FitSugar

Would You Consider Back Fat Surgery?

FitSugar — Mon, 22 Sep 2008 04:30:00 -0700

We all have those little areas on our bodies that we'd like to change. Some people turn to dieting, some people exercise, and others consider plastic surgery. If back fat is your enemy, there's a new surgery known as the bra-line back lift designed to get rid of those bumps and rolls of skin on your back, sort of like a face lift or tummy tuck. Go in with rolls and leave with smoother, even skin.

It's not so much designed for slightly overweight people who carry their fat on their backs; it's more for people who've lost an extreme amount of weight or who have saggy skin from aging or too much sun exposure. After the surgery, you're left with a scar that a bra or bathing suit would hide. The procedure will run you from $7,500 to $10,000, so a flat back doesn't come cheap. Tell me . . .

Source

Physical Traits Give Clues About Your Health Risks

FitSugar — Tue, 06 Oct 2009 08:00:15 -0700

There are many things we can do to enhance our health and prevent illness. Exercising regularly, eating a healthy diet, not smoking, limiting your alcohol intake, and reducing your stress can add years to your life. Who knew that your appearance and physical characteristics such as finger length and your sense of smell could let you know what health risks you might be prone to? Check out the list below from Prevention magazine.

Finger length: For women, if your index finger is shorter than your ring finger, then it means you have double the risk of osteoarthritis of the knee. If yours is longer or even with your ring finger, you're in the clear, but if it's not, do exercises to strengthen your knees, such as squats and lunges. Arthritis and finger length are both related to low levels of estrogen, so that's why the two are connected.
Arm length: Extend your arms in T-position out to the sides and measure the distance form fingertip to fingertip. If the distance is less than 60 inches, you're at a higher risk for Alzheimer's. So do activities that stimulate your brain and your body. Take a painting class, learn to play a musical instrument, play chess, or take dance lessons.

There's more, so keep reading

Cataracts

FitSugar — Wed, 08 Oct 2008 17:35:39 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Medical Societies Issue Tamsulosin (Flomax) Warning

In August 2006, the American Society of Cataract and Refractive Surgery (ASCRS), the American Academy of Ophthalmology, and the American Urological Association (AUA) issued a joint warning concerning Tamsulosin (Flomax). The societies advised patients to be sure to inform their eye surgeons if they are taking this drug. Tamsulosin is frequently prescribed to treat prostate enlargement.

The ACSRS has developed specific cataract surgery techniques for cataract patients who take this drug. Recent research suggests that these new techniques produce successful surgical outcomes.
The AUA warns that while men are primarily at risk, more women may be at risk in the future as Tamsulosin is increasingly being prescribed for urinary retention.

Cost of Cataracts

Cataracts cost the United States nearly $7 billion a year in medical services and pharmaceutical costs, according to a 2006 report in the Archives of Ophthalmology.

Can Statins Reduce Cataract Risk?

Statin drugs, which are used to manage cholesterol levels, are associated with a lower risk of nuclear cataract -- the most common type of age-related cataract -- according to a 2006 study in the Journal of the American Medical Association. Researchers think that the antioxidant properties of statins may account for this association.

Cataract Surgery

A new surgical technique, phacoviscocanalostomy, works well for patients who have both glaucoma and cataracts, suggests a 2006 study in the Journal of Cataract and Refractive Surgery.
Newer methods of administering local anesthesia are resulting in fewer complications than older methods, indicates a 2006 study in the British Journal of Ophthalmology.

Intraocular Lenses (IOLs)

The Tecnis ZM001 IOL helped produce better reading clarity and reading speed than several other newer multifocal IOLs, according to a 2006 comparison study. Multifocal IOLs are used for patients who need correction for both farsightedness and nearsightedness.

Introduction

A cataract is an opacity, or clouding, of the lens of the eye.

The lens of an eye is normally clear. If the lens becomes cloudy or is opacified, it is called a cataract.

The prevalence of cataracts increases dramatically with age. It typically occurs in the following way:

The lens is an elliptical structure that sits behind the pupil and is normally transparent. The function of the lens is to focus light rays into images on the retina (the light-sensitive tissue at the back of the eye).
In young people, the lens is elastic and changes shape easily, allowing the eyes to focus clearly on both near and distant objects.
As people reach their mid-40s, biochemical changes occur in the proteins within the lens, causing them to harden and lose elasticity. This causes a number of vision problems. For example, loss of elasticity causes presbyopia, or far-sightedness, requiring reading glasses in almost everyone as they age.
In some people, the proteins in the lens, notably those called alpha crystallins, may also clump together, forming cloudy (opaque) areas called cataracts. They usually develop slowly over several years and are related to aging. In some cases, depending on the cause of the cataracts, loss of vision progresses rapidly.
Depending on how dense they are and where they are located, cataracts can block the passage of light through the lens and interfere with the formation of images on the retina, causing vision to become cloudy.

Click the icon to see an image of eye anatomy.

Cataracts can form in any of three parts of the lens and are named by their location.

Nuclear cataracts. These form in the nucleus (the inner core) of the lens. This is the most common variety of cataract associated with the aging process.
Cortical cataracts. These form in the cortex (the outer section of the lens).
Posterior subcapsular cataracts. These form toward the back of a cellophane-like capsule that surrounds the lens. They are more frequent in people with diabetes, who are overweight, or those taking steroids.

Causes

Although older age is the primary risk factor for cataracts, experts are still not certain about the exact biologic mechanisms that tie cataracts to aging.

Researchers have been focusing on particles called oxygen-free radicals as a major factor in the development of cataracts. They cause harm in the following way:

Oxygen free radicals (also called oxidants) are molecules produced by natural chemical processes in the body. Toxins, smoking, ultraviolet radiation, infections, and many other factors can create reactions that produce excessive amounts of these oxygen free radicals.
Oxidants are missing an electron, so they are unstable and tend to chemically bind with other molecules in the body. When oxidants are overproduced, these chemical reactions can be very harmful to nearly any type of cell in the body. At times these reactions can even effect genetic material in cells.
Cataract formation is one of many destructive changes that can occur with overproduction of oxidants, possibly in concert with deficiencies of an important protective anti-oxidant called glutathione.
Glutathione occurs in high levels in the eye and helps clean up these free radicals. One theory posits that in the aging eye, barriers develop that prevent glutathione and other protective antioxidants from reaching the nucleus in the lens, thus making if vulnerable to oxidation.

Sunlight and Ultraviolet Radiation. Sunlight consists of ultraviolet (referred to as UVA or UVB) radiation, which penetrates the layers of the skin. Both have destructive properties that can promote cataracts. The eyes are protected from the sun by eyelids and the structure of the face (overhanging brows, prominent cheekbones, and the nose). Long-term exposure to sunlight, however, can overcome these defenses.

UVB radiation produces the shorter wavelength, and primarily affects the outer skin layers. It is the primary cause of sunburn. It is also the UV radiation primarily responsible for cataracts. Long-term exposure to even low levels of UVB radiation can eventually cause changes in the lens, including pigment changes, which contribute to cataract development. (UVB also appears to be responsible for macular degeneration, an age-related disorder of the retina.) Some scientists suggest that global warming and ozone depletion may increase people’s exposure to UVB, leading to a greater incidence of cataracts.
UVA radiation is composed of longer wavelengths. They penetrate more deeply and efficiently into the inner skin layers and are responsible for tanning. The main damaging effect of UVA appears to be the promotion of the release of oxidants.

Radiation Treatments. Cataracts are common side effects of total body radiation treatments, which are administered for certain cancers.

Electromagnetic Waves. Questions have been raised about the hazards of low-level radiation from computer screens. To date, no study has demonstrated an association between cataract development and video display terminals. It is a good idea, in any case, to sit at least a foot away from the front of a screen.

Cataracts are one of the many ill effects caused by smoking. Many studies have implicated smoking in the development of nuclear cataracts. The major damaging effects of cigarette smoke appear to be enhancement of free oxygen radicals, the chemical byproducts in the body that can damage cells, including those in the eye.

Corticosteroids. Long-term use of oral steroids is a well-known cause of cataracts. Studies have been conflicting, however, over whether inhaled and nasal-spray steroids increase the risk for cataracts. Information on cataract risk from inhaled steroids is important because they are commonly used by asthma patients, and steroid spray use is increasing among allergy sufferers. Studies have suggested a higher risk for cataracts among middle-aged and elderly patients treated with beclomethasone (Beclovent, Vanceril). However, newer inhaled steroids are available, and their effects on the eye are unclear. In children, cataracts are rare, and the benefits of inhaled steroids for asthma far outweigh any small additional risk.

Other Medications Associated with Cataracts.

Psoralens, a class of drugs used along with light therapy to treat skin disorders, such as psoriasis
Antipsychotic medications such as chlorpromazine (Thorazine)
Glaucoma medications

Many others drugs have been weakly associated with cataracts, including allopurinol, tamoxifen, amiodarone, tricyclic antidepressants, potassium-sparing diuretics (but not other diuretics), thyroid hormone, tetracyclines, sulfamidase, and mepacrine. According to a 2006 study in the Journal of the American Medical Association, statin drugs (used for managing cholesterol) may possibly reduce the risk for nuclear cataracts.

Click the icon to see an animation about cataracts.

Glaucoma. Glaucoma and its treatments, including certain drugs (notably miotics) and filtering surgery, pose a high risk for cataracts. The glaucoma drugs posing a particular risk for cataracts including demecarium (Humorsol), isoflurophate (Floropryl), and echothiophate (Phospholine).

Uveitis. Uveitis is chronic inflammation in the eye, which is often caused by an autoimmune disease or response. Often the cause is unknown. It is a rare condition that carries a high risk for cataracts.

A number of medical conditions appear to be associated with a higher risk for cataracts either because of a direct effect or because of the medications used for them, or both. They include the following:

Diabetes. Cataracts in patients with diabetes appear to form when high levels of blood sugar react with proteins in the eye to form byproducts that accumulate in the lens (sugar cataracts).
High blood pressure (hypertension).
Autoimmune diseases including rheumatoid arthritis, psoriasis, multiple sclerosis, systemic lupus erythematosus, Behcet's disease, and others.

Rarely, about 1 in every 10,000 births, a baby is born with cataracts (called congenital cataracts).

Inherited disorders are often involved in the development of congenital cataracts in children. Such cataracts are most often due to inborn abnormalities in the structure or shape of the lens, including its capsule. Dozens of variations can affect the lens causing, susceptibility to cataracts. Researchers are also investigating genetic factors that may cause mutations in alpha crystallins -- major proteins in the lens, which form cataracts. (Genetic factors also may play a role in some adult cataract cases. The exact hereditary predispositions have yet to be established.)
Infection during pregnancy can lead to cataracts.
Pregnant women who abuse alcohol or drugs increase the risk for cataracts (along with other more serious birth defects) in their infants.

Surgery in children with early-onset cataracts can help correct this problem in many cases, but it should be performed as soon as possible for full benefit. Experts recommend routine examination of the face of a fetus during ultrasound for abnormalities.

Symptoms

During the early stages, cataracts have little effect on vision. The symptoms of a cataract may include:

Cloudy vision, double vision, or both may be the first signs.
Images may take on a yellowish tint as color vibrancy diminishes.
Reading may become difficult over time because of a reduced contrast between letters and their background.
Sensitivity to bright lights may make it difficult or impossible to drive at night because of glare from the headlights of oncoming cars. (People with diffuse cataracts in the rear walls of their lenses are particularly prone to glare sensitivity because bright light tends to scatter in their lenses.)
In very advanced cases, the pupil, which is normally black, looks milky or yellowish. The patient's vision is reduced to being able only to distinguish light from dark.

This photograph shows a cloudy white lens (cataract) over the pupil. Cataracts are a leading cause of decreased vision in older individuals, but children may have congenital cataracts. With new surgical techniques, the cataract can be removed, a new lens implanted, and the person can usually return home the same day.

Nuclear Cataracts. Cataracts of the lens nucleus are most commonly associated with aging. Symptoms include:

Hazy distance vision and increasing glare.
Progressive nearsightedness and the need for frequent changes in eyeglass prescriptions. This effect may even temporarily counteract age-related farsightedness and provide a temporary improvement in overall vision in some people. The improvement fades when the cataract advances sufficiently to overwhelm the inherent farsightedness. Eventually, as the cataracts grow worse, stronger glasses can no longer correct the patient's vision.

Click the icon to see an image of normal, near, and farsighted vision.

Cortical Cataracts. Cortical cataracts usually start on the outside of the cortex (the outer area of the lens).

They have very little initial effect on vision.
Glare can develop as these cataracts increase and approach the center of the lens.
Problems with distance vision, contrast sensitivity, and clarity may occur as the cataracts progress further.

Posterior Subcapsular Cataracts. Posterior subcapsular cataracts typically start near the center of the back part of the capsule surrounding the lens. These cataracts often advance rapidly. For many patients, major impairment of eyesight, including near-vision problems and glare, develops within several months.

Prognosis

Some cataracts stop progressing after a certain point. Cataracts are never reversible, however, even after eliminating factors, (such as drugs or illnesses), which might have promoted their development. If extensive and progressive cataracts are left untreated they can cause blindness. In fact, cataracts are the leading cause of blindness among adults age 55 and older. About 20.5 million Americans have at least one cataract. By 2020, that number is expected to jump to 30.1 million.

Fortunately, cataracts nearly always can be successfully removed with surgery. However, surgery is unavailable in certain parts of the world, leaving millions at risk for vision loss. Even in the U.S., where surgery has greatly reduced the risk of blindness, tens of thousands still lose their sight and millions more have poor vision because of cataracts. Cataracts also exact a financial burden. According to 2006 data, cataracts cost the U.S. nearly $7 billion each year in medical services and drug treatments.

In a 2001 study, cataracts were associated with a significantly higher mortality rate in older women, although not older men. These higher rates did not seem to be caused by certain health risks (for example, diabetes) that are often associated with both cataracts and lower survival rates. A 2004 study published by scientists in Italy appears to confirm the association between shortened lifespan and cataracts, especially cataracts confined to the lens nucleus and those that had already required surgery. A few other studies have also linked cataracts and vision impairment with poorer survival, regardless of accompanying health problems. One study reported that even middle-aged people with cataracts, particularly those in ethnic minority groups, had lower survival rates than their peers, perhaps because of premature aging.

Effect on Survival by Location of the Cataract. Some studies have suggested poorer survival specifically in patients with nuclear or mixed cataracts but not in those with cataracts in the cortex or capsule. Not all studies have found these differences. In any case, nuclear cataracts are highly associated with smoking and diabetes, although some studies have found lower survival rates in patients with nuclear cataract regardless of these health risks.

A 2002 study reported twice the rate of automobile accidents in patients who do not have cataract surgery compared to those who had surgery. This finding, however, is obscured by the possibility that patients who choose not to have surgery may have other health problems that put them at risk for accidents. Also, driving skills decline with age in nearly everyone. Cataract surgery, then, is no insurance against age-related accidents.

Reduced vision ranks third only behind arthritis and heart disease as a cause of impaired function in older people. Extensive cataracts can compromise the ability to earn a living, read, drive, or live independently. Although vision loss has been associated with a number of major adverse effects, few studies have reported on the effect of vision on daily activities.

Both blurred vision and problems in seeing contrasts contribute to impaired activity. The degree of these impairments, however, may have different effects on disability depending on individual tasks and needs. For example, even a slight loss in vision sharpness and contrast can impair the ability to recognize faces or slow down reading speed. For those who read very quickly, this may not be significant, but it could be very disabling for slower readers. In one study, people under age 65 rated blurred vision as reducing their quality of life more than any other chronic medical problem except shortness of breath.

Nevertheless some people who have small cataracts can see well enough around the clouded areas to live normally. But for many people, cataracts are extensive enough to interfere greatly with daily activities.

Risk Factors

Aging is the primary risk factor for cataracts, but other factors are also involved.

Nearly everyone who lives long enough will develop cataracts to some extent. A major study reported that:

About 40% of people age 55 - 64 years had some opaque areas in their lenses, and 5% had fully-developed cataracts.
About 70% of people age 65 - 74 years had opaque areas, and 18% had cataracts.
More than 90% of people age 75 - 84 years had opaque areas, and almost 50% had cataracts.

One study indicated that posterior subcapsular cataracts are the most common type in people under 70 years old, while nuclear and mixed cataracts are most common in people over age 80. The risk for nuclear cataracts also increases with age.

Women face a higher risk than men. Women who started menstruating late are at an even higher risk.

Eye Features. People who are nearsighted and those with brown eyes may be at higher than average risk. (Not all studies, however, report a higher risk in people with darker eyes.)

Obesity and Height. Studies are now reporting obesity as a risk factor for cataracts, notably posterior subcapsular cataracts, which form toward the back of the lens. A study of 17,150 people found a specifically higher rate of cataracts in overweight people who are tall and whose fat distribution is primarily in the abdomen.

A 9-year population study, published in 2004, revealed that African Americans have nearly twice the risk of developing cataracts than do Caucasians. Analysis of the 3,000 participants also demonstrated for the first time that the risk of cortical cataracts is 3 times higher in African Americans than Caucasians. Earlier studies also identified a higher cataract risk in the black population, suggesting that it may be due to other medical illnesses, particularly diabetes. It has long been known that African Americans are much more likely to become blind from cataracts and glaucoma than Caucasians, mostly due to lack of treatment.

Hispanic Americans are also at increased risk for cataracts. In fact, cataracts are the leading cause of visual impairment among Hispanics. A 2005 study found that cataracts were about 3 times more common in Hispanic patients age 65 - 84 years than in similarly aged white or African Americans. (The study evaluated Hispanic patients of Mexican descent.) As with African Americans, Hispanic patients often face barriers to access to care.

People with certain medical conditions, notably diabetes, are at high risk for cataracts, either because of a direct effect of the disease, its treatments, or both.

Autoimmune Diseases and Conditions Requiring Steroid Use. Medical conditions requiring high use of corticosteroids (commonly called steroids) pose a particularly high risk. Many of these medical conditions are autoimmune diseases, including rheumatoid arthritis, psoriasis, multiple sclerosis, systemic lupus erythematosus, Behcet's disease, and others.

Diabetes and People with High Blood Glucose Levels. People with diabetes type 1 or 2 are at very high risk for cataracts and are much more likely to develop them at a younger age. They also have a higher risk for nuclear cataracts than nondiabetics. Cataract development is significantly related to high levels of blood sugar (called glycemia), and cataracts in people with diabetes are sometimes referred to as so-called sugar cataracts. Even people without diabetes but with higher-than-normal blood sugar levels are at high risk for cataracts. Some doctors now recommend that children with diabetes undergo an eye exam to check for cataracts at the time they are diagnosed.

Insulin is a hormone produced by the pancreas that is necessary for cells to be able to use blood sugar.

Exposure to even low-level UVB radiation from sunlight increases the risk for cataracts. A 2003 study published provided new evidence supporting the link between sun exposure and nuclear cataracts. The risk was highest among those who had significant sun exposure at a young age. Additional studies suggesting risk associated with sunlight exposure report:

The closer people live to the equator the greater the chance for cataracts. As suggested by a study in Southern France, sunlight exposure in these climates also increases the risk for severe cortical or mixed cataracts. In this study, even wearing sunglasses did not reduce the risk for these cataracts, although it did for posterior subcapsular cataracts.
People whose jobs expose them to sunlight for prolonged periods are at higher risk. People in southern climates whose occupations, such as fishing or oyster farming, exposed them to very intense sunlight were at high risk for all cataracts, including posterior subcapsular cataracts. (People in more northern climates with similar occupations may not have as high a risk.)
Occupational exposure to very intense artificial light, such as arc welding, increases the risk for cataracts.

Smokers. A study of nearly 18,000 doctors showed that those who smoked 20 or more cigarettes a day had approximately twice the risk of developing cataracts. Smokers are at particular risk for cataracts located in the nuclear portion of the lens, which limit vision more severely than cataracts in other sites. Quitting smoking may reverse some of this damage.

Alcohol Users. Chronic drinkers are at high risk for a number of eye disorders, including cataracts. Alcohol has been implicated in cataract development in a number of studies. Wine provided the least risk, and the more moderate the drinking the lower the risk. Alcohol may work directly on the proteins in the lens itself and indirectly by affecting absorption of nutrients important to the lens.

Long-term environmental lead exposure may increase the risk of developing cataracts according to a study published in the Journal of the American Medical Association. Researchers assessed bone lead levels in 795 men aged 60 years and older. Because lead tends to accumulate over time in the skeleton, the researchers measured lead levels in the men’s shin bones. Men with the highest levels of lead were three times more likely to have cataracts than men with the least amount of lead.

A poor diet may deprive the body of amino acids and B vitamins that are essential for eye health. A French study of elderly adults found that lower blood levels of the protein albumin were associated with an increased risk of cataracts.

Other conditions that can trigger the process leading to cataracts include:

Physical injury to the eye (such as a hard blow, cut, or puncture)
Chemical burns
Electrical shock injuries
Chronic exposure to intense heat or cold

Prevention

Although cataracts are not completely preventable, their occurrence can be delayed. Quitting smoking, avoiding overexposure to sunlight, drinking alcohol in moderation, and eating plenty of fresh fruits and vegetables can delay the formation of cataracts. No evidence exists that using eye drops or ointments or performing eye exercises will stem the onset of cataracts.

The simplest and most effective way to protect against ultraviolet (UV) radiation is to stay out of the sun. A hat and cover-up should be worn outside, particularly when the sun is most intense (10 AM - 3 PM). A wide-brimmed hat can reduce eye exposure to UVB radiation by 30 - 50%. Because the sun's rays are highly reflective, sitting in the shade or under an umbrella by itself does not guarantee protection.

Clothing that blocks or screens the harmful rays of the sun (UVA and UVB), in combination with wide-brimmed hats, sunglasses, and sunscreen, all help prevent damage to the eyes and skin. Any one of these by itself, even the sunscreen, may not be enough to prevent sun damage.

Note: Avoidance of the sun should not be taken to extremes. Some sunshine is desirable. Moderate sun exposure provides an important source of vitamin D, which is essential for healthy bones. There is a link between lack of sun exposure and depression (known as seasonal affective disorder, or SAD).

Click the icon to see an image of vitamin D.

Sunglasses. Protective sunglasses do not have to be expensive. Sunglasses are classified into three categories based on UVA and UVB protection:

Cosmetic purpose sunglasses block at least 70% UVB and up to 60% UVA. People should avoid these glasses if they have any risk for cataracts or eye problems.
General purpose sunglasses block at least 95% UVB and a minimum of 60% UVA. At the very least, people should purchase general purpose sunglasses that are labeled "Meets ANSI Z80.3 General Purpose UV Requirements." Labels should indicate that sunglasses block UV radiation up to 400 nm.
Special purpose sunglasses block at least 99% UVB and a minimum of 60% UVA rays. These are the optimal sunglasses for people at risk for cataracts. Ideally they should have the Skin Cancer Foundation's Seal of Recommendation for Sunglasses. Special purpose glasses should wrap around the head and block light coming from above, below, and both sides of the glasses. They should also fit snugly on the nose.
Lenses that are simply dark but not coated with UV-absorbing material may actually increase the risk of cataracts because the pupil widens to compensate for the shaded glass. This may allow more harmful ultraviolet waves to enter. Polarized glasses cut glare but have no effect on UV radiation. Mirror finishes without additional processing for UV blockage are also not fully protective. There is some controversy over whether blue light is harmful to the eyes. Some people prefer amber lenses, which block out the blue spectrum.

Antioxidant vitamins C and E. Because of the role oxidants may play in cataract formation, researchers are investigating the benefits of antioxidant vitamins and other food chemicals. Vitamins C, E, and riboflavin (a B vitamin), for example, are helpful in preserving levels of glutathione, an enzyme that helps protect against oxidation in the eye. Low levels of vitamin C in the lens of the eye have been particularly strong predictors of cataracts. Some evidence also suggests that ultraviolet B radiation interacts with deficiencies in certain antioxidants, such as vitamin E and zinc, to increase damage in the corneas and lenses of the eye.

Evidence on the benefits of supplements of vitamin E or C, or vitamin-rich foods, is conflicting. For example, in two identically constructed trials in the US and Britain, the American group derived apparent benefits from vitamins E, C, and beta carotene while the British group reported very little cataract protection. A 2005 study suggested that long-term use of vitamin E supplements may slow cataract development. However, in a major on-going American study called the Age-Related Eye Disease Study (AREDS), researchers reported no difference in the incidence of cataracts after 7 years in people who took the antioxidant vitamins compared to those who took sham vitamins.

High doses of vitamins may have harmful effects. It is always wise, in any case, to pursue a healthy diet that is low in fats, high in complex carbohydrates, and rich in fruits and vegetables.

B vitamins. Some studies report some protection from a number of B vitamins, including vitamins B1 (thiamin) B2 (riboflavin), B3 (niacin) and B12 (folate). Riboflavin, for example, plays a critical role in the production of glutathione, an enzyme that helps protect against oxidation in the eye. All forms of vitamin B are widely available in dairy products, fortified grains, and meat.

Carotenoids. Carotenoids are a group of more than 700 fat soluble nutrients that produce the colors in foods such as carrots, pumpkins, sweet potatoes, tomatoes, and other deep green, yellow, orange, and red fruits and vegetables. Many are proving to be very important for health. Different carotenoids may be more beneficial then others. They include:

Xanthophylls are compounds that form a particular category of carotenoids. The xanthophylls lutein and zeaxanthin are found in the lenses of the eye and may be of significant importance for people at risk for cataracts. Some evidence indicates supplements of xanthophyll-rich foods may help retard the aging process in the eye and protect against cataracts. In fact, some experts suggest that the higher risk of cataracts in women compared to men may be partly due to a lesser ability to transport these carotenoids from the blood into the eye. Xanthophylls can be obtained from dark green leafy vegetables (such as spinach), broccoli, and eggs.
Lycopene is an important carotenoid that may also play an important role in eye health as a person ages. Tomatoes are the importance sources of lycopene.
Beta carotene is the most widely studied carotenoid and is a powerful antioxidant. It has been specifically studied for cataract protection. Most studies, however, have found little or no benefits. A 2003 study did suggest that beta carotene may protect against cataracts in smokers, although it is important to note that other studies report a higher risk for lung cancer in smokers who take beta carotene.

Click the icon to see an image of folate sources.

Click the icon to see an image of vitamin B12 sources.

Click the icon to see an image of riboflavin sources.

Phytochemicals. Phytochemicals are substances in plants that have beneficial effects. Dark colored (green, red, purple, and yellow) fruits and vegetables usually have high levels of important plant chemicals and have been associated with a lower risk for cataracts. Tea contains certain plant chemicals called polyphenols that have been associated with protection against cataracts.

Click the icon to see an image of phytochemicals.

Diagnosis

Either an ophthalmologist or an optometrist can examine patients for cataracts, but only ophthalmologists are qualified to treat cataracts.

An ophthalmologist is a doctor who specializes in the medical and surgical care of the eye.
An optometrist is engaged in the practice of eye care, but is not a doctor and cannot prescribe medication or perform surgery.

The eye professional can observe cloudy areas on the lenses with a direct physical examination, even before the cataracts begin to interfere with vision. Cameras can measure the cataract density. Various vision tests are also performed.

Snellen Eye Chart. To determine how clearly a person can actually see, the Snellen eye chart is used, with rows of letters decreasing in size:

From a specified distance, usually 20 feet, a person reads the letters using one eye at a time.
If a person can read down to the small letters on the line marked 20 feet, then vision is 20/20 (normal vision).
If a person can read only down through the line marked 40 feet, vision is 20/40; that is, from 20 feet the patient can read what someone with normal vision can read from 40 feet.
If the large letters on the line marked 200 feet cannot be read with the better eye, even with glasses, the patient is considered legally blind.

The visual acuity test can be performed in many different ways. It is a quick way to detect vision problems and is frequently used in schools or for mass screening. Driver license bureaus often use a small device that can test the eyes individually and then together.

Other Tests. A number of other tests are used to diagnose cataracts or to determine if surgery is needed.

A chart similar to the Snellen chart, which has the same size letters, but in different contrasts with background, is used to test contrast sensitivity,
Glare sensitivity is tested by having the patient read a chart twice, with and without bright lights.
Tests of macular function, which evaluate the eye's acute vision center, can help the ophthalmologist determine the expected improvement from surgery.
The corneal endothelium, a layer of cells lining the cornea, is sensitive to surgical trauma and should be evaluated before any intraocular operation.
Patients with other eye disorders may require a number of other pre-operative tests.

Although eye tests aid in making a diagnosis for cataracts, results do not always reflect the quality of life and how effectively people function at home:

Some people with cataracts perform poorly on the tests yet appear to have no difficulty functioning normally day-to-day.
Others perform well on the tests but insist that their eyesight is bad enough to curtail ordinary activities, such as driving.

Standard eye tests, therefore, may not be useful for determining whether a patient actually needs cataract surgery.

In general, even if cataracts are diagnosed, the decision to remove them should be based on the patient's own perception of vision difficulties and needs and the effect of vision loss on normal activity. The patient should also be aware of all the risks and costs of surgery. In order to determine the quality of life, the patient may be given a questionnaire such as National Eye Institute Visual Function Questionnaire, which asks 39 questions related to vision and daily activities. This test or others may be useful for determining if eye disease is actually impairing the ability to function.

Treatment

Although surgery is the only remedy for cataracts, it is almost never an emergency. Most cataracts cause no problem other than reducing a person's ability to see, so there is no harm in delaying surgery.

Early cataracts may be managed with the following measures:

Stronger eyeglasses or contact lenses
Use of a magnifying glass during reading
Strong lighting
Medication that dilates the pupil. (May help some people with capsular cataracts, although glare might be a problem with this treatment.)

It is important to note, however, that no treatments will prevent cataract formation or progression or make a cataract disappear.

Progression of Cataracts. Patients and their families usually have plenty of time to consider options carefully and discuss them with an ophthalmologist. There is no constant rate at which cataracts progress:

Some develop to a certain point and then stop.
Even if a cataract does progress, it may be years before it interferes with vision.
Only in a very few, very rare circumstances is it necessary that cataract surgery be performed immediately.

Each year about 2.8 million cataract operations are performed, making it the most common operation in the U.S. for people over age 65. Cataract surgery may be the oldest procedure in the world, having been introduced to Europe from India by Alexander the Great's army.

In the past, cataract surgery was not performed until the cataract had become well developed. Newer techniques, however, have made it safer and even more efficient to operate in earlier stages. In fact, modern cataract techniques not only remove cataracts but are also becoming important procedures for correcting astigmatism. Cataract surgery improves vision in up to 95% of cases and prevents millions of Americans from going blind.

Nevertheless, considerable evidence suggests that, because of the ease and relative safety of the procedure, it may be performed more often than needed. Patients having operations now tend to have better preoperative vision than those operated on 10 or 20 years ago. In a study of 800 cataract operations, 25% of the patients said that clouding had had no obvious effect on their lives before the procedure.

Cataract surgery is very successful. It has the following advantages:

Nearly all patients enjoy better vision after surgery. Advanced procedures in lens development are allowing correction of astigmatism as well as cataract removal. (Patients with significant eye disease, such as glaucoma or corneal or retinal disease, may not experience the same degree of improvement.)
Many people experience significant improvement in quality of life after the operation.
Some studies indicate that better vision might even help slow down age-related health problems unrelated to the eyes.

In general, surgery is indicated for people with cataracts under the following circumstances:

The Snellen eye test reports 20/40 or worse, with the cataract being responsible for vision loss and glasses or visual aids no longer being helpful.
Everyday activities have become difficult to perform to the point that independence is threatened. Questionnaires that assess the effects of cataracts on quality of life have been developed.
The patient is at risk for falling in low light.

These guidelines are general, however. Whether surgery is appropriate or not further depends on the cataract patient's specific condition and needs. Some examples include the following:

Even if the criteria for surgery are met, a very sick, very elderly person in a nursing home may have less need for sharp vision than an active younger adult. Among very elderly patients (85 years and older), especially those with serious health problems, there are also higher risks for complications during surgery and poor outcomes afterward. Nevertheless, these cautions should not prevent the very elderly from having this procedure; vision improvement rates are still over 85%.
Even if the criteria for surgery are not met, some people with eye tests of 20/40 or better might want surgery because of problems with glare, double vision, or the need to have an unrestricted driver's license.
Even if the criteria for surgery are not met, if retinal disease is also suspected (usually a complication of diabetes), the doctor may perform cataract surgery in order to have a clear view of the eye.

Because of the risks, albeit small ones, of poorer vision or blindness, no one should be forced to have cataract surgery if they don't want it or are not strong enough to undergo the procedure. If there are any doubts about whether or not to undergo cataract surgery, a second opinion should be considered.

The patient should ask the ophthalmologist the following questions before agreeing to cataract surgery:

Is my cataract surgery an emergency?
Are the cataracts the only cause of my poor vision?
How much experience do you have with this procedure?
Do I have other eye diseases that might complicate surgery or reduce my benefit?
Do I have other health problems that might further complicate eye surgery?
Will you be able to implant an intraocular lens?
What type of procedure will you use?
Will I have to stay in the hospital overnight?
Afterwards, what are my chances of having poorer vision or becoming totally blind in that eye?
How well should I ultimately be able to see out of the operated eye?
How long will it take to heal?
How long will it take to achieve my best eyesight?
Will I have to wear glasses or contact lenses after surgery?
When will I get my final eyeglass prescription?
How soon after surgery will I be able to see well enough to go back to work? Drive a car? Return to full activity?
What will the surgery cost?

Cataract surgery is now usually done as an outpatient procedure under local anesthesia and takes less than an hour. Preoperative preparations may include:

Having a general physical examination is important for patients with medical problems such as diabetes. Diabetes can cause damage to the blood vessels of the eye’s retina, a condition called diabetic retinopathy. Recent research suggests that patients who have diabetic retinopathy and poor blood sugar control should not have their blood sugar rapidly corrected before cataract surgery. Correcting blood sugar too quickly before surgery can cause vision problems after surgery.
The ophthalmologist will use a painless ultrasound test to measure the length of the eye and determine the type of replacement lens that will be needed after the operation.
Topical application of so-called fluoroquinolone antibiotics (such as ofloxacin or ciprofloxacin) may be applied preoperatively to protect against postoperative infection.
Most healthy patients are given either a local injection or topical anesthetic. The patients who report the least pain during the operation are those given a sedative followed by a local injection rather than just the topical drug.
Some patients may require a general anesthetic, such as those who are very anxious, those who are unable to cooperate with the surgeon, and those who are allergic to local anesthetics.

All cataract procedures involve removal of the cataract-affected lens and replacing it with an artificial lens.

Phacoemulsification. Phacoemulsification (phaco means lens, emulsification means to liquefy) is now the most common cataract procedure in the United States and accounts for 85% of cases. Benefits are greater than with standard extracapsular surgery, and it may be particularly helpful for people with diabetes.

The procedure generally involves:

The surgeon makes an incision, which is much smaller than with standard cataract extraction.
Ultrasound is then used to break up the clouded lens into small fragments.
The tiny pieces are sucked out with a vacuum-like device.
A replacement lens is then usually inserted into the capsular bag where the natural lens used to be. In most cases, this is an intraocular lens (IOL), which is foldable and slips in through the tiny incision.
Because the incision is so small, it is often watertight and does not require a suture afterward, particularly if a foldable lens has been used. A suture may be needed if a tear or break occurs during the procedure or the surgeon inserts a rigid lens that requires a wider incision.

Click the icon to see an illustrated series detailing cataract surgery.

Phacoemulsification requires only local anesthesia. Newer methods for administering local anesthesia produce few complications. Most phacoemulsification procedures now take about 15 minutes, and the patient is usually out of the operating room in about an hour. There is little discomfort afterward and visual rehabilitation takes about 1 - 3 weeks.

Phacoemulsification is sometimes combined with viscocanalostomy, a glaucoma surgical procedure, for patients who have both glaucoma and cataracts. Recent research suggests that phacoviscocanalostomy (as this combined procedure is called) is safe and effective for this group of patients.

Surgeons in the U.S. and Europe are currently investigating Microphaco, a new approach to cataract surgery that uses two smaller (micro) incisions. The smaller incisions measure about 1.6 mm compared to the traditional 3 mm. Experts say this procedure is expected to revolutionize refractive and cataract surgery.

Other Lens Removal Techniques. The AquaLase device uses pulses of fluid to wash away the clouded lens. Some experts believe this approach causes less trauma to the eye, and allows for a quicker recovery time for the patient, than the ultrasound used in phacoemulsification.

Extracapsular or Intracapsular Cataract Extraction. Extracapsular cataract extraction was the original standard procedure, but is now generally used only in patients who have an extremely hard lens. It typically involves the following steps:

The ophthalmologist works under an operating microscope to make a small incision in the cornea of the eye.
The surgeon then extracts the clouded lens through this incision.
The capsule is left in place, which adds structural strength to the eye and enhances the healing process. (Less commonly, in intracapsular cataract extraction, the surgeon removes the lens and the entire capsule. There are greater risks with this procedure for swelling and retinal detachment.)
A replacement lens is then usually inserted.
A small suture is needed to stitch the incision together.

It takes about 2 - 4 weeks to completely restore vision.

With the clouded lens removed, the eye cannot focus a sharp image on the retina. A replacement lens or eyeglass are therefore needed:

Intraocular Lenses (IOL). In about 90% of cataract operations, an artificial lens, known as an intraocular lens (IOLs), is inserted. Until recently, IOLs used a pair of little spring-loaded loops to hold the lens in place. Most IOLs are now foldable, which makes insertion easier. In fact, a prefolded lens is now available that unrolls to fit the eye as body temperature warms it.

IOLs are available as monofocal or multifocal. Monofocal lenses correct only one type of vision range (such as distance vision). Multifocal lenses are designed for patients who need correction for a range of vision. A 2006 study suggested that the Tecnis IOL works particularly well for patients who require a multifocal IOL.

Although all the lens materials are presumably chemically inert, there are some reports of specific problems, notably a risk for causing a reaction that leads to the development of secondary cataracts, a condition called posterior capsular opacification. IOLs include the following materials:

Acrylic: The majority of IOLs are made from acrylic, which allows a controlled unfolding of the lens. Evidence indicates that this material provides a better visual outcome and fewer complications than other standard IOLs.
Polymethylmethacrylate (PMMA): Has the longest safety record. A PMMA IOL coated with heparin, a blood thinner drug, helps protect against the development of a secondary cataract after surgery.
Silicone: Can be inserted through a smaller incision than other materials. It has the highest rates of secondary cataracts. Newer forms of silicon IOLs may pose a lower risk.

Other materials are under investigation.

IOL brands include:

Crystalens: The FDA approved the Crystalens IOL in 2003. It is made from a form of silicone called Biosil. The Crystalens uses "hinges" that allow the lens to move, mimicking the eye's natural ability to focus automatically and seamlessly at all distances. Studies indicate that when used along with standard cataract removal methods, the Crystalens can restore a full range of functional vision, from distance to reading vision, without total dependence on glasses or contact lenses.
Array: The Array lens also uses silicon. It is one of a number of so-called second-generation IOLs that is available as a multifocal lens to help correct presbyopia (nearsightedness).
Tecnis: The Tecnis foldable IOL was specifically designed to improve functional vision of cataract surgery patients. Tecnis has a patented surface that reduces light scattering (spherical aberration) of the cornea, which can negatively affect vision. In April 2004, The FDA approved new labeling claims for Tecnis, stating the lens may help improve driving safety for senior cataract patients. In clinical trials, simulated night driving and visual acuity (20/20, 20/40) results were significantly better in eyes implanted with the Tecnis IOL. In addition, spherical aberrations were significantly less when compared to the traditional lens with the spherical optic.
AcrySof Natural: Approved in 2003, the yellow-tinted Acrysof Natural IOL was the first foldable lens to filter ultraviolet and blue-light. Eliminating both UV and portions of the high-energy blue light help prevent retinal damage. This lens also conforms to the natural shape of the human lens capsule so it remains centered over the eye.
AcrySof ReSTOR: The AcrySof ReSTOR IOL is approved in the U.S. for patients with and without presbyopia. The lens enhances vision at near, intermediate, and distant ranges. In clinical trials, 80% of patients who received the lens did not require glasses after cataract surgery. The FDA approved the AcrySof ReSTOR in March 2005.

IOLs are designed to improve specific aspects of vision. The choices include:

Lenses that address a single fixed focal point. Such lenses are suitable either for reading or for distance vision, but not both. If a distance lens is implanted, the surgeon prescribes glasses or contact lenses for reading. If a reading lens is implanted, lenses for seeing distances will be prescribed.
Lenses that address multifocal points. Multifocal lenses can focus at different points for both reading and distance vision. One study reported that more than 80% of patients with multifocal lenses were able to see 20/40 or better without correction. However, contrast may be reduced and some patients experience glare and halos, particularly at night.
Lenses are available that will correct astigmatism after cataract surgery.

The patients and the doctor must make these decisions based on specific visual needs.

Contact Lenses or Cataract Glasses. A few patients do not receive a new lens and rely solely on corrective eyeglasses or contact lenses. Such patients may include:

Patients who are extremely near-sighted
Patients with other eye disorders

In such cases, the patient typically returns to the ophthalmologist for a check up the day after surgery, and three additional check-ups are scheduled over a 2-month period. The ophthalmologist can usually give a final prescription for eyeglasses or contact lenses about three months after surgery.

Choosing Contact Lenses. Contact lenses allow clear vision but do not magnify, so those who choose contact lenses after surgery may have to wear reading glasses. Contacts can be prescribed either for use only during the day or for extended-wear. Occasionally contact lenses cause problems, such as infection. Those who wear them should call their eye doctor if they have red or watery eyes, pain, or sensitivity to light.
Cataract Glasses. Until the advent of contact lenses, people who had cataract surgery had no choice but to wear glasses with thick lenses, sometimes called Coke-bottle glasses. These glasses have gotten thinner and lighter in recent years, but they may still be cumbersome. Cataract glasses are different from ordinary glasses and are sometimes difficult to adjust to. Images can seem distorted and may appear suddenly within the peripheral vision. Distances may be hard to judge.

Sometimes a patient has two cataracts and needs to wear glasses between the first and second operation. They are particularly troublesome during this period. The treated eye will see images magnified while the other eye will view them as they actually are, and the brain cannot blend the two images. This is a temporary state that is resolved by the second operation.

Modern cataract surgery is one of the safest of all surgical procedures. Most complications, even if they occur, are not serious. They can include the following:

Swelling and inflammation. Risk is about 1%. This complication is particularly harmful for patients with existing uveitis (chronic inflammation in the eye, which can be due to various conditions).
Glare. Patients may experience glare after surgery from light scattering at the edges of the new lens, particularly with square-edged IOLs, which are typically used with posterior capsular cataracts. In most cases, this is a temporary problem that resolves after a few weeks. Sometimes, the problem persists, and the patient requires another operation. Some research suggests that glare can be significantly reduced by texturizing the edges of the square lens.
Materials used in some lenses trigger an immune response in about half of patients. This causes inflammation and tiny deposits of tissue in the eye that lead to secondary cataracts -- called posterior capsule opacification. Studies suggest that silicone implants pose the highest rates for inflammation and secondary cataracts, particularly in patients with other eye diseases. Newer silicon IOLs pose less risk. In one study, the lowest rates were with IOLs made of acrylic and heparin-coated PMMA.
Retinal detachment. In rare cases, the retina at the rear of the eye can become detached. Risk is very low (0.1%), and phacoemulsification poses less of a risk for this than standard surgery.
Atonia (loss of muscle tone that results in a disturbing glare). (Phacoemulsification poses less of a risk than standard surgery.)
Glaucoma. This is an eye condition in which the pressure of fluids inside the eye rises dangerously. Risk is very low, but patients should be sure to avoid activities after surgery that increase pressure.

Glaucoma is a condition of increased fluid pressure inside the eye. The increased pressure causes compression of the retina and the optic nerve which can eventually lead to nerve damage. Glaucoma can cause partial vision loss, with blindness as a possible eventual outcome.

Infection. This is very rare (0.2%), but is devastating if it does develop.
Blisters on the cornea. There is a higher risk of rupture with phacoemulsification, but the risk is extremely low, particularly for experienced eye surgeons. In 2004, the FDA approved the StabilEyes Capsular Tension Ring (CTR) to help support the eye's capsular bag during cataract surgery, especially in those with weak or broken eye fibers (zonules). A CTR is an open ring made of polymethylmethacrylate (PMMA). The ring goes into the capsular bag itself, stabilizing the eye.
Bleeding can develop inside the eye. Risk is about 1% for minor bleeding and 1 in 10,000 for severe bleeding.
An implanted IOL can become damaged or dislocated. Risk is very low.
The surgery itself can produce vision loss or impairment. The risk for this is 1 in 1,000. (Phacoemulsification poses less of a risk than standard surgery.)
Macular degeneration. Macular degeneration, in which the retina breaks down, is a common cause of vision loss in the elderly. In a 5-year study, people who underwent cataract surgery had twice the risk for progression of age-related macular degeneration. Interestingly, another study reported that cataract surgery significantly helped patients who had existing macular degeneration. More research is needed to refute or confirm this finding.

Click the icon to see an image of macular degeneration.

Phacoemulsification does have some specific complications, although they are rare, particularly with experienced eye surgeons. They include:

Rupture of the lens capsule.
Loss of the lens nucleus into the eye fluid. (This will require removal by a specialist and may result in poorer vision.)
Flying fragments of the lens can damage the cornea or threaten the retina.
Pre- and postoperative changes in blood pressure, which are generally not a problem, should be observed carefully, since in some cases the changes may be extreme.

In about 30% of cases patients develop secondary cataracts within 1 - 5 years after either procedure, which require different treatment choices.

Preventing Infection and Reducing Swelling. The ophthalmologist may prescribe the following medications:

A topical antibiotic (neomycin or, more effectively, gentamicin). This drug protects against infection.
Corticosteroid eyedrops or ointments are often used to reduce swelling. Corticosteroids (commonly called steroids) are potent anti-inflammatory drugs. However, they also pose a risk for pressure in the eye and infection. One study reported less visual sharpness with the use of steroids compared to antibiotics. Some newer steroids such as rimexolone, loteprednol, and fluorometholone may pose a lower risk for abnormal pressure.
Nonsteroidal anti-inflammatory drugs (NSAIDs), such as diclofenac, ketorolac, naproxen, and voltaren, also reduce swelling and do not pose the same risks as steroids. Newer NSAIDS that have been approved to treat pain and swelling after cataract surgery include bromfenac (Xibrom) and nepafenac (Nevanac).

In one study, applying an ice pack for 2 hours immediately after phacoemulsification improved comfort level and reduced inflammation, even days after the operation. This simple procedure has no adverse effects and patients should discuss it with their surgeons before the operation.

Factors That Increase Risk for Complications. The risks of complications are greater for the following people:

Patients who have other eye diseases.
People with diabetes. Intracapsular and extracapsular cataract extraction are known to pose a high risk for the development or worsening of retinopathy, a known eye complication of diabetes. Experts have hoped that phacoemulsification would pose a lower risk, but a 2001 study reported a high percentage of retinopathy progression after this procedure. The amount of experience a surgeon has plays a role in whether or not a patient has this complication.
People who have taken tamsulosin (Flomax) or other alpha-1 blocker drugs. Tamsulosin is a muscle relaxant prescribed for treatment of several urinary conditions including benign prostatic hyperplasia (BPH). In 2005, a leading ophthalmologic association and the FDA warned that tamsulosin may cause intraoperative floppy iris syndrome (IFIS), a loss of muscle tone in the iris that can cause complications during eye surgery. Problems have been reported both for patients who were taking the drug during surgery as well as those who had stopped taking the drug weeks or months before surgery. Men who have taken tamsulosin or similar drugs should inform their eye surgeon. The surgeon may need to use different techniques to minimize the risk of IFIS. A 2006 study indicated that patients can have safe and successful surgeries with these modified techniques.

Returning Home and Follow-up Visits.

Patients usually leave the surgical site within an hour of surgery. Cataract surgery almost never requires an overnight hospital stay.
They need to have someone drive them home and stay with them for a few days until their vision is acclimated.
The patient is usually examined the day after surgery and then during the following month. Additional visits are made as required.
Vision usually remains blurred for a while but gradually clears, usually over a 2 - 6 week period. (It can take longer.)
When the doctor decides the condition has stabilized, the patient will receive a final prescription for glasses or contacts.

Protecting the Eye. Postoperative protection of the eye typically involves:

The ophthalmologist usually tapes a bandage over the eye to protect it during the healing process.
When changing the bandage, the eye can be cleaned gently using a washcloth dipped in warm water without soap. A new bandage can then be positioned and taped.
It is very important not to press or rub the eye during this procedure.
An eye shield may be placed over the bandage at night.

Avoiding Glaucoma. Cataract surgery can cause glaucoma, a condition in which the pressure of fluids inside the eye rises dangerously. It is very important to minimize any activity that increases internal eye pressure. Postoperative cataract patients take the following precautions:

Minimize vigorous exercise.
Put on shoes while sitting and without lifting up the feet.
Kneel instead of bending over to pick something up.
Avoid lifting.
Limit reading since it requires eye movement (watching television is all right).
Sleep on the back or on the unoperated side.

Cataracts and Glaucoma. For patients with both glaucoma and cataracts, experts recommend:

In patients with cataracts and poorly controlled glaucoma, a two-step procedure for both eye conditions is needed. The patient first receives a trabeculectomy for glaucoma, followed by cataract surgery. Fluid leakage and the presence of blood in the back chamber of the eye are potential complications of this combined procedure. Phacoemulsification has improved success rates and reduced high complication rates of the double procedure compared with extracapsular cataract extraction. New advances that replace trabeculectomy with nonpenetrating glaucoma surgery may prove to be beneficial.
In patients who have cataracts plus either closed-angle glaucoma or open angle glaucoma that is stabilized with medication, the cataract may be able to be extracted and medication continued for the glaucoma.
A major 2002 analysis suggested that the combined approach generally offers better control over eye pressure for patients with both cataracts and glaucoma. The best surgical procedure, however, is still uncertain.

Cataracts and Corneal Disease. Patients who have both cataracts and corneal disease may undergo one of the following:

Combination Procedure. A single operation that combines three procedures. The combined procedure has been used since the late 1970s and employs extracapsular cataract extraction and intraocular lens insertion with corneal transplantation (called penetrating keratoplasty).
Sequential Procedure. An operation that uses two procedures sequentially. The sequential option performs the cataract procedures and the corneal transplantation separately.

Recovery of vision is usually much more rapid after the combined procedure than after the sequential procedures. Performing the procedures sequentially may also carry a higher rejection rate of the implant, although a 2003 study found no differences in failure rates between the two approaches after a year.

In any case, many experts recommend that for most patients the sequential procedures may be the better option because it appears to have fewer of the following complications than with the combined procedure:

Posterior capsule rupture
Eye fluid loss
Postoperative refractive errors, which result in abnormal distribution of light patterns

The rate of these errors still depends on the skill of the surgeon and the power of the implanted lens no matter what approach is used.

About 30% of patients who undergo extracapsular cataract surgery develop a secondary "after-cataract" called posterior capsular opacification. Posterior capsular opacification generally occurs because of the following events:

After surgery, there are still some natural lens cells left behind that proliferate on the back of the capsule.
The capsule gradually becomes cloudy and interferes with clear vision the same way the original cataract did.

According to a 2001 study, the probability of developing a secondary cataract was 6% at 1 year, 15% at 2 years, 23% at 3 years, and 38% at 9 years. The risk is lower with phacoemulsification. Secondary cataracts are more likely to occur in younger patients, in those with diabetes, or when cataract surgery is combined with vitrectomy (clearance of debris from the fluid in the eye).

Preventing Posterior Capsular Opacification. Studies suggest that acrylic lenses pose the lowest risk for posterior capsular opacification. A number of substances to prevent posterior capsular opacification are under investigation, including tranilast eyedrops, new lens materials, special capsular rings inserted during phacoemulsification, and new coatings on the implanted lens.

Treatment Decisions for Cataracts in the Second Eye. If a person has a cataract in a second eye, the issues for decision making are the same as for the first eye. The time of the procedure in the case of two cataracts is unclear. Doctors have long recommended that surgery on the second eye should be postponed until the first eye has healed and the results known (about a year).

One study has called this recommendation into question. It was conducted in England, where for budgetary reasons, there are long waits for second-eye cataract surgeries. In the study, patients who waited 7 - 12 months for the second-eye surgery reported significant difficulty in reading and performing ordinary tasks during the waiting period. Only 1% of patients who had the second surgery within 6 weeks reported having trouble seeing. In addition, 70% of those who waited experienced problems in depth perception, which can cause difficulty in walking and driving; only 12% who didn't wait reported this problem. Patients with double cataracts should discuss all options with their surgeon.

Treatment for Posterior Capsular Opacification. The standard treatment is laser surgery known as a YAG capsulotomy. (Capsulotomy means cutting into the capsule, and YAG is an abbreviation of yttrium aluminum garnet, the laser most often used for this procedure.)

This is an outpatient procedure and involves no incision.
Using the laser beam, the ophthalmologist makes an opening in the clouded capsule to let light through.
After the procedure the patient should remain in the doctor's office for an hour to be sure that pressure in the eye is not elevated.
An eye examination for any complications should follow within 2 weeks.

Complications. Laser surgery has become so commonplace that some ophthalmologists use it after cataract surgery to prevent later clouding. However, laser surgery carries its own risks and possible complications, similar to those of cataract surgery itself, and can also lead to poorer vision or blindness. About 1% of laser surgery patients develop a detached retina, which is much higher than the risk from the original cataract surgery.

Click the icon to see an image of a detached retina.

In some people, particularly those with glaucoma or who are severely nearsighted, the pressure in the eye may spike after laser surgery. Certain drugs used for treating glaucoma, such as dorzolamide (Trusopt) or apraclonidine (Iopidine), may helpful for preventing this occurrence. It is strongly recommended, however, that this surgery not be performed to prevent a secondary cataract, but only if the lens capsule clouds up again.

Infants. Treatment of infants first depends on whether one or both eyes are affected:

For infants born with cataracts in one eye, the American Academy of Ophthalmology recommends surgery as soon as possible, by 4 months or ideally even earlier. The procedure is followed by contact lens correction and patching of the unaffected eye. Although this approach is successful in many cases, some children still become blind in the affected eye. There is also a high risk for glaucoma after surgery.
In infants with cataracts in both eyes, surgery is not always an option. In some cases, it may be performed sequentially, with the second eye operated on a few days after the first. Phacoemulsification appears to pose a much higher risk for secondary cataracts than standard lens removal.

Toddlers and Older Children. Intraocular lens replacement is now becoming standard treatment for children 2 years and older.

Resources

www.ascrs.org -- The American Society of Cataract and Refractive Surgery
www.aao.org -- American Academy of Ophthalmology
www.nei.nih.gov -- National Eye Institute
www.eyesurgeryeducation.com -- Eye Surgery Education Council
www.lighthouse.org -- Lighthouse International
www.aao.org/aao/find_eyemd.cfm -- Find an ophthalmologist

References

Eke T, Thompson JR. Serious complications of local anaesthesia for cataract surgery: a one-year national survey in the United Kingdom. Br J Ophthalmol. 2006 Nov 23; [Epub ahead of print]

Hutz WW, Eckhardt HB, Rohrig B, Grolmus R. Reading ability with 3 multifocal intraocular lens models. J Cataract Refract Surg. 2006 Dec;32(12):2015-21.

Klein BE, Klein R, Lee KE, Grady LM. Statin use and incident nuclear cataract. JAMA. 2006 Jun 21;295(23):2752-8.

Rein DB, Zhang P, Wirth KE, Lee PP, Hoerger TJ, McCall N, et al. The economic burden of major adult visual disorders in the United States. Arch Ophthalmol. 2006 Dec;124(12):1754-60.

Wishart MS, Dagres E. Seven-year follow-up of combined cataract extraction and viscocanalostomy. J Cataract Refract Surg. 2006 Dec;32(12):2043-9.

Review Date:
3/1/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital

A.D.A.M., Inc. is accredited by URAC, also known as the American Accreditation HealthCare Commission (www.urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows rigorous standards of quality and accountability. A.D.A.M. is among the first to achieve this important distinction for online health information and services. Learn more about A.D.A.M.'s editorial policy, editorial process and privacy policy. A.D.A.M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health on the Net Foundation (www.hon.ch).

A.D.A.M. Copyright

The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed medical professional should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. © 1997-2009 A.D.A.M., Inc. Any duplication or distribution of the information contained herein is strictly prohibited.

adam.com

Gallstones and gallbladder disease

FitSugar — Wed, 08 Oct 2008 17:35:38 -0700

In This Report

Highlights
Introduction
Symptoms
Prognosis
Risk Factors
Prevention
Diagnosis
Treatment
Surgery
Lithotripsy and Dissolution...
Managing Common Bile Duct S...
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Connection to endometrial cancer

Excess estrogen appears to play a role in the development of both gallstones and endometrial cancer. One study found that women who had undergone cholecystectomy (surgery to remove the gallbladder) had a 50% increased risk of developing endometrial cancer. The connection was weaker in women who developed asymptomatic gallstones.

Diet

Men who consume a diet high in foods containing heme iron, such as meat and seafood, are at increased risk for developing gallstones. Gallstones are not associated with diets high in non-heme iron sources, such as beans, lentils, and enriched grains.

Fruits and vegetables appear to substantially reduce the risk of symptomatic gallstone formation. The effect holds true regardless of which fruits or vegetables are consumed. Risk drops in proportion to the percentage of fruits and vegetables in the diet.

Genetics

Studies of twins and families indicate a genetic connection to gallstone formation, but until recently, the mechanism has eluded researchers. Defects in proteins involved in biliary lipid secretion have been identified as a factor predisposing men and women to gallstone disease. But not everyone with these genes develops gallstones. The disease appears to result from the interaction between genetic and environmental factors, with immune and inflammatory mediators possibly playing key roles.

Bariatric Surgery

Patients who undergo bariatric surgery are at increased risk for gallstones and are often required to have their gallbladders removed (cholecystectomy) before their bariatric surgery is performed. Recent studies indicate this practice may not be necessary. In one study, only 8% of patients who did not undergo cholecystectomy before a Roux-en-Y procedure developed symptomatic gallstones. In another study, only 3% of those who underwent lap banding developed symptomatic gallstones.

Prolonged Intravenous Feeding

People who must rely on intravenous nutrition (home parenteral nutrition or total parenteral nutrition) are at greatly increased risk of developing gallstones, possibly due to lack of intestinal stimulation that decreases the flow of bile. However, gallstones in these patients are easily treated and have a low risk of complications.

Introduction

Gallstones are small, hard pellets that can form in the gallbladder, a sac-like organ that lies under the liver on the right side of the abdomen. Most people with gallstones don't even know they have them. But in some cases a stone may cause the gallbladder to become inflamed, resulting in pain, infection, or other serious complication.

The formation of gallstones is a complex process that starts with bile, a fluid composed mostly of water, bile salts, lecithin (a fat known as a phospholipid), and cholesterol. Most gallstones are formed from cholesterol.

Bile is important for the digestion of fat. It is first produced by the liver and then secreted through tiny channels that eventually lead into a larger tube called the common bile duct, which leads to the small intestine.

Only a small amount of bile drains directly into the small intestine, however. Most flows into the gallbladder through the cystic duct, which is a side extension off the common bile duct. This system of ducts through which bile flows is called the biliary tree.

Click the icon to see an image of the biliary tree.

The gallbladder is a 4-inch sac with a muscular wall that is located under the liver. Here, most of the bile fluid (about 2 - 5 cups a day) is removed, leaving a few tablespoons of concentrated bile.
The gallbladder serves as a reservoir until bile is needed in the small intestine to digest fats. This need is triggered by a hormone called cholecystokinin, which is released when food enters the small intestine.
Cholecystokinin signals the gallbladder to contract and deliver bile into the intestine. The force of the contraction propels the bile down the common bile duct and into the small intestine, where it emulsifies (breaks down) fatty molecules.
This part of the digestive process enables the emulsified fat along with important fat-absorbable nutrients (e.g., vitamins A, D, E, and K) to pass through the intestinal lining and enter the blood stream.

Gallstones can range from a few millimeters to several centimeters in diameter. Most are formed from cholesterol. Pigment stones are the second most common type of gallstones (approximately 15% of stones are pigment stones). Patients can also have a mixture of the two. Pigment stones are formed from a brown-colored substance called calcium bilirubinate.

Cholesterol Stones. Although cholesterol makes up only 5% of bile, about three-fourths of the gallstones found in the US population are formed from cholesterol. Cholesterol gallstones typically form in the following way:

Cholesterol is not very soluble, so in order to remain suspended in fluid it must be transported within clusters of bile salts called micelles. If there is an imbalance between these bile salts and cholesterol, then the bile fluid turns to sludge. This thickened fluid consists of a mucus gel containing cholesterol and calcium bilirubinate.
If the imbalance worsens, cholesterol crystals form (a condition called supersaturation), which can eventually form gallstones.
This process of gallstone formation is referred to as cholelithiasis. It is very slow and most often painless.

Click the icon to see an image of gallstones.

Supersaturation and cholelithiasis can occur as a result of various abnormalities, although the cause is not entirely clear. There are many events that may promote cholelithiasis:

The liver secretes too much cholesterol into the bile.
The gallbladder may not be able to empty normally, so bile becomes stagnant.
The cells lining the gallbladder may not be able to efficiently absorb cholesterol and fat from bile.
High levels of bilirubin have been observed in patients with gallstones. Bilirubin is a substance normally formed by the breakdown of hemoglobin in the blood and is excreted in bile. Some experts believe it may play an important role in the formation of cholesterol gallstones.

Pigment Stones. Pigment stones are composed of calcium bilirubinate, or calcified bilirubin. Pigment stones can be black or brown.

Black stones form in the gallbladder and are the more common type. They represent 20% of all gallstones in the US. They are more likely to develop in people with hemolytic anemia (a relatively rare anemia where red blood cells are destroyed) or cirrhosis (scarred liver).
Brown pigment stones are more common in Asian populations. They contain more cholesterol and calcium than black pigment stones and are more likely to occur in the bile ducts. Infection plays a role in the development of these stones. One report suggested that bacteria or other microorganisms may trigger oxidation (a damaging chemical process in the body) which, in this case, can cause changes that lead to pigment stone formation.

Gallstones can also be present in the common bile duct. This is called choledocholithiasis.

Click the icon to see an image of gallstone obstruction.

Secondary Common Bile Duct Stones. In most cases, common bile duct stones originally form in the gallbladder and pass into the common duct (called secondary stones). Choledocholithiasis occurs in about 10% of patients with gallstones.

Primary Common Bile Duct Stones. In less common cases, the stones form in the common duct itself (called primary stones). Primary common duct stones are usually of the brown pigment type and are more likely to cause infection than secondary common duct stones.

Gallbladder disease can occur without stones, a condition called acalculous gallbladder disease. It can be acute (arising suddenly) or chronic (persistent).

Acute acalculous gallbladder disease usually occurs in patients who are very ill from other disorders. In such cases, inflammation occurs in the gallbladder, usually from a diminished blood supply or an impaired ability to contract and empty its bile.
Chronic acalculous gallbladder disease (also called biliary dyskinesia) appears to be caused by muscle defects or other problems in the gallbladder that cause impaired motility.

Diagnosing Acute Acalculous Gallbladder Disease. Symptoms are similar to those of acute cholecystitis with gallstones, but they may be obscured by other medical conditions, since patients with this condition are often critically ill with other illnesses.

Diagnosing Chronic Acalculous Gallbladder Disease. Chronic acalculous gallbladder disease is usually diagnosed when a patient complains of gallbladder symptoms, but no evidence of stones is seen using standard imaging techniques. More than half of patients initially diagnosed with this disease, however, are eventually shown to have small stones or gallbladder sludge. The patient is given the hormone cholecystokinin octapeptide (CCK), which induces gallbladder contraction, followed by a radioisotope scan to determine whether the gallbladder is emptying correctly. If the gallbladder demonstrates difficulty releasing bile, doctors usually consider the diagnosis confirmed.

Treatment for Acute Acalculous Gallbladder Disease. Acute acalculous gallbladder disease has a very high rate of serious complications (gangrene, perforation, and pus in the gallbladder), so emergency removal of the gallbladder is warranted.

Treatment for Chronic Acalculous Gallbladder Disease. Most patients (75 - 90%) diagnosed with chronic acalculous gallbladder disease are relieved of their symptoms by cholecystectomy (removal of the gallbladder). Between 10 - 23%, however, still experience pain. Surgery is most warranted in these patients when the symptoms are caused by impaired emptying of the gallbladder.

Symptoms

About 90% of gallstones provoke no symptoms at all. If problems do develop, the chance of developing pain is about 2% per year for the first 10 years after stone formation. After this, the chance for developing symptoms declines. On average, symptoms take about 8 years to develop. The reason for the decline in incidence after 10 years is not known, although some doctors suggest that "younger," smaller stones may be more likely to cause symptoms than larger, older ones.

The mildest and most common symptom of gallbladder disease is intermittent pain called biliary colic, which occurs either in the mid- or the right portion of the upper abdomen. A typical attack has several features:

The primary symptom is typically a steady gripping or gnawing pain in the upper right abdomen near the rib cage, which can be quite severe and can radiate to the upper back. Some patients with biliary colic experience the pain behind the breast bone.
Nausea or vomiting may occur.
Changes in position, over-the-counter pain relievers, and passage of gas do not relieve the symptoms.
Biliary colic typically disappears after 1 to several hours. If it persists beyond this point, acute cholecystitis or more serious conditions may be present.
The episodes typically occur at the same time of day, but less frequently than once a week. Large or fatty meals can precipitate the pain, but it usually occurs several hours after eating and often awakens the patient during the night.
Recurrence is common, but attacks can be years apart. In one study, for example, 30% of people who had had 1- 2 attacks experienced no further biliary pain over the next 10 years.

Digestive complaints such as belching, feeling unduly full after meals, bloating, heartburn (burning feeling behind the breast bone), or regurgitation (acid back-up in the food pipe) are not likely to be caused by gallbladder disease. Conditions that may cause these symptoms include peptic ulcer, gastroesophageal reflux disease, or indigestion of unknown cause. [See In-Depth Report #19 Peptic Ulcers and In-Depth Report #85 Gastroesophageal Reflux Disease.]

Between 1 - 3% of people with symptomatic gallstones develop inflammation in the gallbladder (acute cholecystitis), which occurs when stones or sludge obstruct the duct. The symptoms are similar to those of biliary colic but are more persistent and severe. They include the following:

Pain in the upper right abdomen is severe and constant and can last for days. Pain frequently increases when drawing a breath.
Pain also may radiate to the back or occur under the shoulder blades, behind the breast bone, or on the left side.
About a third of patients have fever and chills.
Nausea and vomiting may occur.

Anyone who experiences such symptoms should seek medical attention. Infection develops in about 20% of these cases, which increases the danger. Acute cholecystitis can progress to gangrene or perforation of the gallbladder if left untreated. People with diabetes are at particular risk for serious complications.

Chronic gallbladder disease (chronic cholecystitis) is marked by gallstones and low-grade inflammation. In such cases the gallbladder may become scarred and stiff. Symptoms of chronic gallbladder disease include the following:

Complaints of gas, nausea, and abdominal discomfort after meals are the most common, but they may be vague and indistinguishable from similar complaints in people without gallbladder disease.
Chronic diarrhea (4 - 10 bowel movements every day for at least 3 months) may be a common symptom of gallbladder dysfunction.

Stones lodged in the common bile duct (choledocholithiasis) can cause symptoms that are similar to those produced by stones that lodge in the gallbladder, but they may also cause the following symptoms:

Jaundice (yellowish skin)
Dark urine, lighter stools, or both
Heartbeat may become rapid and blood pressure may drop abruptly
Fever, chills, nausea and vomiting, and severe pain in the upper right abdomen. These symptoms suggest an infection in the bile duct (called cholangitis).

As in acute cholecystitis, patients who have these symptoms should seek medical help immediately. They may require emergency treatment.

Prognosis

Asymptomatic gallstones seldom lead to problems. Death, even from symptomatic gallstones, is very rare, accounting for only 0.2% of annual deaths in the United States. Serious complications are rare. If they do occur, complications usually develop from stones in the bile duct or after surgery.

Gallstones, however, can cause obstruction at any point along the ducts that carry bile and, in such cases, symptoms can develop.

In most cases of obstruction, the stones block the cystic duct, which leads from the gallbladder to the common bile duct. This can cause pain (biliary colic), infection and inflammation (acute cholecystitis), or both.
About 10% of patients with symptomatic gallstones also have stones that pass into and obstruct the common bile duct (called choledocholithiasis).

The most serious complication of acute cholecystitis is infection, which develops in about 20% of cases. It is extremely dangerous and life-threatening if it spreads to other parts of the body (septicemia), and surgery is often required. Symptoms include fever, rapid heartbeat, fast breathing, and mental confusion. Among the conditions that can lead to septicemia are the following:

Gangrene or Abscesses. If acute cholecystitis is untreated and becomes very severe, inflammation can cause abscesses or destroy enough tissue in the gallbladder ( necrosis) to lead to gangrene. Studies have reported this complication in between 2 - 30% of cases. The highest risk is in men over 50 with a history of heart disease who have high levels of infection.
Perforated Gallbladder. An estimated 10% of acute cholecystitis cases result in a perforated gallbladder, which is a life-threatening condition. In general, this occurs in people who wait too long to seek help or who do not respond to treatment. This condition is most common in people with diabetes. The risk for perforation increases with a condition called emphysematous cholecystitis, in which gas forms in the gallbladder. Once the gallbladder has been perforated, pain may temporarily decrease. This is a dangerous and misleading event, however, since peritonitis (widespread abdominal infection) develops afterward.
Empyema. Pus in the gallbladder (empyema) occurs in 2 - 3% of patients with acute cholecystitis. Patients usually experience severe abdominal pain for more than 7 days. The physical exam often fails to reveal the underlying cause. The condition can be life-threatening, particularly if infection spreads to other parts of the body.
Fistula. In some cases, the inflamed gallbladder adheres to and perforates nearby organs, such as the small intestine. In such cases a fistula (channel) between the organs develops. Sometimes, in these cases, gallstones can actually pass into the small intestine, which can be very serious and requires immediate surgery.
Gallstone Ileus. A gallstone blocking the intestine is known as gallstone ileus. It primarily occurs in patients over age 65, and can sometimes be fatal. Depending on where the stone is located, surgery to remove the stone may be required.

When gallstones lodge in the common bile duct (choledocholithiasis) instead of the gallbladder, serious complications can occur.

Infection in the Common Bile Duct (Cholangitis). Infection in the common bile duct (cholangitis) from obstruction is common and serious. Those at highest risk for a poor outlook also have one or more of the following conditions:

Kidney failure
Liver abscess
Cirrhosis
Being over 50 years

If antibiotics are administered immediately, the infection clears up in 75% of patients. If cholangitis does not improve, the infection may spread and become life-threatening. Either surgery or a procedure known as endoscopic sphincterotomy is required to open and drain the ducts.

Pancreatitis. Choledocholithiasis is responsible for most cases of pancreatitis (inflammation of the pancreas), a condition that can be life threatening. The pancreatic duct, which carries digestive enzymes, joins the common bile duct right before it enters the intestine. It is therefore not unusual for stones that pass through or lodge in the lower portion of the common bile duct to obstruct the pancreatic duct.

Gallstones are present in about 80% of people with gallbladder cancer. Symptoms of gallbladder cancer usually do not appear until the disease has reached an advanced stage and may include weight loss, anemia, recurrent vomiting, and a lump in the abdomen. When the cancer is caught at an early stage and has not spread beyond the mucosa (the inner lining), removal of the gallbladder results in a 5-year survival rate of 68%. If cancer has spread to deeper layers, more extensive surgery or other treatments may be required.

This cancer is very rare, however, even among people with gallstones. Certain conditions in the gallbladder, however, pose a higher than average risk for cancer.

Gallbladder Polyps and Primary Sclerosing Cholangitis. Polyps (growths) are sometimes detected during diagnostic tests for gallbladder disease. Small gallbladder polyps (up to 10 mm) pose little or no risk, but large ones (greater than 15 mm) pose some risk for cancer, so the gallbladder should be removed. Patients with polyps 10 - 15 mm have a lower risk, but they should still discuss removal of their gallbladder with their doctor.

Primary Sclerosing Cholangitis. Primary sclerosing cholangitis is a rare disease that causes inflammation and scarring in the bile duct. It is associated with a lifetime risk of 7 - 12% for gallbladder cancer. The cause is unknown although it tends to strike younger men with ulcerative colitis. Polyps are often detected in this condition and have a very high likelihood of malignancy.

Anomalous Junction of the Pancreatic and Biliary Ducts. With this rare congenital condition, the junction of the common bile duct and main pancreatic duct is located outside the wall of the small intestine and forms a long channel between them. This problem poses a very high risk of cancer in the biliary tract.

Porcelain Gallbladders. Gallbladders are referred to as porcelain when their walls have become so calcified that they look like porcelain on an x-ray. Porcelain gallbladders have been associated with a very high risk of cancer, although recent evidence suggests that the risk is lower than previously thought. The incidence appears to depend on the presence of specific factors, such as partial calcification involving the mucosal lining. This condition may develop from a chronic inflammatory reaction that may actually be responsible for the cancer risk. Studies are reporting no higher risk with "true" porcelain gallbladders, in which the gallbladder walls are entirely calcified.

Risk Factors

About 20 million Americans harbor gallstones. Only 1 - 3% of the population, however, complains of symptoms during the course of a year, and less than half of these people will experience recurrent symptoms.

Women are much more likely than men to develop gallstones. Gallstones occur in nearly 25% of women in the U.S. by age 60 and as many as 50% by age 75. In most cases, they are asymptomatic. In general, women are probably at increased risk because estrogen stimulates the liver to remove more cholesterol from blood and divert it into the bile.

Pregnancy. Pregnancy increases the risk for gallstones, and pregnant women with stones are more likely to have symptoms than nonpregnant women. Surgery should be delayed until after delivery if possible. In fact, gallstones may disappear after delivery. If surgery is necessary, laparoscopy is the safer approach.

Hormone Replacement Therapy. Several large studies have shown that use of hormone replacement therapy (HRT) doubles or triples the risk for gallstones or gallbladder surgery. A 2005 Journal of the American Medical Association study found that while all types of HRT raise the risks, estrogen alone has higher risks than combined estrogen and progesterone therapy. Estrogen has an effect on the liver and raises triglycerides, a fatty acid that increases the risk for cholesterol stones. Recent studies on HRT reporting negative effects on the heart and increased risks for breast cancer are also making this treatment a less attractive option for most postmenopausal women.

About 20% of men have gallstones by the time they reach age 75. Because most cases are asymptomatic, however, the rates may be underestimated in elderly men. One study of nursing home residents reported that 66% of the women and 51% of the men had gallstones. Men who have their gallbladders removed, moreover, are more likely to have severe disease and operative complications than women.

Gallstone disease is relatively rare in children. When gallstones occur in this age group they are more likely to be pigment stones. Girls do not seem to be more at risk than boys are. The following conditions may put children at higher risk:

Spinal injury
History of abdominal surgery
Sickle-cell anemia
Impaired immune system
Intravenous nutrition

Because gallstones are related to diet, particularly fat intake, the incidence of gallstones varies widely among nations and regions. For example, Hispanics and Northern Europeans have a higher risk for gallstones than people of Asian and African descent do. People of Asian descent who develop gallstones are most likely to have the brown pigment type.

Native North and South Americans, such as Pima Indians in the U.S. and native populations in Chile and Peru, are especially prone to developing gallstones. Pima women have an 80% chance of developing gallstones during their lives, and virtually all native Indian females in Chile and Peru develop gallstones. Such cases are most likely due to a combination of genetic and dietary factors.

Having a family member or close relative with gallstones may increase the risk of gallstones. Up to one-third of cases of painful gallstones may be related to genetic factors.

Defects in transport proteins involved in biliary lipid secretion appear to predispose certain people to gallstone disease, but this alone many not be sufficient to create gallstones. Studies indicate that the disease is complex and may result from the interaction between genetics and environment. Some studies suggest immune and inflammatory mediators may play key roles.

People with diabetes are at higher risk for gallstones and have a higher-than-average risk for acalculous gallbladder disease (without stones). Gallbladder disease may progress more rapidly in patients with diabetes, who tend to suffer worse infections.

In theory, drugs designed to improve insulin resistance should reduce the incidence of gallstones. However, this may not always occur. Researchers were surprised when animal studies showed that the type 2 diabetes drug pioglitazone (Actos) caused gallbladder volume to increase, indicating that its function may be compromised. This may raise the risk of gallstone formation.

Obesity. Being overweight is a significant risk factor for gallstones. In such cases, the liver over-produces cholesterol, which is delivered into the bile and causes it to become supersaturated. Some evidence suggests that specific dietary factors (saturated fats and refined sugars) are the primary culprit in these cases, although studies are conflicting. Animal studies, however, suggest that obesity itself, not any particular foods, triggers the process leading to cholesterol supersaturation and the formation of stones.

Weight Cycling. Rapid weight loss or cycling (dieting and then putting weight back on) further increases cholesterol production in the liver, with resulting supersaturation and risk for gallstones. A 2000 study suggested the following rates for gallstones related to extreme and rapid weight loss:

The risk for gallstones is as high as 12% after 8 -16 weeks of restricted-calorie diets.
The risk is more than 30% within 12 -18 months after gastric bypass surgery.

About one-third of gallstone cases in these situations are symptomatic. The risk for gallstones is highest in the following dieters:

Those who lose more than 24% of their body weight.
Those who lose more than 1.5 kg (3.3. lb.) a week.
Those on very low-fat, low-calorie diets.

Weight cycling also puts people at risk for gallstones. For example, a 16-year study found that the risk for gallstone surgery was 68% higher for women who lost and then regained more than 20 pounds at least once, as compared with women whose weight remained stable.

Men are also at increased risk for developing gallstones when their weight fluctuates. The risk increases proportionately with dramatic weight changes as well as with frequent weight cycling.

Bariatric Surgery. Patients who have either Roux-en-Y or laparoscopic banding bariatric surgery are at increased risk for gallstones. For this reason, many centers request the patient undergo cholecystectomy before their bariatric procedure. Doctors are now questioning this practice. A study of nearly 1,000 patients who did not have gallbladder surgery before their Roux-en-Y found that only 8% developed symptomatic gallstones requiring cholecystectomy, and that all cases occurred within 29 months of the bariatric procedure. In another study of 261 patients who underwent lap banding, only 3 developed symptomatic gallstones after the procedure.

Metabolic syndrome is a cluster of conditions that includes obesity (especially belly fat), low HDL (good) cholesterol, high triglycerides, high blood pressure, and high blood sugar. Research suggests that metabolic syndrome is a risk factor for gallstones.

Although gallstones are formed from supersaturation of cholesterol in the bile, high total cholesterol levels themselves are not necessarily associated with gallstones. Gallstone formation, however, is associated with low levels of "good" HDL cholesterol and high triglyceride levels. Some evidence suggests that high triglycerides may impair the emptying actions of the gallbladder.

Unfortunately, some fibrates (drugs used to correct these conditions) actually increase the risk for gallstones by increasing the amount of cholesterol secreted into the bile. They include gemfibrozil (Lopid), fenofibrate (Tricor), and bezafibrate (Bezalip). Other cholesterol-lowering agents do not have this effect. [See In-Depth Report #23: Cholesterol.]

Prolonged Intravenous Feeding. Prolonged intravenous feeding reduces the flow of bile and increases the risk for gallstones. Up to 40% of patients on home parenteral nutrition develop gallstones, and the risk may be higher in patients on total parenteral nutrition. It is suspected that the cause is lack of stimulation in the gut, since patients who also take some food by mouth have less risk of developing gallstones. However, treatment for gallstones in this population is associated with a low risk of complications.

Crohn's Disease. Crohn's disease, an inflammatory bowel disorder, leads to poor reabsorption of bile salts from the digestive tract and substantially increases the risk of gallbladder disease. Patients over age 60 and those who have had numerous bowel operations (particularly in the region where the small and large bowel meet) are at especially high risk.

Cirrhosis. Cirrhosis poses a major risk for gallstones, particularly pigment gallstones.

Organ Transplantation. Bone marrow or solid organ transplantation increases the risk. The complications can be so severe that some organ transplant centers require the patient's gallbladder be removed before the transplant is performed.

Medications. Octreotide (Sandostatin) poses a risk for gallstones. In addition, the cholesterol-lowering drugs known as fibrates and thiazide diuretics may slightly increase the risk for gallstones.

Blood Disorders. Chronic hemolytic anemia, including sickle cell anemia, increases the risk for pigment gallstones.

Heme Iron. High consumption of heme iron, the type of iron found in meat and seafood, has been shown to lead to gallstone formation in men. Gallstones are not associated with diets high in non-heme iron foods such as beans, lentils, and enriched grains.

Prevention

Diet plays a role in gallstones. The following discussions are some observations on specific dietary factors.

Fats. Although fats (particularly saturated fats found in meats, butter, and other animal products) have been associated with gallstone attacks, some studies have found a lower risk for gallstones in people who consume foods containing monounsaturated fats (found in olive and canola oils) or omega-3 fatty acids (found in canola, flaxseed, and fish oil). Fish oil may be of particular benefit in patients with high triglyceride levels by improving the emptying actions of the gallbladder.

Fiber. High intake of fiber has been associated with a lower risk for gallstones.

Nuts. Studies suggest that people may be able to reduce their risk of gallstones by eating more nuts (peanuts and tree nuts such as walnuts and almonds).

Fruits and Vegetables. Researchers who followed more than 77,000 healthy women for 16 years in the Nurses' Health Study found that those who ate the most fruits and vegetables had the lowest risk of developing symptomatic gallstones requiring removal of the gallbladder. The effect was consistent regardless of which fruits or vegetables they ate.

Vegetable Protein. A 2004 epidemiologic study found evidence that consumption of vegetable protein (such as soybean products) can help to prevent symptomatic gallstones.

Lecithin. Lecithin is a key component of bile. It contains choline and inositol, two compounds that are important for the breakdown of fat and cholesterol. Low levels of lecithin may precipitate the formation of cholesterol gallstones. Animal studies have suggested that lecithin-rich soy and buckwheat protein may protect against gallstones. (Buckwheat may be more protective than soy.) Dietary lecithin is available in health food stores and is found in eggs, soybeans, liver, wheat germ, and peanuts. There is no evidence, however, that lecithin supplements or foods containing it can prevent gallstones in humans.

Sugar. High-intake of sugar has been associated with an increased risk for gallstones. Diets that are high in carbohydrates such as pasta and bread can also increase risk, since carbohydrates are converted to sugar in the body.

Alcohol. A few studies have reported a lower risk for gallstones with alcohol consumption. Even small amounts (1 ounce per day) have been found to reduce the risk of gallstones in women by 20%. Moderate intake (defined as 1 - 2 drinks a day) also appears to have heart protection benefits. It should be noted, however, that even moderate intake increases the risk for breast cancer in women. Pregnant women, people who can't drink moderately, and people with liver disease should not drink at all.

Vitamin C. Ascorbic acid (vitamin C) appears to help break cholesterol down in bile. Vitamin C deficiencies have been associated with a higher risk for gallstones.

Coffee. In one study, men who drank 2 or more cups of regular coffee daily (either instant, filtered, or espresso) had a 40% lower risk of developing gallbladder disease over 10 years than men who did not drink coffee regularly. Those who drank more than 4 cups had the lowest risk. A more recent study in 2000 did not find any general protective effect, although women with gallstones who drank coffee reported fewer symptoms than those who didn't.

Maintaining a normal weight and avoiding rapid weight loss are the keys to reducing the risk of gallstones. Taking the medication ursodiol (also called ursodeoxycholic acid, or Actigall) during weight loss may reduce the risk for people who are very overweight and need to lose weight quickly. This medication is ordinarily used to dissolve existing gallstones. A promising 2001 study suggested that orlistat (Xenical), a drug for treating obesity, may protect against gallstone formation during weight loss. The drug appeared to reduce bile acids and other components involved in gallstone production.

Exercising regularly and vigorously may reduce the risk of gallstones and gallbladder disease, even in people who are overweight. Studies are reporting a lower risk for gallstones in both men and women who exercise. Active sports exercise appears to be most protective for both men and women. A 1999 study of women reported that exercise reduced gallstone risk regardless of whether the women lost weight or not. Some evidence suggests that, in addition to controlling weight, exercise helps reduce cholesterol levels in the biliary tract, which could help prevent gallstones.

Some data have indicated that taking nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin or ibuprofen protects against the development of gallstones. Recent studies have been mixed, although a 2001 study reported significant protection against gallstone recurrence in people who took NSAIDs after being treated with lithotripsy.

NOTE: Long-term use of NSAIDS can cause stomach problems, such as ulcers and bleeding, and possible heart problems. In April 2005, the FDA asked drug manufacturers of NSAIDs to include a warning label on their product that alerts users of an increased risk for cardiovascular events and gastrointestinal bleeding. Talk to your doctor before taking these drugs.

Although it would be reasonable to believe that agents used to lower cholesterol would protect against gallstones, they either have little effect or, in the case of fibrates, actually increase the risk. One study reported a weak association between statins and a lower risk for gallstones. These are the most effective drugs for treating high cholesterol and include lovastatin (Mevacor), pravastatin (Pravachol), simvastatin (Zocor), fluvastatin (Lescol), atorvastatin (Lipitor), and rosuvastatin (Crestor). Most evidence, however, has found no protection even from these agents. Reducing cholesterol itself, then, does not have any effect on cholesterol gallstones.

Diagnosis

The diagnostic challenge posed by gallstones is to verify that abdominal pain is caused by stones and not by some other condition. Ultrasound or other imaging techniques can usually detect gallstones. Nevertheless, because gallstones are common and most cause no symptoms, simply finding stones does not necessarily explain a patient's pain, which may be caused by any number of ailments.

In patients with abdominal pain, causes other than gallstones are usually responsible if the pain lasts less than 15 minutes, frequently comes and goes, or is not severe enough to limit activities.

Irritable Bowel Syndrome. Irritable bowel syndrome (IBS) has some of the same symptoms as gallbladder disease, including difficulty digesting fatty foods. However, the pain of IBS usually occurs in the lower abdomen.

Pancreatitis. It is sometimes difficult to differentiate between pancreatitis and acute cholecystitis, but a correct diagnosis is critical, since treatment is very different. About 40% of pancreatitis cases are associated with gallstones. The risk for gallstone-associated pancreatitis is highest in older Caucasian and Hispanic women. About 25% of pancreatitis cases are severe, and the rate is much higher in people who are obese.

Blood tests showing high levels of pancreatic enzymes (amylase and lipase) usually indicate a diagnosis of pancreatitis. Elevated levels of the liver enzyme alanine aminotransferase (ALT) are very specific in identifying gallstone pancreatitis.

Imaging techniques are useful in confirming a diagnosis. Ultrasound is often used. A computed tomography (CT) scan, along with a number of laboratory tests, can determine the severity of the condition.

Pancreatic Cancer. Symptoms of pancreatic cancer may be very similar to those of gallbladder disease. It should be suspected if such symptoms are accompanied by weight loss or suspicious results from imaging tests of the pancreas.

Other Conditions with Similar Symptoms. Acute appendicitis, inflammatory bowel disease (Crohn's disease or ulcerative colitis), pneumonia, stomach ulcers, gastroesophageal reflux and hiatal hernia, viral hepatitis, kidney stones, urinary tract infections, diverticulosis or diverticulitis, pregnancy complications, and even a heart attack may mimic a gallbladder attack.

In patients with known gallstones, the doctor can often diagnose acute cholecystitis (gallbladder inflammation) based on classic symptoms (constant and severe pain in the upper right quadrant of the abdomen). Imaging techniques are necessary to confirm the diagnosis. There is usually no tenderness in chronic cholecystitis.

Blood tests are usually normal in people with simple biliary colic or chronic cholecystitis. The following abnormalities may indicate gallstones or complications:

The enzyme alkaline phosphatase and bilirubin are usually elevated in acute cholecystitis, and especially choledocholithiasis (common bile duct stones). Bilirubin is the orange-yellow pigment found in bile. High levels cause jaundice, which gives the skin a yellowish tone.
Liver enzymes known as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are elevated when common bile duct stones are present. A threefold or more increase in ALT strongly suggests pancreatitis.

A high white blood cell count is a common finding in many (but not all) patients with cholecystitis.

General Guidelines. Common duct stones (choledocholithiasis) may be detected at one of several points:

When the patient complains of gallbladder symptoms.
At the same time that gallstones are diagnosed. (Common duct stones often accompany gallstones.)
During or after performing surgery to remove the gallbladder for gallstones (cholecystectomy).

If the doctor only suspects common duct stones, however, identifying them is problematic. It requires blood tests, imaging tests, invasive procedures, or some combination that serve both for detection and possibly removal.

Laboratory Tests. Evidence that may suggest common bile duct stones includes dark urine, jaundice, or pancreatitis. In such cases, the doctor may perform certain blood tests. Elevated levels of the following suggest the presence of common duct stones:

Alkaline phosphatase (ALP). Elevated levels of this enzyme are typically the first signs of common bile duct stones.
Bilirubin (the orange-yellow pigment found in bile). Bilirubin levels increase after alkaline phosphatase rises.
Liver enzymes known as aspartate aminotransferase (AST) and alanine aminotransferase (ALT). These enzymes may temporarily spike if the stone passes into the small intestine.

A number of techniques, particularly endoscopic retrograde cholangiopancreatography (ERCP), endoscopic ultrasound (EUS) and magnetic resonance cholangiography (MRC), are proving to be equally effective for detecting common bile duct stones. Only ERCP, however, allows removal of the stones, but it is invasive. A National Institutes of Health expert panel has endorsed the use of ERCP as a diagnostic technique for patients who are clearly ill with symptoms of gallstones. For patients who are not as sick, the panel recommended noninvasive imaging techniques.

Ultrasound. Ultrasound is a simple, rapid, and noninvasive imaging technique. It is the diagnostic method most frequently used to detect gallstones and is the method of choice for detecting acute cholecystitis. The patient must not eat for 6 or more hours before the test, which takes only about 15 minutes. During the procedure, the doctor can check the liver, bile ducts, and pancreas, and quickly scan the gallbladder wall for thickening (characteristic of cholecystitis).

Ultrasound detects gallstones as small as 2 mm in diameter with an accuracy of 90 - 95%. Some experts recommend that if an ultrasound does not detect stones, but gallstones are still strongly suspected, the test should be repeated.

Air in the gallbladder wall may indicate gangrene.

Ultrasound does not appear to be very useful for identifying cholecystitis in symptomatic patients who do not have gallstones. In one study, ultrasound detected some gallbladder abnormalities, no matter what the cause of the abdominal pain. In only a few cases, however, were the symptoms actually caused by cholecystitis.

Ultrasound is also not as useful for common bile duct stones and cannot image the cystic duct. Nevertheless, normal ultrasound results along with normal bilirubin and liver enzyme tests are very accurate indications that there are no stones in the common bile duct.

An ultrasound variation called endoscopic ultrasound (EUS) is accurate and useful for patients with an intermediate risk for common bile ducts stones. Its accuracy is comparable to endoscopic retrograde cholangiopancreatography (ERCP), the standard for diagnosing stones in the common bile duct. However, if common duct stones are detected, they cannot be removed. It is useful, then, when common bile duct stones are suspected, but the patient is not clearly ill.

X-Rays. Standard x-rays of the abdomen may detect calcified gallstones and gas. Variations include oral cholecystography or cholangiography.

In oral cholecystography the patient takes a tablet containing a dye the night before the test. The dye fills the gallbladder, and x-ray images are taken the next day. The test has largely been replaced by ultrasound. It is more sensitive than standard x-rays, however, and may be useful in some cases for determining the structural and functional status of the gallbladder, often before nonsurgical procedures.

Cholangiography uses a dye injected into the bile duct and x-ray to view the common bile duct. It is typically used during operations to provide a clear image of the biliary tract.

Cholescintigraphy (Also Called Gallbladder Radionuclide Scan). Cholescintigraphy, a nuclear imaging technique, is more sensitive than ultrasound for diagnosing acute cholecystitis. It is noninvasive but can take 1 - 2 hours or longer. The procedure involves the following steps:

A tiny amount of a radioactive dye is injected intravenously. This material is excreted into bile.
The patient lies on a table under a scanning camera, which detects gamma rays emitted by the dye as it passes from the liver into the gallbladder.
The test can take up to 2 hours, since each image takes about a minute, and they are taken every 5 -15 minutes.

If the dye does not enter the gallbladder, the cystic duct is obstructed, indicating acute cholecystitis. The scan cannot identify individual gallstones or chronic cholecystitis. Occasionally, the scan gives false positive results (detecting acute cholecystitis in people who do not have the condition). Such results are most common in alcoholic patients with liver disease or patients who are fasting or receiving all nutrition intravenously.

Endoscopic Retrograde Cholangiopancreatography (ERCP). Endoscopic retrograde cholangiopancreatography (ERCP) has been the gold standard for detecting common bile duct stones, particularly because they can be removed during the procedure. However, it is invasive and carries a risk for complications. With the advent of noninvasive imaging techniques, ERCP is now generally limited to patients who have a high likelihood of common bile ducts stones, which would need to be removed.

Computed Tomography. Computed tomographic (CT) scans may be a valuable additional imaging technique if the doctor suspects complicating features, such as perforation, common duct stones, or other problems such as cancer in the pancreas or gallbladder. Helical (spiral) CT scanning is advanced technique that shortens the time and obtains clearer images. With this process, the patient lies on a table while a donut-like, low-radiation x-ray tube rotates around the patient.

Magnetic Resonance Imaging (MRI). MRIs may be very useful for detecting common bile duct stones, particularly a specific MRI technique called magnetic resonance cholangiography (MRC). It employs MRI and cholangiography, in which a dye is injected into the bile duct and x-rays are used to view the duct. MRC is extremely sensitive in detecting biliary tract cancer. This imaging procedure is very expensive, however, and may not detect very small stones or chronic infections in the pancreas or bile duct. As with EUS, it is most likely to be useful in a small subset of patients and would not eliminate the need for ERCP in most patients.

Click the icon to see an image of a cholangiogram.

Virtual Endoscopy. Virtual endoscopy is an investigative technique that uses data from CT and MRI scans to generate a 3-dimensional view of various body structures. The images resemble those used in endoscopy, but the procedure is noninvasive. It one study it was able to detect smaller stones in the common bile duct than MRI. At this time it is still experimental.

Treatment

Acute pain from gallstones and gallbladder disease is usually treated in the hospital, where diagnostic procedures are performed to rule out other conditions and complications. There are 3 approaches to gallstone treatment:

Expectant management ("wait and see")
Nonsurgical removal of the stones
Surgical removal of the gallbladder

Guidelines from the American College of Physicians state that when a person has no symptoms, the risks of both surgical and nonsurgical treatment for gallstones outweigh the benefits. Experts suggest a wait-and-see approach for such patients, which they have termed expectant management. Exceptions to this policy are those at risk for complications from gallstones, including the following:

People at risk for gallbladder cancer
Pima Native Americans
Patients with stones larger than 3 cm

One study reported that very small gallstones increase the risk for acute pancreatitis, a serious condition. Some experts therefore believe that gallstones smaller than 5 mm warrant immediate surgery.

There are some minor risks with expectant management for asymptomatic or low-risk individuals. Gallstones almost never spontaneously disappear, except sometimes when they are formed under special circumstances, such as pregnancy or sudden weight loss. At some point, then, the stones may cause pain, complications, or both, and require treatment. Some studies suggest the patient's age at diagnosis may be a factor in the possibility of future surgery. The probabilities are as follows:

15% likelihood of future surgery at age 70
20% at age 50
30% at age 30

The slight risk of developing gallbladder cancer might encourage young adults who are asymptomatic to have their gallbladders removed.

Gallstones are the most common cause for hospital admissions of patients with severe abdominal pain. Diagnostic tests are performed and, depending on results, the approach may be as follows:

Normal Test Results and No Severe Pain or Complications. If the patient has no fever or underlying serious medical problems and shows no signs of severe pain or complications, and if laboratory tests are normal, then the patients may be discharged with oral antibiotics and pain relievers.

Gallstones and Presence of Pain (Biliary Colic) but No Infection. Patients with pain and tests that indicate gallstones but who do not show signs of inflammation or infection have the following options:

Intravenous painkillers are administered for severe pain. Such drugs include meperidine (Demerol) or the potent NSAID ketorolac (Acular, Toradol). Ketorolac should not be used for patients who are likely to need surgery. These drugs can cause nausea, vomiting, and drowsiness. Opioids such as morphine may have fewer adverse effects, but some doctors avoid them for gallbladder disease.
They may electively choose to have the gallbladder removed (called cholecystectomy) at their convenience.
A minority of such patients may be candidates for a stone-breaking technique called lithotripsy. The treatment works best on solitary stones that are less than 2 cm in diameter.
Drug therapy for gallstones is available for some patients who are unwilling to undergo surgery or who have serious medical problems that increase the risks of surgery. Recurrence rates are high with nonsurgical options. The introduction of laparoscopic cholecystectomy has greatly reduced the use of nonsurgical therapies. Note: Drug treatments are generally inappropriate for patients who have acute gallbladder inflammation or common bile duct stones, since delaying or avoiding surgery could be hazardous.

Acute Cholecystitis (Gallbladder Inflammation). The first step if there are signs of acute cholecystitis is to "rest" the gallbladder in order to reduce inflammation. This involves the following treatments:

Fasting
Intravenous fluids and oxygen therapy
Intravenous painkillers, usually meperidine (Demerol). Potent NSAIDs, usually indomethacin, may be particularly useful. Indomethacin, for example, can reduce pain and inflammation and improve emptying actions of the gallbladder. Some doctors believe morphine should be avoided for gallbladder disease.
Intravenous antibiotics. These are administered if the patient shows signs of infection, including fever or an elevated white blood cell count, or in patients without such signs who do not improve after 12 - 24 hours.

Surgery to remove the gallbladder (called cholecystectomy) is nearly always indicated in people with acute cholecystitis. The most common procedure is now laparoscopy, a less invasive technique than open cholecystectomy (which involves a wide abdominal incision). Timing can be within hours to weeks after the acute episode, depending on the severity of the condition.

Click the icon to see an illustrated series detailing a gallbladder removal.

Gallstone-Associated Pancreatitis. Patients who have developed gallstone-associated pancreatitis almost always require surgery with either laparoscopic or open cholecystectomy.

Common Duct Stones. If noninvasive diagnostic tests suggest obstruction from common duct stones, the doctor will perform a procedure called endoscopic retrograde cholangiopancreatography (ERCP) to confirm the diagnosis and remove stones. This technique is used urgently along with antibiotics if infection is present in the common duct (cholangitis). In most cases, common duct stones are discovered during or after gallbladder removal.

Surgery

The gallbladder is not an essential organ, and even today, only surgical removal of the gallbladder (cholecystectomy ) guarantees that the patient will not suffer a recurrence of gallstones. This is one of the most common surgical procedures performed on women, and it can even be performed on pregnant women with low risk to the baby and the mother. The primary advantages of surgical removal of the gallbladder over nonsurgical treatment are elimination of gallstones and prevention of gallbladder cancer.

Open Procedures versus Laparoscopy. Until the early 1990s, open cholecystectomy (the removal of the gallbladder through a wide abdominal incision) was the standard treatment. Now, laparoscopic cholecystectomy (commonly called lap choly), which uses small incisions, is the most commonly used surgical approach. First performed in 1987, lap choly is now used in most cholecystectomies in the United States. In fact, about 700,000 people now have their gallbladders removed each year -- 200,000 more than before the introduction of laparoscopy. Of concern, then, is a significant increase in its use in patients who have inflammation in the gallbladder but no infection or gallstones and in those who have gallstones but no symptoms.

Laparoscopy has largely replaced open cholecystectomy because of some significant advantages:

The patient can leave the hospital and resume normal activities earlier than with open surgery.
The incisions are small, and there is less postoperative pain and disability than with the open procedure.
Laparoscopy has fewer complications.
It is less expensive than open cholecystectomy in the long term. The immediate treatment cost of laparoscopy may be higher than the open procedure, but the more rapid recovery with lap choly and fewer complications translate into shorter hospital stays and fewer sick days, and so a greater reduction in overall costs.

Some experts believe, however, that the open procedure still has a number of advantages compared to laparoscopy:

It is faster to perform.
It poses less of a risk for bile duct injury, which occurs in only 0.1 - 0.5% of open procedures, compared to about 0.3 - 2% with laparoscopy. Open surgry has more overall complications than laparoscopy, however, and bile-duct injury rates with laparoscopy are declining.

The type of surgery performed on specific patients may vary depending on different factors.

Appropriate Surgical Candidates. Candidates for gallbladder removal often have, or have had, one of the following conditions:

A very severe gallstone attack
Several less severe gallstone attacks
Endoscopic sphincterotomy for common bile duct stones i(n patients with residual gallbladder stones)
Cholecystitis (gallbladder inflammation).
Pncreatitis (inflammation of the pancreas)
High risk for gallbladder cancer (e.g., patients with anomalous junction of the pancreatic and biliary ducts or patients with certain forms of porcelain gallbladder)
Acalculous biliary pain (gallbladder disease symptoms without the presence of gallstones). The best candidates are those with evidence of impaired gallbladder emptying.

Timing of Surgery. Cholecystectomy may be performed within days to weeks after hospitalization for an acute gallbladder attack, depending on the severity of the condition.

Emergency gallbladder removal within 24 - 48 hours is warranted in about 20% of patients with acute cholecystitis. Indications for surgery include deterioration of the patient's condition, or signs of perforation or widespread infection.
The timing and type of surgery in patients with acute cholecystitis whose condition improves and have no signs of severe complications are under debate. Previously, the standard was open cholecystectomy between 6 - 12 weeks after the acute episode. Some evidence now suggests that early surgery performed between 72 - 96 hours after symptoms have lower complications than surgery performed after that.

General Outlook. Although cholecystectomy is very safe, as with any operation, there are risks of complications depending on whether the procedure is done on an elective or emergency basis.

When cholecystectomy is performed as elective surgery, the mortality rates are very low. (Even in the elderly, mortality rates are only 0.7 - 2%.)
Emergency cholecystectomy carries a much higher mortality rate (as high 19% in ill elderly patients).

Long-Term Effects of Gallbladder Removal. Although removal of the gallbladder has not been known to cause any long-term adverse effects aside from occasional diarrhea, some researchers have been concerned about its long-term impact on the body's cholesterol levels.

One study found that within 3 days of the operation, levels of total cholesterol and LDL returned to their preoperative levels. After 3 years, however, some types of cholesterol not ordinarily associated with coronary artery disease had risen significantly. These results did not necessarily indicate any increased risk for coronary artery disease, but they did show that the metabolism of cholesterol by the liver had been altered. People who have had their gallbladders removed should have their cholesterol levels checked periodically, as should every adult. Short-term treatment with the cholesterol-lowering known as statins, such as pravastatin (Pravachol), appears to lower cholesterol levels in surgical patients.


Laparoscopy	Open Cholecystectomy
Treatment of choice for most adult gallstone patients with or without symptoms, who have electively chosen to have their gallbladders removed.	Patients who have had extensive previous abdominal surgery.
Most patients with acute cholecystitis not accompanied by infection or perforation. (Up to 30% will need to convert to open surgery, depending on the severity of the condition.)	Patients with complications of acute cholecystitis (empyema, gangrene, perforation of the gallbladder).
Patients with acalculous gallbladder disease (without stones) who choose to have surgery. (if the patients have inflammation, however, the procedure of choice is percutaneous cholecystostomy to drain the gallbladder.	Very elderly patients. (Those over 80 are likely to have lower complication rates from open cholecystectomy than laparoscopy, although laparoscopy may even be appropriate in these patients.)
Patients with residual gallbladder stones after endoscopic sphincterotomy for common bile duct stones.
Candidates when experienced surgeons are available: Patients with acute gallstone pancreatitis that has subsided. Severely obese patients Patients with prior surgery in the upper abdomen. Patients with severely infected gallbladders. Pregnant women with symptomatic gallstones.	Seriously ill patients with acute cholecystitis who do not respond to fluid aspiration (percutaneous cholecystostomy).

The Procedure. With laparoscopy, removal of the gallbladder is typically performed as follows:

Laparoscopic cholecystectomy requires general anesthesia, although it is now mostly done as outpatient surgery.

The surgeon inserts a needle through the navel and pumps carbon dioxide gas through it to create space in the abdomen. This step may raise blood pressure. The antihypertensive drug clonidine may be helpful during surgery to protect patients with high blood pressure or heart or kidney disease. Of note, a 2000 study recommended that elderly patients not receive gas. Such patients are more likely to require a longer operating time, and the on-going pressure from the carbon dioxide increases the risk for problems that require conversion to an open procedure.
One or two 10 - 12 mm (about one-half inch) and three 5 mm (.20 inches), are made in the abdomen.
The surgeon inserts a laparoscope (a thin telescope) which contains a small surgical instrument and a tiny camera that relays an image to a video monitor.
The surgeon separates the gallbladder from the liver and other areas and removes it through one of the incisions.
Evidence suggests that the use of cholangiography during the operation helps prevent injury in the bile ducts, a serious complication of cholecystectomy. With this procedure, dye is injected into the bile duct, and moving x-rays are used to view the duct.
In general, the patient can go home the same day. In a 2001 study, however, some patients were found to be at higher risk for readmission later on, including those operation took longer than 1 hour or who had thicker gallbladder walls

Risk Factors for Conversion from Laparoscopy to an Open Procedure. In about 5 - 10% of laparoscopies, conversion to open cholecystectomy is required during the procedure. The rate of conversion to open surgery is higher in men than in women. This may be due to the higher rate of inflammation and fibrosis in men with symptomatic gallstones. Other reasons for conversion from laparoscopic to open surgery include:

Possible or known injury to major blood vessels
Internal structures not clearly visible
Unexpected problems that cannot be corrected with laparoscopy
Common bile duct stones that cannot be removed with laparoscopy or subsequent ERCP.
Previous endoscopic sphincterotomy
A thickened gallbladder wall

Complications and Side Effects of Surgery

Pain and fatigue are common side effects of any abdominal surgery. Patients should abstain from light recreational activities for about 2 days and from work and more strenuous activities for about a week.
There is a relatively high incidence of nausea and vomiting after laparoscopic cholecystectomy, which can be treated with injections of metoclopramide. Preoperative anti-nausea agents such as granisteron may prevent these effects. One study reported that patients who received a local anesthesia at the incision sites (in addition to general anesthesia) before surgery had less pain and nausea afterwards.
Injury to the bile duct. Bile duct injury is the most serious complication of laparoscopy. It can include leakage, tears, and the development of narrowing (strictures) that can lead to liver damage. In order to minimize such injuries, some experts recommend that surgeons perform laparoscopy with a procedure called cholangiography, in which a dye is injected into the bile duct and x-rays are used to view the duct. Bile duct injury has been a more common problem than with the open procedure but increasing surgical experience and the use of cholangiography is reducing this complication and studies are now reporting more comparable rates between the two procedures.
In about 6% of procedures, the surgeon misses some gallstones, or they are spilled and remain in the abdominal cavity. In a small percentage of these cases, the stones cause obstruction, abscesses, or fistulas (small channels) that require open surgery.
As with all surgeries, there is a risk for infection, but it is very low.

Patients should not be shy about inquiring into the number of laparoscopies the surgeon has performed (the minimum should be 40). Obese patients were originally thought to be poor candidates for laparoscopic cholecystectomy, but recent research indicates that this surgery is safe for them.

Before the development of laparoscopy, the standard surgical treatment for gallstones was open cholecystectomy (surgical removal of the gallbladder through an abdominal incision), which requires a wide incision and leaves a large surgical scar. In this procedure, the patient usually stays in the hospital for 5 - 7 days and may not return to work for a month. Complications include bleeding, infections, and injury to the common bile duct. The risks of this procedure increase with other factors, such as the age of the patient or if the surgeon needs to explore the common bile duct for stones at the same time.

Whether or not to insert a drain in the wound after surgery is under debate. Many surgeons implant drains primarily to prevent abscess or peritonitis. That practice may change. A recent analysis of all randomized clinical trains comparing drains versus no drains or type of drain used found that patients who received drains had a dramatically increased risk of wound and chest infection. The type of drain used made no difference.

Percutaneous Cholecystostomy. Percutaneous cholecystostomy is a procedure that may be used in seriously ill patients with severe gallbladder infection who cannot tolerate immediate surgery. It is also the standard treatment for patients with acalculous cholecystitis (gallbladder inflammation without stones). This procedure uses a needle to withdraw fluid (aspirate) from the gallbladder. A drainage catheter is inserted through the skin and into the gallbladder while the fluid drains out. In some cases, it may be left in place for up to 8 weeks. After that time, if possible, laparoscopy or an open cholecystectomy may be performed. Without a laparoscopy, recurrence rates with this procedure are high.

Gallbladder Aspiration. With this procedure, fluid is aspirated in one procedure while the gallbladder is viewed using ultrasound. It does not require an indwelling catheter afterward and may have fewer complications than percutaneous cholecystostomy.

Mini-Laparotomy Cholecystectomy. Mini-laparotomy cholecystectomy uses small abdominal incisions but, unlike laparoscopy, it is an "open" procedure, and the surgeon does not operate through a scope. The surgical instruments used are very small (2 - 3 mm in diameter, or about a tenth of an inch). Eventually, this technique may reduce operative time and enable surgeons to obtain better results than with laparoscopy.

Needlescopic Cholecystectomy. Procedures that use even fewer and smaller incisions than laparoscopy are being developed. There are many variations, including those referred to as twin-port, mini-site, or mini- or micro-laparoscopic surgeries. These procedures make even fewer incisions (2 - 3) and smaller ones (1.2 - 3 mm, or less than one-tenth of an inch). It should be noted, however, that these procedures still require one larger incision (10 - 12 mm, or about one-half inch). They are still investigative and have some disadvantages:

Fiberoptics, used to view the surgical areas, do not provide light that is as bright as the light used in conventional laparoscopy.
The instruments are very fragile.
The field of vision is very limited.

Although experience is very limited, studies are showing promise for reducing postoperative pain and improving recovery time beyond that of standard laparoscopy.

Telerobotic Surgery. In one high-tech experiment, surgeons in New York removed the gallbladder of a woman in France in a laparoscopic procedure using tools controlled by a remote robotic device. The procedure took 54 minutes and was free of complications.

Lithotripsy and Dissolution Therapies

Oral agents used to dissolve gallstones, and lithotripsy alone or in combination with other drugs had gained some popularity in the 1990s. But these oral agents have lost favor with the increase in laparoscopy. They still may have some value in specific circumstances.

Oral Dissolution Therapy. Oral dissolution therapy uses bile acids in pill form to dissolve gallstones and may be used in conjunction with lithotripsy, although both techniques are rarely used at present. Ursodiol (ursodeoxycholic acid, Actigall) and chenodiol (Chenix) are the standard oral bile acid dissolution drugs. Most doctors prefer ursodeoxycholic acid, which is considered to be among the safest of common drugs and without significant side effects. Long-term treatment appears to notably reduce the risk of biliary pain and acute cholecystitis. The treatment is only moderately effective, however, since gallstones recur in the majority of patients.

Patients most likely to benefit from oral dissolution therapy are those with small stones (less than 1.5 cm in diameter) that have a high cholesterol content.

Patients who probably will not benefit from this treatment include obese patients and those with gallstones that are calcified or composed of bile pigments

Only about 30% of patients are candidates for oral dissolution therapy; the number actually may be much lower, since compliance is often a problem. The treatment can take up to 2 years and can cost thousands of dollars per year.

Contact Dissolution Therapy. Contact dissolution therapy requires the injection of the organic solvent methyl tert-butyl ether (MTBE) into the gallbladder to dissolve gallstones. This is a somewhat technically difficult and hazardous procedure and performed only by experienced doctors in hospitals where research on this treatment is being done. Preliminary studies indicate that MTBE rapidly dissolves stones. The ether remains liquid at body temperature and dissolves gallstones within 5 - 12 hours. Serious side effects include severe burning pain.

Investigative Agents. Fatty acid bile acid conjugates (FABACs) are experimental agents that are being investigated for dissolving gallstones and for preventing gallstone formation.

Gallstone fragmentation by extracorporeal shock wave lithotripsy (ESWL) may be an appropriate therapy for some patients who cannot undergo surgery, but it is no longer widely used. The treatment works best on solitary stones that are less than two centimeters in diameter. Less than 15% of patients are good candidates for lithotripsy. The typical procedure is as follows:

The patient typically sits in a tub of water.
High-energy, ultrasound shock waves are directed through the abdominal wall toward the stones.
The shock waves travel through the soft tissues of the body and break up the stones.
The stone fragments are then usually small enough to be passed through the bile duct and into the intestines.
Lithotripsy is generally combined with oral dissolution (bile acid) treatment to help dissolve the fragmented pieces of the original gallstone.

Complications. Complications include pain in the gallbladder area and pancreatitis, usually occurring within a month of treatment. In addition, not all of the fragments may clear the bile duct. Adding erythromycin to the treatment regimen may help remove these fragments. About 35% of patients who are left with fragments are at risk for further problems, which can be severe. The chance of recurrence is high with this procedure, and in one study, 45% of patients eventually required surgery. Elderly people may have a lower risk for recurrence than younger adults, which may make this a good choice for some.

Managing Common Bile Duct Stones

Common duct stones (choledocholithiasis) pose a high risk for complications and nearly always warrant treatment. There are various options available. It is not clear yet which one is optimal.

In the past, when common bile duct stones were suspected, the approach was open surgery (open cholecystectomy) and surgical exploration of the common bile duct. This required a wide abdominal incision.
Endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic sphincterotomy (ES) is now the most frequently used procedure for detecting and managing common duct stones. The procedure involves the use of an endoscope (a flexible telescope containing a miniature camera and other instruments), which is passed down the throat to the bile duct entrance.

Laparoscopic cholecystectomy also is increasingly being used for detection and removal of common duct stones. This is an approach through the abdomen but uses small incisions. In such cases, it is used in combination with ultrasound or a cholangiogram (an imaging technique in which a dye is injected into the bile duct and moving x-rays are used to view any stones).

Experts are currently debating the choice between laparoscopy (an abdominal approach) and ERCP (approaching through a tube down the throat). Many surgeons believe that laparoscopy is becoming safe and effective and should be the first choice. Still, laparoscopy for common duct stones should be performed only by surgeons experienced in this technique.


Endoscopic Retrograde Cholangiopancreatography (ERCP)	Laparoscopic Common Bile Duct Exploration	Open Common Bile Duct Exploration (Choledocholithotomy)
Before gallbladder surgeries when there is strong suspicion that common bile duct stones are present. After gallbladder surgeries in which the surgeon detects stones in the common bile duct (only if there are experts in ERCP and equipment is available). For patients with gallstone cholangitis (serious infection in the common bile duct). In such cases urgent ERCP plus antibiotics is required. When acute pancreatitis is caused by gallstones. In such cases urgent ERCP plus antibiotics is required. (The use of ERCP compared to conservative treatment has been controversial. One study reported that only patients who had infection and persistent obstruction in the ducts benefited from urgent ERCP intervention. In a 2000 analysis of four studies, however, ERCP significantly improved survival rates and reduced complications.)	As an alternative to ERCP before gallbladder surgeries when there is high suspicion of common bile duct stones. (Should be performed only in centers with expertise in this procedure, where it may actually be preferable to ERCP.) During gallbladder surgeries when common duct stones are detected or highly suspected. (Only for centers with expertise in this procedure.)	During or after some gallbladder operations when stones are detected. If procedure is laparoscopy, surgeon may convert to open procedure. Less often used now. When ERCP or laparoscopic procedures are not available.

The ERCP and ES Procedure. A typical ERCP and endoscopy sphincterotomy (ES) procedure includes the following steps:

The patient is given a sedative and asked to lie on his or her left side.
An endoscope (a tube containing fiber optics connected to a camera) is passed through the mouth and stomach and into the duodenum (top part of the small intestine) until it reaches the point where the common bile duct enters. This does not interfere with breathing, but the patient may have a sensation of bloating.
A thin catheter (tubing) is then passed through the endoscope.
Contrast material (a dye) is injected through the catheter into the opening of the duct. The dye allows x-ray visualization of the biliary tree (the system of ducts through which bile flows, including the common bile duct) and any stones contained in the area.
Instruments may also be passed through the endoscope to remove any stones that are detected.
The next phase of the procedure is known as endoscopic sphincterotomy (ES). (It is also sometimes referred to as papillotomy, although this is a slightly different variation.) It serves to widen the junction between the common bile duct and intestine (called the ampulla of Vater) so that the stones can be extracted more easily. With ES a tiny incision is usually made in the orifice of the common bile duct and through the muscles that enclose the lower common bile duct (called the sphincter of Oddi).
One recent alternative to ES is the use of a small inflatable balloon (called endoscopic balloon dilation) that opens up the ampulla of Vater to allow stones to pass and so avoid cutting the muscles. According to 2003 studies, it is equal in effectiveness to ES but offers no advantage at this time.
Once the junction has been opened, the stones may pass out on their own or they may be extracted with the use of tiny baskets or balloons.

Complications. Complications of ERCP and ES occur in 5 - 8% of cases, and some can be serious, with mortality rates of 0.2 - 0.5%. They include the following:

Pancreatitis (inflammation of the pancreas) occurs in 3 - 9% of cases and can be very serious. Younger adults are at higher risk than the elderly. The risk is also higher with more complex procedures. The drugs somatostatin or gabexate are sometimes used to reduce the risk, although evidence suggests somatostatin may not reduce this risk. Gabexate appears to be more effective, although studies are mixed on whether its benefits are significant, particularly with short-term administration.
Postoperative infection. Antibiotics may be given before the procedure to prevent infection, although one study reported that they had little benefit.
Bleeding occurs in 2% of cases. There is an increased risk in patients taking anti-clotting drugs and those who have cholangitis. This complication is treated by flushing the area with epinephrine.
Perforations (rare).
Long-term complications include stone recurrence and abscesses.

ERCP and ES are difficult procedures, and patients must be certain their doctor and the medical center have experience with them. The surgeon should have performed at least 180 ERCPs. Under such circumstances, ERCP can usually be performed successfully even in critically ill patients on mechanical ventilators.

ERCP and Gallbladder Removal (Cholecystectomy). ERCP is often performed after gallstones in the common duct are discovered during cholecystectomy (removal of the gallbladder).

In some cases, stones in the gallbladder are detected during ERCP. In such cases laparoscopic cholecystectomy is usually warranted. There is some debate about whether the gallbladder should be removed in such cases at the same time as ERCP or if patients should wait. A 2002 study suggested that immediate gallbladder removal is preferred, since the risk for recurring symptoms is very high.

Surgeons are now increasingly using laparoscopy plus an imaging technique called cholangiography instead of ERCP when common duct stones are suspected. The laparoscopic procedure for common duct stones should be performed only in centers where there is expertise. It generally proceeds as follows:

The initial approach is the same as with laparoscopic cholecystectomy. Small incisions, one or two 10 - 12 mm (around half an inch) and three 5 mm (.20 inches), are made in the abdomen.
A tiny opening is made in the cystic duct that connects the gallbladder to the bile duct, and a thin tube is introduced to perform a cholangiogram. (In this procedure, a dye is administered to reveal the stone's location on x-rays.)
The procedure is typically used in combination with cholangiography, an imaging technique in which a dye is injected into the bile duct and x-rays are used to view any stones. Cholangiography reduces the risk for injury in the common duct.
If stones are identified, the surgeon inserts a tube with an inflatable balloon that is used to widen the duct.
Stones are usually retrieved or withdrawn from the duct either with the use of a balloon or with a tiny basket.
If laparoscopy is unsuccessful, then ERCP or open surgery is performed.

Experts are debating whether the use of this procedure is better than ERCP. Many surgeons believe that laparoscopy is becoming safe and effective and should be the first choice. Still, laparoscopy for common duct stones should be performed only by surgeons experienced in this new and demanding technique.

Choledocholithotomy, or common bile duct exploration, is used to remove large stones or in cases when the duct anatomy is complex. In this procedure, the doctor carries out open abdominal surgery and extracts gallstones through an incision in the common bile duct. Routinely, a so-called "T-tube" is temporarily left in the common bile duct after surgery and the doctor x-rays the bile duct through the tube 7 - 10 days postoperatively to determine if any stones remain in the duct.

Shock wave lithotripsy is an option in certain cases for bile duct stones that cannot be extracted.

Mechanical Endoscopic Lithotripsy. Endoscopy with mechanical lithotripsy employs a tiny steel crushing basket, which is inserted through the endoscope and into the common bile duct. The basket opens to trap and then crush the stone. It is capable of crushing and removing very large stones. The overall success rate is 80 - 90%, although 20 - 30% of patients require more than one treatment.
Extracorporeal Shock Wave Lithotripsy. Extracorporeal shock wave lithotripsy is an option in certain cases of bile duct stones as it is for stones in the gallbladder.

Resources

http://digestive.niddk.nih.gov -- National Digestive Diseases Information Clearinghouse
www.gastro.org -- American Gastroenterological Association
www.acg.gi.org -- American College of Gastroenterology
www.liverfoundation.org -- American Liver Foundation

References

Al-Azzawi HH, Mathur A, Lu D, Swartz-Basile DA, Nakeeb A, Pitt HA. Pioglitazone increases gallbladder volume in insulin-resistant obese mice. J Surg Res. 2003;136(2):192-197.

Dray X, Joy F, Reijasse D, et al. Incidence, risk factors, and complications of cholelithiasis in patients with home parenteral nutrition. J Am Coll Surg. 2007;204(1):13-21.

Grunhage F, Lammert F. Gallstone disease. Pathogenesis of gallstones: A genetic perspective. Best Pract Res Clin Gastroenterol. 2006;20(6):997-1011.

Gurusamy K, Samraj K. Routine abdominal drainage for uncomplicated open cholecystectomy. Cochrane Database Syst Rev. 2007;18;(2):CD006003.

Lyons MA, Wittenburg H. Susceptibility to cholesterol gallstone formation: evidence that LITH genes also encode immune-related factors. Biochim Biophys Acta. 2006;1761(10):1133-1147.

Masannat Y, Masannat Y, Shatnawei A. Gallstone ileus: a review. Mt Sinai J Med. 2006;73(:1132-1134.

Morimoto LM, Newcomb PA, Hampton JM, Trentham-Dietz A. Cholecsytectomy and endometrial cancer: a marker of long-term elevated estrogen exposure? Int J Gynecol Cancer. 2006;16(3):1348-1353.

Myers JA, Fischer GA, Sarker S, Shayani V. Gallbladder disease in patients undergoing laparoscopic adjustable gastric banding. Surg Obes Relat Dis. 2005;1(6)561-563.

Portenier DD, Grant JP, Blackwood HS, Pryor A, McMahon RL, Demaria E. Expectant management of the asymptomatic gallbladder at Roux-en-Y gastric bypass. Surg Obes Relat Dis. 2007. Epub Apr 17 ahead of print.

Sarkio S, Salmela K, Kyllonen L. Rosliakova M, Honkanen E, Halme L. Complications of gallstone disease in kidney transplantation patients. Nephrol Dial Transplant. 2007;22(3):886-890.

Tsai CJ, Leitzmann MF, Willett WC, Giovannucci EL. Fruit and vegetable consumption and risk of cholecystectomy in women. Am J Med. 2006;119(9):760-767.

Tsai CJ, Leitzmann MF, Willett WC, Giovannucci EL. Heme and non-heme iron consumption and risk of gallstone disease in men. Am J Clin Nutr. 2007;85(2):518-522.

Tsai CJ, Leitzmann MF, Willett WC, Giovannucci EL. Weight cycling and risk of gallstone disease in men. Arch Intern Med. 2006;166(21):2369-2374.

Wittenburg H, Lammert F. Genetic predisposition to gallbladder stones. Semin Liver Dis. 2007;237(1):109-121.

Yol S, Kartal A, Vatansev C, Aksoy F, Toy H. Sex as a factor in conversion from laparoscopic cholecystectomy to open surgery. JSLS. 2006;10(3):359-363.

Review Date:
5/15/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Prostate cancer

FitSugar — Wed, 08 Oct 2008 17:35:05 -0700

In This Report

Highlights
Introduction
Prognosis
Risk Factors
Symptoms
Conditions with Similar Sym...
Screening and Diagnosis
Tests to Determine Severity...
Treatment
Treatment Options by Stagin...
Treatment for Localized Pro...
Surgery
Radiation Treatments
Options if Treatments Fail...
Other Treatments
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

New Guidelines for Localized Prostate Cancer

In 2007, the American Urological Association (AUA) released updated guidelines for treatment of localized prostate cancer. The guidelines recommend that:

Patients should be classified as low, intermediate, or high risk, depending on their PSA levels, cancer stage, and tumor aggressiveness.
Doctors need to consider patients’ personal preferences and quality of life concerns as well as their clinical status.
Standard treatment options include active surveillance (watchful waiting), surgery, or radiation therapy. Initial androgen deprivation therapy (hormone therapy) is seldom recommended for localized prostate cancer.

New Guidelines for Androgen Deprivation Therapy

The American Society of Clinical Oncology (ASCO) 2007 guidelines recommend that doctors delay androgen deprivation therapy for advanced prostate cancer until patients develop symptoms. When treatment is started, ASCO recommends either removal of both testicles (orchiectomy) or luteinizing hormone releasing hormone (LHRH) drug treatment.
Androgen deprivation therapy can increase the risks for heart disease death and diabetes, according to a 2006 Journal of Clinical Oncology study.

Diagnosis

Experts do not recommend prostate specific antigen (PSA) tests for men over age 70, yet many of these men continue to receive unnecessary tests, indicates a 2006 Journal of the American Medical Association study.
A new investigational test for early prostate cancer antigen-2 (EPCA-2) may be more accurate than the PSA test and may eventually replace it, suggests a 2007 study in Urology.

Genetic Research

Researchers have identified a set of genetic variations that may account for about 68% of prostate cancer cases in African-American men. Scientists hope that further investigation of this chromosomal region may help in developing genetic tests for prostate cancer.

Introduction

Prostate cancer is a malignant tumor that arises in the prostate gland. As with any cancer, if it is advanced or left untreated in early stages, it can eventually spread through the blood and lymph fluid to other organs. Fortunately, prostate cancer tends to be slow growing compared to other cancers. As many as 90% of all prostate cancers remain dormant and clinically unimportant for decades. This high incidence of latent or incidental malignancy is unique to the prostate gland. Most older men eventually develop at least microscopic evidence of prostate cancer, but it often grows so slowly that, as one specialist has written, many men with prostate cancer "die with it, rather than from it."

The prostate gland is an organ that surrounds the urinary urethra in men. It secretes fluid which mixes with sperm to make semen.

Male hormones (androgens) play major roles in the development of prostate cancer. Some research, for example, reports a higher risk with increasing testosterone and a lower risk with increasing estrogen levels. Dihydrotestosterone (DHT) is the principal male hormone in the prostate gland. It affects the size of the prostate gland itself and may play a role in prostate cancer. Nevertheless, researchers have not yet fully clarified the specific mechanisms that may be important in the development of this disease. Most likely, genetic mutations affecting androgens trigger the process. Certain growth hormones, such as insulin-like growth factor-I, are unrelated to testosterone and may increase the risk for prostate cancer.

Description of the Prostate Gland

The prostate gland is located between the bladder and the rectum and wraps around the urethra (the tube that carries urine through the penis). It is basically composed of three different cell types:

Smooth muscle cells, which contract during sex and squeeze the fluid from the glandular cells into the urethra, where it mixes with sperm and other fluids to make semen
Glandular cells, which produce a milky fluid that liquefies semen
Stromal cells (which form the structure of the prostate)

The central area of the prostate that wraps around the urethra is called the transition zone. The entire prostate gland is surrounded by a dense, fibrous capsule.

Functions of the Prostate Gland

The prostate gland provides the following functions:

The glandular cells produce a milky fluid, and during sex the smooth muscles contract and squeeze this fluid into the urethra. Here, it mixes with sperm and other fluids to make semen.
The prostate gland also contains an enzyme, called 5 alpha-reductase, that converts testosterone to dihydrotestosterone, another male hormone that has a major impact on the prostate.

Changes During the Lifespan

The prostate gland undergoes many changes during the course of a man's life. At birth, the prostate is about the size of a pea. It grows only slightly until puberty, when it begins to enlarge rapidly, attaining normal adult size and shape, about that of a walnut, when a man reaches his early 20s. The gland generally remains stable until about the mid-forties, when, in most men, the prostate begins to enlarge again through a process of cell multiplication.

Click the icon to see an image of the male reproductive anatomy.

Prognosis

Prostate cancer is the most common male cancer in the U.S. Only lung cancer causes more cancer deaths in American men. The lifetime probability of developing prostate cancer is about 16%. Each year, approximately 218,890 men in the United States will be diagnosed with prostate cancer, and about 27,050 will die from the disease. According to the American Cancer Society, 5-year survival rates for all stages of prostate cancer have increased during the past 20 years from 67% to nearly 100%.

A survival rate indicates the percentage of patients who live a specific number of years after the cancer is diagnosed. For prostate cancer, the 10-year survival rate is 93% and the 15-year survival rate is 77%. After 15 years, survival rates stabilize. A 2006 study in the Journal of the American Medical Association found that men who are diagnosed with low-grade prostate cancers have a minimal risk of dying from prostate cancer up to 20 years after diagnosis. However, men diagnosed with more severe forms of prostate cancer have a higher risk of dying within 10 years.

Treatment of prostate cancer varies depending on the stage of the cancer (i.e., spread) and may include surgical removal, radiation, chemotherapy, hormonal manipulation or a combination of these treatments.

Because so many prostate tumors are low-grade and slow growing, survival rates are excellent when prostate cancer is detected in its early stages. Cure rates can be as high as 98% in some cases.

Click the icon to see an image of the pelvic lymph nodes.

Locally Advanced. If the disease is at the locally-advanced stage, in which it has spread beyond the prostate but only to nearby regions, it is more difficult to cure, but survival rates can be prolonged for years in many men. (When cancer has metastasized to the pelvic lymph nodes, the outlook is worse than if it has spread to other areas.)

Metastasized Cancer. If prostate cancer has spread to distant organs (metastasized), average survival time is 1 - 3 years, but some of these patients may live longer or die of other causes.

If cancer recurs after initial treatment for early-stage tumors, it is still potentially curable if it is contained within the prostate, although in most cases the cancer has spread. Hormone treatments for such recurring cancers can often prolong survival for years, although the cancer almost always returns again.

Risk Factors

The major risk factors for prostate cancer include genetic, dietary, and environmental factors that affect male hormones (androgens) and make a man more susceptible to this cancer.

Prostate cancer occurs almost exclusively in men over age 40 and most often after age 50. It is estimated that by age 70, about 65% of men have at least microscopic evidence of prostate cancers. Fortunately, the cancer is often very slow growing and older men with the cancer nearly always die of something else.

Heredity plays a role in some types of prostate cancers. Men with a family history of the disease have a higher risk of developing prostate cancer. Having one family member with prostate cancer doubles a man's own risk, and having three family members increases risk by 11-fold.

In 1998, scientists discovered a gene, located on chromosome 1, which may be involved in 1 in 500 cases of prostate cancer. They named this gene HPC1. (HPC stands for “hereditary prostate cancer.”) In 2005, scientists announced another major breakthrough in understanding the genetic components of prostate cancer. Research published in Science suggested that, in some cases, prostate cancer occurs when a specific set of genes merge. The genes are part of the ETS gene family and include ETV1, ETV4, and ERG.

In 2007, three separate studies published in Nature Genetics focused on DNA variations located on chromosome 8 in the 8q24 region. The research suggested that men who carry these genetic variations have a substantially increased risk of developing prostate cancer. The DNA variations may be associated with as many as 32% of prostate cancers in Caucasian men and 68% of prostate cancer cases in African-American men.

Doctors hope that future research will help develop genetic tests to identify men most at risk and, eventually, targeted drug therapy for prostate cancer.

A gene is a short segment of DNA which is interpreted by the body as a plan or template for building a specific protein. Genes reside within long strands of DNA which in turn make up the chromosomes.

African-American men have the world's highest risk for prostate cancer, more than 50% higher than the risk for Caucasian males. The disease is also more lethal among African-Americans. Men who live in Asia have lower risks for prostate cancer, but their risk increases if they move to North America. This indicates that there are unknown environmental or dietary factors that can alter a man's underlying genetic risk of developing this disease.

Socioeconomic Issues. The higher mortality rates in African-American men may be partly due to socioeconomic factors, such as lack of insurance, irregular screening and a late diagnosis, and unequal access to health care.

Dietary Factors. Dietary factors may play some small role in the higher risk in African-American men. This is suggested by the fact that prostate cancer is rare in many parts of Africa.

Biologic Factors. Evidence suggests that African-American and Asian men have certain genetic factors that may affect male hormones differently and may help account in part for the higher risk in the first group and the lower risk in the second.

Higher PSA Levels. African-American men also tend to have higher PSA levels than Caucasians. They are overdiagnosed with prostate cancer by 37% compared to 15% in Caucasians using PSA screening tests.

Chemicals. The relationship between prostate cancer and chemical exposure is controversial. Men whose work involves heavy labor and those exposed to certain metals and chemicals, including cadmium, dimethylformamide, and acrylonitrile, may be at higher risk for prostate cancer. Some studies have indicated that farmers might be at higher risk.

A 2001 study concluded that certain leisure activities may expose men to the same chemicals as those that pose a possible danger in the industrial setting. These chemicals included:

Home or furniture maintenance
Painting, stripping, or varnishing furniture
Activities that involved exposure to lubricating oils or greases, metal dust, or pesticides or garden sprays

Scientists think that specific genes that affect the body's response to viruses may be associated with certain types of prostate cancer. Some theories suggest that there may be a relationship between prostate cancer and infections, such as herpes virus, human papillomavirus, and cytomegalovirus. In 2006, scientists identified a new virus, XMRV, which is 30 times more common in men with prostate cancer who have a genetic mutation with the HPC1 gene. Scientists know that men who have the HPC1 genetic mutation are more likely to get prostate cancer. This new research suggests that the genetic mutation may make them more vulnerable to a virus that causes the cancer. Researchers will continue to investigate XMRV and other possible infectious causes of prostate cancer.

Obesity. Obesity may increase the risk for prostate cancer, particularly more aggressive forms of the disease. Obesity may also make prostate cancer more difficult to diagnose. A 2005 study found that overweight and obese men were more likely to be diagnosed with advanced prostate cancer and to die of the disease than normal-weight men.

Nonmelanoma Skin Cancers and Sunlight. Some studies report that patients with prostate cancer and a history of nonmelanoma skin may have a higher risk for a poorer outlook. Such skin cancers are highly associated with exposure to sunlight. However, sunlight triggers production of vitamin D in the body, which research indicates may help protect against prostate cancer. Prostate cancer rates are, in fact, lower in southern, sunny regions.

Vasectomy. Because testosterone levels remain higher for a longer period in men who had vasectomy, experts have theorized that such men have a greater chance for developing the cancer. While some studies have suggested a higher risk with vasectomy, other studies have reported no higher danger. A rigorous 2002 study from New Zealand, for example, which has the highest vasectomy rates in the world, found no increased risk of prostate cancer from the procedure, even 25 years after the operation. A 2002 study in California, in fact, reported a lower risk for prostate cancer in men who had had vasectomies. It is possible that the higher rates reported in earlier studies may have been due to earlier prostate screening in men who have had vasectomies. Indeed, one study reported that about 25% of doctors screened men with vasectomies earlier for prostate cancer than those without the operation. [See In-Depth Report #37: Vasectomy.]

Click the icon to see an illustrated series detailing a vasectomy.

Click the icon to see an animation on vasectomy.

A Western lifestyle is associated with prostate cancer, so obesity, high-meat intake, and dietary fats have been intensively studied. Results have been inconsistent, however. Certain factors, such as cancer-causing compounds in well-cooked meat or high-calorie intake, may help explain the associations between such dietary factors and cancer risk.

Click the icon to see an image on different types of weight gain.

Fats. Some studies have found an association between high fat-intake and prostate cancer. This association may be explained by other suspected dietary factors for prostate cancer, such as high-calorie diet, high meat intake, and calcium (found in dairy products), all of which are associated with fat intake. The effects of specific fatty acids (compounds that make up fats) may also help clarify the role of fats in prostate cancer. The omega-3 fatty acids in fish (EPA and DHA) and the omega-3 fatty acids found in certain vegetables (ALA) can all protect the heart, but they may have different effects on the prostate.

Marine Omega-3 Fatty Acids. Research indicates that docosahexanoic acid (DHA) and eicosapentaneoic acid (EPA), the omega-3 fatty acids found in fish, may be protective against prostate cancer. Some studies have reported a lower risk for prostate cancer in men who ate fish frequently (two or more times a week).
Alpha-Linolenic Acid. On the other hand, some research has indicated that alpha-linolenic acid (ALA), the omega-3 fatty acid found in certain plants and nuts (flaxseed, canola, walnuts), may increase the risk of prostate cancer. However, some studies suggest that flaxseed, a plant food that is also rich in omega-3 fatty acids, may help slow the growth of prostate tumors.

Meat and High-Temperature Cooking. Some evidence suggests that a high intake of red meat raises the risk for prostate cancer. Because red meat is high in saturated fat, such findings may explain the inconsistencies found in studies that simply look at fat content as a risk for prostate cancer. High-temperature cooking (grilling, broiling, or pan-frying) of meat or poultry has been specifically associated with increased risk for cancer in some studies. Over-cooking meat increases the amount of compounds called heterocyclic amines, which has been associated with cancerous changes in general and prostate cancer in particular, at least in some studies. Cooking meats in liquid does not appear to increase these compounds. As with all dietary studies, some have observed no association between high intake of well-cooked meat and prostate cancer.

Vegetarian Diet. Small studies suggest that a vegetarian diet may be protective. Specific foods may be especially helpful in reducing the risk of prostate cancer:

Whole grain cereals, seeds, and nuts have been associated with a lower risk for prostate cancer. Part of this protection may be due to their high fiber content. Fiber binds to sex steroids and is excreted, carrying the hormones with it. Whole grains also contain selenium, a trace mineral that may have some protective properties.
Many studies have reported a significantly lower risk for prostate cancer with high intake of cooked tomatoes, which are high in a beneficial plant chemical called lycopene. (However, other studies have not reported such protection.)
Soy may also be protective, which may partially explain the low rate of prostate cancer observed in Japanese men and vegetarians (who typically use soy as a protein replacement). Theoretically soy, which is a rich source of an estrogen-like plant compound, may inhibit hormones that promote prostate cancer. Laboratory studies are mixed on such effects, however.
Cruciferous vegetables (cauliflower and broccoli) may have cancer-fighting chemicals.
Boron-rich foods (nuts, red grapes, avocados, and dried fruits) may also be protective.
Green tea. Scientists have speculated that the antioxidants contained in green tea may help to inhibit prostate cancer growth. Investigators are researching the effects of both green tea and green tea extract supplements, but results to date have been inconclusive.

Dairy Products, Calcium, and Vitamin D. Studies have reported an association between consuming large amounts of dairy products and a modestly increased risk for prostate cancer. (Moderate intake has not been associated with a higher risk.) There is some evidence that calcium (contained in dairy products) may increase the risk for prostate cancer by reducing levels of the most active form of vitamin D (1,25 dihydroxyvitamin D). Many studies indicate that vitamin D may help protect against prostate cancer. Men should make sure they are getting enough vitamin D through sunlight exposure, food, or vitamin supplements.

Getting enough calcium to keep bones from thinning throughout a person's life may be made more difficult if that person has lactose intolerance or another reason, such as a tendency toward kidney stones, for avoiding calcium-rich food sources. Calcium deficiency also affects the heart and circulatory system, as well as the secretion of essential hormones. There are many ways to supplement calcium, including a growing number of fortified foods.

Click the icon to see an image of the benefits of vitamin D.

Click the icon to see an image of the sources of vitamin D.

There is some evidence that certain vitamin and mineral supplements (such as vitamin E and selenium) can protect against prostate cancer, and also some evidence that excessive use of supplements may increase risk. In a 2007 National Institutes of Health study, men who took multivitamin supplements more than seven times a week increased their risks for developing advanced prostate cancer and for dying from the disease. The risks were highest for men who had a family history of prostate cancer and for those who took individual supplements of selenium, beta-carotene, or zinc. However, using multivitamin supplements occasionally or once a day does not appear to increase prostate cancer risk.

The National Cancer Institute is conducting a large-scale clinical trial of more than 35,000 men to investigate whether selenium, vitamin E, or a combination of these two dietary supplements can help to prevent prostate cancer. The Selenium and Vitamin E Cancer Prevention Trial (SELECT) is the largest prostate cancer prevention trial ever initiated.

Click the icon to see an image of the benefits of vitamin E.

Click the icon to see an image of the sources of vitamin E.

In general, a healthy diet with nutritious fruits and vegetables is the best way to meet your daily requirement of vitamins and minerals.

Alcohol consumption does not appear to be associated with increased prostate cancer risk. A recent study, however, suggested a linear trend between red wine consumption and reduced risk of prostate cancer. In a study of over 1,400 newly diagnosed middle-aged patients with prostate cancer, researchers found that each additional glass of red wine consumed per week reduced the relative risk of prostate cancer by 6%. Researchers theorize that the flavonoids contained in red wine may inhibit tumor cell growth. More research is needed to confirm these results.

Regular physical activity may help reduce the risk of prostate cancer and slow the progression of the disease. The beneficial effects of exercise may be particularly important for older men. A 2006 study found that men ages 65 and older who exercised vigorously for at least 3 hours weekly had a 70% lower risk of being diagnosed with advanced prostate cancer.

Finasteride (Proscar) is a drug used to shrink the prostate in men with benign prostatic hyperplasia (BPH). It blocks an enzyme that converts testosterone to dehydroepiandrosterone (DHEA), the form of the male hormone that stimulates the prostate. Researchers are investigating whether finasteride may help prevent prostate cancer. In the 2003 Prostate Cancer Prevention Trial (PCPT), more than 18,000 men were randomly assigned to receive either finasteride or placebo. The men took the pills daily for 7 years. Results, published in 2003 in the New England Journal of Medicine, indicated that men who took finasteride were 25% less likely to develop prostate cancer than men who took placebo. However, although the finasteride group had fewer prostate cancers overall, those that did develop were higher-grade and more aggressive. Men who took finasteride had more sexual problems, including episodes of erectile dysfunction, but were less likely to have urinary problems, such as incontinence. It is still unclear if finasteride is an appropriate preventive approach.

Frequent ejaculations from masturbation or sexual activity have been associated with a lower risk for prostate cancer. Some experts speculate that certain carcinogens may be concentrated in prostate fluid, so that frequent ejaculation helps eliminate them. Of note, risky sexual activity, such as with multiple partners, increases the risk for sexually transmitted disease, which in turn may increase the risk for prostate cancer.

There is some evidence that nonsteroidal anti-inflammatory drugs (NSAIDs) offer some protection against prostate cancer. NSAIDs suppress chemicals in the body called COX-2, a protein that may cause prostate cancer cells to spread. Standard NSAIDs include aspirin, ibuprofen (Advil), and naproxen (Aleve). However, NSAIDs taken on a long-term basis can increase the risk for heart and gastrointestinal problems.

Symptoms

Prostate cancer usually causes no symptoms in the early stages. As the malignancy spreads, it may constrict the urethra and cause urinary problems.

Urine flows from the kidney through the ureters into the urinary bladder where it is temporarily stored. As the bladder becomes distended with urine, nerve impulses from the bladder signal the brain that it is full, giving the individual the urge to void. By voluntarily relaxing the sphincter muscle around the urethra, the bladder can be emptied of urine. Urine then flows out through the urethra.

Later-stage urinary symptoms typically include:

Weak urinary stream
Inability to urinate
Blood in the urine
Interruption of urinary stream (stopping and starting)
Frequent urination (especially at night)
Pain or burning during urination

Significant pain in one or more bones may indicate the occurrence of metastases (spread of disease). This chronic pain occurs most often in the spine and sometimes flares in the pelvis, the lower back, the hips, or the bones of the upper legs. It may be accompanied by significant weight loss.

Conditions with Similar Symptoms

In up to half of men in their 40s, the prostate begins to enlarge through a process of cell multiplication called benign prostatic hyperplasia (BPH). The symptoms of BPH can mirror late-stage prostate cancer because the enlarging inner portion of the prostate puts pressure on the urethra, which can potentially cause urinary problems. About 80% of men eventually develop enlarged prostates, but only some experience significant symptoms. BPH is a normal condition and is not life-threatening. [See In-Depth Report #71: Benign prostatic hyperplasia.]

Benign prostatic hypertrophy (BPH) is a non-cancerous enlargement of the prostate gland, commonly found in men over the age of 50.

Relationship to Prostate Cancer. Because the prostate enlargement in BPH is affected by testosterone, many men are concerned that it may be related to prostate cancer. Fortunately, current evidence indicates that it has no effect one way or the other. The two conditions develop in different parts of the prostate. BPH occurs in the inner zone of the prostate, while cancer tends to develop in the outer area. A 10-year study found no higher risk for prostate cancer in men with BPH.

Click the icon to see an animation about benign prostatic hypertrophy.

Prostatitis is an inflammation of the prostate, often caused by bacterial infections. Symptoms include urgency, frequency, and pain in urination, sometimes accompanied by fever or blood in the urine.

Screening and Diagnosis

The prostate specific antigen (PSA) blood test is widely used for screening men for prostate cancer. However, there is great uncertainty over whether regular screening has major benefits for most men. The most recent guidelines from the U.S. Preventive Services Task Force report that there is no conclusive evidence that routine prostate screening saves lives. Indeed, it may lead to invasive testing, and to treatments for many men who, considering the slow growth of the cancer, might derive no benefits from them. It is a difficult subject, and men must discuss all aspects carefully with their doctor.

A 2006 study in the Archives of Internal Medicine also suggested that screening tests for prostate cancer may not reduce men’s risk of death. The small study of 1,000 men found no differences in survival between men who had prostate specific antigen tests or digital rectal exams, and men who were not screened. Doctors should inform men of the uncertainty of prostate cancer tests so that patients understand the relative risks and benefits of screening

Standard Screening Tests for Early Detection. Two standard tests are used for early detection of prostate cancer:

Digital rectal examination (DRE). With the DRE, a doctor palpates the prostate in order to feel lumps or masses.
PSA test. The PSA blood test measures the level of a protein called prostate-specific antigen. It is able to detect early prostate cancer, although it has limitations.

If the digital rectal examination indicates the possible presence of cancer, regardless of the PSA results, a doctor may also obtain a visual image of the prostate through an ultrasound procedure called transrectal ultrasonography (TRUS). Only a biopsy, however, in which a tiny sample of prostate tissue is surgically removed, can actually confirm a diagnosis of prostate cancer.

Candidates for Annual Screening. Until major studies report on the survival benefits of prostate screening, expert groups recommend the following:

Men ages 50 - 70 should be offered annual screening. (Some experts believe that men whose PSA levels are under 1.0 and possibly under 2.0 may safely be screened only every 2 years thereafter.)
Men with a family history of prostate cancer and all African-American men should consider annual screening at about age 45.
Experts agree that PSA testing is inappropriate for men over age 70. PSA testing in this age group can cause more harm than good by leading to overly aggressive treatment. Despite this fact, many elderly men continue to receive unnecessary PSA tests.

The best age to start annual screening is under debate. Some experts advocate performing a first PSA test in all men aged 40 and then monitoring anyone whose PSA levels are over 0.60 ng/mL. They argue that such men are at high risk for developing prostate cancer within 25 years. A study presented at the 2007 meeting of the American Urological Association suggested that even a small increase in PSA in men age 44 - 50 may predict whether advanced prostate cancer will develop later in life.

Researchers are working on developing more accurate tests that, hopefully, will one day replace the PSA test. A promising test in development measures a protein called early prostate cancer antigen-2 (EPCA-2). A 2007 study suggested that the EPCA-2 test is highly accurate. It can distinguish between benign prostatic hyperplasia (BPH) and prostate cancer and can evaluate whether or not a man has prostate cancer, regardless of what his PSA levels indicate. Researchers hope that this test may eventually provide better diagnoses of prostate cancer, and help prevent men from receiving unnecessary biopsies.


	DRE alone	PSA alone and in Combination with DRE
Chance of Cancer	Only 20% of men with abnormal DREs have cancer. Unfortunately, 70% of prostate cancers detected with DRE alone have already spread beyond the prostate gland.	The odds of cancer with PSA readings are: 3 ng/mL or below indicates 2% or less chance of cancer. 3 - 10 ng/mL indicates about a 25% chance of cancer. 10 ng/mL and over indicates a very strong chance. Men with abnormal results from both DRE plus PSA tests have a 60% chance for cancer.
Risk of Missed Cancers with Normal Results	About 60% of men who have prostate cancer have normal DRE results.	Some evidence suggests that only performing biopsies at levels above 4.0 would miss over 80% of cancers present below that level in men under 60 years and 65% in older men. As a result, some experts recommend biopsies with PSA levels at 3.0 or below in young men. Still, cancer at low PSA levels is very uncommon, particularly in younger men.

About 90% of all prostate cancers arise in the outer part of the prostate where they may be detected by a digital rectal exam (DRE), which is the simplest and most widely-performed screening procedure. The doctor inserts a gloved and lubricated finger into the patient's rectum and feels the prostate for bumps or other abnormalities. The exam is quick and painless but some men find it embarrassing. It is not very accurate in detecting early cancers, but studies indicate that regular DREs still save lives.

Prostate Cancer is the most common cancer in men in the United States. Prostate cancer forms in the prostate gland, and can sometimes be felt on digital rectal examination. This is one of the purposes of the digital rectal exam.

Prostate specific antigen (PSA) is a protein produced in the prostate gland that keeps semen in liquid form. Prostate cancer cells appear to produce this protein in elevated quantities. Measuring PSA levels increases the chance for detecting the presence of cancer when it is microscopic. There are many unresolved questions surrounding PSA testing. The test is not accurate enough to either completely rule out or confirm the presence of cancer. Relying too much on the test may lead to unnecessary biopsies. Not relying on it enough may miss cancers. It is still unclear if PSA testing is actually saving lives.

Click the icon to see an image of a PSA blood test.

Indications for Biopsy. A biopsy is usually performed to confirm or rule out cancer after screening tests that report:

PSA level of 4.0 ng/mL or higher. Some evidence indicates that men with an initial test showing PSA levels above 4.0 should take a second PSA test several weeks afterward before having a biopsy, since many non-malignant factors can increase PSA levels. (Some experts urge biopsies even if PSA levels fall below 4.0 mg, particularly in men under 60, since lower levels do not necessarily rule out cancer.)
Abnormal digital rectal examination (DRE).

Men with abnormal results from both tests have a 60% chance of prostate cancer. The chances for cancer if only one test is abnormal are considerably lower. To further complicate matters, biopsies themselves may miss very small cancers detected by PSA levels alone.

Factors Affecting PSA Levels. A number of factors and noncancerous conditions can influence PSA levels:

Ethnicity. Normal levels in Caucasian males may be different from those for African-American or Asian men. For example, using PSA screening, one study suggested that 15% of Caucasians and 37% of African-Americans are overdiagnosed with prostate cancer based upon PSA results. Some experts believe that there should be different scales for determining risk among these groups, but there is still not enough information to determine a specific range for various ethnic groups.
Age. PSA levels tend to rise naturally with age, so an elevated level in a man who is 70 may be less serious than the same level in a younger man. Some experts believe that men older than 65 who have low PSA levels are at such low risk for prostate cancer that they may be able to forgo further testing.
Benign Prostatic Hyperplasia (BPH) and Its Treatments. Between 25 - 56% of patients with BPH have elevated PSA levels. Certain treatments for this condition can also elevate PSA.
Prostatitis. About half of men with elevated PSA levels but no signs of cancer on biopsy have signs of prostatitis as indicated by urine and prostate secretion tests. (Prostatitis simply means inflammation in the prostate. Inflammation is usually due to bacterial infection, but it can also be caused by nonbacterial factors.) In one study, screening for prostatitis increased the accuracy of the PSA test significantly and reduced the number of unnecessary biopsies.
Other Noncancerous Conditions. Other noncancerous conditions that can increase PSA levels include surgical procedures or drug treatments for BPH, acute urinary retention, digital rectal examinations, and prostate biopsies themselves.
Ejaculation. Ejaculation within 48 hours before testing can raise PSA levels.

Even with its limitation, the PSA test has increased the number of detectable early-stage and therefore treatable cancers. Because of the slow-growing nature of prostate cancer, however, it is not known whether all of these very early cancers will result in significant or life-threatening disease. It is possible that PSA screening could result in the detection of some possible cancers that would never have bothered the patient and would never have posed a threat to his life.

To improve the accuracy of the PSA tests, particularly when PSA levels have risen to an intermediate range of between 4 - 10 ng/mL, researchers are developing methods for measuring other factors. To date, no test has emerged as clearly superior to the PSA test.

Free PSA Test. A small amount of prostate specific antigen leaks out of the prostate into the bloodstream. There, PSA can circulate without binding to other proteins and is referred to as free PSA. It can also form chemical combinations with other proteins. If cancer is present, PSA is more likely to be bound, and so there is less free PSA in circulation. The free PSA blood test, then, is a ratio of free PSA to the total PSA (free PSA plus chemically bound PSA).

The following results are used to determine if an elevated PSA level could mean cancer:

A free-to-total PSA ratio of 20% or lower, plus total PSA levels of 4 - 10 ng/mL, are suggestive of prostate cancer. (Some experts use 25% as a cut-off, but studies suggest that using this cut-off would miss cancers in many African-American and older men.)
A free-to-total PSA level of more than 20% plus normal or even moderately elevated total PSA tend to indicate the presence of other, benign conditions, such as benign prostatic hyperplasia (but it still does not rule out cancer).

Some studies have reported that adding a test for free PSA may improve prostate cancer detection by roughly 40% and may also reduce the need for unnecessary biopsies. In addition, any cancers that the test misses would not develop into significant disease for many years, providing ample opportunity to identify them before they became serious. Not all studies support its advantages, however, compared to measuring total PSA alone, and to date there is no consensus among doctors for how it can be used.

Complexed PSA Test. Complexed PSA (cPSA) is a form of circulating PSA that is bound to a molecule called alpha1-antichymotrypsin. It represents about 90% of the total PSA in men and is significantly higher in men with prostate cancer than in those with BPH. To date, studies have reported conflicting results on its benefits for diagnosing prostate cancer.

Transition Zone PSA Test. Some tests have been developed to measure the density of the PSA in the transition zone of the prostate gland. (The transition zone is the central area of the prostate that wraps around the urethra.) A major comparison study in 2002 reported more accurate results than with complexed PSA.

An ultrasound procedure called transrectal ultrasonography (TRUS) provides a visual image of the prostate and is used if the DRE indicates the presence of cancer. Ultrasound is not effective as a diagnostic tool by itself because it cannot differentiate very well between benign inflammations and cancer, but the procedure may help to confirm an uncertain preliminary diagnosis and is useful as a guide for needle biopsies. Ultrasound enhancements, such as Doppler imaging or computer modeling techniques called artificial neural networks (ANN), may increase the accuracy of TRUS.

Initial Biopsies. If preliminary tests raise the suspicion of cancer, doctors will perform a biopsy. Biopsy is used to diagnose prostate cancer, and is a very accurate method for predicting the severity of an existing cancer. However, biopsies can still miss cancers if they are very small.

Core Biopsy. The standard method is called a core biopsy, which uses a spring-loaded biopsy device inserted into the rectum. The device propels a needle into the prostate, obtaining a core of tissue, which is examined by pathologists.
Fine Needle Aspiration. A more recent procedure, called fine needle aspiration, is less painful and may be as accurate as a core biopsy if the sample obtained is sufficient for analysis and if it is analyzed by a skilled pathologist.

More than half of the men who have a biopsy experience discomfort and anxiety, with men under 60 reporting higher levels of discomfort than older men. Taking a sedative 1 - 2 hours before the procedure can help reduce distress. Complications of biopsy are low, but urinary tract infection, fever, or bleeding occurs in 0.1 - 4% of men.

Repeat Biopsies. Because a biopsy can miss very small cancer cells, sometimes three or even more biopsies are recommended if cancer is still suspected after negative results, such as when:

PSA levels are high. Two or more biopsies may be taken if a man has very high PSA levels and still has normal results on a biopsy. Even men with mildly elevated PSA (between 4 - 10 ng/mL) who test negative may be given a repeat biopsy. Cancer will be detected in about 10% of this group. Whether a third biopsy is useful in these men if they still test negative after a second biopsy is uncertain.
DRE results are abnormal.
Ultrasound results are abnormal.
The initial biopsy yields microscopic findings that are suspicious.
The initial biopsy detects precancerous cells known as high-grade prostatic intraepithelial neoplasia (PIN). No treatment is necessary with this finding, but these patients should be rechecked every 3 - 6 months for the next 2 years, and then annually.

Doctors may also perform a lymph node biopsy to see if the cancer has spread.

Tests to Determine Severity of Cancer

Once cancer is diagnosed, PSA levels may help to determine its extent. If PSA levels are less than 20 ng/mL, it is possible that the cancer has not spread to distant sites. PSA levels over 40 ng/mL are a strong indicator that cancer has metastasized (spread throughout the body). PSA levels are also monitored after treatments begin. Changes in the level can show if a treatment is working or if the cancer has come back.

Doctors also monitor how quickly PSA levels rise over time. This rate is called PSA velocity (PSAV). The PSAV is very helpful in determining when treatment should begin and which treatment should be used. A high rate of PSAV is considered to be 2 ng/mL a year. Recent research suggests that men with early-stage prostate cancer who have a slow PSAV are more likely to live longer than men with rapidly rising PSA levels.

A number of biological factors are being used or investigated as markers for cancer or its severity:

Chromosomal Sets. The number of chromosomal sets in the nucleus of the tumor's DNA, known as its ploidy, is an important marker for patients in late stages of prostate cancer. Tumors with the normal two sets of chromosomes, called diploid tumors, usually have a more favorable outcome than tumors that have four sets of chromosomes (tetraploid tumors) or have an abnormal number of individual chromosomes (aneuploid tumors).

Blood Vessel Density. The density of blood vessels in the tumor is an important indicator of outcome. The greater the density, the more likely the tumor is to be aggressive.

Serum Acid Phosphatase. High levels of this enzyme indicate a more aggressive disease and the need for intensive treatments.

Testosterone Levels. Higher total testosterone levels may increase the risk for metastasis. A 2000 study found an association with low free testosterone and more extensive prostate cancer, suggesting free testosterone could be a marker for aggressive disease. (Free testosterone, as with free PSA, is not chemically bound.)

Genetic Markers. Researchers have identified a genetic marker (EZH2), which may prove to be an important marker for aggressive prostate cancer. It may, in fact, prove to be a better predictor of outcome than the tumor grade, stage, or surgical margins. Other genes being studied are those that regulate tumor growth (p53, p27, bcl-2).

Other Markers. Other markers being investigated for predicting cancer progression include prostate-specific membrane antigen, prostatic acid phosphatase, and growth factors.

The ProstaScint is a scanning technique that uses tiny amounts of radioactive material with a monoclonal antibody that can attach specifically to prostate cancer cells. A special camera then can detect tumor cells that cannot be detected with other diagnostic tools. It may help doctors make better treatment decisions. The role of this test in the routine management of prostate cancer is still being defined.

If the biopsy indicates cancer, the doctor will order other tests to determine whether or how far the cancer has spread.

Bone Scans and X-Rays. Bone scans and x-rays may reveal whether the cancer has invaded the bones. To perform a bone scan, doctors inject low doses of a radioactive substance into the patient's vein, which accumulates in bones that have been damaged by cancer. A scanner then reveals how much of the radioactive material has accumulated. Arthritis and infections may also produce positive scans. Patients with PSA levels below 20 ng/mL are unlikely to have scans that show cancer in the bone.

A radiotracer is injected into a peripheral vein. As the radiotracer decays, gamma radiation is emitted and is detected by a Gamma camera. When the tracer has collected in the target organ the area is scanned. Radionuclide scans can detect abnormalities such as fractures, bone infections, arthritis, rickets, and tumors that have spread, among other diseases.

Computed Tomography and Magnetic Resonance Imaging. Computed tomography (CT) or magnetic resonance imaging (MRI) scans can further pinpoint the location of cancer that has spread beyond the prostate. Advanced MRI techniques are showing promise for staging and planning treatments.

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

Click the icon to see an image of a MRI.

Bone Metastasis Markers. Researchers are investigating chemical markers, such as amino-terminal propeptide of type I procollagen (PINP), as early indicators of bone metastasis.

Treatment

Because BPH rarely causes serious complications, men usually have a choice between treating it or opting for watchful waiting:

Watchful Waiting. Watchful waiting (also called active surveillance) involves lifestyle changes and an annual examination. Even when choosing watchful waiting, an initial examination is critical to rule out other disorders.
Treatment Options. The primary goals of treatment for BPH are to improve urinary flow and to reduce symptoms. Many options are available. They include drug therapies, minimally invasive procedures, and major surgery.

The choice between watchful waiting and treatment usually depends on a number of factors, such as urine flow rates, prostate size, and PSA levels. Men with BPH who develop symptoms at around age 50 are more likely to need treatment within their lifetimes than older men. Unfortunately, there is no current way to determine who specifically might be at risk for serious problems and need early treatment.

The development of the International Prostate Symptoms Score (IPSS) has made the evaluation of symptoms somewhat easier. This scoring service serves as a benchmark for determining severity. The decision to treat or not to treat is typically based on the guidelines described below, but the ultimate choice is often guided primarily by a man's perception of his own symptoms.

Mild, or No, Symptoms. Men with mild, or no, symptoms (IPSS scores of 7 or below) usually choose watchful waiting even if their prostates are enlarged. BPH eventually progresses to the point of needing treatment in about 15% of men with mild symptoms who wait.

Moderate Symptoms. The choice is most difficult for men with moderate symptoms (scores between 8 - 19) and may simply depend on a man's ability to tolerate them. Some studies have reported that up to 40% of men with moderate symptoms eventually seek treatment, and a quarter require surgery. In a small percentage of patients, symptoms improve.

Severe Symptoms. Men with severe symptoms (scores over 20) nearly always choose treatment, although if their prostate glands are small or normal-sized, symptoms may improve.

If a man opts for treatment, there are several choices. Most experts recommend a staged approach as follows:

Mild Symptoms. Medications are the best choice for men with mild symptoms who decide to have their condition treated. There are two standard choices: alpha-blockers and anti-androgens, nearly always finasteride (Proscar). Specific conditions determine the choice, although most men take an alpha-blocker. Men with mild symptoms who choose surgery only experience minor improvement afterward but face the same risks as patients with more severe symptoms.
Moderate-to-Severe Symptoms. Men with moderate-to-severe symptoms often respond to the same medications as men with mild symptoms. (Combinations of alpha-blockers and finasteride are under investigation.) Recent developments in drug therapy have reduced the number of surgical procedures needed and delayed their use. However, a quarter of men with moderate symptoms, and even more men with severe symptoms, eventually need surgery. If a man chooses surgery, there are many choices. Transurethral resection of the prostate (TURP) is the standard procedure, but less invasive procedures, particularly those using heat or lasers to destroy prostate tissue, are gaining prominence.

Click the icon to see an illustrated series detailing transurethral resection of the prostate surgery.

The most common reason for choosing surgery is obstruction of the bladder outlet, which causes urinary retention. Surgery is also typically a reasonable option when BPH is clearly related to one or more of the following conditions:

Recurrent urinary tract infection.
Hematuria (blood in the urine). Studies have suggested that when hematuria is left untreated, two-thirds of patients continue to bleed and one third require surgery. The drug finasteride may help some men with this condition and should probably be tried before surgery.
Bladder stones.
Kidney problems.
Some experts believe that surgery might benefit patients for whom an early diagnosis of prostate cancer is important. Unsuspected prostate cancer is detected during surgery in about 15% of cases.

The greatest improvements resulting from surgery are usually increased urinary flow and reduced urine retention. In one study, men who chose surgery reported more worry and depression before the procedure, but afterward they had less depression and anxiety than those who had chosen medication. Often, however, the benefits of surgery are not permanent.

Treatment Options by Staging and Grading

Stages indicate the extent of the cancer:

Stage I and stage II cancer are considered early stage. The cancer is localized and has not spread outside the prostate gland.
Stage III, locally advanced cancer, means that the cancer has spread into the seminal vesicles (glands at the base of the bladder, which are connected to the prostate gland and help produce semen).
Stage IV is advanced cancer. The cancer has spread to the lymph nodes and other tissues or organs.

Experts have devised treatments based on classification systems, including staging and tumor grade. However, there are no clear-cut answers on the best treatments for particular stages. In addition to staging, other factors must be considered. These factors include the patient’s age, overall health status, and personal preferences concerning side effects and quality of life. In addition to standard treatments, patients may also wish to consider enrolling in clinical trials of investigational treatments.

The U.S. National Cancer Institute recommends the following treatment options by cancer stage:

Tumors: T1a, N0, M0, G1, Stage A

Active surveillance
Radical prostatectomy, usually with pelvic lymphadenectomy, with or without radiation therapy after surgery
External beam radiation therapy
Implant radiation therapy (brachytherapy)
Clinical trial options include high-intensity focused ultrasound

Click the icon to see an illustrated series detailing prostatectomy surgery.

Tumors: T1a - c, N0, M0, any G, Stage A2, B1, or B2

Radical prostatectomy, usually with pelvic lymphadenectomy, with or without radiation therapy after surgery
Active surveillance
External beam radiation therapy with or without hormone therapy
Implant radiation therapy (brachytherapy)
Clinical trial options include radiation therapy with or without hormone therapy; ultrasound-guided cryosurgery; hormone therapy followed by radical prostatectomy

Tumors: T3, N0, M0, any G, Stage C

External beam radiation with or without androgen deprivation therapy (hormone therapy)
Androgen deprivation therapy
Radical prostatectomy, usually with pelvic lymphadenectomy, with or without radiation therapy following surgery
Radiation therapy, androgen deprivation therapy or transurethral resection of the prostate (TURP) to relieve symptoms
Clinical trial options include ultrasound-guided cryosurgery

Click the icon to see an illustrated series detailing transurethral resection of the prostate.

Tumors: Any T, any N, any M, any G, Stage D1 - D2

Androgen deprivation therapy
External beam radiation therapy with or without androgen deprivation therapy
Radiation therapy or transurethral resection of the prostate (TURP) to relieve symptoms
Active surveillance
Clinical trial options include radical prostatectomy with surgery to remove both testicles (orchiectomy)

Treatment options are dependent on various factors, including prior treatment, site of recurrence, coexistent illnesses, and individual patient considerations.

Patients whose cancer recurs locally after prostatectomy: Radiation therapy, androgen deprivation therapy.
Patients whose cancer recurs locally after radiation therapy: Androgen deprivation therapy, prostatectomy (very select patients).
Patients whose recurrent cancer has spread: See treatment options for stage IV.

Treatment for Localized Prostate Cancer

Choosing the best treatment for localized prostate cancer (T1 or T2) is generally based on the patient's age, the stage and grade of the cancer, overall health status, and the patient's personal preferences for the risks and benefits of each therapy.

Patients have three main options:

Active surveillance, also called watchful waiting, involves monitoring the tumor for cancer progression to determine if and when treatment should be started.
Surgery (radical prostatectomy) removes the prostate gland. The vessels that carry semen and surrounding tissue may also be removed. Studies indicate that compared to watchful waiting, radical prostatectomy may lower the risk of cancer recurrence and death, particularly for younger men with aggressive tumors.
Radiation therapy targets the tumor either externally (external beam radiation) or internally (implanted “seeds”).

In 2007, the American Urological Association (AUA) released guidelines for the treatment of localized prostate cancer. The guidelines recommend that patients should be classified as low, intermediate, or high risk. Doctors determine the risk category by using criteria such as PSA tests, tumor aggressiveness, and the clinical stage of the tumor.

Among the AUA’s treatment recommendations:

Compared with active surveillance, radical prostatectomy may lower the risk of cancer recurrence and death.
For men at intermediate and high risk, adding androgen deprivation therapy to external beam radiation may improve survival. A higher dose of external beam radiation also improves the odds for survival.
Initial (first-line) androgen deprivation therapy is seldom recommended for localized prostate cancer except for the relief of symptoms in patients with poor prognoses. Androgen deprivation therapy can increase the risks for diabetes and heart disease.
Patients with localized prostate cancer should have the opportunity to enroll in clinical trials investigating new types of therapy.

Conflicting Data on Survival Rates. To date, neither treatment nor active surveillance has emerged with a definitive survival advantage. Several studies from 2005 and 2006 suggested that treatment provides a survival advantage over watchful waiting for some men with early-stage prostate cancer. A 2005 New England Journal of Medicine study reported that men who had a radical prostatectomy before age 65 had a reduced risk of death from prostate cancer, death from other causes, localized cancer progression, and metastases than men who chose watchful waiting.

Similarly, research presented at the 2006 Prostate Cancer Symposium found in a study of nearly 50,000 men with early-stage prostate cancer that men who had radiation or surgical treatment had a 30% lower risk of death than men who were randomly assigned to watchful waiting. However, a 2005 Journal of the American Medical Association study advised against aggressive treatment for localized low-grade prostate cancer. The study found that men with low-grade prostate cancer had a small risk of cancer progression even after 20 years of watchful waiting or hormonal drug therapy

Imperfection of Classification System. The classification systems are not perfect. Even if tumors are rated in low stages and grades and are treated accordingly, undetected cancer cells may escape and spread beyond the prostate. Other factors, such as the man's age and medical condition, must be included in determining whether aggressive treatments or conservative measures are appropriate.

Specialty Bias. Patients should be aware that doctors may be biased to prefer a specific treatment depending on their specialty. For example, in one study the following treatments were favored for patients who were generally appropriate candidates for either surgery, radiation, or watchful waiting:

93% of urologists recommended radical prostatectomy.
72% of radiation oncologists recommended radiation. (And 82% thought that radical prostatectomy was overused.)
Virtually none of the doctors recommended watchful waiting for higher-risk disease. When in doubt, patients should always seek a second opinion to help them make this important choice.

Quality of Life. Surgery and radiation both have potentially distressing side effects, including the possibility of impotence, incontinence, or both. A man must weigh his own emotional responses to the possibility of these side effects versus the possible stress of watchful waiting.

In general, differences in quality of life after surgery or radiation treatment have to do with the specific effects of each type of treatment:

Radiotherapy generally causes more bowel problems than surgery, 30 - 35% versus 6 - 7%, according to a 2001 study. In a 2003 review, the risk for impotence from radiotherapy varied from 25% with brachytherapy to 45% with external beam radiotherapy.
Prostatectomy causes more urinary incontinence (39 - 49% versus 6 - 7% for radiotherapy patients) than radiotherapy. Risks for impotence range from 66% after nerve-sparing prostatectomy to 87% after cryotherapy. In spite of these adverse effects, a 2002 study reported no meaningful differences in well-being or quality of life during a 4-year period for men who chose surgery versus those who chose watchful waiting.
Active surveillance could lead to cancer growth that eventually obstructs the urinary tract (which can happen with the treatments as well). It may also impose an emotional burden on men who live with the possibility of progressive cancer and its difficult treatments. Some who decide to wait become what some doctors refer to as the "walking worried," men who are constantly concerned with their PSA levels. Because aggressive treatment reduces such anxiety, some studies reported that years after surgery, about 75% of men said they would chose it again, in spite of the significant side effects.

Watchful waiting involves lifestyle change and careful monitoring for cancer progression. Over the last several years, watchful waiting has evolved into a strategy called “active surveillance” or “delayed surgical intervention.” With this approach, patients have a digital rectal exam and PSA blood test every 6 - 12 months. If test results indicate cancer progression, then treatment options (surgery, radiation, drugs) are considered. Patients should exercise and eat healthy foods. Patients should report symptoms such as weight loss, pain, urinary problems, fatigue, or impotence to their doctors.

Candidates. Active surveillance may be most appropriate for the following patients:

Men in their late 70s and older. More aggressive therapies (surgery and radiation) are usually recommended for men in their 50s and younger. The choice for men in their 60s and early 70s is more problematic. The general recommendation is that aggressive therapy is suitable for those who have a life expectancy of more than 10 years and who have localized but mid- to high-grade tumors. The tumor grade may be the best guide for determining the risks in choosing watchful waiting.
Elderly men with early-stage (T0 - T2) low-grade tumors.
Men with low-to-moderate (3 - 13 ng/mL) PSA levels.

Some experts think that because prostate cancer grows so slowly, it is likely that older men will die from causes unrelated to the cancer. There is therefore little potential benefit from surgery or radiation, with both posing a risk for impotence and incontinence. However, some recent surveys suggest that more men are choosing treatment (especially surgery) over active surveillance. The choice is a difficult one. It is important that patients find a doctor who can provide them with all the necessary information so that they can make an informed decision.

In men whose cancer is confined to the prostate, surgical resection (radical prostatectomy) offers the potential for cure. Cure rates from initial surgery in men with localized cancer are about 70%, depending on tumor stage, tumor grade, and PSA levels. Research suggests that surgery provides long-term cancer control. Most patients can consider themselves disease-free if their PSA levels remain undetectable 10 years after surgery.

Candidates. Radical prostatectomy is a consideration for men who meet all of the following criteria:

In good health and with a life expectancy of 10 years or more. As average life expectancy in men has increased, more older men are becoming candidates for surgery. Complication rates are higher the older a man is, however.
The cancer has not spread beyond the prostate gland.
The cancer is potentially life threatening. (In general, a life-threatening tumor is indicated by volumes more than 0.2 cc and Gleason grade scores greater than 5.)

The procedure is more likely to cause incontinence (up to 50%) than radiation treatment but has fewer bowel complications. Impotence rates are about the same. Surgery for prostate cancer may be particularly difficult in men who have had transurethral resection of the prostate (TURP).

Radiation therapy (or radiotherapy) is administered as external beam radiation or as brachytherapy (radiation implants). It may be used as the sole primary treatment for localized prostate cancer; 5-year survival rates are similar to those of surgery.

Candidates. Radiation is considered for men with one or more of the following characteristics:

Being older and, particularly, having other medical problems.
Cancer has extended beyond the prostate capsule but has not spread to the lymph nodes or further.
Being a good surgical candidate, but having decided against an operation.

The risk for incontinence (less than 10%) is much lower than with surgery, although bowel problems occur in about a third of patients. Impotence rates are about the same.

Androgen Deprivation Therapy With Radiation. Hormonal (“androgen deprivation”) drugs combined with radiation therapy may improve survival rates in moderate- or high-risk groups. Patients may need to take these drugs long-term to improve outcomes. Hormonal drugs before radiation (neoadjuvant therapy) may be helpful in shrinking enlarged glands so that brachytherapy (radiation implants) can be used. Hormone therapy can also be given at the same time or following radiation.

An important study published in 2004 in the Journal of the American Medical Association (JAMA) found that for men with localized prostate cancer, a 6-month course of androgen deprivation therapy combined with radiation treatments produced greater survival rates than radiation treatment alone. Standard medical practice has generally indicated that hormone therapy should be given for 3 years; the JAMA study suggests that a shorter regimen may be equally beneficial for some patients and may help reduce the side effects that typically accompany androgen-suppressing drugs.

A 2005 JAMA study suggested that PSA velocity (PSAV) may help doctors decide which patients should receive androgen deprivation drugs along with radiation therapy. PSAV lets doctors calculate how quickly a patient’s PSA level has risen. Researchers found that men who had at least a 2.0 ng/mL increase in PSA levels during the year before their cancer diagnosis had a high risk of dying after external beam radiation therapy, even though they had low-grade prostate cancer. The study suggests that men with this particular PSAV history should consider combining radiation therapy with androgen deprivation drugs.

Surgery

Radical prostatectomy is the surgical removal of the entire prostate gland along with the seminal vesicles (the vessels that carry semen) and surrounding tissue. The incision can be made in one of the following regions:

Retropubicly (through the abdomen and under the pubic bone, exposing the entire surface of the prostate).
Through the perineum (the skin between the scrotum and the anus).

The gland and other structures are then removed. The operation lasts 2 - 4 hours. Advanced surgical techniques, such as minilaparotomy and laparoscopy, are being developed for radical prostatectomy. These techniques use smaller incisions, are less invasive, and may cause fewer complications.

Click the icon to see an illustrated series detailing prostatectomy surgery.

Nerve-Sparing Techniques. Surgical procedures have been refined over the years, and many operations for localized low-grade prostate cancer now spare the nerves that control erection.

A bilateral nerve-sparing procedure saves the nerves on both sides of the sex organs.
A unilateral procedure saves nerves on only one side.

Nerve-sparing techniques can improve quality of life. The ability for sexual intercourse recovers in about a third of patients at 3 years and nearly 60% at 5 years after surgery. (Rates vary depending on certain factors, such as the patient's age -- the younger the better.) In cases where the tumor is bulky and undifferentiated, nerve-sparing techniques may not be appropriate.

Convalescence. Patients remain hospitalized for up to 2 weeks. A temporary catheter used to pass urine is kept in place when the patient is sent home and usually removed about 3 weeks after the operation. The convalescent period at home is about a month. In general, younger patients with early-stage cancers recover fastest and experience the fewest side effects.

Complication rates vary after radical prostatectomy and usually depend on the age of the patient and the experience of the surgeon and medical center. They can range from 4% in men in their 40s to 14% in men over age 70. Complication rates are 10 times higher in patients who have prostatectomy because of cancer recurrence after radiation treatment.

Complications include the usual risks of any surgery, such as blood clots, heart problems, infection, and bleeding. Complications specific to radical prostatectomy, (incontinence, impotence, and contracture of the bladder neck), are discussed below. The mortality rate is very low, about 0.4%.

Quality of life usually improves shortly after surgery, and recovery from certain complications, such as incontinence and sexual function, can continue to occur even over years.

Urinary Incontinence. Urinary incontinence is a common complication and a more distressing side effect of surgery for most men than sexual dysfunction. When the urinary catheter is first removed following surgery, nearly all patients lack control of urinary function and will leak urine for at least a few days and sometimes for months. Major medical centers report that continence returns within about 18 months for nearly all men younger than age 70 and in the great majority of men older than 70. The average time for return of continence in one center was just 1.5 months.

Click the icon to see an image of catheterization.

A number of approaches may help prevent or treat incontinence:

Nerve-sparing techniques can help prevent incontinence, although even in experienced centers, 8% of patients will have some postoperative incontinence, and this rate is much higher (up to 50%) in many community medical centers.
A procedure called endopelvic anterior urethral stitch (EAUS) used with prostatectomy appears to reduce urinary incontinence. In one small study, 75% of selected patients recovered continence in a month. The procedure requires a simple stitch at the front of the urethra.
Kegel exercises, contracting and relaxing the muscles used to shut off the urinary stream, strengthen the muscles on the pelvic floor and are reported to be very beneficial for many men.

If incontinence persists beyond a year, patients may require drug therapy or surgery. Collagen injections into the urethra, bladder neck suspension surgery, or a urinary sphincter implant may be helpful for men who have chronic incontinence. [See In-Depth Report #50: Urinary incontinence.]

Impotence. Studies suggest that about 40% of men have problems with erection after the procedure. In one study, however, more than 70% said they would have the procedure again. Nerve-sparing procedures are proving to be helpful in reducing impotence as well as incontinence.

Sildenafil (Viagra) may help restore potency on average in about a third of patients, but some men may do better than others. In one study, for example, 80% of younger men who were potent before surgery and had bilateral nerve sparing procedures responded to the drug. (Only 40% responded with only unilateral procedure.) Sildenafil is unlikely to be effective for men who had unilateral or no nerve sparing procedures. In those who respond, sildenafil may provide a benefit for years. Sildenafil may take 9 months or longer to become effective. Men who take it may benefit from alprostadil injections started right after surgery to preserve elasticity and help prevent scarring.

Early treatments with alprostadil injections may helpful in restoring erectile function in any case. This treatment maintains blood flow in the penis, and some research suggests that impotence after prostate surgery may be due in part to injury to these blood vessels. In one study, men administered injections every other night for 6 months. They then started taking sildenafil 3 months after surgery. At 6 months, 82% of these men achieved penetration compared to only 52% of men who took Viagra only. The vacuum pump may serve a similar purpose as the injections. [See In-Depth Report #15: Erectile dysfunction.]

Even when erectile function is preserved, men may experience other sexual problems:

Erections may not be as rigid as before the operation.
Orgasm and sexual sensation may be altered.
Patients who retain potency may suffer from retrograde ejaculation, also known as dry ejaculation. During ejaculation, semen travels backward into the bladder, causing infertility.

Fecal Incontinence. Radical prostatectomy can also cause fecal incontinence. The risk may actually be higher in men undergoing nerve-sparing procedures.

Contracture of the Bladder Neck. Another common postsurgical complication is contracture of the bladder neck at the point where it has been stitched to the remainder of the urethra. Contracture usually occurs within the first 3 months after the operation, causing a sharp decrease in urinary stream. The condition can be treated by dilation or surgery on the bladder neck, and rarely recurs.

Pelvic lymphadenectomy is the surgical removal of the pelvic lymph nodes. It is usually performed at the same time as prostatectomy. If the surgeon suspects that cancer has spread beyond the prostate, the surgeon will perform the lymphadenectomy as part of the operation. Some surgeons do this procedure as a matter of course when performing prostatectomy, since it has few complications and adds information on the state of the disease. The lymph nodes are removed through an incision in the lower part of the abdomen, using conventional surgery or laparoscopy, a less invasive variation. The nodes are immediately examined. If they show signs of cancer, metastasis has occurred. In such cases, the operation is usually stopped and the patient is offered radiation or hormone treatments.

Click the icon to see an image of the pelvic lymph nodes.

Transurethral resection of the prostate (TURP) involves removing a section of the prostate with a surgical instrument (resectoscope) that is inserted through the urethra. TURP may be used to control urinary symptoms in men who are not good candidates for curative therapy due to advanced age, health status, or other reasons. TURP is also used as a treatment for benign prostatic hyperplasia (BPH).

Cryosurgery is an alternative to standard prostatectomy. The goal of cryosurgery is destruction of the entire prostate gland and possibly surrounding tissue. Steel probes are inserted through the skin between the anus and the rectum and into the prostate. Liquid nitrogen is pumped through the probes to freeze all prostate cells, both healthy and cancerous. For success, cryosurgery requires a uniformly frozen area. The dead cells are absorbed and eliminated by the body. Patients can leave the hospital in 2 - 3 days.

Candidates. Cryosurgery may be considered for patients with:

Early stage local cancer
Cancer that has recurred after radiation treatments
Large primary tumors that the surgeon wishes to reduce
Possibly tumors that have spread beyond the prostate if they have not yet reached the lymph nodes

Strong predictors of treatment failure include:

A history of both hormonal and radiation treatments
Tumor grades 8 and above
PSA levels of more than 10 ng/mL

Complications. Complications are similar to those of standard prostatectomy, but incontinence rates are much lower. Impotence rates, however, are much higher. Nevertheless, 96% of patients report that they are satisfied with the results. Incontinence and other side effects may be higher in patients who have had previous radiation treatments. Other significant complications include scarring and narrowing of the urethra, and fistulas (abnormal passages from internal organs to the skin or between two internal organs).

Radiation Treatments

The two major radiation treatments are:

External beam radiation
Brachytherapy (internal radiation)

Both treatments have generally equal success rates. Research presented at the 2006 Prostate Cancer Symposium indicated that the two therapies work equally well for treating localized prostate cancer. In some cases, both techniques may be used in high-risk patients.

In external beam radiation therapy, a doctor focuses a beam of radiation directly on the tumor for 35 3-minute treatments given 5 times a week over 7 weeks. 3-D conformal techniques use computers and a three-dimensional image of the prostate to target the tumor precisely, using high-dose radiation beams. It poses a lower risk for inflammation. Men who have had transurethral resection of the prostate (TURP) or have a history of lower urinary tract symptoms may be particularly good candidates for 3D conformal techniques.

According to the 2007 American Urological Association guidelines for treatment of localized prostate cancer, patients considering external beam radiation should know that higher radiation doses may reduce the risk for cancer recurrence and improve survival outcome.

Brachytherapy is an outpatient technique that implants radioactive "seeds" directly into the prostate. Implants can be temporary or permanent. Temporary implants are usually accompanied by external beam radiation. This procedure requires more skill than external beam radiation therapy and, even with experienced doctors, the distribution of radioactive seeds is uneven in 15% of cases, increasing the risk for insufficient doses.

Computerized systems are being developed to help oncologists optimize seed placement and allow precise treatment for each patient and higher radiation doses. Eventually, it could improve tumor control, reduce side effects, and cut costs.

It is common for PSA levels to temporarily rise, or "bounce," following seed implantation without it being a signal for cancer recurrence. This effect can produce anxiety and can interfere with the diagnosis of true recurrence.

Candidates. Studies suggest that brachytherapy is useful for select patients, specifically those with prostate volumes less than 60 mL and who have early-stage prostate cancer (T1 or T2 tumors, a Gleason grade lower than 7, and PSA levels below 10 ng/mL). It may be beneficial in patients with inflammatory bowel disease or with cancer close to the bowel. Poorer candidates for brachytherapy include men who have had TURP and patients with advanced cancer, high-grade tumors, or very enlarged prostate glands.

The side effects of radiation therapy include most of those of surgery, but the risks for impotence and incontinence are considerably lower. A 2000 study concluded that adjuvant radiation therapy (given right after surgery) in moderate doses does not increase the risk for long-term urinary incontinence or sexual dysfunction beyond that of surgery alone.

Gastrointestinal Complications. Complications in the gastrointestinal are common. Short-term effects include nausea and loss of appetite. Diarrhea is a very common side effect and can last for the duration of therapy. It is usually treated with Lomotil. A few patients have diarrhea flare-ups for years afterwards. Less than 1% suffer more serious intestinal problems.

There is potential for injury to the rectum with brachytherapy. Ulcers in the rectum occur in more than 10% of patients, but the risk decreases with greater experience in the technique.

Urinary Problems. The risk for incontinence is about 7 - 20%. Patients treated with radiation may experience a painful, but usually temporary, urinary tract inflammation. About 10 - 15% of patients develop a long-term urgent and frequent need to void their bladder. Brachytherapy carries a lower risk for urinary incontinence.

Scarring and narrowing of the urinary tract (stricture) may occur, particularly in men who had TURP performed within a short time before radiation treatment. In such men, radiation treatments should be delayed by 4 - 6 weeks. If the prostate has been injured or damaged or the bladder is easily irritated, side effects with brachytherapy may actually be worse than with other procedures.

Impotence. In a 2003 review, the risk for impotence following radiotherapy varied from 25% with brachytherapy to 45% with external beam radiotherapy. Still, very few studies on brachytherapy have lasted more than 2 years, so more research is needed.

Sildenafil (Viagra) may help many men experiencing impotence following radiation therapy for local prostate cancer. Early use of both alprostadil injections and sildenafil may be even more effective. Other treatments may also be useful. [See In-Depth Report #15: Erectile dysfunction.]

Investigators are testing radiation treatments that use a combination of neutrons and protons (mixed-beam) or proton beams rather than the standard proton radiation therapy. Intensity-modulated radiation therapy is a promising technique that delivers different doses to multiple target areas using images of specific regions.

High-Intensity Focused Ultrasound (HIFU). Studies are reporting promising results with an intensive ultrasound procedure called transrectal high-intensity focused ultrasound (HIFU). It allows for very precise minimally invasive removal of tissue in local prostate cancers. It may eventually prove to be an alternative to radiation therapy. More research, with long-term follow up, is needed.

Radiofrequency. Radiofrequency is being used to heat and destroy the prostate. Early studies suggest that this is a promising approach.

Options if Treatments Fail

Rising PSA Levels. If prostate cancer has been eliminated, PSA levels should drop to 0.5 ng/mL or less after treatment. A sudden rise or persistently elevated PSA levels after treatment are often indications that prostate cancer persists:

If PSA levels are above 2.0 ng/mL, then cancer is most likely still present.
If PSA levels are between 0.5 - 2.0 ng/mL, the situation is less clear. One study indicated that measuring free PSA may help determine the status of the cancer in such patients. An average free PSA of 27% indicated that cancer had been eliminated, while an average of 15% meant that cancer was still present.

Note: It is common for PSA levels to temporarily rise following radiation seed implantation without signaling cancer recurrence.

Rising PSA levels do not necessarily mean that the cancer has spread or even that the cancer will recur during a man's lifetime. An actual cure is still possible if the cancer is localized within the prostate. In one study, 64% of patients with rising PSA levels after surgery still had cancer confined to the prostate. Indications of a poorer outlook in this study included:

Cancer penetration of the prostate capsule
Positive surgical margins (microscopic evidence of cancer cells at the very edge of the resected specimen)
Invasion of nearby vessels or lymph nodes

Still, among the men in the study, after 7 years only 3% of patients had died of prostate cancer. After 15 years, only 19% had evidence of recurrence. Other markers for persistent cancer are under investigation. For example blood tests that show low levels of acid phosphatase (ACP) before treatments may predict a higher chance for recurrence-free survival.

Treatment for recurring cancer is not always clear-cut. If the cancer recurs locally, cure may still be possible:

Surgery and androgen deprivation therapy may be considered for patients who were first treated with radiation.
For patients who were initially treated with surgery, radiation or androgen deprivation therapy are both options.

If the disease has already spread or if the doctor suspects that it may have spread, the patient is typically given androgen deprivation therapy. Chemotherapy drugs in combination with hormonal drugs are being investigated for patients who fail surgery or radiation.

A 2005 study in the Journal of the American Medical Association suggested three factors that may help doctors and patients decide if additional treatment is needed if cancer recurs after surgery:

How quickly PSA levels double after surgery (shorter time equals higher risk)
How quickly the cancer recurred after surgery (shorter time equals higher risk)
Gleason score (higher score suggests more aggressive tumors and greater risk)

Patients at high risk are more likely to die from the recurrent cancer and should be considered for additional treatments. Patients at low risk face a lower likelihood of death from prostate cancer and probably do not require more treatment. The study found that for patients at low risk, the time to death after cancer recurrence was very long, generally lasting more than 16 years.

Androgen Deprivation Therapy. Androgen deprivation therapy, also called androgen suppression therapy or hormone therapy, involves blocking the effect of male hormones such as testosterone through medical (drugs) or surgical castration. Androgen suppression therapy is not recommended as a first-line approach for most men with localized prostate cancer. It is usually given to patients with recurrent, progressive, or advanced prostate cancer. It may also be given for a relatively brief time in combination with external beam radiation.

Although androgen deprivation therapy slows the growth of most prostate cancers, it can have serious side effects. The American Society of Oncology’s (ASCO) 2007 guidelines do not recommend the early use of hormone therapy. However, ASCO does recommend that patients start therapy once they begin to experience cancer symptoms. Patients who defer therapy should have regular doctor visits every 3 - 6 months to monitor their condition.

Salvage Prostatectomy. Salvage prostatectomy is sometimes performed after unsuccessful radiation treatment if the cancer is still local. The odds of the procedure's success are only 10 - 64%. Many experts recommend against salvage prostatectomy in most cases of radiation failure. Severe complication rates for salvage prostatectomy are very high: 10 times that of men who have not had radiation. For example, incontinence after salvage prostatectomy is often untreatable with medications, collagen implants, or other standard treatment measures.

Salvage Cryosurgery. Salvage cryosurgery may be effective in certain patients who fail external beam radiotherapy. The best candidates are those with Stage II cancer or less and PSA levels below 10 ng/mL.

Adjuvant and Salvage Radiation. Radiation is proving to help patients who still show detectable levels of PSA after surgery (generally 2 ng/mL or less). It may even be useful years after surgery if PSA levels rise. Depending on timing, radiation after treatment failure is referred to as either:

Adjuvant radiation is radiation therapy performed within 6 months after radical prostatectomy. One area of controversy is whether to use adjuvant radiation after surgery on patients whose PSA levels are very low or undetectable but who have other test results that indicate the cancer is likely to spread. Patients with adverse findings and low PSA have to weigh the potential complications of radiation therapy against the odds of recurrence without it, which are about 20 - 30%. A small 2006 study found that adjuvant radiation worked much better than salvage radiation for men with advanced (stage III or IV) local prostate cancer. However, a 2007 study indicated that adjuvant radiation in men with advanced cancer may reduce the risk of cancer recurrence but does not improve length of survival.
Salvage radiation is radiation therapy more than 6 months after surgery. A 2004 study suggested that salvage radiation could be more beneficial than previously thought, even for men with aggressive prostate cancer. Researchers studied 501 men who had undergone radical prostatectomy (surgical removal of the prostate gland) and subsequently received radiation treatment for recurrent cancer (as indicated by rising PSA levels). Men with lower Gleason scores and lower PSA levels benefited the most from salvage radiation. However, even men with higher-grade cancers were able to delay metastatic cancer progression as long as they received radiation at an early stage while their PSA levels were relatively low (less than 2.0 ng/mL).

Other Treatments

Male hormones (called androgens), particularly testosterone and dihydrotestosterone, determine male secondary sex characteristics and stimulate prostate cell growth. When prostate cells, both healthy and cancerous, are deprived of androgens, they no longer proliferate and eventually die.

Androgen deprivation therapy (also called androgen suppression therapy or hormone therapy) uses drugs or surgery (orchiectomy) to suppress or block male hormones (androgen) -- particularly testosterone and dihydrotestosterone -- that stimulate the growth of prostate cells. Androgen deprivation therapy is used for advanced and metastatic cancer and may be used if treatment for localized prostate cancer has failed and cancer recurs (as indicated by rising PSA levels). Side effects can include decreased bone density, decreased muscle mass, hot flashes, depression, fatigue, weight gain, enlarged breasts, and high cholesterol levels. Evidence also indicates that androgen deprivation therapy increases the risk for diabetes and death from heart disease.

There has been some debate about when androgen deprivation therapy should be initiated. In 2007, the American Society of Clinical Oncology (ASCO) published clinical guidelines for androgen deprivation therapy in patients with recurrent, progressive, or advanced prostate cancer. The guidelines recommend that hormone therapy should, in general, be delayed until patients begin to experience symptoms from their cancer. However, when therapy is deferred, patients should regularly visit their doctors every 3 - 6 months for careful monitoring of their condition.

ASCO recommends either removal of both testicles (bilateral orchiectomy) or injections with luteinizing hormone-releasing hormone (LHRH) as initial androgen deprivation treatments. Combining nonsteroidal antiandrogen drug therapy with orchiectomy or LHRH may also be considered.

Doctors vary widely on their opinions of androgen deprivation therapy. A 2006 study found that the decision to use hormonal therapy depends more on a patient’s urologist than on the patient’s tumor or other factors.

Androgen deprivation therapy includes:

Hormonal Drugs. The primary drugs used for suppressing androgens are called luteinizing hormone-releasing hormone (LH-RH) agonists.

Orchiectomy. Orchiectomy is the surgical removal of the testicles. It is the single most effective method of reducing androgen hormones, but it is considered an extreme procedure. Studies do not indicate that it significantly improves survival rates. Orchiectomy plus radical prostatectomy may delay progression in patients with cancers that have spread only to the pelvic lymph nodes. Combining orchiectomy with antiandrogen drug therapy adds a modest benefit.

The median survival rate after the operation is about 55% over a 40-month period. An estimated 25% of patients survive 5 years or more. Nevertheless, orchiectomy, although irreversible, may produce fewer adverse effects than hormonal drugs, and interestingly, many patients report significantly higher quality of life after orchiectomy than those who opt for hormonal treatment, particularly total androgen ablation. Because orchiectomy is irreversible, about 75% of patients with advanced prostate cancer choose hormonal therapy to block androgens. Like all androgen deprivation therapies, orchiectomy increases the risk for osteoporosis.

Many men can still achieve erection after orchiectomy, but there is almost always a decline in sexual drive. Men who cannot achieve erection may be candidates for a penile implant. Patients do not experience a reversal of sex characteristics; the voice does not change and body hair is not affected.

Androgen Deprivation Therapy Before or With Radiation. Hormonal drugs combined with radiation therapy may improve survival rates in moderate- or high-risk groups. Patients may need to take these drugs long-term to improve outcomes. Hormonal drugs before radiation (neoadjuvant therapy) may be helpful in shrinking enlarged glands so that brachytherapy (radiation implants) can be used.

An important study published in 2004 in the Journal of the American Medical Association found that for men with localized prostate cancer, a 6-month course of hormone therapy combined with radiation treatments produced greater survival rates than radiation treatment alone. Standard medical practice has generally indicated that hormone therapy should be administered for 3 years; the JAMA study suggests that a shorter regimen may be equally beneficial for some patients and may help reduce the side effects that typically accompany androgen-suppressing drugs.

Androgen Deprivation Therapy Before or After Surgery. Some studies suggest benefits from using hormone therapy before surgery (neoadjuvant therapy) to reduce the tumor size, although it is not clear yet if this approach has survival benefits. Hormonal treatment may be useful after surgery in men who have high-grade tumors or tumors that have invaded the semen-carrying vessels or lymph nodes. Such men have a risk for failure after surgery of 50 - 80%.

The primary drugs used for suppressing androgens are called luteinizing hormone-releasing hormones (LHRH) agonists. They include:

Leuprolide (Lupron, Leuprogel). Studies report that disease progression is prevented in 72% of men taking daily leuprolide and up to 89% of those taking monthly injections. Certain men, however, may not respond to injections. Drug delivery using implants is under investigation.
Goserelin (Zoladex). Partial responses of 60 - 80% have been reported. A controlled release formulation has been developed that increases the time between injections from 4 weeks to 3 months.
Buserelin.

LHRH drugs block the pituitary gland from producing hormones that stimulate testosterone production. Patients must have injections of LHRH agonists for the rest of their lives.

Testosterone and PSA Surges. Treatment with LHRH agonists produces a testosterone surge in the first week, which may actually intensify symptoms. After this phase, testosterone levels drop to near zero. Leuprogel, a newer leuprolide, may pose a lower risk for this effect. Researchers are investigating other drugs, such as GnRH antagonists, that do not produce this surge.

LH-RH agonists can also cause PSA levels to rise temporarily. Administering flutamide, a drug known as an antiandrogen, for 2 weeks prior to LH-RH agonists may not only prevent PSA surge but also induce early declines in PSA levels.

Side Effects. Side effects include hot flashes and occasionally nipple and breast tenderness.

Gonadotropin-releasing hormone (GnRH) stimulates the pituitary gland to release luteinizing hormone-releasing hormones (LHRH). GnRH antagonist drugs such as abarelix (Plenais) and histrelin (Vanta) block this action. They have two advantages over LHRH agonists:

They do not cause the same testosterone surge that can temporarily worsen cancer symptoms.
They seem to reduce testosterone levels more quickly.

Anti-androgens are drugs used to block the effects of testosterone. They are used alone or in maximal androgen blockage (MAB), in which they are combined with LHRH agonists or orchiectomy to completely block androgen hormones. Anti-androgens are either steroidal or nonsteroidal.

Nonsteroidal Anti-androgens. Nonsteroidal anti-androgen drugs include:

Flutamide (Eulexin, Drogenil). Flutamide has produced extended response in some patients. Side effects may include diarrhea and liver damage, which has been fatal in rare cases; liver function must be monitored closely.
Nilutamide (Nilandron). Nilutamide is associated with reversible interstitial pneumonitis, nausea, alcohol intolerance, and visual disturbances.
Bicalutamide (Casodex). Bicalutamide is effective and appears to have fewer severe side effects than other anti-androgens, including loss of sexual interest, osteoporosis, visual disturbance, and interstitial pneumonia. This drug is proving to have survival rates equal to those of maximal androgen blockage.

Steroidal Antiandrogens. Steroidal antiandrogens act like female hormones and include:

Megestrol uppresses androgen production, but incompletely, and is generally not used as initial therapy.
Cyproterone combined with estrogen may prevent the testosterone surge that occurs with LH-RH agonists.

Men often experience fatigue, loss of energy, and emotional distress from androgen suppression treatment. Hormonal therapy may significantly impair quality of life, particularly in men who had no symptoms beforehand and whose cancer has not metastasized. Common side effects of androgen suppression drugs include:

Osteoporosis, the loss of bone density. This risk is higher with orchiectomy than with androgen suppressants. Some androgen suppressants, such as bicalutamide, may cause less bone loss. The use of estrogens may actually be bone protective. A number of medications, especially bisphosphonates, are available to help prevent or reduce bone loss.
Diarrhea
Loss of muscle mass
Psychological disturbances
Fatigue
Loss of sexual drive and sexual dysfunction
Swelling of the breasts (gynecomastia)
Nausea and vomiting
Hair loss
Anemia

In addition, there is growing evidence that androgen deprivation therapy increases the risks for diabetes and heart disease.

Prostate cancer that does not respond to hormonal treatment is called hormone-resistant, or hormone-refractory, cancer. There are various drug treatments for hormone-resistant cancer:

Docetaxel and Other Chemotherapy. Chemotherapy drugs for prostate cancer include docetaxel (Taxotere), mitoxantrone (Novantrone), estramustine (Emcyt), and various platinum-based drugs, such as carboplatin. These drugs are often combined with other cancer drugs (such as 5-fluorouacil) or corticosteroids (such as prednisone).

Docetaxel-based drug regimens are emerging as the main chemotherapy treatment for hormone-refractory prostate cancer. In 2004, the FDA approved docetaxel injection in combination with prednisone for treatment of patients with hormone-resistant prostate cancer. Patients who received this drug combination survived on average 2.5 months longer than patients who received mitoxantrone and prednisone. Another 2004 clinical trial found that a docetaxel and estramustine combination worked better than mitoxantrone and prednisone for advanced resistant prostate cancer. Side effects can be serious and may include gastrointestinal problems (nausea, vomiting, or diarrhea), fatigue, low blood cell counts, and increased risk for blood clots.

Researchers are continuing to investigate docetaxel combinations and compare them to other chemotherapy regimens. A large 2006 study reported that docetaxel and prednisone worked better than mitoxantrone plus prednisone in improving quality of life, pain relief, and survival. Docetaxel is also being investigated in combination with vitamin D-related drugs. A 2006 trial found that men with advanced prostate cancer who took docetaxel plus high-dose vitamin D (calcitriol) lived about 8 months longer than men who received docetaxel and placebo. Calcitriol also appeared to protect against docetaxel’s side effects, especially gastrointestinal problems and blood clots.

Doctors are also studying other ways to help patients cope with docetaxel’s side effects. Research presented at the 2006 Prostate Cancer Symposium suggested that patients may be able to take periodic breaks from docetaxel treatment instead of having continuous therapy. In the study, patients with advanced prostate cancer were given the option of suspending docetaxel treatment if their PSA levels improved within a certain range. Researchers found that patients were able to take 16-week breaks and still show improvement once they resumed treatment. This approach may work best for patients who experienced a good initial response to docetaxel.

Bisphosphonates. These drugs prevent bone loss and reduce bone pain in metastasized cancers. They are of particular interest because they may inhibit prostate cancer cell growth in the bone. The bisphosphonates showing most promise in prostate cancer are newer drugs called nitrogen-containing bisphosphonates (pamidronate, zoledronic acid).

Immunotherapies. The prostate organ offers special possibilities for genetic therapies because it contains highly specific antigens (factors that the immune system can target). There are a number of approaches currently under investigation, including:

Genetically designed vaccines (Provenge, Gvaz, JBT 1001) inject factors into prostate cancer cells that trick the immune system into attacking the cancer cells.
Antisense therapy for prostate cancer blocks expression of a protein called BCL-2, which tends to be genetically overexpressed in some patients with androgen-independent prostate cancer. This protein prevents apoptosis (a natural process by which all cells, including cancer cells, self-destruct).
Monoclonal antibodies (MAbs) are genetically designed immune factors that target foreign compounds called antigens for attack by the immune system. Monoclonal antibodies are being designed to target prostate-specific antigens.

Angiogenesis 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 ). The spread of new blood vessels is controlled by compounds called growth factors, which may be important in cancer cell proliferation. Researchers are interested in drugs that turn off these growth factors or their receptors, such as epidermal growth factor receptor (EGFR). In doing so, the drugs may be able to cut off cancer's life blood. Gefitinib (Iressa) and erlotinib (Tarceva) are angiogenesis inhibitors that target receptors of epidermal growth factors called tyrosine kinase. They are being used in lung cancer and are being investigated in a number of other cancers, include prostate cancer. Various drugs that inhibit angiogenesis in other ways (thalidomide, endostatin) are also under investigation.

Ketoconazole. Ketoconazole is an antifungal drug that blocks an enzyme that stimulates production of testosterone. It is effective in high doses but can have severe gastrointestinal effects, mainly nausea and anorexia. Long-term use can result in impotence, itchy skin, nail changes, and suppression of stress hormones. One center reported a consistent PSA response in more than 60% of patients who had failed other androgen deprivation treatments.

Aromatase Blockers. Aminoglutethimide (Cytadren) and similar drugs block aromatase, an enzyme important in estrogen production. Because the female hormone estrogen plays such a major role in the development of breast cancer, some experts think that blocking the small amount of estrogen found in men may also affect prostate cancer. Side effects include drowsiness and skin rash.

Atrasentan. Atrasentan is known as an ET(A)-receptor antagonist. It is showing promise in reducing bone loss and delaying progression of prostate cancer in men with advanced disease that no longer responds to hormone therapy. Side effects are relatively mild.

Resources

www.cancer.gov -- National Cancer Institute
www.cancer.org -- American Cancer Society
www.asco.org -- American Society of Clinical Oncology
www.plwc.org -- People Living with Cancer
www.prostatecancerfoundation.org -- Prostate Cancer Foundation
www.fightprostatecancer.org -- National Prostate Cancer Coalition
www.urologyhealth.org -- Urology Health
www.nccn.org -- National Comprehensive Cancer Network
www.cdc.gov/cancer/prostate -- CDC Cancer Prevention and Control
www.psa-rising.com -- PSA Rising: Prostate Cancer Survivor Info
www.ustoo.org -- Us Too! Prostate Cancer Education and Support
www.cancer.gov/clinicaltrials -- Find clinical trials

References

Greenspan SL, Nelson JB, Trump DL, Resnick NM. Effect of once-weekly oral alendronate on bone loss in men receiving androgen deprivation therapy for prostate cancer: a randomized trial. Ann Intern Med. 2007 Mar 20;146(6):416-24.

Gudmundsson J, Sulem P, Manolescu A, Amundadottir LT, Gudbjartsson D, Helgason A, et al. Genome-wide association study identifies a second prostate cancer susceptibility variant at 8q24. Nat Genet. 2007 May;39(5):631-7. Epub 2007 Apr 1.

Haiman CA, Patterson N, Freedman ML, Myers SR, Pike MC, Waliszewska A, et al. Multiple regions within 8q24 independently affect risk for prostate cancer. Nat Genet. 2007 May;39(5):638-44. Epub 2007 Apr 1.

Keating NL, O'Malley AJ, Smith MR. Diabetes and cardiovascular disease during androgen deprivation therapy for prostate cancer. J Clin Oncol. 2006 Sep 20;24(27):4448-56.

Lawson KA, Wright ME, Subar A, Mouw T, Hollenbeck A, Schatzkin A, et al. Multivitamin use and risk of prostate cancer in the National Institutes of Health-AARP Diet and Health Study. J Natl Cancer Inst. 2007 May 16;99(10):754-64.

Leman ES, Cannon GW, Trock BJ, Sokoll LJ, Chan DW, Mangold L, et al. EPCA-2: a highly specific serum marker for prostate cancer. Urology. 2007 Apr;69(4):714-20.

Loblaw DA, Virgo KS, Nam R, Somerfield MR, Ben-Josef E, Mendelson DS, et al. Initial hormonal management of androgen-sensitive metastatic, recurrent, or progressive prostate cancer: 2006 update of an American Society of Clinical Oncology practice guideline. J Clin Oncol. 2007 Apr 20;25(12):1596-605. Epub 2007 Apr 2.

Thompson I, Thrasher JB, Aus G, Burnett AL, Canby-Hagino ED, et al. Guideline for the management of clinically localized prostate cancer: 2007update. J Urol. 2007 Jun;177(6):2106-31.

Thompson IM, Tangen CM, Paradelo J, Lucia MS, Miller G, Troyer D, et al. Adjuvant radiotherapy for pathologically advanced prostate cancer: a randomized clinical trial. JAMA. 2006 Nov 15;296(19):2329-35.

Walter LC, Bertenthal D, Lindquist K, Konety BR. PSA screening among elderly men with limited life expectancies. JAMA. 2006 Nov 15;296(19):2336-42.

Yeager M, Orr N, Hayes RB, Jacobs KB, Kraft P, Wacholder S, et al. Genome-wide association study of prostate cancer identifies a second risk locus at 8q24. Nat Genet. 2007 May;39(5):645-9. Epub 2007 Apr 1.

Review Date:
6/27/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.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.

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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.

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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

Diabetes diet

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

In This Report

Highlights
Introduction
General Dietary Guidelines...
Major Food Components
Weight Control for Type 2 D...
Heart-Healthy Diets
Diabetic Exchange Lists
Exercise
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Lifestyle Changes Essential for People at Risk for Diabetes

Lifestyle interventions that include weight loss, dietary changes, and increased physical activity can definitely help prevent or delay the progression to diabetes among at-risk people, suggest several recent studies. Weight loss through diet and exercise is especially important for overweight people with pre-diabetes.

Grain Fiber Important for Diabetes Prevention

Eating whole-grain, fiber-rich, cereal foods may help reduce the risk of developing type 2 diabetes, indicates a 2007 study in the Archives of Internal Medicine. In the study, people who consumed the most fiber from grains and cereals had a 33% lower risk of developing diabetes than people with the lowest fiber intakes. The study also found an association between high magnesium intake and reduced diabetes risk. Although fruits and vegetables also contain fiber, they did not appear to affect diabetes risk.

Low-Fat Dairy Products

Incorporating low-fat dairy products (such as yogurt and milk) into a healthy diet may help reduce diabetes risk for women, suggests a study in Diabetes Care.

Beware of Internet Dietary Supplement Scams

In 2006, the FDA alerted consumers not to be misled by dietary supplements advertised on the Internet as treatments or cures for diabetes. These products have not been scientifically studied or approved.

Low-Glycemic Index Diets

Food low on the glycemic index -- such as whole grains, fruits, lentils, and soybeans -- can help promote weight loss and heart health. Illustrating the complexity of this area, a 2006 study in the New England Journal of Medicine indicated that a low-carb, low-glycemic index diet was beneficial while another study in the Archives of Internal Medicine suggested advantages for a high-carb, low-glycemic index diet.

Low-Fat Vegan Diets

A low-fat diet that excludes meat and dairy products may help improve glycemic control and increase insulin sensitivity, suggests a Diabetes Care study. Researchers think that the high fiber content of these diets, in addition to their reduced fat, may be a factor.

Introduction

The two major forms of diabetes are type 1, previously called insulin-dependent diabetes mellitus (IDDM) or juvenile-onset diabetes, and type 2, previously called non-insulin-dependent diabetes mellitus (NIDDM) or maturity-onset diabetes. [See In-Depth Report #9: Diabetes - type 1 and In-Depth Report #60: Diabetes - type 2.]

Both type 1 and type 2 diabetes share one central feature: elevated blood sugar (glucose) levels due to absolute or relative insufficiencies of insulin, a hormone produced by the pancreas. Insulin is a key regulator of the body's metabolism. It normally works in the following way:

During and immediately after a meal the process of digestion breaks carbohydrates down into sugar molecules (of which glucose is one) and proteins into amino acids.
Right after the meal, glucose and amino acids are absorbed directly into the bloodstream, and blood glucose levels rise sharply. (Glucose levels after a meal are called postprandial levels.)
The rise in blood glucose levels signals important cells in the pancreas, called beta cells, to secrete insulin, which pours into the bloodstream. Within 10 minutes after a meal insulin rises to its peak level.
Insulin then enables glucose and amino acids to enter cells in the body, particularly muscle and liver cells. Here, insulin and other hormones direct whether these nutrients will be burned for energy or stored for future use. (The brain and nervous system are not dependent on insulin; they regulate their glucose needs through other mechanisms.)
When insulin levels are high, the liver stops producing glucose and stores it in other forms until the body needs it again.
As blood glucose levels reach their peak, the pancreas reduces the production of insulin.
About 2 - 4 hours after a meal both blood glucose and insulin are at low levels, with insulin being slightly higher. The blood glucose levels are then referred to as fasting blood glucose concentrations.

Click the icon to see an image of the liver.

In type 1 diabetes, the disease process is more severe than with type 2, and onset usually begins in childhood:

Beta cells in the pancreas that produce insulin are gradually destroyed. Eventually insulin deficiency is absolute.
Without insulin to move glucose into cells, blood glucose levels become excessively high, a condition known as hyperglycemia.
Because the body cannot utilize the sugar, it spills over into the urine and is lost.
Weakness, weight loss, and excessive hunger and thirst are among the consequences of this "starvation in the midst of plenty."

Click the icon to see an image of the pancreas.

Patients with type 1 diabetes need to take insulin. Dietary control in type 1 diabetes is very important and focuses on balancing food intake with insulin intake and energy expenditure from physical exertion. [See In-Depth Report #9: Diabetes - type 1.]

Type 2 diabetes is the most common form of diabetes, accounting for up to 95% of all diabetes cases. About 20 million Americans have type 2 diabetes, and half are unaware they have it. The disease mechanisms in type 2 diabetes are not wholly known, but some experts suggest that the disease may involve the following three stages in most patients:

The first stage in type 2 diabetes is the condition called insulin resistance. Although insulin can attach normally to receptors on liver and muscle cells, certain mechanisms prevent insulin from moving glucose (blood sugar) into these cells where it can be used. Most patients with type 2 diabetes produce variable, even normal or high, amounts of insulin, and in the beginning this amount is usually sufficient to overcome such resistance. Patients whose blood glucose levels are higher than normal, but not yet high enough to be classified as diabetes, are considered to have “pre-diabetes.” It is very important that people with pre-diabetes control their weight to stop or delay the progression to diabetes.
Over time, the pancreas becomes unable to produce enough insulin to overcome resistance. In type 2 diabetes, the initial effect of this stage is usually an abnormal rise in blood sugar right after a meal (called postprandial hyperglycemia). This effect is now believed to be particularly damaging to the body.
Eventually, the cycle of elevated glucose further impairs and possibly destroys beta cells, thereby stopping insulin production completely and causing full-blown diabetes. This is made evident by fasting hyperglycemia, in which elevated glucose levels are present most of the time.

Obesity is common in patients with type 2 diabetes and this condition appears to be related to insulin resistance. The primary dietary goal for overweight type 2 patients is weight loss and maintenance. Studies indicate that when people with type 2 diabetes maintain intensive exercise and diet modification programs, many can minimize or even avoid medications. Weight loss medications or bariatric surgery may be appropriate for some patients. [See In-Depth Report #60: Diabetes - type 2 and In-Depth Report #53: Weight control and diet.]

General Dietary Guidelines

For people who have pre-diabetes, or who are at high risk of developing type 2 diabetes, lifestyle changes of diet and exercise are extremely important. Several studies have shown that lifestyle interventions are very effective in preventing or postponing the progression to diabetes. These interventions are especially important for overweight people -- even moderate weight loss can help reduce diabetes risk.

The American Diabetes Association recommends that people at high risk for type 2 diabetes eat high-fiber (14g fiber for every 1,000 calories) and whole-grain foods. A 2007 study in the Archives of Internal Medicine also suggested that high intake of fiber and magnesium, especially from whole grain cereals and breads, can help reduce type 2 diabetes risk.

For people who have diabetes, the treatment goals for a diabetes diet are:

Achieve near normal blood glucose levels. People with type 1 diabetes and people with type 2 diabetes who are taking insulin or oral medication must coordinate calorie intake with medication or insulin administration, exercise, and other variables to control blood glucose levels. New forms of insulin are now allowing more flexibility in timing meals.
Protect the heart and aim for healthy lipid (cholesterol and triglyceride) levels and control of blood pressure.
Achieve reasonable weight. Overweight patients with type 2 diabetes who are not taking medication should aim for a diet that controls both weight and glucose. A reasonable weight is usually defined as what is achievable and sustainable, rather than one that is culturally defined as desirable or ideal. Children, pregnant women, and people recovering from illness should be sure to maintain adequate calories for health.
Manage or prevent complications of diabetes. People with diabetes, whether type 1 or 2, are at risk for a number of medical complications, including heart and kidney disease. Dietary requirements for diabetes must take these disorders into consideration.
Promote overall health.

Overall Guidelines. Overall Guidelines. There is no such thing as a single diabetes diet. Patients should meet with a professional dietitian to plan an individualized diet within the general guidelines that takes into consideration their own health needs.

For example, a patient with type 2 diabetes who is overweight and insulin-resistant may need to have a different carbohydrate-protein balance than a thin patient with type 1 diabetes in danger of kidney disease. Because regulating diabetes is an individual situation, everyone with this condition should get help from a dietary professional in selecting the best method.

Healthy eating habits along with good control of blood glucose are the basic goals in managing this complex disease, and several good dietary methods are available to meet them. General dietary guidelines for diabetes recommend:

Carbohydrates should provide 45 - 65% of total daily calories. The type and amount of carbohydrate are both important. Best choices are vegetables, fruits, beans, and whole grains. These foods are also high in fiber. Patients with diabetes should monitor their carbohydrate intake either through carbohydrate counting or meal planning exchange lists.
Fats should provide 25 - 35% of daily calories. Monounsaturated (olive, peanut, canola oils; avocados; nuts) and omega-3 polyunsaturated (fish, flaxseed oil, walnuts) fats are the best types. Limit saturated fat (red meat, butter) to less than 7% of daily calories. Choose nonfat or low-fat dairy instead of whole milk products. Limit trans-fats (hydrogenated fat found in snack foods, fried foods, commercially baked goods) to less than 1% of total calories.
Protein should provide 12 - 20% of daily calories, although this may vary depending on a patient’s individual health requirements. Patients with kidney disease should limit protein intake to less than 10% of calories. Fish, soy, and poultry are better protein choices than red meat.
Lose weight if body mass index (BMI) is 25 - 29 (overweight) or higher (obese).

Several different dietary methods are available for controlling blood sugar in type 1 and insulin-dependent type 2 diabetes:

Diabetic Exchange Lists (for maintaining a proper balance of carbohydrates, fats, and proteins throughout the day)
Carbohydrate Counting (for tracking the number of grams of carbohydrates consumed each day)
Glycemic index (for tracking which carbohydrate foods increase blood sugar)

Tests for Glucose Levels. Both low blood sugar (hypoglycemia) and high blood sugar (hyperglycemia) are of concern for patients who take insulin. It is important, therefore, to monitor blood glucose levels carefully. Patients should aim for the following measurements:

Pre-meal glucose levels of 90 - 130 mg/dL
Bedtime levels of 110 - 150 mg/dL

In general, patients who are tightly controlling glucose levels need to take readings four or more times a day. Blood glucose levels are generally more stable in type 2 diabetes than in type 1, so experts usually recommend that these patients measure blood levels only once or twice a day. Different goals may be required for specific individuals, including pregnant women, very old and very young people, and those with accompanying serious medical conditions.

Tests for Glycosylated Hemoglobin. Another test examines blood levels glycosylated hemoglobin, also known as hemoglobin A1c (HbA1c). Measuring glycosylated hemoglobin is useful for determining the severity of diabetes. The test is not affected by food intake so it can be taken at any time. A home test has been developed that may make it easier to measure HbA1c. In general, measurements suggest the following:

Normal HbA1c levels should be below 7%
Levels of 11 - 12% glycolated hemoglobin indicate poor control of carbohydrates. High levels are also markers for kidney trouble.

Other Tests. Other tests are needed periodically to determine potential complications of diabetes, such as high blood pressure, unhealthy cholesterol levels, and kidney problems. Such tests may also indicate whether current diet plans are helping the patient and whether changes should be made. Annual urine tests showing even microscopic traces of a protein known as albumin can indicate a future risk for serious kidney disease.

For prevention of long-term complications of diabetes, experts now recommend that all patients with diabetes aim at keeping blood levels as close to normal as possible. Such intensive insulin treatment can increase the risk of hypoglycemia, which occurs when blood sugar is extremely low (below 60 mg/dL). The following tips may help avoid hypoglycemia or prepare for attacks.

Patients are at highest risk for hypoglycemia at night. Bedtime snacks may be helpful.
Patients who intensively control their blood sugar should monitor blood levels as often as possible, four times or more per day. This is particularly important for patients with hypoglycemia unawareness.
In adults, it is also particularly critical to monitor blood glucose levels before driving, when hypoglycemia can be very hazardous.
Patients on therapies that put them at risk for hypoglycemia should always carry hard candy, juice, sugar packets, or commercially available glucose substitutes designed for individuals with diabetes.

Food Labels. Every year thousands of new foods are introduced, many of them advertised as nutritionally beneficial. It is important for everyone, most especially people with diabetes, to be able to differentiate advertised claims from truth. The current food labels show the number of calories from fat, the amount of nutrients that are potentially dangerous (fat, cholesterol, sodium, sugars) as well as useful nutrients (fiber, carbohydrates, protein, vitamins).

Labels also show "daily values," the percentage of a daily diet that each of the important nutrients offers in a single serving. Unfortunately, the daily value is based on 2,000 calories, generally much higher than most patients with diabetes should have, and the serving sizes may not be equivalent to those on the Exchange Lists. Most people will need to recalculate the grams and calories listed on food labels to fit their own serving sizes and calorie needs.

Weighing and Measuring. Weighing and measuring food is extremely important in order to get the correct number of daily calories.

Along with measuring cups and spoons, choose a food scale that measures grams. (A gram is very small, about 1/28th of an ounce.)
Food should be weighed and measured after cooking.
After measuring all foods for a week or so, most people can make fairly accurate estimates by eye or by holding food without having to measure everything every time they eat.

Timing. Meals should not be skipped, particularly for those who are on insulin. Skipping meals can upset the balance between food intake and insulin and also can lead to weight gain if the patient eats extra food too often to offset low blood sugar levels.

The timing of meals is particularly important for people taking insulin:

Patients should coordinate insulin administration with calorie intake. In general, they should eat three meals each day at regular intervals. Snacks are often required.
They should try to take an insulin injection 30 minutes before they eat, although this timing could vary, depending on the form. Some experts recommend a fast acting insulin (insulin lispro) at each meal and a longer (basal) insulin at night.

Diabetes can lead to kidney disease and failure. People with early-stage kidney failure need to follow a special diet that slows the build-up of wastes in the bloodstream. The diet restricts protein, potassium, phosphorus, and salt intake. Fat and carbohydrate intake may need to be increased to help maintain weight and muscle tissue.

People who have late-stage kidney disease usually need dialysis. Once patients are on dialysis, they must have more protein in their diet. Patients must still be very careful about restricting salt, potassium, phosphorus, and fluids. Patients on peritoneal dialysis may have fewer restrictions on salt, potassium, and phosphorus than those on hemodialysis.

Major Food Components

Compared to fats and protein, carbohydrates have the greatest impact on blood sugar. Both the amount and type of carbohydrate affect blood glucose. Carbohydrate types are either complex (as in starches) or simple (as in fruits and sugars). One gram of carbohydrates equals four calories. The current general recommendation is that carbohydrates should provide between 40 - 65% of the daily caloric intake. Carbohydrate intake should not fall below 130 grams/day. Most experts do not recommend low-carb diets for diabetes management or weight control.

Vegetables, fruits, whole grains, and beans are good sources of carbohydrates. Whole grain foods provide more nutritional value than pasta, white bread, and white potatoes. Brown rice is a better choice than white rice. Patients should try to consume a minimum of 20 - 35 grams of fiber daily (ideally 50 grams/day), from vegetables, fruits, whole grain cereals, breads, nuts and seeds.

Complex Carbohydrates. Complex carbohydrates found in whole grains and vegetables are preferred over carbohydrates found in starch-heavy foods, such as pastas, white-flour products, and potatoes. Most of these are high in fiber, which is important for health. Whole-grains specifically are extremely important for people with diabetes or at risk for it. [For specific benefits, see Box Whole Grains, Nuts, and Fiber-Rich Foods and Table Some Examples of Healthy Foods.]

Simple Carbohydrates (Sugar). Sugars are generally one of two types:

Sucrose (table sugar). Sucrose has been associated with higher triglycerides and harmful cholesterol levels. A 2002 study suggested that a high level of sugar consumption may also reduce levels of HDL cholesterol, the so-called good cholesterol.
Fructose (sugar found in fruits). Fructose may produce a slower increase in blood sugar than sucrose, which may have some advantages for people with diabetes. Dark-colored fruits are rich in important vitamins and other nutrients, and studies continue to report their benefits for the heart and health in general. Other fruits, such as apples and grapes also have important beneficial food chemicals.

Sugar itself, either as sucrose or fructose, adds calories, increases blood glucose levels quickly, and provides no other nutrients. High levels of sugar consumption -- both fructose and sucrose -- have been associated with higher triglycerides and lower levels of HDL cholesterol, the so-called good cholesterol. The high consumption of sugar is most likely one of the factor in the current obesity epidemic. Soda, other sweetened beverages, and fruit juice in fact may be singled out as major contributors to childhood obesity.

People with diabetes should avoid products listing more than 5 grams of sugar per serving, and some doctors recommend limiting fruit intake. If specific amounts are not listed, patients should avoid products with either sucrose or fructose listed as one of the first four ingredients on the label. [See Box Fat Substitutes and Artificial Sweeteners.]

Of increasing interest to researchers is possible harm from sugar from advanced glycation end-products (called AGEs). These are end-products of the chemical reaction between sugar and protein. This reaction occurs most intensively when cooking at high temperatures -- particularly animal fats. (Steaming or cooking food in water does not produce these chemicals. Low, slow cooking also produces fewer AGEs.) AGEs can also be formed by chemical reactions in the body itself. They may promote factors in the inflammatory response that cause a number of diseases or their complications, including diabetes and other serious conditions (Alzheimer's, atherosclerosis, cataracts, and osteoporosis).

The Carbohydrate Counting System. Some people plan their carbohydrate intake using a system called carbohydrate counting. It is based on two premises:

All carbohydrates (either from sugar or starch) will raise blood sugar to a similar degree. In general, 1 gram of carbohydrates raises blood sugar by 3 points in people who weigh 200 pounds, 4 points for people who weigh 150 pounds, and 5 points for 100 pounds.
Carbohydrates have the greatest impact on blood sugar; fats and protein play only minor roles.

In other words, the amount of carbohydrates eaten (rather than fats or proteins) will determine how high blood sugar levels will rise. There are two options for counting carbohydrates: advanced and simple. Both rely on collaboration with a doctor, dietitian, or both. Once the patient learns how to count carbohydrates and adjust insulin doses to their meals, many find it more flexible, more accurate in predicting blood sugar increases, and easier to plan meals than other systems.

The basic goal is to balance insulin with the amount of carbohydrates eaten in order to control blood glucose levels after a meal. The steps to the plan are as follows:

The patient must first carefully record a number of factors that are used to determine the specific requirements for a meal plan based on carbohydrate grams:

Multiple blood glucose readings (taken several times a day)
The time of meals
Amount in grams of all the carbohydrates eaten
Time, type, and duration of exercise
The time, type, and dose of insulin or oral medications
Other relevant factors, such as menstruation, illness, and stress

The patient works with the dietitian for two or three 45 - 90 minute sessions to plan how many grams of carbohydrates are needed. There are three carbohydrate groups:

Bread/starch
Fruit
Milk

One serving from each group should contain 12 - 15 carbohydrate grams. (Patients can find the amount of carbohydrates in foods from labels on commercial foods and from a number of books and web sites.)

The dietitian creates a meal plan that accommodates the patient's weight and needs, as determined by the patient's record, and makes a special calculation called the carbohydrate to insulin ratio. This ratio determines the number of carbohydrate grams that a patient needs to cover the daily pre-meal insulin needs.

Eventually, patients can learn to precisely adjust their insulin doses to their meals.

Patients who choose this approach must still be aware of protein and fat content in foods. These food groups may add excessive calories and saturated fats. Patients must still follow basic healthy dietary principles.

The Glycemic Index. The glycemic index helps determine which carbohydrate-containing foods raise blood glucose levels more or less quickly after a meal. The index uses a scale of numbers for specific foods that reflect greatest to least delay in producing an increase in blood sugar after a meal. The lower the index number, the better the impact on glucose levels. Some evidence suggests that the benefit of foods with a low glycemic index is due to their ability to increase insulin levels quickly and so remove blood sugar rather than their ability to slow the release of blood sugar itself.

There are currently two indices in use. One uses a scale of 1 - 100 with 100 representing a glucose tablet, which has the most rapid effect on blood sugar [See Table The Glycemic Index of Some Foods]. The other common index uses a scale with 100 representing white bread (so some foods will be above 100).

A major 2003 analysis suggested that choosing foods with a low glycemic index scores may have a small but significant effect on controlling the surge in blood sugar after meals. Many of these foods are also high in fiber and so have heart benefits as well. Substituting low- for high-glycemic index foods may also help prevent weight gain.

One easy way to improve glycemic index is to simply replace starches and sugars with whole grains and legumes (dried peas, beans, and lentils). However, there are many factors that affect the glycemic index of foods, and maintaining a diet with low glycemic load is not straightforward. The following are some considerations:

The numbers attributed to each carbohydrate-rich food cannot be added to equal a certain number. In other words, adding All Bran cereal (index of 49) to a banana (index of 61) does not equal 110.
Adding certain fats to a food (for example butter to potato) can slow down the food's impact on blood sugar. One study reported that when patients ate fatty foods first, their blood glucose levels were significantly lower an hour after the meal than when carbohydrates were eaten first.
Adding foods with organic acids (pickles, yogurt) to meals may reduce the impact of foods with high glycemic scores on blood sugar. (It should be noted that yogurt alone, however, has the same high glycemic index as regular milk.)

No one should use the glycemic index as a complete dietary guide, since it does not provide nutritional guidelines for all foods. It is simply an indication of how the metabolism will respond to certain carbohydrates. Some experts believe it is too complicated to be practical and that simply tracking carbohydrates, eating healthily, and maintaining a healthy weight is sufficient. Nevertheless, a study on children with type 1 diabetes suggested that the glycemic index offered as many choices as the exchange diet, and they did not report feeling any greater limitations. [For additional information on low-glycemic index diets, see "Heart-Healthy Diets" section of this report.]

Fiber is an important component of many complex carbohydrates. It is almost always found only in plants, (particularly vegetables), fruits, whole grains, nuts, and legumes (dried beans, peanuts, and peas). (One exception is chitosan, a dietary fiber made from shellfish skeletons.) Fiber cannot be digested but passes through the intestines, drawing water with it and is eliminated as part of feces content. The following are specific advantages from high-fiber diets (up to 55 grams a day):

Insoluble fiber (found in wheat bran, whole grains, seeds, nuts, legumes, and fruit and vegetable peels) may help achieve weight loss. Consuming whole grains on a regular basis appears to provide many important benefits, especially for people with type 2 diabetes. Whole grains may even lower the risk for type 2 diabetes in the first place. Of special note, nuts, such as almonds, macadamia, and walnuts may be highly heart protective, independent of their fiber content. However, nuts are high in calories.
Soluble fiber (found in dried beans, oat bran, barley, apples, citrus fruits, and potatoes) has important benefits for the heart, particularly for achieving healthy cholesterol levels and possibly reducing blood pressure as well. Evidence on the heart benefits of beans continues to grow. For example, a 2001 study indicated that eating beans four or more times a week reduced the risk for heart disease by 22%.
Soluble fiber supplements, such as those that contain psyllium or glucomannan, may be beneficial. Psyllium is taken from the husk of a seed grown in India. It is found in laxatives (Metamucil), breakfast cereals (Bran Buds), and other products. In a 2002 study, patients with type 2 diabetes who consumed psyllium (Plantaben) for breakfast for 11 weeks experienced lower total and LDL cholesterol levels. There was no difference in glucose or HbA1c levels. Psyllium can increase sodium so people who increase their levels of soluble fiber should also increase water and fluid intake.

Replacing fats and sugars with substitutes may help many people who have trouble maintaining weight. In one 2003 study, people with type 2 diabetes used the artificial sweetener sucralose and a beta-glucan fat replacer (derived from oats) as part of a low-calorie diet. At the end of 4 weeks, they achieved better weight, glucose control, and HDL levels than those on a standard diabetic diet.

Fat Substitutes. Fat substitutes added to commercial foods or used in baking, deliver some of the desirable qualities of fat, but do not add as many calories. It should be stressed that eliminating all fats from your diet can be harmful to general health. Some fat substitutes include:

Stanols. Stanols are plant compounds used in margarines (Benecol, Take Control). Benecol is derived from pine bark and Take Control from soybeans. Two servings a day of either brand as part of a low-fat diet can lower LDL and total cholesterol by impairing its absorption in the intestinal tract. Some studies have reported that their use can allow lower doses of statins (cholesterol -lowering drugs). These products do not appear to block absorption of fat-soluble nutrients or vitamins, as olestra does. They can be hydrogenated, however, and can contain some trans-fatty acids.
Olestra (Olean) passes through the body without leaving behind any calories from fat. Studies suggest that it improves cholesterol levels and helps people lose weight when it is used to replace a third of normal dietary fats. (Simply adding snacks containing olestra do not appear to have any effect on cholesterol or weight loss.) However, it can cause cramping and diarrhea. Of greater concern is the fact that even small amounts of olestra deplete the body of certain vitamins and nutrients that may help protect against serious diseases, including cancer. The FDA requires that the missing vitamins be added back to olestra products, but not other nutrients. The adverse health effects, if any, are unknown.
Beta-glucan is a soluble fiber found in oats and barley. Products using this substance (Nu-Trim) may reduce cholesterol and have additional health benefits.

A number of other fat-replacers are also available. Although studies to date do not show any significant adverse health effects, their effect on weight control is uncertain, since many of the products containing them may be high in sugar.

Artificial Sweeteners. Many artificial or low-calories sweeteners are available. A 2002 study confirmed that people who consumed artificial sweeteners in beverages and foods and reduced their sugar intake weighed less over time than those who ate similar types and amounts of drinks and food containing sugar. However, using these artificial sweeteners should not give dieters a license to increase their fat intake. Studies indicate that consuming some sugar is not a significant contributor to weight gain as long as the total caloric intake is under control. There is some public concern about chemicals used to produce many of these sweeteners and adverse effects in studies using rats. Natural low-calorie sweeteners that may be more acceptable to many people are also available. Low-calorie sweeteners include:

Saccharin (Sugar Twin, Sweet n’Low, Sucaryl, and Featherweight). Saccharin has been used for years but is not used as commonly now. Some studies found that large amounts of saccharin caused bladder cancer in rats. Although the rats were fed huge amounts that do not apply to human diets, some evidence suggests that people who have six or more servings of saccharin per day may have an increased risk.
Aspartame (Nutra-Sweet, Equal, NutraTase). Aspartame has come under scrutiny because of rare reports of neurologic disorders, including headaches or dizziness, associated with its use. People with phenylketonuria (PKU), a rare genetic condition, should not use it. Studies have not reported any serious health dangers, but some people may be sensitive to it.
Sucralose (Splenda). Sucralose has no bitter aftertaste and works well in baking, unlike other artificial sweeteners. It is made from real sugar by replacing hydroxyl atoms with chlorine atoms. Some people are concerned because chlorinated molecules used in major industrial chemicals have been associated with cancer and birth defects. Over 100 studies have been conducted on sucralose over a 20-year period with no reports of such risks.
Acesulfame-potassium (Sweet One, SwissSweet, Sunette). It has been used in the US since 1988 with no reported adverse effects.
Neotame (Neotame). Neotame is a synthetic variation of aspartame but was developed to avoid its side effects. The association with aspartame has raised some concerns. Studies to date have reported no effects that would cause alarm, and it appears to be safe for general consumption.
D-tagatose (Tagatose). This reduced calorie sweetener is a novel low-calorie sweetener derived from lactose, which is found in dairy products and other foods. It may be specifically beneficial for people with type 2 diabetes and have additional benefits that aid the intestinal tract.
Alitame (Aclame) is formed from amino acids. It has the potential to be used in all products that contain sugar, including baked goods.
Stevioside (Stevia). This is a natural sweetener derived from a South American plant. It is available in health food stores. People with diabetes should avoid alcohol-based forms. It has not been rigorously tested.

Other artificial sweeteners being investigated include, glycyrrhizin (derived from licorice), and dihycrochalcones (derived from citrus fruits).


Based on 100 = a Glucose Tablet
BREADS
pumpernickel	49
sour dough	54
rye	64
white	69
whole wheat	72
GRAINS
barley	22
sweet corn	58
brown rice	66
white rice	72
BEANS
soy	14
red lentils	27
kidney (dried and boiled, not canned)	29
chickpeas	36
baked	43
DAIRY PRODUCTS
milk	30
ice cream	60
CEREALS
oatmeal	53
All Bran	54
Swiss Muesli	60
Shredded Wheat	70
Corn Flakes	83
Puffed Rice	90
PASTA
spaghetti-protein enriched	28
spaghetti (boiled 5 minutes)	33
spaghetti (boiled 15 minutes)	44
FRUIT
strawberries	32
apple	38
orange	43
orange juice	49
banana	61
POTATOES
sweet	50
yams	54
new	58
mashed	72
instant mashed	86
white	87
SNACKS
potato chips	56
oatmeal cookies	57
corn chips	72
SUGARS
fructose	22
refined sugar	64
honey	91
Note. These numbers are general values, but may vary widely depending on other factors, including if and how they are cooked and foods they are combined with.

Protein intake in diabetes is complicated. Protein recommendations vary among experts and depend on various factors. These factors include whether a patient has type 1, type 2, or pre-diabetes. There are additional guidelines for patients who show signs of kidney damage (nephropathy).

In general, diabetes dietary guidelines recommend that proteins should provide 12 - 20% of total daily calories. This daily amount poses no risk to the kidney in people who do not have kidney disease. Protein is important for strong muscles and bone. Some experts recommend a higher proportion of protein (20 - 30%) for patients with pre- or type 2 diabetes. They think that eating more protein helps people feel more full and thus reduces overall calories. In addition, protein consumption helps the body maintain lean body mass during weight loss.

Because protein causes the kidneys to work harder, patients with diabetic nephropathy need to limit their intake of protein. A typical protein-restricted diet limits protein intake to no more than 10% of total daily calories. Patients with kidney damage also need to limit their intake of phosphorus, a mineral found in dairy products, beans, and nuts. (However, patients on dialysis need to have more protein in their diets.) Potassium and phosphorus restriction is often necessary as well.

One gram of protein contains 4 calories. Protein is commonly recommended as part of a bedtime snack to maintain normal blood sugar levels during the night, although studies are mixed over whether it adds any protective benefits against nighttime hypoglycemia. If it does, only small amounts (14 grams) may be needed to stabilize blood glucose levels.

Good sources of protein include fish, skinless chicken or turkey, nonfat or low-fat dairy products, soy (tofu), and legumes (kidney beans, black beans, chick peas, lentils).

Fish. Fish is probably the best source of protein. Evidence suggests that eating moderate amounts of fish (twice a week) may improve triglycerides and help lower the risks for death from heart disease, dangerous heart rhythms, blood pressure, a tendency for blood clots, and the risk for stroke.

The most healthy fish are oily fish such as salmon, mackerel, or sardines, which are high in omega-3 fatty acids. Three capsules of fish oil (preferably as supplements of DHA-EPA) is about equivalent to eating one serving of fish.

Some studies have reported a higher incidence of heart attack in men who ate fish daily. Such findings may be due to mercury toxicity, which has harmful effects on the heart. High mercury content has been observed in swordfish and shark and, to some extent, in tuna, trout, pike, tilapia, and bass.

Fish oil supplements may also have some adverse effects on LDL levels and glucose control in type 2 diabetes. More research is needed to further define the risk and benefits of fish, but at this time most guidelines recommend eating fish two or three times a week.

Soy. Soy is an excellent food. It is rich in both soluble and insoluble fiber, omega-3 fatty acids, and provides all essential proteins. Soy proteins have more vitamins and minerals than meat or dairy proteins. They also contain polyunsaturated fats, which are better than the saturated fat found in meat. The best sources of soy protein are soy products (tofu, soy milk, soybeans). Soy sauce is not a good source. It contains only a trace amount of soy and is very high in sodium.

For many years, soy was promoted as a food that could help lower cholesterol and improve heart disease risk factors. But an important 2006 American Heart Association (AHA) review of studies found that soy protein and isoflavone supplement pills do not really have any effects on cholesterol or heart disease prevention. The AHA still encourages patients to include soy foods as part of an overall heart healthy diet, but does not recommend using isoflavone supplements.

Meat and Poultry. Lean cuts of meat are the best choice for heart health and diabetes control. Saturated fat in meat is the primary danger to the heart. The fat content of meat varies depending on the type and cut. For patients with diabetes, experts recommend choosing skinless chicken or turkey over red meat. (Fish is an even better choice.) A large, long-term 2006 study found that high heme iron intake from red meat increases the risk of developing type 2 diabetes in women. Another 2006 study suggested that replacing red meat with chicken improves kidney function and lipid levels in patients with diabetic nephropathy.

Dairy Products. A 2002 study reported that a high intake of dairy products can lower risk factors related to type 2 diabetes and heart disease (insulin resistance, high blood pressure, obesity, and unhealthy cholesterol). Some researchers suggest the calcium in dairy products may be partially responsible for these benefits. However, because many dairy products are high in saturated fats and calories, doctors recommend that patients choose low-fat and nonfat dairy items. Other studies have indicated that increasing the amount of low-fat diary products in a daily diet may help reduce type 2 diabetes risk, particularly for women.

Some fat is essential for normal body function. Fats can have good or bad effects on health, depending on their chemistry. New research suggests that the type of fat is more important than the total amount of fat when it comes to reducing heart disease.

Current dietary guidelines for diabetes and heart health recommend that total fat be 25 - 35% of total daily calories. Monounsaturated fats (olive oil, canola oil, peanut oil, nuts, avocados) and omega-3 polyunsaturated fats (fish, flaxseed, walnuts) should be the first choice for fats. Omega-6 polyunsaturated fats (corn oil, safflower, oil, sunflower oil, soybean oil) are the second choice. Limit saturated fat to less than 7% of total daily calories. Limit trans-fats (margarine, commercial baked goods, snack and fried foods) to less than 1% of total calories.

All fats, good or bad, are high in calories compared to proteins and carbohydrates. In order to calculate daily fat intake, multiply the number of fat grams eaten by nine (1 fat gram is equal to 9 calories, whether it's oil or fat) and divide by the number of total daily calories desired. One teaspoon of oil, butter, or other fats equals about 5 grams of fat. All fats, no matter what the source, add the same calories. The American Heart Association recommends that fats and oils have less than 2 grams of saturated fat per tablespoon.

Try to replace saturated fats and trans fatty acids with unsaturated fats from plant and fish oils. Omega-3 fatty acids, which are found in fish and plant sources, are a good source of unsaturated fats. Generally, two servings of fish per week provide a healthful amount of omega-3 fatty acids.

The Chemistry of Fats and Cholesterol.

Fatty Acids. All fats and oils found in foods are made up of chains of molecules called fatty acids. There are three major chains: saturated fatty acid (found mostly in animal products) and two unsaturated fatty acids -- monounsaturated and polyunsaturated fatty acids (found in plant products). The oils and fats that people and animals eat are nearly always mixtures of these three chains, but one type of fatty acid usually predominates in specific oils or fats.
Essential Fatty Acids. In addition, there are three chemical subgroups of polyunsaturated fatty acids called essential fatty acids: omega-3 and omega-6 polyunsaturated fatty acids, and omega-9 monounsaturated fatty acids.
Trans Fatty Acids. To complicate matters, there are also trans-fatty acids, which are not natural but are manufactured by adding hydrogen atoms to polyunsaturated fatty acids (called hydrogenation).

Harmful Fats. Reducing consumption of saturated fats and trans-fatty acids is the first essential step in managing cholesterol levels through diet.

Saturated Fats. Saturated fats are found predominantly in animal products, including meat and dairy products. They are strongly associated with higher cholesterol levels, and they may be even more dangerous in women than in men. High-fat meals are associated with sudden surges in triglyceride levels and other lipids along with impaired blood flow in the arteries to the heart. (Tropical oils such as palm, coconut, and cocoa butter are also high in saturated fats.)
Trans Fatty Acids. Trans fatty acids are manufactured fats created during a process called hydrogenation, which is aimed at stabilizing polyunsaturated oils to prevent them from becoming rancid and to keep them solid at room temperature. They are particularly dangerous for the heart and may pose a risk for certain cancers. These partially hydrogenated fats are even worse than saturated fats. Studies report that high consumption of these fats reduces HDL and raises LDL cholesterol levels, has harmful effects on the linings of the arteries, and may increase the risk for type 2 diabetes. Hydrogenated fats are used in stick margarine and in many fast foods and baked goods, including most commercially produced white breads. (Liquid margarine is not hydrogenated and is recommended.) The FDA ordered that food labels list the amount of trans fatty acids in food products beginning in January 2006.

Beneficial Fats and Oils. Some fat is essential for health, and fat is essential for healthy development in children. Public attention has mainly focused on the possible benefits or hazards of monounsaturated (MUFA) and polyunsaturated (PUFA) fats.

Polyunsaturated fats are found in safflower, sunflower, corn, and cottonseed oils and fish.
Monounsaturated fats are mostly present in olive, canola, and peanut oils and in most nuts. (Canola is the least saturated of all the fats.) Studies report that replacing carbohydrates with monounsaturated fats improves glucose control after meals and reduces triglycerides in people with type 2 diabetes. Oils are more calorie-dense, however, and such patients should be wary of weight gain.

Researchers are most interested in the smaller fatty-acid building blocks contained in both oils, which may have more specific effects on lipids. Three important fatty acids are the essential fatty acids omega-3, omega-6, and omega-9.

Omega-3 fatty acids are found in fish oil (docosahexaenoic and eicosapentaneoic acids) and plants (alpha-linolenic acid).

Docosahexaenoic (DHA) and Eicosapentaneoic (EPA) Acids. DHA and EPA are found in fish oils, and evidence suggests that they have significant benefits for the heart, including reducing sudden death from heart disease, inflammation, blood clotting factors, blood pressure, and improving triglyceride and HDL levels. Results from a study presented at the 2005 meeting of the American Heart Association suggested that daily EPA supplements plus statin therapy can protect against heart attack, angina, and coronary artery disease. However, although fish and fish oil are good for the heart, patients who have an implantable defibrillator should not take fish oil supplements.

Alpha-linolenic Acid. Alpha-linolenic acid is a plant precursor of DHA, which means the body can convert it to DHA. Sources include canola oil, soybeans, flaxseed, and certain nuts and seeds (walnut, flax, chia and sometimes pumpkin seed). Some, but not all, studies suggest that oils or foods containing these oils may also be heart-protective. Supplements or foods containing these oils may also protest the heart. For example studies have reported heart protection from flaxseed supplements and also from nuts, such as almonds, macadamia, and walnuts. Nuts are high in calories, however.

Omega-6 polyunsaturated fatty acids are found in corn, safflower, soybean, and sunflower oil. PUFA oils containing omega-6 fatty acids constitute most of the oils consumed in the US. Some omega-6 fatty acids are important for health. However, high intake of these fats may be associated with weight gain in the abdomen (the so-called apple shape), a risk factor for heart disease. High consumption is also associated with a higher risk for certain cancer and some chronic diseases.

Omega-9 monounsaturated fatty acids are contained in canola and olive oil, which help protect the heart.

Research suggests that a healthy balance of all these fats may be important and that our current Western diet contains an unhealthy ratio of omega-6 to omega-3 fatty acids (10 to 1). Omega-9 fatty acids may also contain chemicals that block harmful factors found in omega-6 fatty acids. Researchers suggest that the most benefits may be found in mixture of all three fatty acids found in both poly- and monounsaturated oils, but in modest amounts that do not add too many calories.

Fat Substitutes. Fat substitutes added to commercial foods or used in baking, deliver some of the desirable qualities of fat, but do not add as many calories. [See Box Fat Substitutes and Artificial Sweeteners.]

The story on cholesterol found in the diet is not entirely straightforward. The body produces cholesterol naturally or obtains it through meals. Animal-based food products contain cholesterol. High amounts occur in meat, dairy products, egg yolks, and shellfish. (Plant foods, such as fruits, nuts, grains, do not contain cholesterol.) The American Heart Association recommends no more than 300 mg of dietary cholesterol per day for the general population and no more than 200 mg daily for those with high cholesterol.

Antioxidant Vitamins. Vitamins C and E are most studied for their health effects because they serve as antioxidants. Antioxidants are chemicals that act as scavengers of particles known as oxygen-free radicals (also sometimes called oxidants). High intake of foods rich in these vitamins (as well as other food chemicals) have been associated with many health benefits, including prevention of heart problems.

Research on the effects of vitamin supplements on heart disease and diabetes, however, has been mixed. Although some research initially observed favorable effects from vitamin E in preventing blood clots and build-up of plaque on blood vessel walls, most studies found no heart protection from either vitamin E or C supplements. A 2005 Journal of the American Medical Association study found that vitamin E supplements can actually increase the risk of heart failure, especially for patients with diabetes or vascular diseases. In addition, vitamin E had no effect on preventing cancer or heart disease.

Because of the lack of scientific evidence for benefit, the American Diabetes Association does not recommend regular use of vitamin supplements, except for people who have vitamin deficiencies. Researchers, however, are still studying the treatment possibilities of antioxidants. A 2006 study suggested that alpha-lipoic acid, another type of antioxidant, may have promise as a treatment for diabetic peripheral neuropathy, the nerve damage condition that is a common complication of diabetes.

B Vitamins and Folic Acid. Deficiencies in the B vitamins folate (known also as folic acid), B6, and B12 have been associated with a higher risk for heart disease in some studies. Such deficiencies produce higher blood levels of homocysteine, an amino acid that has been associated with a higher risk for heart disease, stroke, and heart failure.

Researchers have been studying whether vitamin B supplements can reduce homocysteine levels and, consequently, heart disease risks. Several major 2006 studies indicated that while B vitamin supplements help lower homocysteine levels, they have no effect on heart disease. The studies, published in the New England Journal of Medicine, examined patients who had either recently had a heart attack or who suffered from diabetes or heart disease. Results showed a similar number of heart attacks and strokes among patients who took folic acid, B6, and B12 vitamins and those who received placebo. Some experts think that homocysteine may be a marker for heart disease rather than a cause of it.

Niacin (vitamin B3) is used for lowering unhealthy cholesterol levels. Although vitamin B3 is available over the counter, it can have significant side effects. A doctor should prescribe niacin in order to ensure its safety and effectiveness.

Patients with type 2 diabetes who take metformin (Glucophage) should be aware that this drug can interfere with vitamin B12 absorption. Calcium supplements may help counteract metformin-associated vitamin B12 deficiency.

Most experts recommend salt restriction in people who have high blood pressure. Some people, however, are much more sensitive to harmful effects from salt than others:

People at Risk for Salt-Sensitivity. About half of people with hypertension have blood pressure that reacts significantly to salt. Such people are known as salt-sensitive. Among those at highest risk for salt sensitivity are African Americans, people with diabetes, and elderly people.
Overweight People. Overweight individuals may absorb and retain sodium differently from people with normal weights. One study reported that high sodium intake was associated with an increased risk of heart disease and all-cause mortality in overweight, but not in normal weight, people. Reducing sodium can also help reduce the risk of stroke in people who are overweight.

Simply eliminating table and cooking salt can be beneficial. Salt substitutes, such as Cardia, (containing mixtures of potassium, sodium, and magnesium) are available, but they are expensive. About 75% of the salt in the typical American diet comes from processed or commercial foods, not from food cooked at home, so the benefits of table-salt substitutes are likely to be very modest. Some sodium is essential to protect the heart, but most experts agree that the amount is significantly less than that found in the average American diet. If people cannot significantly reduce the amount of salt in their diets, adding potassium-rich foods might help to restore a healthy balance.

Calcium. Calcium supplements may be important in older patients with diabetes to help reduce the risk for osteoporosis, particularly if their diets are low in dairy products.

Potassium. Evidence strongly indicates that a potassium-rich diet can help achieve healthy blood pressure levels, and that potassium supplements can lower systolic blood pressure by 1.8 m Hg and diastolic blood pressure by 1 mm Hg. In fact, there is some evidence that a potassium-rich diet can reduce the risk of stroke by 22 - 40%. Current guidelines support the use of potassium supplements or enough dietary potassium to achieve 3,500 mg per day for people with normal or high blood pressure (who have no risk factors for excess potassium levels). This goal is particularly important in people who have high sodium intake. The best source of potassium is from the fruits and vegetables that contain them. Potassium-rich foods include bananas, oranges, pears, prunes, cantaloupes, tomatoes, dried peas and beans, nuts, potatoes, and avocados.

However, patients with diabetic nephropathy (kidney disease) and kidney failure need to restrict dietary potassium, as well as phosphorus. Kidney problems can cause potassium overload and medications commonly used in diabetes, (such as ACE inhibitors or potassium-sparing diuretics), also limit the kidney's ability to excrete potassium. No one should take potassium supplements without consulting a doctor. The best source of potassium is from the fruits and vegetables that contain them.

Magnesium. Magnesium deficiency may have some role in insulin resistance and high blood pressure. Research indicates that magnesium-rich diets may help lower type 2 diabetes risk. Whole grain breads and cereals, nuts (almonds, cashews, soybeans), and certain fruits and vegetables (spinach, avocados, beans) are excellent dietary sources of magnesium. Dietary supplements do not provide any benefit. Persons who live in soft water areas, who use diuretics, or who have other risk factors for magnesium deficiency may require more dietary magnesium than others.

Chromium. Some studies have reported an association between deficiencies in the mineral chromium and a higher risk for type 2 diabetes. Studies on fat rats that were given chromium reported improvement in insulin sensitivity and glucose metabolism. Most studies on type 2 patients, however, reported little or no effect on glucose metabolism and some even reported adverse side effects.

Selenium. Selenium, a trace mineral, does not reduce diabetes risk. In fact, it may increase it. In a 2007 study, researchers found that people who took selenium supplements had more than 1.5 times the risk of developing type 2 diabetes as those who did not take the supplements. The higher the blood level of selenium, the greater the risk. An average healthy diet supplies adequate amounts of selenium and there is no need to take dietary supplements.

Zinc. Many patients with type 2 diabetes are also deficient in zinc; more studies are needed to establish the benefits or risks of taking supplements. Zinc has some toxic side effects, and some studies have associated high zinc intake with prostate cancer.

Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been a number of reported cases of serious and even lethal side effects from herbal products. Patients should always check with their doctors before using any herbal remedies or dietary supplements.

Traditional herbal remedies for diabetes include bitter melon, fenugreek, and Gymnema sylvestre. These herbs may have properties that help lower blood sugar. However, there have been few well-designed studies and there is not enough evidence to recommend them for prevention or treatment of diabetes.

Several recent preliminary studies suggest that cinnamon may help improve blood sugar and lipid levels. One small study found beneficial effects for people with type 2 diabetes who took between 1 - 6 grams (equivalent to 0.25 - 1.25 teaspoons) of cinnamon each day.

Various fraudulent products are often sold on the Internet as “cures” or treatments for diabetes. These dietary supplements have not been studied or approved. In 2006, the FDA and Federal Trade Commission (FTC) launched a crackdown on these scams. The FDA and FTC warn patients with diabetes not to be duped by bogus and unproven remedies.

Water. Many heart risk factors, especially those associated with blood clotting, are elevated with dehydration. In one study, drinking five or more glasses of water a day was significantly associated with a lower risk for fatal heart events than drinking two or fewer glasses a day.

Alcohol. A number of studies have found that light to moderate intake of alcohol may provide protection from heart disease and type 2 diabetes. Some research suggests that alcohol has anti-inflammatory properties that protect arteries from injury. Red wine in particular may have specific benefits for people with type 2 diabetes. It has strong antioxidant effects that benefit the heart. Some evidence also suggests that red wine may improve insulin sensitivity and reduce blood glucose levels and may even protect against type 2 diabetes. The American Diabetes Association recommends limiting alcoholic beverages to 1 drink per day for non-pregnant adult women and 2 drinks per day for adult men.

Tea. Although it contains caffeine, tea, both black and green, is often cited for its health benefits. Green tea is especially is rich in chemicals that offer protection against damaging forms of LDL. In one study, for example, higher intake, particularly by women, was associated with a lower risk for severe coronary artery disease. Black tea has also been associated with heart health. In one study oolong tea, a partially fermented tea, was specifically associated with lower blood sugar levels in patients with type 2 diabetes.

Coffee. Many studies have noted an association between coffee consumption and reduced risk for developing type 2 diabetes. A 2006 study of 29,000 postmenopausal women confirmed this reduced risk. Compared to non-coffee drinkers, women who drank at least 6 cups a day of coffee (either regular or decaf) were 22% less likely to develop type 2 diabetes. Decaffeinated coffee was even more beneficial -- women who drank at least 6 cups a day of decaf were 33% less likely to develop diabetes than women who did not drink coffee. Researchers are still not certain how coffee protects against diabetes. Neither the caffeine in coffee nor the mineral magnesium have a preventive effect. It may be that coffee contains antioxidant properties that protect the pancreas’ insulin-producing cells.

Weight Control for Type 2 Diabetes

The American Diabetes Association recommends that patients aim for a small but consistent weight loss of ½ - 1 pound per week. Most patients should follow a diet that supplies at least 1,000 - 1,200 kcal/day for women and 1,200 - 1,600 kcal/day for men.

Even modest weight loss can reduce the risk factors for heart disease and diabetes. There are many approaches to dieting and many claims for great success with various fad diets. They include calorie restriction, low-fat/high-fiber, or high protein and fat/low carbohydrates. Some evidence suggests that people may respond differently to specific diets depending on whether their weight is overly distributed around the abdomen.

Lifelong changes in eating habits, physical activity, and attitudes about food and weight are essential to weight management. Unfortunately, although many people can lose weight initially, it is very difficult to maintain weight loss. People with type 2 diabetes may have a particularly difficult time. Here are some general suggestions that may be helpful:

Start with realistic goals. When overweight people achieve even modest weight loss they reduce risk factors in the heart. Ideally, overweight patients should strive for 7% weight loss or better, particularly people with type 2 diabetes.
A regular exercise program is essential for maintaining weight loss. If there are no health prohibitions, choose one that is enjoyable. Check with a doctor about any health consideration. [See In-Depth Report #29: Exercise.]
Hunger pangs should not be taken as cues to eat. A stomach that has been stretched by large meals will continue to signal hunger for large amounts of food until its size reduces over time with smaller meals.
Be honest about how much you eat, and track calories carefully. Studies on weight control that depend on self-reporting of food intake frequently reveal that subjects badly misjudge how much they eat (typically underestimating high-calorie foods and overestimating low-calorie foods). In one study, even dietitians underreported their calorie intake by 10%. People who do not carefully note everything they eat tend to take in excessive calories when they believe they are dieting.
For patients who cannot lose weight with diet alone, effective weight-loss medications are now available, including orlistat (Xenical) and sibutramine (Meridia). Orlistat may have particular benefits for patients with type 2 diabetes. This drug may delay or even prevent the onset or progression of diabetes. It may also improve cholesterol levels, regardless of weight loss. A non-prescription form of orlistat, Alli, is now available. Sibutramine is also helpful in weight loss but should not be used by patients with high blood pressure or kidney or liver problems.
Once a person has lost weight, maintenance is required. To maintain a healthy weight, make careful decisions about how many calories you consume in food and how many calories you expend through physical activity. Such thinking will eventually become automatic.
A procedure known as bariatric surgery has been very helpful in producing rapid weight loss and improving insulin and glucose levels in people with diabetes.

Even repeated weight loss failure is no reason to give up. [See In-Depth Report #53: Weight control and diet.]

Calorie restriction has been the cornerstone of obesity treatment. Restricting calories in such cases also appears to have beneficial effects on cholesterol levels, including reducing LDL and triglycerides and increasing HDL levels.

The standard dietary recommendations for losing weight are:

As a rough rule of thumb, 1 pound of fat equals about 3,500 calories, so one could lose a pound a week by reducing daily caloric intake by about 500 calories a day. Naturally, the more severe the daily calorie restriction, the faster the weight loss. Very-low calorie diets have also been associated with better success, but extreme diets can have some serious health consequences.
To determine the daily calorie requirements for specific individuals, multiply the number of pounds of ideal weight by 12 - 15 calories. The number of calories per pound depends on gender, age, and activity levels. For instance a 50-year-old moderately active woman who wants to maintain a weight of 135 pounds and is mildly active might need only 12 calories per pound (1,620 calories a day). A 25-year old female athlete who wants to maintain the same weight might need 25 calories per pound (2,025 calories a day).
Fat intake should be no more than 30% of total calories. Most fats should be in the form of monounsaturated fats (such as olive oil). Avoid saturated fats (found in animal products).

Heart-Healthy Diets

In 2006, the American Heart Association (AHA) issued revised diet and lifestyle recommendations. The current guidelines recommend:

Balance calorie intake and physical activity to achieve or maintain a healthy body weight. (Controlling weight, quitting smoking, and exercising regularly are essential companions of any diet program. Try to get at least 30 minutes, and preferably 60 - 90 minutes, of daily exercise.)
Consume a diet rich in a variety of vegetables and fruits. Vegetables and fruits that are deeply colored (spinach, carrots, peaches, berries) are especially recommended as they have the highest micronutrient content.
Choose whole-grain, high-fiber foods. These include fruits, vegetables, and legumes (beans). Good whole grain choices include whole wheat, oats/oatmeal, rye, barley, brown rice, buckwheat, bulgur, millet, and quinoa.
Consume fish, especially oily fish, at least twice a week (about 8 ounces/week). Oily fish -- such as salmon, mackerel, and sardines -- are rich in the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Consumption of these fatty acids is linked to reduced risk of sudden death and death from coronary artery disease.
Limit daily intake of saturated fat (found mostly in animal products) to less than 7% of total calories, trans fat (found in hydrogenated fats, commercially baked products, and many fast foods) to less than 1% of total calories, and cholesterol (found in eggs, dairy products, meat, poultry, fish, shellfish) to less than 300 mg per day. Choose lean meats and vegetable alternatives (such as soy). Select fat-free and low-fat dairy products. Grill, bake, or broil fish, meat, and skinless poultry.
Use little or no salt in your foods. Reducing salt can lower blood pressure and decrease the risk of heart disease and heart failure.
Limit beverages and foods that contain added sugars (corn syrups, sucrose, glucose, fructose, maltrose, dextrose, concentrated fruit juice, honey).
If you consume alcohol, do so in moderation. The AHA recommends limiting alcohol to no more than 2 drinks per day for men and 1 drink per day for women.

[See In-Depth Report #43: Heart-healthy diet.]

Dietary guidelines from the National Cholesterol Education Program recommend:

Choose five or more servings of fresh fruits and vegetables and six or more servings of whole grains and legumes. Soluble fiber is preferred (from cereal grains, beans, peas, legumes, and many fruits and vegetables).
Fats can be up to 35% of daily calories, but no more than 7% should be from saturated fat. (People with high triglycerides or low HDL or both may need a higher fat intake.) Choose fats containing unsaturated fatty acids (from vegetables, fish, legumes, and nuts). Choose margarines containing sterols or stanols (such as Benecol or Take Control). Avoid trans fatty acids found in commercial products.
Protein choices should be fat-free and low-fat milk products, fish, legumes, skinless poultry, and lean meats.
Limit cholesterol intake to less than 200 mg per day.
Maintain healthy body weight and a healthy level of physical fitness.

The Mediterranean diet is rich in heart-healthy fiber and nutrients, including omega-3 fatty acids and antioxidants. The diet consists of fruits, vegetables, and unsaturated "good" fats, particularly olive oil. Olive oil has been associated with lower blood pressure, a lower risk for heart disease, and other benefits for people with type 2 diabetes.

There are several variations to the Mediterranean diet, but general recommendations include:

Limit red meats.
Drink one or two glasses of wine each day if alcohol is enjoyable and there are no reasons to restrict its use.
Limit dairy products.
Eat moderate amounts of fish and poultry. Fish is the diet's main protein source. Some studies suggest that fish is the primary heart-protective ingredient in this diet.
Eat plenty of fresh fruits and vegetables, nuts, legumes, beans, and whole grains.
Season foods with garlic, onions, and herbs.
Use virgin olive oil.

Low-carb diets, such as South Beach, The Zone, and Sugar Busters, rely on a concept called the "glycemic index (GI)," which ranks foods by how fast and how high they cause blood sugar levels to rise. Foods on the lowest end of the index take longer to digest. Slow digestion wards off hunger pains. It also helps stabilize insulin levels. Foods high on the glycemic index include white bread, white potatoes, and pasta while low-glycemic foods include whole grains, fruit, lentils, and soybeans.

A 2006 study indicated that a high-protein, low-glycemic index diet can help produce better reductions in total and LDL cholesterol than a high-protein, high-glycemic index diet. Reducing glycemic load may also help to promote weight loss, especially for women. However, another 2006 study suggested that low-glycemic index diets that are high in carbohydrates can also promote weight loss and reduce body fat.

A 2006 review of low-carbohydrate diets found that they did help weight loss in the short term. However, while these diets appeared to lower triglyceride levels and raise HDL (“good”) cholesterol levels, they also raised overall and LDL (“bad”) cholesterol levels. A 2007 Journal of the American Medical Association study that compared four different diet plans (Atkins, Zone, Ornish, and LEARN) found that the Atkins diet helped raise HDL levels, and reduce triglyciderides, but had no effect on LDL levels nor insulin or glucose measurements. Women who followed the Atkins diet also had improved blood pressure compared to patients on the other diets. The Atkins diet resulted in slightly better weight loss (an average of 10 pounds over the course of a year versus 4 - 6 pounds for the other diet plans), which in itself may have accounted for the improved heart risk factors. Some experts think that the main finding from this study is that even a moderate weight loss can help improve heart health.

Although low-carbohydrate diets may produce good short-term weight loss, they do not appear to help patients maintain weight loss in the long term. The American Diabetes Association does not recommend low-carb diets (less than 130 g of carbohydrates per day) for treatment of overweight and obesity.

Dietary guidelines recommend keeping total fat intake to 25 - 35% of total daily calories, with saturated fat less than 7% of calories. Low-fat diets generally restrict fat intake to 20% or less of total daily calories. The Ornish program, which is recommended for some heart disease patients, limits fats even more drastically. It aims at reducing saturated fats as much as possible, restricting total fat to 10%, and increasing carbohydrates to 75% of calories.

In 2006, the largest study to date on low-fat diets found that they did not help prevent heart disease or cancer. Women in the study reduced their fat consumption to 24 - 29% of total daily calories. Some critics say that the study did not do enough to distinguish between good types of fats (monounsaturated and omega-3 polyunsaturated) and bad fats (saturated and trans fats).

Another 2006 study indicated that low-fat, vegan diets may help improve glycemic control and increase insulin sensitivity. The higher fiber content of these diets, plus lower intake of total and saturated fat, may account for some of these benefits. A vegan diet eliminates all meat and dairy products.

The DASH diet (Dietary Approaches to Stop Hypertension) is proven to help lower blood pressure. Results are sometimes seen within a few weeks. Restricting sodium improves results. The diet appears to have antioxidant effects and may help lower LDL cholesterol levels, although beneficial HDL levels also decline. This diet is not only rich in important nutrients and fiber but also includes foods that contain far more electrolytes, potassium (4,700 mg/day), calcium (1,250 mg/day), and magnesium (500 mg/day) than are found in the average American diet.

The DASH diet recommends:

Limit salt intake to no more than 2,300 mg a day (a maximum intake of 1,500 mg a day is an even better goal).
Reduce saturated fat to no more than 6% of daily calories and total fat to 27% of daily calories. (But, include dairy products that are non- or low-fat. Low-fat dairy products appear to be especially beneficial for lowering systolic blood pressure.)
When choosing fats, select monounsaturated oils, such as olive or canola oils.
Choose whole grains over white flour or pasta products.
Choose fresh fruits and vegetables every day. In one study people who increased their intake of fruits and vegetables experienced a drop in blood pressure after 6 months. Many of these foods are rich in potassium, fiber, or both, which may help lower blood pressure.
Include nuts, seeds, or legumes (dried beans or peas) daily.
Choose modest amounts of protein (no more than 18% of total daily calories). Fish, skinless poultry, and soy products are the best protein sources.
Other daily nutrient goals in the DASH diet include limiting carbohydrates to 55% of daily calories and dietary cholesterol to 150 mg. Patients should try to get at least 30 g of daily fiber.

Slight changes to the DASH diet might help lower blood pressure even more, as well as improve cholesterol and lipid levels. Researchers reporting in the Journal of the American Medical Association and at the 2005 American Heart Association meeting said that replacing some carbohydrates in the DASH diet with more protein or monounsaturated fats may help reduce heart disease risk factors. [See In-Depth Report #14: High blood pressure.]

Diabetic Exchange Lists

The objective of using diabetic exchange lists is to maintain the proper balance of carbohydrates, proteins, and fats throughout the day. Patients should meet with a dietician or diabetes nutrition expert for help in learning this approach.

In developing a menu, patients must first establish their individual dietary requirements, particularly the optimal number of daily calories and the proportion of carbohydrates, fats, and protein. The exchange lists should then be used to set up menus for each day that fulfill these requirements.

The following are some general rules:

The diabetic exchanges are six different lists of foods grouped according to similar calorie, carbohydrate, protein, and fat content; these are starch/bread, meat, vegetables, fruit, milk, and fat. A person is allowed a certain number of exchange choices from each food list per day.
The amount and type of these exchanges are based on a number of factors, including the daily exercise program, timing of insulin injections, and whether or not an individual needs to lose weight or reduce cholesterol or blood pressure levels.
Foods can be substituted for each other within an exchange list but not between lists even if they have the same calorie count.
In all lists (except in the fruit list) choices can be doubled or tripled to supply a serving of certain foods. (For example 3 starch choices equal 1.5 cups of hot cereal or 3 meat choices equal a 3-ounce hamburger.)
On the exchange lists, some foods are "free." These contain less than 20 calories per serving and can be eaten in any amount spread throughout the day unless a serving size is specified.

The following are the categories on exchange lists:

Starches and Bread. Each exchange under starches and bread contains about 15 grams of carbohydrates, 3 grams of protein, and a trace of fat for a total of 80 calories. A general rule is that a half-cup of cooked cereal, grain, or pasta equals one exchange. One ounce of a bread product is 1 serving.

Meat and Cheese. The exchange groups for meat and cheese are categorized by lean meat and low-fat substitutes, medium-fat meat and substitutes, and high-fat meat and substitutes. Use high-fat exchanges a maximum of 3 times a week. Fat should be removed before cooking. Exchange sizes on the meat list are generally 1 ounce and based on cooked meats (3 ounces of cooked meat equals 4 ounces of raw meat).

Vegetables. Exchanges for vegetables are 1/2 cup cooked, 1 cup raw, and 1/2 cup juice. Each group contains 5 grams of carbohydrates, 2 grams of protein, and 2 - 3 grams of fiber. Vegetables can be fresh or frozen; canned vegetables are less desirable because they are often high in sodium. They should be steamed or cooked in a microwave without added fat.

Fruits and Sugar. Sugars are included within the total carbohydrate count in the exchange lists. Sugars should not be more than 10% of daily carbohydrates. Each exchange contains about 15 grams of carbohydrates for a total of 60 calories.

Milk and Substitutes. The milk and substitutes list is categorized by fat content similar to the meat list. A milk exchange is usually 1 cup or 8 ounces. Those who are on weight-loss or low-cholesterol diets shoudl follow the skim and very low-fat milk lists -- while avoiding the whole milk group. Others should use the whole milk list very sparingly. All people with diabetes should avoid artificially sweetened milks.

Fats. A fat exchange is usually 1 teaspoon, but it may vary. People, of course, should avoid saturated and trans fatty acids and choose polyunsaturated or monounsaturated fats instead.


Calories	1,200	1,500	1,800	2,000	2,200
Starch/Bread	5	8	10	11	13
Meat	4	5	7	8	8
Vegetable	2	3	3	4	4
Fruit	3	3	3	3	3
Milk	2	2	2	2	2
Fat	3	3	3	4	5

Exercise

Sedentary habits, especially watching TV, are associated with significantly higher risks for obesity and type 2 diabetes. Regular exercise, even of moderate intensity (such as brisk walking), improves insulin sensitivity and may play a significant role in preventing type 2 diabetes -- regardless of weight loss. An important study reported a 58% lower risk for type 2 diabetes in adults who performed moderate exercise for as little as 2.5 hours a week.

Aerobic Exercises. Aerobic exercise has significant and particular benefits for people with diabetes. Regular aerobic exercise, even of moderate intensity, improves insulin sensitivity. People with diabetes are at particular risk for heart disease, so the heart-protective effects of aerobic exercise are especially important. Moderate exercise protects the heart in people with type 2 diabetes, even if they have no risk factors for heart disease other than diabetes itself. (In general, patients with diabetes should aim for a heart rate target of 55 - 85% of their maximum heart rate when exercising.)

Strength Training. Strength training, which increases muscle and reduces fat, may also be helpful for people with diabetes.

Some Precautions for People with Diabetes Who Exercise. The following are precautions for all people with diabetes, both type 1 and type 2:

Because people with diabetes are at higher than average risk for heart disease, they should always check with their doctors before undertaking vigorous exercise. For fastest results, frequent high-intensity (not high-impact) exercises are best for people who are cleared by their doctors. For people who have been sedentary or have other medical problems, lower-intensity exercises are recommended.
Strenuous strength training or high-impact exercise is not recommended for people with uncontrolled diabetes. Such exercises can strain weakened blood vessels in the eyes of patients with retinopathy. High-impact exercise may also injure blood vessels in the feet.

Patients who are taking medications that lower blood glucose, particularly insulin, should take special precautions before embarking on a workout program:

Monitor glucose levels before, during, and after workouts (glucose levels swing dramatically during exercise).
Avoid exercise if glucose levels are above 300 mg/dl or under 100 mg/dl.
Inject insulin in sites away from the muscles used during exercise; this can help avoid hypoglycemia.
Drink plenty of fluids before and during exercise; avoid alcohol, which increases the risk of hypoglycemia.
Insulin-dependent athletes may need to decrease insulin doses or take in more carbohydrates prior to exercise, but may need to take an extra dose of insulin after exercise (stress hormones released during exercise may increase blood glucose levels).
Wear good, protective footwear to help avoid injuries and wounds to the feet.

Some blood pressure drugs can interfere with exercise capacity. Patients who use blood pressure medication should consult their doctors on how to balance medications and exercise. Patients with high blood pressure should also aim to breathe as normally as possible during exercise. Holding the breath can increase blood pressure. [See In-Depth Report #29: Exercise.]

Chronic stress has been associated with the development of insulin resistance, a primary factor in diabetes. Stress can also worsen existing diabetes by impairing the patient's ability to manage the disease effectively. Stress-relieving techniques include meditation, biofeedback, relaxation response, and yoga. One study reported that yoga helped patients with type 2 diabetes reduce their need for oral medications. Studies have also indicated that yoga and Tai Chi (an ancient Chinese exercise involving slow relaxing movements) may lower blood pressure almost as well as moderate-intensity aerobic exercises. [See In-Depth Report #31: Stress.]

Resources

www.diabetes.org -- American Diabetes Association
www.niddk.nih.gov -- National Institute of Diabetes and Digestive and Kidney Diseases
www.jdrf.org -- Juvenile Diabetes Research Foundation
www.kidney.org -- National Kidney Foundation
www.joslin.org -- Joslin Diabetes Center
www.eatright.org -- American Dietetic Association
www.nal.usda.gov/fnic -- Food and Nutrition Information Center
www.gourmetconnection.com/diabetic -- Diabetic Gourmet Magazine

References

American Diabetes Association. Nutrition recommendations and interventions for diabetes: A position statement of the American Diabetes Association. Diabetes Care. 2007 Jan;30 Suppl 1:S48-65.

American Heart Association Nutrition Committee; Lichtenstein AH, Appel LJ, Brands M, Carnethon M, Daniels S, et al. Diet and lifestyle recommendations revision 2006: a scientific statement from the American Heart Association Nutrition Committee. Circulation. 2006 Jul 4;114(1):82-96. Epub 2006 Jun 19.

Barnard ND, Cohen J, Jenkins DJ, Turner-McGrievy G, Gloede L, Jaster B, et al. A low-fat vegan diet improves glycemic control and cardiovascular risk factors in a randomized clinical trial in individuals with type 2 diabetes. Diabetes Care. 2006 Aug;29(:1777-83.

Gardner CD, Kiazand A, Alhassan S, Kim S, Stafford RS, Balise RR, et al. Comparison of the Atkins, Zone, Ornish, and LEARN diets for change in weight and related risk factors among overweight premenopausal women: the A TO Z Weight Loss Study: a randomized trial. JAMA. 2007 Mar 7;297(9):969-77.

Gillies CL, Abrams KR, Lambert PC, Cooper NJ, Sutton AJ, Hsu RT, et al. Pharmacological and lifestyle interventions to prevent or delay type 2 diabetes in people with impaired glucose tolerance: systematic review and meta-analysis. BMJ. 2007 Feb 10;334(7588):299. Epub 2007 Jan 19.

Halton TL, Willett WC, Liu S, Manson JE, Albert CM, Rexrode K, et al. Low-carbohydrate-diet score and the risk of coronary heart disease in women. N Engl J Med. 2006 Nov 9;355(19):1991-2002.

Lindstrom J, Ilanne-Parikka P, Peltonen M, Aunola S, Eriksson JG, Hemio K, et al. Sustained reduction in the incidence of type 2 diabetes by lifestyle intervention: follow-up of the Finnish Diabetes Prevention Study. Lancet. 2006 Nov 11;368(9548):1673-9.

Liu S, Choi HK, Ford E, Song Y, Klevak A, Buring JE, et al. A prospective study of dairy intake and the risk of type 2 diabetes in women. Diabetes Care. 2006 Jul;29(7):1579-84.

McMillan-Price J, Petocz P, Atkinson F, O'Neill K, Samman S, Steinbeck K, et al. Comparison of 4 diets of varying glycemic load on weight loss and cardiovascular risk reduction in overweight and obese young adults: a randomized controlled trial. Arch Intern Med. 2006 Jul 24;166(14):1466-75.

Schulze MB, Schulz M, Heidemann C, Schienkiewitz A, Hoffmann K, Boeing H. Fiber and magnesium intake and incidence of type 2 diabetes: a prospective study and meta-analysis. Arch Intern Med. 2007 May 14;167(9):956-65.

Stranges S, Marshall JR, Natarajan R, Donahue RP, Trevisan M, Combs GF, et al. Effects of long-term selenium supplementation on the incidence of type 2 diabetes: a randomized trial. Ann Intern Med. 2007 Jul 9; [Epub ahead of print]

Ting RZ, Szeto CC, Chan MH, Ma KK, Chow KM. Risk factors of vitamin B(12) deficiency in patients receiving metformin. Arch Intern Med. 2006 Oct 9;166(18):1975-9.

Ziegler D, Ametov A, Barinov A, Dyck PJ, Gurieva I, Low PA, et al. Oral treatment with alpha-lipoic acid improves symptomatic diabetic polyneuropathy: the SYDNEY 2 trial. Diabetes Care. 2006 Nov;29(11):2365-70.

Review Date:
7/20/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Breast cancer

FitSugar — Wed, 08 Oct 2008 17:34:59 -0700

In This Report

Highlights
Introduction
Risk Factors
Prevention and Lifestyle Fa...
Symptoms
Diagnosis
Prognosis
Treatment
Surgery
Radiation
Medications
Chemotherapy
Hormone Therapy
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approvals

In September 2007, Evista (raloxifene) was approved for prevention of breast cancer in postmenopausal women with osteoporosis, and postmenopausal women at high risk for invasive breast cancer. Raloxifene and tamoxifen are the only two drugs approved for breast cancer prevention in high-risk women.
In March 2007, lapatinib (Tykerb) was approved in combination with capecitabine (Xeloda) for treatment of advanced HER2-positive breast cancer.
In November 2006, trastuzumab (Herceptin) was approved for treatment of early-stage HER2-positive breast cancer. Trastuzumab is also approved for advanced HER2-positive breast cancer.

Screening

The American College of Physicians’ 2007 guidelines recommend that women with a low risk for breast cancer talk to their doctor before starting to have mammogram screening at age 40. Other associations, including the American Cancer Society, continue to recommend annual mammograms for women age 40 and older.
Women at high risk for breast cancer should have an MRI scan along with their annual mammogram, according to 2007 guidelines from the American Cancer Society.
For women who have been diagnosed with cancer in one breast, an MRI can help detect tumors in the other breast, indicates a 2007 study in the New England Journal of Medicine.

Post-Treatment Guidelines

The American Society of Clinical Oncology (ASCO)’s 2006 post-treatment guidelines recommend regular physical exams, breast self-exam, mammograms, and genetic counseling. Know how to recognize the signs of breast cancer recurrence. ASCO does not recommend blood and imaging tests for routine recurrence screening.

Hormone Replacement Therapy (HRT) and Breast Cancer Risk

Fewer women are using HRT, which may explain why new cases of breast cancer among postmenopausal women have declined, suggests a recent New England Journal of Medicine study.

Aromatase Inhibitors

Drug treatment with aromatase inhibitors is improving survival in women with hormone-sensitive advanced breast cancer, suggest recent studies. Switching from tamoxifen to an aromatase inhibitor may help improve the odds for survival.

Introduction

Breast cancers are potentially life-threatening malignancies that develop in one or both breasts. The structure of the female breast is important in understanding this cancer:

The interior of the female breast consists mostly of fatty and fibrous connective tissues.
It is divided into about 20 sections called lobes.
Each lobe is further subdivided into a collection of lobules, structures that contain small milk-producing glands.
These glands secrete milk into a complex system of tiny ducts. The ducts carry the milk through the breast and converge in a collecting chamber located just below the nipple.
Breast cancer is either noninvasive (referred to as in situ, confined to the site of origin) or invasive (spreading).

The female breast is either of two mammary glands (organs of milk secretion) on the chest.

Noninvasive breast cancers include:

Ductal carcinoma in situ (also called intraductal carcinoma or DCIS). DCIS consist of cancer cells in the lining of the duct. DCIS is a non-invasive, early cancer, but if left untreated, it may sometimes progress to an invasive, infiltrating ductal breast cancer.
Lobular carcinoma in situ, or LCIS. Although noninvasive, lobular carcinoma in situ is a marker for an increased risk of invasive cancer in both breasts. (Some experts prefer to call this condition lobular neoplasia rather than refer to it as a cancer.) According to a 2001 report, for patients with LCIS the risk for developing invasive cancer in the same breast is about 18% -- and 14% in the other breast -- after 20 years. These invasive cancers can be either lobular or ductal.

At the time of diagnosis of these early cancers (DCIS and LCIS), there is no evidence of invasion.

Invasive cancer occurs when cancer cells spread beyond the basement membrane, which covers the underlying connective tissue in the breast. This tissue is rich in blood vessels and lymphatic channels that are capable of carrying cancer cells beyond the breast. Invasive breast cancers include the following:

Infiltrating ductal carcinoma. This is invasive breast cancer that penetrates the wall of a duct. It comprises between 70 - 80% of all breast cancer cases.
Infiltrating lobular carcinoma. This invasive cancer has spread through the wall of a lobule. It accounts for 10 - 15% of all breast cancers. It may sometimes appear in both breasts, sometimes in several separate locations.

Click the icon to see an image of the breast.

There are other less common breast cancers that are not discussed in this report.

Risk Factors

About 12 - 13% of women develop breast cancer in their lifetime. Experts estimate that about 178,480 women will be newly diagnosed with invasive breast cancer in the United States in 2007. Another 2,030 men will be diagnosed with breast cancer during the year. Although breast cancer in men is rare, the incidence has been increasing, and men are diagnosed at a later stage than women. An estimated 40,460 women and 450 men will die from breast cancer in 2007. The earlier breast cancer is diagnosed, the earlier the opportunity for treatment. According to the American Cancer Society, over 2 million women who have been treated for breast cancer are alive today.

Age is a major identifiable risk factor. More than 80% of breast cancer cases occur in women over age 50, and especially in women over age 65. The odds by age are as follows:

From ages 30 - 39, a woman’s chance for being diagnosed with breast cancer is 1 in 233
Ages 40 - 49, the odds are 1 in 69
Ages 50 - 59, the odds are 1 in 38
Ages 60 - 69, the odds are 1 in 27
Ages 70 - 79, the odds are 1 in 11
After age 80, the odds are 1 in 8

Breast cancer is more prevalent among Jewish women of Eastern European (Ashkenazi) descent. Meanwhile, African-American women tend to get breast cancer at an earlier age than Caucasians. Although African-American women have lower overall rates of breast cancer, they represent the highest proportion of women who are diagnosed with the disease before age 45. Comparative studies of breast cancer rates among sub-Saharan Africans suggest a genetic component, as African women are diagnosed most frequently between ages 35 - 45.

The mortality rate in African-Americans is twice that of Caucasians, although it is declining. Social and economic factors make it less likely that African-American women will be screened, so they are more likely to be diagnosed at a later stage. They are also less likely to have access to effective treatments. However, there also appears to be a biological basis for African-American women’s poorer prognosis. According to research presented at the 2007 Breast Cancer Symposium, African-American women are more likely to have estrogen receptor-negative tumors, a type of breast cancer that is more difficult to treat.

An estimated 10% of all women with breast cancer have a very strong family history of the disease. Inherited forms of breast cancer often appear in young women under the age of 50. In such families, some members may also be at higher risk for ovarian cancer. These mutations can be inherited from either a mother or father.

Prior to menopause, a mass on the ovary that is smaller than 2 centimeters is probably a follicle cyst that will go away on its own. However, if the growth is larger and doesn't go away over the course of a few menstrual cycles, then it may need to be removed.

BRCA Genes. Inherited mutations in genes known as BRCA1 or BRCA2 are responsible for 30 - 50% of hereditary breast cancers, ovarian cancers, or both in families with a history of these cancers. According to some studies, the risk each gene carries is:

Between 25 - 35% of BRCA1 carriers develop breast cancer by age 70.
Between 35 - 50% of BRCA2 carriers develop the disease. BRCA2 genes also increase the lifetime risk of breast cancer in men.

These mutations are present in only about 0.5% of the overall population. However, certain ethnic groups -- such as Jewish women of Eastern European (Ashkenazi) descent -- have a higher prevalence (2.5%) of BRCA gene mutations. BRCA gene mutations are also seen in some African-American and Hispanic women.

Screening Guidelines for BRCA Genes. In 2005, the U.S. Preventive Services Task Force (USPSTF) released updated guidelines for BRCA testing. While women at high risk should be tested, the USPSTF does not recommend routine genetic counseling or testing for BRCA genes in low-risk women (no family history of BRCA 1 or 2 genetic mutations).

ESR Genes. Genetic variations in estrogen receptor genes (ESRs) may increase the risk for some women but offer protection to others. Mutations in the ESR1 and ESR2 genes may be associated with breast cancer susceptibility for Ashkenazi women over age 50 years.

Other Genetic Factors. Mutations in the tumor suppressor gene p53 are more common in the breast cancer tumors of African-American women than in Caucasian women. Researchers have also identified other defective genes that contribute to breast cancer, such as NOEY2 (which is inherited from the father), CHEK2, and ATM, a mutant gene for the rare disorder ataxia-telangiectasia. (The disease itself is rare, but 1% of the population carries a single copy -- enough to increase the risk for breast cancer.) Cowden's syndrome is an inherited disorder caused by a defective PTEN gene that is associated with a higher risk of breast cancer.

Not all genetic mutations are inherited. In 2007, scientists announced they had located a genetic mutation found in as many as 30 - 40% of breast cancers. The IKBKE mutation appears to occur during the course of a women’s lifetime. It causes overproduction of a kinase protein (IKK-epsilon) that fuels cell growth and tumor development. By identifying this genetic mutation, scientists hope they can develop drugs that will target and block IKK-epsilon production.

Because growth of breast tissue is highly sensitive to estrogens, the more estrogen a woman is exposed to over her lifetime, the higher her risk for breast cancer.

Duration of Estrogen Exposure. Early age at menarche (first menstrual period) or later age at menopause may slightly increase a women’s risk for breast cancer.

Pregnancy. Women who have never had children or who had their first child after age 30 may have a slightly increased breast cancer risk. Having children at an early age, and having multiple pregnancies, reduces breast cancer risk.

Although a few studies have suggested a slightly increased risk for breast cancer in women who have had abortions, the weight of evidence does not support an association between abortion and breast cancer. A large-scale 2007 study found that neither induced abortions nor spontaneous abortions (miscarriages) increases breast cancer risk. However, interrupting a pregnancy does reduce the protective features of a full-term pregnancy.

Studies have been mixed on whether breast-feeding decreases breast cancer risk. Breast-feeding reduces a woman’s total number of menstrual cycles, and thereby estrogen exposure, which may account for its possible protective effects. Some studies suggest that the longer a woman breast-feeds, the lower her risk.

Oral Contraception. Studies have been conflicting about whether estrogen in oral contraception increases the chances for breast cancer. Some studies have found no evidence that oral contraceptive use increases the risk for breast cancer, even in women who have taken birth control pills for 15 years or more or had taken them at young ages. In contrast, other studies have reported a slightly higher risk in women who are current or recent users and in women who take them for more than 4 years before a first full-term pregnancy.

Hormone Replacement Therapy. Many studies have reported a higher risk for breast cancer in postmenopausal women who take hormone replacement therapy (HRT) that contains both estrogen and progestin. A combination of estrogen and testosterone also increases breast cancer risk. A 2005 study suggested that HRT with no or low progestin is safer than standard estrogen-progestin combination therapy.

Several 2006 studies of women who had a hysterectomy indicated that estrogen alone does not increase overall breast cancer risk when the drug is used for 7 years or less. However, women who take estrogen for 10 - 15 years or more do have an increased risk, especially women who are already at higher risk for breast cancer. In addition, HRT increases breast cancer density, making mammograms more difficult to read. This can cause cancer to be diagnosed at a later stage. Women who take estrogen HRT should be aware that they need frequent mammogram screenings.

As further evidence of the association between HRT and breast cancer, a 2007 New England Journal of Medicine study noted that breast cancer rates have fallen as HRT use has declined. The decline in rates occurred among women over the age of 50 and was particularly associated with cancers that were estrogen receptor-positive. This type of cancer requires estrogen for growth. Experts think that postmenopausal women’s discontinuation of estrogen-containing HRT may explain the decrease in rates of new cases of estrogen receptor-positive cancer.

A 2007 position statement from the North American Menopause Society recommends that women who are at risk for breast cancer should avoid hormone therapy and try other options to manage menopausal symptoms such as hot flashes. At this time, most experts recommend that women use HRT only for short-term relief of menopausal symptoms. [See In-Depth Report #40: Menopause.]

Infertility and Infertility Treatments. There has been concern that infertility treatments using the drug clomiphene may increase the risk for breast cancer. A reassuring 2006 study indicated that ovulation induction with clomiphene does not increase breast cancer risk, and may actually decrease it. (Clomphine is related to tamoxifen, a drug that is used for breast cancer prevention in high-risk women.) The study also suggested that women who are infertile because of ovulatory dysfunction have a 25% lower risk for breast cancer than fertile women.

Abnormalities or Breast Conditions Suggesting a Higher Risk. Certain factors and breast conditions may increase the risk for breast cancer:

Dense breast tissue is associated with a higher risk for breast cancer. Studies suggest that women with highly dense tissue have 2 - 6 times the risk of women with the least dense tissue. Genetic factors play a large role in breast density. Hormone replacement therapy also increases breast density. In addition, dense breasts make mammograms more difficult to read, which increases the likelihood of missing early signs of cancer.
Benign proliferative breast disease, or unusual cell growth known as atypical hyperplasia, is a significant risk factor for breast cancer.

Some common benign breast abnormalities that pose few or no risks include the following:

Cysts. These mostly occur in women in their middle-to-late reproductive years and can be eliminated simply by aspirating fluid from them.

Click the icon to see an image of cysts in the breast.

Fibroadenoma. These are solid benign lumps that occur in women ages 15 - 30.
Breast abscesses during breast-feeding.

Click the icon to see an image of a breast abscess.

Nipple discharge. Discharge from the nipple is worrisome to patients, but is unlikely to be a sign of cancer. Unexplained discharge still warrants evaluation, however.

Click the icon to see an image of nipple discharge.

Mastalgia. This is breast pain that occurs in association with, or independently from, the menstrual cycle. About 8 - 10% of women experience moderate-to-severe breast pain associated with their menstrual cycle. In general, breast pain does not need assessment unless it is severe and prolonged.

The following physical characteristics have been associated with increased risk:

Obesity increases the risk for all types of estrogen receptor-positive breast cancers. Women who gain weight after menopause are most at risk. (On a positive note, losing weight after menopause decreases breast cancer risk.) In postmenopausal women, estrogen is produced in fat tissue. High amounts of fatty tissue increase levels of estrogen in the body, leading to faster growth of estrogen-sensitive cancers.
Estrogen is involved in building bone mass. Therefore, women with heavy, dense bones are likely to have higher estrogen levels and to be at greater risk for breast cancer.
Some studies have found a greater risk for breast cancer in taller women, possibly due to the higher estrogen levels associated with greater bone growth. In one study, regardless of their actual height, women who reached their full height at age 13 or younger had a higher risk than those who attained maximum height at age 18, reflecting higher estrogen levels at an earlier age.

Exposure to Estrogen-like Industrial Chemicals. Chemicals with estrogen-like effects, called xenoestrogens, have been under suspicion for years. There has been particular concern with pesticides containing organochlorines (DDT and its metabolites, such as dieldrin) and pyrethroids (permethrin), but at this time evidence of any causal association is very weak.

Exposure to Diethylstilbestrol. Women who took diethylstilbestrol (DES) to prevent miscarriage have a slightly increased risk for breast cancer. Recent studies also suggest a slightly increased risk for their daughters (commonly called "DES daughters"), who were exposed to the drug when their mothers took it during pregnancy.

Radiation Exposure. Heavy exposure to radiation is a significant risk factor for breast cancer. Girls who received high-dose radiation therapy face an increased risk for breast cancer in adulthood. Low-dose radiation exposure before age 20 may increase the risk for women with BRCA genetic mutations.

Researchers theorize that viruses may be involved in some types of breast cancers. A study of breast cancer samples taken from Tunisian women in North Africa found similarities with a virus known to cause breast cancer in mice. The samples were compared with those taken from women living in other global regions. The researchers suggested that a human breast cancer virus may be more prevalent in specific parts of the world.

Prevention and Lifestyle Factors

Evidence indicates that regular exercise, particularly vigorous exercise, may offer some modest protection against breast cancer. Exercise can help reduce body fat, which in turn lowers levels of cancer-promoting hormones such as estrogen. In fact, a 2006 study suggested that physical activity may help women reduce the risk for developing estrogen receptor-positive tumors.

Exercise can also help women who have been diagnosed with breast cancer. Studies indicate that both aerobic and weight training exercises benefit the body and the mind, and improve quality of life for breast cancer survivors. Even moderate exercise can help improve survival. A 2005 study in the Journal of the American Medical Association reported survival benefits for women diagnosed with breast cancer who walked 3 – 5 hours per week at an average pace. The American Cancer Society recommends engaging in 45 - 60 minutes of physical activity at least 5 days a week. A recent study indicated that diet and exercise can reduce the risk of breast cancer recurrence.

Physical activity contributes to health by reducing the heart rate, decreasing the risk for cardiovascular disease, and reducing the amount of bone loss that is associated with age and osteoporosis. Physical activity also helps the body use calories more efficiently, thereby helping in weight loss and maintenance. It can increase basal metabolic rate, reduces appetite, and helps in the reduction of body fat.

Despite much research on the association between diet and breast cancer, there is still little consensus. The best advice is to eat a well-balanced diet and avoid focusing on one "cancer-fighting" food. The American Cancer Society’s dietary guidelines for cancer prevention recommend that people:

Choose foods and amounts that promote a healthy weight.
Eat 5 or more servings of fruits and vegetables each day.
Choose whole grains instead of refined grain products.
Limit consumption of processed and red meat.
Women should limit alcohol consumption to 1 drink per day (women at high risk for breast cancer should consider not drinking alcohol at all).

For breast cancer survivors, the American Cancer Society recommends diets that include lots of fruits and vegetables, low amounts of saturated fat (from meat and high-fat dairy products), moderation in soy foods, and moderate or no alcohol consumption.

Here are results from recent studies evaluating diet and breast cancer, for preventing both the development of cancer and its recurrence:

Fats. Research is still mixed on the role that fats, and which specific types of fats, play in breast cancer risk and prevention. Several studies have indicated that red meat, which is high in saturated fat, may increase breast cancer risk when eaten in large quantities on a daily basis. (Red meat is also high in iron, which in itself may increase breast cancer risk.) According to results from the 2006 Women’s Health Initiative study of dietary fat and breast cancer, experts cannot yet definitely say that a low-fat diet will help prevent breast cancer. However, the study suggested that women who normally eat a very high-fat diet may benefit by reducing their fat intake. In the study, the low-fat diet reduced blood estrogen levels by 15%. The low-fat diet also appeared to reduce the risk for developing progesterone receptor-negative tumors.

Fruits and Vegetables. Fruits and vegetables are important sources of antioxidants, which may help protect against the tissue damage linked to increased cancer risk. Antioxidants include vitamin C, vitamin E, and carotenoids such as beta-carotene and lycopene. Richly colored fruits and vegetables -- not supplements -- are the best sources for these nutrients. These fiber-rich foods are an essential part of a healthy diet. However, it is not clear whether fruits and vegetables can specifically prevent breast cancer development or recurrence. According to a 2007 study of women with early-stage breast cancer, a low-fat diet very high in vegetables, fruit, and fiber does not work any better in preventing breast cancer recurrence than the standard 5 servings a day of fruits and vegetables. (However, a combination of diet and exercise may help.)

Calcium and Vitamin D. Eating lots of foods rich in calcium and vitamin D (such as yogurt and milk) may modestly reduce the risk of breast cancer for premenopausal -- but not postmenopausal -- women, according to a 2007 study. Low-fat or non-fat dairy products are a healthier choice than high-fat ones.

Click the icon to see an image of vitamin D sources.

Soy. Soy is an excellent low-fat protein alternative to meat. Soy contains phytoestrogens, which are estrogen-like plant chemicals. In particular, soy contains a type of phytoestrogen called isoflavones. Because many soy foods (such as tofu) are eaten in Asian countries where women tend to have a lower incidence of breast cancer, research has focused on whether soy may have a protective effect. To date, the evidence does not indicate that soy foods or supplements can reduce breast cancer risk. In addition, some studies suggest that high intakes of soy may actually increase the risk of estrogen-responsive cancers such as breast cancer. Some animal studies have suggested that the isoflavone compound genistein may reduce the protective properties of tamoxifen, a drug used to prevent breast cancer in high-risk women. The American Cancer Society recommends that women with breast cancer eat only moderate amounts of soy foods and avoid taking dietary supplements that contain high amounts of isoflavones.

Click the icon to see an image of phytochemicals.

Lifestyle Factors. Premenopausal women at higher risk, usually because of family history, should take as many preventive measures as possible, starting at an early age. The following lifestyle choices may be beneficial:

Exercising and eating healthily is the first essential rule.
High-risk premenopausal women may choose alternatives to oral contraceptives and, if feasible, consider having children early in their life.
High-risk postmenopausal women may want to forego hormone replacement therapy.
Any woman at high risk for breast cancer should consider avoiding alcohol or drinking it very sparingly.

In spite of some rumors published in the popular press, antiperspirants or use of deodorants after shaving have not been linked with any higher risk for breast cancer.

Tamoxifen and Raloxifene. Drugs known as selective estrogen-receptor modulators (SERMs) act like estrogen in some tissues but behave like estrogen blockers (anti-estrogens) in others. Two SERMs -- tamoxifen (Nolvadex) and raloxifene (Evista) -- are approved for breast cancer prevention for high-risk women. Tamoxifen and raloxifene are not recommended as prevention for women at low risk for breast cancer or its recurrence. Women at high risk for breast cancer should discuss with their doctors the risks and benefits of SERMs.

Tamoxifen (Nolvadex) is the most studied of these drugs. It is currently used to treat breast cancer and was the first drug approved for prevention. Evidence strongly suggests that it halves the risk for estrogen receptor-positive cancers in high-risk women, including those with BRCA2 mutations (although possibly not BRCA1). It also helps prevent recurrence in women who have been treated for breast cancers. However, it has no protective effects against estrogen receptor-negative (hormone-insensitive) cancers.

Tamoxifen can increase the risk for uterine (endometrial) cancers. It can also increase the risk for blood clots, strokes, and endometriosis. Less serious side effects include hot flashes and vaginal discharge.

Raloxifene (Evista) was approved in 2007 for prevention of breast cancer in postmenopausal women with osteoporosis and postmenopausal women at high risk for invasive breast cancer. Raloxifene was previously approved for prevention and treatment of osteoporosis in postmenopausal women. One of raloxifene’s main benefits is that it has a lower risk than tamoxifen of causing uterine cancer. However, raloxifene also has some serious risks.

According to the prescribing information from the Food and Drug Administration (FDA), raloxifene can increase the risk of blood clots. Women with a history of blood clots in the legs, lungs, or eyes should not take this medicine. Although studies indicate raloxifene does not increase the risk of stroke, it can increase the risk of dying from a stroke. Women with a history of stroke or current risk factors for stroke should discuss with their doctors whether raloxifene is an appropriate choice. Less serious side effects of raloxifene include hot flashes, leg cramps, swelling of the legs and feet, flu-like symptoms, joint pain, and sweating. Raloxifene can cause birth defects and is approved only for postmenopausal women. It should not be taken with the cholesterol-lowering drug cholestyramine (Questran) or with estrogens.

The FDA based its approval of raloxifene on results from several major studies. The comparison trial Study of Tamoxifen and Raloxifene (STAR), published in 2006 in the Journal of the American Medical Association, indicated that raloxifene works as well as tamoxifen in reducing the risk of invasive breast cancer, and has a lower risk of causing blood clots. However, the Raloxifene Use for the Heart (RUTH) trial, published in 2006 in the New England Journal of Medicine, suggested that raloxifene carries its own risks for blood clots and fatal strokes and may not be a safe choice for women at high risk of heart disease.

Investigational Drugs for Breast Cancer Prevention.

Aromatase inhibitors. Aromatase inhibitors such as anastrazole (Armidex), letrozole (Femara), and exemestane (Aromasin) are effective treatments for hormone-receptor positive breast cancer. Like tamoxifen, they are also being investigated for protection in high-risk women. However, these drugs may decrease bone mineral density and cognitive function, and increase the risk for falls.
Retinoids. Analogues of vitamin A called retinoids are being studied for protection against breast cancer. One retinoid, fenretinide, appears to offer some protection against a second breast cancer in previously diagnosed, premenopausal women (but not in postmenopausal women). It can cause birth defects and should not be used during pregnancy.

Symptoms

Breast cancers in their early stages are usually painless. Often the first symptom is the discovery of a hard lump. Fifty percent of such masses are found in the upper outer quarter of the breast. The lump may make the affected breast appear elevated or asymmetric. The nipple may be retracted or scaly. Sometimes the skin of the breast is dimpled like the skin of an orange. In some cases there is a bloody or clear discharge from the nipple. Many cancers, however, produce no symptoms and cannot be felt on examination. They can be detected only with a mammogram.

Monthly breast self-exams should always include: visual inspection (with and without a mirror) to note any changes in contour or texture, and manual inspection in standing and reclining positions to note any unusual lumps or thicknesses.

Diagnosis

Breast Examination by a Health Professional. Early detection of breast cancer significantly reduces the risk of death. Women ages 20 - 49 should have a physical examination by a health professional every 1 - 2 years. Those over age 50 should be examined annually. A breast exam by a health professional can find 10 - 25% of breast cancers that are missed by mammograms. Between 6 - 46% of the lumps detected by examination are malignant. (The yield is lowest in younger women and highest in older women.)

Self-Examinations. Woman have been encouraged to perform a self-examination each month, but well-conducted studies in 2002 reported no difference in mortality rates between women who were intensively instructed in self-examination and those who were not. This does not mean women should stop attempting self-examinations, but they should not replace the annual examination done by a health professional, which evidence suggests is beneficial.

1. Pick a time of the month that is easy to remember and perform self-examination at that time each month. The breast has normal patterns of thickness and lumpiness that change within a monthly period, and a consistently scheduled examination will help differentiate between what is normal from abnormal.

2. Stand in front of a mirror. Breasts should be basically the same size (one may be slightly larger than the other). Check for changes or redness in the nipple area. Look for changes in the appearance of the skin. With hands on the hips, push the pelvis forward and pull the shoulders back and observe the breasts for irregularities. Repeat the observation with hands behind the head. Move each arm and shoulder forward.

3. Lie down on the back with a rolled towel under one shoulder. Apply lotion or bath oil over the breast area.

The finger action should be as follows: Using the 2nd, 3rd, and 4th finger pads (not tips) held together, make dime-sized circles. Press lightly first to feel the breast area, then press harder using a circular motion.

Using this motion, start from the collarbone and move downward to underneath the breast. Shift the fingers slightly over, slightly overlapping the previously checked region, and work upward back to the collarbone. Repeat this up-and-down examination until the entire breast area has been examined. Be sure to cover the entire area from the collarbone to the bottom of the breast area and from the middle of the chest to the armpits. Move the towel under the other shoulder and repeat the procedure.

Examine the nipple area, by gently lifting and squeezing it and checking for discharge.

4. Repeat step 3 in an upright position. (The shower is the best place for this, using plenty of soap.)

Note: A lump can be any size or shape and can move around or remain fixed. Of special concern are specific or unusual lumps that appear to be different from the normal varying thicknesses in the breast.

Click the icon to see an image of a breast self-exam.

Current Recommendations for Screening. Mammograms are very effective low-radiation screening methods for breast cancer. At this time, the U.S. Preventive Services Task Force recommends screening mammograms, with or without breast examination, every 1 - 2 years for all women over age 40.

Guidelines from the American College of Physicians (ACP), however, debate whether women with a low risk for breast cancer should begin mammogram screening at age 40. The 2007 guidelines, instead, recommend that women in their 40s ask their doctor when they should begin having the test. In contrast, the American Cancer Society and the U.S. National Cancer Institute continue to endorse annual screening for women age 40 and older.

The ACP's guidelines have created controversy within the medical community. Supporters of the guidelines believe that these new recommendations reflect some of the risks involved in screening younger women. These risks include radiation exposure and unnecessary biopsies. Mammographies in younger women produce a relatively high rate of false-positive results (when the test falsely indicates breast cancer). Scientists are working on new technologies to improve mammography's accuracy, but more work is needed. For example, a 2007 New England Journal of Medicine study reported that computer-aided detection software, which is used to help radiologists interpret mammograms, may instead make readings less accurate.

Opponents of the ACP guidelines argue that mammograms help catch tumors while they are in their earliest and most treatable stages, and that the most deadly types of breast cancer tend to occur in women in their 40s.

In addition, according to a review in the American Cancer Society's journal, mammography rates have declined since 2000. In fact, while many experts believe that the recent decline in new cases of breast cancer is partially due to reduced use of hormone replacement therapy, other experts are concerned that fewer cases of breast cancer are being detected because fewer mammographies are being performed.

After age 50, all guidelines recommend annual screenings. The older a women gets, the greater her risk for developing breast cancer. (Women over age 65 account for most new cases of breast cancer.) Women with risk factors for breast cancer, including a close family member with the disease, should consider having annual mammograms starting 10 years earlier than the age at which the relative was diagnosed.

Click the icon to see an image of a mammogram.

Magnetic Resonance Imaging and Ultrasound. Magnetic resonance imaging (MRI) and ultrasound techniques can detect very small tumors (less than half an inch). However, they are expensive and time-consuming procedures. Nevertheless, some doctors believe they are important in identifying small tumors missed on mammography in women who are receiving lumpectomy or breast-conserving surgeries. Such findings would allow the surgeons to remove the optimal amount of abnormal tissue. Ultrasound may also be particularly important for women with dense breast tissue who show signs of breast cancer.

In a report published in 2007, the American Cancer Society recommended that high-risk women have an MRI of their breast with their annual mammogram, including those who have:

A BRCA1 or BRCA2 mutation
A first-degree relative (parent, sibling, child) with a BRCA1 or BRCA2 mutation, even if they have yet to be tested themselves
A lifetime risk of breast cancer that has been scored at 20 - 25% or greater
Had radiation to the chest between ages 10 - 30
Li-Fraumeni syndrome, Cowden syndrome, or Bannayan-Riley-Ruvalcaba syndrome, or may have one of these genetic syndromes based on a history in a first-degree relative

For women who have had cancer diagnosed in one breast, MRIs can also be very helpful for detecting hidden tumors in the other breast. A landmark 2007 study in the New England Journal of Medicine reported that MRI scans of women who were diagnosed with cancer in one breast detected over 90% of cancers in the other breast that had been previously missed by mammography or clinical breast exam. Currently, few women who are diagnosed with cancer in one breast are offered an MRI of the other breast. Some experts advocate MRIs for all women newly diagnosed with breast cancer; others oppose this view. MRI scans may be most useful for younger women with breast cancer who have dense breast tissue that may obscure tumors from mammography readings. MRIs are less likely to be helpful for older women with early tumors in one breast and clear mammography readings in the other.

It is very important that women have MRIs at qualified centers that perform many of these procedures each year. MRI is a complicated procedure and requires special equipment and experienced radiologists. MRI facilities should also be able to offer biopsies when suspicious findings are detected.

Scintimammography. In scintimammography, a radioactive chemical is injected into the circulatory system, which is then selectively taken up by the tumor and revealed on mammograms. This method is very accurate in detecting the presence or absence of breast cancer, and some doctors hope that it might eventually reduce the number of unnecessary invasive biopsies. It is used for women who have had abnormal mammograms or for women who have dense breast tissue. It is not used for regular screening or as an alternative to mammography.

A definitive diagnosis of breast cancer can be made only by a biopsy (a microscopic examination of a tissue sample of the suspicious area).

When a lump can be felt and is suspicious for cancer on mammography, an excisional biopsy may be recommended. This biopsy is a surgical procedure for removing the suspicious tissue and typically requires general anesthetic.

Click the icon to see an image of breast biopsy.

A core biopsy involves a small incision and the insertion of a spring-loaded hollow needle that removes several samples. The patient only requires local anesthetic.
A wire localization biopsy may be performed if mammography detects abnormalities but there is no lump. With this procedure, using mammography as a guide, the doctor inserts a small wire hook through a hollow needle and into the suspicious tissue. The needle is withdrawn, and the hook is used by the surgeon to locate and remove the lesion. The patient may receive local or general anesthetic.
A new vacuum-assisted device may be useful for some biopsies. This uses a single probe through which a vacuum is used to draw out tissue. It allows several samples to be taken without having to remove and re-insert the probe.

Final analysis of the breast tissue may take several days.

If breast cancer has been determined, the next diagnostic step is to find out how far it has spread. To do this, the doctor performs a procedure called an axillary lymphadenectomy, which partially or completely removes the lymph nodes in the armpit beside the affected breast (called axillary lymph nodes). It may require a hospital stay of 1 - 2 days.

Click the icon to see an image of the axillary lymph nodes.

Once the lymph nodes are removed, they are analyzed to determine whether subsequent treatment needs to be more or less aggressive:

If no cancer is found in the lymph nodes, the condition is referred to as node negative breast cancer. The chances are good that the cancer has not spread and is still local.
If cancer cells are present in the lymph nodes, the cancer is called node positive. Their presence increases the possibility that the cancer has spread microscopically to other areas of the body. In such cases, however, it is still not known if the cancer has metastasized beyond the lymph nodes or, if so, to what extent. The doctor may perform further tests to see if the cancer has spread to the bone (bone scan), lungs (x-ray or CT scan) or brain (MRI or CT scan).

Side effects of the procedure include increased risk for infection and pain, swelling in the arm from fluid build-up, and impaired sensation and restricted movement in the affected arm. Patients might ask their doctor about the availability of physical therapy or upper-body exercises after treatment. In two studies, such programs resulted in quicker recovery and no fluid build-up in the arm.

A technique known as a sentinel node biopsy is a less invasive alternative to axillary lymph node dissection. This procedure can help determine if cancer has spread beyond the nodes. If the doctor finds no evidence of cancer, the patient may not need to have a complete axillary lymphadenectomy.

Click the icon to see an image of a sentinel node biopsy.

Sentinel node biopsy involves:

The procedure uses an injection of a tiny amount of a tracer, either a radioactively-labeled substance (radioisotope) or a blue dye, into the tumor site.
The tracer or dye then flows through the lymphatic system into the sentinel node. This is the first lymph node to which any cancer would spread.
The sentinel lymph node and possibly one or two others are then removed.
If they do not show any signs of cancer, it is highly likely that the remaining lymph nodes will be cancer free, making further surgery unnecessary.

Patients who have a sentinel node biopsy tend to have better arm function and a shorter hospital stay than those who have an axillary node biopsy. The American Society of Clinical Oncology's 2005 guidelines recommend sentinel node biopsy instead of axillary lymph node dissection for women with early stage breast cancer who do not have nodes that can be felt during a physical exam. It is still not known if the sentinel node biopsy has any survival advantages compared to standard lymph node removal procedures.

Women often have to wait several days for results of sentinel node biopsies to learn whether they will require another surgery to remove additional lymph nodes. In 2007, the Food and Drug Administration approved the GeneSearch BLN Assay to help speed sentinel node biopsy testing. This molecular-based lab test can detect within 40 minutes whether cancer has spread to nearby lymph nodes. Because the test delivers rapid results while the patient is still on the operating table, it may help spare women the discomforts of a second surgical procedure and help them get treatment earlier.

Prognosis

In the U.S., about 40,460 women will die from breast cancer this year, making it the second most lethal cancer in women. (Lung cancer is the leading cancer killer in women.) The good news is that early detection and new treatments have improved survival rates. The 5-year survival rate for women diagnosed with cancer is 80%. About 88% of women diagnosed with breast cancer will survive at least 10 years. Unfortunately, women in lower social and economic groups still have significantly lower survival rates than women in higher groups.

Several factors are used to determine successful treatment and the possibility for a cure. They include:

The location of the tumor and how far it has spread
Whether the tumor is hormone receptor-positive or -negative
Genetic factors
Tumor size and shape
Rate of cell division
Biologic markers

The good news is that women are living longer with breast cancer, and at this time more than 2 million American women are survivors. Due to better treatment options, from 1990 - 2003, breast cancer mortality rates declined by 24%. However, survivors must live with the uncertainties of possible recurrent cancer and some risk for complications from the treatment itself.

Recurrences of cancer usually develop within 5 years of treatment. However, 25% of recurrences and half of new cancers in the opposite breast occur after 5 years. One study suggested that the risk factors for a first breast cancer do not necessarily place a woman at any higher risk for recurrence. (Women with a first cancer, however, do have a higher risk for a new cancer in the opposite breast. The outlook for such new cancers is independent from those of the first one.)

The location of the tumor is a major factor in outlook:

If the cancer is ductal carcinoma in situ (DCIS) or has not spread to the lymph nodes (is node-negative), the 5-year survival rates with treatment are up to 98%. However, cancer recurs in 9 - 30% of women with node-negative cancers. Recurrence is a potentially life-threatening problem, even if the disease relapses locally in the same breast. In one study of DCIS patients with locally invasive recurrence, 8-year mortality rates were only 12%.
If the lymph nodes contain cancer cells (are node positive) then survival rates fall. If the tumor is larger than 5 cm or there is widespread involvement in the lymph nodes, the cancer is sometimes referred to as locally advanced. In such cases, the survival rate drops to about 75% and below.
If the cancer has spread (metastasized) to other sites (most often the lung, liver, and bone), the average survival time is about 2 years (with some patients living for many years). New drug therapies, particularly aromatase inhibitors, have helped prolong survival for women with metastatic cancer.

The location of the tumor within the breast is an important predictor. Tumors that develop toward the outside of the breast tend to be less serious than those that occur more toward the middle of the breast.

Breast cancer cells may contain receptors, or binding sites, for the hormones estrogen and progesterone. Cells containing these binding sites are known as hormone receptor-positive cells. If cells lack these connectors, they are called hormone receptor-negative cells. About 75% of breast cancers are estrogen receptor-positive (ER-positive, or ER+). About 65% of ER-positive breast cancers are also progesterone receptor-positive (PR-positive, or PR+). Cells that have receptors for one of these hormones, or both of them, are considered hormone receptor-positive.

Hormone receptor-positive cancer is also called "hormone sensitive" because it responds to hormone therapy such as tamoxifen or aromatose inhibitors. Hormone receptor-negative tumors are referred to as "hormone insensitive" or "hormone resistant."

Women have a better prognosis if their tumors are hormone receptor-positive because these cells grow more slowly than receptor-negative cells. In addition, women with hormone receptor-positive cancer have more treatment options. (Hormone receptor-negative tumors can be treated only with chemotherapy.) A 2007 study in the Journal of Clinical Oncology indicated that recent declines in breast cancer mortality rates have been most significant among women with estrogen receptor-positive tumors, due in part to the widespread use of post-surgical tamoxifen therapy.

Determining a "genetic signature" for a tumor may prove to be a very powerful predictor of the aggressive nature of a breast cancer. Researchers have focused on 70 genes whose activity patterns may help make such predictions. In 2007, the Food and Drug Administration approved MammaPrint, a DNA microarray diagnostic test that profiles these 70 genes. The molecular test may help predict how likely it is that breast cancer will recur within 5 - 10 years. However, the accuracy of the test depends on a woman’s risk. It is more accurate when predicting a low risk for recurrence than a high risk.

The relevance of the inherited BRCA1 or BRCA2 mutations to survival is controversial. Some studies have suggested that these mutations offer a survival advantage. Others suggest that they make no difference or even worsen prognosis. Women with these genetic mutations do have a greater risk for a new cancer to develop. Patients with BRCA1 mutations tend to develop tumors that are hormone receptor negative, which can behave more aggressively.

Researchers are investigating numerous substances in tumor cells that may indicate whether or not a cancer is likely to spread. Such chemical markers may help doctors determine treatments, and some may even prove to be targets for future drugs. The following are only a few of the more well-researched markers.

HER2. The American Cancer Society recommends that all women newly diagnosed with breast cancer get a biopsy test for a growth-promoting protein called HER2/neu. HER2-positive cancer usually occurs in younger women and is more quickly-growing and aggressive than other types of breast cancer. The HER2 marker is present in about 20% of cases of invasive breast cancer. Two types of tests are used to detect HER2:

Immunohistochemistry (IHC)
Fluorescence in-situ hybridization (FISH)

Some doctors think that FISH is a more accurate test than IHC. According to 2006 HER2 testing guidelines from the American Society of Clinical Oncology and the College of American Pathologists, either test may be used as long as it is performed by an accredited laboratory. Tests that are not clearly positive or negative should be repeated. Treatment with trastuzumab (Herceptin) or lapatinib (Tykerb) may help women who test positive for HER2.

Angiogenesis Factors. Angiogenesis is the growth of new blood vessels. High levels of angiogenesis factors indicate that the tumor is developing its own supply of blood vessels, which enable the tumor to send colonies of cancer cells into the bloodstream and spread to other parts of the body. Specific angiogenesis factors, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), may turn out to be important markers for determining treatment and prognosis. The monoclonal antibody bevacizumab (Avastin) targets VEGF. The drug is showing promise in clinical trials for prolonging progression-free survival in women with metastatic breast cancer.

Others. Many other markers are being investigated, including p53, cathepsin-D, protein c-erbB-2, bcl-2, Ki-67, telomerase, thymidylate synthase, CA 15-3, and carcinogenic embryonic antigen (CEA). The American Society of Clinical Oncology (ASCO) cautions, however, that the value of many of these factors has not yet been confirmed.

Tumor Size and Shape. Large tumors pose a higher risk than small tumors. Undifferentiated tumors, which have indistinct margins, are more dangerous than those with well-defined margins.

Rate of Cell Division. The more rapidly a tumor grows, the more dangerous it is. Several tests measure aspects of cancer cell division and may eventually prove to predict the disease. For example, the mitotic index (MI) is a measurement of the rate at which cells divide. The higher the MI, the more aggressive the cancer. Another test measures cells at a certain phase of their division.

Recent evidence has not supported early reports of survival benefits for women with metastatic breast cancer who engage in support groups. However, some studies have suggested that psychotherapy, group support, or both may relieve pain and reduce stress, particularly in women who are suffering emotionally.

Stress has been ruled out as a risk factor either for breast cancer itself or for its recurrence.

Treatment

The three major treatments of breast cancer are surgery, radiation, and drug therapy. No one treatment fits every patient, and combination therapy is usually required. The choice is determined by many factors, including the age of the patient, menopausal status, the kind of cancer (ductal vs. lobular), its stage, and whether or not the tumor contains hormone-receptors.

Breast cancer treatments are defined as local or systemic:

Local Treatment. Surgery and radiation are considered local therapies because they directly treat the tumor, breast, lymph nodes, or other specific regions. Surgery is usually the standard initial treatment.
Systemic Treatment. Drug treatment is called systemic therapy, because it affects the whole body.

Any or all of these therapies may be used separately or, most often, in different combinations. For example, radiation alone or with chemotherapy or hormone therapy may be beneficial before surgery, if the tumor is large or not easily removed at prevention. Surgery followed by radiation and hormone therapy is usually recommended for women with early-stage, hormone-sensitive cancer. There are numerous clinical trials investigating new treatments and treatment combinations. Patients, especially those with advanced stages of cancer, may wish to consider enrolling in a clinical trial.

Treatment strategies depend in part on the stage of the cancer.

Stage 0 (Carcinoma in Situ). Stage 0 breast cancer is considered non-invasive (‘in situ"), meaning that the cancer is still confined within breast ducts or lobules and has not yet spread to surrounding tissues. Stage 0 cancer is classified as either:

Ductal carcinoma in situ (DCIS). These are cancer cells in the lining of a duct that have not invaded the surrounding breast tissue.
Lobular carcinoma in situ (LCIS). These are cancer cells in the lobules of the breast. LCIS rarely develops into invasive breast cancer, but having it in one breast increases the risk of developing cancer in the other breast.

Treatment options for DCIS include:

Breast-conserving surgery and radiation therapy (followed by hormone therapy for women with hormone-sensitive cancer)
Total mastectomy (followed by hormone therapy for women with hormone-sensitive cancer)
Breast-conserving surgery without radiation therapy

Treatment options for LCIS include:

Regular exams and mammograms to monitor any potential changes (observation treatment)
Hormone therapy to prevent development of breast cancer (for women with hormone-sensitive cancer)
Mastectomy of both breasts was previously used as treatment, but is now rarely recommended

Stage I and II (Early-Stage Invasive). In stage I cancer, cancer cells have not spread beyond the breast, and the tumor is no more than 2 cm (about 3/4 of an inch) across.

Stage II cancer is classified as either stage IIA or stage IIb.

In stage IIA cancer the tumor is either:

No more than 2 centimeters and has spread to the underarm lymph nodes (axillary lymph nodes)
Between 2 - 5 centimeters and has not spread to the underarm lymph nodes

Treatment options for stage I and stage II breast cancer may include:

Breast-conserving surgery (such as lumpectomy) followed by radiation therapy
Modified radical mastectomy with or without breast reconstruction
Post-surgical therapy (adjuvant therapy), including radiation of lymph nodes, chemotherapy, or hormone therapy
Trastuzumab (Herceptin) given along with or following adjuvant chemotherapy for women with HER2-positive cancer

Stage III (Locally Advanced). Stage III breast cancer is classified into several sub-categories: Stage IIIA, stage IIIB, and stage IIIC (operable or inoperable).

In stage IIIA breast cancer, the tumor is usually confined to the underarm lymph nodes. Treatment options for stage IIIA breast cancer are the same as those for stages I and II.

In stage IIIB breast cancer, the tumor has spread to either:

Tissues near the breast (including the skin or chest wall)
Lymph nodes within the breast or under the arm

Stage IIIB treatment options may include:

Chemotherapy, and possibly hormone therapy (sometimes in combination with chemotherapy)
Chemotherapy followed by surgery (breast-conserving surgery or total mastectomy) with lymph node dissection followed by radiation therapy and possibly more chemotherapy or hormone therapy
Clinical trials

Stage IIIC breast cancer is classified as either operable or inoperable.

In operable stage IIIC, the cancer may be found in:

10 or more of the underarm lymph nodes
Lymph nodes beneath the collarbone and near the neck on the same side of the body as the affected breast
Lymph nodes within the breast as well as underarm lymph nodes

Treatment options for operable stage III breast cancer are the same as those for stage I and II breast cancers.

In inoperable stage III breast cancer, the cancer has spread to lymph nodes above the collarbone and near the neck on the same side of the body as the affected breast. Treatment options are the same as those for stage IIIB.

Stage IV (Advanced Cancer). In stage IV, the cancer has spread (metastasized) from the breast to other parts of the body. In about 75% of cases, the cancer has spread to the bone. The cancer at this stage is considered to be chronic and incurable, and the usefulness of treatments is limited. The goals of treatment for stage IV cancer are to stabilize the disease and slow its progression, as well as to reduce pain and discomfort.

Treatment options for stage IV cancer include:

Surgery or radiation for any localized tumors in the breast. A 2006 study indicated that surgical removal of the primary tumor immediately after metastatic cancer diagnosis can dramatically improve survival.
Chemotherapy, hormone therapy, or both. Targeted therapy with trastuzumab (Herceptin) or lapatinib (Tykerb) should be considered for women with HER2-positive cancer.
Cancer that has spread to the brain may require radiation and high-dose steroids.
Cancer that has spread to the bone may be helped by radiation or bisphosphonate drugs. Such treatments can relieve pain and help prevent bone fractures.
Clinical trials of new drugs or drug combinations, or experimental treatments such as high-dose chemotherapy with stem cell transplant.

In 2006, the American Society of Clinical Oncology (ASCO) released updated guidelines on follow-up care for patients who have been treated for breast cancer. ASCO recommends:

Visit your doctor every 3 - 6 months for the first 3 years after your first cancer treatment, every 6 - 12 months during the fourth and fifth year, and once a year thereafter.
Have a mammogram 1 year after the mammogram that diagnosed your cancer (but no earlier than 6 months after radiation therapy), and every 6 - 12 months thereafter.
Perform a breast self-exam every month (however, this is no substitute for a mammogram).
See your gynecologist regularly (women taking tamoxifen should be sure to report any vaginal bleeding).
A year after diagnosis, you can either continue to see your oncologist or transfer your care to your primary care physician.
If you are on hormone therapy, discuss with your oncologist how often to schedule follow-up visits for re-evaluation of your treatment.

ASCO does not recommend the use of laboratory blood tests (complete blood counts, carcinoembryonic antigen) or imaging tests (bone scans, chest x-rays, liver ultrasound, FDG-PET scan, CT scan) for routine breast cancer follow-up.

Genetic counseling may be helpful if you have:

Ashkenazi Jewish heritage
Personal or family history of ovarian cancer
Personal or family history of cancer in both breasts
Any first-degree female relative (mother, sister, daughter) diagnosed with breast cancer before age 50
Two or more first-degree or second-degree (grandparent, aunt, uncle) diagnosed with breast cancer
History of breast cancer in a male relative

Pregnancy after Breast Cancer Treatment. There are no definite recommendations on how long a woman should wait to become pregnant after breast cancer treatment. Because of the connection between estrogen levels and breast cancer cell growth, some experts recommend delaying pregnancy until 2 years after treatment in order to reduce the risk of cancer recurrence and improve odds for survival. However, a 2007 study indicated that conceiving 6 months after treatment does not negatively affect survival. Discuss with your doctor your risk for recurrence, and when it may be safe to attempt pregnancy.

Recurrent breast cancer is considered to be an advanced cancer. In such cases, the disease has come back in spite of the initial treatment. Most recurrences appear within the first 2 - 3 years after treatment, but breast cancer can recur many years later. Treatment options are based on the stage at which the cancer reappears, whether or not the tumor is hormone responsive, and the age of the patient. Between 10 - 20% of recurring cancers are local. Most recurrent cancers are metastatic. All patients with recurring cancer are candidates for clinical trials.

Because most breast cancer recurrences are discovered by patients in between doctor visits, it is important to notify your doctor if you experience any of the following symptoms. These symptoms may be signs of breast cancer recurrence:

New lumps in the breast
Bone pain
Chest pain
Abdominal pain
Shortness of breath or difficulty breathing
Persistent headaches or coughing
Rash on breast
Nipple discharge

Surgery

Surgery forms a part of nearly every patient's treatment for breast cancer. The initial surgical intervention is often a lumpectomy, the removal of the tumor itself. In the past, mastectomy (the removal of the breast) was the standard treatment for nearly all breast cancers. Now, many patients with early-stage cancers can choose breast-conserving treatment, or lumpectomy followed by radiation, with or without chemotherapy.

For invasive breast cancer, studies indicate that lumpectomy or partial mastectomy combined with radiation therapy works as well as a modified radical mastectomy.

Breast-conserving procedures are now appropriate and as successful as mastectomy in most women with early stage breast cancer. All women should discuss these options fully with their doctor. Recurrence rates with conservative surgery are highest in women under age 45. Some women choose mastectomy over breast-conserving treatment even if the latter is appropriate because it gives them a greater sense of security and allows them to avoid radiation therapy.

Lumpectomy. Lumpectomy is the removal of the tumor, often along with lymph nodes in the armpit. It serves as an opportunity for biopsy, a diagnostic tool, and a primary treatment for small local breast tumors. If invasive cancer is found, the doctor will decide to proceed with breast radiation therapy, to remove additional tissue (should the margins of the specimen show signs of cancer), or to perform a mastectomy. Lumpectomy followed by radiation therapy is appropriate and as effective as mastectomy in most women with Stage I or II breast cancers.

Click the icon to see an illustrated series detailing breast lump removal surgery.

Breast-Conserving Surgery (Quadrantectomy). Breast-conserving surgery (sometimes referred to as quadrantectomy) removes the cancer and a large area of breast tissue, occasionally including some of the lining over the chest muscles. It is less invasive than a full mastectomy, but the cosmetic results are less satisfactory than with a lumpectomy. Excellent studies have found that breast-conserving surgeries plus postoperative radiotherapy offer the same survival rates as radical mastectomy in women with early breast cancer. A new technology called partial breast radiation (MammoSite), approved by the Food and Drug Administration in 2002, confines radiation to the tumor site rather than delivering it to the whole breast, and reduces treatment time from 5 weeks to 5 days in women who undergo breast conserving surgery.

Surgery to remove the breast (mastectomy) is important for women with operable breast cancer who are not candidates for breast conserving surgeries. There are different variations on the procedure:

A total mastectomy involves removal of the whole breast and sometimes lymph nodes under the armpit.
A radical mastectomy removes the breast, chest muscles, all of the lymph nodes under the arm, and some additional fat and skin. (A modified radical mastectomy removes the entire breast and armpit lymph nodes, with the underlying chest wall muscle.) A 25-year study supported other research that observed no survival advantages from radical mastectomy compared to the less invasive mastectomies for the great majority of patients. It is rarely used anymore except when cancer is very advanced.

Click the icon to see an illustrated series detailing mastectomy surgery.

Complications and Side Effects of Surgery. Short-term pain and tenderness occur in the area of the procedure, and pain relievers may be necessary.

The most frequent complication of extensive lymph node removal is edema, or swelling, of the arm, which is usually mild and rarely painful but does increase the risk for infection. The likelihood of edema can be lessened by removing only some of the lymph nodes instead of all of them.

Infrequent complications include poor wound healing, bleeding, or a reaction to the anesthesia.

After mastectomy and lymph node removal, women may experience numbness, tingling, and difficulty in extending the arm fully. These effects can last for months or years afterward.

After a mastectomy, some women choose a breast prosthesis or opt for breast reconstruction, which can be performed during the mastectomy itself, if desired. Several studies have indicated that women who take advantage of cosmetic surgery after breast cancer have a better sense of well-being and a higher quality of life than women who do not choose reconstructive surgery. The breast is reshaped using a saline implant or, for a more cosmetic result, a muscle flap is taken from elsewhere in the body. Muscle flap procedures are more complicated, however, and blood transfusions may be required. (It should be noted that implants, including silicone implants, do not appear to put a woman at risk for breast cancer recurrence.) If the nipple is removed, it is rebuilt from other body tissues and color is applied using tattoo techniques. It is nearly impossible to rebuild a breast that is identical to its partner, and additional operations may be necessary to achieve a desirable effect.

Click the icon to see an illustrated series detailing breast reconstruction surgery.

Numerous studies are investigating minimally invasive techniques that use lasers, deep-freezing of cancer cells (cryosurgery), high-intensity ultrasound, and other experimental approaches to kill cancer cells and reduce severe complications of surgery. Radiofrequency ablation, for example, is an approach that uses an electrode inserted into the tumor. It emits radio waves that produce enough heat to destroy cancer cells. Early trials are promising. These procedures, however, are not considered standard at the present time.

Radiation

Radiation therapy uses high-energy x-rays to kill cancer cells or to shrink the size of a tumor in the breast or surrounding tissue. It is used for several weeks following lumpectomy or partial mastectomy, and sometimes after full mastectomy. Radiation therapy can help reduce the chance of breast cancer recurrence in the breast and chest wall. Radiation is also important in advanced stages of cancer for relief of symptoms and to slow progression. Research shows that radiation therapy is helpful for women of all ages, including those over age 65.

Radiation is generally administered in the following ways:

External Beam Radiation. This type of radiation is administered 4 - 6 weeks after surgery and delivered externally by an x-ray machine that targets radiation to the whole breast. It may be delivered to the chest wall in high-risk patients (large tumors, close surgical margins, or lymph node involvement). The treatment is generally given daily (except for weekends) for about 6 weeks. A follow-up boost of radiation therapy in patients with lumpectomies appears to reduce the risk for recurrence.

Brachytherapy. Less commonly, radiation is delivered in implants (called brachytherapy). Implants are most often used as a radiation boost after whole breast radiation. Studies suggest they improve survival in patients at high risk for local recurrence. Some evidence suggests that implants alone can reduce treatment time and may be as effective as external beam radiation in some patients with early stage breast cancer. A new technology for breast brachytherapy (MammoSite) was approved in 2002. The technique provides 5-year local tumor control rates similar to those of whole-breast radiation for selected patients, with much shorter treatment time and good cosmetic results.

Investigators are also testing other approaches to radiation treatment. One uses a combination of neutrons and protons (mixed-beam) or proton beams rather than the standard photon radiation therapy. Intensity-modulated radiation therapy is a promising technique that delivers different doses to multiple target areas using images of specific regions. Such an approach may improve the coverage of breast cancers while reducing the toxic effects to the heart and lungs.

Side effects of radiation include:

Fatigue is very common and increases with subsequent treatments, but most women are able to continue with normal activities. Exercise may be helpful.
Nausea and lack of appetite may develop and worsen as treatment progresses.
Skin changes and burns can occur on the breast skin. Using a cream that contains a corticosteroid, such as mometasone furoate (MMF), may be helpful. After repeated sessions, the skin may become moist and "weepy." Exposing the treated skin to air as much as possible helps healing. (Washing the affected skin with soap and water does not seem to be harmful and in one study was associated with a lower risk for this side effect.)
Uncommonly, the breast may change color, size, or become permanently firm.
Rarely, the nearest arm may swell and develop impaired mobility or even paralysis.

Future complications include:

Radiation to the left breast may increase the long-term risk for developing heart disease and heart attacks.
There is a very small risk (less than 1%) of lung irritation and scarring.
Some studies have reported a higher risk for future cancer in the opposite breast in younger women who have been given radiation to the chest wall.
Radiation therapy can increase the risk of developing other cancers, such as soft tissue malignancies known as sarcomas.

Current advanced imaging techniques use precise radiation that reduces exposure. These newer techniques are likely to reduce the risks for heart disease and other serious complications.

Medications

The most important advances in the cure of breast cancer have come through the use of drug therapy, also called systemic therapy. Surgery and radiation therapy are effective for treating tumors confined to the breast but not for cancer cells that have spread or are at risk of spreading. In such cases, drug therapy is needed.

Drug treatments for breast cancer include:

Chemotherapy. Chemotherapy drugs are "cytotoxic" (cell-killing) drugs. They are given orally or by injection. They work systemically by killing cancer cells throughout the body. (Unfortunately, they also kill normal cells, which accounts for many of their side effects.) Chemotherapy is always used for advanced breast cancer, but may also be used to treat types of early-stage breast cancer.
Hormone Therapy. The goal of hormone therapy is to prevent estrogen from stimulating breast cancer cells. It is recommended for women whose breast cancers are hormone-receptor positive (either estrogen or progesterone), regardless of the size of the tumor and whether or not it has spread to the lymph nodes. Like chemotherapy, hormone therapy works systemically.
Targeted Therapy. Newer biologic drugs target specific proteins involved in cancer. Because they do not work as systemically as chemotherapy or hormone therapy drugs, they tend to cause fewer widespread side effects. Currently, the monoclonal antibody trastuzumab (Herceptin) and the kinase inhibitor lapatinib (Tykerb) are the two targeted therapies approved for breast cancer. These drugs target the HER2/neu protein and are used to treat HER2-positive breast cancers. Bevacizumab (Avastatin) is a monoclonal antibody that targets vascular endothelial growth factor (VEGF), a protein involved in tumor blood vessel formation (angiogenesis). It is being studied in clinical trials for treatment of metastatic breast cancer.

Drug therapy may be used as:

Primary therapy for patients for whom surgery or radiation therapy is not appropriate.
Neoadjuvant therapy (before surgery or radiation) to shrink tumors to a size that can be treated with local therapy.
Adjuvant therapy (following surgery or radiation) to reduce the risk of cancer recurrence.

For metastatic cancer, drugs are used not to cure but to improve quality of life and prolong survival.

Chemotherapy

Chemotherapy needs to be tailored to the type of cancer involved. Women require different treatments depending on whether the tumor is node-negative or -positive, hormone receptor-positive or -negative, or HER2-positive or -negative. Different treatment approaches are also used for early-stage cancer and advanced cancer.

A 2006 study in the Journal of the American Medical Association indicated that women with hormone receptor-negative cancers respond better to chemotherapy than women with hormone receptor-positive cancer. However, some women with hormone receptor-positive cancer do benefit from chemotherapy, as well as from hormone therapy.

Adjuvant chemotherapy is administered following surgery and before radiation therapy. A 2007 study in the Journal of Clinical Oncology suggested that women with early-stage breast cancer can safely wait for up to 12 weeks after surgery before beginning chemotherapy. However, delaying chemotherapy until more than 12 weeks after surgery significantly increases the risk for breast cancer recurrence and can reduce the odds for survival by as much as 60%.

Many different types of chemotherapy drugs are used to treat breast cancer. Common types of chemotherapy drug classes include:

Anthracyclines include doxorubicin (Adriamycin) and epirubicin (Ellence). Anthracycline-based combination regimens are often used to treat early-stage breast cancer, as well as advanced cancer.
Taxanes include paclitaxel (Taxol) and docetaxel (Taxotere). Two 2003 studies suggested that taxane-based therapy is particularly helpful for node-positive breast cancer. A newer formulation of paclitaxel (Abraxane) is used as a secondary treatment for advanced breast cancer.
Platinum-based drugs include oxaliplatin (Eloxatin) and carboplatin (Paraplatin). These drugs may be used in combination regiments for advanced cancer or for cancers associated with BRCA genes.

Some of the abbreviations used for chemotherapy drug combinations (regimens) refer to drug classes rather than drug names. For example, regimens that contain an anthracycline drug (such as doxorubicin) use the letter "A," and regimens that contain a taxane drug (such as docetaxel) use the letter "T." Cyclophosphamide (Cytoxan), fluorouracil (5-FU), and methotrexate (MTX) are standard cancer drugs used in many breast cancer chemotherapy regimens.

Chemotherapy regimens usually consist of 4 - 6 cycles of treatment given over 3 - 6 months. Common chemotherapy regimens for early-stage breast cancer include:

AC (Doxorubicin and cyclophosphamide)
AC followed by T (Doxorubicin and cylophosphamide followed by paclitaxel)
CAF (Cyclophosphamide, doxorubicin, and 5-FU)
CMF (Cyclophosphamide, methotrexate, and 5-FU)
TAC (Docetaxel, doxorubicin, and cyclophosphamide)

Trastuzumab (Herceptin). Trastuzumab is a monoclonal antibody that targets the HER2 protein on cancer cells. HER2-positive cancers account for 15 - 25% of early-stage breast cancer and are associated with more aggressive disease. Younger women tend to be most affected. In November 2006, the Food and Drug Administration approved trastuzumab for treatment of HER2-positive, early-stage breast cancer (cancer confined to the breasts or lymph nodes that has been surgically removed). Trastuzumab is given along with other chemotherapy drugs following lumpectomy or mastectomy. Research indicates that trastuzumab can help prevent cancer recurrence and death among women with early-stage breast cancer, but it increases the risk of heart problems. Trastuzumab can cause heart failure. Women who have heart failure or weak heart muscle (cardiomyopathy) should not use this drug. Women who take trastuzumab need to have regular heart monitoring, especially if they have already have heart problems.

Patients who develop metastatic disease (cancer that spreads throughout the body) are generally not curable. New advances in drug therapies, however, can help shrink tumors, prolong survival, and improve quality of life.

Chemotherapy regimens for advanced cancer may use a single drug or a combination of drugs. Many chemotherapy regimens used for early-stage breast cancer are also used for advanced breast cancer. Some specific combinations for advanced cancer include:

Gemcitabine and paclitaxel. In 2004, the Food and Drug Administration approved the antimetabolite drug gemcitabine (Gemzar) for use in combination with paclitaxel (Taxol) as a first-line treatment option for women with metastatic breast cancer.
Capecitabine (Xeloda) and docetaxel (Taxotere). Capecitabine is an oral drug that is chemically related to 5-FU. It is also being studied in combination with many other drugs.

Numerous chemotherapy drugs and drug combinations are being tested in clinical trials. Patients with advanced breast cancer may also receive other types of drug treatments. Bisphosphonate drugs, such as zoledronic acid (Zometa) and pamidronate (Aredia), are important supportive drugs for preventing fractures and reducing pain in people whose cancer has spread to the bones.

Two targeted therapy drugs are approved for the treatment of HER2-positive advanced breast cancer

Trastuzumab (Herceptin) was approved in 1998 for treatment of metastatic breast cancer. It is used in adjuvant chemotherapy, along with drugs such as paclitaxel.
Lapatinib (Tykerb) was approved in March 2007 for patients who have not been helped by other cancer drugs, including an anthracycline, a taxane, or trastuzumab. Lapatinib is used in combination with capecitabine (Xeloda). Research suggests it may have fewer risks for heart problems than trastuzumab.

Promising new treatments for advanced breast cancer include:

Ixabepilone (BMS-247550). Ixabepilone is the first of a new class of cancer drugs called epothilones. It is showing encouraging results when combined with capecitabine, according to research presented at the 2007 annual meeting of the American Society of Clinical Oncology.
Bevacizumab (Avastin). Bevacizumab is a targeted therapy anti-angiogenesis drug approved for treatment of colorectal and lung cancers. It is being studied in combination with various chemotherapy drugs for treatment of advanced cancer.

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

Common side effects include:

Nausea and vomiting. Drugs known as serotonin antagonists, especially ondansetron (Zofran), can relieve these side effects. In one study, a combination of dexamethasone (a corticosteroid) with ondansetron taken within 24 hours of chemotherapy achieved either a major or complete reduction in nausea and vomiting. Aprepitant (Emend), a new drug for preventing chemotherapy-caused nausea and vomiting, was approved in 2006.
Diarrhea
Temporary hair loss
Weight loss
Fatigue
Depression

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

Anemia. The erythropoietins epoetin alfa (Epogen, Procrit) and darbepoetin alfa (Aranesp) stimulate red blood cell production and can help reduce or prevent anemia, resulting in significant improvement in quality of life. Aranesp persists longer in the blood than epoetin alfa and may therefore require fewer injections.
Increased chance for infection from severe reduction in white blood cells (neutropenia). The addition of a drug called granulocyte colony-stimulating factor (filgrastim and lenograstim) is very helpful in reducing the risk for severe infection.
Liver and kidney damage.
Abnormal blood clotting (thrombocytopenia).
Allergic reaction, particularly to platinum-based drugs.
Menstrual abnormalities and infertility. Premature menopause occurs in about 30% of women, particularly in those over 40. A natural hormone medication called a gonadotropin-releasing hormone analogue, which puts women in a temporary pre-pubescent state during chemotherapy, may preserve fertility in some women. Women may also wish to consider embryo cryopreservation -- the harvesting of eggs, followed by in vitro fertilization and freezing of embryos for later use. The American Society of Clinical Oncology recommends that women being treated for cancer see a reproductive specialist to discuss all available fertility preservation options.
Sexual dysfunction.
Rarely, secondary cancers such as leukemia.
A quarter to a third of women report problems in concentration, motor function, and memory, which can be long-term. In one study, women were having these symptoms 2 years after treatment, although by 4 years they had resolved.
Heart problems. Trastuzumab (Herceptin) may increase the risk for heart failure, particularly in women with pre-existing risk factors. Cumulative doses of anthracyclines (doxorubicin, epirubicin) can also damage heart muscles over time and increase the risk for heart failure.
Taxanes can cause a drop in white blood cells and possible problems in the heart and central nervous system. Allergic reactions can occur, more often in taxol than taxotere. Taking a steroid before taxane administration can help prevent such reactions. Taxane therapy may also cause severe joint and muscle pain in some patients, relievable with corticosteroids.

High-dose chemotherapy along with peripheral-blood stem cell rescue or bone marrow transplantation procedures have been used for cancer that has metastasized and, in some cases, for earlier stages of breast cancer in high-risk patients. The objective of this treatment is to be able to give patients very high toxic doses of cell-killing drugs.

Transplantation procedures are based on stem cells, which are produced in the bone marrow. Stem cells are the early forms for all blood cells in the body (including red, white, and immune cells). Cancer treatments can harm these growing cells as well as cancer cells.

Despite the initial enthusiasm over the use of high-dose therapy for treatment of high risk breast cancer, this approach can no longer be generally recommended and should not be used outside of a clinical trial setting. The results of several randomized studies have failed to show a convincing advantage for the use of high-dose therapy. Nevertheless, some experts believe this approach can still be useful in selected patients, and studies continue. In general, however, transplantation has a limited role in breast cancer management, and its use should be restricted to clinical trials.

Hormone Therapy

Hormone therapy works by blocking estrogen that causes cell proliferation. It is used only for patients with hormone receptor-positive tumors. Different types of hormone therapy work in different ways by:

Blocking estrogen receptors in cancer cells (Tamoxifen)
Suppressing estrogen production in the body (Aromatase inhibitors)
Destroying ovaries, which produce estrogen (Ovarian ablation)

Tamoxifen was the first widely used hormonal therapy drug, but it has been replaced by aromatase inhibitors for some women. Aromatase inhibitors are used only to treat postmenopausal women. Tamoxifen is mainly used as adjuvant therapy for premenopausal women with hormone-sensitive breast cancer.

Tamoxifen (Nolvadex) has been the standard hormonal drug used for breast cancer. It belongs to a class of compounds called selective estrogen receptor modulators (SERMs). SERMs chemically resemble estrogen and trick the breast cancer cells into accepting it in place of estrogen. Unlike estrogen, however, they do not stimulate breast cancer cell growth. Because SERMs block estrogen’s effects on cancer cells, they are sometimes referred to as "anti-estrogen" drugs.

Tamoxifen is used for all cancer stages in women of all ages with hormone receptor-positive cancers. In addition, it is used to prevent breast cancer in high-risk women. Another SERM drug, toremifene (Fareston), is an option for women with advanced cancer, but this drug is rarely used in the United States. A third drug, fulvestrant (Faslodex), works in a similar anti-estrogen way to tamoxifen but belongs to a different drug class. Fulvestrant is approved only for postmenopausal women with hormone-sensitive advanced breast cancer in which tamoxifen or aromatase inhibitors no longer work.

To prevent cancer recurrence, women should take tamoxifen for 5 years following surgery and radiation. Tamoxifen is an effective cancer treatment, but it can cause unpleasant side effects and has small (less than 1%) but serious risks for blood clots and uterine (endometrial) cancer. Immediately report any signs of vaginal bleeding to the doctor, as this may be a symptom of uterine cancer.

Less serious, but discomforting, side effects include hot flashes and mood swings. According to a 2007 study, nearly 25% of women stop taking tamoxifen within 1 year because of these symptoms. By 3.5 years, over 33% stop treatment. Taking tamoxifen for fewer than 5 years, however, increases the risk for cancer recurrence and death. Talk with your doctor about antidepressants or other therapies that may help you cope with tamoxifen’s side effects.

Many doctors now recommend that postmenopausal women switch to an aromatase inhibitor after 2 - 3 years of tamoxifen therapy. Several 2007 studies indicated that switching from tamoxifen to an aromatase inhibitor significantly improves survival rates and reduces the risk of death from breast cancer as well as other causes.

Endometrial cancer is a cancerous growth of the endometrium (lining of the uterus). It is the most common uterine cancer.

Aromatase inhibitors block aromatase, an enzyme that is a major source of estrogen in many major body tissues, including the breast, muscle, liver, and fat. Aromatase inhibitors work differently than tamoxifen. Tamoxifen interferes with tumors’ ability to use estrogen by blocking their estrogen receptors. Aromatase inhibitors reduce the overall amount of estrogen in the body.

Because these drugs cannot stop the ovaries of premenopausal women from producing estrogen, they are recommended only for postmenopausal women.

There are currently three aromatase inhibitors approved for treating early-stage, hormone receptor-positive breast cancer in postmenopausal women:

Anastrazole (Armidex) for treatment after surgery
Exemestane (Aromasin) for women who have taken tamoxifen for 2 - 3 years
Letrozole (Femara) for treatment after surgery or for women who have completed 5 years of tamoxifen therapy

All of these drugs are also approved for women with advanced (metastatic) hormone-sensitive breast cancer. Studies indicate that the introduction of aromatase inhibitors has helped greatly in prolonging survival for women with advanced cancer.

Compared to tamoxifen, aromatase inhibitors are less likely to cause blood clots and uterine cancer. However, these drugs are more likely to cause osteoporosis, which can lead to bone loss and fractures. In general, recent studies indicate that aromatase inhibitors are better than tamoxifen in improving survival and reducing the risk of cancer recurrence. Unfortunately, like tamoxifen, they can cause hot flashes, as well as joint pain.

Ovarian ablation literally shuts down estrogen production from the ovaries. Medications can accomplish ovarian ablation. Destroying the ovaries with surgery or radiation can also shut down estrogen production. (Osteoporosis is one serious side effect of this approach, but several therapies are available to help prevent bone loss.)

Chemical Ovarian Ablation. Drug treatment (non-chemotherapy drugs) to block ovarian production of estrogen is called chemical ovarian ablation. It is often reversible. The primary drugs used are luteinizing hormone-releasing hormone (LHRH) agonists, such as goserelin (Zoladex). (They are also sometimes called GnRH agonists). These drugs block the release of the reproductive hormones LH-RH, therefore stopping ovulation and estrogen production.

Studies suggest that women with estrogen-positive early stage cancer who take goserelin have similar survival rates to those who take standard chemotherapy. They also experience fewer serious side effects. A major analysis of four trials using LHRH agonists plus tamoxifen suggested that this combination should be the standard for patients with advanced breast cancers that are hormone-receptor positive, although this is an area of controversy. (Chemotherapy is still more effective in women with estrogen-negative tumors.)

Ovariectomy. Ovariectomy, the removal of the ovaries, has modestly improved breast cancer survival rates in some premenopausal women whose tumors are hormone receptor-positive. In these women, combining this procedure with tamoxifen may improve results beyond those of standard chemotherapies. Ovariectomy does not benefit women after menopause, and its advantages can be blunted in women who have received adjuvant chemotherapy. The procedure causes sterility and can have a major negative emotional impact on younger patients.

Resources

www.cancer.gov -- National Cancer Institute
www.cancer.org -- American Cancer Society
www.asco.org -- American Society of Clinical Oncology
www.oncolink.org -- Oncolink
www.womenshealth.gov -- National Women's Health Information Center
www.nccn.org -- National Comprehensive Cancer Network
www.plwc.org -- People Living With Cancer
www.cancer.gov/clinicaltrials -- Find clinical trials
www.breastcancer.org -- Find clinical trials

References

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Boccardo F, Rubagotti A, Aldrighetti D, Buzzi F, Cruciani G, Farris A, et al. Switching to an aromatase inhibitor provides mortality benefit in early breast carcinoma: pooled analysis of 2 consecutive trials. Cancer. 2007 Mar 15;109(6):1060-7.

Boehm JS, Zhao JJ, Yao J, Kim SY, Firestein R, Dunn IF, et al. Integrative genomic approaches identify IKBKE as a breast cancer oncogene. Cell. 2007 Jun 15;129(6):1065-79.

Boyd NF, Guo H, Martin LJ, Sun L, Stone J, Fishell E, et al. Mammographic density and the risk and detection of breast cancer. N Engl J Med. 2007 Jan 18;356(3):227-36.

Breen N, A Cronin K, Meissner HI, Taplin SH, Tangka FK, Tiro JA, et al. Reported drop in mammography : is this cause for concern? Cancer. 2007 Jun 15;109(12):2405-9.

Chia SK, Speers CH, D'Yachkova Y, Kang A, Malfair-Taylor S, Barnett J, et al. The impact of new chemotherapeutic and hormone agents on survival in a population-based cohort of women with metastatic breast cancer. Cancer. 2007 Jul 23;110(5):973-979 [Epub ahead of print]

Cho E, Chen WY, Hunter DJ, Stampfer MJ, Colditz GA, Hankinson SE, et al. Red meat intake and risk of breast cancer among premenopausal women. Arch Intern Med. 2006 Nov 13;166(20):2253-9.

Coombes RC, Kilburn LS, Snowdon CF, Paridaens R, Coleman RE, Jones SE, et al. Survival and safety of exemestane versus tamoxifen after 2-3 years' tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial. Lancet. 2007 Feb 17;369(9561):559-70.

Fenton JJ, Taplin SH, Carney PA, Abraham L, Sickles EA, D'Orsi C, et al. Influence of computer-aided detection on performance of screening mammography. N Engl J Med. 2007 Apr 5;356(14):1399-409.

Geiger AM, Thwin SS, Lash TL, Buist DS, Prout MN, Wei F, et al. Recurrences and second primary breast cancers in older women with initial early-stage disease. Cancer. 2007 Mar 1;109(5):966-74.

Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T, et al. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med. 2006 Dec 28;355(26):2733-43.

Ives A, Saunders C, Bulsara M, Semmens J. Pregnancy after breast cancer: population based study. BMJ. 2007 Jan 27;334(7586):194. Epub 2006 Dec 8.

Jatoi I, Chen BE, Anderson WF, Rosenberg PS. Breast cancer mortality trends in the United States according to estrogen receptor status and age at diagnosis. J Clin Oncol. 2007 May 1;25(13):1683-90. Epub 2007 Apr 2.

Kahlenborn C, Modugno F, Potter DM, Severs WB. Oral contraceptive use as a risk factor for premenopausal breast cancer: a meta-analysis. Mayo Clin Proc. 2006 Oct;81(10):1290-302.

Kerlikowske K, Miglioretti DL, Buist DS, Walker R, Carney PA; National Cancer Institute-Sponsored Breast Cancer Surveillance Consortium. Declines in invasive breast cancer and use of postmenopausal hormone therapy in a screening mammography population. J Natl Cancer Inst. 2007 Sep 5;99(17):1335-9. Epub 2007 Aug 14.

Khatcheressian JL, Wolff AC, Smith TJ, Grunfeld E, Muss HB, Vogel VG, et al.American Society of Clinical Oncology 2006 update of the breast cancer follow-up and management guidelines in the adjuvant setting. J Clin Oncol. 2006 Nov 1;24(31):5091-7. Epub 2006 Oct 10.

Lehman CD, Gatsonis C, Kuhl CK, Hendrick RE, Pisano ED, Hanna L, et al. MRI evaluation of the contralateral breast in women with recently diagnosed breast cancer. N Engl J Med. 2007 Mar 29;356(13):1295-303. Epub 2007 Mar 28.

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Lohrisch C, Paltiel C, Gelmon K, Speers C, Taylor S, Barnett J, et al. Impact on survival of time from definitive surgery to initiation of adjuvant chemotherapy for early-stage breast cancer. J Clin Oncol. 2006 Oct 20;24(30):4888-94. Epub 2006 Oct 2.

Michels KB, Xue F, Colditz GA, Willett WC. Induced and spontaneous abortion and incidence of breast cancer among young women: a prospective cohort study. Arch Intern Med. 2007 Apr 23;167(:814-20.

Moss SM, Cuckle H, Evans A, Johns L, Waller M, Bobrow L. Effect of mammographic screening from age 40 years on breast cancer mortality at 10 years' follow-up: a randomised controlled trial. Lancet. 2006 Dec 9;368(9552):2053-60.

North American Menopause Society. Estrogen and progestogen use in peri- and postmenopausal women: March 2007 position statement of The North American Menopause Society. Menopause. 2007 Mar-Apr;14(2):168-82.

Perez EA, Lerzo G, Pivot X, Thomas E, Vahdat L, Bosserman L, et al. Efficacy and safety of ixabepilone (BMS-247550) in a phase II study of patients with advanced breast cancer resistant to an anthracycline, a taxane, and capecitabine. J Clin Oncol. 2007 Aug 10;25(23):3407-14. Epub 2007 Jul 2.

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Qaseem A, Snow V, Sherif K, Aronson M, Weiss KB, Owens DK; Clinical Efficacy Assessment Subcommittee of the American College of Physicians. Screening mammography for women 40 to 49 years of age: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2007 Apr 3;146(7):511-5.

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Saslow D, Boetes C, Burke W, Harms S, Leach MO, Lehman CD, et al. American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography. CA Cancer J Clin. 2007 Mar-Apr;57(2):75-89.

Smith I, Procter M, Gelber RD, Guillaume S, Feyereislova A, Dowsett M, et al. 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet. 2007 Jan 6;369(9555):29-36.

Terry KL, Willett WC, Rich-Edwards JW, Michels KB. A prospective study of infertility due to ovulatory disorders, ovulation induction, and incidence of breast cancer. Arch Intern Med. 2006 Dec 11-25;166(22):2484-9.

Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol. 2007 Jan 1;25(1):118-45. Epub 2006 Dec 11.

Review Date:
1/26/2008
Reviewed By:
A.D.A.M. Editorial Team: David Zieve, MD, MHA, Greg Juhn, MTPW, David R. Eltz, Kelli A. Stacy, ELS. Previously reviewed by Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital (11/01/07).

A.D.A.M. Copyright

adam.com

Weight control and diet

FitSugar — Wed, 08 Oct 2008 17:34:58 -0700

In This Report

Highlights
Introduction
Biological and Medical Caus...
Cultural and Emotional Caus...
Risk Factors
Complications
Weight Loss and Maintenance...
Weight Management
Medications
Other Treatments
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Cancer and Weight Control:

Cancer prevention guidelines from the American Cancer Society stress the importance of maintaining a healthy weight throughout life. A healthy weight is even more important than eating specific healthy foods, when it comes to cancer prevention.

Drug Warning:

The US Food and Drug Administration (FDA) is warning consumers not to buy a product known as the "Brazilian diet pill." This product is labeled as a dietary supplement, but contains several chemicals found in powerful prescription drugs. The products are also known as Emagrece Sim and Herbathin dietary supplements.

New Over-the-Counter Medication:

In February 2007, the FDA approved the first over-the-counter (OTC) weight-loss drug. Orlistat, previously available only by prescription as Xenical, will be available OTC at half its prescription strength. It will be sold under the name alli. Those eager to use the new pill should consider its cost and modest benefits compared with its side effects, most commonly oily diarrhea. This pill, which prevents fat absorption from food, also increases the risk of not absorbing important nutrients from food while using it. The FDA recommends taking a daily multivitamin supplement when using alli.

Research News:

A small study in Norway found that a diet low in fat and high in carbohydrates ("carbs") increases symptoms of psychological distress, such as depression and anger. The study compared three different diets with varying amounts of fat and carbohydrates.
A study released in March 2007 found that obesity in young girls results in early puberty -- as early as age 9.

Effects of Obesity on the Body:

Obesity is associated with certain problems related to infertility, such as uterine fibroids or menstrual irregularities. In men, obesity can contribute to reduced testosterone levels.
People who are obese are at higher risk for carpal tunnel syndrome and other problems involving nerves in their wrists and hands.
The Pickwickian syndrome, named for an overweight character in a Dickens novel, occurs in severe obesity when lack of oxygen produces intense and chronic sleepiness and, eventually, heart failure.

Introduction

A stable weight depends on a good balance between the energy you get from food and the energy you use. You use energy during the day in three ways:

As energy expended during rest (basal metabolism)
As energy used to break down food (thermogenesis)
As energy used during physical activity

Basal metabolism accounts for about two-thirds of spent energy. Your body generally uses this energy to keep your body temperature steady and keep the muscles of your heart and intestine working. Thermogenesis accounts for about 10% of spent energy.

When a person consumes more calories than the energy they use, the body stores the extra calories in fat cells. Fat cells function as energy reservoirs. They enlarge or shrink depending on how people use energy. If people do not balance energy input and output by eating right and exercising, fat can build up. This can lead to weight gain.

When energy input is equal to energy output, there is no expansion of fat cells (lipocytes) to accommodate excess. It is only when more calories are taken in than used that the extra fat is stored in the lipocytes and the person begins to accumulate fat.

Obesity is determined by measuring body fat, not just body weight. People might be over the weight limit for normal standards, but if they are very muscular with low body fat, they are not obese. Others might be normal or underweight, but still have excessive body fat. The following measurements and factors are used to determine whether or not a person is overweight to a degree that threatens their health:

Body mass index (BMI) (a measure of body fat)
Waist circumference (size around the waist)
Waist-hip ratio
Skin fold measurement (anthropometry)
The presence or absence of other disease risk factors (e.g., smoking, high blood pressure, unhealthy cholesterol levels, diabetes, relatives with heart disease)

A person's disease risk factors plus BMI may be the most important components in determining health risks with weight.

The Body Mass Index (BMI). The current standard measurement for obesity is the body mass index (BMI). In general, a BMI of 25 - 29.9 means you are overweight. Obesity is a BMI of 30 and above. Obesity is then classified into three categories:

Class 1: BMI of 30 - 34.9
Class II: BMI 35 - 39.9
Class III: BMI of 40 and greater

These guidelines are very important for people at risk for diabetes, heart disease, or certain cancers. It is also used to determine treatment approaches such as when surgery may be appropriate. The higher the BMI, the greater the risk for significant health problems.

Calculating Body Mass Index (BMI). One's body mass index (BMI) is calculated by multiplying a person's weight in pounds by 703, dividing by the height in inches, and then dividing that number by the height in inches. The steps are as follows:

Multiply one's weight in pounds by 703
Divide that answer by height in inches
Divide that answer again by height in inches

For example, a woman who weighs 150 pounds and is five feet eight inches (or 68 inches) tall has a BMI of 22.8.

Waist Circumference and Waist-Hip Ratio. The extent of abdominal fat can also be used in assessing risk of disease. Some studies suggest that:

Women whose waistlines are over 31.5 inches and men whose waists measure over 37 inches should watch their weight.
A waist size greater than 35 inches in women and 40 inches in men is associated with a higher risk for heart disease, diabetes, and impaired functioning.

Evidence strongly suggests that more body fat around the abdomen and hips (the apple-shape) is a more consistent predictor of heart problems and health risks than BMI.

The distribution of fat can be evaluated by dividing waist size by hip size. For example, a woman with a 30-inch waist and 40-inch hip circumference would have a ratio of 0.75; one with a 41-inch waist and 39-inch hips would have a ratio of 1.05. The lower the ratio the better. The risk of heart disease rises sharply for women with ratios above 0.8 and for men with ratios above 1.0.

Click the icon to see a depiction of the waist-to-hip ratio.

Anthropometry. Anthropometry is the measurement of skin fold thickness in different areas, particularly around the triceps, shoulder blades, and hips. This measurement is useful in determining how much weight is due to muscle or fat.

Biological and Medical Causes

Obesity results when a person consumes more calories than they need for the energy they use. Several different factors may influence weight gain.

About 90% of people who lose weight through dieting gain every pound back regardless of their weight-loss method.

Some evidence suggests that every person has an inherited weight. This range varies by only about 10% either up or down from some set point. For instance, a man whose "genetically-determined" weight is 200 pounds would tend to swing from 180 - 220 pounds. He would be unlikely to lose or gain more than this.

Genetic factors may play some part in 70 - 80% of obesity cases.

Appetite is determined by processes that occur both in the brain and gastrointestinal tract. Eating patterns are controlled by areas in the hypothalamus and pituitary glands (in the brain). The body produces a number of molecules that increases or decreases appetite. In some cases, the following factors may produce imbalances in this process:

Insulin. Insulin is a hormone that helps change blood sugar (glucose) into energy. During digestion, carbohydrates from our diet break down into different types of sugar molecules (including glucose). Proteins from our diet break down into smaller molecules called amino acids. Immediately after eating, blood glucose levels rise. This triggers the release of insulin, which pours into the bloodstream. Insulin pushes the glucose and amino acids into cells and muscles. Insulin and other hormones determine which nutrients will be burned for energy or stored for future use. The inability to use insulin efficiently (insulin resistance) has been associated with both obesity and diabetes.
Leptin. Leptin is a hormone that is released by fat cells. A number of scientists think this hormone may also be released by cells in the stomach. Leptin appears to play an important role in insulin resistance and fat storage in the body, but its role in obesity is unclear. The most likely scenario is that leptin levels rise as the cells store more fat. This increase in leptin levels decreases appetite. Falling levels of leptin make you feel hungry. In people who have genetically lower levels of leptin, however, the brain may be tricked into thinking that it is always starving because there is no leptin to decrease appetite. This can lead to weight gain.
Resistin. Resistin is a hormone produced by fat cells. It makes the body resistant to insulin activity. Some experts believe it may help explain the role of obesity in diabetes type 2.
Intestinal Chemicals. Ghrelin is a chemical produced in the stomach. It appears to be important in triggering the desire to eat. Peptide YY3–36 (PYY) is a substance secreted in the intestines after a meal. The level of PYY is proportionate to the number of calories a person eats. PYY tells the brain that you feel full. Deficiencies in ghrelin and PYY may contribute to some cases of obesity. Researchers are hoping that blocking ghrelin or infusing PYY may be possible treatments for obesity.
Other Chemicals. Many brain chemicals are being studied for their role in appetite stimulation and weight gain. Among them are neuropeptide Y, melanocortins, agouti-related protein, and melanocyte stimulating hormone. Pain-relieving chemicals called endorphins may be critical in reducing appetite and regulating energy use. Cholecystokinin, a hormone released in the upper intestine that stimulates digestive juices, may work to control meal size.

Insulin is a hormone produced by the pancreas that is necessary for cells to be able to use blood sugar.

Genetics may directly contribute to severe obesity in people with family histories of the problem. Genetic factors such as slow metabolisms may also make people more likely to be overweight. At least seven genetic mutations have been associated with specific and uncommon cases of severe obesity. Some are outlined below.

HOB1 (human obesity 1) is a gene that is linked to a high BMI in women.
Leptin gene variants have been linked to leptin deficiencies and obesity.
Melanocortin-4 receptor is a gene that helps turn off the urge to eat. It may not work properly in those with a family history of obesity.
Researchers have also identified a mutation in a gene for a protein called proopiomelanocortin, which results in a syndrome of obesity, red hair, and deficiencies in stress hormones.
A protein called agouti-related protein increases hunger. About 5% of severely obese people have mutations that over-respond to agouti-related protein.

Genetics also determine the number of fat cells a person has. Some people are simply born with more. It should be noted that even when genetic factors are present, a person can still control their diet.

The Thrifty Gene. Some experts think the existence of a so-called "thrifty" gene regulates changes in hormone levels, to accommodate seasonal changes. Theoretically, it works in the following manner:

In certain populations, hormones are released during seasons when food supplies have traditionally been low. This leads to insulin resistance and increased fat storage.
The process is reversed in seasons when food is readily available.
Because modern industrialization has made high carbohydrate and fatty foods available all year long, the gene no longer serves a useful function. Fat, originally stored for famine situations, is not used.

This theory could explain why the previously nomadic Native American tribes who now have Western dietary habits have such high rates of Type 2 diabetes and obesity. In the past, the traditional low-fat, high-fiber foods tribe members ate may have protected them from obesity and type 2 diabetes. Today, these tribes' diet consists of more Western foods, which are higher in fat. Furthermore, these foods are readily available year-round, and many members of the tribe are sedentary. The result is a very high incidence of Type 2 diabetes and obesity. Although genetic abnormalities may make it harder or easier to lose weight, the occurrence of obesity has dramatically increased over the past two decades, and genes cannot have changed within that short amount of time. Our ability to use the food that we eat evolved so that our body could conserve energy and store fat during times of famine. Most cases of obesity now occur in people with normal body function who live in industrialized nations, where there is more than enough food.

A number of medical conditions may contribute to being overweight, but rarely are they a primary cause of obesity.

Hypothyroidism is sometimes associated with weight gain. But, patients with an underactive thyroid generally show only a moderate weight increase of five to 10 pounds.
Very rare genetic disorders, including Froehlich's syndrome in boys, Laurence-Moon-Biedl, and the Prader-Willi syndromes, cause obesity.
Abnormalities or injury to the hypothalamus gland can cause hypothalamic obesity.
Cushing's disease is a rare condition caused by high levels of steroid hormones. It results in obesity, a moon-shaped face, and muscle wasting.
Obesity is also linked to polycystic ovarian syndrome, a hormonal disorder in women.

Click the icon to see an image of polycystic ovaries.

Some prescription medications contribute to weight gain, usually by increasing appetite. Such drugs include the following:

Corticosteroids
Female hormone treatments, including some oral birth control pills (effect is usually temporary), and certain progestins (such as Megestrol) used to treat cancer
Antidepressants and anti-psychotic drugs, including lithium and valproate
Insulin and insulin-stimulating drugs used to treat diabetes often lead to weight gain, a particularly unfortunate conflict of interest for obese individuals with type 2 diabetes

You should not stop taking any medications without your doctor's knowledge.

Cultural and Emotional Causes

Enough food is produced in the US to supply 3,800 calories every day to each man, woman, and child in the country, far more than the average person needs to sustain life. In a 2002 study, participants carefully recorded everything they ate and drank, and all activities and psychological factors surrounding the eating events. The people who gained weight ate more and their portions were larger than those who did not. This may be an obvious conclusion, but the public press often plays up biologic factors involved with obesity and overlooks the simple notion that Americans eat too much and exercise too little.

Obesity is dramatically increasing not only in American children and adults, but also in every country that has adopted similar cultural habits. The World Health Organization now considers obesity to be a global epidemic and a public health problem as more nations become "Westernized." In spite of the proven health risks of obesity, the government, insurance companies, and the medical profession do not spend nearly enough money to balance the commercial and cultural pressures that are producing millions of overweight people.

In 2007, the Robert Wood Johnson Foundation sounded a positive note with the announcement of a $500 million initiative, aimed at “reversing the childhood obesity epidemic by 2015.” The money will be used for research, education, and activities that promote healthy eating among America’s children.

Perhaps the primary reason for the dramatic rise in obesity is the sedentary (inactive) lives led by most Americans, including children and young people. In a 2003 study comparing modern life to the past, researchers found that labor saving devices had reduced a person's energy use by 111 calories a day -- adding up to an extra 11 pounds a year. Half the difference in energy use was due to less walking. At the same time, according to the U.S. Centers for Disease Control and Prevention, between 1970 and 2000 the typical American man increased his caloric intake by 168 calories a day (good for 17 pounds a year) while the average woman added 335 calories a day.

Regular television watching has been singled as the most hazardous pastime. According to a major 2003 study, for every 2 hours a person spends in front of the TV each day, the risk for obesity increases by 23% and for type 2 diabetes by 14%. In the study, TV watching produced the lowest metabolic rates compared to sewing, playing board games, reading, writing, and driving a car. Just the act of watching TV encourages unhealthy snacks and eating patterns. In addition, the advertising on the television complicates the problem by promoting fast foods, cereal, and snack products that are high in salt, fats, and carbohydrates. Even worse, much of these advertisements are directed at children -- the most vulnerable group.

People are not only eating more food than they did 20 years ago, they are also replacing home cooking with packaged foods, fast food, and dining out. This behavior, according to studies, places people at higher risk for obesity. Fast foods may be more harmful than restaurant cooking. These foods tend to be served in larger portions. They generally contain more calories and unhealthy fats, and less nutritious ingredients, than homemade or restaurant meals. Snack foods and sweet beverages, including juice and soft drinks, are specific problems that add to the increasing rates of obesity. Frequent small, healthy meals (instead of two or three large daily meals) have been associated with lower weights.

People react differently to stress. Some overeat and gain weight and others stop eating and lose weight. People who gain weight in response to stress often overeat foods high in sugar, fats, and salt. A 2003 study on rats suggested that stress hormones increase the pleasure of eating such so-called "comfort foods." Furthermore, the study supported previous research showing that stress-related eating was connected to the unhealthy accumulation of abdominal fat.

Risk Factors

Where you live plays a role in your risk for obesity. Simply living in the United States makes a person more susceptible to obesity. The prevalence of obesity in America has risen dramatically over the past few years and continues to increase.

According to the latest figures available, 32.2% of American adults (aged 20 and older) are obese (BMI over 30) -- up from about 23% in the early 1990s.
The number of Americans aged 20 - 74 who were overweight also increased -- from about 44.8% in 1960 to 65.2% in 2002.
The rate of extreme obesity (BMI > 40) increased from 0.8% in 1960 to 4.9% in 2002.
Obesity has increased in every state, in both men and women, across all age groups, and in every ethnic group, although some groups may face slightly higher risks than others.

Fat tends to settle in certain regions, depending on gender. Women gain fat predominantly in the stomach, hips and thighs, while men tend to gain fat in the belly and waist.

Risk by Age. People of any age are at risk for obesity. More children and adolescents are overweight in America than ever before. Gaining some weight is inevitable with age and adding about 10 pounds to a normal base weight over time is not harmful. The current weight gain in American adults over 50, however, is significant. By age 55, the average American has added nearly 40 pounds of fat during the course of adulthood. This condition is made worse by the fact that muscle and bone mass decrease with age.

Risk by Gender. In men, BMI tends to increase until age 50 and then it levels off. In women, weight tends to increase until age 70 before it plateaus. A 2000 study found that there are three high-risk periods for weight gain in women.

The first is at the onset of menstruation, particularly if it is early. In fact, a study released in March 2007 found that obesity in young girls results in early puberty -- as early as age 9. This, in turn, increases the risk for more weight gain as girls enter puberty.
The second is after pregnancy, with higher risk for women who are already overweight.
Finally, many women gain weight after menopause.

These findings are significant because they may allow women to target high-risk times, and consequently prevent unnecessary weight gain.

Risk by Economic Group. Obesity is more prevalent in lower economic groups. One 2002 study reported that women who reported that they did not have enough food were more likely to be overweight than those who said they had sufficient food. Researchers discovered that the low-income women tended to have fewer fruits and vegetables but were actually taking in more calories a day than higher-income women. However, obesity is increasing in young adults with college education as well as in other groups.

Ethnic Groups. Among ethnic groups in general, African-American women are more overweight than Caucasian women but African-American men are less obese than Caucasian men. (Currently, 80% of African-American women are overweight.) Hispanic men and women tend to weigh more than Caucasians.

US Regions. Regionally, the prevalence of obesity is lowest in the Western states and highest in the South.

A number of dietary habits put people at risk for becoming overweight:

Night-Eating Syndrome. Night-eating syndrome is defined as having no appetite in the morning, insomnia, and consuming more than half of daily food intake after 6:00 PM. It is associated with obesity and is difficult to treat. Stress reduction and relaxation techniques may be helpful.
Binge Eating and Eating Disorders. About 30% of people who are obese are binge eaters who typically consume 5,000 - 15,000 calories in one sitting. To be diagnosed as a binge eater, a person has to binge at least twice a week for 6 months. Many experts believe that binge-eating carbohydrates causes an increase in a natural opiate leading to dependence on carbohydrates. Therefore, this condition should be treated as an addiction. Other eating disorders are bulimia and anorexia. Bulimia is binge eating followed by purging in order to lose weight. Anorexia nervosa is a mental illness in which the person refuses to maintain weight at the normal level. The patient with anorexia has a terrible fear of getting fat, and an abnormal perception of what his or her body looks like. Both conditions pose risks for serious medical problems, and anorexia nervosa can be life-threatening. A combined approach using behavioral therapy and antidepressants may help these individuals. [See In-Depth Report #49: Eating disorders.]
Restrained Eating. Some people, mostly middle-aged women who have normal weight, have a pattern referred to as restrained eating. This pattern requires a high level of conscious control and usually maintains a lower weight. However, such restraint places these individuals at higher risk for loss of control and subsequent overeating.
Infrequent Eating. There is some evidence to suggest that eating small frequent meals uses more calories than infrequent large meals. It should be strongly noted, however, that packaged snack foods add calories and some do not produce a feeling of being full, so that people simply eat more than they should.

Anyone with Sedentary Lifestyles. Office workers, drivers, and anyone whose lifestyle involves sitting for long periods are at higher risk for obesity.

Ex-Smokers. The trend toward weight increase has followed the trend for quitting smoking. Nicotine increases the metabolic rate, and quitting, even without eating more, can cause weight gain, which may be considerable. It is important to note that weight control is not a valid reason to smoke. People in previous centuries did not smoke cigarettes, nor were they usually obese.

Shift-Workers. A recent study found that individuals who work late shifts (between 4 p.m. and 8 a.m.) tend to eat more and take longer naps than day workers and are more likely to gain excess weight.

People with Disabilities. Obesity rates are higher than average in people with physical or mental disabilities. Those with disabilities in the lower part of the body, such as the legs, are at highest risk.

Overweight in children and adolescents is rising at an alarming rate. In 2004, 19% of young children aged 6 - 11 were overweight, an increase of 8% from 1994. Among children aged 25, 13.9% were overweight in 2004, up from 7.2% 10 years earlier.

Definition of Overweight in Children

Children and adolescents are considered to be overweight if their BMI is above 95% of the children in their age and sex categories. Ethnic variations, timing of growth spurts, and higher normal fat levels around puberty can affect these measurements.

Causes and Risk Factors for Overweight in Children

Lifestyle Factors. Without educational or parental guidance, children are extremely vulnerable to the intense cultural pressures that are largely responsible for the obesity epidemic. The following are some specific problems created by the culture:

Excessive television watching plays a critical role in obesity in children. Not only is it a sedentary activity, but television also offers innumerable temptations with its advertisements for fast foods, sugar cereals, and unhealthy snacks. In one study obesity rates were lowest in children who watched television 1 hour or less a day and highest in those who watched 4 or more hours.
Sugar, particularly from soda, other sweetened beverages, and fruit juice, may be the major contributor to childhood obesity. One study reported that drinking soda regularly increases a child's risk for obesity by 60%. The average American adolescent consumes 15 - 20 extra teaspoons of sugar a day just from soda and sugary drinks. (Juice, while better than soda, is still filled with sugar.)
Less physical exercise and greater sedentary activities play another significant role in obesity in children. A high level of physical activity -- not just using up energy -- is important for weight control in young people. Unfortunately, according to one study, the annual distance walked by children has fallen by nearly 30% since 1972, partially because more parents are driving their children to school out of fear of abduction, molestation, and traffic accidents. Schools are also offering fewer opportunities for daily physical activities than in the past.

Neither the media nor the educational system has strong well-financed programs that encourage healthy alternatives, including exercise and healthy foods.

Family History. Parental obesity more than doubles the risk that a young child, whether thin or overweight, will become obese as an adult. In older children and teenagers, obesity in parents starts to count less as a predictor for body weight than their own weight. The risk for obesity may be due to environmental or genetic factors, or both.

Ethnic and Socioeconomic Factors. As in adult populations, children from lower socioeconomic groups and minority populations are at higher risk for obesity. For example, among young Mexican Americans and African-Americans, there has been an increase in overweight prevalence of about 13% to over 23%.

Factors Surrounding Birth. The following factors surrounding birth are associated with a child's weight:

Low birth weight is a risk factor for later obesity and diabetes. One theory is that humans have a "thrifty gene" that produces metabolic changes in infants with low birth weight. Such changes affect insulin and fat accumulation, in order to produce a "catch-up" weight in these young children as quickly as possible. This rapid weight gain in infancy increases the risk for obesity in children and young adults.
In a study of African-American children, having an overweight pregnant mother increased the risk for later weight gain, but low birth weight did not.

Although some small studies have reported protection against obesity from breastfeeding, evidence is weak. In a 2003 study, for example, children who were breast fed for 3 - 5 months had a lower risk for obesity, but prolonged breastfeeding had no effect. Nevertheless, given the healthful effects of breast feeding and the possibility that it may have even a slight impact on childhood obesity, it is highly recommended.

Biological Effect of Childhood Overweight on Adult Weight

Achieving a healthy weight becomes more difficult as children get older. The odds of obesity persisting into adulthood ranges from 20% in 4 year olds to 80% in teenagers. One reason for the persistence is biological. The fat cells change in number or mass depending on a person's age:

Fat cells themselves multiply during two growth periods: early childhood and adolescence. Overeating during those times increases the number of fat cells. Some people are also just born with more fat cells.
After adolescence, fat cells tend to increase in mass rather than quantity, so that adults who overeat and gain weight tend to have larger fat cells, not more of them. This growth in mass may be responsible for the greater risk of persistent obesity among teenagers compared to small children who are overweight. Losing weight after adolescence reduces the size of the fat cells but not their number, so weight loss becomes much more difficult.

Health Consequences of Childhood Overweight

Children and adolescents who are overweight have poorer health than other children. Studies are reporting unhealthy cholesterol levels and high blood pressure in overweight children and adolescents. Of great concern is the dramatic increase in type 2 diabetes in young people, which is largely due to the increase in overweight children. Overweight in children is also linked to asthma, gallbladder problems, sleep apnea, and liver abnormalities. Overweight girls are more likely to enter puberty early, according to a new study, and subsequently be at higher risk for breast cancer.

It is not clear yet how many of these childhood problems persist in people who achieve normal weight as adults. Staying overweight into adulthood certainly carries health risks.

Managing Overweight Children

Childhood obesity is best treated by a non-drug, multidisciplinary approach including diet, behavior modification, and exercise. Evidence suggests that reducing calories by only 200 - 260 per day would prevent weight gain in most overweight children. Here some tips for children who are overweight:

Limit (or avoid, if possible) take out, fast foods, high-sugar snacks, commercial packaged snacks, soda, and sugar-sweetened beverages (including too much juice).
Let children snack but make sure the snacks are healthy. Eating small frequent healthy meals (instead of two or three large ones) has been associated with being thinner and having a better cholesterol profile.
Let children choose their own food portions. One study indicated that children naturally ate 25% less when they chose their own portion size. When they were given larger portions their bite sizes were larger and they ate more.
Do not criticize a child for being overweight. It does not help and such attitudes could put children at risk for eating disorders, which are equal or even greater dangers to their health.
Limit television, video games, and computer use to a few hours a week. This can contribute significantly to weight control, regardless of diet and physical activity.
For young children, try the traffic-light diet. Food is designated with stoplight colors depending on their high caloric content: Green for go (low calories); yellow for "eat with caution" (medium calories); red for "stop" (high calories).
Try a low glycemic index diet. This may be as beneficial, and possibly more, than a standard reduced-fat diet in overweight children. Such a diet focuses on certain carbohydrates (for example, dried beans and soy), which raise blood sugar more slowly than other types of carbohydrates. This diet is sometimes used in diabetes, and as a dietary approach in overweight adults. [See In-Depth Report #42: Diabetes diet.]

Click the icon to see an image about TV watching.

Click the icon to see an image of childhood overweight.

Complications

General Adverse Effects of Obesity. Obesity, defined as a BMI of 30 or over, accounts for nearly 300,000 deaths in the U.S. each year. It is associated with more chronic health problems than smoking, heavy drinking, or poverty. Furthermore, given the current increase in obesity, it will surpass smoking as the most important preventable cause of death in America.

Some studies indicate the following health risks by body mass:

The lowest risks for heart disease, diabetes, and some cancers are in people with BMI values of 21 - 25.
The risks increase slightly when BMI values are between 25 - 27.
The risks are significant in BMIs between 27 - 30.
The same risks are dramatic at BMIs over 30.

Anyone with chronic health problems such as heart or lung disease, stroke, or arthritis, should be concerned about extra weight. This same concern also applies to people with known risk factors for such conditions.

Metabolic Changes. As fat stores increase, the fat cells themselves enlarge and produce chemicals that increase the risk for several diseases. Such diseases may include diabetes, high blood pressure, gallbladder disease, and some cancers.
Increased Mass. The increased body weight itself causes problems that result in injury and diseases, including osteoarthritis and sleep apnea.
Harmful Fat Cell Types. Weight concentrated around the abdomen and in the upper part of the body (the apple shape) poses a higher health risk than fat that settles around the hips and flank (the pear shape). Fat cells in the upper part of the body appear to have different qualities from those found in the lower parts. In fact, studies suggest a higher risk for diabetes in people with the "apple shape" and lower risk in those who are "pear shaped."

Weight gain in the area of and above the waist (apple type) is more dangerous than weight gained around the hips and flank area (pear type). Fat cells in the upper body have different qualities than those found in hips and thighs.

General Adverse Effects of Being Overweight (Not Obese). It is still not clear if being overweight (a BMI of 25 - 29.9) hurts healthy people with no risk factors for serious illnesses.

According to one 2001 study, just being overweight increased the risk for developing diabetes, gallstones, hypertension, heart disease, stroke, and colon cancer. The risk rose according to how much the individuals were overweight. In any case, adults who are overweight in middle age face a poor quality of life as they age, with the quality declining the greater the weight. One study suggested, however, that being over 65 and overweight (but not obese) is not associated with higher mortality rates.

Some experts argue, in fact, that in anyone who is not severely obese, it is the unhealthy diet and sedentary lifestyle that causes harm -- not weight per se. In support of this argument, a British study found that overweight fit individuals had half the death rate of unfit trim individuals.

Being somewhat overweight may also have some benefits under specific circumstances:

In older women, some excess fat may produce extra estrogen that helps slow down bone loss, and insulates bones from fall-related injuries. It should be strongly noted, however, that when older overweight women lose weight they report less pain, improved vitality, and improved physical function. The same positive effect of overweight does not appear to hold in older men.
Conditioned athletes may have high BMIs because of very dense muscle tissue. Being fit in general may protect many overweight people.
Some evidence suggests that Caucasians have the lowest mortality with BMIs of 24.3 - 24.7 while African-Americans are better off in the range of 26.8 - 27.1.
Children may have higher normal fat levels during growth spurts and around puberty.

Individuals with a BMI of at least 30 have a 10 - 50% increased rate of death from all causes, compared with individuals with a BMI of 20 - 25. Mortality rates from many causes are higher in obese people, but heart disease is the primary cause of death. People who are obese have almost three times the risk for heart disease as people with normal weights. Being physically unfit adds to the risk.

Weight concentrated around the abdomen and in the upper part of the body (apple shape) is particularly associated with insulin resistance and diabetes, heart disease, high blood pressure, stroke, and unhealthy cholesterol levels. Fat that settles in a pear shape around the hips and lower body appears to have a lower association with these conditions.

Obesity poses many dangers to the heart and circulatory system.

Damage in the Blood Vessels. As people age, changes in body fat (particularly increasing abdominal fat) seem to cause stiffness in the aorta, the major blood vessel leading from the heart. Studies are finding higher levels of a factor called C-reactive protein (CRP) in people with obesity and abdominal fat. CRP is now considered to be a marker for inflammation and damage in the arteries. (Losing weight reduces CRP levels.)

High Blood Pressure. High blood pressure is the health problem most commonly associated with obesity, and the greater the weight, the greater the risk. High blood pressure carries serious risks of stroke, heart attack, and heart failure. The link between obesity and high blood pressure is complex, and may be a combination of genetic, population, and biological factors. Many studies have reported that modest weight loss is beneficial for reducing existing high blood pressure. [See In-Depth Report #14: High blood pressure.]

Heart Failure. An important 2002 study reported that obesity might account for 11% of heart failure cases in men and 14% in women. This link existed independently of other risk factors, such as high blood pressure, sleep apnea, and diabetes, which are also associated with obesity. The biologic mechanisms involved in obesity that lead specifically to heart failure are not clear. [See In-Depth Report #13: Heart failure.]

Unhealthy Cholesterol Levels and Lipid Levels. The effect of obesity on cholesterol levels is complex. Although obesity does not appear to be strongly associated with overall cholesterol levels, among obese individuals triglyceride levels (the major form of fat storage in the body) are usually high, while HDL levels (the "good" cholesterol) tend to be low. Both conditions are risk factors for heart disease. [See In-Depth Report #23: Cholesterol.]

Click the icon to see an image of coronary artery disease.

Stroke. Obesity is also associated with a higher risk for stroke. [See In-Depth Report #45: Stroke.]

Type 2 Diabetes and Insulin Resistance. Most people with type 2 diabetes are obese and, in fact, studies strongly suggest that weight loss may be the key in controlling the current epidemic of type 2 diabetes. The common factor appears to be insulin resistance. Insulin is a critical hormone in the use of sugar. In type 2 diabetes, different factors cause the body to become insulin resistant -- that is, the body can no longer respond properly to insulin. This has the effect of increasing sugar levels in the blood, the hallmark of diabetes. Both obesity and insulin resistance, at different phases, are marked by high levels of certain chemicals. It is not known yet if the higher levels are simply a product of obesity, or play some role in causing diabetes.

Insulin resistance is also associated with high blood pressure and abnormalities in blood clotting. Some research indicates that obesity, in fact, is the one common element linking insulin resistance, diabetes type 2, and high blood pressure. [See In-Depth Report #60: Diabetes - type 2.]

Metabolic Syndrome. Metabolic syndrome (also called syndrome X) is a pre-diabetic condition that is significantly associated with heart disease and higher mortality rates from all causes. The syndrome consists of obesity marked by abdominal fat, unhealthy cholesterol levels, high blood pressure, and insulin resistance. A 2002 study estimated that nearly a quarter of the U.S. population now has this condition. Even worse, according to a 2003 study, nearly a million American teenagers have this syndrome. A combination of weight loss and exercise is an effective treatment for this syndrome.

The American Cancer Society released new cancer prevention guidelines in September 2006. The guidelines stress the importance of keeping a healthy weight throughout life. The Society indicates that healthy weight is even more important than eating specific healthy foods, when it comes to cancer prevention.

Obesity has been associated with a higher risk for cancer in general and specific cancers in particular. Studies have also suggested that restricting calories reduces the risk for cancer. Some experts believe that effective weight control for children and adults could reduce cancer rates by 30 - 40%. One way obesity may increase the risk for cancer is its association with high levels of hormones called growth factors, which can trigger rapid cell production leading to cancer.

Uterine Cancers. The risk of uterine cancer in obese women appears to be two or three times higher than in thinner women.

Prostate Cancer. New studies from 2005 and 2006 report that obesity is associated with an increase in prostate cancer mortality, although not with the risk for less aggressive forms of prostate cancer.

Click the icon to see an image of prostate cancer.

Breast Cancer. Studies are mixed on the association between obesity and breast cancer. A number of studies have linked obesity to breast cancer in postmenopausal women, particularly in women who begin to gain weight after age 18.

Click the icon to see an illustrated series detailing a breast cancer surgery (mastectomy).

Gallbladder Cancer. Obese women are at higher risk for gallbladder cancer.

Gastrointestinal Cancers. A number of cancers in the gastrointestinal tract have been associated with obesity:

Cancer of the esophagus may be due to a higher incidence of gastroesophageal reflux disorder (heartburn) in people who are overweight.
Colon cancer has been linked to increased body mass in both men and women.
Pancreatic cancer and obesity have been weakly linked, with one study reporting a lower risk in overweight people who are physically active.

Click the icon to see an illustrated series detailing a colon cancer surgery.

Muscles and Bones

Obesity places stress on bones and muscles. Studies report that the incidence of osteoarthritis is significantly increased in people who are overweight. People who are obese are also at higher risk for carpal tunnel syndrome and other problems involving nerves in their wrists and hands. It should be noted that some weight may be protective against osteoporosis (loss of bone thickness).

Obesity increases the risk for the following mouth and eye disorders:

Gum disease
Cataracts
Maculopathy, an eye disease related to aging

Infertility. Abnormal amounts of body fat, either 10 - 15% too high or too low, can contribute to infertility in women. Obesity is specially related to certain infertility problems, such as uterine fibroids or menstrual irregularities. In men, obesity can contribute to reduced testosterone levels.

Effect on Pregnancy. Obesity has many dangerous effects on pregnancy. These include high blood pressure, gestational diabetes (diabetes, usually temporary, that occurs during pregnancy), urinary tract infections, blood clots, prolonged labor, and higher fetal death rate in late stages of pregnancy. Obesity is also associated with increased rates of cesarean delivery. Infants of women who are obese are also at higher risk for neural tube birth defects, which affect the brain or spine. Folic acid supplements, ordinarily effective in preventing these conditions, may not be as protective in overweight women.

Obesity is thought to be a risk factor for symptoms of adult-onset asthma. Though there is evidence that obesity causes wheezing and shortness of breath, it does not appear to be strongly associated with the disease mechanisms in the lungs that cause true asthma.

Obesity also puts people at risk for hypoxia, a condition in which there is not enough oxygen to meet the body's needs. Obese people need to work harder to breathe. They tend to have breathing muscles and lungs that do not work as well as those in thinner people.

The Pickwickian syndrome, named for an overweight character in a Dickens novel, occurs in severe obesity when lack of oxygen produces intense and chronic sleepiness and, eventually, heart failure.

Nonalcoholic Fatty Liver Disease. People with obesity, particularly if they also have type 2 diabetes, are at higher risk for a condition called nonalcoholic fatty liver disease, also called nonalcoholic steatohepatitis (NASH). This condition causes liver damage that is similar to liver injury seen in alcoholism. In some cases, it can be very serious and require liver transplantation. It occurs in about half of people with diabetes, and 20 - 50% of obese people, depending on how severe their obesity is. NASH can also occur in overweight children.

Gallstones. The incidence of gallstones is significantly higher in obese women and men. The risk for stone formation is also high if a person loses weight too quickly. In people on ultra-low calorie diets, gallstones may be prevented by taking ursodeoxycholic acid (Actigall).

Click the icon to see an image of gallstones.

People who are obese and nap tend to fall asleep faster and sleep longer during the day. At night, however, it takes them longer to fall asleep, and they sleep less than people with normal weights. In an apparent vicious circle, studies have suggested that obesity not only interferes with sleep but that sleep problems may actually contribute to obesity.

Sleep Apnea. Obesity, particularly the apple shape, is strongly associated with sleep apnea, which occurs when the upper throat relaxes and collapses from time to time during sleep. This collapse temporarily blocks the passage of air. Sleep apnea is increasingly being viewed as a potentially serious health problem, which may lead to complications such as heart disease and stroke. Some studies suggest that among overweight people, those who have sleep apnea have a greater risk of heart disease than those without it. In one study, the more obese a person with sleep apnea was, the higher the pressure on the airway, and therefore the greater the obstruction of the airway. Obstructive sleep apnea may also add to obesity, however, as sleepy people tend to be sedentary. Some studies indicate that treating sleep apnea may help people lose abdominal fat.

Narcolepsy. A small European study found a link between narcolepsy (a sleep disorder characterized by excessive daytime sleepiness with frequent daily sleep attacks) and high BMI.

Depression. A number of studies have reported an association between depression and obesity, particularly in obese women. There may be a number of factors to explain the link. In some cases of atypical depression, people overeat and may gain weight. Overweight people may also become depressed because of social problems and a poor self-image. In these cases, depression usually disappears when people lose weight.

There is evidence, however, that obesity itself may impair levels of tryptophan -- a chemical needed to make serotonin, a brain chemical associated with mental well-being. In one study, even after people lost weight, tryptophan levels were lower than normal.

There does not appear to be any association between depression and obesity in men.

Social Problems. One long-term study reported that overweight young women completed fewer years of school, were 20% less likely to be married, and had 10% higher rates of household poverty than their thinner peer. Obese young men were also less likely to be married, and their incomes were lower than their thinner peers. Nevertheless, studies consistently show that overweight males (both boys and men) are not as severely emotionally affected as females of any age. Women and girls tend to blame themselves for being heavy, while males tend to blame being overweight on outside factors.

Weight Loss and Maintenance

Even modest weight loss can reduce the risk factors for heart disease and diabetes. The simplest (but still difficult) approach to weight loss is reducing calories and exercising at least 150 minutes a week. Behavioral and mental changes in eating habits, physical activity, and attitudes about food and weight are also essential to weight management. For people who are very overweight and cannot lose weight through lifestyle changes, a number of effective weight-loss medications are available. For those with severe obesity, surgical procedures are proving to be very beneficial.

Some Tips for Losing Weight. The following are some general suggestions for dieters:

Start with realistic goals. Diet failure is extremely common, and the odds of significant weight loss are low, particularly in people with the highest weights. People who are able to restrict calories, engage in an exercise program, and get help in making behavioral changes can expect to lose between 5 - 10% of their current body weight. That is generally all that is needed to achieve meaningful health changes. Certainly, the distorted image of a super-thin female shape should not be anyone's goal.
Maintain a regular exercise program, assuming you have no health problems that will stop you. Choose a program that you enjoy. Check with your doctor about any health considerations. [See In-Depth Report #29: Exercise.]
Do not use hunger pangs as cues to eat. A stomach that has been stretched by large meals will continue to signal hunger for large amounts of food until its size reduces over time with smaller meals.
Be honest about how much you eat and start by recording all calories in writing. Studies suggest that when many people report their own calories intake they significantly underestimate their consumption of high-calorie and over-estimate the low-calorie foods. People who do not carefully note everything they eat tend to take in too many calories when they believe they are dieting.
Observe weekend eating. People tend to eat more on the weekends. If it is difficult to monitor all meals during the week, it be may be useful to at least track eating habits during the weekends.
Once the pounds are lost, do your best to keep the healthier weight. Make daily, even hourly, conscious decisions about eating and exercising activities. Such thinking, in many cases, can become automatic and not painful.
Don't give up, even after repeated weight loss failures. Most studies indicate that yo-yo dieting or weight cycling have no bad psychological or physical effects. Repeated dieting also does not harm the body's ability to burn calories efficiently.
Weight loss, in any case, should not be the only or even the primary goal for people concerned about their health. The success of weight loss efforts should be evaluated according to improvements in disease risk factors or symptoms, and by the adoption of healthy lifestyle habits, not just by the number of pounds lost.


Lifestyle	Reduce rate of eating. Keep food records. Eliminate environmental triggers to eating. Identify high-risk situations for overeating. Separate eating from other activities.
Exercise	Face up to emotional barriers to exercise. Understand the link between exercise and weight control. Establish reasonable exercise goals. Develop a plan for regular activity. Add increased activity into daily lifestyle.
Attitudes	Develop reasonable weight-loss goals. Avoid "all or none" thinking. Focus attention away from the scale and toward behavior. Uncouple weight from self-esteem. If you "fall off the wagon," take steps to ensure the situation does not repeat (recover from lapses with constructive action).
Relationships	Understand the key role of social support to health. Identify supportive others. Match personal style to support-seeking activities. Be specific in making support requests. Be assertive but reinforcing in drawing help from others.
Nutrition	Resist the temptation of popular fad diets. Eat with your health in mind; do not concentrate on what should be "off-limits." Eat with moderation in mind. Maximize fiber. Develop a tailored plan.
From Brownell KD. The LEARN Program for Weight Control. 7th ed. Dallas, Tex: American Health Publishing Company; 1998.

Weight Management

There are many approaches to dieting and many claims for great success with various fad diets. To date, although many diets achieve effective immediate weight loss, none has emerged as an effective tool for maintaining healthy weight. The only definite recommendation that can be made about any diet plan is to be sure it includes an exercise program, assuming there are no health problems to forbid it.

The original food pyramid, with four food groups, has been replaced with an updated food guide called "My Pyramid." This illustrates the relative proportions of different foods that make up a nutritious, well-balanced diet and includes exercise.

Calorie restriction has been the cornerstone of obesity treatment. The standard dietary recommendations for losing weight are the following:

As a rough rule of thumb, one pound of fat equals about 3,500 calories. A person could lose a pound a week by reducing daily caloric intake by about 500 calories a day. Naturally, the more severe the daily calorie restriction, the faster the weight loss. Very-low calorie diets have also been associated with better success, but extreme diets can have some serious health consequences.
To determine your daily calories requirements, multiply the number of pounds of ideal weight by 12 - 15 calories. The number of calories per pound depends on gender, age, and activity levels. For instance, a 50-year old woman who wants to maintain a weight of 135 pounds and is mildly active might require only 12 calories per pound (1,620 calories a day). A 25-year old female athlete who wants to maintain the same weight might require 25 calories per pound 2,025 (calories a day).
Fat intake should be no more than 30% of total calories. Most fats should be in the form of monounsaturated fats (such as olive oil). Saturated fats (found in animal products) should be avoided.

Extreme diets of less than 1,100 calories carry health risks. They are also often followed by bingeing or overeating, and a return to the obese state. Such diets often do not have enough vitamins and minerals, which must then be taken as supplements. Most of the initial weight loss is in fluids. Later, fat is lost, but so is muscle, which can account for more than 30% of the weight loss. No one should be on severe diets for longer than 16 weeks, or fast for more than 2 or 3 days. Severe dieting has unpleasant side effects including fatigue, intolerance to cold, hair loss, gallstone formation, and menstrual irregularities. There have been rare reports of death from heart arrhythmias when liquid formulas did not have sufficient nutrients. Pregnant women who excessively diet during the first trimester put their unborn children at risk for birth defects. Of note, those whose diets include a high intake of fluids and much reduced protein and sodium are at risk for hyponatremia, which can cause fatigue, confusion, dizziness, and in extreme cases, coma and death.

This dietary approach requires counting only grams of fat with the goal of achieving 30% or fewer calories from fat. One gram of fat contains nine calories, while one gram of carbohydrates or protein has only four calories. Fat in your diet converts more readily to fat in the body, compared with carbohydrates or proteins. Simply switching to low-fat or skimmed dairy products may be enough for some people.

There are possible drawbacks to this approach:

Some people who reduce their fat intake may not get enough basic nutrients, including vitamins A and E, folic acid, calcium, iron, and zinc. People on low-fat diets should eat a wide variety of foods and take a multivitamin supplement, if appropriate. Calcium deficiencies may be particularly harmful in women at risk for osteoporosis.
Many people start eating foods with too many carbohydrates, believing that they are not adding calories. No one should use a low-fat diet as an excuse for eating too many carbohydrates, particularly starchy foods and sugar. A high-calorie diet from any source will add pounds.
A small study in Norway found that a diet low in fat and high in carbohydrates ("carbs") increases symptoms of psychological distress, such as depression and anger. The study compared three different diets that had varying amounts of fat and carbohydrates in each. The diets contained the same amount of calories, but differed in the percentage and type of fat. People on the low-fat, high-carbohydrate diet reported more anger and depression compared with the other two diets.
Replacing fatty foods, such as cakes, cookies, and chips, with their commercial "low-fat" counterparts does not constitute a low-fat diet. These foods generally contain more sugar and hence calories, not to mention other ingredients, which have virtually no nutritional value. In fact, a 2002 study suggested that increasing sugar may, over time, reduce levels of HDL ("good") cholesterol.
Very low-fat diets may increase the risk for stroke from hemorrhage in the brain.

Some fat in a diet is essential. It should come from plant oils and fish, however, and not from animal products or hardened oils, such as margarine. Trans-fatty acids, found in hardened oils, are actually more of a risk factor for obesity than saturated fats from animal products, although both should be avoided.

Fiber and Complex Carbohydrates. In all cases, complex carbohydrates found in whole grains and vegetables are preferred over those found in starch-heavy foods, such as pastas, white-flour products, and potatoes. Fiber is an important component of many complex carbohydrates. Fiber is almost always found only in plants, particularly vegetables, fruits, whole grains, nuts, and legumes (beans and peas). One exception is chitosan, a dietary fiber made from shellfish skeletons. Fiber cannot be digested but passes through the intestines, drawing water with it, and is eliminated as part of feces content. The following are specific advantages from high-fiber diets (up to 55 grams a day):

Insoluble fiber (found in wheat bran, whole grains, seeds, nuts, and fruit and vegetable peels) has been associated with weight loss. Studies also suggest that diets rich in fiber from whole grains reduce the risk for type 2 diabetes.
Soluble fiber (found in dried beans, oat bran, barley, apples, citrus fruits, and potatoes) has important benefits for the heart, particularly for achieving healthy cholesterol levels and possibly benefiting blood pressure as well. Simply adding breakfast cereal to a diet appears to reduce cholesterol levels. People who increase their levels of soluble fiber should also increase water and fluid intake.

High-protein, low carbohydrate diets, such as the Atkins and South Beach diets, have been touted as effective ways to produce short-term weight loss. Because of their emphasis on fats and proteins, many experts are concerned about long-term health problems. A report in the March 2006 Lancet linked the Atkins diet to life-threatening complications that caused the death of one woman. The 40-year-old woman had a deadly buildup of acids called ketones in her blood, a condition called ketoacidosis. Ketoacidosis can cause coma and death. Ketones are a known by-product of high protein, low carbohydrate diets. At low levels they can cause nausea, lightheadedness, and bad breath.

The long-term effects of these diets are still unknown. For example, the Atkins diet restricts some vegetables and most fruits, which are known to protect against serious diseases such as heart problems and cancer. The diet may also cause too much calcium to build up in the urine. This can increase the risk for kidney stones and osteoporosis. In addition, high-protein intake, particularly from meat, can be harmful in people with kidney problems. Individuals at risk for kidney stones, or those who have other kidney problems, should not go on high-protein diets without talking to their doctor first. Unfortunately, many people with diabetes are at risk of kidney problems, which could reverse any possible benefits a high-protein diet may bring them. Eating a lot of meat has also been associated with certain common cancers, notably prostate and colon cancers. A 2002 study suggested that such diets during pregnancy may increase the risk for high blood pressure in the child.

Still, significant studies say that such diets improve cholesterol and blood sugar levels. Studies in 2002 and 2003 have indicated that these diets lower blood glucose levels, which can be important in people who are diabetic. The diets also reduce triglyceride levels (unhealthy fat molecules) and increases HDL (" good") cholesterol levels. High triglyceride and low HDL levels are important risk factors for heart disease, and are common in people with type 2 diabetes. Studies are mixed on whether this type of diet reduces overall cholesterol or LDL ("bad") cholesterol levels.

Experts that promote the low carbohydrate approach argue that heart problems from obesity are due to insulin disturbances from sugar imbalances. Therefore, they believe that restricting carbohydrates is the best approach for obesity -- especially for overweight people with diabetes. More research is needed, however, to determine the long-term impact of such diets on health.

High-protein, low-carbohydrate diets include Atkins, Protein Power, Sugar Busters, and Dr. Stillman. The Atkins diet is one of the most popular and has a four-phase program:

Induction. For the first 2 weeks, individuals consume no more than 20 grams of carbohydrates a day. The diet consists of pure protein and fats. There is no fruit, bread, grains, starchy vegetables, or dairy products other than cheese, cream, or butter. This phase is not suitable for children, pregnant women, or anyone with kidney disease.
On-going Weight Loss. After the first phase, individuals continue to lose weight while they increase carbohydrate levels by five grams each day.
Premaintenance. When individuals get close to their weight goal, they add another 10 grams of carbohydrates per day as long as they do not begin to gain weight. Weight loss is very slow at this time, but the individual is now getting used to maintenance.
Maintenance. Lifetime maintenance is usually between 40 and 100 grams of carbohydrates a day, depending on steady weight level.

Anyone who chooses this diet should prefer fish or soy products to meat as protein sources. Fish may reduce leptin, a hormone associated with fat storage and heart diseases, and would be the best protein source. People on this diet should also choose monounsaturated fats (as in olive oil) over saturated fats or trans-fatty acids fat. Patients often need supplements, at least a multivitamin and possibly calcium, chromium, omega-3 fatty acids (found in fish oil), and other supplements.

The South Beach and Zone diets encourage healthy fats. They also allow certain carbohydrates. For example the Zone uses healthy carbohydrates (vegetables and dried beans) and unsaturated fats. The South Beach diet uses carbohydrates that have a lower impact on blood sugar levels. This is called a low-glycemic index. Low-glycemic foods include barley, dried bean and peas, milk, strawberries, and apples. High-glycemic foods include refined grains, white bread, white potatoes, and bananas and other tropical fruits. The glycemic index was developed for use in diabetes -- not for weight loss. Nevertheless, there is some evidence that foods with low glycemic indexes may produce a feeling of fullness and so discourage further eating. As with any high-protein diets, people at risk for kidney stones, or those who have other kidney problems, should avoid these plans.

Replacing fats and sugars with substitutes may help many people who have trouble maintaining weight. In fact, in one 2003 study, people with type 2 diabetes used the artificial sweetener sucralose and a beta-glucan fat substitute (derived from oats) as part of a low-calorie diet. At the end of the 4 weeks, they achieved better weight, glucose control, and HDL levels than those on a standard diabetic diet.

Fat Substitutes. Fat substitutes added to commercial foods or used in baking deliver some of the desirable qualities of fat, but do not add as many calories. It should be stressed that eliminating all fats from a diet can be harmful to general health.

Fat substitutes include the following:

Stanols. Stanols are plant compounds used in margarines (Benecol, Take Control). Benecol is derived from pine bark and Take Control from soybeans. Two servings a day of either brand, as part of a low-fat, diet can lower LDL and total cholesterol by impairing its absorption in the intestinal tract. Some studies have reported that the use of stanols can allow lower doses of statins (cholesterol lowering medications). Stanols do not appear to block absorption of fat-soluble nutrients or vitamins, as olestra does.
Olestra (Olean) passes through the body without leaving behind any calories from fat. Studies suggest that it improves cholesterol levels and helps people lose weight when it is used to replace a third of normal dietary fats. (Note that simply adding snacks containing olestra does not appear to have any effect on cholesterol or weight loss.) Early reports of cramps and diarrhea after eating food containing olestra have not proven to be significant. Of greater concern is the fact that even small amounts of olestra deplete the body of certain vitamins and nutrients that may help protect against serious diseases, including cancer. The FDA requires that the missing vitamins be added back to olestra products, but not other nutrients. The side health effects, if any, are unknown.
Beta-glucan is a soluble fiber found in oats and barley. Products using this substance (e.g., Nu-Trim) may reduce cholesterol and have additional health benefits.

A number of other fat-substitutes are also available. Although studies to date are not showing any significant side effects, these products' effect on weight control is uncertain, since many of the products containing them may be high in sugar.

Artificial Sweeteners. Many artificial or low-calories sweeteners are available. A 2002 study confirmed that people who consumed artificial sweeteners and reduced their sugar intake weighed less over time than those who took in similar types and amounts of drinks and food containing sugar. It should be noted that using these artificial sweeteners should not give dieters a license to increase their fat intake. Studies indicate that consuming some sugar is not a significant contributor to weight gain, as long as the total amount of calories in the diet is under control. There is some public concern about chemicals used to produce many of these sweeteners, and the side effects seen in studies using rats. Natural low-calories sweeteners are available that may be more acceptable to many people.

Saccharin (Sugar Twin, Sweet n' Low, Sucaryl, and Featherweight). Saccharin has been used for years. Some studies found that large amounts of saccharin cause bladder cancer in rats. However, the rats were fed huge amounts that do not apply to human diets. Currently there is no evidence that saccharin causes cancer in humans.
Aspartame (Nutra-Sweet, Equal, NutraTase). Aspartame has come under scrutiny because of rare reports of nervous system disorders, including headaches or dizziness, associated with its use. People with phenylketonuria (PKU), a genetic condition, should not use it. Studies have not reported any serious health dangers, but some people may be sensitive to it.
Sucralose (Splenda). Sucralose has no bitter aftertaste and works well in baking, unlike other artificial sweeteners. It is made from real sugar by replacing part of the sugar with chlorine. Some people are concerned because chlorinated molecules used in major industrial chemicals have been associated with cancer and birth defects. Over 100 studies have been conducted on sucralose over a 20-year period, with no reports of such risks.
Acesulfame-potassium (Sweet One, SwissSweet, Sunette). It has been used in the U.S. since 1988 with no reported side effects.
Neotame (Neotame). Neotame is a synthetic variation of aspartame, but was developed to avoid its side effects. The association with aspartame has raised some concerns. Studies to date have reported no effects that would cause alarm, and it appears to be safe for general consumption.
D-tagatose (Tagatose). This reduced-calorie sweetener is made from lactose, which is the sugar found in dairy products and other foods. It may be especially beneficial for people with type 2 diabetes. It may also have additional benefits that help the intestinal tract.
Alitame (Aclame) is formed from amino acids, the building blocks of proteins. It has the potential to be used in all products that contain sugar, including baked goods.
Stevioside (Stevia). This is a natural sweetener derived from a South American plant. It is available in health food stores. People with diabetes should avoid alcohol-based forms. It has not been carefully tested.

Other sugar substitutes being investigated include glycyrrhizin (derived from licorice) and dihycrochalcone (derived from citrus fruits).

Some studies have reported good success with meal replacement beverages (Slim-Fast, Sweet Success). They contain major nutrients needed for daily requirements. Each serving typically contains between 200 - 250 calories and replaces one meal. (Note: Using them for all meals reduces calories to a severe extent and can be harmful.)

One study reported that most subjects who had undergone a 12-week weight loss program and then used Ultra Slim Fast supplements as directed for maintenance kept off more than half their weight loss after more than 3 years. A quarter of the subjects were still losing weight.

Medical evidence suggests that a diet rich in magnesium could reduce a person's risk of metabolic syndrome, a cluster of problems including obesity, high blood pressure, and high cholesterol. Metabolic syndrome can lead to diabetes and heart disease. A long-term study of thousands of Americans found that the risk for metabolic syndrome decreased in those who consumed the most magnesium from meals. The findings were published in the journal Circulation.

Commercial and Non-Profit Support Programs for Weight Loss. There are many different types of weight-loss program. (This report cannot address all of the many commercial and nonprofit weight-loss programs currently available, nor can it assess their claims.)

Taking off Pounds Sensibly (TOPS), a nonprofit support organization with many local chapters, is one of the least expensive programs, costing $20 a year.

Most of the commercial programs such as Weight Watchers, Jenny Craig, and NutriSystem offer individual or group support, lifestyle changes and packaged meals. These programs tend to be expensive. There are few well-conducted studies on these programs. One 2003 study reported modest weight loss over 2 years with Weight Watchers compared to a self-help program. There were no differences in heart risk factors.

Cognitive Behavioral Approaches. Most support programs use some form of cognitive-behavioral methods to change the daily patterns associated with eating. They are very useful for preventing relapse after initial weight loss. The following is a typical approach:

The patient first records in a diary all activity related to eating patterns, including the times of day, length of meal, emotional states, companions, and, of course, the kind and amounts of food eaten. Most people -- even professional dieticians, according to one study -- tend to underreport their daily calorie intake. However, writing it down is still a good method for increasing a person's awareness of eating patterns. (One patient said that recording circumstances surrounding relapses was a particularly valuable guide for understanding the stresses leading to her own eating behaviors.)
The patient reviews the diary with a therapist or group to set realistic goals and identify patterns that the patient can change. For instance, if food is normally eaten while watching television, then the patient may be advised to eat in another room instead.
Good eating habits are reinforced by rewards. These rewards are other pleasures that substitute the high calorie consumption and sedentary activities.

Behavioral modification has been shown to be helpful particularly for people who have an overly strong response to the taste, smell, and appearance of food. It also may be useful for binge eaters.

Stress-Reduction Techniques. Stress reduction and relaxation techniques may be helpful for some people with obesity, such as those whose weight is related to night-eating syndrome. [See In-Depth Report #31: Stress.]

Changing Sedentary Habits. Making even small changes in physical activity can expend energy. For example, simply getting up to turn the TV on and off instead of using the remote, and standing (instead of sitting) while talking on the phone may help a person lose up to five pounds a year. Other suggestions include cooking one's own food (instead of eating take-out or fast food), walking to as many places as possible, using stairs instead of escalators or elevators, and gardening. Even fidgeting may be helpful in keeping pounds off, and, in one study, chewing gum increased energy expenditure.

No one should rely on such mild activities, however, for serious weight loss. Only high levels of physical activity -- not just using up energy -- help prevent obesity.

Approach to Exercise. Exercise, which replaces fat with muscle, is the critical companion for any weight control program. In a one-year study, women who regularly averaged 3.5 days (176 minutes) of exercise each week lost significantly more weight than women who did not exercise regularly. Women who exercised more than 195 minutes a week lost nearly 7% of their abdominal fat.

People who exercise are more apt to stay on a diet plan. Exercise improves psychological well-being and replaces sedentary habits that usually lead to snacking. Exercise may even act as a mild appetite suppressant. Moreover, exercise improves overall health even with modest weight loss. In support of this, a British study found that overweight fit individuals had half the death rate of unfit trim individuals.

Be aware, however, that the pounds won't melt off magically. Losing significant weight requires both intensive exercise and calorie restriction. In addition, if a person exercises but doesn't diet, any actual pounds lost may be minimal, because denser and heavier muscle mass replaces fat. Nonetheless, regardless of weight loss, a fit body will look more toned and be healthier. In addition, exercise benefits the heart even with modest weight loss.

The following are some suggestions and observations on exercise and weight loss:

The more strenuous the exercise, the better the chances for short-term and long-term success. With intense exercise, the metabolism continues to burn calories before returning to its resting level. This state of elevated metabolism can last for as little as a few minutes after light exercise to as long as several hours after prolonged or heavy exercise.
Of the standard aerobic machines, the treadmill burns the most calories. It may be particularly effective when used in short multiple bouts during the day. In fact, frequent exercise sessions as short as 10 minutes in duration (about four times a day) may be the most successful exercise program for obese people.
Resistance, or strength, training is excellent for replacing fat with muscles. It should be performed two or three times a week.
As people slim down, their initial level of physical activity becomes easier and they burn fewer calories per mile of walking or jogging. The rate of weight loss slows down, sometimes discouragingly so, after an initial dramatic head start using diet and exercise combinations. People should be aware of this phenomenon and keep adding to their daily exercise program.
As people age, they also need to exercise more to keep off the same amount of weight.
Changes in fat and muscle distribution may differ between men and women as they exercise. Men tend to lose abdominal fat (which lowers their risk for heart disease faster than reducing general body fat). Exercise, however, does not appear to have the same effect on weight distribution in women. In one interesting study, women in aerobic and strength training programs lost fat in their arms and trunk, but did not gain muscle tissue in these regions.

Warning Note. Because obesity is one of the risk factors for heart disease and diabetes, anyone who is overweight must discuss their exercise program with a doctor before starting. Sudden demanding exercise, in such cases, can be very dangerous. [See In-Depth Report #29: Exercise.]

Medications

There are several different drugs used for weight loss. Unless specifically instructed by a doctor, people should use non-drug methods for losing weight. Except under rare circumstances, pregnant or nursing women should never take diet medications of any sort, including herbal and over-the-counter remedies.

A 2001 study reported that 7% of American adults use nonprescription weight-loss products. People must be cautious when using any weight-loss medications, including over-the counter diet pills and herbal or so-called natural remedies. Buying unverified products over the Internet can be particularly dangerous.

Green tea. Perhaps the best alternative advice for people who are overweight is to drink tea. Studies have indicated that regular tea drinking is associated with lower weight, particularly in people who drink it for years. Green tea specifically has been associated with increased energy expenditure. One study reported that people who took a green tea extract (Exolise) lost weight and reduced their waist size. Better evidence is needed to confirm the results on this supplement.

Thermogenic Approach to Weight Loss. An approach to weight loss called thermogenic (also hepatothermic) therapy is based on the idea that certain natural compounds have properties that enable the liver to increase energy in the cells and stimulate the metabolism. Theoretically, the result would be fat loss. Among the natural substances used in such products are EPA-rich fish oil, sesamin, hydroxycitrate, pantethine, L-carnitine, pyruvate, aloe vera, aspartate, chromium, coenzyme Q10, green tea polyphenols, aloe vera, DHEA derivatives, cilostazol, diazoxide, and fibrate drugs.

Nearly all the current over-the-counter dietary aids contain some combination of these ingredients. There is no evidence that any of these ingredients can produce weight loss, and some may even have harmful effects.

Chromium is a common ingredient in many diet supplements (e.g., Xenadrine, Dexatrim, Acutrim Natural, Twinlab Diet Fuel). It is claimed to specifically promote fat loss, rather than lean muscle loss. Some evidence suggests that niacin-bound chromium may improve insulin sensitivity. On the negative side, animal studies have suggested that chromium may have damaging effects on genetic materials in cells. This could cause sterility.

Ephedra, Ephedrine, and Ma Huang. The FDA does not allow the sale of drugs that contain ephedrine. In May 2004, the FDA banned the sale of dietary supplements that contain ephedra (also called Ma Huang). Ephedra has been linked to serious side effects, including strokes and heart attacks.

Brazilian Diet Pill. The US Food and Drug Administration (FDA) is warning consumers not to buy a product known as the "Brazilian diet pill." This product is labeled as a dietary supplement, but contains several chemicals found in powerful prescription drugs. The products are also known as Emagrece Sim and Herbathin dietary supplements.

Conjugated Linoleic Acid (CLA). Conjugated linoleic acid is found in many dietary products (e.g., Biosculpt Liquid, Body Success, GNC Optibolic Body Answers Dietary Formula). There is no evidence that it produces weight loss. Furthermore, there is some concern that CLA might increase insulin resistance and a dangerous inflammatory response in people with obesity.

Tiratricol. Over-the-counter products containing tiratricol, a thyroid hormone, have been sold for weight loss. Such products may increase the risk for thyroid disorders, heart attack, and stroke.

Laxative Actions in Natural Substances. Many dietary herbal teas contain laxatives, which can cause gastrointestinal distress, and, if overused, may lead to chronic pain, constipation, and dependency. In rare cases, dehydration and death have occurred. Some laxative substances found in teas include senna, aloe, buckthorn, rhubarb root, cascara, and castor oil.

Guar Gum. Some fiber supplements containing guar gum have also caused obstruction of the gastrointestinal tract.

Chitosan. Chitosan, a dietary fiber from shellfish, prevents a small amount of fat from being absorbed in the intestine. Well-conducted studies, however, have not found it to be effective. Products containing it include Cheat & Lean Fat Blocker, Natrol, Chroma Slim, and Enforma. People who are allergic to shellfish should not take these supplements.

Plantain. Dietary remedies that list the ingredient plantain may contain digitalis, a powerful chemical that affects the heart. NOTE: This substance should not be confused with the harmless banana-like plant also called plantain.

Orlistat (Xenical) can help about one-third of obese patients with modest weight loss, and can assist in long-term maintenance of weight loss. It works by slowing the absorption of fat (by about 30%) in the intestine. Studies indicate that between 50 - 80% of patients can achieve weight loss of 5% or greater, depending on other lifestyle changes. However, many people regain a significant portion of this weight back within 2 years. It does not work for all patients, however. In one survey of patients who took it, 10% gained weight or did not lose any, and 43% lost less than 5%. Nevertheless, orlistat may delay or even prevent the onset or progression of diabetes and improve cholesterol levels, regardless of weight loss.

The drug can cause gastrointestinal problems and may interfere with absorption of the fat-soluble vitamins A, D, and E and other important nutrients. The most unpleasant side effect is oily leakage of feces from the anus. Restricting fats can reduce this effect. People with bowel disease should probably avoid it. In spite of these side effects, most patients are able to tolerate this agent.

In February 2007, the FDA approved an over-the-counter (OTC) version of orlistat. It will be sold under the name alli, and will be available at half the prescription strength of Xenical. Those eager to use the new pill should consider its cost and modest benefits compared with its side effects, most commonly oily diarrhea. This pill, which prevents fat absorption from food, also increases the risk of not absorbing important nutrients from food while using it. The FDA recommends taking a daily multivitamin supplement when using alli.

Sibutramine (Meridia) helps balance the brain chemicals serotonin and norepinephrine. This helps increase metabolism, causes a feeling of fullness, and increases energy levels. It may be particularly useful for binge-eaters. Studies indicate that sibutramine is effective in achieving weight loss, although the weight loss slows considerably after the first 3 months. The drug also appears to improve cholesterol and lipid (fat) levels, and may have other effects that benefit the heart.

Side effects of sibutramine are common. They include dry mouth, constipation, and insomnia. In one study, almost half the patients dropped out as a result of these side effects. There have been reports of increases in heart rate and blood pressure while taking this medication, although a 2001 study indicates that blood pressure stabilizes over time.

At this time, people who have a history of high blood pressure, stroke, heart disease, or arrhythmias should not take this drug. People taking decongestants, bronchodilators (such as for asthma), monoamine oxidase inhibitors, or serotonin reuptake inhibitors should also avoid sibutramine.

Phentermine and Other Sympathomimetics. Sympathomimetics are drugs that act like the stress hormone (and chemical messenger) norepinephrine. These medications act as stimulants in the brain. Some are approved for treating obesity, but only for short-term use. They include:

Phentermine (Ionamin, Adipex-P, Fastin)
Benzphetamine (Didrex)
Phendimetrazine (Adipost, Bontril, Melfiat, Plegine, Prelu-2, Statobex)

Phentermine is the most commonly prescribed appetite suppressant, and is less expensive than orlistat or sibutramine. Its effects are not long lasting, however. It can also raise blood pressure. In addition, phentermine is associated with depression, which is already a problem in many cases of obesity. A combination (Phen-Pro) containing phentermine and the antidepressant fluoxetine (Prozac) is being investigated to help reduce this problem. Note: Neither phentermine nor such combinations are associated with the heart problems linked to the previous phentermine combination known as Fen-Phen (phentermine and fenfluramine).

Amphetamines. The amphetamines dextroamphetamine (Dexedrine), methamphetamine (Desoxyn), and phenmetrazine (Pleudin) are powerful stimulants. They were used most often in the past but are no longer prescribed for weight loss. These drugs improve mood and produce some modest weight loss over the short term, but carry serious risks of addiction, agitation, and insomnia.

Rimonabant. Rimonabant (Accompli) belongs to a new class of drugs called selective CB1 blockers. The drug is designed to block receptors in the brain associated with the regulation of eating. Rimonabant also targets receptors in fat tissue. The Rimonabant in Obesity-Lipids (RIO-Lipids) study looked at how rimonabant affected metabolic risk factors in high-risk overweight or obese patients with blood fat disorders. The study involved more than 1,000 participants. The findings, published in the November 2005 New England Journal of Medicine, said that people who took the drug significantly reduced their body weight and size of their waist.

Earlier studies involving the drug reported that obese patients treated with 20 mg of rimonabant lost significantly more weight and inches from their waist than patients who received placebo. The drug also appeared to have beneficial effects on raising HDL ("good") cholesterol levels.

Note: Fake rimonabant has been found for sale on several web sites. Patients should be aware that this drug is still experimental, and rimonabant is not available for sale. Buying and taking counterfeit drugs can have serious health consequences. In addition, an FDA advisory panel in April 2007 rejected the drug, citing fears it may cause psychiatric problems and seizures in some patients.

Axokine. Axokine is a type of drug called a ciliary neurotrophic factor. It signals the brain to suppress one's appetite. It is proving to be effective in achieving weight loss, and also improves cholesterol, lipid, and glucose levels regardless of food intake. It could be particularly helpful for people with type 2 diabetes. Early study results found that severely obese patient who took the drug lost more weight than those who took a dummy pill (placebo). Nearly half (46%) of patients who took the drug lost at least 10 pounds, compared to 5% of those who received the placebo. Study participants tolerated the drug well. There were no reports of serious side effects.

Zonisamide. Zonisamide (Zonegran) is an anti-seizure medication that is also being investigated for weight loss. In one study, patients who took it lost more weight than those on placebo. Zonisamide increases the risk for kidney stones, which can be reduced with increased fluid intake and citrate. It has also been associated with reduced sweating and a sudden rise in body temperature, especially in hot weather. Other side effects include dizziness, forgetfulness, headache, and nausea.

Topiramate. Topiramate (Topamax) is another anti-seizure medication being investigated for weight reduction. Three clinical trials have reported that patients given topiramate lost more weight than those receiving placebo. Weight loss was sustained for up to 1 year. The drug is also being studied for binge-eating disorders associated with obesity.

Other Treatments

Surgical procedures for obesity may be appropriate for some dangerously obese people, and may reduce heart problems and many of the risks associated with obesity. These risks include high blood pressure, sleep apnea, and diabetes. In fact, some evidence suggests that surgery may provide much greater control of weight and diabetes than nonsurgical weight-loss methods. Studies are reporting significant reductions in diabetes, and the need for diabetic medications, after surgery. Other medical conditions that often improve after surgery include heartburn, arthritis, and other joint and circulation problems.

Bariatric surgeries produce weight loss through one of two approaches:

Restrictive Banding Procedures. These procedures restrict the amount of food by closing off parts of the stomach with bands.
Malabsorptive Bypass Procedures. This approach restricts the amount of food and also reduces absorption by using a bypass of parts of the intestine.

The malabsorptive procedures are more successful in achieving weight loss than the banding approach, but they carry a greater risk for nutritional deficiencies.

Most people who have bariatric surgery lose about two-thirds of excess weight within 2 years. In addition, diseases associated with obesity (such as diabetes, high blood pressure, sleep apnea, joint pain, and incontinence) often improve.

Researchers at the Mayo Clinic looked at records from patients who had the surgery between 1990 and 2003. They found that those who had bariatric surgery reduced their risk of cardiovascular events such as a heart attack much more than those who lost weight without surgery. The findings were published in the September 2005 Mayo Clinic Proceedings.

Other studies have shown that even though most patients maintain significant weight loss, the majority regain about to 10% of their weight. Patients must still develop a healthy life style and be calorie conscious after the operation. Follow-up must be life-long.

Any surgical candidate must have failed consistently in losing weight through less invasive methods. Experts recommend bariatric surgery only for the following:

Those whose BMI is above 40 (about 100 pounds overweight)
Those with BMIs of over 35 who have type 2 diabetes or serious obesity-related medical problems
Those with severe obesity that interfered with employment, normal physical activity (e.g., walking), and important relationship

About a third of people who undergo these procedures achieve normal weight, and 80% experience some weigh loss. They are less successful than the bypass procedures, but carry a lower risk of nutritional deficiencies.

Vertical Banded Gastroplasty. Vertical banded gastroplasty (VBG) was the most common restrictive procedure. It involves creating a hole through both stomach walls and sealing the edges with a staple. This narrows the stomach, similar to a funnel, and allows only small amounts of food to pass through.

Laparoscopic Gastric Banding. Laparoscopic gastric banding (the Lap-Band) usually does not require a major incision and avoids some of the major complications of gastric bypass:

It employs an adjustable silicone band that is placed around the upper part of the stomach.
A small balloon-like reservoir attached to the band under the abdominal skin contains saline, which can be added or removed to tighten or loosen the band.
The procedure restricts the amount of food a person can eat and gives the feeling of fullness.

The band is removable, if necessary. Studies to date indicate that the intestinal tract returns to normal afterward. Studies, including those done in the elderly, have reported significant weight loss and improved quality of life with the procedure.

Malabsorptive procedures produce greater weight loss than restrictive procedures. Patients generally achieve about two-thirds of their weight loss within 2 years. Furthermore, in a 2003 study, after standard bypass surgery, 83% of patients with type 2 diabetes experienced normal blood glucose levels and the rest had significant reductions.

Roux-en-Y Gastric Bypass Procedure. This is the most common and successful malabsorptive surgery in the United States. It involves creating a small stomach pouch that serves as a reservoir and restricts food intake. The pouch eventually holds up to 3 ounces of food and has a small outlet that delays emptying and causes a feeling of fullness. Then the surgeon creates a Y-shaped section in the small intestine that attaches to the pouch. This section allows food to bypass the lower stomach and upper part of the intestine. One 2003 study reported that this procedure was associated with significant weight loss, and 80% of patients with type 2 diabetes were able to reduce their medications. A more recent study, published in the March 14, 2006, issue of Archives of Surgery, found that gastric bypass surgery also helps lower the blood pressure of very obese patients.

The procedure produces greater and more sustained weight loss than banding procedures, but it is also more complicated, and carries a higher risk of nutritional deficiencies. Laparoscopy techniques, which are less invasive, are now preferred over open surgery. They achieve equally good results with fewer complications.

Biliopancreatic Diversion. This procedure is more complicated and removes portions of the stomach. The pouch that is created attaches directly to the lower part of the small intestine. It poses a higher risk for nutritional deficiencies than other procedures and is not used as often.

Click the icon to see an image of gastric bypass surgery.

General Side Effects and Complications. Side effects and complications of bariatric procedures are common, and up to 25% of patients require corrective or repeat procedures. After any of these procedures people must chew all their food carefully, and they cannot eat large amounts of food at one time. If patients do not follow these guidelines, they will experience nausea, abdominal distress, or both.

Complications from any bariatric procedure includes the following:

Vomiting: This is the most common complication, and it is most common with banding procedures.
Nutritional deficiencies: There is a strong risk of nutritional deficiencies, particularly with malabsorptive operations. This complication can lead to anemia and increase the risk of bone loss and osteoporosis. Taking enough mineral and vitamin supplements is important after bariatric surgery.
Deep-vein thrombosis: There is a significant risk for deep-vein thrombosis (blood clots in the veins).
Abdominal hernia: This is another common complication. Newer, laparoscopic techniques do not carry this risk, but not all individuals are candidates for this less-invasive approach.
Rapid weight loss after surgery: This complication puts people at high risk for gallstones.
Women who wish to be pregnant should wait until their weight has stabilized. Rapid weight loss and nutritional deficiencies can harm the fetus.

People at highest risk for complications are those with heart or lung problems, severe obesity, and a history of abdominal surgeries. The mortality rate from bariatric surgeries is 0.2%, which is lower than the morality rates from severe obesity itself. Other surgical variations and less invasive techniques using laparoscopy have been developed.

Specific Complications of Restrictive Banding Procedures. Nausea, vomiting, or both occurs in half the patients, and severe heartburn occurs in a third. Device-related complications include band slippage, pouch dilation (widening), or both in nearly a quarter of patients, and obstruction in 12% of patients. Very serious complications are rare, but include blood clots, bleeding, infection, pneumonia, and perforation (tearing) of the stomach.

Specific Complications of Malabsorptive Bypass Procedures. Vomiting often occurs. Nutritional deficiencies occur more often in these procedures. The so-called dumping syndrome is a common unpleasant side effect, which occurs when food waste moves too quickly through the intestine. Symptoms include nausea, weakness, sweating, and faintness (particularly after eating sweets).

Spot Exercising. Anyone seeking to lose weight must expect that the results may not be as cosmetically satisfying as one would wish. Spot exercising (training particular areas of the body) is ineffective in reducing fat in specific locations because exercise draws on fat stores throughout the body. Gimmicky devices such as bust developers, vacuum pants, and exercise belts do absolutely nothing to reduce fat or add bulk in specific locations. Electrical pads wrapped around the waist, arms, or thighs were reported to cause burns and fires.

Cellulite-Removal Creams. Many women try to reduce fat in their thighs (cellulite) with creams that contain aminophylline (Skinny Dip, Thermojetics Body Toning Cream, Smooth Contours). Studies provide no evidence that these creams are effective. Their apparent effect on fat may simply be from narrowing blood vessels and forcing water from the skin, which could be dangerous for people with blood flow problems.

Endermologie. Endermologie uses motorized rollers and regulated suction to smooth out cellulite. In one study, about 28.6% of patients reported improved appearance after using it.

Liposuction. Liposuction eliminates fat in specific areas, such as the abdomen, thighs, buttocks, or knees. Special instruments are inserted through the skin into the pockets and suction is used to move the fat, break it up, and remove it. Small tubes may be used to drain blood and fluid during the first few days. The pain after the operation can be severe and often the skin does not contract, resulting in a flabby look. Complications can include burns from the vibrators, bruising, blood clots, and bleeding. Weight gain generally tends to develop in other locations after the operation. Some doctors are using this procedure in overweight people with diabetes to remove abdominal fat. Although there is no proof that it has an effect on diabetes, some experts believe the procedure deserves attention.

Liposuction is not recommended for major weight loss.

Resources

www.healthierus.gov/dietaryguidelines -- Dietary Guidelines for Americans 2005
www.naaso.org -- North American Association for the Study of Obesity
www.eatright.org -- American Dietetic Association
www.nutrition.gov. -- Nutrition.gov
www.asbs.org -- American Society for Bariatric Surgery
www.cnpp.usda.gov -- Center for Nutrition Policy and Promotion
http://fnic.nal.usda.gov -- Food and Nutrition Information Center
www.americanheart.org -- American Heart Association
www.nationaleatingdisorders.org -- National Eating Disorders Organization
www.aabt.org -- Association for Advancement of Behavior Therapy
www.fda.gov -- Food and Drug Administration
http://win.niddk.nih.gov -- Weight-Control Information Network

References

US Food and Drug Administration FDA Approves Orlistat for Over-the-Counter Use. Rockville, MD: National Press Office; February 7, 2007.

Ogden CL, Carroll MD, Curtin LR, McDowell MA, Tabak CJ, Flegal KM. Prevalence of overweight and obesity in the United States, 1999-2004. Journal of the American Medical Association. 2006; 295:1549-1555.

National Center for Health Statistics. Chartbook on Trends in the Health of Americans. Health, United States, 2005. Hyattsville, MD: Public Health Service. 2005

National Institute of Diabetes and Digestive and Kidney Diseases - Weight-control Information Network. Statistics Related to Overweight and Obesity. Available online.

National Center for Health Statistics. Prevalence of Overweight Among Children and Adolescents: United States, 2003-2004.

Morino M, Toppino M, Bonnet G, Rosa R, et al. Laparoscopic vertical banded gastroplasty for morbid obesity. Assessment of efficacy. Surg Endosc. 2002 Nov;16(11):1566-72.

Brethauer SA, Schauer PR, Chand B. Risks and benefits of bariatric surgery: Current evidence. Cleveland Clinic Journal Of Medicine. 2006 Nov; 73(11): 993-1007.

Rosenthal RJ, Szomstein S, Kennedy CI, et al. Laparoscopic surgery for morbid obesity: 1,001 consecutive bariatric operations performed at The Bariatric Institute, Cleveland Clinic Florida. Obes Surg. 2006 Feb;16(2):119-24.

He K, Liu K, Daviglus ML, et al. Magnesium Intake and Incidence of Metabolic Syndrome Among Young Adults. Circulation. 2006: Published online before print. March 27, 2006.

Chen TY, Smith W, Rosenstock JL, Lessnau KD. A life-threatening complication of Atkins diet. Lancet. 2006 Mar 18;367(9514):958.

Lopez-Jimenez F, Bhatia S, Collazo-Clavell ML, Sarr MG, Somers VK. Safety and efficacy of bariatric surgery in patients with coronary artery disease. Mayo Clin Proc. 2005 Sep;80(9):1157-62.

Sidhaye A, Cheskin LJ. Pharmacologic treatment of obesity. Adv Psychosom Med. 2006;27:42-52.

Fernstrom JD, Courcoulas AP, Houck PR, Fernstrom MH. Long-term changes in blood pressure in extremely obese patients who have undergone bariatric surgery. Arch Surg. 2006 Mar;141(3):276-83.

Despres JP, Golay A, Sjostrom L; Rimonabant in Obesity-Lipids Study Group. Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia. N Engl J Med. 2005 Nov 17;353(20):2121-34.

Lanningham-Foster L, Nysse LJ, Levine JA. Labor saved, calories lost: the energetic impact of domestic labor-saving devices. Obes Res. 2003 Oct;11(10):1178-81.

Review Date:
6/14/2007
Reviewed By:
A.D.A.M. Editorial Team: Greg Juhn, M.T.P.W., David R. Eltz, Kelli A. Stacy. Previously reviewed by Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital (4/30/2007).

A.D.A.M. Copyright

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Liposuction

admin — Thu, 04 Sep 2008 19:03:08 -0700

Overview

Definition
Alternative Names
Description
Indications
Risks
Expectations after surgery
Convalescence

Illustrations

Fat layer in skin

Liposuction - series

HEALTH GUIDE REFERENCE FROM A.D.A.M

Definition

Liposuction is the removal of excess body fat by suction using special surgical equipment. A plastic surgeon typically does the surgery.

Alternative Names

Fat removal - suctioning

Description

Liposuction is a popular type of cosmetic surgery. It removes unwanted deposits of excess fat, to improve body appearance and to smooth irregular or distorted body shapes. The procedure is sometimes called body contouring.

Liposuction may be useful for contouring under the chin, neck, cheeks, upper arms, breasts, abdomen, buttocks, hips, thighs, knees, calves, and ankle areas.

However, liposuction is a serious surgical procedure and may involve a painful recovery. Because liposuction can have serious or occasionally fatal complications, you should carefully think about your decision to have this surgery.

Before your surgery, you will have an initial patient consultation, which will include a history, physical exam, and a psychological evaluation. You may need to bring someone (such as your spouse) with you during the visit. You may need a second consultation to give you time to think over the surgery.

You should feel free to ask questions, and to feel satisfied with the answers to those questions. A properly informed person makes a better patient. You must understand fully the pre-operative preparations, the liposuction procedure, and the post-operative care. Understand that liposuction may enhance your appearance and self-confidence, but it will probably not give you your ideal body.

Several different liposuction procedures exist:

Tumescent liposuction (fluid injection) is the most common type of liposuction. It involves injecting a large amount of medicated solution into the areas before the fat is removed (sometimes, the solution may be up to three times the volume of fat to be removed). The fluid is a mixture of local anesthetic (lidocaine), a drug that contracts the blood vessels (epinephrine), and an intravenous (IV) salt solution. The lidocaine in the mixture helps to numb the area during and after surgery, and may be the only anesthesia needed for the procedure. The epinephrine in the solution helps reduce the loss of blood, the amount of bruising, and the amount of swelling from the surgery. The IV solution helps remove the fat more easily and it is suctioned out along with the fat. This type of liposuction generally takes longer than other types.

The super-wet technique is similar to tumescent liposuction. The difference is that not as much fluid is used during the surgery--the amount of fluid injected is equal to the amount of fat to be removed. This technique takes less time; however, it often requires sedation with an IV or general anesthesia.

Ultrasound-assisted liposuction (UAL) is a fairly new technique, used in the U.S. since 1996. During this technique, ultrasonic vibrations are used to liquefy fat cells. After the cells are liquefied, they can be vacuumed out. UAL can be done in two ways, external (above the surface of the skin with a special emitter) or internal (below the surface of the skin with a small, heated cannula). This technique may help remove fat from dense, fiber-filled (fibrous) areas of the body such as the upper back or enlarged male breast tissue. UAL is often used together with the tumescent technique, in follow-up (secondary) procedures, or for greater precision. In general, this procedure takes longer than the super-wet technique.

Before the day of surgery you may have blood drawn and be asked to provide a urine sample. This allows the health care provider to rule out potential complications. If you are not hospitalized, you will need a ride home after the surgery.

A liposuction machine and special instruments are used for this surgery. The surgical team first preps the operative site and administers either local or general anesthesia. Through a small skin incision, a suction tube with a sharp end is inserted into the fat pockets and swept through the area where fat is to be removed. The dislodged fat is "vacuumed" away through the suction tube. A vacuum pump or a large syringe provides the suction action. Several skin punctures may be needed to treat large areas.

After the fat is removed, small drainage tubes may be inserted into the defatted areas to remove blood and fluid that gather during the first few days after surgery. If you lose a lot of fluid or blood during the surgery, you may meed fluid replacement (intravenously) or a blood transfusion.

After the surgery, bandages are applied to keep pressure on the area and stop any bleeding, as well as to help maintain shape. Bandages are usually kept in place for at least 2 weeks. Your doctor may call you from time to time to check on your health and to monitor your healing. A visit back to the surgeon after 5-7 days is often recommended. Sometimes people gain weight after liposuction. This is due to the increased fluid from surgery.

Liposuction may or may not require a hospital stay, depending on the location and extent of surgery. Liposuction can be done in an office-based facility, in a surgery center on an outpatient basis, or in a hospital. For reasons of cost and convenience, liposuction of smaller volumes is usually done as an outpatient. You may need to stay in a hospital if a larger volume of fat is being removed, or if you are having other procedures done at the same time.

Indications

The following are some of the uses for liposuction:

Cosmetic reasons, including "love handles," fat bulges, or an abnormal chin line.
To improve sexual function by reducing abnormal fat deposits on the inner thighs, thus allowing easier access to the vagina.
Body shaping for people who are bothered by fatty bulges or irregularities that cannot be removed by diet and/or exercise.

Liposuction is generally NOT appropriate for these uses:

As a substitute for exercise and diet, or as a cure for general obesity. However, it may be used to remove fat from isolated areas at different points in time.
As a treatment for cellulite (the uneven, dimpled appearance of skin over hips, thighs, and buttocks).
In certain areas of the body, such as the fat on the sides of the breasts, because the breast is a common site for cancer.

Many alternatives to liposuction exist, including a tummy tuck (abdominoplasty), removal of fatty tumors (lipomas), breast reduction (reduction mammaplasty), or a combination of plastic surgery approaches.

Risks

Certain pre-existing conditions should be checked and brought under control before liposuction, including:

History of heart problems (heart attack)
High blood pressure
Diabetes
Allergic reactions to medications
Pulmonary problems (shortness of breath, air pockets in bloodstream)
Allergies (antibiotics, asthma, surgical prep)
Smoking, alcohol, or drug use

There are also risks associated with liposuction, including:

Shock (usually when not enough fluid is replaced during the surgery)
Fluid overload (usually from the procedure)
Infections (strep, staph)
Bleeding, blood clot
Tiny globules of fat in the bloodstream that block blood flow to tissue (fat embolism)
Nerve, skin, tissue, or organ damage or burns from the heat or instruments used in liposuction
Uneven fat removal (asymmetry)
Drug reactions or overdose from the lidocaine used in the procedure
Scarring (skin surface may be irregular, asymmetric, or even "baggy," especially in older people)

Finally, make sure to review and sign any informed consent (legal) and permission forms for photographs.

Expectations after surgery

Most informed patients are satisfied with the cosmetic result of their surgery. Informed patients understand that there are limits to what liposuction can accomplish.

If you are having a large amount of fat removed, or you are being put to sleep (general anesthesia) for the procedure, you should expect to be admitted to the hospital. If you are having a smaller amount of fat removed with just the area numbed (local anesthesia), you may be able to have it done on an outpatient, same-day basis, as long as the office has the proper equipment and oxygen on hand.

Convalescence

The liposuctioned area may appear larger than before surgery because of swelling. You must wear a tight stocking, girdle, or snug elastic dressing over the treated area to reduce swelling and bleeding, and to help shrink the skin to fit the new contour. You should wear this garment continuously for 2 to 3 weeks.

You will likely have swelling, bruising, numbness, and pain, but it can be managed with medications. The stitches will be removed in 5 to 10 days. Antibiotics may be prescribed to prevent infection.

You may feel sensations such as numbness or tingling, as well as pain, for weeks after the surgery. Walk as soon after surgery as possible to help prevent blood clots from forming in your legs. Avoid more strenuous exercise for about a month after the surgery.

You will start to feel better after about 1 or 2 weeks following liposuction surgery. You may return to work within a few days of the surgery. Bruising and swelling usually go away within three weeks; however, you may still have some swelling several months later.

Your doctor will check your progress through follow-up visits. If you have any questions or problems between office visits, call your doctor. Your new body shape will begin to emerge in the first couple of weeks; however, the improvement won't become more visible until about 4 to 6 weeks after surgery. By exercising regularly and eating a healthy diet, you can help maintain your new shape.

Review Date: 5/3/2007

Reviewed By: Robert A. Cowles, M.D., Assistant Professor of Surgery, Columbia University College of Physicians and Surgeons, New York, NY. Review provided by VeriMed Healthcare Network.

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