FitSugar

5 Ways to Deal with Side Stitches

FitSugar — Wed, 25 Jun 2008 03:30:00 -0700

You're running full speed ahead and suddenly you get an excruciating pain in your side: the dreaded side stitch. Nothing kills a good workout like getting cramps and luckily there are a few things you can do to keep them at bay. Here are five easy to follow tips:

Try to avoid eating one to two hours before a workout. If you must eat then avoid fatty foods and proteins and stick to carbohydrates.
Hydrate before and during exercise; contrary to popular belief, dehydration can increase muscle cramps.
Focus on your breathing. Take a few deep breaths every once in a while to stretch your diaphragm as well as to ensure that all parts of your body are receiving the amount of oxygen they need to keep going.
Once you first experience cramping slow down your pace until the pain subsides.
Massaging or pressing on the area and bending over can help reduce the pain.

Do you have a no-fail remedy for side stitches? Share them below.

Source

You Asked: What Causes Side Stitch When Running?

FitSugar — Mon, 01 Jun 2009 09:00:00 -0700

Dear Fit,
Sometimes when I run, I get this twanging pain right below my rib cage. This side stitch aching is so uncomfortable that I have to stop running and wait for it to go away. What causes this pain and is there anything I can do to prevent it from happening in the first place?
- Stitched Up

I feel your pain and have also been sidelined by the awful stitch in my side. To find out what causes this sensation and how to prevent it read more.

There's actually a very scientific explanation for the side stitch. Researchers believe it's caused when the ligament that attaches your liver to your diaphragm becomes overstretched. Breathing in and out heavily combined with the jarring motions of running can cause this pain, and actually those who exhale when their right foot hits the ground are more prone to side stitches. That's because when the right foot hits the ground, it pulls the liver down and the exhale is simultaneously forcing the diaphragm up, so the ligament gets overstretched, and you're left with that sharp, nagging pain.

To prevent the dreaded side stitch, you can try concentrating on exhaling as your left foot hits the ground, but that may not feel natural to you. So focus on taking deep, even breaths as you run. When you exhale fully, the diaphragm can lower completely, which allows the ligament to relax. Also avoid eating one to two hours before a run, but make sure you've had water since dehydration can lead to muscle cramps.

If you're suffering from a side stitch in the middle of a run, slow down your pace and see if that helps. If not, stop completely and press your hand into the right side of your body and push up. This will lift your liver slightly and bring it closer to your diaphragm, so it's not overstretched. Once the pain goes away, feel free to jump back on the running wagon.

Source

Stitch In the Side Explained

FitSugar — Tue, 06 Mar 2007 08:45:00 -0800

Do you ever get the annoying and painful stitch in your side when you are running? I do and I really don't like the sensation and went looking for a "cure."

It seems that there was no good explanation for the phenomenon until recently, and before that it was just referred to as exercise related transient abdominal pain (ETAP). How's that for vague? The pain is caused when the ligament that attaches your liver to your diaphragm gets stretched. Most runners tend to exhale every 2 to 4 step and those that exhale with stepping on the right foot tend to be the ones who suffer from the stitch. When the right foot hits the ground it pulls the liver down and the exhale is simultaneously forcing the diaphragm up, so the ligament gets over stretched, and that causes the pain.

To cure the pain, stop running immediately, reach your fingers into the right side of your belly and push your liver up. Breathe in and out evenly as you do this. Hopefully you can return to running with no pain.

Fit's Tip: To avoid getting the stitch in the first place, focus on taking deep breaths while running since short and shallow breaths tend to make the diaphragm spasm.

Glaucoma

FitSugar — Wed, 08 Oct 2008 17:35:34 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approval

Bimatoprost (Lumigan) has been approved as a first-line treatment for open-angle glaucoma.

Glaucoma Cases Increasing Worldwide

About 60 million people worldwide will have glaucoma by 2010, and the number will increase to nearly 80 million by 2010, according to a recent study in the British Journal of Ophthalmology.

Weightlifting May Increase Glaucoma Risk

Weightlifting can cause a temporary increase in intraocular eye pressure (IOP), and holding your breath while lifting weights further increases IOP, suggests a 2006 study in the Archives of Ophthalmology. Doctors should ask patients with normal-tension glaucoma if they engage in weightlifting exercise.

IOP and Posture

IOP increases in some people when they are lying prone during sleep, yet glaucoma exams measure IOP in patients while they are sitting upright and awake, notes a 2006 study in the Archives of Ophthalmology. The researchers caution that posture may affect the interpretation of IOP readings.

Pregnancy and Glaucoma

The course of glaucoma is unpredictable during pregnancy -- IOP may remain stable in some women and increase in others, indicates a 2006 study. Although glaucoma eye drops can increase the risk of some pregnancy problems, especially during the first trimester, some pregnant women may need to continue to take glaucoma medication. Be sure your ophthalmologist carefully evaluates your individual case and explains the risks and benefits of taking medication during pregnancy.

Diabetes and Glaucoma

Type 2 diabetes increases the risk for open-angle glaucoma (the most common type of glaucoma). People with type 2 diabetes need to get regular glaucoma screenings.

Glaucoma Surgery

Tube shunts may work better than trabulectomy surgery for some patients with glaucoma, suggests a 2007 study.
Phacoviscocanalostomy, a surgery procedure that combines phacoemulsification (used for cataract surgery) and viscocanalostomy (used for glaucoma surgery), is safe and effective for patients who have both glaucoma and cataracts, indicates a 2006 study.

Introduction

Glaucoma is defined as a disease of the optic nerve, in which the nerve cells in the front of the optic nerve (the ganglion cells) die. The process is irreversible. Previously, it was believed that glaucoma was almost always due to increased intraocular pressure. However, glaucoma has been observed in many patients with normal and even low eye pressure, so the definition now rests on the damage to the optic nerve.

The Aqueous Humor. In understanding of glaucoma, it is important to first consider aqueous humor, the clear, watery fluid that circulates continuously through the front (anterior) chamber of the healthy eye and is a primary focus of glaucoma research. (This fluid is not related to tears, nor is it the dense jelly-like substance called vitreous humor that is contained in the rear chamber.) It serves two important functions in the eye:

It nourishes the area around the colored iris and behind the cornea.
It exerts pressure to help maintain the eye’s shape.

Draining the Fluid and Intraocular Pressure. The aqueous fluid is continuously produced within the front of the eye, causing pressure known as intraocular pressure (IOP). To offset the in-flowing fluid and to maintain normal IOP, the fluid drains out between the iris and cornea (an area known as the drainage angle). It does so through two channels within this angle:

The trabecular meshwork, a sponge-like, porous network, and its connecting passageways are referred to as the "conventional" outflow pathway. Most of the eye fluid outflow occurs in this region and flows from the trabecular meshwork to a group of vessels encircling the anterior chamber, called Schlemm's canal. From here, the fluid enters collection chambers and then flows out into the general blood circulatory system of the body.
The uveoscleral pathway is located behind the trabecular meshwork and is called the "unconventional" pathway. Up to 30% of the fluid flows out through this channel.

Intraocular Eye Pressure. Previously, it was believed that glaucoma was almost always due to an abnormal rise in intraocular 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.

Increased IOP is, indeed, present in most cases of glaucoma, but some patients have normal IOP, which is usually maintained at measurements of 10 - 20 mm Hg. Measurements above this, however, do not necessarily predict glaucoma. For example, only about 10% of people with IOP levels between 21 - 30 mm Hg will actually develop glaucoma. This still puts such individuals at considerable risk for glaucoma, however.

Most people with glaucoma have the form called primary-open-angle glaucoma (also called chronic open-angle glaucoma). Open-angle glaucoma is essentially a plumbing problem.

The disease process may occur as follows:

The drainage angle remains open, but tiny drainage channels in the trabecular meshwork pathway become clogged. This pathway is responsible for most aqueous humor fluid outflow. An imbalance then occurs as fluid continues to be produced but does not drain out efficiently. Experts have still not definitely determined the precise area in the pathway where the blockage is most likely to occur. (In rare instances the pressure is high because the eye produces too much aqueous humor.)
The fluid in the eye’s anterior chamber builds up and increases pressure within the eye. This is called intraocular pressure (IOP).
The intraocular pressure exerts force on the optic nerve at the back of the eye.
Over time, the persistent pressure or other factors irreversibly damages the delicate long fibers of the optic nerve, called axons, which convey images to the brain.
As these axons die, the small cup-like head of the optic nerve may eventually collapse into an enlarged irregular shape.

Optic nerve damage is the basic glaucoma condition. If it is untreated, eventually the nerve deteriorates until a person loses sight, first in the peripheral vision (the vision in the "corner of the eyes"). If it becomes severe, the person loses central vision (in the middle of the eyes), and may eventually become blind. (Blindness is fortunately nearly always preventable with early treatment.)

Primary open-angle glaucoma tends to start in one eye but eventually involves both. In about half of patients the damage in the eye is diffuse, that is the nerve damage is generalized. In the other half the disease is localized, causing wedge-shaped abnormalities in the nerve fiber layers of the retina.

Intraocular eye pressure is normal (between 12 - 22 mmHg) in about 25 - 30% of U.S. glaucoma cases, a condition known as normal-tension glaucoma. (In Japan, the rates may be as high as 70%.) Other factors are present that cause optic nerve damage but do not affect IOP.

Closed-angle glaucoma (also called angle-closure glaucoma) is responsible for 15% of all cases. It is less common than open-angle glaucoma in the U.S., but it constitutes about half of the world's glaucoma cases because of its higher prevalence among Asians. The iris is pushed against the lens, sometimes sticking to it, closing off the drainage angle. This can occur very suddenly, resulting in an immediate rise in pressure. It often occurs in genetically susceptible people when the pupil shrinks suddenly. Closed-angle glaucoma can also be chronic and gradual, a less common condition.

Congenital glaucoma, in which the eye's drainage canals fail to develop correctly, is present from birth. It is very rare, occurring in about 1 in 10,000 newborns. This may be an inherited condition and often can be corrected with microsurgery.

The Light-Processing Parts. To understand sight, one begins with light and its passage through the eye's sensitive camera-like structures:

Light first passes through the cornea, a clear tissue at the front of the eye.
Behind the cornea, the iris (the colored tissues of the eye) opens and closes like a camera shutter to regulate the passage of light.
The lens, located behind the iris, focuses the light, which then hits the retina.
The retina is an electric fragile membrane of nerve cells called photoreceptors that receive light and translate it into signals.
A layer of cells, called the retinal ganglia, receive signals from the retina. These nerve cells are the front ends of the optic nerve cable, which, in turn, receive the signals.
The optic nerve is actually a cable of about 1.2 million nerve fibers called axons. It carries the signals to the brain, which interprets them as images.
They exit the eye through the optic disc, located in the back of the eye.

The Supportive Chambers. To help support and protect these sensitive structures, the eye contains two fluid-filled chambers:

The posterior (rear) chamber is the large area behind the iris.
Fluid passes from the posterior into the anterior (forward) chamber located in the bulging area between the iris and the front of the eye.

Causes

No single factor has been identified as a cause of primary open-angle glaucoma. A number of conditions, alone or in combination, are needed to trigger the processes leading to pressure in the first place and then to the nerve damage that destroys sight. The damage done to the optic nerve in glaucoma is triggered in most cases by the excessive pressure on the optic nerve that, over time, causes damage. Because optic nerve damage occurs in patients with normal as well as high intraocular pressure, however, researchers are investigating several other abnormal events that occur and can damage the optic nerve.

A number of genes have now been identified as possible factors in many cases of glaucoma. A gene called MYOC is of particular interest. Defects in this gene occur in between 3 - 6% of patients with adult-onset and juvenile open-angle glaucoma. They appear to overproduce a sticky protein called myocilin, which clogs the trabecular meshwork. The genes WDR36 and OPTN may cause primary open-angle glaucoma. Researchers hope that identification of genes will help improve screening of high-risk patients.

Specific syndromes have been identified with glaucoma. Many have an inherited component, although in most cases other factors must be present to activate the disease process.

Pseudoexfoliation Syndrome. Pseudoexfoliation (PEX) syndrome (also known as exfoliation syndrome) is the most common identifiable condition associated with glaucoma. In one study, 9% of patients with open-angle glaucoma had the syndrome. PEX occurs when dandruff-like matter flakes off the outer layer of the lens and collects in the drainage angle. The substance is composed of proteins produced by the lens, iris, and other parts of the eye. People can have this condition and not develop glaucoma, but they are at high risk. In one Australian study, 14% of the people with this condition had glaucoma compared to 2% of those without exfoliation. PEX has a strong genetic component but other factors (possibly sunlight, an autoimmune response, or slow virus) may be needed to trigger the disease.

Pigment Glaucoma. Pigment glaucoma starts with a condition called pigment dispersion syndrome, an inherited condition in which granules of pigment (the substance that colors the iris) flakes off into the intraocular fluid. In about 30% of cases, these fragments clog the trabecular meshwork and pressure builds up, causing glaucoma. In one study, 2% of patients had this form of glaucoma.

Irido Corneal Endothelia Syndrome. In irido corneal endothelial syndrome (ICE), cells on the back surface of the cornea spread to the drainage angle, sometimes forming scars that connect the iris to the cornea.

Neovascular Glaucoma. Neovascular glaucoma is always associated with other disorders, usually diabetes, that result in abnormal formation of new blood vessels on the iris and in the drainage system.

Aniridia. Aniridia is a rare inherited disorder (in which the iris is abnormal and increases the risk for glaucoma) that is difficult to treat. (A surgical approach called goniosurgery may help prevent glaucoma in young people with aniridia.)

Congenital Glaucoma. When an infant is born with glaucoma (congenital glaucoma), it is usually caused by an inherited abnormality in the drainage canal. Researchers have identified the gene responsible for 85% of these cases.

A natural process called apoptosis (cellular self-destruction) may contribute to damage in the retinal ganglion nerve cells, the nerve cells that are the front line of the optic nerve. Cell death can occur with or without elevated eye pressure. It is not clear what triggers apoptosis and cell death in such cases, but there are a number of suspects.

Excess Glutamate. Researchers have observed abnormally high levels of glutamate in people and animals with glaucoma. Glutamate is an amino acid that excites nerve cells. In the eye this occurs during vision. Some experts theorize that in glaucoma, either reduced blood flow or increased pressure on nerve cells triggers the release of excess glutamate. In large amounts, glutamate causes the nerve cells to fire intensively, which eventually destroys them.

Reduced Blood Flow. Researchers have observed reduced blood flow to the optic nerve in patients with glaucoma associated with both high and normal IOP. Less blood flow suggests oxygen loss, which may play a role in the destructive process. Some studies suggest that the greatest risk factor for nerve damage in patients is when blood pressure to the eye drops during the night. Ocular pressure at this time is highest, so the risk for nerve damage becomes intensified. Of interest in this regard are reports finding a significant reduction in eye blood pressure at night in patients with normal-tension glaucoma.

Excess Nitric Oxide. Elevated levels of nitric oxide, another nerve-stimulating compound, also plays a role in the nerve-damaging process. Nitric oxide is critical for nerve function and flexible blood vessels, but excess amounts may be toxic to nerves.

Glaucoma and Alzheimer's Disease. Some research has pointed out similarities in the process leading to cell death in glaucoma and Alzheimer's disease. Specifically, in both diseases activation of certain enzymes called caspases occurs and leads to accumulation of fragments of beta amyloid, an insoluble protein that forms sticky patches.

Autoimmunity. Some experts are studying the possibility that normal tension glaucoma may be an autoimmune disease; that is, factors in the immune system, including antibodies, attack cells in the person's own body as if they were foreign substances. In the case of glaucoma, such antibodies would damage parts of the optic nerve.

H. pylori Infection. Some research indicates that glaucoma is associated with Helicobacter (H.) pylori, the bacterium implicated as a major cause of peptic ulcers. Studies have reported over 87% of patients with glaucoma are infected with this bacterium.

People with acute closed-angle glaucoma often have a structural defect that causes a narrow angle between the iris and cornea where the aqueous humor circulates. Conditions that suddenly dilate the pupils may cause this shallow angle to close and precipitate attacks of acute glaucoma in susceptible people. Such conditions may include:

Certain drugs such as antihistamines, tricyclic antidepressants, some asthma medications (nebulized ipratropium), some anti-seizure drugs (topiramate)
Darkness
Emotional stress

When intraocular pressure leading to glaucoma is caused by other diseases or conditions, it is known as secondary glaucoma. Secondary glaucoma may be chronic or acute, mild or severe.

Medical Conditions. A number of diseases can contribute to the development of intraocular pressure leading to glaucoma:

Diseases that affect blood flow to the optic nerve (diabetes, high blood pressure, migraine; people with type 2 diabetes should be regularly screened for glaucoma.)
Hypothyroidism
Sleep apnea
Physical injury in the eye
Extreme nearsightedness (myopia)
Previous eye surgery
Other disorders, including leukemia, sickle cell anemia, and some forms of arthritis

Corticosteroids. Corticosteroids, commonly called steroids, have multiple effects on the trabecular meshwork and may even cause genetic changes. In fact, studying the effects of steroids on the eye is helping researchers understand the glaucoma disease process. Steroids pose a higher or lower risk depending on the form:

Taking topical steroid treatments in the eye poses the highest risk. It must be monitored carefully since, in some cases, damage may be permanent.
Taking oral corticosteroids, particularly in high doses or for long periods, increases the chance of glaucoma. In such cases, the eye disorder typically develops almost immediately and reverses within 2 weeks after the drug has been withdrawn.
Inhaled steroids were not thought to cause glaucoma, but there is some risk in people with a family history of glaucoma and other risk factors.

Symptoms

Chronic glaucoma is insidious. If the pressure increases slowly, it will not produce any symptoms until it has done irreversible damage. In such cases, people may notice visual problems at first only when light is dim. Patients are often sensitive to glare. Eventually they may lose contrast sensitivity; that is, they might have trouble differentiating between varying shades and brightness.

In acute closed-angle glaucoma, the pressure inside the eye increases quickly, and the symptoms are dramatic. Intense pain in the eyebrow area and blurred vision develop usually in one eye, and the patient often feels like the eye will burst (although it won't). The eye usually reddens. A person may see rainbow-like halos around lights. Sometimes nausea and vomiting occur. These symptoms may occur on and off and not appear as a full attack. In either case, they indicate a medical emergency. In chronic closed-angle glaucoma, the process is gradual and painless.

Although congenital glaucoma is usually present at birth, symptoms generally don’t develop in the infant for a few months. If parents notice that an infant’s eyes are enlarging, becoming cloudy, often watering, or tending to close in the presence of light, they should have an ophthalmologist examine the child’s eyes. Port-wine stains on an infant’s face could indicate the Sturge-Weber syndrome, a disorder that occasionally causes glaucoma.

Outlook

Worldwide, glaucoma ranks as one of the leading causes of blindness. Even if people with glaucoma do not become blind, vision can be impaired. In developed countries, most people get treatment in time to preserve their vision. Even so, glaucoma causes between 3 - 6% of blindness cases in Caucasians, and even more cases in African Americans.

In a 20-year study of Caucasian patients with glaucoma, blindness in at least one eye occurred in 27% of patients and blindness in both eyes occurred in 9% of patients. The blindness rates in African Americans are most likely higher. In fact, glaucoma is the leading cause of blindness in African Americans. Despite this higher prevalence, this ethnic group receives surgical treatment at half the rate of Caucasians.

The Process Leading to Vision Loss. Chronic glaucoma is often called “the silent thief of sight," because the afflicted person has no warning sign, no hint that anything is wrong. Untreated, the destruction develops slowly over time:

Over years or decades, the increased pressure compresses nerves at the back of the eyes.
Glaucoma gradually destroys first the outer fibers of the optic nerve, which reduces peripheral vision (the top, sides, and bottom areas of vision), but not central vision.
By the time a person notices that peripheral vision has been lost, permanent damage has already occurred.
If the eye pressure remains high, the destruction can progress until tunnel vision develops, and the person is only able to see objects that are straight ahead.
The last nerve fibers destroyed are those responsible for central vision; if this occurs, the glaucoma victim becomes totally blind.

Although there is no cure for open-angle glaucoma, a number of treatments are available that lower intraocular pressure and slow progression of vision loss.

Risk Factors for Vision Loss. Estimates of progression rates in vision deterioration range from 9 - 30% over a 2 - 7 year period.

According to a study on patients with elevated IOP, for every 1-mm Hg increase in IOP, there is a 10% higher risk of disease progression. A very elevated IOP (above 30 mm Hg) is certainly hazardous. An elevated IOP that is below 30 mm Hg, however, is not necessarily the most important factor in determining the risk for disease progression. Some evidence suggests that frequent and large daily fluctuations in intraocular pressure, not simply high IOP, are associated with the greatest risk for loss of vision. Having normal-tension glaucoma with optic nerve damage also carries a high risk for progression, even if eye pressure is reduced.

In any case, factors other than IOP play a role in increasing the chances for progression and vision loss in patients with slightly elevated IOP and normal tension glaucoma:

Both eyes affected
Pseudoexfoliation (PEX) syndrome. PEX occurs when proteins produced in the eye flake off the outer layer of the lens and collects in the drainage angle.
Bleeding in a specific region called the peripapillary nerve fiber layer
Thin corneas. (People who have thick corneas and elevated IOP may only need to be monitored if they have no other risk factor for vision loss.)
Larger cup-to-optic disc ratio. (The cup of the optic disc is the center portion, which enlarges as nerve damage progresses.)

Non-eye related factors associated with disease progression include being elderly, African American, female, or having a history of migraines.

Acute closed-angle glaucoma is a medical emergency; if the high pressure is not reduced within hours, it may permanently damage vision. Anyone who experiences its symptoms should immediately contact an ophthalmologist or go to a hospital emergency room.

Risk Factors

About 2 million Americans have open-angle glaucoma, but an exact count is unclear. Experts estimate that by 2010, over 60 million people worldwide will have glaucoma, with 74% of these cases due to open-angle glaucoma. Half of people with glaucoma are unaware of this problem because the condition causes no symptoms.

Elevated intraocular pressure in the eye occurs in 5 - 10 million Americans, but only about 10% of such people develop glaucoma because of this pressure. And, in 15% of actual glaucoma cases, IOP is normal. Major studies are helping to clarify the people who are at highest risk for glaucoma and optic nerve damage, including those with normal tension glaucoma.

Elderly. The prevalence of chronic glaucoma increases with age. In a major study, 0.6% of people age 60 - 64 had primary open-angle glaucoma. Among people who were 10 years older, the prevalence had more than doubled to 1.3%, and among those who were age 80 - 84, it had more than doubled again to 3%.

People of African Descent. Across all age groups, according to a 2000 report, the prevalence of glaucoma in African Americans is about 3.5% compared to about 1% in Caucasians. In addition, U.S. studies suggest that glaucoma develops earlier in African American population groups (starting at age 45 instead of age 60 in Caucasians). And, their risk for blindness once they have glaucoma is 14 - 17 times that of Caucasians with glaucoma. African American men are at higher risk than women. African American children who are extremely near-sighted and have relatives with glaucoma should begin regular eye examinations for glaucoma as early as possible.

In a major glaucoma study in Barbados, where most people are of African descent, over 10% of those age 50 and older had open angle glaucoma, and over 15% were afflicted after age 70. About half of the cases had normal or lower eye pressure. An interesting 2001 study suggested that African Americans tend to have significantly thinner central corneas than Caucasians. This could lead to misleadingly lower pressure scores in African American patients who actually may have high IOPs.

Family History. Glaucoma tends to run in families. Brothers and sisters of patients with open angle glaucoma are 5 times more likely to develop glaucoma by the time they are 70 years old than people whose siblings do not have the disease. Previous studies have also found that people with family histories of glaucoma are more likely to already have some vision loss when they are first diagnosed with glaucoma.

Effects of Blood Pressure. The association between a person's blood pressure and intraocular pressure in the eye is not entirely clear. A number of studies have found a higher risk for glaucoma in people with high blood pressure. A 2002 study suggested, however, that people with blood pressure that is low relative to their intraocular pressure may be at higher risk for glaucoma. The same study found no higher risk for glaucoma in people with hypertension, and in fact, high blood pressure was associated with a lower risk.

Having Certain Medical Disorders. Individuals with certain medical or physical conditions, including diabetes, migraine, nearsightedness, and sleep apnea, appear to have a higher risk. Conditions that require the use of any oral or inhaled steroid, particularly high doses for prolonged periods of time, can cause glaucoma. Previous eye surgery also puts people at risk.

Weightlifting. According to a 2006 study, holding your breath while weightlifting can increase the risk for developing normal-tension glaucoma. Weightlifting causes temporary increases in eye pressure; holding your breath during this exercise leads to even greater intraocular pressure.

Risk Factors for Closed-Angle Glaucoma. Chronic closed-angle glaucoma tends to be more common in people of Asian and African descent. Those who have this condition are often extremely farsighted. Acute closed-angle glaucoma occurs much more frequently in women than in men.

Risk Factors for Normal Tension Glaucoma. Risk factors for normal tension glaucoma include Japanese ancestry and a family history of the disease. It is more common in women than in men. A family history of cardiovascular disease also increases the risk.

Risk Factors for Pigmentary Glaucoma. Pigmentary glaucoma occurs three times more often in men then in women and at a younger age.

Risk Factors for Irido Corneal Endothelial Syndrome. This condition occurs more often in light-skinned women.

Diagnosis

A diagnosis of glaucoma no longer simply relies on the presence of pressure within the eye. It requires that there be optic nerve damage or a strong suggestion of damage, which can be clearly seen during a dilated eye examination of the optic nerve. In general, the hallmark sign of this condition is a loss of peripheral vision. With peripheral vision loss, a person can see in front of him- or herself but has lost the vision to the side.

The optic nerve carries the information of vision from the eye to the brain.

Because chronic glaucoma has no warning symptoms, half of its victims are unaware that they have the condition. Early diagnosis, however, is the key to successful treatment of glaucoma. One study reported that the more years since the last visit to an eye professional, the greater the risk for having visual loss.

Everyone over age 65 and African Americans over 40 years old should have periodic eye exams, including tests for glaucoma, every other year.
African Americans between ages 20 - 39 should have eye examinations every 3 - 5 years.
Other people at higher risk (people with diabetes, history of eye injuries, a family history of glaucoma, or those taking corticosteroid medications) should have eye examinations every year after age 35.
People with known glaucoma should have frequent examinations to check peripheral vision and to be sure treatment is maintaining a safe eye pressure. After such examinations, the ophthalmologist will assess current treatment and make necessary adjustments.

Doctors determine the intraocular pressure (IOP) of the aqueous humor inside the eye using tonometry, which measures the force necessary to make an indentation in the eye. There are several methods:

In the Schiotz method, the doctor first anesthetizes the eye with drops, then presses very lightly against it with tonometer, a tiny smooth instrument that is used to measure the pressure.
In the applanation method, the doctor touches a strip of orange-dyed paper to the side of the eye. The stain helps with the examination and rinses out with tearing. The doctor uses a slit-lamp, which is moved forward toward the patient's face until the tonometer touches the eye.
The noncontact approach applies a puff of air and measures the force needed to indent the eye.

Attempting to close the eyelids during the test can increase eye pressure and produce errors in the results.

In general, normal IOP is usually maintained at measurements of 10 - 20 mm Hg. Glaucoma pressure over 21 mm Hg indicates a potential problem. The test is not completely accurate, however. Only about 10% of people with IOP levels between 21 - 30 mm Hg will actually develop glaucoma and optic nerve damage. On the other hand, many people with glaucoma have normal pressure, at least for part of the time.

Changes in posture may also affect IOP. A 2006 study indicated that IOP increases during sleep or when a person is lying down. As IOP tests are generally given in a doctor’s office when a patient is sitting up, they may not provide a completely accurate evaluation of eye pressure.

The cornea thickness may be an important indicator of disease progression in patients with elevated IOP. According to some research, patients with thinner corneas have a significant risk for developing damage from glaucoma, while those with thicker corneas have a low risk.

In order to determine early damage in the optic nerve, a number of diagnostic instruments have been developed to assess the nerve fiber layers at the back of the eye (the fundus) and to check for optic disk cupping. (The cup of the optic disc is the center portion, which enlarges as nerve damage progresses.) The two most common procedures for identifying nerve damage are ophthalmoscopy and fundus photography. Other instruments have been developed, including those that use laser technology and computers, but none have proved to be infallible. No test has proven to be completely accurate, however, and none is routinely performed by all eye professionals.

In order to be accurate, the tests require a skilled professional and there are certain common factors:

The pupils must also be widely dilated using eye drops before the procedure.
Even mild cataracts and a slightly less-than-optimally dilated pupil can degrade the results. Such conditions are common in elderly people, who are the most likely to develop glaucoma.
If the back of the eye is lightly pigmented (colored), the area under observation is less distinct.
If the glaucoma is diffuse and there is a generalized loss of nerve fiber (which occurs in half of patients), it is more difficult to detect than if the glaucoma is more localized.

If IOP is low or normal and tests report optic nerve damage and peripheral visual loss, doctors should also check for other conditions before starting any treatment for glaucoma. Such problems include steroid use, anemia, and previous hemorrhage or severe low blood pressure.

Ophthalmoscopy. The eye professional (or even a primary care doctor) uses an ophthalmoscope to peer through the pupil directly at the optic nerve. The examiner can then check the shape and color of the nerve fibers to evaluate whether they have been damaged by the high pressure of glaucoma. Damaged nerve fibers may be indicated by:

An asymmetrical or elongated cupped optic nerve
The optic nerve color may be pale or an unhealthy-pink

If results show no optic nerve damage in patients who have mild elevations in pressure, the ophthalmologist may want to retest frequently but delay drug treatment, unless the patient has significant risk factors.

Fundus Photography. Fundus photography may be used to take pictures of the optic nerve and can reveal changes years in advance of vision loss. It is an unpleasant procedure requiring drops and a bright flash. This procedure has the same limitations as ophthalmoscopy.

Laser Polarimetry. Polarimetry uses laser technology to scan the eye and does not require any response from the patient. It is reported to be able to measure nerve fiber thickness in the eye and so be able to reveal early signs of deterioration. Preliminary studies have indicated that it has a diagnostic accuracy of over 90% for both confirming and ruling out glaucoma. One study, however, reported that laser polarimetry was sensitive enough to detect glaucoma in only up to 57% of patients with early glaucoma, 71% of those with moderate disease, and 81% of those with severe glaucoma. More research is needed.

Other Devices. Computer-assisted devices, such as the confocal scanning laser ophthalmoscope, are now available that may be useful for evaluating the retinal nerve layer. Another instrument, the optical coherence tomograph, measures the echo time delay of light that is scattered back from different layers in the retina. The value of these tests has not yet been determined.

If there is indication of optic nerve damage, the eye professional will conduct tests of the visual fields (the areas that the patient can see). In most people with glaucoma, the first areas to become noticeably impaired are the peripheral visual fields (areas of sight that are not directly in front of a person but more to the sides).

Click the icon to see an image of the visual field test.

Standard Perimetry Tests. Perimetry tests are used to check peripheral vision. One variation of this test is as follows:

A person sits closely facing a large computer-like monitor.
Small bright white lights flicker on and off hundreds of times, at different places on the screen, while the patient clicks a button whenever one of the lights is seen.
The machine prints out a report that maps any blanked-out areas in the person’s vision.

The test is complex and lengthy; elderly people and those with short attention spans may be inappropriate candidates. Other perimetry tests, some requiring less time to administer and some using "virtual reality" techniques, are currently being developed.

Other Tests. Other visual field tests are being developed that can detect abnormalities years before they can be detected by standard perimetry. Experts recommend some of these tests in selected patients with suspected glaucoma.

For example, a screening test called frequency doubling technology (FDT) checks for changes in particular cells in the retina that are indications of early glaucoma. It takes less than a minute to perform.

Another test called short wave automated perimetry (SWAP) uses colors (blue-on-yellow) and also detects very early abnormalities in the visual field. Testing time is longer than with FDT, however, and the presence of certain types of cataracts can interfere with its accuracy.

ELAM-1. Endothelial leukocyte cell adhesion molecule 1 (ELAM-1) is a molecule that has been found in glaucoma but not in healthy eyes. This molecule may prove to be a "marker" and its presence may be helpful in diagnosing glaucoma.

A simple test using a penlight helps determine the risk for acute closed-angle glaucoma. A beam of light is directed from the side of the face toward the patient's iris. If no shadow appears on the nose, then most likely the angle is wide enough to dilate. Using an instrument called a gonioscope, ophthalmologists can also inspect the front of the eyes and assess the drainage angle between the cornea and the iris and the channels in the trabecular meshwork. This test can differentiate between closed- and open-angle glaucoma.

Treatment

Most treatments for glaucoma aim to reduce ocular pressure and its fluctuations. Early treatment with medications, surgery, or both can nearly always maintain safe pressure of the aqueous humor, thus preventing optic nerve damage and blindness. The choice between surgery and medications and when to start treatment is not always straightforward. For example, with the introduction of beta blockers and newer glaucoma drugs, there has been a decline in surgeries. It is not clear, however, which drugs are more effective than others and if, over time, any will actually prevent surgery. Patients should discuss all issues with their doctors and ophthalmologists.

Many people have high IOP but no sign of nerve damage. Over the course of 20 years, only between 10 - 30% of these people will actually develop glaucoma. Nevertheless, once glaucoma has destroyed optic nerve fibers, no known treatment can reverse the damage.

Indeed, studies suggest that in people with glaucoma, even very small differences in pressure may mean the difference between disease progression and stability. An important trial reported that, on average, treating patients when their glaucoma was first detected reduced IOP by 25%. In addition, treatment reduced the risk for progression by 17%. This study confirmed previous findings supporting early treatment for glaucoma. Another study found that treatment with eye drops halved the risk of developing open-angle glaucoma in African Americans who had elevated IOP. Some evidence suggests that early treatment to lower IOP may be beneficial even in patients with normal tension glaucoma.

However, not all individuals with early signs of glaucoma (elevated IOP or normal-tension glaucoma) develop optic nerve damage and serious vision problems. Nor does treatment prevent progression in a large minority of patients. Medications used for glaucoma also can carry significant side effects and risks.

Some experts suggest that treatment is warranted only in people with early signs of glaucoma who have risk factors for progressive disease and vision loss (thinner corneas, larger cup to optic disc ration, older age, and elevated pressure).

A number of effective drugs are now available for treating glaucoma. The drugs reduce pressure in the eye but all have a number of side effects that affect other parts of the body. Some of these side effects can be quite severe. Many of the drugs used for glaucoma also interact with common medications for other conditions. To compound the difficulties, many patients require multiple drugs. As a result, only about half of patients comply with their treatments.

Experts generally recommend topical drugs first (those that can be used as eye drops or ointments rather than taken by mouth).

Topical beta blockers are the standard first-line drugs, most commonly timolol (Timoptic). Newer beta blockers include betaxolol (Betoptic), levobunolol (Betagan), carteolol (Ocupress), and metipranolol (OptiPranolol). Timolol has been used for years, and these other drugs are also well tolerated.
Topical prostaglandins are alternatives if beta blockers fail. They include latanoprost (Xalatan) and unoprostone (Rescula). Of the standard drugs used for glaucoma, these drugs have the greatest effect on lowering IOPs. They also have fewer widespread effects than the beta blockers.
Topical carbonic anhydrase inhibitors (CAIs) are less effective than standard beta blockers or prostaglandins but have fewer widespread effects than the beta blockers. They may be helpful in certain cases. Topical forms are dorzolamide (Trusopt) and brinzolamide (Azopt). (Oral CAIs are available and more effective, but they have severe side effects and are rarely used for the long term.)
Alpha2-adrenergics, also called selective alpha adrenergics, are effective but may not be as well tolerated as timolol. They include brimonidine (Alphagan).
Miotics, which include pilocarpine and others, were the standard drugs before the introduction of topical beta blockers. They have now been largely replaced by timolol and others, although they are sometimes used in combinations.
Beta blockers and newer drugs (prostaglandins, topical CAIs, and selective alpha adrenergics) are now preferred over the older drugs, which include miotics, oral CAIs, and nonselective alpha adrenergics.

Combinations. Combinations of these drugs can be very effective, because they tend to have different actions. Single medications that contain two drugs are becoming available. For example, Cosopt combines timolol and dorzolamide; Timpilo is a combination of timolol and pilocarpine. Studies of these and other combinations compared to each other to single drugs are ongoing. To date, results on any superior combinations have been mixed. It should be noted that the side effects of each drug apply to any combination.

Treating the Pregnant Patient. Considerations for a pregnant woman with glaucoma can be complicated. All of the drugs used for glaucoma are absorbed by the body, cross the placenta, and are excreted in breast milk. Many have effects that can interfere with or adversely affect pregnancy.

Women should discuss going off medication, particularly during the first trimester, and be monitored during that time for increasing eye pressure. IOP tends to drop during pregnancy, although usually not to a significant degree. In addition, changes in IOP and visual loss vary greatly. Some women experience no IOP change or visual loss during pregnancy, while others may experience an increase in IOP or worsening of visual loss. It is important that your ophthalmologist carefully considers your individual case and discusses with you the risks and benefits of continuing glaucoma medication during pregnancy.

If women need to take medications, they should try to achieve the lowest dose possible. Some drugs have fewer side effects than others. Pregnant women must also be very careful about administering eye drops to allow as little medication as possible to enter the body. When taking eye drops, press your index finger against the corner of the eye near your nose. This helps prevent the eye drop from passing down into the tear duct where it is easily absorbed through the rest of the body. Even this approach, however, does not guarantee complete safety. Women with glaucoma who are planning to become pregnant might want to consider surgery before they conceive.

The object of standard glaucoma surgery is to reduce pressure in the eye by increasing the outflow of the aqueous fluid. Two methods are commonly used:

Filtration surgery (trabeculectomy). This uses standard surgical instruments to open a passage in the eye for draining fluid.
Laser trabeculoplasty. This procedure uses a laser to burn 80 - 100 tiny holes in the drainage area.

Both are effective, but certain patient groups may respond to one more than the other. For example, African Americans may do better with laser surgery while trabeculectomy may be a better choice for Caucasians with no serious medical problems.

In general, surgery is a last resort. Doctors may, however, recommend surgery before drug therapies for patients unlikely to comply with difficult drug regimens or for patients who may have severe reactions from the glaucoma drugs. Women who plan on becoming pregnant should also discuss surgery with their doctor.

Some studies indicate that laser treatment performed as the initial treatment for glaucoma is as effective as medications in some cases. Findings in 2003 from a major comparison study suggested that 4 years after surgery there was little difference in visual field loss between trabeculectomy and medical treatment. There was, however, a higher risk for cataracts and loss of vision sharpness with surgery. On the other hand, side effects from medications may be ongoing and troublesome. It is important to note that even surgery does not cure glaucoma, and over half of patients will require medication within 2 years. Experts who are against early surgeries also argue that studies on their success often omitted serious postoperative problems, such as late-onset infection, and quality of life assessments.

Medications

Nearly all glaucoma medications are prescribed for reducing eye pressure. Lowering IOP is even proving to be beneficial for about two-thirds of patients with normal-pressure glaucoma.

Topical beta adrenoceptor blockers (common called beta-blockers) are the drugs most often prescribed to treat glaucoma. They lower the pressure inside the eye by inhibiting the production of aqueous humor.

Brands. These drugs are categorized as either nonselective or selective beta-blockers:

Nonselective adrenoceptor beta-blockers. Timolol (Timoptic, Betimol) has been the standard beta-blocker for years. Newer nonselective drugs include levobunolol (Betagan), carteolol (Ocupress), and metipranolol (OptiPranolol). A few studies suggest some are more beneficial than timolol with similar side effects.
Selective beta1-adrenoceptor blockers. Betaxolol (Betoptic) and levobetaxolol (Betaxon) are selective beta-blockers. These drugs appear to have fewer adverse effects on the heart than the nonselective beta-blockers, although they still have widespread effects. Studies also suggest that they slow progression more than timolol, although timolol is more effective at lowering IOP. selective beta-blockers may also have nerve-protecting properties.

All beta-blockers are effective and generally well tolerated. Because they cause less eye irritation than many other glaucoma medications, they are often prescribed for patients who also have cataracts.

Side Effects and Complications. After the beta-blocker is administered, only a tiny amount of the drug is absorbed by the cornea. Most of it enters in the bloodstream. These drugs, therefore, can cause side effects in parts of the body other than the eyes ("systemic" side effects):

Common systemic side effects include reduced sexual drive, fatigue, depression, anxiety, severe nausea and vomiting, and breathing difficulties.
Beta-blockers affect the heart. They lower heart rate and reduce blood pressure. (The newer selective beta-1 blockers may not have as bad effects on the heart as the nonselective beta-blockers.) They may also cause unhealthy cholesterol and triglyceride changes.
All beta-blockers can worsen severe asthma or other lung diseases. Beta-blockers should only be used very cautiously or not at all by anyone with asthma, emphysema, bronchitis, or heart disease. In one study, lung function was reduced in 40% of elderly people who took timolol, even those without previous symptoms of lung problems. (Selective beta-blockers may produce fewer of these adverse effects.)
If the patient is switching to a beta-blocker from other glaucoma medication, there may be a sudden rise in eye pressure. It is important that the pressure be checked shortly after the other drug has been withdrawn.
When beta-blockers are used to treat one eye, the other (contralateral) eye also experiences a lesser, but still significant reduction in IOP.

Interactions with Other Medications. The effects of the eye medication may be additive to other oral medications, such as oral beta-blockers, calcium-channel blockers, or the antiarrhythmic drug quinidine. People with diabetes who take insulin or hypoglycemic medications should realize that timolol side effects may resemble and mask the symptoms of hypoglycemia (low blood sugar).

Prostaglandins are hormone-like substances that help open blood vessels. Drugs that resemble prostaglandins increase outflow of aqueous humor (the watery substance in the eye). Drainage of aqueous humor helps reduce intraocular pressure.

Brands. Latanoprost (Xalatan) and unoprostone (Rescula) are the standard brands. Latanoprost was the first prostaglandin to be approved as first-line treatment for elevated eye pressure. Two newer prostaglandins, travoprost (Travatan) and bimatoprost (Lumigan), may help some patients who do not respond to latanoprost. These drugs may also benefit patients with normal-tension glaucoma. Latanoprost, travoprost, and bimatoprost need to be taken only once daily. Unoprostone needs to be taken twice a day and is not as effective as others, but it still can reduce IOP significantly and is the least expensive of these drugs.

Latanoprost has been shown to reduce pressure by between 45 - 70%. Some, but not all studies, have suggested that newer prostaglandins travoprost (Travatan) and bimatoprost (Lumigan) are more effective than latanoprost, but the older drug appears to be better tolerated. All of these drugs may be work better than timolol in lowering IOP. The newer prostaglandins may be especially superior to timolol in treating African American patients. In comparison studies, latanoprost achieved better IOP pressure reduction than brimonidine. Studies have suggested that bimatoprost is more effective in lowering eye pressure than a combination of timolol and dorzolamide (Cosopt). Studies have been mixed on whether latanoprost is superior to the combination.

Side Effects. These drugs do not slow down the heart rate and also appear to be safe for people with asthma. Side effects include itching, redness, and burning during administration. Muscle and joint pain may also occur. All of these drugs may permanently change eye color from blue or green to brown. To date, such color changes do not seem to be hazardous. (The only significant problem may be cosmetic in people who treat only one eye, since the color may differ from the other.) These drugs can increase blood flow in the eye and also make eyelashes become thicker and longer in some patients. (These latter effects are more common with bimatoprost and travoprost than with latanoprost.)

Carbonic anhydrase inhibitors (CAIs) decrease eye pressure by reducing the fluid in the chambers of the eye (aqueous humor). Research suggests that CAIs reduce aqueous humor fluid by as much as 40%. These drugs are used for glaucoma when other drugs do not work. They may be combined with other medications.

CAIs may also improve blood flow in the retina and optic nerve (beta-blockers do not). Improving blood flow can keep the disease from getting worse.

Brands and Side Effects. CAIs are available in the following forms:

Eye-drop CAIs include dorzolamide (Trusopt) and brinzolamide (Azopt). About 10% of patients report fatigue, stinging in the eye, and loss of appetite using dorzolamide. Taste changes can occur. Research suggests that dorzolamide can be helpful for children with glaucoma, including those younger than 6 years old. Brinzolamide is a newer medication that was chemically designed to be closer in pH to human tears and may cause less stinging than dorzolamide.
Oral forms include acetazolamide (Diamox), methazolamide (Neptazane), and dichlorphenamide (Daranide). Although they are more effective than eye drops, they have significantly more side effects and are rarely used for long-term treatment. The oral forms have very unpleasant side effects that include frequent urination, depression, stomach problems, fatigue, weight loss, sexual dysfunction, and, in infants, failure to thrive. Long-term use of the oral forms, in rare cases, can cause serious anemia and kidney problems, including the risk for stones. They can also produce a toxic reaction when taken with large doses of aspirin.

Adrenergic agonists activate muscles in the eye that dilate pupils and, therefore, increase outflow of aqueous fluid. Newer variations called alpha 2-adrenergic agonists reduce production of aqueous humor and also increase outflow through the uveoscleral pathway (the alternative channel to the trabecular meshwork). Older adrenergic agonists include epinephrine.

Alpha 2-Adrenergic Agonists. Apraclonidine (Iopidine) and brimonidine (Alphagan) are alpha 2-adrenergic agonists. These have generally been used before glaucoma surgery, but a number of studies are indicating that they may even be useful as primary therapy when used in combination with beta-blockers or other standard drugs.

Brimonidine is proving to be particularly effective for long-term therapy. (Apraclonidine is used for the short term.) It also may have nerve-protecting properties and may be safer than other drugs during pregnancy and for patients with asthma.

The most common side effects of brimonidine and apraclonidine are dry mouth and altered taste. They also commonly trigger an allergic reaction that causes red and itching eyes and lids, a major drawback. Brimonidine causes less of an allergic response than apraclonidine. Unlike apraclonidine, however, it can cause lethargy and mild low blood pressure. It also appears to remain effective longer.

Miotics, also called cholinergic agonists, narrow the iris muscles and constrict the pupil. This action pulls the iris away from the trabecular meshwork and allows the aqueous humor to flow out through the drainage channels, reducing the pressure inside the front of the eye.

Brands. Pilocarpine (Pilocar, Adsorbocarpine, Almocarpine, Isoptocarpine, Ocusert) was the most widely used anti-glaucoma drug before timolol was introduced. It is the preferred miotic. Because pilocarpine is used up by the body fairly quickly, however, patients must take it several times a day; many people, therefore, fail to take their medication regularly. A combination of timolol or latanoprost with pilocarpine is more effective than either drug used alone. Carbachol is another miotic.

Demecarium (Humorsol), isoflurophate (Floropryl), and echothiophate (Phospholine) are a group of long-acting drugs known as anticholinesterase miotics. Because of their potential for serious side effects, however, some authorities even prefer surgery to their use.

Epinephrine and its derivatives are the older anticholinergics. Epinephrine is now rarely prescribed because of side effects. Dipivefrin (Dipivefrin), a newer form of epinephrine, remains inactive until it reacts with enzymes in the cornea. It is effective in low doses and causes few systemic side effects.

Side Effects. Side effects include:

Teary eyes, brow-aches, eye pain, and allergic reactions.
A miotic narrows the pupil and so can cause nearsightedness. Vision can also become dim and it may difficult to see in darkened rooms or at night, when driving could be hazardous. A gel form administered once a day or wafer placed under the lid once a week may help reduce these side effects.
The anticholinesterase miotics increase the risk of cataract development and are therefore used mostly in patients in whom cataracts have already been removed. Retinal detachment is an uncommon but dangerous side effect in susceptible individuals. Excessive use of these miotics may cause toxic reactions, including convulsions, muscular paralysis, and even death from respiratory failure.
Epinephrine can produce burning in the eyes, enlarged pupils, and allergic reactions. Occasionally it can cause anxiety and headaches. Rare side effects include high blood pressure and disturbances in heart rhythm. It is rarely prescribed now. Although dipivefrin, the newer form of epinephrine, has fewer systemic side effects, it still causes problems in the eyes similar to those of epinephrine.

Cannabinoids. Cannabinoids, compounds in marijuana (cannabis), are being studied for their effects on glaucoma. For example, oral or inhaled tetrahydrocannabinol (THC), the active ingredient in marijuana, has been shown to reduce IOP in 60 - 65% of patients. The effects of smoking marijuana on IOP last only 3 hours, however. THC also increases the release of glutamate -- a nerve-protecting chemical. Experts are hoping that topical use of THC or other cannabinoids may help prevent optic nerve damage without the widespread effects of oral or inhaled administration.

Reasons for Noncompliance. Studies indicate that more than 40% of patients miss 10% of their doses, and 15% of patients miss more than 50% of their doses. Noncompliance is very high for many reasons:

People with chronic glaucoma who are on medication must use eye drops or take pills one or more times a day, usually for the rest of their lives.
Many people require a multi-drug regimen, two or more different kinds of medications that can be used in various combinations, such as eye drops, ointments, or time-release wafers inserted under the eyelid. Such regimens can be very confusing.
The side effects of the drugs are more unpleasant than the disease itself, which has no symptoms until vision is lost. Because the treatment does not usually produce any noticeable improvement, the consequence of not taking the drugs (blindness) may seem far in the future.
Skipping even a few doses can greatly increase the risk of visual loss. It is essential that patients tell their doctor if they are not regularly taking their medication. Otherwise, the doctor may increase the dosage, thereby causing unwelcome side effects.

Patients who do not regularly take their glaucoma medication are at high risk for blindness. If you have problems taking your medications or sticking to the dosing regimen, talk with your doctor.

Hints for Managing a Regimen.

Pharmaceutical manufacturers use colored tops, yellow for timolol, for example, and green for pilocarpine, to help prevent mix-ups. Creating a chart scheduling each drug by color can be helpful.
Small electronic timers are available that will signal times for taking the medications. The timing of these combinations is important. For example, the combination of pilocarpine with latanoprost is most effective when pilocarpine is taken four times a day and when the bedtime dose is administered an hour after latanoprost.
Some patients may be candidates for single medications that combine two drugs, such as Cosopt, which contains both dorzolamide and timolol. This medication requires only one drop twice per day. Patients who need additional glaucoma drugs, however, will need to take these two drugs separately.
When using any drug for a long period of time, side effects are a potential problem. If they become intolerable, patients should discuss with the doctor reducing the dosage or trying other drugs.

Administering Eye Drops. A common reason that medicine does not work is that patients do not take it correctly. Patients should ask the ophthalmologist to watch while they place the drops in their own eyes to make sure the procedure is being done correctly. The following are some recommended steps:

If you use both ointments and eye drops, take the eye drops first.
Wash your hands before applying eye drops.
Hold the bottle upside down.
Tilt your head back and, with one hand, pull the lower eyelid down to form a pocket.
With your other hand, hold the bottle as close as possible to your eye. Don’t let the bottle directly touch your eye or eyelid.
After you have placed the drop, close your eye or press your index finger against the corner of the eye near your nose. Gently move the lower lid upward until the eye is closed. Keep your eye closed for at least 1 minute. This prevents the drop from draining out.
Wait at least 5 minutes before applying another drop or a different medication

In this emergency situation, ophthalmologists may administer a combination of two or more anti-glaucoma medications to reduce eye pressure quickly before it can damage the optic nerve and cause visual loss. Apraclonidine (Iopidine) is a powerful drug used before and after laser surgery to prevent an increase in fluid pressure and is more effective than other medications. In addition to standard drugs, doctors may also administer glycerin (Glyrol, Osmoglyn) by mouth or mannitol or acetazolamide intravenously. Surgery is almost always performed once the pressure is reduced.

Most rare forms of glaucoma respond to the same medications and surgery used for open angle glaucoma. Irido corneal endothelial syndrome (ICE) is difficult to treat and if surgery is required, filtering surgery is the best choice. Neovascular glaucoma is also very hard to treat; researchers are investigating drainage implants for this disorder.

Surgery

If medications do not control eye pressure, or if they create intolerable side effects, surgery may be necessary in a small percentage of people with chronic glaucoma. It may be particularly helpful for patients with pseudoexfoliation glaucoma.

The standard procedures are usually one of the following:

Filtration surgery (trabeculectomy). This procedure opens the full thickness of the drainage area.
Laser trabeculoplasty. This procedure partially opens the drainage area. It does not reduce pressure to the extent of trabeculectomy but it has fewer adverse effects.

African Americans may respond better to initial laser surgery than to conventional trabeculectomy, while the opposite may be true in Caucasians. Some experts now recommend that, in most circumstances, African Americans should start with laser surgery and Caucasians who have no serious medical problems should have trabeculectomy first.

In addition, a number of experimental and less invasive procedures are under development.

The Procedure. Filtration surgery has been used for more than 100 years with only minor modifications. It employs conventional surgical techniques known as full-thickness filtering surgery or guarded filtering surgery (trabeculectomy).

The surgeon creates a sclerostomy, a passage in the sclera (the white part of the eye) for draining excess eye fluid.
A flap is created that allows fluid to escape but which does not deflate the eyeball.
The surgeon may also remove a tiny piece of the iris (called an iridectomy) so that fluid can flow backward into the eye.
A small bubble called a bleb nearly always forms over the opening, which is a sign that fluid is draining out. Although surgeons aim for a thick bleb, which poses less risk than a thin one for later leakage, paradoxically the ideal operation would have no bleb at all.

The procedure has a high success rate. About 50% of patients no longer need medication after surgery. Thirty-five to 40% of those who still need medication have better control of their glaucoma.

A new instrument called a trabectome has allowed for a less invasive type of trabulectomy surgery The trabectome procedure appears to be a safe and simple way to lower eye pressure. It can be performed before a traditional trabulectomy, if needed. Results from a small study, presented at the 2005 meeting of the American Academy of Ophthalmology, showed that the new approach successfully reduced eye pressure in 90% of patients with open-angle glaucoma.

Side Effects. Many of the serious side effects or complications that occur with filtration surgery involve blebs (blister-like bumps).

Bleb Leaks and Infections. Blebs, particularly thin ones, commonly leak. Leakage can occur early on or sometimes as late as months or years after surgery. Untreated, such leaks can be serious and even cause blindness. Late-onset leakage significantly increases the risk for infection as well as a number of other serious conditions, including bleeding, a flattening of the eye ball, and harmful inflammation. Surgical repair is the most effective way of managing leaking blebs, although drug therapies, pressure patching, and other nonsurgical techniques may be tried first. Due to the dangers of leaking blebs, experts recommend lifelong monitoring after surgery. Unfortunately, the incidence of late-onset leaking blebs is increasing due to the use of drugs used in filtration surgery to prevent scarring, another complication.
Scarring. In up to 20% of cases, scars form around the incision, closing up the drainage channels and causing pressure to rebuild. These scars are formed from fibroblasts, which are immature collagen cells that form at the surgical site. Scarring is a particular problem in young patients, African Americans, patients who have taken multiple drugs, have had an inflammatory disease, or have had cataract surgery. Releasing the surgical stitches used in the procedure may help prevent scarring and pressure build-up. A second procedure called bleb needling sometimes can open up the scarred area and restore drainage. With this technique, the tip of a very fine hypodermic needle is used carefully to cut loose the particles closing off the drainage area. A new technique that does not require sutures may prove to be effective and have fewer complications.
Cataracts. The procedure is highly associated with the development of cataracts over time. Because cataracts are associated with glaucoma anyway, it is not entirely clear whether the cataracts are caused by the surgery or would develop in any case.

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

Supportive Medication for Preventing Scarring. Specific drugs, usually mitomycin C, are often used in conjunction with the procedure to prevent scarring and closure. A large review of studies of mitomycin C supported its effectiveness in increasing surgical success in nearly all patients. Fluorouracil (5-FU) appears to be similar in effectiveness but has a high risk for complications and is not used as often as in the past.

The Procedure. Laser trabeculoplasty involves the following steps:

The procedure uses an instrument, usually a YAG laser, to burn 80 - 100 tiny holes in the drainage area.
A tiny scar forms, which increases fluid outflow.
The procedure takes 15 minutes, causes almost no discomfort, and has very few complications.

In a 2-year study, laser surgery of the trabecular meshwork reduced pressure by a third in 70 - 97% of patients. Patients still need to take anti-glaucoma eye drop medications every day.

Laser surgery is not a cure. Within 2 - 5 years, about half of patients need either additional surgery or new medications.

Complications. In about 35% of patients, pressure increases after surgery. In most cases it is temporary, but in rare cases the increased pressure is permanent and vision loss can occur. Use of the drug apraclonidine (Iopidine) or pilocarpine can help prevent this elevated pressure. About a third of patients also develop adhesive-like substances called peripheral anterior synechiae that cause the iris to stick to part of the cornea.

Drainage implants, also known as tube shunts, may be used to drain fluid in certain cases, such as if glaucoma is not responsive to any standard procedure or is caused by certain conditions. A 2007 study suggested that tube shunts work better than filtration surgery (trabulectomy) for some patients. In the study, patients who received tube shunts had more stable IOP over the course of a year than patients who underwent trabulectomy.

Candidates. Success rates are highest (75% pressure control over 5 - 7 years) in appropriate patients. Drainage implants may be useful in the following conditions:

Glaucoma caused by swelling in the iris
Glaucoma caused by abnormal vessel formations
Iridocorneal endothelial (ICE) syndrome

The Procedure. In general, the procedure involves:

An implant, most commonly a 1/2 inch silicone tube, is inserted into the eye's front chamber (anterior). The Molteno implant used with mitomycin C is currently the most effective approach, with reported success rates of 80%. Other implants, such as the Ahmed implant, may have fewer complications.
The tube drains the fluid onto a tiny plate that is sewn to the side of the eye.
Fluid collects on the plate and then is absorbed by the tissues in the eye.

Complications. Complications include:

Hypotony (very low eye pressure) is a serious complication that has been reduced using better techniques and improved implants.
Cataracts, detached retina, breakdown of the cornea, and bleeding are potentially significant complications.
There is also a risk for eye movement disorders, such as strabismus (crossed eyes) or diplopia (double-vision).

The implant often becomes blocked and repeated operations are needed. Some researchers are studying the use of a drug called tissue plasminogen activator (tPA) to open up tubes that have been blocked by blood or blood factors. (This so-called clot-busting drug is normally used to break up blood clots during heart attacks.) In one 2002 study, tPA prevented such blocks in 89% of eyes. Unfortunately, significant complications rates were high (11%).

Deep sclerectomy and viscocanalostomy are less invasive techniques than filtering surgery that leave the anterior chamber (front of the eye) intact and avoid creation of blebs.

In deep sclerectomy, the surgeon removes a deep piece of the sclera (the white part of the eye), part of the trabecular meshwork, and the front of Schlemm's canal (the vessels that return fluid into the bloodstream).

In both deep sclerectomy and viscocanalostomy, the surgeon first creates a flap in the outer part of the sclera (the white part of the eye) and then removes a deep piece of the sclera underneath. This opens up Schlemm's canal (the vessels that return fluid into the bloodstream) and exposes a layer above the anterior chamber called Descemet's membrane. A space has also been created between the inner and outer layers of the sclera.
In deep sclerectomy, this space now serves as a tiny reservoir for aqueous fluid that flows through the membrane and pools here. The fluid then flows out without the surgeon having to open the anterior chamber (as in standard filtering surgery).
In viscocanalostomy, the surgeon typically injects gel-like materials into the ends of Schlemm's canal in order to enlarge the canal for fluid outflow and lower IOP. The tiny reservoir is sewn tightly up.

Many variations are under investigation. In general, the procedures have fewer complications afterward than standard filtering surgery, although they require excellent surgical skill. Nonpenetrating techniques do not lower IOPs as much as conventional surgery does, however. In time, however, these nonpenetrating techniques are expected to be as effective as filtration surgery.

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

In patients with cataracts and poorly controlled glaucoma, a two-step procedure for both eye conditions is needed. Typically the patient will first have a trabeculectomy for glaucoma, followed by cataract surgery such as phacoemulsification (lens removal through ultrasound). Fluid leakage and the presence of blood in the back chamber of the eye are potential complications of this combined procedure.
Phacoemulsification is sometimes combined with viscocanalostomy in a procedure called phacoviscocanalostomy. A 2006 study suggested this approach is safe and effective. The study followed patients for 7 years after they underwent phacoviscocanalostomy and found that no serious complications occurred.
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. However, it is still unclear which specific type of surgical procedure works best. [See In-Depth Report #26: Cataracts.]

Diode laser transscleral cyclophotocoagulation (TSCPC), also called laser cycloablation, reduces aqueous production by destroying the muscles that control the lens for near and far vision (the ciliary body ). There is a chance of vision loss with this procedure, so it is reserved for people with end-stage glaucoma or those who fail to benefit from any other therapies. Nevertheless, researchers continue to explore the possibilities for this effective procedure, especially for people who may not have access to expensive medications. Studies have suggested it may even be suitable as first-line surgery for some patients.

For an acute closed-angle glaucoma attack, emergency microsurgery is usually necessary after reducing pressure with medications.

Iridotomy or Iridectomy. Either laser (iridotomy) or conventional (iridectomy) surgery may be used. With either procedure an ophthalmologist makes a tiny opening in the iris to let the aqueous humor flow out more freely. Because acute glaucoma commonly occurs later in the other eye, surgeons will often recommend surgery in the unaffected eye to prevent a second attack.

Laser iridotomy almost never requires hospitalization, and postsurgical treatment includes only aspirin and eye drops. It has almost completely replaced conventional surgery, which requires anesthesia and hospitalization.

Vision will be blurred, and recovery can take 4 - 8 weeks. Once surgery has been performed, such patients can usually use previously restricted anticholinergic medications, such as antihistamines and certain antidepressants, with safety.

Phacoemulsification and Intraocular Lens Implantation. Phacoemulsification and intraocular lens implantation, a procedure ordinarily used for cataracts, may prove to be beneficial for some patients with acute angle-closure glaucoma requiring surgery. [See In-Depth Report #26: Cataracts.]

Lifestyle Changes

Studies suggest that patients with glaucoma who exercise regularly (at least 3 times a week) may be able to reduce their intraocular pressure by an average of 20%. If they stop exercising for more than 2 weeks, pressure increases again. In one study, those who walked briskly 4 times a week for 40 minutes were able to go off their medications. (Although not confirmed by any evidence, yoga or other exercises that involve head-down or inverted positions may be harmful for patients with glaucoma and should be discussed with the doctor.)

Exercise has no effect on closed-angle glaucoma. It may, in fact, increase eye pressure in patients with pigmentary glaucoma. Vigorous high-impact exercise may cause more pigment to be released from the iris in these patients. Patients should talk to their doctor about an appropriate exercise program.

Antioxidants in Foods and Supplements. Diet most likely plays very little role in glaucoma. For example, a 2003 study found no association between important nutrients associated with protection against other eye disorders, including vitamins C, E, A, and carotenoids.

Caffeine. Some studies have shown that large amounts of caffeine drunk in a short period of time can elevate eye pressure for up to 3 hours. One study suggested that such changes in eye pressure could be significant in patients with both normal eye pressure and high IOP.

Fluids. Drinking large amounts (a quart or more) of any liquid within a short time, about 30 minutes, appears to increase pressure. Patients with glaucoma should have plenty of fluids, but they should drink them in small amounts over the course of a day.

Glaucoma can cause the eyes to be very sensitive to light and glare. Medications can worsen this problem. Sunglasses solve this problem and are important for prevention of cataracts. Protective sunglasses do not have to be expensive. Sunglasses are classified into three categories based on protection against ultraviolet radiation (UV) A or B:

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 and they should be 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 eye disease. 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 increase the risk of cataracts because the pupil widens to compensate for the shaded glass. This may allow more harmful ultraviolet waves to enter the eye. Polarized glasses cut glare but have no effect on UV radiation. Mirror finishes without additional processing for UV blockage also are 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.

Meditation, biofeedback, and relaxation methods can help counteract stress, and there are some reports that they may help some people with open-angle glaucoma. A number of herbal and nontraditional remedies have been advertised as glaucoma remedies. A few studies have reported that the herbal remedy ginkgo biloba may have properties that offer benefits to patients with glaucoma, including increasing blood flow in the eye without altering overall blood pressure, heart rate, or intraocular pressure. More research is, however, needed.

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. Always check with your doctor before using any herbal remedies or dietary supplements.

The following is of special concern for people with glaucoma:

Bilberry, a European blueberry (Vaccinium myrtillus), is sold in natural food stores as a glaucoma remedy. Studies indicate that it may help some people improve night vision and glare, but it is not at all effective in preventing or treating glaucoma.

Resources

www.glaucoma.org -- Glaucoma Research Foundation
www.nei.nih.gov -- National Eye Institute
www.glaucomafoundation.org -- The Glaucoma Foundation
www.aao.org -- American Academy of Ophthalmology
www.glaucomaweb.org -- American Glaucoma Society
www.lighthouse.org -- Lighthouse International

References

Bottaro M, Ritch R. Intraocular pressure variation during weight lifting. Vieira GM, Oliveira HB, de Andrade DT. Arch Ophthalmol. 2006 Sep;124(9):1251-4.

Brauner SC, Chen TC, Hutchinson BT, Chang MA, Pasquale LR, Grosskreutz CL. The course of glaucoma during pregnancy: a retrospective case series. Arch Ophthalmol. 2006 Aug;124(:1089-94.

Gedde SJ, Schiffman JC, Feuer WJ, Herndon LW, Brandt JD, Budenz DL. Treatment outcomes in the tube versus trabeculectomy study after one year of follow-up. Am J Ophthalmol. 2007 Jan;143(1):9-22.

Hara T, Hara T, Tsuru T. Increase of peak intraocular pressure during sleep in reproduced diurnal changes by posture. Arch Ophthalmol. 2006 Feb;124(2):165-8.

Higginbotham EJ. Managing glaucoma during pregnancy. JAMA. 2006 Sep 13;296(10):1284-5.

Pasquale LR, Kang JH, Manson JE, Willett WC, Rosner BA, Hankinson SE. Prospective study of type 2 diabetes mellitus and risk of primary open-angle glaucoma in women. Ophthalmology. 2006 Jul;113(7):1081-6.

Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol. 2006 Mar;90(3):262-7.

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:
3/3/2007
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, 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

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

Rheumatoid arthritis

FitSugar — Wed, 08 Oct 2008 17:35:00 -0700

In This Report

Highlights
Introduction
Causes
Risk Factors
Symptoms
Complications
Diagnosis
Treatment
Medications
Surgery
Lifestyle Changes
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Treatment Approaches

Patients with rheumatoid arthritis who do not respond to single-drug therapy often do better when a combination of drugs is used, indicates a review of 23 clinical trials published in 2007 in the Annals of Internal Medicine. However, the researchers were unable to determine which combinations of drugs work best or which individual drugs are more effective than others.
Combination drug treatment is now becoming a standard approach to treating rheumatoid arthritis while it is still in its early stages. Another 2007 Annals of Internal Medicine study indicated that initial combination therapies slow progression of joint damage more rapidly than single-drug therapy but, after several years, all treatment strategies produce benefits.

Fish Oil for Joint Pain

The omega-3 fatty acids found in fish oil may have anti-inflammatory properties that can help relieve joint pain, indicates a 2007 review in Pain. The researchers found that taking omega-3 fatty acids for 3 - 4 months helped reduce joint pain intensity, minutes of morning stiffness, the number of painful or tender joints, and consumption of non-steroidal anti-inflammatory drugs (NSAIDs). Salmon, mackerel, and herring are types of fish that are particularly high in these fatty acids. Fish oil can also be taken through dietary supplements, but these can interact with some types of prescription medications and may not be safe or appropriate for all patients. (Check with your doctor before taking these or any other supplements.)

Introduction

Rheumatoid arthritis (RA) is a chronic disease in which various joints in the body are inflamed, leading to swelling, pain, stiffness, and the possible loss of function.

Rheumatoid arthritis is an autoimmune disease in which the body's immune system attacks itself. The pattern of joints affected is usually symmetrical, involves the hands and other joints, and is worse in the morning. Rheumatoid arthritis is a systemic (body-wide) disease, involving other body organs, whereas osteoarthritis is limited to the joints. Both forms of arthritis can be crippling.

The process probably develops in the following way:

The disease process leading to rheumatoid arthritis begins in the synovium, the membrane that surrounds a joint and creates a protective sac.
This sac is filled with lubricating liquid called the synovial fluid. In addition to cushioning joints, this fluid supplies nutrients and oxygen to cartilage, a slippery tissue that coats the ends of bones.
Cartilage is composed primarily of collagen, the structural protein in the body, which forms a mesh to give support and flexibility to joints.
In rheumatoid arthritis, an abnormal immune system produces destructive molecules that cause continuous inflammation of the synovium. Collagen is gradually destroyed, narrowing the joint space and eventually damaging bone.
If the disease develops into a form called progressive rheumatoid arthritis, destruction to the cartilage accelerates. Fluid and immune system cells accumulate in the synovium to produce a pannus, a growth composed of thickened synovial tissue.
The pannus produces more enzymes that destroy nearby cartilage, aggravating the area and attracting more inflammatory white cells, thereby perpetuating the process.

This inflammatory process not only affects cartilage and bones but can also harm organs in other parts of the body.

Click the icon to see an image of rheumatoid arthritis.

Causes

Although much has been learned about the process leading to rheumatoid arthritis, researchers have yet to uncover all the factors that lead to this devastating disease. One prevalent theory is that a combination of factors triggers rheumatoid arthritis, including an abnormal autoimmune response, genetic susceptibility, and some environmental or biologic trigger, such as a viral infection or hormonal changes.

The Normal Immune System Response. The inflammatory process is a byproduct of the activity of the body's immune system, which fights infection and heals wounds and injuries:

When an injury or an infection occurs, white blood cells are mobilized to rid the body of any foreign proteins, such as a virus.
The masses of blood cells that gather at the injured or infected site produce factors to repair wounds, clot the blood, and fight any infections.
In the process the surrounding area becomes inflamed and some healthy tissue is injured. The immune system is then called upon to repair wounds by clotting off any bleeding blood vessel and initiating fiber-like patches to the tissue.
Under normal conditions, the immune system has other special factors that control and limit this inflammatory process.

The Infection Fighters. Two important components of the immune system that play a role in the inflammation associated with rheumatoid arthritis are B cells and T cells, both of which belong to a family of immune cells called lymphocytes.

When macrophages recognize foreign particles entering the bloodstream, they are programmed to ingest them, split them into pieces, and bring specific sections of them (antigens) into contact with the surface of the T cell. These antigens are placed within specialized proteins on the surface of the T cell that signal to a T cell and begin a process of immune system inspection. This process involves the interaction of several proteins on B cells and T cells, which seem to signal back and forth.

If the T cell recognizes an antigen as "non-self," it will produce chemicals (cytokines) that cause B cells to multiply and release many immune proteins (antibodies). These antibodies circulate widely in the bloodstream, recognizing the foreign particles and triggering inflammation in order to rid the body of the invasion. T cells can be further categorized as killer T cells or helper T cells. Killer T cells directly attack antigens, such as viruses and tumor cells. Helper T cells recognize antigens that are presented to them by macrophages (or other specialized cells), and can stimulate B cells to mount various kinds of attacks on the antigen. They also produce chemicals (cytokines) that can have a more direct role in the inflammatory process.

For reasons that are still not completely understood, both the T cells and the B cells become overactive in patients with RA. In an immune response it is normal for the antibody response to change over time, particularly if the first antibodies that are made do not eliminate the invading particles. Little by little, the types of antibodies being made undergo changes in an attempt to achieve better recognition and a stronger inflammatory response against a recalcitrant invader. In RA, a complex interaction between activated immune cells and an impaired antigen-elimination process leads to a greater than normal repertoire of what the antibodies recognize. Eventually, antibodies are made that recognize more of the body's own tissues in a stronger or more persistent manner than is healthy, and inflammatory responses are mounted in these tissues.

An antigen is a substance that can provoke an immune response. Typically antigens are substances not usually found in the body.

Cytokines. Cytokines are very important in the destructive process of rheumatoid arthritis, particularly those known as interleukins (ILs) -- notably IL1 and IL6 -- and tumor necrosis factor (TNF). TNF is now known to be the major cause of joint damage and various systemic manifestations of RA, including weight loss.

Leukocytes. The leukocytes, the other major white blood cells in the body, are also spurred into action by the over-zealous T cells. Leukocytes stimulate the production of key players in the inflammatory process, including leukotrienes, prostaglandins, and nitric oxide.

The Hypothalamic-Pituitary-Adrenal Axis and Stress Hormones. Some research suggests that abnormalities in the hypothalamic-pituitary-adrenal axis (HPA axis) may contribute to RA. The HPA system includes two parts of the brain (the hypothalamus and the pituitary) and the adrenal gland.

Click the icon to see an image of the adrenal glands.

The HPA axis regulates a person's response to stress, which includes the release of cortisol (an important stress hormones) and DHEA (a weak male hormone). The cytokines interleukin-6 and TNF-alpha normally stimulate a surge in these hormones, which then block further release of the cytokines. Research suggests, however, that in RA, a defective HPA axis responds to the cytokines with a lower-than-normal release of cortisol and DHEA. Without a strong stress response, the cytokine levels remain high and become destructive, causing inflammation.

Genetic factors play some role in RA, but are clearly not the only important factor. The presence of certain genetic mutations, however, may worsen the disease process. It should be pointed out that defective genes not only can be inherited but they may be changed and mutated by environmental or other factors. More research is needed to determine the specific genetic contributions to this disease.

HLA. HLA (human leukocyte antigen) is a genetically regulated molecule that traps part of antigens and presents them on the surface of cells for destruction by antibodies and T cells. It is designed to recognize self- from non-self cells. A number of HLA genetic forms called HLA-DRB1 alleles are referred to as the RA-shared epitope because of their association with rheumatoid arthritis. These genetic factors do not cause RA, but they may make the disease more severe once it has developed. Genetic variations in the HLA region may also predict drug treatment response to etanercept and the disease-modifying anti-rheumatic drug methotrexate.

Lack of Corticotropin-Releasing Hormone. Some people with RA may have a genetic deficiency of a hormone known as corticotropin-releasing hormone (CRH), which produces corticosteroids, hormones that suppress the inflammatory process.

Infections. Although many bacteria and viruses have been studied, no single organism has been proven to be the primary trigger for the autoimmune response and subsequent damaging inflammation. Higher than average levels of antibodies that react with the common intestinal bacteria E. coli have appeared in the synovial fluid of people with RA. Some experts think they may stimulate the immune system to prolong RA once the disease has been triggered by some other initial infection. Other potential triggers include Mycoplasma, parvovirus B19, retroviruses, mycobacteria, and Epstein-Barr virus.

Chemicals. A number of chemicals are being investigated as triggers of rheumatoid arthritis, but it is very difficult to determine causal effects of any specific trigger.

Risk Factors

Rheumatoid arthritis (RA) is an ancient disease. The condition has been identified in skeletons thousands of years old. According to the Arthritis Foundation, RA affects an estimated 2.1 million Americans.

Although the disease can occur at any age from childhood to old age, it usually starts in young adulthood, with onset peaking between the ages of 20 - 45. Still, about 50,000 children may be afflicted with juvenile rheumatoid arthritis.

Women are more likely to have RA than men. (The risk for women is slightly lower if they have been pregnant.) Women are also at higher risk for the severe type 2 rheumatoid arthritis.

Some people may inherit genes that make them susceptible to RA, but a family history of RA does not appear to increase an individual's risk.

Other factors may place certain susceptible individuals at higher risk for developing RA:

Heavy long-term smoking is a very strong risk factor for RA, particularly in patients without a family history of the disease.
Women who have a shorter fertility time (and so lower levels of reproductive hormones) may be at higher risk.
History of blood transfusions.

Most studies have not found any association between silicone breast implants and rheumatoid arthritis or other autoimmune disease (except possibly Sjögren syndrome).

Reports from a Dutch study suggest that hay fever sufferers have a reduced risk of developing rheumatoid arthritis, and, conversely, arthritis patients are less likely to have hay fever.

Symptoms

The hallmark symptom of rheumatoid arthritis is morning stiffness that lasts for at least an hour. (Stiffness from osteoarthritis, for instance, usually clears up within half an hour.) Even after remaining motionless for a few moments, the body can stiffen. Movement becomes easier again after loosening up.

Swelling and pain in the joints must occur for at least 6 weeks before a diagnosis of rheumatoid arthritis is considered. The inflamed joints are usually swollen and often feel warm and "boggy" when touched. The pain often occurs symmetrically but may be more severe on one side of the body, depending on which hand the person uses more often.

Although rheumatoid arthritis almost always develops in the wrists and knuckles, the knees and joints of the ball of the foot are often affected as well. Indeed, many joints may be involved, including those in the cervical spine, shoulders, elbows, tips, temporomandibular joint (jaw), and even joints between very small bones in the inner ear. Rheumatoid arthritis does not usually show up in the fingertips, where osteoarthritis is common, but joints at the base of the fingers are often painful.

In about 20% of people with RA, inflammation of small blood vessels can cause nodules, or lumps, under the skin. They are about the size of a pea or slightly larger, and are often located near the elbow, although they can show up anywhere. Nodules can occur throughout the course of the disease. Rarely, nodules may become sore and infected, particularly if they are in locations where stress occurs, such as the ankles. On rare occasions, nodules can reflect the presence of rheumatoid vasculitis, a condition that can affect blood vessels in the lungs, kidneys, or other organs.

Fluid may accumulate, particularly in the ankles. In rare cases, the joint sac behind the knee accumulates fluid and forms what is known as a Baker cyst. This cyst feels like a tumor and sometimes extends down the back of the calf causing pain.

Symptoms such as fatigue, weight loss, and fever may accompany early rheumatoid arthritis. Some people describe them as being similar to those of a cold or flu except, of course, RA symptoms can last for years.

In children, juvenile rheumatoid arthritis, also known as Still's disease, is usually preceded by high fever and shaking chills along with pain and swelling in many joints. A pink skin rash may be present.

Complications

Rheumatoid arthritis is not fatal, but complications of the disease may shorten survival by a few years in some individuals. Although type 2 rheumatoid arthritis is progressive and there is no cure, over time the disease becomes less aggressive, and symptoms may even improve.

Treatments for RA are increasingly effective in slowing this debilitating disease, and some may even prevent initial destruction by aggressively reducing inflammation. If bone and ligament destruction and any deformities have occurred, however, the effects are permanent. It is essential, therefore, to seek a doctor's help as soon as symptoms develop. Side effects of the treatments often contribute to the severity of the disease.

Affected joints can become deformed, and the performance of even ordinary tasks may be very difficult or impossible. According to one survey, 70% of patients with rheumatoid arthritis feel the disease prevents them from living a fully productive life. A 2000 study found that about one-third of people with RA stop working within 5 years of onset of the disease.

Rheumatoid arthritis can affect other parts of the body as well as the joints. Some patients with severe disease may then be at higher risk for complications, such as the following:

Peripheral Neuropathy. This condition affects the nerves, most often those in the hands and feet. It can result in tingling, numbness, or burning.
Muscle problems. Many patients have weakness of the muscles.
Anemia. People with RA may develop anemia, which involves a decrease in the production of red blood cells.
Scleritis and Episcleritis. This is an inflammation of the blood vessels in the eye that can result in corneal damage. Symptoms include redness of the eye and a gritty sensation.
Infections. Patients with RA have a higher risk for infections, particularly from some of the immune-suppressing drugs (corticosteroids, anti-tumor necrosis factors, disease modifying drugs) that they take.
Skin Problems. Skin problems are common, particularly on the fingers and under the nails. Some patients develop severe skin complications that include rash, ulcers, blisters (which may bleed in some cases), lumps under the skin, and other problems. Severe skin disease can reflects a more serious case of RA in general.
Osteoporosis. Osteoporosis, a disorder in which bone density decreases, is more common than average in postmenopausal women with RA. The hipbone is particularly affected. The risk for osteoporosis also appears to be higher than average in men with RA who are over 60 years old.
Lung Disease. Patients with RA are susceptible to chronic lung diseases, including interstitial fibrosis, pulmonary hypertension, and other problems. Both rheumatoid arthritis itself and some treatments may cause this damage.
Kidney. Although rheumatoid arthritis only rarely involves the kidney, many of the drugs used to treat it can damage kidneys.
Vasculitis. Vasculitis involves autoimmune inflammatory abnormalities in very small vessels and can affect many organs in the body. Manifestations of vasculitis include mouth ulcers, nerve disorders, rapid worsening of the lungs, inflammation of coronary arteries, and inflammation of the arteries supplying blood to the intestines.
Heart Disease. Inflammation of the heart muscle itself in the sac around the heart can cause many problems. Mounting evidence suggests that RA can increase the risk for heart disease, possibly because of the inflammatory response in RA, which may also injure arteries and heart muscle tissue. Some studies have reported that people with RA are 30 - 50% more likely to suffer heart vessel blockages and 60 - 70% more likely to die as result than people without RA.
Lymphoma and Other Cancers. Research suggests that patients with RA are four times more likely than healthy patients to develop non-Hodgkin’s lymphoma. There has also been concern that some RA treatments may increase the risk for lymphoma. Studies from 2006 indicate that RA’s chronic inflammatory process may play a role in the development of lymphoma. Researchers found that patients with very severe and long-term RA had a substantially increased risk of developing lymphoma. Other 2006 research suggests that RA drugs, such as biologic response modifiers, do not increase lymphoma risk, although they do increase skin cancer risk.
Periodontal Disease. People with RA may be twice as likely as non-arthritic individuals to have periodontal disease. Chronic inflammation and immune dysfunction are central to both diseases.
Pregnancy. Women with RA have an increased risk for premature delivery. They are also three times more likely than healthy women to develop hypertension during the last trimester of pregnancy.

Juvenile rheumatoid arthritis often resolves before adulthood. Patients who experience arthritis in only a few joints do better than those with more widespread (systemic) disease, which is very difficult to treat. Although it can be very serious, very few people die from this condition.

MAS. Macrophage activation syndrome (MAS) is a life-threatening complication of this disorder and requires immediate treatment with high-dose steroids and cyclosporin A. Parents should be aware of symptoms, which include persistent fever, weakness, drowsiness, and lethargy.

Diagnosis

Rheumatoid arthritis can be difficult to diagnose. Many other conditions resemble it and its symptoms can develop insidiously. Blood tests and x-rays may show normal results for months after the onset of joint pain. Even after rheumatoid arthritis has been diagnosed, it is extremely important to determine whether the course of the disease is benign (type 1) or aggressive (type 2) in order to treat the problem appropriately.

Specific findings or presentation more likely to suggest the diagnosis of rheumatoid arthritis include morning stiffness, involvement of three joints at the same time, involvement of both sides of the body, subcutaneous nodules, positive rheumatoid factor, changes in x-rays.

Various blood tests may be used to help diagnose RA, determine its severity, and detect complications of the disease.

Rheumatoid Factor. In RA, antibodies that collect in the synovium of the joint are known as rheumatoid factor. In about 80% of cases of RA, blood tests reveal rheumatoid factor. It can also show up in blood tests of people with other diseases. However, when it appears in patients with arthritic pain on both sides of the body, it is a strong indicator of type 2 RA. The presence of rheumatoid factor plus evidence of bone damage on x-rays also suggests a significant chance for progressive joint damage.

Erythrocyte Sedimentation Rate Test. An erythrocyte sedimentation rate (ESR or sed rate) measures how fast red blood cells (erythrocytes) fall to the bottom of a fine glass tube that is filled with the patient's blood. The higher the sed rate the greater the inflammation. In addition to rheumatoid arthritis, the sed rate can be high in many conditions ranging from infection to inflammation to tumors. The test is used, then, not for diagnosis, but to help determine how serious the condition is.

C-Reactive Protein. High levels of C-reactive protein (CRP) are also indicators of active inflammation. However, because obesity also increases CRP levels, the doctor should consider a patient’s body mass index when evaluating CRP levels during RA diagnosis.

Anti-CCP Antibody Test. The presence of antibodies to cyclic citrullinated peptides (CCP) can identify RA years before symptoms develop. In combination with the test for rheumatoid factor, the CCP antibody test is the best predictor of which patients will go on to develop severe RA. Used in Europe, the test is now beginning to be used somewhat more commonly in the U.S. U.S. laboratories have not yet developed consistent standards for interpreting the test, however.

Tests for Anemia. Anemia is a common complication. Blood tests are needed often to determine the amount of red blood cells (hemoglobin and hematocrit) and iron (soluble transferrin receptor and serum ferritin) in the blood.

Analyzing the synovial fluid might prove to be helpful in detecting markers of joint destruction, but this is not commonly performed. Some investigational examples include the following:

An enzyme called MMP-3 (matrix metalloproteinase 3) is involved with the degradation of cartilage. Its presence in synovial fluid is strongly associated with progressive joint destruction in patients with chronic RA.
High levels urocortin, a member of the peptide family involved in the stress response, may also be a major player in the RA inflammation.

X-Rays. X-rays generally have not been helpful to detect the presence of early rheumatoid arthritis because they cannot show images of soft tissue. The use of a technique known as dual energy x-ray absorptiometry, however, may be useful in detecting early bone loss in rheumatoid arthritis (2 - 27 months after onset). Evidence of damage on x-rays along with elevated rheumatoid factor is a significant predictor for progressive joint destruction.

Ultrasound. Special ultrasound techniques called power Doppler ultrasonography (PDUS) or quantitative ultrasound (QUS) may be helpful in RA. PDUS may be reliable for monitoring inflammatory activity in the joint. QUS, which is used for osteoporosis, can detect bone loss in fingers, which may prove to be a good indicator of early RA.

Magnetic Resonance Imaging. Specially designed magnetic resonance imaging (MRI) equipment called extremity MRI may be able detect bone erosions in the hands of RA patients where x-rays cannot. Further evaluation is necessary.

Symptoms of rheumatoid arthritis can be mimicked by things as benign as a bad mattress or as serious as cancer. A number of rare genetic diseases attack the joints. Physical injuries, infections, and poor circulation are among the many problems that can cause aches and pains. It would be impossible to discuss in this report the dozens of all conditions with symptoms of joint aches and pains.

Osteoarthritis. Osteoarthritis requires some special mention because it is the most common form of arthritis. It differs from RA in several important respects.

Osteoarthritis usually occurs in older people.
It is located in only one or a few joints. (In fact, osteoarthritis is probably most often confused with rheumatoid arthritis if it affects multiple joints in the body.)
The joints are less inflamed.
Progression of pain is almost always gradual.

Gout. Gout also causes swelling and severe pain in a joint, although most commonly starting in one joint. It is particularly difficult to distinguish chronic gout in older people from rheumatoid arthritis, however, since gout in this population can occur in a number of joints. A proper diagnosis can be made with a detailed medical history, laboratory tests, and detection in the affected joint of a salt called monosodium urate (MSU), which identifies gout.


Disease	Specific Subtypes
Osteoarthritis
Infectious Arthritis	Lyme disease, septic arthritis, bacterial endocarditis, mycobacterial and fungal arthritis, viral arthritis
Postinfectious or Reactive Arthritis	Reiter syndrome (a disorder characterized by arthritis and inflammation in the eye and urinary tract), rheumatic fever, inflammatory bowel disease
Crystal Induced Arthritis	Gout and pseudogout
Other Rheumatic Autoimmune Diseases	Systemic vasculitis, systemic lupus erythematosus, scleroderma, Still's Disease (also called juvenile rheumatoid arthritis), Behcet's disease
Other Diseases	Chronic fatigue syndrome, hepatitis C, familial Mediterranean fever, cancers, AIDS, leukemia, bunions, Whipple's disease, dermatomyositis, Henoch-Schonlein purpura, Kawasaki's disease, erythema nodosum, erythema multiforme, pyoderma gangrenosum, pustular psoriasis

Treatment

The treatment of rheumatoid arthritis involves medications and lifestyle changes.

Many drugs are used for managing the pain and slowing the progression of rheumatoid arthritis, but none completely cure the disease. Some experts believe that no single drug will ever cure rheumatoid arthritis because of the many factors that affect the disease at various times. The goals of drug treatment for rheumatoid arthritis include:

Reduce inflammation
Prevent damage to the bones and ligaments of the joint
Preserve movement
To be as inexpensive and as free from side effects as possible over the long-term

The drug categories used for RA include:

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) are the least potent drugs used for RA. These drugs relieve pain by reducing inflammation, but do not affect the course of the disease.
Disease-Modifying Anti-Rheumatic Drugs (DMARDs) are the main drugs used for treating rheumatoid arthritis. They slow the progression of the disease. They are much more effective than NSAIDs but also have more side effects. Methotrexate (Rheumatrex, Trexall) is the most widely used of these drugs.
Biologic Response Modifiers (also known as Biologic DMARDs) are often prescribed to patients who have failed to respond to DMARDs. They may be used alone or in combination with DMARDs such as methotrexate. They modify or block destructive immune factors such as tumor-necrosis factor (TNF). Current anti-TNF drugs include infliximab (Remicade), etanercept (Enbrel), and adalimumab (Humira). Other biologic response modifiers include the interleukin-1 antagonist anakinra (Kineret), the T cell co-stimulation modulator abatacept (Orencia), and rituximab (Rituxan), which targets CD20-positive B cells.
Corticosteroids, or steroids, are powerful anti-inflammatory drugs that are used to quickly reduce inflammation. These drugs include prednisone and prednisolone.

The question of how early and how aggressively to treat RA has been the subject of great debate. Among patients with RA, some will go into remission and remain in remission for the length of their lives even in the absence of treatment, while others will go on to develop active, sometimes severe RA.

Current practice has moved towards treating the disease aggressively while it is in its early stages to help prevent it from reaching a more severe and chronic state. Studies have found less joint damage in patients with early, aggressive treatment, particularly with the use of DMARDs and TNF modifiers in combination with methotrexate. Intensive early dosing of methotrexate may help slow progression of rheumatoid arthritis. Early combination therapy with DMARDs and corticosteroids is also showing good results.

During the first year of treatment, combination therapy appears to reduce the progression of joint deterioration more rapidly and effectively than single drug treatment. In addition, patients who have not been helped by one drug often benefit from a combination of drugs. However, over a longer period of time, it is not clear whether a drug combination approach offers many advantages over single drugs. It is also not certain which combination of drugs works best. Depending on your particular health condition, and how you respond to the drugs prescribed, your doctor may try various treatment strategies.

Medications

Two-thirds of people with RA rank pain as their primary reason for seeking professional help. The most common pain relievers for RA are nonsteroidal anti-inflammatory drugs (NSAIDs). These drugs block prostaglandins, the substances that dilate blood vessels and cause inflammation and pain. There are dozens of NSAIDs:

Over-the-counter NSAIDs include aspirin, ibuprofen (Motrin IB, Advil, Nuprin, Rufen), naproxen (Aleve), ketoprofen (Actron, Orudis KT).
Prescription NSAIDs include ibuprofen (Motrin), naproxen (Naprosyn, Anaprox), flurbiprofen (Ansaid), diclofenac (Voltaren), tolmetin (Tolectin), ketoprofen (Orudis, Oruvail), dexibuprofen (Seractil). In 2004, a new NSAID, meloxicam (Mobic) was approved in the U.S. for the management and treatment of rheumatoid arthritis.

Studies suggest that the best times for taking an NSAID may be after the evening meal and then again on awakening. RA symptoms increase gradually during the night, reaching their greatest severity at the time of awakening. Taking NSAIDs with food can reduce stomach discomfort, although it may slow down the pain-relieving effect.

In April 2005, the Food and Drug Administration (FDA) asked drug manufacturers of prescription NSAIDs to include with their products the same warning label used for the COX-2 inhibitor celecoxib (Celebrex). This "black box" warning, the FDA's strongest warning, emphasizes the increased risks for cardiovascular events and gastrointestinal bleeding associated with these drugs’ use. The FDA also requested manufacturers of OTC NSAIDs to revise their labels to include more specific language concerning potential cardiovascular and gastrointestinal risks. Due to its proven heart benefits, aspirin was excluded from these labeling revisions. In December 2006, the FDA proposed even stronger labeling changes to highlight these drugs’ risk for liver damage as well as alcohol and drug interactions.

Long-term, regular use of NSAIDs can increase the risk for heart attack, especially for people who have a heart condition. Long-term use of NSAIDs is also the second most common cause of ulcers and gastrointestinal bleeding. To reduce the risks associated with NSAIDs, take the lowest dose possible for pain relief.

Other possible side effects of NSAIDs may include:

Upset stomach
Dyspepsia (burning, bloated feeling in pit of stomach)
Drowsiness
Skin bruising
High blood pressure
Fluid retention
Headache
Rash
Reduced kidney function

Long-term use of NSAIDs is the second most common cause of ulcers. Ulcers caused by NSAIDs are more likely to bleed than those caused by the bacteria Helicobacter pylori.

NSAID-related bleeding and stomach problems may be responsible for 107,000 hospital admissions and 16,500 deaths each year. Those at high risk for bleeding include people over age 60, anyone with a history of ulcers of gastrointestinal bleeding, patients with serious heart conditions, people who abuse alcohol, and those who take medications such as anticoagulants (blood thinners) and corticosteroids.

Proton-pump inhibitor (PPI) drugs may help prevent and heal ulcers caused by NSAIDs. PPIs include omeprazole (Prilosec), esomeprazole (Nexium), and lansoprazole (Prevacid).

COX-2 Inhibitors (Coxibs). Coxibs inhibit an inflammation-promoting enzyme called COX-2. This drug class was initially thought to provide benefits equal to NSAIDs but cause less gastrointestinal distress. However, following numerous reports of heart problems, skin rashes, and other adverse effects, the FDA re-evaluated the risks and benefits of this drug class. This lead to the removal of rofecoxib (Vioxx) and valdecoxib (Bextra) from the United States market. Celecoxib (Celebrex) is still available, but patients should ask their doctor whether the drug is appropriate and safe for them. In December 2006, the FDA approved celecoxib for the relief of symptoms of juvenile rheumatoid arthritis in patients ages 2 years and older.

Disease-modifying anti-rheumatic drugs (DMARDs) are the standard treatments for RA. They are used either alone or in combination with newer biologic DMARDs.

DMARDs do not have any common properties other than their ability to slow down the progression of rheumatoid arthritis. Many were used for other diseases and were found accidentally to help RA. DMARDs include:

Methotrexate (considered to be the current standard of care)
Leflunomide
Hydroxychloroquine
Sulfasalazine
Gold
Minocycline
Azathioprine
Cyclosporine

Unfortunately, all DMARDs tend to lose effectiveness over time, even methotrexate. Patients rarely use one drug for more than 2 years. Combining DMARDs with each other or with drugs in other categories offers the best approach for many patients. The addition of a corticosteroid to any combination may also be helpful.

All DMARDs may produce stomach and intestinal side effects, and, over the long-term, each poses some risk for rare but serious reactions. (In some cases, however, they may be less harmful than long-term NSAID treatment.)

Methotrexate. Methotrexate (Rheumatrex, Trexall) acts as an anti-inflammatory drug and is now the most frequently used DMARD, particularly for severe disease. It has a faster mode of action than other DMARDs, (it starts working within 3 - 6 weeks), and its effectiveness as a well proven in studies.

Even this drug loses effectiveness, however, when used alone. It may be more effective when used in combination with other DMARDs or other drugs. Recent studies have focused on combining methotrexate with various biological response modifier drugs, especially for treatment of patients with early aggressive arthritis. The combination appears to work better than single drug therapy.

About 20% of patients withdraw from methotrexate because of its side effects. They include nausea and vomiting, rash, mild hair loss, headache, mouth sores, and muscle aches. Methotrexate reduces levels of folic acid (folate) in the body, which can lead to some of these side effects. Doctors may prescribe folic acid supplements to prevent side effects. However, some research suggests that folic acid may interfere with methotrexate’s effectiveness.

Methotrexate is usually given as pills. Patients who need higher doses can take it as an injection. Methotrexate has fewer serious toxic effects than many DMARDs. Although these severe reactions are rare, they may include:

Kidney and liver damage. People at particular risk for liver damage from methotrexate include those with diabetes, obesity, and alcoholism.
Increased risk for infections
Lung disease occurs in up to 5% of people. People who have poor lung function are most at risk.
The drug increases the risk for birth defects and should not be taken by pregnant women. However, methotrexate will not harm a woman’s chance for future healthy pregnancy.

Leflunomide. Leflunomide (Arava) blocks autoimmune antibodies and reduces inflammation. It also may inhibit metalloproteinases (MMP), which are involved in cartilage destruction. It has the following benefits:

It slows disease progression as early as 6 months into treatment.
Comparison studies with methotrexate report a better quality of life with leflunomide, including more energy, greater vitality, and fewer emotional side effects. (Studies comparing their risk for serious adverse effects are mixed. One, for example, showed fewer problems with leflunomide, while another reported identical rates.)

The combination of methotrexate and leflunomide (which has different effects on the immune system) is very effective compared to either drug alone. (This combination poses a risk for liver toxicity and requires monitoring.)

Reports of adverse effects are comparable to those with methotrexate. Common problems include nausea, diarrhea, hair loss, and rash. Potentially serious side effects include infections and liver injury. Everyone taking leflunomide should be monitored regularly, including blood tests for liver function, and anyone with liver problems should not take this drug. Monitoring of serum concentrations of the most active metabolite of leflunomide may help predict treatment response.

Hydroxychloroquine. Hydroxychloroquine (Plaquenil) was originally used for preventing malaria and is now also used for mild, slowly progressive arthritis. It can help relieve pain and improve mobility. It has one of the least toxic profiles of the DMARDs. The downside is that this drug can take up to 6 months to achieve full benefit. It also does not appear to slow disease progression. One study concluded that joint erosion after 2 years was worse than with no DMARD at all.

As with all DMARDs, gastrointestinal complaints are fairly common. This drug used to be associated with eye and vision problems, but with current lower doses this side effect is rare. If vision problems occur, it is usually with people taking very high doses, those with kidney disease, or those over 60 years of age. Still, you should have regular eye exams while taking this drug and notify your doctor if you experience any sudden changes in vision.

Sulfasalazine. Sulfasalazine (Azulfidine) was developed in the 1930s for treating rheumatoid arthritis, but fell into disfavor when gold treatment emerged. It has regained popularity, however, and is now used for both adult and juvenile RA. It works best when the disease is confined to the joints. Symptom relief occurs within 1 - 3 months.

Side effects are common, particularly stomach and intestinal distress, which usually occur early in the course of treatment. (However, serious gastrointestinal side effects, such as stomach ulcers, occur less frequently with sulfasalazine than with NSAIDs.) A coated-tablet form may help reduce side effects. Other side effects include skin rash and headache. Sulfasalazine increases sensitivity to sunlight. Be sure to wear sunscreen (SPF 15 or higher) while taking this drug. People with intestinal or urinary obstructions or who have allergies to sulfa drugs or salicylates should not take sulfasalazine.

Gold. Gold has been a long-standing DMARD for rheumatoid arthritis, although its use has decreased with the development of disease modifying and biologic drugs. Gold is usually administered in an injected form because the oral form, auranofin (Ridaura), is much less effective. There are two injectable forms of gold: Gold sodium thiomalate (Myochrysine) and aurothioglucose (Solganal). It can take 3 - 6 months before injections have an effect on RA symptoms.

Gold injections cause mouth sores in about a third of patients. Skin side effects include itching and rash, which can be severe in some patients. . The most serious side effects of gold injections, while rare, are kidney damage and decreased white blood cell count. Gold injections are not usually given to pregnant women. It is not definite that gold causes birth defects but doctors generally recommend that women use birth control while receiving this drug.

Minocycline. Minocycline (Minocin) is a tetracycline antibiotic that is usually prescribed for patients with mild RA. It can take 2 - 3 months before symptoms begin to improve and up to a year for full benefit. Side effects include upset stomach, dizziness, and skin rash. Long-term use of minocycline can cause changes in skin color, but this side effect usually disappears once the medication is stopped. Minocycline can cause yeast infections in women. Minocycline increases sensitivity to sunlight and patients should be sure to wear sunscreen. In rare cases, minocycline can affect the kidneys and liver.

Azathioprine. Azathioprine (Imuran) suppresses immune system activity. It takes 6 - 8 weeks for early symptom improvement and up to 12 weeks for full benefit. Azathioprine can cause serious problems with the gastrointestinal tract. About 10 - 15% of patients experience nausea and vomiting, often accompanied by stomach pain and diarrhea. (Taking the medication twice daily, instead of once daily, or taking it after eating may help avoid this problem.) Azathioprine can also cause problems with liver function and pancreas gland inflammation, and can reduce white blood cell count.

Cyclosporine. Like azathioprine, cyclosporine (Sandimmune, Neoral) is an immunosuppressant. It is used for people with RA who have not responded to other drugs. It can take a week before symptoms improve and up to 3 months for full benefit. The most serious and common side effects of cyclosporine are high blood pressure and kidney function problems. While kidney function usually improves once the drug is stopped, mild-to-moderate high blood pressure may continue. Cyclosporine can also cause gout or worsen gout in people who have this condition.

Other common side effects include headache, nausea, vomiting, stomach pain and upset, and swelling of hands and feet. About 10% of patients who take cyclosporine develop tremors, increased hair growth, muscle cramps, and numbing or tingling in hands and feet (neuropathy). Swelling of the gums is also common. Patients should practice good dental hygiene, including regular brushing and flossing.

Biologic response modifiers are drugs made from living cells. These drugs target specific components of the immune system that contribute to the joint inflammation and damage that are part of the rheumatoid arthritis disease process.

Currently approved biologic response modifiers include:

Etanercept (Enbrel). Etanercept is an anti-tumor necrosis factor (anti-TNF) drug. Approved in 1998, etanercept was the first biologic response modifier drug for treatment of rheumatoid arthritis. It is also approved for juvenile RA and psoriatic arthritis.
Infliximab (Remicade). Approved in 1999, infliximab is also an anti-TNF drug. It is used in combination with methotrexate.
Adalimumab (Humira). Adalimumab is another anti-TNF drug. First approved in 2002 as a second-line treatment for RA, adalimumab received additional approvals in 2005 as a first-line treatment for RA and psoriatic arthritis. It is used alone or in combination with methotrexate or other DMARDs. It is also showing promising results in clinical trials for juvenile rheumatoid arthritis.
Anakinra (Kineret). Approved in 2001, anakinra targets interleukin-1 (IL-1), another type of immune factor.
Abatacept (Orencia). Approved in 2005 for adults with moderate-to-severe RA who have not responded to DMARD or anti-TNF drugs. Abatacept is known as a T cell co-stimulation modulator. It blocks T cell activation. It is used alone or in combination with other DMARDs aside from anti-TNF drugs.
Rituximab (Rituxan). Approved in 2006, rituximab targets CD20-positive B cells and blocks their activation. It is used in combination with methotrexate for patients with moderate-to-severe RA who have not responded to anti-TNF therapies.

Some of these drugs are used as first-line treatments for RA. Others are used for patients who have not responded to DMARDs or other types of treatment. Depending on the specific drug, they may be used alone or in combination with the DMARD methotrexate. However, biologic response modifiers are not used in combination with each other, as they can lead to serious infections.

As with other rheumatoid arthritis drugs, these drugs do not cure the disease but can help slow progression and joint damage. In recent clinical trials, some patients have achieved remission using methotrexate in combination with infliximab, adalimumab, or rituximab.

Side Effects and Complications. Etanercept, adalimumab, and anakinra are given by injection and may cause pain at the injection site. To prevent injection reactions, patients are sometimes pretreated with betamethasone, a corticosteroid drug, but some research suggests that the steroid does little good. Infliximab, abatacept and rituximab are given by intravenous infusion. Common infusion reactions include headache, nausea, and flu-like symptoms. Because biologic response modifiers affect the immune system, patients who take these drugs have an increased risk for infections.

Other risks associated with these drugs include:

Anti-TNF drugs (etanercept, infliximab, adalimumab) have been associated with sepsis, pneumonia, and tuberculosis; non-melanoma skin cancer, lymphoma, and other malignancies; lupus; heart failure; blood disorders (including aplastic anemia); palmoplantar psoriasis; lung disease; and liver damage.
Anakinra may cause a sudden drop in white blood cells (leukopenia) that increases the risk for infections.
Abatacept should be used cautiously in patients with chronic obstructive pulmonary disorder (COPD) as it may increase the risk for respiratory complications.
Rituximab has been associated with cases of a rare and deadly brain infection called progressive multifocal leukoencephalopathy (PML). It also may cause hepatitis B reactivation, viral infections, and heart rhythm disturbances and other heart problems.

Corticosteroids work rapidly to control inflammation and pain. Long-time use, however, can have severe adverse effects. Still, they are often used under the following conditions:

Oral corticosteroids, such as prednisolone and prednisone (Deltasone, Orasone), are most often used in combination with DMARDs, which significantly enhances the benefits of DMARDs.
Oral corticosteroids are sometimes used in early stage-RA for patients who cannot tolerate NSAIDs. Studies, in fact, suggest that low-dose corticosteroids may significantly slow joint pain when it is the first drug administered and then used for 2 years. (Even low-dose oral steroids have adverse effects on bone density, blood sugar, and weight.)
Higher doses of corticosteroids are used for flareups of vasculitis and severe reactions to medications.
Corticosteroids may also be used during pregnancy to avoid exposure to more toxic drugs.
Daily, low-dose corticosteroids are also needed in some patients to control their rheumatoid arthritis symptoms.
Corticosteroids are sometimes injected directly into joints for relief of flare-ups when only one or a few joints are affected. Experts suggest no more than three or four injections into a specific joint a year. Steroid injections in the joints may be a safe and effective treatment for juvenile rheumatoid arthritis and reduce the need for oral medication.
Corticosteroid pulse therapy (intravenous administration) may work as well as DMARDs.

Side Effects of Oral Corticosteroids. Serious side effects are associated with long-term use of oral steroids. (Low doses may reduce these risks, but they do not eliminate them.) Osteoporosis is a common and particularly severe long-term side effect of prolonged steroid use. Medications that can prevent osteoporosis include calcium supplements, parathyroid hormone, or bisphosphonates (alendronate etidronate, risedronate). Other adverse effects include cataracts, glaucoma, diabetes, fluid retention, susceptibility to infections, weight gain, hypertension, capillary fragility, acne, excess hair growth, wasting of the muscles, menstrual irregularities, irritability, insomnia, and, rarely, psychosis. Recent research suggests that prednisone can increase the risk of developing non-melanoma skin cancer.

Withdrawal from Long-Term Use of Oral Corticosteroids. Long-term use of oral steroid medications suppresses secretion of natural steroid hormones by the adrenal glands. After withdrawal from these drugs, this so-called adrenal suppression persists and it can take the body a while (sometimes up to a year) to regain its ability to produce natural steroids again. There have been a few cases of severe adrenal insufficiency that occurred when switching from oral to inhaled steroids, which, in rare cases, has resulted in death.

No one should stop taking any steroids without consulting a doctor first, and if steroids are withdrawn, regular follow-up monitoring is necessary. Patients should discuss with their doctor measures for preventing adrenal insufficiency during withdrawal, particularly during stressful times, when the risk increases.

Biologic Drugs. For many years, therapeutic treatment of rheumatoid arthritis focused on T cell mediation. New research is now examining the role of B cells, which become overactive in autoimmune disease, and how B cell depletion may help to reduce disease activity. Other areas of intense research include interleukin receptor antagonists, which target cytokines involved in the inflammatory process.

Many of the current investigational drugs are monoclonal antibodies (MAbs), biologic drugs that are designed to target specific receptors. Promising candidates in late-stage research include tocilizumab (Actemra), golimumab, denosumab, ocrelizumab, ofatumumab, and certolizumab.

Statins. Some research suggests that compounds derived from statins, the highly regarded cholesterol-lowering drugs, may suppress the inflammation responsible for RA damage.

Stem cell transplantation. Stem cells are the early versions of mature, specialized blood cells. Investigators are reporting that transplantation of donated hemopoietic stem cells, which mature into various blood cells, has induced remission in a few children with severe juvenile rheumatoid arthritis. The procedure is promising in select cases, but it can be highly toxic. More studies are needed to determine risks and benefits for RA patients.

Plasmapheresis. A device called the Prosorba column is used to remove inflammatory antibodies from the patient's blood. Small, short-term studies have shown that this therapy may slow or even halt the progression of the disease in a third to a half of patients. Side effects from the Prosorba column may include anemia, fatigue, itching, fever, a drop in blood pressure, and nausea. Nearly all patients experience an immediate flare-up of joint pain that lasts a few days. Some patients develop infection from the catheter used to remove blood. Long-term studies are needed.

Surgery

Certain surgical techniques may be helpful for people with severe deformities or disabilities.

Arthroscopy. Arthroscopy is performed to clean out bone and cartilage fragments that cause pain and inflammation. It is usually performed on the knee, but it also may be done on the hip:

The surgeon makes a small incision and injects a sterile solution to make the joint swell for easier viewing.
A lighted tube, called an arthroscope (which enables the surgeon to view the joint), is then inserted through another small incision.
Through a third incision, the surgeon trims, shaves, or stitches the damaged tissue. (Arthroscopy is most successful when the removal of cartilage only, and not bone, is involved.)

In many cases, the procedure can be done using local anesthetic, and the patient can go home within a day. In the case of knee operations, patients can resume mild activity in a couple of days, but full recovery can take up to 3 months.

Osteotomy. If only a certain section (the medial compartment) of the knee is damaged and deformed, the surgeon may choose to perform osteotomy:

The knee is opened.
A debridement (removal of damaged tissue) is performed in the joint to eliminate the loose or torn fragments that are causing pain and inflammation.
The bone is then reshaped to remove the deformity.

The procedure is best used in heavier adults who are under 60 years old.

Unicompartmental Knee Arthroplasty. Unicompartmental knee arthroplasty (also called unicondylar knee arthroplasty) may be a useful procedure in some cases of limited damage in the knee. It is intended to relieve pain and preserve function as long as possible before a total knee replacement is necessary. The procedure involves a small incision and insertion of small implants. It retains important knee ligaments, which should preserve more movement than a total knee replacement. The procedure is not widely available and is somewhat controversial, since the implants may not be as reliable as those in total knee replacement.

Synovectomy. Synovectomy is a procedure whereby the diseased joint lining is removed. It is used when more conservative measures fail, particularly in the wrist. Studies are suggesting, however, that with the use of lasers for the procedure, eventually synovectomy may prove to be an alternative to DMARD treatments in reducing symptoms and achieving long-term remission.

Joint Replacement Surgery. Eventually, even after these procedures, rheumatoid arthritis may progress to the point that normal functioning is impossible. In such cases, artificial (prosthetic) replacement joint implants may be considered for knees, hips, or other joints. The prosthesis is usually made of a chromium alloy and plastic and may be attached to the adjoining bones using a cement, polymethyl methacrylate, or the prosthesis may be composed of a porous material that allows bone to grow into and eventually adhere to the device.

Although this procedure has usually been performed in people over 60, implants are now lasting 20 years and more and younger patients with severe disability are finding them useful. Uncemented arthroplasty using porous material is showing particularly good results. Studies on hip replacement, for example, now report that after 10 years, 5% of patients require reoperation and 12% of patients report some pain.

Lifestyle Changes

It is important to maintain a balance between rest (which will reduce inflammation) and exercise (which will relieve stiffness and weakness). Studies have suggested that even as little as 3 hours of physical therapy over 6 weeks will help people with RA, and that these benefits are sustained.

The goal of exercise is to:

Maintain a wide range of motion
Increase strength, endurance, and mobility
Improve general health
Promote well-being

In general, doctors recommend the following approaches:

Start with the easiest exercises, stretching and tensing of the joints without movement.
Next attempt mild strength training. (One study found that people with RA who exercised with machines that use compressed air for gentle resistance experienced less pain and increased muscle tone.)
The next step is to try aerobic exercises. These include walking, dancing, or swimming, particularly in heated pools. Avoid heavy impact exercises, such as running, downhill skiing, and jumping.
Tai chi, which uses graceful slow sweeping movements, is an excellent method for combining stretching and range-of-motion exercises with relaxation techniques. It is of particularly value for elderly RA patients who report significantly less pain after practicing this technique.

While traditional guidelines have restricted RA patients to only gentle exercise, recent research suggests that more intense exercise may not only be safe, but may actually produce greater muscle strength and overall functioning. Common sense is the best guide:

If exercise is causing sharp pain, stop immediately.
If lesser aches and pains continue for more than 2 hours afterwards, try a lighter exercise program for a while.
Using large joints instead of small ones for ordinary tasks can help relieve pressure, for instance, closing a door with the hip or pushing buttons with the palm of the hand.

Many patients with RA try dietary approaches, such as fasting, vegan diets, or eliminating specific foods, that seem to worsen RA symptoms. There is little scientific evidence to support these approaches but some patients report anecdotally that they are helpful.

In recent years, a number of studies have suggested that the omega-3 fatty acids contained in fish oil may have anti-inflammatory properties useful for RA joint pain relief. The best source of fish oil is through increased consumption of fatty fish such as salmon, mackerel, and herring. Fish oil supplements are another option, but they may interact with certain medications. If you are thinking of trying fish oil supplements, talk to your doctor first.

Various ointments, including Ben Gay and capsaicin (a cream that use the active ingredient in chilli peppers), may help soothe painful joints.

Orthotic devices are specialized braces and splints that support and help align joints. Many such devices made from a variety of light materials are available and can be very helpful when worn properly.

A number of specially designed appliances and devices are available to ease daily activities.

Although the influence of stress or emotions on the progression of RA is not fully known, having a history of major depression that persists or reoccurs seems to increase the pain, disability, and fatigue. Stress management alone cannot reduce pain, but it may be very helpful in helping people deal with their condition.

One study found that people with RA reported significant clinical improvement after writing about their pain, stress, or other traumatic experiences. Writing for 20 minutes, just a few days a week, resulted in improvement that lasted for months. One study found that spirituality (defined as "a belief in a power outside oneself and one's own existence," as opposed to the practice of any specific religion) is associated with better health, happiness and well-being among RA patients. (Spiritual healing does not appear to offer any advantages.)

People often turn to alternative therapies or nontraditional remedies to relieve the pain of rheumatoid arthritis. Some alternative procedures, such as acupuncture, massage, relaxation techniques, biofeedback, and hypnosis, are not harmful and may be a useful adjunct to standard treatments.

In a small study, acupuncture reduced pain by a third in 73% of patients, and more than half reported at least a 50% improvement in pain. Patients also reduced their use of pain medications. Research presented at the 2006 American College of Rheumatology annual meeting suggested that both electroacupuncture and traditional acupuncture may help reduce joint tenderness.
Balneotherapy, also known as hydrotherapy or spa therapy, is an ancient form of therapy that involves mineral baths to soothe pain, and some patients have reported relief using such baths.
The NIH is conducting clinical trials to examine whether relaxation response, tai chi, stress management, and cognitive-behavioral therapy can help patients with RA feel better.

Herbal remedies used for RA include boswellia, equisetum arvense (horsetail), devil's claw, borage seed oil, and many others. To date, no evidence supports their efficacy.

Researchers are currently conducting studies in animals to determine if supplements extracted from the turmeric spice can help prevent joint inflammation. The U.S. National Institutes of Health is also conducting a clinical trial to compare the clinical effects of the Chinese herb Tripterygium wilfordii Hook F (TwHF) with the pharmaceutical drug sulfasalazine. TwHF is traditionally used in Chinese medicine for its anti-inflammatory properties.

Resources

www.niams.nih.gov -- The National Institute of Arthritis and Musculoskeletal and Skin Diseases
www.rheumatology.org -- American College of Rheumatology
www.arthritis.org -- The Arthritis Foundation
www.fda.gov/cder/drug/infopage/cox2 -- FDA information on COX-2 inhibitors and NSAIDs
www.clinicaltrials.gov -- Find a clinical trial

References

Chen YF, Jobanputra P, Barton P, Jowett S, Bryan S, Clark W, et al. A systematic review of the effectiveness of adalimumab, etanercept and infliximab for the treatment of rheumatoid arthritis in adults and an economic evaluation of their cost-effectiveness. Health Technol Assess. 2006 Nov;10(42):iii-iv, xi-xiii, 1-229.

Donahue KE, Gartlehner G, Jonas DE, Lux LJ, Thieda P, Jonas BL, et al. Systematic Review: Comparative Effectiveness and Harms of Disease-Modifying Medications for Rheumatoid Arthritis. Ann Intern Med. 2007 Nov 19 [Epub ahead of print]

Firestein GS. In: Harris ED Jr, ed. Kelley's Textbook of Rheumatology. 7th ed. Saunders; 2005.

Furst DE, Breedveld FC, Kalden JR, Smolen JS, Burmester GR, Sieper J, et al. Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2007. Ann Rheum Dis. 2007 Nov;66 Suppl 3:iii2-22.

Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, van Zeben D, Kerstens PJ, Hazes JM,, et al. Comparison of treatment strategies in early rheumatoid arthritis: a randomized trial. Ann Intern Med. 2007 Mar 20;146(6):406-15.

Goldberg RJ, Katz J. A meta-analysis of the analgesic effects of omega-3 polyunsaturated fatty acid supplementation for inflammatory joint pain. Pain. 2007 May;129(1-2):210-23. Epub 2007 Mar 1.

Harris ED Jr. In: Harris ED Jr, ed. Kelley's Textbook of Rheumatology. 7th ed. Saunders; 2005. O’Dell JR. In: Goldman, ed. Cecil Medicine. 23rd ed. Saunders; 2007.

Smolen JS, Aletaha D, Koeller M, Weisman MH, Emery P. New therapies for treatment of rheumatoid arthritis. Lancet. 2007 Dec 1;370(9602):1861-74.

Smolen JS, Keystone EC, Emery P, Breedveld FC, Betteridge N, Burmester GR,. et al. Consensus statement on the use of rituximab in patients with rheumatoid arthritis. Ann Rheum Dis. 2007 Feb; 66(2): 143-50.

Review Date:
1/21/2008
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

A.D.A.M. Copyright

adam.com

Urinary incontinence

FitSugar — Wed, 08 Oct 2008 17:34:59 -0700

In This Report

Highlights
Introduction
Stress Incontinence
Urge Incontinence
Overflow Incontinence
Functional Incontinence
Risk Factors
Diagnosis
Prognosis
Treatment
Lifestyle Changes
Other Treatments
Behavioral Treatments
Medications
Surgery
Other Procedures
Catheters and Collection De...
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Sling Procedure Versus Burch Colposuspension

The sling procedure is better than Burch colposuspension in treating stress incontinence but may cause more post-operative urinary complications, according to results from an important 2007 New England Journal of Medicine study. In the first large-scale clinical trial to directly compare these two types of surgery, 47% of women who underwent the sling procedure had no urinary incontinence 2 years after surgery, compared with 38% of women who received the Burch procedure. However, 63% of women who had the sling procedure (and 47% of women who underwent the Burch procedure) experienced urinary tract infections following surgery.

Oxybutynin May Cause Hallucinations

In 2007, the FDA investigated reports that oxybutynin (Detrol) may cause hallucinations, especially in children and older adults. Out of 202 reports of oxybutynin-related central nervous system side effects, hallucinations occurred in 27% of cases involving children and 25% of cases involving adults age 60 years and older. The FDA is considering adding stronger cautions about these risks to oxybutynin’s prescribing label.

Tamsulosin and Tolterodine Combination Treatment

For men with moderate-to-severe lower urinary tract symptoms, including overactive bladder, a combination of tamsulosin (Flomax) and tolterodine (Detrol) works better than either drug alone, according to a study published in 2006 in the Journal of the American Medical Association.

Researchers Investigating Stem Cell Treatment for Stress Incontinence

Muscle stem cell injections may eventually prove to be an effective treatment for stress incontinence, indicate several small studies. Doctors took tissue biopsies from patients’ arm muscles, then isolated and injected the muscle stem cells into areas surrounding the urethra. The injections helped strengthen sphincter muscles and improved bladder control. Researchers presented results of these studies at the 2007 American Urological Association annual meeting and the 2006 Radiological Society of North America annual meeting.

Introduction

Urinary incontinence is the inability to control urination. It may be temporary or permanent, and can result from a variety of problems in the urinary tract. Urinary incontinence is generally divided into four groups, according to the problem involved:

Stress incontinence
Urge incontinence
Overflow incontinence
Functional incontinence

Often, more than one type of incontinence is present, with about 40% of all cases falling into more than one category.

Because incontinence is a symptom, rather than a disease, it is often hard to determine the cause. In addition, a variety of conditions may be the cause.

The urinary system helps to maintain proper water and salt balance throughout the body:

The process of urination begins in the two kidneys, which process fluids and dissolve waste matter to produce urine.
Urine flows out of the kidneys into the bladder through two long tubes called ureters.
The bladder is a sac that acts as a reservoir for urine. It is covered with a membrane and enclosed in a powerful muscle called the detrusor. The bladder rests on top of the pelvic floor. This is a muscular structure similar to a sling running between the pubic bone in front to the base of the spine.
The bladder stores the urine until it is eliminated from the body via a tube called the urethra, which is the lowest part of the urinary tract. (In men it is enclosed in the penis. In women it leads directly out.)
The connection between the bladder and the urethra is called the bladder neck. Strong muscles called sphincter muscles encircle the bladder neck (the smooth internal sphincter muscles) and urethra (the fibrous external sphincter muscles).

Click the icon to see an animation about urination.

The Process of Urination

The process of urination is a combination of automatic and conscious muscle actions. There are two phases: the emptying phase and the filling and storage phase.

The Filling and Storage Phase. When a person has completed urination, the bladder is empty. This triggers the filling and storage phase, which includes both automatic and conscious actions.

Automatic Actions. The automatic signaling process in the brain relies on a pathway of nerve cells and chemical messengers (neurotransmitters) called the cholinergic and adrenergic systems. Important neurotransmitters include serotonin and noradrenaline. This pathway signals the detrusor muscle surrounding the bladder to relax. As the muscles relax, the bladder expands and allows urine to flow into it from the kidney. As the bladder fills to its capacity (about 8 - 16 oz of fluid) the nerves in the bladder send back signals of fullness to the spinal cord and the brain.
Conscious Actions. As the bladder swells, the person becomes conscious of a sensation of fullness. In response, the individual holds the urine back by voluntarily contracting the external sphincter muscles, the muscle group surrounding the urethra. These are the muscles that children learn to control during the toilet training process.

When the need to urinate becomes greater than one's ability to control it, urination (the emptying phase) begins.

The Emptying Phase. This phase also involves automatic and conscious actions.

Automatic Actions. When a person is ready to urinate, the nervous system initiates the voiding reflex. The nerves in the spinal cord (not the brain) signal the detrusor muscles to contract. At the same time, nerves are also telling the involuntary internal sphincter (a strong muscle encircling the bladder neck) to relax. With the bladder neck now open, the urine flows out of the bladder into the urethra.
Conscious Actions. Once the urine enters the urethra, a person consciously relaxes the external sphincter muscles, which allows urine to completely drain out from the bladder.

The female and male urinary tracts are relatively the same except for the length of the urethra.

Stress Incontinence

The primary symptom of stress incontinence is leakage due to activities that apply pressure to a full bladder. High-impact exercise poses the greatest risk for leaking. But stress incontinence can occur with even minor activities, such as:

Coughing
Sneezing
Laughing
Running (sometimes even standing can produce leakage)
Lifting

Leakage stops when the activity stops. If the condition persists, it is more likely to be urge incontinence.

Stress incontinence occurs because the internal sphincter does not close completely. In both men and women, the aging process causes a general weakening of the sphincter muscles and a decrease in bladder capacity. Causes of stress incontinence, however, may differ between men and women.

In women, stress incontinence is nearly always due to one or both of the following:

The urethra fails to close and becomes overly movable (urethral hypermobility).
The muscles around the bladder neck weaken (intrinsic sphincteric deficiency or ISD). Some experts believe that this problem is present to some degree in nearly all women with stress incontinence. (ISD can also occur in anyone from an inborn disorder or injury from surgery or radiation.)

Many women are prone to one or both of these problems, which can occur under the following circumstances:

Having had many children through vaginal deliveries. In such cases, pregnancy and childbirth strain the muscles of the pelvic floor. Prolapsed uterus, in which the uterus protrudes into the vagina, occurs in about half of all women who have given birth. This condition can often cause incontinence.
Menopause. Estrogen deficiencies after menopause can cause the urethra to thin out so that it may not close properly.

Urethral Hypermobility. In urethral hypermobility the urethra does not close properly, allowing it to move too much (hypermobile). This condition typically occurs when the pelvic floor muscles in women become weak, and the following events occur:

The weakened pelvic floor muscles stretch.
This allows the bladder to sag downward within the abdomen.
The sagging bladder pulls on the muscles surrounding the bladder neck (internal sphincter), which are connected to the urethra.

Stress incontinence associated with urethral hypermobility is sometimes categorized as type 1 or type 2.

Type 1 is the less severe form, and the bladder neck and urethra remain incompletely closed.
In type 2, the angle of the bladder neck shifts. In such cases cystocele may occur, in which the bladder muscles bulge (herniate) into the vaginal wall.

Intrinsic sphincteric deficiency (ISD). Intrinsic sphincter deficiency (sometimes called type 3) is the other major cause of stress incontinence in women. It occurs when the bladder neck muscles are damaged or weakened. The result is twofold:

The bladder neck is open during filling.
The closing pressure around the urethra is low.

This is the most severe stress incontinence in women and usually occurs after previous surgeries for incontinence.

Prostate treatments can impair the sphincter muscles. Such treatments are the major causes of stress incontinence in men. They include the following:

Surgery or radiation for prostate cancer. Incontinence occurs in nearly all male patients for the first 3 - 6 months after radical prostatectomy. After a year of the procedure, most men retain continence, although leakage can occur.

Surgery for benign prostatic hyperplasia. Stress incontinence occurs in 1 - 5% of men after transurethral resection of the prostate (TURP), the standard treatment for severe benign prostatic hyperplasia.

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

Incontinence after prostate procedures is often a combination of urge and stress. Because studies often combine the two types of incontinence, it is not always clear which predominates.

Urge Incontinence

The main symptom of urge incontinence (also called hyperactive, irritable, or overactive bladder) is the need to urinate frequently. Patients may go to the bathroom more than 8 times over 24 hours, including 2 or more times a night, and have subsequent leakage. However, most people (60%) with overactive bladder experience only urgency and frequency. In some cases, urge incontinence occurs only at night. This is called nocturnal enuresis.

All cases of urge incontinence involve an overactive bladder. This occurs when the detrusor muscle, which surrounds the bladder, contracts inappropriately during the filling stage. When this occurs, the urge to urinate cannot be voluntarily suppressed, even temporarily. There is usually one of two types:

Idiopathic Detrusor Overactivity (formerly called Detrusor Instability). In this type, the nerves serving the bladder have signaled the brain appropriately that the bladder is full, but the detrusor muscles are unable to be suppressed. The actual cause, however, is not known.
Neurogenic Detrusor Overactivity (formerly called Detrusor Hyperreflexia). With this type, a known neurologic abnormality impairs the signaling systems between the bladder and the central nervous system, and the brain is unable to inhibit the detrusor muscles controlling urination.

Very often, the cause of detrusor instability and bladder hyperactivity is unknown. Some conditions that can produce the disorders leading to urge incontinence include the following:

Benign prostatic hyperplasia (BPH). Detrusor instability occurs in about 75% of men with BPH and causes frequency, urgency, and urination during the night (although incontinence itself occurs only in very severe cases). Urge incontinence only at night can be a sign of severe obstruction in the urinary tract.

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

Prostate surgical procedures. Either prostatectomy for prostate cancer or transurethral resection of the prostate (TURP) for BPH can cause detrusor instability. As with stress incontinence, prostatectomy poses a much higher rate than with TURP, which is very low.
Hysterectomy. Complications of this operation, which removes the uterus, are associated with a higher risk for urge incontinence. In one study, for example, incontinence developed or worsened after hysterectomy in about 16% of women who had only mild or no incontinence before surgery. However, hysterectomies can also significantly improve urinary incontinence in many women who have an existing condition before the procedure. In the same study, 30% of women had severe urinary incontinence before hysterectomy, which declined to 20% afterward and was sustained for at least 2 years.

Click the icon to see an image about hysterectomy.

Damage to the central nervous system. Certain neurologic disorders or injuries can disrupt the passage of nerve messages between the urinary tract and central nervous system. These neurological conditions include stroke, multiple sclerosis, spinal cord or disk injury, and Parkinson's disease.
Infections.
The aging process.
Emotional disorders. Anxiety and possibly even depression have been associated with urge incontinence.
Medications, including some sleeping pills.
Genetic factors may play a role in some cases.

Overflow Incontinence

Overflow incontinence happens when the normal flow of urine is blocked and the bladder cannot empty completely. Overflow incontinence can be due to a number of conditions:

A partial obstruction. In this case the urine cannot flow completely out of the bladder, so it never fully empties.
An inactive bladder muscle. In contrast to urge incontinence, the bladder is less active than normal, not more. It cannot empty properly and so becomes distended, or swells. Eventually this distention stretches the internal sphincter until it opens partially and leakage occurs.

The causes of the conditions leading to overflow incontinence include:

Tumors
Certain medications (anticholinergics, antidepressants, antipsychotics, sedatives, narcotics, alpha-adrenergic agonists, beta-adrenergic agonists, calcium channel blockers)
Benign prostatic hyperplasia (enlarged prostate)
Scar tissue
Nerve damage. In such cases, nerves in the bladder are damaged so that the body cannot feel when the bladder is full, and the bladder does not contract. Such damage can be caused by spinal cord injuries, previous surgery in the colon or rectum, and pelvic fractures. Diabetes, multiple sclerosis, and shingles also can cause this problem.

Functional Incontinence

Patients with functional incontinence have mental or physical disabilities that keep them from urinating, although the urinary system itself is normal. Conditions that can lead to function incontinence include:

Parkinson's disease.
Alzheimer's disease and other forms of dementia. Mental confusion may prevent both recognition of the need to void and locating a bathroom.
Severe depression. In such cases, people may become incontinent because they are indifferent to self-control.

Risk Factors

About 13 million adults experience incontinence at some time. The number, however, may actually be higher because most patients are reluctant to discuss incontinence with their doctors. In fact, research indicates that many patients will not admit to having the problem even when questioned directly. Although a third of American men and women age 30 - 70 have experienced at least some loss of bladder control, most have not been diagnosed by a doctor.

A 2004 survey of more than 1,400 Americans found that despite the prevalence of bladder control loss, an alarming 64% of those experiencing symptoms are not currently taking measures to manage their condition. The survey, sponsored by the National Association for Continence, also found that adults waited an average of 6 years before discussing their symptoms with a doctor. A 2006 study reported that only half of women with urinary incontinence have discussed their condition with a doctor, while only a third had received any treatment.

Incontinence is uncommon in children 5 years and older. However, it may still occur in:

10% of 5 year-olds
5% of 10 year-olds
1% of 18 year-olds

Incontinence that occurs before puberty is twice as common in boys as in girls. Most young people who experience nighttime wetting do not have any serious physical or emotional disorders. It is often difficult to diagnose incontinence in children. Many cases result from a combination of factors, including:

Birth defects or inborn conditions that cause problems in the urinary tract
Slower physical development
An overproduction of urine at night
A lack of ability to recognize bladder filling when asleep
Anxiety
Inherited factors (indicated by a strong family history of bedwetting)

Bedwetting in children is not considered incontinence. However, bedwetting and other urinary problems in childhood may predict the later development of adult urinary incontinence. According to a 2006 study, women who experienced childhood bedwetting, as well as frequent daytime and nighttime urination, had an increased risk of developing adult urge incontinence.

All older adults are susceptible to incontinence. One in 10 people over age 65 have some type of bladder control loss. About 12% of women ages 60 - 64 and 21% of women age 85 and over experience daily urinary incontinence. About half of the elderly who are housebound or in nursing homes experience incontinence.

Urinary incontinence is far more common among women than men. Between 15 - 50% of women experience urinary incontinence during their lifetimes, with the highest rates occurring in women who have had children. Severe urinary continence affects 7 – 10% of women. About 10% of women undergo surgery for urinary incontinence or pelvic organ prolapse.

Birth Conditions. Pregnancy and childbirth may increase the risk for urinary incontinence. The risk is highest with the first child, and there is an increased risk in women who have their first child over age 30. Some studies suggest that women who used the drug oxytocin for inducing labor are at higher risk for developing urinary incontinence. Such medically induced labor tends to subject the muscles and nerves in the pelvis to greater force than does natural labor.

Studies indicate that the method of birth can affect risk later in life. For example, a major 2003 study reported that women who had a cesarean section had a much lower risk for stress incontinence before age 50 than women who had vaginal delivery. However, a 2006 study contradicted many assumptions by suggesting that vaginal delivery is not associated with later development of urinary incontinence in postmenopausal women. The study compared sisters who had either given birth vaginally or had never had children. Researchers found no difference in rates of urinary incontinence. The study suggested that cesarean delivery may not make much difference in preventing urinary incontinence.

Another 2006 study found that episiotomy does not help prevent urinary incontinence. Episiotomy is a surgical incision that is made during childbirth to the perineum, the muscle between the vagina and the rectum. Doctors commonly perform this procedure to help widen the vaginal opening and prevent tearing. The study found that episiotomy does not have many benefits, and may later cause pain during intercourse.

Vaginal birth can cause pelvic prolapse, a condition in which pelvic muscles weaken and the pelvic organs (bladder, uterus) slip into the vaginal canal. Pelvic prolapse, and the surgery used to correct it, can cause incontinence. Sacrocolpopexy is the standard surgical procedure for repairing pelvic prolapse. A 2006 study found that performing a urinary incontinence surgical procedure (Burch colposuspension) at the same time as sacrocolpopexy can help prevent stress incontinence. [See Surgery section.]

High-Impact Exercise. Women who engage in high-impact exercise are susceptible to urinary leakage, particularly women with a low foot arch. Shock to the pelvic area is increased as the foot makes impact with hard surfaces. Those at highest risk for urinary leakage are gymnasts, followed by softball, volleyball, and basketball players.

Smokers. Studies have reported a higher risk for incontinence, notably mixed incontinence, in women who are current or former heavy smokers (more than a pack a day).

Obesity. Being overweight is a major risk factor for all types of incontinence. The more a woman weighs, the greater her risk.

Medical Factors in Older Women. Urge incontinence is more common among postmenopausal women who have a history of:

Diabetes
Higher body mass index (heavier weight)
Hysterectomy
Two or more urinary tract infections within the past year

The rate of incontinence in men (about 1.5 - 5%) is much lower than in women. The risk for urinary incontinence increases with age. In the United States, about 17% of men over age 60 have urinary incontinence. In older men, prostate problems and their treatments are the most common factors that affect the urinary tract. Up to 30% of men who have had surgery to remove their prostate gland experience some degree of urinary incontinence.

Urinary incontinence varies by race and ethnicity. It is most common in non-Hispanic white women. Among men, African-Americans are at highest risk. Some studies suggest that the greatest disparity is with stress incontinence. African-American and Asian American women have a much lower risk for stress incontinence than Caucasian and Hispanic women.

A number of conditions can cause temporary incontinence in anyone:

Urinary tract infections
Excess fluid intake
Constipation
Severe depression
Restricted mobility

Drugs. Drugs are most often the cause of temporary incontinence.

Drugs that affect the adrenergic system (a nerve-cell and hormonal pathway that regulates the sphincter muscle) are common causes of incontinence. For example, alpha-adrenergic blockers, such as terazosin (Hytrin), used for benign prostatic hypertrophy, can cause incontinence by over-relaxing the muscles. On the other hand, men with enlarged prostates who suffer from urinary problems may be helped by the increase of urine flow after using terazosin.
Alpha-adrenergic agonists, such as pseudoephedrine (found in some oral decongestants) strengthen the muscles and may cause overflow incontinence in susceptible people.
Beta-adrenergic blockers, such as propranolol (Inderal), prescribed for hypertension and angina, relax the sphincter.
Diuretics, used for high blood pressure, often rapidly introduce high urine volumes into the bladder.
Calcium-channel blockers can cause overflow incontinence by relaxing the bladder detrusor muscles.
Colchicine, a drug used for gout, can cause urge incontinence.
Other medications and substances that increase the risk for incontinence are caffeine, sedatives, antidepressants, antipsychotics, and antihistamines.

Diagnosis

Fewer than half of the patients who have urinary incontinence tell their doctor about the problem. In many cases, patients simply feel that incontinence is part of the aging process. And, in spite of the commonness of this problem, two-thirds of doctors never ask their older patients if they experience incontinence.

It is important, however, for both the doctor and the patient to raise the issue.

The first step in the diagnosis of incontinence is a detailed history. The doctor should ask questions about the patient's present and past medical conditions and patterns of urination. Patients should tell the doctor the following information:

When the problem began
Frequency of urination
Amount of daily fluid intake
Use of caffeine or alcohol
Frequency and description of leakage or urine loss, including activity at the time, sensation of urge to urinate, and approximate volume of urine lost
Frequency of urination during the night
Whether the bladder feels empty after urinating
Pain or burning during urination
Problems starting or stopping the flow of urine
Forcefulness of the urine stream
Presence of blood, unusual odor or color in the urine
A list of major surgeries with their dates, including pregnancies and deliveries, and other medical conditions
Any medications being taken

A 2006 study suggested a simpler way of diagnosing incontinence using a test that asks 3 questions:

During the last 3 months, have you leaked urine (even a small amount)?
When did you leak urine? (During physical activity; when you could not reach the bathroom quickly enough; without physical activity or bladder urge.)
When did you leak urine most often? (Physical activity; bladder urge; without or about equally with physical activity or bladder urge.)

Based on the patient’s answers, the “3IQ” test may help a doctor distinguish between urge and stress urinary incontinence.

Voiding Diary. The patient might find it helpful to keep a diary for 3 to 4 days before the office visit. This diary, sometimes referred to as a voiding diary or log, should be a detailed record of:

Daily eating and drinking habits
The times and amounts of normal urination

For each incident of incontinence, the log should also detail:

The amount of urine lost (the patient is often asked to catch and measure urine in a measuring cup during a 24-hour period)
Whether the urge to urinate was present
Whether the patient was involved in physical activity at the time

The office visit should consist of a thorough physical examination, checking for abnormalities or enlargements in the rectal, genital, and abdominal areas that may cause or contribute to the problem.

One of the important measurements for urinary incontinence is the postvoid residual urine volume (PVR). This is the amount of urine left in the bladder after urination:

Normally, about 50 mL or less of urine is left
More than 100 mL suggests an abnormality and requires further tests
More than 200 mL is a definite sign of abnormalities

Use of a Catheter. The most common method for measuring PVR uses a catheter, which is inserted into the urethra after a few minutes of urination. The advantage of the catheter is that it can also collect urine for analysis.

Ultrasound. Ultrasound is useful in determining the volume of urine.

Cystometry measures the bladder's ability to retain urine at different capacities and pressures. It uses a catheter and can be performed at the same time as the PVR test.

Subtraction Cystometry. Although procedures vary, the basic steps for the technique are as follows:

The patient empties the bladder as much as possible.
Two catheters are inserted into the urethra until they reach the bladder. One is used to fill the bladder with water. The other is used to measure pressure. Another catheter is inserted into the rectum or vagina, which is used to measure abdominal pressure.
While water is instilled through the tube into the bladder, the pressure in the bladder and abdomen are measured and the results are recorded in a computing device.
During the process, the patient informs the doctor about any changes in the need to urinate, including the initial need to urinate, a normal desire to urinate, and a strong need to urinate.
Often during this process, the patient is asked to cough, bounce up and down, or even walk in place. The patient may also be asked to strain as if he or she is having a bowel movement. This is called the Valsalva maneuver. The point at which leakage occurs during this action is called the Valsalva leak point pressure, which might be a useful measurement for determining treatment.
When the urge to urinate is strong, the doctor stops this portion of the test.
A calculation is then made using bladder and abdominal pressure measurements as well as volume and flow rate of the urine. The result provides the doctor with an assessment of detrusor contractions.

The detrusor muscles of a normal bladder will not contract during bladder filling. Severe contractions at low amounts of administered fluid (less than 200 mL) indicate urge incontinence. Stress incontinence is suspected when there is no significant increase in bladder pressure or detrusor muscle contractions during filling, but the patient experiences leakage if abdominal pressure increases.

Video Cystometry. Video cystometry combines a computer reading of bladder pressures and pictures of the bladder itself. It is most useful in cases where the more standard tests have not yielded satisfactory results.

To determine whether the bladder is obstructed, the speed of urine flow is measured electronically using a test called uroflowmetry. The test involves the following steps:

Patients are instructed not to urinate for several hours before the test and to drink plenty of fluids so they have a full bladder and a strong urge to urinate.
To perform this test, a patient urinates into a special toilet equipped with a uroflowmeter.
It is important that patients remain still while urinating to help ensure accuracy, and that they urinate normally and do not exert strain to empty their bladder or attempt to retard their urine flow.

Many factors can affect urine flow (such as straining or holding back because of self-consciousness) so experts recommend that the test be repeated at least twice.

Q[max]. The rate of urine flow is calculated as milliliters of urine passed per second (mL/s). At its peak, the flow rate measurement is recorded and referred to as the Q[max]. The higher the Q[max], the better the patient's flow rate. Men with a Q[max] of less than 12 mL/s have four times the risk for urinary retention than men with a stronger urinary flow.

The Q[max] measurement is sometimes used as the basis for determining the severity of obstruction and for judging the success of treatments. It is not very accurate, however, for a number of reasons:

Urine flow varies widely among individuals as well as from test to test.
The patient's age must be considered. Flow rate normally decreases as men age, so the Q[max] typically ranges from more than 25 mL/s in young men to less than 10 mL/s in elderly men.

The Q[max] level does not necessarily coincide with a patient's perceptions of the severity of his own symptoms.

Urethrocystoscopy. Urethrocystoscopy, also called cystourethroscopy or cystoscopy, detects structural abnormalities, inflammation of the bladder wall, or masses that might not show up on x-ray.

The patient is given a light anesthetic, and the bladder is filled with water.
Next, a thin flexible tube called a cystoscope is inserted through the urethra into the bladder.
The end of the cystoscope contains a tiny microscope-like instrument.
The doctor uses the cystoscope to look for abnormalities in the interior of the bladder.

Cystoscopy is a procedure that uses a flexible fiber optic scope, which is inserted through the urethra into the urinary bladder. The doctor fills the bladder with water and inspects the interior of the bladder. The image seen through the cystoscope may also be viewed on a color monitor and recorded on videotape for later evaluation.

The procedure has some risks. Complications are uncommon, but can include allergic response to the anesthetic, urinary tract infection, bleeding, and urine retention.

Intravenous Pyelogram. Intravenous pyelogram (IVP) may be used to diagnose urge incontinence. It is performed as follows:

A dye is injected into the patient's vein and is processed by the kidneys.
A series of x-ray pictures are taken of the kidneys, ureter, and bladder as the dye passes through them. This provides a dynamic picture of the relationship between the patient's urinary system and urinary functioning.

Click the icon to see an image of an intravenous pyelogram.

IVPs can detect structural abnormalities, urethral narrowing, or incomplete emptying of the bladder. This test should not be used on pregnant women or patients with kidney failure. There is a risk for an allergic reaction to standard dyes, although newer, less allergenic ones are becoming available.

Ultrasound. Ultrasound plays a role in many cases of incontinence. For example, it is useful for men with prostate problems. It is helpful in measuring urine volume in the bladder. Ultrasound may also be useful in many cases of female stress incontinence, by identifying abnormalities in the bladder neck, and in assessing the urinary tract before and after surgery. It also may eventually be useful in diagnosing detrusor instability.

Chain Cystogram. In cases of stress incontinence, a chain cystogram may also be performed. With this procedure, a beaded chain is positioned in the bladder and urethra. The x-ray image of the chain reveals the angle of the bladder neck. This test should not be performed on pregnant women.

Electrophysiologic sphincter testing, also referred to as electromyography (EMG), evaluates two important factors:

The function of the nerves serving the sphincter and pelvic floor muscles.
The patient's ability to control these muscles.

Using a technique similar to that of an electrocardiogram, the doctor places electrodes on the affected areas to observe electrical activity in the muscles.

Urethral pressure profile is used to investigate urethral blockage. A probe is placed in the urethra to determine pressure at different points along this pathway during urination and the exact location of any obstruction in the urethra.

Prognosis

Incontinence is rarely life threatening. In most cases, if treated promptly, physical complications are not serious.

Urinary incontinence can have severe emotional effects. Depression is very common in women with incontinence. For example, in a 2003 study, 82% of women with severe incontinence and 41% of those with moderate incontinence reported at least 2 weeks of depression during the preceding year. Incontinence also has emotional effects on men. A number of studies of prostate cancer patients suggest that incontinence is a much more distressing side effect for men than impotence (also a side effect of prostate cancer treatment).

Other negative emotional effects reported include:

Loneliness and humiliation. Because little public attention has been paid to this problem, the incontinent person often feels alone and humiliated. Many people with incontinence do not even seek medical advice for the problem. In one survey of doctors, nearly all of them reported that a patient's embarrassment and reluctance to discuss bladder problems is a major barrier to successful treatment.
Shame. Many people experience a sense of personal failure.
Helplessness. Patients often feel helpless and angry.
Introversion. Patients may eventually curtail social activities, or even give them up entirely.
Lack of confidence. Many people with incontinence believe that they are unemployable.

To prevent humiliation due to wetness or odors, people with incontinence may have to alter their way of life.

Errands become very difficult and need advanced planning.
Public bathrooms may difficult to locate or unavailable. The problem is particularly severe for those with urge incontinence who have little time to reach a bathroom and have large volume spills.

Incontinence is particularly serious in older adults:

Older adults who are otherwise healthy may stop exercising because of leakage, which can increase their impairment.
Incontinence can result in loss of independence and quality of life.
It is a major reason for nursing home placement.
Severe incontinence may require catheterization. This is the insertion of a tube that allows urine to continually pass into an external collecting bag. In such cases, complications are common, particularly infections.
There is a strong association between urge incontinence and falls and injuries. In one large study, over half of women who reported incontinence experienced at least one fall over a 3-year period. This high incidence of falls may be due in part to the rush to the toilet in the middle of the night. Keeping a pan or portable commode near the bed may prevent injuries as well as improve sleep and general convenience.

Treatment

The treatment for temporary incontinence can be rapid, simple, and effective. If urinary tract infections are the cause, they can be treated with antibiotics. Any related incontinence will often clear up in a short time. Medications that cause incontinence can be discontinued or changed to halt episodes.

Chronic incontinence may require a variety of treatments, depending on the cause. Treatment options are listed below in the order in which they are usually tried, from least-to-most invasive:

Behavioral techniques, which include Kegel exercises and bladder training, are sometimes all a person needs for achieving continence. A number of devices can also be used to strengthen muscles and prevent urine leakage. Bladder training is useful for urge incontinence.
Medications are tried next. These may include anticholinergics and antispasmodics. Estrogen or estrogen plus progesterone used to be recommended, but recent research has shown that these hormone treatments can actually make urinary incontinence worse.
Surgery. Surgery is the last resort; there are many effective procedures available for stress incontinence.

Lifestyle techniques to improve quality of life and improve hygiene are part of all treatments.

Lifestyle measures, including dietary recommendations, bladder training, and continent aids, are useful for anyone with incontinence. Other treatments vary depending on whether the patient has stress or urge incontinence. In people who have both, the treatment usually is aimed at the predominant form.

Treating Stress Incontinence. The general goal for women with stress incontinence is to strengthen the pelvic muscles. Typical steps for treating women with type 1 stress incontinence are:

Devices and continent aids for blocking urine in the urethra (vaginal pessaries, adhesive pads, and others).
Behavioral techniques and noninvasive devices, including Kegel exercises, weighted vaginal cones, and biofeedback.
Medications. Alpha-adrenergic agonists and possibly tricyclic antidepressants.
Surgery is a reasonable option if symptoms do not improve with noninvasive methods. Many are available, and most are designed to restore the bladder neck and urethra to their anatomically correct positions.

Treating Urge Incontinence. The goal of most treatments for urge incontinence is to reduce the hyperactivity of the bladder. The following methods may be helpful:

Behavioral methods
Medications (anticholinergics, anti-spasmodics, and alpha blockers)
Procedures that stimulate the pelvic floor or nerves in the tailbone (the sacral nerves), which help retrain the bladder

Lifestyle Changes

Many products are now available that help patients avoid embarrassment and, in some cases, prevent leakage. With recent improvements in paper technology, pads are now thin enough to be worn undetected, and a spare can be hidden in a purse or pocket. Proper hygiene is also essential for patients with incontinence.

Keeping Skin Clean. To avoid skin irritation and infection associated with incontinence, keep the area around the urethra clean. The following tips may be helpful:

After a urinary accident, clean any affected areas right away.
When bathing, use warm water and don't scrub forcefully; hot water and scrubbing can injure the skin.
A number of cleansers are available that are specially created for incontinence and allow frequent cleansing without over-drying or causing irritation to the skin. Most do not have to be rinsed off; the area is simply wiped with a cloth.
After bathing, a moisturizer plus a barrier cream should be applied. Barrier creams include petroleum jelly, zinc oxide, cocoa butter, kaolin, lanolin, or paraffin. These products are water repellent and protect the skin from urine.
Anti-fungal creams that contain miconazole nitrate are used for yeast infections.

Preventing or Reducing Odor. Certain methods may help reduce odor from accidents. They include:

Deodorizing tablets, such as Derifil, Nullo, Devrom, and Chlorofresh can be taken by mouth or used in appliances. Most contain chlorophyll.
Taking an alfalfa pill four times a day may reduce odor, and is not believed to interfere with any other medications. Alfalfa is a common grass, and some people with seasonal allergies may experience an allergic reaction. Talk to your doctor before taking any type of supplement.
Drinking more water, not less, will also reduce odors. Drinking more water may actually help reduce leakage, too.
To remove odors from mattresses, some experts recommend a solution of equal parts vinegar to water. Once the mattress has dried, baking soda can be applied on the stain, rubbed in, and then vacuumed off.

Weight Control. In women, pelvic floor muscle tone weakens with significant weight gain, so women are urged to eat healthy foods in moderation and to exercise regularly.

Fluid Intake. A common misconception among people with incontinence is that drinking less water will prevent accidents. In reality, limiting fluid intake has the following effects:

The lining of the urethra and bladder becomes irritated, which may actually increase leakage.
Concentrated urine also has a stronger pungency, so drinking plenty of fluids can help reduce odor.

Some experts recommend drinking two to three quarts a day.

Drinking plenty of cranberry juice may be particularly helpful. It is known to help prevent urinary tract infections. (Low calorie juices are available.)

People with incontinence, however, should stop drinking beverages 2 - 4 hours before going to bed, particularly those who experience leakage or accidents during the night.

Fiber-Rich Foods. Constipation can worsen urinary incontinence, so diets should be high in fiber, fruits, and vegetables.

Fluid and Food Restrictions. A number of foods and beverages may increase incontinence. Some experts suggest that people who eat or drink the following items should try eliminating one a day over a 10-day period and check to see if removing them improves continence:

Caffeinated beverages. (In one major 2003 study, tea drinking -- but not coffee drinking -- was associated with incontinence. In general, however, it might be useful to try avoiding coffee as well, including decaf coffee.)
Carbonated beverages such as soda
Alcoholic beverages
Citrus fruits and juices
Tomatoes and tomato-based foods
Spicy foods
Chocolate
Sugars and honey
Artificial sweeteners
Milk and milk products

Some otherwise healthy adults stop exercising because of leakage. There are a number of methods for preventing or stopping leakage during exercise. The following are some tips:

Limit fluid intake before exercising (but be sure not to become dehydrated)
Urinate frequently, including right before exercise
Women can try wearing pads or urethral inserts

A variety of absorbent pads and undergarments are quite effective in catching spills and leaks. Many undergarments developed for incontinence are almost indistinguishable from regular briefs and underpants.

For women, the following are available:

Normal and even attractive looking washable underwear that contains waterproof panels is available for women. Even stomach-control panties are available for women with incontinence.

For men, the following are available:

Drip collectors are available which can be worn under briefs and are not noticeable under normal clothing. Lined with absorbent material, the pouch-like collector surrounds the penis or scrotum and is fastened with a belt or pins.
Washable briefs made from polyester have a fully functional fly and waterproof panel and look and feel like normal underwear. Boxer shorts are also available that look regular but have a protective pouch.

Even for men and women with severe incontinence, disposable undergarments can be purchased that have a normal look to them.

All absorbent undergarments should be changed when wet to limit problems of chafing or infection.

A specially shaped plastic urinal (Feminal) is available for women. It avoids the use of a bedpan, and can be used while the woman is lying down, seated, or even standing.

Urinals for men are available that attach to athletic-like supporters.

Other Treatments

Foam pads (Miniguard, UroMed, Impress, Softpatch) with an adhesive coating have been developed for women with stress incontinence. They work as follows:

The pad is placed over the opening of the urethra where it creates a seal, preventing leakage.
It is removed before urinating and replaced with a new one afterwards.
The pad can be worn up to 5 hours a day and through the night.
It can be used during physical activity, although it may change position during vigorous exercise.
It should not be worn during sexual intercourse.

In one study of women who used these products, the average number of leaks per week dropped from 14 to 5. Women with more severe incontinence (an average of 34 leaks a week) had only 10 events, and when leakage occurred, it was slight.

Adhesive pads should not be used by women with the following conditions:

Urinary tract or vaginal infections
Urge or other forms of nonstress incontinence
A history of surgery for incontinence

Urethral Shields. Shields or caps (CapSure, Bard Cap Sure, FemAssist) that fit over the urethral opening are safe and effective in managing many forms of incontinence.

In a study of patients with stress incontinence, CapSure reduced urine loss by 96% within a week, and 82% of patients were completely dry. Side effects include irritation and urinary tract infections, although they are not severe.
In another study, 47% of women who used FemAssist reported complete continence, and 33% of the women reported continence was improved by more than half. FemAssist offered equal benefits for women with stress, urge, or mixed incontinence.

Urethral Tubes or Sleeves. Tubes or sleeves (Reliance Urinary Control Device, FemSoft) that fit into the urethra are also available for female incontinence.

The Reliance Urinary Control Device for women is a small tube inserted into the urethra using a reusable syringe. The device must be prescribed by a doctor, who measures the woman's urethra to determine the right size. The tip of the tube contains a balloon that is inflated against the urethra and blocks urine, preventing leakage. Every time a woman urinates, she pulls a string that deflates the balloon, then throws the old device away and replaces it with a new one. It is effective, but carries a high risk for urinary tract infections and most women report discomfort and irritation.
FemSoft is a silicone tube insert surrounded by a liquid-filled sleeve. When the tube is inserted into the urethra, the sleeve conforms to its shape and creates a seal at the bladder neck, preventing leakage. It is intended for one-time use and is replaced after voiding. This is a relatively new product and information is lacking on its comfort and risk for urinary tract infections.

Vaginal Devices. Devices that support the vaginal wall also help support the urethra that is located next to it:

Tampons. Mild stress incontinence in women, particularly when induced by exercise, may be managed by using a tampon. Specially designed tampons (such as the Contrelle Continence Tampon) are available, but even simple menstrual tampons may be helpful. (Keep in mind that tampons can only be worn for a few hours.) As tampons push on the vaginal wall, it compresses the urethra. In one study, 86% of women with mild incontinence remained continent during exercise sessions when using tampons. Out of this group, however, only 29% with severe incontinence remained dry.
Vaginal Pessaries. Vaginal pessaries are devices inserted into the vagina that support the inside of the vaginal walls. Pessaries are usually made of silicon and come in various forms, including donut or cube-shapes. They must be fitted by a health professional and are effective for vaginal prolapse or other vaginal structural problems. Serious complications are rare but can occur if the pessary is not replaced periodically.
Introl Bladder Neck Support. The Introl bladder neck support prosthesis is a flexible ring that is inserted into the vagina and has two ridges that press against the walls, supporting the urethra. Sizing the Introl is difficult, but success rates of 83% have been reported in women with stress incontinence. It can be left in during urination but must be removed and cleaned afterward. Introl can cause vaginal or urethral infections and may also be uncomfortable.

Behavioral Treatments

With the exception of functional incontinence, most cases of incontinence will almost always improve with behavioral techniques. There are a variety of methods, but the focus is usually on strengthening or retraining the bladder. Studies indicate that such exercises are very effective, even for men recovering from surgery for prostate cancer.

To enhance bladder training for incontinent patients who are in nursing rooms, nurses may need to check patients for dryness and regularly remind them to urinate. As an extra tip for older people with severe incontinence, keeping a pan or portable commode near the bed may prevent injuries from falling as well as improve general convenience.

Perhaps the best first-line approach for any form of incontinence is a combination of Kegel exercises and bladder training. In one study, women who used this combination approach experienced an average 50% reduction in incontinence episodes, with nearly 40% of them achieving complete continence. It was equally effective for urge, stress, or mixed incontinence.

Studies also report that between 50 - 75% of patients who perform only Kegel exercises experience a substantial improvement in their symptoms, including elderly people who have had the problem for years. A 2006 review suggested that Kegel exercises are especially helpful for women in their 40s and 50s who suffer from stress incontinence. The women participated in a supervised Kegel exercise program for at least 3 months.

Pelvic Floor Muscle (Kegel) Exercises. Kegel exercises are designed to strengthen the muscles of the pelvic floor that support the bladder and close the sphincters.

Stress incontinence is an involuntary loss of control of urine that occurs at the same time abdominal pressure is increased as in coughing or sneezing. It develops when the muscles of the pelvic floor have become weak.

Dr. Kegel first developed these exercises to assist women before and after childbirth, but they are very useful in helping to improve continence for both men and women. Kegel exercises are particularly useful for the following conditions:

Stress incontinence. Some experts believe that Kegel exercises should be the primary treatment for stress incontinence.
Urge incontinence. They can also be helpful for urge incontinence in cases that are not caused by nerve damage. In one study, 85% of women reported satisfaction with this program.

The general approach for learning and practicing Kegel exercises is as follows:

Since the muscles are sometimes difficult to isolate, the best method is to first learn while urinating. The patient begins to urinate and then contracts the muscle in the pelvic area with intention of slowing or stopping the flow of urine. Women should contract the vaginal muscles as well. They can detect this by inserting a finger inside the vagina. When the vaginal walls tighten, the pelvic muscles are being correctly contracted.
An alternate approach is to isolate the muscles used in Kegel contractions by sensing then squeezing and lifting the muscles in the rectum that are used in passing gas. (Again, women should contract the vaginal muscles as well.)
Patients should place their hands on their abdomen, thighs, and buttocks to make sure there is no movement in these areas while exercising.
In order to achieve success, some experts recommend performing two exercises that have different timing for the hold and release of the contraction. Both should be done regularly.
The first method is used for strengthening the pelvic floor muscles. The patient slowly contracts and lifts the muscles and holds for 5 seconds, then releases them. There is a rest of 10 seconds between contractions.
The second method is simply a quick contraction and release. The object of this exercise is to learn to shut off the urine flow rapidly.
In general, patients should perform 5 - 15 contractions, three to five times daily.

Some notes of caution:

Once learned, Kegel exercises should not be performed while urinating more than about twice a month, since this practice may eventually weaken the muscles.
In women, incorrect or overly vigorous exercises may cause vaginal muscles to tighten excessively, resulting in pain during sexual intercourse.
Over-exercise can also tire muscles and cause more leakage.
Incontinence will return to its original severity if these exercises are discontinued, so commitment to the program must be high and possibly life-long.
It may be several months before the patient sees significant improvement.

Bladder Training. Bladder training involves a specific, graduated schedule for increasing the time between urinations:

Patients start by planning short intervals between urinations, then gradually progressing with a goal of voiding every 3 - 4 hours.
If the urge to urinate arises between scheduled voidings, patients should remain in place until the urge subsides. At the time, the patient moves slowly to a bathroom. (In a small study, 73% of women with stress incontinence were helped by an absurdly simple and obvious movement: crossing the legs whenever a cough or sneeze was coming on.)

This system uses a set of weights to improve pelvic floor muscle control. The cones are inexpensive, relatively simple to use, and evidence suggests that they are as effective as Kegel exercises or electrostimulation:

The typical set includes five cones of graduated weights ranging from 20 grams (less than 1 ounce) to 65 grams (slightly over 2 ounces).
Starting with the lightest, the woman places the cone in her vagina while standing and attempts to prevent the cone from falling out. The muscles used to hold the cone are the same ones needed to improve continence.

As with standard Kegel exercises, frequent repetition is required, but most women will eventually be able to use the heavier weights and build up the ability to prevent stress and urge incontinence.

Women who are unable to learn Kegel muscle contraction and release with verbal instructions can be helped with the use of biofeedback:

Biofeedback uses a vaginal or rectal probe inserted by the patient that relays information to monitoring equipment.
The patient isolates the pelvic floor and bladder muscles and performs Kegel exercises.
The monitor emits auditory or visual signals that indicate how strongly the patient is contracting the proper pelvic floor muscles and how effectively the bladder muscles are being released.
The apparatus is designed for home use.

As with any Kegel exercise regimen, biofeedback must be used for several months before it is effective. In one major study, 75% of women with urge incontinence reported satisfaction with biofeedback, although women who were simply given verbal cues were even more satisfied (85%). A 2005 study of older women found that biofeedback worked better than oxybutynin (Ditropan) in controlling nighttime urge incontinence. Biofeedback that teaches control of pelvic muscles may even be very helpful in children who have daytime wetting, frequent urinary tract infections, or both.

A treatment called extracorporeal magnetic innervation therapy stimulates pelvic muscles to automatically perform Kegel exercises:

The patients stay fully dressed and sit on a special chair during the treatment.
Highly focused magnetic fields penetrate the pelvic area to stimulate the nerves.
Sessions are twice a week for about 6 weeks, although it may take more than 8 weeks to build up the muscles.

Studies report that patients experience fewer leaks, need fewer pads, and have fewer voiding episodes throughout the day and night. Comparison studies of magnetic therapy and sham (or "dummy") treatments are mixed, however, with some reporting no differences. More studies are needed to determine whether extracorporeal magnetic innervation therapy has any value.

Electrical stimulation of the pelvic floor muscles has been a common treatment for years. The procedure uses a probe inserted into the anus or vagina, which produces a contraction in the pelvic floor muscles. Success rates range from 50 - 90% for urge incontinence. (It may also be useful for some patients with stress incontinence.) A recent study regarding patient-adjusted intermittent electrostimulation in women with stress or mixed urinary incontinence using a new implanted stimulator found the concept promising. Researchers, however, encouraged further investigation regarding the effectiveness and safety of the technique. The procedure requires frequent visits, and it takes 2 - 3 months before the patient feels the benefits. It is often not covered by insurance. Side effects can be distressing and include abdominal cramps, diarrhea, bleeding, and infection.

Medications

A number of medications are available that increase sphincter or pelvic muscle strength or relax the bladder, improving the ability to hold more urine. Medications are prescribed for all kinds of incontinence, but they are generally most helpful for urge incontinence.

Anticholinergics. Anticholinergics work in the following ways:

Inhibit the involuntary contractions of the bladder
Increase capacity of the bladder
Delay the initial urge to void

A major 2003 analysis reported that these drugs produce small but significant improvements. However, the medications have not been rigorously compared with behavioral methods, such as bladder training and Kegel exercises, which are very effective for most cases of urge incontinence. Anticholinergics can have distressing side effects, notably dry mouth.

Anticholinergics include:

Propantheline (ProBanthine). This drug used to be the most commonly prescribed anticholinergic, but has been largely replaced by newer anticholinergics with fewer side effects.
Oxybutynin (Ditropan, Oxytrol)
Tolterodine (Detrol)
Hyoscyamine (Levbid, Cystospaz)

Extended-release versions of oxybutynin (Ditropan XL) and tolterodine (Detrol LA) are proving to be especially effective. They improve continence and have fewer adverse effects than short-acting forms. In a major 2003 comparison study of the extended release drugs, oxybutynin was slightly better than tolterodine, but dry mouth was reported more often. A skin patch form of oxybutynin (Oxytrol) is now available. It appears to work better and have fewer side effects, such as dry mouth and constipation, than the pill form.

Oxybutynin may cause more severe central nervous side effects than previously thought, especially for children and older adults. In 2007, the FDA reviewed 202 cases of oxybutynin-related central nervous system problems. Hallucinations were reported in 27% of pediatric cases and 25% of cases involving adults age 60 and older. Eleven percent of adults age 17 – 59 years experienced hallucinations. The FDA recommends that doctors monitor patients for these symptoms.

According to one study of tolterodine, the drug also improved quality of life. A 2006 study reported that tolterodine is helpful for men with overactive bladder and urge urinary incontinence. A 2006 study, published in the Journal of the American Medical Association, suggested that a combination of tolterodine and the alpha-blocker drug tamsulosin (Flomax) may work better than either drug alone for men with lower urinary tract symptoms, including overactive bladder.

Overactive Bladder Treatments for Children

Oxybutynin (Ditropan X) is approved for pediatric use in children ages 6 and older. The recommended dose is 5 mg once a day. A 2006 study suggested that children who have fewer episodes of daytime wetting may benefit most from this drug.
A 2004 analysis found that tolterodine is also effective and well tolerated in children with urinary symptoms due to overactive bladder.

Side effects of anticholinergic drugs include:

Dry eyes (a particular problem for people who wear contact lenses; patients who wear contacts may wish to start with low doses of medication and gradually build up)
Dry mouth
Headache
Constipation
Rapid heart rate
Confusion, forgetfulness, and possible worsening of mental function, particularly in older people with dementia, such as those with Alzheimer's disease
Hallucinations, possibly, especially for children and older adults
Glaucoma, in rare cases

Antispasmodics. Antispasmodic drugs help relax the bladder muscle and are used for urge incontinence. Before bladder relaxants are prescribed, a thorough evaluation for obstructions in the ureter must be performed to avoid excessive urine retention.

Flavoxate (Urispas) and dicyclomine (Bentyl), the most common antispasmodics, have been used for years, although studies suggest that Urispas has very little benefit for the majority of patients with urge incontinence. The drugs also have anticholinergic properties. In May 2004, the FDA approved a new antispasmodic, trospium chloride (Sanctura), for the treatment of overactive bladder with symptoms or urge incontinence.

Possible side effects reported with use of antispasmodic drugs include:

Weakness
Dizziness
Drowsiness
Hallucinations
Insomnia
Dry mouth
Impotence
Restlessness

M3 selective receptor antagonists. In 2004, the FDA approved darifenacin (Enablex) for treatment of urge incontinence and overactive bladder. Some clinical trials suggested that darifenacin could help reduce weekly incontinence episodes by 83%. The drug’s most common side effects are dry mouth and constipation. For elderly patients, darifenacin may have less negative effects on memory than oxybutynin.

Capsaicin and Analogs. Studies have reported beneficial effects from instillation of capsaicin, a component of hot red chili peppers, into the bladder of people with hyperactive and hypersensitive bladders. Temporary adverse effects, however, can be distressing. A capsaicin analog called resiniferatoxin may be more effective than capsaicin and have fewer side effects.

Alpha-Blockers. Alpha-blockers are drugs that relax smooth muscles and improve urine flow. They are useful for men with benign prostatic hyperplasia who also have urge incontinence. They include terazosin (Hytrin), doxazosin (Cardura), tamsulosin (Flomax), and alfuzosin (Xatral). Tamsulosin may be particularly beneficial. A 2006 study published in the Journal of the American Medical Association reported that the combination of tamsulosin and tolterodine works better than either drug alone for men with moderate-to-severe lower urinary tract symptoms, including overactive bladder. Men in the study were age 40 years and older and had symptoms related to overactive bladder and benign prostatic hyperplasia.

Alpha-Adrenergic Agonists. Alpha-adrenergic agonists are used to strengthen the smooth muscle that opens and closes the internal sphincter. They include ephedrine and pseudoephedrine, which are common ingredients in numerous over-the-counter decongestants and appetite suppressants.

Such drugs may be helpful for patients with mild stress incontinence not caused by nerve damage, although evidence on their benefits is weak. They also can have significant side effects, particularly ephedrine. In fact, products containing a similar drug, phenylpropanolamine (PPA), have been taken off the market because of reports of a higher risk for stroke in some women who took it.

Side effects may include agitation, insomnia, and anxiety. They may have adverse effects on the heart in people with existing heart problems. People with glaucoma, diabetes, hyperthyroidism, heart disease, or high blood pressure should avoid alpha-adrenergic agonists.

Nitrovasolidators. Deficiencies in nitric oxide, a gas that keeps blood vessels open, have been associated with many disorders, including incontinence. Drugs that release nitric oxide, such as nitroflurbiprofen, are being investigated for urinary incontinence.

Evidence indicates that both urge and stress incontinence are affected, in part, by central nervous system processes, particularly signal transmission. Investigators are particularly interested in serotonin and noradrenaline, which are chemical messengers (called neurotransmitters) that affect pathways involved with urination. (These neurotransmitters are also important for many other emotional and physical functions.) Antidepressants targeting one or both of these neurotransmitters are sometimes used for urge incontinence and may also be helpful for some people with stress incontinence.

Tricyclic Antidepressants. Tricyclic antidepressants include imipramine (Janimine, Tofranil), doxepin (Sinequan), desipramine (Norpramin), and nortriptyline (Pamelor). They provide multiple benefits for both urge and stress incontinence. They act as anticholinergic drugs and relax the bladder. They also strengthen the internal sphincter. These drugs should be used carefully. They pose some risk for adverse effects on the heart and possibly the lungs, and they have other severe side effects in older adults. These antidepressants produce side effects similar to anticholinergic drugs, and may cause drowsiness. They may also backfire and actually cause overflow incontinence in some people.
Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs). SNRIs are specially designed antidepressants that are similar to tricyclics but do not have the same side effects. The neurotransmitters serotonin and norepinephrine are thought to play key roles in the normal action of bladder muscles and nerves. Increased neurotransmitter activity stimulates the nerve that controls the urethral sphincter. The SNRI duloxetine (Cymbalta) is approved in Europe for treatment of stress urinary incontinence. (It is approved in the U.S. for other conditions, but not stress urinary incontinence.) In 2005, the manufacturer of duloxetine withdrew its drug application after a small number of women in duloxetine urinary incontinence trials tried to commit suicide. The FDA is investigating whether duloxetine can cause suicidal behavior.

Desmopressin. Studies have reported that desmopressin (DDAVP), a drug used for bedwetting in children, may be helpful in treating adults with urinary incontinence that occurs during sleep. The drug affects sodium levels, and there is a slight risk for water intoxication with this drug.

Botulinum (Botox). Botulinum, the deadly toxin that sometimes contaminates improperly cooked foods, is also a powerful muscle-relaxant. Tiny injected amounts of a purified form (Botox) can relax the muscles and may help control overactive bladder that causes urge incontinence. It may also help relieve urinary retention that might occur after incontinence surgeries.

Stem Cells. Researchers are investigating muscle stem cell injections as a treatment for stress incontinence. Several small studies have indicated promising results. In these experiments, a doctor took a biopsy of skeletal muscle tissue from a patient’s arm. Stem cells were cultured and isolated from the biopsy sample. The doctor then injected the muscle-derived stem cells into the area surrounding the patient’s urethra that is close to the damaged sphincter muscle. In research results presented at the 2007 American Urological Association annual meeting and the 2006 Radiological Association of North American Meeting, patients experienced sustained improvements in bladder control and quality of life.

Surgery

There are nearly 200 procedures for incontinence. Most are designed to restore the bladder neck and urethra to their anatomically correct positions in patients with stress incontinence.

The American Urological Association suggests that surgery should actually be considered as initial therapy for women with severe stress incontinence. It is an effective and safe alternative when conservative treatments fail. Many of the procedures are safe even for women up to 80 years old who do not have serious medical conditions. Potential complications of all procedures include obstruction of the outlet from the bladder, causing difficulty in urination and irritation.

Deciding which procedure to choose is difficult and often depends on the factors causing the incontinence and whether anatomical abnormalities are involved. It should be noted that although hysterectomy has been shown to improve incontinence, it must not be performed only as a cure for incontinence.

In general, patients should weigh all options carefully. They should discuss the situation with their doctor, and ask about their surgeon's experience. As a general rule, the more times a surgeon has successfully performed a procedure, the better.

Retropubic Colposuspension Surgery. Retropubic colposuspension using standard "open" surgery is an effective treatment for stress incontinence, especially over the long term. ("Open" surgery implies the use of a wide incision in order to "open" the area.) Long-term continence rates can range from 85 - 90%.

The goal of colposuspension is to correct the position of the bladder and urethra by sewing the bladder neck and urethra directly to the surrounding pelvic bone or nearby structures. There are many variants, but, in general, they are effective only for women with urethral hypermobility. Most procedures require a general or spinal anesthetic and a 2-day hospital stay.

Burch colposuspension (sometimes called colpocystourethropexy) is a standard approach. It requires a wide abdominal incision and is often performed during abdominal surgeries such as hysterectomy or hernia operations. It is also performed along with sacrocolpopexy, a surgical procedure used to repair pelvic organ prolapse. (Pelvic organ prolapse occurs when the uterus or bladder slips from the pelvic cavity into the vagina. It is often due to pelvic muscle weakness that develops after childbirth.) Prolapse can lead to stress incontinence. However, prolapse surgery itself sometimes causes incontinence. A 2006 study suggested that a Burch colposuspension performed at the same time as sacrolpopexy can help reduce postsurgical stress incontinence.

The surgeon secures the urethra and bladder neck with lateral (sideways) sutures that pass through thick bands of muscle tissue running along the pubic bones. Unlike an older suspension procedure, this procedure poses a much lower risk for obstruction of the urethra. It is more effective in premenopausal than postmenopausal women and may not be appropriate for all women.

A rigorous 2007 study published in the New England Journal of Medicine compared the effectiveness of the Burch colposuspension to the sling procedure, another type of surgical treatment for stress incontinence. The study found that the sling procedure had better results for achieving dryness. However, more women who had the sling procedure had post-operative urinary problems, especially urinary tract infections. Overall, women were satisfied with the outcomes of both procedures. Eighty-six percent of women who had a sling procedure and 78% of women who had a Burch colposuspension reported satisfaction with their treatment.

Marshall-Marchetti-Krantz (MMK). The MMK approach requires a wide abdominal incision. The surgeon then elevates the urethra and bladder neck using sutures. These structures are then secured and anchored in nearby cartilage. This approach is one of the most reliable, but is used less often because of the risk for scarring and because the incision limits the surgeon's ability to correct any potential hernias (cystoceles).

Click the icon to see an illustrated series detailing bladder neck surgery.

Laparoscopy. Other less invasive procedures use laparoscopy, which requires only one or two small incisions over the pubic bone. Evidence suggests that laparoscopy, performed by an experienced surgeon, works just as well as standard surgery. While laparoscopy has a higher complication rate, it also has a faster recovery time and less postoperative pain. Still, well-conducted long-term studies are needed for an accurate comparison with standard colposuspension.

Needle Suspension. Needle suspensions include a number of approaches, including the Pereyra, Stamey, Raz, and Gittes procedures. The basic approach places stitches on either side of the bladder and ties them to muscle tissue or the pubic bone. Some of these procedures use transvaginal suspension, which requires only a small abdominal incision or no incision at all. In this case, the surgeon works through the vagina and places sutures through the vaginal walls. Transvaginal suspension works only if the walls of the vagina are strong enough to withstand the procedure. Some studies report poor long-term results, particularly compared to colposuspension. In one study, only 35% of patients who had transvaginal suspension reported success after 6 years. In another study, the failure rate was 83% after 4 - 5 years. Additional research has indicated that 20% of women have worse sexual function after the procedure.

Postoperative Considerations for Most Procedures. Following most standard procedures, patients usually leave the hospital on the second or third day, but need a urinary catheter for about 10 days. Newer procedures may require shorter stays and less intensive postoperative care.

Complications after surgery include:

Some risk of damage to the surrounding nerves or vessel. This can result in internal sphincter deficiency. (In some cases it may already have been present before the operation.)
Difficulty in urinating from surgical overcorrection. (This may require additional surgery.)
Poor wound healing.
Adhesions (scar tissue) that obstruct the urethra. This complication is higher with older standard procedures.
Vaginal abnormalities (prolapsed vagina).

A sling procedure may be a good option for severe stress incontinence in women who have either intrinsic sphincter deficiency or urethral hypermobility. The method is even proving to help women with mild-to-moderate incontinence and young girls with severe incontinence. It may also be useful for managing female urge incontinence. Sling procedures are also available for men who experience incontinence after prostatectomy.

Until recently, there were few clinical trials that directly compared the sling procedure with Burch colposuspension. In 2007, the New England Journal of Medicine published the results of the largest and most rigorous clinical trial conducted on these two types of surgery. In this study of 655 women with stress incontinence, half of the women underwent the sling procedure and half had open surgery with the Burch colposuspension.

Two years after surgery, success rates were highest for women who had the sling procedure. Forty-seven percent of women who had the sling procedure reported no urinary incontinence (either stress or urge) compared to 38% of women who had the Burch procedure. For stress-only incontinence, 66% of women who had the sling procedure and 49% of women who had the Burch procedure were dry. Eighty-six percent of women who had the sling procedure and 78% of the Burch group reported satisfaction with their treatment.

However, women who had the sling procedure did experience more post-operative urinary problems. The most common complication was urinary tract infections, which affected 63% of women who had a sling procedure compared with 47% of women who had the Burch procedure. A small number of women who had a sling procedure also reported difficulty voiding and urge incontinence.

The Percutaneous Sling Procedure for Women. The procedure generally works as follows:

The surgeon makes an incision above the pubic bone and removes a layer of abdominal fasci (tissue that covers muscle fibers). This muscle strip is set aside and later serves as the sling. (The uses of fasci taken from a cadaver or synthetic slings are also being investigated. However, the natural muscle strip may last longer than some of the common synthetic materials.)
The surgeon makes an incision in the vaginal wall. The piece of muscle fiber or material is attached under the urethra and bladder neck, somewhat like a hammock, and secured to the abdominal wall and pelvic bone.
This sling then compresses the urethra back to its original position. The sling must be supportive without being too tense, which can cause urinary obstruction.

Complications can include infection, bleeding, and the formation of fistulas (holes that form and are usually infected).

Vaginal Sling and Tape Procedures for Women. Newer outpatient procedures do not use abdominal incisions. Instead, they are performed through a small incision in the vagina. Typically, two small tacks are placed in the pubic bone. A sling is inserted into the vagina and is attached to the tack.

The tension-free vaginal tape (TVT) procedure uses a special gauze tape covered by a polypropylene coating, which is attached on each side of the urethra. The patient remains conscious and is asked to cough during the procedure so that the surgeon can determine if the tape is secure. Small early studies showed that the procedure worked as well as colposuspension (the standard suspension procedure), with stress incontinence cure rates of 84 - 100%. According to a 2005 study, the benefits of TVT can last for up to 8 years for women with stress incontinence. However, women with mixed incontinence (a combination of stress and urge) did not fare as well. Women with mixed incontinence had a 60% cure rate during the first 4 years following surgery, but the cure rate declined to 30% within 4 - 8 years post-surgery.

Sling Procedures in Men. For some men who have prostatectomy-induced incontinence, sling procedures may be a good option. Researchers have reported an 80% success rate, the same as an artificial urinary sphincter, which is the standard surgical treatment for such patients. The sling procedure has been less effective in men who have had radiation therapy, although improved techniques are making this approach useful even for these patients. Minimally invasive procedures are also being tested.

Artificial Sphincter. In cases of sphincter incompetence, or complete lack of sphincter function, an artificial internal sphincter may be implanted. This procedure is useful for appropriate male and female candidates of any age, including children. It is particularly helpful for men after radical prostatectomy. Studies have found poor results for patients with incontinence due to radiation therapies, although a 2001 study of men with prostatectomy indicated that it was useful regardless of previous radiation therapy.

Click the icon to see an illustrated series detailing artificial sphincter surgery.

This device uses a balloon reservoir and a cuff around the urethra that is controlled with a pump. The patient opens the cuff manually by activating the pump. The urethra opens and the bladder empties. The cuff closes automatically several minutes later. The two major drawbacks of the internal sphincter implant are:

Malfunction. If the implant malfunctions, the surgery must be performed again.
Infection. Infection is more serious as it can cause erosion of the urethra or bladder neck underneath the implant. Such infections not only require removal of the device, but also may worsen the incontinence. Fortunately, techniques have improved so that infection is uncommon.

In a 2001 study, after an average of 7 years, 70% of female patients with stress incontinence had either the original implant or a replacement, and 82% had urination properly restored. (Only 37% still had the original implant, however.) Studies on men have reported similar findings, although newer devices that use narrow cuffs may significantly improve re-implantation rates. Nearly all patients still need to use pads for leakage.

Injections of materials, such as collagen, that provide bulk to help support the urethra are proving to be beneficial for the following patients:

Women (even the elderly) with severe stress incontinence who cannot or do not wish to have surgery that involves anesthesia.
Men who have slight incontinence caused by prostate surgery. Men who have bulking injections after TURP (transurethral resection of the prostate) have a continence rate that is equal to the rate in women. After radical prostatectomy (removal of the prostate gland in prostate cancer), collagen injections can achieve some level of continence in up to nearly half of men. (Collagen injections are not beneficial after radiation therapy for prostate cancer.)

The Procedure.

First, bladder instability or hyperactivity should be medically treated and managed to control muscle activity before having the procedure. Otherwise it is likely to fail.
The basic procedure involves injecting bulking material into the tissue surrounding the urethra.
The material used is usually animal or human collagen. (Collagen is the basic protein in bones, muscles, and all connective tissue.) Synthetic bulking materials, such as carbon-coated beads, are also being used.
The doctor passes the collagen-containing needle through a cystoscope, a tube that has been inserted into the urethra. The collagen can also be injected into the skin next to the sphincter.
The injected collagen tightens the seal of the sphincter by adding bulk to the surrounding tissue.
The procedure takes about 20 - 40 minutes, and most people can go home immediately afterward.
Two or three additional injections may be needed to achieve satisfactory results.

Postoperative Care. People may experience immediate improvement followed by a temporary relapse after a week or so. Patients must be taught to use a catheter tube for withdrawing urine for a few days following the procedure. In general, it takes about a month for the full benefits to be apparent.

Complications.

There is a risk for infection and urinary retention, although these conditions are temporary.
An increase in autoimmune disease has been reported in a small number of cases.
The procedure may not be appropriate for patients with certain cardiac conditions.

Duration of Effectiveness. Collagen is absorbed over time, so injections generally need to be repeated every 6 - 18 months. According to one study, however, after a year 44% of women who had the implants still experienced the same level of improvement. (Synthetic materials may last longer than collagen from other sources, but they pose a risk for rejection as well as migration to the lymph nodes and other parts of the body.)

Anterior vaginal repair procedures that correct a prolapsed (fallen) uterus or vagina can often correct incontinence in women who have these conditions. The anterior vaginal repair (also called a bladder tuck) requires an incision to be made through the vagina. This releases part of the anterior (front) vaginal wall, which is attached to the base of the bladder. The pubocervical fascia (the supportive tissue between the vagina and bladder) is folded and stitched to bring the bladder and urethra into proper position. Several variations on this procedure may be necessary, depending on the severity of the prolapse. It is not as effective as retropubic suspension procedures, however, and should not be used as the primary method for correcting incontinence.

An interesting investigative approach uses radiofrequency energy to shrink tissue that supports the bladder neck and reduces hypermobility. Early studies are promising. In one, for example, the cure rate was nearly 80% at the end of a year, and 83% of patients reported satisfaction with the procedure.

Other Procedures

The sacral nerves, located in the tail bone, appear to play an important role in regulating bladder control. A sacral nerve stimulation system (InterStim) is now available for patients with urge incontinence. The system sends electrical pulses to the sacral nerves to help retrain them. InterStim is reserved for the treatment of urinary retention and the symptoms of overactive bladder in patients who have failed or cannot tolerate less invasive treatments. The system works as follows:

A stopwatch-size device is implanted under the skin in the abdomen.
A wire connected to it runs to the sacral nerves in the lower back.
The device, a battery-operated generator, produces electrical pulses.
The pulses are sent to the sacral nerves and reduce the hyperactivity of the bladder.
The sensation of the electrical pulse is similar to a slight pulling sensation in the pelvic area. Sometimes it can cause a small jolt or shock if the patient changes posture quickly. It should not cause pain. (If it does, something is wrong with the device.)

Complications include infection, lower back pain, and pain at the implant site. The system, however, does not cause nerve damage and can be removed at any time.

Patients have reported improvement in the frequency and volume of urination, as well as the intensity of urgency and their quality of life. Studies report complete dryness in nearly half of patients, with about 75% of patients experiencing relief from heavy leaking.

Transcutaneous Neuromodulation. The use of electrodes on the surface of the skin, called transcutaneous neuromodulation, may prove to be beneficial and particularly attractive for children.

Percutaneous Stoller Afferent Nerve Stimulation. The percutaneous stoller afferent nerve system (PerQ SANS System) has also been approved for urge incontinence.

In this therapy, a very thin needle is inserted a short distance above the ankle bone.
The needle is applied to the tibial nerve in the ankle, which connects with the sacral nerve complex.
Low-frequency electrical stimulation is applied for 30 minutes once a week for about 3 months.
After that, depending on the patient's response, treatments are given every week to every other week.
Short-term results are promising, but more research is needed.

Catheters and Collection Devices

A catheter is a slim flexible tube inserted into the urethra. They are mainly used for cases of severe urge incontinence.

A catheter (a hollow tube) may be inserted into the urinary bladder when there is a urinary obstruction, following surgical procedures to the urethra, in unconscious patients (due to surgical anesthesia, coma, etc.), or for any other problem in which the bladder needs to be kept empty (decompressed) and urinary flow assured.

Click the icon to see an image of male bladder catheterization.

Temporary Catheterization. For people who are still active, catheterization is often very distressing. If possible, temporary, also called intermittent, catheterization is usually the best choice. Patients insert the catheter tube into their urethras, generally every 3 - 4 hours. This type of catheterization carries few risks and empties the bladder completely. Some patients report that they can maintain an active life with no significantly increased risk for infection with some simple precautions:

Sterilize catheters at home.
Use a Zip Lock plastic bag for carrying them when leaving home.
Use another plastic bag for antiseptic cleansing solution.
When using public bathrooms, wash before and after catheterization. Touch as few places in the bathroom as possible.

Permanent Catheterization. People who are mentally or physically incapable of self-catheterization may need permanent catheterization.

The permanent catheter is inserted by a doctor or nurse into the opening of the bladder and a cuff is inflated to hold the tube in place.
Urine drains to an external collection device, which is generally strapped to the leg and must be emptied periodically.

The procedure is not painful, but there is a substantial increased risk of infection. Many experts feel that the catheter is overused, especially in the elderly.

Condom Catheters. Condom catheters are much more satisfactory than standard catheters for many male patients, although there is more spillage.

The condom is worn all day.
At night it is removed and washed for reuse the next day.

Collection Devices Attached to the Leg. For chronic or severe incontinence, collective devices drain urine into a bag that is attached to the lower leg and emptied periodically. These are generally more successful for men. Urine can be funneled into the tube by a pouch surrounding the penis. The positioning of the collecting device is difficult for women, and more accidents occur. For both men and women, irritation of the area around the urethral opening is a problem, since urine is in contact with the area for long periods.

Resources

www.nafc.org -- National Association for Continence
www.simonfoundation.org -- The Simon Foundation for Continence
www.niddk.nih.gov -- National Kidney and Urologic Diseases Information
www.acog.org -- American College of Obstetricians and Gynecologists
www.augs.org -- American Urogynecologic Society
www.kegel-exercises.com -- Information on Kegel Exercises
www.urologyhealthy.org -- Urology Health from the American Urological Association

References

Albo ME, Richter HE, Brubaker L, et al. Burch colposuspension versus fascial sling to reduce urinary stress incontinence. N Engl J Med. 2007 May 24;356(21):2143-2155. Epub 2007 May 21.

Harris SS, Link CL, Tennstedt SL, Kusek JW, McKinlay JB. Care seeking and treatment for urinary incontinence in a diverse population. J Urol. 2007 Feb;177(2):680-4.

Kaplan SA, Roehrborn CG, Rovner ES, Carlsson M, Bavendam T, Guan Z. Tolterodine and tamsulosin for treatment of men with lower urinary tract symptoms and overactive bladder: a randomized controlled trial. JAMA. 2006 Nov 15;296(19):2319-28.

Litwin MS, Saigal CS, editors. Urologic Diseases in America. US Department of Health and Human Services, Public Health Service, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. Washington, DC: US Government Printing Office, 2007; NIH Publication No. 07–5512.

Review Date:
6/15/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Crohn's disease

FitSugar — Wed, 08 Oct 2008 17:35:29 -0700

In This Report

Highlights
Introduction
Causes
Symptoms
Complications
Risk Factors
Diagnosis
Dietary Factors
Symptom Management
Medications
Surgery
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Biologic Drugs

In February 2007, the FDA approved adalimumab (Humira) for treatment of adult patients with moderate-to-severe Crohn’s disease. Adalimumab and infliximab (Remicade) are now the two biologic drugs approved for Crohn’s disease. Infliximab is approved for treating both adults and children.
As of August 2007, the FDA was considering approving natalizumab (Tysabri) for moderate-to-severe Crohn’s disease in patients who have not responded to, or cannot tolerate, other therapies. However, natalizumab has serious risks -- in 2007, the European medicine agency rejected natalizumab for Crohn’s disease treatment.
Certolizumab (Cimzia) is another biologic drug that is showing promise for Crohn’s disease, according to several 2007 studies in the New England Journal of Medicine.
The risks of biologic drugs need to be weighed against their potential benefits, according to a 2007 consensus statement from the American Gastroenterological Association. These drugs may be appropriate as initial treatments for select patients who have fistulas or for patients who have not been helped by corticosteroid drugs.

Genetic Research

In 2006 and 2007, scientists achieved major breakthroughs in identifying specific genes associated with Crohn’s disease. Among these recent discoveries:

The interleukin-23 receptor (IL23R) gene is associated with variations that can either increase or decrease the risk for Crohn’s disease and ulcerative colitis.
The ATG16L1 gene regulates a process called autophagy, which involves how a cell digests itself. Scientists think that waste build-up from improperly regulated autophagy may play a role in the inflammatory response associated with Crohn’s disease.
Other recently identified genes that may be linked with Crohn’s disease include PHOX2B and NCF4.

Pregnancy Complications

According to a 2007 review in Gut, inflammatory bowel disease significantly increases the risk for pregnancy complications, such as premature birth, low birth weight, and birth defects. Women who experience disease flares during pregnancy are especially at risk.

Introduction

Inflammatory bowel disease (IBD) is a general term that covers two disorders:

Ulcerative colitis (UC)
Crohn's disease (CD)

Some evidence suggests that these two diseases are part of a biologic continuum. At this time, however, they are considered distinct disorders with somewhat different treatment options. The basic distinctions between UC and CD are location and severity. However, as many as 10% of patients with IBD have features and symptoms that match the criteria for both disorders, at least in the early stages. (This is called indeterminate colitis.)

Crohn's disease, also called regional enteritis, is a chronic inflammation of the intestines which is usually confined to the terminal portion of the small intestine, the ileum. Ulcerative colitis is a similar inflammation of the colon, or large intestine. These and other IBDs (inflammatory bowel disease) have been linked with an increased risk of colorectal cancer.

Crohn's Disease. Crohn's disease is an inflammation that extends into the deeper layers of the intestinal wall. It is found most often in the area bridging the small and large intestines, specifically in the ileum and the cecum, sometimes referred to as the ileocecal region. Crohn's disease occurs less frequently in other parts of the gastrointestinal tract, including the anus, stomach, esophagus, and even the mouth. It may affect the entire colon or form a string of contiguous ulcers in one part of the colon. It may also develop as multiple scattered clusters of ulcers throughout the gastrointestinal tract, skipping healthy tissue in between.

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

Ulcerative Colitis. Ulcerative colitis is an inflammatory disease of the large intestine. Ulcers form in the inner lining, or mucosa, of the colon or rectum, often resulting in diarrhea, blood, and pus. The inflammation is usually most severe in the sigmoid and rectum and typically diminishes higher in the colon. The disease develops uniformly and consistently until, in some people, the colon becomes rigid and foreshortened. [See In-Depth Report #69: Ulcerative colitis.]

Click the icon to see an image of the structure of the colon.

The gastrointestinal tract (the digestive system) is a tube that extends from the mouth to the anus. It is a complex organ system that first carries food from the mouth down the esophagus to the stomach and then through the small and large intestine to be excreted out through the rectum and anus.

Esophagus. The esophagus, commonly called the food pipe, is a narrow muscular tube, about 9 1/2 inches long, that begins below the tongue and ends at the stomach.

Stomach. In the stomach, acids and stomach motion break food down into particles small enough so that nutrients can be absorbed by the small intestine.

Small Intestine. The small intestine, despite its name, is the longest part of the gastrointestinal tract and is about 20 feet long. Food that passes from the stomach into the small intestine first passes through three parts:

First it enters the duodenum
Then the jejunum, and
Finally the ileum

Most of the digestive process occurs in the small intestine.

Large Intestine. Undigested material, such as plant fiber, is passed to the large intestine, mostly in liquid form. The large intestine is approximately 6 feet long and is the final portion of the digestive tract. It follows the small intestine and includes the cecum, the appendix, the colon, and the rectum, which extends to the anus.

Cecum and Appendix. The cecum and the appendix are located in the lower-right quadrant of the abdomen.

Colon. The colon absorbs excess water and salts into the blood. The remaining waste matter is converted to feces through bacterial action. The colon is divided into four major sections.

The first section, the ascending colon, extends upward from the cecum on the right side of the abdomen.
The second section, the transverse colon, crosses the upper abdomen to the left side.
The third section extends downward on the left side of the abdomen toward the pelvis and is called the descending colon.
The final section is the sigmoid colon.

Rectum and Anus. Feces are stored in the descending and sigmoid colon until they are passed through the rectum and anus. The rectum extends through the pelvis from the end of the sigmoid colon to the anus.

Click the icon to see an image of the digestive system.

Click the icon to see an image of the stomach.

Click the icon to see an image of the structure of the small intestine.

Click the icon to see an image of the structure of the colon.

Causes

Inflammatory bowel disease has many different causes. It is due in many cases to a genetic susceptibility that enables an organism such as a virus or bacteria to trigger an abnormal immune reaction, which in turn, causes an inflammatory response in the intestines. Although Crohn's disease has features that resemble an autoimmune disease (in which the body's immune system attacks its own cells), some researchers think that it may be due to initial immune deficiencies.

The Immune System's Infection Fighters. The primary infection-fighting units are two types of white blood cells: lymphocytes and leukocytes.

Lymphocytes include two subtypes known as T cells and B cells. Both types of cells are designed to recognize foreign invaders (antigens) and to launch an offensive or defensive action against them:

B cells produce antibodies, which are separate substances that can either ride along with a B cell or travel on their own to attack the antigen.
T cells have special receptors attached to their surface that recognize the specific antigen.

T cells are further categorized as killer T cells or helper T cells.

Killer T cells directly attack antigens that occur in any cells that contain a nucleus.
Helper T cells also recognize antigens, but their role is two fold. They stimulate B cells and other white cells to attack the antigen. They also produce cytokines, powerful immune factors that have an important role in the inflammatory process.

Helper T cells and Inflammatory Bowel Disease. The actions of the helper T cells (TH cells) are of special interest in inflammatory bowel disease:

TH cells stimulate other white blood cells called B cells to produce antibodies. In this case, however, they appear to direct the B cells to produce autoantibodies, which are directed against the body's own cells.
TH cells also secrete or stimulate the production of powerful immune factors called cytokines. In small amounts, cytokines are indispensable for healing. If overproduced, however, they can cause serious damage, including inflammation and cellular injury. Cytokines, particularly specific ones known as tumor necrosis factor, interferon-gamma, and interleukins, cause intestinal inflammation and damage, which, in a vicious cycle, attract even more helper T cells.

Helper T cells are further categorized as TH1 and TH2. An imbalance in these two types appear to occur in IBD, although each disorder has a different balance:

Ulcerative colitis patients favor a TH2 response, which activates the interleukins IL-5, IL-6, and IL-10. These mostly affect mucosal areas in the intestine.
Research indicates that patients with Crohn's disease have increased activity in TH1 cells, activating interleukin-2 (IL-2) and interferon-gamma, which affect intestinal cells. Tumor necrosis factor (TNF) may be a particularly potent immune factor in Crohn's disease. It is important in properties that regulate inflammation and cell proliferation. If genetic or other factors increase production of this immune compound, it can lead to great harm.

Interleukin 6 appears to play a part in both IBDs, by inhibiting a natural process called apoptosis, in which cells self-destruct. As a result, cells proliferate faster than they die, causing an excessively strong immune response.

Adhesion Molecules. Increased levels of certain molecules called E-selectin and intercellular adhesion molecule-1 (ICAM-1) also appear to play a major role in the inflammatory process by causing damaging immune factors to build up on intestinal cells.

Matrix Metalloproteinase. Greater activity of enzymes called matrix metalloproteinase has been detected in the colons of patients with IBD. These increased levels tend to break down the extracellular matrix, a barrier composed of structural proteins and elastic fibers that surrounds and supports cells, in this case in the colon. Researchers suggest that this activity may cause persistent damage once the inflammatory process has triggered IBD.

Although the causes of inflammatory bowel disease are not yet known, genetic factors certainly play some role. Between 10 - 20% of people with ulcerative colitis have family members with the disease. Several identified genes and chromosome locations play a role in the development of ulcerative colitis, Crohn's disease, or both. Genetic factors appear to be more important in Crohn's disease, although there is evidence that both forms of inflammatory bowel disease have common genetic defects.

Specific Genes Involved. The first important genetic discovery for Crohn’s disease was the identification of the genetic variant CARD15 (also called NOD2), which alters the immune system so that it launches an over-reaction in response to bacteria, causing inflammation. However, this genetic factor only affects a small percentage of Crohn’s disease cases and is not involved with ulcerative colitis.

In 2006, scientists made a significant genetic research breakthrough by identifying the interleukin-23 receptor (IL23R) as a major link to the development of both Crohn’s disease and ulcerative colitis. Interleukin 23 is a cytokine that plays an important part in the inflammatory response and inflammatory diseases. Interestingly, scientists found that certain variations in the IL23 receptor gene can either increase or decrease the risk for inflammatory bowel disease. Further research in 2007 indicated that IL23R gene variants may also increase or decrease the risk for Crohn’s disease in children.

Also in 2007, scientists identified several other genetic risk factors for Crohn’s disease, including the genes PHOX2B, NCF4, and ATG16L1. Scientists are particularly interested in the ATG16L1 gene. This gene regulates autophagy, the process in which a cell digests its own cytoplasm, including cellular waste products such as bacteria. Problems with autophagy may lead to a build-up of unprocessed waste products within the cell. This build-up may then provoke the inflammatory response associated with Crohn’s disease. Mutations of the ATG16L1 gene have been linked to increased susceptibility to Crohn’s disease in both adults and children.

Future genetic research may help develop targeted drug therapy for treatment of inflammatory bowel disease.

One theory suggests that viruses or bacteria within the intestine may alter properties in the lining and intestinal tract. Over time, these changes may trigger the processes that lead to inflammatory bowel disease.

Measles. Some studies report that children with IBD may have had more and earlier childhood infections. The measles virus has been of particular interest. According to the U.S. Centers for Disease Control, and many studies, the measles virus does not cause Crohn’s or IBD.

Much publicity has centered on whether the vaccine for measles, mumps, and rubella (the MMR vaccine) causes conditions such as autism and Crohn’s disease. This theory has been rigorously reviewed and refuted in many well-conducted studies, including several published in 2006. The evidence clearly indicates that the MMR vaccine does not increase the risk of Crohn’s disease, other inflammatory bowel disease, or autism.

Mycobacteria. A type of bacterium associated with tuberculosis is another possible candidate for an infectious cause of Crohn’s disease.

Escherichia coli. The intestine normally harbors E. coli bacteria. In most cases, the bacteria are harmless and even protective. Some E. coli strains, however, can bind to the intestinal walls and penetrate the lining. These damaging strains may be associated with Crohn’s disease.

Cytomegalovirus. Cytomegalovirus (CMV) is a common virus that is also under suspicion as a contributor to severe cases of IBD.

Inflammatory bowel disease is much more prevalent in industrialized nations and in higher-income groups. Diet may play some role, although studies have been conflicting over its importance.

Symptoms

The two major inflammatory bowel diseases (IBDs), ulcerative colitis and Crohn's disease, share certain characteristics:

Symptoms usually appear in young adults.
Symptoms can develop gradually or have a sudden onset.
Both are chronic. In either disease, symptoms may flare up (relapse) after symptom-free periods (remission) or symptoms may be continuous without treatment.
Symptoms can be mild or very severe and disabling.
The severity of symptoms and relapse rates of both IBDs vary with seasons, with the highest risk in the winter and autumn and lowest in summer.

The two disorders, however, have different symptom profiles and is it important to differentiate between them, since they require different treatments.


Symptoms	Ulcerative Colitis	Crohn's Disease
Diarrhea	Recurrent diarrhea is very common, but onset may be very gradual and mild or it may not be present. Feces may also contain mucus.	Recurrent diarrhea is fairly common.
Rectal Bleeding	Blood is almost always present in stools. It may be readily visible or visible only using a microscope (called occult blood).	Bleeding not as common as in UC, but can occur.
Constipation	Constipation can be a symptom of UC, but not as common as diarrhea. Can occur during flare-ups. May occur when the inflamed rectum triggers a reflex response in the colon that causes it to retain the stool.	Constipation in Crohn's disease is usually a symptom of obstruction in the small intestine.
Abdominal Symptoms	Pain is not prominent symptom, but can vary. May cause vague discomfort in the lower abdomen, an ache around the top of the hipbone, or cramps in the middle of the abdomen. Severe pain can occur during flare-ups. Vomiting and nausea.	Main symptom is recurrent episodes of pain in the lower right part of the abdomen or above the pubic bone. Often preceded by and relieved by defecation. Bloating, nausea, and vomiting may also occur. Intestinal pain may also be an indication of a serious condition, such as an abscess, or a perforation of the intestinal wall.
Fever	May occur with severe attacks.	Usually low-grade. Spiking fever and chills indicates complications.
Loss of appetite, weight loss, and impaired growth in children	Often not evident in mild or even moderately severe UC. Occasionally impairs growth in children and teenagers.	Common. Typical weight loss is 10 - 20% of normal. Commonly impairs growth in children and teenagers.
Abnormal defecation: Increased frequency, a feeling of incomplete evacuation, and tenesmus (a painful urge for a bowel movement even if the rectum is empty). Fecal incontinence.	Symptoms may be mild or severe.	Can occur in active stages.
Anal ulcers and fistulas: (channels that can burrow between organs, loops of the intestine, or between the intestines and skin).	Almost never a symptom.	Fistulas and ulcers around the anus may be early symptoms.
Neurologic or psychiatric symptoms	No.	May be early signs of Crohn's disease when accompanied by gastrointestinal problems.

There are three body views (front, back and side) that may be helpful if you are uncertain of a body area. Many areas are referred to by both descriptive and technical names. For example, the back of the knee is called the popliteal fossa. However, areas like the "flank" may not have both names, so the location may be unclear.

Click the icon to see a depiction of an anorectal fistula.

Complications

The outlook for Crohn's disease varies widely. Crohn's disease can range from being benign (such as when limited Crohn's disease occurs only around the anus in older people) or it can be very severe. At the extreme end, some patients may experience only one episode and others suffer continuously. Although recurrences tend to be the norm, disease-free periods can last for years or decades in some patients. Although Crohn's disease cannot be cured even with surgery, treatments are now available that can offer significant help to most patients. Crohn's disease is rarely a direct cause of death, and most people can live a normal lifespan with this condition.

Mild Crohn's Disease. The fewer bowel movements, the milder the disease. In mild disease, abdominal pain is absent or minimal. The patient has a sense of well-being that is normal or close to normal. There are few, if any, complications outside the intestinal tract. The doctor does not detect any mass when pressing the abdomen. The red blood cell count is normal or close to normal, and the patient is not underweight.

Severe Crohn's Disease. In severe Crohn's disease, the patient has bowel movements frequent enough to require opiates or other potent anti-diarrhea medication. Abdominal pain is severe and usually located in the lower right quadrant of the abdomen. (The location of the pain might not indicate the site of the actual problem, a phenomenon known as referred pain.) The red blood cell count is low. The patient has a poor sense of well-being and experiences complications that may include weight loss, joint pain, inflammation in the eyes, reddened or ulcerated skin, fistulas, abscesses, and fever. The surgical and medical treatments of Crohn's disease, as with ulcerative colitis, have complications of their own that can be severe.

Malabsorption and malnutrition. Malabsorption is the inability of the intestines to absorb nutrients. In IBD, this occurs as a result of bleeding and diarrhea, as a side effect from some of the medications, and as a result of surgery. Malnutrition usually develops slowly and tends to become severe, with multiple nutritional deficiencies. It is very common, ranging from 25 - 80% of patients with Crohn's disease.

Ulcer, Fistulas, and Abscesses. Between 30 - 40% of patients with Crohn's disease experience complications around the anal area from inflammation. Fistulas (channels beneath the skin) frequently develop from the deep ulcers that can form with Crohn's. If fistulas develop between the loops of the small and large intestines, they can interfere with absorption of nutrients. They often form pockets of infection or abscesses, which may become life threatening without treatment.

Bleeding. Massive bleeding can occur in 1 - 2% of cases and may be recurrent. Bleeding is usually from a localized area in the intestine. Surgery may be performed to remove the bleeding sites.

Colorectal Cancers. Patients with inflammatory bowel disease have a slightly higher risk for colorectal cancer. The risk is greater for patients with severe ulcerative colitis than for those with Crohn’s disease. Patients with Crohn’s disease do have a 40-fold increased risk for small bowel cancer. (However, small bowel cancer is a very rare type of cancer.) The risk increases with the severity of the condition and the length of time the patient has had Crohn’s. [See In-Depth Report #55: Colon and rectal cancers.]

Intestinal Blockage. Inflammation from Crohn's disease produces scar tissue known as strictures that can constrict the intestines, causing bowel obstruction with severe cramps and vomiting. Strictures usually occur in the small intestine but can also occur in the large intestine.

Intestinal Infections. Inflammatory bowel disease can increase patients’ susceptibility to Clostridium difficile, a species of intestinal bacteria that causes severe diarrhea. As its name implies, C. difficile is difficult to treat and is resistant to many types of antibiotics. It is usually acquired in a hospital. However, several 2007 studies indicated that C. difficile is increasing among patients with inflammatory bowel disease and that many patients acquire this infection outside of the hospital setting. Patients with ulcerative colitis are at particularly high risk.

People with inflammatory bowel disease have a higher risk of developing other inflammatory diseases that affect the lungs and central nervous system.

Asthma. According to a 2005 study, people with IBD are 1.5 times more likely to have asthma than people without IBD. Of all the conditions that can accompany IBD, asthma is the most common. People with IBD are also at increased risk for bronchitis and other lung inflammations

Eyes. Inflammation in the eyes may sometimes be an early sign of Crohn’s disease. Retinal disease, including detachment, can occur but is rare. People with accompanying arthritic complications may be at higher risk for eye problems.

Joints. Inflammation causes arthritis and stiffness in the joints. The back is commonly affected. Patients with Crohn’s disease are also at risk for clubbing (abnormal thickening and widening at the ends of fingers and toes).

Click the icon to see an image of nail clubbing.

Bones. Crohn’s disease, and the corticosteroid drugs used to treat it, can cause osteopenia (low bone density) and osteoporosis (bone loss).

Anemia. Internal blood loss from ulcers in the intestine is a particular problem in Crohn's disease because of the impaired ability to absorb vitamins and minerals necessary for blood production.

Liver and Gallbladder Disorders. Patients have a higher than average risk for mild but not severe liver problems. They have double the normal risk for gallstones.

Click the icon to see an image of gallstones.

Mouth Sores. Canker sores are common, and when they occur they persist. Those at higher risk are males and younger people. Mouth yeast infections also common in people with Crohn's disease.

Skin Disorders. Patients with Crohn’s disease are likely to develop red knot-like swellings. Such swellings or other skin lesions, such as ulcers, may spread to sites far removed from the colon, (including the arms and legs). People with Crohn's disease have an increased risk for psoriasis.

Thromboembolism (Blood Clots). Clots may occur, most likely in the legs and pelvic area.

Click the icon to see an image of a thrombus.

Urinary Tract and Kidney Disorders. Urinary tract infections are common. Patients have an increased risk for kidney stones. Amyloidosis (deposits of a protein called amyloid in the kidney or other organs) is a rare but very serious kidney condition.

Click the icon to see an image of kidney stones.

Delayed Growth and Development in Children. Up to half of children with Crohn’s disease have impaired physical growth, and nearly all are underweight. About 30% reach puberty late, but once it occurs, hormonal cycles tend to be normal.

Infertility. Infertility rates are only slightly lower than average. Active disease at conception increases risk for miscarriage or prematurity. Men may have lower sperm count during active disease or because of impaired nutrition, but in general fertility is normal.

Pregnancy. Inflammatory bowel disease doubles the risk of pregnancy complications. According to a 2007 review, women with inflammatory bowel disease are nearly twice as likely to give birth prematurely. Children born to mothers with this disease are more than twice as likely to be below normal weight and to have birth defects. If a woman experiences active bouts of disease during the course of her pregnancy, her risk for complications increases.

Menstrual Problems. Menstrual problems in women are common, including premenstrual disorder, abnormal bleeding, and pain. Pain with intercourse occurs in about half of patients. Sexual function may be impaired, not only because of the emotional impact, but also by treatment side effects and complications of the disease, such as fistulas.

Neurologic Factors. Inflammatory bowel disease has been associated with neurologic complications, including a higher risk for dementia, movement disorder, and stroke. People with IBD have a higher risk for developing multiple sclerosis and inflammation of the optic nerve (optic neuritis).

Emotional Factors. The emotional consequences of UC cannot be overestimated, particularly in children. Eating becomes associated with fear of abdominal pain before the end of the meal. Frequent attacks of diarrhea can cause such a strong sense of humiliation that social isolation and low self-esteem may result. Adolescents with IBD may have added problems that increase emotional distress, including weight gain from steroid treatments and delayed puberty.

Risk Factors

About 1 - 2 million Americans suffer from inflammatory bowel disease (IBD), and about 400,000 of these patients have Crohn's disease. (This wide variation is due to the difficulty in diagnosing these disorders and because people in remission may not be identified.) The number of people with Crohn's disease may be increasing, and Crohn's disease is now considered to be the second most common chronic inflammatory disorder (after rheumatoid arthritis).

IBD often runs in families. The incidence may vary depending on gender, age, and geography:

Women may be slightly more at risk for Crohn's disease than men. Both genders are equally at risk for ulcerative colitis.
IBDs in general are diagnosed most often in young people age 10 - 19, but they can occur at any age. Another lesser peak onset occurs in people ages 50 - 80. About 2% of IBD cases appear in children below age 10. Between 10 - 15% of patients with Crohn's are children, and the childhood prevalence appears to be increasing.
IBD occurs four times more often in Americans of Northern European descent than in African-Americans. Scandinavia has the highest rate of Crohn's disease in the world. Studies in Britain suggest, however, that Asians may have a higher rate of IBD than people of European descent. Ashkenazi Jewish people have an even higher risk, five times that of the general population.
IBD seems to be more common among city than country dwellers and occurs more frequently in developed than in less developed nations, indicating that both genetic factors and environmental conditions, such as diet, may be involved in its development.
People who are left-handed have a significantly higher risk for both IBDs as well as certain other diseases associated with problems in the immune system.

Diagnosis

The doctor will take a history and perform a thorough physical examination. The disease is particularly difficult to diagnose in children. In children, IBD may be mistaken for an infection or even depression if other characteristic symptoms, such as bloody diarrhea and weight loss, are not present. Slow growth may be a key feature in making a diagnosis, particularly of Crohn's disease, in children.

Several laboratory tests may be performed:

Blood tests are used for various purposes. An increased number of white blood cells may indicate the presence of inflammation. Blood tests are used to determine the presence of anemia and to measure liver enzymes. (They are abnormal in about 3% of ulcerative colitis patients.) New blood tests that measure certain antibodies may make it easier to differentiate Crohn's disease from ulcerative colitis in children.
A stool sample is taken and examined for blood, infectious organisms, or both.

Standard Endoscopic Procedures. Flexible sigmoidoscopy and colonoscopy are procedures that involve snaking a fiberoptic tube called an endoscope through the rectum to view the lining of the colon. The doctor can also insert instruments through it to remove tissue samples.

Sigmoidoscopy, which is used to examine only the rectum and left (sigmoid) colon, lasts about 10 minutes and is done without sedation. It may be mildly uncomfortable, but it is not painful.
Colonoscopy allows a view of the entire colon and requires a sedative, but it is still performed on an outpatient basis. It is important in differentiating between Crohn's disease and ulcerative colitis and in screening for colon cancer.

There are three basic tests for colon cancer: a stool test (to check for blood); sigmoidoscopy (inspection of the lower colon); and colonoscopy (inspection of the entire colon). All three are effective in catching cancers in the early stages, when treatment is most beneficial.

The procedures may help the doctor to distinguish between ulcerative colitis and Crohn's disease, as well as other diseases. A variation called chromoendoscopy uses a blue stain during the process to reveal fine details on the intestinal lining. It might prove to be useful for identifying areas that may be precancerous and need to be biopsied.

Wireless Capsule Endoscopy. Wireless capsule endoscopy (WCE) is a newer imaging approach that is very useful for diagnosing Crohn's disease. With WCE, the patient swallows a capsule containing a tiny camera that records and transmits images as it passes through the gastrointestinal tract. Some studies have found it to be much more accurate for evaluating small bowel disease than barium x-rays or CT scans. Patients also find it easier to tolerate than standard endoscopy.

Ultrasound. Intestinal wall ultrasound is proving to be useful for identifying the extent and severity of Crohn's disease. It is uncertain if ultrasound is useful for an initial diagnosis.

Upper and Lower Gastrointestinal Barium X-Rays. An upper gastrointestinal barium x-ray may be used if Crohn's disease is suspected in the small intestine. Swallowed barium passes into the small intestine and shows up on an x-ray image, which may reveal inflammation, ulcers, and other abnormalities.

Click the icon to see an image of the barium enema procedure.

Positron Emission Tomography (PET) and Computed Tomography (CT) Scans. PET/CT scans are proving to be extremely useful in evaluating active IBD. With Crohn's disease, CT scans may show thickened walls and complications, such as fistulas, which occur outside the intestine.

Magnetic Resonance Imaging (MRI). Magnetic resonance imaging is another advanced imaging technique that may be useful for detecting abscesses and other injuries related to Crohn's disease in the pelvis. A variant called magnetic resonance spectroscopy (MRS) may prove to be useful for differentiating between Crohn's disease and ulcerative colitis.


Endoscopy	Ulcerative colitis almost always involves the lower left colon and rectum and can be diagnosed using sigmoidoscopy. Crohn's disease may require colonoscopy as well. Endoscopy often reveals ulcers, diseased regions that have a cobblestone-like appearance in Crohn's disease, but not in ulcerative colitis.
X-Rays (Barium Enema) or Computed Tomography Scans	In ulcerative colitis, inflammation is usually evenly distributed on the surface lining of the intestine, and the bowel wall bleeds easily when touched with a swab. The pattern observed in Crohn's disease is usually one of scattered patches of ulcers that are deep, thick, and large. Crohn's disease produces pockets (fissures) or channels (fistulas). They do not occur with UC. In ulcerative colitis the ileum (the lower part of the small intestine) is often dilated while it is narrowed in Crohn's disease.
Laboratory Tests	Tissue samples obtained from a patient with Crohn's disease may reveal granulomas, small collections of inflammatory cells. Granulomas may also be present in other conditions, however. Tissue samples should also be examined for the presence of cancerous cells. About 70% of antibody tests for patients with UC will show immune factors called perinuclear-staining antineutrophil cytoplasmic antibodies, and over 50% of Crohn's patients have anti-Saccharomyces cerevisiae antibodies. Each antibody group shows up only occasionally in the other disorder. Researchers are also investigating other antibodies, such as antilaminaribioside and antichitobioside, which may serve as new markers for Crohn’s disease.

Irritable Bowel Syndrome. Irritable bowel syndrome (IBS), also known as spastic colon, functional bowel disease, and spastic colitis cause many of the same symptoms as inflammatory bowel disease (IBD). (However, it is NOT the same as inflammatory bowel disease.) Bloating, diarrhea, constipation, and abdominal cramps are all symptoms of IBS. Irritable bowel syndrome is not caused by inflammation, however, and no fever or bleeding occurs. Behavioral therapy may be helpful in treating IBS. (Psychological therapy does not improve inflammatory bowel disease.)

Microscopic Colitis. Microscopic colitis causes chronic watery diarrhea, but the colon lining shows little or no signs of inflammation. It may be genetically linked to celiac sprue. Most patients can expect to improve.

Celiac Sprue. Celiac sprue, or celiac disease, is an intolerance to gluten (found in wheat) that triggers inflammation in the small intestine and causes diarrhea, vitamin deficiencies, and stool abnormalities. It occurs in a significant number of people with inflammatory bowel disease and is usually first noticed in children.

Click the icon to see foods to avoid if you have celiac sprue.

Interstitial Cystitis. Interstitial cystitis (IC) is an inflammation of the bladder wall that occurs almost exclusively in women. Some evidence suggests that the risk for IBD in these patients is 100 times above that in the general population and that there may be some common factor to both conditions. The average age of patients with interstitial cystitis is 40, but 25% of cases occur in women under age 30. Symptoms are very similar to urinary tract infections, but no bacteria are present. Pain during sex is a very common complaint in these patients, and stress may intensify symptoms.

Infections. If endoscopy reveals inflammation, a doctor must always rule out possible infections before confirming a diagnosis of inflammatory bowel disease.

Acute Appendicitis. Crohn's disease may cause tenderness in the right lower part of the abdomen, where the appendix is located, that resembles an appendicitis.

Click the icon to see an image of the appendix.

Cancer. Colon or rectal cancers must always be ruled out when symptoms of IBD occur.

Intestinal Ischemia. Symptoms similar to IBD can be caused by blockage of blood flow in the intestine. This is more likely to occur in elderly people.

Dietary Factors

The role of diet and nutrition is very important in Crohn's disease and should be considered for four separate situations:

As important add-on treatment to medical therapies for maintaining nutrition and correcting any nutritional deficiencies
As primary treatment for reducing disease activity
As maintenance therapy on a long-term basis in the case of severe intestinal failure or short-bowel syndrome
For reversing growth-failure in children

Malnutrition is very common in Crohn's disease. In fact, patients with Crohn's appear to burn fat calories at a higher rate than the general population and most patients are underweight. Some experts recommend that children with inflammatory bowel disease increase their calorie and protein intake by 150% of the daily recommended allowance for their specific ages and heights. Studies indicate that nutritional support in children is as important as medications for achieving remission. People whose weights are normal or no less than 90% of normal do not need to add extra calories.

Fluids (non-caffeinated). Drinking plenty of water is extremely important. Vegetable juice and sports drinks may be helpful for restoring important minerals. People with inflammatory bowel disease (IBD) should avoid caffeinated beverages in general, although green tea may have some benefits for Crohn's disease.

Protein. Proteins are very important for growth in children and for repair of cells. Diarrhea can cause protein deficiency, and patients with inflammatory bowel disease may need more protein than the general population. Oily fish, such as salmon and tuna, may be particularly beneficial in Crohn's disease. Other options are poultry and lean meats. Dried beans and legumes also provide protein.

Complex Carbohydrates. Complex carbohydrates, found in whole grains, fruits, and vegetables, should make up half of a patient's calories. Fresh fruit (such as apples, grapefruit, oranges, plums, blueberries, raspberries, and strawberries) may actually be specifically protective for IBD and may possibly reduce the risk for colon cancer. (Simple sugars can increase inflammation, however, so patients should avoid dried fruits and high-sugar fruits, such as grapes, pineapple, and watermelon.)

Foods made up of complex carbohydrates are also often a good source of fiber, which may help reduce damage in the intestinal tract caused by inflammation. However, high-fiber foods can cause gas, bloating, and pain, particularly in IBD patients. Commercial products (such as Beano) are available that can reduce gas. Eating small, frequent meals can also help.

Liquid Supplements. Over-the-counter liquid diets that meet full nutritional needs and are absorbed in the upper intestine, such as Ensure, Sustacal, and other products, may be helpful for some patients with Crohn's. However, it is important to note that no studies have determined this.

Potassium-rich Foods. Examples are potatoes, avocados, and bananas.

Exclusion Diets. Exclusion diets are those that eliminate certain foods that may cause allergies or irritate the intestine. To determine these foods, patients use an "elimination/challenge" approach. First, they remove all suspect foods from their diet for 2 weeks and then reintroduce one food every 3 days. Patients then watch for any symptoms that might indicate an allergic or irritant response, including gastrointestinal problems, headaches, and flushing. This approach, however, may be very difficult, and studies are weak in confirming its value for maintaining remission.

Typical foods people with inflammatory bowel disease (IBD) may avoid include:

Fats. Fats appear to worsen intestinal inflammation in Crohn's disease. Patients should limit fats, particularly saturated fats, found in meat and dairy products. However, certain fatty acids, such as those found in fish oil, may be helpful. The optimal balance between a low-fat diet with addition of these fatty acids is under investigation.
Milk products. Some people with IBD are lactose intolerant (unable to digest the sugar lactose, found in milk products). However, milk, along with the calcium it contains, has been associated with a lower risk for colon cancer. Taking lactase tablets or specially prepared dairy products may help. (Many lactose-intolerant patients are still able to eat yogurt with active cultures, which could be helpful for IBD.)
Foods associated with inflammation (alcohol, simple sugars, and caffeine).
Fruits may be protective, but patients should avoid dried fruits or high-sugar fruits, such as grapes, watermelon, or pineapple.
Products containing corn or gluten (those made from wheat, oats, barley, or triticale).
Common allergenic foods, such as soy, eggs, peanuts, tomatoes.
Foods that may irritate the intestine, particularly so-called Brassica vegetables (cabbage, Brussels sprouts, broccoli, cauliflower, kale).

Kidney stones are painful and common complications in inflammatory bowel disease (IBD), particularly in patients who have had intestinal surgery. IBD patients are at risk for the most common types of kidney stones -- those composed of either calcium oxalate or uric acid crystals. The following are some considerations in reducing the risk for stones:

The most important dietary recommendation is to increase fluid and restrict sodium intake.
Limiting protein is recommended for reducing kidney stones. However, people with IBD who have frequent diarrhea are protein deficient. Having enough protein in the diet, particularly in children with IBD, is very important. Patients should weigh the importance of protien against any risk for kidney stones.
Patients should eat more potassium-rich foods (bananas, watermelon, cantaloupe, oranges, tomatoes, beans).
Patients should try to correct any dietary habits that cause acidic or alkaline imbalances in the urine that promote stone formation.
Many kidney stones are formed from calcium-oxalate stones. Patients should avoid or limit intake of oxalate-rich foods, such as beets, beet tops, black tea, chenopodium, chocolate, cocoa, dried figs, ground pepper, lamb quarters, lime peel, nuts, parsley, poppy seeds, purslane, rhubarb, sorrel, spinach, and Swiss chard. A high calcium diet does not appear to increase the risk for kidney stones as long as it also contains plenty of fluids, dietary potassium, and phosphate. Importantly, calcium is associated with protection against colon cancer and osteoporosis -- two conditions that are associated with IBD.
Patients who have stones associated with short-bowel syndrome should eat less fat and foods that contain oxalates. In these people, calcium may bind to unabsorbed fat instead of to oxalates, which increase oxalate levels.

The general recommendations for avoiding kidney stones need to be tailored to the dietary requirements of IBD. Patients should work with their doctors to develop a plan.

Researchers are currently investigating bacteria (called probiotics) and specific foods (called prebiotics) that are metabolized by these bacteria, and the compounds they produce (called synbiotics). Some evidence suggests that alone or in combination, they may have significant benefits in the intestine.

Probiotics are bacterial strains that by themselves may provide a barrier against harmful bacteria, possibly through various mechanisms such as excreting certain acids (lactate, acetate) that inhibit harmful bacteria or compete with them for nutrients. It has been suggested that probiotics may help maintain remission in patients with inflammatory bowel disease (IBD). The specific bacterial strains that might be beneficial, however, are not fully known. The most well-known probiotics are the lactobacilli strains, such as acidophilus, which are found in yogurt and other fermented milk products. Others, however, may prove to be more important, such as bifidobacteria and GG lactobacilli. Other probiotics that may be beneficial for patients with IBD include lactobacilli rhamnosus, casel, plantarium, bulgaricus, and salivarius, and also Enterococcus faecium and Streptococcus thermophilus.
Prebiotics are specific non-digestible molecules called fructo-oligosaccharides, which stimulate the growth of probiotics. These molecules are found in many foods, including Jerusalem artichokes, onions, salsify, bananas, honey, garlic, and leeks. (However, some of these foods can irritate the intestine in patients with IBD.)

Researchers are investigating probiotics, prebiotics, or both for intestinal protection, including benefits for patients with IBD. Foods and supplements containing these substances are available in the U.S. and are heavily marketed in Europe, Japan, and Australia. To date, however, no studies have determined any clear benefits of any specific organism or formulation.

Crohn's disease and surgical procedures that remove parts of the small intestine can inhibit absorption of vitamins, fats, and other important supplements. Taking certain supplements -- such as fish oil, antioxidants, and mineral supplements -- may be beneficial for patients with Crohn's disease.

Vitamins. Deficiencies of vitamins A, C, D, E, B12, and folate (a B vitamin) may result from malabsorption. In general, vitamin supplements may be recommended for everyone with inflammatory bowel disease (IBD), particularly for children to avoid growth retardation. Vitamins A, C, and E are antioxidants, which are scavengers of damaging particles in the body. Folic acid supplements are particularly important for patients who must restrict fresh fruits and vegetables and for those taking sulfasalazine. Folate deficiencies may contribute to the increased risk for colon cancer. Monthly injections of vitamin B-12 may be necessary. Vitamin D is necessary for bone protection. Because some vitamins, such as A and D, can be toxic at high doses, patients should discuss specific dosages with their doctors.

Omega-3 Fatty Acids. The role of fats in inflammatory bowel disease is complex and not fully known. Some evidence suggests that patients with Crohn's burn fat calories at a higher rate than the general population. Patients with IBD may be deficient in essential fatty acids, particularly omega-3 fatty acids (polyunsaturated fats found in oily fish and certain vegetable products such as flaxseed and canola oils). Such fatty acids are also available in supplements as docosahexaenoic (DHA) and eicosapentaneoic (EPA) acids, which are specific compounds found in fish oil.

Omega-3 fatty acids, found plentifully in oily fish and flaxseed and canola oils, are beneficial to people afflicted with inflammatory bowel disease.

Mineral Supplements. Supplements of calcium, magnesium, zinc, selenium, and iron may be needed to offset deficiencies in patients with severe IBD.

Calcium and magnesium are critical for health and strong bones. Many patients with IBD suffer from calcium and vitamin D deficiencies, which cause low bone density. Studies indicate that calcium and vitamin D supplements may be adequate to increase bone density without drugs.
Selenium is a potent antioxidant.
Zinc is important for wound healing, and deficiencies may promote fistulas in Crohn's disease.
Iron supplements may be required for anemia. However, iron overdose is very dangerous. As few as three adult iron tablets can poison children, even fatally. No one, even adults, should take a double dose of iron if one is missed. A doctor should advise patients on correct dosage.

Enteral Nutrition. Enteral nutrition uses a feeding tube that is inserted either through the nose and down through the throat or directly through the abdominal wall into the gastrointestinal tract. It is the preferred method for feeding patients with malnutrition who cannot tolerate eating by mouth. The nutritional formulas used in enteral administration include:

Polymeric diets (containing a balance of standard nutrients).
Elemental diets (predigested nutrients that are absorbed in the first meter of the small intestine). These diets are used less commonly than polymeric diets.

In children, enteral nutrition is given for 6 - 8 weeks. Simple foods are then introduced (chicken, potato, rice), and more complex foods (milk, fiber, wheat-based foods) are then added gradually. However, relapse is still common.

Total Parenteral Nutrition. Total parenteral nutrition (TPN), or hyperalimentation, is the intravenous administration of nutrients through an indwelling catheter (tube). It is used for very severe IBD when patients cannot tolerate any nutrition by mouth or with a feeding tube, and may even be useful as a primary therapy for patients with Crohn's (although not for those with fistulas). It is usually given in the hospital, although increasingly people are giving it to themselves at home. The procedure carries a risk for complications, some serious, including infection, blood clots, and liver failure.

Symptom Management

The following are some ways of managing diarrhea, constipation, or both:

Mild-to-moderate diarrhea may be reduced by taking 1 teaspoon of psyllium hydrophilic colloid (Metamucil) twice a day in a glass of water.
Antidiarrheal drugs include loperamide (Imodium) and a combination of atropine and diphenoxylate (Lomotil). In very ill patients, large doses of some antidiarrheal drugs, such as Lomotil, can trigger the onset of toxic megacolon. Toxic megacolon is a life-threatening complication of other intestinal conditions. It is characterized by a very inflated colon, abdominal distention, and sometimes fever, abdominal pain, or shock.
Opiates or drugs used to relax muscle spasms may help relieve mild-to-moderate diarrhea and abdominal cramps, but they should be used for very short periods and not for severe cases.
Cholestyramine (Questran) has been found to be useful for reducing diarrhea in patients who have had ileal resections.
Bulk-type laxatives can help constipation.

Iron supplements may be required for anemia. Intravenous iron with or without erythropoietin (a hormone that acts in the bone marrow to increase the production of red blood cells) is effective for severe anemia in IBD that does not respond to iron alone. Patients with Crohn's disease benefit most from the combination.

Antidepressants may help relieve emotional problems. However, inflammatory bowel disease is not a psychological disorder, and these drugs will not affect the basic illness.

Acetaminophen (Tylenol) and nonsteroidal anti-inflammatory drugs (NSAIDs) are used for relieving mild pain. NSAIDs include aspirin, ibuprofen (Advil, Motrin), naproxen (Aleve), and celecoxib (Celebrex), the only COX-2 inhibitor left on the market. NSAIDs have been thought to cause symptom flare-ups in patients with inflammatory bowel disease (IBD). However, a comprehensive 2006 study concluded that these drugs are as safe for patients with IBD as for other people, and that they can help prevent relapse as well as provide short-term pain relief. Still, long-term use of NSAIDs can cause stomach bleeding and, with the exception of aspirin, may increase the risks for heart attack and stroke. Acetaminophen can cause liver damage if taken in high doses or combined with alcoholic drinks. Discuss with your doctor whether acetaminophen, NSAIDs, or other pain relievers are appropriate for you.

Although stress is not a cause of inflammatory bowel disease, there are reports of an association between stress and symptom flare-ups. Although no evidence exists to confirm that stress reduction techniques such as relaxation methods, meditation, or cognitive therapy, manage the disease, they might be helpful.

The effects of exercise in Crohn's disease are uncertain. Some research indicates that moderate exercise may trigger excess production of chemicals that could cause flare-up. One small study, however, reported significant improvement in patients who had been sedentary but then embarked on a 12-week exercise program. They walked a little over 2 miles three times a week. During that period there were no flare-ups, and they felt physically and emotionally better than before.

Medications

The primary goal of drug therapy is to reduce inflammation in the intestine. Drugs are effective in reducing the inflammation and accompanying symptoms in up to 80% of patients. Unfortunately, relapses are still frequent, and researchers continue to look for the optimal treatments that will both control symptoms and prevent relapse.

Drugs Used for Crohn's Disease. Drug therapies for Crohn’s disease aim to resolve symptoms (induce remission) and prevent flare-ups (maintain remission). The drugs used depend on the severity of the condition:

Mild-to-moderate Crohn's disease is generally treated with antibiotics and an oral aminosalicylate, such as mesalamine or sulfasalazine. (Some researchers suggest, however, that corticosteroids may be more effective than these drugs in patients with disease in the small intestine and ascending colon. Furthermore, new forms of oral corticosteroids, such as budesonide, may have a lower risk for adverse effects.)

Moderate-to-severe Crohn's disease is treated with corticosteroids, immunosuppressants, or biologic drugs such as infliximab or adalimumab. These drugs may be used alone or in combinations. Some patients with severe Crohn's may be candidates for surgery.

Determining Success. Therapy is considered successful if it can push the disease into remission (and keep it there) without causing significant side effects. The patient's condition is generally considered in remission when the intestinal lining has healed, and symptoms, such as diarrhea, abdominal cramps, and tenesmus (painful defecation), are normal or close to normal. It is sometimes difficult to define remission in Crohn's disease because diagnostic test results do not always correlate with a patient's symptoms or complications outside the intestine.

Aminosalicylates contain the compound 5-aminosalicylic acid, or 5-ASA, which helps reduce inflammation. These drugs are used to prevent relapses and maintain remission in mild-to-moderate Crohn’s disease.

The standard aminosalicylate drug is sulfazine (Azulfidine). This drug combines the 5-ASA drug mesalamine with sulfapyridine, a sulfa antibiotic. While sulfazine is cheap and effective, the sulfa component of the drug can cause unpleasant side effects, including headache, nausea, and rash.

Patients who cannot tolerate sulfazine, or who are allergic to sulfa drugs, have other options for aminosalicylate drugs, including mesalamine (Asacol, Pentasa), olsalazine (Dipentum), and balsalazide (Colazal). These drugs, like sulfazine, are available as pills. Mesalamine is also available in enema (Rowasa) and suppository (Canasa) forms.

Mesalamine can cause kidney problems and should be used with caution by patients with kidney disease. Common side effects of aminosalicylate drugs include:

Abdominal pain and cramps (mesalamine, balsalazide)
Diarrhea (mesalamine, olsalazine)· Gas (mesalamine)
Nausea (mesalamine)
Hair loss (mesalamine)
Headache (mesalamine, balsalazide)
Dizziness (mesalamine)

All mesalamine preparations, including sulfasalazine, appear to be safe for children, and for women who are pregnant or nursing.

General Guidelines. Corticosteroids (commonly called steroids) are powerful anti-inflammatory drugs used for treating Crohn's disease in adults. Because of their severe side effects, steroids should be reserved for those with moderate-to-severe disease or those who relapse after other therapies. Steroids appear to be safe for pregnant women and can be used if necessary during pregnancy.

Corticosteroids are frequently combined with other drugs, such as 5-aminosalicylic acid (or 5-ASA) drugs, to produce more rapid symptom relief and to allow quicker withdrawal, although such combinations do not improve remission time.

In general, corticosteroids are recommended only for short-term use for achieving remission in active Crohn's disease. The lowest possible dose should be used for the shortest amount of time. Long-term treatments cause significant side effects, and alternative drugs exist. Corticosteroids do not prevent flare-ups and are rarely used for maintenance treatment.

Patients who are malnourished are less likely to respond to steroids, and those who had an initial inadequate response to steroids are also less likely to do well with repeat therapy. Some patients who have had Crohn's disease for a long time may have partial or complete resistance to corticosteroids.

Corticosteroid Types. Prednisone (Deltasone), methylprednisolone (Medrol), and hydrocortisone (Cortef, Cortisol) are the most common corticosteroids. Newer steroids, such as budesonide (Entocort), affect only local areas in the intestine and do not circulate throughout the body. Such drugs may avoid the widespread side effects that are a serious problem with long-term treatment using older conventional steroids. Recent studies suggest that budesonide can help prolong and maintain remission periods in patients with Crohn’s disease.

Administering Corticosteroids. Most corticosteroids can be taken as a pill. For patients who cannot take oral forms, methylprednisolone and hydrocortisone may also be given intravenously or rectally as a suppository, enema, or foam. The severity or location of the condition often determines the form.

Side Effects of Corticosteroids. Standard steroids can have distressing and sometimes serious long-term side effects, including:

Susceptibility to infection
Weight gain (particularly increased fatty tissue on the face and upper trunk and back)
Acne
Excess hair growth
High blood pressure (hypertension)
Weakened bones (osteoporosis)
Cataracts and glaucoma
Diabetes
Muscle wasting
Menstrual irregularities
Upper gastrointestinal ulcers
Personality change, including irritability, insomnia, psychosis, and depression; such emotional changes are sometimes severe enough to produce suicidal thoughts

Withdrawing from Corticosteroids. Once the intestinal inflammation has subsided, steroids must be withdrawn very gradually in order to give the body time to recover its own ability to produce natural steroids. Withdrawal symptoms, including fever, malaise, and joint pain, may occur if the dosage is lowered too rapidly. If this happens, the dosage is increased slightly and maintained until symptoms are gone. More gradual withdrawal is then resumed.

For very active inflammatory bowel disease that does not respond to standard treatments, immunosuppressant drugs are used for long-term therapy. Such drugs suppress or limit actions of the immune system and therefore its inflammatory response, which causes Crohn's disease. Immunosuppressants may help maintain remission in Crohn's disease and heal fistulas and intestinal ulcers caused by this disease. These drugs are sometimes combined with a corticosteroid drug for treating active disease flares.

Azathioprine (Imuran, Azasan) and 6-mercaptopurine (6-MP, Purinethol) are the standard oral immunosuppressant drugs. However, it can take 3 - 6 months for these drugs to have an effect. To speed up the response, they are sometimes prescribed along with a corticosteroid drug. Lower steroid doses are then needed, resulting in fewer side effects. Corticosteroids may also be withdrawn more quickly. For this reason, immunosuppressants are sometimes referred to as steroid-sparing drugs.

Other pill forms of immunosuppressants include cyclosporine A (Sandimmune, Neoral) and tracrolimus (Prograf). These drugs are quicker-acting than azathiopine and 6-mercaptopurine. Cyclosporine A generally takes 1 - 2 weeks to take effect. For patients who have Crohn’s disease accompanied by fistulas, Cyclosporine A may be given intravenously. For patients whose condition affects the mouth or area around the anus, tracrolimus is available as a topical ointment.

Methotrexate (MTX, Rheumatrex, Mexate) is another fast-acting type of immunosuppressant. It is given by weekly injections and may be an option for patients with severe Crohn’s disease who have not been helped by other immunosuppressant drugs. However, methotrexate can cause miscarriages and birth defects. Because of these pregnancy complications, both men and women who take methotrexate should use birth control.

General side effects of immunosuppressants may include nausea, vomiting, and liver or pancreatic inflammation. Patients should receive frequent blood tests to monitor bone marrow, liver, and kidneys. Patients who take cyclosporine A or tacrolimus need to have their blood pressure and kidney function checked regularly.

Antibiotics are often used to induce remission in mild-to-moderate Crohn's disease. They are also important for treating fistulas, bacterial overgrowth, abdominal abscesses, and any infections around the anus and genital areas. Stopping antibiotics brings on relapse, so long-term therapy is required, carrying a risk for side effects.

The standard antibiotics used for inducing remission in Crohn's disease are ciprofloxacin (Cipro) and metronidazole (Flagyl). Ciprofloxacin is the antibiotic of choice. Over time, metronidazole can cause peripheral neuropathy, a nerve disorder that can cause numbness and tingling in the hands and feet. Other side effects associated with netronidazole include nausea, vomiting, diarrhea, loss of appetite, dizziness, and headaches.

Although ciprofloxacin causes fewer side effects than metrondizaole, it can interact with antacids (Rolaids, Tums) and vitamin and mineral supplements that contain calcium, iron, or zinc. Do not take antacids or vitamin supplements at the same time as the ciprofloxacin dose.

Biologic response modifiers are genetically engineered drugs that target specific proteins involved with the body’s inflammatory response. Of special interest for patients with Crohn's disease are drugs such as infliximab and adalimumab, which target the inflammatory immune factor known as tumor necrosis factor (TNF).

According to a 2007 consensus statement from the American Gastroenterological Association, biologic drugs are generally not used as first-line treatment for most patients with Crohn’s disease. However, some patients -- especially those who have not responded to corticosteroids or who suffer from fistulas -- may benefit from initial treatment with infliximab or other biologic drugs. In all cases, the benefits of biologic drugs need to be weighed against their potential risks, which can include increased risk for infections, lymphoma, and drug-related side effects.

Infliximab (Remicade) acts against TNF and was the first biologic drug approved for treating adults with Crohn's disease. It is made from a genetically designed antibody called a monoclonal antibody (MAb) that blocks the activity of tumor necrosis factor-alpha (TNF-a). In 2006, the FDA approved infliximab for children with active Crohn’s disease.

Infliximab cannot cure Crohn’s disease, but it can help control symptoms and, possibly, keep the disease in remission. Studies suggest that up to 80% of patients respond initially, and about a third of all patients remain in remission after a single infusion. Remissions last a few weeks to several months. A 6-week course of infliximab helps close and heal fistulas in half of patients and reduces drainage in 70%. The drug is also being studied for maintenance therapy, although given some significant side effects, it will most likely be reserved for active disease that does not respond to other treatments.

Infliximab’s severe side effects may include tuberculosis, pneumonia, and other infections; lymphoma (a type of cancer); liver failure; and aplastic anemia.

Adalimumab (Humira) was approved early in 2007 for treating adult patients with moderate-to-severe Crohn's disease. Like infliximab, adalimumab blocks TNF. Also approved for treating symptoms of rheumatoid arthritis, adalimumab requires injections to initiate treatment, followed by a maintenance shot every other week.

Adalimumab's label includes a boxed warning. The medicine has been associated with serious, sometimes fatal, infections, including tuberculosis and sepsis. Other severe side effects may include lymphoma, upper respiratory infections, sinusitis, and nausea.

Several other TNF modifiers are being investigated. Among the most promising, according to several 2007 studies in the New England Journal of Medicine, is certolizumab (Cimzia).

Selective adhesion molecule inhibitors block the genetic expression of cell adhesion molecules (CAMs). CAMs play an important role in the accumulation of immune factors that cause the inflammatory response. Natalizumab (Tysabri) is a monoclonal antibody that blocks alpha4 integrin, a protein that binds to CAMs. This drug is approved to treat multiple sclerosis and is also being studied for Crohn’s disease. Studies have suggested that natalizumab can help patients with Crohn’s disease achieve and maintain remission.

However, natalizumab is associated with severe side effects, including a rare neurological condition called progressive multifocal leukoencephalopathy (PML). A 2006 study found that patients who take natalizumab have a very low risk for PML. Still, the potential benefits of natalizumab need to be weighed against its risks for serious side effects. As of summer 2007, the FDA was considering approving natalizumab for treatment of moderate-to-severe Crohn’s disease in patients who have failed or cannot tolerate other therapies

Other Biologic Therapies. Investigators are researching other biologic therapies that target other types of immune factors that play a role in the inflammatory response. These factors include interferons, anti-interferon antibodies, anti-interleukin antibodies, p65 anti-sense oligonucleotides, growth factors, and others. Several 2006 studies indicated that fontolizumab (HuZaf), an anti-interferon gamma monoclonal antibody, shows promise as a treatment for Crohn’s disease. Sargramostim (Leukine), a granulocyte-macrophage colony stimulating factor, is another biologic drug that may help improve symptoms and quality of life for patients with active Crohn’s disease. Visilizumab (Nuvion), which targets the CD3 receptor on T cells, is another biologic drug being investigated. More research in each of these areas is needed.

Parasites. Inflammatory bowel disease is rare in countries where intestinal infection with parasites called helminthes is common. Small studies have reported significant remission rates in patients with Crohn's disease or ulcerative colitis who have swallowed the eggs of a specific parasitic worm. The parasite does not invade tissue or spread other diseases. The parasite induces production of specific T cells, called TH-2, which are immune factors that may be protective against overactivity of cytokines that trigger Crohn's. More research is needed.

Growth Factors. Growth factor hormones increase immune factors, so one would think they might be harmful for patients with Crohn's disease. However, some research suggests that growth factors may be helpful for speeding healing in certain patients, including children. More research, however, is needed.

Surgery

Between two-thirds to three-quarters of patients with Crohn's eventually need surgery when medication cannot control symptoms. Among children with Crohn's, half require surgery within 5 years of diagnosis.

In general, surgery is used to remove damaged areas of the colon:

The entire colon (proctocolectomy) or a section of it (subtotal colectomy) may need to be removed in cases of extensive disease in the large intestine.
Resection or strictureplasty, which removes limited sections of the colon, may be appropriate for many patients.

Surgery is useful only for reducing symptoms. It cannot cure Crohn's disease because new disease can appear in other areas of the intestine. Surgery may be helpful for relieving symptoms and to correct blockage, perforation, fistulas, or bleeding.

Surgery has reportedly improved the quality of life in most patients, except for those who continued to have active disease. Many children with Crohn's who have suffered growth problems catch up to near-normal growth levels after surgery. Some experts urge, in fact, that many patients should consider surgery in the early stages of the disease.

Some patients may be candidates for a procedure called strictureplasty, which involves cutting and stitching only the areas obstructing the intestine, so that it widens the intestine without removing sections of it. It involves the following:

A balloon attached to a catheter (a thin tube) is passed along the intestine.
If it becomes blocked, then a stricture (an obstruction) is indicated.
The surgeon widens the intestine at the point, but does not remove sections of it.
The procedure is by no means foolproof. Nearly half of patients require re-operation, but strictureplasty in the jejunum and ileum of the small intestine is safe and generally effective over the long term. It may not be useful for Crohn's disease in duodenum (the first section of the small intestine).

The invasiveness of the surgical procedure to remove damaged portions of the colon depends on the severity of the disease.

Resection of the Colon. In most cases of Crohn's disease, only a part of the colon needs to be removed, a procedure called resection.

Click the icon to see an illustrated series depicting large bowel resection surgery.

Subtotal Colectomy. Subtotal colectomy is more extensive than resection and removes more of the colon. Disease in the upper parts of the small intestine tends to require more extensive surgery than in the lower small intestine.

In general, either procedure requires a general anesthetic and involves the following:

An incision is made in the abdomen.
The diseased portion of the colon is identified and removed. (Strictureplasty is sometimes used alone with resection.)
Once a diseased segment of the colon is removed, the two ends are reconnected, and this connection is called an anastomosis.

Open Surgery or Laparoscopy. Resection or subtotal colectomy may be performed using one of two surgical approaches:

Open surgery, which requires a wide abdominal incision.
Laparoscopy, which uses a few small incisions through which a tube is inserted containing a tiny camera for viewing the area. To date, however, this procedure is best suited for patients with short-segment disease in the ileum who also have no other complications, such as fistulas and abscesses.

Click the icon to see an image of a laparoscopy procedure.

Short-bowel syndrome. If large segments of the small intestine are removed, the patient is at higher risk for short-bowel syndrome, a complication in which there is a problem absorbing nutrients. The risk is far lower with strictureplasty. The condition used to be fatal, but patients now can live normal and productive lives using total parenteral nutrition (the intravenous administration of nutrients), which can be self-administered at home in many cases.
Leakage or obstruction in the areas where the colon has been reconnected (the anastomosis).
Infections. In a 2003 study, the use of drugs that modify the immune system (azathioprine, 6-MP, methotrexate, and infliximab) was effective in reducing the risk for serious infection in the abdomen.

Proctocolectomy with ileostomy is removal of the entire colon and creation of an ileostomy. It involves the following:

To perform proctocolectomy, the surgeon removes the entire colon, including the lower part of the rectum and the sphincter muscles that control bowel movements.
To perform ileostomy, the surgeon makes a small opening in the lower right corner of the abdomen called a stoma. The surgeon then connects cut ends of the small intestine to this opening. A bag is placed over the opening and accumulates waste matter. It requires emptying several times a day.

Recurrence of Crohn's disease is very common after any procedure. The risk may be 7 - 25% for each year after resection, with an average risk of 50% at 5 years after resection. (Even if the entire colon is removed, there is still a high chance of recurrence in the rectum and a somewhat lower risk for recurrence in the small intestine.)

Patients at highest risk for recurrence include:

Smokers
Those whose disease occurred in the ileum (the lowest part of the small intestine) and colon
Those with abscesses or fistulas
Those have had previous surgeries

Various drugs are used to prevent recurrence. They include the antibiotic metronidazole (Flagyl), mesalamine, infliximab, and mercaptopurine. These drugs can have severe side effects. And, it is not clear if these or any other drugs are effective in preventing recurrence. Even if medications can help prevent recurrence in some patients, it is not yet known how to identify this subset of patients. (In any case, steroids do not appear to help prevent recurrence.)

In some cases, surgery is needed for emergency conditions that can occur with Crohn's disease. Emergency surgery is used to:

Stop severe intestinal bleeding
Clear small bowel obstruction
Drain and heal abscesses or fistulas
Repair perforation

Procedures for transplanting the small intestine in patients with intestinal failure are under investigation. These are still experimental and are being tested in patients who have lost so much of their small intestine that they must rely on total parenteral nutrition (intravenous administration of nutrition). Small-bowel transplantation is a more difficult procedure than some other transplants, because of the high rate of potential complications, including infection and organ rejection. Patients who have transplants must take immunosuppressant drugs for the rest of their lives. Furthermore, there is some evidence that Crohn's disease recurs in the transplanted bowel.

Resources

www.ccfa.org -- Crohn's & Colitis Foundation of America
www.gastro.org -- American Gastroenterological Association
www.acg.gi.org -- American College of Gastroenterology
www2.niddk.nih.gov -- National Digestive Diseases Information Clearinghouse

References

Baldassano RN, Bradfield JP, Monos DS, Kim CE, Glessner JT, Casalunovo T, et al. Association of the T300A non-synonymous variant of the ATG16L1 gene with susceptibility to paediatric Crohn's disease. Gut. 2007 Aug;56(:1171-1173.

Baldassano RN, Bradfield JP, Monos DS, Kim CE, Glessner JT, Casalunovo T, et al. Association of variants of the interleukin-23 receptor gene with susceptibility to pediatric Crohn's disease. Clin Gastroenterol Hepatol. 2007 Jul 5; [Epub ahead of print]

Clark M, Colombel JF, Feagan BC, Fedorak RN, Hanauer SB, Kamm MA, et al. American gastroenterological association consensus development conference on the use of biologics in the treatment of inflammatory bowel disease, June 21-23,2006. Gastroenterology. 2007 Jul;133(1):312-39.

Cornish J, Tan E, Teare J, Teoh TG, Rai R, Clark SK, et al. A meta-analysis on the influence of inflammatory bowel disease on pregnancy. Gut. 2007 Jun;56(6):830-7. Epub 2006 Dec 21.

Cummings JR, Cooney R, Pathan S, Anderson CA, Barrett JC, Beckly J, et al. Confirmation of the role of ATG16l1 as a Crohn's disease susceptibility gene. Inflamm Bowel Dis. 2007 Aug;13(:941-6.

Dotan I, Fishman S, Dgani Y, Schwartz M, Karban A, Lerner A, et al. Antibodies against laminaribioside and chitobioside are novel serologic markers in Crohn's disease. Gastroenterology. 2006 Aug;131(2):366-78.

Dubinsky MC, Wang D, Picornell Y, Wrobel I, Katzir L, Quiros A, et al. IL-23 receptor (IL-23R) gene protects against pediatric Crohn's disease. Inflamm Bowel Dis. 2007 May;13(5):511-5.

Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, et al. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science. 2006 Dec 1;314(5804):1461-3. Epub 2006 Oct 26.

Issa M, Vijayapal A, Graham MB, Beaulieu DB, Otterson MF, Lundeen S, et al. Impact of Clostridium difficile on inflammatory bowel disease. Clin Gastroenterol Hepatol. 2007 Mar;5(3):345-51.

Rioux JD, Xavier RJ, Taylor KD, Silverberg MS, Goyette P, Huett A, et al. Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis. Nat Genet. 2007 May;39(5):596-604. Epub 2007 Apr 15.

Rodemann JF, Dubberke ER, Reske KA, Seo da H, Stone CD. Incidence of Clostridium difficile infection in inflammatory bowel disease. Clin Gastroenterol Hepatol. 2007 Mar;5(3):339-44.

Sandborn WJ, Feagan BG, Stoinov S, Honiball PJ, Rutgeerts P, Mason D, et al. Certolizumab pegol for the treatment of Crohn's disease. N Engl J Med. 2007 Jul 19;357(3):228-238.

Schreiber S, Khaliq-Kareemi M, Lawrance IC, Thomsen OO, Hanauer SB, McColm J, et al. Maintenance therapy with certolizumab pegol for Crohn's disease. N Engl J Med. 2007 Jul 19;357(3):239-250.

Tremaine WJ. Inflammatory bowel disease and Clostridium difficile-associated diarrhea: a growing problem. Clin Gastroenterol Hepatol. 2007 Mar;5(3):310-1.

Tremelling M, Cummings F, Fisher SA, Mansfield J, Gwilliam R, Keniry A, et al. IL23R variation determines susceptibility but not disease phenotype in inflammatory bowel disease. Gastroenterology. 2007 May;132(5):1657-64. Epub 2007 Feb 24.

Review Date:
8/30/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Foot pain

FitSugar — Wed, 08 Oct 2008 17:35:02 -0700

In This Report

Highlights
Introduction
Causes
Risk Factors
Treatment: Corns and Callus...
Treatment: Bunions
Treatment: Hammertoes
Treatment: Ingrown Toenails...
Treatment: Forefoot Pain...
Treatment: Heel Pain
Treatment: Flat Feet
Treatment: Abnormally High ...
Treatment: Tarsal Tunnel Sy...
Treatment: Foot Injury
Prevention
Shoes
Insoles and Orthotics
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Treatment for Ingrown Toenail:

Orthonyxia, a surgical technique that implants a small metal brace into the top of the nail, was as effective as traditional surgical techniques for preventing ingrown toenail from recurring, according to one study.
A nonsurgical method for treating ingrown toenail with chemicals uses either sodium hydroxide or phenol, but one study shows that sodium hydroxide procedures have a better outcome and faster recovery than phenol procedures.

Treatment for Forefoot Pain:

Ultrasound-guided injection of alcohol might provide relief from Morton's neuroma, according to one study. Symptoms improved in 94% of patients who had the treatment, a success rate comparable to that of surgery.

Treatment for Heel Pain:

NSAIDs reduce pain and disability in people with plantar fasciitis when used with other techniques, such as night splints and stretching.
Studies show that extracorporeal shockwave therapy provides a very small reduction in heel pain without side effects. It may be a good option for patients who haven't responded well to conservative treatment.

Work-related Foot Problems:

An estimated 120,000 job-related foot injuries occur every year, about a third of them involving the toes. A number of foot problems -- including arthritis of the foot and ankle, toe deformities, pinched nerves between the toes, plantar fasciitis, adult-acquired flat foot, and tarsal tunnel syndrome -- have been attributed to repetitive use at work.

Introduction

Foot pain is very common. About 75% of people in the United States have foot pain at some time in their lives. Most foot pain is caused by shoes that do not fit properly or that force the feet into unnatural shapes (such as pointed-toe, high-heeled shoes).

The foot is a complex structure of 26 bones and 33 joints, layered with an intertwining web of more than 120 muscles, ligaments, and nerves. It serves the following functions:

Supports weight
Acts as a shock absorber
Serves as a lever to propel the leg forward
Helps maintain balance by adjusting the body to uneven surfaces

Because the feet are very small compared with the rest of the body, the impact of each step exerts tremendous force upon them. This force is about 50% greater than the person's body weight. During a typical day, people spend about 4 hours on their feet and take 8,000 - 10,000 steps. This means that the feet support a combined force equivalent to several hundred tons every day.

Foot pain generally starts in one of three places: the toes, the forefoot, and the hindfoot.

The Toes. Toe problems most often occur because of the pressure imposed by ill-fitting shoes.

The Forefoot. The forefoot is the front of the foot. Pain originating here usually involves one of the following bone groups:

The metatarsal bones (five long bones that extend from the front of the arch to the bones in the toe)
The sesamoid bones (two small bones embedded at the top of the first metatarsal bone, which connects to the big toe)

The Hindfoot. The hindfoot is the back of the foot. Pain originating here can extend from the heel, across the sole (known as the plantar surface), to the ball of the foot (the metatarsophalangeal joint).

Condition	Location	Symptoms	Recommended Footwear
Toe Pain
Corns and calluses	Around toes, usually little toe, bottom of feet or areas exposed to friction.	Hard, dead, yellowish skin.	Wide (box-toed) shoes; soft cushions under heel or ball of foot, or customized or gel insoles for calluses. Doughnut-shaped pads for corns.
Ingrown toenails	Toenails.	Nail curling into skin causes pain, swelling, and, in extreme cases, infection.	Sandals, open-toed shoes.
Bunions and bunionettes (tailor's bunion)	Big toe (bunions) or little toe (bunionettes).	The following can occur alone or in combination: Metatarsus primus varus. The first (big toe) metatarsal bone shifts away from the second, and the big toe points inward. Medial exostosis. This is a bony bump at the base of the big toe, which protrudes outward. Area next to bony bump is red, tender, and occasionally filled with fluid. Toe joint may be inflamed. Hallux valgus. This is a deformity in which the bone and joint of the big toe shift and grow inward, so that the second toe crosses over the big toe.	Soft, wide-toed shoes or sandals. Bunion shields or splints. Thick doughnut-shaped moleskin pads, custom-made orthotics or foot slings, if necessary. Avoid shoes with stitching along the side of the "bump."
Morton's neuroma (also called interdigital neuroma)	Inflammation of the nerve, usually between the third and fourth toes and bottom of the foot near these toes.	Cramping and burning pain, or electric-shock sensation. The condition may produce a thick protective sheath around the nerve that feels like a ball. This may be detected by pressing top to bottom on the top of the foot using one hand and moving the other hand from side to side. Morton's neuroma is aggravated by prolonged standing and relieved by removal of the shoes and forefoot massage.	Wide (box-toed) shoes. Orthotic or insole with pad that reduces stress on the painful area.
Hammertoe or claw toe	Usually second toe, but may develop in any or all of the three middle toes.	Toes form hammer or claw shape. In hammertoe, the first knuckle of the toe is mainly affected. In claw toe the entire toe is deformed. No pain at first, but pain increases as tendon becomes tighter and toes stiffen.	Wide (box-toed) shoes. Toe pads or specially designed shields, splints, caps, or slings. (Splints or slings are not for people with diabetes.)
Front-of-the-Foot Pain
Metatarsalgia	Ball of the foot.	Acute, recurrent, or chronic pain without a known cause.	Wide (box-toed) shoes. Orthotic with pad that reduces metatarsal pressure. Gel cushions. Metatarsal bandage.
Stress fracture	Most often in the area beneath the second or third toe.	Sudden pain (which persists) when injury occurs.	Low-heeled shoes with stiff soles.
Sesamoiditis	Ball of foot beneath big toe.	Pain and swelling.	Low-heeled shoe with stiff sole and soft padding inside.
Heel and Back-of-the-Foot Pain
Plantar fasciitis or heel spurs	Back of the arch right in front of heel.	At onset, some people report a tearing or popping sound. Pain is most severe with first steps after getting out of bed. Pain decreases after stretching, returns after inactivity.	Over-the-counter foot insole (cut quarter-size hole surrounding painful area). Possible night splints. Orthotics if necessary.
Bursitis of the heel	Center of the heel.	Pain, with warmth and swelling. Increases during the day.	Heel cup.
Haglund's deformity (pump bump)	Fleshy area on the back of the heel.	Tender swelling aggravated by shoes with stiff backs.	Soft shoes. Heel pads. Possible orthotic to support heel.
Achilles tendinitis	Achilles tendon: area along the back between calf muscles and heel.	Pain worsens during physical activities (particularly running), after which the tendon usually swells and stiffens. If it ruptures, popping sound may occur followed by acute pain similar to a blow at the back of the leg.	Insoles, tendon strap, heel cups.
Arch and Bottom-of-the Foot Pain
Tarsal tunnel syndrome	Anywhere along the bottom of the foot.	Numbness, tingling, or burning sensations, pain, most commonly felt at night.	Specially designed orthotics to relieve pressure.
Flat feet or posterior tibial tendon dysfunction (PTTD)	The arch.	No arch. Often no pain or discomfort. Three stages in PTTD: Pain and weakness in the tendon. The arch flattens but is still flexible. The foot becomes rigid and possibly painful at the ankle. Sometimes people report fatigue, pain, or stiffness in the feet, legs, and lower back.	For children, possible custom-made insoles.
High arches (hollow feet)	The arch.	High arches. Lower back pain, possible tendency to lower limb injuries.

Causes

Nearly all causes of foot pain can be grouped under one of the following:

Ill-fitting shoes. Poorly fitting shoes are a frequent cause of foot pain. High-heeled shoes concentrate pressure on the toes and can aggravate, if not cause, problems with the toes.
Certain medical conditions. Any medical condition that causes a disturbance in the way a person walks can contribute to foot pain. This may include diseases or conditions that lead to pain or numbness in the feet (such as diabetes), leg and foot deformities, spinal problems, and neurological disorders such as Parkinson's disease or cerebral palsy.
High-impact exercise. High-impact exercising, such as jogging or strenuous aerobics, can injure the feet. Common injuries include corns, calluses, blisters, muscle cramps, acute knee and ankle injuries, plantar fasciitis, and metatarsalgia.

Arthritic Conditions. Arthritic conditions, particularly osteoarthritis and gout, can cause foot pain. Although rheumatoid arthritis almost always develops in the hand, the ball of the foot can also be affected.

Diabetes. Diabetes is an important cause of serious foot disorders. [For more information, see In-Depth Report #9: Diabetes - type 1 and In-Depth Report #60: Diabetes - type 2.]

Obesity. Obesity can cause foot and ankle pain.

Pregnancy. Pregnancy can cause fluid buildup and swollen feet. The increased weight and imbalance of pregnancy contributes to foot stress.

Medications. Some medications, such as calcitonin and drugs used for high blood pressure, can cause foot swelling.

Click the icon to see an image of foot inspection.

Risk Factors

A risk factor is anything that increases your chances of getting a disease or condition. The following are factors that increase your risk for foot pain:

Elderly people are at very high risk for foot problems. As you age, your feet widen and flatten, and the fat padding on the sole of the foot wears down. The skin on the feet also becomes dryer. Foot pain in older adults may be the first sign of age-related conditions, such as arthritis, diabetes, and circulatory disease. Foot problems can also impair balance and function in this age group.

Taking fashion to extreme limits, some people have turned to cosmetic surgery as a drastic way to fit into high-heeled shoes. Procedures include surgical shortening of the toes, narrowing of feet, or injecting silicone into the pads of the feet. Such methods may increase your risk for future foot pain. The American Orthopaedic Foot and Ankle Society (AOFAS) and other foot-related medical associations have expressed concern over this trend. The AOFAS strongly advises against cosmetic foot surgery and urges consumers to carefully consider the relative risks and benefits of undergoing unnecessary surgical procedures.

Women are at higher risk than men for severe foot pain, probably because of high-heeled shoes. Severe foot pain appears to be a major cause of general disability in older women.

An estimated 120,000 job-related foot injuries occur every year, about a third of them involving the toes. A number of foot problems -- including arthritis of the foot and ankle, toe deformities, pinched nerves between the toes, plantar fasciitis, adult-acquired flat foot, and tarsal tunnel syndrome -- have been attributed to repetitive use at work.

For example, in a study of New York police officers who walked an average of 3 miles a day, 20% experienced foot pain at the end of their workday. (Insoles can relieve much of this pain.) No studies, however, have scientifically distinguished between injuries due to work versus those due to regular use. This is an important issue because of its potential impact on disability claims.

Pregnant women have an increased risk of foot problems due to weight gain, swelling in their feet and ankles, and the release of certain hormones that cause ligaments to relax. These hormones help when bearing the child, but they can weaken the feet.

People who engage in regular high-impact aerobic exercise are at risk for plantar fasciitis, heel spurs, sesamoiditis, shin splints, Achilles tendon, and stress fractures. Women are at higher risk for stress fractures than are men.

Gaining weight puts added stress on the feet and can lead to foot or ankle injuries. The added pressure on the soft tissues and joints of the foot in overweight people increases the likelihood of developing tendinitis and plantar fasciitis.

Treatment: Corns and Calluses

A corn is a protective layer of dead skin cells that forms due to repeated friction. It is cone-shaped and has a knobby core that points inward. This core can put pressure on a nerve and cause sharp pain. Corns can develop on the top of, or between, toes. If a corn develops between the toes, it may be kept pliable by the moisture from perspiration and is therefore called a soft corn.

Corns develop as a result of friction from the toes rubbing together or against the shoe. They often occur from the following:

Shoes, socks, or stockings that fit too tightly around the toes
Pressure on the toes from high-heeled shoes
Shoes that are too loose, due to the friction of the foot sliding within the shoe
Deformed and crooked toes

Calluses are composed of the same material as corns. Calluses, however, develop on the ball or heel of the foot. The skin on the sole of the foot is ordinarily about 40 times thicker than the skin anywhere else on the body, but a callus can even be twice as thick. A protective callus layer naturally develops to guard against excessive pressure and chafing as people get older and the padding of fat on the bottom of the foot thins out. If calluses get too big or too hard, they may pull and tear the underlying skin.

Risk factors for calluses include the following:

Poorly fitting shoes
Walking regularly on hard surfaces
Flat feet

Of note, in people with diabetes, the presence of calluses is a strong predictor of ulceration, particularly in those who have a history of foot ulcers.

Preventing Corns and Calluses and Relieving Discomfort. To prevent corns and calluses and relieve discomfort if they develop:

Do not wear shoes that are too tight or too loose. Wear well-padded shoes with open toes or a deep toe box (the part of the shoe that surrounds the toes). If necessary, have a cobbler stretch the shoes in the area where the corn or callus is located.
Wear thick socks to absorb pressure, but do not wear tight socks or stockings.
Apply petroleum jelly or lanolin hand cream to corns or calluses to soften them.
Use doughnut-shaped pads that fit over a corn and decrease pressure and friction. They are available at most drug stores.
Place cotton, lamb's wool, or mole skin between the toes to cushion any corns in these areas.

Removing Corns and Calluses. To remove a corn or callus, soak it in very warm water for 5 minutes or more to soften the hardened tissue, then gently sand it with a pumice stone. Several treatments may be necessary. Do not trim corns or calluses with a razor blade or other sharp tool. Unsterile cutting tools can cause infection, and it is easy to slip and cut too deep, causing excessive bleeding or injury to the toe or foot.

Medicated Solutions and Pads. There are numerous over-the-counter pads, plasters, and medications for removing corns and calluses. These treatments commonly contain salicylic acid, which may cause irritation, burns, or infections that are more serious than the corn or callus. Use caution with these medications. The following people should not use them:

Patients with diabetes
Patients with reduced feeling in the feet due to circulation problems or neurological damage
Patients who do not have the flexibility or eyesight to use them properly

Treatment: Bunions

A bunion is a deformity that usually occurs at the head of one of the five long bones (the metatarsal bones) that extend from the arch of the foot and connect to the toes. A bunion typically develops in the following way:

Most often it occurs in the first metatarsal bone (the one that attaches to the big toe). A bunion may also develop in the bone that joins the little toe to the foot (the fifth metatarsal bone), in which case it is known as either a bunionette or a tailor's bunion.
A bunion begins to form when the big or little toe is forced in toward the rest of the toes, causing the head of the metatarsal bone to jut out and rub against the side of the shoe.
The underlying tissue becomes inflamed, and a painful bump forms.
As this bony growth develops, the bunion is formed as the big toe is forced to grow at an increasing angle toward the rest of the toes. One important bunion deformity, hallux valgus, causes the bone and joint of the big toe to shift and grow inward, so that the second toe crosses over it.

Several conditions can cause bunions:

Narrow high-heeled shoes with pointed toes can put enormous pressure on the front of the foot.
Injury in the joint may cause a bunion to develop over time.
Genetics play a role in 10 - 15% of all bunions.

Flat feet, gout, arthritis, and occupations (such as ballet) that place undue stress on the feet can also increase the risk for bunions.

Shoes and Protective Pads. Pressure and pain from bunions and bunionettes can be relieved by wearing appropriate shoes, such as the following:

Soft, wide, low-heeled leather shoes that lace up
Athletic shoes with soft toe boxes
Open shoes or sandals with straps that don't touch the irritated area

A thick doughnut-shaped, moleskin pad can protect the protrusion. In some cases, an orthotic can help redistribute weight and take pressure off the bunion. Nonsteroidal anti-inflammatory drugs (NSAIDs) or corticosteroid injections may offer some pain relief.

Surgery. If discomfort persists, surgery may be necessary, particularly for more serious conditions, such as hallux valgus. There are more than 100 surgical variations, ranging from removing the bump to realigning the toes.

The most common surgery, an office procedure known as bunionectomy, involves shaving down the bone of the big toe joint. In one procedure the surgeon uses a very small incision, through which the bone-shaving drill is inserted. The physician shaves off the bone, guided by feel or x-ray. This technique is not a cure, but patient satisfaction is high and results are long-lasting.

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

More extensive surgeries may be required to realign the toe joint. Although there are variations of each, they generally involve one or more of the following:

Osteotomy (cutting and realigning the joint). Long-term studies on osteotomies report that 90% of patients are satisfied with the procedure.
Exostetectomy (removal of the large bony growth). This technique is only useful when there is no shift in the toe bone itself.
Arthrodesis (removal of damaged portion of the joint, followed by implantation of screws, wires, or plates to hold the bones together until they heal). This is the gold standard procedure for very severe cases or when previous procedures have failed. Most patients report good results.
Arthroplasty (removal of damaged portion of the joint with the goal of achieving a flexible scar). This technique offers symptom relief and faster rehabilitation than arthrodesis, but it can cause deformity and some foot weakness. Arthroplasty tends to be used in older patients. Biologic or synthetic implants for supporting the toes are showing promise as part of this procedure.
Tendon and Ligament Repair. If tendons and ligaments have become too loose, the surgeon may tighten them.

In severe cases, surgeons are testing bone grafts to restore bone length in patients who have had previous bunion surgeries or damage from osteoarthritis.

Complications, though uncommon in even the most complex procedures, can include:

Continued pain
Infection
Possible numbness
Irritation from implants used to support the bone
An excessively shortened metatarsal bone

Recovery from more invasive procedures, such as arthrodesis or osteotomy, may take 6 - 8 weeks, and it can be that long before a patient can put full weight on the foot. In such cases, the patient will need to wear a cast or use crutches. Elderly patients may need wheelchairs.

Treatment: Hammertoes

A hammertoe is a permanent deformity of the toe joint, in which the toe bends up slightly and then curls downward, resting on its tip. When forced into this position long enough, the tendons of the toe shrink, and the toe stiffens into a hammer- or claw-like shape.

Hammertoe is most common in the second toe, but it can develop in any or all of the three middle toes if they are pushed forward and do not have enough room to lie flat in the shoe. The risk is increased when the toes are already crowded by the pressure of a bunion. Risks include:

Lying down for long periods
Diabetes
Diseases that affect the nerves and muscles

Click the icon to see an image of a hammertoe.

Treatment for Hammertoe. At first, a hammertoe is flexible, and any pain it causes can usually be relieved by putting a toe pad, sold in drug stores, into the shoe. To help prevent and ease existing discomfort from hammertoes, shoes should have a deep, wide toe area. As the tendon becomes tighter and the toe stiffens, other treatments, including exercises, splints, and custom-made shoe inserts (orthotics) may help redistribute weight and ease the position of the toe.

Surgery. Patients with severe cases of hammertome may need surgery. If the toe is still flexible, only a simple procedure that releases the tendon may be involved. Such procedures sometimes require only a single stitch and a Band-Aid. If the toe has become rigid, surgery on the bone is necessary, but it can still be performed in the doctor's office. A procedure called PIP arthroplasty involves releasing the ligaments at the joint and removing a small piece of toe bone, which restores the toe to its normal position. The toe is held in this position with a pin for about 3 weeks, and then the pin is removed. One study reported that 92% of patients who had arthroscopy were still pain free after 5 years.

Treatment: Ingrown Toenails

Ingrown toenails can occur on any toe but are most common on the big toes. They usually develop when tight-fitting or narrow shoes put too much pressure on the toenail and force the nail to grow into the flesh of the toe. Incorrect toenail trimming can also contribute to the risk of developing an ingrown toenail. Other causes are:

Fungal infections
Injuries
Abnormalities in the structure of the foot
Repeated impact on the toenail from high-impact aerobic exercise

An ingrown toenail is a condition in which the edge of the toenail grows into the skin of the toe. The big toe is most commonly affected. Symptoms include pain, redness, and swelling around the toenail.

Caring for Toenails. Trim toenails straight across and keep them long enough so that the nail corner is not visible. If the nail is cut too short, it may grow inward. If the nail does grow inward, do not cut the nail corner at an angle. This only trains the nail to continue growing inward. When filing the nails, file straight across the nail in a single movement, lifting the file before the next stroke. Do not saw back and forth. A cuticle stick can be used to clean under the nail.

Treatments. To relieve pain from ingrown toenails, try wearing sandals or open-toed shoes. Soaking the toe for 5 minutes twice a day in a warm water solution of Domeboro or Betadine can help. People who are at increased risk for infections, such as those with diabetes, should have professional treatment.

Antibiotic ointments can treat ingrown toenails that are infected. Apply the ointment by working a wisp of cotton under the nail, especially the corners, to lift the nail up and drain the infection. The cotton will also help force the toenail to grow out correctly. Change the cotton daily, and use the antibiotic consistently.

In severe cases, more intensive treatments are needed. Surgery involves simply cutting away the sharp portion of ingrown nail, removing the nail bed, or removing a wedge of the affected tissue. One study found that orthonyxia, a newer surgical technique that implants a small metal brace into the top of the nail, is as effective as traditional surgical techniques for preventing ingrown toenails from recurring.

Nonsurgical methods can also treat ingrown toenails. One technique uses chemicals to remove the skin. Both sodium hydroxide and phenol may be used, but research shows that sodium hydroxide produces a better outcome and faster recovery than phenol. Other nonsurgical methods include using cauterization (heating), or lasers, to remove the skin.

Treatment: Forefoot Pain

Forefoot pain refers to pain and discomfort felt toward the top of the foot. The rate of forefoot pain and deformity increases with age. When a cause cannot be determined, any pain on the ball of the foot is generally referred to as metatarsalgia.

Forefoot pain may be due to:

Morton's neuroma
Sesamoiditis
Stress fractures

A neuroma usually means a benign tumor of a nerve. However, Morton’s neuroma, also called interdigital neuroma, is not actually a tumor. It is a thickening of the tissue surrounding the nerves leading to the toes. Morton’s neuroma usually develops when the bones in the third and fourth toes pinch together, compressing a nerve. It can also occur in other locations. The nerve becomes enlarged and inflamed. The inflammation causes a burning or tingling sensation and cramping in the front of the foot. Other causes of this condition include:

Tight, poorly-fitting shoes
Injury
Arthritis
Abnormal bone structure

Treatment for Neuromas. Pain from Morton's neuroma can be reduced by massaging the affected area. Roomier shoes (box-toed shoes), pads of various sorts, and cortisone injections in the painful area are also helpful. A combination of cortisone injections and shoe modifications provides better immediate relief than changes in footwear alone. Ultrasound-guided injection of alcohol might also provide relief from Morton's neuroma, research finds.

If these treatments are not effective, the enlarged area may need to be surgically removed. In one long-term study of one surgeon's experience, 85% of patients reported good to excellent satisfaction nearly 6 years after surgery. About 65% were pain free. Some numbness is common afterward, but it rarely bothers patients. Occasionally, the nerve tissue may re-grow and form another neuroma.

Sesamoiditis is an inflammation of the tendons around the small, round bones that are embedded in the head of the first metatarsal bone, which leads to the big toe. Sesamoid bones bear much stress under ordinary circumstances; excessive stress can strain the surrounding tendons. Often there is no clear-cut cause, but sesamoid injuries are common among people who participate in jarring, high-impact activities, such as ballet, jogging, and aerobic exercise.

Treatment for Sesamoiditis. Rest and reducing stress on the ball of the foot are the first lines of treatment for sesamoiditis. A low-heeled shoe with a stiff sole and soft padding inside is all that is usually required. In severe cases, surgery may be necessary.

A stress fracture in the foot, also called fatigue or march fracture, usually results from a break or rupture in any of the five metatarsal bones (mostly the second or third). These fractures are caused by overuse during strenuous exercise, particularly jogging and high-impact aerobics. Women are at higher risk for stress fracture than men.

A fracture in the first metatarsal bone, which leads to the big toe, is uncommon because of the thickness of this bone. If it occurs, however, it is more serious than a fracture in any of the other metatarsal bones because it dramatically changes the pattern of normal walking and weight bearing.

Treatment for Stress Fractures. Patients should seek treatment if pain persists for 3 weeks. In a study of young athletes, treatment after that time reduced the chance that they could return to their sport. Surgery may be needed if conservative measures fail. In most cases, however, stress fractures heal by themselves if you avoid rigorous activities. Some health care providers recommend moderate exercise, particularly swimming and walking. It is best to wear low-heeled shoes with stiff soles. Occasionally, a health care provider may recommend wearing a special wooden shoe and a compressive wrap to make walking more comfortable.

Treatment: Heel Pain

The heel is the largest bone in the foot. Heel pain is the most common foot problem and affects 2 million Americans every year. It can occur in the front, back, or bottom of the heel. Types of heel pain include:

Achilles tendinitis
Bursitis of the heel
Excess pronation
Haglund's deformity
Heel spur syndrome
Plantar fasciitis

Each type of heal pain is described in more detail below. General treatment guidelines are as follows:

The American Orthopaedic Foot and Ankle Society (AOFAS) suggests shoe inserts, medications, and stretching as a first line of therapy for heel pain. One study found that 95% of women who used an insert and did simple stretching exercises for the Achilles tendon and plantar fascia experienced improvement after 8 weeks.
If these treatments fail, the patient may need prescription heel orthotics and extended physical therapy. Surgery may be an option if other methods have failed.

Achilles tendinitis is an inflammation of the tendon that connects the calf muscles to the heel bone. It is caused by small tears in the tendon from overuse or injury. This condition is most common in people who engage in high-impact exercise, particularly jogging, racquetball, and tennis.

People at highest risk for this disorder from these activities are those with a shortened Achilles tendon. Such people tend to roll their feet too far inward when walking, and may bounce when they walk. A shortened tendon can be due to an inborn structural abnormality, or it can develop from regularly wearing high heels.

An inflamed or torn Achilles tendon causes intense pain and affects mobility.

Evidence is uncertain about the best way to treat either acute or chronic Achilles tendinitis. Some approaches include:

Treatments to Relieve Pain and Reduce Inflammation. Nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin or ibuprofen (Advil), may help ease pain and reduce inflammation. It is also helpful to apply ice for 20 - 30 minutes, four or five times a day. (Note: Corticosteroid injections are sometimes used, although evidence suggests they don't help very much, and they can pose a risk for rupture of the tendon.)

Gentle Stretching. Gentle calf muscle stretches may also help reduce pain and spasms. If the calf is swollen, elevate the leg. Exercise is safe when the heel is no longer swollen or tender, even if pain is still present. If pain increases with exercise, stop immediately.

Laser Therapy. Low-level laser therapy that emits energy directed at pain trigger points has helped some patients. No strong evidence supports its use to date, however.

Surgery vs. Nonsurgical Treatment. Chronic inflammation may lead to rupture of the Achilles tendon. If pain continues, the ruptured tendon will require a cast and perhaps surgery, called tendon transfer. Although some experts believe a cast without surgery is a sufficient treatment for such rupture, there is a chance the tendon may rupture again in the future, even after it heals. Some experts suggest surgery for active people and nonsurgical treatment for older people.

Surgery requires a long incision with a postoperative period of immobilization that can average 6 weeks. Complications can include a significant surgical scar, infection, and muscle atrophy, although surgery reduces pain and preserves foot function in the long term. Less invasive techniques are being tested. In one study, selected patients with ruptured tendons were hospitalized for about 5 days and fitted with special footgear (Variostabil, which continuously raised the back of the foot). The footgear was effective for most patients, and the tendon ruptured again in only 5% of cases.

Bursitis of the heel is an inflammation of the bursa, a small sack of fluid beneath the heel bone. Nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin or ibuprofen (Advil), and steroid injections will help relieve pain from bursitis. Applying ice and massaging the heel are also beneficial. A heel cup or soft padding in the heel of the shoe reduces direct impact when walking.

Pronation is the normal motion that allows the foot to adapt to uneven walking surfaces and to absorb shock. Excessive pronation occurs when the foot has a tendency to turn inward and stretch and pull the fascia. It can cause not only heel pain, but also hip, knee, and lower back problems.

Haglund's deformity, known medically as posterior calcaneal exostosis, is a bony growth surrounded by tender tissue on the back of the heel bone. It develops when the back of the shoe repeatedly rubs against the back of the heel, aggravating the tissue and the underlying bone. It is commonly called pump bump because it frequently occurs with high heels. (It can also develop in runners, however.)

Treatment for Haglund's Deformity. Applying ice followed by moist heat will help ease discomfort from a pump bump. Nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin or ibuprofen (Advil), will also reduce pain. Your doctor may recommend an orthotic device to control heel motion. Corticosteroid injections are not recommended because they can weaken the Achilles tendon.

In severe cases, surgery may be necessary to remove or reduce the bony growth. According to one study, however, surgery was not effective for more than 30% of patients and, in fact, the condition worsened in 14% of patients who had surgery. A more recent study reported that surgery cured 90% of cases, but patients took 6 months to 2 years to fully recover. Experts advise patients to try all conservative measures before choosing surgery.

Plantar fasciitis is a common foot problem that accounts for 1 million office visits per year. Plantar fasciitis occurs from small tears and inflammation in the wide band of tendons and ligaments that stretches from the heel to the ball of the foot. This band, much like the tensed string in a bow, forms the arch of the foot and helps serve as a shock absorber for the body.

The term plantar means the sole of the foot, and fascia refers to any fibrous connective tissue in the body. Most people with plantar fasciitis experience pain in the heel with their first steps in the morning. The pain also often spreads to the arch of the foot. The condition can be temporary, or it may become chronic if ignored. Resting can provide relief, but only temporarily.

Heel spurs are calcium deposits that can develop under the heel bone as a result of the inflammation that occurs with plantar fasciitis. Heel spurs and plantar fasciitis are sometimes blamed interchangeably for pain, but plantar fasciitis can occur without heel spurs, and spurs commonly develop without causing any symptoms at all.

Causes of Plantar Fasciitis. The cause of plantar fasciitis is often unknown. It is usually associated with overuse during high-impact exercise and sports. Plantar fasciitis accounts for up to 9% of all running injuries. Because the condition often occurs in only one foot, however, factors other than overuse are likely to be responsible in many cases. Other causes of this injury include poorly-fitting shoes, lack of calf flexibility, or an uneven stride that causes an abnormal and stressful impact on the foot.

Treatment Goals. The three major treatment goals for plantar fasciitis are:

Reducing inflammation and pain
Reducing pressure on the heel
Restoring strength and flexibility

Embarking on an exercise program as soon as possible and using NSAIDs, splints, or heel pads as needed can help relieve the problem. Pain that does not subside with NSAIDs may require more intensive treatments, including leg supports and even surgery.

Exercises to Restore Strength and Flexibility. Stretching the plantar fascia is the mainstay therapy for restoring strength and flexibility. One exercise involves the following:

Put the hands on a wall and lean against them.
Place the uninjured foot on the floor in front of the injured foot.
Raise the heel of the injured foot.
Gently stretch the injured leg and foot.

With stretching treatments, the plantar fascia nearly always heals by itself but it may take as long as a year, with pain occurring intermittently. A moderate amount of low-impact exercise (such as walking, swimming, or cycling) also seems to be beneficial.

Treatment. Inflammation and pain is most commonly treated with ice and over-the-counter nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin or ibuprofen. NSAIDs reduce pain and disability in people with plantar fasciitis when used with other techniques, such as night splints and stretching.

Corticosteroids are powerful anti-inflammatory agents. An injection of a steroid plus a local anesthetic (such as xylocaine) may provide relief in severe cases of plantar fasciitis. (Steroid injections are not used for pain that is only due to heel spurs). For athletes or performers who need immediate relief, an effective method is to administer the steroid dexamethasone using a procedure called iontophoresis, which introduces the drug into the foot's tissue using an electrical current.

Several non-drug approaches can relieve pressure on the heel, including:

Sturdy Shoes and Insoles. It is important to wear comfortable but sturdy shoes that have thick soles, rubber heels, and a sole insole to relieve pressure. (An insole with an arch support might also be helpful.) Cutting a round hole about the size of a quarter in the sole cushion under the painful area may help support the rest of the heel while relieving pressure on the painful spot. Heel cups are not very useful. When combined with exercises that stretch the arch and heel cord, over-the-counter insoles may offer the same relief as prescribed orthotics.
Night Splints. Some evidence suggests that splints worn at night may be helpful for some people. One device, for example, uses an Ace bandage and an L-shaped fiberglass splint to keep the foot stretched while the patient is sleeping. This allows the muscle to heal. One study reported that nearly any splint, regardless of cost, is equally effective in about three-quarters of patients. Although patient compliance may be better with custom-made prescribed orthotics than with tension night splints, one study found they are equally effective in improving pain.
Elevated Heels. Some people report relief from mild symptoms with the use of shoes or cowboy boots that have elevated heels. This approach, however, may not work in some people and is not recommended for anyone with a moderate-to-severe condition. (Heel cups have not been proven to be very useful.)
Orthotics. For severe conditions, such as fallen arches or structural problems that cause imbalance, insoles, called orthotics, molded from a plaster cast of the patient's foot may be needed. (See "Insoles and Orthotics" section).
Extracorporeal Shock Wave Therapy (ESWT). ESWT may be used as an alternative to surgery for patients who have not responded to other treatments. The therapy uses low-dose sound waves to injure the surrounding tissues in the heel, which is believed to trigger healing of the tissues that are causing the pain. Studies show that the treatment provides a very small reduction in heel pain without side effects. It can be considered as an option for patients who haven't responded well to extensive conservative treatment.
Surgery. Surgery may be needed for some patients, typically those who have disabling heel pain that does not respond to other treatments for at least a year. A typical surgery is called instep plantar fasciotomy. It relieves pressure on the nerves that are causing pain by removing and therefore releasing part of the plantar fascia. A less invasive method uses a procedure called endoscopy, which requires smaller incisions. Wearing a below-the-knee walking cast after surgery for 2 weeks may reduce the need for pain relief and speed recovery time compared to the use of crutches.
Botox. Small studies show that injections of botulinum toxin (Botox), a protein used to temporarily paralyze certain muscles, reduces pain and improves patients' future ability to walk. More research is needed on this treatment.

Treatment: Flat Feet

Flat foot, or pes planus, is a defect of the foot that eliminates the arch. The condition is most often inherited. Arches, however, can also fall in adulthood, in which case the condition is sometimes referred to as posterior tibial tendon dysfunction (PTTD). This occurs most often in women over age 50, but it can occur in anyone. The following are risk factors for PTTD:

Wearing high heels for long periods of time is a particular risk for flat feet. Over the years, the Achilles tendon in the back of the calf shortens and tightens, so the ankle does not bend properly. The tendons and ligaments running through the arch then try to compensate. Sometimes they break down, and the arch falls.
Some studies have indicated that the earlier a person starts wearing shoes, particularly for long periods of the day, the higher the risk for flat feet later on.
Other conditions that can lead to PTTD include obesity, diabetes, surgery, injury, rheumatoid arthritis, or the use of corticosteroids.

Some research suggests that flat feet in adults can, over time, actually exert abnormal pressure on the ankle joint that can cause damage. One indirect complication of flat arches may be urinary incontinence or leakage during exercise. The less flexible the arch, the more force reaches the pelvic floor, jarring the muscles that affect urinary continence. Nevertheless, whether flat feet pose any significant problems in adults is unknown. For example, one study on athletes with flat feet indicated that they had no higher risk for leg or foot injuries than did athletes with normal arches.

Treatment for Flat Feet in Children. Doctors usually can't diagnose flat feet until a child is 6 years old. Children with flat feet typically don't have symptoms, and often outgrow the condition. Children who are experiencing symptoms might need to change shoes or wear arch supports. In rare cases, minimally invasive joint insert surgery may be an option.

Treatment for Flat Feet in Adults. In general, conservative treatment for flat feet acquired in adulthood (posterior tibial tendon dysfunction) involves pain relief and insoles or custom-made orthotics to support the foot and prevent progression.

In severe cases, surgery may be required to correct the foot posture, usually with procedures called osteotomies or arthrodesis that typically lengthen the Achilles tendon and adjust tendons in the foot. One procedure uses an implant to support the arch. These procedures have potential complications. Conservative methods should be tried first.

Treatment: Abnormally High Arches

An overly-high arch (hollow foot) can cause problems. Army studies have found that recruits with the highest arches have the most lower-limb injuries and that flat-footed recruits have the least. Contrary to the general impression, the hollow foot is much more common than the flat foot.

Clawfoot, or pes cavus, is a deformity of the foot marked by very high arches and very long toes. Clawfoot is a hereditary condition, but can also occur when muscles in the foot contract or become unbalanced due to nerve or muscle disorders.

Claw toe is a deformity of the foot in which the toes are pointed down and the arch is high, making the foot appear claw-like. Claw toe can be a condition from birth or develop as a consequence of other disorders.

Treatment: Tarsal Tunnel Syndrome

Tarsal tunnel syndrome results from compression of a nerve that runs through a narrow passage behind the inner ankle bone down to the heel. It can cause pain anywhere along the bottom of the foot. It can occur with:

Diabetes
Back pain
Arthritis
Injury to the ankle
Abnormal blood vessels
Scar tissue that press against the nerve

Magnetic resonance imaging (MRI) and the dorsiflexion-eversion test can diagnose this syndrome.

Treatment for Tarsal Tunnel Syndrome. Specially designed shoe inserts called orthotics can relieve pain from tarsal tunnel syndrome, because they help redistribute weight and take pressure off the nerve. Corticosteroid injections may also help. Surgery is sometimes performed, particularly if symptoms persist for more than a year, although its benefits are a matter of debate. Tarsal tunnel syndrome caused by known conditions, such as tumors or cysts, may respond better to surgery than tarsal tunnel syndrome of unknown cause. It can take months after this surgery for a person to recover and resume normal activities. Only experienced surgeons should perform tarsal tunnel syndrome surgery.

Treatment: Foot Injury

If you suspect that you have broken or fractured bones in a toe or foot, call a doctor, who will probably order x-rays. Even if you can walk, you still might have a fracture. People are often able to walk even if a foot bone has been fractured, particularly if it is a chipped bone or a toe fracture.

Over-the-counter nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat mild pain caused by muscle inflammation. Aspirin is the most common NSAID. Others include ibuprofen (Motrin, Advil, Nuprin, Rufen), ketoprofen (Actron, Orudis KT), naproxen (Aleve, Naprelan), and tolmetin (Tolectin). A gel containing ibuprofen can be applied to sore joints. Acetaminophen (Tylenol) is not an NSAID, and although it is a mild pain reliever, it will not reduce inflammation. It is important to note that high doses or long-term use of any NSAID can cause gastrointestinal disturbances with sometimes serious consequences, including dangerous bleeding. No one should take NSAIDs for prolonged periods of time without consulting a doctor.

The acronym RICE stands for rest, ice, compression, and elevation -- the four basic elements of immediate treatment for an injured foot.

Rest. Patients should get off injured foot as soon as possible.
Ice. This is particularly important to reduce swelling and promote recovery during the first 48 hours. Wrap a bag or towel containing ice around the injured area on a repetitive cycle of 20 minutes on, 40 minutes off.
Compression. Lightly wrap an Ace bandage around the area.
Elevation. Elevate the foot on several pillows.

Minor injuries like sprains may be treated at home if broken bones are not suspected. The acronym RICE is helpful for remembering how to treat minor injuries: "R" stands for rest, "I" is for ice, "C" is for compression, and "E" is for elevation. Pain and swelling should decrease within 48 hours, and gentle movement may be beneficial, but don't put pressure on a sprained joint until the pain is completely gone (one to several weeks).

Prevention

The American Podiatric Medical Association offers the following tips for preventing foot pain:

Don't ignore foot pain -- it's not normal. If the pain persists, see a doctor who specializes in podiatry.
Inspect feet regularly. Pay attention to changes in color and temperature. Look for thick or discolored nails (a sign of developing fungus), and check for cracks or cuts in the skin. Peeling or scaling on the soles of feet could indicate athlete's foot. Any growth on the foot is not considered normal.
Wash feet regularly, especially between the toes, and dry them completely.
Trim toenails straight across, but not too short. (Cutting nails in corners or on the sides increases the risk for ingrown toenails.)
Make sure shoes fit properly. Purchase new shoes later in the day when feet tend to be at their largest, and replace worn out shoes as soon as possible.
Select and wear the right shoe for specific activities (such as running shoes for running).
Alternate shoes. Don't wear the same pair of shoes every day.
Avoid walking barefoot, which increases the risk for injury and infection. At the beach or when wearing sandals, always use sunblock on your feet, as you would on the rest of your body.
Be cautious when using home remedies for foot ailments. Self-treatment can often turn a minor problem into a major one.
It is critical that people with diabetes see a podiatric physician at least once a year for a checkup. People with diabetes, poor circulation, or heart problems should not treat their own feet, including toenails, because they are more prone to infection.

Skin creams can help maintain skin softness and pliability. A pumice stone or loofah sponge can help get rid of dead skin.

Taking a warm footbath for 10 minutes two or three times a week will keep the feet relaxed and help prevent mild foot pain caused by fatigue. Adding 1/2 cup of Epsom salts increases circulation and adds other benefits. Taking footbaths only when the feet are painful is not as helpful.

In addition to wearing proper shoes and socks, walking often -- and properly -- can prevent foot injury and pain. The head should be erect, the back straight, and the arms relaxed and swinging freely at the side. Step out on the heel, move forward with the weight on the outside of the foot, and complete the step by pushing off the big toe.

Exercises specifically for the toe and feet are easy to perform and help strengthen them and keep them flexible. Helpful exercises include the following:

Raise and curl the toes 10 times, holding each position for a count of five.
Put a rubber band around both big toes and pull the feet away from each other. Count to five. Repeat 10 times.
Pick up a towel with the toes. Repeat five times.
Pump the foot up and down to stretch the calf and shin muscles. Perform for 2 or 3 minutes.

Early Development. The first year of life is important for foot development. Parents should cover their babies' feet loosely, allowing plenty of opportunity for kicking and exercise. Change the child's position frequently. Children generally start to walk at 10 - 18 months. They should not be forced to start walking early. Wearing just socks or going barefoot indoors helps the foot develop normally and strongly and allows the toes to grasp. Going barefoot outside, however, increases the risk for injury and other conditions, such as plantar warts.

Shoes. Children should wear shoes that are light and flexible, and since their feet tend to perspire, their shoes should be made of materials that breathe. Replace footwear every few months as the child's feet grow. Footwear should never be handed down. Protect children's feet if they participate in high-impact sports.

Shoes

In general, the best shoes are well cushioned and have a leather upper, stiff heel counter, and flexible area at the ball of the foot. The heel area should be strong and supportive, but not too stiff, and the front of the shoe should be flexible. New shoes should feel comfortable right away, without a breaking-in period.

Well-fitted shoes with a firm sole and soft upper are the best way to prevent many problems with the feet. They should be purchased in the afternoon or after a long walk, when the feet have swelled. There should be 1/2 inch of space between the longest toe and the tip of the shoe (remember, the longest toe is not always the big toe), and the toes should be able to wiggle upward.

Stand when being measured, and have both feet sized, buying shoes that fit whichever foot is largest. Wear the same socks as you would regularly wear with the new shoes. Women who are accustomed to wearing pointed-toe shoes may prefer the feel of tight-fitting shoes, but with wear their tastes may adjust to shoes that are less confining and properly fitted.

Ideally, the shoe should have a removable insole. Thin, hard soles may be the best choice for older people. Elderly people wearing shoes with thick inflexible soles may be unable to sense the position of their feet relative to the ground, significantly increasing the risk for falling.

High heels are the major cause of foot problems in women. Although people believe that foot binding is a problem limited to Chinese women of the past, many fashionable high heels are designed to constrict the foot by up to an inch. Women who insist on wearing high-heeled shoes should at least look for shoes with wide toe room, reinforced heels that are relatively wide, and cushioned insoles. They should also keep the amount of time they spend wearing high heels to a minimum.

The way shoes are laced can be important for preventing specific problems. Laces should always be loosened before putting shoes on. People with narrow feet should buy shoes with eyelets farther away from the tongue than people with wider feet. This makes for a tighter fit for narrower feet and a looser fit for wider feet. If, after tying the shoe, less than an inch of tongue shows, the shoes are probably too wide. Adjust tightness both at the top and bottom of the shoe. When shoes with high arches cause pain, skip eyelets when lacing them to relieve pressure.

If shoes need breaking in, place moleskin pads next to areas on the skin where friction is likely to occur. Once a blister occurs, moleskin is not effective. Change shoes during the day, and rotate between different pairs of shoes. As soon as the heels show noticeable wear, replace the shoes or their heels.

Avoid extreme variations between exercise, street, and dress shoes.

Exercise and Sports. Shoes purchased for exercise should be specifically designed for a person's preferred sport. For instance, a running shoe should especially cushion the forefoot, while tennis shoes should emphasize ankle support. Athletic socks are almost as important as shoes. Experts often recommend padded acrylic socks.

Occupational Footwear. Because a number of occupations put the feet in danger, workers in high-risk jobs should be sure their footwear is protective. For example, non-electric workers at risk for falling or rolling objects or punctures should wear shoes with steel toes and possibly other metal foot guards. Electric workers should wear footgear with no metal parts (or insulated steel toes) and rubber soles and heels. Chemical workers should wear shoes made of synthetics or rubber, not leather.


Aerobic Dancing	Sufficient cushioning to absorb shock and pressure, which should be many times greater than shock from walking. Arches that maintain side-to-side stability. Thick upper leather support. Box toe. Orthotics may be required for people with ankles that over-turn inward or outward. Soles should allow for twisting and turning.
Cycling	Rigid support across the arch to prevent collapse during pedaling. Heel lift. Cross-training or combo hiking/cycling shoes may be sufficient for the casual biker. Toe clips or specially designed shoe cleats for serious cyclers. In some cases, orthotics may be needed to control arch and heel and balance the forefoot.
Running	Sufficient cushioning to absorb shock and pressure. Fully bendable at the ball of the foot. Enough traction on the sole to prevent slipping. Consider insole or orthotic with arch support for problem feet.
Tennis	Allows side-to-side sliding. Low-traction sole. Snug fitting heel with cushioning. Padded toe box with adequate depth. Soft-support arch.
Walking	Lightweight. Breathable upper material (leather or mesh). Wide enough to accommodate ball of the foot. Firm padded heel counter that does not bite into heel or touch anklebone. Low heel close to ground for stability. Good arch support. Front provides support and flexibility.

Insoles and Orthotics

Insoles are flat cushioned inserts that are placed inside the shoe. They are designed to reduce shock, provide support for heels and arches, and absorb moisture and odor. In general, they can be very helpful for many people.

People respond very differently to specific insoles. What may work for one person may not for another. Consider the thickness of socks when purchasing insoles to be sure they do not squeeze the toes up against the shoes. Insoles can be purchased in athletic and drug stores. Shoe stores that specialize in foot problems often sell customized, but more expensive, insoles. In general, over-the-counter insoles offer enough support for most people's foot problems. Most well-known brands of athletic shoes have built-in insoles.

Brands and Materials. There are many types of insoles available. They are composed of various materials, such as cork, leather, plastic foam, and rubber. Very effective insoles are now made from viscoelastic polymers (such as Sorbothane, Airplus, Spenco, Dr. Scholl's Massaging Gel, and others), which are gel-like materials that act both as liquids and solids.

Heel Cushions for Shortened Achilles Tendons. People who have developed short, tightened Achilles tendons (usually women who have worn high-heeled shoes for prolonged periods) should consider using heel cushions. Like insoles, heel cushions are inserted inside the shoes. They should be at least 1/8 inch thick, but not more than 1/4 inch thick.

For severe conditions, such as fallen arches or structural problems that cause imbalance, podiatrists or physicians may need to fit and prescribe orthotics, or orthoses, which are insoles molded from a plaster cast of the patient's foot. Orthotics are usually categorized as rigid, soft, or semi-rigid.

Before seeking prescription orthotics, people with less severe problems should consider testing the lower-priced, over-the-counter insoles.

Types of orthotics include:

Rigid Orthotics. Rigid orthotics are used to control motion in two major foot joints that lie directly below the ankle. They are often used to prevent excessive pronation (the turning in of the foot) and are useful for people who are very overweight or have uneven leg lengths. Some experts warn that rigid orthotics may cause sesamoiditis or benign tumors from pinched nerves.
Soft Orthotics. Soft orthotics are designed to absorb shock, improve balance, and remove pressure from painful areas. They are made from a lightweight material and are often beneficial for people with diabetes or arthritis. Soft orthotics need to be replaced periodically, and because they are bulkier than rigid orthotics, they may require larger shoes.
Semi-Rigid Orthotics. Semi-rigid orthotics are designed to provide balance, often for a specific sport. They are typically made of layers of leather and cork reinforced by silastic.

Resources

www.apma.org -- American Podiatric Medical Association
www.aofas.org -- American Orthopaedic Foot and Ankle Society
www.acfas.org -- American College of Foot and Ankle Surgeons
www.aapsm.org -- American Academy of Podiatric Sports Medicine
www.apta.org -- American Physical Therapy Association
www.diabetes.org -- American Diabetes Association
http://ndep.nih.gov/campaigns/Feet/Feet_overview.htm -- National Diabetes Education Program
www.arthritis.org -- Arthritis Foundation
www.podiatrynetwork.com -- Podiatry Network

References

Bostanci S, Kocyigit P, Gurgey E. Comparison of phenol and sodium hydroxide chemical matricectomies for the treatment of ingrowing toenails. Dermatol Surg. 2007;33:680-685.

Donley BG, Moore T, Sferra J, Gozdanovic J, Smith R. The efficacy of oral nonsteroidal anti-inflammatory medication (NSAID) in the treatment of plantar fasciitis: a randomized, prospective, placebo-controlled study. Foot Ankle Int. 2007;28:20-23.

Frey C, Zamora J. The effects of obesity on orthopaedic foot and ankle pathology. Foot Ankle Int. 2007;28:996-999.

Gollwitzer H, Diehl P, von Korff A, Rahlfs VW, Gerdesmeyer L. Extracorporeal shock wave therapy for chronic painful heel syndrome: a prospective, double blind, randomized trial assessing the efficacy of a new electromagnetic shock wave device. J Foot Ankle Surg. 2007;46:348-357.

Hughes RJ, Ali K, Jones H, Kendall S, Connell DA. Treatment of Morton's neuroma with alcohol injection under sonographic guidance: follow-up of 101 cases. Am J Roentgenol. 2007;188:1535-1539.

Kruijff S, van Det RJ, van der Meer GT, van den Berg IC, van der Palen J, Geelkerken RH. Partial matrix excision or orthonyxia for ingrowing toenails. J Am Coll Surg. 2008;206:148-153.

Malay DS, Pressman MM, Assili A, Kline JT, York S, Buren B, Heyman ER, Borowsky P, LeMay C. Extracorporeal shockwave therapy versus placebo for the treatment of chronic proximal plantar fasciitis: results of a randomized, placebo-controlled, double-blinded, multicenter intervention trial. J Foot Ankle Surg. 2006;45:196-210.

Review Date:
12/14/2007
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

A.D.A.M. Copyright

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