FitSugar

My Virtual Model

FitSugar — Tue, 28 Nov 2006 09:30:00 -0800

Working hard at losing (or gaining) those few extra pounds and want to get an idea of how you're going to look when you've reached your goal?

The things you can do online never cease to amaze me. My Virtual Model is this cool site that allows you to basically create a virtual you. The best is that you can dress yourself up in clothing from participating retailers.

Pretty cool! Here is mine:

What do you think -- Does it look like me? To do your own Virtual Model, go here.

Cervical cancer

FitSugar — Wed, 08 Oct 2008 17:34:57 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Human Papilloma Virus (HPV) Prevalence

About 25% of women age 14 - 59 are infected with the human papilloma virus (HPV), indicates a 2007 study in the Journal of the American Medical Association (JAMA). HPV prevalence is highest (45%) among women age 20 - 24. HPV is the main cause of cervical cancer.

Immunization Guidelines

In 2006, the FDA approved the first vaccine to prevent cervical cancer. Gardasil protects against human papilloma virus (HPV) 16 and 18, the strains most likely to cause cervical cancer, and HPV 6 and 11, the strains most likely to cause genital warts. In 2007, several expert groups released immunization guidelines for the cervical cancer vaccine. Guidelines from the U.S. Centers for Disease Control’s Advisory Committee on Immunization Practices recommend:

Routine vaccination for girls age 11 - 12 with a vaccine series of 3 doses. Girls as young as 9 years old may be vaccinated at their doctors’ discretion.
Catch-up vaccination for girls and women age 13 - 26 who have not been previously vaccinated or who have missed doses.

Vaccine Effectiveness

The vaccine prevents human papilloma virus (HPV) infection caused by four HPV strains but cannot treat pre-existing HPV infection, confirms a 2007 JAMA study
The vaccine is nearly 100% effective in preventing cervical cancer and genital warts when it is administered before females become sexually active, indicate several 2007 studies.

HPV and Throat Cancer

Human papilloma virus (HPV) 16 increases the risk of oropharyngeal cancers of the throat, tonsils, and back of the tongue, according to several 2007 studies. HPV can be transmitted during oral sex, causing infection in the mouth. (However, not all people who engage in oral sex or who have oral HPV infection will develop throat cancer. The virus usually goes away on its own.) Previously, alcohol and tobacco use were considered the main risk factors for oropharyngeal cancer.

Introduction

The cervix is the lower third portion of the uterus (womb). It serves as a neck to connect the uterus to the vagina. The opening of the cervix, called the os, remains small and narrow, except during childbirth when it widens to allow a baby to pass from the uterus into the vagina.

The uterus is a hollow muscular organ located in the female pelvis between the bladder and rectum. The ovaries produce the eggs that travel through the fallopian tubes. Once the egg has left the ovary it can be fertilized and implant itself in the lining of the uterus. The main function of the uterus is to nourish the developing fetus prior to birth.

Cervical cancer develops in the thin layer of cells called the epithelium, which cover the cervix. Cells found in the this tissue have different shapes:

Squamous cells (flat and scaly). Most cervical cancer arises from changes in the squamous cells of the epithelium (squamous cell carcinoma).
Columnar cells (column-like). These cells line the cervical glands and cancers here are known as adenocarcinomas.
In rare cases, cancer can occur in cells that form the supportive tissue around the cervix (the stroma).

Cervical cancer usually begins slowly with precancerous abnormalities, and even if cancer develops, it generally progresses very gradually. Cervical cancer is the most preventable type of cancer and is very treatable in its early stages. Regular Pap tests and human papilloma virus (HPV) screening can help detect this disease early.

Dysplasia. Dysplasia is a term that refers to a precancerous condition. It may become cancerous, but not always. In the case of cervical cancer, dysplasia indicates that the layer of cells that covers the cervix (squamous epithelial cells) are abnormal in size and shape and are beginning to grow.

Cervical Intraepithelial Neoplasia. Dysplastic changes seen on a Pap smear may indicate the presence of cervical intraepithelial neoplasia (CIN). This means precancerous changes are found within the lining of the cervix. The changes are categorized according to severity: CIN I, CIN II, and CIN III.

With CIN I, there are mild abnormalities that rarely develop into cervical cancer. This condition may progress if untreated but often goes away without treatment.
In CIN II, the lesions often appear more aggressive under the microscope and may turn into cancer unless treated.
CIN III is the most aggressive form of dysplasia. If not removed, there is a high chance that it will turn into invasive cancer. CIN III includes carcinoma in situ (CIS). CIS is an early stage of non-invasive cancer -- the cells are confined within the tissue where they grew and have not yet invaded surrounding tissue. However since CIS can progress to invasive cancer, this condition should be treated as soon as possible.

Click the icon to see an image of cervical dysplasia.

The cells of the epithelium rest on a very thin layer called the basement membrane. Invasive cervical cancer occurs when cancer cells in the epithelium cross this membrane and invade the stroma, the underlying supportive tissue of the cervix.

In later stages, the original cancer may spread to areas surrounding the uterus and cervix or near organs such as the bladder or rectum. It may also spread to distant sites in the body through the bloodstream or the lymph nodes.

Causes

The human papillomavirus (HPV) has been detected in virtually all invasive cervical cancers and has been confirmed as the major cause of this cancer.

How HPV Is Transmitted. HPV is spread primarily by having sex with an infected partner. Most sexually active young women become infected with this virus, but only 10% remain infected for more than 5 years. Only those infected for longer than 5 years have a higher risk (about 50% above normal). Other factors are then needed to trigger the disease.

How HPV Contributes to Cervical Cancer. Researchers believe that most cervical cancers develop when various aggressive genetic HPV strains activate certain oncogenes (cancer-causing genes). Oncogenes called E6 and E7 are particularly important because they interfere with certain protective proteins, such as p53 and pRb, respectively. Under normal conditions, these proteins limit cell growth. Once they are blocked, cell growth can run rampant, leading to tumor development and cancer.

HPV Genetic Types. More than 30 genetic variants of human papillomaviruses can be passed through sexual contact form one person to another. The severity, however, varies widely according to genetic type. (Women initially infected by one type of HPV are still at risk for infection from other types.)

In women with cervical intraepithelial neoplasia I , the HPV viruses that are present are often types 6 and 11, which are low risk. Other low-risk HPV genetic types are 40, 42, 43, 44, 54, 61, 70, 72, and 81. These viral types often produce genital warts (condylomata) that rarely lead to cancer. (These warts usually affect the woman's genitals, the vagina, and vulva, rather than the cervix.)

Of the high-risk types, HPV types 16 and 18 have long been known to be particularly dangerous. These two genetic types and six others (31, 33, 35, 45, 52, and 58) account for 95% of HPV-related cervical cancers. Other high-risk types are 39, 51, 56, 59, 68, 73, and 82. All are associated with moderate cervical intraepithelial neoplasia II and cervical intraepithelial neoplasia III. Types 26, 53, and 66 are also considered high-risk.

In 2007, several studies indicated that HPV-16 infection in the mouth is associated with increased risk for oropharyngeal cancer. (Oropharyngeal cancer develops in the throat, just behind the mouth. It includes the base of the tongue, soft palate, tonsils, and side and back walls of the throat.) Prior to this research, alcohol and tobacco were thought to be the main risk factors for this type of cancer. According to the studies, oral sex (both fellatio and cunnilingus) significantly increases the risk of HPV-16 transmission and, therefore, the risk of developing oropharyngeal cancer. While the risk of HPV-16 causing oropharyngeal cancer is lower than the risk of it causing cervical cancer, experts think that the HPV vaccine may help reduce the incidence of throat, tonsil, and tongue cancers, as well as cervical cancer.

High-risk types of HPV have also been associated with an increased risk for other cancers, including other genital and lung cancers. The high-risk viruses generally produce flat and nearly invisible growths, compared to the usually harmless warts caused by low-risk HPV viruses.

Herpes viruses. Certain herpes viruses, including herpes simplex virus 6, 2, 7, and cytomegalovirus, have been detected in women with cervical cancer. herpes simplex virus 6 is under particular suspicion for playing a role in activating the papilloma virus gene. The presence of these very common viruses, however, may simply be coincidental, and they may serve no purpose other than being bystanders.

Chlamydia Trachomatis. Studies are finding an especially strong association between the incidence of Chlamydiatrachomatis, a sexually transmitted infection, and HPV. (Chlamydia trachomatis should not be confused with Chlamydia pneumoniae, a common cause of mild pneumonia in young adults. Chlamydia pneumonia e is not associated with cervical cancer.)

Other Sexually Transmitted Diseases. Other sexually transmitted diseases that have been associated with cervical cancer include HIV and gonorrhea. These infections, however, also may only be markers of increased sexual activity and may not themselves cause cancer.

Risk Factors

According to the American Cancer Society, about 11,150 new cases of invasive cervical cancer will be diagnosed in the U.S. in 2007. However, the number of new cervical cancer cases has been declining steadily over the past decades. Fifty percent of cervical cancer diagnoses occur in women ages 35 - 55, and slightly more than 20% occur in women over 65 years of age.

Some women (15%) develop cervical cancer before the age of 30. Although cervical cancer is rare in women under age 20, cancer rates in younger women are on the rise. Many young women are infected with multiple types of human papillomavirus, which can increase their risk of getting cervical cancer. Young women with early abnormal changes who do not have regular examinations are at high risk for localized cancer by the time they are age 40, and for invasive cancer by age 50.

Although it is the most preventable type of cancer, cervical cancer is ranked as the second most common cause of female death. Each year it kills an estimated 3,700 women in the U.S. and nearly 300,000 women worldwide.

In the United States, cervical cancer mortality rates plunged by 74% from 1955 - 1992 thanks to increased screening and early detection with the Pap test.

Although the rate of cervical cancer has declined in both Caucasian and African-American women over the past decades, it remains much more prevalent in African-Americans -- whose death rates are twice as high as Caucasian women. Hispanic American women have more than twice the risk of invasive cervical cancer as Caucasian women, also due to a lower rate of screening.

These differences, however, are almost certainly due to social and economic differences. Numerous studies report that high poverty levels are linked with low screening rates. In addition, lack of health insurance, limited transportation, and language difficulties hinder a poor woman’s access to screening services. Researchers are investigating programs that provide screening and treatment for women with abnormal Pap smears in a single visit.

The human papilloma virus (HPV) is the primary cause of cervical cancer. According to a 2007 study in the Journal of the American Medical Association, about 1 in 4 U.S. females ages 14 - 59 are infected with HPV. The prevalence of HPV is highest (45%) in women age 20 - 24.

The risk for cervical cancer in infected women appears to be highest in those infected with HPV for more than 6 months. In most people, the virus goes away within a year. However, it persists in about 10% of infected women.

High Sexual Activity. In adults, the most important risk factor for HPV is sexual activity with an infected person. Women most at risk for cervical cancer are those with a history of multiple sexual partners, sexual intercourse at 17 years or younger, or both. A woman who has never been sexually active has a very low risk for developing cervical cancer. Sexual activity with multiple partners increases the likelihood of many infections in addition to human papilloma virus.

Douching. Women who douche on a weekly basis are more likely to contract cervical cancer than those who do not. Douching may destroy the natural antiviral substances normally present in the vagina, making women more susceptible to HPV.

Pessaries. Use of a pessary (a ring-shaped plastic device that keeps the vagina and uterus from collapsing) increases the risk of chronic inflammation and viral infection at the insertion site and therefore may increase the risk for cervical cancer.

Risk Factors for HPV in Children and Infants. HPV also can occur in children and even newborns. The virus may also be transmitted by an infected mother. In children, HPV is usually the harmless form that cause skin warts.

In one analysis, 15 - 20% of women with cervical cancer had at least one close relative with the disease. Two studies have also reported that in families with cervical cancer there have also been higher rates of other human papilloma virus-related and smoking-associated cancers. Inherited factors in such cases most likely cause changes in the immune system that make such people more susceptible to human papilloma virus or other viruses.

Several studies, including a major analysis, have reported a strong association between cervical cancer and long-term use of oral contraception (OC). Women who have taken OCs for more than 10 years have a much higher risk of human papilloma virus (HPV) infection (up to four times higher) than those who do not use OCs. (Women taking OCs for fewer than 5 years have no significantly higher risk.) The reasons for this risk from OC use are not entirely clear. Women who use OCs may be less likely to use a diaphragm, condoms, or other methods that offer some protection against sexual transmitted diseases, including HPV. Some researchers also suggest that the hormones in OCs might help the virus enter the genetic material of cervical cells.

Studies indicate that having many children increases the risk for developing cervical cancer, particularly in women with human papilloma virus.

Smoking is associated with a higher risk for precancerous changes (dysplasia) in the cervix and for progression to invasive cervical cancer. Smoking may cause human papilloma virus (HPV) to grow faster and increase its likelihood of causing cancer. According to a 2006 study, women smokers who have HPV-16 are 14 times more likely to develop cervical pre-invasive cancer than smokers who do not have the virus. By contrast, non-smokers with HPV-16 were only 6 times more likely to develop cancer than those who were not infected.

Secondhand smoke is also linked to increased risk for cervical cancer tumors. It is not clear if this association is due to cigarette smoke’s direct cancer-causing effects or general damage to the immune system. Cigarette smokers are also deficient in folate, a B vitamin. Folate deficiency may play a role in the development of dysplasia.

Diethylstilbestrol. From 1938 - 1971, diethylstilbestrol, an estrogen-related drug, was widely prescribed to pregnant women to help prevent miscarriages. The daughters of these women face a higher risk for cervical cancer, genital tract abnormalities, and miscarriage.

Environmental Chemicals. Long-term exposure to certain types of agricultural and industrial chemicals may increase the risk for cervical cancer.

Prognosis

The following are some examples of the time it takes for early stages of cervical dysplasia to progress to the next stage:

Only about 1% of untreated mild cervical dysplasia (CIN I) cases progress to severe dysplasia or cancer each year.
In women with untreated moderate dysplasia (CIN II), 16% will progress to the next stage in 2 years, while 25% will progress after 5 years.
Most untreated pre-invasive cancer will develop into invasive cancer over a period of 10 - 12 years.

Over the past 30 years, the death rate from cervical cancer has declined significantly. In general, 71% of women with invasive cervical cancer survive for 5 years or more. African-American women tend to have poorer 5-year survival rates than Caucasian women, although survival rates have significantly increased in African-American women in recent years.

The outlook for specific women varies depending on different factors:

In women who receive treatment when cervical cancer is still local, the cure rate is about 90%. Experts say universal screening could essentially reduce the cervical cancer death rate to zero. Still, only 12 - 15% of women have routine Pap smears. As a result, only 55% of Caucasian women and 44% of African-American women are diagnosed at early stages.
If the cancer cells have spread beyond the cervix, the average 5-year survival rates may drop to 50% and below, depending on how much it has spread and the type of cancer cell.

Identifying what type of human papilloma virus (HPV) a woman has may help determine outlook and the severity of cervical cancer. For example, HPV-18 and HPV-16 are associated with severe cases. HPV-16 has also been linked to a rare form of cervical and uterine cancers.

Other biochemical markers in the body may also help predict outcome and treatment. For example, women with cervical cancer who have high levels of an enzyme called cyclooxygenase (COX-2) may need more aggressive treatments than those with low levels.

The treatments for advanced cervical cancer also add to the emotional burden in premenopausal women, because they nearly always prevent future childbearing.

Symptoms

Most women with dysplasia or pre-invasive cancer have no symptoms. Screening tests, therefore, are very important.

When the cancer becomes invasive, unusual bleeding can occur. Bleeding may stop and start again between regular periods or there may be bleeding after menopause. Unexpected bleeding can also occur after intercourse or a pelvic exam. Periods sometimes last longer or are heavier than usual. Increased vaginal discharge may be noticeable as well. Pelvic pain can occur, but it is not common.

These symptoms are not exclusive to cervical cancer. Sexually transmitted diseases, for instance, can cause similar symptoms.

Prevention

The best way to prevent cervical cancer is to avoid getting infected with human papilloma virus (HPV). Because HPV is sexually transmitted, practicing safe sex and limiting the number of sexual partners can help reduce risk. A vaccine can protect against the major cancer-causing HPV strains. Regular Pap tests remain the most effective way of preventing the development of invasive cervical cancer.

In 2006, the FDA approved the first human papilloma virus (HPV) vaccine to prevent cervical cancer. Gardasil has been tested in more than 12,000 uninfected girls and women in 13 countries. Studies show it provides nearly 100% protection against HPV-16 and HPV-18, the viruses that cause 70% of cases of cervical cancer. Gardasil also protects against HPV-6 and HPV-11, which cause 90% of cases of genital warts.

Gardasil is approved for girls and women ages 9 - 26. Current immunization guidelines recommend:

Routine vaccination for girls ages 11 - 12 years. The vaccine should be administered in 3 doses, with the second and third doses administered 2 and 6 months after the first dose. The HPV vaccine can be given at the same time as other vaccines.
Girls as young as age 9 can receive the vaccine at their doctors’ discretion.
Girls and women ages 13 - 26 who have not been previously immunized or who have not completed the full vaccine series should get vaccinated to catch up on missed doses. [The U.S. Advisory Committee on Immunization Practices (ACIP) and the American Academy of Pediatrics (AAP) recommend catch-up doses for ages 13 - 26. The American Cancer Society (ACS) recommends catch-up for ages 13 - 18. The ACS suggests that women ages 19 - 26 discuss with their doctors the relative risks and benefits of vaccination.]
Women should not get the vaccine during pregnancy.

The HPV vaccine can only prevent -- not treat -- HPV infection, genital warts, and cervical cancer. Because the vaccine cannot protect females who are already infected with HPV, doctors recommend that girls get vaccinated before they become sexually active. Several 2007 studies indicated that the vaccine is nearly 100% effective in preventing cervical cancer and genital warts when given prior to HPV exposure. However, young women who are sexually active may still derive some benefit from the vaccine, at least for protection against any of the four HPV strains that they have not yet acquired.

The FDA is considering approving another type of cervical cancer vaccine (Cervarix). Cervarix protects against HPV-16 and HPV-18, as well as the cancer-causing strains HPV-31 and HPV-45. It does not protect against genital warts.

The FDA is not yet sure how long Gardasil’s protection lasts or when patients may need a booster shot. A 2006 study of the Cervarix vaccine found that protection lasted for at least 4.5 years.

These vaccines do not protect against all types of cancer-causing HPV. The FDA still recommends that women receive annual screening to detect any early signs of cervical cancer. For girls and women who have been sexually active before they receive the vaccine, screening still provides the best protection against cervical cancer.

Use of barrier contraceptives such as condoms is associated with a reduced risk of cervical cancer, even in women already infected with human papilloma virus (HPV). HPV can exist outside the area protected by the male condom, so this method is not foolproof in preventing an initial infection. However, a 2006 New England Journal of Medicine study found that when men used condoms every time they had sexual intercourse, their female partners had less than half the rate of HPV infection as women whose partners used condoms less than 5% of the time. The female condom is becoming increasingly popular in developing countries. It may prove to be particularly effective against sexually transmitted diseases in these regions.

A 2002 study reported that men who are circumcised have a lower risk for carrying human papilloma virus (HPV) and therefore reduce the risk for cervical cancer in their female partners.

Some studies have suggested possible protective benefits against cervical cancer from certain vitamins.

High blood levels of vitamins E and C have been linked with lower rates of some cancers, including cervical cancers.

Although vitamin E is a fat-soluble vitamin, there are no known toxic effects of megadoses.

Click the icon to see sources of food which contain vitamin E.

Click the icon to see the benefits of vitamin C.

Click the icon to see sources of food which contain vitamin C.

Folic acid, a B vitamin, prevents birth defects and may also lower the risk for development of dysplasia (precancerous changes) leading to cervical cancer. It is not clear how strong this association is, or why this would occur. Some evidence points to its actions in reducing levels of homocysteine, a compound associated with a higher risk of cervical cancer.

There is no definitive evidence, however, that taking vitamins can prevent any cancer. Eating healthy foods rich in such vitamins and other important nutrients is, in any case, the best approach for overall good health.

Diagnosis

The changes that lead to cervical cancer develop slowly. Screening tests performed during regular gynecologic examinations can detect early changes.

Every year in the U.S. about 50 million women have a Papanicolaou test (the Pap smear). Use of the Pap smear has reduced the annual death rate from cervical cancer from 26,000 in 1941 to 3,700 in 2005.

Forty percent of women who have a Pap smear fail to follow-up for retesting and treatment. Most cases of cervical cancer occur in women who have not had regular Pap tests.

The Procedure. The most accurate test results are obtained 12 - 14 days after menstruation begins. Women should not douche or have intercourse within 48 hours of the test. Douches and spermicidal creams may clean out abnormal cells and interfere with the results of a Pap smear. (In general, douching is not recommended at all.) A Pap smear is usually painless, although some women may have some discomfort.

The test is done in a doctor's office. The woman removes her clothes from the waist down and puts on a medical gown. She lies on her back on the examination table, bends her knees, and puts her feet in supports (called stirrups) at the end of the table.
A doctor inserts a metal device into her vagina to widen it.
Using a spatula, brush, or both, the doctor gently scrapes the surface of the cervix, and sometimes the upper vagina, to gather living cells. The doctor will also obtain cells from inside the cervical canal. Such cells include squamous and glandular cells and those that lie higher up in the cervical canal (known as the endocervix). Using both a brush and spatula helps gather better samples to detect the presence of cancer.
The cells are preserved, stained for microscopic viewing, and then analyzed under a microscope by a specialist known as a cytopathologist.

A Pap test is a simple, relatively inexpensive procedure that can easily detect cancerous or precancerous conditions.

Reliability and Accuracy. Over the course of a lifetime of regular screening, a woman faces a 40% chance of being told her Pap smear is abnormal. The Pap smear is not, however, a perfectly reliable measure of a woman's risk for cervical cancer.

In general, about 10% of Pap smears have abnormal results, but only about 0.1% of the women who have these results actually have cancer. In most cases, abnormal cells are low grade and not likely to progress to cancer or are due to benign conditions, including natural cell changes after menopause.

No test is 100% accurate, and it is possible for the Pap smear to miss the presence of cancer. However, if abnormal cells are missed on one test they are likely to be spotted during the next one without a significant danger.

Newer, thin-layer liquid based tests (ThinPrep, SurePath) use the original cervical sample, which is rinsed in a special solution to thin the mucus (rather then dried). The result is a clear, clean sample that may be able to accurately reveal abnormal cells. The fluid can also be examined for evidence of human papilloma virus (HPV) and other early abnormalities. Some -- but not all -- studies have found this test to be more accurate than the standard Pap smear. A rigorous 2006 review of 56 studies found that liquid-based tests were no more accurate than conventional Pap smears.

The U.S. Preventive Service Task Force (USPST), the American Cancer Society (ACS), and the American College of Obstetricians and Gynecologists (ACOG) have all released guidelines for cervical cancer screening. ACOG and ACS have established separate screening criteria for women below and above 30 years of age. Although there are some small differences between these three sets of guidelines, they generally make similar recommendations as summarized below:

Recommendations for Initial Screening. Women should begin to undergo Pap tests within 3 years of onset of sexual activity or at age 21 (whichever comes first).

Women with no history of sexual activity should still have Pap smears. They are at low risk for squamous cell carcinoma, but adenocarcinoma (cancer that occurs in cervical glands) can occur, although this is very uncommon.

Women Up to Age 30. Women under age 30 should receive annual screening with the conventional Pap smear. The American Cancer Society (ACS) offers the alternative of screening every 2 years using the newer liquid-based testing. HPV testing is not recommended for this age group because HPV infections in women under age 30 tend to resolve on their own.

Women Age 30 and Over. Women in this age group who have received three consecutive negative (normal) annual Pap tests have two screening options:

Screening with standard or liquid-based Pap tests every 2 - 3 years. Women in high-risk groups (DES exposure, HIV infection, weakened immune system, or previous diagnosis of cervical cancer) should continue to receive annual tests.
Screening with Pap test plus HPV DNA test. If a woman tests negative on both of these tests, then she can be rescreened no more frequently than once every 3 years. If one of the tests is positive, she will need to be screened more frequently.

Elderly Women. In its 2003 guidelines, the U.S. Preventive Service Task Force recommended against routine screening in women over age 65 with low or no risk factors. (The ACS recommends stopping at age 70, while the American College of Obstetricians and Gynecologists declines to set an upper age limit.) Such women have had at least three previous normal screenings and have had no abnormal results for at least 10 years. According to the guidelines, older women should be screened if they have not been screened before or if there is a possibility that they have not been screened (for example, if the woman is from a country that does not do routine screening). However, a 2006 study of more than 15,000 postmenopausal women recommended continued screening for elderly women who are sexually active but not monogamous. (Women in the study had a uterus.) The researchers note that about 25% of new cervical cancer cases, and 41% of cervical cancer deaths, occur among women 65 years and older.

After a Hysterectomy. The 2003 guidelines recommend against routine screening for women who have undergone a total hysterectomy for benign causes. Women who have had a hysterectomy that preserves the cervix (called a supracervical hysterectomy) should continue with Pap screening.

If Pap smear results are normal for 3 consecutive years, most expert groups recommend a Pap test every 2 - 3 years thereafter in most women over 30 years of age. (The American Cancer Society suggests that such women wait until they are 30 before extending the interval to 3 years.)

Both the American Cancer Society and the American College of Obstetricians and Gynecologists recommend that annual screening should continue in women in high-risk categories. High risk categories may include the following, depending on the medical group:

Women who have had multiple sexual partners or whose male sexual partners have had multiple partners.
Women who engaged in sexual activity at a young age.
Women whose male sexual partners have had other sexual partners with cervical cancer.
Women with current or prior HPV infection.
Women who are HIV-positive or who are immunosuppressed.
Women with a history of sexually transmitted diseases.
Smokers and substance or drug abusers.
Women who have a history of cervical dysplasia or cervical, endometrial, vaginal, or vulvar cancer.
Women in lower socioeconomic groups, particularly if they have not been able to obtain regular gynecologic screening and care.

Any abnormal result, even a mild abnormality, requires follow-up visits and additional tests. The extent of these tests depends on the degree of abnormalities.

New tests and methods have been developed to improve the accuracy of the Pap smear in detecting cancer cells. For example, there are several computerized Pap test systems (FocalPoint, PAPNET) that are used to rescreen the original smear. These systems are either used to detect abnormal samples that may have been missed by manual review methods or are used in place of a human cytotechnologist. According to the U.S. Preventive Services Task Force (USPSTF), there is not yet enough evidence to know whether or not computerized methods are superior to conventional Pap testing.

There are tests for identifying the high-risk types of human papilloma virus (HPV) that are known to cause cervical cancer. The presence of these types is a strong predictor of high-grade aggressive abnormalities or cancer itself. Testing for HPV does not replace the Pap smear, but when used adjunctively with the Pap test this screening combination may help to more accurately detect cervical cell abnormalities than either test alone.

In 2003, the FDA approved the Hybrid Capture 2 (HC2) HPV DNA test for use with the Pap test for cervical cancer screening in women over 30 years of age. The HPV DNA test can identify 13 types of the high-risk HPV that are most frequently implicated in the development of cervical cancer. At this time, the test is recommended as an adjunct to the Pap test but not as the sole method for primary screening.

Other screening tests are being investigated for use in combination with the Pap smear for improving accuracy. For example, combinations with human papilloma virus (HPV) DNA tests or cervicography may prove to be more effective for detecting cervical intraepithelial neoplasia I and II dysplasia (potentially invasive cells) than Pap smears alone.

Cervicography. Cervicography uses a photograph of the cervical region (a cervigram), which is then highly magnified and examined. It may prove to be a useful companion to a Pap test, particularly in high-risk younger women. It is painless, easy to use, provides documentation of the area, and is highly sensitive to abnormal changes. (It also, however, picks up abnormalities that are not cancerous.)

Acid Test. A diluted solution of acetic acid (similar to vinegar) is applied to the cervix. When viewed through a special green lens, this solution makes abnormal cells look white, whereas normal cells appear pink. Skilled doctors may also be able to spot abnormal blood vessel patterns indicative of cancer areas on the cervix. This is an inexpensive and simple test.

Fluorescence Spectroscopy. Small noninvasive probes that can be swept across the surface of the cervix to detect cancer are showing promise as an effective screening tool for cervical cancer. One probe emits a laser light. The head of the probe catches the return signals from the woman's cervical cells and compares them with a computer library of cancer cells. In one comparison test, fluorescent spectroscopy was more accurate than the Pap smear but not as effective as other screening methods.

Other Investigative Tests. Experts are working on an antibody-based method for improving the identification of true cancerous cells in a cervical smear, which could significantly reduce the need for expensive and distressing tests in women who do not actually have cancer. In addition, they are looking for biologic markers to improve diagnosis, such as specific proteins that indicate the presence of cancer cells.

The cells viewed in a cervical smear sample are classified on a scale representing the spectrum of cell changes from normal to cancerous. The smear is first characterized as either "normal" or "abnormal."

Once abnormal cells are identified, the doctor must decide whether the patient needs only repeat Pap smears, a test for the human papilloma virus (HPV) virus, or colposcopy (a procedure used to magnify the cervix and permit detection of lesions for biopsy). To help the doctor make the decision, the abnormal cells are divided into categories, depending on the degree of abnormality. These classifications are based on the 2001 Bethesda System (TBS), which is formulated to standardize the reporting of Pap test results.

Atypical Squamous Cells. Atypical squamous cells (ASC) are mildly abnormal cells on the surface of the cervix. They may simply represent inflammation. Over 80% of these cells normalize, but unfortunately, between 5 - 17% of these women have a chance for having cervical intraepithelial neoplasia II and III dysplasia (potentially invasive cells). Researchers have further categorized atypical squamous cells as the following:

ASCUS. These atypical squamous cells of undetermined significance are the lowest risk abnormal cells. Women with these cells should be tested for human papillomavirus infection (HPV). If results indicate they are infected with HPV, they should receive colposcopy, a more invasive diagnostic procedure, to determine if the condition is actually at a more aggressive stage. If they do not have HPV they are simply monitored with repeat Pap smears.
ASC-H. This category refers to the presence of atypical squamous cells, but a doctor cannot exclude possible high-grade squamous intraepithelial lesions. Such women have a 24 - 94% chance of having cervical intraepithelial neoplasia II and III. All are referred for colposcopy.

Among those with atypical squamous cells, immunosuppressed women and those with high-risk human papilloma virus infections are at higher risk for cervical intraepithelial neoplasia II and III and should always be given colposcopy. Postmenopausal women with normal immune systems have a lower risk than younger women. It should be strongly noted, however, that actual risk for cervical cancer in general in women with atypical squamous cells is only 0.1 - 0.2%.

Low Grade Squamous Intraepithelial Lesions. Low-grade squamous intraepithelial lesions (LSIL) are typically associated with human papilloma virus changes, with or without early dysplasia. Between 15 - 30% of women with LGIL, however, may have cervical intraepithelial neoplasia II or III on biopsy. Women with LSIL are either monitored with repeat Pap smears or given colposcopy. Doctors recommending colposcopy argue that these are high-risk women who risk delaying a diagnosis of cancer using only repeat Pap smears.

High-Grade Squamous Intraepithelial Lesions. High-grade squamous intraepithelial lesions (HSIL) are associated with moderate dysplasia and other cervical intraepithelial neoplasia II or III. Such women are always referred to colposcopy for biopsy. Even if colposcopy results report only cervical intraepithelial neoplasia I, over a third of these women are likely to have cervical intraepithelial neoplasia II or III. Experts, therefore, recommend a careful review of the tests in such cases. Pregnancy poses a problem since it increases the chance in HSIL for both normal and abnormal results. In nonpregnant women, particularly when fertility is not an issue, immediate treatment with loop electrosurgical excision procedure may be appropriate.

Atypical Glandular Cells. Atypical glandular cells are uncommon, but pose a higher risk for cancerous changes than atypical squamous cells or low-grade squamous intraepithelial lesions. Between 9 - 54% have some cervical intraepithelial neoplasia, 0 - 8% have pre-invasive cancer, and 1 - 9% have invasive cancer. Doctors recommend that the next step should be a colposcopy (rather than a repeat Pap smear).

The Pap smear shows only the presence of abnormal cells. It is useful simply as a screening test that identifies women who may have preinvasive or early cancerous changes. For a definitive diagnosis, the next step is usually colposcopy, during which the cervix is visualized under low power magnification. The surgeon takes samples of suspicious cells for biopsies. A biopsy will determine the stage of the precancerous growth or whether invasive cancer is present.

The Procedure. Colposcopy can be performed in a doctor's office without anesthesia in 10 - 15 minutes. It causes about as much discomfort as mild menstrual cramps:

First, using a speculum to keep the vagina open, the doctor aims a light at the cervix.
The doctor then looks through the eyepiece of a special microscope, known as a colposcope, to view the cervix. (Some colposcopies include a TV attachment that transmits the picture to a nearby monitor for easier viewing.)
A biopsy (a sampling of the tissue) is taken of suspicious areas, of the endocervical canal (the inner part of the cervix and uterus), and any abnormal-looking areas. This may cause cramping or pinching.

Click the icon to see an image of a colposcopy-directed biopsy.

After the colposcopy, the woman may have a brownish discharge from an iron solution called Monsel's solution, which the doctor applies to prevent bleeding. The doctor usually advises sexual abstinence for 1 - 2 weeks.

Follow-Up Procedures. Women with evidence of cervical intraepithelial neoplasia (CIN) or cervical cancer require treatment. Women with biopsies that show low-grade abnormal cells (LGSIL), but whose cervix is otherwise normal, are generally given follow-up colposcopies.

Treatment for Cervical Intraepithelial Neoplasia and Pre-invasive Cancer

Treatment of cervical intraepithelial neoplasia (CIN), including pre-invasive cancer, depends on the type and extent of abnormal changes. Some of the treatments for CIN are also used for early-stage cancer.

CIN I often goes away on its own. Careful follow up is required to make certain that the Pap smear and colposcopic exam return to normal.
CIN II or CIN III may turn into invasive cancer if the suspicious area is not removed. This is often done using an outpatient technique called loop electrosurgical excision procedure (LEEP). [See next section.]
If doctors cannot see extensive areas of CIN II or III with colposcopy or if they sthese areas pread into the mucous membrane in the cervical canal, a more aggressive procedure called conization (cone biopsy) may be required.

The cold cone biopsy is a surgical procedure that requires general anesthesia. It is performed when there are severe precancerous changes in the cervix.

Treatment for Adenocarcinoma. An adenocarcinoma is cancer inside tissue that looks like or functions as a gland. (A gland is a group of cells that secretes a substance to be used by or removed from the body.) Adenocarcinomas tend to be more aggressive than the more common pre-invasive cancer, which grows in the lining of tissue (mucous membrane). Some evidence suggests that adenocarcinomas develop in numerous sites rather than a single location. Hysterectomy is generally recommended. For women who wish to retain fertility, a docotor may perform a cone biopsy, although this procedure sometimes causes sterility and it does not always remove all adenocarcinomas.

Follow-Up. Patients treated for CIN need to be monitored. Testing for human papilloma virus (HPV) may prove to be useful in determining whether repeat colposcopies may or may not be needed. One study strongly suggested that if both HPV and Pap smear tests are normal on two consecutive visits, treatment most likley was successful. If either the HPV or Pap smear is abnormal, it may be reasonable to consider another colposcopy.

Loop electrosurgical excision procedure (LEEP), also called large loop excision of the transformation zone (LLETZ), uses a high frequency electrical current to cut away diseased tissue.

A local anesthetic is applied to the cervix, and a wire loop is inserted into the vagina.
A button-sized slice of tissue is removed from the cervix for examination.
A deeper slice is used to evaluate the endocervical canal.

The procedure is done in one office visit. Extensive and deep sections of damaged tissue can be effectively removed in this visit. Disease can be cured in one treatment. When used for dysplasia, it appears to be as effective as more invasive procedures.

The only downside of LEEP may be its simplicity. Doctors may be tempted to use it for more serious conditions best treated by a procedure called conization. It also may impair the ability to detect hidden invasive cancer. Patients should be monitored closely if the biopsies on the cervical tissue removed by LEEP suggest that the cells may become invasive.

LLETZ is becoming increasingly popular as a treatment for cervical intraepithelial neoplasia. However, women of child-bearing age should be aware that it may later cause pregnancy problems, such as preterm delivery and low birth weight. Women who have this procedure may also be more likely to break their water too early (premature rupture of membranes).

Conization is a surgical procedure that removes suspicious sections of cells covering an abnormally large area, or those extending into the cervical canal. Conization is preferred over Loop electrosurgical excision procedure (LEEP) or large loop excision of the transformation zone (LLETZ) for lesions that are so big they require a larger biopsy for their complete removal. As in LEEP, patients should be monitored closely if patients are infected with human papilloma virus (HPV) virus or the biopsies on the cervical tissue removed show aggressive-grade cells.

The surgery can be performed under general anesthesia in the operating room with either traditional surgical instruments or lasers.

A technique called frozen section examination (FSE) freezes the margins of the area being removed. Studies suggest that FSE allows immediate and precise evaluation of areas that may harbor invasive cancer cells, and may be an important addition to this procedure in women with high-grade cervical intraepithelial neoplasia.

With conization, the ability to become pregnant can be preserved in many (but not all) cases. In women who do become pregnant, some studies have indicated that this procedure increases the risk for low-birth weight infants, so careful prenatal care is essential. Conization can also increase the risk for preterm delivery and Cesarean section. Patients who have this treatment must have follow-up evaluations.

Cryosurgery is not usually feasible for large abnormal areas. The procedure removes abnormal, but noncancerous, tissue by freezing it. Cryosurgery can be performed in a doctor's office in 15 minutes without medication.

The vagina is opened with a speculum and a probe transmits gas (either nitrous oxide or carbon dioxide), which freezes the surface of the cervix.
The gas is applied for 3 minutes or until ice crystals form on the targeted tissue.
After waiting 3 minutes, freezing can be repeated for another 3 minutes.

Click the icon to see an image of cervical cryosurgery.

Side effects from this procedure include cramping, sometimes painful, for a few hours or days and a heavy, watery discharge for 2 - 4 weeks. The discharge can be irritating, have a bad odor, and may be blood-tinged. Symptoms that may indicate serious complications are fever and chills, heavy clotted bleeding, or extreme pain in the abdomen or back.

The patient may have a temporary change in menstrual periods. The menstrual periods may be heavier or lighter, or come later or earlier. Tampons, douching, bathing, swimming, and intercourse should be avoided for several weeks after cryosurgery to prevent infection.

Patients who have this treatment must be willing to commit to regular follow-up examinations.

Treatment for Cervical Cancer

In contrast to cervical intraepithelial neoplasia, cervical cancer represents true invasion of cells beyond the epithelium into surrounding tissue. Cervical cancer may be detected in a biopsy performed during colposcopy for an abnormal Pap smear, or it may be visible to the naked eye when the doctor performs a speculum exam.

Imaging Tests to Determine Extent of Tumor Spread. If a biopsy detects invasive cancer, the patient will need additional tests to find out how far the cancer has spread. How fart the cancer has spread determines whether the cancer is operable.

An abdominal computed tomography (CT) scan is commonly used to check for spread of the disease to lymph nodes and areas around the pelvic area.

In computed tomography (CT), a thin x-ray beam rotates around the area of the body. Using very complicated mathematical processes called algorithms, a computer is generates a 3-D image of a section of the body.

Other procedures may be used to find out if cancer has spread to areas around the uterus. X-ray images are taken of the bladder and urinary system (known as intravenous pyelography, or IVP) or of the lower intestinal tract (known as a barium enema).

Click the icon to see an image of intravenous pyelography.

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

If these tests detect cancer in any of these surrounding sites, the patient will need more tests :

Cystoscopy is performed to examine and take tissue from the bladder for biopsy.

Click the icon to see an image of cystoscopy.

Sigmoidoscopy is used to evaluate the rectum. (In this procedure and a cystoscopy, a tube with a lighting device is inserted to view internal areas.)

Click the icon to see an image of sigmoidoscopy.

Magnetic resonance imaging (MRI) is a sensitive and noninvasive procedure that is occasionally useful for finding tumors in the tissues surrounding the uterus.

Click the icon to see an image of a MRI.

Sentinel Node Biopsy. One technique is called a sentinel node biopsy. It has been used in patients with breast cancer to help determine if cancer has spread beyond the lymph nodes. It is now being investigated for patients with early cervical cancer and may be helpful in determining which patients need to have lymph nodes removed in their pelvic area:

The procedure uses an injection of a tiny amount of a blue dye, into the tumor site.
These substances then flow via the lymphatic system into the sentinel node. This is the first lymph node to which any cancer would spread.
The sentinel lymph node and possibly one or two others are then removed.
If these nodes do not show signs of cancer, the rest of the lymph nodes may be cancer-free, making further removal of lymph nodes unnecessary.

After making a diagnosis, the doctor will classify the stage of the cancer according to how far the disease has spread into the lining of the cervix, throughout the cervix, or beyond. Doctors use these classifications to determine treatment and outlook.

Patients who have been diagnosed with cervical cancer need to know the normal treatments for their particular stage, so they may compare their doctor's suggestions with these norms.

Stage 0 is pre-invasive cancerconfirmed by biopsy and confined to the first layer of cervical tissue (the epithelium). Treatment options include loop electrosurgical excision procedure (LEEP), laser therapy, conization, and cryotherapy.

Stage I is invasive cancer, but the tumor is confined to the cervix. This stage is further categorized as IA and IB.

Stage IA. Five-year survival rates for stage IA can be 95% or more.

In stage IA1 cancer cells are microscopic, there is minimal invasion (less than 3 mm) into the supportive tissue around the cervix (the stroma), and the horizontal extent of the tumor is less than 7 mm. Treatment is usually a simple hysterectomy. Conization is sometimes possible for women who want to remain fertile and who have a nonaggressive tumor that has spread less than 3 mm, with no lymph or blood vessel involvement. Trachelectomy has been investigated for women who want to preserve fertility. More research is needed.
In stage IA2 there is deeper invasion (greater than 3 mm but less than 5 mm) and the horizontal extent of the tumor is less than 7 mm. Radical hysterectomy with surgical lymph node removal (lymphadenectomy) is a common treatment.

Note on Stage IA2 through IIA: Postoperative concurrent radiation and platinum-based chemotherapy may be considered for stages IA2 through IIA tumors if the following high risk features are found at the time of primary surgery: lymph node involvement, cancerous cells found in the margins of the tumor, and involvement of the parametrium.

Stage IB and Locally Advanced Cancer. Five-year survival rates for stage IB can be 80 - 90% with either radiation or surgery. Survival rates are lower if the cancer has spread to the lymph nodes.

In stage IB1 the tumor is typically visible (not usually microscopic), and the diameter may be up to 4 cm. Radical hysterectomy with pelvic lymph node removal (lymphadenectomy) is the recommended treatment. Primary radiation can be used instead of surgery in patients who eitehr are poor surgical candidates or do not plan on being sexually active.
In stage IB2 the tumor is more than 4 cm and considered "bulky." Relapse rates after surgery are higher than in stage 1B1. Primary treatment with radiation therapy with concurrent platinum-based chemotherapy is reasonable. Some women in stage IB may receive combinations of radiation and surgery, although the benefits of such combinations are unclear for most women, particularly given a higher risk for severe side effects.

Note on Locally Advanced Cervical Cancer: Stages IB2 through IVA are often referred to collectively as locally advanced cancer and are frequently treated similarly. Standard treatment includes radiotherapy with concurrent platinum-based chemotherapy. Experimental approaches for some women with locally advanced cervical cancer use radiation therapy with hyperthermia (high heat often provided by ultrasound) and neoadjuvant (preoperative) chemotherapy and radical surgery. More research is necessary.

Stage II invasive cancer has spread beyond the cervix, but it has not spread to the pelvic side wall. This stage is further categorized as IIA and IIB.

Stage IIA. Cure rates for stage IIA can be as high as 75 - 80% with either radiation or radical hysterectomy. Survival rates are lower if cancer has spread to the lymph nodes. In stage IIA, cancer has spread to the upper two thirds of the vagina but not to the parametrium (the connective tissue between the pelvic floor and upper part of the cervix). Radical hysterectomy with pelvic lymph node removal (lymphadenectomy) is the recommended treatment. Primary radiation can be used instead of surgery in patients who eitehr are poor surgical candidates or do not plan on being sexually active. If the tumor is bulky, however, primary treatment with radiation therapy with concurrent platinum-based chemotherapy is reasonable. Some women in stage IB may receive combinations of radiation and surgery.

Stage IIB. For stage IIB 5-year survival rates are about 60%. In stage IIB the cancer has spread to the parametrium. Recommended treatment is radiation therapy with concurrent cisplatin-based chemotherapy.

In stage III, the cancer is invasive, extending to the lower third of the vagina (stage IIIA) or to the side walls of the pelvis (stage IIIB). The kidney may be affected. Recommended treatment is radiation therapy with concurrent cisplatin-based chemotherapy. Five-year survival rates are about 40%.

In stage IV, invasive cancer has spread beyond the pelvis or to the mucosal lining of the bladder or rectum. Five-year survival rates are less than 20%.

Stage IV. In stage IVA, the cancer has spread to the inner lining of the bladder or rectum. Recommended treatment is radiation therapy with concurrent cisplatin-based chemotherapy.

Stage IVB. In stage IVB, the cancer has spread beyond the pelvis. Recommended treatment is radiation therapy to relieve symptoms and chemotherapy (usually cisplatin or carboplatin combined with other drugs such as topotecan). Platinum-based chemotherapy yields short-lived response in 20% of patients. Clinical trial participation is reasonable.

Cervical cancer may recur locally in the lymph nodes near the cervix, it may spread to distant sites, such as the lung or bones, or it may appear both locally and in distant locations.

Recommended treatment is pelvic exenteration if cancer has spread to only local areas. (This involves removal of the cervix, uterus, vagina, and perhaps the bladder, lower colon, or rectum. It is an aggressive surgical approach that may lead to cure in a small percentage of patients with recurrent cervical cancer.) Radiotherapy is another option if it is technically possible -- generally if patients did not have it previously. If cancer has spread, platinum-based chemotherapy is reasonable. Other drugs may be useful under certain circumstances.

Only 1% of cervical cancers occur during pregnancy or shortly afterwards. To diagnose the condition, a cervical biopsy, in which a small amount of tissue is removed for diagnosis, can be performed anytime during the pregnancy. However, a cone biopsy, which removes larger amounts of tissue, is typically delayed until after the first trimester to reduce the risk of abortion. Treatment options may be as follows:

If the abnormality is diagnosed as dysplasia or even pre-invasive cancer, treatment is sometimes delayed until a few weeks after the mother gives birth, and vaginal delivery may still be possible. The pregnant woman should discuss the risks and benefits of this approach, however, with her doctor.
If early-stage cancer is diagnosed in the late second or third trimester, a woman may sometimes be able to delay treatment until the baby is delivered. A Cesarean section is the preferred delivery method. The cancer treatment of choice is started shortly afterward.
More locally advanced invasive cancer is nearly always treated, particularly if is diagnosed within the first 20 weeks of the pregnancy.

Treatment for Invasive Cervical Cancer

Radiation therapy and surgery are about equally effective as a single option for treating very small cervical cancers in their earliest stages. Survival rates in the appropriate patients can be about 85 - 90%. Factors influencing the choice between radiation therapy and surgery in women with invasive cancer include the patient's age and health and the amount of cancer. Both surgery and radiation therapy eliminate the possibility of having children in premenopausal women.

Although treatments for cervical cancer have several potentially severe side effects, they are usually well-tolerated. Women undergoing any of these treatments should feel free to seek support groups and counseling, which can be as important for their outlook as medical therapies.

Surgery. Surgery almost always involves a hysterectomy, an operation that removes the uterus and sometimes other areas in the pelvic region as well. It does not, however, usually impair sexual activity.

In general, surgery is the better choice when small cancers are confined to the cervix in women who wish to remain sexually active.

Radiation. Radiation treatments to the pelvis often inhibit ovarian function. Early menopause often occurs. Radiation also may cause vaginal scarring. Treatments are available that may reduce these problems, and women should not be shy about discussing them with their doctor. Radiation therapy is usually the choice under the following circumstances:

Cancers have spread beyond the cervix to the pelvis, lower vagina, and urinary tract.
When certain tumor features indicate a high risk for recurrence after surgery.

Important studies now strongly suggest that radiation along with chemotherapy can improve survival rates improve in patients with stages IB to IVA compared to radiation alone. The benefits are greatest in stages I and II.

In the early stages of cervical cancer, surgery is often the preferred primary treatment approach since it preserves normal sexual function. Some patients desiring fertility who have early stage I cancer may be candidates for cervical cone biopsy.

Hysterectomy. A hysterectomy attempts to eliminate the cancerous tissue by removing the uterus. There are several variations of this operation, depending on the location of the tumor. In women of childbearing age, the ovaries can usually be left intact. Although a woman who has a hysterectomy but retains her ovaries cannot bear children, she will not go into premature menopause. (Studies indicate that leaving the ovaries intact is safe for most women and does not pose any greater risk for cervical cancer recurrence.)

A simple hysterectomy involves the removal of the uterus and the cervix, but leaves the parametrium (tissue surrounding the uterus) and vagina intact. Lymph nodes in the pelvis are not usually removed.

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

A radical hysterectomy removes not only the uterus and the cervix but also the parametrium, the supporting ligaments, the upper vagina, and some or all of the local lymph nodes (a procedure called lymphadenectomy).

If the cancerous tumor recurs within the pelvis after primary treatment, the patient may need a more extreme procedure called a pelvic exenteration, which combines radical hysterectomy with removal of the bladder and rectum. (In such cases, plastic surgery may be needed afterward to recreate an artificial vagina.) Patients undergoing this procedure are physically and psychologically screened in advance to determine whether it is an appropriate choice. The success rate for pelvic exenteration in halting the progression of the disease is about 25 - 45%.

Any form of hysterectomy is major surgery and requires at least a 3 - 5 day hospital stay. Although hysterectomy typically uses a wide abdominal incision, less invasive techniques that allow shorter recovery time may be possible for some women with early stage cancers if performed by experienced surgeons.

Side effects include difficulty emptying the bladder or bowels and a painful lower abdomen. Urinary tract infections are very common. Complications include fistulas (abnormal channels within the pelvis, which in this case are a result of surgery), bladder dysfunction, and cysts.

Normal activity, including intercourse, can be resumed in about 4 - 8 weeks. Once the uterus is removed, menstruation will cease. If the ovaries are removed, the symptoms of menopause will begin. These symptoms are likely to be more severe in surgical menopause than in natural menopause. The pateint should discuss the benefits and risks of hormone replacement therapy with her doctor.

Trachelectomy. An experimental procedure called trachelectomy is being investigated for preserving fertility in certain women in early-stage cervical cancer, but it is highly controversial and appropriate in only about 5% of patients. In the procedure, only the cancerous portion of the cervix is removed, while the uterus and the rest of the cervix are left intact. The cervix is closed with a suture.

The procedure is primarily performed outside the U.S., and few American surgeons are skilled in this surgery at this time. Throughout the world, in fact, only about a few hundred of these procedures have been performed to date. Larger and longer-term studies are needed to confirm its long-term safety.

Radiation therapy is an alternative approach for early stage cervical cancer. Radiation with concurrent cisplatin-based chemotherapy is now the standard treatment for locally advanced cervical cancer. Radiation therapy uses high-energy rays aimed at the body from an outside machine (external beam radiation) and radioactive materials placed inside the body against the cervix (intracavitary radiation).

External beam radiation is given first and aimed at the lymph nodes along the pelvic wall. It usually involves a short period of direct-radiation 5 days a week for about 6 weeks in an outpatient setting.
Intracavitary radiation (also called brachytherapy) follows and is designed to deliver high doses of radiation to the local tumor area. Radioactive material, typically cesium-137, is encapsulated in both gold and platinum. These capsules are inserted in a long stainless steel tube called a tandem, which is inserted in the uterus. and in small stainless steel cylinders, called colpostats, which are placed against the cervix as close to the cancerous cells as possible. Commonly, two or more radiation treatments are administered for about 35 hours each time. Radiation implants may also be inserted directly into the tumor using a needle.

In order to be effective, radiation therapy must be powerful enough to destroy the cancer cells' capacity to grow and divide. This means that normal cells are also affected, which may cause significant side effects. Fortunately, healthy cells usually recover quickly from the damage, whereas abnormal cells do not.

Advanced methods that target radiation more precisely and limit the damage to healthy tissue are now available. They include 3-D conformal radiation and intensity-modulated radiation therapy (IMRT):

3-D conformal techniques use computers and a three-dimensional image of the cervix to provide precise targeting of the tumor using multiple high-dose radiation beams.
IMRT also uses 3-D techniques and employs very thin and precise beam at various intensities.

Side Effects. Side effects of radiation therapy include fatigue, redness or dryness in the treated area, diarrhea, frequent or uncomfortable urination, and vaginal dryness, itching, or burning. After treatment, side effects usually disappear.

Long-Term Complications. Complications include proctitis (inflammation of the rectum) and cystitis (inflammation of the bladder). Bowel obstruction is an uncommon complication. Radiation therapy may also cause vaginal scarring, sexual difficulties, and premature menopause in younger women. Occasionally an abnormal tunnel between the bladder and the vagina, known as a vesicovaginal fistula, will develop and may require surgery.

Click the icon to see an image of the female anatomy.

Investigative temporary silicone implants or a noninvasive device called the belly board may protect the small intestine during radiation therapy and help reduce complications.

Radiation itself may increase the risk for later development of cancer in the area surrounding the treated tissue. Although newer more precise radiotherapy approaches should reduce this risk, there is some concern that IMRT may double the incidence of secondary cancers over time compared to 3-D conformal techniques. This is of particular concern in younger patients.

Radiation and Hyperthermia. Investigators are studying hyperthermia (use of high heat often provided by ultrasound) in combinations with radiation therapy. This approach has shown some promise in achieving significant response rates in small studies. Comparison studies are important to determine if this approach would be as beneficial with radiation therapy as concurrent chemotherapy.

Chemotherapy uses cell-killing drugs called cytotoxic drugs to destroy widespread cancer cells that have spread from the primary tumor and can no longer be treated with surgery or radiation.

For many years, chemotherapy was only used to reduce symptoms in women with very advanced disease. Today, platinum-based chemotherapy drugs (see below) are being used in many situations for cervical cancer, such as:

In combination with radiation therapy to improve survival rates in certain women, including some with locally advanced cancer.
In some women with locally advanced cancer to reduce tumors to the point where the cancer may be operable.
When cancer has spread (metastasized), mostly to reduce symptoms such as pain.

Platinum-Based Drugs. Platinum-based drugs cisplatin and carboplatin are often used for treating various stages of cervical cancer. These drugs are usually used in combination with radiation therapy or other chemotherapy drugs. In 2006, the FDA approved a combination of cisplatin and topotecan (another type of chemotherapy drug) for treatment of late-stage cervical cancer in women who are unlikely to be helped by surgery or radiation therapy. Women with stage IVB cervical cancer who received the combination treatment survived around 3 months longer (9.5 months versus 6.5 months) than women who received only cisplatin.

Other drugs. Other drugs, mostly used in combinations, have also been investigated with some promise. They include epirubicin, irinotecan, paclitaxel, bleomycin, mitomycin, vinorelbine, gemcitabine, and doxifluridine.

Administration. Chemotherapy may be given by mouth or as an injection. This may be done at a medical center, doctor's office, or even a patient's home. Some patients receiving chemotherapy may need to remain in the hospital for several days so the effects of the drugs can be monitored. The drugs are often given in cycles with a period of rest following a period of treatment, to allow recovery from the side effects.

Side Effects. Chemotherapy affects all fast-growing cells, including healthy ones. So, side effects are inevitable. Side effects occur with all chemotherapeutic drugs. They are more severe with higher doses and increase over the course of treatment.

Common side effects include the following:

Nausea and vomiting. Drugs known as serotonin antagonists, especially ondansetron (Zofran), can relieve these side effects in nearly all patients given moderate drugs and in most patients who take more powerful drugs.
Diarrhea
Temporary hair loss
Weight loss
Fatigue
Anemia
Depression

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

Increased chance for infection. Chemotherapy suppresses the immune system.
Severe drop in white blood cell count (neutropenia). Certain drugs, such as taxanes, pose a higher risk for this than other chemotherapeutic drugs. White blood cell count may be improved with the addition of a type of drug called granulocyte colony-stimulating factor (either filgrastim or lenograstim).
Liver and kidney damage.
Abnormal blood clotting (thrombocytopenia).
Allergic reaction, particularly to platinum-based drugs. (A simple skin test that may identify people with a potential allergic response is under investigation .)
Menstrual abnormalities. These are common. Premature menopause occurs in about 30% of women, particularly in those over 40.
Secondary cancers such as leukemia (rare).
Problems in concentration, motor function, and memory, which may be long-term. Between a quarter and a third of women report such problems. This may be due to a drop in estrogen levels after treatments.

Resources

www.cancer.gov -- National Cancer Institute
www.cancer.org -- American Cancer Society
www.acog.org -- American College of Obstetricians and Gynecologists
www.ashastd.org -- American Social Health Association
www.arhp.org -- Association of Reproductive Health Professionals
www.nccc-online.org -- National Cervical Cancer Coalition
www.cervicalcancercampaign.org -- Cervical Cancer Public Education Campaign
www.fda.gov/womens/getthefacts/hpv.html -- FDA HPV Fact Sheet
www.thegcf.org -- Gynecologic Cancer Foundation
www.wcn.org -- Women's Cancer Network
www.plwc.org -- People Living with Cancer
www.gothpv.net -- HPV Support Site

References

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Committee on Infectious Diseases. Prevention of human papillomavirus infection: provisional recommendations for immunization of girls and women with quadrivalent human papillomavirus vaccine. Pediatrics. 2007 Sep;120(3):666-8.

Davey E, d'Assuncao J, Irwig L, Macaskill P, Chan SF, Richards A, et al. Accuracy of reading liquid based cytology slides using the ThinPrep Imager compared with conventional cytology: prospective study. BMJ. 2007 Jul 7;335(7609):31. Epub 2007 Jun 29.

D'Souza G, Kreimer AR, Viscidi R, Pawlita M, Fakhry C, Koch WM, et al. Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med. 2007 May 10;356(19):1944-56.

Dunne EF, Unger ER, Sternberg M, McQuillan G, Swan DC, Patel SS, et al. Prevalence of HPV infection among females in the United States. JAMA. 2007 Feb 28;297(:813-9.FUTURE II Study Group. Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. N Engl J Med. 2007 May 10;356(19):1915-27.

Garland SM, Hernandez-Avila M, Wheeler CM, Perez G, Harper DM, Leodolter S, et al. Quadrivalent vaccine against human papillomavirus to prevent anogenital diseases. N Engl J Med. 2007 May 10;356(19):1928-43.

Gunnell AS, Tran TN, Torrang A, Dickman PW, Sparen P, Palmgren J, et al. Synergy between cigarette smoking and human papillomavirus type 16 in cervical cancer in situ development. Cancer Epidemiol Biomarkers Prev. 2006 Nov;15(11):2141-7. Epub 2006 Oct 20.

Hildesheim A, Herrero R, Wacholder S, Rodriguez AC, Solomon D, Bratti MC, et al. Effect of human papillomavirus 16/18 L1 viruslike particle vaccine among youngwomen with preexisting infection: a randomized trial. JAMA. 2007 Aug 15;298(7):743-53.

Markowitz LE, Dunne EF, Saraiya M, Lawson HW, Chesson H, Unger ER; Centers for Disease Control and Prevention (CDC); Advisory Committee on Immunization Practices (ACIP). Quadrivalent human papillomavirus vaccine: Recommendations of the AdvisoryCommittee on Immunization Practices (ACIP). MMWR Recomm Rep. 2007 Mar 23;56(RR-2):1-24.

Ronco G, Cuzick J, Pierotti P, Cariaggi MP, Dalla Palma P, Naldoni C, et al. Accuracy of liquid based versus conventional cytology: overall results of new technologies for cervical cancer screening: randomised controlled trial. BMJ. 2007 Jul 7;335(7609):28. Epub 2007 May 21.

Saslow D, Castle PE, Cox JT, Davey DD, Einstein MH, Ferris DG, et al. American Cancer Society Guideline for human papillomavirus (HPV) vaccine use to prevent cervical cancer and its precursors. CA Cancer J Clin. 2007 Jan-Feb;57(1):7-28.

Sturgis EM, Cinciripini PM. Trends in head and neck cancer incidence in relation to smoking prevalence: an emerging epidemic of human papillomavirus-associated cancers? Cancer. 2007 Aug 27; [Epub ahead of print]Weller SC, Stanberry LR. Estimating the population prevalence of HPV. JAMA. 2007 Feb 28;297(:876-8.

Review Date:
9/1/2006
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

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Non-small cell lung cancer

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

In This Report

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

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Research News:

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

Treatment News:

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

Introduction

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Click the icon to see an image of adenocarcinoma.

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

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

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

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

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

Causes

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

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

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

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

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

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

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

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

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

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

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

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

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

Symptoms

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

Early symptoms may include the following:

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

Later-stage symptoms include the following:

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

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

Risk Factors

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

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

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


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

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

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

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

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

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

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

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

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

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

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

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

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

Lifestyle Changes

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

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

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

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

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

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

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

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

Click the icon to see an image of phytochemicals.

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

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

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

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

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

Click the icon to see the benefits of vitamin A.

Click the icon to see dietary sources of vitamin A.

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

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

Click the icon to see the benefits of selenium.

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

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

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

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

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

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

Diagnostic Tests

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Click the icon to see an image of bronchoscopy procedure.

Click the icon to see an image of a bronchoscope.

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

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

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

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

Staging Systems

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Surgical Procedures

Surgery is performed in the following circumstances:

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Radiation Treatments

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Treatment Options by Stages

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

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

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

Treatment Options:

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Treatment Options are:

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

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

Treatment Options are:

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

Chemotherapy Treatments

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Investigative Agents

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

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

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

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

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

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

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

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

Resources

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

References

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

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

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

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

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

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

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

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

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

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

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

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

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

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

A.D.A.M. Copyright

adam.com

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

Impotence (Erectile dysfunction)

FitSugar — Wed, 08 Oct 2008 17:35:36 -0700

In This Report

Highlights
Introduction
Risk Factors
Lifestyle or Psychological ...
Physical Causes
Prognosis
Diagnosis
Treatment
Lifestyle Changes
Medications
Injections or Topical Treat...
Other Treatments
Natural Remedies
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

FDA Warns about Dietary Supplements

In 2006 and 2007, the FDA issued numerous warnings about “natural” dietary supplements promoted for erectile dysfunction and sexual enhancement. These products -- marketed under names such as “True Man,” “Energy Max,” “Rhino Max”-- contain illegal substances that can interact with prescription drugs and dangerously lower blood pressure. The interaction risks are greatest for men with diabetes, high blood pressure, high cholesterol, or heart disease who take prescription drugs that contain nitrates. The FDA has not approved any of these products and warns that consumers should not buy or use them.

Viagra and Similar Drugs Safe for Men with Diabetes

Phosphodiesterase inhibitors (PDE-5 inhibitors) are generally safe and often effective for men with diabetes, at least in the short term, according to a 2007 review published in the Cochrane Database. However, there is not enough evidence to determine if these drugs are safe for men with diabetes if used on a long-term basis. PDE-5 inhibitors include sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis). These drugs should be used with caution in men who have unstable heart disease, poorly controlled high blood pressure, or history of stroke. Discuss with your doctor whether a PDE-5 inhibitor drug is safe for you.

Testosterone Therapy Guidelines

In 2007, the Endocrine Society issued guidelines for testosterone treatment. The Endocrine Society advises that testosterone therapy works best for men who have been diagnosed with low testosterone levels and who demonstrate clear clinical symptoms such as erectile dysfunction. For patients with low libido or erectile dysfunction, but normal testosterone levels, it is unclear that testosterone therapy offers any benefits. Most experts recommend that patients with low testosterone levels and erectile dysfunction combine testosterone replacement therapy with a PDE-5 inhibitor drug.

Metabolic Syndrome Increases Risk for Erectile Dysfunction

Metabolic syndrome is a risk factor for erectile dysfunction, according to several recent studies. Metabolic syndrome is a cluster of conditions that include abdominal obesity, unhealthy cholesterol and triglyceride levels, high blood pressure, and insulin resistance.

Introduction

Erectile dysfunction (impotence) is the inability to achieve or maintain an erection sufficiently rigid for sexual intercourse, ejaculation, or both. Sexual drive and the ability to have an orgasm are not necessarily affected. Because all men experience erection problems from time to time, doctors consider impotence to be present if attempts at intercourse fail at least 25% of the time.

Erectile dysfunction is new in neither medicine nor human experience, but it is not easily or openly discussed. Cultural expectations of male sexuality inhibit many men from seeking help for a disorder that can, in most cases, benefit from medical treatment. The term "impotence" comes from Latin and means loss of power; a more accurate term is "erectile dysfunction."

The Structure of the Penis. The penis is composed of the following structures:

Two parallel columns of spongy tissue called the corpus cavernosa, or erectile bodies.
A central spongy chamber called the corpus spongiosum, which contains the urethra, the tube that carries urine from the bladder through the penis.

These structures are made up of erectile tissue. Erectile tissue is rich in tiny pools of blood vessels called cavernous sinuses. Each of these vessels are surrounded by smooth muscles and supported by elastic fibrous tissue composed of a protein called collagen.

Erectile Function and Nitric Oxide. The penis is either flaccid or erect depending on the state of arousal. In the flaccid, or unerect, penis, the following normally occurs:

Small arteries leading to the cavernous sinuses contract, reducing the inflow of blood.
The smooth muscles regulating the many tiny blood vessels also stay contracted, limiting the amount of blood that can collect in the penis.

During arousal the following occurs:

The man's central nervous system stimulates the release of a number of chemicals, including nitric oxide, which is now considered the main contributor for eliciting and maintaining erection.
Nitric oxide stimulates production of cyclic GMP, a chemical that relaxes the smooth muscles in the penis. This allows blood to flow into the tiny pool-like cavernous sinuses, flooding the penis.
This increased blood flow nearly doubles the diameter of the spongy chambers.
The veins surrounding the chambers are squeezed almost completely shut by this pressure.
The veins are unable to drain blood out of the penis and so the penis becomes rigid and erect.
After ejaculation or arousal, cyclic GMP is broken down by an enzyme called phosphodiesterase-5 (PDE5), and other compounds are released that cause the penis to become flaccid (unerect) again.

A proper balance of certain chemicals, gases, and other substances is critical for erectile health:

Collagen. The protein collagen is the major component in structural tissue in the body, including in the penis. Excessive amounts, however, form scar tissue, which can impair erectile function.

Oxygen. Oxygen-rich blood is one of the most important components for erectile health. Oxygen affects two substances that are important in achieving erection:

Oxygen suppresses transforming growth factor beta 1 (TGF-B1). TGF-B1 is a component of the immune system called a cytokine and is produced by smooth muscle cells. It appears to stimulate collagen production in the corpus cavernosum, which can lead to erectile dysfunction.
Oxygen enhances the activity of prostaglandin E1. Prostaglandin E1 is produced during erection by the muscle cells in the penis. It activates an enzyme that initiates calcium release by the smooth muscle cells, which relaxes them and allows blood flow. Prostaglandin E1 also suppresses production of collagen.

Oxygen levels vary widely from reduced levels in the flaccid state to very high in the erect state. During sleep, oxygen levels are high and a man can normally have three to five erections per night, each one lasting from 20 - 40 minutes.

Testosterone and Other Hormones. Normal levels of hormones, especially testosterone, are essential for erectile function, though their exact role is not clear.

Erectile dysfunction most commonly occurs when the penis is deprived of oxygen-rich blood. When oxygen levels to the penis are low, an imbalance occurs in two important substances, TGF-B1 and prostaglandin E1:

TGF-B1 levels increase, which trigger production of collagen, a tough protein that forms all types of connective tissue, including scar tissue.
In addition, there is a reduction in prostaglandin E1, a chemical that suppresses collagen production and relaxes the smooth muscles to allow blood flow resulting in an erection.

When TGF-B1 levels increase and prostaglandin E1 levels decrease, smooth muscles waste away and collagen is overproduced, causing scarring, loss of elasticity, and reduced blood flow to the penis. A number of conditions can deprive the penis of oxygen-rich blood.

Blockage of Blood Vessels (Ischemia). The primary cause of oxygen deprivation is ischemia-- the blockage of blood vessels. The same conditions that cause blockage in the blood vessels leading to heart problems may also contribute to erectile dysfunction. For example, when cholesterol and other factors are imbalanced, a fatty substance called plaque forms on artery walls. As the plaque builds up, the arterial walls gradually narrow, reducing blood flow. This process, known as atherosclerosis, is the major contributor to the development of coronary heart disease. It may also play a role in the development of erectile dysfunction.

Risk Factors

More than 18 million American men over age 20 have erectile dysfunction, and about 600,000 men age 40 - 70 experience erectile dysfunction to some degree each year.

For most men, erectile dysfunction is primarily associated with older age. While ED affects less than 10% of men in their 20s, and 20 – 46% of men age 40 – 69, about 80% of men age 75 or older have ED. Nevertheless, impotence is not inevitable with age. In a survey of men over 60 years old, 61% reported being sexually active, and nearly half derived as much if not more emotional benefit from their sex lives as they did in their 40s.

Severe erectile dysfunction in elderly men may have more to do with disease than age itself. In particular, older men are more likely to have heart disease, diabetes, and high blood pressure than younger men. Such conditions and some of their treatments are major risk factors for erectile dysfunction. Smoking and obesity are also prime risk factors for ED.

Many physical and psychological situations can cause erectile dysfunction, and brief periods of impotence are normal. Every man experiences erectile dysfunction from time to time. Nevertheless, if the problem is persistent, men should seek professional help, particularly since erectile dysfunction is usually treatable and may also be a symptom of a more widespread problem.

Lifestyle or Psychological Causes

Over the past decades, the medical perspective on the causes of erectile dysfunction has shifted. Common wisdom used to attribute almost all cases of impotence to psychological factors. Now investigators estimate that up to 85% of impotence cases are caused by medical or physical problems. Only 15% are psychologically based.

It is often difficult to determine if the cause of erectile dysfunction is a physical or psychological one, or even some combination. The following may be helpful:

Physical impotence can be caused by internal medical causes (diabetes, high blood pressure) or by external causes (surgery, injury, medications). Erectile dysfunction due to medical conditions usually develops gradually but continuously over a period of time. If impotence persists over a 3-month period and is not due to a stressful event, drug use, alcohol, or known medical conditions, then the patient needs medical attention by a urologist specializing in impotence.
Psychological impotence tends to develop rapidly and be related to a recent situation or event. The patient may be able to have an erection in some circumstances but not in others. Being able to experience or maintain an erection upon waking up in the morning suggests that the problem is psychological rather than physical.

In virtually every case of erectile dysfunction there are emotional issues that can seriously affect the man's self-esteem and relationships. Negative emotions may even perpetuate erectile dysfunction that has been caused by a medical condition that has been successfully treated. Many men tend to fault themselves for their impotence even if it is clearly caused by physical problems over which they have little or no control.

Anxiety. Anxiety has both emotional and physical consequences that can affect erectile function. It is among the most frequently cited contributors to psychological impotence. Excessive concern about sexual performance is often referred to as performance or "honeymoon" anxiety and may provoke an intense fear of failure and self-doubt. It can sometimes set off a cycle of chronic impotence. In response to anxiety, the brain releases chemicals known as neurotransmitters that constrict the smooth muscles of the penis and its arteries. This constriction reduces the blood flow into and increases the blood flow out of the penis. Even simple stress may promote the release of brain chemicals that disrupt potency in a similar way.

Depression. Depression is strongly associated with erectile dysfunction. In one study, 82% of men who reported moderate-to-severe erectile dysfunction also had symptoms of depression. Depression can certainly reduce sexual desire, but it is often not clear which condition came first.

Troubles in relationships often have a direct impact on sexual functioning. Partners of men with erectile dysfunction may feel rejected and resentful, particularly if the affected man does not confide his own anxieties or depression. Both partners commonly experience guilt for what they each perceive as a personal failure. Tension and anger frequently arise between people who are unable to discuss sexual or emotional issues with each other. It can be very difficult for the man to perform sexually when both partners harbor negative feelings.

Losing a job or having lower income or education increases the risk for impotence.

Smoking contributes to the development of impotence, mainly because it increases the effects of other disorders of the blood vessels, including high blood pressure and atherosclerosis. A 2006 study found that men who smoked at least a pack a day were 39% more likely to experience ED than non-smokers. Research presented at the 2006 meeting of the American Urological Association indicated that quitting smoking helps reverse ED.

Alcohol has also been implicated in causing impotence. A small amount releases inhibitions, but having more than one drink can depress the central nervous system and impair sexual function.

Some evidence suggests that exposure to estrogen-like chemicals, such as those found in DDT and other pesticides, may contribute to erectile dysfunction. (Such chemicals have been associated with low sperm counts and infertility in men.)

Infrequent erections deprive the penis of oxygen-rich blood. Without daily erections, collagen production increases and eventually may form a tough tissue that interferes with blood flow. The spontaneous erections men have while sleeping or awake may be a natural protection against this process.

Physical Causes

A number of conditions share a common problem with erectile dysfunction -- the impaired ability of blood vessels to open and allow normal blood flow. Such conditions include diabetes, hypertension, coronary artery disease, kidney failure, peripheral artery disease, and stroke. Increasingly, researchers are studying the role of nitric oxide, which plays a major role in keeping blood vessels open, in all of these disorders.

The following diseases are highly associated with erectile dysfunction:

Heart Disease. Erectile problems may be a warning sign of heart disease. Several important studies in 2005 and 2006 firmly established this link. The studies indicated that men with ED are more likely to have coronary artery disease (CAD) and high blood pressure, and more severe forms of heart disease, than men without erectile problems. In fact, the studies suggested that ED is a stronger predictor of CAD than smoking, family history, cholesterol levels, or high blood pressure. Men who experience ED are at greater risk for angina, heart attack, or stroke. Many experts now recommend that men with erectile dysfunction undergo a complete cardiovascular evaluation.
High Blood Pressure (Hypertension). Erectile dysfunction is a very common problem in men with high blood pressure. More than 40 percent of men with erectile dysfunction have hypertension. The disease process is the major contributor to impotence, but many of the drugs used to treat hypertension also cause it. Newer anti-hypertensive drugs, including angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) are less likely to cause erectile dysfunction. In fact, ARBs may be particularly effective in restoring erectile function in men with high blood pressure who suffer from impotence.
Diabetes. Diabetes is a major risk factor for erectile dysfunction. It may increase the risk for ED by as much as 169% and contribute to as many as 40% of impotence cases. Between a third and a half of all men with diabetes report some form of sexual difficulty. Blocked arteries and nerve damage are both common complications of diabetes. When the blood vessels or nerves of the penis are involved, erectile dysfunction can result. Diabetes is also associated with heart disease, another risk factor for ED.
Obesity. Obesity increases the risk for diabetes, heart disease, and erectile dysfunction. According to a 2006 study, obese men are 60% more likely to develop ED than normal weight men.
Metabolic Syndrome. Metabolic syndrome -- a cluster of conditions that includes obesity and abdominal fat, unhealthy cholesterol and triglyceride levels, high blood pressure, and insulin resistance -- is also a risk factor for erectile dysfunction in men older than 50 years.

Parkinson's Disease. As a risk factor for impotence, Parkinson's disease (PD) is an under-appreciated problem. It is estimated that about a third of men with PD experience impotence. The physical cause of PD-related impotence is most likely an impaired nervous system. Depression and lowered self-esteem also contribute to erectile dysfunction in these patients.

Multiple Sclerosis. Multiple sclerosis (MS), which affects the central nervous system, also precipitates sexual dysfunction in as many as 78% of male patients. (Corticosteroids, which are common treatments for MS, may improve sexual function.)

Other Common Medical Conditions. Other medical conditions that have been associated with erectile dysfunction include allergies, thyroid problems, lung disease, and epilepsy.

Advanced prostate cancer can damage nerves needed for erectile function. Prostate surgery and surgical and radiation treatments for prostate cancer can also cause impotence. A number of treatments for sexual dysfunction are available that may help some men. [See In-Depth Report #33: Prostate cancer.]

Prostate Cancer Surgery (Radical Prostatectomy). The first nationally representative study to evaluate long-term outcomes after radical prostatectomy concluded that impotence occurs far more frequently than previously reported. Those who have so-called nerve-sparing surgeries have better results than those whose surgeries affect the nerves around the prostate. Some evidence also suggests that sexual function rates might improve if the nerve-sparing prostate surgeries also spare the ducts that carry semen.

Some studies suggest that impotence after prostate surgery may in part be due to injury to the smooth muscles in the blood vessels. Early treatments to maintain penile blood flow may help restore erectile function. Some men may benefit from PDE5 inhibitor drugs such as sildenafil (Viagra), tadalafil (Cialis), or vardenafil (Levitra). Other men may need alprostadil injections or suppositories. The vacuum pump is another option.

Radiation. Although it is generally believed that radiation poses a lower risk for impotence than does surgery, studies have reported similar rates after 3 years. Experts suggest radiation injures the blood vessels, leading to erectile dysfunction over time. Some studies report a lower risk for impotence from brachytherapy, a radiation technique that involves the implantation of radioactive "seeds" compared to external-beam radiation. Still, there have been very few studies that have lasted more than 2 years. One 5-year study reported a high long-term rate of impotence (53%) with brachytherapy, which is close to that of standard externally administered radiation. Early use of alprostadil injections and sildenafil (Viagra) may help these men as well as those who had surgery.

Drug Treatments. Prostate cancer medical treatments commonly employ androgen-suppressive treatments, which cause erectile dysfunction.

Surgery for Colon and Rectal Cancers. Surgical and radiation treatments for colorectal cancers can cause impotence in some patients. In general, colostomy does not usually affect sexual function. However, wide rectal surgery can cause short-term or long-term sexual dysfunction. Total mesorectal excision (TME) may pose fewer risks than standard surgery. Sildenafil (Viagra) may help many men who experience this after surgery.

Surgical Treatment of Inflammatory Bowel Disease. Rectal excision for inflammatory bowel disease (IBD) can cause impotence, but rates are low (2 - 4%). Sildenafil (Viagra) is very effective in restoring potency after IBD surgery.

Operations for Fistulas. Surgery to repair anal fistulas can affect the muscles that control the rectum (external anal sphincter muscles), sometimes causing impotence. (Repair of these muscles may restore erectile function.)

Surgery and drug treatments for benign prostatic hyperplasia (BPH) can also increase the risk for impotence, although to a much lesser degree than surgery for prostate cancer.

Between 4 - 10% of patients who have transurethral resection of the prostate (TURP) and open prostatectomy for BPH report impotence afterward. The risk is very low, however, in men who were functioning normally before surgery.
Finasteride (Proscar) has been associated with impotence in 6 - 19% of patients. Anti-androgen drugs used to treat BPH can also cause erectile dysfunction.

About a quarter of all cases of impotence can be attributed to medications. Many drugs pose a risk for erectile dysfunction. Some experts think that nearly every drug, prescription or nonprescription, can be a cause of temporary erectile dysfunction.

Drugs that commonly cause impotence may include:

Drugs used in chemotherapy.
Many drugs taken for high blood pressure, particularly diuretics and beta-blockers.
Most drugs used for psychological disorders, including anti-anxiety drugs, anti-psychotic drugs, and antidepressants, especially selective serotonin reuptake inhibitors (SSRIs). Newer antidepressants pose fewer problems.
Anti-androgens, including drugs known as gonadotropin-releasing hormone agonists. They are used in prostate cancer and also for treating BPH.

Drugs that sometimes cause impotence include:

Older anti-ulcer medications (cimetidine)
Anticholinergic drugs (including some antihistamines)
Antinausea drugs, particularly metoclopramide (Reglan)
Antifungal drugs (especially ketoconazole)
Nonsteroidal anti-inflammatory drugs (NSAIDs), when used on a daily basis

Injury to the Spine. Spinal cord injury and pelvic trauma, such as a pelvic fracture, can cause nerve damage that results in impotence. Other conditions that can injure the spine and effect impotence include spinal cord tumors, spina bifida, and a history of polio.

Orthopedic surgery. Erectile dysfunction can sometimes result from orthopedic surgery. A study of young men who underwent surgical repair (“intramedullary nailing”) for a broken thighbone reported that about 40% of these patients experienced erectile dysfunction after surgery. The researchers theorized that the surgery affected pelvic nerves that play a key role in erection. Patients who received a higher dose of muscle relaxant during surgery had better sexual function outcomes.

Bicycling. Studies have indicated that frequent bicycling may pose a risk for erectile dysfunction by reducing blood flow to the penis. The greatest risk is in cyclers who sit upright while cycling. In addition, a 2004 report in the Journal of Urology found that long distance cyclers may reduce their risk by riding a road bike instead of a mountain bike and by choosing saddles without a cutout.

Note: Vasectomy does not cause erectile dysfunction. When impotence occurs after this procedure, it is often in men whose female partners were unable to accept the operation.

Hypogonadism (Testicular Failure). Hypogonadism in men is a deficiency in male hormones, usually due to an abnormality in the testicles, which secrete these hormones. It affects 4 - 5 million men in the United States. In addition to impotence, hypogonadism causes reductions in energy, sex drive, lean body mass, and bone density. Hypogonadism can be caused by a number of different conditions. Among them are:

Disorders in the pituitary or hypothalamus glands
Malnutrition
Genetic factors
Myotonic dystrophy.
Orchitis (inflammation of the testicles)
Physical injury
Mumps
Radiation treatments
Exercise-induced hypogonadism. Only a few cases of exercise-induced hypogonadism have been identified in men. Some researchers believe, however, that certain athletes may be at risk, including those who began endurance training before full sexual maturity, have very low body weight, and have a history of stress fractures.

Low Testosterone Levels. Only about 5% of men who see a doctor about erectile dysfunction have low levels of testosterone, the primary male hormone. In general, lower testosterone levels appear to reduce sexual interest, not cause impotence.

Other Hormonal Abnormalities. Other hormonal abnormalities that can lead to erectile dysfunction include:

High levels of the female hormone estrogen (which may occur in men with liver disease).
Abnormalities of the pituitary gland that cause high levels of the hormone prolactin are particularly likely to cause impotence.
Other uncommon hormonal causes of impotence include an underactive or overactive thyroid or adrenal gland abnormalities.

A varicocele is an enlarged (varicose) vein in the cord that connects to the testicle. Varicoceles are found in 15 - 20% of all men and in 25 - 40% of infertile men. When varicoceles occur in both testicles, they may contribute to hormone imbalances that cause erectile dysfunction.

Premature Ejaculation. Premature ejaculation is the most common male sexual dysfunction and occurs in as many as 40% of men. It is defined as the inability to delay ejaculation to the point where both partners are satisfied. This can vary widely depending on the preferences of the partners. Younger men tend to have this problem more than older men. Anxiety is a major factor at any age. In general, the longer the duration between ejaculations, the faster they are. Various techniques are available to help delay orgasm.

The standard medications used for this condition are selective serotonin reuptake inhibitors (SSRIs), which include Prozac and Paxil. Some studies suggest that sildenafil (Viagra) in combination with an SSRI may be helpful. A new serotonin-related drug, dapoxetine, showed promise in several clinical trials but was ultimately rejected by the FDA in 2005. There is still no drug specifically approved for treating premature ejaculation.

Peyronie's Disease. Peyronie's disease is an accumulation of scar tissue within the penis shaft, which causes it to curve. The curvature can make erection and intercourse difficult and painful. This condition may be associated with an injury to the penis, but no clear information exists on its origin. Some men may not even be aware that they have it, and there is some evidence that it may be more common than currently believed. In one study, 6.7% of men with an average age of 62 had signs of curvature, but only 2.2% were aware of any difficulties. The disease often goes into a type of spontaneous remission, and some individuals who had previously experienced erectile dysfunction are able to resume sexual activity. Scarring may still cause erection problems, however, even in these cases.

Treatment for Peyronie's Disease. If Peyronie's disease is treated early, ultrasound, heat application, and anti-inflammatory drugs may help reduce scar formation. Some experts believe that the extracorporeal shock wave therapy (ESWT) is the safest and most effective first-line therapy. ESWT uses sound waves to break up scar tissue. It has been used with some success.

Studies also suggest that the calcium channel blocker verapamil may be very beneficial. It can be administered using injection, as a gel patch, or through a process called electromotive drug administration (EMDA), also referred to as iontophoresis. EMDA delivers the drug through an electrical transport of charged molecules. Some studies are reporting good success with EMDA delivery of verapamil along with the steroid dexamethasone.

In severe cases of scarring, the only treatment is surgery to straighten the penis and reduce the curve. Penile implants may also be beneficial.

Priapism. Priapism is a sustained, painful, and unwanted erection that persists despite a lack of sexual stimulation. Generally, priapism results when the smooth muscle tissue remains relaxed so that a constant flow of blood into the vessels of the penis occurs with no leakage back out. The development of priapism has been associated with urinary stones, certain medications, neurologic disorders, and, more recently, with self-injection therapy used for impotence.

Treatment of Priapism. If priapism occurs, applying ice for 10-minute periods to the inner thigh may help reduce blood flow. Erections that last 4 hours or longer require emergency care.

Prognosis

Temporary erectile dysfunction is very common and usually not a serious problem. Nevertheless, if the condition is persistent, psychological effects can be significant. Erectile dysfunction can have a devastating impact on a relationship and can cause extreme depression, which may become chronic if not treated. When a consistent pattern of sexual dysfunction extends over a prolonged period of time, a serious physical or emotional disorder may be present.

Persistent impotence may also be a symptom of a serious medical condition, such as heart disease, diabetes, hypertension, sleep disorders, or circulatory problems. For example, in a study of men who had suffered heart attacks, 75% of them had experienced erectile dysfunction on average 68 months before the heart attack.

Erectile dysfunction can also indicate the presence of injuries or the long-term effects of smoking, heavy drinking, or unhealthy diet.

Diagnosis

The doctor typically interviews the patient about many physical and psychological factors.

Medical and Personal History. The doctor should take a medical and personal history and may ask about the following:

Past and present medical problems
Medications or drugs being used
Any history of psychological problems, including stress, anxiety, or depression

Sexual History. In addition the doctor will ask about the patient's sexual history, which may include:

The nature of the onset of the dysfunction
The frequency, quality, and duration of any erections, and whether they occur at night or in the morning
The specific circumstances when erectile dysfunction occurred
Details of technique
The patient's motivation for and expectations of treatment
Whether problems exist in the current relationship

Interviewing the Sexual Partner. If appropriate, the doctor might also interview the sexual partner. In fact, including the partner in the counseling process is proving to be an important component in making the best treatment choices.

The doctor should perform a careful physical exam, including examination of the genital area and a digital rectal examination (the doctor inserts a gloved and lubricated finger into the patient's rectum) to check for prostate abnormalities.

A useful approach is to administer a treatment for erectile dysfunction and then observe the response. Doctors usually recommend a trial of sildenafil (Viagra) to test for an erection response 30 - 60 minutes after the drug is administered. This drug is replacing more invasive and expensive tests, such as an injection of papaverine or prostaglandin E1, medications that dilate blood vessels in the penis. They produce an erection in about 15 minutes.

After administering the treatment and waiting the appropriate amount of time, the doctor then observes the erectile response, curvature of the penis, and response after erection, sometimes using an ultrasound scanner to assess blood flow.

Blood Tests for Hormonal Abnormalities. Blood tests may be used to measure testosterone levels and, if necessary, prolactin levels to determine if there are hormone problems. The doctor may also screen for thyroid and adrenal gland dysfunction. In addition, various specific tests for erectile dysfunction can be performed.

Tests for Medical Conditions That May be Causing Erectile Dysfunction. Evidence of other medical conditions should be sought, particularly high blood pressure, diabetes, atherosclerosis, and nerve damage.

Tests that monitor nighttime erections may be used to determine if the causes of erectile dysfunction are more likely to be psychological than physical.

Snap-Gauge Test. The snap-gauge test monitors the man's ability to achieve an erection during sleep. It is a very simple test.

When the man goes to bed, he places bands around the shaft of his penis.
If one or more breaks during the course of the night, it provides evidence of an erection. In this case, a psychological basis for the erectile dysfunction is likely.

RigiScan Monitor. A more sophisticated and expensive device is the RigiScan monitor, which makes repetitive measurements of rigidity around the base and tip of the penis. This test is quite accurate but may fail to detect mild cases of erectile dysfunction.

The penile brachial index is a measurement that compares blood pressure in the penis with the blood pressure taken in the arm. Problems with the arterial flow to the penis can be detected using this method.

Imaging tests may be used in certain cases, but they are expensive and often limited to younger men. Anyone considering these tests should have them done in a specialized setting by professionals experienced in their use.

Dynamic Infusion Cavernosometry and Cavernosography. Dynamic infusion cavernosometry and cavernosography (DICC) is usually given only to young men in whom some blockage of the penis or physical injury of the pelvic area is suspected. After an erection is induced with drugs, the following four steps are taken:

The penile brachial index is taken.
The storage ability of the penis is gauged.
An ultrasound of the penile arteries is performed.
An x-ray of the erect penis is taken.

Unfortunately, this test and other similar imaging techniques used to determine blood flow in the penis are not very effective or accurate in diagnosing and determining treatment.

Duplex Doppler Ultrasound. An ultrasound technique called duplex Doppler ultrasound may be useful alone or with sildenafil (Viagra) in determining the severity of condition and also to determine impaired blood flow through the arteries.

Treatment

The cause of impotence dictates the mode of treatment. The first step is to define the cause, if possible, and then try the simplest and least-risky solution.

Before a certain treatment is prescribed, the following factors should be considered:

Any pre-existing illnesses and medications
The degree of comfort with the treatment method
Partner satisfaction and safety profiles need to be considered. Experts strongly recommend that the patient's partner be involved to help with any necessary sexual adjustment.

No matter what the treatment, embarking on a healthy lifestyle is the first and critical step for maintaining and restoring erectile function.

Medical and Surgical Treatments. Sildenafil (Viagra), the first effective oral drug for erectile dysfunction, has been on the market since 1998 and rapidly became the treatment of choice for most men with erectile dysfunction. In 2003, the FDA approved two other oral medications, vardenafil (Levitra) and tadalafil (Cialis), for the treatment of erectile dysfunction.

Men who cannot or choose not to take the drugs still have many other options, including:

Medications inserted or injected into the penis
Vacuum devices
Intracavernosal injection therapy
Invasive procedures, such as penile implants or surgery (limited to those for whom other treatments haven't worked and who have been carefully screened)

Ultimately, how successful the medical treatment is and how well it is accepted depends, in large part, on the man's expectations and how he and his partner both adapt to the procedure.

Psychotherapies. Some form of psychological, behavioral, or sexual therapy is often recommended for individuals suffering from severe impotence, regardless of cause.

Lifestyle Changes

Because many cases of erectile dysfunction are due to reduced blood flow from blocked arteries, it is important to maintain the same lifestyle habits as those who face an increased risk for heart disease.

Diet. Everyone should eat a diet rich in fresh fruits and vegetables, whole grains, and fiber and low in saturated fats and sodium. Because erectile dysfunction is often related to circulation problems, diets that benefit the heart are especially important.

Foods that some people claim to have qualities that enhance sexual drive include chilies, chocolate, scallops, oysters, olives, and anchovies. No hard evidence exists for these claims.

Exercise. A regular exercise program is extremely important. One study reported that older men who ran 40 miles a week boosted their testosterone levels by 25% compared to their inactive peers. Another study found that men who burned 200 calories or more a day in physical activity (which can be achieved by 2 miles of brisk walking) cut their risk of erectile dysfunction by half compared to men who did not exercise.

A study in the Journal of the American Medical Association found that adopting healthy lifestyle changes improved sexual function in obese men (BMI less than 30) with erectile dysfunction. After 2 years, a third of the study participants on the reduced calorie diet and an increased exercise regimen regained sexual function.

Limit Alcohol and Quit Smoking. Men who drink alcohol should do so in moderation. Quitting smoking is essential.

Staying sexually active can help prevent impotence. Frequent erections stimulate blood flow to the penis. It may be helpful to note that erections are firmest during deep sleep right before waking up. Autumn is the time of the year when male hormone levels are highest and sexual activity is most frequent.

The Kegel exercise is a simple exercise commonly used by people who have urinary incontinence and by pregnant women. It may also be helpful for men whose erectile dysfunction is caused by impaired blood circulation. The exercises consist of tightening and releasing the pelvic muscle that controls urination:

Since the muscle is internal and is sometimes difficult to isolate, practice first while urinating. (Once learned, however, Kegel exercises should not be regularly performed while urinating because doing them at that time may eventually weaken the muscles.)
Try to contract the muscle until the flow of urine is slowed or stopped. Attempt to hold each contraction for 10 seconds.
Then release the muscle.
Perform about 5 - 15 contractions three to five times daily.

It may be several months before the patient sees significant improvement.

If medications are causing impotence, the patient and doctor should discuss alternatives or reduced dosages.

Even if erectile dysfunction is caused by a physical problem, interpersonal, supportive, or behavioral therapy are often helpful for patients. Therapy may also ease the adjustment period after the initiation or completion of treatment. It is beneficial to have the partner involved in this process.

Medications

Three medicines taken by mouth are approved for the treatment of erectile dysfunction: Sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis). All three belong to a class of drugs called selective enzyme inhibitors. Sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis) block the enzyme phosphodiesterase-5 (PDE5). Blocking this enzyme helps maintain levels of cyclic guanosine monophosphate (GMP), a chemical produced in the penis during sexual arousal. Balanced levels of GMP cause the smooth muscles of the penis to relax and increase blood flow.

Good Candidates for PDE5 Inhibitors. PDE5 inhibitors are a good choice for men at any age and in any ethnic group who are in good health and who do not have conditions that preclude taking them (such as the use of nitrates or alpha-blockers; see Higher-risk candidates in this section.)

Effectiveness of PDE5 Inhibitors.

Tadalafil (Cialis). Tadalafil usually takes effect in 15 - 30 minutes. It is the only oral ED treatment shown to improve erectile dysfunction for up to 36 hours in most men. A randomized study of over 2,000 men found that nearly two-thirds reported successful intercourse attempts 24 - 36 hours after taking the drug.
Vardenafil (Levitra). Extensive clinical studies indicate that vardenafil improves erectile dysfunction in up to 85% of men with the condition. It also works well in patients with diabetes and in those who have had a radical prostatectomy.
Sildenafil (Viagra). Studies indicate that overall, sildenafil may help more than 70% of patients achieve sexual function.

Studies indicate that PDE5 inhibitors are safe and effective for many men whose erectile dysfunction is related to the following conditions:

Hormonal problems or psychologically induced impotence. These men achieve the highest success rates (80 - 100%).
Stable heart disease. However, PDE5 inhibitors should not be used by men who take nitrate drugs for chest pain or heart problems.
Mild-to-moderate heart failure. A study in the Archives of Internal Medicine found that men with moderate heart failure and ED can safely use sildenafil to improve their sexual function and overall quality of life, provided the men are not taking nitrates for their heart condition. Other research has also suggested that sildenafil is safe for this group of men.
Controlled high blood pressure.
Controlled diabetes (type 1 or 2). Diabetes has been associated with a lower than average response to sildenafil. Still, in a 2002 study over half of patients with type 2 diabetes achieved at least one successful sexual event.
Kidney conditions, including those that require chronic dialysis or kidney transplantation.
Parkinson's disease. Some evidence suggests that sildenafil may have properties that improve depression and help brain functions (attention, memory).
Depression. PDE5 inhibitors may help men who take antidepressant drugs that cause sexual dysfunction, notably selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine (Prozac).

PDE5 inhibitors may also help restore erectile dysfunction in some men who have had the following conditions or treatments:

Treatments for prostate cancer. In men who have had radiation, advanced techniques, such as 3D conformal therapy, along with PDE5 inhibitors offer the best chances for success. In men who have had surgery, PDE5 inhibitors are most effective in younger men who were potent before surgery and who had bilateral nerve-sparing procedures. It is unlikely to be effective for men over age 55 who had unilateral or non-nerve-sparing procedures. Starting first with alprostadil injections right after treatment, followed by a PDE5 inhibitor, may be the best approach and considerably improve success rates.
Diabetes. PDE5 inhibitors appear to be safe and effective, at least in the short term, for most men with diabetes. There is not yet enough evidence to know whether these drugs are safe for long-term use.
Colon surgeries for cancer or inflammatory bowel disease.
Spina bifida, a congenital defect of the spinal cord.
Spinal cord injury. PDE5 inhibitors can be very effective in many of these men, especially those in which there is some erectile response and when the injuries are in the upper part of the spine.

Higher-Risk Candidates. PDE5 inhibitors are not suitable for everyone. Men who take nitrate drugs for angina, anticoagulants for heart conditions, or certain types of alpha-blockers for high blood pressure and benign prostatic hyperplasia (BPH), should not take PDE5 inhibitors. Men with the following conditions should not take PDE5 inhibitors without the recommendation of their doctors and even then should use them with caution:

Severe heart disease, such as unstable angina, a history of heart attack, or arrhythmias. Sildenafil increases nerve activity associated with cardiovascular function, especially during physical and mental stress. Men with heart disease may benefit from an exercise test to determine whether resuming sexual activity increases their risk of a heart attack.
Recent history of stroke
Hypotension (very low blood pressure)
Uncontrolled hypertension (high blood pressure)
Uncontrolled diabetes
Severe heart failure
Retinitis pigmentosa. (With this genetic disease, people do not produce phosphodiesterase-5 and do not respond to PDE5 inhibitors.)

Administration and Effect. PDE5 inhibitors work only when the man experiences some sexual arousal. They are generally effective within 30 - 120 minutes when taken on an empty stomach. Sildenafil should be taken on an empty stomach; vardenafil and tadalafil may be taken with or without food. The effects of these drugs may last for several hours. PDE5 inhibitors should not be used more than once a day.

Success rates increase with the number of attempts, so a man should not be discouraged if the drug does not work at first.

PDE5 inhibitors can also be used in combination with testosterone replacement therapy, but this combination may cause a number of side effects.

Side Effects and Other Limitations. Common side effects of PDE inhibitors include flushing, upset stomach, headache, nasal congestion, back pain, and dizziness.

Effects on the Heart. There have been reports of fatal heart attacks in a small percentage of men taking sildenafil (Viagra). Viagra can cause sudden and dangerous drops in blood pressure when the drug is taken with nitrate drugs, such as nitroglycerine, which are used for angina. No one taking nitrates, including the recreational drug amyl nitrate, should take sildenafil or any other PDE5 inhibitors.

Visual Effects. About 2.5% of men experience abnormal visual effects that include seeing a blue haze, temporary increased brightness, and even temporary vision loss in a few cases. Experts believe that visual disturbances are related to the inhibition of phosphodiesterase enzymes in the retina, but the effect appears to be temporary and insignificant, lasting a few minutes to several hours. Men at risk for eye problems who take PDE5 inhibitors regularly should have frequent eye examinations with an ophthalmologist. Men should also see an eye doctor if visual problems last more than a few hours.

In 2005, the FDA began investigating reports of partial vision loss in men who took sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis). The vision loss was caused by non-arteric anterior ischemic optic neuropathy (NAION), a condition that occurs from poor blood flow to optic nerves. However, experts note that erectile dysfunction is itself linked to the same vascular problems that cause NAION. Patients who suffer from diabetes, high blood pressure, and heart disease are at higher risk for erectile dysfunction as well as other vascular problems such as NAION. Information concerning vision loss has been added to the labels of these drugs, but the risk of blindness appears small. Still, patients who use this medication and experience a sudden loss of vision should immediately stop taking the drug and contact their doctor.

Seizures. There have been a few reports of seizures in men taking sildenafil. These are rare occurrences and it is not clear if there is any causal association.

Risk of Priapism. PDE5 inhibitors pose a very low risk for priapism in most men. (Priapism is sustained, painful, and unwanted erection.) Exceptions are young men with normal erectile function.

Interactions with Other Drugs. In addition to serious interactions with nitrates, PDE5 inhibitors may also interact with certain antibiotics, such as erythromycin, and acid blockers, such as cimetidine (Tagamet). Patients should tell their doctor about any medications they are taking.

Decrease in Effectiveness. Over time, PDE5 inhibitors may lose effectiveness. A 2001 study found that after 2 years, 20% of patients had increased their dose of sildenafil to achieve the same effect, and 17% had discontinued the drug due to loss of efficacy. It is possible that these men were suffering from heart disease or other problems that made their impotence worse. An earlier study found that 96% of men who had been taking sildenafil for 2 - 3 years remained satisfied with the treatment. In addition, some research indicates that sildenafil treatment may be less effective in men with diabetes.

Other PDE5 Inhibitors. Avanafil and SLX-2101 are new PDE5 inhibitors that are showing promising results in clinical trials.

Melanocortin receptor agonists. Melanocortin receptor agonists work on the central nervous system instead of the vascular system. Bremelanotide (formerly PT-141) is the first of these drugs to be investigated in clinical trials. Researchers are testing the drug as a nasal spray given either alone or in combination with a PDE5 inhibitor.

Gene Therapy. Researchers are investigating gene transfer therapy as a possible cure for erectile dysfunction. Promising results from the first human trial were presented at the 2006 American Urological Association meeting. The gene-based therapy, called hMaxi-K, uses injections of a gene that helps the body manufacture proteins to improve smooth muscle relaxation. The treatment requires injections twice a year. It is still in the very early stages of research.

Injections or Topical Treatments

Penile injections have now largely been replaced by PDE5 inhibitors, such as sildenafil. Nevertheless, injection therapies use various drugs that have properties that help achieve erection, even in many men who do not succeed with PDE5 inhibitors. The standard drugs used in injections include:

Alprostadil
Phentolamine
Papaverine

Although any or all of these drugs are very effective, injections or other invasive methods of administration are awkward and uncomfortable.

Alprostadil is derived from a natural substance, prostaglandin E1, and acts by opening blood vessels. It is an effective treatment for some men. It can be administered by:

Injection into the erectile tissue of the penis (Caverject, Edex)
A device that administers the drug through the urethra (MUSE system)

Candidates. Regardless of how it is administered, alprostadil works in many men with a wide range of medical disorders related to erectile dysfunction, including men with:

Diabetes
Prostate cancer treatments (early use of alprostadil injections after prostate cancer treatment, particularly when followed by a PDE5 inhibitor, may be helpful)
Cholesterol problems treated with nitrates
Injury

Alprostadil is not an appropriate choice for men with:

Severe circulatory or nerve damage
Bleeding abnormalities or men who are taking medications that thin the blood, such as heparin or warfarin
Penile implants

Injected Alprostadil. Injected alprostadil (Caverject, Edex) uses a very small needle that the man injects into the erectile tissue of his penis. About 80% of men describe the pain of administering the injection as very mild. Edex is a newer and less expensive form of injected alprostadil. In one 12-month study of 894 patients, Edex injections achieved erections in 95% of attempts.

The drug should not be injected more than 3 times a week or more than once within a 24-hour period.

MUSE System. The MUSE system delivers alprostadil through the urethra. It works in the following way:

The device is a thin plastic tube with a button at the top.
The man inserts the tube into his urethral opening right after urination. (Urinating or urine leakage right after administration may reduce the amount of medication.)
He presses the button, which releases a pellet containing alprostadil.
The man rolls his penis between his hands for 10 - 30 seconds to evenly distribute the drug. To avoid discomfort, the man should keep the penis as straight as possible during administration.
The man should be upright, either sitting, standing or walking for about 10 minutes after administration. By that time, he should have achieved an erection that lasts between 30 - 60 minutes. (If a man lies on his back too soon after administration, blood flow to the penis may decrease and the erection may be lost.)
The erection may continue after orgasm.

The MUSE system should not be used more than twice a day and is not appropriate for men with abnormal penis anatomy.

Side Effects of Most Alprostadil Methods. Certain side effects are common to all methods of administration, although they may differ in severity depending on how the drug is given:

Pain and burning at the application site. In one study half of the men who injected alprostadil experienced some burning and pain at the injection site.
Scarring of the penis (Peyronie's disease), which is most likely to occur with injections.
Sudden, low blood pressure. Symptoms include dizziness, lightheadedness, and fainting. If these symptoms occur, the man should lie down immediately with his legs raised.
Priapism (prolonged erection). Possible with any method, but less chance with the MUSE system than with injections. If priapism occurs, applying ice for 10-minute periods to the inner thigh may help reduce blood flow. Erections that last 4 hours or longer require emergency care.
Women partners may experience vaginal burning or itching. The drug may have toxic effects if it reaches the fetus in pregnant women, so men should not use alprostadil for intercourse with pregnant women without the use of a condom or other barrier contraceptive device.
Other side effects. Other side effects include minor bleeding or spotting, redness in the penis, and aching in the testicles, legs, and area around the anus.

Until the introduction of alprostadil, the two drugs used for injection therapy had been papaverine (Pavabid, Cerespan) and phentolamine (Regitine). Adverse reactions are usually minor but include pain, ulcers, and prolonged erections (priapism).

According to 2006 guidelines from the Endocrine Society, testosterone replacement therapy works best for men with erectile dysfunction who have been diagnosed with hypogonadism (low testosterone levels). For these men, experts recommend combination of testosterone and other ED treatments, such as PDE-5 inhibitors. Men who have ED and normal testosterone levels are not likely to benefit from testosterone therapy.

Forms of testosterone therapy include:

Muscle injections using testosterone enanthate (Andryl, Delatestryl) or cypionate (Andro-Cyp, Depo-Testosterone, Virion). This has been the standard administration.
Skin patch (Testoderm, Testoderm TTS, Androderm). Depending on the brand, patches may be applied to the skin of the scrotum every 24 hours or to the abdomen, back, thighs, or upper arm. In the latter case, two patches are required every 24 hours. Testoderm and Testoderm TTS may cause less skin irritation than Androderm.
Skin gel (Androgel, Testim). At this time, the gel is applied only to the same parts of the body as the patch. A gel applied to the penile skin is being investigated for men with hypogonadism and erectile dysfunction. Pregnant women must avoid contact with the gel because theoretically the testosterone could harm the fetus.

Oral forms of testosterone are not recommended because of the risk for liver damage when taken for long periods of time.

Testosterone therapy may increase the risk for the following adverse effects, particularly in men with normal testosterone levels:

Lowering of HDL ("good" cholesterol)
Rapid growth of prostate tumors in men with existing prostate cancers. (Taking testosterone does not appear to increase the risk for prostate cancer, but experts remain concerned.)
Lower sperm count
Sleep apnea
Polycythemia, an abnormal increase in red blood cells
Benign prostatic hyperplasia

Other Treatments

Vacuum devices, or external management systems, are effective, safe, and simple to use for all forms of impotence except when severe scarring has occurred from Peyronie's disease.

Using the Device. Patients must receive thorough instructions in the proper use of such devices. They typically work as follows:

The man places the penis inside a plastic cylinder.
A vacuum is created, which causes blood to flow into the penis, thereby creating an erection.
A band is tightly secured around the base of the penis, which retains the erection, and the cylinder is removed.
It takes about 3 - 5 minutes to produce an erection.

Lack of spontaneity is this method's major drawback. The erection involves only part of the penis shaft, and the process will certainly seem peculiar in the beginning. When these psychological obstacles are overcome, many couples find the result highly satisfactory.

Success Rates. Studies have found that success with the vacuum device is about equal to other methods. Between 56 - 67% of men using it reported the device to be effective. In one study of men who had used the vacuum device for many years, almost 79% reported improvement in their relationships with their sexual partners, and 83.5% said they had intercourse whenever they chose. Nevertheless, dropout rates are high. In one study, for example, the overall drop out rate was 65%. Even in a high-success group, over half stopped using it.

Side Effects. Side effects include blocked ejaculation and some discomfort during pumping and from use of the band. Minor bruising may occur, although infrequently. It is very important to use a medically approved pump. There have been reports of injury from vacuum devices that do not have a pressure-release valve or other safety elements.

Vacuum-less devices that trap blood within the penis are also available. They are called venous flow controllers or simple constricting devices. These devices are typically rubber or silicone rings or tubes that are placed at the base of the erect penis to trap the erection. They can be used by men who can achieve erections but lose them easily. These devices should not be used for longer than 30 minutes or lack of oxygen can damage the penis, and they should not be used by patients who have bleeding problems or are taking anticoagulant medicines ("blood thinners").

Penile implants are available for men who cannot take medication or who fail less invasive treatments. A 2006 study reported that penile implants helped restore sexual function to 89% of men who had the procedure, and 81% of men were satisfied with the results.

Three types of surgical implants are used for the treatment of erectile dysfunction:

A hydraulic implant consists of two cylinders placed within the erection chambers of the penis and a pump. The pump releases a saline solution into the chambers to cause an erection, and removes the solution to deflate the erection.
A penile prosthesis is composed of two semi-rigid but bendable rods that are placed inside the erection chambers of the penis. The penis can then be manipulated to an erect or non-erect position.
A third implant uses interlocking soft plastic blocks that can be inflated or deflated using a cable that passes through them.

There appear to be no long-term immune problems related to the silicon or other materials in the devices.

Limitations. Erectile tissue is permanently damaged when these devices are implanted and procedures are irreversible. Although uncommon, mechanical breakdown can occur, or the device can slip or bulge, especially if the patient coughs or vomits vigorously after the operation. In addition, a less than optimal quality of erection may result. (Using the MUSE system may restore or improve the function of a penile prosthesis in patients with a failed device.)

Complications. Infection is the major concern with these devices. Redness and fever often accompany a full-blown infection. Any intermittent pain that continues to occur after an implant may be an indicator of a low-grade infection. If the infection can be caught early enough, implant failure can be prevented. Most infections are treated with antibiotics for at least 10 - 12 weeks. If antibiotics fail, a surgical exchange, in which the infected implant is simultaneously replaced with a new one, should be considered. This is a complex procedure, but some surgeons have reported a 90% success rate.

For men whose impotence is caused by damage to the arteries or blood vessels, vascular surgery might be an option. Two types of operations are available: revascularization (bypass) surgery, and venous ligation. The American Urologic Association stresses that vascular surgery is still investigational.

Revascularization. The revascularization procedure usually involves taking an artery from a leg and then surgically connecting it to the arteries at the back of the penis, bypassing the blockages and restoring blood flow. In a related procedure called deep dorsal vein arterialization, a penile vein is used for the bypass. Young men with local sites of arterial blockage or those with pelvic injuries generally achieve the best results. In studies of selected patients there was improvement in erectile dysfunction in 50 - 75% of men after 5 years.

Venous Ligation. Venous ligation is performed when the penis is unable to store a sufficient amount of blood to maintain an erection. This operation ties off or removes veins that are causing an excessive amount of blood to drain from the erection chambers. The success rate is estimated at between 40 - 50% initially, but drops to 15% over the long term. It is important to find a surgeon experienced in this surgery. In a variation of this technique called venous ablation, ethanol is injected into the deep dorsal vein, the main vein that drains blood from the penis. The ethanol causes scarring that closes off smaller veins and prevents blood leakage, thereby bolstering erectile function.

Natural Remedies

Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been a number of reported cases of serious and even lethal side effects from herbal products. Patients should always check with their doctors before using any herbal remedies or dietary supplements.

The following are special concerns for people taking alternative remedies for erectile dysfunction:

Yohimbe. Yohimbe, which is similar to yohimbine, is derived from the bark of a West African tree. Side effects include nausea, insomnia, nervousness, and dizziness. Large doses of yohimbe can increase blood pressure and heart rate and may cause kidney failure.

Gamma-Butyrolactone (GBL). GBL is found in products marketed for improving sexual function (Verve, Jolt). This substance can convert to a chemical that can cause toxic and life-threatening effects, including seizures and even coma.

Gingko. Although the risks for gingko appear to be low, there is an increased risk for bleeding at high doses and interaction with vitamin E, anti-clotting medications, and aspirin and other NSAIDs. Large doses can cause convulsions. Commercial gingko preparations have also been reported to contain colchicine, a substance that can be harmful in people with kidney or liver problems.

L-arginine (also called arginine). Arginine may cause gastrointestinal problems. It can also lower blood pressure and change levels of certain chemicals and electrolytes in the body. It may increase the risk for bleeding. Some people have an allergic reaction to it, which in some cases may be severe. It may worsen asthma.

DHEA. DHEA is a supplement related to certain male and female hormones. Studies show inconclusive results in its treatment for erectile dysfunction. DHEA may interact dangerously with other medications.

Aphrodisiacs. Aphrodisiacs are substances that are supposed to increase sexual drive, performance, or desire. Examples include:

Viramax is a well-marketed product that contains yohimbine and three herbal aphrodisiacs: catuaba, muira puama, and maca. It has not been proven to be either effective or safe, and interactions with medications are unknown.
Spanish fly, or cantharides, which is made from dried beetles, is the most widely-touted aphrodisiac but can be particularly harmful. It irritates the urinary and genital tract and can cause infection, scarring, and burning of the mouth and throat. In some cases, it can be life threatening. No one should try any aphrodisiac without consulting a doctor.

Other Alternative Products Marketed for Erectile Dysfunction. Vinarol is an over-the-counter supplement that was recalled by the FDA in 2003 after reports surfaced that it contained the same ingredients found in Viagra. Herbal supplements sold as Viagro and Vaegra have no association with Viagra. There are numerous other products marketed as “all-natural” dietary supplements and promoted as treatments for erectile dysfunction and sexual enhancement. The FDA has not approved any of these products and has issued many warnings concerning them. In 2006 and 2007, the FDA warned that “True Man,” “Energy Max,” “Rhino Max,” “VMax,” Libidus,” and similar dietary supplements contain illegal chemicals that can interact with prescription drugs and cause dangerously low blood pressure. These products are particularly dangerous for men with diabetes, high blood pressure, high cholesterol, or heart disease who take prescription drugs that contain nitrates.

Resources

www.niddk.nih.gov -- National Kidney and Urologic Diseases Information
www.auanet.org -- American Urologic Association
www.urologyhealth.org -- Urology Health

References

Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, et al. Testosterone therapy in adult men with androgen deficiency syndromes: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2006 Jun;91(6):1995-2010. Epub 2006 May 23.

Heidler S, Temml C, Broessner C, Mock K, Rauchenwald M, Madersbacher S, et al. Is the metabolic syndrome an independent risk factor for erectile dysfunction? J Urol. 2007 Feb;177(2):651-4.

Selvin E, Burnett AL, Platz EA. Prevalence and risk factors for erectile dysfunction in the US. Am J Med. 2007 Feb;120(2):151-7.

Vardi M, Nini A. Phosphodiesterase inhibitors for erectile dysfunction in patients with diabetes mellitus. Cochrane Database Syst Rev. 2007 Jan 24(1):CD002187.

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

Sinusitis

FitSugar — Wed, 08 Oct 2008 17:35:28 -0700

In This Report

Highlights
Introduction
Causes
Risk Factors
Symptoms
Complications
Diagnosis
Prevention
Treatment for Acute Sinusit...
Treatment for Chronic Sinus...
Surgery
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Restriction

In February 2007, the FDA announced that the antibiotic telithromycin (Ketek) should no longer be used for treatment of acute bacterial sinusitis. In June 2006, the FDA reported that several people had died of liver damage after taking this drug. Telithromycin is now only approved for treatment of community-acquired pneumonia.

Acute Sinusitis Treatment

Antibiotics are widely over-prescribed for acute sinusitis, according to a 2007 study. Researchers also reported that inhaled corticosteroids are frequently prescribed for acute sinusitis, despite little evidence for their efficacy. Most cases of acute sinusitis resolve on their own and do not require antibiotic treatment.

Allergic Fungal Sinusitis

Allergic fungal sinusitis should be considered a distinct form of chronic sinusitis, according to research presented at the 2007 annual meeting of the American Academy of Allergy, Asthma, & Immunolology. Researchers found that patients with allergic fungal sinusitis have an increased allergic and inflammatory response to fungi compared to patients with other types of chronic sinusitis.

Anti-Fungal Drugs

Allergic fungal sinusitis is currently treated with oral corticosteroids such as prednisone, but researchers are investigating whether anti-fungal drugs may help. The anti-fungal drug Amphotericin B (SinuNase) is currently in Phase III trials for patients with chronic sinusitis who have had sinus surgery but are still experiencing sinusitis symptoms. However, several 2006 studies indicated disappointing results.

Balloon Sinuplasty

Balloon sinuplasty is a relatively new procedure that uses a catheter-inserted balloon to gently open and drain nasal passages. In a study of 115 patients with chronic sinusitis, balloon sinuplasty achieved promising results, according to research presented at the 2007 meeting of the American Academy of Otolaryngology–Head and Neck Surgery Foundation. However, some experts believe that it is still too early to recommend this procedure for wide-scale use, especially until further large-scale clinical trials are conducted.

Introduction

The skull contains a number of air-filled spaces called sinuses. They perform the following functions:

Reduce the weight of the skull
Provide insulation for the skull
Provide resonance for the voice

Four pairs of sinuses, known as the paranasal air sinuses, connect to the nasal passages (the two airways running through the nose) and are those that are involved in sinusitis. These sinuses are the following:

Frontal sinuses (behind the forehead)
Maxillary sinuses (behind the cheekbones)
Ethmoid sinuses (between the eyes)
Sphenoid sinuses (behind the eyes)

Healthy sinuses are sterile and contain no bacteria. (The nasal passage, on the other hand, normally contains many bacteria that enter through the nostrils.) Maintaining sinus health depends on a cycle that involves a number of important factors and processes:

The sinuses are lined with a membrane that secretes mucus. Mucus drains down into the nasal passage from a small channel in each sinus. The mucous membranes must be intact and free of injury.
The mucus must be fluid in order to flow freely while being sticky enough to absorb pollutants and entrap bacteria.
The mucus must also contain sufficient amounts of bacteria-fighting substances, including immune factors called antibodies.
Small, hair-like projections called cilia must beat in unison to propel mucus outward, expelling bacteria and other particles.
The sinus passages must be open to allow mucus drainage and the circulation of air through the nasal passage.

Click the icon to see an image of an antibody.

The Disease Process. Sinusitis is an infection that occurs if one or more of the defense processes or factors are amiss, causing obstruction, and bacterial growth occurs in the paranasal sinuses. Among the many causes of such obstruction or congestion are the common cold, allergies, certain medical conditions, abnormalities in the nasal passage, and change in atmosphere. In any of these cases, sinusitis can develop as follows:

Mucus drainage and airflow are blocked.
Secretions build up, encouraging the growth of certain bacteria.
The resulting infection, swelling, and inflammation create further blockage, which may cause the sinuses to close up completely.

Forms of Sinusitis. Sinusitis is classified as acute, subacute, or chronic, or recurrent. The classification is based on how long symptoms last:

Acute: Less than 4 weeks
Subacute: 4 - 8 weeks
Chronic: 8 weeks or longer
Recurrent: 3 or more acute episodes in 1 year

Causes

Bacteria are the most common direct cause of acute sinusitis. (Other organisms might be the infecting cause in less common cases.) The ability of bacteria or other organisms to infect the sinuses, however, must first be set up by conditions that create a favorable environment in the sinus cavities. Sinusitis is most often an acute condition, which is self-limiting and treatable. In some cases, however, the inflammation in the sinuses persists or is chronic do begin with. The causes for such chronic sinusitis cases are sometimes unclear.

The typical process leading to acute sinusitis starts with a flu or cold virus. Viruses themselves do not usually cause sinusitis directly and are implicated in only about 10% of sinusitis cases. Instead, they set the stage by causing inflammation and congestion in the nasal passages (called rhinitis) that leads to obstruction in the sinuses. This creates a hospitable environment for bacterial growth, which is the direct cause of sinus infection. In fact, rhinitis is the precursor to sinusitis in so many cases that expert groups now refer to most cases of sinusitis as rhinosinusitis.

Rhinosinusitis tends to involve the following sinuses:

The maxillary sinuses (behind the cheekbones) are the most common sites.
The ethmoid sinuses (between the eyes) are the second most common sites affected by colds.
The frontal (behind the forehead) and sphenoid (behind the eyes) sinuses are involved in about a third of cold-related cases.

Nearly everyone with colds has inflamed sinuses. These inflammations are typically brief and mild, however, and most people with colds do not develop true sinusitis.

Chronic or recurrent acute sinusitis typically results from one of the following conditions:

Untreated acute sinusitis that results in damage to the mucous membranes
Chronic medical disorders that cause inflammation in the airways or persistent thickened stagnant mucus (such as diabetes, AIDS or other disorders of the immune system, hypothyroidism, cystic fibrosis, Kartagener's syndrome, and Wegener's granulomatosis)
Structural abnormalities
Allergic reaction to fungi

Chronic or recurrent acute sinusitis can be a lifelong condition.

The Role of Bacteria. The role of bacteria or other infectious organisms is complicated in chronic sinusitis. They may play a direct, an indirect, or, in some patients, no role at all. For example, one study reported the following for patients with chronic sinusitis who had not responded to antibiotics:

30% had no evidence of bacteria in their passageways.
20% had bacteria unrelated to infection.

Inflammatory Response, Allergies, and Asthma. The absence of bacterial organisms as a causal factor in many cases suggests that some instances of chronic sinusitis may be due to a continuing inflammatory condition. Such on-going inflammation may have been triggered immune factors that were produced in response to injuries from acute sinusitis. Many of the immune factors observed in people with chronic sinusitis resemble those that appear in allergic rhinitis, suggesting that sinusitis in some individuals is due to an allergic response.

Allergies, asthma, and sinusitis often overlap. Those with allergic rhinitis (so-called hay fever and rose fever) often have symptoms of sinusitis, and true sinusitis can develop as a result of the mucus blockage it causes. A causal association, however, has not been proved, and many experts believe allergies themselves rarely predispose to sinusitis. People with chronic sinusitis may also have an allergic reaction to fungal organisms.

Severe asthma (which is often associated with allergies) and chronic sinusitis often overlap, although the relationship is unclear. Between 53 - 75% of children with asthma caused by allergies have sinus abnormalities, and various studies have shown that between 17 - 30% of asthmatic patients develop true sinusitis. In fact, chronic sinusitis may actually be the cause of asthma in some cases.

Abnormalities of the Nasal Passage. Abnormalities in the nasal passage can cause blockage and thereby increase the risk for chronic sinusitis. Some abnormalities include:

Polyps (small benign growths) in the nasal passage block mucus drainage and restrict airflow. Polyps themselves may be consequences of previous sinus infections that caused overgrowth of the nasal membrane.
Enlarged adenoids can lead to sinusitis.

Adenoids are masses of tissue located high on the posterior wall of the pharynx. They are made up of lymphatic tissue, which trap and destroy pathogens in the air that enter the nasopharynx.

Cleft palate
Tumors
Deviated septum (a common structural abnormality in which the septum, the center section of the nose, is shifted to one side, usually the left)

Click the icon to see an image of a deviated septum.

The bacteria most commonly implicated in sinusitis include:

Streptococcus pneumoniae (also called pneumococcal pneumonia or pneumococci). This bacterium is found in between 20 - 43% of adults and children with sinusitis.
H. influenzae (a common bacterium associated with many upper respiratory infections). This bacterium colonizes nearly half of all children by age 2, and causes about 25% of sinusitis cases in this group. Studies have reported the presence of this bacterium in 22 - 35% of adult sinusitis patients.
Moraxella catarrhalis. Over 75% of all children harbor this bacterium, which causes about 25% of sinusitis cases.

Other possible bacterial culprits include:

Other streptococcal strains
Staphylococcus aureus

While fungi are an uncommon cause of sinusitis, the incidence of such infections is increasing. At least 5 - 10% of chronic rhinosinusitis patients may actually have allergic fungal sinusitis. At the 2007 meeting of the American Academy of Allergy, Asthma, & Immunology (AAAAI), experts presented evidence suggesting that allergic fungal sinusitis is a distinct form of chronic rhinosinusitis. Research indicates that allergic fungal sinusitis may provoke a distinct immune response. In the AAAAI study, patients with allergic fungal sinusitis showed increased antibody levels of immunoglobulin E (IgE) and immunoglobulin G (IgG) compared to patients with other types of chronic rhinosinusitis.

In earlier research from 2004, scientists from the U.S. National Institute of Allergy and Infectious Diseases exposed immune cells from patients with chronic sinusitis and healthy volunteers to four common types of fungi: Alternaria, Aspergillus, Penicillium, and Cladosporium. The study’s findings suggested that some people who suffer from chronic sinusitis have an extreme immune and inflammatory response to fungi and may benefit from anti-fungal treatment.

Fungi involved in sinusitis include:

Aspergillus is the most common cause of all forms of fungal sinusitis.
Other fungi include Curvularia, Bipolaris, Alternaria, Dreschslera, Cryptococcus, Candida, Sporothrix,Exserohilum, and Mucormycosis.
There have been a few reports of fungal sinusitis caused by Metarrhizium anisopliae, which is used in biological insect control.

There are four categories of fungal sinusitis:

Acute or invasive fungal sinusitis - This infection is most likely to affect people with diabetes and compromised immune systems.
Chronic or indolent fungal sinusitis - This form is generally found outside the U.S., most commonly in the Sudan and northern India.
Fungus ball (mycetoma) - This fungal sinusitis is noninvasive and occurs usually in one sinus, most often the maxillary sinus.
Allergic fungal sinusitis - This form typically occurs because of an allergy to the fungus Aspergillus (rather than being caused by the fungus itself). In such cases, a peanut butter-like fungal growth occurs in the sinus cavities that may cause nasal passage obstruction and the erosion of the bones.

Fungal infections can be very serious, and both chronic and acute fungal sinusitis require immediate treatment. Fungal ball is not invasive and is nearly always treatable.

Fungal infections should be suspected in people with sinusitis who also have diabetes, leukemia, AIDS, or other conditions that impair the immune system. Fungal infections can also occur in patients with healthy immune systems but they are far less common.

Risk Factors

Sinusitis is one of the most common diseases in the United States. According to the National Institute of Allergies and Infectious Diseases (NIAID), it affects an estimate 37 million Americans each year. However, a 2004 report in the Archives of Otolaryngology - Head and Neck Surgery suggests that sinusitis may not be as common as previously reported. The researchers found that accounts that rely solely on patient self-reporting may be exaggerated.

Everyone gets viral colds and flu, and most people develop symptoms in the upper respiratory tract (air passages in the head and neck) at some point. Over 85% of people with colds have inflamed sinuses. These inflammations are typically brief and mild, however, and only between 0.5 - 10% of people with colds develop true sinusitis. (One study suggested that nose blowing during a cold may transmit bacteria back into the sinuses and increase the risk for sinusitis.) Studies suggest that the following population groups have higher risks for sinusitis:

Young children and the elderly are at higher risk for more serious upper respiratory tract infections and for complications from them.
Women appear to be at higher risk than men.
People living in the Midwest and South have a higher incidence of sinusitis than those in the Northeast and West.
People in higher income and educational groups appear to have a greater risk than those in lower groups.
Caucasian and African Americans have a higher rate than Hispanic Americans.

Before the immune system matures, all infants are susceptible to respiratory infections, with a possible frequency of one cold every 1 - 2 months. Young children are prone to colds and may have 8 - 12 bouts every year. Smaller nasal and sinus passages also make children more vulnerable to upper respiratory tract infections than older children and adults. Ear infections such as otitis media are also associated with sinusitis. Nevertheless, true sinusitis is very rare in children under 9 years of age. Some experts believe it is greatly overdiagnosed in this population.

The elderly are at specific risk for sinusitis. Their nasal passages tend to dry out with age. In addition, the cartilage supporting the nasal passages weakens causing airflow changes. They also have diminished cough and gag reflexes and faltering immune systems and are at greater risk for serious respiratory infections than are young and middle-aged adults.

People with asthma, allergies or both are at higher risk for non-infectious inflammation in the sinuses. The risk for sinusitis is higher in patients with severe asthma. People with a combination of polyps in the nose, asthma, and sensitivity to aspirin (called Samter's or ASA triad) are specifically at very high risk for chronic or recurrent acute sinusitis.

Hospitalized patients are at higher risk for sinusitis, particularly those with:

Head injuries
Conditions requiring insertion of tubes through the nose
Antibiotics or steroids treatment
Breathing aided by mechanical ventilators. (Such patients may have a significantly higher risk for maxillary sinusitis. In fact, treating sinusitis in such patients may significantly reduce the risk for ventilator-associated pneumonia.)

A number of medical conditions put people at risk for chronic sinusitis. They include:

Diabetes
Gastroesophageal reflux disease
Nasal polyps or septal deviation
AIDS and other disorders of the immune system predispose the patient to sinusitis (fungal infections are especially risky)
Pregnancy -- may cause temporary congestion and symptoms of sinusitis
Hypothyroidism -- causes congestion that clears up when the condition is treated
Cystic fibrosis -- a genetic disorder in which the mucus is very thick and builds up
Kartagener's syndrome
Wegener's granulomatosis -- a serious but very rare illness that causes long-term swelling and tumor-like masses in air passages

Dental Problems. Anaerobic bacteria are associated with infections from dental problems or procedures, which precipitate about 10% of cases of sinusitis.

Changes in Atmospheric Pressure. People who experience changes in atmospheric pressure, such as while flying, climbing to high altitudes, or swimming, risk sinus blockage and therefore an increased chance of developing sinusitis. (Swimming increases the risk for sinusitis for other reasons, as well.)

Cigarette Smoke and Other Air Pollutants. Air pollution from industrial chemicals, cigarette smoke, or other pollutants can damage the cilia responsible for moving mucus through the sinuses. Whether air pollution is an important cause of sinusitis and, if so, which pollutants are critical factors is still not clear. Cigarette smoke, for example, poses a small but increased risk for sinusitis in adults. Second-hand smoke does not appear to have any significant effect on adult sinuses, although it does seem to pose a risk for sinusitis in children.

Symptoms

Symptoms Indicating a Bacterial Infection. Sinus symptoms are very common during a cold or the flu, but in most of these cases they are due to the effects of the infecting virus and resolve when the infection does. It is important to differentiate between inflamed sinuses associated with cold or flu virus and sinusitis caused by bacteria. With true acute bacterial sinusitis, the signs and symptoms typically have the following course:

Nasal congestion and discharge comes first and is typically thick with pus that is yellowish to yellow-green.
Pain in the teeth is increased by bending over. Symptoms may vary, however, depending on the sinuses involved.
Symptoms continue for 10 days or more after the start of a cold or flu.
They worsen after 5 - 7 days, or they return after initial improvement in a cold (called double sickening).

Other symptoms of acute sinusitis that usually occur in adults include:

Severe headache and pain or pressure in specific areas in the face -- eyes may be red, bulging or painful eyes if the sinus infection occurs around the eyes; in some cases, patients may also have double vision and even temporary vision loss.
A persistent cough (particularly during the day)
Fever
Fatigue (from lack of good rest)
Lack of response to decongestants or antihistamines

Sneezing, sore throat, and muscle aches may be present, but they are rarely caused by sinusitis itself. Muscle aches may be caused by fever, sore throat by post-nasal drip, and sneezing from cold or allergies.

Rare complications of sinusitis can produce additional symptoms, which may be severe or even life threatening.

Symptoms in Children. Children are most likely to develop infection in the ethmoid sinuses, located between the eyes. Children with sinusitis are also less likely to experience facial pain over the affected sinus and headache, which are the primary signs in adults. Symptoms of bacterial sinusitis may be less specific than in adults and include:

Persistent nasal discharge (of any type) and day time cough for more than 10 days, or
Severe symptoms last for at least 3 - 4 days in a row and include thick, greenish nasal discharge plus a fever of at least 102° F.

Other symptoms in children may include:

Irritability
Vomiting
Gagging on mucus
Cough

Recurrent acute and chronic sinusitis tend to take the following course:

Symptoms are more vague and generalized than acute sinusitis.
They last longer than 4 weeks. (Subacute sinusitis lasts longer than 4 weeks but less than 8 weeks. Chronic sinusitis lasts 8 weeks or longer.)
They occur throughout the year, even during nonallergy seasons.

Specifically symptoms may include:

Nasal congestion and obstruction
Chronic cough (day and night) -- research suggests that sinusitis is one of the main causes of chronic cough
Bad breath
Postnasal drip (which can cause repeated throat clearing)
Facial tenderness or pressure --patients do not usually experience facial pain unless the infection is in the frontal sinuses

Specific symptoms depend on the location of the infection:

Frontal sinusitis causes pain across the lower forehead.
The pain in maxillary sinusitis occurs over the cheeks and may travel to the teeth, and the hard palate in the mouth sometimes becomes swollen.
Ethmoid sinusitis causes pain behind the eyes and sometimes redness and tenderness in the area across the top of the nose.
Sphenoid sinusitis rarely occurs by itself; when it does, the pain may be experienced behind the eyes, across the forehead, or in the face.



ETHMOID SINUSITIS
Ethmoid sinuses are located between the eyes. They resemble a honeycomb and are vulnerable to obstruction. This is a common location for sinusitis in children.	Nasal congestion. Nasal discharge or postnasal drip. Pain or pressure around the inner corner of the eye or down one side of the nose. Headache in the temple or surrounding the eye. Symptoms worse when coughing, straining, or lying on the back and better when the head is upright. Fever. Symptoms of maxillary sinusitis often occur. Symptoms indicating medical emergency: Increasing severity of symptoms. Fever, swelling and drooping eyelid, loss of eye movement (possible orbital infection, which is in the eye socket). Fever, vision changes, pupil fixed or dilated. Symptoms spreading to both sides of face (may indicate blood clot).	Chronic nasal discharge, obstruction, and low-grade discomfort usually across the bridge of the nose. Symptoms worse in the late morning or when wearing glasses. Chronic sore throat and bad breath. Sinusitis also can recur in other sites.
ACUTE MAXILLARY SINUSITIS
Maxillary sinuses are located behind the cheek bones. They are present at birth and continue to develop as long as teeth erupt. Tooth roots, in some cases, can penetrate the floor of these sinuses.	Pain across the cheekbone, under or around the eye, or around the upper teeth; may occur on one or both sides of the face. Area over the cheekbone is tender and may be red or swollen. Possibly tooth pain. Symptoms are worse when the head is upright and improve when patient reclines. Nasal discharge or postnasal drip. Fever.	Discomfort or pressure below the eye. Chronic toothache. Symptoms become worse with colds, flu, or allergies. Discomfort increases during the day. Coughing increases at night.
FRONTAL SINUSITIS
Frontal sinuses are located on both sides of the forehead. These sinuses are late in developing, so infection here is uncommon in children.	Severe headache in the forehead. Fever (common but not always present). Symptoms are worse when lying on the back and when pressing against the area over the eye on the side closest to the nose. Symptoms are better when the head is upright. Nasal discharge or postnasal drip. Symptoms indicating medical emergency: Increasing severity of symptoms, particularly severe headache, altered vision, mild personality or mental changes (may indicate spread of infection to brain). Fever, vision changes, fixed or dilated pupil. Symptoms spreading to both sides of face (may indicate blood clot). Headache, fever, along with a soft swelling over the bone (may indicate bone infection).	Persistent, low-grade headache in the forehead. History of physical injury or other damage to the sinus area.
SPHENOID SINUSITIS
Sphenoid sinuses are located behind the eyes. They usually are present by age 3 and are fully developed by age 12.	Deep headache with pain in many places, including the back and top of the head, across the forehead, and behind the eye. Fever. Symptoms are worse when lying on the back or bending forward. Nasal discharge or postnasal drip. Symptoms indicating medical emergency: Increasing severity of symptoms, particularly severe headache, altered vision, mild personality or mental changes (may indicate spread of infection to brain).	Low grade, general headache (although not always present).

Complications

Bacterial sinusitis is nearly always harmless (although uncomfortable and sometimes even very painful). If an episode becomes severe, antibiotics generally eliminate further problems. In rare cases, however, sinusitis can be very serious.

Osteomyelitis. Adolescent males with acute frontal sinusitis are at particular risk for severe problems. One important complication is infection of the bones (osteomyelitis) of the forehead. In such cases, the patient usually experiences headache, fever, and a soft swelling over the bone known as Pott's puffy tumor.

Infection of the Eye Socket. Infection of the eye socket, or orbital infection, which causes swelling and subsequent drooping of the eyelid, is a rare but serious complication of ethmoid sinusitis. In these cases, the patient loses movement in the eye, and pressure on the optic nerve can lead to vision loss, which is sometimes permanent. Fever and severe illness are usually present.

Blood Clot. Another danger, although rare, from ethmoid or frontal sinusitis are blood clots. If a blood clot forms in the sinus area around the front and top of the face, symptoms are similar to orbital infection. In addition, the pupil may be fixed and dilated. Although symptoms usually begin on one side of the head, the process usually spreads to both sides.

Widespread Infection. The most dangerous complication of sinusitis, particularly frontal and sphenoid sinusitis, is the spread of infection by anaerobic bacteria to the brain, either through the bones or blood vessels. Abscesses, meningitis, and other life-threatening conditions may result. In such cases, the patient may experience mild personality changes, headache, altered consciousness, visual problems, and, finally, seizures, coma, and death.

Chronic and acute fungal sinusitis caused by the fungi Aspergillus and mucormycosis is difficult to treat and potentially lethal, particularly in people with diabetes and compromised immune systems. Mucormycosis is particularly dangerous if it is not treated quickly. Fungal ball (mycetoma) is not invasive and is nearly always treatable with surgery. Recurrence is rare.

The relationship between sinusitis and asthma is unclear. A number of theories have been proposed for a causal or shared association between sinusitis and asthma. Some include the following:

Stimulation of nerve pathways, inflammation, and overproduction of mucus in the nasal passages and sinus cavities may eventually affect the airways in the lung, causing them to hyperreact.
Breathing through the mouth when the sinuses are blocked allows in large particles that would other wise be filtered by the nasal defense system. Such particles could trigger allergic responses in the lungs that can trigger asthma in susceptible people.
Air breathed through the mouth is colder than air warmed in the nasal passages. Cold air is a known trigger of asthma.
Both may share similar immune abnormalities that cause inflammation in the airways in the lungs and sinuses.

Successful treatment of both allergic rhinitis and chronic sinusitis in children who also have asthma may reduce symptoms of asthma. It is particularly important to treat any coexisting bacterial sinusitis in people with asthma. They might not respond to asthma treatments unless the infection is cleared up first.

Pain and other symptoms of chronic sinusitis can have significant effects on the quality of life. This condition can cause emotional distress, impair normal activity, and reduce attendance at work or school. According to the American Academy of Allergy, Asthma, and Immunology, the average sinusitis patient misses about 4 work days a year. In fact, a 2003 study placed sinusitis in the top 10 medical conditions that most adversely affect American employers. In addition, some people may lose their sense of smell. Surgery or medical treatments can help restore this sense.

Diagnosis

Patients who have sinusitis symptoms that do not clear up within a few days, are severe, or are accompanied by high fever or acute illness should see a doctor. However, that only one-half to two-thirds of patients with such symptoms actually have sinusitis. Some experts complain that too many patients are diagnosed with true sinusitis and given unnecessary antibiotics when their symptoms would actually resolve easily in days with over-the-counter medications or no drugs at all. Others believe that true sinusitis is often mistakenly diagnosed as an allergy and not treated, which could lead to serious illness.

The first goal in diagnosing sinusitis is to rule out other possible causes of symptoms, and then determine:

The site where the infection has occurred
Whether the condition is acute or chronic
The organism causing the infection (if possible)

Ruling Out Sinus Symptoms Due to Cold or Flu Viruses. It is often difficult to tell when a viral infection converts to a bacterial infection. Studies have found that between 40 - 85% of patients with the common cold show signs of inflamed sinuses on x-rays or CT scans. A cold, however, unlike sinusitis, typically clears up without treatment within a week. (Only about 0.5 - 2% of adults with viral colds or flus actually develop bacterial infections.) In general, the doctor should suspect a bacterial infection under the following circumstances:

If sinus symptoms persist for 10 days or longer after a cold or flu, or
If symptoms become worse after 5 - 7 days

Ruling Out Allergies. Symptoms of both sinusitis and allergic rhinitis include nasal obstruction and congestion. The conditions often occur together. People with allergies and no sinus infection may have:

Thin, clear, and runny nasal discharge
Itchy nose, eyes, or throat (do not occur with bacterial sinusitis)
Recurrent sneezing
Symptoms of allergies appear only during exposure to allergens

Ruling Out Migraine and Other Headaches. Many primary headaches, particularly migraine or cluster, may closely resemble sinus headache. In fact, results presented at a 2004 meeting of the American Headache Society suggest that 90% of people who thought they had a sinus headache actually had migraines. Migraine and sinus headaches may even coexist in many cases. Sinus headaches are usually more generalized than migraines, but it is often difficult to tell them apart, particularly if headache is the only symptom of sinusitis. The following symptoms suggest a migraine rather than a sinus headache:

The headache is recurrent
It has a significant impact on daily activities
The headache does not get worse over time

Ruling Out Neuralgia. In some cases, headache that persists after successful treatment of chronic sinusitis may be due to neuralgia (nerve-related pain) in the face. This condition requires specific drugs, such as tricyclic antidepressants or carbamazepine. Trials using such drugs may identify patients with neuralgia and help avoid unnecessary invasive treatments for chronic sinusitis.

Ruling Out Other Conditions. A number of other conditions can mimic sinusitis. They include:

Dental problems
A foreign object in the nasal passage
Temporal arteritis (headache caused by inflamed arteries in the head and neck)
Persistent upper respiratory tract infections
Chronic fatigue syndrome (CFS) or fibromyalgia. However, researchers reported in the Archives of Internal Medicine that there may be a link between CFS and sinusitis. In the study, patients with unexplained chronic fatigue were nine times more likely to suffer sinus problems than those without fatigue.
Temporomandibular disorders (problems in the joints and muscles of the jaw hinges)
Vasomotor rhinitis, a condition in which the nasal passages become congested in response to irritants or stress. It often occurs in pregnant women.

Medical History. The patient should describe all symptoms such as nasal discharge and specific pain in the face and head, including eye and tooth pain.

After assessing symptoms, the doctor should take a thorough medical history of the patient:

Any history of allergies or headaches
Recent upper respiratory infection (colds, flus, infection)
History of sinusitis episodes that is unresponsive to antibiotic treatment. (In such cases, the doctor will usually diagnose chronic or recurrent acute sinusitis and refer the patient to a specialist for more advanced testing.)
Exposure to cigarette smoke or other environmental pollutants
Recent travel
Recent dental procedures, particularly if there is pain toward the back of the mouth
Medications being taken (particularly decongestants)
Any known structural abnormalities in the nose and face
Injury to the head or face
History of medical conditions, such as chronic fatigue syndrome or fibromyalgia, which can produce tender areas in the face or sinus regions and nonspecific symptoms of ill health
Any family history of allergies, immune disorders, cystic fibrosis, or immotile cilia syndrome
In small children with sinusitis, whether they attend a day care center or nursery school

The doctor will press the forehead and cheekbones to check for tenderness and check for other signs of sinusitis, including yellow to yellow-green nasal discharge. The doctor will also check the inside of the nasal passages using a device with a bright light to check the mucus and look for any structural abnormalities.

In some cases, tests may be used to detect that presence of immune factors in sinus tissues that would suggest persistent inflammation. Such findings would strongly suggest a chronic or allergic condition. In 2005, a new laboratory test became available for diagnosing chronic sinusitis. The CRS Fungal Profile tests mucus samples for eosinophil major basic protein (a protein involved in allergic and inflammatory reactions) and a type of fungi.

Nasal endoscopy, or rhinoscopy, is now used for diagnosing chronic and recurrent acute sinusitis and for differentiating between allergies and true acute sinusitis. It involves the insertion of a flexible tube into the nasal passage and the use of a fiberoptic light that enables the doctor to see inside the sinuses. Endoscopy allows detection of even very small abnormalities in the sinuses. It can determine whether surgery is necessary and if medications are having any effect. Bacterial cultures can also be taken from samples removed using endoscopy. (Endoscopy is also used for treating sinusitis.)

Computer Tomography. Computed tomography (CT) scanning is the best method for viewing the paranasal sinuses. There is little relationship, however, between symptoms in most patients and findings of abnormalities on a CT scan. CT scans are recommended for acute sinusitis only if there is a severe infection, complications, or a high risk for complications. CT scans are useful for diagnosing chronic or recurrent acute sinusitis and for surgeons as a guide during surgery. They show inflammation and swelling and the extent of the infection, including that in deep hidden air chambers missed by x-rays and nasal endoscopy. Often, they can detect the presence of fungal infections.

X-Rays. Until the availability of endoscopy and CT scans, x-rays were commonly used. They are not as accurate, however as these procedure in identifying abnormalities in the sinuses. For example, more than one x-ray is needed for diagnosing frontal and sphenoid sinusitis. X-rays do not detect ethmoid sinusitis at all, which can be the primary site of an infection that has spread to the maxillary or frontal sinuses.

Magnetic Resonance Imaging. MRI is not as effective as CT in defining the paranasal anatomy and therefore is not typically used to image the sinuses for suspected sinusitis. MRI is also more expensive than CT. However, it can help rule out fungal sinusitis and may help differentiate between inflammatory disease, malignant tumors, and complications within the skull. It may also be useful for showing soft tissue involvement.

Transillumination is a procedure aimed at visualizing maxillary and frontal sinuses. First the doctor shines a bright light against the patient's cheek or forehead in a completely darkened room. If the sinuses are clear, the doctor will observe a glow on the hard palate of the open mouth or in the areas of the cheek where the sinus passages are located. It is fast, safe, and inexpensive, but it is useful only in adults and only to rule out any problems. It has largely been supplanted by more accurate diagnostic techniques.

Sinus puncture with bacterial culture is the gold standard for diagnosing a bacterial sinus infection. It is invasive, however, and is performed only when antibiotics have not worked. Sinus puncture involves using a needle to withdraw a small amount of fluid from the sinuses. It requires a local anesthetic and is performed by a specialist. The fluid is then cultured to determine what type of bacteria is causing sinusitis.

Prevention

The best way to prevent sinusitis is to avoid colds and influenza. If you are unable to avoid them, the next best way to prevent sinusitis is to effectively treat colds and influenza.

Colds and flu are spread primarily when an infected person coughs or sneezes near someone else. A very common method for transmitting a cold is by shaking hands. Everyone should always wash their hands before eating and after going outside. Ordinary soap is sufficient. Waterless hand cleaners that contain an alcohol-based gel are also effective for every day use and may even kill cold viruses. (They are less effective, however, if extreme hygiene is required. In such cases, alcohol-based rinses are needed.) Antibacterial soaps add little protection, particularly against viruses. In fact, one study suggests that common liquid dish washing soaps are up to 100 times more effective than antibacterial soaps in killing respiratory syncytial virus (RSV), which is known to cause pneumonia. Wiping surfaces with a solution that contains one part bleach to 10 parts water is very effective in killing viruses.

Colds are not caused by insufficiently warm clothes or by going outside with wet hair. A 2002 study reported, however, that in older adults cold temperatures can thicken the blood and may increase the risk for respiratory infections and even circulatory and heart problems.

Foods Containing Lactobacilli (Good Bacteria). Researchers are studying the possible protective value of certain strains of lactobacilli bacteria found in the intestines. Some of these strains, particularly acidophilus, are used to make yogurt. According to one study, milk containing the strain lactobacilli GG helped reduce respiratory infections in children attending day care by 10 - 20%.

Vitamins. Studies are mixed whether vitamin supplements protect against upper respiratory infections. Large doses of vitamin C, for example, may help reduce the duration of a cold, but they do not appear to protect against one in the first place, even after exposure to a cold virus. Two studies in 2002 on multivitamins reported opposite results, with one finding fewer infections and one finding no difference. It is possible that vitamin C or multivitamin supplements may be helpful in specific people, such those who are vitamin deficient or have medical problems that impair their immune systems.

Studies on vitamin E specifically have been largely negative. A 2002 study, in fact, reported a higher incidence and greater severity of respiratory infections in older adults who took 200 mg of vitamin E daily.

Breastfeeding. Evidence suggests that women who breastfeed reduce the risk of respiratory infections in their children. The American Academy of Pediatrics recommends that babies be fed exclusively breastmilk for their first 6 months.

Low Stress and Active Social Life. More than one study has reported that people with low stress who also have an active social life have fewer colds than people who have high stress levels or those who have low stress and few social connections.

Zinc appears to have certain important effects on the immune system and it may have a direct effect on viruses. How it works is not entirely clear, however. Zinc preparations in lozenge or nasal gel form are now available as cold treatments. Studies are very mixed on the effects of zinc on colds.

A nasal gel (Zicam), which contains zinc gluconate, has shown some success, possibly because the gel sticks to the nasal passages long enough for the zinc to interact with the virus. In a 2003 study, for example, the nasal gel shortened the duration and severity of the cold compared to placebo when it was started within 14 - 48 hours of the onset of symptoms. The supports earlier studies reporting that it shortened the duration of a cold by about 2 days.
Zinc lozenges are showing mixed results. One 2000 study suggested that the use of zinc acetate lozenges may be more effective and have a better taste than other formulations, such as zinc gluconate. On the other hand, a 2002 study reported that zinc gluconate reduced cold duration significantly. To further confuse matters, the two zinc lozenge preparations were directly compared in a 2000 study, and neither was effective.

In any case, no one with an adequate diet and a healthy immune system should take zinc for prolonged periods for preventing colds. Long-term use of zinc (100 mg or higher daily) has been associated with heart problems, anemia, and other conditions.

Side Effects. Side effects of zinc include:

Dry mouth
Constipation
Nausea
Bad taste (possibly only with zinc gluconate lozenges)
Overdose may cause severe vomiting, dehydration, and restlessness. Call a doctor if any of these symptoms occur.
In rare cases, an allergic response may occur.

Food and Drug Interactions. Zinc may also interact with drugs or food:

Zinc may reduce absorption of certain antibiotics.
Foods high in calcium or phosphorus may reduce zinc absorption.
In high doses, and for long periods of time, zinc can cause copper deficiencies.

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 are special concerns for people taking natural remedies for sinusitis:

Echinacea is commonly taken to prevent onset and ease symptoms of cold or flu. However, a rigorous study published in 2005 in the New England Journal of Medicine determined that echinacea does not help to prevent or treat colds. In addition, allergic reactions have been reported. People with autoimmune diseases or plant allergies should particularly avoid this herbal remedy. Echinacea has also been associated with a reaction called erythema nodosum. This involves a rash, sometimes accompanied by fever, headache, muscle and joint aches, and sore throat.
Grapeseed extract is sometimes touted as a natural antihistamine. A 2002 study, however, reported no benefits from it.
Chinese herbal products containing aristolochic acid have been associated with several reports of kidney failure in Europe. Some studies suggest that up to 30% of herbal patent remedies imported from China are laced with potent pharmaceuticals such as phenacetin and steroids. Chinese herbal remedies can also contain toxic metals such as lead.

Vaccines against influenza use inactivated (not live) viruses. Because influenza viruses change from year to year, influenza vaccines are redesigned annually to match the anticipated viral strains. Experts recommend that people receive annual influenza vaccinations in October or November. People who should definitely be vaccinated include: all adults 65 years or older; children age 6 months - 5 years; other adults or children who are at high risk for developing serious medical complications from influenza; health care workers and others who care for individuals who are at high risk for influenza complications. [See In-Depth Report #94: Colds and influenza.]

The pneumococcal vaccine protects against S. pneumoniae (also called pneumococcal) bacteria, the most common cause of respiratory infections. There are two effective vaccines available, one called a 23-valent polysaccharide vaccine (Pneumovax, Pnu-Immune) for adults and a 7-valent conjugate vaccine (Prevnar or PCV7) for infants and young children. Experts are now recommending that more people, including healthy elderly people, be given the pneumococcal vaccine, particularly in light of the increase in antibiotic-resistant bacteria. [See In-Depth Report #64: Pneumonia.]

Treatment for Acute Sinusitis

The primary objectives for treatment of sinusitis are reduction of swelling, eradication of infection, draining of the sinuses, and ensuring that the sinuses remain open. Less than half of patients reporting symptoms of sinusitis need aggressive treatment. Home remedies can be very useful.

Home remedies that open and hydrate sinuses may, indeed, be the only treatment necessary for mild sinusitis that is not accompanied by signs of acute infection.

Drinking plenty of fluids and getting lots of rest when needed is still the best bit of advice to ease the discomforts of the common cold. Water is the best fluid and helps lubricate the mucous membranes. (There is no evidence that drinking milk will increase or worsen mucus, although milk is a food and should not serve as fluid replacement.)
Chicken soup does indeed help congestion and aches. The hot steam from the soup may be its chief advantage, although laboratory studies have actually reported that ingredients in the soup may have anti-inflammatory effects. In fact, any hot beverage may have similar soothing effects from steam. Ginger tea, fruit juice, and hot tea with honey and lemon may all be helpful.
Spicy foods that contain hot peppers or horseradish may help clear sinuses.
Inhaling steam 2 - 4 times a day is extremely helpful, costs nothing, and requires no expensive equipment. The patient should sit comfortably and lean over a bowl of boiling hot water (no one should ever inhale steam from water as it boils) while covering the head and the bowl with a towel so the steam remains under the cloth. The steam should be inhaled continuously for 10 minutes. A mentholated or other aromatic preparation may be added to the water. Long, steamy showers, vaporizers, and facial saunas are alternatives.

Many people take medications to reduce mild pain and fever. Adults most often choose aspirin, ibuprofen (Advil), or acetaminophen (Tylenol).

The following are recommendations for children:

Acetaminophen (Tylenol) or ibuprofen (usually Advil or Motrin) is the pain-reliever of choice in children. Most pediatricians advise such medications for children who run fevers over 101°F.
Aspirin and aspirin-containing products are virtually never recommended for children or adolescents. Reye syndrome, a very serious condition, has been associated with aspirin use in children who have flu symptoms or chicken pox.

Some studies suggest that these anti-fever drugs may actually reduce the body's immune response against cold and flu viruses and prolong symptoms. A 2000 study, for example, reported a longer flu duration in people who took aspirin or acetaminophen (although people still felt better). Nevertheless, most doctors strongly recommend lowering fevers in children, since high fevers can sometimes cause seizures.

A nasal wash can be helpful for removing mucus from the nose. A saline solution can be purchased at a drug store or made at home. (Mix 1 teaspoon of table salt with a pinch of baking soda in 2 cups of warm water.) The nasal wash should be performed several times a day. Researchers have reported that daily irrigation of the nasal passages with a hypertonic saline solution relieves sinusitis symptoms and also reduces antibiotic use and the occurrence of acute exacerbations. Patients in the study had 72% fewer sinus infections, a 69% improvement in breathing, and they reduced medication usage by more than half.

A simple method for administering a nasal wash is:

Lean over the sink head down.
Pour some solution into the palm of the hand and inhale it through the nose, one nostril at a time.
Spit the remaining solution out.
Gently blow the nose.

The solution may also be inserted into the nose using a large rubber ear syringe, available at a pharmacy. In this case the process is:

Lean over the sink head down.
Insert only the tip of the syringe into one nostril.
Gently squeeze the bulb several times to wash the nasal passage.
Then press the bulb firmly enough so that the solution passes into the mouth.
The process should be repeated in the other nostril.

Decongestants are drugs that help reduce nasal congestion. They are available in a pill or nasal form. However, decongestants will not cure sinusitis. Nasal decongestants can actually worsen sinusitis by increasing sinus inflammation. Due to the lack of evidence for nasal decongestants’ benefits for sinusitis, the FDA has ruled that manufacturers of over-the-counter (OTC) nasal decongestant products remove from their labeling all references to sinusitis.

Your doctor may still recommend that you take either an OTC or prescription nasal decongestant to help relieve blockage symptoms associated with sinusitis. If you think you have sinusitis, it is important that you check with your doctor before taking a decongestant. Do not try to treat sinusitis by yourself.

Nasal Decongestants. Nasal decongestants come in long-acting or short-acting forms. The effects of short-acting decongestants last about 4 hours; long-acting decongestants last 6 - 12 hours. The active ingredients in nasal decongestants include oxymetazoline, xylometazoline, and phenylephrine.

Tips for Use. The following precautions are important for people taking nasal decongestants:

When using a nasal spray, spray each nostril once. Wait a minute to allow absorption into the mucosal tissues, and then spray again.
Do not share droppers and inhalators with other people.
Discard sprayers, inhalators, or other decongestant delivery devices when the medication is no longer needed. Over time, these devices can become reservoirs for bacteria.
Discard the medicine if it becomes cloudy or unclear.

Decongestants Taken by Mouth. Pseudoephedrine is the only decongestant taken by mouth that is currently available over-the-counter (OTC) in the United States. It decreases the volume of mucous in the nose, as well as within the Eustachian tubes. Many brands of OTC oral decongestants are available. A common brand is Sudafed. Oral decongestants such as Sudafed can also be helpful for relieving cough associated with postnasal drip.

Warning: Anyone with old forms of any decongestant should check the labels and discard them if they contain phenylpropanolamine. In November 2000, the FDA banned products, including decongestants, which contained phenylpropanolamine (PPA). This action was in response to a few reports of an increased risk of stroke. (Stroke tended to occur in people who took diet suppressants containing PPA rather than decongestants. In any case, serious events were still very rare.) All major brands that previously contained PPA have now substituted other active ingredients (usually pseudoephedrine) and are safe to use.

Side Effects of Decongestants. Decongestants have certain adverse effects, which are more apt to occur in oral than nasal decongestants and include:

Agitation and nervousness
Drowsiness (particularly with decongestants taken by mouth and in combination with alcohol)
Changes in heart rate and blood pressure
Avoid combinations of oral decongestants with alcohol or certain drugs, including monoamine oxidase inhibitors (MAOI) and sedatives

Individuals at Risk for Complications from Decongestants. People who may be at higher risk for complications are those with certain medical conditions, including disorders that make blood vessels highly susceptible to contraction. Such conditions include:

Heart disease
High blood pressure
Thyroid disease
Diabetes
Prostate problems that cause urinary difficulties
Migraines
Raynaud's phenomenon
High sensitivity to cold
Emphysema or chronic bronchitis. (Such individuals should particularly avoid high-potency short-acting nasal decongestant.)
People taking medications that increase serotonin levels, such as certain antidepressants, anti-migraine drugs, diet pills, St. John's wort, and methamphetamine. The combinations can cause blood vessels in the brain to narrow suddenly, causing severe headaches and even stroke.

Anyone with these conditions should not use either oral or nasal decongestants without a doctor's guidance. Other groups who should not use these drugs without first consulting a doctor include:

Pregnant women
Children. The American College of Chest Physicians advises against the use of over-the-counter decongestants and other cold medications in children ages 14 years or younger. Children are at particular risk for side effects that depress the central nervous system. Such symptoms cause changes in blood pressure, drowsiness, deep sleep, and, rarely, coma. In 2007, the FDA began reviewing the safety and effectiveness of cough and cold remedies for children.

Older antihistamines such as diphenhydramine (Benadryl) are helpful in relieving cough when used alone or in combination with a decongestant.

Expectorants are drugs that cause mucus to be coughed up from the lungs. The most common type used is guaifenesin, which is found in many over-the-counter (OTC) cough syrups as well as prescription products. Expectorants used to be recommended for treatment of sinusitis-associated cough, but some recent guidelines advise against their use. According to the American College of Chest Physicians (ACCP), expectorants and cough suppressants do not help treat cough. The ACCP recommends that adults instead take a decongestant or antihistamine to relieve cough. The ACCP also recommends against OTC cold and cough medicine for children ages 14 years and younger. Parents should talk with their child’s pediatrician for advice on treating cough.

Overview on Antibiotics and Their Overuse. Sinusitis is the fifth most common diagnosis for antibiotic prescriptions. And, there is much evidence that antibiotics are inappropriately prescribed for many patients:

According to a 2007 study of recent treatment patterns for acute and chronic sinusitis, antibiotics are widely overused. The researchers noted that viruses (not bacteria) account for a large percentage of acute sinusitis cases and that most acute sinusitis cases clear up on their own. The study also indicated that inhaled corticosteroids are frequently prescribed for acute sinusitis despite a lack of evidence for their benefit.
A major analysis reported that antibiotics helped only 1 child in 8 who had persistent nasal discharge for at least 20 days. Even when antibiotics were helpful, benefits were modest in reducing duration of the infection. This study supports other research that has found no significant benefit from antibiotics for most children. In a 2001 study, for example, 87% of children improved regardless of their treatment.

The intense and widespread use of antibiotics -- not only for sinusitis but also for other upper respiratory tract infections -- is leading to a serious global problem, which is bacterial resistance to common antibiotics. For example, according to reports in 2002 and 2001, in Canada 15% of S. pneumoniae strains are resistant to penicillin; in the U.S. 30 - 40% are resistant; in Hong Kong 70 - 80% of strains no longer respond to penicillin. Furthermore, in the U.S. about 23% of S. pneumoniae are currently resistant to at least three antibiotics. High rates of resistance strains are even being observed in infants. In general, regions with the highest rate of resistance are those in which antibiotics are the most heavily prescribed. Encouraging studies are now reporting that inappropriate antibiotic prescriptions are on the decline.

When to Use Antibiotics. Because the majority of sinusitis cases resolve on their own, doctors generally wait 10 - 14 days before prescribing antibiotics. However, antibiotics may be prescribed sooner if severe symptoms develop. These symptoms include:

Fever
Facial pain or tenderness
Swelling around the eyes

Antibiotic Regimens

The standard first-line antibiotic treatment for acute bacterial sinusitis is a 10 - 14 day course of amoxicillin. Trimethoprim-sulfamethoxazole is an alternative choice.
If no change occurs within 3 - 5 days, the doctor may prescribe a different type of antibiotic such as amoxicillin-clavulanate, cephalosporin, or a macrolide.
If the patient does not respond after 21 - 28 days, broad-spectrum antibiotics such as amoxicillin-clavulanate, cefuroxime, or cefpodoxime may be used. Other choices include clarithromycin or azithromycin (macrolides) or levofloxacin (a fluoroquinolone).

Side Effects of Antibiotics. Most antibiotics have the following side effects (although specific antibiotics may have other side effects or fewer of the standard ones):

The most common side effect for nearly all antibiotics is gastrointestinal distress.
Antibiotics double the risk for vaginal infections in women. Taking supplements of acidophilus or eating yogurt with active cultures may help restore healthy bacteria that offset the risk for such infections.
Allergic reactions can also occur with all antibiotics but are most common with medications derived from penicillin or sulfa. These reactions can range from mild skin rashes to rare but severe, even life-threatening anaphylactic shock.
Certain drugs, including some over-the-counter medications, interact with antibiotics; patients should inform the doctor of all medications they are taking and of any drug allergies.

Beta-Lactams

The beta-lactam antibiotics share common chemical features and include penicillins and cephalosporins. Their primary action is to interfere with bacterial cell walls.

Penicillins. Amoxicillin (Amoxil, Polymox, Trimox, Wymox, or any generic formulation) has been the most widely prescribed antibiotic for acute sinusitis. This penicillin is both inexpensive and at one time was highly effective against the S. pneumoniae bacteria. Unfortunately, bacterial resistance to amoxicillin has increased significantly, both among S. pneumoniae and H. influenzae, and penicillin is no longer as reliable as it once was.

Amoxicillin-clavulanate (Augmentin) is a type of penicillin that works against a wide spectrum of bacteria. An extended release form has been approved for treating adults with sinusitis infections that have become resistant to penicillin.

Many people have a history of an allergic reaction to penicillin, but some evidence is suggesting that the allergy may not recur in a significant number of adults. Skin tests are available that could determine if some people previously allergic could use these important antibiotics.

Cephalosporins. These drugs are also effective against S. pneumoniae. They are often classed by generation:

First generation includes cephalexin (Keflex), cefadroxil (Duricef, Ultracef), and cephradine (Velosef).
Second generation include cefaclor (Ceclor), cefuroxime (Ceftin), cefprozil (Cefzil), and loracarbef (Lorabid).
Third generation include cefpodoxime (Vantin), cefdinir (Omnicef) cefditoren (Sprectracef), cefixime (Suprax), and ceftibuten (Cedex). Ceftriaxone (Rocephin) is an injected cephalosporin. These are effective against a wide range of bacteria.

The later-generation antibiotics cefpodoxime, cefdinir, and cefuroxime are good choices for penicillin-allergic patients with mild-to-moderate sinusitis who have been treated in the previous 4 - 6 weeks. Penems, a type of beta-lactam antibiotic, are also being investigated for sinusitis treatment.

Macrolides and Azalides

Macrolides are a class of antibiotics that are divided into different sub-groups. Azalides are one of those sub-groups. This type of antibiotic is often used to treat mild-to-moderate bacterial sinusitis in patients who are allergic to penicillin. Some of the most common macrolids/azalides are azithromycin (Zithromax), clarithromycin (Biaxin), and roxithromycin (Rulid). An extended-release form of azithromycin (Zmax) was approved in 2005 as a single dose treatment for mild-to-moderate acute bacterial sinusitis. These antibiotics are also effective against many strains of S. pneumoniae and M. catarrhalis, but macrolide-resistance rates doubled between 1995 - 1999 as the number of children treated with the antibiotics increased. Erythromycin is not effective against H. influenzae.

Macrolides have anti-inflammatory actions, which may have benefits for some patients with chronic sinusitis. Investigators are studying long-term low-dose macrolide treatments, which are not intended to eliminate bacteria, but to reduce inflammation. Studies suggest that this approach may be effective without increasing the risk for bacterial resistance.

Trimethoprim-Sulfamethoxazole

Trimethoprim-sulfamethoxazole (Bactrim, Cotrim, Septra) is another first-line antibiotic for sinusitis. It is less expensive than amoxicillin and particularly useful for patients with mild sinusitis who are allergic to penicillin. It is no longer effective, however against certain streptococcal strains. It should not be used in patients whose infections occurred after dental work or in patients allergic to sulfa drugs. Allergic reactions can be very serious.

Fluoroquinolones (Quinolones)

Fluoroquinolones (also simply called quinolones) interfere with the bacteria's genetic material so they cannot reproduce.

Newer generation fluoroquinolones, which include levofloxacin (Levaquin), sparfloxacin (Zagam), gatifloxacin (Tequin), and moxifloxacin (Avelox), are currently the most effective antibiotics against the common bacteria that cause sinusitis. They are recommended for adults with moderate sinusitis who have already been treated with antibiotics within 6 weeks or who are allergic to beta-lactam antibiotics.

Some of the newer fluoroquinolones only need to be taken once a day, which make compliance easier. Some, but not all, quinolones cause photosensitivity. S. pneumoniae strains resistant to the quinolones have been uncommon in the U.S. but their numbers are increasing. In fact, levofloxacin was the first drug approved specifically for penicillin-resistant S. pneumoniae. Unfortunately, studies are now finding resistance to this drug as well.

Lincosamide

Lincosamides prevent bacteria from reproducing. The most common lincosamide is clindamycin (Cleocin). This antibiotic is useful against many S. pneumoniae bacteria but not against H. influenzae.

Tetracyclines

Tetracyclines inhibit bacterial growth. They include doxycycline, tetracycline, and minocycline. They can be effective against S. pneumoniae and M. catarrhalis, but bacteria that are resistant to penicillin are also often resistant to doxycycline. Tetracyclines have unique side effects among antibiotics, including skin reactions to sunlight, possible burning in the throat, and tooth discoloration.

Ketolides

In February 2007, the FDA withdrew approval of telithromycin (Ketek) for treatment of acute bacterial sinusitis. The agency decided that the serious risks of telithromycin outweigh its benefits for sinusitis treatment. The decision followed several 2006 reports of patient deaths due to severe liver damage. Telithromycin is now approved only for treatment of community-acquired pneumonia (CAP).

In 2003, research suggested that delivering medications directly to the sinus passages (instead of the bloodstream, like a pill might) significantly increases the amount of time chronic sinusitis patients remain infection free. The treatment, called nebulized antibiotic therapy, requires that patients inhale antibiotics in mist form to topically treat their sinusitis. The study showed that nebulization therapy increased the infection free period for some patients by almost 300% when compared to other treatments.

Patients who show signs that infection has spread beyond the nasal sinuses into the bone, brain, or other parts of the skull require emergency care. High dose antibiotics are administered intravenously, and emergency surgery is almost always necessary in such cases.

Severe Fungal Sinusitis. Sinusitis caused by severe fungal infections is a medical emergency. Treatment is aggressive surgery, and high-dose antifungal chemotherapy with a drug such as amphotericin B can be life saving. The use of oxygen administered at high pressure (hyperbaric oxygen) is showing promise as additional therapy for potentially deadly fungal infections.

Treatment for Chronic Sinusitis

Determining and Treating any Underlying Conditions. A thorough diagnostic work-up should be performed to rule out any underlying conditions, including but not limited to allergies, asthma, any immune problems, gastroesophageal reflux disorder, and structural problems in the nasal passages. If a primary trigger for chronic sinusitis can be identified, it should be treated or controlled if possible.

Initial Treatment of Sinusitis. For treatment of chronic sinusitis itself, some doctors recommend:

A wide spectrum antibiotic (one that can eliminate a wide range of bacteria) taken for at least 30 days.
Alternatively, an antibiotic that attacks anaerobic pathogens.
A corticosteroid nasal spray -- some doctors also recommend oral corticosteroids (such as prednisone) for patients who do not respond to nasal corticosteroids or for those patients who have nasal polyps. Prednisone is also used for patients who have allergic fungal sinusitis.
Saline nasal washes.
The expectorant guaifenesin with a decongestant taken by mouth.
Antihistamines.

If the condition dramatically improves between 1 - 2 months, then the antibiotics are stopped. The patient should continue with both the steroid and saline nasal solutions. If there is no improvement after this time, the surgery may be considered. For some people with chronic sinusitis, however, the condition is not curable, and the goal of treatment is to improve the quality of life.

Chronic sinusitis is often the result of damage to the mucous membrane from a past, untreated acute sinus infection. The aerobic and anaerobic bacteria present in chronic sinusitis are often different from those that cause the acute form. The role of antibiotic treatment for chronic sinusitis is controversial. Special types of antibiotics may be used, and treatment may be needed for a longer time.

Intravenous antibiotic therapy may be required for some patients with chronic sinusitis, particularly those with underlying medical disorders that can worsen the condition. They are typically administered 2 weeks before surgery and continued for about month afterward.

Some studies have reported good results in using antibiotics that are sprayed into the nasal passages using a nebulizer. In one study, patients preferred this method to either oral or intravenous treatments.

Benefits of Corticosteroid Nasal Sprays. Nasal-spray corticosteroids, most commonly called steroids, are effective drugs for treating allergic rhinitis. They also are proving to be very important in the treatment of chronic sinusitis and are sometimes used for acute sinusitis. Some studies have reported that, when combined with antibiotics, they speed recovery and improve healing rates of sinusitis compared to antibiotics alone. Nasal spray steroids are proving to be safe and have the following benefits:

They reduce inflammation and mucus production.
They improve night sleep and daytime alertness in patients with perennial allergic rhinitis.
They appear to be beneficial in treating polyps in the nasal passages.

Nasal-Spray Brands. Corticosteroids available in nasal spray form include:

Triamcinolone (Nasacort). Approved for children over age 6.
Mometasone furoate (Nasonex). Approved for use in patients as young as age 3.
Fluticasone (Flonase, Flounce). Approved for children over age 4.
Beclomethasone (Beconase, Vancenase), flunisolide (Nasalide), and budesonide (Rhinocort). Approved for children over age 6.

Side Effects. Corticosteroids are powerful anti-inflammatory drugs. Although oral steroids can have many side effects, the nasal-spray form affects only local areas, and the risk for wide spread side effects is very low unless the drug is used excessively.

Dryness, burning, stinging in the nasal passage
Sneezing
Headaches and nosebleed (these side effects are uncommon but should be reported to your doctor immediately)

Possible Long-Term Complications. Corticosteroids suppress stress hormones, which are known to produce some serious long-term complications in people who take oral steroids. Researchers have found far fewer concerns with nasal administration or inhaled forms, but there may be certain problems.

Effect on growth. The major concern for children is whether nasal steroids, like other forms of steroids, will adversely affect growth. Studies report either only a temporary and slight (about half an inch) early effect on growth or no effect at all.
Effect on eyes. Glaucoma is a known side effect of oral steroids. Some ophthalmologists have observed higher pressure in the eye (a sign of glaucoma) in some patients taking nasal steroid sprays. Studies have found no increased risk for cataracts in young people who have taken intranasal steroids. All the conditions resolve after stopping the steroid, although periodic eye examinations are advised.
Use during pregnancy. Steroids are most likely safe during pregnancy, but pregnant women should discuss all options carefully before taking them.
Nasal passage injury. Steroid sprays may injure the nasal septum (the bony area that separates the nasal passage) if the spray is directed onto it. This complication is very rare.
Lower resistance to infection. People with any infectious disease or injury in the nose should not take these drugs until the disease or wound has been treated and cured. People should avoid steroids if they have not been vaccinated or have had chicken pox or measles.
In some cases, people become insensitive to the effects of corticosteroids and they stop working.

Leukotriene-antagonists are oral drugs that block leukotrienes, powerful immune system factors that are important in causing airway constriction and mucus production in allergy-related asthma. Leukotriene-antagonists include zafirlukast (Accolate), montelukast (Singulair), (Ziflo), and pranlukast (Ultair, Onon). They may also be useful in certain cases of chronic sinusitis, including sinusitis due to polyps, when allergies are the cause, or in some cases when the cause is unknown.

Scientists are investigating whether antifungal drugs may help treat chronic sinusitis. One such drug, Amphotericin B (SinuNase), is currently in Phase III trials for patients who have had sinus surgery but are still experiencing recurrent sinusitis. Results from previous clinical trials have been mixed.

Patients often have various combinations of allergies, sinusitis, and asthma. Treating each condition is important for improving them all. In addition to decongestants, pain relievers, and expectorants, other remedies are available for people who suffer from nonbacterial sinusitis during allergy season.

Anti-Inflammatory Drugs. Nasal spray corticosteroids (commonly called steroids) are important for reducing the inflammatory response in the nasal passages and airways. They are important in the treatment of asthma and are now considered to be the most effective measure for preventing allergy attacks. Leukotriene-antagonists are also useful for sinusitis symptoms.
Antihistamines. Antihistamine tablets relieve sneezing and itching and can prevent nasal congestion before an allergy attack. Many brands are available by prescription and over the counter.
Immunotherapy. Immunotherapy, commonly referred to as "allergy shots," may be considered for patients with severe seasonal allergies that do not respond to treatment. Immunotherapy is the only treatment that affects the cause of allergies. In one year-long study using immunotherapy, over half of young patients participating experienced improvement in overall sinusitis symptoms, and nearly all felt better in general. Immunotherapy also may prevent asthma and the development of new allergies in children. Newer immunotherapeutic approaches using specially designed antibodies and vaccines are also showing promise.
All drug treatments have side effects, some very unpleasant and, in rare cases, serious. Patients may need to try different drugs until they find one that relieves symptoms without producing excessively distressing side effects.

Surgery

Surgery is used to unblock the sinuses when drug therapy is not effective or if there are other complications, such as structural abnormalities or fungal sinusitis.

The simplest surgical approach is the insertion of a drainage tube into the sinuses followed by an infusion of sterile water to flush them out.

In the past few years there has been a major advance in the surgical treatment with a minimally invasive technique called functional endoscopic sinus surgery (FESS). The procedure allows correction of obstructions, including any polyp and ventilation and drainage to aid healing.

Candidates for the Procedure.

FESS may be a good choice for people with chronic sinusitis associated with structural abnormalities. In one study, the best results were seen in people with polyps (but not those associated with ASA triad, the combination of polyps in the nose, asthma, and sensitivity to aspirin).
Several studies are finding it to be safe and effective in children with chronic sinusitis or whose sinuses have not developed. It does not have an adverse effect on facial growth.
Surgery may help patients with HIV who have chronic or recurrent sinusitis.
It may benefit appropriate candidates who have both sinusitis and asthma. One study suggested that lung function may improve afterward in some patients.

Surgery may not be as effective for patients with the ASA triad, fungus infections, or severe chronic sinusitis, although endoscopy is proving to be beneficial even for these conditions with the use of more powerful instruments.

Procedure. The surgery generally proceeds as follows:

Adults require only a local anesthetic for the procedure, though a general anesthetic is needed for children.
Before the procedure, a computed tomography (CT) scan is taken for use by the surgeon in planning the procedure and as a guide to the sinuses during surgery. Some doctors are now using a device called a depth of field image (DOFI) video enhancement screen that displays a holographic 3-D image. It allows the surgeon an excellent view of the sinus cavities and may prove to significantly reduce complications.
A flexible tube, a miniature camera, and a fiberoptic light source are inserted through a single small opening.
Instruments are then used to remove diseased bone or tissue and clear obstructions. For instance, shavers are used to gently remove soft tissue. Bone cutters are sometimes employed to open the floor of the frontal sinus and restore drainage (called the modified Lothrop procedure). Lasers are also being investigated to remove bone, coagulate the passageways, or clear obstructions.

Complications. Serious complications of FESS are very rare, but the following have been reported in a few cases:

Cerebrospinal fluid leak is the most common major complication, but it occurs in only 0.2% of cases and is usually easily repaired during surgery.
Other very rare complications include meningitis, hemorrhage, infection, or vision loss.
Patients can develop infections afterward that are very difficult to treat. Interesting studies are reporting good to excellent results in these patients by spraying antibiotics into the nasal passages using a nebulizer.

Postsurgical Care. Postsurgical care involves the following:

The patient will experience a dull ache around the nose and sinus cavity that can be treated with pain medication.
Following surgery, the patient should flush the sinuses twice daily with a saline or alkaline solution.
Antibiotics may be prescribed for several weeks until postnasal drip has stopped, and corticosteroid sprays and antihistamines may be needed.

Success Rates. It may take several months for the mucous membranes to completely recover, but between 85 - 90% of patients experience good to excellent symptomatic relief after surgery. Children may require a second procedure 2 - 3 weeks after the first surgery to remove crusty matter.

A high-pressure water jet (HPWJ) treatment that flushes diseased mucus that remains after FESS surgery is being investigated for those whose symptoms do not clear. One 2000 study found the procedure an effective therapy that may even be safe for children.

A new type of surgical procedure threads a small balloon through the sinus passages. As the balloon is gently opened, the sinus passages expand and drainage occurs. Some experts think that this procedure is only appropriate for select patients with sinusitis disease in the maxillary (behind cheek bones), frontal (behind the sides of the forehead), and sphenoid (behind the eyes) sinus regions. It may not work for patients with disease in the ethmoid (between the eyes) sinuses, even though this a common sinusitis location.

Endoscopy is now used in most cases of chronic sinusitis, but in severe cases, invasive surgery using conventional scalpel techniques to remove infected areas may be required. This may be the case with acute ethmoid sinusitis in which pus breaks through the sinus and threatens the eye, with very severe frontal sinusitis, with invasive fungal sinusitis, or when cancer is present in the sinuses.

Resources

www.entnet.org -- American Academy of Otolaryngology - Head and Neck Surgery
www.aaaai.org --American Academy of Allergy, Asthma, and Immunology
www.acaai.org --American College of Allergy, Asthma, and Immunology
www.niaid.nih.gov -- National Institute of Allergy and Infectious Disease
www.american-rhinologic.org -- American Rhinologic Society
www.cdc.gov/nip -- National Immunization Program

References

Brown CL, Bolger WE. Safety and feasibility of balloon catheter dilation of paranasal sinus ostia: a preliminary investigation. Ann Otol Rhinol Laryngol. 2006 Apr;115(4):293-9.

Clay KD, Hanson JS, Pope SD, Rissmiller RW, Purdum PP 3rd, Banks PM. Brief communication: severe hepatotoxicity of telithromycin: three case reports and literature review. Ann Intern Med. 2006 Mar 21;144(6):415-20.

Ebbens FA, Scadding GK, Badia L, Hellings PW, Jorissen M, Mullol J, et al. Amphotericin B nasal lavages: not a solution for patients with chronic rhinosinusitis. J Allergy Clin Immunol. 2006 Nov;118(5):1149-56.

Sharp HF, Denman D, Puumala S, Leopold DA. Treatment of acute and chronic rhinosinusitis in the United States, 1999-2002. Arch Otolaryngol Head Neck Surg. 2007 March;133(3):260-265.

Weschta M, Rimek D, Formanek M, Podbielski A, Riechelmann H. Effect of nasal antifungal therapy on nasal cell activation markers in chronic rhinosinusitis. Arch Otolaryngol Head Neck Surg. 2006 Jul;132(7):743-7.

Review Date:
3/23/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Brain tumors - primary

FitSugar — Wed, 08 Oct 2008 17:35:12 -0700

In This Report

Highlights
Introduction
Symptoms
Risk Factors
Causes
Prognosis
Diagnosis
Common Brain Tumors
Treatment
Surgery
Radiotherapy
Chemotherapy
Other Treatments
Treatment of Complications...
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Radiation Therapy Complications

Radiation therapy in children with cancer increases the risk of new brain and spinal cord tumors, suggests a study in the Journal of the National Cancer Institute. The risk appears to increase along with the radiation dosage. Children who receive radiotherapy before age 5 are especially at risk for second primary tumors.
Survivors of childhood brain tumors who received cranial radiotherapy as part of their treatment are at risk for later having a stroke, indicates a study in the Journal of Clinical Oncology. The average length of time from brain tumor diagnosis to post-treatment stroke was 14 years.

Radiation Therapy for Elderly Patients

Radiotherapy provides modest improvement in survival for elderly patients (age 70 years and older) with glioblastoma, with no detriment to quality of life or cognition function, according to a 2007 study in the Journal of the American Medical Association.

Temozolomide (Temodar)

The chemotherapy drug temozolomide (Temodar) has become an important and effective treatment for patients newly diagnosed with glioblastoma. However, not all patients respond equally well to this drug. A 2007 study in the journal Neurology suggests that a patient’s genotype may explain differences in response. Though genetic testing, researchers found that temozolomide works best in people who are missing a particular gene.

Investigational Treatments

Vorinostat (Zolinza), a cancer drug used for T-cell lymphoma, may help patients with recurrent glioblastoma multiforme, according to research presented at the 2007 annual meeting of the American Society of Clinical Oncology.
Bevacizumab (Avastin), a targeted therapy drug used for lung and colorectal cancers, may help prolong survival in patients with advanced glioma, indicates a 2007 study in Clinical Cancer Research. Another anti-angiogenesis drug, cediranib (Recentin), may help make glioblastomas more responsive to chemotherapy and radiotherapy, according to recent interim trial results.
Vitespen (Oncophage), an experimental vaccine for glioma, is showing promise in early clinical trials, suggests research presented at the 2007 meeting of the American Association of Neurological Surgeons.

Introduction

Brain tumors are composed of cells that exhibit unrestrained growth in the brain.

The major areas of the brain have one or more specific functions.

They can be benign (noncancerous, meaning that they do not spread elsewhere or invade surrounding tissue) or malignant (cancerous).

Cancerous brain tumors are further classified as either primary or secondary tumors. Primary tumors start in the brain, whereas secondary tumors spread to the brain from another site such as the breast or lung. (In this report, the term "brain tumor" will refer mainly to primary malignant tumors, unless otherwise specified.)

Benign tumors represent half of all primary brain tumors. Their cells look relatively normal, grow slowly, and do not spread (metastasize) to other sites in the body. Benign tumors can still be serious and even life-threatening if they are in vital areas in the brain where they exert pressure on sensitive nerve tissue or if they increase pressure within the brain. While some benign brain tumors may pose a health risk, including risk of disability and death, most are usually successfully treated with techniques such as surgery.

Click the icon to see an image of a primary brain tumor.

A secondary (metastatic) brain tumor occurs when cancer cells spread to the brain from a primary cancer in another part of the body. Secondary tumors are about three times more common than primary tumors of the brain. Usually, multiple tumors develop. Solitary metastasized brain cancers may occur but are less common. Most often, cancers that spread to the brain to cause secondary brain tumors originate in the lung, breast, kidney, or from melanomas in the skin.

A primary malignant brain tumor is one that originates in the brain itself. Although primary brain tumors often shed cancerous cells to other sites in the central nervous system (the brain or spine), they rarely spread to other parts of the body.

Brain tumors are generally named and classified according to the following:

The normal brain cells from which they originate, or
The location in which the cancer develops

The biologic diversity of these tumors, however, makes classification difficult, and some experts believe that more specific categories are needed.

About half of all primary brain tumors are known collectively as gliomas. They are cancerous forms of glial cells, the building-block cells of the connective, or supportive, tissue in the central nervous system. There are several glial cells types from which gliomas form. Their names are:

Astrocytomas are primary brain tumors derived from astrocytes, which are star-shaped glial cells. Normal astrocytes provide nutrients, support, and insulation for nerve cells and are one of the primary neurologic cells in the body. The malignant astrocytomas called glioblastomas account for 23% of brain tumors and are the most common ones.
Oligodendrogliomas develop from oligodendrocyte glial cells, which form the protective coatings around nerve cells. Although oligodendrogliomas were thought to represent about 5% of all gliomas, more recent evidence suggests they may comprise about 20% of gliomas. Pure oligodendrogliomas, however, are rare. In most cases they occur in mixed gliomas.
Ependymomas are derived from ependymal cells, which line the ventricles (fluid-filled cavities) in the lower part of the brain and the central canal of the spinal cord. They constitute about 6% of all primary tumors in the central nervous system. About 30% of these tumors occur in the spinal cord.
Mixed gliomas contain a mixture of malignant gliomas. About half of these tumors contain cancerous oligodendrocytes and astrocytes.

It should be noted that gliomas may also contain cancer cells derived from brain cells other than glial cells.

Some brain tumors are categorized by their location in the brain. Such tumors often contain gliomas but are also frequently a mixture of different cell types.

Meningiomas. Meningiomas are usually benign tumors that develop in the membranes that cover the brain and spinal cord (the meninges).

Click the icon to see an image of the meninges.

They are not technically classified as brain tumors, but they have similar symptoms and develop within the brain. So in practical terms, they are considered brain tumors. In fact, meningiomas comprise 20% of all primary brain tumors. They occur more often in women than in men. Most grow very slowly, and the majority of people who have them never know they are present. Malignant forms called anaplastic meningiomas and hemangiopericytomas are less common and are difficult to remove surgically.

Cerebral Astrocytomas. Gliomas that develop inside the brain often occur in the cerebral hemispheres (the right and left sides of the brain). In such cases, they are referred to as cerebral astrocytomas. Gliomas sometimes occur in another part of the brain, called the cerebellum. The cerebellum is responsible for balance and coordination. In such cases, the term cerebellar astrocytoma is used.

Click the icon to see an image of the function of the left cerebral hemisphere.

Click the icon to see an image of the function of the right cerebral hemisphere.

Brain Stem Gliomas. Brain stem gliomas develop in the lowest portion of the brain. The brain stem connects the cerebrum (the higher centers of the brain) to the spinal cord. The brain stem is thought to be the primitive brain because it controls the most basic functions.

Click the icon to see an image of the function of the brainstem.

The brain stem consists of three primary parts:

The medulla regulates breathing, swallowing, blood pressure, and heart rate.
The pons links the cerebellum to the cerebrum.
The midbrain helps control vision and hearing.

Click the icon to see an image of the structures of the brain.

Medulloblastomas. Medulloblastomas are always located in the cerebellum, which is at the base and toward the back of the brain. They represent about 3% of all brain tumors.

Click the icon to see an image of the function of the cerebellum.

Pituitary Tumors. Pituitary tumors comprise about 10% of primary brain tumors and are often benign, slow-growing masses in the pituitary gland.

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

Other Brain Tumor Locations. Optic nerve gliomas occur in the optic nerve, which is located behind the eye. Acoustic neuromas make up 7.5% of brain tumors.

Click the icon to see an image of the optic nerve.

Symptoms

Brain tumors produce a variety of symptoms, ranging from headache to stroke. They are great mimics of other neurologic disorders. Symptoms occur if the tumor directly damages the nerves in the brain or central nervous system or if its growth imposes pressure on the brain. Some gliomas develop gradually, and symptoms may be subtle for a long time, making an early diagnosis difficult.

Headache is probably the most common symptom of a brain tumor. It should be strongly emphasized, however, that everyone has headaches, and they rarely represent an underlying brain tumor. Headaches caused by brain tumors may vary depending on the location, and many different features.

Steady and worse upon waking in the morning and clears up within a few hours
Persistent non-migraine headache that occurs while sleeping and is also accompanied by at least one other symptom (such as vomiting or confusion)
May or may not be throbbing, depending on location of the tumor
Accompanied by double vision, weakness, or numbness
May worsen with coughing or exercise or with a change in body position
Sometimes accompanied by neck pain

Gastrointestinal symptoms, including nausea, are also common. Nausea and vomiting, in fact, often occur in children with brain tumors and in all people with brain stem cell tumors.

Seizures occur in between 15 - 95% of patients, depending on the location of the tumor.

Tumors are more likely to be localized and affect one area of the brain. In such cases they can cause partial seizures. In this case, a person does not lose consciousness but may experience confusion, jerking movements, tingling, or odd mental and emotional events.
Generalized seizures, which can cause loss of consciousness, are less common, since they are caused by disturbances of nerve cells in diffuse areas of the brain.

Sometimes the only symptoms are mental changes, which may include the following:

Memory loss
Impaired concentration
Problems with speech and reasoning
Increased sleep

Gradual loss of movement or sensation in an arm or leg
Unsteadiness
Unexpected visual disturbance (especially if it is associated with headache), including vision loss (usually of peripheral vision) in one or both eyes or double vision
Hearing loss with or without dizziness
Speech difficulty

Specific symptom syndromes may help identify the tumor. The following are some examples.

Symptoms of Brain Stem Gliomas. Sudden onset of symptoms that include vomiting (usually just after waking), a clumsy walk, muscle weakness on one side of the face, difficulty in swallowing, slurred or nasal speech, as well as impaired hearing or vision.

Symptoms of Glioblastoma Multiforme. Rapid onset and worsening of symptoms that include headaches, seizures, memory loss, and changes in behavior.

The below symptoms indicate an emergency condition and require immediate medical attention:

Pupil dilation
A fixed gaze
Paralysis on one or both sides of the body
Blindness or defective vision in one eye

Risk Factors

Nearly 360,000 people in the U.S. are living with brain cancer. Men are at higher risk than women for most brain tumors. Primary malignant brain tumors are still uncommon and represent only 1.3% of all cancers diagnosed in the United States and 2.4% of all deaths due to cancer.

Primary brain cancers are rare, occurring in slightly more than 11 people per 100,000 per year. There has been some evidence of a growing incidence of brain cancer among the elderly since the 1980s. The increase, however, is most likely due to the rise in incidence of non-Hodgkin's lymphomas -- which can occur in the brain. When this malignancy is eliminated, any increase in other tumors is not significant.

The average age of diagnosis for brain tumors is 57, and about 90% of primary brain tumors occur in adults. These tumors can develop at all ages, usually peaking in two age groups.

In adults, ages 55 - 65
In children, ages 3 - 12

Risk Factors in Children. Tumors in the central nervous system are now the most common primary cancers in children, but they are still rare. An estimated 3,110 benign or malignant brain tumors are expected to be diagnosed in children each year. Brain tumors in children are more likely to occur in the cerebellum, the midbrain, or the optic nerve.

The incidence has increased over the past years, but there is some evidence that this increase is only due to better diagnostic procedures. The mortality rate has actually decreased. Researchers have attempted to uncover risk factors for childhood brain cancer. There may be some association between a higher risk and the following conditions:

Children treated with radiation to the head for leukemia and who have a specific genetic defect may face a high risk for brain cancer. (It should be noted that for children without this defect, the risk is very small.)
Having parents with specific cancers. (According to one study, having parents with nervous system cancers, colon cancer, or cancer in the salivary glands increased the risk of specific brain tumors in their children.)

Click the icon to see an illustrated series detailing colon cancer surgery.

The risk for primary brain tumors in Caucasians is higher -- as much as twofold depending on type -- than in African-Americans.

Radiation Exposure. People who receive radiation therapy to the head during cancer treatment have an increased risk of developing brain tumors 10 - 15 years later. Workers in the nuclear industry are also at increased risk.

There is no evidence that electromagnetic field exposure from power lines or household appliances poses any risk. Several recent epidemiological studies, including a 2006 study in the British Medical Journal, found that cell phones, cordless phones, and wireless devices are also safe and do not increase the risk for gliomas.

Chemical and Metals in Brain Tumors. High exposure to numerous metals and chemicals have been associated with brain tumors:

Industrial chemicals, including vinyl chloride and petroleum products
Lead, arsenic, or mercury exposure
Exposure to pesticides. A major study of pesticides is underway, but results are not in yet. A 2003 study indicated that parental exposure to pesticides or herbicides did not appear to be important in increasing risk for brain cancer in their children.

Brain cancer is uncommon, and, over the course of their lifetime, many people are exposed to these chemicals, many of which are very common. To date, there has been no clear evidence that implicates any specific industrial chemical or metal.

One study reported a higher risk for brain cancers in patients who had undergone organ transplantations. Researchers believed that the drugs used to suppress the immune response after the procedures may increase the risk.

One study reported lower risks for brain cancers in individuals with allergies and autoimmune diseases (such as type 1 diabetes). Autoimmune diseases were also associated with a lower risk for meningiomas. The cause of this possible association remains unknown.

Studies have also found an association between lower risk for gliomas and a history of infection with varicella zoster, the virus that causes chicken pox and shingles.

Click the icon to see an image of the chicken pox.

Causes

Only 5 - 10% of primary brain tumors are associated with genetic disorders. These inherited conditions and associated genes include:

Von Recklinghausen disease, also called neurofibromatosis 1 (NF1 gene) and neurofibromatosis 2 (NF2 gene)
Turcot's syndrome (APC gene)
Gorlin syndrome, also called basal cell naevus syndrome (PTCH gene)
Tuberous sclerosis (TSC1 and TSC2 genes)
Li-Fraumeni syndrome (TP53 gene)

Certain types of brain tumors are specifically linked with these genetic conditions. For example, neurofibromatosis 1 is associated with about 15% of cases of pilocytic astrocytomas, the most common type of childhood glioma. Neurofibromatosis results from defects in the tumor suppressor genes NF1 and NF2. Li-Fraumeni syndrome results from mutations in the tumor suppressor gene TP53. These mutations affect the production of tumor suppressor protein p53.

Tumor suppressor genes regulate cell division and help repair DNA damage. When mutations that affect protein encoding occur, unregulated cell division and growth can lead to the development of a tumor. Tumor suppressor genes are sometimes described as being in a tug-of-war with cancer-causing genes called oncogenes. Oncogenes derive from mutations or overexpressions of proto-oncogenes. Proto-oncogenes encode for proteins that regulate cell growth and differentiation. When proto-oncogenes become oncogenes, normal cells start to grow uncontrollably. Cancer can occur when tumor suppressor genes are turned off, or when oncogenes are turned on.

Many different oncogenes are involved in cancer. Growth factors are a particularly important type of oncogene associated with brain tumors. Growth factors attach to receptors (connectors) that stimulate cell growth. Epidermal growth factor receptor (EGFR) has been shown to play a role in high-grade brain tumors such as glioblastoma multiforme. In 2007, scientists identified insulin-like growth factor binding protein (IGFBP2) with an oncogene that may be associated with the development of astrocytoma and oligodendroglioma.

Knowing the molecular origin of a brain tumor may help determine the treatment course, both for standard chemotherapy and "targeted therapy" biologic drugs. For example, patients with tumors marked by high EGFR proliferation may benefit from treatment with the EGFR kinase inhibitor drugs gefitinib (Iressa) or erlotinib (Tarceva).

Most genetic abnormalities that cause brain tumors are not inherited but occur as a result of environmental or other factors that affect genetic materials (DNA) in the cells. Researchers are studying various environmental factors (viruses, hormones, chemicals, radiation) that may trigger the genetic disruptions that lead to brain tumors in susceptible individuals. They are also working to identify the specific genes that are affected by these environmental triggers. For example, in a 2007 study, scientists proposed that genetic susceptibility may explain why some people develop meningioma, a rare type of brain tumor, following exposure to ionizing radiation. Future investigations will hopefully identify the specific genes involved and help determine which people would potentially be most at risk.

Prognosis

About 13,100 people die from cancerous brain tumors each year. Recent advances in surgical and radiation treatments have significantly extended average survival times and can reduce the size and progression of malignant gliomas. In general, survival rates are highest in younger people and lowest in the elderly.


Age	Survival Rates
0 - 19 years	63.1%
20 - 44 years	50.4%
45 - 64 years	14.2%
Over 65	4.9%
Data From: 2002 - 2003 Primary Brain Tumors in the United States Statistical Report. Fact Sheet (1973- 1999 data). Brain Tumor Registry of the United States www.cbtrus.org/factsheet/factsheet.html.

In general, studies are reporting that patients who survive the first 2 years after a diagnosis of a brain tumor have at least a 70% chance of surviving for at least 5 years. The best recent progress has been made for:

Medulloblastomas in both children and adults. Long-term survival rates are now about 60% in children after treatment for medulloblastomas, the most common malignant brain tumor in this age group. (New treatments, however, may significantly improve these rates.)
Nonmalignant astrocytomas and oligodendrogliomas in adults.

Unfortunately, the majority of primary brain tumors, notably anaplastic astrocytomas and glioblastoma multiforme, are only rarely curable.

The specific effects of tumors on the brain can cause seizures, mental changes, and mood, personality, and emotional changes. Such effects can be devastating to the patient and the caregivers. Numerous treatments are available that help alleviate these complications, and patients and family members should discuss these with their doctors.

Diagnosis

A neurological exam is usually the first test given when a patient complains of symptoms that suggest a brain tumor. The exam includes checking eye movements, hearing, sensation, muscle movement, sense of smell, and balance and coordination. The doctor will also test mental state and memory.

X-rays of the skull were once standard diagnostic tools but are now performed only when more advanced procedures are not available. Advanced imaging techniques have dramatically improved the diagnosis of brain tumors in recent years.

Magnetic Resonance Imaging. Magnetic resonance imaging (MRI) is the gold standard for diagnosing a brain tumor. It does not use radiation and provides pictures from various angles that can enable doctors to construct a three-dimensional image of the tumor. It gives a clear picture of tumors near bones, smaller tumors, brainstem tumors, and low-grade tumors. MRI is also useful during surgery to show tumor bulk, for accurately mapping the brain and for detecting response to therapy.

An MRI (magnetic resonance imaging) of the brain creates a detailed image of the complex structures in the brain. An MRI creates a three-dimensional picture of the brain, which allows doctors to more precisely locate problems such as tumors or aneurysms.

A variant called magnetic resonance spectroscopy (MRS) is capable of providing information on the activity of the brain using magnetic resonance imaging. MRS is proving to be accurate for distinguishing dead (necrotic) tissue caused by previous radiation treatments from recurring tumor cells in the brain, a difficult diagnostic issue.

Computed Tomography. Computed tomography (CT) uses a sophisticated x-ray machine and a computer to create a detailed picture of the body's tissues and structures. It is not as accurate as an MRI and does not detect about half of low-grade gliomas. It is useful in certain situations, however. Often, doctors will inject the patient with an iodine dye, called contrast material, to make it easier to see abnormal tissues. A CT scan helps locate the tumor and can sometimes help determine its type. It can also help detect swelling, bleeding, and associated conditions. In addition, computed tomography is used to check the effectiveness of treatments and watch for tumor recurrence.

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

Positron Emission Tomography. Positron emission tomography (PET) provides a picture of the brain's activity rather than its structure by tracking substances that have been labeled with a radioactive tracer. As with magnetic resonance spectroscopy (MRS), it is also able to distinguish between recurrent tumor cells from dead cells or scar tissue, although MRS is more widely available. PET is not routinely used for diagnosis, but it may supplement MRIs to help determine tumor grade after a diagnosis. Data from PET may also help improve the accuracy of newer radiosurgery techniques.

Other Imaging Techniques. Numerous other advanced imaging techniques may be used for specific purposes, if available or under investigation.

Single photon emission tomography (SPECT) is similar to PET but is not as effective in distinguishing tumor cells from destroyed tissue after treatments.
Magnetoencephalography (MEG) scans measure the magnetic fields created by nerve cells as they produce electrical currents.
Cerebral angiography involves x-rays of blood vessels in the brain. A long, thin tube (catheter) is threaded through blood vessels from a distant site to the brain, and a radiopaque substance (a substance that is impenetrable to x-rays) is injected through it. The role of angiography in glioma is usually limited to planning surgical removal of a tumor suspected of having a large blood supply.
Radionuclide brain scintigraphy uses a radioactive substance that is administered and absorbed by capillaries in the tumor, which are then viewed using imaging techniques.
Digital holography, a new technique that provides full three-dimensional mapping, is under investigation.

A lumbar puncture is used to obtain a sample of spinal fluid, which is examined for the presence of tumor cells. A computed tomography (CT) scan or magnetic resonance imaging (MRI) should generally be performed before a lumbar procedure to be sure that the procedure will be safe.

Click the icon to see an image of a lumbar puncture.

A biopsy is a surgical procedure in which a small sample of tissue is taken from the suspected tumor and examined under a microscope for malignancy. The results of the biopsy also provide information on the cancer cell type.

In some cases, such as brain stem gliomas, a biopsy might be too hazardous because removing any healthy tissue from this area can affect vital functions. In such cases, diagnosis must rely on less invasive and possibly less accurate measures. Of promise is the stereotactic technique (also called stereotaxy), which uses computers to provide three-dimensional views of very small areas. This may allow precise biopsies of cancer cells without affecting healthy brain tissue. Expertise in this technique is extremely important, however, and the technique is not widely available.

The survival rates in people with brain tumors depend on many different variables:

Whether the tumor is malignant or benign
Cancer cell type and location (location affects whether the tumor can be removed surgically or not)
The tendency to spread and the growth rate (tumor grade)
Patient's age
Patient's ability to function
Duration of symptoms

The outlook is poorer in the very youngest and very oldest patients, although younger patients who survive 2 years after diagnosis have a much better outlook than older patients.

Grading Tumors. Malignant primary brain tumors are classified according to tumor grade. Grade I is the least cancerous, and Grades IV and V are the most dangerous. Grading a tumor attempts to predict its tendency to spread and its growth rate. It is based on the appearance of the tumor cells as seen under a microscope.

Lower-grade (I and II) tumor cells are well defined and almost normal-shaped. (Some primary low-grade brain tumors are curable by surgery alone, and some are curable by surgery and radiotherapy. Low-grade tumors tend to have the most favorable survival rates and high-grade the least. However, this is not always the case. For example, some low-grade II gliomas are at very high risk for progression.)
Higher-grade (III and IV) tumor cells are abnormally shaped and are more diffuse, which indicates more aggressive behavior. (High-grade brain tumors usually require surgery, radiotherapy, chemotherapy, and possibly investigational treatments.)
In tumors that contain a mixture of different-grade cells, the tumor is graded using the highest-grade cells in the mixture, even when there are very few of them.

Biologic Markers. Elevated levels of certain cancer-associated molecules or compounds may be correlated with prognosis. For example, evidence of genetically mutated p53 indicates a poorer prognosis in younger patients with glioblastoma multiforme.

Elevations of epidermal growth factors (EGF) or vascular endothelial growth factors (VEGF) suggest aggressive tumors. High levels of the receptor for EGF (EGFR), in fact, are found in 70% of glioblastoma specimens.

Genetic Profiles of Cancer Cells. Analyses that identify genetic types may soon help clinicians determine if patients with specific brain tumor cells might respond better to one treatment than another. For example, specific genetic profiles of oligodendrogliomas can help predict how patients respond to nitrosourea alkylating drugs such as carmustine. Genetic variation tests are also being used to determine how patients may respond to epidermal growth factor receptor (EGFR) kinase inhibitors, such as erlotinib (Tarceva) and gefitinib (Iressa).

A genetic profile can also help give doctors a better idea of a patient’s prognosis and survival. In a 2006 study of patients with anaplastic oligodendroglioma, the status of specific chromosomal deletions within tumors was a better predictor of survival than which kind of treatment patients received. In fact, the researchers suggested that gliomas be classified according to chromosomal deletion status, and recommended that chromosomal testing be a regular part of diagnosis and treatment decisions.

Common Brain Tumors


GENERAL DESCRIPTION OF ASTROCYTOMAS: Derived from star-shaped glial cells called astrocytes.

Low-Grade (Usually I) Astrocytomas. Pilocytic gliomas.	Pilocytic gliomas occur mostly in children. Tumors are well differentiated. Cells are relatively normal and rarely metastasize. They grow relatively slowly. Pilocytic astrocytomas have the highest 5-year survival rates (greater than 70%). However, even well differentiated astrocytomas are life threatening if they are inaccessible.	Cancer may sometimes be completely removed through surgery, particularly if it occurs in the cerebellum. For recurrence or residual tumors, reoperation, radiotherapy, or chemotherapy may be given, depending on the circumstances. Repeat surgery for cerebellar astrocytoma is often very successful. For those who fail radiotherapy and chemotherapy, investigative drugs are used.
Low-Grade (II) Astrocytomas. Fibrillary, protoplasmic, and protoplasmic astrocytomas. Some pleomorphic xanthoastrocytomas.	Tumors are well differentiated. Cells are relatively normal and less malignant than those in higher grades. They grow relatively slowly but can spread. Survival rates average 5 years, but people can survive for a decade or more. Pleomorphic xanthoastrocytomas have a relatively favorable prognosis, but can recur and demonstrate aggressive clinical behavior. Low-grade astrocytomas generally occur in young adulthood, with a peak incidence in 30s and 40s.	Surgery, if possible, plus radiotherapy. Surgery alone in certain children, if possible. Trials on postoperative radiotherapy include the following: radiotherapy with or without chemotherapy; low-versus-high radiotherapy doses (studies suggest results are the same and high-dose causes more side effects); deferring radiotherapy until tumor progresses and symptoms occur. (A major study confirmed earlier ones that suggest that this approach has the same 5-year survival benefits -- about 65% -- as immediate postoperative radiotherapy.)
Malignant (High-grade III and IV) Astrocytomas. Anaplastic astrocytoma (gemistocytic and some pleomorphic xanthoastrocytomas). Usually mid-grade (III).	Tumors grow more rapidly than lower grades and infiltrate other nearby healthy cells. Not well-differentiated. Five-year survival rates are about 30%. Recurrence is common.	Treatment same for all high-grade malignant astrocytomas. Surgery, with removal of as much of tumor as possible followed by radiotherapy, with or without chemotherapy. The addition of chemotherapy, particularly being able to take more than 6 cycles, appears to improve survival rates. Carmustine (BCNU) most effective drug at this time. Other drugs and treatment sequences are under investigation. For example, temozolomide is showing promise for many patients, including the elderly. Topotecan may also be useful with other drugs or with radiation. For recurring gliomas, surgery with placement of wafers that release carmustine (Gliadel wafers) is the only proven beneficial therapy to date. Combinations, such as procarbazine and carmustine, provide benefits for recurrent anaplastic astrocytomas. Single drugs may be less toxic and as helpful for other recurrent gliomas. Temozolomide has been approved in Europe for high-grade recurrent gliomas and is proving to be beneficial. Other trials include the following: drugs that block small molecules involved in tumor growth; radioimmunotherapy using monoclonal antibodies; advanced radiotherapy techniques; intraarterial chemotherapy.
High-grade (IV and V). Glioblastoma (notably glioblastoma multiforme or GBM).	Very rapidly growing tumors that spread quickly. Represents about 25% of all primary brain tumors. Most common in older adults (over age 55) and affect more men than women. Recurrences are common in patients who achieve long-term survival.


GENERAL DESCRIPTION OF EPENDYMOMAS: Derived from cells that line the ventricles (fluid-filled brain cavities) and spinal cord central canal. Do not usually spread into normal brain tissue. Can block exits for cerebrospinal fluid and cause hydrocephalus. They constitute about 4% of all central nervous system tumors in adults and 10% of these tumors in children. About 30% of ependymomas develop in the spinal column.

Low-grade (I). Myxopapillary ependymoma (found in the spine). Subependymoma (found in one of the ventricles).	No or very slow growth. In addition to grade, risk is also based on location of the tumor. Tumors on the spinal cord are more accessible than those in the fourth ventricle or in the middle of the lower back portion of the brain.	Can often be removed and cured with surgery, particularly those on spinal cord. Radiation may be needed. Chemotherapy (avoid radiation, if possible) in children under age 6).
Low-grade (II). Papillary, cellular, and clear cell ependymomas.	Slow growth. Usually affect adults.	Surgery alone or followed by radiotherapy. For those who fail radiotherapy, possible use of nitrosourea-based chemotherapies or investigative drugs.
Grade III. Anaplastic ependymomas.	Spreads to the spinal fluid.	Surgery followed by radiotherapy to brain and spinal cord. Possible shunt.
Grade IV. Primitive neuroecto-dermal tumor (PNET). Composed of malignant forms of early, undeveloped nerve cells called neuroblasts. (This malignancy is also referred to as neuroblastoma.)	Very rare, but more common in children. Primitive nerve cells that grow very rapidly. Usually occur in cerebellum.	Surgery followed by radiotherapy to brain and spinal cord. Chemotherapy in young children. Investigative high-dose chemotherapy with stem cell rescue for children with relapsed cancer.


DESCRIPTION OF OLIGODENDROGLIOMAS: They develop from oligodendrocyte glial cells. These cells form the protective coatings around nerve cells. Pure cell types are rare. Most often occur in mixed gliomas. Categorized as either low- or high-grade. Most are low-grade II.

Low-grade: Low grade difficult to tell from astrocytomas, although they are usually calcified. Very likely to bleed. Usually spread along nerve pathways of the brain and spine and rarely outside this area. In spite of difficulty in removing surgically, in some patients survival can be 30 - 40 years. Usually have better prognosis than astrocytomas of equal grade. Occur mostly in middle-aged adults, although there is also a small peak of incidence in children.	Treatment usually delayed until progression causes symptoms. Surgery to remove whole tumor. Radiotherapy often follows in all adults over age 40 or in anyone in which tumor cannot be completely removed. Solid evidence is lacking on this approach, however, and there is some debate on its benefits. Trials using chemotherapy after radiation are promising. Two-thirds of patients respond to PCV (combination of procarbazine, lomustine and vincristine.) Sustained remissions averaging 16 years often achieved. Pure oligodendrogliomas respond better than mixed gliomas. Temozolomide is showing promise as second-line treatment. Others under investigation. Trials of additional chemotherapy for less well-differentiated tumors or for residual tumors after surgery.
High-grade. Anaplastic oligodendrogliomas.	Immediate treatment. Surgery to remove the whole tumor, if possible. Radiation typically follows surgery. Chemotherapy treatments either before or with radiation. Standard drugs are limited. Experts recommend trying investigative drugs. Temozolomide and retinoic acid may be useful. Possible additional drugs include melphalan, thiotepa, carboplatin, cisplatin, and etoposide. (Numerous biologic markers may help identify specific oligodendrogliomas that will respond better or worse to specific treatments.)


GENERAL DESCRIPTION OF MIXED GLIOMAS: Mixed gliomas contain a mixture of malignant gliomas. About half of these tumors contain cancerous oligodendrocytes and astrocytes.

Grade determined by the highest-grade cell present in the tumor.	Same as for oligodendroglioma.



Meningiomas	They are found in the membranes around the brain and spinal column. They are usually benign and rarely invasive. In such cases, long-term outlook is very favorable. (Malignant forms, anaplastic meningiomas, and hemangiopericytomas are uncommon and occur in about 2% of cases.)	Usually watchful waiting. Aggressive surgery the treatment of choice, if possible, although 20% recur after 10 years. Malignant forms and those at the base of the skull difficult to impossible to remove surgically. Stereotactic radiosurgery or fractionated external beam radiotherapy showing promising results for some patients.
Cerebellar astrocytomas (located in cerebellum)	Located in the cerebellum. Usually low-grade, but depends on cell type. If surgical removal is complete, up to 90% survival rates. More common in children than adults.	Surgery primary treatment. Radiotherapy if removal is incomplete.
Brain Stem Gliomas	About 60 - 70% of brain stem tumors are diffuse, which are likely to spread and have a rapid onset of symptoms. Focal tumors tend to be solid or cyst-like. They generally develop gradually. Occurs in both children and young adults.	Radiation is usual treatment. Tumors in this area are rarely removed surgically since the nerve tissue in this area is responsible for vital life functions. Slow-growing tumors may only require watchful waiting. Trials using advanced radiotherapy techniques, gene therapy, immunotherapy, and other experimental drugs.
Medulloblastomas	Occurs in cerebellum (the lower portion of the brain), brainstem, and spinal cord. Usually fast-growing aggressive cells. Most common brain tumors in children and young people, causing between 15 - 20% of brain tumors. With aggressive therapy, in children 5-year survival rates between 60 - 80%. In patients who survive for 2 years after diagnosis, long-term survival rate is nearly 80%.	Treatment is usually surgery and radiotherapy followed by chemotherapy. A 2005 study found that a combination chemotherapy regimen may replace radiation for very young children. A 2006 study suggested that radiation and chemotherapy doses should be adjusted based on disease severity.
Optic Tract Gliomas	Spread along the optic nerve. Usually slow growing. Most often in children under age 10. Children with these tumors often have vision and hormonal problems.	Usually surgery if one eye is involved. Possible chemotherapy or radiation.

Treatment

The approach for treating brain tumors is to reduce the tumor as much as possible using surgery, radiation treatment (also called radiotherapy), chemotherapy, or investigative procedures. Such treatments are used alone or, more commonly, in combinations. With some very slow-growing cancers, such as those that occur in the midbrain or optic nerve pathway, patients may be closely observed and not treated until the tumor shows signs of growth. The intensity, combination, and sequence of these treatments depends on the glioma subtype, its size and location, and patient age, health status, and medical history.

Recent advances in surgical and radiation treatments have significantly extended average survival times compared to those of standard therapy. Investigative treatments, such as monoclonal antibodies, are also showing promise. Patients or their caretakers should discuss all options thoroughly with a specialist in brain cancer. Different specialists may be needed to help manage symptoms.

Because of the low-cure rates of most malignant brain tumors, support for the patients and their families is a critical component of treatment and management. In response to one survey of patients with gliomas, experts made several recommendations to help both patients and caregivers:

Any physical impairment that could benefit from home equipment or physical therapy should be identified and treated.
Patients should discuss emotional as well as physical issues with their doctors. Depression, for instance, can be medically treated. Caregivers should also seek help for the inevitable stress, depression, and tension arising from their difficult role.
Relaxation techniques, meditation, and spiritual resources can be extremely helpful. Support groups are beneficial, but experts recommend separate groups for patients and their families.

Surgery

Surgery is usually the first step in treating most brain tumors. In some cases, however, such as most brain stem gliomas, it may be too dangerous to perform surgery. The object of most brain tumor surgeries is to remove or reduce as much of its bulk as possible. By reducing the size, other therapies, particularly radiotherapy, can be more effective. (Although there have been significant advances in brain surgeries, some experts argue that in high-grade gliomas extensive surgery may not improve survival rates at all and patients are best served by radiation therapy.)

The standard procedure is called craniotomy.

The neurosurgeon removes a piece of skull bone to expose the area of brain over the tumor.
The tumor is located and then removed.

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

There are various surgical options for breaking down and removing the tumor. They include:

Standard surgical procedures
Laser microsurgery (which produces great heat and vaporizes tumor cells)
Ultrasonic aspiration (which uses ultrasound to break the glioma tumor into small pieces, which are then suctioned out)

Relatively benign, grade I gliomas may be treated only by surgery. Some controversy exists over whether surgery for low-grade astrocytomas improves survival, although insufficient research has been conducted to prove its benefits for these gliomas. Most malignant tumors require additional treatments, including repeat surgery.

The surgeon's skill in removing the tumor as completely as possible is critical to survival. No one should be shy about asking the surgeon the number of similar procedures they have performed. (Asking for complication rates may not be useful, since a very experienced surgeon might operate on many high-risk patients.)

In most cancers outside the brain, surgical removal of a tumor usually involves taking out surrounding healthy tissue to be sure all cancer cells are gone. In the brain, however, removing healthy nearby nerve tissue can be as disastrous for the patient as the cancer itself. Special techniques have been developed to allow maximum removal of tumors while protecting healthy brain cells.

Stereotaxy. Stereotaxy has become a useful adjunct to both surgery (stereotactic surgery) and radiotherapy (stereotactic radiotherapy).

Cortical Localization. Cortical localization, or stimulation, uses a probe that passes a tiny electrical current to delicately stimulate a specific area of the brain. This produces a visible response of the body part (such as a twitch in a leg), which the stimulated region of the brain controls. The surgeon then knows to avoid those areas during the operation.

Image-Guided Surgery. Image guided surgery uses a three-dimensional picture of the patient's brain derived from computed tomography (CT) or magnetic resonance imaging (MRI) scans. An advanced technique called high-field interventional MR imaging (iMRI) is particularly accurate in identifying the tumor, but it is not widely available. The image, with various views of the brain, is displayed on a monitor in the operating room. During surgery, as the surgeon's instrument touches a part of the brain, a camera sends the image to a computer, which calculates the position of the surgical tool and displays it in its proper location on the 3-D image. The surgeon then can look at the monitor and see what structures to avoid.

Magnetic-Tipped Catheters. Neurosurgeons are investigating a technique in which external magnetic fields direct a magnet-tipped flexible catheter to the tumor site through a path that avoids harming certain important areas of the brain.

Heparin. Heparin, a blood-thinning drug, should be given at the time of surgery to help prevent blood clots.

Radiotherapy

Radiotherapy plays a central role in the treatment of most brain tumors, whether benign or malignant.

Radiotherapy after Surgery. Even when it appears that the entire tumor has been surgically removed, microscopic cancer cells often remain in the surrounding brain tissue. Radiation targets the residual tumor with the goal of reducing its size or stopping its progression. If the entire tumor cannot be removed safely, postoperative radiotherapy is often recommended. Even some benign gliomas may require radiation, since they may be life-threatening if their growth is not controlled.

Radiotherapy When Surgery Is not Appropriate. Radiotherapy may be used instead of surgery for inaccessible tumors or for tumors that have properties that are particularly responsive to radiotherapy.

Radiotherapy and Chemotherapy (Radiochemotherapy). Combining chemotherapy with radiotherapy is beneficial in some patients with high-grade tumors.

Various radiation treatments are now available.

Conventional radiotherapy uses external beams aimed directly at the tumor and is usually recommended for large or infiltrating tumors. It begins about a week after surgery and continues 5 days per week for 6 weeks. Older adults tend to have a more limited response to external-beam radiation therapy than younger people. According to a 2007 study in the New England Journal of Medicine, radiotherapy leads to a modest improvement in survival in elderly patients (70 years or older) with glioblastoma, and causes few negative impacts on quality of life or cognition.

For tumors that are highly localized, the radiation therapist has a choice of other radiation treatments:

Brachytherapy (also called interstitial radiation) uses radioactive "seeds" implanted directly in the tumor site. It is used as a booster to external beam radiation for patients with malignant astrocytoma. Brachytherapy appears to prolong survival in some aggressive gliomas. It may also be a safe and effective treatment for some children.
Intensity-modulated radiation therapy (IMRT) uses high-dose radiation beams that conform to the three-dimensional shape of the tumor.
Hyperfractionated radiation uses many small radiation doses to deliver a high total dosage of radiation.
A balloon catheter (GliaSite) that delivers radiation to the tumor cavity after surgery is showing promise.

Stereotactic radiosurgery has been developed to allow highly targeted radiation to be delivered directly to the small tumors while avoiding healthy brain tissue. The term radiosurgery is used because the destruction is so precise that it acts almost like a surgical knife. Some studies suggest that stereotactic radiosurgery improves survival, even in patients with the highly aggressive glioblastoma multiforme brain cancer. The procedure is being tested to boost standard radiotherapy.

Benefits of Stereotaxy. There are numerous benefits for stereotaxy:

Stereotaxy allows precisely focused, high-dose beams to be delivered to gliomas less than 1.25 inch in diameter.
Investigators have found that stereotactic radiosurgery can help them reach small tumors located deep in the brain that were previously considered inoperable.
Sometimes with stereotaxy only a single treatment may be needed.
Unlike traditional radiotherapy, stereotactic radiotherapy can be repeated, so it is useful for recurrent tumors when a patient has already received standard radiation treatments.
Combining stereotaxy with techniques that gauge speech and other mental functions in patients who are awake during the procedure can allow removal of brain tissue with a lower risk for complications in areas that affect such functioning.

The Planning Procedure. Stereotactic radiosurgery usually begins with a series of steps designed to plan the radiation target:

First, the patient is given a local anesthetic. In the standard operation, the patient's head must be totally immobilized by screwing a device known as a stereotactic frame into the patient's skull. (The frame procedure is effective only on brain tumors that have regular margins.) The frame is removed as soon as the whole procedure has been completed (about 3 - 4 hours).
A three-dimensional map, usually using magnetic resonance imaging (MRI) scans, is made of the patient's brain.
A computer program calculates dosage levels and specific areas for radiation targeting.

Advanced imaging techniques are now allowing frameless stereotaxy, which eliminates the frame and may be effective on more tumors. For example, high-field interventional MR imaging (iMRI) uses a guidance system based on cruise-missile technology to calculate the slightest variations in movements of the head and the location of the tumor relative to these movements. These calculations are then used to target the radiation beams directly on the tumor, even if the patient's head is moving slightly.

Delivery of Radiation Beams. Once the preliminary planning stage has been completed, treatment begins. Several advanced machines, such as the gamma knife, adapted linear accelerator (LINAC), and cyclotron, are being used with stereotaxy and can deliver very focused beams of radiation. Actual treatment takes 10 minutes to 1 hour.

The gamma knife uses gamma rays that are sent from multiple points to converge at a single point on the tumor. Although each gamma-ray beam is very low dosage, when the beams converge, the intensity and destructive power is very high. The gamma knife is limited to very small tumors and so is generally useful as a booster after standard radiation, surgery, chemotherapy, or combinations.
The linear accelerator (LINAC) produces photons (positively-charged atomic particles) in patterns that are matched to the tumor shape. The patient is positioned on a bed that can be moved to allow flexible positioning. It allows treatment over multiple sessions of small doses (fractionated stereotactic radiotherapy), instead of a single session. This means that larger tumors can be treated.
The cyclotron is basically an atom smasher, which produces protons that can be directed toward the tumor. As part of this procedure, some researchers are using boron neutron capture therapy (BNCT). BNCT employs intravenous administration of a boron compound, which is picked up more selectively by tumor cells than by normal brain tissue. The cyclotron delivers a single dose of radiation that triggers the release of high-energy particles from the boron to destroy nearby tumor cells. The cyclotron is available only in a very few locations, and there have been few trials to date.

Researchers are studying drugs that may be used along with radiation to increase the effectiveness of the treatment.

Radioprotectors. Drugs such as amifosistine (Ethyol) may protect healthy cells during radiation.

Radiosensitizers. Drugs such as fluorouracil (5-FU) and cisplatin (Platinol) may help make cancerous cells more sensitive to radiation.

Common Side Effects. Side effects of radiotherapy may vary depending on the tumor type and radiation treatment. Side effects may include hair loss, fatigue, and nausea and vomiting. Skin irritation and sensitivity may develop in the areas being treated. To prevent further irritation, avoid scratching or rubbing, avoid direct sunlight and heating pads, and do not attempt to treat the symptoms yourself. (Ask your doctor or radiation therapist for advice.) Brain swelling (edema) is another common radiotherapy side effect, which can sometimes cause an increase in brain tumor symptoms. Edema can be treated with steroids.

Tissue Injury. Radiation necrosis (total destruction of nearby healthy tissue) occurs in about 25% of patients treated with intensive radiation. Radiation necrosis can cause brain swelling and reduction in mental functions. The condition is treated with steroids. If steroids prove ineffective, surgery may be required to remove the damaged tissue.

New Tumors. Radiation therapy for childhood cancer is the most important risk factor for developing new brain and spinal column tumors, according to a 2006 study. The risk appears greatest for children who received radiation therapy before age 5. Researchers found that the risk of second primary tumors increased in relation to the radiation dose used to treat the first cancer.

Stroke. Survivors of childhood brain tumors who were treated with high doses of cranial radiation (especially doses greater than 50Gy) may be at increased risk of having a stroke later in life. In a study of nearly 2,000 brain tumor survivors, the average length of time from cancer diagnosis to stroke was 14 years.

Chemotherapy

Chemotherapy involves the use of drugs to kill or alter cancer cells. Chemotherapy is not an effective initial treatment for low-grade brain tumors, mostly because standard drugs cannot pass through the blood-brain barrier, the functional system that protects the brain by preventing certain molecules from reaching the central nervous system. In addition, not all types of brain tumors respond to chemotherapy. In general, chemotherapy for brain tumors is usually administered following surgery or radiation therapy.

The type of drug determines how it is administered. "Systemic delivery" drugs, which pass to the brain from the bloodstream, may be given by mouth, injected into a vein through an IV, or injected into an artery or a muscle. "Local delivery" drugs are placed within or around the brain tumor.

Scientists are working on several approaches to overcome the blood-brain barrier. Newer delivery methods include:

Interstitial chemotherapy uses disc-shaped polymer wafers (known as Gliadel wafers) soaked with carmustine, the standard chemotherapeutic drug for brain cancer. The surgeon implants the wafer directly into the surgical cavity after a tumor is removed.
Intrathecal chemotherapy delivers chemotherapeutic drugs directly into the spinal fluid.
Intraarterial chemotherapy delivers high-dose chemotherapy into arteries in the brain using tiny catheters. In one study, this approach was used within 2 weeks of radiotherapy in patients with high-grade astrocytomas, and the survival rates for glioblastoma multiforme tripled (20 months) compared to those who had chemotherapy and radiation at the same time.
Convection-enhanced delivery (CED) involves placing catheters into the brain tumor or nearby brain tissue to deliver slowly and continuously a cancer drug over several days.

Many different drugs, and drug combinations, are used for chemotherapy. Standard ones include:

Temozolomide (Temodar). Temozolomide, the first new drug approved for brain tumors in several decades, is taken by mouth as a pill. Temozolomide was first approved in 1999 for adult patients with anaplastic astrocytoma that did not respond to other treatments. In 2005, it was approved for use during and after radiation therapy for patients newly diagnosed with glioblastoma multiforme. The current first-line treatment for patients with glioblastoma is combined radiotherapy and temozolomide, followed by monthly doses of temozolomide after radiation treatment ends. A 2005 study, published in the New England Journal of Medicine, reported that adults with newly diagnosed glioblastoma who received temozolomide during and after radiation therapy had a higher rate of 2-year survival than patients who received radiation alone. A 2007 study in Neurology suggested that temozolomide works best for patients who are missing a particular gene (1p/19q). Temozolomide’s side effects are relatively minor, but may include constipation, nausea and vomiting, fatigue, and headache.

Carmustine (BCNU, BiCNU). Carmustine is used to treat many types of brain tumors, including glioblastoma, medulloblastoma, and astrocytoma. Carmustine is usually administered into the vein by IV. It can also be delivered through a wafer implant (Gliadel), which is surgically placed into the brain cavity after tumor removal. If carmustine is administered intravenously, side effects may include nausea and vomiting, fatigue, respiratory problems, and lung scarring (pulmonary fibrosis). Intravenous carmustine may cause bone marrow impairment, which results in decreased production of blood cells (a condition called myelosuppression). If carmustine is delivered through a wafer, side effects may include seizures, brain swelling, and infection within the brain cavity.

PCV Drug Regimen. PCV is an abbreviation for a chemotherapy regimen that combines procarbazine (Matulane), lomustine (CCNU), and vincristine (Oncovin). PCV is commonly used to treat oligodendrogliomas and oligoastrocytomas. The drugs may also be used alone or in other combinations. Procarbazine and lomustine are taken by mouth. Vincristine is given by either injection or IV. These drugs can cause significant side effects, including a drop in blood cell counts, nausea and vomiting, constipation, fatigue, and mouth sores. Procarbazine can cause high blood pressure when taken with foods high in tyramine. Patients should avoid foods such as beer, red wine, cheese, chocolate, processed meat, yogurt, and certain fruits and vegetables.

Platinum-Based Drugs. Cisplatin (Platinol) and carboplatin (Paraplatin) are standard cancer drugs that are sometimes used to treat glioma, medulloblastoma, and other types of brain tumors. These drugs are delivered by IV. In addition to nausea and vomiting, carboplatin can cause hair loss, and cisplatin can cause muscle weakness.

Patients with brain tumors, especially tumors that are in advanced stages, should consider enrolling in clinical trials. Many clinical trials are conducted through academic medical centers. Some promising areas of drug research include:

Other Chemotherapy Drugs. Researchers are investigating whether drugs used to treat other types of cancer may have benefits for brain tumors. These drugs include tamoxifen (Nolvadex) and paclitaxel (Taxol), which are used to treat breast cancer; topotecan (Hycamtin), which is used to treat ovarian and lung cancers; and vorinostat (Zolinza), which is approved for treatment of cutaneous T-cell lymphoma. Research presented at the 2007 meeting of the American Society of Clinical Oncology indicated that vorinostat may help patients with glioblastoma multiforme. Irinotecan (Campath) is another cancer drug that is being studied in combination treatment.

Molecular Targeted Therapy Drugs. One of the most promising developments in cancer treatment research has been the emergence of so-called "targeted therapies." Traditional chemotherapy drugs can be effective, but because they do not distinguish between healthy and cancerous cells their generalized toxicity can cause severe side effects. Targeted therapies work on a molecular level by blocking specific mechanisms associated with cancer cell growth and division. Because they selectively target cancerous cells, they may induce less severe side effects. In addition, these drugs hold the promise of creating options for more individualized cancer treatment based on a patient's genotypes.

Promising targeted therapies for brain tumors include:

Anti-angiogenesis drugs block molecules involved with the growth of blood vessels that feed the tumor (a process called "angiogenesis," which is particularly important in the growth of glioblastomas.) These drugs starve tumors of vital nutrients and oxygen. Bevacizumab (Avastin) is being studied in combination with irinotecan for treatment of recurrent malignant gliomas. Bevacizumab targets vascular endothelial growth factor (VEGF), a specific angiogenesis growth factor. Cediranib (Recentin, AZD2171) is another VEGF inhibitor. In 2007 clinical trials, cediranib appeared to help make recurrent glioblastomas more responsive to chemotherapy and radiation treatment.
Tyrosine kinase inhibitor drugs block proteins involved in tumor cell growth and production. Drugs that specifically target epidermal growth factor receptors (EGFR) are a type of tyrosine kinase inhibitor of special interest in brain tumor research. These drugs include erlotinib (Tarceva), imatinib (Gleevac), and gefitinib (Iressa).
Farnesyl protein transferase inhibitors, such as tipifarnib (Zarnestra) and lonafarnib (Sarasar), are drugs that target a protein involved in the functioning of the cancer-causing Ras protein. Lonafarnib is being studied in combination with temozolomide, and tipifarnib in combination with radiation therapy.
MTOR inhibitors target other enzymes involved in cell growth and replication. Everolimus (RAD-001) is being studied for glioblastoma multiforme and astrocytoma. Everolimus is related to rapamycin (Siroliumus) and tacrolimus (Prograf), which are also being investigated for brain tumor treatment. These drugs are commonly used to suppress the immune system to prevent rejection after organ transplantation.

Other Treatments

Researchers are testing several drugs that target specific mechanisms associated with brain cancer. Combinations of some of these drugs, with or without standard chemotherapy and radiotherapy, may prove to be more effective than the use of any one treatment. It should be noted that none of these drugs at this time are producing cures, although some are improving survival.

Immunotherapy aims at using modalities that boost the patient's own immune system's ability to seek out and destroy cancerous cells.

Radioimmunotherapy with Monoclonal Antibodies. Radioimmunotherapy is showing special promise as a treatment approach to brain tumors. It typically uses monoclonal antibodies (MAbs), genetically engineered drugs designed to work against a specific target. MAbs are bound with radioactive substances and delivered directly into the brain and sometimes into the tumor. The MAbs are specifically designed to lock with the surface of certain cells in the tumor. Once they do so, the radioactive substances destroy the cell. The approach is essentially mini-radiation therapy without the damage or severe side effects of standard radiation treatments. Numerous different radioimmunotherapies are being investigated, and trials of some are reporting improved survival rates in high-grade gliomas. Some doctors believe this approach could prove to be the most effective therapy against these cancers.

Interleukins. Interleukins are natural proteins created by the immune system. Certain tumor cells carry receptors for specific interleukins, which are being investigated for a possible therapeutic role. For example, some drugs combine an interleukin with a drug that is toxic to cancer cells. The interleukin locks onto the receptor on the cancer cell, and the toxic chemical enters the tumor with the intent to kill it. Some interleukins are also being investigated alone for their own tumor-cell killing properties.

Tumor Vaccines. Tumor vaccines are being created, in which tumor cells are removed from the patient and inactivated. When the tumor cells are transferred back to the patient, they are harmless but can elicit a powerful immunologic response against the tumor. Vitespan (Oncophage) is a tumor vaccine that is showing promise against recurrent high-grade glioma, according to preliminary results from early trials presented at the 2007 annual meeting of the American Association of Neurological Surgeons.

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). Such drugs, when effective, would starve tumors of vital nutrients and oxygen. Angiogenesis is particularly important in the growth of glioblastomas, the most malignant brain tumors. Of particular promise are drugs that inhibit enzymes called tyrosine kinase, farnesyl protein transferase, and matrix metalloproteinase, which play critical roles in angiogenesis.

Farnesyl Protein Transferase Inhibitors. Farnesyl protein transferase inhibitors, such as tipifarnib, also called R115777 (Zarnestra) and lonafarnib (Sarasar), are drugs in a new class that block a mutated gene called the Ras gene, which is responsible for about 30% of cancers. Lonafarnib is in early trials in combination with temozolomide. Tipifarnib is also currently in early trials and may prove to be effective.

Tyrosine Kinase Inhibitors. Drugs that target growth factor receptors, such as tyrosine kinase, interfere with the pathway leading to angiogenesis. Some tyrosine kinase inhibitors -- including erlotinib (Tarceva), imatinib (Gleevac), gefitinib (Iressa), and others -- are being investigated in early trials for brain tumor treatment. Side effects include rash, diarrhea, nausea and vomiting. Some of these drugs may reduce white blood cell count or cause liver damage. Researchers are trying to identify biomarkers that could help predict which patients would best respond to tyrosine kinase inhibitor therapy.

Matrix metalloproteinase Inhibitors. Matrix metalloproteinase is an important enzyme in angiogenesis. Inhibitors of these enzymes, including marimastat, metastat, and prinomastat, are in early trials. Marimastat has been studied and has shown some benefits in early trials for patients with recurrent glioblastoma and anaplastic gliomas, particularly in combination with temozolomide.

Phophoinositide 3-Kinse (Pi3K) Inhibitors. Rapamycin and its analog (CCI-779) inhibit Pi3K, an enzyme involved in cell growth. Early trials using CCI-779 are underway. (Another rapamycin analog, everolimus, has different effects but is also being studied for its actions in inhibiting cell growth.)

Other Drugs that Block Angiogenesis. Thalidomide was one of the first drugs used to inhibit angiogenesis and has undergone several trials. There is some evidence that it may work more effectively for metastasized brain tumors than primary tumors. Other drugs in early trials with various effects on tumor growth include suramin, cilengitide, semaxanib, PTK787, and atrasentan.

Retinoids. Retinoids are vitamin A derivatives and act as differentiating drugs in cancer treatments. That is, they can convert immature, dividing tumor cells into mature cells, stopping tumor growth. Studies suggest that they have little benefits as single drugs. Combination with radiotherapy and other drugs may hold promise.

Inactivated Viruses. Investigators are finding that certain genetically inactivated viruses, such as the poliovirus or herpes virus, may prove to be valuable fighters of brain cancers. Such viruses can enter cells and destroy them but do not pose any danger for infection. For example, one specially designed herpes virus targets the enzyme thymidine kinase (an enzyme that promotes tumor growth). Some researchers believe that a combination of this virus with retinoids may be effective with few serious side effects. Other viruses are being investigated. A drug based on this model is years away, however.

Immunotoxins. Drugs called immunotoxins use natural toxins to kill malignant brain cells.

Drugs that use diphtheria toxins, including TransMID-107R and DAB(389)EGF), are the first immunotoxins to show some promise. Clinical trials are investigating them for gliomas and metastatic brain cancers. Other toxins under investigation include irofulven (a mushroom toxin) and chlorotoxin (a substance derived from scorpions).

Taurolidine. Taurolidine is a unique drug that prevents tumor formation and growth in animals. An early clinical trial in patients with high-grade gliomas is under way.

Protein-Blocking Drug. Another development is the discovery of a protein called BEHAB (Brain-Enriched Hyaluronan Binding Protein). BEHAB is produced only by invasive glioma tumor cells, not by normal brain tissue or noninvasive tumor cells. Breakdown of BEHAB releases a substance called HABD (hyaluronan-binding domain), which appears to give glioma cells the ability to invade other areas of the brain. Both BEHAB and HABD represent potential targets for new therapies.

Chemotherapy destroys not only cancer cells but also healthy cells, including special blood cells in the bone marrow called stem cells. Stem cells are immature cells from which all blood cells develop. Transplantation procedures using bone marrow or stem cells allow high-dose chemotherapy to be administered while protecting blood cells. The procedures are being tested for patients with recurrent brain tumors, such as medulloblastoma, primitive neuroectodermal tumors, and germ cell tumors. A 2003 study reported long-term survival in some patients who underwent this procedure

Photodynamic therapy uses a special drug (Photofrin) that is absorbed by the tumor and causes the cancer cells to become fluorescent when a laser is directed at them. It is being investigated in trials in combination with other treatments. A 2003 study reported encouraging results, notably in patients with recurring glioblastoma multiforme. In the study, more than half of these patients survived for at least a year.

Treatment of Complications

Some tumors, particularly medulloblastomas, interfere with the flow of cerebrospinal fluid and cause hydrocephalus (accumulation of fluid in the skull). This causes a build-up fluid in the ventricles (the cavities) in the brain. Symptoms include nausea and vomiting, severe headaches, lethargy, difficulty staying awake, seizures, visual impairment, irritability, and tiredness.

The ventricles of the brain are hollow chambers filled with cerebrospinal fluid (CSF), which supports the tissues of the brain.

Corticosteroids (commonly called steroids) such as dexamethasone (Decadron), prednisolone, and prednisone are used to treat hydrocephalus. Side effects include high blood pressure, mood swings, increased risk of infection, stronger appetite, facial swelling, and fluid retention.

Human corticotropin-releasing factor (hCRF), a naturally occurring neurohormone, appears to possess substantial anti-swelling properties and thus has been proposed as an alternative to corticosteroids in brain edema, with potentially fewer side effects. A hCRF drug called Xerecept is currently in clinical trials.

A shunt procedure may be performed to drain fluid. Shunts are flexible tubes used to reroute and drain the fluid.

Seizures are common in brain tumor cases, with younger patients having higher risks than older ones. Anti-epileptic medications, such as carbamazepine or phenobarbital, may treat seizures and are helpful in preventing recurrence. These drugs are not useful in preventing a first seizure, however, and they should not be used routinely to treat patients with newly diagnosed brain tumors. Anti-seizure medications should be used only for patients who are experiencing seizures. Despite these guidelines, a 2005 study in the Journal of the American Medical Association reported that nearly 90% of patients with newly diagnosed malignant glioma are treated with anti-epileptic drugs, although only 32% of the patients actually have seizures. Anti-seizure medications can interact with some of the chemotherapies used to treat brain cancers, including paclitaxel, irinotecan, interferon, and retinoic acid. Patients should discuss these interactions with their doctors.

Antidepressants are very useful for treating the emotional side effects of this disease. However, according to a 2005 Journal of the American Medical Association study, only 8% of patients with malignant gliomas receive antidepressant medication even though over 90% report depressive symptoms. Support groups can also have great benefit for both patients and families.

Resources

www.abta.org -- American Brain Tumor Association
www.cbtf.org -- Children's Brain Tumor Foundation
www.virtualtrials.com -- Musella Foundation for Brain Tumor Research and Information
www.braintumor.org -- National Brain Tumor Foundation
www.neurosurgery.org -- American Association of Neurologic Surgeons
www.cancer.org -- American Cancer Society
www.cancer.gov -- National Cancer Institute
www.asco.org -- American Society for Clinical Oncology
www.cancer.gov/clinicaltrials -- Find clinical trials
www.radiologyinfo.org -- RadiologyInfo
www.plwc.org -- People Living with CAncer

References

Bowers DC, Liu Y, Leisenring W, McNeil E, Stovall M, Gurney JG, et al. Late-occurring stroke among long-term survivors of childhood leukemia and brain tumors: a report from the Childhood Cancer Survivor Study. J Clin Oncol. 2006 Nov 20;24(33):5277-82. Epub 2006 Nov 6.

Dunlap SM, Celestino J, Wang H, Jiang R, Holland EC, Fuller GN, et al. Insulin-like growth factor binding protein 2 promotes glioma development and progression. Proc Natl Acad Sci U S A. 2007 Jul 10;104(28):11736-41. Epub 2007 Jul 2.

Flint-Richter P, Sadetzki S. Genetic predisposition for the development of radiation-associated meningioma: an epidemiological study. Lancet Oncol. 2007 May;8(5):403-10.

Kaloshi G, Benouaich-Amiel A, Diakite F, Taillibert S, Lejeune J, Laigle-Donadey F, et al. Temozolomide for low-grade gliomas: predictive impact of 1p/19q loss on response and outcome. Neurology. 2007 May 22;68(21):1831-6.

Keime-Guibert F, Chinot O, Taillandier L, Cartalat-Carel S, Frenay M, Kantor G, et al. Radiotherapy for glioblastoma in the elderly. N Engl J Med. 2007 Apr 12;356(15):1527-35.

Neglia JP, Robison LL, Stovall M, Liu Y, Packer RJ, Hammond S, et al. New primary neoplasms of the central nervous system in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. J Natl Cancer Inst. 2006 Nov 1;98(21):1528-37.

Sharma MK, Mansur DB, Reifenberger G, Perry A, Leonard JR, Aldape KD, et al. Distinct genetic signatures among pilocytic astrocytomas relate to their brain region origin. Cancer Res. 2007 Feb 1;67(3):890-900.

Vredenburgh JJ, Desjardins A, Herndon JE 2nd, Dowell JM, Reardon DA, Quinn JA,et al. Phase II trial of bevacizumab and irinotecan in recurrent malignant glioma. Clin Cancer Res. 2007 Feb 15;13(4):1253-9.

Review Date:
11/1/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

CT scan

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

Back

HEALTH GUIDE REFERENCE FROM A.D.A.M

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

Review Date:
5/7/2007
Reviewed By:
Harvey Simon, M.D., 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

Back pain and sciatica

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

In This Report

Highlights
Introduction
Causes
Risk Factors
Diagnosis
Medications
Complementary and Alternati...
Exercise and Physical Thera...
Surgery
Other Treatments
Specific Treatment for Acut...
Specific Treatment for Chro...
Prognosis
Complications
Prevention
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Surgery

Kyphoplasty, a surgical technique used to treat spinal fractures, does not improve a person's back pain or quality of life, according to a review published in 2006 by a nonprofit health services research agency. Kyphoplasty should only be done if bed rest, medicines, and physical therapy do not relieve back pain.

Ultrasound

Therapeutic ultrasound uses sound waves to deliver gentle vibrations to an area of the body. Scientists in England are studying whether therapeutic ultrasound may help relieve pain and disability due to sciatica.

Acupuncture

Studies continue to show that acupuncture helps some patients with low back pain. Now, research published in the British Medical Journal online says the alternative treatment seems to be worth the price in the long run.

Stem Cells

Researchers in England have pioneered a new technique to grow new spinal tissue using stem cells. Stem cells are the building blocks of specific cells. Every cell in the human body starts (or "stems") from a stem cell. Researchers say a patient's stem cells may someday be used to grow new tissue that can replace damaged discs.

Back pain tied to brain changes

Chronic back pain appears to be linked to tiny structural changes in the brain. German researchers have found that persons with chronic back pain have more activity in the parts of the brain involved in pain processing and emotional responses. It is unclear if the brain changes came before the pain or if they occurred in response to the pain. The scientists presented their findings at the 2006 Radiological Society of North American annual meeting.

Introduction

Back pain is one of the most common reasons people visit their doctor. According to the National Institute of Arthritis and Musculoskeletal and Skin Diseases, 8 out of 10 people have some type of backache.

Back pain can be acute or chronic.

Acute pain develops suddenly and goes away within 6 weeks. Acute pain is the most common type of back pain.
Chronic pain can come on fast or slow, but it lasts longer than 3 months. Back pain can occur in any area of the back, but it is more common in the lower part, which supports most of the body’s weight.

The back is highly complex, and pain may result from damage or injury to any of various bones, nerves, muscles, ligaments, and other structures. Still, despite sophisticated techniques that provide detailed anatomical images of the spine and other tissues, the cause of most cases of back pain remain elusive.

Vertebrae. The spine is a column of small bones, or vertebrae, that support the entire upper body. The column is grouped into three sections.

The cervical (C) vertebrae are the seven spinal bones that support the neck.
The thoracic (T) vertebrae are the twelve spinal bones that connect to the rib cage.
The lumbar (L) vertebrae are the five lowest and largest bones of the spinal column. Most of the body's weight and stress falls on the lumbar vertebrae.

Click the icon to see an image of the spine.

Below the lumbar region is the sacrum, a shield-shaped bony structure that connects with the pelvis at the sacroiliac joints.

At the end of the sacrum are two to four tiny, partially fused vertebrae known as the coccyx or "tail bone."

Click the icon to see an image of the sacrum.

Each vertebra is designated by using a letter and number, which allows the doctor to determine where it is in the spine.

The letter reflects the spinal region where the vertebra is located: C=cervical (neck region), T=thoracic (chest, or middle back, region), and L=lumbar (lower back).
The number signifies the vertebra's place within that spinal region. The numbers start with 1 at the top of a region and count up as the vertebrae descend within the region. For example, C4 is the fourth bone down in the cervical region and T8 is the eighth thoracic vertebrae.

The Disks. Vertebrae in the spinal column are separated from each other by small cushions of cartilage known as intervertebral disks. The disks have no blood supply of their own. They need to rely on nearby blood vessels to keep them nourished.

Click the icon to see an image of an intervertebral disk.

Each disk is 80% water and contains two structures.

Inside each disk is a jelly-like substance called the nucleus pulposus.
The nucleus pulposus is surrounded by a tough, fibrous ring called the annulus.

Click the icon to see an image of the nucleus pulposus.

Processes. Each vertebra in the spine has a number of bony projections called processes. The spinal and transverse processes attach to the muscles in the back and act like little levers, allowing the spine to twist or bend. The particular processes form the joints between the vertebrae themselves, meeting together and interlocking at the zygapophysial joints (more commonly known as facet or z joints ).

Spinal Canal. Each vertebra and its processes surround and protect an arch-shaped central opening. These arches, aligned to run down the spine, form the spinal canal, which encloses the spinal cord.

Click the icon to see an image of the vertebrae and spinal cord.

Spinal Cord. The spinal cord is the central trunk of nerves that connects the brain with the rest of the body. Each nerve root passes from the spinal column to other parts of the body through small openings bounded on one side by the disk and the other by the facets. When the spinal cord reaches the lumbar region, it splits into four bundled strands of nerve roots called the cauda equina (meaning horsetail in Latin).

Click the icon to see an image of the cauda equina.

Causes

In about 85% of back pain cases, the origin of the pain is unknown, and imaging studies usually fail to determine the cause. Disk herniation and disk degeneration due to aging are the most common causes of low back pain. Other problems can also cause this pain, however.

Over the years, the disk can wear away (degenerate), causing inflammation and irritation. This age-related condition is a major source of chronic low back pain.

A herniated disk, sometimes, but incorrectly, called a slipped disk, is widely held to be the most common cause of severe back pain and sciatica. A disk in the lumbar area becomes herniated when it ruptures or thins out and degenerates to the point that the gel within the disk (nucleus pulposus) pushes outward. The damaged disk can take many forms.

A bulge -- The gel has been pushed out slightly from the disk and is evenly distributed around the circumference.
Protrusion -- The gel has pushed out slightly and asymmetrically in different places.
Extrusion -- The gel balloons extensively into the area outside the vertebrae or breaks off from the disk.

There is some debate, however, about how pain develops from a herniated disk and how frequently it causes low back pain. Many people have disks that bulge or protrude and do not suffer back pain. Extrusion (which is less common than the other two conditions) is highly associated with back pain, since the gel is likely to extend out far enough to press against the nerve root, most often the sciatic nerve. Extrusion is very uncommon, however, while sciatic and low-back pain are very common. But there may be other causes of low back pain

Ordinarily, at the time of any injury, the immune system triggers key factors that are designed to promote healing. Evidence is now pointing to an abnormal and persistent immune response in the cells of the nucleus pulposus that may be responsible for nerve injury and pain in the lower back. In such cases, the nucleus pulposus in the herniated disk overproduces certain factors known as cytokines -- notably tumor necrosis factor (TNF) -- that, in high levels, cause inflammation and cell damage. Evidence now suggests that such cytokines cause a biochemical reaction in the regions surrounding the bulging or protruded nucleus pulposus, which results in pain.

Abnormalities in the Annular Ring. Research has also focused on tears in the annular ring -- the fibrous band that surrounds and protects the disk. The annular ring contains a dense nerve network and high levels of peptides that heighten perception of pain. Tears in the annular ring are a frequent finding in patients with degenerative disk disease. Some cases of chronic low back pain may be caused by inward growth of nerve fibers into the annular ring, which triggers pain within the intervertebral disk.

At some time, up to 40% of people have pain called sciatica. This condition occurs when the sciatic nerve is trapped or inflamed.

The Sciatic Nerve. The sciatic nerve has an extensive pathway.

It first branches from the nerve roots that descend off the lowest part of the spinal cord (in the lumbar and sacral areas). Each of the two branches of the sciatic nerve is about as wide as a thumb.
Each branch of the nerve threads through the pelvis and deep into either side of the buttocks.
The nerve branches then pass down each hip and along the back of each thigh to the foot.

Causes of Sciatica. A herniated disk pressing on the sciatic nerve is the most common cause of sciatica, although spinal stenosis or other vertebral abnormalities that press on the sciatic nerve can also cause pain.

The main nerve traveling down the leg is the sciatic nerve. Pain associated with the sciatic nerve usually originates when nerve roots in the spinal cord become compressed or damaged. Symptoms can include tingling, numbness, or pain that radiates to the buttocks, legs, and feet.

Symptoms of Sciatica

Pain due to sciatica can vary widely. It may feel like a mild tingling, dull ache, or a burning sensation. In some cases, the pain is severe enough to cause immobility.

The pain most often occurs on one side. Some people have sharp pain in one part of the leg or hip and numbness in other parts. The affected leg may feel weak.

The pain often starts slowly. Sciatica pain may get worse:

At night
After standing or sitting for long periods of time
When sneezing, coughing, or laughing
After bending backwards or walking more than 50 - 100 yards (particularly if it is caused by spinal stenosis)

Sciatica pain usually goes away within 6 weeks, unless there are serious underlying conditions. Pain that lasts longer than 30 days, or gets worse with sitting, coughing, sneezing, or straining may indicated a longer recovery.

Other than age-related degenerative disk disorders, injuries in the muscles and ligaments supporting the back are the major causes of low back pain. Of note, is the iliac crest pain syndrome (iliolumbar syndrome), in which there are tears in the ligaments that help support the pelvic bone.

Spinal stenosis is the narrowing of the spinal canal. This typically develops as a person ages and the disks become drier and start to shrink. At some point in this process, any disruption, such as a minor injury that results in disk inflammation, can cause impingement on the nerve root and trigger pain. Pain from spinal stenosis can occur in both legs, or it can be felt as sciatica. Spinal stenosis occurs mostly in the elderly with degenerative osteoarthritis, but it can sometimes be caused by other problems, including infection and birth defects.

Spondylosis is a condition in which the fourth or fifth lumbar vertebrae degenerate or develop small fractures. This condition affects 4 - 6% of the general population, and the rates may be higher in certain populations. As it progresses, the spine can become unstable and lead to spondylolisthesis, in which one vertebra slips forward over the other and causes sciatica. The condition most often occurs in older individuals with women having a higher risk than men. It is also a common cause of back pain from stress fractures in young athletes and can also be due to inherited problems, injury, or bone disease.

Some cases of sciatica pain may occur when a muscle located deep in the buttocks pinches the sciatic nerve. This muscle is called the piriformis. The resulting condition is called piriformis syndrome. Piriformis syndrome usually develops after an injury. In rare cases leg swelling, deep-vein blood clots, or both may occur. Piriformis syndrome is sometimes difficult to diagnose.

Ankylosing spondylitis is a chronic inflammation of the spine that may gradually result in a fusion of vertebrae. Symptoms include a slow development of back discomfort, with pain lasting for more than 3 months. The back is usually stiff in the morning; pain improves with exercise. In severe cases, the patient must continually stoop over. It can be quite mild, however, and it rarely affects a person's ability to work. It occurs mostly in young Caucasians in their mid-20s. The disease is more common in men, but about 30% of the cases are in women. Researchers believe that in most cases it is hereditary. About 20% of people with inflammatory bowel disease and about 20% of people with psoriasis develop a form of ankylosing spondylitis. There are few effective treatments for this potentially disabling disease, although etanercept (Enbrel) and infliximab (Remicade), anti-inflammatory agents known as TNF-blockers, are proving to be beneficial.

Any abnormality in joints, vertebrae, or nerve roots can cause back pain:

The facet (z-joints) joints can wear down. In such cases, pain occurs on arching the back or when walking.
In some cases a segment (consisting of two vertebrae and their common joint and disk) becomes unstable when its parts wear down.
Injury to nerve roots, notably deep root ganglia (nerve cells in the spine whose fibers extend from skin to muscle tissue), may be important in some cases. Some patients may have scar tissue that traps the nerve roots in the lower spine and causes sciatica.

Risk Factors

In most known cases, pain begins with an injury, after lifting a heavy object, or after making a sudden movement. Not all people have back pain after such events, however. In the majority of back pain cases, the causes are unknown.

Some evidence suggests that after episodes of back pain, some people may experience changes in brain structure and chemicals that produce an exaggerated response in nerve cells. In fact, a 2005 study suggested that chronic back pain actually shrinks the brain by as much as 11%. Such brain changes may cause a persistent perception of pain even though the actual injury has healed.

German researchers have found that chronic back pain appears to be linked to tiny structural changes in the brain. Using a specialized imaging method, they learned that persons with chronic back pain seemed to have a different, more complex structure to their brain and more activity in the areas involved in pain processing and emotional responses. It is unclear if the brain changes occurred before the pain or in response to the pain.

A number of conditions may make people more or less susceptible to low back pain.

Intervertebral disks begin deteriorating and growing thinner by age 30. One-third of adults over 20 show signs of herniated disks (although only 3% of these disks cause symptoms). As people continue to age and the disks lose moisture and shrink, the risk for spinal stenosis increases. The incidence of low back pain and sciatica increases in women at the time of menopause as they lose bone density. In older adults, osteoporosis and osteoarthritis are also common. However, the risk for low back pain does not mount steadily with ever-increasing age, which suggests that at a certain point, the conditions causing low back pain plateau.

Inherited Spinal Structure Abnormalities. Many people have a genetic susceptibility to low back pain, usually from inheriting spinal structural abnormalities.

Inherited Weakened Disks. Studies are finding that specific mutations of the COL9A gene may play a role in about 10% of sciatica cases. The gene is normally involved in producing collagen, the protein building block in all structural tissue in the body. When defective, it may cause the disk to be less able to resist compressive forces. One 2001 study found the defective gene was present in twice as many patients with disk problems as in patients without back pain.

The likelihood of experiencing back pain increases as children age. Some studies suggest that pain is more common among girls than boys. A common cause of temporary back pain is carrying backpacks that are too heavy for children. Backpacks should not weigh more than 20% of the child's body weight. They should weigh even less for very young children. Emotional or behavioral problems may also contribute to back pain in children.

Jobs that involve lifting, bending, and twisting into awkward positions, as well as those that cause whole-body vibration (usually due to long-distance truck driving), place workers at particular risk for low back pain. The longer a person continues such a job, the higher the risk. Some workers wear back support belts, but evidence strongly suggests that they are useful only for people who are currently have low back pain. The belts offer little added support for the back and do not prevent back injuries. In one study, workers who wore the belt for prevention reported more back pain than the workers who did not wear them.

A number of companies are developing programs to protect against back injuries. Although studies are mixed on the outcome of company interventions, one analysis suggested that they do have a positive effect. Employers and workers should make every effort to create a safe working environment. Office workers should have chairs, desks, and equipment that support the back or help maintain good posture.

Infections. A number of common and uncommon infections are a cause of back pain. Chronic uterine or pelvic infections can cause low back pain in women. Osteomyelitis is infection in the spine, a rare cause of back pain. Other infections that cause back pain include Lyme disease, septic arthritis, bacterial endocarditis, Reiter syndrome, mycobacterial, fungal arthritis, and viral arthritis. Chlamydia pneumonia, an atypical organism that is a common cause of mild pneumonia in young adults, is now believed to cause widespread inflammation in the body's tissue, including blood vessels, and may be responsible for a number of chronic conditions, including heart disease. Some evidence further suggests it may cause inflammation in arteries of the lower spine and contribute to spinal stenosis.

Many medical conditions are associated with back pain.

Osteoporosis is a disease of the skeleton in which the amount of calcium present in the bones slowly decreases to the point where the bones become fragile and prone to fracture. It usually does not cause pain unless the vertebrae collapse suddenly, in which case the pain is often severe. Studies indicate, however, that the incidence of low back pain and sciatica increase around the time of menopause, and very tiny fractures in the vertebrae caused by osteoporosis may be an undetected cause of back pain in many elderly women.
Osteoarthritis occurs in joints where cartilage is damaged and then destroyed, usually as a result of aging. In reaction to this destruction, the bones associated with the joints develop abnormalities. When osteoarthritis affects the spine, it may damage the cartilage in the disks, the moving joints of the spine, or both. The nerves may become pinched, causing pain and in advanced cases, numbness and muscle weakness. The patient may also experience muscle spasms and diminished mobility.
Inflammatory disorders, such as Crohn's disease and rheumatoid arthritis, can produce inflammation in the spine (sacroiliitis), although the spine is less commonly affected than other locations.
Other conditions that can directly cause pain include fibromyalgia, Paget's disease, Parkinson's disease, abscesses, blood clots, and cancer.
Other medical conditions cause referred back pain, which occurs in conjunction with problems in organs unrelated to the spine (although usually located near it). Such conditions include ulcers, kidney disease (including kidney stones), ovarian cysts, and pancreatitis.

Osteoporosis is a condition characterized by progressive loss of bone density, thinning of bone tissue and increased vulnerability to fractures. Osteoporosis may result from disease, dietary or hormonal deficiency or advanced age. Regular exercise and vitamin and mineral supplements can reduce and even reverse loss of bone density.

It should be noted, however, that a number of medical conditions, such as lung and heart problems and chronic headaches, commonly occur with low back pain. A causal relationship among them, however, is uncertain.

Persistent low back pain in children is more likely to have a serious cause that requires treatment than back pain in adults. According to one small study, one third of children being treated at a hospital for back pain were found to have serious underlying problems.

Stress fractures (spondylolysis) in the spine are a common cause of back pain in young athletes. Sometimes a fracture may not show up for a week or two after an injury. Spondylolysis can cause spondylolisthesis, a condition in which the spine becomes unstable and the vertebrae slip over each other.

Hyperlordosis is an inborn exaggerated inward curve in the lumbar area. Scoliosis, an abnormal curvature of the spine in children, does not usually cause back pain.

Juvenile chronic arthropathy is an inherited form of arthritis. It can cause pain in the sacrum and hip joints of children and young people. It used to be grouped under juvenile rheumatoid arthritis, but is now defined as a separate problem.

Injuries, benign tumors such as osteoblastoma or neurofibroma and cancers, including leukemia, can also cause back pain in children.

Medications may trigger back pain. For example, anticoagulants can cause bleeding or an internal bruise. Long-term steroid use can cause infection or compression fractures.

Some research is suggesting that some people have motor control abnormalities in the deep muscles near the spine. Such lack of control causes instability in the spine that can lead to pain.

Pregnant women are prone to back pain due to a shifting of abdominal organs, the forward redistribution of body weight, and the loosening of ligaments in the pelvic area as the body prepares for delivery. Tall women are at higher risk than short women. Although some earlier research had suggested that the use of epidurals for pain relief during labor could lead to chronic back pain, studies in 2002 reported no increased risk.

Psychological factors are known to play a strong influential role in three phases of low back pain:

Some evidence suggests preexisting depression and the inability to cope may be more likely to predict the onset of pain than physical problems. For example, a British study reported that people who showed emotional distress at age 23 were nearly twice as likely to suffer from back pain 10 years later. A 2005 study found that a “passive” coping style (not wanting to confront problems) was strongly associated with the risk of developing disabling neck or low back pain.
The perception of pain. Social and psychological factors play a role in the severity of a person's perception of back pain. For example, one study compared truck drivers and bus drivers. Nearly all the truck drivers liked their work. Half of them reported low back pain but only 24% lost time at work. Bus drivers, on the other hand, reported much lower job satisfaction than truck drivers, and these workers with back pain had a significantly higher absentee rate than truck drivers in spite of less stress on their backs. Similarly, another study found that pilots, who generally reported "loving their jobs," reported far fewer back problems than their flight crews. And yet another study reported that low rank, low social support, and high stress in soldiers was associated with a higher risk for disabling back pain.
Chronic pain. Depression and a tendency to develop physical complaints in response to stress also increase the likelihood that acute back pain will become a chronic condition. The way a patient perceives and copes with pain at the beginning of an acute attack may actually condition the patient to either recover or develop a chronic condition. Those who over-respond to pain and fear for their long-term outlook tend to feel out of control and become discouraged, increasing their risk for long-term problems.

Studies also suggest that patients who reported prolonged emotional distress have less favorable outcomes after back surgeries. It should be strongly noted that the presence of psychological factors in no way diminishes the reality of the pain and its disabling effects. Recognizing it as a strong player in many cases of low back pain, however, can help determine the full range of treatment options.

Diagnosis

Because nearly all cases of low back pain clear up in a short time and are not due to serious problems, a medical history and a brief physical examination are almost always sufficient.

Still, with very severe or chronic back pain, it is important that any serious medical causes as well as cauda equina syndrome and progressive nerve damage be ruled out first. If the doctor suspects a serious underlying cause, the approach to determining the origin of back pain involves answering three questions:

Is some general medical disorder present that could be causing the pain?
Are there social or emotional factors that might be intensifying the pain?
Are the nerves in the spine involved in the pain (such as in sciatica)?

Such questions can usually be answered with a medical history and physical examination.

A patient should report any serious health problems and concerns during a medical and family history, especially those listed below.

Previous episodes of back pain
Any injuries or accidents involving the neck, back, or hips
History of cancer
Unexplained weight loss or chronic infection
The frequency, duration, and nature of the back pain
When the back pain occurs
What triggered the pain (such as lifting a heavy object)
Conditions that make the pain worse such as coughing
Any situation that relieves the pain
Urination of bowel movement problems
Other relevant symptoms such as morning stiffness, weakness, or numbness in the legs.

The main goal of a physician exam is to try and determine the source of the pain and to determine limits of movement.

Patients are asked to sit, stand, and walk in different ways (flat-footed, on the toes, and on their heels).
In some cases they are asked to walk on a treadmill to test for weakness in toe or heel walking (which may indicate stenosis).
Patients will be requested to bend forward, backward, and sideways and to twist.
Patients will be asked to lift their leg straight up while lying down. The doctor will also move the patient's legs in different positions and bend and straighten the knees. (Pain caused by sciatica can be intensified by lifting the affected leg straight in the air. It is usually sharp, localized, and accompanied by numbness or tingling. Pain caused by inflammation is duller and more generalized and not affected by lifting a straight leg.)
The doctor may measure the circumference of the calves and thighs to look for muscle deterioration.
To test nerve function and reflexes, doctors will tap the knees and ankles with a rubber hammer. The doctor may also touch parts of the body lightly with a pin, cotton swab, or feather to test for numbness and nerve sensitivity.

Because most patients with back pain are on the mend or completely recovered within 6 weeks, imaging techniques such as x-rays or scans are rarely recommended in the first month unless a tumor, fracture, infection, cauda equina syndrome, or progressive neurologic disease is suspected.

Patients who have the following symptoms or experienced certain events may need imaging studies.

Pain that lasts more than a month
Very severe or progressive pain, numbness
Muscle weakness
A previous accident or injury that might have affected the back
A history of cancer
Indications of an underlying disease such as fever or unexplained weight loss
Pain that occurs in patients over 65 years of age

If these conditions exist, usually an x-ray is used first. If results are inconclusive, either computed tomography (CT) or magnetic resonance imaging (MRI) may be performed. (Ultrasound is not useful.)

X-Rays. Although many patients with acute and uncomplicated low back pain believe that plain x-rays of the spinal column are important in a diagnosis, they are not very helpful in most patients except for reducing anxiety. If pain persists after 6 - 8 weeks, then x-rays are usually warranted. In such cases, x-rays may reveal signs of injury, infection, tumors, stenosis, or changes in the vertebrae that may be causing inflammation or compression on the nerve. There are many different types of x-rays for the spine.

A diskography is an x-ray of the disk. This procedure requires injections into disks suspected of being the source of pain and disks nearby. It can be painful and is generally only used for patients who are undergoing back surgery to identify the location of the injured disk.
An x-ray myelogram is an x-ray of the spine that requires a spinal injection of a special dye and the need to lie still for several hours to avoid a very painful headache. It has value only for select patients with pain on moving and standing. It has largely been replaced by CT and MRI scans.

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

Magnetic Resonance Imaging (MRI). Magnetic resonance imaging (MRI) can provide very well-defined images of soft tissue and bone. It is not painful, but some people may feel claustrophobic in scanners that are fully enclosed. MRIs can detect annular tears, or disk fragments, and non-spinal causes of back pain, including infection and cancer. However, MRIs are no more effective than x-rays in identifying arthritis, and they are more expensive. Some medical evidence suggests that relying on MRI images of disk abnormalities to determine treatment has resulted in many unnecessary surgeries. At least 40% of all adults have bulging or protruding vertebral disks, and most have no back pain. The degree of disk abnormalities revealed by MRIs often have very little to do with the severity of the pain or the need for surgery. Disk abnormalities in people who have back pain may simply be a coincidence rather than an indication for treatment.

Click the icon to see an image of a MRI machine.

Advanced imaging techniques should be used only when underlying infection, cancer, or nerve involvement is suspected.

Magnetic Resonance Neurography. This imaging exam looks at the nerves in the pelvic area. Researchers reporting in the Journal of Neurosurgery found that it helped reveal pinched nerves that can cause leg pain. The findings could lead to new ways to diagnose sciatica and piriformis syndrome.

Bone Scintigraphy and SPECT Imaging.In rare cases, doctors may use bone scintigraphy (bone scanning) to determine abnormalities in the bones. The technique may be useful for early detection of spinal fractures, cancer that has spread to the bone, or osteoarthritis. During this exam, a small amount of radioactive material is injected into a vein. It circulates through the body, and is absorbed by the bones. The bones can then be visualized using x-rays or single photon emission computed tomography (SPECT). A study in the February 2006 journal Radiology found that SPECT can help determine which patients would get low back pain relief from spinal injections. Forty-seven patients were randomly divided into two groups: One group received SPECT before they were scheduled for an injection, the other group did not. Those who showed spinal problems on the SPECT images received an injection in the area of the abnormalities. Those who had a normal SPECT, as well as those who did not have the test at all, received injections in the area recommended by their referring physician. After a month, those who had targeted injections using the SPECT images had greater pain relieve than those who did not.

Electrodiagnostic tests that analyze the electric waveforms of nerves and muscles may be useful for detecting nerve abnormalities that may be causing back pain and identifying possible injuries. They are also useful to determine if any abnormal structural findings on an MRI or other imaging test have real significance as a cause of the back pain. It should be noted that any nerve injuries that affect these tests may not be present for 2 - 4 weeks after symptoms begin.

Nerve conduction studies and electromyography are the electrodiagnostic tests most commonly performed.

Nerve Conduction Studies. To perform nerve conduction studies, surface electrodes are attached to the skin. Small electric shocks are then applied to measure the speed of nerve conduction.

Electromyography. To perform electromyography, a fine, sterile, wire electrode is inserted briefly into a muscle and the electrical activity is displayed on a viewing screen. Electromyography can be quite painful, and some experts question, in fact, whether it adds any valuable diagnostic information. They suggest it be limited to unusual cases or when other tests indicate that the condition is aggressive and may increase the risk for rapid, significant injury.

Blood and urine samples may be used to test for infections, arthritis, or other conditions.

Injecting a drug that blocks pain into the nerves in the back helps locate the level in the spine where problems occur.

A procedure called a facet block is also useful in locating areas of specific damage.

Provocative diskometry is a test that uses an injection of saline solution into the suspected disk to reproduce the pain, which is then followed by injection of an anesthetic to dull the pain.

Medications

The most commonly prescribed medications for the treatment of back pain are nonsteroidal anti-inflammatory drugs (NSAIDs). These drugs block prostaglandins, the substances that dilate blood vessels and cause inflammation and pain. Evidence suggests that short-term use of NSAIDs brings effective relief in patients with acute back pain. The benefits for chronic back pain are less certain.

There are dozens of NSAIDs. The most common are the following:

Over-the-counter NSAIDs include aspirin, ibuprofen (Advil, Nuprin, Motrin IB, Rufen), naproxen (Aleve), ketoprofen (Actron, Orudis KT).
Prescription NSAIDs include ibuprofen (Motrin), naproxen (Naprosyn, Anaprox), flurbiprofen (Ansaid), diclofenac (Voltaren), tolmetin (Tolectin), ketoprofen (Orudis, Oruvail), nabumetone (Relafen), dexibuprofen (Seractil), and indomethacin (Indocin).
Topical NSAIDs delivered in gels, creams, or patches do not appear to provide any long-term benefits in reducing arthritic pain.

Many experts now recommend that patients who take NSAIDs by mouth only do so for a short period of time. A 2004 review published in the British Medical Journal suggested that long-term use of NSAIDs does not actually reduce osteoarthritis pain and may increase patients’ risk of experiencing side effects. High dosages of NSAIDs can cause heart problems such as increased blood pressure, kidney problems, and stomach bleeding.

In April 2005, the FDA asked drug manufacturers of prescription NSAIDs to place an alert on their medicines warning people that the drugs have been linked to an increased risk for cardiovascular events and gastrointestinal bleeding. The FDA also requested manufacturers of OTC NSAIDs to revise their labels to include more specific language concerning potential cardiovascular and gastrointestinal risks. Aspirin does not contain such warning labels.

Long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) is the second most common cause of ulcers and the rate of NSAID-caused ulcers is increasing. Ulcers caused by nonsteroidal anti-inflammatory drugs (NSAIDs) are also more likely to bleed than those caused by the bacterium H. pylori.

Doctors cannot predict which patients taking these drugs will develop bleeding.

Among the groups at high risk for bleeding are elderly people, anyone with a history of ulcers of GI bleeding, patients with serious heart conditions, alcohol abusers, and those on certain medications, such anticoagulants ("blood thinners"), corticosteroids, or bisphosphonates (drugs used for osteoporosis).

Proton-pump inhibitors may help to prevent and heal ulcers caused by NSAIDs. Proton-pump inhibitors include omeprazole (Prilosec), esomeprazole (Nexium), and lansoprazole (Prevacid).

An ulcer is a crater-like lesion on the skin or mucous membrane that is caused by an inflammatory, infectious, or cancerous condition. To avoid irritating an ulcer, stop smoking and try to eliminate certain substances from your diet, including caffeine and alcohol. Prescription medicines are available to suppress the acid in the stomach that causes erosion of the stomach lining. Endoscopic therapy can be used to stop ulcer-related bleeding.

Coxibs block an inflammation-promoting enzyme called COX-2. This drug class was initially thought to work as well as NSAIDs, while causing less gastrointestinal distress. However, following numerous reports of cardiovascular events, gastrointestinal problems, and skin rashes, the FDA is currently re-evaluating the relative risks and benefits of this drug class. Rofecoxib (Vioxx) and valdecoxib (Bextra) have been withdrawn from the United States market. Celecoxib (Celebrex) is still available, but patients should ask their doctor if this drug is appropriate and safe for them.

Tramadol (Ultram) is a pain reliever that has been used as an alternative to opioids. It has opioid-like properties, but is not as addictive. (Dependence and abuse have been reported, however.) It can cause nausea, but does not cause the severe gastrointestinal problems that NSAIDs can. Some patients who take tramadol experience severe itching. A combination of tramadol and acetaminophen (Ultracet) is now available. It provides more rapid pain relief than tramadol alone.

Narcotics are pain-relieving and sleep-inducing drugs that act on the central nervous system. They are the most powerful medications available for the management of pain.

There are two types of narcotics:

Opiates are derived from natural opium such as morphine and codeine.
Opioids are synthetic drugs and include oxycodone (Percodan, Percocet, Oxycontin), hydrocodone (Vicodin), and oxymorphone (Numorphan).

Novel ways to deliver pain medicine have been developed. A skin patch containing an opioid called transdermal fentanyl (Duragesic) may relieve chronic back pain more effectively than oral opioids. For very severe pain, a small, patient-controlled pump called SynchroMed may be used. This device is implanted under the skin in the abdomen and delivers pulses of pain-relieving opioids to the spinal canal.

Common side effects of opioids include anxiety, constipation, nausea and vomiting, dizziness, drowsiness, paranoia, urinary retention, restlessness, and labored or slow breathing. Addiction is a risk, although less than is commonly believed when these medications are used for pain relief. In fact, when prescribed properly, use of opioids for chronic pain can be safer in some cases than on-going use of NSAIDs. Unfortunately, opioid abuse among young people is a major concern. Unless the pain is very severe, experts advise against routinely prescribing opioids.

Injections of different substances are sometimes used to treat low back pain caused by nerve impingement. The injection is usually an epidural, which is directed into the spaces between the outer membrane of the spine and the vertebrae. None of these substances cure the problem.

Corticosteroids. An injection of a corticosteroid (commonly called a steroid) is directed as close to the injured location as possible. Corticosteroids reduce inflammation. This approach may temporarily relieve sciatic pain until the body heals itself. Studies that measure the benefits of steroids on sciatica or low back pain are conflicting. There is some evidence that patients can experience rebound pain within a few months. Some experts have also raised concerns that even a single injection can cause serious and painful side effects, including meningitis and inflammation, although such risks are very low.
Hypertonic saline (salt water solution). Epidural injections of saline are being investigated for breaking up scar tissue. One 2001 study compared targeted injections of saline and steroids directed at the nerve root. Although steroid injections had more immediate benefits, both products offered improvement. By the third month, patients who had saline injections experienced less pain than the steroid group. A 2003 study found that epidural corticosteroid injections provided no greater benefit than saline injections for patients with sciatica.
Local anesthetics. Injections of anesthetics such as Xylocaine or bupivacaine may help some patients, although studies on their benefits are mixed.
Botulinum. Researchers are investigating whether injections of botulinum toxin (Botox) in the lower back can safely and effectively relieve pain. Very small amounts of Botox temporarily paralyzes muscle tissue. Botox is commonly used to smooth out wrinkles. Some studies have suggested that Botox may be very helpful in relieving chronic low back pain and sciatica caused by piriformis syndrome. In a 2001 study, the benefits of Botox injections for low back pain subsided within 6 months.

A 2002 review of studies concluded that antidepressants may lessen pain severity in some patients, although they had little effect on daily functioning. Antidepressants called tricyclics can be effective painkillers in non-depressed people with chronic back pain. Such antidepressants include amitriptyline (Elavil, Endep), desipramine (Norpramin), doxepin (Sinequan), imipramine (Tofranil), amoxapine (Asendin), nortriptyline (Pamelor, Aventyl), and maprotiline (Ludiomil). It should be noted that tricyclics can have severe side effects. Nonetheless, experts believe there is a useful role for these drugs that warrants further investigation.

A combination of nonsteroidal anti-inflammatory drugs (NSAIDs) and muscle relaxants such as cyclobenzaprine (Flexeril), diazepam (Valium), carisoprodol (Soma), or methocarbamol (Robaxin) are sometimes used for patients with acute low back pain. Medical evidence has found that they can help relieve non-specific low back pain, but some experts have warned that these drugs should be used cautiously, since they target the brain, not the muscles. Patients who take muscle relaxants may experience a number of central nervous system side effects such as drowsiness. The muscle relaxant Soma can be addictive and does little more than produce sleep.

Tumor-Necrosis Factor (TNF) Modifiers. TNF modifiers block the action of tumor necrosis factor, a protein involved in inflammatory response. Because of their anti-inflammatory properties, TNF modifier drugs are being investigated for the treatment of the nerve dysfunction and pain that occurs in sciatica. Some small studies indicate that infliximab (Remicade) may help reduce sciatica pain. Early studies suggest that another TNF modifier, etanercept (Enbrel), may be useful for treating sciatica and back pain. TNF modifiers are powerful drugs that can cause severe side effects.

Lidocaine Patch. A skin patch containing lidocaine, a local anesthetic, has been used specifically for herpes zoster pain. Early studies suggest that this patch, called Lidoderm, may provide significant relief for people who suffer from low back pain with very few adverse effects, even with continuous use of four patches a day. If further studies support its benefits, the patch could prove to be an important treatment

NO-NSAIDs. NO-NSAIDs are drugs that combine NSAIDs and nitric oxide (NO), a substance that enhances blood flow to the stomach and increases levels of protective mucus and bicarbonate. These agents show particular promise in providing pain relief and reducing the risk for GI problems.

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.

Most herbal remedies used for back pain have both pain-relief and anti-inflammatory effects. Popular herbs for back pain relief include:

White willow bark (Salix alba) contains salicylates, the same chemicals found in aspirin.
Bromelain is an enzyme found in pineapple.
Boswellia (Boswellia serrata) is an herb commonly used in Indian Ayurvedic medicine.
Devil’s claw (Harpagophytum procumbens) is an African herb sometimes used to relieve arthritic pain.

White willow bark, bromelain, and Boswellia have blood-thinning properties and can interfere with anticoagulant medications such as warfarin (Coumadin).

Complementary and Alternative Medicine

A number of complementary and alternative treatments are used to relieve back pain. Complementary means it is used together with conventional medicine. Alternative means it is done in place of conventional medicine.

Acupuncture is now a common alternative treatment for certain kinds of pain. It involves inserting small needles or exerting pressure on certain "energy" points in the body. When the pins have been placed successfully, the patient is supposed to experience a sensation that brings a feeling of fullness, numbness, tingling, and warmth with some soreness around the acupuncture point. Unfortunately, rigorous studies of acupuncture are difficult to perform, and most evidence on its benefits is weak. In any case, it may be specifically helpful for certain patients with back pain, such as pregnant women, who must avoid medications. Anyone who undergoes acupuncture should be sure it is performed in a reputable location by experienced practitioners who use sterilized equipment.

Click the icon to see an image of acupuncture.

A number of well-conducted studies have supported the benefits of massage therapy for patients with chronic or acute back pain, especially when it is combined with exercise and patient education. In fact, one analysis in 2003 suggested it may reduce the costs of care. However, it is usually not covered by insurance.

According to a 2001 review of studies, only intensive programs that include both psychological and physical rehabilitation therapies were successful in reducing chronic low back pain and improving function. A number of effective approaches to low back pain -- collectively called mind-body techniques -- employ psychological, behavioral, or physical methods to promote relaxation and reduce stress. Although many may be helpful, evidence is lacking on the specific approaches that would be most successful and which patients would most likely benefit.

Stress Reduction. Stress reducing techniques, including relaxation methods and meditation, may be helpful. One study, for example, reported that meditation was beneficial in reducing pain and improving mood among chronic pain sufferers who had not responded to traditional care. Another found that after 3 weeks, patients who were in pain after back surgery had less discomfort and slept better after practicing relaxation imagery techniques while listening to music for 25 minutes a day.

Cognitive-Behavioral Therapy. Studies report that a course of cognitive-behavioral therapy helps reduce chronic back pain or at least enhances the patient's ability to deal with it. The primary goal of this form of therapy in such cases is to change the distorted perceptions that patients have of themselves and their approach to pain. Using specific tasks and self-observation, patients gradually shift their fixed ideas that they are helpless against the pain that dominates their lives to the perception that pain is only one negative and, to a degree, a manageable experience among many positive ones. In one study, therapists also taught relaxation techniques and methods to improve posture. The sessions lasted for 2.5 hours each week for 12 weeks. More research is needed.

Patient Education and Support Groups. A 2002 study reported that patients with chronic low back pain who participated in an expert-moderated e-mail support and discussion group had less pain and disability after 12 months. An Australian massive public-health campaign that educated patients and doctors about the importance of staying active and dispelled fears about long-term impairment from back pain dramatically reduced disability and worker compensation claims.

Spinal Manipulation for Uncomplicated Acute Low Back Pain. Spinal manipulation may be useful for acute back pain that persists beyond 2 - 3 weeks. There are a number of variations, but one example of a spinal manipulation technique is the following:

The patient first lies on their side.
The practitioner grasps the exposed shoulder and either the hip or knee and then presses the upper and lower portions of the body in opposite directions, so that the torso rotates.
The shifting vertebrae make a cracking or popping sound, indicating that they have exceeded the normal range of motion.
Often this results in a greater sense of ease and mobility. (The effect, however, may be temporary.)

Whether on-going manipulations relieve pain better that just one visit is a subject of debate. Some patients consider spinal manipulation to be highly effective for chronic low back pain. A major 2003 analysis, however, reported that current evidence did not support the benefits of spinal manipulation over general medical care or physical therapy for either acute or chronic back pain. [It was better than sham (fake) therapy, however.]

Spinal manipulations are typically performed by chiropractors, but osteopathic doctors also perform them.

One in three people with low back pain seek treatment from a chiropractor. Chiropractic was founded in the U.S. in the late 1800s. The specific goal of chiropractors is to perform spinal manipulations to improve nerve transmission. Many studies have now confirmed that patients feel more satisfied with their chiropractic care than with treatment from general practitioners.
Osteopathy was also founded in the 1800s. Its core approach to healing also involves physical manipulation. Osteopathy manipulates the bones, muscles, and tendons to optimize blood circulation. The general direction of osteopathy over the years has widened to employ a broader range of treatments that now approach those of standard medicine. One 1999 study reported that osteopathy was as effective as medical treatment in relieving low back pain and patients required far less medication and physical therapy. Osteopathic treatment was also far less expensive than traditional back pain treatments.

Both chiropractors and osteopaths offer verbal assurance and a precise treatment regimen. The direct physical connection through spinal manipulation reinforces the patient-practitioner relationship. The emotional effects of such connections may be as important for healing as the treatments themselves.

Mild and temporary side effects from spinal manipulation are common. The potential for serious adverse effects from low back manipulations is low. It should be strongly noted, however, that serious complications (including stroke or spinal cord or neck injury) have been reported with manipulations of the neck. Although little research has been done on such complications, an English survey indicated that they are more frequent than commonly thought.

Some chiropractors may take a lot of x-rays, particularly those of the full spine, which may have long-term harmful consequences. Patients should also be aware that some chiropractors use alternative treatments that have not been proven or rigorously studied. All patients should require objective evidence on the benefits of their treatments.

Vertebral Axial Decompression. Vertebral axial decompression (VAX-D) may reduce pain and improve function in patients with chronic low back pain, including sciatic pain that radiates down the leg. The patient lies face down on a special table, clutching hand grips and wearing a pelvic harness. The traction-like action alternately decompresses and relaxes the spine over 1-minute intervals. Each session lasts about 30 minutes. Ten to 20 sessions on successive days are often required. The procedure is thought to alleviate pain and enhance healing by relieving pressure within the disks, promoting the in-flow of oxygen, fluids, and nutrients to the spinal column. Some evidence supports its benefits, with reported success rates of around 70%. Because it is considered experimental, it is not yet covered by most insurers. More studies are needed to confirm its possible benefits.

Percutaneous Neuromodulation Therapy. A technique called percutaneous neuromodulation therapy (PNT) uses a small device delivers electrical stimulation to deep tissues and nerve pathways near the spine. It has shown some initial promise for relief of chronic back pain and may also improve mobility and sleep. Treatment sessions are conducted in the doctor's office and last about 30 minutes. A correct pattern of stimulation appears to be important for optimal relief and needs to be determined.

Electric Nerve Stimulation. Transcutaneous electric nerve stimulation (TENS) uses low-level electrical pulses to suppress back pain. A variant, percutaneous electrical nerve stimulation (PENS), applies these pulses through a small needle to acupuncture points. The standard procedure is to give 80 - 100 pulses per second for 45 minutes three times a day. The patients are barely aware of the sensation. Although a 2002 analysis of trials could find no direct evidence of benefit, small studies have reported some relief for chronic low back pain from either TENS or PENS. It is not known if these effects are long lasting. Neither approach is helpful for relief of acute low back pain in most patients.

Muscle Stimulation. Two investigative procedures called automated or electrical twitch obtaining intramuscular stimulation (ATOIMS or ETOIMS) are showing promise. ATOIMS uses an automated mechanical device that vibrates the muscle using a tiny pin. (The sensation is described as similar to a mosquito bite.) ETOIMS uses an extremely mild electrical current. They can also be used together. Both approaches cause the muscles to twitch and then relax then the process is stopped. Discomfort is minimal. Small studies are reporting some help in relieving a number of condition the cause chronic pain, including low back pain.

Therapeutic ultrasound. Therapeutic ultrasound involves placing a small wand or probe directly onto the skin. The wand gives off sound waves, which gently vibration the area. Scientists in England are studying whether therapeutic ultrasound may help relieve pain and disability due to sciatica.

Intradiscal Electrothermal Treatment (IDET). Intradiscal electrothermal treatment (IDET) uses electricity to heat a painful disk. Heat is applied for about 15 minutes. Pain may temporarily feel worse, but after healing, the disk shrinks and becomes desensitized to pain. However, healing takes several weeks. The surgery may not work in obese patients.

Some studies have reported positive benefits to IDET; others say it does not significantly reduce pain. A randomized, blinded study published in the November 2005 journal Spine found that IDET was no better than a sham (fake) procedure in relieving chronic back pain due to disk disease. For the study, patients were randomly selected to receive either IDET or a sham procedure. After 6 months, there was no difference in pain symptoms between the two groups.

Exercise and Physical Therapy

Incorrect movements or long-term high-impact exercise is often a cause of back pain in the first place. People vulnerable to back pain should avoid activities that put undue stress on the lower back or require sudden twisting movements, such as football, golf, ballet, and weight lifting.

Exercise does not help acute back pain. In fact, overexertion may cause further harm.

An incremental aerobic exercise program (such as walking, stationary biking, swimming) may begin within 2 weeks of symptoms. Jogging is usually not recommended, at least not until the pain is gone and muscles are stronger.

Patients should avoid exercises that put the lower back under pressure until the back muscles are well toned. Such exercises include leg lifts done in a facedown position, straight leg sit-ups, and leg curls using exercise equipment.

In all cases, patients should never force themselves to exercise if, by doing so, the pain increases.

Exercise plays a very beneficial role in chronic back pain. Repetition is the key to increasing flexibility, building endurance, and strengthening the specific muscles needed to support and neutralize the spine. Exercise should be considered as part of a broader program to return to normal home, work, and social activities. In this way, the positive benefits of exercise not only affect strength and flexibility but they also alter and improve patients' attitudes toward their disability and pain. Exercise may also be effective when combined with a psychological and motivational program, such as cognitive-behavioral therapy.

There are different types of back pain exercises. A 2005 review in the Annals of Internal Medicine found that stretching exercises worked best for reducing pain, while strengthening exercises were best for improving function.

Back pain exercises include:

Low Impact Aerobic Exercises. Low-impact aerobic exercises, such as swimming, bicycling, and walking, can strengthen muscles in the abdomen and back without over-straining the back. Programs that use strengthening exercises while swimming may be a particularly beneficial approach for many patients with back pain. Medical research has shown that pregnant women who engaged in a water gymnastics program have less back pain and are able to continue working longer.
Lumbar Extension Strength Training. Exercises called lumbar extension strength training are proving to be effective. Generally, these exercises attempt to strengthen the abdomen, improve lower back mobility, strength, and endurance, and enhance flexibility in the hip and hamstring muscles and tendons at the back of the thigh.
Yoga, Tai Chi, Chi Kung. Practices originating in Asia that combine low-impact physical movements and meditation may be very helpful. They are designed to achieve a physical and mental balance and can be very helpful in preventing recurrences of low back pain.
Pilates, an exercise practice that uses yoga principles, may be specifically helpful.
Flexibility Exercises. Flexibility exercises may help reduce pain. A stretching program may work best when combined with strengthening exercises.
Retraining Deep Muscles. Some studies suggest a link between low back pain and impaired motor control of deep muscles of the back and trunk. According to these studies, contraction exercises specifically designed to retrain these muscles may be effective for patients with both acute and chronic pain.

Perform the following exercises at least three times a week:

Partial Sit-ups. Partial sit-ups or crunches strengthen the abdominal muscles.

Keep the knees bent and the lower back flat on the floor while raising the shoulders up 3- 6 inches.
Exhale on the way up and inhale on the way down.
Perform this exercise slowly 8 - 10 times with the arms across the chest.

Pelvic Tilt. The pelvic tilt alleviates tight or fatigued lower back muscles.

Lie on the back with the knees bent and feet flat on the floor.
Tighten the buttocks and abdomen so that they tip up slightly.
Press the lower back to the floor, hold for one second, and then relax.
Be sure to breathe evenly.

Over time increase this exercise until it is held for 5 seconds. Then, extend the legs a little more so that the feet are further away from the body and try it again.

Stretching Lower-Back Muscles. The following are three exercises for stretching the lower back:

Lie on the back with knees bent and legs together. Keeping arms at the sides, slowly roll the knees over to one side until totally relaxed. Hold this position for about 20 seconds (while breathing evenly) and then repeat on the other side.
Lying on the back, hold one knee and pull it gently toward the chest. Hold for 20 seconds. Repeat with the other knee.
While supported on hands and knees, lift and straighten right hand and left leg at the same time. Hold for 3 seconds while tightening the abdominal muscles. The back should be straight. Alternate with the other arm and leg and repeat on each side 8 - 20 times.

Note: No one with low back pain should perform exercises that require bending over right after getting up in the morning. At that time, the disks are more fluid-filled and more vulnerable to pressure from this movement.

Physical therapy with a trained professional may be useful if pain has not improved within the first 3 weeks. It is, in fact, important for any person who has chronic low back pain to have an exercise program guided by professionals who understand the limitations and special needs of back pain and who can address individual health conditions. One study indicated that patients who planned their own exercise did worse than those in physical therapy or doctor-directed programs.

Physical therapy typically includes the following:

The first stage involves patient education and training the patient in correct movement. Sometimes heat or electro-therapies (such as therapeutic ultrasound or low-energy lasers) are used, although their benefits are unproven.
If back pain persists beyond 5 weeks, physical therapy is used for rehabilitation. It uses exercises to help the patient keep the spine in neutral positions during all daily activities.

Surgery

Diskectomy is the surgical removal of the diseased disk. The procedure relieves pressure on the spine. It has been performed for 40 years with increasingly less invasive techniques being developed over time. However, few studies have been conducted to determine its real effectiveness. In appropriate candidates it provides faster immediate relief than medical treatment, but long-term benefits (over 5 years) are uncertain. A number of minimally invasive variations are now available.

When the soft, gelatinous central portion of an intervertebral disk is forced through a weakened part of a disk, it is called a slipped disk. Most slipped disks (herniated disks) take place in the lumbar area of the spine. Slipped disks are one of the most common causes of lower back pain. The mainstay of treatment is an initial period of rest with pain and anti-inflammatory medications followed by physical therapy. If pain and symptoms persist, surgery to remove the herniated portion of the intervertebral disk may be needed.

Microdiskectomy. Microdiskectomy is the current standard procedure. It is performed through a small incision (1 to 1-1/2 inch). The back muscles are lifted and moved away from the spine. After identifying and moving the nerve root, the surgeon removes the injured disk tissue under it. The procedure does not change any of the structural supports of the spine, including joints, ligaments, and muscles.

Other less invasive procedures that are available including the following:

Endoscopic Diskectomy. Endoscopy employs a catheter (a thin tube) that contains tiny cameras and surgical instruments that are inserted through small incisions. Various endoscopic approaches are proving to be useful for back surgery.
Percutaneous Diskectomy. Percutaneous diskectomy (PAD). This approach uses a tube with a device at the tip that cuts away some of the nucleus pulposus and a vacuum that then sucks this gelatinous matter out.
Laser Diskectomy. A number of investigative surgical procedures employ lasers. For example, endoscopic laser foraminoplasty (ELF) uses lasers to locate the likely source of pain and remove diseased tissue. The incision requires little more than a Band-Aid and complications are minimal. Long-term benefits are unknown, however.

It is not clear yet if any of these less-invasive procedures are any more effective than the standard microdiskectomy.

Complications and Outlook. Many patients still have back pain after diskectomy that delays discharge from the hospital. Narcotics are usually needed. Adding an injected NSAID may speed resolution of pain.

Scar tissue is a significant problem, since it can cause persistent low back pain afterward. Anti-scarring agents or certain devices may help reduce surgical scars and thereby postoperative pain. Other complications of spinal surgery can include nerve and muscle damage, infection, and the need for reoperation.

Patients now often remain in bed only 3 - 4 days after disk surgery. It may take 4 - 6 weeks for full recovery, however. Gentle exercise may be recommended at first. Starting intensive exercise 4 - 6 weeks after a first-time disk surgery appears to be very helpful for speeding up recovery.

Operations that remove a vertebra (laminectomy) or shave off part of one (laminotomy) may be used in certain cases of spinal stenosis or spondylolisthesis to decompress the nerve. They may also be used to remove benign tumors on the spine.

Click the icon to see an illustrated series detailing lumbar spinal surgery.

Although either procedure often brings immediate relief from pain, a 1999 statistical study suggested that it is inappropriately performed in 60% or more of sciatica cases. There are small risks to the operation, and it is not always successful. Some recurrence of back pain and sciatica occurs in half to two-thirds of postoperative patients. Minimally invasive variations are under investigation.

In cases where abnormal vertebrae position or movement is responsible for severe and chronic back pain, such as spinal stenosis or spondylolisthesis, surgeons may fuse vertebrae together. Fusion uses a bone graft or some other device to join the vertebrae together. In a 2001 study of patients with severe long-term back pain, 33% of patients who had spinal fusion had less back pain after 2 years, compared to 7% who received conservative treatment with physical therapy. Pain improved most in the 6 months following surgery. However, a 2005 clinical trial found that spinal fusion surgery worked no better than intensive rehabilitation in reducing disability. The intensive rehabilitation program included both physical and cognitive-behavioral therapy.

Many spinal fusion surgeries use a tiny hollow metal cage, which is implanted into the disk space. Bone is then removed from the patient's hip and packed inside the cage. Over time the bone grows through the holes and around the device, fusing the vertebrae. Alternatively, rather than performing a bone graft, the cage is filled with a sponge-like material containing a genetically-engineered protein called InFuse (rhBMP-2) that promotes bone to grow.

Click the icon to see an illustrated series detailing spinal fusion.

A number of video-assisted techniques have been developed. The new techniques are less invasive than standard "open" surgical approaches, which uses wide incisions. To date, however, the newer procedures have higher complication rates than the open approaches and some medical centers have abandoned them.

Percutaneous Vertebroplasty. Percutaneous vertebroplasty involves the injection of a cement-like bone substitute into vertebrae with compression fractures. It is done under endoscopic and x-ray guidance. The technique is proving useful for stabilizing the spine and relieving pain in patients with spinal compression fractures due to osteoporosis or cancer. A Mayo Clinic study found that patients who have the procedure have less back pain during rest and activity. A survey of records from more than 100 vertebroplasty patients revealed that most patients are more functional than before the procedure, and the benefits lasted for up to a year. Warning: The FDA has warned consumers that polymethylmethacrylate bone cement, used during vertebroplasty, could leak. Such leakage could cause damage to soft tissues and nerves. It is extremely important that the patient is sure that the health care provider has had significant experience performing the vertebroplasty procedure.

Percutaneous kyphoplasty. The health care provider injects bone cement into the space surrounding a fractured vertebra. (Vertebroplasty injects the cement directly into the vertebra.) Kyphoplasty is used to stabilize the spine and return spinal cord height to as normal as possible. However, a review published in 2006 by a nonprofit health services research agency found that the technique does not improve a person's back pain or quality of life. Kyphoplasty should only be done if bed rest, medicines, and physical therapy do not relieve back pain. Those with severe fractures or spinal infections should not have kyphoplasty.

Artificial Disk Replacement. Total disk replacement is an investigative procedure for some patients with severely damaged disks. The technique implants artificial disks (ProDisc, Link, SB Charite) consisting of two metal plates and a soft core. The surgery can be performed using a minimally invasive laparoscopic procedure, which is performed through tiny cuts using miniature tools and viewing devices. A study in 2003 was the first to suggest that it may eventually achieve results that are comparable to standard surgeries for disk herniation. An artificial cushioning device called the prosthetic disk nucleus (PDN) replaces only the inner gel-like core (nucleus pulposus) within the intervertebral space, rather than the entire disk. It is showing promise in early studies.

Nerve Blocks. A number of surgical techniques are available for relieving pain by impairing nerves that are causing pain due to impingement. Medical research has shown that 60% of the patients who received electrical stimulation to block the nerves reported at least 90% relief of pain after a year; 87% reported at least 60% relief.

Other Treatments

Radiofrequency Nerve Destruction. Radiofrequencies are being used to destroy nerves involved in the facet joints (or z-joints), which connect the vertebrae. Evidence is still weak on its benefits. A 2003 analysis suggested that it may be beneficial, however, for relief of neck pain and possibly for low back pain caused by problems in the facets joints. Serious infections have been reported.

Stem cell treatments. Researchers in England have pioneered a new technique to grow new spinal tissue using the patient's own stem cells. Stem cells are the building blocks of specific cells. Every cell in the human body starts (or "stems") from a stem cell. The new tissue will replace damaged spinal tissue and may relieve low back pain. Researchers expect the treatment to enter pre-clinical trials in about 1 year.

Specific Treatment for Acute Low Back Pain

Patients with short-term acute low back pain usually have the best results with the least aggressive treatments. The general approach is as follows:

Patients with no serious underlying cause should stay as active as possible within the limits of the back pain. (Bed rest is not recommended.)
Physical therapy or spinal manipulations may be helpful if pain continues for more than 2 - 3 weeks.
The patient should seek a specialist if pain continues for more than 1 month. (Some patients may need to see a specialist sooner if there is an underlying disorder, nerve damage, or injury.) Back pain due to medical conditions such as arthritis, osteoporosis, or pregnancy either goes away when the underlying condition disappears or is treated.

Home Care Tips for Relieving Pain

Resume normal activity as soon as possible. Bed rest is no longer recommended and may delay recovery. Activities should be done without strain or stretching.
Avoid intense exercise and physical activity, particularly heavy lifting and trunk twisting if there is acute back pain.
Try an over-the-counter nonsteroidal anti-inflammatory such as aspirin or ibuprofen. These medicines often provide significant benefits.
Apply heat (104°) to the painful area. Heat may work better than ibuprofen or acetaminophen. One group of researchers found that people with low back pain who wear low-level heat wraps for 8 hours a day have significant less pain and disability.
Try alternating between hot and cold packs. Some doctors recommend changing from hot to cold every 3 minutes and repeating this sequence three times. Others believe ice packs should be applied first. This routine should be done two or three times during the day. (Note: Heat or cold treatments do not have much effect on sciatica.)
Supportive back belts, braces, or corsets may help some people temporarily, but these products can reduce muscle tone over time and should be used only briefly.
Get plenty of sleep. Healthy sleep plays a vital role in recovery. Avoid caffeine in the afternoon and evening, and unwind before bed by taking a warm bath or practicing relaxation techniques. It is often difficult to get a good night's sleep when suffering from back pain, particularly because the pain can intensify at night. Some people may need medicine to help manage nighttime pain or treat sleeplessness. Lying curled up in a fetal position with a pillow between the knees or lying on the back with a pillow under the knees may help.

Prescription muscle relaxants may help some patients, although their benefits are uncertain. Once started, medications should be taken on a regular schedule in order to maintain consistent effectiveness.

Massage therapy may help relieve both acute and chronic low back pain. Several well-conducted studies have shown some benefit and suggest it may reduce the costs of care. Massage therapy may not be covered by health insurance.

Spinal manipulation may help, although it is not clear if it works any better than physical therapy or general care. Some experts recommend delaying this treatment until pain has persisted for 3 weeks, if possible, since the back pain will most likely have gone away on its own by then.

Acupuncture has not proven to have any value for acute low back pain in most patients, but may provide some help for patients with chronic low back pain.

Be aware of and avoid approaches that are not helpful. Certain approaches may even be harmful for acute low back pain. For example, permanent bipolar magnets (magnet therapies) can deactivate heart devices and must be kept at least six inches away from pacemakers or implantable cardioverter defibrillators. These magnets have gained some popularity as a non-invasive method of relieving pain, but no studies support the claims.

Specific Treatment for Chronic Low Back Pain

Evidence strongly suggests that only intensive treatment, involving both physical and psychological rehabilitation programs, can reduce pain and improve function in patients with chronic low back pain. Even with the best treatments, many patients with chronic back pain fail to have complete pain relief. They often must develop methods for coping with persistent pain.

Early treatments for severe or chronic low back pain are similar to those of acute uncomplicated low back pain.

Pain relievers, particularly non-steroidal anti-inflammatory drugs (NSAIDs), may help relieve symptoms, although they can have severe effects on the gastrointestinal tract over time. Some doctors have recommended long-term opioids for patients with severe chronic pain, but studies suggest they do not improve activity levels and can have significant side effects.

Corticosteroid injections and tricyclic antidepressants may be helpful for some patients.

Specific and regular exercise under the guidance of a trained professional is important for reducing pain and improving function, although patients often find it difficult to maintain therapy.

A new type of physical therapy, called Souchard's global postural re-education, helps relieve back pain symptoms due to degenerative disk disease, according to research presented at the 2005 American Academy of Neurology Annual Meeting. The method involves stretching weakened muscles around the spine and stomach. Researchers studied 102 people who had at least 7 months of severe back pain due to disk disease and who had received different types of treatment for more than 6 months. They attended the new physical therapy sessions two times the first week, then once a week for an average of 5 months. Ninety-two percent had significant pain relief and returned to their normal daily activities. The majority of those who had pain relief felt better after 3 weeks, and remained pain free for almost 2 years.

Alternative therapies may help. Transcutaneous electrical nerve stimulation (TENS) and massage may relieve pain. Mind-body techniques such as relaxation and meditation may be help reducing stress-related pain. Cognitive-behavioral therapy helps change behavior and attitudes toward pain.

Acupuncture may provide longer-lasting pain relief than physical therapy, according to a study in the British Medical Journal. For the study, 129 people were given either 6 acupuncture or physical therapy sessions. The study authors cautioned that the benefit of acupuncture greatly depended on the health care provider’s experience. Another study, published in the Archives of Internal Medicine, reported that acupuncture worked better than no treatment at all.

Yoga relieves low back pain better than conventional exercise or self-help books, according to a study published in the December 20, 2005, issue of Annals of Internal Medicine. For the study, 101 adults with low back pain who were randomly assigned to one of three groups. One group attended yoga classes and lessons; the second did aerobics, weight training, and stretching; and third group read a self-help book about back pain. After 12 weeks, those who took yoga could better perform daily activities requiring the back than those in the other two groups. After 26 weeks, those who took yoga had less pain and better back function, and used fewer pain relievers than the others.

Patients should always try all possible non-surgical treatments before opting for surgery. The most common reasons for surgery for low back pain are sciatica and spinal stenosis. Some experts believe that less than 1% of back pain patients need aggressive medical or surgical treatments.

Nevertheless, when it is appropriate, surgery can provide great relief. Many approaches and procedures are available or being investigated. However, there have been few well-conducted studies to determine if any type of back pain surgery works better than others, or if a single procedure is better than no surgery at all.

People who are obese and have low back pain may benefit from surgical weight loss surgery. A study in the journal Obesity Surgery found that bariatric (stomach stapling) surgery significantly improves the degree of disability in morbidly obese patients who have low back pain.

Before having any surgery, it is extremely important that the patient is sure that the surgeon has had significant experience with the procedure.

Nonsurgical Procedures. Patients with herniated disks should try nonsurgical treatments for at least 1 month before considering surgery. Nonsurgical procedures include spinal manipulation, massage therapy, and physical therapy. Patients should wait at least 2 - 3 weeks before using spinal manipulation.

Surgery. According to a 2001 review of studies, about 10% of patients have such bad back pain after 6 weeks that a diskectomy may be considered. Diskectomy is the standard procedure for herniated disks. For many of these patients, surgery may bring significant relief. In one study, 70% of patients with moderate-to-severe sciatica who had had surgery reported improvement. In most patients, the improvement was better than that achieved by 4 years of nonsurgical treatments. It is not clear if surgery maintains its advantage for longer periods of time.

Preventing Falls. Falling is a risk for patients with spinal stenosis. They should avoid alcohol and sedatives. Leg strengthening exercises such as walking and cycling may be helpful.

Nonsurgical Treatments. The use of common pain relievers such as NSAIDs, physical therapy, and spinal injections may be helpful for some patients.

Surgery. If pain is persistent, patients may require surgery, most often a procedure called decompressive laminectomy. Some patients may require spinal fusion as well. Studies suggest that surgery reduces back pain in many patients with spinal stenosis, at least for a few years. However, by 4 years after surgery, 30% of patients have severe pain again, and 10% have another operation. It should be noted that surgery does not always improve outcome and, in some cases, can even make it worse. Surgery can be an extremely effective approach, however, for certain patients whose severe back pain does not respond to conservative measures.

The general approach for patients with piriformis syndrome is corticosteroid injections and physical therapy. Botox injections are showing promise.

In carefully selected patients who do not respond to physical therapy and injections, some studies report dramatic pain relief with a surgical procedure that releases the piriformis muscle.

Prognosis

Most people with acute low back pain are back at work within a month and fully recover within a few months. According to one study, about a third of patients with uncomplicated low back pain significantly improved after a week; two-thirds recovered by 7 weeks.

However, studies now suggest that up to 75% of patients suffer at least one recurrence of back pain over the course of a year. In another study, after 4 years, less than half were symptom-free. Some doctors are approaching the problem as one that is not necessarily curable and which needs a consistent on-going approach.

Specific conditions can determine the rate of improvement:

In the majority of patients with herniated disks, the condition improves (although the actual physical improvement may be slower than the reduction in pain). Researchers attempted to identify factors most likely to predict an elevated risk for recurrent pain and found that only depression was a significant factor in the majority of those who had not recovered.
Spinal stenosis stabilizes in about 70% of cases and worsens in 15%.

Studies have found that when people stay home because of back injury, only 65% are back at work within a week. Nearly 14% are still absent at one month. If someone is on disability for more than 6 months, the chance of them returning to work is only 50%.

Low back pain accounts for significant losses in work days and dollars. In 1990, it cost the U.S. $23 billion in direct medical costs and possibly as much as $85 billion in total costs (such as lost productivity). Chronic back pain has become one of the most expensive causes of disability among workers under the age of 45. One study found that, although severe back pain comprised only 10% of workers compensation cases, it accounted for 86% of compensation costs.

Complications

Certain warning signs should alert a patient to see a doctor immediately for low back pain. Any very severe back pain warrants attention, particularly if any of the following conditions are present:

Being over 50
Recent injury
Severe pain
Pain awakens the person at night
Pain accompanied by fever (possible infection)
Pain increased by lying down
Pain unrelated to movement
Pain lasts for a month, and is accompanied by unexplained fever or weight loss
History or chronic use of corticosteroids
Intravenous drug use
History of urinary tract infection
In children, any severe neck or back pain or pain that persists for more than 3 days

Cauda equina syndrome is the impingement of the cauda equina (the four strands of nerves leading through the lowest part of the spine). It is an emergency condition that can cause severe complications of the bowel or bladder. Cauda equina syndrome is usually caused by massive extrusion of the disk material. It can cause permanent incontinence if not promptly treated with surgery. Symptoms of the cauda equina syndrome include:

Dull back pain
Weakness or numbness in the buttocks, in the area between the legs, or in the inner thigh, backs of legs, or feet. May cause difficulty in standing or stumbling.
An inability to control urination and defecation
Pain accompanied by fever (can indicate an infection)

Prevention

Exercise, diet, stress, and weight all have a significant influence on back pain. Changing certain lifestyle factors can help reduce and, possibly, prevent backaches.

Smokers are at higher risk for back problems, perhaps because smoking decreases blood circulation. The link may also be due to an unhealthy lifestyle in general. A British study found that young adults who were long-term smokers were nearly twice as likely to develop low back pain as nonsmokers.

Sedentary Lifestyle. People who do not exercise regularly face an increased risk for low back pain, especially when they perform sudden, stressful activities such as shoveling, digging, or moving heavy items. Although no definitive studies have been done to prove the relationship between lack of exercise and low back pain, some doctors believe that an inactive lifestyle may be to blame in some cases. Lack of exercise leads to the following conditions that may threaten the back:

Stiff muscles can make it hard to move, rotate, and bend the back.
Weak stomach muscles can increase the strain on the back and cause an abnormal tilt of the pelvis.
Weak back muscles may increase the risk for disk compression.
Obesity puts more weight on the spine and increase pressure on the vertebrae and disks. However, studies report only a weak association between obesity and low back pain.

Improper or Intense Exercise. Improper or excessive exercise may also increase one's chances for back pain.

Some research suggests that over time, high-impact exercise may increase the risk for degenerative disk disease. A survey of people who played tennis, however, found no increased risk for low back pain or sciatica.
Between 30 - 70% of cyclists experience low back pain. One 1999 study reported that 70% of cyclists reported improvement simply by adjusting the angle of the bicycle seat.
Improper exercise instruction and inattention to body movements can lead to back trouble. For example, a single jerky golf swing or incorrect use of exercise equipment (especially free weights, nautilus, and rowing machines) can cause serious back injuries.

The way a person moves, stands, or sleeps plays a major role in back pain.

Maintaining good posture is very important. This means keeping the ears, shoulders, and hips in a straight line with the head up and stomach pulled in. It is best not to stand for long periods of time. If it is necessary, walk as much as possible and wear shoes without heels, preferably with cushioned soles. Use a low foot stool and alternate resting each foot on top of it.
Sitting puts the most pressure on the back. Chairs should either have straight backs or low-back support. If possible, chairs should swivel to avoid twisting at the waist, have arm rests, and adjustable backs. While sitting, the knees should be a little higher than the hip, so a low stool or hassock is useful to put the feet on. A small pillow or rolled towel behind the lower back helps relieve pressure while either sitting or driving.
Riding in and driving a car for long periods of time increases stress. Move the car seat as far forward as possible to avoid bending forward. The back of the seat should not be reclined more than 30 degrees. If possible, the seat bottom should be tilted slightly upward in front. A traveler should stop and walk around about every hour. Avoid lifting or carrying objects immediately after the ride.

Anyone who engages in heavy lifting should take precautions when lifting and bending.

If an object is too heavy or awkward, get help.
Spread your feet apart to give a wide base of support.
Stand as close as possible to the object being lifted.
Bend at the knees, not at the waist. As you move up and down, tighten stomach muscles and tuck buttocks in so that the pelvis is rolled under and the spine remains in a natural "S' curve. (Even when not lifting an object, always try to use this posture when stooping down.)
Hold objects close to the body to reduce the load on the back.
Lift using the leg muscles, not those in the back.
Stand up without bending forward from the waist.
Never twist from the waist while bending or lifting any heavy object. If you need to move an object to one side, point your toes in that direction and pivot toward it.
If an object can be moved without lifting, pull it, don't push.

There are four natural curves in the spinal column: the cervical, thoracic, lumbar, and sacral curvature. The curves, along with the intervertebral disks, help to absorb and distribute stresses that occur from everyday activities such as walking or from more intense activities such as running and jumping.

Resources

www.niams.nih.gov -- National Institute of Arthritis and Musculoskeletal and Skin Diseases
www.aaos.org -- American Academy of Orthopaedic Surgeons
www.arthritis.org -- Arthritis Foundation
www.spine.org -- North American Spine Society
www.apta.org -- American Physical Therapy Association
www.ampainsoc.org -- American Pain Society
www.theacpa.org -- American Chronic Pain Association
www.iasp-pain.org -- International Association for the Study of Pain

References

Apkarian AV, Sosa Y, Sonty S, Levy RM, Harden RN, Parrish TB, et al. Chronic back pain is associated with decreased prefrontal and thalamic gray matter density. J Neurosci. 2004;24(46):10410-10415.

Fairbank J, Frost H, Wilson-MacDonald J, Yu LM, Barker K, Collins R; Spine Stabilisation Trial Group. Randomised controlled trial to compare surgical stabilisation of the lumbar spine with an intensive rehabilitation programme for patients with chronic low back pain: the MRC spine stabilisation trial. BMJ. 2005;330(7502):1233.

Filler AG, Haynes J, Jordan SE, Prager J, Villablanca JP, Farahani K, et al. Sciatica of nondisc origin and piriformis syndrome: diagnosis by magnetic resonance neurography and interventional magnetic resonance imaging with outcome study of resulting treatment. J Neurosurg Spine. 2005;2(2):99-115.

Freeman BJ, Fraser RD, Cain CM, Hall DJ, Chapple DC. A randomized, double-blind, controlled trial: intradiscal electrothermal therapy versus placebo for the treatment of chronic discogenic low back pain. Spine. 2005 Nov 1;30(21):2369-77; discussion 2378.

Friedrich M, Gittler G, Arendasy M, Friedrich KM. Long-term effect of a combined exercise and motivational program on the level of disability of patients with chronic low back pain. Spine. 2005;30(9):995-1000.

Frost H, Stewart-Brown S. Acupressure for low back pain. BMJ. 2006 Mar 25;332(7543):680-1.

Hayden JA, van Tulder MW, Malmivaara AV, Koes BW. Meta-analysis: exercise therapy for nonspecific low back pain. Ann Intern Med. 2005;142(9):765-775.

Hayden JA, van Tulder MW, Tomlinson G. Systematic review: strategies for using exercise therapy to improve outcomes in chronic low back pain. Ann Intern Med. 2005;142(9):776-785.

Mercado AC, Carroll LJ, Cassidy JD, Cote P. Passive coping is a risk factor for disabling neck or low back pain. Pain. 2005;117(1-2):51-57.

Melissas J, Kontakis G, Volakakis E, Tsepetis T, Alegakis A, Hadjipavlou A. The effect of surgical weight reduction on functional status in morbidly obese patients with low back pain. Obes Surg. 2005 Mar;15(3):378-81.

Pneumaticos SG, Chatziioannou SN, Hipp JA, Moore WH, Esses SI. Low back pain: prediction of short-term outcome of facet joint injection with bone scintigraphy. Radiology. 2006 Feb;238(2):693-8.

Ratcliffe J, Thomas KJ, MacPherson H, Brazier J. A randomised controlled trial of acupuncture care for persistent low back pain: cost effectiveness analysis. BMJ. 2006 Sep 23;333(7569):626.

Richardson SM, Curran JM, Chen R, et al. The differentiation of bone marrow mesenchymal stem cells into chondrocyte-like cells on poly-L-lactic acid (PLLA) scaffolds. Biomaterials. 2006 Aug;27(22):4069-78.

Sherman KJ, Cherkin DC, Erro J, Miglioretti DL, Deyo RA. Comparing Yoga, Exercise, and a Self-Care Book for Chronic Low Back Pain: A Randomized, Controlled Trial. Ann Intern Med. 2005; 143: 849 - 856.

Tao XG, Bernacki EJ. A randomized clinical trial of continuous low-level heat therapy for acute muscular low back pain in the workplace. J Occup Environ Med. 2005 Dec;47(12):1298-306.

Trout AT, Kallmes DF, Gray LA, Goodnature BA, Everson SL, Comstock BA, Jarvik JG. Evaluation of vertebroplasty with a validated outcome measure: the Roland-Morris Disability Questionnaire. Am J Neuroradiol. 2005 Nov-Dec;26(10):2652-7.

Review Date:
3/19/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Hypertension

FitSugar — Wed, 08 Oct 2008 17:34:55 -0700

Overview

Signs and Symptoms
Causes
Risk Factors
Diagnosis
Preventive Care
Treatment
Other Considerations
Supporting Research

HEALTH GUIDE REFERENCE FROM A.D.A.M

Hypertension, or high blood pressure, is a serious condition that affects 50 million Americans -- one in four adults. It is defined as an average systolic blood pressure above 140 mm Hg, a diastolic blood pressure above 90 mm Hg, or both. High blood pressure increases the risk of heart disease and stroke, the first and third most common causes of death among Americans. In the early and middle adult years, men are more likely than women to develop the condition, but as men and women age, the reverse is true -- more women older than the age of 55 have high blood pressure than men of the same age. While hypertension generally develops in people older than 20 years of age, more than half of all Americans over the age of 65 have the condition.

Signs and Symptoms

Most people who have high blood pressure do not know they have it because they generally experience no symptoms at all. Occasionally, some individuals may experience a mild headache when their blood pressure is high. Serious cases of hypertension, which happen infrequently, may produce the following symptoms:

Severe headache
Confusion
Nausea
Visual disturbances
Seizure

Causes

There are two major types of hypertension: essential (primary) and secondary. Essential hypertension is by far the most common, accounting for more than 95% of all cases. The cause of this form of hypertension is not known for certain, but is likely a combination of factors, including:

Genes for high blood pressure
Low levels of nitric oxide, a naturally occurring agent responsible for the dilation of blood vessels (African Americans are believed to have low levels of this substance)
Insulin resistance
Obesity

The causes of secondary hypertension include:

Kidney disorders
Endocrine disorders, such as Cushing's syndrome
Obstructive sleep apnea (episodes during sleep when breathing stops due to obstruction of the air passages)
Stress
Chronic heavy alcohol consumption (accounts for 10% of cases of secondary high blood pressure)
Long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs), particularly in the elderly
Use of certain medications, including oral contraceptives, pseudoephedrine, hormone replacement therapy, and steroids
Heavy coffee drinking (5 or more cups per day), particularly in those who have previously had high blood pressure
Use of cocaine, nicotine, or other stimulants or the herb licorice (Glycyrrhiza glabra) can cause or worsen existing hypertension.

Risk Factors

The following factors increase an individual's risk for high blood pressure:

Family history of hypertension
Alcohol abuse
High sodium intake
Inactive lifestyle
Being overweight
Mood disorders, particularly depression and anxiety. They may have a direct impact on blood vessels or they may lead to unhealthy behaviors such as alcohol and substance abuse or poor weight management.
Hypertension is more common among African Americans than Whites. This may be due to nitric oxide levels or to social factors such as chronic life stressors.

Diagnosis

Blood pressure is the force of the blood pushing against the walls of the arteries. Each time the heart beats, or contracts, it pumps blood into the arteries. This is called systolic blood pressure, when blood pressure is at its maximum at this time. When the heart is at rest, between beats, the blood pressure falls, which is known as the diastolic pressure. A person with hypertension has an average systolic blood pressure above 140 mm Hg and/or a diastolic blood pressure above 90 mm Hg (usually written as 140/90).

To diagnose hypertension, a physician will obtain a blood pressure measurement during a routine physical examination. An inflatable cuff is wrapped around the arm, and the person taking the blood pressure listens with a stethoscope over the artery. If blood pressure is elevated, the doctor will check the pulse rate, examine the neck for swollen veins or an enlarged thyroid gland, listen to the heart for murmurs, feel the abdomen, and examine the eyes for damaged blood vessels in the retina. If the doctor suspects hypertension, additional laboratory and blood tests will help determine if it is secondary hypertension or essential hypertension.

Preventive Care

Studies suggest that the following lifestyle factors can help prevent hypertension:

Maintaining a desirable weight

According to several large-scale, population-based studies, being overweight is one of the strongest predictors of development of high blood pressure, including in adolescents and young adults. Similarly, maintaining a normal body weight is one of the most effective ways to prevent high blood pressure. Therefore, weight reduction, in overweight individuals of any age, should be a priority goal in the prevention of hypertension.

Reducing salt intake

Although population-based studies suggest a link between salt intake and prevalence of high blood pressure in particular groups of people (African Americans, for example), how each individual responds to sodium in his or her diet is quite variable. Since reducing dietary salt is generally considered safe, however, low-salt diets are recommended, particularly for those at risk for developing hypertension or heart disease.

Increasing physical activity

Several studies suggest that physically inactive people may be at an increased risk for developing hypertension. According to some population-based studies, men who lead physically active lives can reduce their risk of developing hypertension by 35 - 70 %. Although the duration and frequency of exercise necessary to prevent or treat hypertension is not well established, some evidence suggests that low to moderate intensity exercise may be more effective than higher intensity exercise training.

Limiting alcohol consumption

Studies suggest that people who consume three or more alcoholic beverages per day increase their risk for developing hypertension. If an individual is going to drink alcohol, therefore, intake should be limited to no more than two drinks per day. Also, drinking red wine may have more health benefits than other forms of alcoholic beverages.

Eating a diet rich in fruits and vegetables

People who consume vegetarian diets have significantly lower blood pressure than those who do not. The specific nutrients responsible for lowered blood pressure remain largely unknown, however.

Treatment

The goal in treating hypertension is to reduce the risk of serious complications, including heart disease and stroke. While the optimum blood pressure is 120/80 mm Hg, even partial reduction in blood pressure is beneficial. Prescription medications are often needed to treat hypertension, but lifestyle modifications -- including diet, exercise, and relaxation -- are necessary with or without medications.

A National Institute of Health (NIH) statement issued in 1996 asserts that behavioral and relaxation therapies must be integrated into conventional medical treatment of high blood pressure. Examples of relaxation techniques include biofeedback, massage, meditation, and qi gong. Often, in the early stages of hypertension when blood pressure elevation is mild, the doctor will recommend lifestyle modifications alone for a period of 6 - 12 months. After this time, if blood pressure is still high, medication will likely be prescribed.

Medications

Medication is recommended for people with sustained systolic pressure above 160 mm Hg or diastolic pressure above 100 mm Hg. There are several medications available to treat hypertension, and the medications prescribed depend on each individual case. Ten percent of hypertension patients may require as many as three drugs to control their condition.

Some of the most commonly prescribed medications include:

Diuretics

Diuretics help the kidneys eliminate sodium and water from the body. This decreases the volume of blood in the body and lowers blood pressure.

There are three types of diuretics: thiazide, loop, and potassium-sparing. The effects of these and other types of medications used to treat hypertension follow.

Thiazide diuretics (such as hydrochlorothiazide) -- tend to deplete potassium and may increase cholesterol and blood sugar.
Loop diuretics (such as furosemide and bumetanide) -- also tend to lower potassium levels
Potassium-sparing diuretics (such as spironolactone) -- this class does not lower potassium

Other medications used to treat hypertension include:

Beta-blockers (such as acebutolol, atenolol, metoprolol, nadolol, and propranolol) -- slow the heart rate down (thereby reducing the workload on the heart) and diminish stress hormones in the body (which allows blood vessels to relax).
Angiotensin-converting enzyme (ACE) inhibitors (such as benazepril, captopril, enalapril, lisinopril, and ramipril) -- by inhibiting a chemical reaction in the body, these drugs decrease production of a substance in the body that, in susceptible individuals, increases blood pressure.
Calcium-channel blockers (such as amlodipine, felodipine, nifedipine, nicardipine, and verapamil) -- relax blood vessels, thereby lowering blood pressure. Side effects may include constipation, nausea, and headache.
Angiotensin II receptor blockers (such as losartan, valsartan, candesartan, irbesartan, and telmisartan) -- block the effects of a particular chemical in the body, thereby preventing it from increasing blood pressure.

Nutrition and Dietary Supplements

Generally, small frequent meals are recommended for individuals prone to motion sickness. A comprehensive treatment plan for recovering from motion sickness may include a range of complementary and alternative therapies. Ask your team of health care providers about the best ways to incorporate these therapies into your overall treatment plan. Always tell your health care provider about the herbs and supplements you are using or considering using.

Following these nutritional tips may help reduce symptoms and improve overall health:

Try to eliminate potential food allergens, including dairy, wheat (gluten), corn, preservatives, and food additives. Your health care provider may want to test for food sensitivities.
Eat antioxidant foods, including fruits (such as blueberries, cherries, and tomatoes) and vegetables (such as squash and bell peppers).
Eat foods high in B-vitamins and calcium, such as almonds, beans, whole grains (if no allergy), dark leafy greens (such as spinach and kale), and sea vegetables.
Avoid refined foods, such as white breads, pastas, and especially sugar.
Limit your salt intake.
Eat fewer red meats and more lean meats, cold-water fish, tofu (soy, if no allergy), or beans for protein.
Use healthy oils in foods, such as olive oil or vegetable oil.
Reduce or eliminate trans-fatty acids, found in commercially baked goods such as cookies, crackers, cakes, French fries, onion rings, donuts, processed foods, and margarine.
Avoid coffee and other stimulants, alcohol, and tobacco.
Drink 6 - 8 glasses of filtered water daily.
Exercise at least 30 minutes daily, 5 days a week.

You may address nutritional deficiencies with the following supplements:

A multivitamin daily, containing the antioxidant vitamins A, C, E, the B-complex vitamins, and trace minerals such as magnesium, calcium, zinc, and selenium.
Magnesium citrate, 200 - 400 mg daily, for blood pressure regulation.
Omega-3 fatty acids, such as fish oil, 1 - 2 capsules or 1 tablespoonful oil one to three times daily, to help decrease inflammation and help with immunity. Cold-water fish, such as salmon or halibut, are good sources.
Resveratrol (from red wine), 50 - 200 mg daily, to help decrease inflammation and for antioxidant effects.
SAMe (s-adenosyl-L-methionine), 100 - 200 mg before breakfast daily, for stress and mood improvement.
Lycopene, 5 mg one to three times daily, for antioxidant and blood pressure lowering activity.
Coenzyme Q10, 100 - 200 mg at bedtime, for antioxidant, blood pressure lowering, and muscular support.
L-theanine, 200 mg one to three times daily, for stress and nervous system support.
L-arginine, 1 -2 gm three times daily, for blood vessel and immune support.

Herbs

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

Green tea (Camellia sinensis) standardized extract, 250 - 500 mg daily, for antioxidant and heart health effects. Use caffeine-free products. You may also prepare teas from the leaf of this herb.
Ginkgo (Ginkgo biloba) standardized extract, 40 - 80 mg three times daily, for antioxidant and heart health support.
Reishi mushroom (Ganoderma lucidum), 150 - 300 mg two to three times daily, for blood pressure support. You may also take a tincture of this mushroom extract, 30 - 60 drops two to three times a day.
Garlic (Allium sativum), standardized extract, 400 mg two to three times daily, for heart health.
Rhodiola (Rhodiola rosea ) standardized extract, 100 - 600 mg daily, for stress reducing activity.

Acupuncture

Several studies involving small numbers of people with hypertension showed a reduction in blood pressure with the use of acupuncture. While these clinical trials were conducted over a short period of time, the encouraging results suggest that it would be worthwhile for scientists to conduct long-term research of acupuncture for treating high blood pressure.

Chiropractic

Preliminary evidence suggests that people with high blood pressure who receive spinal manipulation receive a significant reduction in their blood pressure, but more research is needed to confirm its use for hypertension. In fact, on rare occasions, a spinal manipulation session may actually cause extremely low blood pressure leading to dizziness or lightheadedness.

Massage and Physical Therapy

Massage may be particularly helpful for people with hypertension brought on by stress. This is because the beneficial effects of massage are due at least in part to a reduction in stress. One recent study revealed that people with hypertension who receive massage showed significant reductions in blood pressure and steroid hormones, an indicator of stress. Although more studies are needed to evaluate the long-term safety and effectiveness of massage, people with hypertension who tend to have high levels of stress in their lives may benefit from massage therapy. In addition, massage tends to help people stick with healthy behaviors such as eating healthfully and not smoking.

Mind-Body Medicine

Although the association between ongoing life stress and hypertension is complex and somewhat controversial, many believe that relaxation techniques may be helpful in alleviating feelings of stress, which is often a contributing factor to hypertension. While the results of studies investigating this relationship have been mixed, one study of older African Americans living in an urban setting found that those who participated in a transcendental meditation (TM) or progressive muscle relaxation (PMR) program had a significant reduction in blood pressure compared to those who participated in a lifestyle education program. While both techniques were beneficial, TM was twice as effective as PMR.

In addition to TM and PMR, other mind-body techniques such as self-hypnosis and biofeedback have shown promising results in recent studies. Biofeedback in particular may reduce elevated blood pressure from stress and help individuals achieve healthful lifestyle modifications, such as stopping smoking and losing weight.

Other Considerations

Pregnancy

Blood pressure is monitored frequently during pregnancy because some women may develop high blood pressure for the first time while pregnant. If this occurs, medication may be needed. In addition, a condition known as preeclampsia is very serious and even life-threatening. Preeclampsia is high blood pressure during pregnancy that occurs along with other symptoms and signs, such as swelling of the ankles and legs, blurred vision, liver test abnormalities, and protein in the urine.

Warnings and Precautions

Avoid fish high in mercury, which may increase blood pressure.
The use of cocaine, nicotine, or licorice (Glycyrrhiza glabra) can cause or worsen existing hypertension.
Caffeine can exacerbate high blood pressure.

Prognosis and Complications

If left untreated, hypertension can cause several serious complications, including:

Stroke
Coronary artery disease and heart attack
Congestive heart failure
Kidney disorder
Disorders of the retina, which can ultimately lead to blindness
Impotence in men and decreased orgasm in women
Memory impairment and dementia

Fortunately, there are several treatment options for hypertension. Comprehensive treatment, including lifestyle modifications and blood pressure medications, usually results in much lower risk for complications and a generally good prognosis.

Supporting Research

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Review Date:
10/20/2006
Reviewed By:
Ernest B. Hawkins, MS, BSPharm, RPh, Health Education Resources; and Steven D. Ehrlich, N.M.D., private practice specializing in complementary and alternative medicine, Phoenix, AZ. Review provided by VeriMed Healthcare Network.

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