[Extracted from Medicine.Net.Com]
Insect stings overview
Bee and wasp stings are common causes of medical problems. Bees and wasps, together with fire ants, are all related insects that belong to the Hymenoptera order. Bee and wasp stings can cause significant reactions, ranging from localized pain and swelling to serious and even potentially fatal conditions. At least 40 deaths occur each year in the U.S. as a result of bee or wasp stings.
What are the types of wasps ?
There are over 25,000 species of wasps found throughout the world. Some of the most common wasps include :
* The yellow jacket and hornet, both of which live in groups, or colonies, in temperate climates.
* Yellow jackets, which have black and yellow stripes on the abdomen, form underground nests.
* Hornets are predominantly black with some yellow markings on the head and thorax. Hornets form paper-like nests that are attached to trees, bushes, or buildings.
What are the types of bees ?
Bees include the honey bee, the so-called Africanized honey bee (also known as "killer bee"), and the bumble bee. Bumble bees are large, furry-appearing bees that fulfill the beneficial role of pollinating many plants. Honeybees, also active plant pollinators, are found all over the world. While honey bees are not usually aggressive, they will sting if bothered or threatened. Because their wings flap so rapidly, their presence is associated with a buzzing sound. Although the venom of the "killer bees" found in the Western and Southern U.S. is no more potent than that of regular honeybees, their behavior may be more aggressive. Killer bees may chase victims when agitated and may also attack in greater numbers, thereby increasing the chances of a severe reaction to their stings. Overall, there are more than 20,000 species of bees found worldwide.
What are causes of Bee and Wasp stings ?
Most stings arise because an insect perceives a threat to their colony. Bees and wasps commonly sting because an intruder has neared the hive or nest. Loud noises (such as lawn mowers), bright or dark colors, and certain perfumes or perfumed body products may also encourage stings. Some types of insect venom contain pheromones, which attract other members of the colony and induce them to sting.
When bees or wasps sting an individual, they inject venom under the skin of their victim.
* Honey bees, including killer bees, have barbed stingers that tear off when they try to fly away after stinging, so these bees die after the sting and thus can sting only one time. In this case the stinger and venom sac typically remain embedded in the skin of the victim.
* Bumble bees, hornets, yellow jackets, and wasps are able to sting multiple times, since their stingers are smooth and can be easily withdrawn from the victim's skin.
Bee and wasp venoms vary according to species but typically contain toxic components as well as antigens that stimulate an immune response.
What are the symptoms of a bee or wasp sting?
Insect stings may produce four types of reactions, each with characteristic symptoms as below:
1. Local reactions are the most common type of reaction to a bee or wasp sting. Symptoms include pain, swelling, warmth, and redness at the site of the sting. Itching may also be present. These symptoms begin immediately following the sting and often last for only a few hours. Depending upon the type of insect, the stinging apparatus may still be visible in the affected skin. Large local reactions have a greater degree of swelling that can last for up to a week, sometimes associated with nausea and/or tiredness. These reactions are not allergic reactions.
2. Systemic (body-wide) allergic reactions occur in people who have produced a type of antibody known as IgE antibody against the same insect venom as a result of a previous sting. Systemic allergic reactions are estimated to occur in 0.3% to 3% of stings. Symptoms include hives and flushing of the skin and difficulty breathing due to swelling of the pharynx and epiglottis and narrowing of the bronchial passages. The reaction may vary in severity from mild skin hives to life-threatening reactions. The most severe immunologic reactions are known as anaphylaxis and occur more commonly in males and in people under 20 years of age. In severe reactions, hypotension (low blood pressure), circulatory disturbances, and breathing difficulty can progress to fatal cardiorespiratory arrest. Most people who develop anaphylactic reactions have experienced previous stings with few problems. Once an individual has experienced an anaphylactic reaction, the risk of having a recurrent episode is about 60%.
3. Toxic reactions are a direct result of toxins in the venom rather than the body's immune response. Most often these are due to multiple simultaneous stings that introduce an unusually large amount of venom into the body. Symptoms can include fever, nausea, vomiting, diarrhea, headache, fainting or dizziness, and convulsions. Hives, rash, and skin symptoms are less common in toxic reactions than in allergic reactions. Because bee and wasp venom are strong stimulants of the immune response, people who have experienced toxic reactions may produce antibodies to the venom and be at risk for future systemic anaphylactic reactions to stings.
4. Delayed reactions are uncommon and occur even days to weeks after the sting. These reactions constitute less than 0.3% of all reactions to insect stings. The individual's own medical history and condition may play a role in determining whether delayed reactions occur. Symptoms can vary widely and may include inflammation of the brain (encephalitis), the nerves (neuritis), blood vessels (vasculitis), or kidneys (nephritis) as well as blood clotting disturbances. Serum sickness is a type of delayed reaction that occurs a week to 10 days after a sting and may cause itching, rash, fever, joint pain, fatigue, and swollen lymph nodes.
When should I call a doctor about a bee or wasp sting ?
Most bee and wasp stings can be treated at home, but some cases require medical attention. If there is any suspicion at all that a person is having a systemic allergic reaction, seek immediate emergency medical assistance. Signs that a person may be having a systemic reaction include widespread hives or rash, wheezing, difficulty breathing, and swelling in the mouth and throat areas. If a person is stung by an insect whose sting has previously caused an anaphylactic reaction, he or she should also access emergency medical care even if no symptoms are present.
You should also seek medical care if any of the following conditions are present :
* If you have received multiple stings
* If the sting is located in the eye or eye area
* If symptoms of infection (pus, drainage, fever, increasing pain and redness) develop
* If the initial symptoms worsen or persist for longer than 24-48 hours
* If a sting produces severe symptoms in young children, the elderly, or those with chronic medical problems
How is a bee or wasp sting diagnosed ?
In most cases the victim or an observer will have witnessed the sting. Depending upon the type of insect, the stinging apparatus may be found embedded in the skin, but this is not the case with wasps and some types of bees. The characteristic symptoms for each type of reaction along with the history of a sting are typically sufficient to establish a diagnosis.
What is the treatment for a bee or wasp sting ?
Treatment for a mild allergic reaction
* First aid for a bee sting involves cleansing the site, immediate removal of the stinging apparatus (if present), and application of ice or cold packs to the affected area.
* Antihistamines such as diphenhydramine (Benadryl) may be taken to relieve itching and burning. Acetaminophen (Tylenol) or ibuprofen (Motrin, Advil) may be taken for pain relief.
* If the sting site becomes infected, your doctor may prescribe a course of antibiotics.
* If it has been more than 10 years since your last tetanus booster immunization, get a booster within the next few days.
Treatment for a mild allergic reaction (such as a rash without any breathing difficulty) usually involves the administration of antihistamine medications and sometimes steroid medications to reduce inflammation.
Treatment for anaphylactic reaction
The treatment of choice for life-threatening anaphylactic reactions is epinephrine. Emergency medical treatments may also include steroid and antihistamine medications and insertion of a breathing tube. Intravenous fluids and medications to support cardiovascular function may also be required. Treatment may be begun at the scene by emergency medical personnel and continued in the hospital.
Doctors can prescribe an allergy kit containing self-administered epinephrine (Epi-Pen) for persons at risk for a severe allergic reaction, including those with known allergy to bee or wasp stings. These self-administered injectable epinephrine treatments can be life-saving in many cases. It is important to have kits readily available at home, in the car, at work, etc. and to know how to use them properly.
Immunotherapy is sometimes recommended for those with a history of severe allergic reactions to stings. In this treatment, a series of shots ("allergy shots") are used to provide low-dose exposure to venom. This type of treatment may significantly reduce the chance of future severe allergic reactions.
What are the complications of a bee or wasp sting ?
Complications can include the development of infection at the sting site requiring treatment with antibiotics. Systemic allergic reactions can be life-threatening, as discussed above.
How can I prevent a bee or wasp sting?
You can take preventive measures to decrease your chance of being stung by an insect. Effective prevention tips include the following:
* Avoid, and do not disturb, hives and nests
* When participating in outdoor activities, avoid
fragranced body products, bright colors, and sugary drinks
* Wear long sleeves and long pants outdoors
* Do not walk barefoot outdoors
* Do not swat at swarming bees or wasps
* Exercise caution around fruit trees and blooming flowers
* Keep garbage away from outdoor activity areas
Bee and Wasp Sting At A Glance
* Bees and wasp stings may produce local reactions or systemic (body-wide) allergic reactions.
* Localized pain, redness, and swelling are the most common reaction to a sting.
* Severe allergic reactions to stings are known as anaphylactic reactions and may be life-threatening.
* Treatment of a local reaction involves cleansing, removal of the stinging apparatus if present, and application of ice packs.
* Epinephrine is the treatment of choice for severe allergic reactions.
* A self-administered injectable form of epinephrine is available for individuals at risk for anaphylactic reactions.
Wednesday, November 18, 2009
Causes of Bad Breath !
[Extracted from Medicine.Net.Com]
Bad breath, medically called halitosis, can result from poor oral hygiene habits and may be a sign of other health problems. Bad breath can also be made worse by the types of foods you eat and other unhealthy lifestyle habits.
How Does What You Eat Affect Breath ?
Basically, all the food you eat begins to be broken down in your mouth. As foods are digested and absorbed into your bloodstream, they are eventually carried to your lungs and given off in your breath. If you eat foods with strong odors (such as, garlic or onions), brushing and flossing - even mouthwash - merely covers up the odor temporarily. The odor will not go away completely until the foods have passed through your body.
Why Do Poor Habits Cause Bad Breath ?
If you don't brush and floss your teeth daily, food particles can remain in your mouth, which promotes bacteria growth between teeth, around the gums, and on the tongue. This causes bad breath. In addition, odor-causing bacteria and food particles can cause bad breath if dentures are not properly cleaned.
Smoking or chewing tobacco-based products can also cause bad breath, stain teeth, reduce your ability to taste foods, and irritate gum tissues.
What Health Problems Are Associated With Bad Breath ?
Persistent bad breath or a bad taste in your mouth may be warning signs of gum disease. Gum disease is caused by the buildup of plaque on teeth. The bacteria cause toxins to form in the mouth, which irritate the gums. If periodontal disease continues untreated, it can damage the gums and jawbone.
Other dental causes of bad breath include poorly fitting dental appliances, yeast infections of the mouth and dental caries.
The medical condition dry mouth (also called xerostomia) can also cause bad breath. Saliva is necessary to moisten and cleanse the mouth by neutralizing acids produced by plaque and washing away dead cells that accumulate on the tongue, gums, and cheeks. If not removed, these cells decompose and can cause bad breath. Dry mouth may be caused by the side effects of various medications, salivary gland problems, or continuous breathing through the mouth.
Many other diseases and illnesses may cause bad breath. Here are some to be aware of: respiratory tract infections such as pneumonia or bronchitis, chronic sinus infections, postnasal drip, diabetes, chronic acid reflux, liver or kidney problems.
What Can I Do to Prevent Bad Breath ?
Bad breath can be reduced or prevented if you :
1. Practice good oral hygiene. Brush twice a day with fluoride toothpaste to remove food debris and plaque. Brush your teeth after you eat (keep a toothbrush at work or school to brush after lunch). Don't forget to brush your tongue, too. Replace your toothbrush every 2 to 3 months. Use floss or an interdental cleaner to remove food particles and plaque between your teeth once a day. Dentures should be removed at night and cleaned thoroughly before being placed in your mouth the next morning.
2. See your dentist regularly - at least twice a year. He or she will conduct an oral examination and professional teeth cleaning and will be able detect and treat periodontal disease, dry mouth, or other problems that may be the cause of bad mouth odor.
3. Stop smoking/chewing tobacco-based products. Ask your dentist for tips on kicking the habit.
4. Drink lots of water. This will keep your mouth moist. Chewing gum (preferably sugarless) or sucking on candy (preferably sugarless) also stimulates the production of saliva, which helps wash away food particles and bacteria.
5. Keep a log of the foods you eat. If you think the foods that you eat may be causing your bad breath, record what you eat so that you can determine which foods may be contributing to the problem. Bring the log to your dentist to review. Similarly, make a list of the medications you take. Some medications may play a role in creating mouth odors.
Who Treats Bad Breath ?
In most cases, your dentist can treat the cause of bad breath. If your dentist determines that your mouth is healthy and that the odor is not of oral origin, you may be referred to your family doctor or to a specialist to determine the odor source and treatment plan. If the odor is due to gum disease, for example, your dentist can either treat the disease or refer you to a periodontist, a dentist who specializes in treating gum conditions.
What Products Can I Use to Eliminate Bad Breath ?
You can buy a number of mouthwashes over-the-counter that claim to eliminate bad breath. However, keep in mind that many of these mouthwashes generally provide only a temporary way to mask unpleasant mouth odor. There are, however, several antiseptic mouth-rinse products available that instead of simply masking breath odor kill the germs that cause bad breath. Ask your dentist about which product is best for you.
Bad breath, medically called halitosis, can result from poor oral hygiene habits and may be a sign of other health problems. Bad breath can also be made worse by the types of foods you eat and other unhealthy lifestyle habits.
How Does What You Eat Affect Breath ?
Basically, all the food you eat begins to be broken down in your mouth. As foods are digested and absorbed into your bloodstream, they are eventually carried to your lungs and given off in your breath. If you eat foods with strong odors (such as, garlic or onions), brushing and flossing - even mouthwash - merely covers up the odor temporarily. The odor will not go away completely until the foods have passed through your body.
Why Do Poor Habits Cause Bad Breath ?
If you don't brush and floss your teeth daily, food particles can remain in your mouth, which promotes bacteria growth between teeth, around the gums, and on the tongue. This causes bad breath. In addition, odor-causing bacteria and food particles can cause bad breath if dentures are not properly cleaned.
Smoking or chewing tobacco-based products can also cause bad breath, stain teeth, reduce your ability to taste foods, and irritate gum tissues.
What Health Problems Are Associated With Bad Breath ?
Persistent bad breath or a bad taste in your mouth may be warning signs of gum disease. Gum disease is caused by the buildup of plaque on teeth. The bacteria cause toxins to form in the mouth, which irritate the gums. If periodontal disease continues untreated, it can damage the gums and jawbone.
Other dental causes of bad breath include poorly fitting dental appliances, yeast infections of the mouth and dental caries.
The medical condition dry mouth (also called xerostomia) can also cause bad breath. Saliva is necessary to moisten and cleanse the mouth by neutralizing acids produced by plaque and washing away dead cells that accumulate on the tongue, gums, and cheeks. If not removed, these cells decompose and can cause bad breath. Dry mouth may be caused by the side effects of various medications, salivary gland problems, or continuous breathing through the mouth.
Many other diseases and illnesses may cause bad breath. Here are some to be aware of: respiratory tract infections such as pneumonia or bronchitis, chronic sinus infections, postnasal drip, diabetes, chronic acid reflux, liver or kidney problems.
What Can I Do to Prevent Bad Breath ?
Bad breath can be reduced or prevented if you :
1. Practice good oral hygiene. Brush twice a day with fluoride toothpaste to remove food debris and plaque. Brush your teeth after you eat (keep a toothbrush at work or school to brush after lunch). Don't forget to brush your tongue, too. Replace your toothbrush every 2 to 3 months. Use floss or an interdental cleaner to remove food particles and plaque between your teeth once a day. Dentures should be removed at night and cleaned thoroughly before being placed in your mouth the next morning.
2. See your dentist regularly - at least twice a year. He or she will conduct an oral examination and professional teeth cleaning and will be able detect and treat periodontal disease, dry mouth, or other problems that may be the cause of bad mouth odor.
3. Stop smoking/chewing tobacco-based products. Ask your dentist for tips on kicking the habit.
4. Drink lots of water. This will keep your mouth moist. Chewing gum (preferably sugarless) or sucking on candy (preferably sugarless) also stimulates the production of saliva, which helps wash away food particles and bacteria.
5. Keep a log of the foods you eat. If you think the foods that you eat may be causing your bad breath, record what you eat so that you can determine which foods may be contributing to the problem. Bring the log to your dentist to review. Similarly, make a list of the medications you take. Some medications may play a role in creating mouth odors.
Who Treats Bad Breath ?
In most cases, your dentist can treat the cause of bad breath. If your dentist determines that your mouth is healthy and that the odor is not of oral origin, you may be referred to your family doctor or to a specialist to determine the odor source and treatment plan. If the odor is due to gum disease, for example, your dentist can either treat the disease or refer you to a periodontist, a dentist who specializes in treating gum conditions.
What Products Can I Use to Eliminate Bad Breath ?
You can buy a number of mouthwashes over-the-counter that claim to eliminate bad breath. However, keep in mind that many of these mouthwashes generally provide only a temporary way to mask unpleasant mouth odor. There are, however, several antiseptic mouth-rinse products available that instead of simply masking breath odor kill the germs that cause bad breath. Ask your dentist about which product is best for you.
What is Neutropenia ?
[Extracted from Medicine.Net.Com]
"Neutropenia" is a condition in which the number of neutrophils in the bloodstream is decreased. Neutrophils are a type of white blood cell also known as polymorphonuclear leukocytes or PMNs. Neutropenia affects the body's ability to fight off infections.
White blood cells are also known as Leukocytes. There are five major types of white blood cells :
1. Basophils,
2. Eosinophils,
3. Lymphocytes (T-cells and B-cells),
4. Monocytes, and
5. Neutrophils.
Some white blood cells, called granulocytes, are filled with microscopic granules that are little sacs containing Enzymes (compounds that digest microorganisms). Neutrophils, eosinophils, and basophils are all granulocytes and are part of the innate immune system with somewhat nonspecific, broad-based activity. They do not respond exclusively to specific antigens, as do the lymphocytes (B-cells and T-cells).
Neutrophils contain enzymes that help the cell kill and digest microorganisms it has engulfed by a process known as phagocytosis. The mature neutrophil has a segmented nucleus (it is often called a 'seg' or 'poly'), while the immature neutrophil has a band-shape nucleus (it is called a band). Neutrophils are made in the bone marrow and released into the bloodstream. The neutrophil has a life-span of about three days.
How is Neutropenia defined ?
The white blood cell count (WBC) is the number of white blood cells in a volume of blood. The normal range for the WBC varies slightly among laboratories but is generally between 4,300 and 10,800 cells per microliter or cubic millimeter (cmm). The WBC can also be referred to as the leukocyte count and can be expressed in international units as 4.3 x 109to 10.8 x 109 cells per liter. The percentage of the different types of white blood cells in the WBC is called the WBC differential.
The absolute neutrophil count (ANC) is determined by the product of the white blood cell count (WBC) and the fraction of neutrophils among the white blood cells as determined by the WBC differential analysis. For example, if the WBC is 10,000 per microliter and 70% are neutrophils, the ANC would be 7,000 per microliter.
An ANC of less than 1500 per microliter (1500/microL) is the generally accepted definition of neutropenia. Neutropenia is sometimes further classified as :
* mild if the ANC ranges from 1000-1500/microL,
* moderate with an ANC of 500-1000/microL, and
* severe if the ANC is below 500/microL.
Some medical terms may be used synonymously with neutropenia, even though their precise definitions are different.
* Leukopenia refers to a reduced number of white blood cells in general, while granulocytopenia refers to a decreased number of all the granulocyte-type blood cells (neutrophils, eosinophils, and basophils).
* Since neutrophils normally far outnumber the other types of granulocytes, this term is sometimes used to refer to neutropenia.
* Finally, agranulocytosis literally refers to a complete absence of all granulocytes, but this term is sometimes used to refer to severe neutropenia.
What are the clinical consequences of Neutropenia ?
Neutropenia results in an increased susceptibility to bacterial infections. The degree of risk depends upon the cause and severity of the neutropenia, the underlying medical condition of the patient, and the presence or absence of bone marrow reserves for the production of neutrophils.
The most common type of infections seen in neutropenic patients are caused by bacteria normally found on the skin (such as Staphylococcus aureus) or from the gastrointestinal and urinary tract. Fungal infections are also more frequent in patients with neutropenia. The infections may be limited to certain areas of the body (commonly the oral cavity, genital area, and skin) or may spread via the bloodstream to the lungs and other organs in severe, prolonged neutropenia.
What causes Neutropenia ?
Neutropenia can be present (though it is relatively uncommon) in normal healthy individuals, notably in some persons of African or Arabic descent and and Yemenite Jews. Neutropenia may arise as a result of decreased production of neutrophils, destruction of neutrophils after they are produced, or pooling of neutrophils (accumulation of the neutrophils out of the circulation).
Neutropenia may arise as a result of numerous medical conditions :
* Infections (more commonly viral infections, but also bacterial or parasitic infections). Examples include: HIV, tuberculosis, malaria, Epstein Barr virus (EBV);
* Medications that may damage the bone marrow or neutrophils, including cancer chemotherapy;
* Vitamin deficiencies (megaloblastic anemia due to vitamin B12 and/or folate deficiency);
* Diseases of the bone marrow such as leukemias, myelodysplastic syndrome, aplastic anemia, myelofibrosis;
* Radiation therapy;
* Congenital (inborn) disorders of bone marrow function or of neutrophil production, for example, Kostmann syndrome;
* Autoimmune destruction of neutrophils (either as a primary condition or associated with another disease such as Felty's syndrome) or from drugs stimulating the immune system to attack the cells
* Hypersplenism, which refers to the increased sequestration and/or destruction of blood cells by the spleen.
How is Neutropenia diagnosed ?
Neutropenia is diagnosed by a blood cell count performed on a sample of blood removed from a vein. To determine the specific cause of neutropenia in a given situation, other tests may be required. Sometimes a bone marrow biopsy may be required to diagnose the specific cause of neutropenia.
How is Neutropenia treated ?
Treatment of neutropenia is based upon the underlying cause, severity, and the presence of associated infections or symptoms as well as the overall health status of the patient. Obviously, treatment must also be directed toward any underlying disease process. Treatments that directly address neutropenia may include (note that all of these treatments may not be appropriate in a given setting):
* antibiotic and/or antifungal medications to help fight infections;
* administration of white blood cells growth factors (such as recombinant granulocyte colony-stimulating factor (G-CSF, filgrastim) in some cases of severe neutropenia;
* granulocyte transfusions; or
* corticosteroid therapy or intravenous immune globulin for some cases of immune-mediated neutropenia.
Preventive measures may also be implemented in neutropenic patients to limit risk of infections. These measures might include strict attention to hand washing, use of private rooms, or in some cases, use of gloves, gowns, and/or face masks by caregivers.
Neutropenia At A Glance
* Neutropenia is a condition in which the number of Neutrophils (a type of white blood cell) in the bloodstream is decreased, affecting the body's ability to fight off infections.
* Neutropenia is defined as an absolute neutrophil count (ANC) of less than 1500 per microliter (1500/microL)
* Neutropenia may be caused by or associated with numerous medical conditions
* Most infections that occur as a result of neutropenia are due to bacteria that are normally present on the skin or in the gastrointestinal or urinary tract.
* Treatment depends upon the cause and severity of he condition as well as the underlying disease state responsible for the neutropenia.
"Neutropenia" is a condition in which the number of neutrophils in the bloodstream is decreased. Neutrophils are a type of white blood cell also known as polymorphonuclear leukocytes or PMNs. Neutropenia affects the body's ability to fight off infections.
White blood cells are also known as Leukocytes. There are five major types of white blood cells :
1. Basophils,
2. Eosinophils,
3. Lymphocytes (T-cells and B-cells),
4. Monocytes, and
5. Neutrophils.
Some white blood cells, called granulocytes, are filled with microscopic granules that are little sacs containing Enzymes (compounds that digest microorganisms). Neutrophils, eosinophils, and basophils are all granulocytes and are part of the innate immune system with somewhat nonspecific, broad-based activity. They do not respond exclusively to specific antigens, as do the lymphocytes (B-cells and T-cells).
Neutrophils contain enzymes that help the cell kill and digest microorganisms it has engulfed by a process known as phagocytosis. The mature neutrophil has a segmented nucleus (it is often called a 'seg' or 'poly'), while the immature neutrophil has a band-shape nucleus (it is called a band). Neutrophils are made in the bone marrow and released into the bloodstream. The neutrophil has a life-span of about three days.
How is Neutropenia defined ?
The white blood cell count (WBC) is the number of white blood cells in a volume of blood. The normal range for the WBC varies slightly among laboratories but is generally between 4,300 and 10,800 cells per microliter or cubic millimeter (cmm). The WBC can also be referred to as the leukocyte count and can be expressed in international units as 4.3 x 109to 10.8 x 109 cells per liter. The percentage of the different types of white blood cells in the WBC is called the WBC differential.
The absolute neutrophil count (ANC) is determined by the product of the white blood cell count (WBC) and the fraction of neutrophils among the white blood cells as determined by the WBC differential analysis. For example, if the WBC is 10,000 per microliter and 70% are neutrophils, the ANC would be 7,000 per microliter.
An ANC of less than 1500 per microliter (1500/microL) is the generally accepted definition of neutropenia. Neutropenia is sometimes further classified as :
* mild if the ANC ranges from 1000-1500/microL,
* moderate with an ANC of 500-1000/microL, and
* severe if the ANC is below 500/microL.
Some medical terms may be used synonymously with neutropenia, even though their precise definitions are different.
* Leukopenia refers to a reduced number of white blood cells in general, while granulocytopenia refers to a decreased number of all the granulocyte-type blood cells (neutrophils, eosinophils, and basophils).
* Since neutrophils normally far outnumber the other types of granulocytes, this term is sometimes used to refer to neutropenia.
* Finally, agranulocytosis literally refers to a complete absence of all granulocytes, but this term is sometimes used to refer to severe neutropenia.
What are the clinical consequences of Neutropenia ?
Neutropenia results in an increased susceptibility to bacterial infections. The degree of risk depends upon the cause and severity of the neutropenia, the underlying medical condition of the patient, and the presence or absence of bone marrow reserves for the production of neutrophils.
The most common type of infections seen in neutropenic patients are caused by bacteria normally found on the skin (such as Staphylococcus aureus) or from the gastrointestinal and urinary tract. Fungal infections are also more frequent in patients with neutropenia. The infections may be limited to certain areas of the body (commonly the oral cavity, genital area, and skin) or may spread via the bloodstream to the lungs and other organs in severe, prolonged neutropenia.
What causes Neutropenia ?
Neutropenia can be present (though it is relatively uncommon) in normal healthy individuals, notably in some persons of African or Arabic descent and and Yemenite Jews. Neutropenia may arise as a result of decreased production of neutrophils, destruction of neutrophils after they are produced, or pooling of neutrophils (accumulation of the neutrophils out of the circulation).
Neutropenia may arise as a result of numerous medical conditions :
* Infections (more commonly viral infections, but also bacterial or parasitic infections). Examples include: HIV, tuberculosis, malaria, Epstein Barr virus (EBV);
* Medications that may damage the bone marrow or neutrophils, including cancer chemotherapy;
* Vitamin deficiencies (megaloblastic anemia due to vitamin B12 and/or folate deficiency);
* Diseases of the bone marrow such as leukemias, myelodysplastic syndrome, aplastic anemia, myelofibrosis;
* Radiation therapy;
* Congenital (inborn) disorders of bone marrow function or of neutrophil production, for example, Kostmann syndrome;
* Autoimmune destruction of neutrophils (either as a primary condition or associated with another disease such as Felty's syndrome) or from drugs stimulating the immune system to attack the cells
* Hypersplenism, which refers to the increased sequestration and/or destruction of blood cells by the spleen.
How is Neutropenia diagnosed ?
Neutropenia is diagnosed by a blood cell count performed on a sample of blood removed from a vein. To determine the specific cause of neutropenia in a given situation, other tests may be required. Sometimes a bone marrow biopsy may be required to diagnose the specific cause of neutropenia.
How is Neutropenia treated ?
Treatment of neutropenia is based upon the underlying cause, severity, and the presence of associated infections or symptoms as well as the overall health status of the patient. Obviously, treatment must also be directed toward any underlying disease process. Treatments that directly address neutropenia may include (note that all of these treatments may not be appropriate in a given setting):
* antibiotic and/or antifungal medications to help fight infections;
* administration of white blood cells growth factors (such as recombinant granulocyte colony-stimulating factor (G-CSF, filgrastim) in some cases of severe neutropenia;
* granulocyte transfusions; or
* corticosteroid therapy or intravenous immune globulin for some cases of immune-mediated neutropenia.
Preventive measures may also be implemented in neutropenic patients to limit risk of infections. These measures might include strict attention to hand washing, use of private rooms, or in some cases, use of gloves, gowns, and/or face masks by caregivers.
Neutropenia At A Glance
* Neutropenia is a condition in which the number of Neutrophils (a type of white blood cell) in the bloodstream is decreased, affecting the body's ability to fight off infections.
* Neutropenia is defined as an absolute neutrophil count (ANC) of less than 1500 per microliter (1500/microL)
* Neutropenia may be caused by or associated with numerous medical conditions
* Most infections that occur as a result of neutropenia are due to bacteria that are normally present on the skin or in the gastrointestinal or urinary tract.
* Treatment depends upon the cause and severity of he condition as well as the underlying disease state responsible for the neutropenia.
Wednesday, October 28, 2009
What is Sun Allergy ?
[Extracted from Wisegeek.com]
A sun allergy is a condition in which someone's skin reacts to sunlight, developing redness, itching, and hives as a result of sun exposure. There are several different types of sun allergy, and sometimes a sun allergy can be a symptom of an underlying medical problem, so it is a good idea to seek medical advice for sun allergy symptoms or any other dermatological problem. For people with sun allergies, there are several different treatment options to consider, depending on the cause of the allergy.
The signs of a sun allergy look a lot like a sunburn, except that skin irritation in reaction to sunlight, known as photodermatosis, emerges within minutes of sun exposure, rather than developing after hours of exposure. The patient may feel itchy or tingly, and the area of skin exposed to the sun turns red and bumpy. Sometimes, a sun allergy may emerge under lightweight clothing as well. The area of irritation usually returns to normal within a day, unlike a sunburn, which can take days or weeks to heal.
When photodermatosis appears, there are several potential causes, including polymorphous light eruption, actinic prurigo, and solar urticaria. These reactions are usually caused by a confused immune system which reacts to compounds in sun-exposed skin. Several proteins change structure when they are exposed to sunlight, making them potential targets of the immune system. It is also possible to develop what is known as a photoallergic eruption in response to the use of medications which increase sun sensitivity, causing rashes, hives, and redness on sun-exposed skin.
A doctor usually diagnoses a sun allergy by exposing skin to wavelengths commonly found in sunlight. If the patient reacts, additional testing may be conducted to determine the cause. Sometimes, a sun allergy can be resolved with desensitization therapy, in which a dermatologist carefully exposes the patient for set periods of time. Antihistamines and topical creams may also be used to treat the symptoms of a sun allergy, and to reduce the severity of future outbreaks.
Some conditions like porphyria can also cause what looks like a sun allergy, which is why it is important to seek medical care. In rare cases, people have developed very aggressive immune responses to sunlight, resulting in anaphylactic shock after sun exposure, which is another critical reason to seek medical attention for a suspected sun allergy.
A sun allergy is a condition in which someone's skin reacts to sunlight, developing redness, itching, and hives as a result of sun exposure. There are several different types of sun allergy, and sometimes a sun allergy can be a symptom of an underlying medical problem, so it is a good idea to seek medical advice for sun allergy symptoms or any other dermatological problem. For people with sun allergies, there are several different treatment options to consider, depending on the cause of the allergy.
The signs of a sun allergy look a lot like a sunburn, except that skin irritation in reaction to sunlight, known as photodermatosis, emerges within minutes of sun exposure, rather than developing after hours of exposure. The patient may feel itchy or tingly, and the area of skin exposed to the sun turns red and bumpy. Sometimes, a sun allergy may emerge under lightweight clothing as well. The area of irritation usually returns to normal within a day, unlike a sunburn, which can take days or weeks to heal.
When photodermatosis appears, there are several potential causes, including polymorphous light eruption, actinic prurigo, and solar urticaria. These reactions are usually caused by a confused immune system which reacts to compounds in sun-exposed skin. Several proteins change structure when they are exposed to sunlight, making them potential targets of the immune system. It is also possible to develop what is known as a photoallergic eruption in response to the use of medications which increase sun sensitivity, causing rashes, hives, and redness on sun-exposed skin.
A doctor usually diagnoses a sun allergy by exposing skin to wavelengths commonly found in sunlight. If the patient reacts, additional testing may be conducted to determine the cause. Sometimes, a sun allergy can be resolved with desensitization therapy, in which a dermatologist carefully exposes the patient for set periods of time. Antihistamines and topical creams may also be used to treat the symptoms of a sun allergy, and to reduce the severity of future outbreaks.
Some conditions like porphyria can also cause what looks like a sun allergy, which is why it is important to seek medical care. In rare cases, people have developed very aggressive immune responses to sunlight, resulting in anaphylactic shock after sun exposure, which is another critical reason to seek medical attention for a suspected sun allergy.
Tuesday, October 13, 2009
How Does our Bodies Age ?
http://www.washingtonpost.com/wp-dyn/content/graphic/2006/12/04/GR2006120400761.html
Friday, October 9, 2009
World’s deadliest delicacies
[Extracted from Hotel Club Travel Blog]
Some people are really careful about what they eat, try to cut down on fats and sugar to ensure a healthy life, others just don’t care and stuff themselves with all kinds of junk foods. But there’s another type of people, those that gamble with their lives for a rush of adrenalin or for a taste they find irresistible.
Here are the world’s deadliest delicacies:
Cassava
Cassava crops are very common in Africa and South America because they have the ability to grow in unfertile soil and withstand long droughts extremely well. They are very hard to find in other parts of the world and are richer in carbohydrates than maize and cereal crops.
They do however have a major flaw, the ability to kill a person. Cassava roots contain cyanogenic glycosides that are converted into hydrogen cyanide by an enzyme called linamarase. This happens when the plant’s cells are ruptured, most often when it is eaten. That’s why Cassava has to be processed very carefully, if consumed raw it can cause death.
Ackee
Ackee has become the national fruit of Jamaica, even though it is not native to the island. It was imported around 1780 from West Africa. Ackee fruits are rich in essential fatty acids, vitamin A, zinc and protein and are an important ingredient in many Caribbean dishes.
Still, if you’re ever in Jamaica, don’t go stuffing your face with Ackee fruits, it may be the last thing you do. Unripe Ackee fruits contain dangerous alkanoid poisons that provoke serious vomiting, seizures and even fatal hypoglycemia. Even when ripe, Ackees are not eaten entirely, the shiny black seeds and the red shell are discarded, only the soft inside is edible.
Apple
An apple a day keeps the doctor away! Entirely true, but, if you eat the seeds, he might stay away because there’s nothing he can do to help you.
Scientists have discovered that eating a large quantity of apple seeds is extremely hazardous to our health, because they contain a certain amount of cyanogenic glycoside, commonly known as cyanide. The amount of seed necessary to cause damage isn’t known yet, but the seeds of just one apple should have no negative effect on an adult. Children are more vulnerable however and should be taught to avoid eating the apple whole.
Symptoms of apple-seed intoxication include abdominal pains, vomiting, excessive sweating, coma and even death.
Snake
Like scorpions, tarantulas and other spiders, snake poison is neutralized when the meat is cooked, so you shouldn’t be worried about side effects if you don’t eat them raw. However in China and other Asian countries, snake parts are sometimes eaten raw, like the snake blood, a delicacy many of us probably couldn’t stomach. The snake is gutted, the blood gathered in a small glass and then mixed with the bile.
Chinese believe this a powerful aphrodisiac that also has the power to cure sexual deficiencies. Normally there shouldn’t be any danger, since the venom is collected in the snake’s head, but it can sometimes be present in its blood. So if you’re going to try snake blood, make sure you say a prayer before.
Puffer Fish
Definitely the world’s most popular toxic delicacy, the Puffer Fish may look funny but it’s definitely no joke. It contains high levels of tetrodotoxin, a powerful poison that paralyzes the muscles, eventually killing the victim through asphyxiation. The poison is present mostly in the liver, ovaries and skin and only licensed chefs are allowed to cook this dangerous meal. Seems only normal if we remember that, in medieval times, the chef had to share the client’s fate if he didn’t remove the poison correctly.
People die every year from fugu poisoning since there is still no cure for tetrodotoxin, all doctors can do is sustain the respiratory and circulatory systems until the poison wears off. Despite all this, Fugu is as popular as ever.
Some people are really careful about what they eat, try to cut down on fats and sugar to ensure a healthy life, others just don’t care and stuff themselves with all kinds of junk foods. But there’s another type of people, those that gamble with their lives for a rush of adrenalin or for a taste they find irresistible.
Here are the world’s deadliest delicacies:
Cassava
Cassava crops are very common in Africa and South America because they have the ability to grow in unfertile soil and withstand long droughts extremely well. They are very hard to find in other parts of the world and are richer in carbohydrates than maize and cereal crops.
They do however have a major flaw, the ability to kill a person. Cassava roots contain cyanogenic glycosides that are converted into hydrogen cyanide by an enzyme called linamarase. This happens when the plant’s cells are ruptured, most often when it is eaten. That’s why Cassava has to be processed very carefully, if consumed raw it can cause death.
Ackee
Ackee has become the national fruit of Jamaica, even though it is not native to the island. It was imported around 1780 from West Africa. Ackee fruits are rich in essential fatty acids, vitamin A, zinc and protein and are an important ingredient in many Caribbean dishes.
Still, if you’re ever in Jamaica, don’t go stuffing your face with Ackee fruits, it may be the last thing you do. Unripe Ackee fruits contain dangerous alkanoid poisons that provoke serious vomiting, seizures and even fatal hypoglycemia. Even when ripe, Ackees are not eaten entirely, the shiny black seeds and the red shell are discarded, only the soft inside is edible.
Apple
An apple a day keeps the doctor away! Entirely true, but, if you eat the seeds, he might stay away because there’s nothing he can do to help you.
Scientists have discovered that eating a large quantity of apple seeds is extremely hazardous to our health, because they contain a certain amount of cyanogenic glycoside, commonly known as cyanide. The amount of seed necessary to cause damage isn’t known yet, but the seeds of just one apple should have no negative effect on an adult. Children are more vulnerable however and should be taught to avoid eating the apple whole.
Symptoms of apple-seed intoxication include abdominal pains, vomiting, excessive sweating, coma and even death.
Snake
Like scorpions, tarantulas and other spiders, snake poison is neutralized when the meat is cooked, so you shouldn’t be worried about side effects if you don’t eat them raw. However in China and other Asian countries, snake parts are sometimes eaten raw, like the snake blood, a delicacy many of us probably couldn’t stomach. The snake is gutted, the blood gathered in a small glass and then mixed with the bile.
Chinese believe this a powerful aphrodisiac that also has the power to cure sexual deficiencies. Normally there shouldn’t be any danger, since the venom is collected in the snake’s head, but it can sometimes be present in its blood. So if you’re going to try snake blood, make sure you say a prayer before.
Puffer Fish
Definitely the world’s most popular toxic delicacy, the Puffer Fish may look funny but it’s definitely no joke. It contains high levels of tetrodotoxin, a powerful poison that paralyzes the muscles, eventually killing the victim through asphyxiation. The poison is present mostly in the liver, ovaries and skin and only licensed chefs are allowed to cook this dangerous meal. Seems only normal if we remember that, in medieval times, the chef had to share the client’s fate if he didn’t remove the poison correctly.
People die every year from fugu poisoning since there is still no cure for tetrodotoxin, all doctors can do is sustain the respiratory and circulatory systems until the poison wears off. Despite all this, Fugu is as popular as ever.
The Most Dangerous Creatures of the Sea
[Extracted from Hotel Club Travel Blog]
As quiet as the sea may seem, you should keep in mind the dangers lurking beneath the surface. Here’s a look at the deadliest creatures living in the water.
Lionfish
Members of the Scorpaenidae fish family, the Lionfish are native to the Indian and Pacific oceans but various species can be found all over the world. Also known as the Turkey Fish or Dragon Fish, it has long poisonous spines that are deadly to many marine creatures. The Lionfish sting is not usually deadly to humans but it will cause severe pain, headaches and vomiting.
Lionfish don’t attack people unless provoked, but in case you get stung you should immediately soak the area in hot water and seek medical help.
Stonefish
The Stonefish is a master of camouflage, which makes it even more dangerous, as people often get to close without realizing it. They can be found on the sea bottom and around coral reefs, disguised as rocks. The Stonefish is the most poisonous fish in the world. It has 13 spikes on its back, all filled with extremely potent, protein-based venom. Depending on how deep the sting is, this venom can kill a person in a few hours unless he receives medical attention.
Getting stung by a Stonefish causes excruciating pain, shock and paralysis. Surviving victims of Stonefish encounters have been known to suffer nerve damage which leads to muscle atrophy.
Sea Urchins
No one in his right mind would get close to anything as spiny as a sea urchin, but walking in the water makes it easier for people to step on them. Sea Urchins have long sharp spines that penetrate very deep and sometimes break, causing severe pain and infection. In most sting cases, the spines have to be removed surgically.
Not all Sea Urchins are venomous but one of the most dangerous, the Flower urchins can be deadly. It looks like its body is covered by flowers instead of thorns, but they are in fact venomous and can cause paralysis or, even worse, death. There have been several reports of people killed by Flower Urchins around Japan.
Catfish
They may look innocent and peaceful with their cute little whiskers, but Catfish are dangerous creatures if provoked. When it feels threatened, the Catfish pulls out three barbed spines from its back and side fins. They are venomous and cause severe pain. Although rare, throughout the years there have been cases when catfish attacks proved deadly.
Catfish venom remains active for several days after the fish dies so even refrigerated ones must be handled with care.
Box Jellyfish
Often referred to as the Box of Death, the Box Jellyfish is indeed one of the deadliest sea-creatures on earth. It has up to 60 tentacles which can be even 5 meters long and have 5,000 million stinging cells. It’s enough for a full grown adult to come in contact with just 3 tentacles to risk death. Box Jellyfish are very fragile organisms, even a small fish could tear through it like butter, so it needs to kill aggressors and its food at first contact.
Box Jellyfish are so dangerous because they frequent a number of very popular beaches and because of their translucent bodies they are extremely hard to spot.
Sharks
Just like crocodiles, sharks are perfect killers in the water, just seeing them on television makes everyone’s heart beat a little faster. But, contrary to popular belief, sharks don’t usually attack unless provoked, most species don’t attack humans at all.
The best way to avoid a shark attack is to stay away from shallow waters where sharks are known to be feeding in, that’s the most common mistake people make, they ignore warnings and end up having their limbs bitten off or even worse.
Stingrays
Not many people really knew how dangerous stingrays really were until the terrible accident in which Steve Irwin lost his life. The truth is stingrays kill a lot more people than sharks for example. They are not aggressive creatures and when attacked, most of the time they just flee, but when stepped on, stingrays whip their tail stinger.
A way to avoid getting pierced by this dangerous weapon is to slide your feet through the sand instead of actually stepping, this way the stingray detects you and runs away.
As quiet as the sea may seem, you should keep in mind the dangers lurking beneath the surface. Here’s a look at the deadliest creatures living in the water.
Lionfish
Members of the Scorpaenidae fish family, the Lionfish are native to the Indian and Pacific oceans but various species can be found all over the world. Also known as the Turkey Fish or Dragon Fish, it has long poisonous spines that are deadly to many marine creatures. The Lionfish sting is not usually deadly to humans but it will cause severe pain, headaches and vomiting.
Lionfish don’t attack people unless provoked, but in case you get stung you should immediately soak the area in hot water and seek medical help.
Stonefish
The Stonefish is a master of camouflage, which makes it even more dangerous, as people often get to close without realizing it. They can be found on the sea bottom and around coral reefs, disguised as rocks. The Stonefish is the most poisonous fish in the world. It has 13 spikes on its back, all filled with extremely potent, protein-based venom. Depending on how deep the sting is, this venom can kill a person in a few hours unless he receives medical attention.
Getting stung by a Stonefish causes excruciating pain, shock and paralysis. Surviving victims of Stonefish encounters have been known to suffer nerve damage which leads to muscle atrophy.
Sea Urchins
No one in his right mind would get close to anything as spiny as a sea urchin, but walking in the water makes it easier for people to step on them. Sea Urchins have long sharp spines that penetrate very deep and sometimes break, causing severe pain and infection. In most sting cases, the spines have to be removed surgically.
Not all Sea Urchins are venomous but one of the most dangerous, the Flower urchins can be deadly. It looks like its body is covered by flowers instead of thorns, but they are in fact venomous and can cause paralysis or, even worse, death. There have been several reports of people killed by Flower Urchins around Japan.
Catfish
They may look innocent and peaceful with their cute little whiskers, but Catfish are dangerous creatures if provoked. When it feels threatened, the Catfish pulls out three barbed spines from its back and side fins. They are venomous and cause severe pain. Although rare, throughout the years there have been cases when catfish attacks proved deadly.
Catfish venom remains active for several days after the fish dies so even refrigerated ones must be handled with care.
Box Jellyfish
Often referred to as the Box of Death, the Box Jellyfish is indeed one of the deadliest sea-creatures on earth. It has up to 60 tentacles which can be even 5 meters long and have 5,000 million stinging cells. It’s enough for a full grown adult to come in contact with just 3 tentacles to risk death. Box Jellyfish are very fragile organisms, even a small fish could tear through it like butter, so it needs to kill aggressors and its food at first contact.
Box Jellyfish are so dangerous because they frequent a number of very popular beaches and because of their translucent bodies they are extremely hard to spot.
Sharks
Just like crocodiles, sharks are perfect killers in the water, just seeing them on television makes everyone’s heart beat a little faster. But, contrary to popular belief, sharks don’t usually attack unless provoked, most species don’t attack humans at all.
The best way to avoid a shark attack is to stay away from shallow waters where sharks are known to be feeding in, that’s the most common mistake people make, they ignore warnings and end up having their limbs bitten off or even worse.
Stingrays
Not many people really knew how dangerous stingrays really were until the terrible accident in which Steve Irwin lost his life. The truth is stingrays kill a lot more people than sharks for example. They are not aggressive creatures and when attacked, most of the time they just flee, but when stepped on, stingrays whip their tail stinger.
A way to avoid getting pierced by this dangerous weapon is to slide your feet through the sand instead of actually stepping, this way the stingray detects you and runs away.
Friday, September 4, 2009
What are Bedsores ?
[Extracted from wisegeek.com]
Bedsores are lesions which are typically caused by periods of prolonged immobility. A mild bedsore can generally be easily treated, but more severe sores can cause serious problems, and they require surgical intervention. Bedsores strike people who are bedridden, paralyzed, or dealing with other limited mobility issues, and prevention of bedsores is a major part of training for health providers who deal with at-risk individuals.
These lesions are also known as pressure ulcers, decubitis ulcers, or skin ulcers. If left untreated, bedsores can cause sepsis, cellulitis, gangrene, and deep infections of the bones and joints. Bedsores have also been linked with carcinoma and necrotizing fasciitis, an infection which literally eats away otherwise healthy tissues. People in wheelchairs or people who are bedbound are at risk for skin ulcers, as are long-term hospital patients, individuals in nursing homes, and people with conditions such as diabetes, which interferes with circulation.
There are three primary causes for bedsores. The first is simply prolonged pressure, which can cause bedsores to appear on places like hips and shoulder blades. Bedsores also form through friction and shear as the patient's body rubs against a bed or wheelchair. Active people rarely get such sores because they make small adjustments to their position throughout the day and while they sleep. Someone who has a limited range of motion can get a bedsore in only a few hours if he or she is positioned in a way which cuts off circulation.
There are four different stages of bedsores. A stage one bedsore manifests as an area of tenderness and mild inflammation, and it generally vanishes shortly after the pressure on the area is relieved. A stage two bedsore is characterized by some skin loss, forming an open blister or wound which is also discolored; with rapid treatment, this type of sore generally heals quickly. Stage three bedsores are deeper, while stage four bedsores can be extremely deep fissures surrounded by dead tissue. A stage four bedsore is also characterized by damage to the underlying muscle and bone, and it represents a serious medical problem.
There are a number of ways to avoid bedsores. The first is frequent positional changes such as turning, accompanied by the use of supportive pads which can reduce pressure on problem areas like the hips. Caregivers also need to carefully inspect their patients for the early signs of bedsores, and patients generally benefit from nutritional support and physical therapy as well.
Are bed sores painful ?
Yes. Bed sores can be excruciatingly painful due to the fact that they are essentially an open wound in the body and they frequently develop in areas where it is essentially unavoidable to put pressure (such as the back, buttocks or heels).
For this reason, even the most mundane everyday activities such as sitting, turning, lifting cleaning and dressing changes, can cause intense pain.
What is Septicemia ?
[Extracted from Wisegeek.com]
Septicemia is a serious medical condition characterized by inflammation of the whole body. It is caused by bacteria which enter the bloodstream, triggering an immune response which results in inflammation and a slow shutdown of the body's systems for handling infection. This medical condition can be deadly, especially if the patient is allowed to progress into the stage of shock, and onset can be alarmingly rapid. If septicemia is suspected, a patient should be taken to a hospital for immediate medical attention.
The causes of septicemia are quite varied. Typically, the patient is vulnerable because of his or her age or condition, and bacteria simply takes advantage of the situation. Surgery, latent infections, and burns can all lead to septicemia, which is one very good reason to monitor any infections to ensure that they do not spread. A case of septicemia starts with bacteria or toxins that they produce entering the bloodstream, resulting in a coagulation of the blood as the body tries to fight the bacteria.
A patient with septicemia tends to look very bad. The condition is marked by confusion, chills, sweating, a very high fever, weakness, a rash, and an elevated heart rate. Respiration is also often rapid, and the patient may turn pale as well. If the condition progresses, the patient's blood pressure will drop, and the bacteria will start attacking major organs of the body, including the brain, rapidly causing severe damage which can be very difficult to treat.
This condition is also known as “blood poisoning,” in a reference to the fact that the patient's entire vascular system is compromised. Some people also refer to it as sepsis, a term which actually refers to any sort of inflammation response as a result of infection. One of the primary treatments for septicemia is antibiotics, which are administered to kill the bacteria causing the condition. Transfusions of blood may also be utilized, along with dialysis and fluid replacement for patients suffering from diarrhea. Patients with severe septicemia may be put on life support to help them breathe and to stabilize their heart rates.
Prevention of septicemia is, of course, preferable to treatment. Unfortunately, many cases are hard to prevent, as this condition can strike unpredictably. Maintaining good hygiene and general health is a good way to start, because it minimizes exposure to bacteria and ensures that your body can resist bacterial infections when it is exposed to harmful organisms. If you have had surgical procedures, you should keep an eye on the site where the procedure was performed, and do not be afraid to speak up about soreness, swelling, and general discomfort. It is also important to receive medical treatment for deep cuts and puncture wounds so that these sites can be flushed and you can take prophylactic antibiotics to prevent sepsis and the potential onset of septicemia.
Septicemia is a serious medical condition characterized by inflammation of the whole body. It is caused by bacteria which enter the bloodstream, triggering an immune response which results in inflammation and a slow shutdown of the body's systems for handling infection. This medical condition can be deadly, especially if the patient is allowed to progress into the stage of shock, and onset can be alarmingly rapid. If septicemia is suspected, a patient should be taken to a hospital for immediate medical attention.
The causes of septicemia are quite varied. Typically, the patient is vulnerable because of his or her age or condition, and bacteria simply takes advantage of the situation. Surgery, latent infections, and burns can all lead to septicemia, which is one very good reason to monitor any infections to ensure that they do not spread. A case of septicemia starts with bacteria or toxins that they produce entering the bloodstream, resulting in a coagulation of the blood as the body tries to fight the bacteria.
A patient with septicemia tends to look very bad. The condition is marked by confusion, chills, sweating, a very high fever, weakness, a rash, and an elevated heart rate. Respiration is also often rapid, and the patient may turn pale as well. If the condition progresses, the patient's blood pressure will drop, and the bacteria will start attacking major organs of the body, including the brain, rapidly causing severe damage which can be very difficult to treat.
This condition is also known as “blood poisoning,” in a reference to the fact that the patient's entire vascular system is compromised. Some people also refer to it as sepsis, a term which actually refers to any sort of inflammation response as a result of infection. One of the primary treatments for septicemia is antibiotics, which are administered to kill the bacteria causing the condition. Transfusions of blood may also be utilized, along with dialysis and fluid replacement for patients suffering from diarrhea. Patients with severe septicemia may be put on life support to help them breathe and to stabilize their heart rates.
Prevention of septicemia is, of course, preferable to treatment. Unfortunately, many cases are hard to prevent, as this condition can strike unpredictably. Maintaining good hygiene and general health is a good way to start, because it minimizes exposure to bacteria and ensures that your body can resist bacterial infections when it is exposed to harmful organisms. If you have had surgical procedures, you should keep an eye on the site where the procedure was performed, and do not be afraid to speak up about soreness, swelling, and general discomfort. It is also important to receive medical treatment for deep cuts and puncture wounds so that these sites can be flushed and you can take prophylactic antibiotics to prevent sepsis and the potential onset of septicemia.
Tuesday, August 18, 2009
What is Tamiflu ?
Generic Name: oseltamivir
Brand Names: Tamiflu
Tamiflu is an antiviral medication that blocks the actions of influenza virus types A and B in your body.
Tamiflu is used to treat flu symptoms caused by influenza virus in patients who have had symptoms for less than 2 days. Tamiflu may also be given to prevent influenza in people who may be exposed but do not yet have symptoms. It will not treat the common cold.
Tamiflu may also be used for other purposes not listed in this medication guide.
Important information about Tamiflu
Tamiflu is used to treat flu symptoms caused by influenza virus in patients who have had symptoms for less than 2 days. Tamiflu may also be given to prevent influenza in people who may be exposed but do not yet have symptoms. Oseltamivir will not treat the common cold.
Before taking Tamiflu, tell your doctor if you have received a nasal flu vaccine within the past 2 weeks, or if you have kidney disease, heart disease, lung disease, or any other serious disease or health problem. Also tell your doctor if you have any condition causing swelling or disorder of the brain.
Treatment with Tamiflu should start as soon as possible when flu symptoms appear, such as fever, chills, muscle aches, sore throat, and runny or stuffy nose.
Take Tamiflu for as many days as it has been prescribed for you even if you begin to feel better. Your symptoms may start to improve before the infection is completely treated. Some people using this medicine have had rare side effects of sudden confusion, delirium, hallucinations, unusual behavior, or self-injury. These symptoms have occurred most often in children. It is not known whether Tamiflu was the exact cause of these symptoms. However, anyone using this medicine should be watched closely for signs of confusion or unusual behavior. Call a doctor at once if you or the child using Tamiflu has any of these symptoms. Oseltamivir should not be used in place of getting a yearly flu shot. The Centers for Disease Control recommends an annual flu shot to help protect you each year from new strains of influenza virus.
Before using Tamiflu
Tamiflu should not be used in place of getting a yearly flu shot. The Centers for Disease Control recommends an annual flu shot to help protect you each year from new strains of influenza virus.
You should not use Tamiflu if you are allergic to oseltamivir.
Before taking Tamiflu, tell your doctor if you have used a nasal flu vaccine (FluMist) within the past 2 weeks, or if you have :
* kidney disease;
* heart disease;
* lung disease;
* a condition causing swelling or disorder of the brain; or
* any other serious disease or health problem.
Vaccines may be harmful to an unborn baby and generally should not be given to a pregnant woman. However, not vaccinating the mother could be more harmful to the baby if the mother becomes infected with a disease that this vaccine could prevent. Your doctor will decide whether you should receive this vaccine, especially if you have a high risk of infection with H1N1 influenza (also called "swine" flu). It is not known whether oseltamivir passes into breast milk or if it could harm a nursing baby. Do not take this medication without telling your doctor if you are breast-feeding a baby. Do not give this medication to a child younger than 1 year old.
Brand Names: Tamiflu
Tamiflu is an antiviral medication that blocks the actions of influenza virus types A and B in your body.
Tamiflu is used to treat flu symptoms caused by influenza virus in patients who have had symptoms for less than 2 days. Tamiflu may also be given to prevent influenza in people who may be exposed but do not yet have symptoms. It will not treat the common cold.
Tamiflu may also be used for other purposes not listed in this medication guide.
Important information about Tamiflu
Tamiflu is used to treat flu symptoms caused by influenza virus in patients who have had symptoms for less than 2 days. Tamiflu may also be given to prevent influenza in people who may be exposed but do not yet have symptoms. Oseltamivir will not treat the common cold.
Before taking Tamiflu, tell your doctor if you have received a nasal flu vaccine within the past 2 weeks, or if you have kidney disease, heart disease, lung disease, or any other serious disease or health problem. Also tell your doctor if you have any condition causing swelling or disorder of the brain.
Treatment with Tamiflu should start as soon as possible when flu symptoms appear, such as fever, chills, muscle aches, sore throat, and runny or stuffy nose.
Take Tamiflu for as many days as it has been prescribed for you even if you begin to feel better. Your symptoms may start to improve before the infection is completely treated. Some people using this medicine have had rare side effects of sudden confusion, delirium, hallucinations, unusual behavior, or self-injury. These symptoms have occurred most often in children. It is not known whether Tamiflu was the exact cause of these symptoms. However, anyone using this medicine should be watched closely for signs of confusion or unusual behavior. Call a doctor at once if you or the child using Tamiflu has any of these symptoms. Oseltamivir should not be used in place of getting a yearly flu shot. The Centers for Disease Control recommends an annual flu shot to help protect you each year from new strains of influenza virus.
Before using Tamiflu
Tamiflu should not be used in place of getting a yearly flu shot. The Centers for Disease Control recommends an annual flu shot to help protect you each year from new strains of influenza virus.
You should not use Tamiflu if you are allergic to oseltamivir.
Before taking Tamiflu, tell your doctor if you have used a nasal flu vaccine (FluMist) within the past 2 weeks, or if you have :
* kidney disease;
* heart disease;
* lung disease;
* a condition causing swelling or disorder of the brain; or
* any other serious disease or health problem.
Vaccines may be harmful to an unborn baby and generally should not be given to a pregnant woman. However, not vaccinating the mother could be more harmful to the baby if the mother becomes infected with a disease that this vaccine could prevent. Your doctor will decide whether you should receive this vaccine, especially if you have a high risk of infection with H1N1 influenza (also called "swine" flu). It is not known whether oseltamivir passes into breast milk or if it could harm a nursing baby. Do not take this medication without telling your doctor if you are breast-feeding a baby. Do not give this medication to a child younger than 1 year old.
Monday, August 17, 2009
Why Does Lung Cancer Occur in Non-Smokers ?
[Extracted from MedicineNet.Com]
The dangers of secondhand smoke While cigarette smoking is an undisputed cause of lung cancer, not all cases of lung cancer occur in smokers or former smokers. Each year, over 170,000 Americans develop lung cancer, and approximately ten per cent of lung cancers, or 17,000 cases, occur in non-smokers. Although not every non-smoker suffering from lung cancer will have an identifiable risk factor for development of the disease, a number of conditions and circumstances have been identified that will increase a non-smoker’s chance of developing lung cancer.
Passive smoking, or the inhalation of tobacco smoke from other smokers sharing living or working quarters, is an established risk factor for the development of lung cancer. Non-smokers who reside with a smoker have a 24% increase in risk for developing lung cancer when compared with other non-smokers. Each year, up to 3,000 lung cancer deaths are estimated to occur in the U.S. that are attributable to passive smoking.
The Dangers of Secondhand Smoke !
Secondhand smoke is a mixture of the smoke exhaled by smokers and the smoke that comes from the burning end of a cigarette, cigar, or pipe. You also may have heard it called environmental tobacco smoke (ETS), passive, or involuntary smoke. Secondhand smoke contains more than 4,000 substances. Many of them are dangerous poisons and can cause cancer. Anyone exposed to secondhand smoke inhales these substances.
Lung disease, including lung cancer, is the third leading cause of death in the U.S. Secondhand smoke :
* Can cause lung cancer in nonsmokers; the U.S. Environmental Protection Agency lists it as a Group A carcinogen, a rating used only for substances (i.e., asbestos) proven to cause cancer in humans.
* Will cause an estimated 3,000 lung cancer deaths this year.
* Can be a direct health threat to people who already have heart and lung diseases.
* Increases the risk of serious lung disease during the first two years of a child's life.
Did You Know ?
* Nonsmokers who live with smokers are more likely to develop lung cancer than other nonsmoking adults.
* If you have asthma, secondhand smoke can make your breathing problems worse.
* Young children are especially sensitive to secondhand smoke. A baby who lives in a home where one or both parents smoke is more likely to have lung disease serious enough to need treatment in a hospital during the first two years of life.
* Children exposed to secondhand smoke in the home are more likely to cough and wheeze and to have middle ear problems.
How To Protect Your Family At Home ?
* Don't allow smoking in your home. Ask smokers to smoke outside or, if you must, limit smoking to a separately ventilated room.
* Be supportive. Help the smoker to quit.
* Place "Thank You for Not Smoking" signs around the house.
* Do not allow babysitters or others who work in your home to smoke in the house.
What If People Smoke Where You Work ?
NIOSH (National Institute for Occupational Safety and Health) has determined that secondhand smoke may cause lung cancer in exposed workers.
* On-the-job exposure to secondhand smoke can be four times higher than in the home.
* Secondhand smoke can irritate your eyes, nose and throat.
* Some workers are already exposed to substances that can cause lung disease. Secondhand smoke in the workplace can only increase the danger.
* To protect nonsmokers from secondhand smoke, the workplace must be totally smoke free or smoking must be limited to a separate, enclosed area with its own ventilation system. As of 1991, about 4 out of 10 American companies with smoking policies were smoke free.
A Special Message For Smokers
Smoke-free worksites can be tough on smokers. Here are some tips for coping :
* In smoke free areas, do something to take your mind off smoking. Take a walk or stretch. Have a glass of water or a light snack.
* If you must smoke, make sure you are not in a "No Smoking" area before you light up and don't let cigarettes smolder in ashtrays.
* Try to quit smoking. See if your company offers any programs to help you quit or contact one of the organizations listed on the back of this booklet.
Monday, July 27, 2009
Gynecologic Tumor Markers
[Extracted from Emedicine.medscape.com]
Tumor markers are glycoproteins that are usually detected by monoclonal antibodies. Each tumor marker has a variable profile of usefulness for screening, determining diagnosis and prognosis, assessing response to therapy, and monitoring for cancer recurrence. They are produced by tumor cells in response to cancer or certain benign conditions and indicate biological changes that signal the existence of malignancy. These soluble molecules can usually be detected in elevated quantities in the blood, urine, or body tissues of patients with certain types of cancer. They are produced by the tumor itself or by the body in response to the presence of cancer or certain benign conditions. The levels of tumor marker are not altered in all cancer patients, especially in early stage cancer. The level of some tumor markers can be elevated in patients with noncancerous conditions. Following the development of monoclonal antibodies, many new tumor markers have been discovered during the past 2 decades.
Gynecologic malignancies include ovarian cancer, uterine cervical cancer, endometrial cancer, and trophoblastic neoplasms.
Due to the location of ovarian tumors within the abdominal cavity, making a preoperative pathological diagnosis of cancer is difficult without laparotomy. From this point of view, the use of tumor markers that consist of carbohydrate antigens, such as CA-125, in addition to diagnostic imaging are useful in the diagnosis of ovarian cancer. SCC antigen, a marker for squamous cell carcinoma, is clinically useful in the management of advanced cervical cancer. At present, no useful tumor markers exist for endometrial cancer that exhibit both high sensitivity and specificity, although CA-125 is often used in clinical practice. Finally, human chorionic gonadotropin (hCG) serves as an ideal tumor marker for trophoblastic disease; however, the incidence of trophoblastic neoplasms has decreased dramatically with the incorporation of strict clinical management of postmolar disease as well as with the overall decrease in the number of pregnancies.
The use of a tumor marker not only depends on its sensitivity and specificity, but also on its ability to influence decisions between alternative plans for patient management. Use of beta human chorionic gonadotropin (beta-hCG) for monitoring gestational trophoblastic neoplasia has set the standard to which other assays must be compared. Beta-hCG and alpha-fetoprotein have provided useful markers for ovarian germ cell tumors.
Recently, a monoclonal antibody-based immunoassay for CA-125 has been used to monitor the treatment of epithelial ovarian carcinomas. Persistent elevation of CA-125 in serum has generally reflected persistence of disease at second look surveillance procedures. However, CA-125 levels can return to within normal limits and residual disease can be found at laparoscopy or laparotomy. CA-125 shows promise for distinguishing benign from malignant pelvic masses. Several trials are ongoing to determine the potential of CA-125 in combination with other markers to increase earlier detection of occult ovarian cancer.
Tumor markers are glycoproteins that are usually detected by monoclonal antibodies. Each tumor marker has a variable profile of usefulness for screening, determining diagnosis and prognosis, assessing response to therapy, and monitoring for cancer recurrence. They are produced by tumor cells in response to cancer or certain benign conditions and indicate biological changes that signal the existence of malignancy. These soluble molecules can usually be detected in elevated quantities in the blood, urine, or body tissues of patients with certain types of cancer. They are produced by the tumor itself or by the body in response to the presence of cancer or certain benign conditions. The levels of tumor marker are not altered in all cancer patients, especially in early stage cancer. The level of some tumor markers can be elevated in patients with noncancerous conditions. Following the development of monoclonal antibodies, many new tumor markers have been discovered during the past 2 decades.
Gynecologic malignancies include ovarian cancer, uterine cervical cancer, endometrial cancer, and trophoblastic neoplasms.
Due to the location of ovarian tumors within the abdominal cavity, making a preoperative pathological diagnosis of cancer is difficult without laparotomy. From this point of view, the use of tumor markers that consist of carbohydrate antigens, such as CA-125, in addition to diagnostic imaging are useful in the diagnosis of ovarian cancer. SCC antigen, a marker for squamous cell carcinoma, is clinically useful in the management of advanced cervical cancer. At present, no useful tumor markers exist for endometrial cancer that exhibit both high sensitivity and specificity, although CA-125 is often used in clinical practice. Finally, human chorionic gonadotropin (hCG) serves as an ideal tumor marker for trophoblastic disease; however, the incidence of trophoblastic neoplasms has decreased dramatically with the incorporation of strict clinical management of postmolar disease as well as with the overall decrease in the number of pregnancies.
The use of a tumor marker not only depends on its sensitivity and specificity, but also on its ability to influence decisions between alternative plans for patient management. Use of beta human chorionic gonadotropin (beta-hCG) for monitoring gestational trophoblastic neoplasia has set the standard to which other assays must be compared. Beta-hCG and alpha-fetoprotein have provided useful markers for ovarian germ cell tumors.
Recently, a monoclonal antibody-based immunoassay for CA-125 has been used to monitor the treatment of epithelial ovarian carcinomas. Persistent elevation of CA-125 in serum has generally reflected persistence of disease at second look surveillance procedures. However, CA-125 levels can return to within normal limits and residual disease can be found at laparoscopy or laparotomy. CA-125 shows promise for distinguishing benign from malignant pelvic masses. Several trials are ongoing to determine the potential of CA-125 in combination with other markers to increase earlier detection of occult ovarian cancer.1
Tumor markers are glycoproteins that are usually detected by monoclonal antibodies. Each tumor marker has a variable profile of usefulness for screening, determining diagnosis and prognosis, assessing response to therapy, and monitoring for cancer recurrence. They are produced by tumor cells in response to cancer or certain benign conditions and indicate biological changes that signal the existence of malignancy. These soluble molecules can usually be detected in elevated quantities in the blood, urine, or body tissues of patients with certain types of cancer. They are produced by the tumor itself or by the body in response to the presence of cancer or certain benign conditions. The levels of tumor marker are not altered in all cancer patients, especially in early stage cancer. The level of some tumor markers can be elevated in patients with noncancerous conditions. Following the development of monoclonal antibodies, many new tumor markers have been discovered during the past 2 decades.
Gynecologic malignancies include ovarian cancer, uterine cervical cancer, endometrial cancer, and trophoblastic neoplasms.
Due to the location of ovarian tumors within the abdominal cavity, making a preoperative pathological diagnosis of cancer is difficult without laparotomy. From this point of view, the use of tumor markers that consist of carbohydrate antigens, such as CA-125, in addition to diagnostic imaging are useful in the diagnosis of ovarian cancer. SCC antigen, a marker for squamous cell carcinoma, is clinically useful in the management of advanced cervical cancer. At present, no useful tumor markers exist for endometrial cancer that exhibit both high sensitivity and specificity, although CA-125 is often used in clinical practice. Finally, human chorionic gonadotropin (hCG) serves as an ideal tumor marker for trophoblastic disease; however, the incidence of trophoblastic neoplasms has decreased dramatically with the incorporation of strict clinical management of postmolar disease as well as with the overall decrease in the number of pregnancies.
The use of a tumor marker not only depends on its sensitivity and specificity, but also on its ability to influence decisions between alternative plans for patient management. Use of beta human chorionic gonadotropin (beta-hCG) for monitoring gestational trophoblastic neoplasia has set the standard to which other assays must be compared. Beta-hCG and alpha-fetoprotein have provided useful markers for ovarian germ cell tumors.
Recently, a monoclonal antibody-based immunoassay for CA-125 has been used to monitor the treatment of epithelial ovarian carcinomas. Persistent elevation of CA-125 in serum has generally reflected persistence of disease at second look surveillance procedures. However, CA-125 levels can return to within normal limits and residual disease can be found at laparoscopy or laparotomy. CA-125 shows promise for distinguishing benign from malignant pelvic masses. Several trials are ongoing to determine the potential of CA-125 in combination with other markers to increase earlier detection of occult ovarian cancer.1
Some tumor markers can be used for screening, diagnosis, management, determining response, and recurrence. Some markers show promise as prognostic indicators.
The following are important gynecologic tumor markers :
a) Cancer antigen 125 (CA-125)
b) Beta chorionic gonadotropin (beta-hCG)
c) Alpha-fetoprotein (AFP)
d) Inhibin
e) Estradiol
f) Müllerian inhibiting substance (MIS)
g) Carbohydrate antigen 19-9
h) Ferritin
i) Topoisomerase II
j) Urinary gonadotropin fragment
k) Carcinoembryonic antigen (CEA)
m) Human telomerase reverse transcriptase (hTERT)
n) Others :
1) Tumor-associated trypsin inhibitor
2) Cyclin E
3) Lysophosphatidic acid (a lipid found to be elevated in serum and ascites fluid)
4) Mesothelin
5) HE4
6) Osteopontin
7) Vascular endothelial growth factor (VEGF)
8) Interleukin 8
9) Macrophage colony-stimulating factor
10) Insulinlike growth factor–binding protein-3
11) OVX1
No marker is completely specific; therefore, diagnostic immunohistochemistry testing must be used in conjunction with morphologic and clinical findings.
Cancer Antigen 125
After its initial discovery in the early 1980s, the serum CA-125 level has been widely used as a marker for a possible epithelial ovarian cancer in the primary assessment of a pelvic mass. In this setting, false-positive results may derive from several conditions, especially those associated with peritoneal inflammation, such as endometriosis, adenomyosis, pelvic inflammatory disease, menstruation, uterine fibroids, or benign cysts. Malignancies other than ovarian cancer can also increase CA-125 levels, but the most marked elevations (>1500 U/mL) are generally seen with ovarian cancer.
The primary use of CA-125 measurement is to monitor the disease status of patients with ovarian cancer, such as detecting early recurrence or assessing chemoresponse during chemotherapy. Serum CA-125 levels are also included in the American College of Obstetricians and Gynecologists and Society of Gynecologic Oncologists guidelines for referring patients to a gynecologic oncologist.
Postmenopausal women with serum levels of CA-125 higher than 35 U/mL or premenopausal women with CA-125 levels higher than 200 U/mL should be referred to a gynecologic oncologist. In an attempt to improve CA-125 measurement for the detection of epithelial ovarian cancers, especially at an early stage, recent studies have identified several new candidates for markers. Examples include lysophosphatidic acid (a lipid found to be elevated in serum and ascites fluid), mesothelin, HE4, osteopontin, vascular endothelial growth factor (VEGF) and interleukin 8, macrophage colony-stimulating factor, and different kallikreins. Interestingly, among these potential markers, HE4 has sensitivity similar to CA-125 in detecting late-stage disease but greater specificity than CA-125 in diagnosing early ovarian cancer. Validation of HE4 as a diagnostic biomarker in detecting ovarian cancer at early stages is currently ongoing.
Approximately 90% of ovarian cancers are celomic epithelial carcinomas and contain a celomic epithelium–related glycoprotein-designated CA-125. CA-125 can be localized in most serous, endometrioid, and clear cell ovarian carcinomas; mucinous tumors express this antigen less frequently. CA-125 is also found in the epithelium of the fallopian tubes, endometrium, and uterine cervix.
Ovarian carcinoma is the leading cause of death from gynecologic malignancies. CA-125 is an important tumor marker for the diagnosis, treatment, and follow-up care of patients with epithelial ovarian cancer and has been recommended for screening; however, CA-125 may not lead to early diagnosis because it is not perfectly sensitive or specific for ovarian cancer. CA-125 can be used clinically to determine response to treatment, relapse, and survival.
Although CA-125 is most consistently elevated in patients with epithelial ovarian cancer, it can be expressed in a number of gynecologic (eg, endometrium, fallopian tube) and nongynecologic (eg, pancreas, breast, colon, lung) cancers. CA-125 levels are frequently elevated with tumor spread beyond the uterus and have been found highly sensitive in detecting extrauterine disease.
Serum CA-125 markers are primarily used to monitor the progress of ovarian cancer. An increase in CA-125 levels during or after treatment is a strong predictor of future disease progression. A rapid decrease in CA-125 levels during initial treatment correlates with longer progression-free intervals and survival. A CA-125 level less than 15 U/mL after a standard 6-course treatment generally correlates with longer progression-free intervals, although it does not predict whether microscopic disease is present. A CA-125 value greater than 35 U/mL after a standard 6-course chemotherapy treatment predicts the presence of disease. Disease progression may also occur when CA-125 values are stable.
Standardized CA-125 definitions have the potential of complementing or, in some cases, replacing current response definitions in a cost-effective way. The rate of CA-125 decline during primary chemotherapy is an important independent prognostic factor. Persistent elevation of CA-125 levels at the time of a second-look surgical surveillance procedure predicts residual disease with at least a 95% specificity. Rising CA-125 values have preceded clinical detection of recurrent disease by at least 3 months. Given the modest activity of salvage chemotherapy, this information has not yet influenced survival rates. Rising CA-125 level during subsequent chemotherapy is associated with progressive disease in at least 90% of cases. CA-125 may serve as an effective surrogate marker for clinical response in clinical trials of new drugs.
The measurement of CA-125 levels, usually in combination with other modalities (eg, bimanual pelvic examination, transvaginal ultrasonography) is a proposed method of early detection of ovarian cancer, which is the most promising application of this tumor marker. CA-125 levels can help distinguish malignant and benign pelvic masses, which permits effective triage of patients for primary surgery. In addition, an algorithm has been developed that estimates the risk of ovarian cancer based on the level and trend of CA-125 values.
Screening using CA-125
Early-stage ovarian cancer has excellent prognosis after definitive therapy. Therefore, early detection is vital in reducing mortality due to this disease. However, no screening program for ovarian cancer has achieved this goal. Several studies have been launched to identify the best strategy for detecting early-stage disease and reducing mortality by using either CA-125 or ultrasonography as the primary screening test. In a cohort of roughly 15,500 women, the positive predictive value for ultrasonography screening ranged from 1.5% when abdominal ultrasonography was used to close to the screening-recommended 10% when transvaginal ultrasonography was used. This low positive predictive value is due to the commonality of benign pelvic lesions, even in postmenopausal women.
High specificity is important in screening strategies for ovarian cancer because a positive test result generally requires definitive surgical assessment. Given the relatively low prevalence of ovarian cancer, a test with 95% specificity would result in 50 surgical procedures for every ovarian cancer detected. Einhorn and colleagues screened 5550 women with CA-125 alone and this screening approach resulted in an unacceptable 29 surgeries for every cancer detected. Another major limitation of CA-125 screening is that serum levels are elevated in only about 50% of patients with stage I disease.
Because several gynecologic and nongynecologic conditions can elevate CA-125 levels, combination test strategies have been tried to improve the predictive value of CA-125. Jacobs and colleagues randomized 22,000 postmenopausal women to be screened with 3 annual CA-125 measurements or no screening. Those patients with CA-125 levels higher than 30 U/mL underwent transvaginal ultrasonography. Twenty-nine women were referred for surgical exploration, and 6 women were diagnosed as having ovarian cancer (3 of whom had stage I). The positive predictive value was 20.7%. Ten additional women in the screening arm developed ovarian cancer during follow-up. Twenty women in the control arm developed ovarian cancer. The investigators were able to show a median survival benefit (73 months in the screened arm vs 42 months in the control group; P =.01)
Two large randomized studies are currently ongoing. The NIH Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial4 enrolled 75,000 women aged 55-74 years from 1992-2001. The study randomly assigned women to screening (ie, annual pelvic examination, transvaginal ultrasonography, and CA-125 assay) or no screening. The recently published prevalence data from this study revealed familiar findings: 31 women operated on for every invasive cancer detected and a high proportion of advanced-stage cancers. However, these initial results are affected greatly by the benign and malignant conditions prevalent at a woman’s first screening evaluation. The true effectiveness of the screening strategy will now be tested by its ability to detect new cancers during the next several years.
The second study, started in 2001, called the UK Collaborative Trial of Ovarian Cancer Screening, has completed randomization of 200,000 postmenopausal women to transvaginal ultrasonography, multimodality screening, or a control group. These studies will answer the question of whether ultrasonography with or without CA-125–based screening in women with ovarian cancer can reduce mortality due to ovarian cancer.
Currently new screening approaches are being studied including high-throughput techniques using microarray technology and proteomic screening to identify panels of novel markers that may be altered early in the disease.
Ovarian epithelial tumors are histologically classified into serous tumors, mucinous tumors, endometrioid tumors, clear cell tumors, Brenner tumors, undifferentiated tumors, mixed epithelial tumors (composed of ≥2 of the 5 major cell types of common epithelial tumors), and intraperitoneal cancer (the ovaries appear to be incidentally involved and not the primary origin, which should be classified as extraovarian peritoneal cancer).
Serous tumors are the most common type, accounting for almost half of all epithelial ovarian cancers. These cells histologically resemble cells that line the fallopian tube. They tend to be high grade and are the cancers most often seen in BRCA mutation carriers. Endometrioid cancers resemble the cells that line the endometrium. These cancers are sometimes associated with endometriosis. Clear cell tumors are relatively uncommon, occurring most often in women in their 40s. Approximately 50% of women with clear cell tumors have associated endometriosis. Although most clear cell cancers are diagnosed at an early stage, these tumors are aggressive. The cells of mucinous tumors resemble those of the cervix or intestine. Mucinous tumors are more likely to be found in younger women, and 75-80% are benign and develop in only 1 ovary. Cancerous mucinous tumors are more common in older women and do not produce CA-125.
Epithelial tumors of the ovary are also subclassified by grading: Gx, grade cannot be assessed; G1, well differentiated; G2, moderately differentiated; and G3, poorly differentiated. Grade is related to prognosis in ovarian cancer, with patients with low-grade cancers doing better. Grade information is considered in treatment decisions for women with stage I disease.
Borderline ovarian tumors, or tumors of low malignant potential, also develop in the epithelial cells that cover the surface of the ovaries. Although borderline tumors have some malignant features, such as malignant-appearing histologic features and excess proliferation, they generally behave in an indolent manner. One important feature of borderline tumors is that they do not invade the stroma of the ovary. Borderline tumors make up 10-15% of all epithelial ovarian tumors. Approximately 3000 women in the United States are diagnosed with borderline tumors every year. Although these tumors can occur in women of all ages, they commonly occur in younger woman compared to epithelial ovarian cancers, and they have the same risk factors as epithelial ovarian cancer.
At diagnosis, approximately 20% of borderline tumors have spread beyond the ovary via peritoneal implants, but unlike epithelial ovarian cancer implants, these borderline peritoneal implants are noninvasive. However, in less than 5% of borderline tumors, so-called invasive implants can be found that invade below the peritoneal surface layer. A borderline tumor with invasive implants behaves more aggressively than does a borderline tumor with noninvasive implants. Surgery is the mainstay of treatment for women with borderline tumors of the ovary. Chemotherapy can be given to those patients that have more aggressive features, such as invasive implants or rapid recurrence after surgery.
CA-125 can be elevated up to 3% more than normal postmenopausal women. Therefore, screening using the CA-125 test has not been effective enough for widespread use. For ovarian cancer to be detected in 1 additional patient using CA-125 as the primary screening tool, another 100-150 women would have to receive evaluation and approximately 30 diagnostic operations be performed. To enhance the use of CA-125 for ovarian cancer screening, the change in CA-125 concentration in the bloodstream over time is being investigated as compared to just depending upon the absolute value.
Ovarian cancer screening is not recommended for women with no risk factors (RR≤3). For women with increase risk (RR=3-6 times), after evaluating risks and benefits, ovarian cancer screening with CA-125 and/or transvaginal ultrasonography can be done, usually by clinical trials. In women at inherited risk (RR>6 times), usually with mutations in ovarian cancer susceptibility genes, should receive screening by a combination of transvaginal ultrasonography and CA-125. For patients with mutations in BRCA1 or the mismatch repair genes, MLH1, MSH2, and MSH6, screening should begin around 30-35 years of age. For patients with mutations in BRCA2, ovarian cancer screening should be performed around 35-40 years of age.
The Gynecologic Cancer Intergroup uses the Rustin definition to define a rise in CA-125. If the CA-125 level becomes normal after surgery, a subsequent level twice the upper limit of normal is consistent with progression. If the CA-125 level is not normal after surgery, then a subsequent level twice the patient's nadir value signifies progressive disease.
Serum CA-125 level has been widely used as a marker for a possible epithelial ovarian cancer in the primary assessment of a pelvic mass. The predominant use of CA-125 measurement is to monitor disease status of patients with ovarian cancer, such as detecting early recurrence or assessing response during chemotherapy. CA-125 has provided a useful first-generation marker for monitoring ovarian cancer and triaging patients with pelvic masses, despite limitations in sensitivity and specificity. In the next decade, the challenge will be to identify new markers that will complement CA-125 in monitoring ovarian cancer and facilitate screening for occult early-stage disease. The expression of growth factors and their receptors and application of monoclonal antibodies to immunohistochemistry and radionuclide imaging may also provide new areas of diagnostic application for monoclonal antibodies in gynecologic oncology.
Other Gynecologic Tumor Markers
human chorionic gonadotropin
Beta-hCG is expressed in human fetal tissue and cancer cells of various histologic types. It is degraded to the beta-core fragment, which is concentrated in urine and is also known as urinary gonadotropin peptide. Urinary gonadotropin fragment and lipid-associated sialic acid levels are elevated in up to 60% of patients with endometrial cancer.
Increased levels of beta-hCG occur in patients with choriocarcinoma of the uterus, embryonal carcinomas, polyembryomas, mixed cell tumors, and, less commonly, dysgerminomas. Both beta-hCG and human placental lactogen (hPL) are the most useful markers for trophoblastic disease and can be localized in syncytiotrophoblasts of partial and complete hydatidiform moles. The intensity and pattern of reactivity for these antigens differ in partial and complete moles. Gestational choriocarcinomas demonstrate variable but positive staining results for beta-hCG and hPL. The hPL immunostaining differentiates placental-site trophoblastic tumors from choriocarcinomas. The use of beta-hCG is not limited to trophoblastic diseases because it has been localized in a wide array of nontrophoblastic gynecologic neoplasms.
The following diagnostic criteria is commonly used for malignant gestational trophoblastic disease :
a) lateauing of beta-hCG levels over at least 3 weeks
b) 10% or greater rise in beta-hCG for 3 or more values over at least 2 weeks
c) Persistence of beta-hCG 6 months after molar evacuation
d) Histologic identification of choriocarcinoma
Patients who have undergone molar pregnancy evacuation should undergo weekly beta-hCG monitoring until normal levels are achieved, then monthly monitoring until 6-12 months of normal values have been achieved. About 20% patients undergoing evacuation of molar pregnancy will develop postmolar gestational trophoblastic disease, usually manifesting as failure to normalize the postevacuation beta-hCG levels. A 10% rise in beta-hCG over 3 or more weekly titers or a beta-hCG titer of 40,000 mIU/L 4-5 months after uterine evacuation constitutes a serological diagnosis of postmolar trophoblastic disease.
For metastatic malignant trophoblastic disease, beta-hCG monitoring is recommended every 6 months for an indefinite period of time because late recurrence is a possibility.
The beta subunit of human chorionic gonadotropin (beta-hCG) is normally produced by the placenta. Elevated b-hCG levels are most commonly associated with pregnancy, germ cell tumors, and gestational trophoblastic disease. False-positive levels occur in hypogonadal states and with marijuana use.
Both AFP and beta-hCG play crucial roles in the management of patients with nonseminomatous germ cell tumors. The AFP or beta-hCG level is elevated in 85% of patients with these tumors but in only 20% of patients with stage I disease. Hence, these markers have no role in screening.
In patients with extragonadal disease or metastasis at the time of diagnosis, highly elevated AFP or beta-hCG values can be used in place of biopsy to establish a diagnosis of nonseminomatous germ cell tumor. AFP values in excess of 10,000 ng/mL or beta-hCG levels above 50,000 mIU/mL at initial diagnosis portend a poor prognosis, with a 5-year survival rate of 50%. Similarly staged patients with lower AFP and beta-hCG levels have a cure rate above 90%.
Following AFP and beta-hCG levels is imperative in monitoring response to treatment in patients who have nonseminomatous germ cell tumors. Patients with AFP and beta-hCG levels that do not decline as expected after treatment have a significantly worse prognosis, and changes in therapy should be considered. Because curative salvage therapy is possible, the tumor markers are followed every 1-2 months for 1 year after treatment, then quarterly for 1 year, and less frequently thereafter. AFP or beta-hCG level elevation is frequently the first evidence of germ cell tumor recurrence; a confirmed elevation should prompt reinstitution of therapy.
In spite of complete clinical response after chemotherapy, almost 50% of patients with stage III/IV disease have residual tumor. Among patients with persistent elevation of CA-125, about 90-95% will have residual tumor. The beta-hCG level is used for monitoring response to therapy and detecting early relapse. Testing for the beta-hCG is an integral part of the diagnosis, management, and response to treatment for gestational trophoblastic disease and in selected patients with epithelial carcinomas of the ovary. Combined AFP and beta-hCG testing is an essential adjunct in the evaluation and treatment of nonseminomatous germ cell tumors, and in monitoring the response to therapy. AFP and beta-hCG may also be useful in evaluating potential origins of poorly differentiated metastatic cancer.
Human telomerase reverse transcriptase (hTERT)
Human telomerase reverse transcriptase (hTERT) is a novel and newly available biomarker for patients with ovarian and uterine cancers. The hTERT mRNA level has a significant correlation with CA-125 and with histological findings in ovarian cancer. Serum hTERT mRNA is useful for diagnosing gynecologic cancer and is superior to conventional tumor markers. Upregulation of hTERT may play an important role in the development of cervical intraepithelial neoplasia (CIN) and cervical cancer; hTERT could be used as an early diagnostic biomarker for cervical cancer in the future.
Inhibin
Inhibin is a peptide hormone normally produced by ovarian granulosa cells. It inhibits the secretion of follicle-stimulating hormone (FSH) by the anterior pituitary gland. It reaches a peak of 772 +/- 38 U/L in the follicular phase of the menstrual cycle and is normally undetectable in the serum of menopausal women. Granulosa-cell tumors produce inhibin and its serum levels reflect the the tumor burden. Measurement of inhibin can be used as a marker for primary as well as recurrent granulosa cell tumor.
The recent availability of markers of ovarian stroma, including melan-A and inhibin-alpha, has provided a means for the positive identification of ovarian stromal tumors, which can manifest in a myriad of histological appearances.
The hormonal activity of granulosa cell tumors permits the use of a variety of serum tumor markers in the diagnostic evaluation. Clinically, the most useful serum marker for granulosa cell tumors is inhibin. Inhibin exists in 2 different isoforms, inhibin A and inhibin B. Both isoforms consist of a dimer of 2 subunits, the alpha and beta subunits. The alpha subunit is the same for both isoforms, while the beta subunits differ (beta A and beta B) and show about 64% homology. The 3 subunits (alpha, beta A, beta B) are produced on separate genes located on chromosomes 2 (alpha and beta B) and 7 (beta A).
Inhibin usually becomes nondetectable after menopause. However, certain ovarian tumors, mostly mucinous epithelial ovarian carcinomas and granulosa cell tumors, produce inhibin. An elevated inhibin level in a postmenopausal woman or a premenopausal woman presenting with amenorrhea and infertility is suggestive of the presence of a granulosa cell tumor, but not specific. Inhibin levels can also be used for tumor surveillance after treatment to assess for residual or recurrent disease. Although most commercial laboratories only provide assays for inhibin A, serum levels of inhibin B seem to be more frequently elevated. Whenever available, the use of assays is suggested that detect both isoforms. The free alpha subunit can also be measured.
Estradiol
Estradiol was one of the first markers identified in the serum of patients with granulosa cell tumors. In general, estradiol is not a sensitive marker for the presence of a granulosa cell tumor. About 30% of tumors do not produce estradiol due to lack of theca cells, which produce androstendione, a necessary precursor for estradiol synthesis. However, following serum estradiol levels postoperatively may be useful for detecting recurrence of an estradiol-secreting tumor.
Müllerian inhibiting substance
Müllerian inhibiting substance (MIS) is produced by granulosa cells in the developing follicles. It has emerged as a potential tumor marker for granulosa cell tumors. As with inhibin, MIS is typically undetectable in postmenopausal women. The elevated MIS level is highly specific for ovarian granulosa cell tumors; however, this test is not commercially available for clinical use.
Topoisomerase II
Topoisomerase II expression is detected in tumor samples by immunohistochemistry and has emerged as a promising, clinically relevant biomarker for survival in patients with advanced epithelial ovarian cancer.
Carbohydrate antigen 19-9
Serum carbohydrate antigen 19-9 levels are elevated in up to 35% of patients with endometrial cancer and can be used in a follow-up evaluation of patients with mucinous borderline ovarian tumors. Measurement of serum tumor markers in the follow-up care of these patients may lead to earlier detection of recurrence in only a very small proportion of patients; the clinical value of earlier detection of recurrence remains to be established. Carbohydrate antigen is not specific for ovarian cancer.
Cancer antigen 27-29
Elevated cancer antigen 27-29 levels are associated with cancers of the colon, stomach, kidney, lung, ovary, pancreas, uterus, and liver. First-trimester pregnancy, endometriosis, ovarian cysts, benign breast disease, kidney disease, and liver disease are noncancerous conditions that are also associated with increased cancer antigen 27-29 levels.
Markers for Response to Therapy and Relapse
The following tumor markers are helpful in assessing response to chemotherapy and in determining relapse when monitoring patients with complete remission.
Squamous cell carcinoma antigen
The squamous cell carcinoma antigen level can be increased in patients with epidermoid carcinoma of the cervix, benign tumors of epithelial origin, and benign skin disorders.
Carcinoembryonic antigen
Most sweat gland tumors of the vulva stain positively for carcinoembryonic antigen (CEA). In most instances, the reaction for CEA occurs in cells that line cysts, form glands, or are arranged around a lumen. The reaction for CEA does not differentiate eccrine from apocrine adnexal tumors. In patients with vaginal adenosis, both surface columnar epithelium and glands may show focal cytoplasmic membrane staining for CEA. As the columnar cells are gradually replaced by the process of squamous metaplasia, CEA positivity may be observed in the cytoplasm of metaplastic cells. Malignant vulvar tumors of sweat gland origin stain positively for CEA. Both in situ and invasive adenocarcinomas underlying extramammary Paget disease of the anogenital area express CEA. CEA is also demonstrable in Paget cells at metastatic sites such as lymph nodes. CEA is present in most urothelial adenocarcinomas of the female urethra.
CEA levels are elevated in up to 35% of patients with endometrial cancer. CEA immunohistochemistry cannot distinguish between benign and malignant glandular proliferations of the uterine cervix; therefore, CEA staining is of no value in the differential diagnosis of endocervical and endometrial adenocarcinomas.
Most epithelial neoplasms of the ovary also express CEA. The neoplasms include, with decreasing intensity and frequency, Brenner, endometrioid, clear cell, and serous tumors. CEA is frequently present in patients with cancer that has metastasized to the ovary because the primary cancer is generally mammary or gastrointestinal in origin and these tumors frequently contain CEA.
Alpha-fetoprotein
Alpha-fetoprotein (AFP) is a normal fetal serum protein synthesized by the liver, yolk sac, and gastrointestinal tract that shares sequence homology with albumin. AFP is a major component of fetal plasma, reaching a peak concentration of 3 mg/mL at 12 weeks of gestation. Following birth, AFP rapidly clears from the circulation because its half-life is 3.5 days. AFP concentration in adult serum is less than 20 ng/mL.
Most endodermal sinus tumors of the ovary express AFP. AFP is present within the cytoplasm of tumor cells and in the characteristic hyalin globules observed in the endodermal sinus tumor. AFP is also expressed by ovarian embryonal cell carcinoma, immature teratomas, and polyembryomas.
Lysophosphatidic acid
Lysophosphatidic acid stimulates cancer cell proliferation, intracellular calcium release, and tyrosine phosphorylation, including mitogen-activated protein kinase activation. Lysophosphatidic acid has been shown to be a multifunctional signaling molecule in fibroblasts and other cells. It has been found in the ascitic fluid of patients with ovarian cancer and is associated with ovarian cancer cell proliferation. Further studies are needed to determine the role of these markers.
MIB1-determined tumor growth fraction has recently been studied as an additional tool for the decision of adjuvant therapy in patients with very early stages of ovarian carcinomas. In one study, MIB1 predicted tumor recurrences in 84% of the ovarian cancers.
L1 (CAM)
According to Daponte et al, L1 (CAM) immunoreactivity correlates with stage and grade of ovarian cancer. It increases from benign tumors to early carcinomas and to advanced stage carcinomas progressively and significantly. L1 (CAM) expression represents a novel diagnostic marker in serous ovarian neoplasms that shows characteristics of tumor progression. L1 expression is associated with chemotherapy response.6
Normalization of tumor markers
Normalization of tumor marker values may indicate cure despite radiographic evidence of persistent disease. In this situation, the residual tumor is frequently nonviable. Sometimes, tumor marker levels may rise after effective treatment (due to cell lysis), but the increase may not portend treatment failure. A consistent increase in tumor marker levels, combined with lack of clinical improvement, may indicate treatment failure. Residual elevation after definitive treatment usually indicates persistent disease.
Screening
Screening tests require high sensitivity to detect early-stage disease. These tests also must have sufficient specificity to protect patients with false-positive results from unnecessary diagnostic work up.
So far, no tumor marker has demonstrated a survival benefit in randomized controlled trials of screening in the general population. However, these tumor markers can play a crucial role in detecting disease, assessing response to therapy, and monitoring for disease recurrence.
The NCI is currently conducting the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) screening trial to determine if certain screening tests, including CA-125 to screen for ovarian cancer, reduce the number of deaths from these cancers.
Proteomics are being investigated for developing better cancer screening and treatment options. Proteomics may also help to identify new proteins that serve as tumor markers in early stages and to predict the effectiveness of treatment and probability of recurrence.
Tumor markers are glycoproteins that are usually detected by monoclonal antibodies. Each tumor marker has a variable profile of usefulness for screening, determining diagnosis and prognosis, assessing response to therapy, and monitoring for cancer recurrence. They are produced by tumor cells in response to cancer or certain benign conditions and indicate biological changes that signal the existence of malignancy. These soluble molecules can usually be detected in elevated quantities in the blood, urine, or body tissues of patients with certain types of cancer. They are produced by the tumor itself or by the body in response to the presence of cancer or certain benign conditions. The levels of tumor marker are not altered in all cancer patients, especially in early stage cancer. The level of some tumor markers can be elevated in patients with noncancerous conditions. Following the development of monoclonal antibodies, many new tumor markers have been discovered during the past 2 decades.
Gynecologic malignancies include ovarian cancer, uterine cervical cancer, endometrial cancer, and trophoblastic neoplasms.
Due to the location of ovarian tumors within the abdominal cavity, making a preoperative pathological diagnosis of cancer is difficult without laparotomy. From this point of view, the use of tumor markers that consist of carbohydrate antigens, such as CA-125, in addition to diagnostic imaging are useful in the diagnosis of ovarian cancer. SCC antigen, a marker for squamous cell carcinoma, is clinically useful in the management of advanced cervical cancer. At present, no useful tumor markers exist for endometrial cancer that exhibit both high sensitivity and specificity, although CA-125 is often used in clinical practice. Finally, human chorionic gonadotropin (hCG) serves as an ideal tumor marker for trophoblastic disease; however, the incidence of trophoblastic neoplasms has decreased dramatically with the incorporation of strict clinical management of postmolar disease as well as with the overall decrease in the number of pregnancies.
The use of a tumor marker not only depends on its sensitivity and specificity, but also on its ability to influence decisions between alternative plans for patient management. Use of beta human chorionic gonadotropin (beta-hCG) for monitoring gestational trophoblastic neoplasia has set the standard to which other assays must be compared. Beta-hCG and alpha-fetoprotein have provided useful markers for ovarian germ cell tumors.
Recently, a monoclonal antibody-based immunoassay for CA-125 has been used to monitor the treatment of epithelial ovarian carcinomas. Persistent elevation of CA-125 in serum has generally reflected persistence of disease at second look surveillance procedures. However, CA-125 levels can return to within normal limits and residual disease can be found at laparoscopy or laparotomy. CA-125 shows promise for distinguishing benign from malignant pelvic masses. Several trials are ongoing to determine the potential of CA-125 in combination with other markers to increase earlier detection of occult ovarian cancer.
Tumor markers are glycoproteins that are usually detected by monoclonal antibodies. Each tumor marker has a variable profile of usefulness for screening, determining diagnosis and prognosis, assessing response to therapy, and monitoring for cancer recurrence. They are produced by tumor cells in response to cancer or certain benign conditions and indicate biological changes that signal the existence of malignancy. These soluble molecules can usually be detected in elevated quantities in the blood, urine, or body tissues of patients with certain types of cancer. They are produced by the tumor itself or by the body in response to the presence of cancer or certain benign conditions. The levels of tumor marker are not altered in all cancer patients, especially in early stage cancer. The level of some tumor markers can be elevated in patients with noncancerous conditions. Following the development of monoclonal antibodies, many new tumor markers have been discovered during the past 2 decades.
Gynecologic malignancies include ovarian cancer, uterine cervical cancer, endometrial cancer, and trophoblastic neoplasms.
Due to the location of ovarian tumors within the abdominal cavity, making a preoperative pathological diagnosis of cancer is difficult without laparotomy. From this point of view, the use of tumor markers that consist of carbohydrate antigens, such as CA-125, in addition to diagnostic imaging are useful in the diagnosis of ovarian cancer. SCC antigen, a marker for squamous cell carcinoma, is clinically useful in the management of advanced cervical cancer. At present, no useful tumor markers exist for endometrial cancer that exhibit both high sensitivity and specificity, although CA-125 is often used in clinical practice. Finally, human chorionic gonadotropin (hCG) serves as an ideal tumor marker for trophoblastic disease; however, the incidence of trophoblastic neoplasms has decreased dramatically with the incorporation of strict clinical management of postmolar disease as well as with the overall decrease in the number of pregnancies.
The use of a tumor marker not only depends on its sensitivity and specificity, but also on its ability to influence decisions between alternative plans for patient management. Use of beta human chorionic gonadotropin (beta-hCG) for monitoring gestational trophoblastic neoplasia has set the standard to which other assays must be compared. Beta-hCG and alpha-fetoprotein have provided useful markers for ovarian germ cell tumors.
Recently, a monoclonal antibody-based immunoassay for CA-125 has been used to monitor the treatment of epithelial ovarian carcinomas. Persistent elevation of CA-125 in serum has generally reflected persistence of disease at second look surveillance procedures. However, CA-125 levels can return to within normal limits and residual disease can be found at laparoscopy or laparotomy. CA-125 shows promise for distinguishing benign from malignant pelvic masses. Several trials are ongoing to determine the potential of CA-125 in combination with other markers to increase earlier detection of occult ovarian cancer.1
Tumor markers are glycoproteins that are usually detected by monoclonal antibodies. Each tumor marker has a variable profile of usefulness for screening, determining diagnosis and prognosis, assessing response to therapy, and monitoring for cancer recurrence. They are produced by tumor cells in response to cancer or certain benign conditions and indicate biological changes that signal the existence of malignancy. These soluble molecules can usually be detected in elevated quantities in the blood, urine, or body tissues of patients with certain types of cancer. They are produced by the tumor itself or by the body in response to the presence of cancer or certain benign conditions. The levels of tumor marker are not altered in all cancer patients, especially in early stage cancer. The level of some tumor markers can be elevated in patients with noncancerous conditions. Following the development of monoclonal antibodies, many new tumor markers have been discovered during the past 2 decades.
Gynecologic malignancies include ovarian cancer, uterine cervical cancer, endometrial cancer, and trophoblastic neoplasms.
Due to the location of ovarian tumors within the abdominal cavity, making a preoperative pathological diagnosis of cancer is difficult without laparotomy. From this point of view, the use of tumor markers that consist of carbohydrate antigens, such as CA-125, in addition to diagnostic imaging are useful in the diagnosis of ovarian cancer. SCC antigen, a marker for squamous cell carcinoma, is clinically useful in the management of advanced cervical cancer. At present, no useful tumor markers exist for endometrial cancer that exhibit both high sensitivity and specificity, although CA-125 is often used in clinical practice. Finally, human chorionic gonadotropin (hCG) serves as an ideal tumor marker for trophoblastic disease; however, the incidence of trophoblastic neoplasms has decreased dramatically with the incorporation of strict clinical management of postmolar disease as well as with the overall decrease in the number of pregnancies.
The use of a tumor marker not only depends on its sensitivity and specificity, but also on its ability to influence decisions between alternative plans for patient management. Use of beta human chorionic gonadotropin (beta-hCG) for monitoring gestational trophoblastic neoplasia has set the standard to which other assays must be compared. Beta-hCG and alpha-fetoprotein have provided useful markers for ovarian germ cell tumors.
Recently, a monoclonal antibody-based immunoassay for CA-125 has been used to monitor the treatment of epithelial ovarian carcinomas. Persistent elevation of CA-125 in serum has generally reflected persistence of disease at second look surveillance procedures. However, CA-125 levels can return to within normal limits and residual disease can be found at laparoscopy or laparotomy. CA-125 shows promise for distinguishing benign from malignant pelvic masses. Several trials are ongoing to determine the potential of CA-125 in combination with other markers to increase earlier detection of occult ovarian cancer.1
Some tumor markers can be used for screening, diagnosis, management, determining response, and recurrence. Some markers show promise as prognostic indicators.
The following are important gynecologic tumor markers :
a) Cancer antigen 125 (CA-125)
b) Beta chorionic gonadotropin (beta-hCG)
c) Alpha-fetoprotein (AFP)
d) Inhibin
e) Estradiol
f) Müllerian inhibiting substance (MIS)
g) Carbohydrate antigen 19-9
h) Ferritin
i) Topoisomerase II
j) Urinary gonadotropin fragment
k) Carcinoembryonic antigen (CEA)
m) Human telomerase reverse transcriptase (hTERT)
n) Others :
1) Tumor-associated trypsin inhibitor
2) Cyclin E
3) Lysophosphatidic acid (a lipid found to be elevated in serum and ascites fluid)
4) Mesothelin
5) HE4
6) Osteopontin
7) Vascular endothelial growth factor (VEGF)
8) Interleukin 8
9) Macrophage colony-stimulating factor
10) Insulinlike growth factor–binding protein-3
11) OVX1
No marker is completely specific; therefore, diagnostic immunohistochemistry testing must be used in conjunction with morphologic and clinical findings.
Cancer Antigen 125
After its initial discovery in the early 1980s, the serum CA-125 level has been widely used as a marker for a possible epithelial ovarian cancer in the primary assessment of a pelvic mass. In this setting, false-positive results may derive from several conditions, especially those associated with peritoneal inflammation, such as endometriosis, adenomyosis, pelvic inflammatory disease, menstruation, uterine fibroids, or benign cysts. Malignancies other than ovarian cancer can also increase CA-125 levels, but the most marked elevations (>1500 U/mL) are generally seen with ovarian cancer.
The primary use of CA-125 measurement is to monitor the disease status of patients with ovarian cancer, such as detecting early recurrence or assessing chemoresponse during chemotherapy. Serum CA-125 levels are also included in the American College of Obstetricians and Gynecologists and Society of Gynecologic Oncologists guidelines for referring patients to a gynecologic oncologist.
Postmenopausal women with serum levels of CA-125 higher than 35 U/mL or premenopausal women with CA-125 levels higher than 200 U/mL should be referred to a gynecologic oncologist. In an attempt to improve CA-125 measurement for the detection of epithelial ovarian cancers, especially at an early stage, recent studies have identified several new candidates for markers. Examples include lysophosphatidic acid (a lipid found to be elevated in serum and ascites fluid), mesothelin, HE4, osteopontin, vascular endothelial growth factor (VEGF) and interleukin 8, macrophage colony-stimulating factor, and different kallikreins. Interestingly, among these potential markers, HE4 has sensitivity similar to CA-125 in detecting late-stage disease but greater specificity than CA-125 in diagnosing early ovarian cancer. Validation of HE4 as a diagnostic biomarker in detecting ovarian cancer at early stages is currently ongoing.
Approximately 90% of ovarian cancers are celomic epithelial carcinomas and contain a celomic epithelium–related glycoprotein-designated CA-125. CA-125 can be localized in most serous, endometrioid, and clear cell ovarian carcinomas; mucinous tumors express this antigen less frequently. CA-125 is also found in the epithelium of the fallopian tubes, endometrium, and uterine cervix.
Ovarian carcinoma is the leading cause of death from gynecologic malignancies. CA-125 is an important tumor marker for the diagnosis, treatment, and follow-up care of patients with epithelial ovarian cancer and has been recommended for screening; however, CA-125 may not lead to early diagnosis because it is not perfectly sensitive or specific for ovarian cancer. CA-125 can be used clinically to determine response to treatment, relapse, and survival.
Although CA-125 is most consistently elevated in patients with epithelial ovarian cancer, it can be expressed in a number of gynecologic (eg, endometrium, fallopian tube) and nongynecologic (eg, pancreas, breast, colon, lung) cancers. CA-125 levels are frequently elevated with tumor spread beyond the uterus and have been found highly sensitive in detecting extrauterine disease.
Serum CA-125 markers are primarily used to monitor the progress of ovarian cancer. An increase in CA-125 levels during or after treatment is a strong predictor of future disease progression. A rapid decrease in CA-125 levels during initial treatment correlates with longer progression-free intervals and survival. A CA-125 level less than 15 U/mL after a standard 6-course treatment generally correlates with longer progression-free intervals, although it does not predict whether microscopic disease is present. A CA-125 value greater than 35 U/mL after a standard 6-course chemotherapy treatment predicts the presence of disease. Disease progression may also occur when CA-125 values are stable.
Standardized CA-125 definitions have the potential of complementing or, in some cases, replacing current response definitions in a cost-effective way. The rate of CA-125 decline during primary chemotherapy is an important independent prognostic factor. Persistent elevation of CA-125 levels at the time of a second-look surgical surveillance procedure predicts residual disease with at least a 95% specificity. Rising CA-125 values have preceded clinical detection of recurrent disease by at least 3 months. Given the modest activity of salvage chemotherapy, this information has not yet influenced survival rates. Rising CA-125 level during subsequent chemotherapy is associated with progressive disease in at least 90% of cases. CA-125 may serve as an effective surrogate marker for clinical response in clinical trials of new drugs.
The measurement of CA-125 levels, usually in combination with other modalities (eg, bimanual pelvic examination, transvaginal ultrasonography) is a proposed method of early detection of ovarian cancer, which is the most promising application of this tumor marker. CA-125 levels can help distinguish malignant and benign pelvic masses, which permits effective triage of patients for primary surgery. In addition, an algorithm has been developed that estimates the risk of ovarian cancer based on the level and trend of CA-125 values.
Screening using CA-125
Early-stage ovarian cancer has excellent prognosis after definitive therapy. Therefore, early detection is vital in reducing mortality due to this disease. However, no screening program for ovarian cancer has achieved this goal. Several studies have been launched to identify the best strategy for detecting early-stage disease and reducing mortality by using either CA-125 or ultrasonography as the primary screening test. In a cohort of roughly 15,500 women, the positive predictive value for ultrasonography screening ranged from 1.5% when abdominal ultrasonography was used to close to the screening-recommended 10% when transvaginal ultrasonography was used. This low positive predictive value is due to the commonality of benign pelvic lesions, even in postmenopausal women.
High specificity is important in screening strategies for ovarian cancer because a positive test result generally requires definitive surgical assessment. Given the relatively low prevalence of ovarian cancer, a test with 95% specificity would result in 50 surgical procedures for every ovarian cancer detected. Einhorn and colleagues screened 5550 women with CA-125 alone and this screening approach resulted in an unacceptable 29 surgeries for every cancer detected. Another major limitation of CA-125 screening is that serum levels are elevated in only about 50% of patients with stage I disease.
Because several gynecologic and nongynecologic conditions can elevate CA-125 levels, combination test strategies have been tried to improve the predictive value of CA-125. Jacobs and colleagues randomized 22,000 postmenopausal women to be screened with 3 annual CA-125 measurements or no screening. Those patients with CA-125 levels higher than 30 U/mL underwent transvaginal ultrasonography. Twenty-nine women were referred for surgical exploration, and 6 women were diagnosed as having ovarian cancer (3 of whom had stage I). The positive predictive value was 20.7%. Ten additional women in the screening arm developed ovarian cancer during follow-up. Twenty women in the control arm developed ovarian cancer. The investigators were able to show a median survival benefit (73 months in the screened arm vs 42 months in the control group; P =.01)
Two large randomized studies are currently ongoing. The NIH Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial4 enrolled 75,000 women aged 55-74 years from 1992-2001. The study randomly assigned women to screening (ie, annual pelvic examination, transvaginal ultrasonography, and CA-125 assay) or no screening. The recently published prevalence data from this study revealed familiar findings: 31 women operated on for every invasive cancer detected and a high proportion of advanced-stage cancers. However, these initial results are affected greatly by the benign and malignant conditions prevalent at a woman’s first screening evaluation. The true effectiveness of the screening strategy will now be tested by its ability to detect new cancers during the next several years.
The second study, started in 2001, called the UK Collaborative Trial of Ovarian Cancer Screening, has completed randomization of 200,000 postmenopausal women to transvaginal ultrasonography, multimodality screening, or a control group. These studies will answer the question of whether ultrasonography with or without CA-125–based screening in women with ovarian cancer can reduce mortality due to ovarian cancer.
Currently new screening approaches are being studied including high-throughput techniques using microarray technology and proteomic screening to identify panels of novel markers that may be altered early in the disease.
Ovarian epithelial tumors are histologically classified into serous tumors, mucinous tumors, endometrioid tumors, clear cell tumors, Brenner tumors, undifferentiated tumors, mixed epithelial tumors (composed of ≥2 of the 5 major cell types of common epithelial tumors), and intraperitoneal cancer (the ovaries appear to be incidentally involved and not the primary origin, which should be classified as extraovarian peritoneal cancer).
Serous tumors are the most common type, accounting for almost half of all epithelial ovarian cancers. These cells histologically resemble cells that line the fallopian tube. They tend to be high grade and are the cancers most often seen in BRCA mutation carriers. Endometrioid cancers resemble the cells that line the endometrium. These cancers are sometimes associated with endometriosis. Clear cell tumors are relatively uncommon, occurring most often in women in their 40s. Approximately 50% of women with clear cell tumors have associated endometriosis. Although most clear cell cancers are diagnosed at an early stage, these tumors are aggressive. The cells of mucinous tumors resemble those of the cervix or intestine. Mucinous tumors are more likely to be found in younger women, and 75-80% are benign and develop in only 1 ovary. Cancerous mucinous tumors are more common in older women and do not produce CA-125.
Epithelial tumors of the ovary are also subclassified by grading: Gx, grade cannot be assessed; G1, well differentiated; G2, moderately differentiated; and G3, poorly differentiated. Grade is related to prognosis in ovarian cancer, with patients with low-grade cancers doing better. Grade information is considered in treatment decisions for women with stage I disease.
Borderline ovarian tumors, or tumors of low malignant potential, also develop in the epithelial cells that cover the surface of the ovaries. Although borderline tumors have some malignant features, such as malignant-appearing histologic features and excess proliferation, they generally behave in an indolent manner. One important feature of borderline tumors is that they do not invade the stroma of the ovary. Borderline tumors make up 10-15% of all epithelial ovarian tumors. Approximately 3000 women in the United States are diagnosed with borderline tumors every year. Although these tumors can occur in women of all ages, they commonly occur in younger woman compared to epithelial ovarian cancers, and they have the same risk factors as epithelial ovarian cancer.
At diagnosis, approximately 20% of borderline tumors have spread beyond the ovary via peritoneal implants, but unlike epithelial ovarian cancer implants, these borderline peritoneal implants are noninvasive. However, in less than 5% of borderline tumors, so-called invasive implants can be found that invade below the peritoneal surface layer. A borderline tumor with invasive implants behaves more aggressively than does a borderline tumor with noninvasive implants. Surgery is the mainstay of treatment for women with borderline tumors of the ovary. Chemotherapy can be given to those patients that have more aggressive features, such as invasive implants or rapid recurrence after surgery.
CA-125 can be elevated up to 3% more than normal postmenopausal women. Therefore, screening using the CA-125 test has not been effective enough for widespread use. For ovarian cancer to be detected in 1 additional patient using CA-125 as the primary screening tool, another 100-150 women would have to receive evaluation and approximately 30 diagnostic operations be performed. To enhance the use of CA-125 for ovarian cancer screening, the change in CA-125 concentration in the bloodstream over time is being investigated as compared to just depending upon the absolute value.
Ovarian cancer screening is not recommended for women with no risk factors (RR≤3). For women with increase risk (RR=3-6 times), after evaluating risks and benefits, ovarian cancer screening with CA-125 and/or transvaginal ultrasonography can be done, usually by clinical trials. In women at inherited risk (RR>6 times), usually with mutations in ovarian cancer susceptibility genes, should receive screening by a combination of transvaginal ultrasonography and CA-125. For patients with mutations in BRCA1 or the mismatch repair genes, MLH1, MSH2, and MSH6, screening should begin around 30-35 years of age. For patients with mutations in BRCA2, ovarian cancer screening should be performed around 35-40 years of age.
The Gynecologic Cancer Intergroup uses the Rustin definition to define a rise in CA-125. If the CA-125 level becomes normal after surgery, a subsequent level twice the upper limit of normal is consistent with progression. If the CA-125 level is not normal after surgery, then a subsequent level twice the patient's nadir value signifies progressive disease.
Serum CA-125 level has been widely used as a marker for a possible epithelial ovarian cancer in the primary assessment of a pelvic mass. The predominant use of CA-125 measurement is to monitor disease status of patients with ovarian cancer, such as detecting early recurrence or assessing response during chemotherapy. CA-125 has provided a useful first-generation marker for monitoring ovarian cancer and triaging patients with pelvic masses, despite limitations in sensitivity and specificity. In the next decade, the challenge will be to identify new markers that will complement CA-125 in monitoring ovarian cancer and facilitate screening for occult early-stage disease. The expression of growth factors and their receptors and application of monoclonal antibodies to immunohistochemistry and radionuclide imaging may also provide new areas of diagnostic application for monoclonal antibodies in gynecologic oncology.
Other Gynecologic Tumor Markers
human chorionic gonadotropin
Beta-hCG is expressed in human fetal tissue and cancer cells of various histologic types. It is degraded to the beta-core fragment, which is concentrated in urine and is also known as urinary gonadotropin peptide. Urinary gonadotropin fragment and lipid-associated sialic acid levels are elevated in up to 60% of patients with endometrial cancer.
Increased levels of beta-hCG occur in patients with choriocarcinoma of the uterus, embryonal carcinomas, polyembryomas, mixed cell tumors, and, less commonly, dysgerminomas. Both beta-hCG and human placental lactogen (hPL) are the most useful markers for trophoblastic disease and can be localized in syncytiotrophoblasts of partial and complete hydatidiform moles. The intensity and pattern of reactivity for these antigens differ in partial and complete moles. Gestational choriocarcinomas demonstrate variable but positive staining results for beta-hCG and hPL. The hPL immunostaining differentiates placental-site trophoblastic tumors from choriocarcinomas. The use of beta-hCG is not limited to trophoblastic diseases because it has been localized in a wide array of nontrophoblastic gynecologic neoplasms.
The following diagnostic criteria is commonly used for malignant gestational trophoblastic disease :
a) lateauing of beta-hCG levels over at least 3 weeks
b) 10% or greater rise in beta-hCG for 3 or more values over at least 2 weeks
c) Persistence of beta-hCG 6 months after molar evacuation
d) Histologic identification of choriocarcinoma
Patients who have undergone molar pregnancy evacuation should undergo weekly beta-hCG monitoring until normal levels are achieved, then monthly monitoring until 6-12 months of normal values have been achieved. About 20% patients undergoing evacuation of molar pregnancy will develop postmolar gestational trophoblastic disease, usually manifesting as failure to normalize the postevacuation beta-hCG levels. A 10% rise in beta-hCG over 3 or more weekly titers or a beta-hCG titer of 40,000 mIU/L 4-5 months after uterine evacuation constitutes a serological diagnosis of postmolar trophoblastic disease.
For metastatic malignant trophoblastic disease, beta-hCG monitoring is recommended every 6 months for an indefinite period of time because late recurrence is a possibility.
The beta subunit of human chorionic gonadotropin (beta-hCG) is normally produced by the placenta. Elevated b-hCG levels are most commonly associated with pregnancy, germ cell tumors, and gestational trophoblastic disease. False-positive levels occur in hypogonadal states and with marijuana use.
Both AFP and beta-hCG play crucial roles in the management of patients with nonseminomatous germ cell tumors. The AFP or beta-hCG level is elevated in 85% of patients with these tumors but in only 20% of patients with stage I disease. Hence, these markers have no role in screening.
In patients with extragonadal disease or metastasis at the time of diagnosis, highly elevated AFP or beta-hCG values can be used in place of biopsy to establish a diagnosis of nonseminomatous germ cell tumor. AFP values in excess of 10,000 ng/mL or beta-hCG levels above 50,000 mIU/mL at initial diagnosis portend a poor prognosis, with a 5-year survival rate of 50%. Similarly staged patients with lower AFP and beta-hCG levels have a cure rate above 90%.
Following AFP and beta-hCG levels is imperative in monitoring response to treatment in patients who have nonseminomatous germ cell tumors. Patients with AFP and beta-hCG levels that do not decline as expected after treatment have a significantly worse prognosis, and changes in therapy should be considered. Because curative salvage therapy is possible, the tumor markers are followed every 1-2 months for 1 year after treatment, then quarterly for 1 year, and less frequently thereafter. AFP or beta-hCG level elevation is frequently the first evidence of germ cell tumor recurrence; a confirmed elevation should prompt reinstitution of therapy.
In spite of complete clinical response after chemotherapy, almost 50% of patients with stage III/IV disease have residual tumor. Among patients with persistent elevation of CA-125, about 90-95% will have residual tumor. The beta-hCG level is used for monitoring response to therapy and detecting early relapse. Testing for the beta-hCG is an integral part of the diagnosis, management, and response to treatment for gestational trophoblastic disease and in selected patients with epithelial carcinomas of the ovary. Combined AFP and beta-hCG testing is an essential adjunct in the evaluation and treatment of nonseminomatous germ cell tumors, and in monitoring the response to therapy. AFP and beta-hCG may also be useful in evaluating potential origins of poorly differentiated metastatic cancer.
Human telomerase reverse transcriptase (hTERT)
Human telomerase reverse transcriptase (hTERT) is a novel and newly available biomarker for patients with ovarian and uterine cancers. The hTERT mRNA level has a significant correlation with CA-125 and with histological findings in ovarian cancer. Serum hTERT mRNA is useful for diagnosing gynecologic cancer and is superior to conventional tumor markers. Upregulation of hTERT may play an important role in the development of cervical intraepithelial neoplasia (CIN) and cervical cancer; hTERT could be used as an early diagnostic biomarker for cervical cancer in the future.
Inhibin
Inhibin is a peptide hormone normally produced by ovarian granulosa cells. It inhibits the secretion of follicle-stimulating hormone (FSH) by the anterior pituitary gland. It reaches a peak of 772 +/- 38 U/L in the follicular phase of the menstrual cycle and is normally undetectable in the serum of menopausal women. Granulosa-cell tumors produce inhibin and its serum levels reflect the the tumor burden. Measurement of inhibin can be used as a marker for primary as well as recurrent granulosa cell tumor.
The recent availability of markers of ovarian stroma, including melan-A and inhibin-alpha, has provided a means for the positive identification of ovarian stromal tumors, which can manifest in a myriad of histological appearances.
The hormonal activity of granulosa cell tumors permits the use of a variety of serum tumor markers in the diagnostic evaluation. Clinically, the most useful serum marker for granulosa cell tumors is inhibin. Inhibin exists in 2 different isoforms, inhibin A and inhibin B. Both isoforms consist of a dimer of 2 subunits, the alpha and beta subunits. The alpha subunit is the same for both isoforms, while the beta subunits differ (beta A and beta B) and show about 64% homology. The 3 subunits (alpha, beta A, beta B) are produced on separate genes located on chromosomes 2 (alpha and beta B) and 7 (beta A).
Inhibin usually becomes nondetectable after menopause. However, certain ovarian tumors, mostly mucinous epithelial ovarian carcinomas and granulosa cell tumors, produce inhibin. An elevated inhibin level in a postmenopausal woman or a premenopausal woman presenting with amenorrhea and infertility is suggestive of the presence of a granulosa cell tumor, but not specific. Inhibin levels can also be used for tumor surveillance after treatment to assess for residual or recurrent disease. Although most commercial laboratories only provide assays for inhibin A, serum levels of inhibin B seem to be more frequently elevated. Whenever available, the use of assays is suggested that detect both isoforms. The free alpha subunit can also be measured.
Estradiol
Estradiol was one of the first markers identified in the serum of patients with granulosa cell tumors. In general, estradiol is not a sensitive marker for the presence of a granulosa cell tumor. About 30% of tumors do not produce estradiol due to lack of theca cells, which produce androstendione, a necessary precursor for estradiol synthesis. However, following serum estradiol levels postoperatively may be useful for detecting recurrence of an estradiol-secreting tumor.
Müllerian inhibiting substance
Müllerian inhibiting substance (MIS) is produced by granulosa cells in the developing follicles. It has emerged as a potential tumor marker for granulosa cell tumors. As with inhibin, MIS is typically undetectable in postmenopausal women. The elevated MIS level is highly specific for ovarian granulosa cell tumors; however, this test is not commercially available for clinical use.
Topoisomerase II
Topoisomerase II expression is detected in tumor samples by immunohistochemistry and has emerged as a promising, clinically relevant biomarker for survival in patients with advanced epithelial ovarian cancer.
Carbohydrate antigen 19-9
Serum carbohydrate antigen 19-9 levels are elevated in up to 35% of patients with endometrial cancer and can be used in a follow-up evaluation of patients with mucinous borderline ovarian tumors. Measurement of serum tumor markers in the follow-up care of these patients may lead to earlier detection of recurrence in only a very small proportion of patients; the clinical value of earlier detection of recurrence remains to be established. Carbohydrate antigen is not specific for ovarian cancer.
Cancer antigen 27-29
Elevated cancer antigen 27-29 levels are associated with cancers of the colon, stomach, kidney, lung, ovary, pancreas, uterus, and liver. First-trimester pregnancy, endometriosis, ovarian cysts, benign breast disease, kidney disease, and liver disease are noncancerous conditions that are also associated with increased cancer antigen 27-29 levels.
Markers for Response to Therapy and Relapse
The following tumor markers are helpful in assessing response to chemotherapy and in determining relapse when monitoring patients with complete remission.
Squamous cell carcinoma antigen
The squamous cell carcinoma antigen level can be increased in patients with epidermoid carcinoma of the cervix, benign tumors of epithelial origin, and benign skin disorders.
Carcinoembryonic antigen
Most sweat gland tumors of the vulva stain positively for carcinoembryonic antigen (CEA). In most instances, the reaction for CEA occurs in cells that line cysts, form glands, or are arranged around a lumen. The reaction for CEA does not differentiate eccrine from apocrine adnexal tumors. In patients with vaginal adenosis, both surface columnar epithelium and glands may show focal cytoplasmic membrane staining for CEA. As the columnar cells are gradually replaced by the process of squamous metaplasia, CEA positivity may be observed in the cytoplasm of metaplastic cells. Malignant vulvar tumors of sweat gland origin stain positively for CEA. Both in situ and invasive adenocarcinomas underlying extramammary Paget disease of the anogenital area express CEA. CEA is also demonstrable in Paget cells at metastatic sites such as lymph nodes. CEA is present in most urothelial adenocarcinomas of the female urethra.
CEA levels are elevated in up to 35% of patients with endometrial cancer. CEA immunohistochemistry cannot distinguish between benign and malignant glandular proliferations of the uterine cervix; therefore, CEA staining is of no value in the differential diagnosis of endocervical and endometrial adenocarcinomas.
Most epithelial neoplasms of the ovary also express CEA. The neoplasms include, with decreasing intensity and frequency, Brenner, endometrioid, clear cell, and serous tumors. CEA is frequently present in patients with cancer that has metastasized to the ovary because the primary cancer is generally mammary or gastrointestinal in origin and these tumors frequently contain CEA.
Alpha-fetoprotein
Alpha-fetoprotein (AFP) is a normal fetal serum protein synthesized by the liver, yolk sac, and gastrointestinal tract that shares sequence homology with albumin. AFP is a major component of fetal plasma, reaching a peak concentration of 3 mg/mL at 12 weeks of gestation. Following birth, AFP rapidly clears from the circulation because its half-life is 3.5 days. AFP concentration in adult serum is less than 20 ng/mL.
Most endodermal sinus tumors of the ovary express AFP. AFP is present within the cytoplasm of tumor cells and in the characteristic hyalin globules observed in the endodermal sinus tumor. AFP is also expressed by ovarian embryonal cell carcinoma, immature teratomas, and polyembryomas.
Lysophosphatidic acid
Lysophosphatidic acid stimulates cancer cell proliferation, intracellular calcium release, and tyrosine phosphorylation, including mitogen-activated protein kinase activation. Lysophosphatidic acid has been shown to be a multifunctional signaling molecule in fibroblasts and other cells. It has been found in the ascitic fluid of patients with ovarian cancer and is associated with ovarian cancer cell proliferation. Further studies are needed to determine the role of these markers.
MIB1-determined tumor growth fraction has recently been studied as an additional tool for the decision of adjuvant therapy in patients with very early stages of ovarian carcinomas. In one study, MIB1 predicted tumor recurrences in 84% of the ovarian cancers.
L1 (CAM)
According to Daponte et al, L1 (CAM) immunoreactivity correlates with stage and grade of ovarian cancer. It increases from benign tumors to early carcinomas and to advanced stage carcinomas progressively and significantly. L1 (CAM) expression represents a novel diagnostic marker in serous ovarian neoplasms that shows characteristics of tumor progression. L1 expression is associated with chemotherapy response.6
Normalization of tumor markers
Normalization of tumor marker values may indicate cure despite radiographic evidence of persistent disease. In this situation, the residual tumor is frequently nonviable. Sometimes, tumor marker levels may rise after effective treatment (due to cell lysis), but the increase may not portend treatment failure. A consistent increase in tumor marker levels, combined with lack of clinical improvement, may indicate treatment failure. Residual elevation after definitive treatment usually indicates persistent disease.
Screening
Screening tests require high sensitivity to detect early-stage disease. These tests also must have sufficient specificity to protect patients with false-positive results from unnecessary diagnostic work up.
So far, no tumor marker has demonstrated a survival benefit in randomized controlled trials of screening in the general population. However, these tumor markers can play a crucial role in detecting disease, assessing response to therapy, and monitoring for disease recurrence.
The NCI is currently conducting the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) screening trial to determine if certain screening tests, including CA-125 to screen for ovarian cancer, reduce the number of deaths from these cancers.
Proteomics are being investigated for developing better cancer screening and treatment options. Proteomics may also help to identify new proteins that serve as tumor markers in early stages and to predict the effectiveness of treatment and probability of recurrence.
Saturday, July 18, 2009
What is Henoch-Schonlein Purpura (HSP) ?
[Extracted from MedicineNet.Com]
Henoch-Schonlein purpura (HSP) is a form of blood vessel inflammation or vasculitis. There are many different conditions that feature vasculitis. Each of the forms of vasculitis tends to involve certain characteristic blood vessels. HSP affects the small vessels called capillaries in the skin and frequently the kidneys. HSP results in skin rash (most prominent over the buttocks and behind the lower extremities) associated with joint inflammation (arthritis) and sometimes cramping pain in the abdomen. Henoch-Schonlein purpura is also referred to as anaphylactoid purpura.
What causes HSP ?
HSP occurs most often in the spring and frequently follows an infection of the throat or breathing passages. HSP seems to represent an unusual reaction of the body's immune system that is in response to this infection (either bacteria or virus). Aside from infection, drugs can also trigger the condition. HSP occurs most commonly in children, but people of all age groups can be affected.
What are symptoms of HSP ?
Classically, HSP causes skin rash, pain in the abdomen, and joint inflammation (arthritis). Not all features need be present for the diagnosis. The rash of skin lesions appears in gravity-dependent areas, such as the legs. The joints most frequently affected with pain and swelling are the ankles and the knees. Patients with HSP can develop fever. Inflammation of the blood vessels in the kidneys can cause blood and/or protein in the urine. Serious kidney complications are infrequent but can occur.
Symptoms usually last approximately a month. Recurrences are not frequent but do occur.
How is HSP diagnosed ?
HSP is usually diagnosed based on the typical skin, joint, and kidney findings. Throat culture, urinalysis, and blood tests for inflammation and kidney function are used to suggest the diagnosis. A biopsy of the skin, and less commonly kidneys, can be used to demonstrate vasculitis. Special staining techniques (direct immunofluorescence) of the biopsy specimen can be used to document antibody deposits of IgA in the blood vessels of involved tissue.
What is the treatment for HSP ?
While HSP is generally a mild illness that resolves spontaneously, it can cause serious problems in the kidneys and bowels. The rash can be very prominent, especially on the lower extremities.
The treatment of HSP is directed toward the most significant area of involvement. Joint pain can be relieved by antiinflammatory medications such as aspirin or ibuprofen (Motrin). Some patients can require cortisone medications, such as prednisone or prednisolone, especially those with significant abdominal pain or kidney disease. With more severe kidney disease, involvement called glomerulonephritis or nephritis, cyclophosphamide (Cytoxan), azathioprine (Imuran), or mycophenolate mofetil (Cellcept) have been used to suppress the immune system. Infection, if present, can require antibiotics.
What is the prognosis for patients with HSP ?
The prognosis for patients with HSP is generally excellent. Nearly all patients have no long-term problems. The kidney is the most serious organ involved when it is affected. Rarely, patients can have serious long-term kidney damage or an abnormal bowel folding called intussusception. Some patients have recurrences of symptoms, particularly skin rash, for months to a year after the onset of the illness.
Recent data show that HSP in adults is generally more severe than in children. Adults have more severe kidney involvement and can require more aggressive treatment. The ultimate outcome, however, is usually very good for both adults and children.
Henoch-Schonlein Purpura At A Glance
* Henoch-Schonlein purpura is a particular form of blood vessel inflammation called vasculitis.
* Henoch-Schonlein purpura frequently follows an infection of the throat or breathing passages, but it can be induced by certain medications.
* Henoch-Schonlein purpura causes skin rash, pain in the abdomen, and joint inflammation (arthritis).
* The treatment of Henoch-Schonlein purpura is directed toward the most significant area of involvement.
* The prognosis for patients with Henoch-Schonlein purpura is generally excellent.
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