness)
Recommendations for public health personnel
For interviews of healthy individuals (i.e. without a current respiratory illness), including close contacts of cases of confirmed swine influenza virus infection, no personal protective equipment or antiviral chemoprophylaxis is needed. See section on antiviral chemoprophylaxis for further guidance.
For interviews of an ill, suspected or confirmed swine influenza A virus case, the following is recommended:
•Keep a distance of at least 6 feet from the ill person; or
•Personal protective equipment: fit-tested N95 respirator [if unavailable, wear a medical (surgical mask)].
For collecting respiratory specimens from an ill confirmed or suspected swine influenza A virus case, the following is recommended:
•Personal protective equipment: fit-tested disposable N95 respirator [if unavailable, wear a medical (surgical mask)], disposable gloves, gown, and goggles.
•When completed, place all PPE in a biohazard bag for appropriate disposal.
•Wash hands thoroughly with soap and water or alcohol-based hand gel.
Infection Control
Recommended Infection Control for a non-hospitalized patient (ER, clinic or home visit):
1.Separation from others in single room if available until asymptomatic. If the ill person needs to move to another part of the house, they should wear a mask. The ill person should be encouraged to wash hand frequently and follow respiratory hygiene practices. Cups and other utensils used by the ill person should be thoroughly washed with soap and water before use by other persons.
Antiviral Treatment
Suspected Cases
Empiric antiviral treatment is recommended for any ill person suspected to have swine influenza A (H1N1) virus infection. Antiviral treatment with either zanamivir alone or with a combination of oseltamivir and either amantadine or rimantadine should be initiated as soon as possible after the onset of symptoms. Recommended duration of treatment is five days. Recommendations for use of antivirals may change as data on antiviral susceptibilities become available. Antiviral doses and schedules recommended for treatment of swine influenza A (H1N1) virus infection are the same as those recommended for seasonal influenza:
Confirmed Cases
For antiviral treatment of a confirmed case of swine influenza A (H1N1) virus infection, either oseltamivir (Tamiflu) or zanamivir (Relenza) may be administered. Recommended duration of treatment is five days. These same antivirals should be considered for treatment of cases that test positive for influenza A but test negative for seasonal influenza viruses H3 and H1 by PCR.
Pregnant Women
Oseltamivir, zanamivir, amantadine, and rimantadine are all "Pregnancy Category C" medications, indicating that no clinical studies have been conducted to assess the safety of these medications for pregnant women. Only two cases of amantadine use for severe influenza illness during the third trimester have been reported. However, both amantadine and rimantadine have been demonstrated in animal studies to be teratogenic and embryotoxic when administered at substantially high doses. Because of the unknown effects of influenza antiviral drugs on pregnant women and their fetuses, these four drugs should be used during pregnancy only if the potential benefit justifies the potential risk to the embryo or fetus; the manufacturers' package inserts should be consulted. However, no adverse effects have been reported among women who received oseltamivir or zanamivir during pregnancy or among infants born to such women.
Antiviral Chemoprophylaxis
For antiviral chemoprophylaxis of swine influenza A (H1N1) virus infection, either oseltamivir or zanamivir are recommended. Duration of antiviral chemoprophylaxis is 7 days after the last known exposure to an ill confirmed case of swine influenza A (H1N1) virus infection. Antiviral dosing and schedules recommended for chemoprophylaxis of swine influenza A (H1N1) virus infection are the same as those recommended for seasonal influenza:
Antiviral chemoprophylaxis (pre-exposure or post-exposure) with either oseltamivir or zanamivir is recommended for the following individuals:
1.Household close contacts who are at high-risk for complications of influenza (persons with certain chronic medical conditions, elderly) of a confirmed or suspected case.
2.School children who are at high-risk for complications of influenza (persons with certain chronic medical conditions) who had close contact (face-to-face) with a confirmed or suspected case.
3.Travelers to Mexico who are at high-risk for complications of influenza (persons with certain chronic medical conditions, elderly).
4.Border workers (Mexico) who are at high-risk for complications of influenza (persons with certain chronic medical conditions, elderly).
5.Health care workers or public health workers who had unprotected close contact with an ill confirmed case of swine influenza A (H1N1) virus infection during the case's infectious period.
Antiviral chemoprophylaxis (pre-exposure or post-exposure) with either oseltamivir or zanamivir can be considered for the following:
•Any health care worker who is at high-risk for complications of influenza (persons with certain chronic medical conditions, elderly) who is working in an area with confirmed swine influenza A (H1N1) cases, and who is caring for patients with any acute febrile respiratory illness.
•Non-high risk persons who are travelers to Mexico, first responders, or border workers who are working in areas with confirmed cases of swine influenza A (H1N1) virus infection.
Will a face mask protect me from getting the swine flu, and are there differences in face masks?
Information on the effectiveness of facemasks and respirators for the control of influenza in community settings is extremely limited. Thus, it is difficult to assess their potential effectiveness in controlling swine influenza A (H1N1) virus transmission in these settings. In the absence of clear scientific data, the interim recommendations below have been developed on the basis of public health judgment and the historical use of facemasks and respirators in other settings.
In areas with confirmed human cases of swine influenza A (H1N1) virus infection, the risk for infection can be reduced through a combination of actions. No single action will provide complete protection, but an approach combining the following steps can help decrease the likelihood of transmission. These actions include frequent handwashing, covering coughs, and having ill persons stay home, except to seek medical care, and minimize contact with others in the household. Additional measures that can limit transmission of a new influenza strain include voluntary home quarantine of members of households with confirmed or probable swine influenza cases, reduction of unnecessary social contacts, and avoidance whenever possible of crowded settings.
When it is absolutely necessary to enter a crowded setting or to have close contact3 with persons who might be ill, the time spent in that setting should be as short as possible. If used correctly, facemasks and respirators may help reduce the risk of getting influenza, but they should be used along with other preventive measures, such as avoiding close contact and maintaining good hand hygiene. A respirator that fits snugly on your face can filter out small particles that can be inhaled around the edges of a facemask, but compared with a facemask it is harder to breathe through a respirator for long periods of time.
When crowded settings or close contact with others cannot be avoided, the use of facemasks or respirators in areas where transmission of swine influenza A (H1N1) virus has been confirmed should be considered as follows:
1.Whenever possible, rather than relying on the use of facemasks or respirators, close contact with people who might be ill and being in crowded settings should be avoided.
2.Facemasks should be considered for use by individuals who enter crowded settings, both to protect their nose and mouth from other people's coughs and to reduce the wearers' likelihood of coughing on others; the time spent in crowded settings should be as short as possible.
3.Respirators should be considered for use by individuals for whom close contact with an infectious person is unavoidable. This can include selected individuals who must care for a sick person (e.g., family member with a respiratory infection) at home.
These interim recommendations will be revised as new information about the use of facemasks and respirators in the current setting becomes available.
What are the types of face masks and respirators?
•Unless otherwise specified, the term "facemasks" refers to disposable masks cleared by the U.S. Food and Drug Administration (FDA) for use as medical devices. This includes facemasks labeled as surgical, dental, medical procedure, isolation, or laser masks. Such facemasks have several designs. One type is affixed to the head with two ties, conforms to the face with the aid of a flexible adjustment for the nose bridge, and may be flat/pleated or duck-billed in shape. Another type of facemask is pre-molded, adheres to the head with a single elastic band, and has a flexible adjustment for the nose bridge. A third type is flat/pleated and affixes to the head with ear loops. Facemasks cleared by the FDA for use as medical devices have been determined to have specific levels of protection from penetration of blood and body fluids.
•Unless otherwise specified, "respirator" refers to an N95 or higher filtering facepiece respirator certified by the U.S. National Institute for Occupational Safety and Health (NIOSH).
•Three feet has often been used by infection control professionals to define close contact and is based on studies of respiratory infections; however, for practical purposes, this distance may range up to 6 feet. The World Health Organization uses "approximately 1 meter"; the U.S. Occupational Safety and Health Administration uses "within 6 feet." For consistency with these estimates, this document defines close contact as a distance of up to 6 feet.
Lung Cancer
Lung Cancer Symptoms
Up to one-fourth of all people with lung cancer may have no symptoms when the cancer is diagnosed. These cancers usually are identified incidentally when a chest x-ray is performed for another reason. The majority of people, however, develop symptoms. The symptoms are due to direct effects of the primary tumor, to effects of metastatic tumors in other parts of the body, or to disturbances of hormones, blood, or other systems caused by the cancer.
Symptoms of primary lung cancers include cough, coughing up blood, chest pain, and shortness of breath.
•A new cough in a smoker or a former smoker should raise concern for lung cancer.
•A cough that does not go away or gets worse over time should be evaluated by a health-care provider.
•Coughing up blood (hemoptysis) occurs in a significant number of people who have lung cancer. Any amount of coughed-up blood is cause for concern.
•Chest pain is a symptom in about one-fourth of people with lung cancer. The pain is dull, aching, and persistent and may involve other structures surrounding the lung.
•Shortness of breath usually results from a blockage to the flow of air in part of the lung, collection of fluid around the lung (pleural effusion), or the spread of tumor throughout the lungs.
•Wheezing or hoarseness may signal blockage or inflammation in the lungs that may go along with cancer.
•Repeated respiratory infections, such as bronchitis or pneumonia, can be a sign of lung cancer.
Symptoms of metastatic lung tumors depend on the location and size. About 30%-40% of people with lung cancer have some symptoms or signs of metastatic disease.
•Lung cancer most often spreads to the liver, the adrenal glands, the bones, and the brain.
•Metastatic lung cancer in the liver usually does not cause symptoms, at least by the time of diagnosis.
•Metastatic lung cancer in the adrenal glands also typically causes no symptoms by the time of diagnosis.
•Metastasis to the bones is most common with small cell cancers but also occurs with other lung cancer types. Lung cancer that has metastasized to the bone causes bone pain, usually in the backbone (vertebrae), the thighbones, and the ribs.
•Lung cancer that spreads to the brain can cause difficulties with vision, weakness on one side of the body, and/or seizures.
Paraneoplastic syndromes are the remote, indirect effects of cancer not related to direct invasion of an organ by tumor cells. Often they are caused by chemicals released from the cancers. Symptoms include the following:
•clubbing of fingers-the depositing of extra tissue under the fingernails
•new bone formation-along the lower legs or arms
•anemia-low numbers of red blood cells and high calcium level or low sodium level in the blood
•other effects-muscle weakness, skin rashes, and degeneration of the brain
•weight loss
•fatigue
•low sodium levels
When to Seek Medical Care
See a health-care provider as soon as possible if any of the following develop:
•any symptom of lung cancer,
•new cough or change in an existing cough,
•hemoptysis (flecks of blood in the sputum when coughing),
•unexplained weight loss,
•unexplained persistent fatigue, or
•unexplained deep aches or pains.
Go immediately to the nearest hospital emergency department if any of the following occur:
•coughing up a large amount of blood,
•sudden shortness of breath,
•sudden weakness,
•sudden vision problems, or
•persistent chest pain.
Up to one-fourth of all people with lung cancer may have no symptoms when the cancer is diagnosed. These cancers usually are identified incidentally when a chest x-ray is performed for another reason. The majority of people, however, develop symptoms. The symptoms are due to direct effects of the primary tumor, to effects of metastatic tumors in other parts of the body, or to disturbances of hormones, blood, or other systems caused by the cancer.
Symptoms of primary lung cancers include cough, coughing up blood, chest pain, and shortness of breath.
•A new cough in a smoker or a former smoker should raise concern for lung cancer.
•A cough that does not go away or gets worse over time should be evaluated by a health-care provider.
•Coughing up blood (hemoptysis) occurs in a significant number of people who have lung cancer. Any amount of coughed-up blood is cause for concern.
•Chest pain is a symptom in about one-fourth of people with lung cancer. The pain is dull, aching, and persistent and may involve other structures surrounding the lung.
•Shortness of breath usually results from a blockage to the flow of air in part of the lung, collection of fluid around the lung (pleural effusion), or the spread of tumor throughout the lungs.
•Wheezing or hoarseness may signal blockage or inflammation in the lungs that may go along with cancer.
•Repeated respiratory infections, such as bronchitis or pneumonia, can be a sign of lung cancer.
Symptoms of metastatic lung tumors depend on the location and size. About 30%-40% of people with lung cancer have some symptoms or signs of metastatic disease.
•Lung cancer most often spreads to the liver, the adrenal glands, the bones, and the brain.
•Metastatic lung cancer in the liver usually does not cause symptoms, at least by the time of diagnosis.
•Metastatic lung cancer in the adrenal glands also typically causes no symptoms by the time of diagnosis.
•Metastasis to the bones is most common with small cell cancers but also occurs with other lung cancer types. Lung cancer that has metastasized to the bone causes bone pain, usually in the backbone (vertebrae), the thighbones, and the ribs.
•Lung cancer that spreads to the brain can cause difficulties with vision, weakness on one side of the body, and/or seizures.
Paraneoplastic syndromes are the remote, indirect effects of cancer not related to direct invasion of an organ by tumor cells. Often they are caused by chemicals released from the cancers. Symptoms include the following:
•clubbing of fingers-the depositing of extra tissue under the fingernails
•new bone formation-along the lower legs or arms
•anemia-low numbers of red blood cells and high calcium level or low sodium level in the blood
•other effects-muscle weakness, skin rashes, and degeneration of the brain
•weight loss
•fatigue
•low sodium levels
When to Seek Medical Care
See a health-care provider as soon as possible if any of the following develop:
•any symptom of lung cancer,
•new cough or change in an existing cough,
•hemoptysis (flecks of blood in the sputum when coughing),
•unexplained weight loss,
•unexplained persistent fatigue, or
•unexplained deep aches or pains.
Go immediately to the nearest hospital emergency department if any of the following occur:
•coughing up a large amount of blood,
•sudden shortness of breath,
•sudden weakness,
•sudden vision problems, or
•persistent chest pain.
Friday, August 7, 2009
Mesothelioma
Mesothelioma is a form of cancer that is almost always caused by exposure to asbestos. In this disease, malignant cells develop in the mesothelium, a protective lining that covers most of the body's internal organs. Its most common site is the pleura (outer lining of the lungs and internal chest wall), but it may also occur in the peritoneum (the lining of the abdominal cavity), the heart,the pericardium (a sac that surrounds the heart) or tunica vaginalis.
Most people who develop mesothelioma have worked on jobs where they inhaled asbestos particles, or they have been exposed to asbestos dust and fiber in other ways. It has also been suggested that washing the clothes of a family member who worked with asbestos can put a person at risk for developing mesothelioma.Unlike lung cancer, there is no association between mesothelioma and smoking, but smoking greatly increases risk of other asbestos-induced cancer.Compensation via asbestos funds or lawsuits is an important issue in mesothelioma (see asbestos and the law).
The symptoms of mesothelioma include shortness of breath due to pleural effusion (fluid between the lung and the chest wall) or chest wall pain, and general symptoms such as weight loss. The diagnosis may be suspected with chest X-ray and CT scan, and is confirmed with a biopsy (tissue sample) and microscopic examination. A thoracoscopy (inserting a tube with a camera into the chest) can be used to take biopsies. It allows the introduction of substances such as talc to obliterate the pleural space (called pleurodesis), which prevents more fluid from accumulating and pressing on the lung. Despite treatment with chemotherapy, radiation therapy or sometimes surgery, the disease carries a poor prognosis. Research about screening tests for the early detection of mesothelioma is ongoing.
Signs and symptoms
Symptoms of mesothelioma may not appear until 20 to 50 years after exposure to asbestos. Shortness of breath, cough, and pain in the chest due to an accumulation of fluid in the pleural space are often symptoms of pleural mesothelioma.
Symptoms of peritoneal mesothelioma include weight loss and cachexia, abdominal swelling and pain due to ascites (a buildup of fluid in the abdominal cavity). Other symptoms of peritoneal mesothelioma may include bowel obstruction, blood clotting abnormalities, anemia, and fever. If the cancer has spread beyond the mesothelium to other parts of the body, symptoms may include pain, trouble swallowing, or swelling of the neck or face.
These symptoms may be caused by mesothelioma or by other, less serious conditions.
Mesothelioma that affects the pleura can cause these signs and symptoms:
Chest wall pain
Pleural effusion, or fluid surrounding the lung
Shortness of breath
Fatigue or anemia
Wheezing, hoarseness, or cough
Blood in the sputum (fluid) coughed up (hemoptysis)
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.
Diagnosing mesothelioma is often difficult, because the symptoms are similar to those of a number of other conditions. Diagnosis begins with a review of the patient's medical history. A history of exposure to asbestos may increase clinical suspicion for mesothelioma. A physical examination is performed, followed by chest X-ray and often lung function tests. The X-ray may reveal pleural thickening commonly seen after asbestos exposure and increases suspicion of mesothelioma. A CT (or CAT) scan or an MRI is usually performed. If a large amount of fluid is present, abnormal cells may be detected by cytology if this fluid is aspirated with a syringe. For pleural fluid this is done by a pleural tap or chest drain, in ascites with an paracentesis or ascitic drain and in a pericardial effusion with pericardiocentesis. While absence of malignant cells on cytology does not completely exclude mesothelioma, it makes it much more unlikely, especially if an alternative diagnosis can be made (e.g. tuberculosis, heart failure).
If cytology is positive or a plaque is regarded as suspicious, a biopsy is needed to confirm a diagnosis of mesothelioma. A doctor removes a sample of tissue for examination under a microscope by a pathologist. A biopsy may be done in different ways, depending on where the abnormal area is located. If the cancer is in the chest, the doctor may perform a thoracoscopy. In this procedure, the doctor makes a small cut through the chest wall and puts a thin, lighted tube called a thoracoscope into the chest between two ribs. Thoracoscopy allows the doctor to look inside the chest and obtain tissue samples.
If the cancer is in the abdomen, the doctor may perform a laparoscopy. To obtain tissue for examination, the doctor makes a small incision in the abdomen and inserts a special instrument into the abdominal cavity. If these procedures do not yield enough tissue, more extensive diagnostic surgery may be necessary.
Screening
There is no universally agreed protocol for screening people who have been exposed to asbestos. Screening tests might diagnose mesothelioma earlier than conventional methods thus improving the survival prospects for patients. The serum osteopontin level might be useful in screening asbestos-exposed people for mesothelioma. The level of soluble mesothelin-related protein is elevated in the serum of about 75% of patients at diagnosis and it has been suggested that it may be useful for screening.[4] Doctors have begun testing the Mesomark assay which measures levels of soluble mesothelin-related proteins (SMRPs) released by diseased mesothelioma cells.[5]
Staging
Staging of mesothelioma is based on the recommendation by the International Mesothelioma Interest Group.[6] TNM classification of the primary tumor, lymph node involvement, and distant metastasis is performed. Mesothelioma is staged Ia–IV (one-A to four) based on the TNM status.[6][7]
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).[8] 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.[9]
Mesothelioma development in rats has been demonstrated following intra-pleural inoculation of phosphorylated chrysotile fibres. It has been suggested that in humans, transport of fibres to the pleura is critical to the pathogenesis of mesothelioma. This is supported by the observed recruitment of significant numbers of macrophages and other cells of the immune system to localised lesions of accumulated asbestos fibres in the pleural and peritoneal cavities of rats. These lesions continued to attract and accumulate macrophages as the disease progressed, and cellular changes within the lesion culminated in a morphologically malignant tumour.
Experimental evidence suggests that asbestos acts as a complete carcinogen with the development of mesothelioma occurring in sequential stages of initiation and promotion. The molecular mechanisms underlying the malignant transformation of normal mesothelial cells by asbestos fibres remain unclear despite the demonstration of its oncogenic capabilities. However, complete in vitro transformation of normal human mesothelial cells to malignant phenotype following exposure to asbestos fibres has not yet been achieved. In general, asbestos fibres are thought to act through direct physical interactions with the cells of the mesothelium in conjunction with indirect effects following interaction with inflammatory cells such as macrophages.
Analysis of the interactions between asbestos fibres and DNA has shown that phagocytosed fibres are able to make contact with chromosomes, often adhering to the chromatin fibres or becoming entangled within the chromosome. This contact between the asbestos fibre and the chromosomes or structural proteins of the spindle apparatus can induce complex abnormalities. The most common abnormality is monosomy of chromosome 22. Other frequent abnormalities include structural rearrangement of 1p, 3p, 9p and 6q chromosome arms.
Common gene abnormalities in mesothelioma cell lines include deletion of the tumor suppressor genes:
Neurofibromatosis type 2 at 22q12
P16INK4A
P14ARF
Asbestos has also been shown to mediate the entry of foreign DNA into target cells. Incorporation of this foreign DNA may lead to mutations and oncogenesis by several possible mechanisms:
Inactivation of tumor suppressor genes
Activation of oncogenes
Activation of proto-oncogenes due to incorporation of foreign DNA containing a promoter region
Activation of DNA repair enzymes, which may be prone to error
Activation of telomerase
Prevention of apoptosis
Asbestos fibers have been shown to alter the function and secretory properties of macrophages, ultimately creating conditions which favour the development of mesothelioma. Following asbestos phagocytosis, macrophages generate increased amounts of hydroxyl radicals, which are normal by-products of cellular anaerobic metabolism. However, these free radicals are also known clastogenic and membrane-active agents thought to promote asbestos carcinogenicity. These oxidants can participate in the oncogenic process by directly and indirectly interacting with DNA, modifying membrane-associated cellular events, including oncogene activation and perturbation of cellular antioxidant defences.
Asbestos also may possess immunosuppressive properties. For example, chrysotile fibres have been shown to depress the in vitro proliferation of phytohemagglutinin-stimulated peripheral blood lymphocytes, suppress natural killer cell lysis and significantly reduce lymphokine-activated killer cell viability and recovery. Furthermore, genetic alterations in asbestos-activated macrophages may result in the release of potent mesothelial cell mitogens such as platelet-derived growth factor (PDGF) and transforming growth factor-β (TGF-β) which in turn, may induce the chronic stimulation and proliferation of mesothelial cells after injury by asbestos fibres.
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.[10] 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.[11] 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.[12] 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.
Environmental exposures
Incidence of mesothelioma had been found to be higher in populations living near naturally occurring asbestos. For example, in central Cappadocia, Turkey, mesothelioma was causing 50% of all deaths in three small villages — Tuzköy, Karain and Sarıhıdır. Initially, this was attributed to erionite, a zeolite mineral with similar properties to asbestos, however, recently, detailed epidemiological investigation showed that erionite causes mesothelioma mostly in families with a genetic predisposition.
Occupational
Exposure to asbestos fibres has been recognized as an occupational health hazard since the early 1900s. Several epidemiological studies have associated exposure to asbestos with the development of lesions such as asbestos bodies in the sputum, pleural plaques, diffuse pleural thickening, asbestosis, carcinoma of the lung and larynx, gastrointestinal tumours, and diffuse mesothelioma of the pleura and peritoneum.
The documented presence of asbestos fibres in water supplies and food products has fostered concerns about the possible impact of long-term and, as yet, unknown exposure of the general population to these fibres. Although many authorities consider brief or transient exposure to asbestos fibres as inconsequential and an unlikely risk factor, some epidemiologists claim that there is no risk threshold. Cases of mesothelioma have been found in people whose only exposure was breathing the air through ventilation systems. Other cases had very minimal (3 months or less) direct exposure.
Commercial asbestos mining at Wittenoom, Western Australia, occurred between 1945 and 1966. A cohort study of miners employed at the mine reported that while no deaths occurred within the first 10 years after crocidolite exposure, 85 deaths attributable to mesothelioma had occurred by 1985. By 1994, 539 reported deaths due to mesothelioma had been reported in Western Australia.
Paraoccupational secondary exposure
Family members and others living with asbestos workers have an increased risk of developing mesothelioma, and possibly other asbestos related diseases. 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.
Treatment
Treatment of malignant mesothelioma using conventional therapies in combination with radiation and or chemotherapy on stage I or II Mesothelioma have proved on average 74.6 percent successful in extending the patients life span by five years or more [commonly known as remission][this percentage may increase or decrease depending on date of discovery / stage of malignant development] (Oncology Today, 2009). Treatment course is primarily determined by the staging or development. This is unlike traditional treatment such as surgery by itself which has proved only be 16.3 percent likely to extend a patient's life span by five years or more [commonly known as remission]. Clinical behavior of the malignancy is affected by several factors including the continuous mesothelial surface of the pleural cavity which favors local metastasis via exfoliated cells, invasion to underlying tissue and other organs within the pleural cavity, and the extremely long latency period between asbestos exposure and development of the disease.
Surgery
Surgery, by itself, has proved disappointing. However, research indicates varied success when used in combination with radiation and chemotherapy (Duke, 2008) A pleurectomy/decortication is the most common surgery, in which the lining of the chest is removed. Less common is an extrapleural pneumonectomy (EPP), in which the lung, lining of the inside of the chest, the hemi-diaphragm and the pericardium are removed.
Chemotherapy
Chemotherapy is the only treatment for mesothelioma that has been proven to improve survival in randomised and controlled trials. The landmark study published in 2003 by Vogelzang and colleagues compared cisplatin chemotherapy alone with a combination of cisplatin and pemetrexed (brand name Alimta) chemotherapy) in patients who had not received chemotherapy for malignant pleural mesothelioma previously and were not candidates for more aggressive "curative" surgery.[19] 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.
In January 2009, the United States FDA approved using conventional therapies such as surgery in combination with radiation and or chemotherapy on stage I or II Mesothelioma after research conducted by a nationwide study by Duke University concluded an almost 50 point increase in remission rates.
Immunotherapy
Treatment regimens involving immunotherapy have yielded variable results. For example, intrapleural inoculation of Bacillus Calmette-Guérin (BCG) in an attempt to boost the immune response, was found to be of no benefit to the patient (while it may benefit patients with bladder cancer). Mesothelioma cells proved susceptible to in vitro lysis by LAK cells following activation by interleukin-2 (IL-2), but patients undergoing this particular therapy experienced major side effects. Indeed, this trial was suspended in view of the unacceptably high levels of IL-2 toxicity and the severity of side effects such as fever and cachexia. Nonetheless, other trials involving interferon alpha have proved more encouraging with 20% of patients experiencing a greater than 50% reduction in tumor mass combined with minimal side effects.
Heated Intraoperative Intraperitoneal Chemotherapy
A procedure known as heated intraoperative intraperitoneal chemotherapy was developed by Paul Sugarbaker at the Washington Cancer Institute.[21] 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.
Most people who develop mesothelioma have worked on jobs where they inhaled asbestos particles, or they have been exposed to asbestos dust and fiber in other ways. It has also been suggested that washing the clothes of a family member who worked with asbestos can put a person at risk for developing mesothelioma.Unlike lung cancer, there is no association between mesothelioma and smoking, but smoking greatly increases risk of other asbestos-induced cancer.Compensation via asbestos funds or lawsuits is an important issue in mesothelioma (see asbestos and the law).
The symptoms of mesothelioma include shortness of breath due to pleural effusion (fluid between the lung and the chest wall) or chest wall pain, and general symptoms such as weight loss. The diagnosis may be suspected with chest X-ray and CT scan, and is confirmed with a biopsy (tissue sample) and microscopic examination. A thoracoscopy (inserting a tube with a camera into the chest) can be used to take biopsies. It allows the introduction of substances such as talc to obliterate the pleural space (called pleurodesis), which prevents more fluid from accumulating and pressing on the lung. Despite treatment with chemotherapy, radiation therapy or sometimes surgery, the disease carries a poor prognosis. Research about screening tests for the early detection of mesothelioma is ongoing.
Signs and symptoms
Symptoms of mesothelioma may not appear until 20 to 50 years after exposure to asbestos. Shortness of breath, cough, and pain in the chest due to an accumulation of fluid in the pleural space are often symptoms of pleural mesothelioma.
Symptoms of peritoneal mesothelioma include weight loss and cachexia, abdominal swelling and pain due to ascites (a buildup of fluid in the abdominal cavity). Other symptoms of peritoneal mesothelioma may include bowel obstruction, blood clotting abnormalities, anemia, and fever. If the cancer has spread beyond the mesothelium to other parts of the body, symptoms may include pain, trouble swallowing, or swelling of the neck or face.
These symptoms may be caused by mesothelioma or by other, less serious conditions.
Mesothelioma that affects the pleura can cause these signs and symptoms:
Chest wall pain
Pleural effusion, or fluid surrounding the lung
Shortness of breath
Fatigue or anemia
Wheezing, hoarseness, or cough
Blood in the sputum (fluid) coughed up (hemoptysis)
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.
Diagnosing mesothelioma is often difficult, because the symptoms are similar to those of a number of other conditions. Diagnosis begins with a review of the patient's medical history. A history of exposure to asbestos may increase clinical suspicion for mesothelioma. A physical examination is performed, followed by chest X-ray and often lung function tests. The X-ray may reveal pleural thickening commonly seen after asbestos exposure and increases suspicion of mesothelioma. A CT (or CAT) scan or an MRI is usually performed. If a large amount of fluid is present, abnormal cells may be detected by cytology if this fluid is aspirated with a syringe. For pleural fluid this is done by a pleural tap or chest drain, in ascites with an paracentesis or ascitic drain and in a pericardial effusion with pericardiocentesis. While absence of malignant cells on cytology does not completely exclude mesothelioma, it makes it much more unlikely, especially if an alternative diagnosis can be made (e.g. tuberculosis, heart failure).
If cytology is positive or a plaque is regarded as suspicious, a biopsy is needed to confirm a diagnosis of mesothelioma. A doctor removes a sample of tissue for examination under a microscope by a pathologist. A biopsy may be done in different ways, depending on where the abnormal area is located. If the cancer is in the chest, the doctor may perform a thoracoscopy. In this procedure, the doctor makes a small cut through the chest wall and puts a thin, lighted tube called a thoracoscope into the chest between two ribs. Thoracoscopy allows the doctor to look inside the chest and obtain tissue samples.
If the cancer is in the abdomen, the doctor may perform a laparoscopy. To obtain tissue for examination, the doctor makes a small incision in the abdomen and inserts a special instrument into the abdominal cavity. If these procedures do not yield enough tissue, more extensive diagnostic surgery may be necessary.
Screening
There is no universally agreed protocol for screening people who have been exposed to asbestos. Screening tests might diagnose mesothelioma earlier than conventional methods thus improving the survival prospects for patients. The serum osteopontin level might be useful in screening asbestos-exposed people for mesothelioma. The level of soluble mesothelin-related protein is elevated in the serum of about 75% of patients at diagnosis and it has been suggested that it may be useful for screening.[4] Doctors have begun testing the Mesomark assay which measures levels of soluble mesothelin-related proteins (SMRPs) released by diseased mesothelioma cells.[5]
Staging
Staging of mesothelioma is based on the recommendation by the International Mesothelioma Interest Group.[6] TNM classification of the primary tumor, lymph node involvement, and distant metastasis is performed. Mesothelioma is staged Ia–IV (one-A to four) based on the TNM status.[6][7]
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).[8] 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.[9]
Mesothelioma development in rats has been demonstrated following intra-pleural inoculation of phosphorylated chrysotile fibres. It has been suggested that in humans, transport of fibres to the pleura is critical to the pathogenesis of mesothelioma. This is supported by the observed recruitment of significant numbers of macrophages and other cells of the immune system to localised lesions of accumulated asbestos fibres in the pleural and peritoneal cavities of rats. These lesions continued to attract and accumulate macrophages as the disease progressed, and cellular changes within the lesion culminated in a morphologically malignant tumour.
Experimental evidence suggests that asbestos acts as a complete carcinogen with the development of mesothelioma occurring in sequential stages of initiation and promotion. The molecular mechanisms underlying the malignant transformation of normal mesothelial cells by asbestos fibres remain unclear despite the demonstration of its oncogenic capabilities. However, complete in vitro transformation of normal human mesothelial cells to malignant phenotype following exposure to asbestos fibres has not yet been achieved. In general, asbestos fibres are thought to act through direct physical interactions with the cells of the mesothelium in conjunction with indirect effects following interaction with inflammatory cells such as macrophages.
Analysis of the interactions between asbestos fibres and DNA has shown that phagocytosed fibres are able to make contact with chromosomes, often adhering to the chromatin fibres or becoming entangled within the chromosome. This contact between the asbestos fibre and the chromosomes or structural proteins of the spindle apparatus can induce complex abnormalities. The most common abnormality is monosomy of chromosome 22. Other frequent abnormalities include structural rearrangement of 1p, 3p, 9p and 6q chromosome arms.
Common gene abnormalities in mesothelioma cell lines include deletion of the tumor suppressor genes:
Neurofibromatosis type 2 at 22q12
P16INK4A
P14ARF
Asbestos has also been shown to mediate the entry of foreign DNA into target cells. Incorporation of this foreign DNA may lead to mutations and oncogenesis by several possible mechanisms:
Inactivation of tumor suppressor genes
Activation of oncogenes
Activation of proto-oncogenes due to incorporation of foreign DNA containing a promoter region
Activation of DNA repair enzymes, which may be prone to error
Activation of telomerase
Prevention of apoptosis
Asbestos fibers have been shown to alter the function and secretory properties of macrophages, ultimately creating conditions which favour the development of mesothelioma. Following asbestos phagocytosis, macrophages generate increased amounts of hydroxyl radicals, which are normal by-products of cellular anaerobic metabolism. However, these free radicals are also known clastogenic and membrane-active agents thought to promote asbestos carcinogenicity. These oxidants can participate in the oncogenic process by directly and indirectly interacting with DNA, modifying membrane-associated cellular events, including oncogene activation and perturbation of cellular antioxidant defences.
Asbestos also may possess immunosuppressive properties. For example, chrysotile fibres have been shown to depress the in vitro proliferation of phytohemagglutinin-stimulated peripheral blood lymphocytes, suppress natural killer cell lysis and significantly reduce lymphokine-activated killer cell viability and recovery. Furthermore, genetic alterations in asbestos-activated macrophages may result in the release of potent mesothelial cell mitogens such as platelet-derived growth factor (PDGF) and transforming growth factor-β (TGF-β) which in turn, may induce the chronic stimulation and proliferation of mesothelial cells after injury by asbestos fibres.
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.[10] 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.[11] 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.[12] 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.
Environmental exposures
Incidence of mesothelioma had been found to be higher in populations living near naturally occurring asbestos. For example, in central Cappadocia, Turkey, mesothelioma was causing 50% of all deaths in three small villages — Tuzköy, Karain and Sarıhıdır. Initially, this was attributed to erionite, a zeolite mineral with similar properties to asbestos, however, recently, detailed epidemiological investigation showed that erionite causes mesothelioma mostly in families with a genetic predisposition.
Occupational
Exposure to asbestos fibres has been recognized as an occupational health hazard since the early 1900s. Several epidemiological studies have associated exposure to asbestos with the development of lesions such as asbestos bodies in the sputum, pleural plaques, diffuse pleural thickening, asbestosis, carcinoma of the lung and larynx, gastrointestinal tumours, and diffuse mesothelioma of the pleura and peritoneum.
The documented presence of asbestos fibres in water supplies and food products has fostered concerns about the possible impact of long-term and, as yet, unknown exposure of the general population to these fibres. Although many authorities consider brief or transient exposure to asbestos fibres as inconsequential and an unlikely risk factor, some epidemiologists claim that there is no risk threshold. Cases of mesothelioma have been found in people whose only exposure was breathing the air through ventilation systems. Other cases had very minimal (3 months or less) direct exposure.
Commercial asbestos mining at Wittenoom, Western Australia, occurred between 1945 and 1966. A cohort study of miners employed at the mine reported that while no deaths occurred within the first 10 years after crocidolite exposure, 85 deaths attributable to mesothelioma had occurred by 1985. By 1994, 539 reported deaths due to mesothelioma had been reported in Western Australia.
Paraoccupational secondary exposure
Family members and others living with asbestos workers have an increased risk of developing mesothelioma, and possibly other asbestos related diseases. 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.
Treatment
Treatment of malignant mesothelioma using conventional therapies in combination with radiation and or chemotherapy on stage I or II Mesothelioma have proved on average 74.6 percent successful in extending the patients life span by five years or more [commonly known as remission][this percentage may increase or decrease depending on date of discovery / stage of malignant development] (Oncology Today, 2009). Treatment course is primarily determined by the staging or development. This is unlike traditional treatment such as surgery by itself which has proved only be 16.3 percent likely to extend a patient's life span by five years or more [commonly known as remission]. Clinical behavior of the malignancy is affected by several factors including the continuous mesothelial surface of the pleural cavity which favors local metastasis via exfoliated cells, invasion to underlying tissue and other organs within the pleural cavity, and the extremely long latency period between asbestos exposure and development of the disease.
Surgery
Surgery, by itself, has proved disappointing. However, research indicates varied success when used in combination with radiation and chemotherapy (Duke, 2008) A pleurectomy/decortication is the most common surgery, in which the lining of the chest is removed. Less common is an extrapleural pneumonectomy (EPP), in which the lung, lining of the inside of the chest, the hemi-diaphragm and the pericardium are removed.
Chemotherapy
Chemotherapy is the only treatment for mesothelioma that has been proven to improve survival in randomised and controlled trials. The landmark study published in 2003 by Vogelzang and colleagues compared cisplatin chemotherapy alone with a combination of cisplatin and pemetrexed (brand name Alimta) chemotherapy) in patients who had not received chemotherapy for malignant pleural mesothelioma previously and were not candidates for more aggressive "curative" surgery.[19] 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.
In January 2009, the United States FDA approved using conventional therapies such as surgery in combination with radiation and or chemotherapy on stage I or II Mesothelioma after research conducted by a nationwide study by Duke University concluded an almost 50 point increase in remission rates.
Immunotherapy
Treatment regimens involving immunotherapy have yielded variable results. For example, intrapleural inoculation of Bacillus Calmette-Guérin (BCG) in an attempt to boost the immune response, was found to be of no benefit to the patient (while it may benefit patients with bladder cancer). Mesothelioma cells proved susceptible to in vitro lysis by LAK cells following activation by interleukin-2 (IL-2), but patients undergoing this particular therapy experienced major side effects. Indeed, this trial was suspended in view of the unacceptably high levels of IL-2 toxicity and the severity of side effects such as fever and cachexia. Nonetheless, other trials involving interferon alpha have proved more encouraging with 20% of patients experiencing a greater than 50% reduction in tumor mass combined with minimal side effects.
Heated Intraoperative Intraperitoneal Chemotherapy
A procedure known as heated intraoperative intraperitoneal chemotherapy was developed by Paul Sugarbaker at the Washington Cancer Institute.[21] 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.
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