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Who Is Your Favourite T4 Presenter?

PopSugarUK — Sun, 09 Nov 2008 00:00:00 -0800

Can you believe it, T4 is 10 years old today! The show has become a must-have hangover companion on Sunday mornings for our generation, with past presenters including Dermot O'Leary, Vernon Kay, June Sarpong, Ben Shephard, and Margherita Taylor. There are various celebratory shenanigans on Channel 4 today to help mark the occasion, and I want to know your thoughts on the current presenters Rick Edwards, Miquita Oliver, Steve Jones and Alexa Chung. Which of them is your favourite T4 presenter? Or does one of the past presenters take the crown?

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The Stars Come Out For Jimmy Choo in London

PopSugarUK — Fri, 30 Oct 2009 06:00:00 -0700

Last night in London, Tamara Mellon hosted a party for Jimmy Choo Project PEP, attracting celebs like Guy Ritchie and Claudia Winkleman. T4 presenters Steve Jones and Jameela Jamil hung out at the party, ahead of T4's Stars of 2009 which will feature The Saturdays, N-Dubz and Kasabian. Jameela looked gorgeous in her dress and bright lipstick, while Martine McCutcheon softened her leather jacket with a pretty skirt and Jo Whiley DJ'd in her black dress. FabUK wants to know who you think is the best dressed, so let her know!

To see more photos from the party, just read more.

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Pixie Channels Pebbles While Liv, Gwyneth & Stella Reunite

PopSugarUK — Wed, 23 Sep 2009 05:21:00 -0700

Pixie Geldof looked like she was dressed up as Pebbles from The Flintstones as she took to the catwalk for Jeremy Scott on the last day of London Fashion Week yesterday. Meanwhile good friends Liv Tyler, Gwyneth Paltrow and Stella McCartney posed for photos at the Established & Sons private viewing also in London, alongside Stella's sister Mary, Sam Taylor-Wood and gorgeous Brit actor Aaron Johnson from Angus, Thongs and Perfect Snogging. Back at Fashion Week, Estelle was in the front row to watch Pixie strut her stuff, while T4 presenter Jameela Jamil and model Ben Grimes hung out at the Charlotte Olympia Tea Party. Finally, Thandie Newton and Erin O'Connor supported designer Jonathan Saunders at his show. That concludes another Fashion Week - ICYMI, catch up with all our coverage!

To see more photos of the last day of London Fashion Week, including Pixie modelling and Aaron Johnson meeting Gwyneth, just read more.

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Trend Alert: Mod Pink Lipstick at T4 On The Beach

BellaSugarUK — Mon, 20 Jul 2009 07:30:00 -0700

At yesterday's T4 On The Beach concert in Weston-Super-Mare, performers gathered despite grey skies, wearing stylish outfits and funky hairstyles. Next to all of green and blue eye shadow present, perhaps the most popular lipstick shade I saw on Sophie Ellis-Bextor, Tulisa and Alesha Dixon was mod (retro) pink lipstick. It's fun to see this colour make a comeback and what better a venue than at a rockin' concert. Recently, I wore Creme de la Femme by MAC for a night out on the town and loved it. Do you have a new favourite pink lipstick?

Hypothyroidism

FitSugar — Wed, 08 Oct 2008 17:35:30 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Congenital Hypothyroidism and Maternal Hyperthyroidism

Thyroid-lowering medications used for treating Graves’ disease, the most common cause of hyperthyroidism (overactive thyroid), can cause babies to be born with hypothyroidism (underactive thyroid). Research presented at the 2006 annual meeting of the American Thyroid Association suggests that hyperthyroidism can be effectively managed during pregnancy without causing newborn hypothyroidism. The researchers suggest that:

Pregnant women with Graves’ disease should take the lowest possible dose of their thyroid medication
It is safe for women with Graves’ disease to maintain thyroid levels in the upper-normal range while pregnant

Low-Normal Thyroid and Metabolic Syndrome

Thyroid levels in the low-normal range may increase the risk of unhealthy cholesterol levels, high blood sugar, and abdominal obesity -- indicators of metabolic syndrome -- according to a 2006 study in the Journal of Clinical Endocrinology and Metabolism.
Metabolic syndrome is a cluster of conditions, (including abdominal obesity, high blood sugar, and unhealthy cholesterol levels), which increases the risk for heart disease. However, many experts do not believe that treating subclinical hypothyroidism (mildly underactive thyroid) can help prevent heart problems. More research is underway.

Subclinical Hypothyroidism and Mood

A large study of elderly people, published in the Annals of Internal Medicine, suggests that subclinical hypothyroidism does not cause depression, anxiety, or impaired cognition. The study included nearly 6,000 people age 65 years and older.

Introduction

The thyroid is a small, butterfly-shaped gland located in the front of the neck that produces hormones, notably thyroxine (T4) and triiodothyronine (T3), which stimulate vital processes in every part of the body. These thyroid hormones have a major impact on the following functions:

Growth
Use of energy and oxygen
Heat production
Fertility
The use of vitamins, proteins, carbohydrates, fats, electrolytes, and water
Immune regulation in the intestine

These hormones can also alter the actions of other hormones and drugs.

The thyroid gland, a part of the endocrine (hormone) system, plays a major role in regulating the body's metabolism.

Regulating thyroid function is a complex and important process that involves several factors, including iodide and four thyroid hormones. Any abnormality in this intricate system of hormone synthesis and production can have far-reaching consequences on health.

Iodide. An understanding of the multi-step thyroid hormone process begins with iodide, a salt that is extracted from the blood and trapped by the thyroid gland. Iodide is converted to iodine in the thyroid gland. (Eighty percent of the body's iodine supply is stored here.) Iodine is the material used to make the hormone thyroxine (T4).

Thyroid Hormones. Four hormones are critical in the regulation of thyroid function:

Thyroxine (T4) and Triiodothyronine (T3). Thyroxine (T4) is the key thyroid hormone. Low levels of T4 produce hypothyroidism, and high levels produce hyperthyroidism. Thyroxine converts to triiodothyronine (T3), which is a more biologically active hormone. Only about 20% of triiodothyronine is actually formed in the thyroid gland. The rest is manufactured from circulating thyroxine in tissues outside the thyroid, such as those in the liver and kidney. Once T4 and T3 are in circulation, they typically bind to substances called thyroid hormone transport proteins, after which they become inactive.
Thyrotropin. Thyrotropin (also called thyroid-stimulating hormone or TSH) is another very important hormone in the process. Secreted by the pituitary gland, this hormone directly influences the process of iodine trapping and thyroid hormone production. When thyroxine levels drop even slightly, the pituitary gland goes into action to pump up secretion of thyrotropin so that it can stimulate thyroxine production. So, when T4 levels fall, TSH levels increase.
Thyrotropin-releasing hormone (TRH), the final critical thyroid hormone, is produced in a region in the brain called the hypothalamus, which monitors thyrotropin levels.

Click the icon to see an image of the pituitary gland.

Click the icon to see an image of the pituitary gland and TSH.

Hypothyroidism occurs when thyroxine (T4) levels drop so low that body processes begin to slow down. Hypothyroidism was first diagnosed in the late nineteenth century when doctors observed that surgical removal of the thyroid resulted in the swelling of the hands, face, feet, and tissues around the eyes. They named this syndrome myxedema and correctly concluded that it was the outcome of the absence of substances, thyroid hormones, normally produced by the thyroid gland. Hypothyroidism is usually progressive and irreversible. Treatment, however, is nearly always completely successful and allows a patient to live a fully normal life.

Subclinical hypothyroidism (mildly underactive thyroid), also called early-stage hypothyroidism, is a condition in which thyrotropin (TSH) levels have started to increase in response to an early decline in T4 levels in the thyroid. However, blood tests for T4 are still normal. The patient may have mild symptoms (usually slight fatigue) or none at all. Mildly underactive thyroid is very common (affecting about 10 million Americans) and is a topic of considerable debate among professionals because it is not clear how to manage this condition.

For instance, mildly underactive thyroid does not progress to the full-blown disorder in most people. Experts estimate that each year approximately 2 - 5% of people with mildly underactive thyroid will go on to develop overt hypothyroidism. Other factors associated with a higher risk include being an older woman (up to 20% of women over age 60 have subclinical hypothyroidism), having a goiter (enlarged thyroid gland) or thyroid antibodies, or harboring immune factors that suggest an autoimmune condition.

Mildly underactive thyroid is determined on the basis of the TSH laboratory blood tests. According to a 2004 consensus statement from the American Thyroid Association, the American Association of Clinical Endocrinologists, and the Endocrine Society, the normal range of TSH concentration falls between 0.45 and 4.5 mU/L. Patients with mildly underactive thyroid have TSH levels between 4.5 mU/L and 10mU/L. Patients with levels greater than 10mU/L are considered to have overt hypothyroidism and should be treated with medication.

For patients in the mildly underactive thyroid range, treatment decisions are less clear. The consensus committee recommended against routine treatment for patients with mildly underactive thyroid , but did suggest repeat screenings of thyroid function every 6 - 12 months to detect any changes in TSH levels. However, these are general guidelines, and individual cases and risk factors may differ. Patients should discuss with their doctor the course of action that is most appropriate for them.

Causes

Many permanent or temporary conditions can reduce thyroid hormone secretion and cause hypothyroidism. About 95% of hypothyroidism cases occur from problems that originate in the thyroid gland. In such cases, the disorder is called primary hypothyroidism. (Secondary hypothyroidism is caused by disorders of the pituitary gland. Tertiary hypothyroidism is caused by disorders of the hypothalamus.)

The two most common causes of primary hypothyroidism are:

Hashimoto's thyroiditis. This is an autoimmune condition in which the body's immune system attacks its own cells.
Overtreatment of hyperthyroidism (an overactive thyroid).

Hashimoto's thyroiditis, atrophic thyroiditis, and postpartum thyroiditis are all autoimmune diseases of the thyroid. An autoimmune disease occurs when the immune system mistakenly attacks the body's own healthy cells. In the case of autoimmune thyroiditis, a common form of primary hypothyroid disease, the cells under attack are in the thyroid gland.

All forms of thyroid autoimmunity typically start with T and B cells:

Important immune factors called T and B cells infiltrate the thyroid gland in equal numbers. These white blood cells are the primary infection-fighting immune cells. T cells identify invasive molecules, such as viral proteins, and help B cells to produce antibodies that are designed specifically to attack these invaders.
In cases of autoimmunity, T cells are tricked into classifying molecules on the body's own cells as invaders. In such cases, B cells then produce antibodies, called autoantibodies, which attack those cells.
In most cases of thyroid autoimmunity, the autoantibodies launch an attack on a thyroid protein called thyroid peroxidase; this attack appears to destroy thyroid cells.

Experts do not know why the immune system starts the process that injures the thyroid. Some theories follow:

One theory starts with a virus that has a protein resembling a thyroid protein. During an infection, T cells induce B cells to secrete specific antibodies that attack the invasive viral protein. Unfortunately, the T cells are also tricked into inducing a B-cell attack on the similar thyroid protein.
Genetic factors most likely play some role in autoimmune thyroiditis. For example, many patients with Hashimoto's thyroiditis express a gene called the Fas gene, which interacts with thyroid cells and triggers a process called apoptosis, in which the cells begin to self-destruct. The Fas gene is linked to genes that regulate tumor necrosis factors, which are products of the immune system that trigger a damaging inflammatory response in cells.
In some women, thyroid autoimmunity may have developed while they were pregnant. In such cases, some evidence suggests that fetal cells accumulated in the mother's thyroid gland, triggering an immune attack.
In some cases of Hashimoto's thyroiditis, antibodies block a receptor on thyroid cells that bind to thyrotropin (TSH). This effect is more likely to be involved in worsening the disorder, but does not explain initial destruction.
Some evidence suggests that excess iodine intake triggers the process leading to Hashimoto's thyroiditis.

Hashimoto's Thyroiditis. The most common form of hypothyroidism in the U.S. is Hashimoto's thyroiditis, a genetic disease named after the Japanese doctor who first described thyroid inflammation. It occurs in about 0.3 - 5 people per 1,000 per year, and women are 15 - 20 times more likely than men to develop this disease.

Click the icon to see an image of Hashimoto's thyroiditis.

An enlargement of the thyroid gland, called a goiter, is almost always present and may appear as a cyst-like or fibrous growth in the neck. Hashimoto's thyroiditis is permanent and requires lifelong treatment. Both genetic and environmental factors appear to play a role in its development.

One theory proposes that Hashimoto's thyroiditis and Graves' disease (a form of hyperthyroidism) are caused by a similar immunologic dysfunction. Similar immune system substances called antibodies are present in both diseases, and some experts believe that the predominance of one or another antibody determines which of the diseases become manifest. The two diseases, then, are essentially two sides of a single coin.

Click the icon to see an image of Grave's disease.

Atrophic Thyroiditis. Atrophic thyroiditis is similar to Hashimoto's thyroiditis, except a goiter is not present.

Riedel's Thyroiditis. Riedel's thyroiditis is a rare autoimmune disorder, in which scar tissue progresses in the thyroid until it produces a hard stony mass that suggests cancer. Hypothyroidism develops as the scar tissue replaces healthy tissue. Surgery is usually required, although early stages may be treated with tamoxifen, corticosteroids, or other immunosuppressive drugs.

Autoimmune Thyroiditis Due to Pregnancy. Hypothyroidism may also occur in women who develop antibodies to their own thyroid during pregnancy, causing an inflammation of the thyroid after delivery.

Subacute thyroiditis is a temporary condition that passes through three phases: hyperthyroidism, hypothyroidism, and a return to normal thyroid levels. Patients may exhibit symptoms of both hyperthyroidism and hypothyroidism (rapid heartbeat, nervousness, weight loss), and they can feel extremely sick. Symptoms last about 6 - 8 weeks and then resolve in most patients, although each form carries some risk for becoming chronic. Experts estimate that subacute thyroiditis is responsible for 10% of all cases of hypothyroidism.

The three forms of subacute thyroiditis follow a similar course:

Painless Postpartum Subacute Thyroiditis. Postpartum thyroiditis is an autoimmune condition that occurs in up to 10% of pregnant women and tends to develop between 4 - 12 months after delivery. In most cases, a woman develops a small, painless goiter. Although 80% of women with this condition have normal thyroid function within a year, some evidence suggests that half of women with this condition develop permanent hypothyroidism within 7 years. Women who have had recurrent episodes after previous pregnancies and women who have other autoimmune disorders are at higher risk for this form of subacute thyroiditis. It is generally self-limiting and requires no therapy unless the hypothyroid phase is prolonged. In such cases, therapy may be thyroxine replacement for a few months. A doctor will prescribe beta blockers if the hyperthyroid phase requires treatment.

Painless Sporadic, or Silent, Thyroiditis. This painless condition is very similar to postpartum thyroiditis except it can occur in both men and women and at any age. About 20% of patients with silent thyroiditis may develop chronic hypothyroidism. Treatment considerations are the same as for postpartum subacute thyroiditis.

Painful, or Granulomatous, Thyroiditis. This condition comes on suddenly with flu-like symptoms and severe neck pain and swelling. It generally occurs in the summer and is five times more common in women. It recurs in about 2% of patients. Hypothyroidism persists in about 5%. Treatments typically include pain relievers and, in severe cases, corticosteroids.

Up to half or more of patients who receive radioactive iodide treatments for an overactive thyroid develop permanent hypothyroidism within a year of therapy. This is the standard treatment for Graves' disease, which is the most common form of hyperthyroidism, a condition caused by excessive secretion of thyroid hormones.

By the end of 5 years, about 65% of treated patients have developed hypothyroidism, after which the rate of this condition levels off to about 1% a year. Such patients need to take thyroid hormones for the rest of their lives. Other forms of treatment for overactive thyroid glands using either antithyroid drugs or surgery may also result in hypothyroidism.

Too much or too little iodide can cause hypothyroidism. If there is a deficiency of iodide, the body cannot manufacture thyroxine. About 200 million people around the world have hypothyroidism because of insufficient iodine in their diets. Too much iodide is a signal to inhibit the conversion process of thyroxine to T3. The end result in both cases is inadequate production of thyroid hormones. Some evidence suggests that excess iodine triggers the process leading to Hashimoto's thyroiditis.

Complete removal (total thyroidectomy) of the thyroid to treat thyroid cancer requires a lifetime of treatment with an appropriate dosage of thyroid hormone. Removing one of the two lobes of the thyroid gland (hemithyroidectomy), usually because of benign growths on the thyroid gland, rarely produces hypothyroidism. The remaining thyroid lobe will generally enlarge so that it can produce sufficient amounts of thyroid hormone for normal function. Many doctors recommend thyroid hormone treatment, however, to prevent the formation of additional nodules.

Click the icon to see an illustrated series detailing thyroid removal.

A small percentage of Graves disease patients who require surgery to remove most of both thyroid lobes (subtotal thyroidectomy) may develop hypothyroidism. It is important to find an experienced surgeon for this procedure and to have the thyroid checked at 6- or 12-month intervals.

Researchers have identified several additional syndromes that also cause hypothyroidism. These generally involve abnormalities in thyroid hormone itself or genetic deficiencies in certain proteins that impair thyroid hormone conversion processes or responses.

Lithium. Lithium, a drug widely used to treat psychiatric disorders, has multiple effects on thyroid hormone synthesis and secretion. Up to 50% of patients who take lithium develop a goiter, with 20% developing symptomatic hypothyroidism, and another 20 - 30% developing hypothyroidism without symptoms.

Amiodarone. The drug amiodarone (Cordarone), which is used to treat abnormal heart rhythms, contains high levels of iodine and can induce hyper- or hypothyroidism, particularly in patients with existing thyroid problems. Hypothyroidism occurs in 20% of patients and is the more common effect in the U.S. and other countries where dietary iodine is abundant. Hyperthyroidism is a less common effect in these regions.

Other Drugs. Drugs used for treating epilepsy, such as phenytoin and carbamazepine, can reduce thyroid levels. Certain antidepressants may cause hypothyroidism, although this is rare. Interferons and interleukins are used for treating hepatitis, multiple sclerosis, and other conditions. Evidence suggests that these drugs increase antibodies that put patients at risk for hypo- or hyperthyroidism. Some drugs used in cancer chemotherapy, such as sunitinib (Sunent) or imatinib (Gleevec), can also cause or worsen hypothyroidism.

High-dose radiation for cancers of the head or neck and for Hodgkin's disease causes hypothyroidism in up to 65% of patients within 10 years after treatment.

In rare instances, usually due to a tumor, the pituitary gland will fail to produce thyrotropin (TSH), the hormone that stimulates the thyroid to produce its hormones. In such cases, the thyroid gland withers. When this happens, secondary hypothyroidism occurs.

Hypothyroidism in newborns (known as congenital hypothyroidism) occurs in one in every 3,000 - 4,000 births, making it the most common hormonal disorder in infants. In 90% of these cases, it persists throughout life.

Permanent Congenital Hypothyroidism. In up to 85% of permanent congenital hypothyroidism cases, the thyroid gland is missing, underdeveloped, or not properly located. In most cases the cause or causes of these conditions are unknown. In about 10 - 15% of cases, processes involved in hormone production are impaired, most likely because of genetic abnormalities. In less than 5% of cases, the pituitary or hypothalamus function abnormally.

Temporary Hypothyroidism in Infants. Temporary hypothyroidism can also occur in infants. In about 20% of cases, the cause remains unknown. The known causes stem from various immunologic, environmental, and genetic factors, including those in the mother:

Hypothyroidism. Women who have an underactive (“low”) thyroid, including those who develop the problem during pregnancy, are at increased risk for delivering babies with congenital (newborn) hypothyroidism. Maternal hypothyroidism can also cause premature delivery and low-birth weight.
Hyperthyroidism. Graves disease is the most common cause of maternal hyperthyroidism (overactive or “high” thyroid). Some of the drugs used to treat hyperthyroidism can cause hypothyroidism in the infant. Some research indicates that using the lowest possible dose of thyroid-lowering medication can minimize the risk of congenital hypothyroidism. (The research also suggests that it is safe for women with Graves’ disease to remain in a mildly hyperthyroid state during pregnancy.
Iodine deficiency. This may cause temporary hypothyroidism. (Exposure to too much iodine immediately after birth, for example, from iodine-containing disinfectants or medicines, can also cause thyroid dysfunction.)
Being premature.
Kidney disease. Temporary hypothyroidism in infants can occur in premature babies and, rarely, in those with kidney disease.
The central nervous system connections between the hypothalamus and pituitary gland may also mature late; this condition generally resolves 4 - 16 weeks after birth.

Children with temporary congenital hypothyroidism should be followed-up regularly during adolescence and adulthood for possible thyroid problems. The risk for further thyroid problems is highest in these adult women during pregnancy. Newborn siblings of these children should also be screened for possible thyroid defects.

Symptoms

Early Symptoms. Early symptoms of hypothyroidism are subtle and, in older people, can be easily mistaken for symptoms of stress or aging. They include:

Chronic fatigue
Sensitivity to cold
Headache
Muscle and joint aches
Weight gain, despite diminished appetite
Constipation
Dry skin

In premenopausal women, early symptoms can interfere with fertility. They may experience heavy periods or, in rare cases, a milky discharge from the breasts. A history of miscarriage may be a sign of impending hypothyroidism. Studies suggest that even if thyroid levels are normal, women who have a history of miscarriages often have antithyroid antibodies during early pregnancy and are at risk for developing autoimmune thyroiditis over time.

Later Symptoms. As free thyroxine levels fall over the following months, other symptoms may develop:

Impaired mental activity, including concentration and memory, particularly in the elderly.
Depression. Some experts believe that even mild thyroid failure may increase susceptibility to major depression.
Muscle weakness, numbness, pain, and cramps. This can cause an unsteady gait. Muscle cramps are common, and carpal tunnel syndrome or symptoms similar to arthritis sometimes develop. In some cases, the arms and legs may feel numb.
Numbness in the fingers.
Hearing loss.
Husky voice.
Continuing weight gain and possible obesity, in spite of low appetite.
Some people experience less sweating, and their skin becomes pale.
Skin and hair changes. Skin becomes pale, rough, and dry. Patients may sweat less. Hair coarsens and even falls out. Nails become brittle.
Snoring and obstructive sleep apnea (a condition in which in the soft palate in the throat collapses at intervals during sleep, thereby blocking the passage of air).

Secondary hypothyroidism, caused by tumors or other growths on the pituitary, produces the usual symptoms of primary hypothyroidism. In addition, sexual drive and fertility may be impaired in both men and women. Patients may also feel exhausted, crave salt, and have low blood pressure. Headaches and visual disturbances may develop, which are directly related to the pituitary tumor.

Hypothyroidism occurs when the thyroid gland is underactive. The condition may affect all body functions. The rate of metabolism slows, causing mental and physical sluggishness. Myxedema, a medical emergency, is the most severe form of hypothyroidism. A problem with the thyroid itself (primary) or malfunction of the pituitary gland (secondary) or hypothalamus (tertiary) can cause hypothyroidism.

All babies are now screened for hypothyroidism in order to prevent retardation that can occur if treatment is delayed. Symptoms of hypothyroidism in children vary depending on when the problem first develops.

Most children who are born with a defect that causes congenital hypothyroidism have no obvious symptoms. Symptoms that do appear in newborns may include jaundice (yellowish skin), noisy breathing, and an enlarged tongue.
Early symptoms of undetected and untreated hypothyroidism in infants include feeding problems, failure to thrive, constipation, hoarseness, and sleepiness.
Later on, symptoms in untreated children include protruding abdomens; rough, dry skin; and delayed teething. Rarely, in advanced cases, yellow raised bumps (called xanthomas) may appear under the skin, the result of cholesterol build-up.
If they do not receive proper treatment in time, children with hypothyroidism may be extremely short for their age, have a puffy, bloated appearance, and have below-normal intelligence. Any child whose growth is abnormally slow should be examined for hypothyroidism.

Diagnosis

Advances in diagnostic methods now make it possible to detect hypothyroidism in almost all cases before severe symptoms develop. Doctors can diagnosis hypothyroidism after completing a history and physical exam of the patient and performing sensitive laboratory tests on the patient's blood.

The doctor will check the heart, eyes, hair, skin, and reflexes for signs of hypothyroidism.

Goiter. The presence of a goiter (an enlarged thyroid), especially a rubbery, painless one, may be an indication of Hashimoto's disease. If the thyroid is tender and enlarged but not necessarily symmetrical, the doctor may suspect subacute thyroiditis. A diffusely enlarged gland may occur in hereditary hypothyroidism, in postpartum patients, or from use of iodides or lithium. Goiters may also develop in people with iodide deficiency.

Thyroid Neck Check. Women who are experiencing menopausal symptoms that may be masking those of hypothyroidism should perform a simple self-examination called the Thyroid Neck Check:

Hold a mirror in front of the area of the neck where the thyroid gland is located. This area is just below the Adam's apple and right above the collarbone. (Note: The Adam's apple is not the thyroid location.)
Tip the head back.
Take a drink of water and swallow, watching the neck during the process.
Check for any bulging or protrusions. If any is detected, call a doctor for a check up.

In diagnosing hypothyroidism, blood tests measuring hormone levels are needed to make a correct diagnosis. In some cases, antibody tests are also helpful.

Thyroxine (T4). Hypothyroidism is a condition marked by low thyroxine (T4) hormone levels, and a test can measure levels of this hormone in the blood. However, this test is usually inadequate for the following reasons:

T4 levels can be normal early in the disease process leading to hypothyroidism. If hypothyroidism is suspected, other tests are needed.
T4 levels can be low in patients who do not have hypothyroidism. For instance, thyroxine can be extremely variable in very elderly or seriously ill patients and during pregnancy.

Measuring thyroxine is usually performed using a process called a T3 resin uptake to correct for the presence of medications (such as birth control pills, aspirin, and others) that could distort the results. Other tests are needed to confirm a diagnosis of hypothyroidism.

Thyrotropin (Thyroid-Stimulating Hormone or TSH). Measuring TSH is the most sensitive indicator of hypothyroidism. (As with thyroxine levels, however, TSH levels can vary in pregnant women and patients who are ill with other conditions.) In general, results indicate the following:

TSH levels over 10mU/L. This is a clear indicator of hypothyroidism if T4 levels are low -- and, in most cases, even if they are normal. Patients usually require thyroxine (T4) replacement therapy. They should also be tested for high cholesterol levels and antithyroid antibodies.
Levels between 4.5 mU/L - 10 mU/L. Patients with signs and symptoms of hypothyroidism usually need thyroxine replacement therapy. Patients without symptoms have subclinical hypothyroidism and should be rechecked every 6 - 12 months. Antibody tests may also be performed.
TSH levels between 0.45 mU/L - 4.5 mU/L. These indicate normal thyroid function. (Abnormally low levels suggest hyperthyroidism, which is overactive thyroid.)
Specific TSH measurement -- even if it is significantly higher than 10 mU/L -- is not associated with the severity of the condition. This can be determined only by measuring thyroxine levels and evaluating the patient's symptoms.

Antithyroid Antibodies. If TSH levels suggest hypothyroidism or subclinical hypothyroidism, the doctor may choose to perform a blood test for specific antithyroid antibodies that act against a factor called thyroperoxidase (TPO). Tests can also check for antibodies to thyroglobulin. Results depend on the patient's condition:

Patients with confirmed hypothyroidism (TSH levels over 10 mU/L). Positive test results in such patients confirm the need for thyroxine replacement therapy. (Even if antibody results are negative, these patients usually require thyroxine replacement therapy.) About 90% of patients with Hashimoto's thyroiditis test positive for antibodies to thyroperoxidase, and up to half have thyroglobulin antibodies.
Patients with subclinical hypothyroidism (TSH between 4.5 mU/L - 10 mU/L). If antibody levels are high, thyroxine therapy is usually warranted, since it indicates an underlying autoimmunity condition that poses a high risk for later thyroid failure. If the tests are negative, but patients have thyroid-related problems (such as high cholesterol, female infertility), they should be monitored annually with hormone tests.

About 10% of the American population and 25% of women over 60 years old carry these antibodies, and the majority of these women have no thyroid problems. Only about 0.5% have full-blown hypothyroidism, and 10% have subclinical hypothyroidism. In one 10-year study, however, people with normal thyroid results and high levels of antibodies still had an annual risk of 2 - 4% for developing hypothyroidism.

Other Hormone Tests Used for Thyroid Function. Other hormone tests are done if hyperthyroidism is suspected. They include tests for triiodothyronine (T3) and thyroglobulin (also called thyroid binding globulin). Such measurements, however, may also be helpful in detecting sudden temporary increases in thyroid hormone (thyrotoxicosis) that can precede certain forms of autoimmune thyroiditis.

Thyroid Scintigraphy. Thyroid scintigraphy tests scan the thyroid and pick up images highlighted by small amounts of radioactive substances. Thyroid scans can be used to determine whether the thyroid is producing normal amounts of hormone. The patient drinks a small amount of radioactive iodine or technetium and waits until the substance has passed through the thyroid. Images of a properly functioning thyroid would show uniform levels of absorption throughout the gland. Overactive areas show up white, and underactive areas appear dark. Thyroid scans are usually unnecessary unless the doctor needs to rule out suspected cancer.

Ultrasound. Ultrasound has limited value, but it can visualize the thyroid and specific abnormalities, such as nodules. (It cannot measure the thyroid gland's function, however.)

Click the icon to see an image of thyroid ultrasound.

More Advanced Imaging Tests. If laboratory tests suggest that a pituitary or hypothalamus problem is causing hypothyroidism, the doctor will usually order brain imaging procedures using computed tomography (CT) scans or magnetic resonance imaging (MRI). MRIs may also be used for determining the extent of thyroid cancers and of goiters. MRIs are also being used for investigating hypothyroidism in infants and for determining widespread effects of autoimmune thyroiditis (such as Hashimoto's hypothyroidism).

Needle aspiration biopsy is used to obtain thyroid cells for microscopic evaluation. It may be useful to rule out thyroid cancer in patients with suspected Hashimoto's hypothyroidism, especially if they have difficulty swallowing or develop a goiter. Much like drawing blood, the doctor injects a small needle into the thyroid gland and draws cells from the gland into a syringe. The cells are put onto a slide, stained, and examined under a microscope.

Cholesterol levels need to be checked. Other blood tests may be performed to detect levels of calcitonin, calcium, prolactin, and thyroglobulin and to check for anemia and liver function, all of which may be affected by hypothyroidism.

Screening in Older Adults. Some doctors believe that because thyroid problems are so common in the elderly and thyroid hormone tests are so inexpensive, blood tests for thyroid function should be routine. Undiagnosed hypothyroidism in elderly patients can develop into a serious and even life-threatening situation. Hyperthyroidism also poses many health risks. In fact, during the period around menopause, the symptoms of menopause and hypothyroidism are similar and can easily be confused with each other.

Professional organizations differ widely on screening recommendations. Most do not recommend widespread screening for healthy adults:

The American College of Physicians recommends that women over 50 years old be screened for thyroid disorders every 5 years. The American Academy of Family Physicians believes that adults do not have to be screened until they are over 60.
The American Thyroid Association, however, recommends that all adults, both men and women, begin their screening at age 35 and every 5 years thereafter. Experts in this organization argue that such early screening is inexpensive and would prevent progression to hypothyroidism, and therefore possibly heart disease, in people with subclinical hypothyroidism. Such an approach would also eliminate the need for expensive anti-cholesterol drugs.

Screening in Pregnant Women. Untreated hypothyroidism in a pregnant woman, particularly in the first trimester, may cause premature delivery and birth defects. Birth defects can affect a baby’s intelligence, mental development, and motor skills. Subclinical hypothyroidism also increases the risk for premature delivery and birth defects.

Some experts propose that screening be done on any woman who is planning a pregnancy to help determine those who may be at increased risk for hypothyroidism and, if needed, begin treatment as early as possible during the critical first trimester. Women who have a personal or family history of hypothyroidism should have their thyroid checked within the first weeks of pregnancy and should be retested during each trimester.

Screening in Infants. It is very difficult to diagnose hypothyroidism in newborns by symptoms alone. Fortunately, almost all newborns with hypothyroidism are identified shortly after birth through an effective national screening program using a thyroid blood test.

Because the symptoms of hypothyroidism are so similar to common conditions, including aging, diagnosis can be difficult.

Conditions That Cause Thyroid Abnormalities. Some conditions may cause thyroid abnormalities without symptoms and must be differentiated from subclinical hypothyroidism. They include, although are not limited to:

Inadequate response to thyroid therapies in people with hypothyroidism
Recovery from a severe illness that is unrelated to thyroid disorders
Chronic kidney failure
Failure of the adrenal gland

Aging-Related Disorders. Some symptoms of hypothyroidism and aging are very similar. Menopausal symptoms often resemble hypothyroidism. Many other problems related to aging -- such as vitamin deficiencies, Parkinson's and Alzheimer's diseases, and arthritis -- also have characteristics that can mimic hypothyroidism.

Obesity. Many people who are overweight believe that they have an underactive thyroid gland, but only a very small percentage of obese people actually have hypothyroidism. Patients with hypothyroidism generally show only a moderate weight increase of 5 - 10 pounds, mainly from accumulation of fluid, and in fact they often have a decreased appetite.

Depression. A lack of interest in personal relationships, drowsiness, an increase in sleep, slowing of speech, and general apathy are signs of clinical depression as well as hypothyroidism. The two disorders often coexist, particularly in older women, so diagnosing one does not rule out the presence of the other.

Diseases of Muscles and Joints. Joint and muscle aches may be the first symptoms of hypothyroidism. Most likely, however, such pain is not caused by hypothyroidism if other thyroid symptoms remain absent. Numerous conditions can cause muscle and joint pain, and if thyroid levels are normal the doctor should look for other causes.

Risk Factors

About 15 million Americans have unrecognized thyroid disease, mostly subclinical hypothyroidism (mildly underactive thyroid). Less than 2% of the U.S. population has full-blown hypothyroidism.

Women. Women have 10 times the risk of hypothyroidism as men, with the difference being significant after age 34. In one study, nearly 6% of women over 60 had hypothyroidism, and some experts estimate that as many as 20% of women in this age group have a subclinical condition. Because the symptoms of hypothyroidism and menopause are so similar, hypothyroidism may easily be missed.

Pregnancy is a major factor in the higher risk in women. It affects the thyroid in a number of ways and poses a high risk for hypothyroidism, both during pregnancy and afterward. For one, iodine requirements are high in both the mother and the fetus. Changes in reproductive hormones also cause changes in thyroid hormone levels. In addition, some women develop antibodies to their own thyroid during pregnancy, causing a condition known as postpartum autoimmune, or subacute, thyroiditis. This occurs in up to 10% of pregnant women and tends to develop between 4 - 12 months after delivery. It is a limited condition and nearly always clears up. However, it does pose a risk for the development of permanent hypothyroidism later on.

Age. The elderly are most susceptible, but hypothyroidism can affect people of all ages. For example, 1 in every 3,000 - 4,000 infants is born with congenital hypothyroidism. Female infants are at higher risk than males.

Ethnicity. African-Americans may be less likely to have thyroid disease than Caucasians and Asians.

Genetics plays a role in many cases of underactive and overactive thyroid. The genetics involved with hypothyroidism are complicated, however. Certain genetic features, for example, appear to play a role in Hashimoto's thyroiditis and postpartum thyroiditis in Caucasians, but others affect different ethnic groups. Thyroid disease will often skip generations. For example, someone with an underactive thyroid may have healthy parents but have grandparents who had thyroid troubles. Some people inherit a tendency to thyroid problems but never become ill, while others become very sick.

Smoking significantly increases risk for thyroid disease, particularly autoimmune Hashimoto's thyroiditis and postpartum thyroiditis. Chemicals in cigarette smoke called thiocyanates appear to have especially harmful effects on the thyroid. Smoking also increases the negative effects of hypothyroidism, notably on the arteries and heart.

People with certain medical conditions have a higher risk for hypothyroidism. These conditions include:

Autoimmune diseases. People with many autoimmune diseases have a higher risk for hypothyroidism. Type 1 (insulin-dependent) diabetes poses a higher risk and is a special problem since hypothyroidism can affect insulin requirements. Women with other autoimmune diseases, including systemic lupus erythematosus, pernicious anemia, and rheumatoid arthritis, are also at higher risk for hypothyroidism. Pregnant women with autoimmune conditions have a 25% risk for hypothyroidism during gestation.
Breast cancer. There may be a link between breast cancer and thyroid levels, but the evidence is unclear. Some studies have indicated that women with breast cancer may be more susceptible to hypothyroidism. Other studies suggest the opposite. Several studies indicate that hypothyroidism itself may protect against breast cancer. In addition, when women with hypothyroidism develop breast cancer, it is often a less aggressive and more easily treated form.
Gout. Hypothyroidism and gout often coexist and may have biologic mechanisms in common.
Addison's disease.
Myasthenia gravis.
Polycystic ovarian syndrome.
Anorexia or bulimia. People with eating disorders are at risk for hypothyroidism. In these cases, however, reduced thyroid function may be an adaptation to malnutrition and, therefore, some experts think that only the eating disorder should be treated, not hypothyroidism.
Turner syndrome. As many as half of patients with Turner syndrome have hypothyroidism, usually in the form of Hashimoto's thyroiditis. This inherited condition is one of the most common genetic diseases in women.
Glaucoma. A 2004 study of male veterans suggested that hypothyroidism may be associated with increased risk for developing open-angle glaucoma.

Click the icon to see an animation about gout.

Click the icon to see an image of polycystic ovarian syndrome.

Many drugs affect the thyroid, so anyone being treated for a chronic disease, patients who are taking thyroid medication, and those who are at risk for a thyroid disorder should discuss the impact these drugs may have on their thyroid.

Hypothyroidism is associated with premature gray hair and left-handedness.

Complications

Hypothyroidism carries serious physical and mental risks for all ages. Studies indicate that subtle adverse health effects occur even with subclinical hypothyroidism, a condition in which the patient has no symptoms but blood tests indicate hypothyroidism. Fortunately, hypothyroidism is now easily diagnosed, and treatment will restore normal thyroid function and relieve symptoms and physical signs of the disease. With treatment, a patient should expect to live a normal life, free of harmful consequences. Iodine deficiency and goiter are still major problems in less developed nations and cause varying degrees of mental retardation in millions of people.

Myxedema Coma. Myxedema coma is a rare, life-threatening complication of untreated hypothyroidism. Symptoms include a severe drop in body temperature (hypothermia), delirium, reduced lung function, slow heart rate, constipation, urine retention, seizures, stupor, fluid build-up, and finally coma. It is uncommon, but may develop in untreated patients subjected to severe stress, such as infection, surgery, or extreme cold. Certain drugs (such as sedatives, painkillers, narcotics, amiodarone, and lithium) may increase the risk. Emergency treatment is required. Mortality rates are high (between 30 - 60%) with the highest risks in older patients and those with persistent hypothermia or heart problems.

Suppurative Thyroiditis. Suppurative thyroiditis is a life-threatening infection of the thyroid gland. It is very rare, since the thyroid is normally immune to infection. People with pre-existing thyroid diseases, such as Hashimoto's thyroiditis, however, may be at higher than average risk for it. It often begins with an upper respiratory infection. Symptoms include fever, neck pain and rash, and trouble swallowing and speaking. Immediate treatment is critical.

Thyroid hormones, notably triiodothyronine (T3), affect the heart directly and indirectly. They are closely linked with heart rate and heart output. T3 provides particular benefits by relaxing the smooth muscles of blood vessels. This helps keep the blood vessels open so that blood flows smoothly through them.

Hypothyroidism is associated with:

Unhealthy cholesterol levels. Hypothyroidism raises levels of total cholesterol, LDL (the so-called bad cholesterol), triglycerides, and other lipids (fat molecules) associated with heart disease. Treating the thyroid condition with thyroid replacement therapy can significantly reduce these levels.
Mild high blood pressure. Hypothyroidism may slow the heart rate to less than 60 beats per minute, reduce the heart's pumping capacity, and increase the stiffness of blood vessel walls. All of these effects may lead to high blood pressure. Indeed, patients with hypothyroidism have triple the risk of developing hypertension. All patients with chronic hypothyroidism, especially pregnant women, should have their blood pressures checked regularly.
Heart failure. Hypothyroidism can affect the heart muscle’s contraction and increase the risk of heart failure in people with existing heart disease.

The evidence for subclinical hypothyroidism and heart disease is mixed. Some studies suggest that subclinical hypothyroidism increases the risks for coronary artery disease and heart failure. A 2007 study indicated that low-normal thyroid function may increase the risk for metabolic syndrome (a cluster of symptoms that include abdominal obesity, high blood sugar, and unhealthy cholesterol levels). However, a 2006 study in the Journal of the American Medical Association found that while subclinical hypothyroidism was associated with atrial fibrillation (irregular heart beat), it was not associated with other types of heart disease. Many experts believe that treatment of subclinical hypothyroidism will not help prevent or improve heart problems. More research is underway.

Depression. Depression is common in hypothyroidism and can be severe. Some psychiatrists suspect that even subclinical hypothyroidism may contribute to depression. The two disorders may have some common physiological basis. Adding thyroid hormones to antidepressants may hasten a depressed patient's recovery, even in some patients who have not been diagnosed with hypothyroidism. Hypothyroidism should be considered as a possible cause of any chronic depression, particularly in older women.

Mental and Behavioral Impairment. Untreated hypothyroidism can, over time, cause mental and behavioral impairment and eventually, even dementia. Whether treatment can completely reverse problems in memory and concentration is uncertain, although many experts believe that only mental impairment in hypothyroidism that occurs at birth is permanent.

A 2006 study of nearly 6,000 people age 65 years and older concluded that subclinical hypothyroidism is not associated with depression, anxiety, or mental impairment in elderly patients.

The following medical conditions have been associated with hypothyroidism. Often the causal relationship is not clear in such cases:

Iron deficiency anemia.
Respiratory problems.
Kidney function.
Glaucoma. (Some research has associated hypothyroidism with an increased risk for glaucoma.)
Headache. (Hypothyroidism may worsen headaches in people predisposed to them.)
Thyroid lymphoma. (Patients with Hashimoto's thyroiditis are at higher risk for this rare form of cancer.)
Joint stiffness. (Women with hypothyroidism may actually have fewer problems with joint stiffness than women with normal thyroid.)

Most women with hypothyroidism fail to produce eggs, and many younger women with hypothyroidism are diagnosed with the condition for the first time during a fertility evaluation. A pregnant woman with hypothyroidism has a fourfold risk for miscarriage. In one study, nearly 40% of women with a history of miscarriages and normal thyroid levels had antithyroid antibodies (immune factors that attack thyroid tissue). Those who continue to have hypothyroidism near the time of delivery are in danger of developing high blood pressure and premature delivery. They are also prone to postpartum thyroiditis, which is said to be a contributor to postpartum depression.

Children of Untreated Mothers. Children born to untreated pregnant women with hypothyroidism are at risk for impaired mental performance, including attention problems and verbal impairment. Studies on the effects on children of women with subclinical hypothyroidism are less clear, with some reporting lower IQs in such children and others reporting no significant problems.

Effects of Hypothyroidism During Infancy. Transient hypothyroidism is common among premature infants. Although temporary, severe cases can cause difficulties in neurologic and mental development.

Infants born with permanent congenital (inborn) hypothyroidism need to receive treatment as soon as possible after birth to prevent mental retardation, stunted growth, and other aspects of abnormal development (a syndrome referred to as cretinism). It has been estimated that untreated infants can lose up to three to five IQ points per month during the first year. An early start of lifelong treatment avoids or minimizes this damage. Even with early treatment, however, mild problems in memory, attention, and mental processing may persist into adolescence and adulthood.

Effects of Childhood-Onset Hypothyroidism. If hypothyroidism develops in children older than 2 years, mental retardation is not a danger, but physical growth may be slowed and new teeth delayed. If treatment is delayed, adult growth could be affected. Even with treatment, some children with severe hypothyroidism may have attention problems and hyperactivity.

Two million Americans, mostly children, received x-ray treatments to the head or neck between 1920 - 1960 for acne, enlarged thymus gland, recurrent tonsillitis, or chronic ear infections. The risk of developing thyroid nodules and thyroid cancers is increased in these individuals, especially if they have hypothyroidism. Cancer can develop as late as 40 years after the original treatment. Everyone who has had head and neck radiation should be sure to have their thyroid glands examined regularly.

Treatment

Various tests are used when deciding whether to treat a patient for hypothyroidism:

First, an elevated TSH (thyrotropin) level should be confirmed and thyroxine (T4) level determined.
Testing for antithyroid antibodies and determining cholesterol levels is also important.

Treating Hypothyroidism. Patients with full-blown hypothyroidism, indicated by clear symptoms and blood tests that show high TSH (generally 10 mU/L and above) and low thyroxine (T4) levels, must be treated with thyroid replacement.

Treating Subclinical Hypothyroidism. Considerable debate exists about whether to treat patients with subclinical hypothyroidism (slightly higher than normal TSH levels, normal thyroxine levels, and no obvious symptoms). Some doctors opt for treatment because of the following benefits, although evidence remains uncertain:

Preventing progression to full-blown hypothyroidism. Treating subclinical hypothyroidism will prevent progression to overt hypothyroidism. Only a minority of people with subclinical hypothyroidism go on to develop the active condition, however.
Preventing heart disease. Some studies have shown that treating subclinical hypothyroidism lowers cholesterol levels and may improve other heart functions, including blood pressure, endothelial function, and heart rate. However, current research from 2006 suggests that subclinical hypothyroidism poses little risk for heart disease and that untreated subclinical hypothyroidism will not increase heart disease risks.
Improving well-being. Some studies report that treating subclinical hypothyroidism may improve mild psychological symptoms, such as impaired mental functioning and depression. About 25% of patients with subclinical hypothyroidism report feeling better after taking thyroid medication even if they have not previously reported symptoms.

It is not clear, then, if the benefits of treating subclinical hypothyroidism outweigh the higher costs of testing and treatments. Experts against treatment argue that thyroid levels can vary widely, and subclinical hypothyroidism may not persist. In such cases, overtreatment leading to hyperthyroidism is a real risk.

In spite of such uncertainties, three out of four major medical organizations recommend treatment for subclinical hypothyroidism, particularly in patients who have:

High total or LDL cholesterol levels
Blood tests that show autoantibodies indicating a future risk for Hashimoto's thyroiditis or other forms of other autoimmune hypothyroidism·
Blood tests that show TSH levels greater than 10 mU/L
Goiter

Experts also recommend treating subclinical hypothyroidism in:

Pregnant women
Women with infertility that may be associated with subclinical hypothyroidism

Treatment is optional in patients with subclinical hypothyroidism who have no obvious symptoms and normal cholesterol levels. If they forego treatment, however, they should be tested yearly for TSH and thyroxine.

Treating Patients with Hypothyroidism Symptom and Normal Thyroid Tests. Some doctors treat patients who have a normal or below normal thyroid function test. Some experts believe it is irresponsible to treat such patients with thyroid replacement since such symptoms can occur with many physical and psychological conditions. In any case, studies have not found any benefits from T4 replacement therapies in this group.

In the 19th century, doctors observed the relationship between myxedema (swelling of the hands, face, feet, and tissues around the eyes) and surgical removal of the thyroid gland. Some doctors began to feed patients with myxedema with whole or powdered extracts of animal thyroid glands. Using thyroid hormone to treat hypothyroidism was one of the first successful medical treatments based on careful scientific observation. With only some modifications, this approach has varied little for over a century.

A synthetic thyroid hormone called levothyroxine is currently the treatment of choice for hypothyroidism. This drug is a synthetic derivative of T4 (thyroxine), and it normalizes blood levels of TSH, T4, and T3. Nevertheless, the therapeutic principle for hypothyroidism is the same as it was more than 100 years ago: To provide the body with replacement thyroid hormone when the gland is not able to produce enough itself.

Brand Names. A number of levothyroxine brands are available in the U.S. and overseas. Synthroid is the oldest brand and has been used for over 40 years. In the past, manufacturers of levothyroxine have not had to meet as strict standards as in the production of other drugs. This resulted in thyroid products with varying quality. The FDA has issued stronger requirements that have largely corrected this problem.

Generics versus Brand-Name Products. Generic brands are available and are subject to the same guidelines as brand-name products. There is still considerable debate over whether generic thyroid preparations are as effective as brand products.

In addition, the amount of T4 in some generic products is outside the FDA range, which requires additional testing of thyroid hormone levels. Many doctors, then, prefer to use brand-name products, noting that the cost difference between brand and generic thyroid drugs is not substantial. Regardless of which type is used, once a patient has been stabilized, doctors generally recommend sticking with one type or brand since potency often varies from one drug to the next.

Natural Thyroid Hormone. Dried powdered thyroid hormone (Armour Thyroid, S-P-T, Thyrar, Thyroid Strong) is made from animal glands. It was once the most common form of thyroid therapy but is no longer generally recommended because potency varies. Some people argue that with stricter FDA regulations, this natural form is better controlled and may even reduce the risk of developing autoimmunity factors. Dried thyroid also contains both T3 and T4 and is favored as a natural treatment by many alternative practitioners. However, studies need to be conducted to evaluate its benefits.

T3 and T4 Combinations. Triiodothyronine (T3), the other important thyroid hormone, is not ordinarily prescribed except under special circumstances. Most patients respond well to thyroxine (T4) alone, which is converted in the body into T3. In addition, the use of T3 may cause disturbances in heart rhythms. Some patients treated only with thyroxine continue to have mood and memory problems or other symptoms.

Combination products containing T4 and T3, such as liotrix (Thyrolar), are available, but there is some controversy concerning their benefits. Several 2005 studies suggested that although some patients may prefer combination therapy, T3 and T4 together do not work better than T4 alone. Patients might like the combined drugs because they cause more weight loss, or a placebo effect may be involved. It does not appear that combination products offer any advantage for normalizing TSH levels.

Levothyroxine only needs to be taken once a day. It is slowly assimilated by body organs, so it usually takes up to 6 weeks before symptoms improve in adults. Nevertheless, many patients feel better after 2 - 3 weeks of treatment. The speed at which specific symptoms improve varies:

Weight loss, less puffiness, and improved pulse usually occur early in the treatment.
Improvements in anemia and skin, hair, and voice tone may take a few months.
High LDL ("bad cholesterol") levels decline very gradually. HDL ("good cholesterol") levels are not affected by treatment.
Goiter size declines very slowly, and some patients may require high-dose thyroid hormone (called suppressive thyroid therapy) for a short period.

Levothyroxine reduces blood pressure in about half of hypothyroid patients with hypertension, although blood pressure medications may still be needed.

Appropriate Dosage Levels. Initial dosage levels are determined on an individual basis and can very wide depending on a person's age, medication condition, other drugs they are taking, and, in women, whether they are pregnant or not. For example, pregnant women with hypothyroidism may require higher than normal doses.

Starting out. Most individuals need to build up gradually until they reach a maintenance dose. In uncomplicated cases, the dose typically starts at 50 micrograms per day, which then increases in 3- to 4-week intervals until thyroid hormone levels are normal. Seniors and those with heart disease may start at 12.5 - 25 micrograms per day. On the other hand, young adults with a short history of hypothyroidism might be able to tolerate a full maintenance dosage right away.
Maintenance dose. Maintenance dose for most patients averages 112 micrograms but it can vary between 75 - 260 micrograms. If conditions such as pregnancy, surgery, or other drugs alter hormone levels, the patient's thyroid needs will have to be reassessed.

Daily Regimen. Because thyroid replacement is usually lifelong, setting up a regular daily routine is helpful. Here are some tips to remember:

Establish a habit of taking the medication at the same time each day. This may help prevent missed doses.
Levothyroxine is very forgiving. The hormone remains in the body for several days, so one missed dose should not cause a noticeable decline in well-being. The patient can safely take two doses the next day.
Fiber and common daily supplements, such as calcium, may interfere with thyroxine absorption. Although levothyroxine can be taken at any time of day either with or without food, some experts recommend taking thyroid hormone upon awakening and at least 30 minutes before consuming anything, including breakfast or supplements.

Annual Evaluation. Thyroid failure is an ongoing process and so is its treatment. Many factors can cause changes that require modifying the thyroxine dosages.

A dose that is appropriate for 1 year may be too low the next. To maintain normal thyroid levels, some patients may need to take gradually increasing doses of thyroid hormone every year or two. Experts recommend that patients be reevaluated 6 months after normal TSH levels have been reached and then once a year thereafter.

Specific factors, such as changes in health or diet, new medications for other conditions, or simply switching brands, can also cause changes in thyroid hormone levels that require different doses. If patients change dose levels or thyroxine brands then they should be checked again at least 6 weeks later.

Because levothyroxine is identical to the thyroxine the body manufactures, side effects are rare. Over- or under-dosing, however, is fairly common, although rarely serious in the short term.


Under-Dosing	Over-Dosing
Sluggishness	Heart symptoms (rapid heart beat, palpitations, and wide variations in pulse; possible angina or congestive heart failure)
Mental dullness	Agitation (tremor, nervousness, insomnia, excessive sweating)
Feeling cold	Pain (headache and muscle pain)
Muscle cramps	Intestinal and metabolic symptoms (change in appetite, diarrhea, weight loss)
	Fever and intolerance to heat

No Symptom Improvement When Normal Thyroid Levels Are Reached. Some patients fail to feel significantly better even when their thyroid levels become normal after taking thyroid replacement.

Some experts argue that many patients become symptom-free only if their thyroid replacement achieves high-normal T4 and low-normal TSH levels (rather than just normal levels). They believe that slightly higher thyroxine levels will not be harmful. Research is needed to confirm these claims.

Some patients with persistent symptoms may benefit from triiodothyronine (T3), the other important thyroid hormone. In such cases, either a combination of a lower-dose of thyroxine with a small amount of T3 or natural dried thyroid hormone, which contains T3, may be helpful.

Side Effects of Under-Dosing. If the levothyroxine dose is not sufficient to restore normal thyroid levels, or if the patient frequently forgets to take the medication, the patient may continue to experience symptoms of hypothyroidism. Even mild hypothyroidism without any symptoms can eventually lead to an increase in cholesterol levels. In a 2000 study, 40% of people taking thyroid medication still had abnormal levels of TSH. To avoid these problems, patients should take the proper dosage of levothyroxine as prescribed and have regular check-ups that include measurement of blood TSH.

Side Effects of Over-dosing: Thyrotoxicosis. Over-dosing can cause thyrotoxicosis, or the symptoms of hyperthyroidism. A patient with too much thyroid hormone in the blood is at an increased risk for abnormal heart rhythms, rapid heartbeat, congestive heart failure, and possibly a heart attack if the patient has underlying heart disease. Excess thyroid hormone is particularly dangerous in newborns, and their drug levels must be carefully monitored to avoid brain damage.

Side Effects of Long-Term Treatment. Patients with hypothyroidism usually receive lifelong levothyroxine therapy. There has been some concern that long-term use will increase the risk of osteoporosis, as suppression therapy does. Studies indicate that postmenopausal women who are taking long-term normal replacement thyroxine have no out-of-the-ordinary risk for osteoporosis.

Drug Interactions with Levothyroxine. Many drugs interact with levothyroxine and may either enhance or interfere with its absorption. These drugs include amphetamines, anticoagulants (blood thinners), tricyclic antidepressants, anti-anxiety drugs, arthritis medications, aspirin, beta-blockers, insulin, oral contraceptives, digoxin, and certain cancer drugs. Large amounts of dietary fiber may also reduce the drug’s effectiveness. People whose diets are consistently high in fiber may require larger doses of the drug. Since thyroid hormones regulate the metabolism and can affect the actions of a number of medications, dosages may also need to be adjusted if a patient is being treated for other conditions. Even changing thyroxine brands can have a different effect.

Suppressive thyroid therapy involves taking levothyroxine in doses that are high enough to block the production of natural TSH but too low to cause hyperthyroid symptoms. It may used for patients with large goiters or thyroid cancer.

Suppressive thyroid therapy places patients, particularly postmenopausal women, at risk for accelerated osteoporosis, a disease that reduces bone mass and increases risk of fractures. Some researchers suggest, however, that such bone loss is too slight to pose any significant risk for fracture. Furthermore, the cholesterol-lowering benefits of suppressive therapy outweigh this small risk. A small study found that premenopausal women taking suppressive therapy for more than 10 years were also at increased risk of bone loss by the time they reach menopause, although more research is needed to confirm this.

Bone density loss can be reduced or avoided by taking no higher a dose of thyroxine than necessary to restore normal thyroid function. In any case, doses of T4 must be continuously and carefully tailored in all patients to avoid adverse effects on the heart.

A number of medications are also available that can help preserve bone in postmenopausal women. Women on hormone replacement therapy may need to increase their dose of thyroid hormone.

Drugs that Inhibit Thyroid Hormone

Drugs that are Enhanced by Thyroid Hormone

Drugs that are Suppressed by Thyroid Hormone

Drugs that Reduce Natural Thyroid Hormone Levels and May Cause Hypothyroidism

Iron supplements (even low doses found in multivitamins)

Calcium carbonate supplements

Aluminum-containing antacids (Maalox)

Drugs used to reduce cholesterol levels by binding bile acids (colestipol and cholestyramine)

Estrogens in oral contraceptives and hormone replacement therapy (may need to increase thyroid hormone while taking estrogen)

Raloxifene (Evista), a designer-estrogen used for osteoporosis

Sucralfate (Carafate)

Epinephrine (adrenaline) injections. Thyroid hormone may increase the risk of serious side effects in heart disease patients given this drug.

Warfarin, a blood thinner. Doses of this medication may need to be reduced if thyroid treatment is started after blood thinning treatments have begun.

Many antidepressants. In some cases, potency of both antidepressants and thyroid hormones may increase.

Diabetes drugs. Patients taking thyroid hormone may need additional insulin or oral hypoglycemic drugs. Stopping or reducing thyroid hormone may increase the risk of low blood sugar.

Digoxin. Patients with heart disease may need to increase their dosage of digoxin.

Lithium. This drug, used for bipolar disorder, has multiple effects on thyroid hormone synthesis and secretion.

Amiodarone (Cordarone). This drug, used to treat abnormal heart rhythms, contains iodine and can induce hyper- or hypothyroidism, particularly in patients with an existing thyroid problem.

Antiseizure drugs used for epilepsy, including phenytoin and carbamazepine.

Interferons and interleukins used in hepatitis, multiple sclerosis, and other conditions.

Rifampin, used for tuberculosis.

Some drugs used for cancer chemotherapy.

Interferon.

Large doses of selenium, a dietary supplement.

Treating the Elderly and Patients with Heart Disease. Thyroid dysfunction is common in elderly patients, with most having subclinical hypothyroidism. There is no evidence that this condition poses any great harm in this population, and some experts recommend treating only high-risk patients. One study suggested many elderly patients have been treated unnecessarily for hypothyroidism for years. In the study, half the patients taking thyroid hormone were taken off the medication successfully. Such patients may have been inappropriately diagnosed years ago, when testing was less accurate. More sensitive tests available now should reduce this risk.

Elderly patients, particularly people with heart conditions, usually start with lower doses of thyroid replacement, since a large initial dose may be a shock to the heart. Thyroid treatment may aggravate angina in about 20% of patients with the heart condition. About 40% of patients who have heart disease must take lower-than-average maintenance doses. Experts do not recommend treatment for subclinical hypothyroidism in elderly patients with heart disease whose test show only minimal thyroid hormone abnormalities and who have no anti-thyroid antibodies. Such patients should be closely monitored, however.

Preliminary research indicates that in patients undergoing cardiac bypass surgery, administration of triiodothyronine at the time of surgery may improve blood flow, heart rate, and cardiac output. Patients with advanced heart failure may also benefit from supplementary thyroid hormone.

Treating the Mentally Ill. Patients with psychiatric illness often forget to take their medications regularly. In these patients, once- or twice-weekly dosing of thyroid medications is often safe and effective and may improve compliance.

Treating Newborns and Infants with Hypothyroidism. Babies who are born with hypothyroidism (congenital hypothyroidism) should be treated with levothyroxine (T4) as soon as possible to prevent complications. Early treatment can help improve IQ and other developmental factors. However, even with early treatment, mild problems in mental functioning may persist into adulthood. In general, children who are born with milder forms of hypothyroidism will fare better than those who have more severe forms.

Single oral doses of levothyroxine (T4) can usually restore normal thyroid hormone levels within 1 - 2 weeks. It is critical that normal levels are achieved within a 2-week period. If thyroid function is not normalized within 2 weeks, it can pose greater risks for developmental problems. Some experts urge treating newborns at slightly higher than recommended doses for the first 2 weeks and then reducing the dosage once normal thyroid levels have been reached. Infants should continue to be monitored closely to be sure that thyroxine levels remain as consistently close to normal as possible. These children need to continue lifelong thyroid hormone treatments.

Treatment During Pregnancy and for Postpartum Thyroiditis. Women who have hypothyroidism before becoming pregnant may need to increase their dose of levothyroxine during pregnancy. In very rare cases, women may develop hypothyroidism while pregnant and need to be treated with levothyroxine in full replacement doses to reduce the risk of stillbirth. The developing baby is not affected when the pregnant woman takes thyroid hormones. The pregnant woman with hypothyroidism should be monitored regularly and doses adjusted as necessary. If postpartum thyroiditis develops after delivery, any thyroid medication should be reduced or temporarily stopped during this period.

Treatment for Myxedema Coma. Myxedema coma is an emergency situation, and the patient should be given intravenous doses of thyroid hormone, which could be triiodothyronine, levothyroxine, or both. Lower doses may be safer in elderly patients. Oftentimes, hydrocortisone, a corticosteroid, is also administered. Any other accompanying critical condition, including low body temperature, slow heart rate, low blood sugar, and difficulty in breathing, should also be treated immediately.

Treatment of Secondary Hypothyroidism. The small percentage of patients who have hypothyroidism due to a pituitary or hypothalamus problem should take levothyroxine along with their other medication to treat the primary disorder. In secondary hypothyroidism, the adrenal gland is often impaired. This means that the increased activity in the metabolic rate that occurs after thyroid replacement therapy may trigger a severe and even life-threatening condition called addisonian crisis, which is caused by a sudden demand for the depleted stress hormones secreted by the adrenal gland. Before administering thyroid replacement, the doctor should initiate a test that stimulates release of ACTH, one of the hormones secreted by the adrenal gland. If there is insufficient ACTH, then before thyroid replacement is started, the patient is usually treated with cortisone acetate, a stress hormone.

In one study of those taking thyroid hormone, 12% of women and 29% of men took it inappropriately. In some cases of infertility, women with menstrual problems and repeated miscarriages and men with low sperm counts have been treated with thyroid hormones even when there was no evidence of thyroid abnormalities. (Women showing high levels of TSH, however, may benefit from levothyroxine therapy.)

Other inappropriate uses for thyroid hormones are for weight loss and to reduce high cholesterol levels. Thyroid hormones have also been given to treat so-called metabolic insufficiency. Vague symptoms suggesting low metabolism, such as dry skin, fatigue, slight anemia, constipation, depression, and apathy, should not be treated indiscriminately with thyroid hormone. No evidence exists that thyroid therapy is beneficial unless the patient has proven hypothyroidism. Indiscriminate use of thyroid hormones can weaken muscles and, over the long term, even the heart. One exception is the use of thyroxine to enhance drugs used for the treatment of severe depression.

Treating Hypothyroidism and Iodide Deficiency. People who are iodide deficient may be able to be treated for hypothyroidism simply by using iodized salt. In addition to iodized salt, seafood is a good source. Except for plants grown in iodine-rich soil, most other foods do not contain iodine. The current RDA for iodide is 150 micrograms for both men and women, with an upper limit of 1,100 micrograms to avoid thyroid injury.

Iodine Restriction in Patients with Hashimoto's Thyroiditis. Some evidence suggests that excess iodine triggers Hashimoto's thyroiditis. Small studies report that restricting iodine intake restored thyroid levels to normal in up to 75% of these patients. More research is needed.

Resources

www.aace.com -- American Association of Clinical Endocrinologists
www.thyroid.org -- American Thyroid Association
www.tsh.org -- Thyroid Foundation of America
www.endo-society.org -- Endocrine Society

References

Desai J, Yassa L, Marqusee E, George S, Frates MC, Chen MH, et al. Hypothyroidism after sunitinib treatment for patients with gastrointestinal stromal tumors. Ann Intern Med. 2006 Nov 7;145(9):660-4.

Roberts LM, Pattison H, Roalfe A, Franklyn J, Wilson S, Hobbs FD, et al. Is subclinical thyroid dysfunction in the elderly associated with depression or cognitive dysfunction? Ann Intern Med. 2006 Oct 17;145(:573-81.

Roos A, Bakker SJ, Links TP, Gans RO, Wolffenbuttel BH. Thyroid function is associated with components of the metabolic syndrome in euthyroid subjects. J Clin Endocrinol Metab. 2007 Feb;92(2):491-6.

Review Date:
3/20/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

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adam.com

Shirtless Steve Holidays With Hayden

PopSugarUK — Tue, 19 May 2009 00:17:36 -0700

Steve Jones was spotted in Cannes yesterday, having fun on a yacht with friends including Heroes star Hayden Panettiere. The T4 presenter got shirtless in the sun, while Hayden covered up in a robe over her bikini as she and Steve looked happy as they relaxed on the boat. There's a twelve year age gap between the two, who definitely seem to be spending some serious time getting to know each other. Hayden's ex-boyfriend Milo Ventimiglia was eleven years older than her, so it seems she's generally attracted to older men. Still, when they look like Steve, who wouldn't be?!

View 5 Photos ›

BigPicturesPhoto.com

Ed Westwick Works His Way Through The UK

PopSugarUK — Mon, 27 Apr 2009 05:16:29 -0700

We saw lovely Ed Westwick looking dashing on the BAFTA TV Awards red carpet last night, but he had a busy weekend before that too! On Friday he appeared on GMTV and spoke to presenter Andrew Castle about all things Gossip Girl as well as the LA charity football game he will be taking part in. I have to say I think his rather sexy charisma comes through with his British accent just as well as his American - check out the interview under the cut and let me know what you think!

He also made appearances on T4 and Radio One, and as he left the BBC studios he had a devoted crowd of fans waiting for him. I'd definitely like to see more of Ed in the UK, although with the success of Gossip Girl it looks like his work will keep him in the US for quite some time!

View 5 Photos ›

To see Ed on the GMTV sofa, just read more.

WENN.com

Non-small cell lung cancer

FitSugar — Wed, 08 Oct 2008 17:35:06 -0700

In This Report

Highlights
Introduction
Causes
Symptoms
Risk Factors
Lifestyle Changes
Diagnostic Tests
Staging Systems
Surgical Procedures
Radiation Treatments
Treatment Options by Stages...
Chemotherapy Treatments
Investigative Agents
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Research News:

About 3,000 nonsmokers die each year of lung cancer resulting from exposure to secondhand smoke, according to a 2006 Surgeon General report.
Advexin, a genetic therapy that contains the p53 tumor-suppressor gene, is showing promise. A 2006 study in Japan found that out of 13 patients with advanced NSCLC receiving Advexin, 10 had stabilized. Advexin is in Phase II clinical trials for NSCLC.
Studies are finding that NSCLC tumors in people who never smoked have a much higher rate of epithelial growth-factor receptor (EGFR) mutations. EGFR helps new blood vessels grow to feed tumors. This discovery may help tailor future treatments to specific patient populations. It also helps explain why some newer treatments seem effective mostly in patients who never smoked.

Treatment News:

Video-assisted thoracic surgery (VATS) is a new, less-invasive surgical technique that uses a thin tube containing a miniature camera and surgical instruments. Though the procedure is not appropriate in all cases, it offers significant advantages, especially in older or frail patients, in the treatment of early stage non-small cell lung cancer (NSCLC).
Bevacizumab, a monoclonal antibody, was approved in October 2006 as a first-line treatment (in combination with carboplatin and paclitaxel) for inoperable, locally advanced, metastatic, or recurrent non-squamous, non-small cell lung cancer.
Gefitinib (Iressa), a drug that targets EGFR, proved disappointing in final clinical trials. However, erlotinib (Tarceva), a drug that targets a different part of the EGFR molecule, has shown benefits. Erlotinib is now approved as a second-line chemotherapy to treat patients with locally advanced or metastatic NSCLC after a previous course of chemotherapy failed.

Introduction

Although lung cancer accounts for only 13% of all cancers, it is among the most lethal, accounting for over 28% of all cancer deaths. It is more deadly than colon, breast, and prostate cancers combined. An estimated 160,390 people will die from lung cancer in 2007. Death rates have been declining in men over the past decade, and they have now stabilized in women.

The lungs are two spongy organs surrounded by a thin moist membrane called the pleura. Each lung is composed of smooth, shiny lobes: the right lung has three lobes, and the left has two. About 90% of the lung is filled with air; only 10% is solid tissue.

Air is carried from the trachea (the windpipe) into the lung through flexible airways called bronchi.
Like the branches of a tree, the bronchi in turn divide into over a million smaller airways called bronchioles.
The bronchioles lead to grape-like clusters of microscopic sacs called alveoli.
In each adult lung, there are about 300 million of these tiny alveoli. A thin membrane makes up the alveoli sacs. Oxygen and carbon dioxide pass through this membrane to and from capillaries.
Capillaries, the smallest of our blood vessels, carry blood throughout the body.

The major features of the lungs include the bronchi, the bronchioles, and the alveoli. The alveoli are the microscopic blood vessel-lined sacks in which oxygen and carbon dioxide gas are exchanged.

Lung cancer develops when genetic mutations (changes) occur in a normal cell within the lung. As a result, the cell becomes abnormal in shape and behavior, and reproduces endlessly. The abnormal cells form a tumor that, if not surgically removed, invades neighboring blood vessels and lymph nodes and spreads to nearby sites. Eventually, the cancer can spread (metastasize) to locations throughout the body.

The two major categories of lung cancer are small cell lung cancer and non-small cell lung cancer. Most lung cancers are non-small cell cancer, the subject of this report. Less common cancers of the lung are known as carcinoids, cylindromas, and certain sarcomas (cancer in soft tissues).

Some experts believe all primary lung cancers come from a single common malignant (cancerous) stem cell that, as it copies itself, can develop into any one of these cancer types in different individuals.

In addition, cancers in the lung may have spread from other primary sites, such as the breast, thyroid, or colon. In these cases, doctors name the cancer after its original location; for example, "breast cancer with lung metastases."

Non-small cell lung cancers are categorized into three types: squamous cell carcinoma (also called epidermoid carcinoma), adenocarcinoma, and large cell carcinoma. These separate types are grouped together because, in early stages before the cancers have spread, they all can be treated surgically.

Squamous Cell Carcinoma. Squamous cells are formed from reserve cells, which are round cells that replace injured or damaged cells in the lining (the epithelium) of the bronchi, the major airways. Tumors formed from squamous cells are usually found in the center of the lung, either in a major lobe or in one of the main airway branches. They may grow to large sizes and form cavities in the lungs.

Click the icon to see an image of squamous cell carcinoma.

When squamous cell cancer metastasizes, it may travel to the bone, adrenal glands, liver, small intestine, and brain.

Squamous cell carcinoma is nearly always caused by smoking and used to be the most common cancer. It still makes up 25 - 40% of all lung cancers.

Adenocarcinoma. Adenocarcinomas usually arise from the mucus-producing cells in the lung. About two-thirds of adenocarcinomas develop in the outer regions of the lung, while one-third develop in the center of the lung. In 1965, 12% of lung cancers were adenocarcinomas. They are now estimated to account for 30 - 50% of all lung cancers and are the most common lung cancers in many countries. They are also the most common lung cancers in women. In fact, a 2000 European study showed that nearly 34% of the women with lung cancer under investigation had adenocarcinoma, compared to 26.4% who had squamous cell carcinoma, and 22.3% with small cell lung cancer. Adenocarcinoma is also increasing dramatically in men. Until recently, adenocarcinoma was only weakly linked to smoking. Experts now suggest, however, that the dramatic increase in recent decades in this lung cancer type may be due to low-tar, filtered cigarettes. People who smoke them draw tiny particles deeper into the lungs, thereby possibly increasing the risk for adenocarcinoma.

The course of this cancer varies widely. Most often, it develops slowly and causes few or no symptoms until it is far advanced. In some cases, however, it can be extremely aggressive and rapidly fatal. In 50% of cases in which this cancer spreads, it spreads only to the brain. Other common locations it spreads to include the other lung, the liver, the adrenal glands, and bone.

Click the icon to see an image of adenocarcinoma.

Bronchoalveolar Lung Cancer. Bronchoalveolar lung cancer is actually a subtype of adenocarcinoma. It develops as a layer of column-like cells on the lung and spreads through the airways, causing great volumes of sputum. This cancer also is increasing in incidence.

Large Cell Carcinoma. Large cell carcinoma, which makes up about 10 - 20% of lung cancers, includes cancers that cannot be identified under the microscope as squamous cell cancers or adenocarcinomas.

Click the icon to see an image of large cell carcinoma.

Small cell lung cancer may, like squamous cells, be derived from reserve cells or other cells in the epithelium. It causes 15 - 25% of all lung cancers; without chemotherapy, it is very aggressive and usually rapidly fatal. It requires a different treatment approach from non-small cell lung cancer, so it is not discussed in this report.

Click the icon to see an image of small cell carcinoma.

Causes

Cigarette Smoke. Smoking causes 87% of lung cancer deaths, accounting for 30% of all cancer deaths. Cigarettes, nicotine, or both may contribute to lung cancer in one or more of the following ways:

In general, chronic exposure to nicotine may cause an acceleration of coronary artery disease, peptic ulcer disease, reproductive disturbances, esophageal reflux, hypertension, fetal illnesses and death, and delayed wound healing.

The smoke is the most dangerous component of the cigarette. Chemicals formed during smoking trigger genetic mutations that lead to cancer. When people inhale cigarette smoke, they bring into their lungs tar that includes over 4,000 chemicals, some of which are carcinogenic (cancer-causing). Other inhaled chemicals in cigarette smoke that may increase the risk for cancer include cyanide, benzene, formaldehyde, methanol (wood alcohol), acetylene (the fuel used in torches), and ammonia. Smoke also contains nitrogen oxide and carbon monoxide, both of which are harmful gases.
Nicotine itself may be a hazard. A 2000 laboratory study suggested that the human body might be converting inhaled nicotine into a chemical called aminoketone, which has been linked to the formation of tobacco-related lung cancer. A 2001 study reported that nicotine triggered new blood vessel growth, which could, in theory, promote growth of any existing tumors. A study published in 2005 found that nicotine was responsible for disabling a gene that induces the death of cancer cells in lung tumors. Whether or not these studies apply to long-term use of nicotine replacement products (such as patches), or to cigarette smoking, is still unclear. The studies should certainly not discourage people from using nicotine replacement methods for quitting. However, these studies may indicate that people should not use these devices on a long-term basis.

Radon. Radon is a gas produced naturally by the breakdown of uranium. It is often present in the soil and in water and can seep into any dwelling. Radon may be responsible for between 10% and 14% of lung cancer deaths, making it, after smoking, the second leading cause of this cancer.

Other Contributors. Toxic particles leading to precancerous changes in the lung are also found in marijuana. In one study, 53.8% of cigarette smokers, 66.7% of marijuana smokers, and all of those subjects who smoked both substances showed evidence of precancerous changes in the lungs.

There is considerable debate over the lung cancer risk posed by depleted uranium used in military weapons (such as in the Gulf and Balkan conflicts). A 2001 study estimated that it would cause an additional 8 deaths from lung cancer out of every 10,000 people or soldiers who were highly exposed to this substance. The study was based on a mathematical model, however, and the issue is not settled.

Other lung carcinogens include asbestos, arsenic, certain petrochemicals (materials made from crude oil or natural gas), and other airborne (carried through the air) byproducts of various mining and manufacturing processes.

Click the icon to see an image of the tobacco plant.

Genetic mutations that cause cancer generally occur in two types of genes:

Tumor-suppressor genes, which prevent cells from endlessly copying themselves
Proto-oncogenes, which encourage cells to keep making copies of themselves [when a proto-oncogene changes (becomes mutated), it is then called an oncogene]

Damage to either type of gene can cause a mutation that results in an uncontrolled division of cells. This uncontrolled division forms tumors.

It is unlikely that a single specific abnormality causes all lung cancer. It probably takes a variety of mutations to start the devastating chain of events leading to cancer. The following mutations are among those under investigation:

BPDE-caused mutations: The chemical BPDE, a byproduct of tobacco smoke, is involved with a number of genetic mutations, including those to an oncogene called K-ras and to three tumor-suppressor genes known as p53, PPP2R1B, and p16. When normal, the tumor-suppressor genes are involved in cell repair and healthy copying of the cell. When they are damaged or blocked, out of control cell production can occur, leading to cancer. About 10% of the population may carry a gene that protects against lung cancer, by reducing levels of BPDE.
Chemotherapy resistance genes: Tumors that contain the p53 mutation may also be more resistant to chemotherapy.
Rb Mutations: Another important contributor to lung cancer is a genetically defective protein called retinoblastoma (Rb), which is associated with very aggressive tumors. Low levels of the normal Rb gene may sometimes predict aggressive cancer, especially in patients with small cell lung cancer.
Mutations to the FHIT gene: Another potentially important mutation may be an abnormality in the FHIT gene. This mutation causes the cells lining the lung to become more vulnerable to the effects of tobacco smoke and other carcinogens.

Symptoms

Lung cancer is unlikely to produce symptoms until the disease is advanced. When symptoms develop, they may result from the lung tumor itself, from its effects on tissues outside the lung, or from the spread of malignant cells to other organs.

Early symptoms may include the following:

Frequent bouts of pneumonia, or pneumonia that does not clear up in a normal period of time
Coughing (particularly coughing up blood)
Weight loss
Fever
Shortness of breath
Chest pain

Later-stage symptoms include the following:

Shortness of breath: This common symptom is the result of cancer that has spread in the lung and the pleura, the membrane covering the lung.
Superior vena cava syndrome: In some cases, tumor growth or spreading of the cancer presses against the superior vena cava, a large vein that returns blood from the upper part of the body to the heart. When this happens, a condition called superior vena cava syndrome may occur, leading to obvious swelling in the arms and face.
Trouble swallowing: The esophagus is the pipe that takes food from the mouth to the stomach. The cancer may spread to or press against the esophagus, interfering with swallowing and nutrition.
Hoarseness: Cancer can damage the nerves that control the voice box, causing hoarseness.
Pancoast syndrome: Damage to the brachial plexus, a group of nerves branching from the neck, can cause pain, weakness, or numbness in the arm or hand (Pancoast syndrome).
Bronchoalveolar lung cancer may produce very large amounts of mucus.
Hypercalcemia: Some lung cancers produce substances that remove calcium from bone and release it into the bloodstream, causing a condition called hypercalcemia. Patients with this disorder can experience nausea, vomiting, constipation, weakness, and fatigue.

Other lung cancers (usually small cell cancer) cause the body to retain water, lowering the blood's sodium levels. This condition, called hyponatremia, can produce confusion, weakness, and even seizures.

Risk Factors

Before cigarettes became popular in the beginning of the 20th century, lung cancer was rare. In 2007, lung cancer is expected to strike up to 213,380 Americans, and about 160,390 are expected to die from it.The disease usually occurs in people over 50 years old. Men have a significantly greater incidence of lung cancer compared to women. On the encouraging side, the rate of lung cancer in men has been declining significantly over the past decade. While lung cancer rates have been increasing dramatically in women (by 600% from 1950 to 2000), they now appear to be stabilizing.

Smoking appears to be the primary risk factor in 85 - 90% of lung cancers. About 15% of all people who smoke develop lung cancer. The risk depends on the duration of the addiction and the number of pack years. (One pack year equals the number of packs of cigarettes smoked per day, multiplied by the number of years that the person has smoked.) Genetic damage in the lung occurs in nearly all chronic smokers, even if cancer has not developed.

An elevated risk for lung cancer can persist for more than 20 years after quitting smoking, although the risk drops significantly even in the first year after quitting. And, there are benefits to quitting smoking even for people who are well into middle age.


Quitting Age	Percentage
30	2%
40	3%
50	6%
60	10%

Second-Hand Smoke. The Environmental Protection Agency has classified second-hand smoke as a carcinogen (cancer-causing chemical). Exposure to second-hand tobacco smoke increases the risk of lung cancer in the nonsmoker by about 20 - 30%. A 2006 Surgeon General report found that about 3,000 nonsmokers die each year of lung cancer resulting from exposure to secondhand smoke.

There may be some ethnic differences in lung cancer risk. For example, African-Americans face a risk that is two to four times higher than that in Caucasians, regardless of smoking status. It is not clear what factors are responsible for this higher risk. Some African-Americans appear to have a genetic vulnerability to the harmful chemicals in cigarette smoke.

In China, an estimated one third of all young male smokers will eventually die because of tobacco-related illnesses. Their risk for lung cancer, however, is much less than it is for chronic lung disease, the opposite of the Western trend. A 2001 study reported that the lower rate of lung cancer among Chinese people might be due to a slow rate of clearing nicotine, which results in smoking fewer cigarettes.

People with High Exposure to Radon. Studies have shown that radon raises the risk of lung cancer in underground miners by 40%. It is unclear whether the results of these studies would apply to people exposed to radon in their homes One study suggests that people with intense or prolonged exposure to radon in their homes do indeed face the same risk as miners exposed to similar levels of radon. A cumulative long-term exposure to radon and smoking also increases the danger. Most people move an average of 10 or 11 times over their lifetime, so the risk of developing lung cancer through radon exposure is very low in most individuals, even for those who lived for awhile in areas with high radon levels. People with homes that have high radon levels and those who sleep or spend many hours to days in basements with detectable but moderate levels should consider taking protective measures.

Workers Highly Exposed to Carcinogens. An estimated 9,000 - 10,000 men and 900 - 1,900 women develop lung cancer each year because of occupational exposure to carcinogens. More than half of these cases are attributable to past exposure to asbestos, which has long been known to be a risk factor for mesothelioma (cancer of the pleura, the lining around the lung) and can increase the risk of lung cancer in smokers. With better protective measures, these rates are expected to fall in the future.

Other chemicals that put workers at risk for lung cancer include:

Arsenic (insecticide and herbicide sprayers, tanners, oil refinery workers)
Chloromethyl methyl ether (workers exposed to certain polymers, water repellents, or products using chloride and formaldehyde)
Chromium compounds (workers using certain alloys, paints, pigments, and preservatives)
Depleted uranium (soldiers exposed to weapons during battlefield conditions)
Crystalline silica

By contrast, agricultural workers seem to have a lower lung cancer rate, despite their possible occupational exposures to risky chemicals. While this rate has traditionally been attributed to good health habits, including low tobacco use, a 2000 study suggests that agricultural workers' exposure to endotoxin may be responsible. Endotoxin is a component of common bacteria found in soil and animals and may have cancer-preventing effects on the immune system.

Exposure to Smoke from Grills. Grilling and high-heat frying emit chemicals called heterocyclic amines, which are known to be carcinogenic. A 2000 study of Chinese women found that smokers who stir-fried meat daily and inhaled cooking fumes had a higher risk of lung cancer than did those who stir-fried meat less frequently. No higher risk was found among nonsmokers.

Air Pollution. Although any risk from air pollution is very small, it nevertheless may be a contributor to those lung cancers not obviously related to smoking. Some studies, including a major analysis of vital statistics in 2002, have found an association between increased risk for lung cancer and long-term exposure to very small particulates, especially sulfates, present in polluted air. The risk, if any, is very small.

A family history of lung cancer may play a role in increasing susceptibility to this disease. In one study, people who had parents or siblings with respiratory tract cancers had a 30% higher risk for lung cancer, compared to people without a family history. Women with mothers or sisters with lung cancer had triple the risk. A higher risk occurred in both smokers and nonsmokers. There was no association between a history of other cancers and lung cancer. Both genetic factors and secondhand smoke appeared to contribute to the danger in these individuals.

Smokers with emphysema or chronic inflammatory lung diseases, such as asthma, are at increased risk for lung cancer. Both smokers and nonsmokers whose lungs are scarred from recurrent lung diseases, such as pneumonia or tuberculosis, are also at increased risk, particularly for bronchoalveolar lung cancer.

Lifestyle Changes

Quitting improves lung function almost immediately. Some evidence suggests that the benefits for the lungs are even more significant for women who quit than for men. It should be noted, however, that it can take 20 years or longer, particularly in heavy smokers, for the lungs to be restored to a fully healthy condition in which the risk for lung cancer is as low as for nonsmokers. Quitting is extremely difficult. No one should be discouraged if they relapse. Everyone should keep trying to quit. With continued efforts, many people succeed.

The many methods of quitting smoking include counseling and support groups, nicotine patches, gums and sprays, and incremental reduction.

At this time perhaps the most effective method for quitting is a combination of the following:

Nicotine replacement products that reduce withdrawal symptoms and cravings.
The antidepressants bupropion (Zyban) or nortriptyline (Pamelor, Aventyl), which reduce emotional effects and cravings associated with withdrawal, and improve abstinence rates.
Professional counseling or support organizations that may be effective, in addition to the medication, in helping people maintain abstinence.

[See In-Depth Report #41: Smoking.]

While people are in the process of quitting (and afterwards), they should maintain as healthy a lifestyle as possible.

Phytochemicals. Some data suggest that diets rich in fresh fruits and vegetables may be protective against lung cancer in both smokers and non-smokers. Some studies have reported protection from specific plant chemicals (phytochemicals), such as the following:

Isothiocyanates. These chemicals are found in cruciferous vegetables (broccoli, cauliflower, and Brussels sprouts). They may help block the effects of carcinogens in smoke, suppress tumor growth, and inhibit growth-promoting steroid hormones.
Flavonoids. Major sources are apples, grapefruit, onions, red wine, and tea. In one study on flavonoids, apple eaters had the lowest cancer risk, 68% less than those who ate fruit infrequently. In another, those who ate relatively more onions, apples, and white grapefruit had less than half the lung cancer risk as people who ate relatively small amounts of these foods. Flavonoids are also found in soybeans, berries, broccoli, carrots, citrus fruits, eggplant, peppers, squash, and tomatoes. Specific flavonoids in dark chocolate may be protective against lung cancer (but not other cancers).
Lycopene. Lycopene is found in tomatoes, which have been associated with a lower risk for lung cancer. Cooking the tomatoes appears to increase the potency of lycopene.
Cryptoxanthin. Some studies suggest that eating foods rich in cryptoxanthin, a yellow-orange pigment, reduces the risk for lung cancer. Foods with high amounts of cryptoxanthin include pumpkin, corn, papaya, red bell peppers, tangerines, oranges, and peaches. More research is needed in this area, however.
Isoflavones. Isoflavones, found in soy beans and flax seed, behave like estrogen in some ways and not in others. Some evidence suggests the genistein (a type of isoflavone) in soy may have properties that are protective against lung cancer.

Click the icon to see an image of phytochemicals.

Note: Studies on these chemicals are not consistent. It is unlikely that individual phytochemicals offer protection, but rather that the benefits come from a collection of vitamins and plant chemicals contained in fruits and vegetables. Fruit, especially, appears to be protective.

Fats and Oils. Some studies have indicated that diets high in animal fats increase the risk for lung cancer. Others have suggested some protection from cod liver oil, which contains omega-3 fatty acids (found in fatty fish), omega-6 fatty acids (found in flax and in soybean and canola oils), and monounsaturated oils (found in olive and canola oils). Of interest was a 2002 study reporting that women who had a high intake of cheese had a lower risk of lung cancer. Despite these intriguing pieces of information, the ability of these substances to protect against lung cancer remains controversial, and discontinuation of smoking remains the best advice.

Click the icon to see an image of fats and oils.

Vitamin Supplements. Even with a healthful diet, smoking reduces the levels of a number of vitamins, importantly vitamin C. There is no evidence, however, to support any protection from antioxidant supplements, including vitamins E, A, or beta carotene.

In fact, evidence is now suggesting that high doses of vitamin C, vitamin E, and beta carotene supplements may have harmful effects. A 2000 study, for example, reported a higher risk for cancer in male smokers who took multivitamins plus A, C, or E. The strongest studies to date on negative effects of antioxidant supplements have reported an increase in lung cancer and overall mortality rates among smokers who took beta carotene supplements. In determining reasons for this disturbing effect, one animal study suggested that beta carotene increased enzymes in the lungs that actually promote cancerous changes. In other words, antioxidants may actually be harmful in people who already harbor cancer cells. This is particularly important information for smokers, who may carry precancerous or cancerous cells for years prior to developing the disease. The best way of achieving healthy levels of important nutrients is from healthy foods.

Click the icon to see the benefits of vitamin A.

Click the icon to see dietary sources of vitamin A.

Trace Element Supplements. Trace elements may be important in cancer risk and prevention.

Selenium appears to inhibit cell production and may have other anti-cancer properties. A few studies have reported some protection with selenium. However, a major 2002 analysis supports previous work, indicating that taking selenium helps only people who are deficient to begin with.

Click the icon to see the benefits of selenium.

Zinc may prove to be more important than selenium. Some research suggests that zinc may help protect smokers by blocking cadmium. Smokers have higher levels of cadmium in their body, and there may be a link between cadmium and a higher risk for lung cancer. Some laboratory studies have indicated that zinc might help protect against tumor progression. There is no evidence that taking zinc supplements will reduce the risk for lung cancer, however.

A 2003 study reported a lower risk in lung cancer in men and women who were physically active. Both moderate and intensive exercises were associated with protection.

People concerned about radon in their home or area can purchase a test approved by the Environmental Protection Agency. Methods for removing radon include installing a soil suction system. It should be noted, however, that home prevention measures rarely reduce radon levels to zero. Simply sleeping by an open window reduces the risk.

Nonsteroidal anti-inflammatory drugs (NSAIDs) and COX-2 inhibitors (coxibs) both block cyclooxygenase (COX) enzymes. NSAIDs block COX-1 and 2, and coxibs selectively block COX-2. Evidence now strongly suggests that the COX-2 enzyme plays a role in blood vessel growth (angiogenesis) that can feed lung cancers.

NSAIDs. NSAIDs include aspirin, ibuprofen (Advil), and naproxen (Aleve, Naprosyn, Naprelan, Anaprox). These agents inhibit COX-2, but they also target another COX enzyme. Studies are now reporting an association between regular use of aspirin or other NSAIDs and a reduced risk for non-small cell lung cancer.

COX-2 Inhibitors. The COX-2 inhibitors are more recent forms of NSAIDs. Currently, only celecoxib (Celebrex) is still on the market. Rofecoxib (Vioxx) and valdecoxib (Bextra) were withdrawn from the market due to their high risk of causing strokes and heart attacks. Because they target the COX-2 enzyme specifically, researchers are focusing on these drugs for a possible role in treating lung cancer and preventing recurrence.

Diagnostic Tests

Chest X-Rays. In a small percentage of cases, a routine chest x-ray reveals the first signs of lung cancer. Usually, however, symptoms of existing lung cancer, such as coughing, chest pain, and blood in the sputum, will lead to a chest x-ray. If non-small cell lung cancer is present, chest x-rays may show lesions (damaged or abnormal tissue) in the center of the lung, cavities formed by squamous cell carcinoma, or lace-like pattern of cells spreading through the lungs. By the time lung cancer is diagnosed by chest x-rays, however, it has often spread so far that it cannot be surgically cured. Four major studies found no survival benefits in early detection from chest x-rays and sputum screening. Regular screening for lung cancer using x-rays is therefore not currently recommended.

Computed Tomography. Computed tomography (CT), particularly the specific technique called low-dose spiral (or helical) CT, is more effective than x-rays for detecting cancer in patients with suspected lung cancer. It is the standard imaging procedure for determining if and where the cancer has spread (metastasized). Surgeons also use CT scans to evaluate patients before lung surgery.

CT stands for computerized tomography. In this procedure, a thin x-ray beam is rotated around the area of the body to be visualized. Using very complicated mathematical processes called algorithms, the computer is able to generate a 3-D image of a section through the body. CT scans are very detailed.

The use of helical CT for early screening is still controversial. Studies of CT scans in smokers suggest that early screening will detect about 2% of lung cancers, most of these in early stages. In the studies, 62 - 82% of the patients with stage 1A cancer (when the tumor has not spread yet) were still alive at 5 years. Neither study, however, was controlled (compared with other groups, such as non-smokers). The survival figures were likely to be higher than in actual practice.

Click the icon to see an image of a CT scan of the chest.

Evidence regarding the survival benefits of early detection is not clear. Many experts are highly opposed to widespread screening for lung cancer. Some evidence, for example, suggests that lung cancer cells in non-small cell lung cancer are often very aggressive at microscopic levels (before a tumor is formed). If this were true, the cancer would be highly likely to have already spread, long before it was visible with CT scans. Moreover, some studies have found no association between tumor size at the time of diagnosis and survival times. On the other hand, some suspicious areas detected by CT scans may actually be innocent, and these patients might be more likely to die from aggressive treatments than from the disorder itself.

It should also be noted that about 98% of suspicious areas seen on CT scans turn out to be benign. Even after rescreening, many scans will show suspicious areas that turn out to be harmless but will require invasive and expensive biopsies. Additional experience with CT scans, however, may allow experts to better determine which abnormalities are likely to be benign.

High-risk individuals who are still interested in early screening with CT scans should ask their doctor about available clinical trials.

Computed tomography is the standard imaging procedure for determining if and where the cancer has spread (metastasized). Other imaging tests, however, may be useful for staging and tracking lung cancers (staging means finding out how advanced the cancer is).

Positron Emission Tomography. Positron emission tomography (PET), specifically a technique known as FDG/PET, is the most accurate noninvasive test for detecting early lung cancer. It is also the best imaging technique for staging lung cancers, not only those located in the lungs, but also those that have spread, particularly into the space between the two lungs (the mediastinum). With this imaging test, the patient is first injected with a specially formulated liquid sugar (called FDG), and then viewed with a machine that records energy given off by tumor cells.

PET is expensive and not widely available. However, its supporters suggest that it may prevent many unnecessary surgeries by identifying patients whose cancer has advanced past the stage at which surgery is helpful. There is some evidence that FDG/PET scan can detect a metabolic (processing) response to treatments that may help predict the outlook for the patient.

Scintigraphy. Scintigraphy is an imaging procedure in which patients are administered low-level radioactive agents that bind to cancer cells, which then can be tracked by special cameras to reveal the cancer cells' location and intensity. Agents selected are those that can best bind successfully with specific tumor types. For example, a 2001 study of the binding agent 111In-DOTA-LAN demonstrated excellent results in identifying non-small cell lung tumors. This study further suggests the possibility of using such highly-targeted binding agents as lung cancer treatments.

Magnetic Resonance Imaging. Magnetic resonance imaging (MRI), an imaging procedure that uses radio wave energy, is frequently used instead of CT scanning to locate brain and bone metastases that can be associated with lung cancer.

Biopsies of lung tissue are needed to confirm lung cancer. This requires invasive procedures that may vary from simple needle aspiration to chest surgery.

Needle Aspiration. Sometimes, a biopsy specimen is obtained by inserting a needle between the ribs, and then guiding it with the use of computed tomography scans, ultrasound, or fluoroscopy (a device allowing an x-ray view). Specific techniques include transbronchial or transthoracic needle aspiration (TBNA or TTNA) or endoscopic ultrasound-guided needle aspiration (EUS-NA). Their use depends on how much of the area can be observed with less invasive imaging methods. There is a 5 -10% risk for bleeding or collapsed lung with needle aspiration.

Thoracoscopy. Thoracoscopy is usually very effective for diagnosing cancer in the outer areas of the lungs, or those involving the pleura (membrane surrounding the lungs). This is a surgical procedure that uses a fiber-optic tube to view the area:

The procedure requires general anesthesia.
The surgeon passes surgical instruments and a fiber-optic tube through a small incision in the chest. The tube has a camera in it, which allows the surgeon to look at the lungs on a video screen.

Bronchoscopy. To locate cancer that develops in the central areas and major airways of the lung (usually squamous or small cell cancer), bronchoscopy is typically performed. The procedure is done as follows:

The patient is given a local anesthetic, supplementary oxygen, and sedatives.
The doctor inserts a bronchoscope, a hollow flexible tube often containing a fiber-optic light source, into the lower respiratory tract through the nose or mouth.
The tube acts like a telescope into the body, allowing the doctor to see the windpipe and major airways. In a procedure called fluorescence bronchoscopy, the doctor injects the patient with a drug that makes cancer tissue appear red when exposed to laser light from the bronchoscope.
The surgeon removes specimens for biopsy, ideally combining techniques to include cutting tissue, brushings, and a washing process called bronchoalveolar lavage (BAL). BAL involves injecting saline through the bronchoscope into the lung and then immediately suctioning the fluid back through the hollow tube of the bronchoscope; the fluid is then analyzed in the laboratory. Both brushing and washing procedures may be very valuable additions.

Advances in this procedure, such as laser-induced fluorescence endoscopic bronchoscopy, may improve early detection of cancer.

Bronchoscopy is usually very safe, but complications can occur; they include allergic reactions to the sedatives or anesthetics, asthma attacks in susceptible patients, and bleeding. Fever may follow the procedure.

Click the icon to see an image of bronchoscopy procedure.

Click the icon to see an image of a bronchoscope.

Mediastinoscopy. Mediastinoscopy uses a tube inserted between the lungs to locate the appropriate areas for biopsy. It is performed if the physician suspects that cancer has spread to nearby lymph nodes but has not yet metastasized.

Sputum Analysis for Presence of Cancer Cells. Some experts are now recommending an analysis of coughed-up sputum as a useful and cost-effective measure for identifying cancer cells, particularly those located in central areas of the lung. However, although sputum analysis appears to be as accurate as any other screening test currently conducted, it may miss cancers such as adenocarcinoma, which form in mucus-producing cells typically in the outer portion of the lungs. If a sputum analysis does not show cancer cells, but other signs of lung cancer are present, including blood in the sputum and suspicious areas on x-rays, other tests are performed.

Biomarkers. Biologic markers, called biomarkers, are high levels of substances that are released by tumors and indicate the presence of specific cancers. Biomarkers can be found in sputum, blood, and tissue samples. They can include enzymes, hormones, amino-acid compounds, antigens (identified by antibodies that specifically target them), growth factors, and other chemicals. Some biomarkers may prove to reveal the presence of cancer cells before they are evident on CT scans or other imaging tests. For example, genetic mutations, notably K-ras and p53, can now be detected in cells found in sputum, or cells taken during bronchoscopy. Such mutations occur only with cancerous changes and may enable early detection. Other markers that prove to be important for predicting aggressive cancers are high levels of matrix metalloproteinase (MMP9) and vascular endothelial growth factor (VEGF), which are compounds involved with angiogenesis (the process in which blood vessels serving the tumor develop).

As part of the doctor's initial examination, patients may have a pulmonary function test to evaluate lung health and capacity. In addition, since the heart and lungs are often involved in complications following lung cancer surgery, the doctor may be especially interested in taking a complete history of those systems in patients who might need surgery.

Staging Systems

Tests to Determine Cancer Stage. After diagnosing non-small cell lung cancer, the doctor makes treatment choices by determining the cancer's stage (how large the tumor is and how far the cancer has spread). To stage the cancer and determine other aspects of the disease, a number of tests are conducted:

The cancer cells are examined microscopically for size, shape, and other configurations.
Computer tomography (CT), magnetic resonance imaging (MRI), or both, are used to scan the lung and perhaps other locations, such as the liver, upper abdomen, and brain, to determine the extent of the disease.

Physical Examination. A detailed physical examination of the whole body is very important to identify or rule out the spread of cancer to other areas, and to determine the general condition of the patient. For example, questions about dizziness or headaches can help the doctor determine if the cancer has spread to the brain, while bone or joint pain might suggest that the cancer has spread to the bone. The doctor will also look for head and neck symptoms that might reveal the presence of other tumors. Also, according to a 2000 review, the patient's weight loss and ability to function are two very important factors for predicting survival following treatment. Patients who are mobile and have lost less than 10% of their pre-treatment weight tend to have better survival rates.

In lung cancer, the stage of the disease at the time of diagnosis is a major factor in determining how to treat the cancer, and how long the patient can expect to live. In general, survival is longest for patients with very early-stage disease and shortest for patients with very advanced disease that has spread to several regions of the body. Staging is based on the results of physical and surgical examinations, and laboratory and imaging tests, including biopsies.

To determine the stage, medical professionals first categorize each tumor by size and by how far it has extended. This identification method is called the TNM system.

The TNM categories then determine the stage (numbered 0 to IV), indicating how advanced the cancer is.

TNM stands for Tumor, regional lymph Nodes, and Metastasis (cancer spread beyond the original tumor).

T refers to the size and extension of the tumor itself. In TX and T0, the tumor is indicated by cancer cells in sputum or lung samples but cannot be seen. Tis: Carcinoma in situ. The cells are cancerous, but the tumor does not show evidence of spreading. In T1, the tumor is 3 cm or less in size, is still contained in the lung or the membrane covering the lung, and has not reached the main airway.

In T2, the tumor has one or more of the following features:

It is greater than 3 cm
It involves the main airway
It is 2 cm or more away from the ridge (the carina) at the lowest part of the windpipe
It has invaded the pleura
It is associated with collapsed lung tissue (atelectasis) or swelling that blocks part (but not all) of the lung

In T3, a tumor of any size has directly invaded any of the following:

Chest wall
Diaphragm
The membrane covering organs and structures in the chest
The outer wall of the membrane around the heart (pericardium)

In addition, one or more of the following conditions are present:

The tumor is in the main airway, less than 2 cm away from the carina, but is not in the trachea (windpipe).
The tumor is associated with a collapsed lung or swelling that blocks the entire lung.

In T4, the tumor has invaded any of the following:

The area between the lungs (mediastinum)
The heart
The great vessels (the blood vessels that carry blood from the heart)
Carina, trachea, or esophagus
Main portion of the spine

In addition, one or both of the following occurs: separate tumors are present in the same lobe; the tumor is accompanied by an increased amount of fluid between the pleural membrane and the lung.

N followed by a number from 0 to 3 refers to whether the cancer has reached regional (in the area of tumor) lymph nodes. In stage N0, the regional lymph nodes are still cancer-free.

In N1, the cancer has spread to the nearest lymph nodes around the airways, to the hilum (a central zone in the lung where blood and lymph vessels enter), or both. The tumor has extended directly into lymph nodes within the lung. In N2, the cancer has spread to lymph nodes in the middle of the chest that are still next to the affected lung, to the nodes below the carina, or to both regions.

In N3 the cancer has spread to lymph nodes in the middle of the chest that are next to the opposite lung, to the hilum in the opposite lung, to lymph nodes in nearby or opposite muscle tissue, or to lymph nodes above the collar bone.

M Stages refer to metastasis. In M0, metastasis has not occurred.

In M1 distant metastasis has occurred. This includes the presence of a separate tumor in a different lobe.

Staging factors are used to help determine treatment and outlook. The following suggest a more aggressive disease:

The presence of respiratory symptoms
A tumor larger than 3 cm
High numbers of blood vessels in the tumor

Researchers are always looking for more accurate ways to determine a treatment and outlook for lung cancer. For example, some research involves specific biomarkers and related blood vessel development within tumors. These markers might eventually help determine how aggressive a cancer is likely to be, and what the best treatment approach is.

If the cancer is still localized, surgery can produce 5-year survival rates of up to 75% in stage I patients and up to 50% in stage II patients. Unfortunately, very few patients are diagnosed at such early stages. In locally advanced stages, the standard treatment is concurrent radiation and chemotherapy. However, even with this approach average survival times are less than 2 years. Even if an initial tumor has been surgically removed or irradiated, cancer recurrence rates are very high. The risk for recurrence is lower in smokers who quit after treatment.

On an encouraging note, advances in therapies for later stage lung cancer are now offering some hope for improving survival. Still at this time, the mortality rate for lung cancer is still extremely high, and reports of improved response or survival rates using drugs or combinations of therapies do not mean cures. Ultimately, the patient must weigh a diminished quality of life using aggressive treatments against a chance for a modestly prolonged life.

Surgical Procedures

Surgery is performed in the following circumstances:

The surgical removal of an entire lobe or parts of a lung is the primary treatment for eligible patients in early stages of cancer. Recurrence is high after surgery, although the new tumor is often operable.
Some patients with stage IIIA cancer may also benefit from surgery. The intent at this stage is to extend survival time, rather than cure the disease.
Surgery is not out of the question in rare cases of metastasis when the cancer appears in a single operable location, such as the brain.

Unfortunately, lung surgery may be too risky for patients with other lung diseases or serious medical conditions, and because lung cancers tend to occur in smokers over 50, such health problems are likely to be present. Long-term survival rates appear to be better in patients treated at hospitals that perform large numbers of lung cancer surgeries, and when surgeries are performed by thoracic surgeons, who specialize in chest procedures.

The type of surgery depends on the amount of lung or other tissue that needs to be removed.

Wedge Resection or Segmentectomy. Wedge resection and segmentectomy remove only a small part of the lung; consequently, they preserve almost normal breathing function after the operation.

Lobectomy. Removal of one of the lobes of the lung is called lobectomy. The patient's lung function must be adequate before undergoing this procedure. The operation carries an overall mortality rate of 3 - 5%, with older patients having the highest risk.

Click the icon to see an illustrated series detailing surgery to remove diseased lobes of the lung.

Pneumonectomy. Pneumonectomy removes the entire lung. The procedure itself carries a mortality rate of 5 - 8%, with the oldest patients having the greatest risk. In such patients, recurrence almost always occurs.

Surgical advances are allowing a wider range of options, including minimal surgeries for early cancers and surgeries that relieve cancer symptoms in late stages of the disease.

Thoracoscopy. Thoracoscopy, also known as video-assisted thoracic surgery (VATS), is a less-invasive technique that employs a thin tube containing a miniature camera and surgical instruments. It requires much smaller incisions than open surgery and speeds recovery to the point that patients are up within hours. Though the procedure is not appropriate in all cases, it offers significant advantages, especially in older or frail patients. The death and complication rates following VATS are lower than those following conventional surgeries. Pain is reduced, and patients are released from the hospital quicker. Several studies found that the 5-year survival and recurrence rates in patients with stage I NSCLC treated with VATS were comparable to those in patients treated with traditional open chest surgeries.

Laser Surgery. Laser surgeries allow removal of minimal amounts of lung tissue and are proving useful for improving symptoms in stage II and IIIA patients. They may also be beneficial in treating cancers that have spread to the throat, obstructing it.

Photodynamic Therapy. Photodynamic therapy uses bronchoscopy and special laser light beams combined with a light-sensitive drug, called porfimer sodium (Photofrin), to kill cancer cells. The most common side effect is sun sensitivity. Serious side effects include bleeding in the lungs. Photodynamic therapy may be considered for patients in early-stage disease who are not candidates for other surgical procedures. It may also be used to reduce symptoms in late-stage disease.

Cryosurgery. Cryosurgery uses a probe chilled to below freezing to destroy the tumor cells on contact and is being investigated in combination with radiation therapy. It may also be an alternative in early stage cancer for patients who cannot have surgery.

Electric Cauterization. Electric cauterization, the use of electricity to produce heat that destroys tissue, is also under investigation as a treatment for early-stage disease.

Back Surgery. Spinal cord compression is a common cause of pain in patients with advanced lung cancer. Because such patients can live for a year or longer, some research indicates that back surgery followed by radiation therapy can significantly improve the quality of life for many of these patients.

Radiation Treatments

In addition to surgery, radiation is the other primary treatment for early-stage lung cancer. Doctors are also studying the benefits of radiation treatment in advanced lung cancer.

Radical Radiation in Early-Stage Cancer. Radical radiation is used as the sole procedure in stage I and some stage II patients who have adequate lung function but, for medical or other reasons, cannot be treated with surgery. In these cases, the 5-year survival rate is about 20%, and the cancer is likely to recur. Survival rates may be higher or lower, depending on the tumor size. In general, treatment with radiation therapy alone shows less benefit with larger tumors. A 2002 analysis suggested that the use of radiotherapy after surgery in patients whose tumors had been completely removed might be associated with reduced survival rates. Nevertheless, a recent study confirmed earlier results that show that radiation therapy by itself is as effective as surgery in patients who are unable or unwilling to have surgery for early stage non-small cell lung cancer.

Combined Treatments for Improving Survival in Advanced Cancer. Radiation is also being investigated in various combinations with chemotherapy, surgery, or both. At this time, concurrent radiation treatment plus platinum-based chemotherapy may extend survival times in advanced lung cancer. Other combinations are showing promise.

Palliative Radiation. Doctors use palliative radiation to shrink tumors and reduce pain and symptoms. Palliative radiation is appropriate for patients with advanced disease and poor lung functions, or in those with metastasized cancer. In up to 85% of patients with advanced disease, palliative radiation therapy helps relieve pain, shortness of breath, the superior vena cava syndrome, coughing up blood, and symptoms caused by brain metastases. Radiation, in these cases, is not generally used with the intention of reducing mortality rates, although it may increase survival in some patients, such as those with excellent lung function whose tumors are small.

Delaying radiation therapy until symptoms develop does not appear to reduce survival times or impair quality of life compared to starting it right away, in patients with minimal or no symptoms.

Radiation Therapy in Metastasis to the Brain. Radiation is the primary treatment when cancer has spread to the brain unless the cancer is small enough to be treated surgically. When radiation is used, a technique called stereotactic radiosurgery may be used to deliver powerful, highly targeted radiation to specific areas in the brain. Some trials are investigating using radiation to the head to prevent metastasis to the brain.

The goal of radiation treatment is to administer doses as high as possible to kill as many cancer cells as possible, without destroying surrounding healthy tissues or causing a dangerous reaction. Doctors may try different procedures for the same patient. The exact radiation procedure depends on the site of the cancer or how far it has spread:

External-Beam Radiation. External-beam radiation therapy focuses a beam of radiation directly on the tumor. It is generally used for metastasized cancer.
Brachytherapy. Brachytherapy involved the implantation of radioactive seeds through thin tubes directly into the cancer sites. Brachytherapy may be used for lung cancers that have spread to the throat and caused obstruction. High-dose-rate brachytherapy may also have some value for patients with inoperable tumors in the central region of the lung.

Hyperfractionated radiotherapy gives smaller than standard doses a number of times a day (usually two or three). This allows doctors to use a higher cumulative dose over the whole course of treatment. It is not as useful as therapy by itself, but should be combined with chemotherapy to have any survival benefits.

Hyperfractionated Accelerated Radiotherapy. Continuous hyperfractionated accelerated radiotherapy (CHART) administers multiple doses per day but uses standard doses. This allows the total dose of radiation to be administered over a shorter time period than the standard 6 weeks. CHART is proving to extend survival rates of patients with localized cancer over that of standard radiotherapy or non-accelerated hyperfractionated radiation. It can cause severe swallowing problems. A modification in which treatment is suspended for 2 days out of 7 may help reduce this effect.

Three-dimensional (3-D) conformal radiotherapy delivers external-beam radiation designed to closely match the specific targeted organs or tissues. This allows significantly higher doses to attack the cancer while reducing the risk to healthy cells. In a 2003 report, 3-year survival rates in stage IIIA patients were nearly 60%, and nearly half the patients experienced no side effects.

Stereotactic body radiotherapy, an advance on conformal radiation, uses a body frame and an abdominal press to immobilize the patient's body and limit breath movement. This allows a more accurate delivery of high-energy radiation. The technique is still investigational.

Radiation can have significant side effects when used as part of intensive treatments, such as hyperfractionated radiotherapy or radiotherapy in combination with chemotherapy. Among the most serious problems is severe inflammation in the esophagus (esophagitis) or the lungs (pneumonitis). Infection is also a danger.

The use of targeted approaches, such as conformal radiotherapy, may help reduce these complications. Investigators are also studying drugs, notably amifostine, which appear to help reduce throat and lung inflammation caused by radiation, without reducing its cancer-fighting effects.

Treatment Options by Stages

In the occult stage (TX, N0, M0), cancer cells are found in a sample of a patient's coughed-up sputum, but no cancer cells have yet been detected in the lung.

Treatment Options. Surgical removal of the tumor, if one can be located, allows identification of its stage and often results in cure.

Stage 0 or carcinoma in situ (Tis, N0, M0) are noninvasive cancers and only a few layers of cancer cells are detected within one local area. The cancer has not grown through to the top lining in the lung and can be surgically removed. There is a high risk for development of a second tumor, however.

Treatment Options:

Surgery, often a limited procedure, where only part of a lobe is removed from the lung.
In patients who cannot be treated surgically, consider photodynamic therapy, cryotherapy, or brachytherapy.

In stage I, the cancer has reached higher layers of the lung but has not spread into the lymph nodes or beyond the lung.

General Treatment Options. The primary treatment is surgery, such as lobectomy (removal of a whole lobe), if possible. Patients with poor lung function should undergo partial lobectomy, if possible. Radiation treatments may be appropriate and beneficial for patients who cannot have surgery. It is not clear if early-stage lung cancer patients, who have radiation or chemotherapy in addition to surgery, have higher survival rates. A 2002 analysis suggested that the use of radiotherapy after surgery in patients whose tumors had been completely removed might be associated with reduced survival rates. An analysis of studies using chemotherapy in addition to surgery or radiotherapy, however, indicated benefits in survival. The overall 5-year survival rates for early stage-cancer are in the range of 30 - 50%. Patients should consider clinical trials for prevention of recurring (returning) cancer after the initial treatment. The risk for recurrence is highest in patients who continue to smoke.

Stage IA (T1, N0, M0). The 5-year survival rates for stage IA patients after successful treatment can be as high as 80%. Treatment options are:
- Lobectomy or sometimes pneumonectomy (removal of one lung)
- Wedge or segment removal, particularly in patients with poor lung function who cannot withstand lobectomy
- Radiation in selected patients whose condition is inoperable (for example, frail patients with T1 tumors); 5-year survival rates can be equal to those with surgery, between 32 - 60%
- Clinical trials of adjuvant chemotherapy following surgery

Stage 1B (T2, N0, M0). Stage IB survival rates after treatment can be better than 60%. Treatment options are:
- Lobectomy or sometimes pneumonectomy; wedge or segment removal, particularly patients with poor lung function
- Clinical trials of chemotherapy following surgery
- Clinical trials of chemotherapy before surgery (induction therapy; studies are promising)
- Clinical trials for radiation treatments in selected patients whose condition is inoperable
- Clinical trials of chemotherapy before, after, or during radiation treatments

In stage II the cancer cells have spread to nearby lymph nodes.

General Treatment Options. Surgery, usually removal of a lobe (lobectomy) or one lung (pneumonectomy), is the treatment of choice. Five-year survival rates associated with stage II surgery can vary. A 2000 review of existing research places the numbers as high as 40 - 50%, but notes that they can drop to 25% and below if the cancer has spread beyond the immediate lymph nodes.

Patients whose cancer is inoperable may consider radiation treatments. In patients who can complete treatment, 5-year survival rates average 20 - 30%, with higher rates for stage IIA. Patients should consider clinical trials for prevention of recurring cancer after primary treatment. To date, however, supplementing surgical treatment with radiation or chemotherapy does not appear to prolong survival rates.

Stage IIA (T1, N1, M0). Survival rates can be as high as 60%. Treatment options are:
- Surgery
- Radiation
- Clinical trials of chemotherapy following surgery
- Clinical trials of chemotherapy before, after, or during radiation treatments
- Clinical trials of chemotherapy to reduce tumor size before surgery (induction therapy)
Stage IIB (T2, N1, M0) or (T3, N0, M0). Survival rates can be over 40%. Treatment options are:
- Surgery
- Radiation
- Clinical trials of chemotherapy following surgery
- Clinical trials of chemotherapy before surgery (induction therapy)
- Clinical trials of chemotherapy before, after, or given at the same time as radiation treatments

In stage III, the cancer cells have spread beyond the lung to the chest wall, diaphragm, or further lymph nodes, such as those in the neck.

General Treatment Options. Generally, the treatment of choice for stage III tumors is radiation and sometimes surgery, chemotherapy, or combinations of all three.

Combination approaches may be significantly more effective than single treatments. For example, of particular interest is a treatment approach that starts with chemotherapy and radiation, given at the same time, followed by surgery. In one study, 5-year survival in stage III patients treated this way was nearly 50%.

Stage IIIA (T1, N2, M0) or (T2, N2, M0) or (T3, N1, M0) or (T3, N2, M0).
- Surgery, if the tumor and affected lymph nodes can be completely removed. Consider platinum-based chemotherapy or radiation therapy after surgery.
- Radiation treatment plus platinum-based chemotherapy, given at the same time, is an option for those in otherwise good health. This regimen should be followed by surgery, if possible.
- Consider clinical trials using advanced radiation techniques, including continuous hyperfractionated accelerated radiation, or 3-D conformal radiation.
- Consider other clinical trials, including those of various combination treatments, preventive radiation therapy to the brain, and new second-line drugs.
Stage IIIB (Any T, N3, M0) or (T4, Any N, M0). Some patients may consider surgery if there is no lymph node involvement (T4, N0), and tumor can be removed. Surgery is not an option for other patients with stage IIIB cancer. Treatment options are:
- Radiation alone, usually for symptom control; it may improve survival in certain patients, such as those with lymph node involvement above the collar bone
- Chemotherapy alone
- Concurrent (given at the same time) cisplatin-based chemotherapy plus radiation, sometimes followed by surgery if possible
- Clinical trials using induction chemotherapy alone to shrink tumors, which may then be treated with surgery or radiation
- Clinical trials using advanced radiation techniques, including continuous hyperfractionated accelerated radiation, or 3-D conformal radiation
- Other clinical trials, including those of various combination treatments, preventive radiation therapy to the brain, and new second-line drugs

In stage IV (any T, any N, M1), the cancer has spread (metastasized) to other parts of the body.

Treatment Options are:

Combination of two- or three-drug chemotherapies that include platinum-based drugs and newer agents; the best patient candidates are those in otherwise good health, who have a limited number of distant metastasized sites. Chemotherapy is not recommended for patients who are too ill
External-beam radiation for symptom relief
Paclitaxel or gemcitabine as a single medication
Other clinical trials
If metastasized cancer involves only one or two areas in the brain, it may respond to surgery followed by radiation to the brain

Recurring or additional new tumors occur, usually in the lung again, in half of treated patients. Research shows that a single tumor in the lung is more often a new tumor that, in many cases, may be operable.

Treatment Options are:

Radiation for symptom control
Chemotherapy with or without bevacisumab (Avastin)
If the cancer spread to only one site in the brain, it may respond to surgery, followed by whole-brain radiation. Extended disease-free survival is possible. If the brain tumor is not operable, it is treated with radiation. Even if cancer returns in the brain (in 50% of cases), treating it again is possible in many patients, if the disease has not spread elsewhere
Laser therapy or interstitial radiation for tumors inside the airways
Stereotactic radiosurgery (in a few selected patients)

Chemotherapy Treatments

Chemotherapy is the use of drugs given by mouth or by injection to destroy cancer cells that may have spread beyond the tumor. Until recently, there has been some doubt about the effectiveness of chemotherapy for lung cancer. A major 2002 analysis of 52 trials supported its use, particularly with platinum-based regimens, and with the use of supportive care.

Chemotherapy in early stages: Chemotherapy is proving to be beneficial in many patients as an additional (adjuvant) treatment with surgery or radiation.
Chemotherapy in advanced disease: Chemotherapy may be used as first-line treatment in patients with inoperable or metastasized lung cancer. It is typically used in late stages to reduce symptoms and, in some cases, extend survival. Since 2006, the combination of bevacizumab (Avastin, a monoclonal antibody) and platinum-based chemotherapy is also a first line treatment choice for such patients, if the cancer is the non-squamous type

Powerful platinum compounds, either cisplatin (Platinol) or carboplatin (Paraplatin), are the basis for most chemotherapy regimens. Two-drug combinations, with one drug being a platinum-based agent, are currently the preferred regimens. Reasonable combinations include paclitaxel (Taxol) and carboplatin or cisplatin. This regimen can also include gemcitabine, docetaxel, or vinblastine or its derivative (vindesine or vinorelbine). There does not seem to be any significant differences in effectiveness among them. Gemcitabine and vinorelbine combination might be a good option for patients who cannot tolerate platinum compounds. Chemotherapy for lung cancer may have reached its peak. Still, investigative chemotherapeutic drugs may yet improve response. Many experts are pinning their hope on agents called biologic response modifiers, such as gefitinib (Iressa) or LY900003 (Affinitak). To date, however, they have not achieved better results than standard platinum-based chemotherapies. Gefitinib (Iressa), a second-line therapy for non-small cell lung cancer (NSCLC), is now available only for a limited group of patients. These patients have benefited from gefitinib in the past, or they are enrolled in a clinical study with the drug. While this medicine initially showed great promise in clinical trials, results from a newer study failed to show that it prolonged survival in advanced lung cancer patients who failed other treatments.

If you are currently taking gefitinib, do not stop taking it without talking to your doctor.

Erlotinib (Tarceva) is in the same medication class as gefitinib. It is approved for patients with locally advanced or metastatic NSCLC, who have failed one type of chemotherapy treatment in the past (it is a second-line treatment). Unlike gefitinib, erlotinib shows survival and progression-free benefits compared to placebo. However, it should not be combined with platinum-based chemotherapy.

Chemotherapy treatments are usually performed in an outpatient setting and in regular cycles for several months. How many chemotherapy cycles to administer in late-stage cancers, the timing of those cycles, and the sequences of the drugs are still matters of investigation. For instance, research suggests that a three- or four-course cycle may achieve the same survival times and better quality of life than the standard of six or more course cycles. Changing even one day in a drug sequence can sometimes significantly affect outcome. Such fine-tuning of chemotherapy regimens is likely to have the most effect on patients with advanced-stage disease, which requires more tailored treatment than early-stage disease.

Treatment for lung cancer depends on the type of cancer and the stage of the disease. Chemotherapy is a form of treatment for lung cancer that may cure, shrink, or keep the cancer from spreading.

Side effects of chemotherapy treatments are common, and they are more severe with higher doses. Side effects increase over the course of treatment. Some trials suggest that they can be reduced by giving the drugs for shorter durations, without loss of cancer-killing effects. Common side effects include the following:

Diarrhea
Temporary hair loss
Weight loss
Fatigue
Depression
Nausea and vomiting: Drugs known as serotonin antagonists, especially ondansetron (Zofran), can relieve these two side effects. Serotonin antagonists work well in nearly all patients given moderate drugs, and in most patients who take drugs that are more powerful. In one study, a combination of dexamethasone (a steroid) with ondansetron, taken within 24 hours of chemotherapy, achieved either a major or complete reduction in nausea and vomiting.
Anemia: Anemia, an abnormally low number of red blood cells, is common in lung cancer. Treatments include transfusions or injections of erythropoietin, an agent that causes more red blood cell production. Erythropoietin is available as epoetin alfa (Epogen, Procrit) and darbepoetin alfa (Aranesp), which requires fewer injections. These agents improve well-being and quality of life. Trials are in progress to determine if they may have survival benefits as well.

These side effects are nearly always temporary. Most patients are able to continue with normal activities for all but perhaps 1 or 2 days per month.

Serious complications of chemotherapy can also occur and may vary depending on the specific drugs. They include the following:

Increased chance for infection from suppression of the immune system.
Severe drops in white blood cells (neutropenia): Certain chemotherapy drugs, such as taxanes, pose a higher risk for this complication than other drugs. White blood cell count can improve with the addition of a type of drug called granulocyte colony-stimulating factor (filgrastim and lenograstim).
Liver and kidney damage: Amifostine (Ethyol) reduces the risk for kidney damage in patients taking repeated regimens of cisplatin-based therapy. It is also a radioprotector; that is, it helps prevent severe effects in the esophagus from radiotherapy, with or without chemotherapy.
Abnormal blood clotting (thrombocytopenia).
Allergic reaction, particularly to platinum-based agents: A simple skin test is under investigation that may identify people with a potential allergic response.

Second-line chemotherapy is used for patients whose cancers have recurred after first-line chemotherapy. Some experts believe that the longer survival rates for advanced lung cancer seen for the past 5 years may be due to these drugs. Because platinum-based agents are most often used first, they are not beneficial for second-line therapy. The following are commonly used second-line agents.

Docetaxel (Taxotere). Docetaxel is the drug of choice at this time for cancers that do not respond to initial chemotherapy. Studies have reported that it achieves longer survival times than supportive care alone. It is usually given every 21 days. This regimen causes more side effects than pemetrexed, the newer major second-line drug. Weekly doses of docetaxel are effective and less toxic than the 3-week schedule. It is not clear if survival rates are comparable to those of pemetrexed with that schedule, however.

Pemetrexed (Alimta). Pemetrexed, known as an anti-folate, is another promising new agent for second-line therapy and possibly for first-line treatment as well. The drug targets a number of enzymes that play a role in how cancer cells increase. Some research suggests that it is as effective as docetaxel. Pemetrexed does have some serious toxic effects, but they can be significantly reduced with folic acid and vitamin B12 supplements. It is then less toxic than docetaxel, when docetaxel is given every 21 days, but not when it is given weekly.

Gefitinib (Iressa) and Other Tyrosine Kinase Inhibitors. Much research is focusing on drugs that block small molecules involved with the growth of blood vessels that feed the tumor (a process called angiogenesis). Compounds called growth factors, which may be important in cancer cell production, control the growth of these new blood vessels. Researchers, then, are interested in medications that literally turn off these growth factors or their receptors, such as epidermal growth factor receptor (EGFR). In so doing, the agents may be able to cut off cancer's lifeblood. Gefitinib and erlotinib are angiogenesis inhibitors that target receptors of an epidermal growth factor called tyrosine kinase. Interestingly, studies are finding that NSCLC tumors in people who have never smoked have a much higher rate of EGFR mutations. This helps to explain why gefitinib and erlotinib are more effective in treating NSCLC in people who have never smoked.

Gefitinib (Iressa) was approved in 2003 as a second-line therapy for non-small cell lung cancer. Many patients report significant improvement in symptoms and quality of life, and the drug initially showed great promise. In one study, gefitinib reduced tumor size by 50% in about 10% of the patients. However, recent large-scale clinical trial results have failed to confirm any survival advantage for most patients. At this time, gefitinib is available only for patients who have benefited from it in the past.
Erlotinib (Tarceva) was approved as a single agent second-line therapy in November 2004. Study results show that the drug prolonged survival by several more months than placebo (6.7 versus 4.7 months). Erlotinib is administered orally and has very low toxicity (rash and diarrhea are common).

Chemotherapy Following Surgery (Adjuvant Chemotherapy). Chemotherapy is being evaluated in combination with surgery, radiation therapy, or both. Fairly strong evidence is now supporting the use of platinum-based chemotherapy as adjuvant treatment after surgery in patients with lung cancers in stages Ib-IIIa, with some research indicating a 5% improvement in five-year survival rates. Not all studies confirm survival benefits, however, and trials are ongoing.

Chemotherapy before Surgery (Induction Chemotherapy). Some researchers are testing induction chemotherapy, which is used to shrink potentially operable tumors before surgery. Studies have been mixed in reporting any survival benefits in patients with advanced lung cancer.

Combined and Multi-Modal Therapy. In stage III cancers, investigators are researching very intensive treatments that use two or more combinations of chemotherapy, radiation, and surgery.

For example, radiation plus chemotherapy may be helpful in patients whose tumors are surgically removable.

In inoperable lung cancer, combining radiation with chemotherapy is proving to extend the time to recurrence, the overall duration of survival, or both, compared to radiation alone. Evidence also suggests that giving radiation treatments at the same time as chemotherapy (instead of in separate cycles) improves 5-year survival rates, compared to a sequential approach (separate cycles following each other). Chemotherapy and radiation treatments given at the same time are more toxic, however.

Other approaches use even more intensive multi-modal therapy. For example, some trials use radiation therapy with chemotherapy, followed by surgery. Patients are then sometimes given additional chemotherapy or radiation. In other promising regimens, patents are given concurrent radiation and chemotherapy followed by chemotherapy alone. Such approaches are very toxic but appear to improve survival in selected patients.

Severe inflammation in the esophagus is the most common severe side effect of the radiation and chemotherapy combination. There is also a very high risk of serious infections, including pneumonia, herpes zoster, and cytomegalovirus. Long-term antibiotic therapy may be needed.

Although patients over 70 may suffer more from toxic effects than younger patients, studies now suggest that they can achieve survival rates with combined treatments that are equal to those in younger patients.

There are many painkilling medications available. Research shows that aggressive pain relief can help patients manage cancer treatment symptoms (in addition to pain) better. For example, a 2001 study suggested that reducing pain in elderly cancer patients markedly lowered their fatigue levels, and improved other symptoms as well.

Opioids are the most potent painkillers. The correct use of these strong medications is very important for reaching acceptable pain relief, and preventing a toxic response. For example, the long-lasting version of oxycodone (OxyContin) must be swallowed whole; chewing, inhaling, or injecting it can create a deadly overdose.

Investigative Agents

According to a 2001 article, of the nearly 500 cancer drugs currently in development, 58 of them (about 13%) are aimed at fighting lung cancer. Only the number of breast cancer drugs exceeded that percentage. Unfortunately, none to date have shown any real benefit in terms of patient survival. However, some drugs are showing promise, and at this time, these agents are the best hope for improving lung cancer survival rates.

Monoclonal antibodies (MAbs) are genetically designed immune factors. MAbs mark foreign compounds called antigens for attack by the immune system. Trastuzumab (Herceptin) and cetuximab (Erbitux) are MAbs under investigation for lung cancer. Bevacizumab (Avastin) was approved in October 2006 as a first-line treatment (in combination with carboplatin and paclitaxel) for inoperable, locally advanced, metastatic, or recurrent non-squamous, non-small cell lung cancer.

All three of these MAbs block epidermal growth factor. These agents are of particular interest for patients who have cancers that produce too much of the protein called HER2. These agents show great promise in combination with chemotherapies and newer drugs, such as the tyrosine kinase inhibitors. For example, the disease-free survival time in patients with advanced NSCLC is longer when adding bevacizumab to platinum-based chemotherapy.

Antisense oligonucleotides are drugs being used to block molecules that result in too many cells that cause cancers. LY900003 (Affinitak), for example, targets an enzyme called PKC-alpha, which promotes tumor growth. Early studies with Affinitak showed some promising results. However, a 2003 study found no difference in survival when patients received Affinitak in combination with platinum-based chemotherapy, compared to patients receiving chemotherapy alone.

Genasense (G3139, oblimersen) blocks Bcl-2. Bcl-2 is a protein that is expressed in abnormally high amounts in some cancers. This antisense drug is also under investigation.

Advexin, a genetic therapy that contains the p53 tumor-suppressor gene, is showing promise. In one early study, 60% of patients experienced partial or total tumor shrinkage when the agent was used in combination with radiation therapy. A 2006 study in Japan found that out of 13 patients with advanced NSCLC receiving Advexin, 10 had stabilized. Three of the stabilized patients remained stable for over 9 months. One patient had a partial response to Advexin. The only side effect of the multiple doses given was a passing fever that disappeared within 24 hours. Advexin is in Phase II clinical trials for NSCLC.

Vaccines use inactivated genetic materials from cancer cells, such as defective p53 or ras genes, to cause a highly targeted immune response to attack the cancer.

Retinoids are vitamin A-like antioxidant chemicals that help repair cell damage and appear to support growth of lung cells. A number of retinoid-like agents (retinal palmitate, TAC-101, 23-cis-retinoic acid, N-acetyl-cysteine) are being studied for the treatment or prevention of lung cancer.

Resources

www.cancer.gov -- National Cancer Institute
www.cancer.org -- American Cancer Society
www.cancercare.org -- Cancer Care
www.lungusa.org -- The American Lung Association
www.asco.org -- American Society of Clinical Oncology
www.alcase.org -- Alliance for Lung Cancer
www.lungcancer.org -- Joint project of Cancer Care and the Oncology Nursing Society
www.nccn.org -- National Comprehensive Cancer Network
www.lungcanceronline.org -- Lung cancer information
www.epa.gov/iaq/radon -- National radon information
www.clinicaltrials.gov -- Find clinical trials
www.cancer.gov/clinicaltrials -- Find clinical trials

References

Abeloff MD, Armitage JO, Niederhuber JE, Kastan MB, McKena WG. Clinical Oncology. 3rd ed. Orlando, Fl: Churchill Livingstone; 2004:1690-1701.

American Cancer Society. Cancer Facts and Figures 2006. Atlanta, Ga: American Cancer Society; 2006.

American Cancer Society. Cancer Facts and Figures 2007. Atlanta, Ga.: American Cancer Society; 2007:34.

Janne PA. Non-small Cell Lung Cancer in Never-smokers: A Biologically and Clinically Distinct Type of Lung Cancer. In: ASCO 2007 Educational Book. Meeting of the American Society of Clinical Oncology, Chicago, Ill.: June 1-5, 2007.

Kagawa S, Fujiwara T, Saijo Y, et al. A multicenter phase I study of adenoviral p53 (ADVEXIN) in Japanese patients with advanced non-small cell lung cancer. Journal of Clinical Oncology. 2006 ASCO Annual Meeting Proceedings Part I. Vol 24, No. 18S (June 20 Supplement), 2006: 2564.

Mehra R, Moore BA, Crothers K, Tetrault J, Fiellin DA. The association between marijuana smoking and lung cancer: a systematic review. Arch Intern Med. 2006 Jul 10;166(13):1359-67.

National Cancer Institute. Lung Cancer Home Page. Bethesda, Md.: U.S. National Institutes of Health. Available online.

National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Non-Small Cell Lung Cancer. Version 1.2007. Available online.

Tarceva [Package Insert]. Melville, NY: OSI Pharmaceuticals; 2005.

U.S. Department of Health and Human Services. The Health Consequences of Involuntary Exposure to Tobacco Smoke: A Report of the Surgeon General. Atlanta, Georgia: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, Coordinating Center for Health Promotion, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2006.

U.S. Food and Drug Administration, Center for Drug Evaluation and Research. List of Approved Oncology Drugs with Approved Indications. In: Oncology Tools. Available online.

U.S. Preventive Services Task Force. Lung cancer screening. Ann Int Med. 2004;140:738-739.

Xin M, Deng X. Nicotine Inactivation of the Proapoptotic Function of Bax through Phosphorylation. J Biol Chem. 2005 Mar 18;280(11):10781-9.

Review Date:
8/3/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Thyroiditis

FitSugar — Wed, 08 Oct 2008 17:35:33 -0700

Overview

Signs and Symptoms
What Causes It?
What to Expect at Your Provider's Office
Treatment Options
Following Up
Special Considerations
Supporting Research

HEALTH GUIDE REFERENCE FROM A.D.A.M

Thyroiditis is an inflammation of the thyroid gland. There are several types of thyroiditis. Most result in three phases: overactive thyroid (hyperthyroidism), underactive thyroid (hypothyroidism), and return to normal. When the thyroid is inflamed, it often releases an excess of thyroid hormone, resulting in hyperthyroidism. As the supply of thyroid hormone is depleted, the body has too little, and hypothyroidism the results. Young to middle-aged women seem most at risk, although some forms of thyroiditis occur in both men and women of all ages. With some forms, hypothyroidism may develop years later even if the thyroiditis has resolved.

Signs and Symptoms

Depending on the type of thyroiditis, the thyroid gland can have one of the following characteristics:

Firm and enlarged, but not tender
Enlarged and painful, with pain extending to the jaw or ears
Enlarged but not painful
Enlarged on only one side, hard like a stone, and sticking to other neck structures

You may also have one or more of the following symptoms:

Cool, dry skin, slow pulse rate (less than 60 beats per minute), swelling around the eyes, hoarseness, or slow reflexes
No desire to eat, feeling tired and unenergetic, and a slight fever
A rapid heartbeat, slight nervousness, anxiety, weight loss of 5 - 10 pounds, and increased sweating

What Causes It?

Immune disorders, viruses, and fever disorders can cause thyroiditis. Sometimes thyroiditis develops if you have Graves' disease (an autoimmune disorder that causes hyperthyroidism). In some cases, there is no identifiable cause.

What to Expect at Your Provider's Office

Your health care provider will feel your neck to see what the thyroid gland feels like and may order blood tests to check the levels of thyroid hormones and other factors. You may be given pain medication or something to help you feel more normal.

Natural medicine practitioners often take a different view of laboratory analysis of thyroid function. Many naturally oriented physicians pay particular attention to levels of T3 hormone, the active form of thyroid hormone that is converted in the body from T4, an inactive thyroid hormone. Conventional lab tests usually monitor T4 and thyroid stimulating hormone (TSH) without examining levels of T3. People with hypothyroidism may be treated with T4 to bring their levels of T4 to normal limits. Meanwhile, if you are unable to convert T4 to T3, your tests may be normal but you may still experience the symptoms of hypothyroidism. Talk to your doctor about including T3 lab tests in the treatment of hypothyroidism.

Treatment Options

Thyroiditis generally involves three phases: overactive phase, underactive phase, and return to normal. Treatment is individualized to type and phase.

Drug Therapies

Depending on the particular type of thyroiditis, a physician may prescribe one or some of the following treatments:

Levothyroxine, if hypothyroidism or large goiter present
Aspirin, to relieve pain and inflammation
Corticosteroid medications (such as prednisone or dexamethasone), to reduce inflammation in severe cases
Propanolol, for hyperthyroidism
Thyroxine, to replace thyroid hormone (in cases of hypothyroidism)
Short-term beta-blockers, for hyperthyroid symptoms
Antibiotics

Surgical and Other Procedures

Rarely, partial thyroid removal may relieve pressure.

Complementary and Alternative Therapies

Alternative therapies can help when used along with the medications your health care provider prescribes, but do not replace your conventional medications.

Nutrition and Supplements

Foods that depress thyroid activity are broccoli, cabbage, brussels sprouts, cauliflower, kale, spinach, turnips, soy, beans, and mustard greens. You should include these foods in a diet for hyperthyroid conditions -- and avoid them if you have a hypothyroid condition. Use caution because people with thyroiditis can switch from hyperthyroidism to hypothyroidism very quickly.
Avoid refined foods, sugar, dairy products, wheat, caffeine, alcohol.
Essential fatty acids (1,000 - 1,500 mg three times per day), found in flaxseed oil, fish oil, and borage oil, are anti-inflammatory and necessary for hormone production.
Bromelain (250 - 500 mg three times per day between meals), an enzyme from the pineapple plant, may reduce inflammation.
Vitamin C (1,000 mg per day), vitamin A (10,000 - 25,000 IU per day), B complex [(50 -100 mg per day), augmented with vitamins B2 (riboflavin, 10 mg), B3 (niacin, 10 - 25 mg), and B6 (pyridoxine, 5 - 15 mg)], selenium (200 mcg per day), vitamin E (400 IU per day), and zinc (30 mg per day) are necessary for normal thyroid hormone production.
Calcium (1,000 mg per day) and magnesium (200 - 600 mg per day) may help metabolic processes function correctly.
If you take thyroid hormone medication, talk to your doctor before consuming soy products. Some evidence suggests that soy may interfere with absorption of thyroid hormone.
Iron may also interfere with the absorption of thyroid hormone medication.

Your health care provider may also recommend specific nutritional supplements for a hyperthyroid or hypothyroid condition.

Herbs

Herbs are generally a safe way to strengthen and tone the body's systems. As with any therapy, you should work with your health care provider to get your problem diagnosed before starting any treatment. You may use herbs as dried extracts (capsules, powders, teas), glycerites (glycerine extracts), or tinctures (alcohol extracts). Unless otherwise indicated, you should make teas with 1 tsp. herb per cup of hot water. Steep covered 5 - 10 minutes for leaf or flowers, and 10 - 20 minutes for roots. Drink 2 - 4 cups per day. You may use tinctures alone or in combination as noted.

Talk to your health care provider before taking herbs for thyroiditis, particularly if you are also taking prescription medication.

For hyperthyroid conditions:

Bugleweed (Lycopus virginica) and lemon balm (Melissa officinalis) help normalize the overactive thyroid. Steep the following amount in one cup of boiling water. Strain and cool. For bugleweed, 1 - 2 g; for lemon balm, 2 tablespoons. These herbs may be combined.
Motherwort (Leonurus cardiaca) can help regulate rapid heartbeat. Steep 2 g in one cup of boiling water. Strain and cool. Drink three times per day.
Turmeric (Curcuma longa) makes the effect of bromelain stronger and should be taken between meals, 500 mg three times per day.
Avoid ashwagandha (Withania somnifera) and bladderwrack (Fucus vesiculosus ), as they can stimulate hyperthyroidism.

For hypothyroid conditions:

Coleus forskohlii (50 - 100 mg two to three times per day) may stimulate thyroid function to increase thyroid hormone.
Herbs such as guggul (Commiphora mikul) (25 mg of guggulsterones three times per day) and hawthorne (Crataegus monogyna) (500 mg twice a day) are taken to counteract high cholesterol, which often accompanies hypothyroidism.

You should carefully monitor any treatment for lowering or raising thyroid function because thyroiditis may switch from hyperthyroidism to hypothyroidism very quickly.

Homeopathy

Homeopathy may be useful as a supportive therapy for both "hyper" and "hypo" conditions of the thyroid.

Physical Medicine

Exercise helps improve thyroid function for both hypothyroidism and hyperthyroidism..

Acupuncture

Acupuncture may help correct hormonal imbalances and address underlying deficiencies and excesses involved in thyroiditis.

Massage

Therapeutic massage may relieve stress and increase the sense of well-being.

Following Up

You may need to see your health care provider each year.

Special Considerations

If you are pregnant or just had a baby, you may develop Hashimoto's thyroiditis.

Supporting Research

Blumenthal M, ed. The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. Boston, Mass: Integrative Medicine Communications; 1998:432.

The Burton Goldberg Group, compilers. Alternative Medicine: The Definitive Guide. Tiburon, Calif: Future Medicine Publishing Inc; 1997.

Ferri FF. Ferri's Clinical Advisor: Instant Diagnosis and Treatment. St. Louis, Mo: Mosby-Year Book;1999.

Hoffman D. The New Holistic Herbal. New York, NY: Barnes & Noble Books; 1995:95.

Messina M, Redmond G. Effects of soy protein and soybean isoflavones on thyroid function in healthy adults and hypothyroid patients: a review of the relevant literature. Thyroid. 2006 Mar;16(3):249-58.

Murray MT, Pizzorno JE. Encyclopedia of Natural Medicine. 2nd ed. Rocklin, Calif: Prima Publishing; 1998:386-390.

Noble J, ed. Textbook of Primary Care Medicine. 2nd ed. St. Louis, Mo: Mosby-Year Book; 1996.

Panda S, Kar A. Changes in thyroid hormone concentrations after administration of ashwagandha root extract to adult male mice. J Pharm Pharmacol. 1998;50:1065-1068.

Roger PP, Servais P. Dumont JE. Regulation of dog thyroid epithelial cell cycle by forskolin, an adenylate cyclase activator. Exp Cell Res. 1990;172:282-92.

Tierney LM Jr, McPhee SJ, Papadakis MA, eds. Current Medical Diagnosis and Treatment. Norwalk, Conn: Appleton & Lange; 1994.

Review Date:
6/15/2006
Reviewed By:
Steven D. Ehrlich, N.M.D., private practice specializing in complementary and alternative medicine, Phoenix, AZ. Review provided by VeriMed Healthcare Network.

A.D.A.M. Copyright

adam.com

Melanoma and other skin cancers

FitSugar — Wed, 08 Oct 2008 17:35:01 -0700

In This Report

Highlights
Introduction
Melanoma
Nonmelanoma Skin Cancer
Precancerous Skin Condition...
Causes
Risk Factors
Prevention
Screening
Diagnosis
Staging
Treatment for Melanoma
Treatment for Nonmelanoma S...
Prognosis
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Risk factors

According to a report in the Archives of Dermatology, marathon runners are more likely than the general population to develop skin changes that increase the risk for melanoma.

Prevention

A study published in The Lancet indicates that the best ways to avoid sun damage are to reduce the time you spend in the sun and to wear a hat and clothing to protect as much of your skin as possible. Fabrics that are thick and tightly woven offer the best protection.

The U.S. Food and Drug Administration has approved a new type of sunscreen that may more effectively block UVA than products currently available in the United States. UVA light penetrates the skin deeper than other forms of sunlight. Exposure to UVA is believed to contribute to skin cancers. The new sunscreen, called Anthelios SX, is available over the counter.

Screening

A study published in CANCER has shown that older men are more likely to undergo a whole body skin exam if they understand their personal risk factors for melanoma and know where to go to have such an exam. The study emphasizes the importance of skin cancer awareness and education.

One-time melanoma screening for adults over age 50 seems to be as cost-effective as other nationally recommended cancer screening programs, according to a report in the Archives of Dermatology. The study authors also found that screening brothers and sisters of someone with melanoma every 2 years may also be cost-effective.

Diagnosis

Dermatologists detect melanoma earlier than other health care providers, according to an article in the Archives of Dermatology. The earlier melanoma is diagnosed and treated, the greater your chances of survival.

Introduction

Skin cancer is cancer that starts in the skin. Skin cancers are divided into two major groups:

Nonmelanoma, which includes basal cell cancer and squamous cell cancer
Melanoma, the deadliest form of skin cancer

Different skin cancers start in different layers or cells of the skin. To understand how skin cancer develops, it is useful to know something about the skin.

The Skin. The skin is the largest organ in the body and consists of layers.

The outermost layer of the skin is called the epidermis. It is only about 20 cells deep, roughly as thick as a sheet of paper.
The dermis ranges in thickness from 1 - 4 millimeters (about 1/32 - 1/8 inch). The dermis contains tiny blood and lymph vessels, which increase in number deeper in the skin.

The skin is the largest organ of the body. The skin and its derivatives (hair, nails, sweat, and oil glands) make up the integumentary system. One of the main functions of the skin is protection. It protects the body from external factors, such as bacteria, chemicals, and temperature. The skin contains secretions that can kill bacteria, and the pigment melanin provides a chemical pigment defense against ultraviolet light that can damage skin cells. The skin also helps control body temperature.

Melanocytes. A layer of cells between the epidermis and the dermis, called melanocytes, produces a brown-black skin pigment ( melanin) that determines skin and hair color. Melanin also helps protect against the damaging rays of the sun.

As a person ages, melanocytes often proliferate, forming concentrated clusters that appear on the surface as small, dark, flat, or dome-shaped spots, which are usually harmless moles or liver spots.

When cell proliferation occurs in a controlled and contained manner, the resulting lesion is benign and is commonly referred to as a mole or nevus.
Sometimes, however, pigment cells grow out of control and become a cancerous and life-threatening melanoma.

Click the icon to see an image of melanin.

Melanoma

At first, melanoma cells are found in the epidermis and top layers of the dermis. However, once they grow downward into the dermis, the cancer can come into contact with lymph and blood vessels. The thicker the melanoma, the greater the likelihood that it could spread to distant sites.

Removal of the lesion before it reaches the deeper layers of the skin is important for achieving a cure.

Superficial Spreading Melanoma. Superficial spreading melanoma is the most common and most curable. It is flat, asymmetrical, unevenly colored, and usually grows outward across the surface of the skin.

Nodular Melanoma. Nodular melanoma appears as a fast-growing brown or black lump, and its characteristics do not always fit the definitions described above. It is important to check for this type of melanoma because it is associated with an outbreak of other tumors.

Lentigo Maligna. Lentigo maligna (sometimes called Hutchinson's freckle) usually occurs in elderly people and is marked by flat, mottled, tan-to-brown freckle-like spots with irregular borders. These lesions often appear on the face or other sun-exposed areas and typically enlarge slowly for 5 - 15 years before cancer appears.

Acral Lentiginous Melanoma. Although rare, acral lentiginous melanoma is the most common melanoma among African and Asian populations. It commonly appears as a dark patch on the palms, soles, fingers, toes, under fingernails or toenails, or in mucous membranes.

Melanoma cells usually spread first through the lymph vessels or glands. Melanoma cells can also spread by way of blood vessels to various organs, spreading cancer to the liver, lungs, brain, or other sites.

Melanomas tend to grow in stages:

Most melanomas tend to be flat initially and spread laterally across the skin surface as they grow. At this early stage, which can last 1 - 5 years or longer, removal of the growth has an excellent chance of curing the melanoma. Still, there is a chance that some of these melanomas are invasive, and they should be treated aggressively.
Lesions that become raised or dome-shaped over at least part of their surface indicate that downward growth has occurred. In some cases, this growth is very rapid, occurring over a period of weeks to months.

Any suspicious lesion should be checked immediately, particularly if it has grown quickly or is partially flat and partially raised.

Common sites of melanoma in men include:

Head
Middle of the body (trunk)
Neck

Common sites of melanoma in women include:

Arms
Legs

However, any area of the skin may be affected. You may not notice melanomas if they appear on areas that are difficult to examine, such as the scalp or the back.

Less common sites for melanoma include:

Fingers
Palms
Soles of the feet
Genitals
Lips
Under the fingernails or toenails

The presence of a dark lesion under the nail that runs into the adjoining skin and doesn't heal may signal melanoma.

Rarely, melanomas appear in the mouth, in the iris of the eye, or in the retina at the back of the eye, where they may be detected during dental or eye examinations.

Click the icon to see an image of melanoma.

Nonmelanoma Skin Cancer

The two other types of skin cancers are called basal cell cancer and squamous cell cancer. These are nonmelanoma skin cancers.

Basal cell cancer starts in the lowest part of the epidermis in round cells called basal cells. Basal cell is the most common form of skin cancer. It occurs in about 800,000 - 900,000 people every year.

Basal cell cancer usually develops later in life in areas that have received the most sun exposure, such as the head, neck, back, and especially the nose. However, some basal cell cancers appear in areas not exposed to the sun.

Basal cell cancers have many different appearances:

They usually appear as a round area of thickened skin that does not change color or cause pain or itching.
Very slowly, the lesion spreads out and develops a slightly raised edge, which may be translucent and smooth. Infrequently, basal cell cancers resemble malignant melanomas in color.
Eventually, the center becomes hollowed and covered with a thin skin, which can become sore and open.
A form known as aggressive-growth basal cell cancer resembles a scar with a hard base. This type is more likely to spread and must be treated very aggressively.

Basal cell cancer is a cancerous (malignant) skin tumor involving basal skin cells. Basal cell skin cancers usually occur on areas of skin that are regularly exposed to sunlight or other ultraviolet radiation. Once a suspicious lesion is found, a biopsy is needed to prove the diagnosis of basal cell cancer. Treatment varies depending on the size, depth, and location of the cancer.

Basal cell cancers are sometimes hard to tell from benign skin conditions. For instance, occasionally they arise in unexposed skin, where they may mimic an ordinary mole, cyst, or pimple. They may be particularly difficult to distinguish from benign cysts when they occur near the eyes.

Usually, basal cells grow slowly. They are rarely deadly. Most basal cell cancers need not be treated as an emergency, although late treatment can cause disfigurement, so they should be removed as early as possible.

Basal cell cancers that are most likely to spread include those that are larger than 1 centimeter, scar-like, and those located on the cheek, nose, neck, earlobe, eyelid, or temple.

Some studies have shown that people with basal cell cancer may be at higher risk for second cancers, including melanoma, cancer of the lip, salivary glands, larynx, lung, breast, and kidney, and non-Hodgkin's lymphoma. Those at higher risk for such cancers appear to be men and anyone diagnosed before 60 with basal cell cancer.

Squamous cell cancer develops from flat, scale-like skin cells called keratinocytes, which lie under the top layer of the epidermis. Most squamous cell cancers occur on sun-exposed areas, especially the forehead, temple, ears, neck, and back of the hands. People who have spent considerable time sunbathing may develop them on their lower legs.

Types of squamous cell cancer:

Squamous cell carcinoma in situ (also called Bowen's disease) is the earliest form of this type of cancer. The cancer has not spread. Cancer areas appear as large reddish patches (often over 1 inch) that are scaly and crusted.
Invasive squamous cell carcinoma is highly likely to spread (metastasize). The skin cancer lesions can grown rapidly (over months) or slowly (over years). Eventually they become ulcerated.

Click the icon to see an image of squamous cell cancer.

Prompt treatment is desirable because squamous cell cancers are more likely to spread to local lymph nodes than basal cell cancer. Squamous cell cancers most likely to spread include:

Deep lesions, those larger than 2 cm in diameter, or patches with poorly defined margins
Recurrent lesions
Squamous cell cancer on neck, earlobe, eyelid, lips, or temple
Squamous cell cancer that develops in ulcers
Squamous cell cancer that develops on skin areas that have been previously treated with radiation or exposed to cancer-killing chemicals

People with squamous cell cancers seem to be at higher risk for other cancers, including melanoma, lung cancer, non-Hodgkin's lymphoma, bladder cancer, leukemia, testicular and prostate cancer in men, and breast cancer in women.

Precancerous Skin Conditions

Actinic (Solar) Keratosis. Actinic keratosis (also called solar keratosis) is a precancerous skin lesion caused by too much sun exposure. Such lesions can turn into cancer, but not always.

Actinic keratoses occur after years of sun exposure. They appear predominantly on sun-exposed skin, such as the face, neck, back of the hands and forearms, upper chest, and upper back. Men may develop keratoses along the rim of the ear.

Actinic keratoses have the following characteristics:

Lesions typically occur on the surface of the skin and have a sandpaper-like feel. In fact, they are sometimes more easily felt than seen.
Most lesions are pink and even flesh-colored. Some are red or brown, scaly, and tender. At times, they can resemble melanomas; even dermatologists may have trouble telling the two apart.
They can range in size from microscopic to several inches in diameter.

Keratoacanthomas. Keratoacanthomas closely resemble squamous cell cancers, but they are not malignant. The majority occur in sun-exposed skin, usually on the hands or face. They are typically skin colored or slightly red when they first develop, but their appearance typically changes:

In the early stages, keratoacanthomas are smooth, red, and dome shaped.
Within a few weeks, they can grow rapidly, usually to 1 or 2 centimeters. Some reach the size of a quarter in less than a month and can be rather disfiguring.
They eventually stop growing and become crater-like with a surrounding outer rim of tissue and sometimes have a crusty interior.

Most will spontaneously get better within 1 year, but they almost always scar after healing. Also about 25% develop into squamous cell cancers, most frequently in older people and in sun-exposed areas. Removal by surgery (sometimes by radiation) is recommended. They may also be treated with 5-fluorouracil, either as a cream or injections.

Causes

You cannot overestimate the role of the sun as the most important cause of prematurely aging skin (called photoaging ) and skin cancers.

Long-term repetitive and cumulative exposure to sunlight appears to be responsible for the vast majority of undesirable consequences of aging skin, including basal cell and squamous cell cancers.

Melanoma is more likely to be caused by intense exposure to sunlight in early life.

UVA and UVB Radiation. When sunlight penetrates the top layers of the skin, ultraviolet (UVA or UVB) radiation strikes the DNA inside the skin cells and damages it.

UVB is the main type of radiation responsible for sunburns. It primarily affects the outer skin layers. This type of ultraviolet light is most intense at midday when sunlight is brightest.
UVA penetrates more deeply and efficiently. Unlike UVB, window glass does not filter out UVA rays.

Damaging Effects of UV Radiation. Both UVA and UVB rays cause damage, including genetic injury, wrinkles, lower immunity against infection, aging skin disorders, and cancer, although the mechanisms are not yet fully clear. The following are some ways in which cancer may develop and some defensive actions that the skin uses to defend itself against DNA damage.

Oxidation and Antioxidants. The effects of UV radiation are implicated in the production of oxidants, also called free radicals. Free radicals are unstable molecules produced by normal chemical processes in the body that, in excess, can damage the body's cells and even alter the DNA. This contributes to the aging process and sometimes to cancer.
Defective DNA Repair and Protective Enzymes. Some skin cancers are caused by a breakdown in the body's mechanisms that help repair DNA damage. For example, xeroderma pigmentosum (XP) is a rare genetic disease in which the body cannot repair damage caused by ultraviolet light. Normally, a number of enzymes in the skin help protect against this damage.
Breakdown of Immune Protection. Specific immune factors protect the skin, including white blood cells called T lymphocytes and specialized skin cells called Langerhans cells. These immune system cells attack developing cancer cells at the very earliest stages. However, certain substances in the skin, particularly a chemical called urocanic acid, can suppress such immune factors when exposed to sunlight.

Defective Cell Death (Apoptosis). Apoptosis is the last defense of the immune system. It is a natural process of cell-suicide, which occurs when cells are very severely damaged. Apoptosis in the skin kills off cells harmed by UVA so that they do not turn cancerous. The peeling after sunburn is the result of these dead skin cells. However, some gene defects or other factors interfere with apoptosis. If this occurs, damaged cells can continue to spread, resulting in skin cancer.

A number of genetic factors are being investigated for their role in melanomas, including inherited genes and genetic defects that are acquired from environmental assaults (particularly sunlight).

Mutations in Genes that Regulate Cell Growth. Noninherited mutations in a number of genes that block tumor growth or other cell-protecting properties may account for cancerous changes in moles and for aggressive melanomas. The following are some examples.

Important studies have now identified a mutation in the BRAF gene that appears to be the most common event in the process that leads to melanoma. Some researchers have observed mutations in 66% of malignant melanomas. Researchers hope that agents that block this gene may be a viable treatment path.
P16 is a tumor suppressive gene that may be abnormal in some melanoma cases.
Genetic mutations that regulate Ku70 and Ku80 proteins may disrupt processes that repair strands of DNA.
Researchers are also studying mutations in a gene that encodes for a substance called epidermal growth factor (EGF). EGF plays a role in skin cell growth and wound healing, and may account for many sporadic (non-inherited) cases of melanoma.
Of further interest are mutations in genes that regulate Fas proteins, which are involved in apoptosis, a natural process of cell self-destruction. When apoptosis goes awry in melanoma cells, proliferation can become rampant.

CDKN2A Mutations. Mutations in a gene regulator called CDKN2A are the most common causes of inherited melanoma, which is still very uncommon. Mutations in this gene also appear in non-inherited cases of melanoma. Genetic tests are being developed for CDKN2A, although it is not clear if knowing the results of the test would benefit people carrying the gene.

Variations in the Melanocortin-1 Receptor Gene. One study found that the greater the number of variations from normal in a gene called the melanocortin-1 receptor gene, the greater the risk for melanoma. The gene plays an important role in determining if a person has red hair, fair skin, and sensitivity to UV radiation. Interestingly, people who had olive and darker skin and who carried one or more variations of the gene had a higher than average risk for melanoma.

Aging may weaken the body's ability to fend off impending cancers, including melanomas. As a person ages, they lose Langerhans cells that help fight off early skin cancers. The number of these immune cells decreases with age, possibly setting the stage for skin cancers in later life.

Risk Factors

In the United States, the rate of melanoma is rising more rapidly than any other cancer. According to the American Cancer Society, about 59,940 persons will be diagnosed with melanoma in 2007. More than 8,000 people will die from the cancer.

Survival rates have been improving, however, and the increase in melanomas has occurred principally with thin, less aggressive forms of the disease. Some experts believe this is due to the increased awareness from effective public programs and earlier diagnosis.

A risk factor is anything that increases your chance of getting a disease. The following factors increase your risk for skin cancer:

Age over 40
Being male
Fair skin
Too much exposure to sunlight and ultraviolet radiation
Personal history of skin cancer
Family history of skin cancer
Smoking
Certain chronic or severe skin problems
Certain medical conditions or treatments that affect your immune system
Exposure to chemicals or radiation

Melanoma in Adults. Melanoma is most common in people over 40, and the incidence increases significantly as people get older. Before age 40, melanomas are slightly more common in women than men, but after age 40 men are more often affected. Men are also more likely to have invasive and fatal melanoma than are women, although some research suggests that the higher rates are only because men fail to seek a diagnosis of suspicious skin changes before they become dangerous. The rate in women levels off somewhat between age 45 and 60; researchers speculate that menopause could have some sort of protective effect during those years.

Melanoma in Children. Melanoma is rare in children under age 10. Among children ages 10 - 14 the incidence is only 0.3 per 100,000. Between ages 14 - 19, it is still very rare, 1.3 per 100,000. Parents, then, should not be unduly alarmed by every minor skin imperfection in their children. Nevertheless, melanoma is as serious in children as in adults, and early detection is still critical.

Skin cancer is associated with both duration and intensity of sun exposure. Risk of melanoma increases with excessive sun exposure during the first 10 - 18 years of life. Sunburns are also dangerous, with five or more sunburns doubling the risk of developing cancer. Cancer typically arises many years later.

Marathon runners are more likely than the general population to develop skin changes that increase your risk for melanoma. That's because marathon runners spend a lot of time outdoors. The study findings are published in the Archives of Dermatology.

Tanning Devices. Tanning beds and sunlamps increase the risk for developing melanoma, according to a 2005 review of epidemiologic studies. Previous findings have suggested that women who use tanning devices more than once a month significantly increase their melanoma risk. Women in their 20s, as well as blondes and redheads, are especially at risk.

Ethnic Groups and Complexion. People with light skin, blue, gray, or green eyes, red or blond hair, and lots of freckles are at highest risk for developing melanoma. The risk increases for those who are easily sunburned and rarely tan, particularly if they live close to the equator where sunlight is most intense. Darker ethnic groups or those with swarthy complexions are not immune, however.

Experts have devised a classification system for skin phototypes (SPTs) based on the sensitivity to sunlight. It ranges from SPT I (lightest skin plus other factors) to IV (darkest skin). Tanning and Sunburn Risk People with skin types I and II are at highest risk for photoaging skin diseases, including cancer. It should be noted, however, that premature aging from sunlight can affect people of all skin shades.


Skin Type	Tanning and Burning Risk
I	Always burns, never tans, sensitive to sun exposure.
II	Burns easily, tans minimally.
III	Burns moderately, tans gradually to light brown.
IV	Burns minimally, always tans well to moderately brown.
V	Rarely burns, tans profusely to dark.
VI	Never burns, deeply pigmented, least sensitive.

Australia has the highest melanoma rate in the world. In the United States the rate is highest in California, Florida, and Texas. The disease is by no means limited to such sunny states and countries, however. In general, the risks are highest in regions where the population tends to be blonde and fair-skinned. Norway, for example, has had the highest rate of melanoma in Europe, and rates are soaring in the UK, particularly among men, perhaps because Britons are increasingly vacationing in sunny climates.

Melanoma. Individuals who have been diagnosed with melanoma are at increased risk for a second primary melanoma. According to one 2003 study, the risk over time for developing a second melanoma is 1% in the first year after diagnosis, 2.1% at 5 years, 3.2% at 10 years, and 5.3% at 20 years. The risk is especially higher in older men and in those with first melanomas on the upper body and face.

People with family members who have or had melanoma should also be considered at high risk and examined on a regular basis.

Nonmelanoma Skin Cancers. Nonmelanoma skin cancers, including basal and squamous cell carcinomas, increase the risk of dying from other cancers, including melanoma itself, lung cancer, non-Hodgkin's lymphoma, bladder cancer, and leukemia as well as testicular and prostate cancers (in men) and breast cancer (in women).

Psoriasis. Psoriasis increases the risk for squamous cell carcinoma, but studies conflict on whether it has any effect on melanoma. One study, in fact, reported a lower risk. Nevertheless, there is some evidence that long-term treatment for psoriasis using UVA radiation (PUVA) may increase the risk for melanoma. In one study, there was a significantly higher risk even with relatively few treatments. In one study, invasive melanoma had occurred in 2.8% of patients 15 or more years after the initial treatment.

Moles (Nevi) and Other Dark Blemishes. Certain moles and dark blemishes increase the risk for skin cancer. Any mole ( nevus) or other blemish that seems new, changing, or unusual in any way should be evaluated by a health care professional.

Some specific moles or dark blemishes that are risk factors for melanoma include:

Freckles. Freckles typically appear in children on sun-exposed areas and are usually evenly brown or tan. The more freckles a person develops as a child, the greater the risk for melanoma in adulthood.
Dysplastic (or Atypical) Nevi. About 30% of the population has moles called dysplastic nevi, or atypical moles. They are larger than ordinary moles (most are 5 mm across, about the size of a pencil eraser, or larger), have irregular borders, and are various shades or colors. Individuals who have dysplastic nevi plus a family history of melanoma (a syndrome known as FAMM) are at a high risk for developing melanoma at an early age (younger than 40). The risk for those with atypical moles and no family history of melanoma is less clear.
Large birthmarks (giant congenital nevi). Very large birthmarks more than 8 inches across are major risk factors for melanoma. In such cases, cancer usually appears by age 10. Medium-sized congenital nevi do not appear to increase the risk for melanoma. Whenever possible, very large birthmarks should be removed during infancy. Experts disagree, however, about whether small birthmarks need to be removed. Parents should watch any birthmark for changes.

The more moles one has the higher the risk that one of them will become cancerous, although the danger is still very small. A 2003 study estimated that the risk for a single mole to develop into melanoma by age 80 is 1 in 3,164 in men and 1 in 10,800 for women.

The risk is higher, however, with atypical moles. One study of people with melanoma indicated that the presence of even one atypical mole doubled the normal risk.

Some skin blemishes can look like -- but are not -- melanoma. Noncancerous moles typically have the following characteristics:

They generally remain small with clearly defined, regular borders, and uniform coloration. Some have a regular stippled or net-like pattern of pigmentation, however, and may even resemble early melanoma.
They typically first appear during childhood, puberty, or young adulthood. They may naturally grow, darken, or increase in number at certain times of life, such as adolescence or pregnancy.

Examples of moles or blemishes that may resemble skin cancer include:

Blue nevus. A benign mole that may easily be mistaken for melanoma. It is a blue-black, smooth, raised nodule and commonly occurs on the buttocks, hands, or feet.

Liver Spots. Liver spots are usually evenly brown or tan sun-induced lesions that are universal signs of aging. Occurring most noticeably on the hands and face, these harmless blemishes tend to enlarge and darken over time.

Spindle Cell (Spitz) Nevus. Children may develop a benign lesion called a spindle cell (or Spitz) nevus. The mole is firm, raised, and pink or reddish-brown. It may be smooth or scaly and usually appears on the face, particularly the cheeks. It is not harmful, but it may be difficult to differentiate from a melanoma, even for experts.

Non-Hodgkin's Lymphoma. Survivors of either non-Hodgkin's lymphoma or melanoma face a higher risk for the other malignancy. These may have common causes, such as exposure to UV radiation or shared genetic factors.

Human papillomavirus (HPV). Genital warts (human papillomavirus, or HPV) may also increase the risk of squamous cell cancer in the genital and anal areas and around fingernails.

Immunosuppression. Skin cancer risk is increased in persons whose immune systems are suppressed because of certain medications, organ transplantation, or medical conditions such as AIDS. Melanoma has also developed in patients who received heart transplants from donors who had the disease. Immune-suppressing drugs used to treat autoimmune disorders may also increase the risk of skin cancer. Potential skin cancer risks have been associated with the eczema drugs pimecrolimus (Elidel) and tacrolimus (Protopic).

Rheumatoid arthritis. Despite previous concerns, the rheumatoid arthritis drug etanercept (Enbrel) does not raise the risk for developing squamous cell skin cancer. The findings are reported in the Archives of Dermatology. Etanercept works by blocking tumor necrosis factor (TNF), an immune system chemical messenger that is involved in inflammatory processes and diseases.

Occupational exposure to radiation, such as in health care or industrial settings, may increase the risk for melanoma. Airline pilots, too, are at increased risk for melanoma. It is uncertain, however, whether this higher risk is from excessive exposure to ionizing radiation at high altitudes or because they have more opportunity to spend time in sunny regions. Experts disagree over whether frequent flyers are also at increased jeopardy.

Prevention

The best way to lower the risk your risk of skin cancer is to protect your skin from the sun and UV light.

Wear sunscreen. The use of sunscreens is complex, and everyone should understand how and when to use them. Follow instructions closely and reapply as directed after swimming or sweating. The bottom line is not that people should avoid sunscreens or sunblocks, but that they should always use them in combination with other sun-protective measures.

Many parents are now taking effective steps to protect their children, although experts worry that they are relying too much on sunscreen and less on other protective measures. Adolescents are at special risk for sun-related cancers because, according to a 2002 study, most of them do not take protective measures when out in the sun. According to the study, boys are less likely to use sunscreen than girls, but girls are more likely to get sunburn and use tanning salons more often.

The best way to prevent skin damage in any case is to avoid episodes of excessive sun exposure. The following are some specific guidelines:

Use sunscreens that block out both UVA and UVB radiation. Do not rely on sunscreen alone for sun protection. Also wear protective clothing and sunglasses.
Avoid exposure particularly during the hours of 10 a.m. to 4 p.m., when UV rays are the strongest.
Clouds and haze do not protect you from the sun and in some cases may intensify UVB rays.
Avoid reflective surfaces such as water, sand, concrete, and white-painted areas.
UV intensity depends on the angle of the sun, not heat or brightness. The dangers are greater the closer to the start of summer.
Skin burns faster at higher altitudes. One study suggested that an average complexioned person burns in 6 minutes at 11,000 feet at noon compared to 25 minutes at sea level.
Avoid sun lamps, tanning beds, and tanning salons. The machines use mostly high-output UVA rays. Some experts believe that 15 - 30 minutes at a tanning salon are as dangerous as a day spent in the sun. People should not be misled by advertising claims of "safe" tanning.

Wear protective clothing, sunglasses, and a hat to shield your face from the sun's rays. Special clothing can block out UV rays and is rated using sun protection factor (SPF) ratings or a system called the UPF (ultraviolet protection factor) index, with 50 UPF being the highest. (According to one study, this is a very reliable indicator of protection.) The clothing is expensive, however.

Everyone, including children, should wear hats with wide brims. (Even wearing a hat, however, may not be fully protective against skin cancers on the head and neck.)
People should look for loosely fitted, unbleached, tightly woven fabrics. The tighter the weave the more protective the garment.
Washing clothes over and over improves UPF by drawing fabrics together during shrinkage. An easy way to assess protection is simply to hold the garment up to a window or lamp and see how much light comes through. The less the better.
Everyone over age 1 should wear sunglasses that block all UVA and UVB rays when in the sun.

Click the icon to see a depiction of sun protection.

When choosing a sunscreen, look at the ingredients. Preparations that help block UV radiation are sometimes classified as sunscreens or sunblocks, according to the substances they contain. In general, sunscreens contain organic formulas and sunblocks inorganic formulas. However, the term sunblock is used less and less as sunscreens increasingly contain both kinds of ingredients:

Organic formulas contain UV-filtering chemicals such as octocrylene, octyl salicylate, homosalate, and octyl methoxycinnamate (block UVB), avobenzone-Parsol 1789 (blocks UVA), cinoxate, ethylhexyl p-methoxycinnamate (blocks UVB and small amounts of UVA), oxybenzone, and benzophenone-3 (blocks UVA/UVB). People should look for a wide-spectrum sunscreen that contains combinations of these ingredients and filter both UVA and UVB. Of note: para-amino benzoic acid (PABA), once a popular ingredient, is now used infrequently. PABA may actually break down in the presence of UV exposure and release harmful oxidants. And many people have an allergic reaction to it. Some products contain PABA derivatives, such as padimate O or octyl dimethyl PABA.
Inorganic formulas contain the UV-blocking pigments zinc oxide or titanium dioxide. Zinc and titanium oxides lie on top of the skin and are not absorbed. They prevent nearly all UVA and UVB rays from reaching the skin. Older sunblocks are white, pasty, and unattractive, but current products use so-called microfine oxides, either zinc (Z-Cote) or titanium. They are transparent and nearly as protective as the older types. Microfine zinc oxide may be more protective and less pasty-colored than microfine titanium oxide.

Inexpensive products work as well as expensive ones with the same ingredients. Unfortunately, there are still no standards for sunscreens, and even those claiming UVA protection may offer very little.

Organic formulas and inorganic microfine oxides do not protect against visible light, which is a problem for people who have light-sensitive skin conditions, including actinic prurigo, porphyria, and chronic actinic dermatitis.

Calculating the SPF. SPF is a ratio based on the amount of UVB radiation needed to turn sunscreen- or sunblock-treated skin red compared to non-treated skin. For instance, people who sunburn in 5 minutes and who want to stay in the sun for 150 minutes might use an SPF 30. The formula would be: 30 (the SPF number) times 5 (minutes to burn) = 150 minutes in the sun.

Protection offered by sunscreens may be classified as follows:

Minimal: SPF 2 to 11
Moderate: SPF 12 through 29
High: 30+

Although some sunscreens claim SPFs higher than 30, the added protection at such higher levels is insignificant.

SPF Levels by Age Group. Although sunscreens are safe in most toddlers and children, they should not be the first and only lines of defense. All young children should be well-covered with clothing, sunglasses, and hats. Children should be kept out of the sun during peak sunlight periods. Do not use sunscreens on babies younger than 6 months without consulting a doctor.

Older children and adults (even those with darker skin) benefit from using SPFs of 15 and over. Some experts recommend that most people should use SPF 30 on the face and 15 on the body.

Adults who burn easily instead of tanning and anyone with risk factors for skin cancer should use at least SPF 30.

Timing and Amount of Application. Apply sunscreen or sunblock liberally as follows:

Adults should include sunscreen every day, even if going outdoors for only a short time.
Apply a large amount to all exposed areas, including ears and feet. To achieve protection as indicated by the sunscreen's SPF, experts recommend half a teaspoon each for the head, neck, and each arm and a teaspoon each for the chest area, the back, and each leg.
Apply initially 30 minutes before venturing outdoors for best results. This allows time for the sunscreen to be absorbed. Then reapply every 15 - 30 minutes while being in the sunlight.
Also reapply each time after exercise or swimming. Choose a waterproof or water-resistant formula even if activities don't include swimming. Waterproof formulas last for about 40 minutes in the water, whereas water-resistant formulas last half as long.
Insect repellents reduce sunscreen SPFs by up to one-third. Use higher SPFs and very liberal application when applying both.

Possible Hazards of Sunscreens, Sun Avoidance, or Both. When used generously and appropriately, sunscreen products and sun avoidance help reduce the severity of many aging skin disorders, including squamous cell cancers. There are certain concerns, however. Sunscreens do not appear to provide protection against melanoma and some basal cell cancers. In fact, some studies have reported a higher association with sunscreen use and these skin malignancies, though not all studies report such negative results.

The reasons for this possible increased risk are unclear, though some theories include:

Until recently, many sunscreens blocked only or predominantly blocked UVB rays and not UVA, the more deeply penetrating rays now known to be especially dangerous. Studies then may not have reflected the effects of the broad-spectrum sunscreens now available, which block both UVA and UVB.
People who apply sunscreens may stay out too long during peak sunlight hours. Even if a person doesn't sunburn, UVA rays can still penetrate the skin and do harm.
People may not put on enough sunscreen. A 2002 study found that people generally apply only 20 - 60% of the recommended amount, which can provide significantly less protection than the given SPF. A later study reported that when applied at the recommended amount, a broad-screen sunscreen prevents DNA damage from UV exposure.

Underexposure to sunlight. There is some major concern that underexposure to sunlight, due to the use of sunscreens or sun-avoidance measures, may produce other health problems such as:

Vitamin D deficiency. The body makes vitamin D through a chemical reaction to UVB sunlight. Too many sun-protection measures may increase the risk for developing vitamin D deficiency. Vitamin D helps prevent rickets, osteoporosis, and some cancers, including melanoma. People who need to avoid sunlight and whose diet is low in foods that contain vitamin D should check with their doctor about taking supplements. (Warning: Vitamin D is poisonous when taken in high doses.) People with darker skin are at higher risk for deficiencies from sun protection than those with whiter skin.
Other Cancers. Although sunlight is implicated in skin cancers, it is also associated with lower risks for breast, prostate, ovarian, and colon cancers. Some protection against these cancers may be related to vitamin D production by sunlight.
Depression. Many people suffer from seasonal affective disorder (SAD), a form of depression that generally occurs in winter and is associated with exposure to less sunlight.

The bottom line is that some sunlight is important and even necessary.

A study published in 1994 in the New England Journal of Medicine found that persons with a history of nonmelanoma skin cancer who ate a low-fat diet were much less likely to develop actinic keratosis, a precancerous skin condition.

However, the low-fat diet did not appear to have any effect on the development of basal cell cancer.

Chemoprevention is the use of a substance to prevent or reduce your risk of cancer. Certain drugs have been used to help block the development of skin cancers, including melanoma. For example, a medicine called imiquimod is approved to prevent skin cancer in certain individuals. This medicine prompts the immune system to fight off foreign substances, including cancer cells. Chemopreventive agents under investigation and showing promise for skin cancer include:

Nonsteroidal anti-inflammatory drugs
Difluoromethylornithine (DFMO)
Catechins (phytochemicals found in certain foods)
Anti-aging drugs called retinoids (vitamin A derivatives)

Retinoids have been shown to prevent nonmelanoma skin cancer in patients with basal cell nevus syndrome, xeroderma pigmentosum, and transplanted organs. Oral retinoids include isotretinoin and acitretin. They may also prevent the development of squamous cell carcinoma in patients who are taking such medicines to treat psoriasis.

Early animal studies had suggested that cholesterol-lowering statins or fibrates may reduce the risk of skin cancer, but human studies have produced inconsistent results. A review of several studies has concluded that such drugs do not decrease your risk of melanoma. The findings are published in the Journal of the National Cancer Institute.

Researchers are also studying chemopreventative compounds that target genetic mechanisms in the skin. They may prove to be beneficial ingredients in creams or lotions used to prevent skin cancers on a molecular level. They include cytokine interleukin-12 and T4 endonuclease 5 (T4N5).

Studies have shown that mice with round-the-clock access to an exercise wheel developed skin cancer more slowly when exposed to UVB. Their tumors were also fewer in number and smaller. Analysis of the data suggested that exercise might trigger the death of the developing cancer cells faster than they can grow. Exercise also made the mice lose weight, and the number of tumors decreased as fat disappeared.

Antioxidants are chemicals or drugs that help prevent cell damage from unstable molecules called free radicals. Antioxidants promote to protect the skin include vitamins C and E, and coenzyme Q10 (CoQ10).

Studies suggest that vitamin E creams, particularly those made from a type of Vitamin E called alpha tocopherol, decreased skin roughness, length of facial lines, and wrinkle depth. Studies on mice have also shown that such creams reduce UV-related skin cancer.

Vitamin C is a very potent antioxidant. It is also called ascorbic acid. Most studies on the effects of antioxidants on the skin have used this vitamin. In laboratory studies, large amounts reduced skin swelling and protected immune factors from sunlight.

Selenium in the form of L-selenomethionine has protected against sun damage and even delayed skin cancer in animal studies. It is not known if such benefits apply to people.

Click the icon to read about the antioxidant selenium.

Antioxidant Skin Creams. There are wide claims about the benefits of antioxidants for wrinkles when used in skin creams. However, to date, only vitamin E, C, and selenium-based skin products have been shown to help reduce sun damage to the skin. However, most available brands contain very low concentrations of these antioxidants. In addition, the antioxidants are also not well absorbed by the skin, so the effect may be short-term.

Antioxidant Pills. One small study found that taking a combination of vitamins C and E supplements by mouth may help reduce sunburn reactions, although the protection is much less than from sunscreens. Taking the vitamins alone does not appear to have the same effect.

Other Natural Substances. The following natural substances have antioxidant properties and are being tried for sun-protection:

Both green and black tea appear to have properties that may provide some protection against skin cancers and photoaging. A 2001 study using extracts of topical green tea suggested that it might protect against ultraviolet damage. Green tea skin care products are now available, but their quality is unregulated.
Ginger also appears to have some sun protective qualities.
Silymarin, a substance found in the milk thistle family (which includes artichokes), may prevent UVB-promoted cancers in animals.
Garlic has been shown to protect animals against UVB damage. Whether these results may be applied to humans, and what quantities of garlic might be beneficial, is still unknown.

Warning Note: A wide range of herbal products may contribute to dermatological problems. Some Chinese herbal creams have been found to contain corticosteroids. Mercury or arsenic contaminants have been found in some Ayurvedic therapies. In addition, several oral herbal remedies used for medical or emotional conditions may produce irritation in reaction to sunlight (photosensitivity). They include, but are not limited to, St. John's wort, kava, and yohimbe.

Screening

Education and prevention programs have led to improved screening for skin cancer, which in turn has improved diagnosis and survival rates for melanoma. For example, a study published in CANCER has shown that older men are more likely to undergo a whole body skin exam if they were aware of personal risk factors and where they could go to have an exam performed.

Skin cancers may have many different appearances. They can be small, shiny, or waxy, scaly and rough, firm and red, crusty or bleeding, or have other features. Itching, tenderness, scaling, bleeding, crusting, or sores can signal potentially cancerous changes in any mole.

A mnemonic device, ABCDE, is used to describe several features that help to distinguish skin cancer from noncancerous growths.

Asymmetry (A). Skin cancers usually grow in an irregular, asymmetric fashion. That means one half of the abnormal skin area is different than the other half.
Border Irregularity (B). Noncancerous lesions generally have clearly defined borders. Melanoma lesions often have notched or indistinct borders that may signal ongoing growth and spread of the cancer.
Color Variation (C). One of the earliest signs of melanoma may be the appearance of various colors within the lesion. Because melanomas arise within pigment-forming cells, they are often varicolored lesions of tan, dark brown, or black, reflecting the production of melanin pigment at different depths within the skin. Occasionally, lesions are flesh colored or surrounded by redness or lighter areas of depigmentation.
- Pink or red areas may result from inflammation of blood vessels within the skin.
- Blue areas reflect pigment in the deeper layers of the skin.
- White areas can arise from dead cancerous tissue.
Diameter (D). A diameter of 6 millimeters or larger (about the size of a pencil eraser) is worrisome. Melanomas start out small; by the time a lesion has grown this large, other abnormalities will most likely be present. A doctor should examine any suspicious lesion, no matter what size it is.
Evolution (E). A lesion that is growing or changing deserves evaluation.

The ABCDE plan is a general guide. It will not help detect the early stages of nodular melanoma and may also miss amelanotic melanoma, which is not pigmented.

You should keep in mind that the most important warning sign of melanoma is a new or changing skin lesion, regardless of size or color. Changes that occur over a short period of time (particularly over a few weeks) are most worrisome.

Anyone with risk factors for skin cancer should check the entire body about once a month. People who regularly check moles on their skin may have a lower risk of developing advanced melanoma.

Experts suggest drawing a map of the body, indicating locations of moles, areas of discoloration, lumps, or other blemishes. Whenever a person conducts a self-examination, they should compare their body to the map to check for new lesions, lumps, or moles and for changes in shape, color, and size.

Some experts have defined three specific body areas to look for skin cancers, including melanomas:

Areas visible to anyone, such as the arms or face -- about 60% of melanomas are found on such areas.
Areas usually covered with clothing and visible only to the patients or their partners -- about 34% of melanomas are detected in these areas.
Hidden areas such as the scalp, buttock folds, and mouth -- about 6% of melanomas, usually more advanced, are found here.

Ask a partner to help you check these areas. Turn on a hair dryer to separate hair and examine the scalp.

Some experts recommend that everyone, especially those with a high risk of developing melanoma, have a dermatologist perform a whole body skin exam. Dermatologists detect melanoma earlier than other health care providers, according to an article in the Archives of Dermatology.

High-risk people include those with a personal or family history of melanoma and individuals with atypical nevi (irregular moles that are also larger than normal).

Such people should protect themselves from overexposure to sunlight and have a medical examination of the entire skin surface every 3 - 12 months, with the frequency depending on risk factors. Doctors may take photographs of any moles at each visit and compare them with previous photos for any changes.

Examinations for Patients Previously Treated for Melanoma. People who have had melanoma and have been treated successfully are at risk for recurrence or a second primary melanoma. Based on recurrence rates by cancer stage, a team of researchers suggested the following guidelines for being reexamined by the doctor after treatment:

Stage I patients: Yearly exam
Stage II patients: Every 6 months for years 1 and 2 and annually thereafter
Stage III patients: Every 3 months for the first year, every 4 months for year 2, and every 6 months for years 3 to 5

All patients should be checked annually after year 5. These are guidelines only and may be changed, depending on individual patient characteristics.

Some studies also suggest that regular screening of family members of people with melanoma could prevent a number of serious cases. A 2007 report in the Archives of Dermatology has called for expanded melanoma screening programs. The study found that one-time melanoma screening for adults over age 50 seems to be as cost-effective as other recommended cancer screenings. The study authors also found that screening brothers and sisters of someone with melanoma every 2 years may also be cost-effective.

Diagnosis

An experienced doctor should first rule out benign conditions that resemble melanoma, such as a noncancerous mole called a melanocytic nevi.

In rare instances, a melanoma will be difficult to detect. For example, an uncommon form, called a myxoid melanoma, may be mistaken for a benign skin disorder known as a myxoid fibrohistiocytic lesion. Other opinions from a second pathologist, computerized image processing or advanced staining techniques, may help to confirm the diagnosis.

A study published in the Archives of Internal Medicine has found that melanoma tends to be diagnosed at a later stage in persons who are not light-skinned. The study involved nearly 50,000 patients with melanoma, and included Caucasians, Hispanics, Asian/Pacific Islanders, African-Americans, and American Indians.

Some doctors now use dermoscopy (also called dermatoscopy or epiluminescence microscopy). This technique uses a handheld scope-like device that enhances the suspected lesion. It is still not clear if such devices are any better than the naked eye of a trained professional. Of interest, however, was a 2002 study suggesting that it was very useful in identifying possible melanomas in suspicious nail abnormalities and therefore avoiding many painful biopsies in this area. A 2004 study confirmed that adding dermoscopy to conventional naked-eye examination leads to fewer biopsies than using naked-eye examination alone.

A recently developed Australian device (the Solarscan) may improve detection. It is shaped like a hair dryer and takes an image of the suspicious lesion; it then reads the image and compares it with a databank of melanoma images to help determine if it is cancerous. It can also store the image of the lesion and compare it for changes with later images taken at subsequent check ups. The device is not yet used in the United States. It still requires FDA approval. Testing is under way to confirm its accuracy.

A skin biopsy is the removal of skin tissue for examination under a microscope. The exact type of biopsy depends on how deep the lesion has penetrated the skin.

Shave biopsy uses a thin surgical blade to shave off the top layers of skin. The doctor may use this type of biopsy to diagnose basal cell cancer.
Punch biopsy uses a round, cookie-cutter-like tool. It is used to take a deeper sample skin.
Incisional and excisional biopsies remove tumors that have grown deep into the skin. An incisional biopsy cuts out part of the tumor. An excisional biopsy removes the entire tumor. These biopsies are used to diagnose melanoma.

All of the above-mentioned biopsies can be done using local anesthesia.

A lymph node biopsy helps the doctor determine whether cancer has spread to one or more lymph nodes.

A procedure called sentinel lymph node (SLN) biopsy is now recommended for cancers that are thicker than 1 millimeter and generally unnecessary for those thinner than 0.75 millimeter, unless they are ulcerated. Although some evidence suggests this procedure may improve survival, no clinical trials have proven to date that this procedure improves the outlook in persons with melanoma.

Sentinel node biopsy is a technique that helps determine if a cancer has spread. When a cancer has been detected, often the next step is to find the lymph node closest to the tumor site and retrieve it for analysis. The concept of the "sentinel" node, or the first node to drain the area of the cancer, allows a more accurate staging of the cancer, and leaves unaffected nodes behind to continue the important job of draining fluids. The procedure involves the injection of a dye (sometimes mildly radioactive) to pinpoint the lymph node which is closest to the cancer site. Sentinel node biopsy is used to stage many kinds of cancer, including melanoma.

This procedure involves the following:

A tiny amount of a tracer, either a radioactively labeled substance (radioisotope) or a blue dye, is injected into the tumor site.
These substances then flow through the lymph system into the sentinel node, the first lymph node to which any cancer would spread.
The sentinel lymph node and possibly one or two others are then removed and biopsied.

The results of the biopsy can help doctors decide whether or not to remove other lymph nodes:

If the sentinel node and others shows signs of cancer then the nearby lymph nodes are removed.
If they do not, then the remainder of the lymph nodes will likely be cancer-free, and further surgery is not needed.

If melanoma has been diagnosed, the doctor will perform other tests to see if the cancer has spread, such as a chest x-ray.

Blood tests that show high levels of lactate dehydrogenase suggest that the cancer has spread. Blood tests to assess liver function and other factors to help determine specific sites where the cancer may appear.

Advanced imaging techniques, such as computed tomography (CT) or positron emission tomography (PET), may also be used. PET is particularly accurate. One study reported that PET was able to diagnose melanoma that had spread even when other tests, including CT, did not. PET can also be very accurate for identifying recurrent melanomas.

Biomarkers are specific substances that are linked to cancer. Blood tests to detect biomarkers may be used to identify microscopic cancers if sentinel node biopsy results are uncertain. Researchers are continually investigating other biomarkers that may indicate whether the cancer had spread or how severe it is, which would help determine whether treatments should be more or less aggressive.

A number of proteins and other factors detected in blood tests are showing promise as markers for microscopic metastasis. Examples include antibodies to MART-1, Melan-A, tyrosinase, and microphthalmia transcription factor (Mitf). Combinations of some of these factors may improve detection rates.

Staging

Staging is the process used to determine the size of the tumor and where and how far it has spread. When a cancer spreads, it’s said to have metastasized. Staging helps the health care team plan for appropriate treatment.

Basal cell cancer is rarely staged, because it doesn't usually spread to other organs. However, it may be staged if it's very, very large.
Squamous cell cancer may be staged in persons who have a high risk of the cancer spreading.
Melanoma is always staged.

Health professionals have come up with various methods for staging the cancer. This report uses the TNM staging system recommended by American Joint Committee on Cancer.

T = tumor. T is followed by a number to indicate thickness.
N = node. N is followed by numbers to indicate the number of lymph nodes involved.
M = metastasis. Metastasis is the spread of cancer to far away sites.

In addition a stage will include whether the melanoma is ulcerated or not, an indication of severity. Ulceration is determined if skin layers over the tumor appear indistinct under the microscope.

In general, the thicker the lesion and the farther the cancer has spread, the higher the assigned stage. The higher the stage, the worse the long-term outlook.

The earliest melanomas, which do not penetrate beneath the surface of the skin and are known as melanoma in situ, are highly curable and are called stage 0 or not given a stage.
Melanomas less than 4 mm thick suggest Stage I or II cancers, and the next step is to attempt to determine if they have spread or are likely to spread to the lymph nodes.
Melanomas that are over 4 mm thick indicated later stages. In such cases, the lymph nodes are sometimes removed to attempt to prevent the cancer from spreading, although about 70% of these melanomas have already spread.

Specific stages are as follows:

Stage I. Cure rates are excellent with surgical removal, since they are least likely to have spread.

Stage 1A. Tumor has not spread to the nodes. It is less than 1 mm and is not ulcerated.
Stage IB. Tumor has not spread to the nodes. It is less than 1 mm, but is ulcerated, or the tumor is between 1.01 and 2 mm but is not ulcerated.

Stage II. Melanomas can be cured, but the success rate lags behind that of Stage I because a small number of cancer cells may have spread to distant sites. In addition to surgery, other forms of therapy may be recommended.

Stage IIA. Tumor has not spread to the nodes. It is between 1.01 and 2 mm and is ulcerated, or it is 2.01 to 4 mm without ulceration.
Stage IIB. Tumor has not spread to the nodes. It is between 2.01 and 4 mm and is ulcerated or greater than 4 mm without ulceration.

Stage III. Survival rate is lower than earlier stages.

Stage IIIA. Tumor has spread to 1 node and it is up to 4 mm without ulceration. Sentinel biopsy has detected microscopic evidence of tumor cells in the node (micrometastasis).
Stage IIIB. Tumor is up to 4 mm without ulceration and has spread to one node or there is evidence of micrometastasis in two nodes.
Stage IIIC. Tumor is any thickness and ulceration may or may not be present. It has spread to 2 or 3 nodes. Additional "satellite" melanomas on the skin more than 2 cm (about an inch) from the original lesion may be present; these are sometimes called "metastases in transit."

Treatment for Melanoma

Treatment for melanoma depends on various factors, including:

The site of the original lesion
The stage of the cancer
The patient's age and general health

Treatment options include:

Surgery to remove the melanoma cancer cells
Chemotherapy
Immunotherapy
Radiation therapy
Palliative therapy

Surgery is the primary treatment for all stages of melanoma. Some or all of the melanoma is often removed during the diagnosis biopsy. If cancerous tissue still remains after such a biopsy, a surgeon will cut away additional tissue from the surrounding area to remove any stray cancer cells.

Mohs micrographic surgery is a technique used to remove very thin layers of skin one at a time. Each layer is examined immediately under a microscope. When the layers are shown to be cancer-free, the surgery is complete.

The amount of tissue removed depends on the size, depth, and degree of invasion:

Stage I lesions that are less than 1 mm deep require the smallest surgical cuts, usually about 1 cm off each side and downward from the original lesion.
For melanomas that are 2 mm or thicker, a margin of 3 cm is important for reducing the risk of recurrence.
Thicker lesions require wider surgical cuts.

It used to be customary to remove a large area, regardless of the stage of cancer. This potentially disfiguring approach has been abandoned because studies have shown that excising wider margins does not improve survival. Nevertheless, sometimes skin grafts may need to be taken from other body sites to help cover the wound.

Lymph Node Removal. If there is evidence that melanoma has spread to nearby lymph nodes but has not spread beyond, removing them may reduce the chance of recurrence and help patients live longer.

Surgery for Metastatic Melanoma. In some cases, surgical removal of distant tumors may be possible and prolong survival, since often in melanoma the cancer spreads first only to a single site, such as the lung or the brain.

Cryosurgery. Cryosurgery freezes skin tissue and destroys it. This procedure is not useful for most melanomas, but it might have some value in specific situations. For example, it may be effective for smaller melanomas in the eye, a location that is difficult to treat with traditional surgery. It may be useful to eliminate residual cancer cells after standard surgery for lentigo maligna melanomas, an atypical form of melanoma that has a wide surface and is difficult to treat.

Recurrence rates are very high with lentigo maligna after conservative surgery. Although this is a very slowly progressive condition, lentigo maligna can develop into melanoma. Most of these lesions appear on the face and neck, so extensive surgery can be disfiguring. Patients should discuss with their doctor carefully staged surgery to remove all diseased tissue with as little cosmetic harm as possible.

Chemotherapy is often used to treat recurrent or metastatic melanomas. This type of therapy is not intended as a cure but can prolong life and improve its quality.

Drugs Used. The following are some of the chemotherapy drugs used to treat melanoma. They may be used alone or in combination under specific situations.

Methylating agents impair the ability of cancer cells to divide. Dacarbazine (DTIC) and temozolomide (Temodar) are the ones most often used.
Nitrosoureas, which include carmustine (BCNU) and lomustine (CCNU) are often used.
Taxanes, such as docetaxel (Taxotere) and paclitaxel (Taxol), are showing some low-level activity against melanoma.

Researchers continue to investigate other chemotherapy drugs and combinations of drugs to see which works best.

Side Effects. Side effects occur with all chemotherapy drugs. They are more severe with higher doses and increase over the course of treatment.

Common side effects include the following:

Nausea and vomiting
Diarrhea
Temporary hair loss
Weight loss
Fatigue
Anemia
Depression

Serious short- and long-term complications can also occur and may vary depending on the specific agents used. They include the following:

Increased chance for infection from suppression of the immune system.
Severe drops in white blood cells (neutropenia). Certain agents, such as taxanes, pose a higher risk for this than other chemotherapeutic drugs. White blood cell count may be improved with the addition of a drug called granulocyte colony-stimulating factor (either filgrastim or lenograstim).
Liver and kidney damage.
Abnormal blood clotting (thrombocytopenia).
Allergic reaction.
Menstrual abnormalities and infertility in women. A natural hormone medication called a gonadotropin-releasing hormone analogue that puts women in a temporary pre-pubescent state during chemotherapy may preserve fertility in some women.
Rarely, secondary cancers such as leukemia.
Problems in concentration, motor function, and memory, which may be long-term.

Treating Side Effects

Drugs known as serotonin antagonists, especially ondansetron (Zofran), can relieve nausea and vomiting in nearly all patients given moderate drugs and most patients who take more powerful drugs.

Erythropoietin stimulates red blood cell production and can help reduce or prevent anemia related to chemotherapy. It is available as epoetin alfa (Epogen, Procrit) and darbepoetin alfa (Aranesp). Aranesp persists longer in the blood than epoetin alfa and so requires fewer injections.

Benefits of Chemotherapy. About 20% of cancers shrink in response to one or more of these drugs, but the effects last only 3 - 6 months. If the tumors completely disappear, the cancer may stay in remission much longer, but in virtually all cases it returns.

Chemotherapeutic regional perfusion (also called isolated limb perfusion) is a technique used to give a person very high-dose chemotherapy. It is often used effectively for metastasized or recurrent melanoma that occurs on the arm or leg. It does not appear to be useful for preventing metastasis after a first occurrence of melanoma in one of these locations.

This technique involves the following:

The blood supply to the limb with melanoma is temporarily interrupted using a tourniquet and then rechanneled through a heart-lung machine.
Anticancer drugs are added to the blood in doses up to 10 times the standard doses.
The blood is then heated to enhance the drug's potency.
The chemo-infused blood is then sent directly to the melanoma site, minimizing the likelihood of drug toxicity.
Adverse effects occur in less than 1% of cases and include severe problems in the treated limb (rarely leading to amputation) and drug leakage into the bloodstream. This can severely reduce white blood cells and lead to serious infection.

In addition to arms and legs, perfusion techniques have been tested for the pelvis, head, neck, skin of the breast, and even the abdomen.

Immunotherapy uses drugs to boost the patient's own immune system. Immunotherapy after surgery may help prevent recurrence in certain persons with melanoma.

Cytokines. Cytokines are small proteins that play an important role in the body's immune response. Certain cytokines called interferons are used as a therapy for metastatic melanoma. These medicines are usually given along with chemotherapy or other immunotherapies, or both.

A number of cytokines and combinations are being investigated. They include:

Interferon alpha-2b (Intron) is the only FDA approved immunotherapy for late stage melanoma. The most common side effects are fatigue, depression, and flu-like symptoms, which can be severe. Starting an antidepressant, such as paroxetine (Paxil), several weeks before interferon therapy may help prevent depression.
Pegylated interferon and natural human interferon are long-acting forms are under investigation. One study showed that low-dose natural interferon after chemotherapy increased the 5-year relapse-free survival rate.
Interleukin-2 (Proleukin) is a hormone-like substance that stimulates the growth of cancer-fighting white blood cells. High-dose interleukin-2 has been shown to help patients with metastatic melanoma. The drug can cause significant side effects, including very low blood pressure, heart rhythm abnormalities, severe infections, and shortness of breath. The side effects are manageable and nearly always reversible.
Granulocyte-macrophage colony stimulating factor (GM-CSF, Leukine, Sargramostim) is an injectable cytokine under study. The drug boosts production of immune cells in the blood and bone marrow. An inhaled form of the drug is being tested for melanoma that has spread to the lungs.
T-cell therapy uses white blood cells, called tumor-infiltrating lymphocytes (TIL), that taken from the patient. The cells are modified so they better fight cancer and are then reinjected back into the patient. T-cell therapy is showing promising results, especially for patients with advanced melanoma who have failed to respond to other treatments.

A chemical called histamine is a powerful inhibitor of reactive oxygen species, ROS, which may inactivate immune cells that fight cancer. Researchers are investigating to see if it can be used along with interleukin-2 cytokine therapy. In one study, the added benefits of histamine were modest except in patients with liver metastatic; in these patients, survival improved by 129 days, which was significant.

Vaccine Immunotherapy. Vaccine immunotherapy is the use of a specific vaccine to treat an existing cancer. In this case, the vaccine targets one or more proteins that are uniquely expressed by melanoma cells.

Many therapeutic melanoma vaccines are in advanced stages of development, but none is approved for use in the United States.

There are two basic types of therapeutic vaccines:

Autologous vaccines
Allogenic vaccines

Sometimes a combination of the two are used. In this case, it's called a hybrid.

Autologous vaccines are made from the patient's own cancer cells. This produces a very specific immune response that can target the patient's cancer precisely. Oncophage (HSPPC-96) and M-Vax are autologous vaccines for melanoma that have shown promise in early clinical trials. One problem with the autologous approach is that there is no way to scientifically assess outcome or even guarantee repeated success since each vaccine is unique to the individual patient. This approach is also appropriate only for select patients.

Allogenic vaccines are made in a laboratory using cells from someone other than the patient. They may be made from proteins from tumor cells, genetic material, or even bacteria. One such vaccine is Canvaxin. Early studies showed this vaccine increased survival rates in some patients with Stage 3 melanoma. However, a later trial was halted because the vaccine did not appear to improve make such patients live any longer.

Vaccine immunotherapy requires the body to build up its own defenses. It can take months before beneficial effects occur, but when they do, tumor reduction is much more lasting than with chemotherapy. Vaccines also seem to have fewer side effects than interleukin and interferon.

Antisense Compounds. Antisense compounds can prevent defective cancer genes from being translated into proteins that cause abnormal cell proliferation.

Monoclonal Antibodies (MAb). Antibodies are natural substances produced by immune cells that home in and destroy cancer cells. Scientists are identifying specific antibodies that may attack melanoma cells and cloning them to create monoclonal antibodies. MAbs have shown promise for other cancers and are now being tested for melanoma, often in combination with vaccines and other forms of immunotherapy.

In general, radiation is used to help relieve pain and discomfort caused by cancer that has spread or recurred. Radiation is not used as often for treating melanoma as it is for other forms of cancer because melanoma cells tend to be more resistant to its effects. It may be useful in some cases, however.

In some patients with tumors less than 3 cm deep, however, radiation may help slow down metastasis when combined with a super-heating process using microwaves.
Brachytherapy, in which radioactive seeds are implanted close to the tumor, has also been used with success for melanoma of the eye.
Lentigo maligna may sometimes be treated successfully with specific radiation treatments called soft, or Grenz, x-rays.
Radiotherapy using a so-called gamma knife (very focused gamma radiation) is also effective for cancer that has metastasized to the brain, in some cases halting the growth and, in rare situations, even eliminating it.

The goal of palliative therapy is to improve the patient's quality of life and relieve symptoms. It is not a cure. Advanced melanoma that has spread to distant sites often cannot be cured, although surgical removal of metastatic tumors may provide some benefit by easing pain, increasing the general quality of life, and lengthening survival.

Patients should ask their doctor's about clinical trials, studies that examine new immunotherapies (vaccines, cytokines), gene therapies, chemotherapy combinations, or other treatments.

Tetracyclines. Chemically modified tetracyclines, a common antibiotic, have been shown to modify metalloproteinase, an enzyme in the skin that promotes skin cancers, including melanoma.

Anti-Angiogenesis Agents. An anti-angiogenesis drug is one that blocks the formation of new blood vessels. The growth of new blood vessels helps cancer cells grow and spread. The anti-angiogenesis drug thalidomide (Thalomid) is approved for treatment of melanoma but requires special prescribing precautions. This drug had gained notoriety in the 1960s because of devastating birth defects in the children of women who took it during pregnancy. Scientists are investigating drugs that are chemically similar to thalidomide but have fewer side effects.

Curcumin. The yellow spice found in turmeric and curry powders may contain cancer-fighting properties. In a preliminary laboratory study, curcumin stopped the growth of melanoma cells. It is far too early, however, to recommend curcumin for clinical use.

Treatment for Nonmelanoma Skin Cancer

A number of options are available for treating nonmelanoma skin cancer, including surgery, cryosurgery, phototherapy, radiation, and topical 5-fluorouracil.

For any skin cancer and for some keratoses that require removal, surgery is the first treatment. It is usually one of the following:

Excisional Surgery. This is the surgical removal of the cancerous lesion.

Curettage and Electrodesiccation. This procedure involves scraping away of the cancerous tissue followed by electric cauterization to stop the bleeding.

Mohs Micrographic Surgery. Mohs surgery is a meticulous procedure used for skin cancers at high risk for recurrence or becoming invasive. The technique removes very thin layers of skin one at a time. Each layer is examined immediately under a microscope. When the layers are shown to be cancer-free, the surgery is complete. A human skin substitute (Apligraf) is applied to the surgical area. It helps speed up wound healing to achieve a better cosmetic effect.

Good candidates for Mohs surgery include:

Persons with squamous cell cancer
Persons with basal cell cancer greater than 1 cm (about half an inch)
Persons with basal cell cancer on the face, ear, or neck
Young people with skin cancer

Mohs surgery saves more healthy tissue than other procedures and is highly effective. It results in a 99% cure rate for primary tumors and a 95% cure rate for recurrent ones. It can be safely performed in the doctor's office. Complications are uncommon but can include bleeding and infection.

Lasers. Laser surgery may be useful for certain basal cells and for keratoses that appear on the lips, although it is not clear whether lasers offer any advantages over other surgical treatments. Lasers do not appear to be very effective for thick or tough squamous cell cancers.

Cryosurgery removes skin cancer cells or actinic keratoses by freezing the affected tissue with liquid nitrogen. Studies have shown that cyrosurgery can be used to remove even wide areas of actinic keratoses and that it may be more successful over the long term than treatment with 5-fluorouracil, the standard drug. Cryosurgery also appears to reduce the risk for squamous cell cancer in these patients.

A head-to-head comparison of a freezing technique with Mohs micrographic surgery in patients with basal cell cancer reported similar recurrence rates with each approach. Over 85% of the patients with the freezing technique were satisfied with the appearance of the area afterwards. Five-year recurrence rates were only 2.1%.

Cryotherapy achieves good cosmetic results for many patients. However, it may cause blistering and ulceration, leading to pain and infection, as well as harmless, but undesirable, skin-color changes.

In unusual cases where the skin cancer may be in an inoperable position (such as the eyelid or the tip of the nose) or if cancer has recurred multiple times, radiation therapy may be indicated. Radiation is directed at the tumor. It may take 1 - 4 weeks with treatments performed several times a week. One technique being investigated for basal and squamous cell cancer uses radiation implants (brachytherapy) and custom-made molds to specifically target the radiation to the cancer site. Studies suggest that this treatment is very effective with few complications.

Topical phototherapy with the drug aminolevulinic acid (ALA) is a nonsurgical method that is proving to be a good choice for treating actinic keratoses and nonmelanoma skin cancers. The technique involves shining blue light onto the cancer area after that patient has taken ALA. ALA accumulates in the skin cells. When the cells are exposed to intense light, the chemical causes them to die. This approach allows precise targeting of one or more lesions, leaving healthy skin unaffected.

It does not penetrate deeper than the epidermis (the top layer of the skin), so it does not produce scarring or changes in skin color, as cryotherapy or other more invasive treatments do.

It can cause pain and irritation, including stinging, itching, and burning, but in one study only 3% of patients stopped using it for these reasons. In a 2002 study, the procedure was more painful for patients with actinic keratoses than for those with nonmelanoma skin cancers. It was also painful when large areas were affected, and men experienced more pain than women.

ALA Phototherapy for Actinic Keratoses. Phototherapy works best on flat lesions performed in two treatments, and is more effective for clearing lesions on the face than those on the scalp. Phototherapy can also treat multiple lesions at the same time instead of sequentially, as in cryotherapy. Studies suggest that it may work as well as cryotherapy and achieve better cosmetic results. (More patients report burning and itching with phototherapy, however.) Phototherapy is also equal to topical 5-fluorouracil in effectiveness and achieving a satisfactory appearance.

ALA Phototherapy for Nonmelanoma Skin Cancers. In patients with squamous cell cancer-in-situ and basal cell cancer, phototherapy has been equal to cryotherapy, with superior healing and appearance afterward. A 2003 study reported that it was more effective than topical 5-fluorouracil for patients with Bowen's disease, and there were fewer side effects.

Some studies have shown that about 10% of patients using phototherapy have a recurrence within 1 year. These recurrence rates are higher than with surgery and other standard treatments. Longer-term studies are required before ALA phototherapy can be recommended for most patients with nonmelanoma skin cancers.

Chemical peeling, or exfoliation, is useful for solar keratoses on the face, especially in people with fair, dry skin. Alpha-hydroxy acids, for example, are being investigated for keratoses. Dermabrasion, which "sands" the skin, may also be effective, although scarring is possible. A 2002 study found laser resurfacing to treat severe sun damage on the face; however, it may not prevent nonmelanoma skin cancers.

A number of medications are being used for keratoses and some may be helpful for skin cancers as well. Besides cryotherapy, 5-fluorouracil is the other most commonly used treatment for actinic keratoses. Other medications are also available.


Medication	Skin Conditions Affected	Oral or Topical		Comments
5-Fluorouracil	Actinic keratoses, Bowen's disease and small nonmelanoma skin cancers.		Topical cream (Efudex, Fluoroplex) or injected gel containing 5-FU and epinephrine (AccuSite).	5-Fluorouracil (5-FU) removes actinic keratoses and is useful for some patients with a large number of lesions. It requires twice daily application for 3 - 4 weeks. It can cause significant redness, irritation, swelling, and crusting, which takes 2 - 4 weeks to heal. Newer preparations are reducing these side effects. It is still unclear if this medication protects against recurrent keratoses or future skin cancer. Of concern is the possibility that (5-FU) will clear the top of a skin cancer and obscure the rest of the cancer that lies beneath the surface of the skin. A 10-year 2003 study of patients with Bowen's disease reported that 5-FU was safe and effective, with only 2 out of 26 cancers recurring.
Diclofenac and hyaluronan (Solaraze)	Actinic keratoses (approved). Investigated for basal cell.		Topical gel applied twice a day.	Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID). When used to treat actinic keratoses, it is delivered to the skin with hyaluronan, a water-seeking molecule that helps maintain skin tension. It has modest effects and when healing occurs, it may not be evident for at least a month after treatment ends. However, it causes less irritation than 5-FU and may be useful for some people.
Imiquimod (Aldara)	FDA approved for the treatment of superficial basal cell cancer. Previously approved for treating actinic keratoses. Investigated for Bowen's disease and squamous cell cancer.		Imiquimod is a topical cream.	Imiquimod triggers the production of immune factors that help fight cell proliferation. Aldara should be used only when surgery for basal cell cancer is inappropriate. It is not approved for use on the face.
Alpha-Interferons	Basal cell cancer, squamous cell cancer.		Require injections administered three times a week.	Interferons are immune factors that are being used to treat a number of serious conditions. Alpha-interferon injections may be effective against skin cancers that are hard to treat using conventional surgical measures. Cosmetic results reported to be good or very good by 83% of patients.

Prognosis

Virtually all basal and squamous type skin cancers can be cured if treated early.

The outlook for melanoma depends on when it is diagnosed.

If melanoma is detected in its earliest form, the 5-year survival rate is 99%. Other localized forms of melanoma have very favorable outlooks.

If the cancer is found after the melanoma has spread, the 5-year survival rate drops.

If melanoma spreads to nearby areas (regional metastatic), the rate is 65%.
If melanoma has spread to distant areas of the body, the survival rate is 15%.

In general, after patients are treated for melanoma, the longer they remain free of cancer recurrence following treatment the better the chance of remaining disease-free. However, relapses are not uncommon in those whose initial melanoma was large.

Anyone who has recovered from melanoma should be especially strict about adhering to preventive guidelines and remain vigilant for suspicious lesions, since the risk for developing a new melanoma is increased even if the first one was successfully cured. Such relapses may occur years after the original diagnosis.

Resources

www.aad.org -- American Academy of Dermatology
www.cancer.org -- American Cancer Society
www.asds.net -- American Society for Dermatologic Surgery
www.mpip.org -- Melanoma Patients' Information Page
www.cancer.gov -- National Cancer Institute
www.nccn.org -- National Comprehensive Cancer Network
www.skincancer.org -- The Skin Cancer Foundation
www.epa.gov/sunwise/uvindex.html -- UV index information

References

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Review Date:
6/29/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

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