FitSugar

Organ Lessons: The Pancreas

FitSugar — Tue, 10 Nov 2009 03:47:02 -0800

It's time to take some organ lessons, but not the musical kind. I'm going to teach you about your internal organs, starting with the pancreas.

November is National Pancreatic Cancer Awareness Month, devoted to educating people about the disease that took the life of Patrick Swayze earlier this year. If you're like most people, you probably don't know exactly what the pancreas does, so read on to learn more.

Patrick Swayze Remaining Positive But Realistic About Cancer

FitSugar — Wed, 07 Jan 2009 12:00:00 -0800

Dirty Dancing star, Patrick Swayze, was diagnosed with pancreatic cancer last year. Though he's outlived his early bleak prognosis, Swayze refuses to give up. Patrick realizes his days are running out but hopes he has at least two years left and is hoping that doctors will find a cure in that time frame. Although admittedly scared, he's living "moment to moment," and Swayze continues the battle saying, "So far, I've got potential for a lot of quality of life."

Patrick hasn't spoken much about his condition since being diagnosed; this changes tonight. This evening on 20/20, he answers questions and talks candidly about his experience in an interview with Barbara Walters, in a special called Patrick Swayze: The Truth.

To see a clip of the interview read more.

We are rooting for Patrick, and with him, we are hoping for the best.

Source

Healthy Gums May Prevent Pancreatic Cancer

FitSugar — Mon, 29 Jan 2007 13:15:00 -0800

All cancer is bad news, but what makes pancreatic cancer so awful is that only 5% of people diagnosed with it will live another 5 years.

There are no recommended screening tests, early warning signs or symptoms to alert a person or their doctor that they have pancreatic cancer.

Some risk factors that could make you more susceptible to pancreatic cancer include cigarette smoking and possibly diabetes and obesity.

Oddly enough, periodontal disease (gum inflammation) and tooth loss may also be associated in some way with an increased risk of pancreatic cancer.

The connection it seems is that over time, the bacterial infection that causes gum disease can also cause loss of the bone that anchors the teeth. The inflammation from the infection may set the stage for other serious diseases, like pancreatic cancer.

There has also been recent interest in a possible link between gum disease and coronary artery disease, based on the theory that gum disease may lead to increased levels of inflammation throughout our bodies.

Fit's Tips: So take care of your teeth and gums people. Get regular dental cleanings twice a year, and whatever you do - don't forget to floss.

Colon and rectal cancers

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

In This Report

Highlights
Introduction
Causes
Symptoms
Risk Factors
Dietary Factors
Prevention
Diagnosis
Staging
Prognosis
Surgery
Medications
Radiation Treatment
Follow-up Testing
Treatment for Metastasized ...
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approval

In September 2006, the Food and Drug Administration approved panitumumab (Vectibix) for the treatment of patients with colorectal cancer that has spread to other parts of the body following chemotherapy. Like cetuximab (Ertibux), panitumumab targets the epidermal growth factor receptor (EGFR) on cancer cells. Panitumumab is the first new colorectal cancer drug approved since 2004. The FDA granted accelerated approval to panitumumab based on a clinical trial of patients with metastatic cancer. The average time to disease progression or death was 96 days in patients treated with panitumumab compared to 60 days in patients who received standard care.

Diet and Colorectal Cancer Recurrence

Evidence indicates that diet plays a role in colorectal cancer prevention. Now, a 2007 study in the Journal of the American Medical Association (JAMA) suggests that dietary factors also affect the risk of cancer recurrence. Patients with stage III colorectal cancer who ate lots of red meat, refined grains, and sweets had a higher risk of cancer recurrence and death than patients whose diets were high in fruits and vegetables, poultry, and fish.

Folic Acid No Good for Prevention?

Many experts have long believed that folic acid supplements may help protect against colorectal cancer. But according to a 2007 JAMA study, high-dose folic acid supplements may not prevent colorectal cancer and may actually increase the risk for adenomatous polyp formation. Adenomatous polyps are benign colorectal tumors that can potentially become cancerous. In the study, patients who took folic acid supplements had a greater risk of developing new, more numerous, and larger adenomatous polyps than patients who did not take the supplements.

NSAIDS Not Recommended for Colorectal Cancer Prevention

In March 2007, the U.S. Preventive Services Task Force (USPSTF) recommended against the routine use of aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) to prevent colorectal cancer in people who are at average risk for this disease. Several recent studies have indicated that aspirin, and NSAIDs such as celecoxib (Celebrex), can help prevent colorectal cancer. But the USPSTF notes that the risks of these drugs outweigh the benefits. Long-term daily use of NSAIDs increases the risk for gastrointestinal bleeding, kidney function problems, and heart attack and stroke.

Introduction

Cancers of the colon and rectum, often referred to collectively as colorectal cancer, are life-threatening tumors that develop in the large intestine.

More than 80% of colorectal tumors evolve from adenomatous polyps. These gland-like growths develop on the mucous membrane that lines the large intestine. They are usually either:

Tubular polyps, which protrude mushroom-like
Villous adenomas, which are flat and spreading and are more apt to become malignant (cancerous)

Polyps are very common and almost always benign. Their numbers increase with age. Polyps are found in about 25% of people by age 50, and 50% of people by age 75. Fewer than 1% of polyps under 1 centimeter (slightly less than half an inch) become cancerous. About 10% of larger polyps become cancerous within 10 years, and about 25% of these larger polyps become cancerous after 20 years. Certain inherited polyps can become cancerous more rapidly.

Digestion takes place in the gastrointestinal (GI) tract, essentially a long tube that extends from the mouth to the anus. It is a complex organ system that first carries food from the mouth down the esophagus to the stomach. Food then travels through the small and large intestines before being excreted through the rectum and out the anus.

The esophagus, stomach, large and small intestine -- aided by the liver, gallbladder, and pancreas -- convert the nutritive components of food into energy and break down the non-nutritive components into waste to be excreted.

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

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

Click the icon to see an image of stomach anatomy.

The small intestine, despite its name, is the longest part of the gastrointestinal tract, extending for about 20 feet. Food passes from the stomach through its three parts: first the duodenum, then the jejunum, and finally the ileum. Most of the digestive process occurs in the small intestine.

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

Undigested material, such as plant fiber, is passed next to the large intestine, mostly in liquid form. The large intestine is wider than the small intestine but only about 6 feet long. It is the final portion of the digestive tract and includes the cecum, the appendix, the colon, and the rectum, which extends to the anus.

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

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

Click the icon to see an image of large intestine anatomy.

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

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

Causes

In most cases of colon or rectal cancers, the cause or causes are unknown. Defects in genes that normally protect against cancer play the major role in causing polyp cells to continuously spread and become cancerous. Some of these cases are caused by inherited genetic defects, and such patients usually have family histories of colorectal cancer. Most of the genetic mutations involved in colon cancers, however, appear to arise spontaneously (no strong family history) rather than being inherited. In such cases, environmental or other factors trigger genetic changes in the intestine that lead to cancer.

About 6% of cases of colon cancer are due to inherited factors.

APC Gene and Familial Adenomatous Polyposis (FAP). When the adenomatous polyposis coli (APC) gene is normal, it helps suppress tumor growth. In its defective form, it permits high levels of the protein beta-catenin to accumulate, which accelerates cell growth leading to polyps. Various genetic mutations that affect the APC gene directly or indirectly have been identified:

Familial adenomatous polyposis (FAP) is a rare and serious disorder in which the patient inherits an adenomatous polyposis coli (APC) mutation from either parent. It occurs in about 1 in 8,000 people. During early adulthood, hundreds to thousands of polyps grow in the colon. FAP causes less than 1% of all cases of colorectal cancer, but if untreated, virtually everyone who inherits this condition develops cancer before the age of 40. Many of the deaths attributed to FAP can be prevented with early and aggressive surgical treatment.
Non-inherited mutations of the APC gene have been detected in nearly all patients with spontaneous colon cancers.

Hereditary Nonpolyposis Colorectal Cancer (HNPCC). Hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome, accounts for at least half of colorectal cancers that run in families. (However, only 3% or less of all colorectal cancers are due to this problem). About 50 - 80% of people who inherit the abnormal gene will develop colon cancer. HNPCC tends to develop in the right side of the colon, often in young individuals. (Left-sided cancers can still occur as well.)

People who inherit HNPCC and other defects are prone to other cancers, including uterine and ovarian cancers, as well as cancers of the small intestine and kidney system (very rare). HNPCC is highly associated with genes containing an abnormality called microsatellite instability (MSI), which is a sign of defective DNA repair. Testing tumors for MSI in people with newly diagnosed colon cancer who also have a family history of the disease may prove to be an effective method for identifying patients with hereditary nonpolyposis colorectal cancer. Tests are being developed that can detect the actual HNPCC genetic abnormality (mutation) that was inherited from a father or mother. The two most commonly affected genes are MSH2 and MLH1.

Cyclooxygenases and Prostaglandins. Cyclooxygenase 1 and 2 (COX-1 and COX-2) are enzymes involved in the production of prostaglandins, substances produced by the body that cause inflammation, widen and narrow blood vessels, control muscle contractions, and inhibit hormones that regulate fat metabolism. COX-2, but not COX-1, appears to play a role in the development and spread of colorectal tumors. COX-2 increases the levels of prostaglandin E2 (PGE2), which, in turn, stimulates factors that inhibit apoptosis, the natural process whereby all cells, including cancerous ones, self-destruct. It also activates interleukin-6 (IL-6), a factor in the immune system that is associated with cancer cell invasion.

C-Reactive Protein (CRP). CRP is another indicator of inflammation. In a 2004 study published in the Journal of the American Medical Association, elevated CRP levels predicted the development of colon -- but not rectal -- cancer.

Bile Acid Salts. Deoxycholic acid, which is found in the fat-digesting bile salts released by the gallbladder, appears to have carcinogenic properties. Its effects are now believed to play a role in some cases of colon cancer. Levels of the acid can rise as a result of high-fat diets or certain diseases.

Growth Factors. Chronically higher circulating levels of growth factors, including insulin-like growth factor, have been associated with colorectal cancer.

Inflammatory bowel diseases include Crohn's disease and ulcerative colitis. These chronic disorders cause persistent injuries in the intestinal tract that can, in some cases, produce cancerous changes.

Symptoms

It is possible to have colon or rectal cancer without symptoms. Many patients are free of symptoms until their tumors are quite advanced.

Weight loss and changes in bowel movements are general symptoms for colon cancer, but these symptoms also occur in many other diseases.

Blood in the stools is a common sign of many intestinal cancers. It may appear red if it is fresh or black if it is old. It should be reported to a doctor immediately, even though it is often caused by conditions other than cancer, including:

Hemorrhoids
Minor tears around the rectal or anal areas
Diverticulosis

In addition, stool can change color by:

Eating certain red foods, such as beets or red licorice (red)
Taking iron supplements and medications that have bismuth subsalicylate, most commonly Pepto-Bismol (black)

Nevertheless, blood in the stools is an abnormal finding that should never be ignored. Always report it to your doctor for further advice.

Symptoms of colorectal cancer vary widely depending on the location of the cancer within the large intestine.

Tumors in the Cecum and Ascending Colon (Right Colon). The waste matter in the first portion of the colon is in liquid or semi-liquid form. Tumors that develop here do not change bowel habits or stool formation, but they may cause intermittent or chronic bleeding. Although the stools look normal, patients may develop symptoms of anemia from iron deficiency. Such symptoms include weakness, fatigue, heart palpitations, shortness of breath, and exercise intolerance.

Tumors in the Transverse Colon. As waste material passes across the upper quadrants of the abdomen (the transverse colon), the intestine absorbs water, and the waste matter becomes more solid. In addition to bleeding, tumors here may cause cramps, gas, partial or complete obstruction, and even perforation of the bowel. Anemia can also occur.

Tumors in the Descending Colon and Rectum (Left Colon). When tumors partially block the lower intestine, thin, pencil-shaped stools may form. Bowel habits can change. Tumors in the rectum and lowest part of the intestine can cause pain and a feeling of fullness. Defecation may be painful, or patients may feel the urge to defecate but nothing happens. Bleeding from these locations may be brisk and bright red or maroon, but cancer is often detected before symptoms of chronic anemia develop.

Risk Factors

Colorectal cancer is the third most common cancer in the U.S., with Americans facing a lifetime chance of 5.5 - 6% for this cancer. In 2007, colorectal cancer was expected to cause 153,760 new cases and 52,180 deaths in the United States. About 73% of cancers occur in the colon and 27% in the rectum.

The lifetime risk of cancer of the colon or rectum is 5.9% for men and 5.5% for women.

Colorectal cancer risk increases with age. More than 90% of these cancers occur in people over age 50. The rate of colorectal cancer in patients under 20 years is less than 1 in 100,000 per year. At age 50 about 1 in 2,000 people per year will develop colorectal cancer. After age 65, this rate increases to almost 3 in 1,000.

African-Americans have the highest risk of being diagnosed with, and dying from, colorectal cancer. Among Caucasians, Jews of Eastern European (Ashkenazi) descent have an elevated rate of colorectal cancer. Asian Americans/Pacific Islanders, Hispanics/Latinos, and American Indians/Alaska Natives have a lower risk than Caucasians.

About 20 - 25% of colorectal cancers occur among people with a family history of the disease. (Seventy-five percent of cases are due to other causes.) People who have more than one first-degree relative (sibling or parent) with the disease are especially at high risk. The risk is even higher if the relative was diagnosed with colorectal cancer before the age of 60.

About 5 - 10% of patients with colorectal cancer have an inherited genetic abnormality that causes the disease. Genetic mutations associated with colorectal cancer include familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer.

The risks for colon cancer are far higher in industrialized nations than less developed countries. A Western lifestyle, being sedentary, smoking, and having excess weight have all been associated with increased risk for colorectal cancer. (However, about 75% of cases occur without a known predisposing factor.)

Dietary Factors. Eating a lot of red meat increases the risk for colorectal cancer. Other types of animal protein (low-fat dairy products, fish, poultry) may decrease the risk of developing polyps and colorectal cancer. Studies on fruits, vegetables, and fiber are mixed. Some evidence suggests that diets very low in fruits and vegetables may increase the risk. In any case, eating a variety of fruits and vegetables should be part of a healthy diet.

A 2007 study in the Journal of the American Medical Association suggested that diet may play a role in colorectal cancer recurrence, as well as prevention. The study evaluated patients with stage III colon cancer who had been treated with surgery and chemotherapy. Patients who ate diets high in red and processed meats, refined grains, and sweets had a higher risk of cancer recurrence and poorer survival than patients whose diets were high in fruits and vegetables, poultry, and fish.

Alcohol and Smoking. Alcohol use and smoking increase the risk for colorectal cancer. Patients who smoke and drink may also be diagnosed with colorectal cancer at a younger age than non-drinkers and non-smokers. Several studies suggest that women who smoke are at especially high risk of developing colorectal cancer.

Obesity. There is a demonstrated link between body mass and colon cancer risk for both men and women. The Centers for Disease Control and Prevention has reported that the risk of colon cancer rises as body mass index increases. Obesity has been associated biologically with higher circulating levels of insulin and a hormone called insulin-like growth factor. Chronically high levels of these substances may increase colorectal cancer risk.

Physical Inactivity. More than 50 studies from around the world suggest that physical activity helps prevent colon cancer. In contrast, exercise does not protect against rectal cancer.

Crohn's disease and ulcerative colitis are chronic afflictions of the large intestine known as inflammatory bowel diseases (IBD). Both have been linked to increased risk for colorectal cancer. (Patients with ulcerative colitis have a higher risk than those with Crohn's disease.) Family histories are helpful in determining risk associated with inflammatory bowel disease. Some studies suggest the following:

Patients with IBD who have a family history of colorectal cancer face up to a five-fold risk of colon cancer themselves.
Individuals without IBD who have relatives who suffered from both IBD and colorectal cancer may face a higher risk for developing colorectal cancer themselves.
Individuals without IBD but with a family history of IBD and no colon cancer most likely face no higher risk for cancer themselves.

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

Polyps. Polyps are tissue growths, usually benign, that develop in the color or rectum, most often in patients over 50 years of age. When pathologists examine polyps removed from the colon, they classify them as either hyperplastic or adenomatous. Both types are benign, but some adenomas will become malignant. As a preventive measure, polyps should be removed (polypectomy).

Ureterosigmoidostomy. People who have had ureterosigmoidostomy, a surgical procedure to correct a birth defect in the bladder or to treat some bladder cancers, may develop tumors near the site of the defect, which is chronically exposed to urine and feces. Such patients have a 5 - 10% chance of developing colon cancer 15 - 30 years after the operation.

Diabetes. Many studies have identified an association between type 2 diabetes and colon cancer. Both diseases share common risk factors of obesity and physical inactivity, but diabetes itself is a risk factor for colorectal cancer. Both men and women who have diabetes are at risk.

Heart Disease. Coronary artery disease (CAD) increases the risk for colorectal cancer. Both CAD and colorectal cancer share important risk factors, including smoking, high fat diet, sedentary lifestyle, and obesity.

Dietary Factors

Some, but not all, studies have suggested that a high intake of fruits and vegetables can lower the risk for colorectal cancer. One study, for example, reported that these foods do not prevent polyps from forming but may help prevent them from becoming cancerous.

Phytochemicals. Many studies have demonstrated the cancer-fighting effects of plant chemicals called phytochemicals. Fruits and vegetables that contain phytochemicals can often be identified by colors:

Dark green (broccoli, spinach, kale, collard greens, mustard greens). These vegetables contain chemicals called isothiocyanates, which have been associated with a lower risk for cancer in general.
Red (red pepper, tomatoes, watermelon, raspberries, pink grapefruit). Lycopene is a chemical found in these foods that may have strong cancer-protective properties. Cooking tomatoes appears to increase their benefits.
Yellow-orange (carrots, pumpkin, sweet potatoes, oranges, tangerines). The colors in these foods are due to carotenoids. Carotenoids have been associated with health protection, although they may not have much effect on colon cancer itself.
Blue-black (many berries). Dark berries appear to have potent antioxidant chemicals that may be protective against cancer.

Organosulfurs are important food chemicals that are part of the allium family. Studies have reported health benefits from foods containing them. These compounds are found in garlic, leeks, onions, chives, scallions, and shallots. A review of 300 studies concluded that people who eat raw or cooked garlic regularly experience about two-thirds the risk of colorectal cancer as people who eat little or none. Another analysis, however, found the available evidence about garlic to be inconclusive. Garlic supplements, in any case, do not appear to be protective.

Fiber. Studies have been mixed on whether fiber (found in fruits, vegetables, and whole grains) protects the colon from cancer. For example, three major studies in 2002 and 2003 reported no difference in the development of colorectal polyps or cancer recurrence with high intake of fiber. On the other hand, results of the 2003 European Prospective Investigation into Cancer and Nutrition (EPIC) -- the largest study ever conducted on the role of diet in the development of cancer -- suggested that fiber is protective regardless of its source. However, in the study, the greatest benefits were observed for the left side of the colon and the least for the rectum. In any case, fiber, which is only found in plant products, may be beneficial for the heart and have other health advantages.

The role of fats in inflammatory bowel disease is complex and not fully known. A 2006 study from the Women’s Health Initiative found that a low-fat diet did not help reduce the risk for colorectal cancer. However, the study did not distinguish between types of fat.

Monounsaturated fats (olive, peanut, canola oils; avocados, nuts) and omega-3 polyunsaturated fats (fish, flaxseed oil, walnuts) are the healthiest types of fats.
Saturated fats (red meat, butter, high-fat dairy products) and trans-fats (hydrogenated fat found in snack foods, fried foods, commercial baked goods) are unhealthy types of fats.

Dietary guidelines recommend that adults limit the total fat in their diet to 25 - 35% of total daily calories. Saturated fat intake should be less than 7%, and trans fats less than 1%, of total daily calories. (Patients with heart disease or diabetes may need to limit unhealthy fat in their diet even further.) Most fats should come from polyunsaturated and monounsaturated fat sources.

[See In-Depth Report #43: Heart healthy diet; and #42: Diabetes diet.]

Evidence strongly suggests that red meat raises the risk for colon cancer development, and perhaps also recurrence. Red meat contains dietary iron, which has been associated with a higher risk for colon cancer.

High-temperature cooking (grilling, broiling, or pan-frying) has been specifically associated with increased risk for colon polyps and colon cancer. Overcooking meat increases the amount of carcinogens called heterocyclic amines, which has been associated with cancerous changes.

Milk, Lactose, and Probiotics. In one study, adults who drank the most milk had the lowest risk for colon cancer. A 2004 study published in the Journal of the National Cancer Institute supported this conclusion. In this review of 10 epidemiologic studies that included more than 500,000 people, those who consumed more milk and calcium had a lower risk of developing colorectal cancer. Milk contains not only calcium but also other compounds, such as lactose, that may help protect against colon cancer.

Yogurt specifically has been associated with a lower risk for colon cancer if it contains live active bacterial cultures, such as Lactobacillus acidophilus, that are called probiotics. These "friendly bacteria" appear to protect the colon from cancerous changes. (Acidophilus and other probiotic capsules are also available in health food stores.)

Calcium. Calcium, which is found in dairy products, is associated with colon cancer protection. Many studies have shown a possible protective effect from either high-calcium diets or calcium supplements. However, a 2006 study from the Women’s Health Initiative found that calcium and vitamin D supplements do not reduce women’s colorectal cancer risk. Many doctors still recommend that postmenopausal women take these supplements for bone health.

Obesity has been associated with colon cancer. In some studies of people under 67 years old, the amounts of fat and protein were less important than the total number of calories consumed: the higher the energy intake, the greater the risk for developing colon cancer. In older adults, high calorie intake did not make any significant difference. Other studies have indicated that eating too much sugar may increase the risk for colon cancer.

Studies conducted in several countries have found that drinking four or more cups of coffee a day is associated with a lower risk for colorectal cancer. Green tea may have also beneficial properties, but more research is needed in both of these areas.

Folate and B Vitamins. For years, many doctors have believed that the B vitamin folate (called folic acid) may help protect against colorectal cancer, particularly for people who are genetically predisposed to this disease. Folate is found in beans, citrus fruits, and green vegetables, but some studies have indicated that the greatest protective benefits come from taking supplements.

However, an important study published in 2007 in the Journal of the American Medical Association challenged this assumption. The study suggested that high-dose folic acid supplements do not prevent colorectal cancer, and may actually increase the risk for developing certain types of colorectal tumors. The study evaluated over 1,000 men and women who had a recent history of non-cancerous colorectal polyps. (Adenomatous polyps, also called colorectal ademomas, are the most common type of polyp found in colorectal cancer screenings.) The results indicated that patients who took 1 mg/day of folic acid supplements were more likely to develop new adenomatous polyps than patients who did not take supplements. Patients in the folic acid supplement group were also more likely to have advanced adenomas and more numerous adenomas.

Adenomatous polyps are benign tumors, but they can potentially develop into cancerous tumors. Researchers are continuing to investigate the role that folic acid plays in colorectal cancer risk and prevention. It is possible that folic acid may help prevent the initial appearance of adenomatous polyps, but increase the risk for additional polyp formation once they have begun to occur.

Antioxidant Supplements. Antioxidants are chemicals that help eliminate harmful particles called oxygen-free radicals that have been associated with cancerous changes. Some studies have associated supplements of the antioxidants selenium and vitamins A, C, D, and E with lower colon cancer risk, but most studies have found no protective effect.

Prevention

Studies indicate that daily exercise is one of the best ways to reduce the risk of colorectal cancer. The more vigorous the activity, the greater the benefit, but even moderate exercise (walking, stair-climbing) can help reduce colorectal cancer risk. The American Cancer Society (ACS) recommends that people engage in at least moderate exercise for 30 minutes or more at least 5 days a week. The ACS also notes that 45 minutes or more of moderate-to-vigorous activity at least 5 days a week may help further reduce cancer risk.

Some studies also suggest that regular exercise may be beneficial for patients who have been diagnosed with colorectal cancer. Two 2006 studies indicated that exercise may reduce the risk of colorectal cancer recurrence and death for patients with stage I - III cancer.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are very common pain relievers that are available over-the-counter and by prescription. They include aspirin, ibuprofen (Motrin), naproxen (Aleve), and the COX-2 inhibitor celecoxib (Celebrex). Several studies have reported that NSAIDs help reduce the risk of colorectal cancer. However, regular use of NSAIDs, even in low doses, can increase the risk of gastrointestinal bleeding and stomach ulcers. Long-term use of NSAIDs can also increase the risk for heart attack and stroke, especially in people who have a history of heart disease. Several 2006 and 2007 studies in the New England Journal of Medicine reported that celecoxib prevented precancerous polyps, but the drug more than doubled patients’ risk for heart attack and other cardiovascular events.

A 2005 Nurse’s Health Study found that aspirin, but not other NSAIDs, does provide protection against colorectal cancer. However, the risk was only reduced for women who took 2 aspirin a day for more than 10 years. In addition, this dose level greatly increases the risk for gastrointestinal bleeding. Furthermore, a 2007 study in the New England Journal of Medicine suggested that aspirin’s protective effects may only apply to some types of colorectal cancer tumors. Another 2007 study, published in the Lancet, indicated that long-term daily use of aspirin can protect against polyps and colorectal cancer, but experts agree that aspirin’s risks do not outweigh its benefits for most people. (Some people who are at high risk for developing colorectal cancer may benefit from aspirin therapy.)

In March 2007, the U.S. Preventive Services Task Force (USPSTF) recommended against the routine use of aspirin and other NSAIDs to prevent colorectal cancer in people at average risk for this disease. (This recommendation does not apply to people who have a family history of colorectal cancer or who are at high risk for developing colorectal cancer due to other risk factors.) Long-term use of NSAIDs can increase the risk for gastrointestinal bleeding, kidney function problems, and heart problems. Aspirin can also increase the risk for hemorrhagic stroke. Due to these risks, the American Cancer Society and other professional associations also recommend against the use of NSAIDs or other types of medications for colorectal cancer prevention.

Medications containing 5-aminosalicylate (5-ASA) are sometimes given to patients with ulcerative colitis to help control inflammation. These drugs, which include sulfasalazine and mesalamine, are chemically related to aspirin. A 2005 review of clinical trials found that patients with ulcerative colitis who used 5-ASA were 49% less likely to develop colorectal cancer than patients who did not use these drugs

Some studies have suggested that cholesterol-lowering statin drugs may help reduce colorectal cancer risk. A 2006 study in the Journal of the National Cancer Institute did not find any protective benefit for statins.

Estrogen has been associated with a lower risk for colon cancer, perhaps because of specific enzymes that prevent cell proliferation. Drugs containing estrogen, then, may help high-risk women:

There is some evidence that hormone replacement therapy (HRT) reduces the risk of colon cancer in postmenopausal women. It carries other risks, however, including a higher risk for breast and uterine cancer and blood clots. A 2004 New England Journal of Medicine study found that while short-term use of estrogen plus progestin reduced the risk of developing colon cancer, combination HRT users who were diagnosed with the disease had more advanced forms of the cancer. Older women who are at higher risk for colon cancer might discuss risks and benefits of HRT with their doctor.
Oral contraceptives may reduce younger women's risk of colon cancer. Duration of use does not seem to be associated with decreased risk, but protection appears stronger for women who have more recently used oral contraceptives.

Diagnosis

Colon and rectal cancers are diagnosed using the screening tests discussed below. These tests can detect precancerous polyps and colorectal cancers at stages early enough for complete removal and cure.

Unfortunately, only 30 - 40% of adults over 50 years old (mostly in the upper socioeconomic group) have regular screening tests that could detect a cancer early enough for curative treatment. A survey reported that many people are not screened because they are too embarrassed. Those who had already had the tests were willing to have them again if they saved one additional day of their lives.

There is some debate about what is the best screening method. Current screening guidelines offer several different options for patients. Doctors agree that not enough people are screened and that these tests, if adopted with the same regularity as such screening tests as Pap smears, would save many lives. It is especially important for anyone at increased risk or with symptoms, such as rectal bleeding or ulcerative colitis, to have testing at an earlier age.

There is also debate about when people should stop being screened. A 2006 study in the Journal of the American Medical Association indicated that screening provides little benefit for elderly people, especially because colorectal cancers grow very slowly. The researchers suggest that doctors should carefully consider the risks versus benefits of screening patients age 80 and older.

Individuals should discuss with their doctors the risks and benefits of all screening procedures. Some controversy exists over how often people without risk factors for cancer should be screened and which detection method should be used for them.

Guidelines for Adults Age 50 and Over with Average Risk. The following are the five screening options recommended for people age 50 and over who have no symptoms and no family history of colon cancer:

Fecal occult blood test (FOBT) or fecal immunochemical test (FIT) every year
Flexible sigmoidoscopy every 5 years
FOBT or FIT every year plus sigmoidoscopy every 5 years
Double-contrast barium enema every 5 years
Colonoscopy every 10 years

Choosing between Colonoscopy and Sigmoidoscopy. The choice between colonoscopy and sigmoidoscopy for routine screening for older adults with average risk is an area of intense debate. The issues are as follows:

Sigmoidoscopy is less costly, less invasive, quicker, and safer than colonoscopy. Although it allows inspection of only the left side of the colon, any abnormal findings from sigmoidoscopy trigger a full colonoscopy. Therefore, experts estimate that sigmoidoscopy can detect 80% of all significant problems.
Colonoscopy is more sensitive than any other current screening method for detecting colon cancer. It can find 75 - 90% of colorectal cancers. If the goal were to reduce the number of cancer cases, regardless of cost, colonoscopy would be the preferred approach. Colonoscopy, however, is more expensive than sigmoidoscopy and has a slightly higher risk for complications (bowel tears or bleeding when a polyp is removed).

There are 3 basic tests for colon cancer: a stool test (to check for blood), sigmoidoscopy (inspection of the lower colon), and colonoscopy (inspection of the entire colon). All 3 are effective in catching cancers in the early stages, when treatment is most beneficial.

Screening, particularly with colonoscopy, in increased- and high-risk populations can save lives. The most important risk factors are a family history of colorectal cancer and personal history of colorectal cancer, polyps, or chronic inflammatory bowel disease. People with these risk factors should be screened before age 50 and may need more frequent screenings.

Guidelines for Increased-Risk Groups. Anyone with first-degree relatives diagnosed with colon cancer younger than 60, or with two relatives who have been diagnosed with colon cancer at any age, should consider beginning the standard screening regimen with a colonoscopy every 5 years, beginning at age 40 or 10 years before the youngest case in the family (whichever is earlier).

Men of African descent are also considered to be at increased risk for colon cancer and should discuss similar screening guidelines with their doctors.

Guidelines for High-Risk Groups. The following guidelines may be useful for specific high-risk groups.

People who have the mutated hereditary nonpolyposis colorectal cancer gene (MSH2 or MLH-). Frequent colonoscopy (for instance, every 1 - 2 years) beginning in their early 20s. (Regular screening for other cancers, such as uterine cancer, is also reasonable.)
People who have the mutated familial adenomatous polyposis (FAP) gene. Frequent screening with endoscopy (flexible sigmoidoscopy or colonoscopy) beginning in early puberty. Genetic testing is now recommended for family members of people with known FAP.
People with predisposing intestinal problems, such as widespread and active ulcerative colitis or Crohn's disease. Annual screening with colonoscopy with biopsies of suspicious areas.

Guidelines for Follow-Up After Detection of Precancerous Polyps. Patients who have had a previous examination in which polyps were detected (and removed) should have a repeat colonoscopy 1 - 3 years later, depending on the size, number, and type of polyps removed.

The digital rectal examination is used to detect tumors in the rectum, lower intestine, and prostate gland. The doctor inserts a lubricated-gloved finger into the patient's rectum and feels for lumps or other abnormalities. The exam is quick and painless but embarrassing for some. Fewer than 10% of colon cancers develop within the region that can be evaluated by a DRE, so it is not useful as a sole screening test.

Blood in bowel movements is not always visible, in which case it is called occult (hidden) blood. Fecal occult blood tests (FOBTs) are used to detect this hidden blood. The most common FOBT method is called the guaiac-based test. The patient is asked to supply up to six stool specimens in a specially prepared package. A small quantity of feces is smeared on specially treated paper, which reacts to hydrogen peroxide. If blood is present, the paper turns blue.

Accuracy. FOBTs can miss more than 75% of advanced cancers. Nevertheless, large studies have indicated that this simple test, performed annually, saves lives and may reduce the risk of dying from colon cancer by 15 - 33%. The following factors may affect its accuracy:

The levels of iron in the blood can affect results. Patients should not take iron supplements or eat red meats several days before the test.
Certain raw fruits and vegetables that contain the chemical peroxidase (cauliflower, horseradish, radishes, melons, and turnips) can cause a positive test reaction even if no blood is present.
Aspirin and NSAIDs are anticoagulants that can cause minor bleeding. They should not be taken for a week before the test. However, a 2005 study suggested that the prescription anticoagulant warfarin does not affect FOBT results.
Vitamin C and foods rich in this vitamin may cause a false negative reaction and should be avoided a few days before the test.
Bleeding from other causes, such as menstruation, hemorrhoids, gingivitis, or urinary infections, can produce blood in the stools and affect results.

Even if none of these conditions is present, a test that shows hidden blood does not necessarily mean that cancer is present. About 20 - 30% of people with occult blood have noncancerous polyps or other conditions, such as gastritis, and only 5 - 10% actually have cancer. Any abnormal result, however, requires further testing, such as colonoscopy.

Lack of Compliance. Compliance is a major problem. Patients are asked to perform the tests at home and send the test cards to the laboratory. Only 35 - 50% of patients actually follow through. Occult-blood tests that give results at home are available but are extremely inaccurate. In one large study, these tests failed to detect advanced cancer in about 62% of cases, although they may detect some early cancers.

If a digital rectal exam (DRE) or fecal occult blood test (FOBT) shows signs of trouble, several methods to visualize the colon are available. They include colonoscopy, sigmoidoscopy, and double-contrast barium enema. They have the following similarities and differences:

Sigmoidoscopy can only view the rectum and the left side of the colon, while colonoscopy and barium enemas allow a view of the entire large intestine.
Both flexible sigmoidoscopy and colonoscopy involve snaking a fiber optic tube through regions of the rectum and colon to view the walls of the intestine. The tube contains a tiny camera that transmits the image to a video screen. The use of an ultrasound (sound wave) scanner is proving to enhance viewing quality. Barium enemas simply use x-rays.
During either sigmoidoscopy or colonoscopy, the doctor is able to remove polyps or other abnormalities revealed by these procedures with surgical instruments inserted through the tube. It is not possible to remove polyps with a barium enema, which is not invasive.

Sigmoidoscopy. Sigmoidoscopy examines the rectum and the lower two feet of the colon. It cannot, however, detect the roughly half of cancers that occur in the right colon. Right-sided cancers are more common in older people.

The procedure uses a flexible fiber optic tube (it is thus referred to as flexible sigmoidoscopy) that contains a tiny camera and surgical instruments.
It lasts about 10 minutes and may be mildly uncomfortable, but it is not painful and is generally very safe. In one study, 70% of patients reported that the procedure was far less unpleasant than they had expected.

This procedure has been found to reduce the risk of fatal cancers in the rectal and sigmoid area by 60%. If polyps are detected, a colonoscopy is then used.

Colonoscopy. Colonoscopy is the most accurate testing method and can reduce cancer incidence by up to 90%. It is clearly indicated for anyone with an increased risk for colorectal cancer, including those with a personal or family history of the disease. As with sigmoidoscopy, a colonoscopy uses a flexible tube, but it is snaked through the entire large intestine.

For about a day before the procedure the patient eats nothing and drinks a laxative solution that cleans out the colon. The taste of the solution is unpleasant, although it has improved in recent years.
The procedure typically uses a sedative that produces a "twilight" sleep and often makes the procedure more comfortable than sigmoidoscopy.
Air may be introduced into the intestine to widen it and allow the tube to navigate curves. A colonoscopy avoids the risk of radiation associated with a barium enema, but it is important to note that even a colonoscopy does not detect all cancers.

Complications are rare, but include the following:

Hyponatremia. Hyponatremia is a low concentration of sodium in the blood. The complication may be caused by the effects of bowel cleaning before the procedure that can result in water retention and reductions in sodium. When severe, it can cause temporary neurological symptoms, such as confusion, lethargy, unsteadiness, and slurred speech. Researchers suggest that sodium concentrations be measured in patients who develop such symptoms after colonoscopy.
Bowel perforation (very low risk, about 2 in 1,000 procedures). The risk for bowel perforation is greater with colonoscopy than flexible sigmoidoscopy.
Bleeding at the site of biopsy or polyp removal.

Overall, colonoscopy is a safe procedure. However, according to a 2006 study in the Annals of Internal Medicine, serious complications occur in about 5 of every 1,000 colonoscopies. Most of these complications occurred when a biopsy or polyp removal was performed. (The risk for complications without biopsy or polyp removal is about 1 in every 1,000 colonoscopies.) This study looked at colonoscopies in general, including those that are done to diagnose the causes of a patient's symptoms. The risk may be lower for colonoscopies performed solely to screen for colorectal cancer.

Barium Enema. The double-contrast barium enema, which uses an x-ray image, is the less expensive alternative for viewing the entire colon. It is not as accurate as colonoscopy, and if any polyps or abnormalities are revealed on x-ray, a colonoscopy is then required to remove suspicious tissue, so it is now recommended much less often than in the past.

The barium enema is a valuable diagnostic tool that helps detect abnormalities in the large intestine (colon). The barium enema, along with colonoscopy, remains the standard in the diagnosis of colon cancer, ulcerative colitis, and other diseases of the colon.

Screening for familial adenomatous polyposis. Genetic screening for familial adenomatous polyposis (FAP) and hereditary nonpolyposis colon cancer (HNPCC) is now available and may be recommended for high-risk patients. The test for FAP detects a mutation in the adenomatous polyposis coli in up to 90% of people who carry it. Testing for HNPCC mutation is somewhat more complex.

Screening for insulin-like growth factor. A gene that regulates insulin-like growth factor (IGF-2) is functional during fetal development and then becomes inactive. Some evidence now suggests that people who have IGF-2 in adulthood have a higher risk for colon cancer. Blood tests for detecting IGF-2, then, may be helpful in identifying patients who should have more intensive screening. Currently, however, this is only used as a research tool.

Stool DNA Testing. A promising technique for colorectal cancer screening is the detection of altered DNA in cancer cells that have shed from the colon and are excreted in the stool. Such tests may prove to detect both inherited and noninherited genetic mutations. This may become a widely used tool in the future. However, larger clinical studies are needed.

Virtual Colonoscopy. A promising experimental technique called virtual colonoscopy allows three-dimensional imaging of the colon without using invasive instruments. As with standard colonoscopy, the patient takes a laxative first to clear out the intestine. The procedure itself involves pumping air into the colon and scanning the intestine using computed tomography (CT). It is very safe and takes about only 10 minutes. The procedure is similar in accuracy to conventional colonoscopy for detection of larger polyps (6 mm or more in diameter) and is also potentially less expensive. Colonoscopy is required, however, if suspicious areas are found, which may occur frequently with the CT procedure, since it erroneously identifies a high number of nonexistent polyps.

A study published in April 2004 in the Journal of the American Medical Association compared results of standard colonoscopy versus virtual colonoscopy in over 600 patients at nine major medical centers. Virtual colonoscopy had much lower rates of successfully finding polyps than standard colonoscopy. Virtual colonoscopy detected polyps of at least 6 mm in 39% of patients and polyps of at least 10 mm in 55% of patients. By contrast, standard colonoscopy detected 99% of polyps of at least 6 mm, and 100% of polyps of at least 10 mm. In addition, accuracy rates varied widely among the different hospitals. The authors advised that until more improvement in training and technique is achieved, virtual colonoscopy "is not yet ready for widespread clinical application."

Magnetic Resonance Colonography. Magnetic resonance colonography (MRC) is another non-invasive technique for visualizing the colon. The patient receives an enema containing a contrast substance, and then magnetic resonance images are taken. MRC is fast, comfortable, and less invasive than colonoscopy. Currently, however, there is a poor detection rate for flat tumors and for polyp tumors less than 10 mm in diameter.

Staging

A diagnosis of cancer will lead to staging and other tests to help determine the outlook and the appropriate treatments.

The large intestine is a long hollow organ lined with mucous membrane (mucosa). Muscle layers wrap around the entire length and help move food material through to the rectum.

Unlike many other cancers, the size of the tumor is not a major factor in determining the outcome of colorectal cancer. Of greater importance is how far the cancer has spread. To determine this, doctors will assign a stage to the tumor. There are several methods for staging. The older system, known as Dukes', categorizes four basic stages: A, B, C, and D. A more recent system refers to these stages as I, II, III, and IV but divides the categories slightly differently. The term "5-year survival" means that patients have lived at least 5 years since diagnosis. Most patients who live 5 years without a recurrence are considered to be cured of their disease.


Stage	Condition	5-Year Survival
A or I	Tumor superficially involves the inner lining of the intestine.	More than 90%
B or II	Tumor has penetrated through the muscle wall of the intestine but has not reached the lymph nodes.	70 - 85%
C or III	Lymph nodes are involved.	65% or below
D or IV	Tumor has spread to other organs (metastasized), usually the liver first.	5 - 9%

Click the icon to see an image of the stages of cancer.

Researchers are continually seeking to identify tumor markers, substances (usually found in blood samples) that will assist in the diagnosis of cancer and in monitoring effects of treatment.

Carcinoembryonic Antigen. High blood levels of a protein called carcinoembryonic antigen (CEA) sometimes indicate the presence of colon cancer. Unfortunately, it is also elevated in other cancers and in some noncancerous conditions. CEA is not effective as a screening tool for healthy people, but might eventually be helpful for patients with cancer.

An advanced diagnostic technique called polymerase chain reaction (PCR) can detect genetic evidence of CEA. One study indicated that when these microscopic footprints of colon cancer are detected in the lymph nodes of patients with Stage II cancer (whose lymph nodes otherwise appear to be not involved with cancer), the outlook is similar to that of patients with Stage III cancer. Patients without this so-called micrometastasis have a very favorable prognosis. Further research is needed, however, before PCR can be used in widespread practice.
In patients with a history of, or active, colon cancer, follow-up measuring of blood CEA levels may be helpful in detecting recurrence of the cancer and effectiveness of treatments.

Defective P53 Gene. The presence of a defective p53 gene is a marker for very poor prognosis in patients with advanced colon cancer. In its normal state, the gene is important for regulation of cell growth. Testing for this abnormality, however, is not widely done because it is not clear how to use this information.

Other Tumor Markers. Other tumor markers under investigation include a protein called GLUT1, cancer antigen 19-9 (CA 19-9), matrix metalloproteinase-9 (MMP-9) RNA, HER-2/neu oncoprotein, transforming growth factor beta-1 (TGF-beta-1), and CD44.

Click the icon to see an image of drawing blood for culture.

A technique known as a sentinel node biopsy is increasingly performed by experienced surgeons in selected patients. This procedure is used to determine if cancer has spread beyond the nodes, possibly reducing the need for complete axillary lymphadenectomies. It involves the following:

The procedure uses an injection of a tiny amount of a tracer, either a radioactively-labeled substance (radioisotope) or a blue dye, into the tumor site.
The tracer or dye then flows via the lymphatic system into the so-called sentinel node. This is the first lymph node to which any cancer would spread.
The sentinel lymph node and possibly one or two others are then removed.
If they do not show any signs of cancer, it is highly likely that the remainder of the lymph nodes will be cancer free, and further surgery becomes unnecessary.

It is still not known if the sentinel node biopsy has any survival advantages compared to the standard procedures with lymph nodes removal. However, one study indicated that careful and complete removal of potentially cancerous lymph nodes is still very important for improving survival in patients with Stage II and III colorectal cancer.

Whole-body imaging scans that combine positron emission tomography (PET) and computed tomography (CT) may be helpful in accurately staging colorectal cancer, according to preliminary research published in 2006 in the Journal of the American Medical Association.

Prognosis

Survival rates for colorectal cancer have been rising in recent years. The 5-year survival rate is as high as 90% for cancer that has not spread to the lymph nodes (localized cancer). When cancer has spread to lymph nodes and other parts of the body, survival rates drop to 65% and below. Because many cancers are detected at later stages, the overall survival rate is currently about 60%. African-Americans and other minorities tend to have lower survival rates than Caucasians. Studies suggest, however, these higher mortality rates are largely due to less access to optimal health care, including appropriate surgical care and aggressive treatments.

In most cases, age is not a factor in treatment success. Good survival rates are achieved in the elderly as well as in young people. Chances for survival are less in Stage II cancers if the intestine is obstructed or perforated. If cancer has spread to lymph nodes (Stage III), the outlook is better if three or fewer lymph nodes are involved. Treatment can prolong life even when cancer has spread.

Surgery

Surgical removal of the tumor ("resection") along with any affected surrounding tissue is the standard initial treatment for potentially curable colorectal cancers (cancers that have not spread beyond the colon or lymph nodes). Drug and radiation therapy are often used for advanced cancers and are continuously being tested with surgery in different combinations and sequences.

Although choosing a qualified surgeon is critical, choosing a hospital experienced in procedures is also important. The more often colon cancer surgery is performed at a given hospital, the lower the mortality rate at that hospital is likely to be.

Unless cancer is very advanced, most tumors are removed by an operation known as colectomy:

Colectomy involves removing the cancerous part of the colon and nearby lymph nodes.
The surgeon then reconnects the intestine.
If the surgeon cannot reconnect the intestine, usually because of infection or obstruction, the surgeon will perform a colostomy. The need for colostomies is higher after surgery for rectal cancer. In most cases of colon cancer, colostomies are not needed. [See "Colostomy" below.]

Click the icon to see an illustrated series detailing colon cancer treatment.

The Surgical Approach. The standard technique for a colectomy is open, invasive surgery. Laparoscopy, sometimes called “keyhole surgery,” is a less invasive method. Laparoscopy is still considered an investigational technique for treating colon cancer, but it is gaining more acceptance and showing good results in clinical trials.

Open Surgery:

Open surgery uses a wide incision to open the patient's abdomen. The surgeon then performs the procedures with standard surgical instruments. This is the usual method for performing colectomy.

Laparoscopy:

Laparoscopy uses a few small incisions through which the surgeon passes a fiber optic tube (laparoscope) containing a small camera or tiny instruments. It is generally used for early colon cancer (for tumors less than 2 centimeters or for well-defined tumors less than 3 centimeters).
A 2004 New England Journal of Medicine study found that patients who received laparoscopic colectomy had similar rates of surgical complications, cancer recurrence, and survival as those who received traditional open surgery. However, the patients who had laparoscopy recovered faster and did not need as many narcotic painkillers.
Several 2005 studies indicated that laparoscopy works as well as conventional surgery for treatment of colon cancer. However, laparoscopy does not appear to be as effective for rectal cancer.

Click the icon to see an image detailing pelvic laparoscopy.

Click the icon to see an illustrated series detailing a resection of the large intestine.

Other Investigational Measures. Researchers are testing expandable metal tube-like devices called stents to keep the intestine open. Stents may be used before a procedure to allow bowel cleansing or for long-term use to keep open colons that can't be operated on.

A colostomy is performed in order to bypass or remove the lower colon and rectum. The procedure generally involves creating a passage, called a stoma, through the abdominal wall that is connected to the colon. The feces pass through this passage and are eliminated. Patients must learn how to care for the stoma and keep the area sanitary.

A colostomy usually will have one opening (single-barreled), or there may be two loops opening through the skin (double-barreled).

Usually the colostomy is temporary and can be reversed by a second operation after about 3 - 6 months. It the rectum and sphincter muscles in the rectum need to be removed, the colostomy is permanent. Permanent colostomies are more common when the cancerous regions are within 2 - 3 centimeters of the anus. Fortunately, surgical advances and knowledge of the extent of safe margins are reducing the need for permanent colostomies.

Click the icon to see an illustrated series detailing a colostomy procedure.

Managing Permanent Colostomies. In cases where the colostomy is permanent, the patient must wear a colostomy pouch, which sticks to the skin using a special glue. Pouches are available as one- or two-piece systems. The one-piece system is simpler, but the two piece system allows replacement of the pouch without removing the tape.

For best results, the pouch should be emptied when about one-third full. It should be replaced 1 - 2 times a week, depending on signs of leakage (itching or burning of the skin near the stoma). The pouches are odor proof.

Surgical treatments for cancer in the rectum are complex since they involve muscles and tissue that are critical for urinary and sexual function.

Local Excision or Polypectomy for Early Stages. In order to preserve the function of the anal sphincter and prevent the need for colostomy, Stage I and Stage II tumors may be removed by local excision, sometimes followed by chemotherapy and radiation. In this procedure, the tumor is cut out without removal of a major section of rectum. In some cases cancer recurs, but a second operation may be possible. Another treatment for early-stage rectal cancer, called electrocoagulation, destroys tumors using a high frequency electric current. It is being tested in clinical trials.

Radical Resection. In about a third of cases of rectal cancer, the cancer occurs in the lower part of the rectum, where between 70 - 80% of cancers have spread beyond the rectal wall. These patients need a radical resection, in which surrounding structures, including the sphincter muscles that control bowel movements, must often be removed.

The use of chemotherapy and radiation prior to surgery may prevent the need for permanent colostomy in some patients. This is an active area of clinical research, and trials are under way to address this issue. Another technique, called coloanal anastomosis, reconstructs the area to avoid the need for colostomy, and may be appropriate in some patients.

Total Mesorectal Excision. Total mesorectal excision (TME) involves dissection and removal of the entire cancerous area of the rectum along with surrounding fatty regions where the lymph nodes are located (the mesorectum). When successful, TME preserves the sphincter muscle, reducing the need for a permanent colostomy. Increasing use of this procedure is resulting in lower recurrence rates, lower levels of impotence and incontinence, and better overall survival rates compared to other resection techniques. Some experts now recommend it as a first choice for certain patients with locally advanced rectal cancer.

Combining chemotherapy and radiation either before or after TME is yielding promising long-term results and a low risk for local recurrence. There are many questions, however, and it is not clear which approach is better for specific patients.

Side effects of colon surgery include:

Sexual dysfunction. This is of particular concern. In general, colostomy does not usually affect sexual function. However, wide rectal surgery can cause short- or long-term sexual dysfunction. Sildenafil (Viagra) may help men who experience this after surgery.
Irregular bowel movements.
Gas and flatulence. Pouching filters are available to reduce gas. Certain foods produce more gas than others -- usually within 6 - 8 hours after ingestion for colostomy patients. They include beans, oat bran, most fruit, and certain vegetables (cabbage, cauliflower, Brussels sprouts, broccoli, and asparagus). To prevent swallowing air, patients should avoid sipping through straws, chewing gum, and chewing with their mouths open.
Diarrhea.
Bladder complications.
Sense of urinary urgency.
Fecal incontinence. Patients with rectal surgery have a higher risk for bowel dysfunction than those who had a colostomy.
Complications in or around the stoma. These can occur early after surgery to many years after the procedure. They include skin infection or breakdown, hernias, narrowing of the stoma, bleeding, and collapse.

There are no dietary restrictions, although many patients avoid foods that can produce gas. Everyone should drink plenty of fluids and get sufficient fiber.

The potential side effects of sexual and bowel dysfunction for colorectal surgical patients can be devastating, although many patients do very well and live normal productive lives. Positive emotions play a strong role in recovery. Patients who are depressed should discuss with a doctor all aspects of treatment that affect the quality of life, and consider seeking support groups.

Medications

Chemotherapy uses drugs that kill cancer cells throughout the body. There are two situations in which chemotherapy is used:

The adjuvant setting. Adjuvant refers to the use of chemotherapy after surgery in patients with Stage III tumors and selected patients with high-risk Stage II tumors (disease that is potentially curable). The goal of this therapy is to eliminate any cancer cells that surgery may have missed, thereby preventing recurrence and increasing the chance of cure. Patients of all ages, including the elderly, can benefit.
In metastatic disease. In patients with metastatic disease (where the cancer has spread to other parts of the body) the goal of chemotherapy is to shrink tumors, improve symptoms and quality of life, and lengthen life.

In the adjuvant setting, there are some differences in chemotherapy treatments between colon and rectal cancers:

Chemotherapy for Stage II is considered standard care for Stage II rectal cancer but is under debate for colon cancer.
Chemotherapy is standard for patients with Stage III colon cancer. Chemotherapy is also standard for patients with Stage III rectal cancer but is used in combination with radiation.

Chemotherapy for Stage II Colon Cancer. Adjuvant chemotherapy for Stage II colon cancer is controversial. Such patients tend to have a good outcome after surgery, and the positive effects of chemotherapy have been difficult to demonstrate. To date, the survival advantage of adjuvant chemotherapy in this group has been reported to be only in the range of 2%. However, better trials are still needed to confirm or refute the benefits in specific patient groups.

Although not yet known with certainty, some data suggest that certain patients with Stage II cancer may be at higher risk of recurrence and would theoretically benefit from adjuvant therapy. These include patients with cancers that have:

Obstructed the bowel
Perforated the wall of the colon
Adhered to structures outside the intestine

Advanced diagnostic techniques are under investigation for helping to select appropriate candidates for adjuvant therapy. None of these methods, however, are ready to be used routinely to help make treatment decisions. The decision whether to pursue chemotherapy for Stage II disease should be made after careful discussion between the patient and their oncologist, especially after features, such as bowel perforation or obstruction, are taken into account.

Chemotherapy for Stage III Colon Cancer. Since the early 1990s, adjuvant chemotherapy with 5-FU and leucovorin has been the standard of care for Stage III colon cancer. In recent years, the FOLFOX (5-FU, leucovorin, oxaliplatin) regimen has also been used for chemotherapy following surgery. Numerous trials have shown that adjuvant chemotherapy in this setting reduces the absolute risk of death from colon cancer by about one-third and improves survival by 10%. Clinical trials are also investigating combinations of other drugs.

Chemotherapy for Advanced Colorectal Cancer. Chemotherapy is either given directly into the arteries of the liver or intravenously (through a vein) with 5-FU and leucovorin. Oxaliplatin is sometimes added, but recent evidence suggests that the targeted therapy biologic drug bevacizumab may be a better addition. Other alternative chemotherapy choices are capecitabine, or irinotecan combined with cetuximab. Radiation therapy may be used in place of chemotherapy or in combination with it. Studies indicate that chemotherapy offers only a modest improvement in survival, but may help reduce symptoms.

Seven drugs are currently approved for colorectal cancer chemotherapy:

5-fluorouracil (5-FU, Adrucil), which is often given in combination with leucovorin (Wellcovorin). Leucovorin is a vitamin that helps boost the effectiveness of 5-FU.
Capecitabine (Xeloda)
Oxaliplatin (Eloxatin)
Irinotecan (Camptosar)
Bevacizumab (Avastin)
Cetuximab (Erbitux)
Panitumumab (Vectibix)

Capecitabine is a pill form of 5-FU. The other drugs are administered intravenously. Many of these drugs are given in combination with each other. Common chemotherapy combination regimens include:

5-FU / LV (5-FU and leucovorin)
FOLFOX (5-FU with leucovorin and oxaliplatin)
FOLFORI (5-FU with leucovorin and irinotecan)
IFL (Irinotecan, 5-FU, leucovorin)
XELOX (Capecitabine and oxaliplatin)

Side effects occur with all chemotherapeutic drugs. They are more severe with higher doses and increase over the course of treatment. Because cancer cells grow and divide rapidly, anticancer drugs work by killing fast-growing cells. This means that healthy cells that multiply quickly can also be affected. The fast-growing normal cells most likely to be affected are blood cells forming in the bone marrow, and cells in the digestive tract, reproductive system, and hair follicles. Nausea and vomiting is a very common side effect, but drugs such as ondansetron (Zofran) can help provide relief. In general, side effects are nearly always temporary, and medications can help manage them. Most patients are able to continue with normal activities for all but perhaps 1 - 2 days a month.

5-Fluorouracil (5-FU) with Leucovorin. Adjuvant therapy using 5-fluorouracil, either alone or with leucovorin (5-FU/LV), is the standard treatment for patients with high-risk colon cancer (Stage III or select patients with Stage II tumors). Leucovorin, also called folinic acid, is a form of the B vitamin folic acid, which helps increase 5-FU’s effectiveness. Patients are given a series of cycles that usually continue for at least 6 months.

There are many different ways of giving 5-FU, including intravenously over several hours once a week, intravenously daily for 5 consecutive days every month, or as continuous infusion with a portable pump.

The side effects can be quite different, depending on the way 5-FU is given, and women may be more susceptible than men. In one analysis, 53% of women and 40% of men experienced severe side effects, while response rates and survival were similar for both sexes. Many patients, however, tolerate 5-FU with leucovorin well, with manageable side effects. The most common side effects include nausea and vomiting, diarrhea, loss of appetite, hair loss, swelling of hands and feet, rashes, and mouth sores.

Irinotecan. Irinotecan (Camptosar) blocks an enzyme essential for cell division. Irinotecan can be given alone or in combination with 5-FU and leucovorin. This combination therapy (irinotecan plus 5-FU/LV) is also referred to as the "Salz regimen," or IFL. When it was approved in the mid 1990s, irinotecan was the first new drug developed for colon cancer in over 30 years. Studies have shown that irinotecan combined with 5-fluorouracil and leucovorin (5-FU/LV) significantly delays the time at which tumors progress and improves survival in metastatic cancer compared to 5-FU/LV alone. While the survival advantage is small, the combination has become the standard of care for metastatic cancer. Of concern, however, are studies that have reported an increased risk of death from toxic effects with the use of the three-drug combination. These deaths appeared to be related to blood-clotting complications. Doctors should carefully monitor dosages. Diarrhea is a common side effect of irinotecan.

Capecitabine. Capecitabine (Xeloda), an oral form of 5-FU, was approved in 2001 as a treatment for metastatic colorectal cancer. It is the only pill approved for colorectal cancer. A major 2005 study, published in the New England Journal of Medicine, found that capecitabine works as well as the standard 5-FU/LV regimen and causes significantly fewer side effects. The study involved patients with Stage III colon cancer who had undergone surgical removal of the tumor. In 2005, capecitabine was approved for postsurgical treatment of patients with Dukes’ C colon cancer. Capecitabine is also showing promise in combination with radiation therapy for rectal cancers.

Oxaliplatin. Oxaliplatin (Eloxatin) is related to cisplatin, a widely used platinum-based chemotherapy drug. Oxaliplatin is used in combination with 5-FU and leucovorin. (This triple combination therapy is called the FOLFOX regimen.) Oxaliplatin was first approved in 2002 for use in combination with 5-FU and leucovorin as a second-line treatment for cancer that has progressed after initial therapy.

Since 2002, oxaliplatin has received additional approvals as a first-line treatment for advanced colorectal cancer, and as a post-surgical treatment for patients who have undergone tumor resection.

Oxaliplatin can cause pain and tingling sensations in the hands and feet (neuropathy) that is worsened by exposure to cold. Recent research suggests that adding xaliproden (Xaprila) to the FOLFOX regimen may help reduce the frequency of neuropathy without interfering with the benefits of chemotherapy. Xaliproden is a drug used to treat the neurological disease amyotrophic lateral sclerosis (also known as Lou Gehrig's disease).

Bevacizumab. Bevacizumab (Avastin) was approved in February 2004 as a first-line treatment for patients with metastatic colorectal cancer (advanced cancer that has spread in the body). It is used in combination with IFL (irinotecan, 5-FU, leucovorin). Bevacizumab is a genetically engineered monoclonal antibody that targets and inhibits vascular endothelial growth factor (VEGF), a protein that regulates angiogenesis (the development of new blood vessels that feed a tumor's blood supply). It is the first anti-angiogenic therapy approved for the treatment of colorectal cancer.

In a study of 800 patients with metastatic colorectal cancer, bevacizumab administered intravenously along with IFL extended survival by about 5 months longer than IFL alone. Common side effects of bevacizumab include nosebleeds, fatigue, diarrhea, and high blood pressure. Less common side effects include stroke, heart attacks, angina, and formation of holes in the colon and stomach (gastrointestinal perforation).

Cetuximab. Cetuximab (Erbitux) was approved in February 2004 for the treatment of metastatic colorectal cancer. This monoclonal antibody drug targets epidermal growth factor receptor (EGFR), a protein required by cancer cells in order to proliferate. It can be used either in combination with irinotecan or alone for patients who have not responded to irinotecan. Studies of the cetuximab-irinotecan combination suggest it can help in tumor shrinkage. It has a modest effect on survival, prolonging patients’ lives by about an additional month.

Panitumumab. Panitumumab (Vectibix) was approved in September 2006 for treatment of colorectal cancer that has metastasized following standard chemotherapy. Like cetuximab, panitumumab is a monoclonal antibody drug that targets EGFR. In clinical trials, panitumumab helped delay disease progression and prolong survival by about 3 months. About 8% of patients experienced tumor shrinkage. Common side effects of this drug include skin rash, fatigue, abdominal pain, nausea, and diarrhea or constipation. Serious side effects include pulmonary fibrosis, severe skin rash, and skin reactions at the infusion site.

One of the most promising recent 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 genotype. In the future, diagnostic tests may help doctors identify which patients are more likely to respond successfully to specific drugs.

Biologic therapies use the body's immune system to attack the cancer (immunotherapy). These drugs are derived from biological sources and include vaccines, monoclonal antibodies (MAbs), and gene therapies. Many targeted therapies are classified as biologics. Bevacizumab (Avastin), cetixumab (Erbitux), and panitumumab (Vectibix) are currently the three biologic drugs approved for colorectal cancer treatment, but many other drugs are in development.

Targeted therapies involve many different types of drugs and molecular pathways. These include:

Angiogenesis Inhibitors. Anti-angiogenesis drugs inhibit the formation of new blood vessels that supply tumors with the blood, oxygen, and nutrients vital to tumor growth. Angiogenesis inhibitors, such as the monoclonal antibody bevacizumab (Avastin), target vascular endothelial growth factor (VEGF). Cediranib (Recentin), formerly AZD2171, is a new angiogenesis inhibitor that is in Phase III clinical trials for treatment of colorectal cancer.

Tumor Growth Factor Inhibitors. Tumor growth factors, such as epidermal growth factor, stimulate cell growth. Cetixumab (Erbitux) and panitumumab (Vectibix) are the two currently approved colorectal cancer drugs that target the epidermal growth factor receptor (EGFR). Nimotuzumab (TheraCIM) is currently being studied in combination with irinotecan in Phase III trials.

Tyrosine Kinase Inhibitors. Tyrosine kinase is an enzyme associated with EGFR that is involved with the signaling mechanisms that prompt cell growth. The EGFR/tyrosine kinase inhibitor erlotinib (Tarceva), which is approved for the treatment of pancreatic and lung cancers, is being investigated as an adjuvant treatment for metastatic colorectal cancer. Sunitinib (Sutent), which is approved for renal cell carcinoma, is another tyrosine kinase inhibitor in Phase III trials for colorectal cancer.

Radiation Treatment

Radiation therapy uses x-rays to kill cancer cells that might remain after an operation or to shrink large tumors before an operation so that they can be removed surgically. The object of radiation therapy is to damage the tumor as much as possible without harming surrounding tissues. Radiation may be administered in the following ways:

Externally by an x-ray machine (external beam radiation).
By passing radioactive pellets through thin plastic tubes inserted into the intestine.
By implanting tiny radiation seeds directly into the tumor (brachytherapy).
Computer imaging techniques providing 3-dimensional pictures of the cancerous area are allowing precise targeting of radiation to the tumor.

Postoperative radiation treatment combined with chemotherapy is common practice for patients with rectal cancer in Stages II and III. Such patients are at risk of recurrence both at the site of their original tumor and elsewhere in the body. Although there can be significant long-term side effects, the combination of 5-FU and radiation is still considered standard after surgery.

The standard procedure in the U.S. is to apply radiation after surgery (postoperative). Pre-operative chemotherapy and radiation, however, are sometimes used to preserve sphincter-muscle function and reduce the chance that a patient will need a colostomy. Furthermore, some studies suggest that the use of radiation before surgery reduces the likelihood of recurrences and may slightly prolong survival in some patients with rectal cancer. (It has no additional advantages, however, if the subsequent surgery does not completely remove the cancerous regions.) Studies comparing preoperative and postoperative chemotherapy and radiation are currently under way.

Radiation therapy can also be used during surgery (a procedure called intra-operative radiotherapy). It allows the surgeon to move healthy tissue out of the path of the radiation beam.

Short-term side effects of radiation include:

Diarrhea
Skin irritation around the anus
Incontinence
Fatigue
Bowel movement problems

Longer-term complications may include:

Incontinence
Hip and pelvic fractures
Diarrhea
Increased risk for bowel obstruction

Follow-up Testing

The American Society of Clinical Oncology (ASCO) sets guidelines for follow-up testing to detect recurring cancer after the completion of treatment. The following guidelines are based on ASCO’s 2005 updated recommendations.

Most colorectal cancer recurrences happen within 3 years after surgery. American Society of Clinical Oncology recommends that a colorectal cancer patient sees their doctor for a physical examination every 3 - 6 months for the first 3 years, every 6 months for the fourth and fifth years, and at the doctor's and patient's discretion during subsequent years.

Patients should have a colonoscopy 3 years after surgery. If the results are normal, patients should then receive a colonoscopy every 5 years. Some patients with hereditary types of colorectal cancer may need more frequent screenings.

A flexible sigmoidoscopy is recommended every 6 months for 5 years for patients with Stage II or III rectal cancer who did not receive radiation therapy.

Carcinoembryonic antigen (CEA) levels should be measured every 3 months after surgery for 3 years in patients with Stage II or III cancer. High CEA levels in the blood may indicate that the cancer has spread to other parts of the body.

Patients at high risk for cancer recurrence should receive an annual computerized tomography (CT) scan for the first 3 years after treatment. The CT scan can help determine if cancer has spread to the lungs or liver. Patients who have had rectal cancer, and did not have radiation therapy, should receive a pelvic CT scan. The scan is not recommended for most lower-risk patients with Stage I or II colorectal cancer.

American Society of Clinical Oncology does not recommend other follow-up blood tests such as complete blood count, liver function tests, fecal occult blood tests. There appears to be no additional benefit for these tests.

Treatment for Metastasized Colorectal Cancer

The liver is the most frequent site for colorectal cancers to spread (metastasized). Here, treatments may slow the spread of cancer and even prolong survival. Cure is very rare.

When cancer has spread, surgery to remove or bypass obstructions in the intestine may be performed. In these circumstances, surgery is considered palliative in that it may improve symptoms but will not lead to cure. In rare cases, metastatic colon cancer may be cured with surgical removal of tumors in areas to which the cancer has spread, such as the liver, ovaries, and lung. The liver is the most common site of spread. Only selected patients may be eligible for such surgery, but in these patients, 5-year survival has been 25% or higher.

Chemotherapy may help improve symptoms and possibly prolong survival in metastasized colorectal cancers. Several investigational drugs are being tested. Doctors are also testing chemotherapy administered directly into the liver -- a treatment called hepatic arterial infusion (HAI). A 2006 study found that hepatic arterial infusion improves survival and quality of life for patients whose cancer has spread to the liver. The study indicated that HAI works better for these patients than chemotherapy delivered intravenously.

Other investigative techniques used to destroy liver tumors include:

Cryosurgery. This approach freezes the tumor or surrounding tissue.
Embolization. Embolization employs a catheter to deliver substances into the liver that block blood vessels and therefore starve the tumor. Chemotherapy is often administered during this procedure.
Radiation.

For end-stage cancer, hospice care is a compassionate option.

Resources

www.cancer.org -- American Cancer Society
www.cancer.gov -- National Cancer Institute
www.oncolink.org -- OncoLink cancer information
www.asco.org -- American Society of Clinical Oncology
www.plwc.org -- People Living with Cancer
www.nccn.org -- National Comprehensive Cancer Network
www.cancer.gov/clinicaltrials -- Find clinical trials

References

Chan AT, Ogino S, Fuchs CS. Aspirin and the risk of colorectal cancer in relation to the expression of COX-2. N Engl J Med. 2007 May 24;356(21):2131-42.

Cole BF, Baron JA, Sandler RS, Haile RW, Ahnen DJ, Bresalier RS, et al. Folic acid for the prevention of colorectal adenomas: a randomized clinical trial. JAMA. 2007 Jun 6;297(21):2351-9.

Flossmann E, Rothwell PM; British Doctors Aspirin Trial and the UK-TIA AspirinTrial. Effect of aspirin on long-term risk of colorectal cancer: consistent evidencefrom randomised and observational studies. Lancet. 2007 May 12;369(9573):1603-13.

Kerr DJ, Dunn JA, Langman MJ, Smith JL, Midgley RS, Stanley A, et al. Rofecoxib and cardiovascular adverse events in adjuvant treatment of colorectal cancer. N Engl J Med. 2007 Jul 26;357(4):360-9.

Levin TR, Zhao W, Conell C, Seeff LC, Manninen DL, Shapiro JA, Schulman J. Complications of colonoscopy in an integrated health care delivery system. Ann Intern Med. 2006 Dec 19;145(12):880-6.

Meyerhardt JA, Niedzwiecki D, Hollis D, Saltz LB, Hu FB, Mayer RJ, et al. Association of dietary patterns with cancer recurrence and survival in patients with stage III colon cancer. JAMA. 2007 Aug 15;298(7):754-64.

U.S. Preventive Services Task Force. Routine aspirin or nonsteroidal anti-inflammatory drugs for the primary prevention of colorectal cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2007 Mar 6;146(5):361-4.

Veit-Haibach P, Kuehle CA, Beyer T, Stergar H, Kuehl H, Schmidt J, et al. Diagnostic accuracy of colorectal cancer staging with whole-body PET/CT colonography. JAMA. 2006 Dec 6;296(21):2590-600.

Review Date:
9/8/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

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adam.com

Ovarian cancer

FitSugar — Wed, 08 Oct 2008 17:34:58 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Ovarian Cancer Symptoms

Even early-stage ovarian cancer can produce symptoms, according to a 2007 consensus statement issued by the American Cancer Society, the Gynecologic Cancer Foundation, and the Society of Gynecologic Oncologists. Because ovarian cancer can grow very rapidly, early detection is extremely important. Contact your doctor (preferably a gynecologist) if you experience these symptoms on a daily basis for more than a few weeks:

Bloating
Pelvic or abdominal pain
Difficulty eating or feeling full quickly
Urgent or frequent urination

Hormone Replacement Therapy (HRT) Increases Ovarian Cancer Risk

Post-menopausal women who use hormone replacement therapy (HRT) for more than 5 years are 20% more likely to develop ovarian cancer than women who do not use HRT, suggests a 2007 study in the Lancet. Researchers analyzed data from more than 1 million women.
A similar association between HRT use and ovarian cancer, especially for women who have not had a hysterectomy, was reported in a 2006 study in the Journal of the National Cancer Institute.

Surgery

About 1 in 3 women with ovarian cancer fail to receive recommended surgical treatment, according to a 2007 study in Cancer. The study found that women who are poor, African-American or Hispanic, or over age 70 are least likely to receive adequate care. Another Cancer study suggested that although experienced cancer centers may cost more than other facilities, they are more cost-effective over the long term than less experienced medical facilities.
For optimal ovarian cancer treatment, it is best to seek care from an experienced gynecologic oncologist and specialized cancer center.

Investigational Drugs

Aflibercept (VEGF-TRAP), an experimental anti-angiogenesis drug, may benefit patients with epithelial ovarian cancer who have not been helped by platinum-based chemotherapy, according to interim results of a Phase II study presented at the 2007 annual meeting of the American Society of Clinical Oncology. Anti-angiogenesis drugs prevent tumors from growing and spreading by starving them of their blood supply.

Introduction

The ovaries are two small, almond-shaped organs located on either side of the uterus. They are key components of a woman's reproductive system:

Ovaries store 200,000 - 400,000 follicles, tiny sacs that are present from birth, that nurture immature eggs (ova).
During each normal (usually monthly) reproductive cycle, a follicle in one ovary bursts and releases a mature or "ripened" egg. The egg travels down the fallopian tube into the uterus, where it either is fertilized by a man's sperm or, if unfertilized, breaks down and is excreted as part of the menstrual cycle.
Ovaries also secrete the important reproductive hormones estrogen and progesterone.

The uterus, commonly called the womb, 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.

Ovarian cancers are potentially life-threatening malignancies that develop in one or both ovaries. Malignant ovarian tumors generally fall into three primary classes:

Epithelial tumors
Germ cell tumors
Stromal tumors

Epithelial Tumors. Epithelial tumors account for up to 90% of all ovarian cancers and therefore are the primary focus of this report. These cancers develop in a layer of cube-shaped cells known as the germinal epithelium, which surrounds the outside of the ovaries.

Germ Cell Tumors. Germ cell tumors, which account for about 3% of all ovarian cancers, are found in the egg-maturation cells of the ovary. They occur most often in teenagers and young women. Although they progress rapidly, they are very sensitive to treatments. About 90% of patients with germ cell malignancies can be cured, often preserving fertility.

Stromal Tumors. Stromal tumors, which account for 6% of all ovarian cancers, develop from connective tissue cells that hold the ovary together and that produce the female hormones, estrogen and progesterone. Stromal tumors do not usually spread, in which case the prognosis is good. If they spread, however, they can be more difficult to treat than others.

Click the icon to see an image of ovarian cancer.

Ovarian cancer is called the silent killer because it progress almost silently, with vague symptoms. By the time symptoms do appear, the ovarian tumor may have grown large enough to shed cancer cells throughout the abdomen. At such an advanced stage, the cancer is more difficult to cure.

Ovarian cancer cells that have spread outside the ovaries are referred to as metastatic ovarian cancers. Ovarian tumors tend to spread to the following locations:

Diaphragm
Intestine
Omentum (a fatty layer that covers and pads organs in the abdomen)

Cancer cells can also spread to other organs through lymph channels and the bloodstream.

Not all ovarian tumors are malignant. Benign cysts, dermoid tumors, and borderline malignant tumors all are distinct from ovarian cancer.

Benign Cysts. Benign cysts are common. They typically develop in one of two ways:

Follicular Cysts. During normal ovulation, follicles (the little sacs in the ovary) expel eggs. If the egg is not expelled, fluids and other substances can build up inside the follicle, forming a follicular cyst.
Corpus Luteum Cysts. Benign cysts may form when an egg has been released, but the emptied follicle (now called the corpus luteum) does not break down normally, instead filling with blood from nearby blood vessels.

Both follicular cysts and corpus luteum cysts are normal parts of the menstrual cycle and nearly always resolve within one or two cycles without treatment.

Dermoid Tumors. Dermoid tumors are benign growths that occur when an egg begins to develop without fertilization by a sperm; they can contain hair, teeth, and cartilage. They are easily removed by surgery.

Borderline Ovarian Tumors. About 15% of ovarian tumors are referred to as "borderline" because their appearance and behavior under the microscope is between benign and malignant. These tumors are often referred to as carcinomas of low malignant potential because they rarely metastasize or cause death. Even when borderline carcinomas do spread outside the ovary, only 10 - 20% are fatal.

Symptoms

Ovarian cancer used to be considered a “silent killer." Symptoms were thought to appear only when the cancer was in an advanced stage. Now, experts know this is not true -- even early-stage ovarian cancer can produce symptoms.

In June 2007, the Gynecologic Cancer Foundation, the Society of Gynecologic Oncologists, and the American Cancer Society released a consensus statement concerning ovarian cancer symptoms. If you have the following symptoms on a daily basis for more than a few weeks, you should see your doctor (preferably a gynecologist):

Bloating
Pelvic or abdominal pain
Difficulty eating or feeling full quickly

Ovarian cancer grows quickly and can progress from early to advanced stages within a year. Paying attention to symptoms can help improve a woman's chances of being diagnosed and treated promptly. Detecting cancer while it is still in its earliest stages can help improve prognosis. Even a few months delay in detection may affect survival.

Other symptoms are also sometimes associated with ovarian cancer. These symptoms include fatigue, indigestion, back pain, pain during intercourse, constipation, and menstrual irregularities. However, according to experts, these symptoms are not as useful in diagnosing ovarian cancer, because they are also commonly experienced by women who do not have cancer.

Based on the symptoms and physical examination, the doctor may order pelvic imaging tests or a CA-125 blood test. If these tests reveal signs of cancer, patients should be referred to a gynecologic oncologist or a surgeon who specializes in female reproductive system cancers.

Causes

About 22,430 new cases of ovarian cancer are expected in the United States in 2007. Evidence suggests that the incidence of ovarian cancer is declining. The average age for the onset of ovarian cancer is about 60, although ovarian cancer can develop in women from the ages of 20 - 90. The lifetime risk of ovarian cancer in women with no family history of the disease is approximately one in 70 (1.4%).

Women with a history of ovarian cancer in one first-degree relative (mother or sister) have an overall 5% risk of developing the disease, but it may be higher in women with specific genetic factors. The majority of women with ovarian cancer have no family history of the disease, however, meaning that genetic inheritance is not the only risk factor.

Genetic mutations causing abnormal cell growth and differentiation are the basis for all cancer. The great majority of genetic defects that cause cancer are due to unknown causes. Most likely overexposure to environmental assaults, or errors that occur during cell division, play a role in many cases.

Several circumstances that create hormonal changes may increase the risk of ovarian cancer.

Number of Ovulations. Risk of ovarian cancer is directly related to the number of times a woman ovulates, which is indicated by the total number of menstrual periods she has had. A lower number of ovulations occur when the menstrual periods are shut off (as in pregnancy), so the risk of developing ovarian cancer is reduced.

The following women have a lower risk for ovarian cancer:

Women with a history of multiple pregnancies.
Women who took birth control pills (these shut off the menstrual period).
Women who breast-fed. (The body usually does not release eggs while a woman is breast-feeding.)

Some researchers theorize that ovarian cancer develops in women with a higher number of ovulations because of persistent damage to the epithelial cells as the egg passes through during ovulation. Researchers postulate that the recurring cell division needed to heal these tiny wounds to the ovaries, month after month and year after year, creates opportunities for errors in cell reproduction that lead to the formation of cancerous cells. Therefore, the more ovulations, the more risk of ovarian cancer. Ovulation temporarily ceases during pregnancy, breast-feeding, and birth control pill use.

Gonadotropins and Fertility Drugs. Gonadotropins are hormones produced in the pituitary gland that stimulate the ovaries to secrete estrogen and cause the follicles to produce and release eggs.

The pituitary is a gland attached to the base of the brain which secretes hormones that govern the onset of puberty, sexual development and reproductive function.

In a few studies, elevated levels of gonadotropins have been associated with an increased risk for ovarian cancer. These hormones are the basis for many fertility drugs, including human menopausal gonadotropin (Pergonal, Repronal, Metrodin) and clomiphene (Clomid, Serophene). Although there has been concern about an increased risk for ovarian cancers in women, a growing body of evidence is finding no higher risk from the drugs themselves. Instead, evidence suggests that ovarian cancers are most likely caused by factors contributing to the infertility -- not the drugs used to treat it.

Hormone Replacement Therapy. Hormone replacement therapy (HRT) appears to increase the risk for ovarian cancer. A 2007 UK study of nearly 1 million women found that women who used HRT for more than 5 years were 20% more likely to develop and die from ovarian cancer than women who had never taken HRT. Another important study, from the U.S. National Cancer Institute, indicated that 5 or more years of combination HRT (estrogen and progestin) increases the risk of ovarian cancer for women who have not had a hysterectomy.

Family history plays a role in 5 - 10% of women who have ovarian cancer. Certain genes are being investigated and identified that are responsible for some of these cases. Depending on the particular genetic type, the lifetime risk for ovarian cancer in women who carry these genes ranges from 16 - 65%.

BRCA1 and 2 Genes. Inherited mutations in genes known as BRCA1 or BRCA2 are now believed to be responsible for 30 - 50% of breast cancers, ovarian cancers, or both in patients with a strong family history of these cancers.

According to some studies, the risks are as follows:

Studies indicate that about 25 - 40% of women who carry the abnormal BRCA1 gene may develop ovarian cancer.
The risk for women with the BRCA2 gene mutation is generally believed to be lower, about 9 - 15%.

The mutated genes are linked to an even higher risk for developing breast cancer. These mutations are present in only about 0.5% of the U.S. population overall but occur in about 2.5% of all Jewish women of Eastern European (Ashkenazi) descent. These mutations are not restricted to the Ashkenazi population and may occur in women of any ethnicity, including women of Asian and African descent.

Either a mother or father can pass down BRCA mutations to the daughter. These mutations may also occur in 5 - 10% of ovarian cancer patients who have no family history of breast or ovarian cancer. A number of studies have suggested that women with BRCA-mutated ovarian cancers tend to have better survival rates than other women.

A 2005 study in the Journal of the National Cancer Institute indicated that women who have a family history of breast cancer, but no history of BRCA genetic mutations, are not at increased risk for ovarian cancer.

Other Genetic Mutations. Women who carry the hereditary nonpolyposis colorectal cancer (HNPCC) gene have about a 9% chance of developing ovarian cancer.

Risk Factors for Inherited Ovarian Cancer. Women are considered at high risk for ovarian cancer if they have:

A first-degree relative (mother, sister, or daughter) with ovarian cancer at any age. The risk increases with the number of affected first-degree relatives.
A first-degree relative (or two second-degree relatives on the same side) with early onset breast cancer (occurring before age 50).
A family member with both breast and ovarian cancer.
A family history of male breast cancer (which might indicate a BRCA2 mutation).
A family history of hereditary nonpolyposis colorectal cancer.

When a woman describes her family history to her doctor, she should include the history of cancer in women on both the mother's and the father's side. Both are significant.

Screening High-Risk Women. It is now possible to test for genetic mutations in the BRCA1 and BRCA2 genes and for hereditary nonpolyposis colorectal cancer (HNPCC) and Peutz-Jeghers syndrome in high-risk women. Any positive result raises difficult issues:

The presence of a mutation in any of these genes does not predict with absolute certainty that either breast cancer or ovarian cancer will occur. The lifetime risk for BRCA1, for example, is significantly higher (up to 40%) than for BRCA2 (about 10 - 15%).
Surgical preventive strategies, which can involve both mastectomy and removal of the ovaries, do not completely eliminate the risk for cancer, since malignant cells may occur in nearby regions. Removal of the ovaries will reduce ovarian cancer risk, however, and may also reduce breast cancer risk in mutation carriers.

Screening Guidelines for BRCA Genes. In 2005, the U.S. Preventive Services Task Force (USPSTF) released updated guidelines for BRCA testing. While women at high risk should be tested, the USPSTF does not recommend routine genetic counseling or testing for BRCA genes in low-risk women (no family history of BRCA1 or BRCA2 genetic mutations).

Most ovarian cancers are the result of genetic mutations that are not inherited but occur from environmental or other factors that cause damage to genetic material over time. Such genetic changes are referred to as sporadic (as opposed to inherited). Genetic alterations that have been observed in ovarian cancers involve the p53 tumor suppressor gene, the HER2/neu gene, and the PIC3KA gene.

Some research indicates that ovarian cancer occurs more often in North America and Northern Europe and among middle-to-upper socioeconomic class women from highly industrialized countries. Ovarian cancer is also much more common in Caucasian women than in African-American women. Japan has a low, but rising, number of ovarian cancer cases. One study observed that when Japanese women immigrate to the United States, they and their daughters have an incidence of ovarian cancer that approaches that of Caucasian women, although another study did not support such findings.

Pregnancy. Women who have never had children are more likely to develop ovarian cancer than women who have had children. The more children a woman has had, the lower her risk for ovarian cancer.

Obesity. Obesity may increase the risk of developing more aggressive types of ovarian tumors. A 2006 study indicated that a higher body mass index was associated with poorer survival.

Endometriosis. Women with endometriosis may have some higher risk for ovarian cancer. However, endometriosis is very common and ovarian cancer is not, so the risk is still very low. Some research suggests that ovarian cancer associated with endometriosis may differ from most ovarian cancer cases and, in fact, have a better outlook.

Click the icon to see an image of endometriosis.

Fat Intake. Fats have been under scrutiny for some time for putting some women at higher risk for ovarian cancer. A review study reported an association between a high intake in animal fats and a greater risk. However, other studies on this subject have found no correlation between fat intake and ovarian cancer.

Prevention

No specific lifestyle factors are proven to protect against ovarian cancer, although the following study results suggest some lower or higher risk:

Some studies have suggested a lower rate of ovarian cancer in women who eat a diet rich in vegetables. The American Cancer Society recommends that women eat 5 servings of fruits and vegetables a day, and limit consumption of high-fat red meat.
A 2005 study of more than 61,000 women suggested that tea consumption may reduce the risk of ovarian cancer. Women in the study who drank at least 2 cups of tea a day (mainly black tea) had a lower risk of ovarian cancer than women who did not drink tea.
Exercise, which protects against many diseases and even some cancers, appears to have no effect on ovarian cancer. However, obesity is associated with poorer ovarian cancer survival. Women who are obese also have a higher risk for breast cancer. Regular exercise is a good idea in any case.
Smokers should quit. Although evidence of an association with ovarian cancer is weak, it is always wise to stop smoking.

In general, factors or behaviors that limit stimulation of the ovaries or inhibit ovulation appear to be protective.

Pregnancy. The more times a woman has been pregnant the less likely she is to develop ovarian cancer. One study indicated that ovarian cancer was reduced by 40% with one pregnancy and by an additional 14% with each subsequent pregnancy.

Breast-feeding. Breast-feeding, even for only 1 - 2 months, may also reduce the risk for ovarian cancer by as much as 40%. A longer duration of breast-feeding does not appear to increase its protective benefits.

Oral Contraceptives and Progestin. Studies have suggested that routine use of birth control pills that contain the female hormones estrogen and progestin, even low-dose forms, reduces a woman's risk of ovarian cancer by about 50% when compared to women who have never taken oral contraceptives. The longer a woman takes oral contraceptives the greater the protection and the longer protection lasts after stopping oral contraceptives.

Click the icon to see an illustrated series detailing the birth control pill.

Pregnant women or women with breast cancer should not take birth control pills. Other conditions that may preclude taking oral contraceptives include:

Liver disease
Migraines
Coronary artery disease and any risk factors for heart disease or stroke (particularly smoking, obesity, high blood pressure, blood clotting disorders, or diabetes)

Tubal Ligation. Tubal ligation, a method of sterilization that ties off the fallopian tubes, has been associated with a decreased risk for ovarian cancer in some -- but not all -- studies.

Click the icon to see an image of tubal ligation.

Surgical removal of the ovaries, called oophorectomy, significantly reduces the risk for ovarian cancer. When it is used to specifically prevent ovarian cancer in high-risk women, the procedure is called a prophylactic oophorectomy. Prophylactic oophorectomy is approximately 95% protective against ovarian cancer. It is sometimes recommended for women at high risk for ovarian cancer. These women generally have the BRCA1 or BRCA2 genetic mutation, or have two or more first-degree relatives who have had ovarian cancer.

Bilateral oophorectomy is the removal of both ovaries. Bilateral salpingo-oophorectomy is the removal of both fallopian tubes plus both ovaries. Several recent studies indicate that salpingo-oophorectomy is very effective in reducing risk for ovarian cancer in women who carry the BRCA1 or BRCA2 mutation.

A 2006 Journal of the American Medical Association study reported that bilateral salpingo-oophorectomy reduces ovarian cancer risk by 80% for women with certain mutations in the BRCA1 and BRCA2 genes. A study presented at the 2006 meeting of the American Society of Clinical Oncology (ASCO) indicated that this procedure is most effective for reducing ovarian cancer risk in women with the BRCA1 gene mutation. For women with BRCA2 gene mutation, the procedure was better at reducing the risk for breast cancer.

Even after oophorectomy, women in high-risk groups for ovarian cancer still have a risk for the development of cancer in the peritoneum (the sac inside the abdomen that holds the intestines, uterus, and ovaries).

Premenopausal women should realize that oophorectomy causes immediate menopause, which poses a risk for several health problems, including osteoporosis, heart disease, and reduction in muscle tone. Estrogen replacement can help offset these problems. Women who have a bilateral oophorectomy and do not receive hormone replacement therapy may experience more severe hot flashes than women who enter menopause naturally.

Diagnosis

Up to 95% of women diagnosed with ovarian cancer will survive longer than 5 years if their cancers are treated before they have spread beyond the ovaries. Unfortunately, there are no screening tests for ovarian cancer that are the equivalent to mammography for early detection of breast cancer. Therefore, only about 25% of ovarian cancer cases are diagnosed at such early stages. It is possible to perform genetic screening in high-risk women, but this raises some complex issues.

Every woman should have a regular annual examination with her doctor that includes:

Pelvic examination. Routine exams called bimanual pelvic examinations are a reasonable precaution, although they are not perfect screening methods due to their low sensitivity. This exam can be performed two ways. In the more common method, the doctor inserts two fingers into the vagina while palpating the abdomen with the other hand. The other method, called a bimanual rectovaginal exam, involves the insertion of one finger into the vagina and another into the rectum.

Either exam enables the doctor to assess the size of the ovaries as well as the contour and mobility of the uterus and to feel for masses and growths. The rectovaginal exam may reveal rectal lesions that may otherwise go unnoticed and is particularly important for women over 50. A mass felt on pelvic exam often requires further evaluation by ultrasound and sometimes requires surgery to make a definitive diagnosis.

Pap smear. This test is specifically designed to detect cervical cancer. In very rare instances, however, it may reveal abnormal ovarian cells, which might indicate the presence of an ovarian cancer.

Click the icon to see an image of a pap smear.

Unfortunately, ovarian cancer rarely produces changes that are detectable during a regular checkup.

An estimated 290,000 women are hospitalized each year in the United States because of ovarian growths or lesions. Many more women find out about some ovarian abnormality during their annual Ob/Gyn check up. The vast majority of conditions are noncancerous. They include:

Benign functional ovarian cysts
Abscesses and infection
Fibroids

Click the icon to see an image of a fibroid tumor.

Endometriosis
Polycystic ovaries

Click the icon to see an image of a polycystic ovary.

Ectopic pregnancies

Click the icon to see an image of an ectopic pregnancy.

Meig syndrome (which involves a benign ovarian growth associated with fluid buildup in the abdomen and around the lungs)
Ovarian hyperstimulation syndrome following fertility treatments.

Once a growth is detected, additional tests [below] may help the doctor gauge the risk for it being cancerous.

Ultrasound. Ultrasound is a noninvasive diagnostic tool that can evaluate tumors and masses discovered during the rectovaginal exam:

Typically, a probe is placed in the vagina and emits sound waves (ultrasound). The sound waves bounce off tissues, organs, and masses in the pelvic cavity. These echoes are collected and converted into a picture of the area called a sonogram.

Click the icon to see an image of transvaginal ultrasound.

The ultrasound probe may also be placed on abdominal walls above the ovaries (transabdominal ultrasound), but it does not provide as clear a picture of the ovaries. Healthy tissue, fluid-filled cysts, and solid tumors produce different sound waves.

Ultrasound is not helpful for identifying early-stage ovarian cancer in high-risk women. (Researchers hope that blood tests for protein markers may eventually provide a better method for diagnosing early-stage ovarian cancer.) In addition, ultrasound does not provide enough specific information to reliably determine which abnormal masses are cancerous or noncancerous.

Studies suggest that small so-called simple cysts (fluid-filled without an associated mass) are usually noncancerous, particularly when they appear in premenopausal women whose blood tests for the protein CA-125 are normal. Such women are sometimes given oral contraceptives and observed for a few months to see if the cyst goes away.
Postmenopausal women with small simple cysts and normal CA-125 levels may sometimes be observed for a time if they have no other risk factors or symptoms of ovarian cancer.
In contrast, a "complex" cyst (one that shows a mass or other abnormalities) is often surgically removed, since it has a higher chance of being malignant. Only a small percentage of these cysts turn out to be cancerous. (In one study 6% of complex cysts were actually cancerous.)

Click the icon to see an image of an ovarian cyst.

Other Imaging Techniques. Other imaging techniques are less common for the diagnosis or evaluation of suspected ovarian cancer but may help determine if cancer has spread to other parts of the body:

Computed tomography (CT). Computed tomography records x-ray absorption rates of tissue and bone. These data is converted into clear images on a screen. CT scans help determine if cancer has spread to the lymph nodes, abdominal organs, abdominal fluid, and the liver.

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

Magnetic resonance imaging (MRI). MRI creates multiple cross-sectional images of the pelvis and abdominal organs, which are assembled into three-dimensional images. An MRI is not usually used to diagnose ovarian cancer, but may help determine if cancer has spread to the brain or spinal cord.

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

Chest x-rays. Find cancer that has spread to the lungs.

Click the icon to see an image of an x-ray machine.

CA-125 is a protein that is secreted by ovarian cancer cells and is elevated in over 80% of patients with ovarian cancer. The CA-125 blood test is not approved for screening in the general population. Oncologists will usually only obtain a blood test for this protein if ovarian cancer is strongly suspected or has been diagnosed. In general, a CA-125 level is considered to be normal if it is less than 35 U/mL (microns per milliliter). The test may also be useful for evaluating tumor growth and predicting survival in patients with recurrent cancer who have been treated with topotecan or paclitaxel-carboplatin chemotherapy regimens.

The test is not useful for diagnosis or early screening, however. In about half of women with very early ovarian cancer, CA-125 levels are not elevated above the normal standard at all. Furthermore, an elevated level can be caused by a number of other conditions including:

Endometriosis (which may be a risk factor for ovarian cancer)
Fibroids
Noncancerous ovarian cysts
Pregnancy
Pelvic inflammatory disease
Liver diseases
Other tumors, such as breast, colon, lung, and pancreatic cancers
Age and menstrual status can also affect the levels of CA-125

Research is under way to find better tests that will detect this cancer in early stages.

Proteomics. A promising new approach relies on a technique called proteomics. Proteomics is the analysis of certain proteins. In this approach, researchers are looking at a unique pattern of proteins produced by ovarian cancer cells. Studies suggest this set of proteins serves as an early biomarker for detecting ovarian cancer. Scientists at the National Cancer Institute (NCI) and Food and Drug Administration (FDA) have developed a blood test to check for the presence of these abnormal proteins. In one study, the proteomics tool identified 100% of patients with ovarian cancer and incorrectly diagnosed cancer in only 3 out of 66 of women who were actually cancer-free. A clinical trial is now under way comparing the proteomics test to the CA-125 test. OvaCheck, another investigational ovarian cancer blood test, is based on principles similar to the NCI and FDA platform, but is being developed independently by a private corporation.

Osteopontin. Scientists are also looking into the possibility that the protein osteopontin may be a biomarker for ovarian cancer. Studies have shown that osteopontin is overexpressed in tumors and serum of women with ovarian cancer.

Other Biomarkers. Researchers have also had preliminary success with a blood test that measures osteopontin along with three additional protein markers in blood: leptin, prolactin, and insulin-like growth factor-II. In early trials, prolactin and osteopontin levels were significantly elevated in women with early ovarian cancer. The other two proteins were greatly reduced. When measured collectively, these four proteins completely distinguished between healthy women and those with early ovarian cancer, according to the results published in the May 2005 journal of the Proceedings of the National Academy of Sciences.

An exploratory surgical procedure called laparotomy generally is required for the definitive diagnosis of ovarian cancer. Laparotomy involves the following steps:

It requires general anesthesia and employs standard surgical techniques to make a vertical, midline incision from the pubic bone to the navel.
Such an incision ensures careful evaluation of the entire abdominal area. After the incision is made, the surgeon assesses the fluid and cells in the abdominal cavity.
During this procedure, cysts or other suspicious areas will be removed and biopsied (tested for cancer).
If the lesion is cancerous, the surgeon continues with a process called surgical staging to find out how far the cancerous tumor has spread and to remove the ovaries and any cancerous tissue.

Investigators are also studying laparoscopy -- instead of more invasive surgery -- for initial surgical evaluation (staging).

Click the icon to see an image of pelvic laparoscopy.

Prognosis

Ovarian cancer ranks behind lung, breast, and colorectal cancer as the fourth most common cause of female cancer death in this country. About 15,280 American women are expected to die from ovarian cancer in 2007.

In general, overall 5-year survival rates (all stages combined) increased from 37% in 1974 to greater than 50% currently. Survival rates vary depending on different factors, including age and the stage at which it is detected.

The survival rate also varies according to the cancer stage:

Five-year survival rates are over 90% if the cancer is still confined to the ovary at diagnosis. However, only 19% of ovarian cancers are found at this stage.
If the cancer has spread to nearby regions in the pelvis, the survival rate drops to 60 - 80%.
If the cancer has spread to sites outside the pelvis, the 5-year survival rates are only 10 - 30%.

Unfortunately, most patients with ovarian cancer are not diagnosed until the disease is advanced. This usually means the cancer has spread to the upper abdomen. In order to establish a prognosis and determine treatment, the doctor needs to know the cell type, stage, and grade of the disease.

About 90% of ovarian epithelial cancers fall into one of four major subtypes based on their origin and shape as viewed under a microscope:

Serous. (This is the most common type.)
Endometrioid. (This is sometimes associated with endometriosis and tends to have a more favorable outlook.)
Mucinous. (The presence of malignant mucinous cells indicates a poorer outlook if the disease is advanced.)
Clear cell. (Clear cell carcinomas are the most difficult to treat even when the malignancy is still confined to the ovary.)

The remaining 10% of common epithelial cancers are referred to as undifferentiated, because their exact cell of origin cannot be determined microscopically. These epithelial ovarian carcinomas tend to grow and spread quickly.

Cancers are staged (I through IV) according to whether they are still localized (remaining in the ovary) or have spread beyond the original site.

Tumors are also graded according to how well or poorly organized they are (their differentiation). Ovarian tumors are graded on a scale of 1, 2, or 3. Grade 1 tends to closely resemble normal tissue and has a better prognosis than grade 3, which indicates very abnormal, poorly defined tissue.

Age. In general, younger women have a better prognosis than older women although stage and grade of tumor also are important to the prognosis.

BRCA Carriers. Some studies have reported that women who carry mutated BRCA genes may have better survival rates than non-carriers. The survival advantages may be due to having a slower course or being more responsive to therapies than sporadic ovarian cancers, although this is controversial.

Angiogenesis. Experimentally, the level of biochemicals stimulating the formation of new blood vessels that support tumor growth (angiogenesis) appears to correlate with prognosis. The more angiogenic factors present in a tumor population, the more new blood vessels will form, encouraging both tumor growth and metastasis.

Overexpression of p53 Mutations. High levels of a defective p53 gene (which regulates cell growth) are associated with a poorer outlook.

Women who survive ovarian cancer have a high risk for psychological stress. Support groups can be very helpful.

Treatment

In general, the course of treatment is determined by the stage of the cancer. Stages range from I to IV based on the cancer's specific characteristics, such as whether it has spread beyond the ovaries.

In stage I, the cancer has not spread. It is confined to one ovary (stage IA) or both ovaries (stage IB). In stages IA and IB, the ovarian capsules are intact, and there are no tumors on the surface. Stage IC can affect one or both ovaries, but the tumors are on the surface, or the capsule is ruptured, or there is evidence of tumor cells in abdominal fluid (ascites). The overall 5-year survival rate for stage IA or IB can be as high as 90%, but the presence of other factors may affect this rate. For example, non-clear-cell well-differentiated cancer cells or borderline tumors have a favorable prognosis. Clear cells or those that are more poorly differentiated have a worse outlook. Stage IC has a poorer outlook than the earlier stages. It is very important that women receive an accurate staging assessment, including a pathologic review conducted by a gynecologic pathologist.

Treatment Options: Treatment for most women with stage IA and IB includes surgical removal of the uterus and both ovaries and fallopian tubes (total hysterectomy and bilateral salpingo-oophorectomy), partial removal of the omentum (the fatty layer that covers and pads organs in the abdomen), and surgical staging of the lymph nodes and other tissues in the pelvis and abdomen. (Carefully selected premenopausal women in Stage I with the lowest-grade tumors in one ovary may sometimes be treated only with the removal of the diseased ovary and tube in order to preserve fertility.) Patients with stage IA or B disease, grade 1 (or sometimes grade 2), usually do not need further therapy after surgery. However, higher risk patients (stage IC, stage I/grade 3) are usually treated with platinum-based chemotherapy to reduce their risk of subsequent relapse.

A 2005 study suggested that adjuvant platinum-based chemotherapy (chemotherapy added to surgical treatment) can improve survival and reduce cancer recurrence. With the considerable adverse effects of chemotherapy, more research is needed to determine which stage 1 patients would benefit most from this adjuvant treatment.

Click the icon to see an illustrated series detailing hysterectomy.

In stage II, the cancer has spread to other areas in the pelvis. It may have advanced to the uterus or fallopian tubes (stage IIA), or other areas within the pelvis (stage IIB), but is still limited to the pelvic area. Stage IIC indicates capsular involvement, rupture, or positive washings (that is, they contain malignant cells). The 5-year survival rate for stage II is about 60 - 80%.

Treatment Options: Surgical management for most women in this stage is total hysterectomy, bilateral salpingo-oophorectomy, and removal of as much cancer in the pelvic area as possible (tumor debulking). Surgical staging should be performed.

After the operation, treatment with chemotherapy is usually necessary in an attempt to eradicate residual cancer and decrease the chance for relapse.

In stage III, one or both of the following are present: (1) The cancer has spread beyond the pelvis to the omentum (the fatty layer that covers and pads organs in the abdomen) and other areas within the abdomen, such as the surface of the liver or intestine. (2) The cancer has spread to the lymph nodes. The average 5-year survival rate for this stage is 20%.

Click the icon to see an image of the lymph system located near the ovaries.

Treatment Options: Surgical management for most women in this stage is total hysterectomy and bilateral salpingo-oophorectomy and removal of as much cancer as possible (tumor debulking).

Following surgery, chemotherapy is usually needed for any remaining cancer cells. Several approaches are under investigation for reducing high rates of recurrence (about 80%). These approaches include the following:

Experimental chemotherapy drugs
Anti-angiogenic therapies
Gene and biological therapies
Intraperitoneally administered high-dose chemotherapy
Neoadjuvant therapy (chemotherapy before surgery)
High-dose chemotherapy
Peripheral blood stem cell transplantation (to date this approach has proven to be very toxic with no convincing improvement in survival)

Stage IV is the most advanced cancer stage. The cancer may have spread to the inside of the liver or spleen. There may be distant spreading of the cancer, such as ovarian cancer cells in the fluid around the lungs. The average 5-year survival rate for this stage is less than 10%.

Treatment Options: Tumor debulking may be performed before chemotherapy.

Although not standard practice in the United States, a surgical procedure called retroperitoneal lymphadenectomy is sometimes performed. This procedure involves removal of aortic and pelvic lymph nodes from the rear of the abdomen. Results from a 2005 randomized controlled trial suggest that while retroperitoneal lymphadenectomy does help reduce cancer progression, it does not prolong survival.

Treatment Options: If ovarian cancer returns, chemotherapy is the mainstay of treatment, although it is not generally curative in the setting of relapsed disease.

If the interval between the last platinum-containing chemotherapy (carboplatin or cisplatin) and relapse is long (greater than 6 months), it is reasonable to attempt a repeat trial of platinum-based chemotherapy, with or without paclitaxel.

If the interval is short, or if these drugs fail to control the tumor, other second-line drugs may be useful in achieving a response. They include topotecan, liposomal doxorubicin, etoposide, docetaxel, gemcitabine, or tamoxifen. There is no evidence that second-line drug combinations are any more effective than single drugs, although they are generally more toxic.

Clinical trials using various investigative approaches are under way. It is not clear if there is a role of a second debulking surgical procedure. A 2004 study published in the New England Journal of Medicine found that additional debulking did not prevent cancer progression or prolong survival.

Surgery

Surgery for ovarian cancer uses laparotomy, a major abdominal operation. It is the primary diagnostic tool for ovarian cancer and also plays a role in treatment. Complete surgical intervention includes the following:

Surgical staging (examining all tissues and organs in the pelvic cavity for accurate assessment of the disease stage).
Debulking (removal of as much of the cancerous tissue as possible). This is an important component of ovarian cancer management and should be performed by a surgeon trained in cancer surgery techniques.

Patients with ovarian cancer should see a qualified gynecologic oncologist (a surgical specialist in female reproductive cancers) and a qualified medical oncologist with special expertise in the chemotherapeutic management of gynecologic cancer. Studies indicate that it is best for patients, especially those with advanced-stage ovarian cancer, to receive care at medical centers that specialize in cancer treatment and surgery.

According to a 2007 study, 1 in 3 patients with ovarian cancer fails to receive recommended surgical treatment. Women over age 70, poor patients, and African-American or Hispanic patients were least likely to receive proper treatment. Women who were not treated by gynecologic oncologists were also less likely to receive optimal surgical care.

Surgical staging includes biopsies of the following:

The undersurface of the diaphragm
The omentum (the fatty layer that covers and pads organs in the abdomen)
Sometimes lymph nodes along the abdominal aorta

An abdominal wash is performed by injecting a salt solution into the abdominal cavity to facilitate microscopic detection of cancerous cells not visible to the naked eye. The surgeon then evaluates the pelvis and abdomen and removes suspected cancer tissue. The entire affected ovary is usually removed (oophorectomy) during surgical staging if the surgeon believes it might be cancerous. The tissue is sent to a laboratory for an immediate evaluation called a frozen section diagnosis. The doctor will also examine the bowel and bladder for cancer invasion.

If the tumor is in an early stage on one ovary and a young woman wants to retain her ability to have children, the surgeon may be able to remove only the affected ovary and perform surgical staging. Chemotherapy follows in selected patients. Studies indicate that in carefully selected young patients, many can expect normal fertility afterward. However, most women with ovarian cancer are not candidates for this procedure.

The goal of surgery is to remove as much of the tumor as possible (called debulking or cytoreductive surgery) for improving symptoms and increasing the effectiveness of chemotherapy. The surgery itself is typically performed as follows:

In premenopausal women in later stages, and in all postmenopausal women, the surgeon usually removes the uterus (a hysterectomy) and both ovaries and fallopian tubes (a bilateral salpingo-oophorectomy).
In addition, the surgeon usually removes the omentum (omentectomy), any growths on the diaphragm and intestine, and possibly certain lymph nodes (lymphadenectomy).

If surgical staging reveals that the cancer has invaded the bowel, a portion of the intestine may have to be removed as well.

Postoperative Care. If possible, a patient should ask a family member or friend to help out for the first few days at home. The following are some of the precautions and tips for postoperative care:

For 1 - 2 days after surgery, the patient is given medications to prevent nausea and painkillers to relieve pain at the incision site.
As soon as the doctor recommends it, usually within a day of the operation, the patient should get up and walk in order to help prevent pneumonia, reduce the risk of blood-clot formation, and to hasten recovery.
Walking and slow, deep breathing exercises may help to relieve gas pains, which can cause major distress for the first few days.
Coughing can cause pain, which may be reduced by holding a pillow over a surgical abdominal wound or by crossing the legs after vaginal surgery.
Patients are advised not to lift heavy objects (including small children), not to douche or take baths, and not to climb stairs or drive for several weeks.
For the first few days after surgery, many women weep frequently and unexpectedly. These mood swings may be due to depression from the loss of reproductive capabilities and form abrupt changes in hormones, particularly if the ovaries have been removed.

The patient should talk to their doctor about when they can start exercise programs that are more intense than walking. The abdominal muscles are important for supporting the upper body, and recovering strength may take a long time. Even after the wound has healed, the patient may experience an on-going feeling of overall weakness, which can be demoralizing, particularly in women used to physical health. Some women do not feel completely well for as long as a year. Others may recover in only a few weeks.

Complications Following the Procedure. Minor complications after hysterectomy are very common:

Women may develop minor and treatable urinary tract infections.
There is usually light vaginal bleeding and pain after the operation, which can be well-controlled with pain medications.

More serious complications are uncommon but patients should be aware of their symptoms and call the doctor immediately if they occur:

Infection occurs in 10 - 15% of patients, with the risk being higher with abdominal than with vaginal surgery. Symptoms might include continuing or increasingly severe pain, fever, heavy discharge, or bleeding. Antibiotics given at the time of surgery help to reduce this risk. Other risk factors for infection include obesity, a longer than normal operative time, and low socioeconomic status.
There is a slight risk for small blood clots, usually in veins of the legs (thrombophlebitis). A sudden swelling or discoloration in the leg can indicate this condition and requires immediate medical attention.

This picture shows a red and swollen thigh and leg caused by a blood clot (thrombus) in the deep veins in the groin (iliofemoral veins), preventing normal return of blood from the leg to the heart.

Other serious and even life-threatening complications, though rare, include pulmonary embolism (blood clots that travel to the lung), abscesses, perforation of the bowel, fistulas (a passage that bores from an organ to the skin or to another organ), or dehiscence (the opening of the surgical wound).

Treating Menopausal Symptoms and Premature Menopause after Hysterectomy. After hysterectomy, premenopausal women usually have hot flashes, a symptom of menopause. Symptoms come on abruptly and may be more intense than those of natural menopause. Symptoms include hot flashes, vaginal dryness and irritation, and insomnia. A significant number of women gain weight.

The most important complications that occur in women who have had their ovaries removed are due to estrogen loss, which places women at risk for osteoporosis (loss of bone density) and a possible increase in risks for heart disease. Women have typically taken hormone replacement therapy (HRT) after surgery if their ovaries have been removed. There have been concerns however about health risks, including the risk for breast cancer and stroke, that have now limited its use. Risks in premenopausal women who have had a hysterectomy have not yet been clarified. Several nonhormonal drugs, however, can help protect both bones and heart.

After chemotherapy is completed, surgeons used to perform an exploratory procedure called second-look laparotomy. Although this procedure is the most sensitive way of detecting residual cancer that remains after chemotherapy, it has no proven impact on patient survival. Its use is restricted to patients being treated in clinical trials.

Bowel obstruction is common in ovarian cancer. Surgery can be very helpful for selected patients with this problem.

Medications

Following surgery, patients (other than those with early-stage, low-grade disease) usually have chemotherapy. Unlike surgery and radiation, which treat the cancerous tumor and the area surrounding it, drug therapy destroys rapidly dividing cells throughout the body, so it is as systemic therapy.

Ovarian cancers are very sensitive to chemotherapy and often respond well initially. Unfortunately, in most cases, ovarian cancer recurs. With treatment advances, however, more than half of women now survive 5 years or longer. Doctors are now approaching this disease as a chronic and potentially long-term illness that requires the following:

Identifying the disease recurrence as soon as possible
Administering treatments that are as effective as possible without causing suffering
Partnering with the patient in determining her own best course

Standard Chemotherapy. The standard initial chemotherapy uses a combination of:

A platinum-based drug, such as carboplatin (Paraplatin) or cisplatin (Platinol). Carboplatin is preferred over cisplatin in the combination. Carboplatin works as well as cisplatin but is less toxic and can be administered in a more convenient, outpatient regimen.
A taxane, such as paclitaxel (Taxol) or docetaxel (Taxotere). Currently paclitaxel is the drug most often used as initial therapy in combination with a platinum drug. Docetaxel, however, is less toxic to the nervous system (but has more adverse effects on blood cell production). Taxotere is now commonly substituted for Taxol.

Paclitaxel-carboplatin chemotherapy will reduce tumor size in about 70% of women. Older women (over age 60) may benefit as much as younger ones from this regimen.

Other drugs that may prove to be useful first-line treatments are gemcitabine (Gemzar) and doxorubicin (Doxil). A third drug, topotecan (Hycamtin), is not helpful for first-line treatment for advanced ovarian cancer, according to recent studies. In an important 2006 study, topotecan following paclitaxel-carboplatin therapy did not help prolong survival, and it caused many serious side effects, including anemia and infections.

Chemotherapy Drugs Studied for Relapsed or Refractory Cancer. Unfortunately, some ovarian tumors are resistant to platinum drugs. Even in patients who respond, the disease eventually becomes resistant to the first-line drugs, and the cancer returns. Various approaches for increasing responsiveness to these drugs are being investigated. Investigators are studying two approaches for preventing relapse after remission:

Developing more effective drug combination regimens to increase initial response rates and duration of the response.
Developing maintenance drugs to prevent or delay relapse.

Once cancer recurs or continues to progress, several second-line chemotherapies are available or under investigation. The following lists some drugs that are being used, usually as single drugs, for relapsed or refractory cancers:

Nucleoside analogs, including gemcitabine (Gemzar). In 2006, gemcitabine was approved as a treatment for recurrent ovarian cancer. It is used in combination with carboplatin for women with advanced ovarian cancer that has relapsed at least 6 months after initial therapy.
Paclitaxel or carboplatin alone or in combination. A landmark study published in the July 2003 Journal of Clinical Oncology, found that additional cycles of paclitaxel significantly delayed disease progression in women with advanced ovarian cancer.
Pegylated liposomal doxorubicin (Doxil) is a form of standard doxorubicin (Adriamycin) that remains in the bloodstream longer, tends to spare the bone marrow, and moves selectively through the tumor. It is showing promise in clinical trials and also may have fewer toxic effects than standard doxorubicin and other drugs used for ovarian cancer. Studies show that peglyated liposomal doxorubicin is very well tolerated, with a total response rate of about 20 - 30% in patients with recurrent cancer. This compares favorably with other drugs, such as topotecan, carboplatin, and taxol.
Topoisomerase I inhibitors, including topotecan (Hycamtin) and irinotecan (Campto).
Topoisomerase II alpha inhibitors, including etoposide (VePesid).
Alkaloids, including vinorelbine (Navelbine).
Hormonal drugs: tamoxifen (Nolvadex) or anastrozole (Arimidex).
Valspodar and capecitabine (Xeloda) are oral drugs that may help improve response to other drugs, although data are preliminary.

In addition to studying individual drugs in different combinations, investigators are looking for the optimal sequence, dosages and timing of administering them. In general, the typical regimen is as follows:

Paclitaxel and carboplatin are administered in an outpatient clinic within several weeks of the surgery.
Each treatment takes about 4 - 5 hours to complete.
It is repeated every 3 weeks for a total of six times. (Each 3-week interval is known as a cycle of chemotherapy.)

Such chemotherapy is usually administered intravenously (by vein). However, an important 2006 study in the New England Journal of Medicine found that patients with Stage III ovarian cancer who received intraperitoneal chemotherapy had a significant survival advantage compared with patients who received standard intravenous chemotherapy. (Intraperitoneal chemotherapy involves administering the drugs directly into the abdominal cavity.) Patients in the intraperitoneal group did have more severe side effects than those who had intravenous chemotherapy. Researchers are continuing to investigate ways to reduce these side effects. Another 2006 study noted that intraperitoneal chemotherapy requires careful catheter insertion and maintenance, and that doctors need to be well trained to perform this procedure.

Side effects occur with all chemotherapeutic drugs. They are more severe with higher doses and increase over the course of treatment. Some may be long-lasting. In one study of ovarian cancer survivors, 20% had long-term treatment side effects, such as gynecologic and abdominal problems. Even so, most enjoyed a high quality of life that was comparable to other cancer survivors and peers without a history of cancer.

Common side effects include:

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

Serious short- and long-term complications can also occur and may vary depending on the specific drugs used. The following list includes some of these complications and a few of their treatments:

Anemia. Erythropoietin stimulates red blood cell production and can help reduce or prevent this side effect. It is available as epoetin alfa (Epogen, Procrit) and darbepoetin alfa (Aranesp). Aranesp stays in the blood longer than epoetin alfa, so fewer injections are needed.
Increased chance for infection from severe reduction in white blood cells (neutropenia). The addition of a drug called granulocyte colony-stimulating factor (filgrastim and lenograstim) is very helpful in reducing the risk for severe infection in selected patients.
Liver and kidney damage.
Abnormal bleeding (thrombocytopenia).
Allergic reaction, particularly to platinum-based drugs.
Rarely, secondary cancers such as leukemia.
Between a quarter and a third of women report problems in concentration, motor function, and memory. These problems may be long-term and may be due to reductions in estrogen levels after treatments.
Cumulative doses of anthracyclines can damage heart muscles over time and increase the risk for heart failure. An encapsulated form doxorubicin (Myocet, Doxil) may reduce the risk for toxic effects on the heart.
Taxanes can cause a drop in white blood cells and possible problems in the heart and central nervous system. Allergic reactions can occur. Talking a corticosteroid before taxane administration can help prevent such reactions. Taxane therapy may also cause severe joint and muscle pain in some patients, which is relievable with corticosteroids.

Physical Exam and CA-125 Blood Test. During treatment, the effectiveness of the chemotherapy is evaluated primarily with a physical examination and the CA-125 blood test. Falling CA-125 levels indicate effective treatment and persistently elevated levels indicate resistance to the chemotherapy.

Second Look Laparotomy. Second-look laparotomy is sometimes considered after completion of chemotherapy for patients who are participating in clinical trials.

Comparative Computed Tomography Scans. Another method for evaluating the success of chemotherapy is to compare computed tomography (CT) scans of the pelvis and abdomen before and after chemotherapy to check the size of any residual tumors that persisted after the original surgery. CT scanning is not always required, however.

Positron Emission Tomography ). Positron emission tomography (PET) scans have no proven role in the management of patients with ovarian cancer. More study is needed to determine their utility in diagnosing relapsed disease.

Any patient with ovarian cancer is a candidate for clinical trials. In addition to testing high-dose or combinations of chemotherapy, drugs with unique actions are being investigated.

Anti-angiogenesis drugs. Angiogenesis, the formation of new blood vessels that feed the growth of a cancerous tumor, is a critical process in the spread of ovarian cancer. Drugs that block this process are under investigation for ovarian cancer. Some of these drugs target vascular endothelial growth factor (VEGF), a protein involved in tumor cell growth. Results of a phase II study, presented at the 2007 meeting of the American Society of Clinical Oncology, indicated that the anti-angiogenesis drug aflibercept (VEGF-TRAP) may benefit patients with epithelial ovarian cancer who are resistant to platinum-based chemotherapy. Such drugs include thalidomide, gefinitib (Iressa), and carboxyamido-triazole (CAI).

Aromatase inhibitors. Aromatase inhibitors block aromatase, an enzyme that is a major source of estrogen in many body tissues. Aromatase inhibitors are used for treatment of estrogen-sensitive breast cancer. These drugs include anastrozole (Arimidex) and letrozole (Femara). Studies indicate that they may provide an alternative to chemotherapy for types of ovarian cancers that are responsive to anti-estrogen hormonal therapy.

Multiple signal transduction regulators. Phenoxodiol is an multiple signla transduction regulator that is being developed as a broad-spectrum anti-cancer drug. It is currently being evaluated in phase III clinical trials, in combination with other drugs, such as carboplatin, for its ability to shrink tumors or stop tumor growth in women with ovarian or fallopian cancer who have failed other forms of chemotherapy.

HER Dimerization Inihibitors. Pertuzumab (Omnitarg) is the first of a new class of drugs called HER dimerization inhibitors. It is designed to inhibit tumor growth for tumors that express the HER2 receptor protein. Pertuzumab is currently in phase II trials in combination with gemcitabine for women with platinum-resistant ovarian, peritoneal, or fallopian cancer.

Immunotherapy. Several therapies under investigation use the body's immune response to attack ovarian cancer cells. Experimental immunotherapies include vaccines designed to treat -- not prevent -- cancer. Some of these vaccines use specially designed antibodies (called monoclonal antibodies, or MAbs) to boost the immune responses against tumor-associated factors, such as CA125 or HER-2/neu. Vaccine therapy is still in early-stage clinical research and is being studied in combination with various chemotherapy drugs.

Epothilones. Epothilones are a new class of anti-cancer drugs that are similar to taxanes (paclitaxel) but are more potent. One of these drugs, ixabepilone (BMS-247550), is being studied for ovarian cancer.

Radiation Therapy

Radiation therapy is not typically used in ovarian cancer. This is because radiation would need to be given to the entire abdomen and pelvis, increasing its toxicity. Radiation is sometimes useful to treat isolated areas of tumor that are causing pain and are no longer responsive to chemotherapy.

Resources

www.cancer.gov -- National Cancer Institute
www.cancer.org -- American Cancer Society
www.aacr.org -- American Association for Cancer Research
www.asco.org -- American Society of Clinical Oncology
www.plwc.org -- People Living with Cancer
www.ovarian.org -- National Ovarian Cancer Coalition
www.ovariancancer.org -- Ovarian Cancer National Alliance
www.sgo.org -- Society of Gynecologic Oncologists
www.wcn.org -- Women's Cancer Network
www.ovariancancer.com -- The Gilda Radner Familial Ovarian Cancer Registry
www.cancer.gov/clinicaltrials -- Find clinical trials

References

Beral V; Million Women Study Collaborators; Bull D, Green J, Reeves G. Ovarian cancer and hormone replacement therapy in the Million Women Study. Lancet. 2007 May 19;369(9574):1703-10.

Bristow RE, Santillan A, Diaz-Montes TP, Gardner GJ, Giuntoli RL 2nd, Meisner BC, et al. Centralization of care for patients with advanced-stage ovarian cancer: a cost-effectiveness analysis. Cancer. 2007 Apr 15;109(:1513-22.

Goff BA, Mandel LS, Drescher CW, Urban N, Gough S, Schurman KM, et al. Development of an ovarian cancer symptom index: possibilities for earlier detection. Cancer. 2007 Jan 15;109(2):221-7.

Goff BA, Matthews BJ, Larson EH, Andrilla CH, Wynn M, Lishner DM, et al. Predictors of comprehensive surgical treatment in patients with ovarian cancer. Cancer. 2007 May 15;109(10):2031-42.

Lacey JV Jr, Brinton LA, Leitzmann MF, Mouw T, Hollenbeck A, Schatzkin A, et al. Menopausal hormone therapy and ovarian cancer risk in the National Institutes of Health-AARP Diet and Health Study Cohort. J Natl Cancer Inst. 2006 Oct 4;98(19):1397-405.

[No authors listed] An experiment in earlier detection of ovarian cancer. Lancet. 2007 Jun 23;369(9579):2051.

Smyth JF, Gourley C, Walker G, MacKean MJ, Stevenson A, Williams AR, et al. Antiestrogen therapy is active in selected ovarian cancer cases: the use of letrozole in estrogen receptor-positive patients. Clin Cancer Res. 2007 Jun 15;13(12):3617-22.

Review Date:
10/16/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Gallstones and gallbladder disease

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

In This Report

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

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Connection to endometrial cancer

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

Diet

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

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

Genetics

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

Bariatric Surgery

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

Prolonged Intravenous Feeding

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

Introduction

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

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

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

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

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

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

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

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

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

Click the icon to see an image of gallstones.

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

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

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

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

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

Click the icon to see an image of gallstone obstruction.

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

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

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

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

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

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

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

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

Symptoms

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

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

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

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

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

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

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

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

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

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

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

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

Prognosis

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

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

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

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

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

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

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

Kidney failure
Liver abscess
Cirrhosis
Being over 50 years

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

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

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

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

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

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

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

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

Risk Factors

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Prevention

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Diagnosis

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Air in the gallbladder wall may indicate gangrene.

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

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

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

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

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

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

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

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

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

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

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

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

Click the icon to see an image of a cholangiogram.

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

Treatment

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Surgery

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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


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

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

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

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

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

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

Complications and Side Effects of Surgery

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

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

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

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

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

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

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

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

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

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

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

Lithotripsy and Dissolution Therapies

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

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

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

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

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

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

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

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

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

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

Managing Common Bile Duct Stones

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

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

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

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


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

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

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

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

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

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

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

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

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

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

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

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

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

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

Resources

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

References

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

A.D.A.M. Copyright

adam.com

Pancreatic cancer, CT scan

admin — Thu, 04 Sep 2008 19:23:14 -0700

Back

HEALTH GUIDE REFERENCE FROM A.D.A.M

A CT scan of the upper abdomen showing a tumor (pancreas carcinoma) in the head of the pancreas, seen here in the middle of the picture.

Review Date: 5/1/2006

Reviewed By: Benjamin Taragin, M.D., Department of Radiology, Columbia Presbyterian Medical Center, New York, NY. Review Provided by VeriMed Healthcare Network.

A.D.A.M. Copyright

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Source Doc: 2_1192

Prostate cancer

FitSugar — Wed, 08 Oct 2008 17:35:04 -0700

Overview

Signs and Symptoms
Causes
Risk Factors
Diagnosis
Preventive Care
Treatment
Other Considerations
Supporting Research

HEALTH GUIDE REFERENCE FROM A.D.A.M

Prostate cancer is a cancerous (malignant) tumor that originates in the prostate gland and can eventually spread to other organs, bones, and tissues. The prostate is a cluster of small glands located beneath the bladder that surrounds the urethra, the tube that carries urine from the bladder out through the penis. Its principle function is to manufacture fluid that constitutes a portion of the semen.

Prostate cancer is the third most common cause of death from cancer in men of all ages and is the most common cause of death from cancer in men over 75 years old. Prostate cancer is rarely found in men younger than 40. Men at higher risk include African-America men older than 60, farmers, tire plant workers, painters, and men exposed to cadmium. The lowest number of cases occurs in Japanese men and those who do not eat meat (vegetarians).

Fortunately, prostate cancer tends to be slow-growing compared to many other cancers -- the majority of prostate cancers either do not spread or cause harm for decades.

Signs and Symptoms

Many people with prostate cancer experience no symptoms at all.

Some symptoms that may indicate prostate cancer include:

Difficult and painful urination
Frequent urination and a feeling that one has to urinate even when the bladder is empty
Incomplete emptying of the bladder, which may lead to dribbling of urine
Awakening frequently in the night to urinate
Decreased force of urine stream
Blood in the urine
Hip and back pain

When the cancer has spread to other parts of the body, symptoms can include:

Bone pain
Weakness or paralysis caused by compression of the spinal cord
Weight loss
Anemia
Kidney failure

Causes

The cause of prostate cancer is unknown, although some studies have shown a relationship between high dietary fat intake and increased testosterone levels.. The influence of genes on the development of prostate cancer is suggested by the fact that prostate cancer tends to occur in men who are related to one another (see Risk Factors section). In addition, researchers have identified a gene that is associated with 30% of family-related prostate cancers.

Reports also indicate that farmers as well as men who work in tire, rubber, and sheet metal factories tend to have high rates of prostate cancer or more aggressive forms of the cancer. Some researchers speculate that environmental exposure to cadmium (present in commercial fungicides) and other harmful substances may be responsible for the high rates of prostate cancer in these men.

Nutrition has been implicated in the development of prostate cancer because disease rates among men from countries with low prostate cancer rates (such as Japan) increase when they immigrate to the United States. This rise in incidence is thought to be due to the switch to a typical American diet, which is high in saturated fat. Elevated levels of male sex hormones, such as testosterone, may also play a role in the development of prostate cancer.

Risk Factors

The following factors may increase a man's risk for prostate cancer:

Older age -- prostate cancer is most common among men who are older than 55.
Race -- African-Americans have a greater risk of developing prostate cancer than Caucasians who, in turn, have a greater risk than Native and Latin Americans.
Family history of prostate cancer -- having a brother with prostate cancer makes a man 4.5 times more likely to develop the disease. Having a father with prostate cancer makes a man 2.3 times more likely to develop prostate cancer.
High-fat diet -- foods rich in saturated fat may increase testosterone levels.
Lack of exercise may increase the risk in those who eat a high-fat diet.
Occupation -- people who are regularly exposed to the chemicals dimethyl formamide and acrylonitrate, and the metal cadmium (such as metal workers and farmers), have high rates of prostate cancer.

Diagnosis

Two standard tests are used for early detection of prostate cancer:

Digital rectal exam (DRE) -- in this test, the physician inserts a gloved, lubricated finger into the patient's rectum in order to feel the prostate for bumps or other abnormalities. Many malignant tumors originate in the outer part of the prostate where they may be detected by this exam. Some men find this test embarrassing, but the DRE is quick and relatively painless, and helps detect many prostate cancers. Although some tumors identified using DRE have already spread outside of the prostate gland, studies indicate that regular DREs still save lives.
PSA test -- blood test measuring the level of prostate-specific antigen (PSA), a protein produced in the prostate gland that keeps semen in liquid form. Prostate cancer cells produce elevated quantities of PSA, so measuring PSA levels allows physicians to detect cancer while it is still microscopic. Unfortunately, the test is not accurate enough to definitively rule out or confirm cancer. For example, advancing age and benign conditions such as enlarged prostate can also elevate PSA levels.

If either the DRE or PSA test suggests the possible presence of cancer, the following tests will be performed to make a definite diagnosis:

Transrectal Ultrasound -- a visual image of the prostate is obtained by using ultrasound.
Biopsy of the prostate -- a tissue sample is obtained through the rectum and examined for cancerous cells under the microscope.

If the biopsy confirms the presence of cancer, several tests will be performed to detect any spread of the disease. This information gauges how serious the prostate cancer is at the time of diagnosis. Likely tests include the following:

Imaging tests (CT and MRI) -- computerized tomography (CT) or magnetic resonance imaging (MRI) scans may pinpoint the location of cancer that has spread beyond the prostate.
Bone scans and x-rays -- these techniques look for spread of cancer to the bones.
Lymph node dissection -- this is part of a surgical procedure to determine if the cancer has spread to the lymphatic system.

Preventive Care

Regular screening with the DRE and PSA exams by a doctor may help detect prostate cancer in the early stages, before it has spread. Both the American Cancer Society and the American Urological Association recommend that men between the ages of 50 - 70 should have annual DRE or PSA tests. African-American men or those with a family history of prostate cancer should begin screening at age 40.

Studies also suggest that the following lifestyle modifications may minimize the risk of prostate cancer:

Consuming a low-fat diet, rich in fruits and vegetables
Eating foods rich in selenium (such as brewer's yeast, wheat germ, chicken liver, nuts and seeds, tuna and herring) and vitamin E (such as wheat germ, organ meats, sweet potatoes, leafy vegetables including spinach, nuts and seeds, eggs, soybeans, and lima beans)
Exercising regularly, because exercise temporarily lowers testosterone

Treatment

Treatment for prostate cancer depends on the stage of the disease, the age of the individual, the presence of other medical conditions, and the man's preferences in conjunction with the physician's recommendations.

If prostate cancer is detected early, treatment usually involves either surgical removal of the prostate or radiation therapy. For more advanced cases of prostate cancer, or if cancer spreads beyond the prostate, hormone medications are the preferred treatment.

If the man is older than 70 and has only a slow-growing tumor, the physician may adopt a strategy called "watchful waiting," in which the man returns frequently for check-ups. Treatment occurs only if the man's condition worsens.

Dietary modifications may slow the growth of the cancer in men undergoing watchful waiting, as well as those who have had surgery or are being treated iwth with medication or radiation. For example, eating a low-fat diet, rich in fruits, vegetables, soy, selenium, and fiber has been associated with a decreased risk of prostate cancer.

Saw palmetto, a widely studied herb, appears to significantly reduce symptoms associated with benign prostatic hypertrophy (BPH) and may be used in prostate cancer, but only under the supervision of a doctor.

Acupuncture can relieve pain and the side effects of surgery while meditation and massage may reduce stress and anxiety associated with having prostate cancer.

Medications

Medications are considered the best therapy for people with advanced stages of prostate cancer or when cancer spreads from the prostate to other parts of the body. Drugs may also be prescribed prior to radiation therapy or when surgical procedures fail to lower PSA levels. Most medications for prostate cancer lower levels of male sex hormones (such as testosterone). Lowering testosterone levels can cause tumors to shrink or slow their growth.

Some commonly prescribed medications include:

Luteinizing Hormone-Releasing Hormone (LH-RH) agonists (such as leuprolide, goserelin, and buserelin) -- LH-RH is natural hormone, released by the hypothalamus in the brain, that lowers the production of testosterone, and the medication encourages the release of this natural hormone. Side effects can include hot flashes, weight gain, development of male breast tissue, breast pain, and nausea.
Hormones including antiandrogens (such as flutamide, bicalutamide, and nilutamide) and estrogens (such as diethylstilbestrol) -- these medications reduce testosterone levels, but side effects can include reduced sex drive, fatigue, nausea, impotence, diarrhea, and hot flashes.
Chemotherapeutic medications (such as mitoxantrone and estramustine) -- improve symptoms in advanced cancer but do not increase life expectancy

Surgery and Other Procedures

Removal of the prostate (prostatectomy) -- offers an excellent cure for men with prostate cancer that is completely confined to the prostate, and is performed if life expectancy is at least 10 years and cancer is confined to the prostate. Side effects include incontinence and impotence, but new procedures that spare nerves near the prostate preserve sexual function in 25 - 90 % of men.
Surgical exploration of lymph nodes -- may be performed to evaluate whether prostate cancer has spread to the lymphatic system.
Resection of the prostate (called TURP or transurethral resection of the prostate) -- removal of all or part of the prostate gland to eliminate cancer and to relieve obstruction of urine.
Removal of the testes (orchiectomy) -- lowers testosterone levels, but side effects can include impotence and hot flashes.

In addition to these surgical procedures, radiation therapy may be effective for cancer confined to the prostate, particularly for older men. Radiation can be administered through an external source, or irradiated seeds can be placed internally near the prostate. Using irradiated seeds actually lowers the risk of damage to organs surrounding the prostate from radiation because administration can be more precise in both amount and location. Side effects can include proctitis (inflammation of the lining of the rectum), urinary tract infections, and impotence.

Nutrition and Dietary Supplements

A comprehensive treatment plan for support of the health of men living with prostate cancer may include a range of complementary and alternative therapies. Preliminary studies suggest that nutritional supplements may reduce the symptoms of some prostate cancer. 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:

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. A study found that men who consumed 28 or more servings of vegetables per week were 35% less likely to develop prostate cancer than those who had less than 14 servings per week.
Eat antioxidant foods, including fruits (such as blueberries, cherries, and tomatoes) and vegetables (such as squash and bell peppers).
Avoid refined foods, such as white breads, pastas, and especially sugar.
Quality protein sources, such as organic meat and eggs, whey, and vegetable protein shakes, may be used as part of balanced program aimed at gaining muscle and preventing weight loss that can sometimes be a side effect of cancer therapy. Try to eat fewer red meats and more lean meats such as chicken and fish, tofu (soy, if no allergy), or beans for protein.
Eat cruciferous vegetables (such as broccoli, cabbage, and cauliflower) -- they contain special cancer fighting chemicals.
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 daily multivitamin, containing the antioxidant vitamins A, C, E, the B-complex vitamins, and trace minerals such as magnesium, calcium, and selenium.
Calcium D-glucarate, 200 - 400 mg daily, for support of immunity and anticancer effects.
Omega-3 fatty acids, such as fish oil, 1 - 2 capsules or 1 - 3 tablespoonfuls 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 but not substitutes for supplementation.
Whey protein, 10 - 20 grams daily mixed in favorite beverage, when needed as a protein supplement for support of immunity and weight gain; or creatine, 5 - 7 grams daily, when needed for muscle weakness and wasting. Talk with your health care provider.
N-acetyl cysteine, 200 mg one to three times daily, for antioxidant effects.
Probiotic supplement (containing Lactobacillus acidophilus among other strains), 5 - 10 billion CFUs (colony forming units) a day, when needed for maintenance of gastrointestinal and immune health. You should refrigerate your probiotic supplements for best results.
Astaxanthin, 2 - 6 mg daily, for immune and antioxidant support.
Coenzyme Q10, 100 - 200 mg at bedtime, for antioxidant and immune activity.
Vitamin C, 500 - 1,000 mg one to three times daily, as an antioxidant and for immune support. Some doctors will use higher doses in alternative cancer therapies. Check with your health care provider.
Lycopene, 5 mg one to three times daily, for antioxidant and anticancer activity. In a large study, lycopene levels were significantly lower in those with prostate cancer compared to those without.
L-glutamine, 500 - 1,000 mg three times daily, for support of gastrointestinal health and immunity.
Melatonin, 2 - 5 mg one hour before bedtime, for sleep and immune protection. Ask your health care provider about potential drug interactions with the use of melatonin.

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.

Green tea (Camellia sinensis) standardized extract, 250 - 500 mg daily, for antioxidant, anti-inflammatory and immune effects. Use caffeine-free products. You may also prepare teas from the leaf of this herb.
Saw palmetto (Serenoa repens) standardized extract, 160 mg two times daily, for hormonal support. There has been some concern that saw palmetto could mask prostate cancer by lowering prostate-specific antigen (PSA) levels. However, a randomized study of more than 1,000 patients did not demonstrate this effect on PSA levels. Talk to your health care provider about using saw palmetto for your condition.
Fermented wheat germ extract, 1 packet dissolved in favorite beverage once daily, for anticancer and immune effects. Ask your health care provider for more about this supplement.
Bitter Melon (Momordica charantia) standardized extract, 200 mg two to three times daily, for anticancer and immune support.
Maitake mushroom (Grifola frondosa) standardized extract (D-fraction), 600 mg twice daily, for immune and antiviral effects. 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 antibacterial or antifungal and immune activity.

Acupuncture

Acupuncture may provide relief from side effects of orchiectomy (removal of the testes). Studies also support the use of acupuncture for the pain that often occurs when cancer has spread beyond the prostate (particularly to the bones). A National Institutes of Health statement released in 1997 also supports the use of acupuncture to alleviate nausea associated with chemotherapy.

Evidence suggests acupuncture can be a valuable therapy for cancer-related symptoms (particularly nausea and vomiting that often accompanies chemotherapy treatment). Studies have also indicated that acupuncture may help reduce pain and shortness of breath. Acupressure (pressing on rather than needling acupuncture points) has also proved useful in controlling breathlessness and is a technique that patients can learn and then use to treat themselves.

Massage and Physical Therapy

Studies suggest that massage reduces stress and boosts immune function, so it may help relieve anxiety for men undergoing treatment for prostate cancer.

Pelvic floor exercises -- the repetitive use of muscles that start and stop the flow of urine -- may help decrease incontinence caused by prostatectomy (removal of the prostate). This therapeutic approach is often combined with biofeedback.

Mind-Body Medicine

Meditation

Meditation may benefit men with prostate cancer by helping them to reduce stress, ease anxiety, and regain a sense of self-control.

Biofeedback and Pelvic Muscle Training (PMT)

Several studies have found that learning to start and stop the flow of urine by repeatedly using the muscles of the pelvis (PMT) in combination with biofeedback can reduce the duration of incontinence after prostate cancer surgery. Other studies suggest however, that PMT alone, with or without biofeedback, is responsible for the beneficial effects. Either way, both PMT and biofeedback are safe, noninvasive therapies that may benefit men who suffer from incontinence following either surgical removal of the prostate or other treatments for prostate cancer.

Other Considerations

Prognosis and Complications

Most complications from prostate cancer result from specific treatments. These include:

Prostatectomy -- can cause incontinence and impotence
Radiation therapy -- can cause proctitis (inflammation of the lining of the rectum), bladder infections, and impotence
Hormone medications -- can cause loss of libido, impotence, hot flashes, excessive development of male breasts, and tenderness in male breast tissue
Removal of testes -- can cause impotence and hot flashes

The outlook for a man with prostate cancer depends on his age, the stage of tumor growth, whether he has any underlying medical illnesses, and his PSA levels. The prognosis for men with cancer that has not spread beyond the prostate is quite good. Most of these cancers are curable with appropriate treatment, and after 15 years the same number of these men will be alive as those who never had prostate cancer. If the cancer spreads beyond the prostate and does not respond to hormone medications, however, there is little hope for a cure. Still, prostate tumors are slow-growing, and even men with advanced prostate cancer can survive for 5 years or more.

Supporting Research

Alimi D, Rubino C, Leandri EP, Brule SF. Analgesic effects of auricular acupuncture for cancer pain [letter]. J Pain Symptom Manage. 2000;19(2):81-82.

Aronson WJ, Glaspy JA, Reddy ST, Reese D, Heber D, Bagga D. Modulation of omega-3/omega-6 polyunsaturated ratios with dietary fish oils in men with prostate cancer. Urology. 2001;58(2):283-288.

Bairati I, Meyer F, Fradet Y, Moore L. Dietary fat and advanced prostate cancer. J Urol. 1998;159:1271-1275.

Bales GT, Gerber GS, Minor TX, et al. Effect of preoperative biofeedback/pelvic floor training on continence in men undergoing radical prostatectomy. Urology. 2000;56(4):627-630.

Cabrera C, Artacho R, Gimenez R. Beneficial effects of green tea -- a review. J Am Coll Nutr. 2006;25(2):79-99.

Chan JM, Giovannucci E, Andresson SO, Yuen J, Adami HO, Wolk A. Dairy products, calcium, phosphorous, vitamin D, and risk of prostate cancer (Sweden). Cancer Causes Control. 1998;9(6):559-566.

Clark LC, Combs GF, Turnbull BW, et al. Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group. JAMA. 1996;276(24):1957-63.

Cohen JH, Kristal AR, Stanford JL. Fruit and vegetable intakes and prostate cancer risk. J Nat Can Inst. 2000;92(1):61-68.

Coker KH. Meditation and prostate cancer: Integrating a mind/body intervention with traditional therapies. Sem Urol Oncol. 1999;17(2):111-118.

Cook NR, Stampfer MJ, Ma J, et al. Beta-carotene supplementation for patients with low baseline levels and decreased risks of total and prostate carcinoma. Cancer. 1999;86(9):1783-1792.

Doron S, Gorbach SL. Probiotics: their role in the treatment and prevention of disease. Expert Rev Anti Infect Ther. 2006;4(2):261-75.

Ezzo J, Berman B, Hadhazy VA, Jadad AR, Lao L, Singh BB. Is acupuncture effective for the treatment of chronic pain? A systematic review. Pain. 2000;86:217-225.

Filshie J, Penn K, Ashley S, Davis CL. Acupuncture for the relief of cancer-related breathlessness. Palliat Med. 1998;10:145-150.

Fleshner NE, Klotz LH. Diet, androgens, oxidative stress and prostate cancer susceptibility. Cancer and Metastasis Reviews. 1999;17:325-330.

Franke JJ, Gilbert WB, Grier J, Koch MO, Shyr Y, Smith JA. Early post-prostatectomy pelvic floor biofeedback. J Urol. 2000;163:191-193.

Fraschini F, Demartini G, Esposti D, Scaglione F. Melatonin involvement in immunity and cancer. Biol Signals Recept. 1998;7(1):61-72.

Freeman VL, Meydani M, Yong S, Pyle J, Flanigan RC, Waters WB, Wojcik EM. Prostatic levels of fatty acids and the histopathology of localized prostate cancer. J Urol. 2000;164(6):2168-2172.

Gann PH, Ma J, Giovannucci E, et al. Lower prostate cancer risk in men with elevated plasma lycopene levels: results of a prospective analysis. Cancer Research. 1999;59:1225-1230.

Giovannucci E, Rimm EB, Wolk A, et al. Calcium and fructose intake in relation to risk of prostate cancer. Cancer Res. 1998;58(3):442-447.

Giovannucci E, Ascherio A, Rimm EB, Stampfer MJ, Colditz GA, Willett WC. Intake of carotenoids and retinol in relation to risk of prostate cancer. J Natl Cancer Inst. 1995;87(23):1767-1776.

Grant WB. An ecologic study of dietary links to prostate cancer. Altern Med Rev. 1999;4(3):162-169.

Hammar M, Frisk J, Grimas O, Hook M, Spetz AC, Wyon Y. Acupuncture treatment of vasomotor symptoms in men with prostatic carcinoma: A pilot study. J Urol. 1999;161:853-856.

Hayes RB, Ziegler RG, Gridley G, et al. Dietary factors and risks for prostate cancer among blacks and whites in the United States. Cancer Epidemiol Biomarkers Prev. 1999;8(1):25-34.

Helzlsouer KJ, Huang HY, Alberg AJ, et al. Association between alpha-tocopherol, gamma-tocopherol, selenium and subsequent prostate cancer. J Natl Cancer Inst. 2000:92(24):2018-2023.

Hirsch IH. Integrative urology: a spectrum of complementary and alternative therapy. Urology. 2000:56:185-189.

Jackson J, Emerson L, Johnston B, Wilson J, Morales A. Biofeedback: a noninvasive treatment for incontinence after radical prostatectomy. Urol Nurs. 1996:16(2):50-54.

Kelly GS. Clinical applications of N-acetylcysteine. Altern Med Rev. 1998;3(2):114-127.

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Review Date:
11/7/2006
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.

A.D.A.M. Copyright

adam.com

Vitamins

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

In This Report

Highlights
Introduction
Carotenoids
Phytochemicals
Healthy Foods
Dietary Health Benefits
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Cancer

Growing evidence suggests that vitamins and micronutrients, especially from foods, may play important roles in the prevention or treatment of certain cancers:

One study found that the risk of prostate cancer risk dropped as consumption of vegetables high in vitamin C, such as broccoli and bell peppers, rose.
A diet high in cruciferous vegetables has been found to reduce the risk of kidney cancer; low consumption of cruciferous vegetables increases the risk.

On the other hand, high amounts of folic acid (a B vitamin) may be associated with colorectal cancer, and beta-carotene supplements are associated with increased lung cancer risk in smokers and people exposed to asbestos.

Macular Degeneration

In 2007, the National Eye Institute recommended that people with intermediate or advanced macular degeneration in one eye take a vitamin formula shown to reduce the risk of macular degeneration in the other eye by 25%. The formula contains vitamin C, vitamin E, beta-carotene, and zinc.

Osteoporosis

Vitamin K is widely used in Japan to treat osteoporosis, and studies suggest it also may be effective in treating rheumatoid arthritis.

Heart Disease

Although people with high levels of homocysteine are prone to developing blood clots in their arteries and veins, a 2007 study found that lowering homocysteine with B vitamins and folic acid does not reduce the incidence of deep vein thrombosis (DVT). A 2007 trial in adults with stable coronary artery disease found that lowering homocysteine levels 33% with folic acid and other B vitamins had no effect on arterial inflammation, meaning that lower levels were unlikely to offer protection against heart attack or stroke.

Introduction

Vitamins do not share a common chemistry, but they do share certain characteristics. They are all organic nutrients that are necessary in small amounts for normal metabolism and good health. Your diet or supplements provide most vitamins. The body can manufacture only three vitamins (D, K, and the B vitamin biotin) from nondietary sources. Unlike carbohydrates, fats, and proteins, vitamins are not sources of energy. Instead, vitamins are chemical partners for the enzymes involved in the body's metabolism, cell production, tissue repair, and other vital processes.

Vitamins are either fat soluble or water soluble. The fat-soluble vitamins, which include A, D, E, and K, are absorbed by the body using processes that closely parallel the absorption of fat. They are stored in the liver and used up by the body very slowly. The water-soluble vitamins include C and the B complex vitamins. The body uses these vitamins very quickly. Excess amounts are eliminated in urine.

The Recommended Daily Allowance (RDA) for vitamins, set by the Food and Nutrition Board of the National Academy of Sciences-National Research Council, has been used for years as a guide for determining the amount of vitamins needed for a healthy diet. The RDA refers to an estimate of the average daily requirement. It is not completely adequate, however, for informing people about the amounts of vitamins they may need.

The RDA is gradually being enhanced using a new standard called the Dietary Reference Intake (DRI). The DRI is based on the following ratings, which will eventually appear on labels:

The recommended daily allowance (RDA). This is the current rating on most vitamins.
The estimated average requirement (EAR). This is the amount adequate for 50% of all people, which will be put on labels when it can be calculated.
Adequate intake (AI). This is an amount that will be used if there is insufficient data to calculate the EAR.
Tolerable upper intake level (UL). This is the maximum dose likely to be safe in nearly all individuals. It will be included on labels if this amount is known.

Food and supplement labels now typically list the Daily Value (DV). This is the percentage of the amount of a nutrient that experts believe a person needs in their daily diet. On food labels it is usually based on one serving size for a person who takes in 2,000 calories a day.

Regulation of dietary supplements by the U.S. Food and Drug Administration (FDA) is a complex issue.

Labels on vitamins and other dietary supplements now include nutrient information and list all ingredients, including identifying parts of plants from which ingredients may be taken. Unlike the labels for drugs, however, labels for vitamins and supplements may not claim to prevent or treat any specific disease. Labels for vitamins and supplements include one of the following:

Health claim -- description of how the substance may reduce the risk of a health-related condition
Nutrient claim -- description of the amount of the nutrient in the product or
Structure or function claim -- description of how the product may affect organs or systems of the body, without claiming to prevent or treat specific disease

The quality of dietary supplements depends on the manufacturer and is not ensured by FDA. The U.S. government does not require that supplements be standardized, meaning that the amounts or quality of nutrients may vary depending on the batch. So, more expensive supplements are not necessarily better than the less expensive ones. Government regulations are in the process of catching up to the boom in the supplement industry. In the meantime, some companies voluntarily adhere to rigorous quality controls, while others do not.

The U.S. Pharmacopeia (USP), an independent organization that sets quality standards for drugs, has also implemented standards for vitamins. Consumers may look for the USP label on products of companies that adhere to these standards. USP verification means the following:

What is in the bottle matches what is listed on the label.
There are no harmful levels of contaminants.
The supplement will be absorbed properly into the body.
It has been produced according to good manufacturing standards.

Before selling any supplement introduced after 1994, manufacturers must submit information as to why the product is considered safe for people. The FDA may refuse to allow it on the market if it finds the evidence insufficient. The FDA does not require manufacturers to provide any scientific evidence that dietary supplements are safe and effective before a product is sold (unlike drugs, which must be proven both safe and effective through clinical trials). If a supplement causes side effects in people once it is for sale, the government may place restrictions on the supplement or withdraw it from the market. The FDA may also withdraw products from the market if their labels are misleading or false.

About 30% of Americans take at least one vitamin or mineral supplement daily. In a large study that examined the death rates of 11,000 people, however, there was no difference in mortality rate between those who took vitamin supplements and those who didn't. Most people who have a healthy diet do not need vitamins, but there are some exceptions.

Pregnant and Breast-Feeding Women. Women who are pregnant or who are breast-feeding generally need additional vitamins. Vitamins B6, B12, and folic acid are particularly important. Women who are vegetarians must be sure to avoid deficiencies, which can harm their offspring. Folic acid reduces the risk for neural tube defects and possibly facial abnormalities, such as cleft palate. Studies also show that low folate levels during pregnancy are associated with low birth weight, a risk factor for the development of cardiovascular disease in adulthood. Multivitamins that contain folic acid also appear to be somewhat protective. A woman's best approach is to take extra folic acid plus multivitamin supplements (which have additional benefits), starting them before becomming pregnant.

The human body stores several years' worth of vitamin B12, so nutritional deficiency of this vitamin is extremely rare. Although, people who follow a strict vegetarian diet and do not consume eggs or dairy products may require vitamin B12 supplements.

Pregnant women with healthy diets may have low folate levels and need to take supplements. Requirements are as follows:

The recommended daily allowance (RDA) for folic acid prior to conception and during pregnancy is 400 mcg.
During breast-feeding 260 - 280 mcg is recommended.

The following vitamins may have some value for pregnant women:

Choline, another vitamin B, is also essential for pregnant (450 mg) and nursing women (550 mg). Choline plays a key role in brain development. Not getting enough during pregnancy can lead to memory and cognitive defects in the baby. Choline supplements can also lessen the cognitive defects of prenatal alcohol exposure.
Vitamin B6 may help improve morning sickness.
Vitamin C may reduce the risk of urinary tract infections during pregnancy.
Vitamin D may help prevent preeclampsia.
One study also suggested that if pregnant women took vitamin K supplements, their infants might not need the required injection of this vitamin after birth, but supplements of vitamin K during pregnancy are not currently recommended.

Some women have low vitamin A reserves in their liver. It is important to note, however, that too much vitamin A significantly increases the risk for birth defects. Daily amounts of 10,000 IU (international units) of vitamin A in supplements and food (an amount not far above the RDA level) can pose a danger. Experts recommend that pregnant women take in no more than 8,000 IU per day and avoid eating liver.

Infants and Children. Infants who are breast-fed by healthy mothers receive enough vitamins except, in some cases, vitamins K and D. Human milk has low levels of K, and the newborn's immature intestinal tract may not produce enough of the baby's own supply. Most babies are given an injection of this vitamin at birth. Infants being breast-fed by malnourished women or those who lack sufficient exposure to sunlight may be deficient in vitamin D. In these cases, supplements of 200 - 300 IU are recommended. Formulas are required to contain sufficient vitamins and minerals. One study suggests that vitamin supplements for infants under 1 year of age may help protect them from developing type 1 diabetes later on. Beyond infancy, most American children receive all the vitamins they need from their diet unless they are living in severely deprived circumstances.

Smokers. Smoking interferes with absorption of several vitamins, importantly vitamins C and D. In one study nearly 25% of female smokers and 31% of male smokers were deficient in vitamin C. Smoking can interfere with the metabolims of vitamin D, resulting in poor muscle function. Taking high doses of antioxidant vitamins, however, may actually be harmful in smokers, especially beta carotene. Instead of taking supplements, most smokers should be sure their diets are rich in fresh fruits and vegetables and whole grains. Of course, smoking cessation is the most important intervention of all.

Click the icon to see an image of sources for vitamin C.

Alcoholics. Alcoholics often suffer from multiple vitamin deficiencies. The most dangerous deficiencies are from vitamins B1 (thiamin), folic acid, B6 (pyridoxine), B2 (riboflavin), and vitamin C. Low levels of B6 are associated with increased risk of colorectal cancer in men who drink large amounts of alcohol.

Overweight Adults. Overweight and obesity causes many problems that often result in metabolic syndrome or type 2 diabetes. Evidence suggests that isoflavones can help regulate cholesterol levels and reduce body weight and fat mass. Because some medications used to control blood sugar levels reduce folic acid and vitamin B12, some people may need vitamin supplements.

People Who Have Had Gastric Bypass Surgery. Vitamin deficiency is a recognized complication of gastric bypass surgery. Women, African-Americans of both sexes, and adults who have had laparoscopic Roux-en-Y bypass surgery are at highest risk. The deficiency is treated with water-soluble vitamin supplements.

Strict Vegetarians. Strict vegetarians need supplements of vitamin B12, unless they get enough of it from fortified cereals and other grain products.

Dieters and Vegetarians. People on weight-reduction diets with less than 1,000 calories a day should probably take a multivitamin and should also check regularly with a physician.

Vegetarians may need riboflavin, vitamin B12, and vitamin D supplements. Vegans, who do not eat dairy or eggs as well as meat, may be at further risk for vitamin A deficiencies if they do not also have plenty of dark colored fruits and vegetables. Those who eat eggs and dairy products need only watch their iron levels.

Deficiencies in vegetarian children may be particularly harmful. (One study, for example, reported that adolescents who had been on macrobiotic diets before age 6 and were deficient in vitamin B12 scored lower on psychological tests.) Pregnant and breast-feeding women who are vegetarians must be sure to have sufficient vitamins. Of special note, maternal deficiencies in vitamin B12 may cause delayed growth and neurologic problems in their newborns.

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

Older Adults. Deficiencies of vitamins and important minerals have been observed in almost a third of elderly people. Often their dietary habits slip and they fail to eat balanced meals regularly. Multiple drug regimens may prevent absorption of some vitamins. Elderly people, particularly if they are not exposed to sunlight, may be deficient in vitamin D. They also may have low levels of important B vitamins. (Older adults showing signs of dementia should be checked for B12 deficiencies as well as other disorders causing mental disturbances.) One study reported that the immune systems of elderly people may benefit from higher levels of vitamin E than the daily recommended dosage. It should be noted, however, that metabolism slows down as a person ages, and in elderly people it takes the liver longer to eliminate drugs and vitamins from the body. The effect of some vitamin supplements, therefore, may be intensified. Dosage levels of vitamin A, for instance, which might be harmless in a younger adult, could be toxic in an elderly patient. Nevertheless, experts are increasingly recommending extra vitamin and mineral supplements for older people.

People Who Need to Avoid Sunlight. People who need to avoid sunlight or are housebound, and whose diet is low in foods that contain vitamin D should take supplements. People with darker skin are at higher risk for deficiencies than those with whiter skin. (Note: vitamin D is toxic in high doses, and no one should exceed the recommended daily intake of vitamin D except under the direction of a physician.)


Benefits	Essential for growth, bone development, night vision, reproduction, and healthy skin.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	Vitamin A RDA and Upper Limit (when toxicity is risk) are the following: For children: 1,000 IU ages one to three (upper limit is 2,000 IU); 1,333 IU ages 4 - 8 (upper limit is 3,000 IU); and 2,000 IU for 9 - 13 (upper limit is 5,665 IU). For nonpregnant women: 2,330 IU ages 14 through adulthood. (Upper limit is 9,335 IU for ages 14 - 18 and 10,000 IU for women over 19.) For pregnant women: 2,500 IU for pregnant women under 18; 2,565 IU for pregnant women over 19. (Upper limit is 9,335 IU for ages 14 - 18 and 10,000 IU for women over 19. It should be noted that some experts recommend 8,000 IU as the upper limit during pregnancy.) Warning: Use of the topical acne medication tretinoin, a vitamin A derivative, during pregnancy can cause birth defects. For nursing women: 4,000 IU for nursing mothers under 18; 4,335 IU for nursing mothers over 19. (Upper limit is 9,335 IU for ages 14 - 18 and 10,000 IU for women over 19.) For men: 3,000 IU ages 14 - 18; 3,000 IU for ages 19 and above. (Upper limit is 10,000 IU.) Note: In determining the daily vitamin A allowance, experts also take note of provitamins, such beta carotene, that convert to vitamin A. Some experts recommend 3 - 6 mg of beta-carotene. Vitamin A is also now being measured with a new unit called the Retinol Activity Equivalent (RAE or RE). One RE is equal to 1 mcg. Retinol is the most active form of vitamin A and it is also converted in the liver from carotenoids. One RE is equal to 12 mcg of beta-carotene or 24 mcg of alpha-carotene or beta-cryptoxanthin).
Foods containing the vitamin	Animal products, such as liver, dairy products, eggs, and fish liver oil. Provitamin A carotenoids are also found in dark red, green, and yellow vegetables and fruits. Requires some dietary fat to be absorbed.
Effects of deficiencies	Skin disorders, severe diarrhea, and eye damage. In less developed countries severe deficiencies cause blindness in 250,000 children each year. Diets low in vitamin A may also increase the risk of developing cancer. Low dietary intake of vitamin A has been associated with impaired lung function in children.
People at risk for deficiencies	Preschool children and any child with inadequate intake of protein, calories, and zinc. Iron deficiency may also impair metabolism of vitamin A. People with asthma. People with serious disorders in the intestine, liver or pancreas, such as cystic fibrosis, steatorrhea, biliary obstruction, inflammatory bowel disease, cirrhosis, and others. People who have undergone Roux-en-Y gastric bypass surgery. Vegans (vegetarians who do not eat eggs and dairy). Such individuals should be sure to have plenty of deep-colored fruits and vegetables. People who abuse alcohol. It should be noted, however, that people with alcoholism may be at risk for vitamin A deficiency, but a combination of high-dose vitamin A and alcohol may cause toxic effects in the liver. Healthy adults usually have a year's store of vitamin A in the liver, so temporary nutritional deficiencies or problems with fat absorption are unlikely to cause serious vitamin A deficiency problems.
Toxicities	Very toxic when taken in high-dose supplements for long periods of time. Symptoms of overdose include dizziness, nausea, vomiting, headache, skin damage, mental disturbances, and, in women, infrequent periods. Can affect almost every part of the body, including eyes, bones, blood, skin, central nervous system, liver, and genital and urinary tracts. Severe toxicity can cause blindness and may even be life threatening. In children, chronic overdose can cause fluid on the brain and as well as adult complications. High consumption of vitamin A may also increase the risk of gastric cancer and the risk of osteoporosis and fractures in both men and women. Pregnant women who take amounts not much higher than RDA levels increase the risk for birth defects in their children. Liver damage can occur in children who take RDA-approved adult levels over prolonged periods of time or in adults who take as little as five times the RDA-approved amount for 7 - 10 years.


	B Vitamins: General Information	Vitamin B1 (thiamin)
Benefits	The B vitamins have a wide and varied range of functions in the human body. Most B vitamins are involved in the process of converting blood sugar into energy.	Essential for converting blood sugar into energy and is involved in metabolic activities in nerves, heart, and muscles and in the production of red blood cells.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)		RDA is 1.2 mg per day for men and 1.1 mg for women.
Foods containing the vitamin		Best source is pork and good sources are dried fortified cereals, oatmeal, corn, nuts, cauliflower, and sunflower seeds. Supplements for people with normal diets and health are unnecessary.
Effects of deficiencies	Deficiencies are uncommon in the U.S., but when they occur, they usually involve several B vitamins, since many of them come from the same food groups.	Severe vitamin B1 deficiency is known as beriberi. It can cause visual disturbances, paralysis, staggering, loss of sensation in the legs and feet, psychosis, and congestive heart failure.
People at risk for deficiencies	Alcohol interferes with these vitamins, and some of the physical and mental problems that alcoholics experience may be attributed to a deficiency of B vitamins. Elderly people are also at risk for deficiencies because of inadequate diets and potential interference with B-vitamin absorption by medications. Deficiencies can occur in severely malnourished people or in those receiving long-term dialysis or intravenous feeding. Vegetarians may be at risk.	See general vitamin B description.
Toxicities	Because the B vitamins are water-soluble and eliminated in the urine, toxic reactions from oral administration of most of them are extremely rare. (Exceptions are niacin and B6.) It should be noted that substances known as B15 (pangamic acid) and B17 (laetrile) are neither vitamins nor nutrients; both chemicals are highly dangerous and have no proven nutritional or health value.	No toxic effects have been reported from thiamin.


	Vitamin B2 (riboflavin)	Vitamin B3 (niacin) also known as nicotinic acid	Vitamin B5 (Pantothenic Acid)
Benefits	Important in the production of energy.	Helps break down blood sugar for energy. Acts as a vasodilator, widening blood vessels and increasing blood flow. May be prescribed for improving cholesterol levels.	Important for metabolism of fats, carbohydrates, and proteins, as well as production of steroid hormones and other important chemicals.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	DRI is 1.7 mg.	DRI is 20 mg.	Adequate intake (AI) is 4 - 7 mg.
Foods containing the vitamin	Liver, dried fortified cereals, dairy products, fish. Some dark green vegetables. Supplements for people with normal diets and health are unnecessary.	Mackerel, swordfish, chicken, veal, dried fortified cereals, pork, salmon, and beef liver. Supplements are unnecessary in people with normal health and diets.	Whole grains, beans, milk, eggs, and liver. Supplements are unnecessary in people with normal health and diets.
Effects of deficiencies	Deficiencies affect the skin and mucous membranes and can cause cracks on the lips or corners of the mouth, eczema of the face and genitals, a burning sensation on the tongue, eye irritation. May contribute to anemia when iron levels are low and contribute to elevated levels of homocysteine, a heart risk factor.	Deficiency causes pellagra; symptoms can include eczema, intestinal and stomach distress, depression, headache, thinning of the hair, and excess saliva production.	Deficiency is unlikely except in company with other B vitamin deficiencies. Symptoms include abdominal distress, burning sensation in the heels, and sleep problems.
People at risk for deficiencies	See general vitamin B description.	Alcoholics and any malnourished persons.	Alcoholics and any malnourished persons.
Toxicities	Until recently, no toxic effects had been reported even from large doses of riboflavin. However, one study indicated that high consumption of vitamin B2 might increase the risk of stomach cancer. More research is needed. (In the same study, vitamins B1, B3, and B6 were protective.)	Even mildly high doses of niacin can cause hot flushing of the face and shoulders, headache, itchiness, and stomach problems. Some report heart disturbances and temporarily lowered blood pressure. Large doses may produce ulcers, gout, diabetes, and liver damage, which are usually reversed when high doses are discontinued.	Although no toxicity has been reported in humans, high dosages have caused liver damage in rats.


	Vitamin B6 (pyridoxine)	Vitamin B12 (cobalamin)
Benefits	Has an effect on over 60 proteins in the body, importantly, those that play a role in the nervous system, in red and white blood cell production, and in heart disease.	Essential for the production of blood cells, manufacturing genetic material, and for healthy functioning of the nervous system. New evidence suggests that high levels of B12 may protect against colon and rectal cancer.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	RDA is 1.3 mg in adults under 50 and 1.7 mg for older men and 1.5 for older women. (Some experts recommend 3 to 6 mg for people who need heart protection.) Upper limit is 100 mg for adults.	RDA is 2.4 mcg in men and nonpregnant women, 2.6 mcg in pregnant women, and 2.8 mcg in nursing mothers.
Foods containing the vitamin	Meats, oily fish, poultry, whole grains, dried fortified cereals, soybeans, avocados, baked potatoes with skins, watermelon, plantains, bananas, peanuts, and brewer's yeast.	The only natural dietary sources are animal products, including meats, dairy products, eggs, and fish (clams and oily fish are very high in B12). Like other B vitamins, however, B12 is added to commercial dried cereals.
Effects of deficiencies	Increased levels of homocysteine, associated with heart disease and possibly Alzheimer's disease. Skin problems and nervous system disorders, including impaired memory and concentration. Increased risk for kidney stones. One study found a correlation between vitamin B6 deficiency and inability to conceive or carry a child to term. In unborn children, some evidence shows that lack of vitamin B6, in addition to vitamin B12 and folic acid, may be responsible for defects such as cleft lip and palate and spina bifida. Supplementation with these vitamins is advised during pregnancy. Note: People who have been taking more than 50 mg for some time and stop suddenly are at risk for a so-called rebound deficiency. When people stop, they should taper off slowly.	Deficiencies elevate homocysteine, a possible risk factor for heart disease and Alzheimer's disease. Increased risk of bone fractures. Abnormal gaits in the elderly. May cause severe depression, memory loss, instability, disorientation, and decreased reflexes, and possibly hearing loss. Children who are deficient may experience growth failure. Deficiencies in pregnant and breast-feeding women may cause neurologic harm in their offspring. A genetic defect that causes vitamin B12 deficiencies is responsible for pernicious anemia, a serious disorder that causes rapid heart rate, shortness of breath, dizziness, weakness, and fatigue. It must be treated with injections of vitamin B12 or else neurologic damage may occur.
People at risk for deficiencies	Alcoholics and any malnourished person. In rare cases, infants are born unable to metabolize pyridoxine; in such cases, seizures or convulsions can occur and vitamin B6 must be administered.	Alcoholics and any malnourished persons. Evidence suggests deficiencies may be caused by Helicobacter pylori (H. pylori) bacteria (a cause of ulcers). Nearly 30% of patients with inflammatory bowel disease have vitamin B6 deficiency, as well as low levels of iron and vitamin D. People who take the antibiotic isoniazid, high blood pressure medication hydralazine, and the drug penicillimine are at risk for vitamin B6 deficiency. The elderly and people with Crohn’s disease and those who have undergone ileal and ileocolonic resection may have trouble absorbing natural vitamin B12 and require supplements. Some evidence shows that patients with Parkinson’s disease treated with levodopa plus dopa decarboxylase inhibitor (DDC-i) and catechol-O-methyltransferase inhibitor (COMT-i) have low levels of both vitamin B12 and folate. As a result, they need to take supplements of these vitamins. Other studies have found that patients with diabetes treated with metformin, but not roziglitazone, are at risk for low levels of vitamin B12. Vitamin B12 deficiency is also common in patients with polyneuropathy. In up to one-third of patients, vitamin B12 deficiency is the sole or major contributing cause of their neuropathy. Treatment with vitamin B12 has a high success rate in improving the symptoms. Vegetarians are at higher risk for deficiencies.
Toxicities	Very high doses can cause nerve damage with symptoms of instability and numbness in the feet and hands, which may be permanent in some cases. Of specific concern are possible adverse effects on nerve development in the offspring of pregnant women who take large doses, such as for morning sickness.	There is no evidence of toxicity with this vitamin.


	Biotin (a B vitamin)	Choline (a B vitamin)	Folate, or Folic Acid, its synthetic form (a B vitamin)
Benefits	Involved in the production of amino acid proteins and fatty acids.	Essential for fetal brain development and for learning and memory.	Important for many metabolic processes in the body. It is used in the manufacturing of neurotransmitters (chemical messengers in the brain), in protecting the heart, and for synthesizing genetic materials (DNA) in the cells. It may improve blood flow.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	There is no DRI for biotin; some experts suggest 30-100 mcg.	RDA 425 mg for nonpregnant women, 450 mg for pregnant women, and 550 mg for nursing women.	Supplements may be folate (natural) or folic acid (synthetic). Folic acid is nearly twice as potent as folate. DRI is 400 mcg (.4 mg) of folate for the general population, 600 mcg during pregnancy and 500 mcg while nursing. Women who are planning to be pregnant should certainly take 400 mcg of folic acid before conception, during pregnancy, and while nursing.
Foods containing the vitamin	Dietary sources are eggs, milk, liver, mushrooms, bananas, tomatoes, whole grains, nuts, and brewer's yeast. Also produced by bacteria in the intestines.	Peanuts, eggs, cauliflower, and meats, especially liver.	Avocado, bananas, orange juice, cold cereal, asparagus, green leafy vegetables, dried beans and peas, and yeast. Folic acid supplements are now added to commercial breads and cereals.
Effects of deficiencies	Deficiencies are almost unheard of.	Low levels during pregnancy increase risk of birth defects in newborns.	As with vitamins B6 and B12, deficiencies of folate elevate levels of homocysteine, an amino acid in the body that may increase the risk for heart disease, and possibly Alzheimer's disease. Folic acid supplements lower homocysteine levels, but with little or no impact on risk of atherosclerotic disease in the heart or in the peripheral arteries and veins. This suggests that homocysteine may be a marker of cardiovascular disease, rather than a cause. This being said, one 2007 study found that folic acid supplementation in patients with low folic acids levels substantially reduced the risk of a first stroke. Low levels during pregnancy increase risk of birth defects in newborns, and folic acid supplementation plays a key role in preventing birth defects. Folic acid deficiencies Deficiencies can also cause depression and megaloblastic anemia and impair concentration, memory, and hearing.
People at risk for deficiencies			Alcoholics, malnourished persons, people with conditions that disturb the small intestine, people taking certain drugs, particularly methotrexate. Other risk factors for deficiency: high-dose aspirin, smoking, treatment for seizures, taking oral contraceptives.
Toxicities		Excessive doses can cause intestinal problems, and there is also some concern that high doses can be carcinogenic.	Possible connection between high consumption of folate/folic acid and colorectal cancer now under exploration. Some link between high doses and central nervous system disorders, zinc deficiency, and seizures in epileptics. This risk appears to be low, but results indicate that megadoses should be avoided. High amounts in the elderly may mask symptoms of vitamin B12 deficiencies.


Benefits	Vitamin C is a water-soluble vitamin. Acts as an antioxidant (reduces harm from damaging chemical processes in the body). Essential for the production of collagen, the basic protein in bones, cartilage, tendons, and ligaments. A 2007 study found that vitamin C supplements can help prevent the development of complex regional pain syndrome following wrist fracture. Another study found that prostate cancer risk dropped as consumption of vegetables high in vitamin C, such as broccoli and bell peppers, rose. It may also protect against brochoconstriction during exercise in people with asthma. May help boost the immune system.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	DRI is 75 mg (women) and 90 mg (men). (Smokers need an additional 35 mg.)
Foods containing the vitamin	Citrus fruits and juices, papayas, hot chili peppers, bell peppers, broccoli, potatoes, dark leafy greens, kale, red cabbage, cauliflower, cantaloupe, sweet potatoes, and Brussels sprouts. Orange juice is the most important source of vitamin C in the U.S., with frozen juice being the best source of the vitamin.
Effects of deficiencies	Scurvy is the primary deficiency disease. Affects most body tissues, particularly bones, teeth, and blood vessels. Early symptoms include tiredness, weakness, irritability, weight loss, and vague muscle aches. Later symptoms are bleeding gums, wounds that won't heal, rough skin, and wasting away of the muscles. Deficiencies may contribute to periodontal disease and gallstones. Low dietary intake of vitamin C has been associated with impaired lung function in children. Low intake may also increase lead levels in the blood.
People at risk for deficiencies	Deficiency has been uncommon in the U.S., usually occurring in the elderly, alcoholics, cancer patients, and some people on severely limited diets low in fresh fruits and vegetables. Surprisingly, however, studies now suggest that as many as 16% of middle-aged Americans, with the highest risk in smokers and middle aged men, are deficient in vitamin C. High doses of aspirin taken over a long period of time can interfere with vitamin C.
Toxicities	Tolerable upper limit is 2000 mg/day. High doses may cause headaches and diarrhea. Long-term high doses may increase risk for kidney stones. Ascorbic acid increases iron absorption so people with blood disorders, such as hemochromatosis, thalassemia, or sideroblastic anemia, should avoid high doses. Large doses may also thin blood and interfere with anticoagulant medications, blood tests used in diabetes, and stool tests. Rebound scurvy can occur after abrupt withdrawal from long-term large doses. This may affect infants or pregnant women who withdraw suddenly from high doses.


Benefits	Vitamin D is actually a single term for several hormones that are stored mainly in the liver and also in fat and muscle tissue. It is essential for the absorption of calcium into the bone and for normal bone growth.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	RDA is 200 IU (5 mcg) per day for children and most adults to age 50, 400 IU (10 mcg) for people between ages 50 and 60, and 600 IU over age 70. and 1000 IU (15 mcg) for those over 70. People who are housebound, do not have sufficient exposure to sunlight, or are dark-skinned individuals, as well as breast-fed infants, should take need vitamin D supplements. The maximum tolerated dose after the age of 12 months is 2,000 IU/day
How the body gets the vitamin	There are two forms of vitamin D. Vitamin D3 is made in the body from a chemical reaction to the ultraviolet radiation in sunlight. Vitamin D2 is found in a few food sources, including vitamin D fortified milk, fatty fish, egg yolk, and liver.
Effects of deficiencies	Softening of the bones caused by low levels of calcium and phosphorous (called rickets in children and osteomalacia in adults). Also increases the risk for bone-related knee problems, and hip fractures in postmenopausal women. Associated with a higher risk for prostate cancer and breast cancer risk. Evidence suggests that vitamin D deficiency may be responsible for poor muscle strength after bone fracture. The deficiency is associated with high blood pressure and diabetes, but it is unknown whether supplementation with vitamin D impacts these diseases. Studies now suggest vitamin D plays a role in age-related macular degeneration (AMD), and that drinking milk with added vitamin D can help protect against AMD.
People at risk for deficiencies	Older people, particularly if they live in the North, who are underexposed to sunlight. Obesity may also increase risk. There is some concern, in fact, that vitamin D deficiency may be a growing problem in the US among younger adults as sunscreen use becomes widespread. Individuals at highest risk for vitamin D deficiency are those who assiduously avoid the midday sun, wear protective clothing, regularly use sunscreen, and have dark skin. Exposure to sunlight for about 15 - 20 minutes at mid-morning or mid-afternoon three times a week is recommended for most people who live in temperate climates.
Toxicities	Vitamin D is very toxic in high doses. In infants, daily amounts higher than 1,000 IU can cause mental and growth retardation, kidney failure, and death. In children and adults, daily amounts over 50,000 IU can cause weakness, anorexia, vomiting, diarrhea, and mental changes. Prolonged use of megadoses can cause calcification of soft tissue and life-threatening kidney failure. Low-calcium diets and withdrawal from the vitamin can usually reverse the side effects except for kidney failure.


	Vitamin E (Tocopherol or Tocotrienol)	Vitamin K
Benefits	A fat-soluble antioxidant vitamin that helps prevent cell membrane damage and may inhibit oxidation of LDL cholesterol (a process that increases its harmful effects on arteries). Researchers once thought that vitamin E might protect against cardiovascular disease. This theory has been debunked. However, a 2007 study found that vitamin E supplementation reduced the risk of deep vein thrombosis (DVT) in women at risk for, or with a history of, DVT. Vitamin E supplements have also been shown to produce a statistically significant decrease in menopausal hot flashes. There is also early evidence that vitamin E may protect against ovarian cancer.	The most important function of vitamin K is its role in blood clotting and prevention of bleeding. As a result, the vitamin may be able to help treat hepatoma, leukemia, and hepatocellular carcinoma, a form of liver cancer. The vitamin also contributes to maintaining healthy bones and healing fractures. Vitamin K is widely used in Japan to treat osteoporosis, and studies suggest it may be effective in treating rheumatoid arthritis.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	RDA is 15 mg (22 IU) for all adults, including pregnancy women. Nursing mothers need 19 mg (28 IU). (Supplements should be taken along with some oil or fat to be absorbed.) Vitamin E is composed of 8 compounds (four tocopherols and four tocotrienols). Vitamin E is most often available as supplements of dl alpha tocopherol (a synthetic form). Other vitamin E compounds may prove to be more active than the standard synthetic supplement. They include natural vitamin E, called d-alpha- or RRR-alpha-tocopherol succinate (VES). Other vitamin E compounds of interest are tocotrienol and beta and gamma tocopherol. Supplements that contain a combination of some of these forms may be most beneficial.	RDA is 60 - 65 micrograms (women) and 70 - 80 micrograms (men).
Foods containing the vitamin	Vegetable oils (particularly wheat germ oil), sweet potatoes, turnip greens, mangos, avocados, nuts, sunflower seeds, and soybeans. Tocotrienol (a possibly beneficial form) is found in natural tropical oils. Palm oil sold in the US is refined and does not contain tocotrienol.	Best dietary sources are canola oil, cruciferous vegetables, and soybean oil. Good sources are beef liver, bran, and olive oil. Also produced by bacteria in the intestines.
Effects of deficiencies	Deficiencies have not been established.	Easy bruising, bleeding. May increase the risk of hip fractures in women.
People at risk for deficiencies	Low-birth weight infants. People who eat a low-fat diet. People with medical problems that impair fat absorption, such as Crohn's disease, cystic fibrosis, steatorrhea, liver diseases (such as cirrhosis). People with abetalipoproteinemia, a rare genetic disorder that impairs fat metabolism.	Deficiency may occur in patients who have problems absorbing fats, such as those with cirrhosis, people who are on long-term antibiotic therapy, or who are taking other medications, including cholestyramine, Dilantin, and phenobarbital. Some evidence suggests that more young people may be deficient than previously believed.
Toxicities	Upper level recommended is 1,500 IU of alpha tocopherol. Large doses may cause bleeding problems, particularly in people taking anti-clotting medications. Some research now indicates that vitamin E, like other antioxidants, may have pro-oxidant and damaging effects. Although vitamin E is one of the best studied vitamins, research has yielded conflicting results, and definitive conclusions about the benefits and toxicity of vitamin E have not yet been determined. In a major 2005 study, there was no significant difference in cancer rates between people who took 400 IU of vitamin E daily and those who did not, although those who took the supplement had a higher risk of heart failure. Additional studies also link high levels of vitamin E with a slightly increased risk of heart failure and death. On the other hand, studies show that vitamin E may reduce heart problems in high-risk patients such as certain people with diabetes.	Allergic-type responses, including rash and itching, to high doses have been reported. Those who are taking Coumadin, an anticoagulant, should not take vitamin K without consulting a physician. Vitamin K deficiency can cause anorexia, lethargy, growth retardation, bone loss, soft tissue calcification, and death.

Carotenoids

Carotenoids are a group of more than 700 fat soluble nutrients that produce the colors in foods such as carrots, pumpkins, sweet potatoes, tomatoes, and other deep green, yellow, orange, and red fruits and vegetables. Many are proving to be very important for health. Beta carotene is the most widely studied carotenoid, but others are proving to be of great interest. As with some, but not all, carotenoids, beta carotene is known as a provitamin A because it converts to the vitamin in the body.

They are categorized as either xanthophylls or carotenes according to their chemical composition.

Carotenes are hydrocarbons and most are found in yellow, orange, and red vegetables. They include beta and alpha carotene and lycopene.

Beta Carotene and other Provitamin A Carotenoids. Beta carotene, alpha-carotene, and beta-cryptoxanthin are carotenes that are converted into vitamin A or retinol (the active form of vitamin A) in the body. They are found in many yellow fruits and vegetables. Beta carotene is the most widely studied carotenoid. Evidence now strongly suggests that when taken as a separate supplement it can have harmful effects.
Lycopene. Lycopene is responsible for the red color in fruits and vegetables, including tomatoes, red grapes, watermelon, and pink grapefruit. It is also found in papayas and apricots. It does not convert to vitamin A but may have important cancer fighting properties and other health benefits.
The beneficial actions of most carotenes such as those tomatoes, corn, and carrots, appear to be enhanced by cooking them, especially in oil (preferably olive, canola, or another monounsaturated oil). (Note: Cooking can also destroy certain nutrients, such as vitamin C, in these vegetables.)

Xanthophylls contain oxygen and most are found in green vegetables, such as broccoli, cabbage, and kale. They are also in yellow fruits and vegetables. Xanthophylls include lutein and zeaxanthin, which are both stored in the retina of the eye. Neither converts to vitamin A. Both are powerful antioxidants and may be very important for healthy eyes. Unlike carotenes, cooking may reduce the antioxidant activity of some xanthophylls in foods, although probably not to any significant degree.

Phytochemicals

The word phytochemicals means plant chemicals. Hundreds of phytochemicals are being studied. Many are believed to have a major positive impact on human health. Some contribute to the bright and vivid colors found in fruits and vegetables. The results of studies on specific phytochemicals are not necessarily applicable to the vegetables or fruits that harbor small concentrations of these chemicals.

Nevertheless, it is obvious that vegetables and fruits are healthful, which is probably due to some balance of phytochemicals, carotenoids, vitamins, fibers, and minerals rather than any single substance.

The benefits of individual phytochemical supplements are largely unproven. Furthermore, they are not regulated and high concentrations of some may behave like drugs and can be toxic and possibly even contribute to cancer cell growth.

Polyphenols are important phytochemicals, and flavonoids (or catechins) are members of the polyphenol family that may have significant health benefits. Laboratory studies have shown that specific flavonoids suppress tumor growth, interfere with sexual hormones, prevent blood clots, and have anti-inflammatory properties. In general, flavonoids are found in celery, cranberries, onions, kale, dark chocolate, broccoli, apples, cherries, berries, tea, red wine or purple grape juice, parsley, soybeans, tomatoes, eggplant, and thyme. Most common berries contain flavonoids and are particularly rich in potent antioxidants.

Among the important flavonoids are resveratrol, quercetin, and catechin. Evidence suggests that resveratrol (found in red wine, grapes, olive oil) may be extremely potent. In laboratory studies, it increases cell survival and has been shown to increase the life span of worms and fruit flies. Catechins are the primary flavonoids in tea and may be responsible for its possible beneficial effects. Flavonoids in dark chocolate may also be health protective.

Isoflavones, commonly known as phytoestrogens, have actions that are similar to the female hormone estrogen. A high consumption of soy, which is primarily composed of isoflavones, may reduce symptoms resulting from estrogen depletion during menopause. In a recent study, supplementation with isoflavones decreased hot flashes by 57% and night sweats by 43%, but other research is less favorable.

Lignan is another phytoestrogen and is found in the fiber layers of whole-grains, berries, some seeds, some vegetables, and a few fruits.

Isothiocyanates and related substances, indoles, are also known as mustard oils and are responsible for the sharp taste in cruciferous (also called brassica) vegetables. Such vegetables include broccoli, cabbage, Brussels sprouts, cauliflower, collards, kale, kohlrabi, mustard greens, rutabaga, turnips, and bok choy. Isothiocyanates also stimulate enzymes that convert estrogen to a more benign form and may block steroid hormones that promote breast and prostate cancers. (Cruciferous vegetables are also high in fiber, vitamin C, and selenium.)

Monoterpenes have two important phytochemicals, perillyl alcohol and limonene. They block proteins that stimulate cell growth and reproduction and are being tested for actions against cancer. Limonene is found in the peels of citrus fruits.

Organosulfurs are part of the allium family of phytochemicals. Compounds, such as allicin, may have benefits on the immune system, assist the liver in rendering carcinogens harmless, and reduce production of cholesterol in the liver. These compounds are found in garlic, leeks, onions, chives, scallions, and shallots.

Capsaicin seems to reduce levels of substance P, a compound that contributes to inflammation and the delivery of pain impulses from the central nervous system. Research suggests that it may inhibit cancer-generating substances. It is found in hot red peppers.

Sterols, which include sitosterol, stigmasterol, campesterol, and squalene, are found in vegetable oils. Sitosterol is the most studied and appears to have cholesterol-lowering effects.

Beta-sitosterols may help improve urine flow and urinary symptoms in men with enlarged prostate glands (benign prostatic hyperplasia, or BPH). A recent review study of five randomized trials (519 men) found that urinary flow and other urinary symptoms improved in men who took the herbal remedy from 4 - 26 weeks. The study’s authors cautioned that while beta-sitosterols show effectiveness in the short term, their long-term effectiveness, ability to prevent complications from BPH, and safety are not known. More research is necessary. Beta-sitosterols come from South African star grass, Hypoxis rooperi, or species of Pinus and Picea.

Healthy Foods

Evidence increasingly suggests that a varied diet, not individual food chemicals, is essential for basic health and a longer life. Such diets are rich in fresh fruits and vegetables and whole grains, and low in saturated fats.


Foods	Phytochemicals and Carotenoids	Vitamins and other valuable food components	Benefits
Apples	Flavonoids		May have activity against certain cancers (lung). Also may help maintain healthy cholesterol. May protect against asthma.
Beans	Flavonoids	Folate, iron, potassium, and zinc	Some experts believe beans are the perfect food.
Berries, all kinds of dark colored	Ellegic Acid	Vitamin C, minerals	The anthocyanins in berries such as bilberries, blueberries, cranberries, elderberries, and others, have numerous healthful properties including anti-cancer and antioxidant effects. Bilberry (Vaccinium myrtillis) is widely used to prevent macular degeneration. Blueberries may protect the aging brain. (In one study blueberries were most effective.)
Broccoli (also kale, Brussels sprouts, cauliflower)	Flavonoids, isothiocyanates, lutein, beta and alpha carotene. Note: Young sprouts of broccoli and cauliflower contain much higher levels of isothiocyanates than their mature forms.	Vitamin C, folate, fiber, and selenium	Anticancer properties. Protective against heart disease and stroke.
Carrots and other bright yellow vegetables	Lutein, beta carotene and other provitamin A carotenoids	Vitamin A (converted from carotenoids), vitamin C	Protects eyes, lungs. (Cooking carrots may increase the potency of food nutrients.)
Chocolate, dark. Note: Milk chocolate does not have benefits.	Flavonoids		Heart protective (may improve lipids and help prevent blood clotting. May have protective properties against lung cancer (not other cancers).
Eggs	Lutein	Many B vitamins, vitamin A, vitamin D	Although egg yolks are high in cholesterol, very little of it has a negative effect on people with normal levels. And the health benefits of eggs are now known to be very high. (People with diabetes or those with high cholesterol should restrict eggs, however.)
Fish, oily (mackerel, salmon, sardines)		Vitamin B3, B12. Essential fatty acids, selenium	Heart and brain protective.
Garlic	Allium (organosulfurs)		Possibly protective against certain cancers, heart diseases, and infection. Heating garlic can reduce benefits. Allowing crushed fresh garlic to stand 10 minutes before heating, however, may preserve beneficial chemicals while cooking.
Ginger	Zingiberaceae		Cancer fighting properties.
Grains (whole)	Lignans (phytoestrogens)	Vitamin B, Selenium (important antioxidant mineral), fiber, folate	May help reduce the ability of cancer cells to invade health tissue.
Grapes, including purple grape juice, and red wine	Flavonoids, (resveratrol, quercetin and catechin)		Fight heart disease and cancer. May help lower the risk for asthma.
Nuts		Vitamin E, vitamin B1, essential fatty acids, folate	Protects the heart and may help prevent stroke.
Onions	Flavonoids, allium (organosulfurs)		May have activity against certain cancers (lung).
Oranges	Monoterpenes	Vitamin C, folate, potassium.	Many health benefits. Increases HDL levels.
Potatoes (Sweet)		Vitamin C, vitamin E, vitamin A	Many health benefits.
Soy. The best products are tofu, soy milk, or whole soy protein.	Isoflavones (phytoestrogens), flavonoids, phytosterol, phytate, saponins.		May have effects similar to estrogen, including maintaining bone and benefiting the heart in women. May also be protective against prostate cancer and possibly other cancers. More studies are needed. Effects on breast cancer are uncertain. (Note: Soy may have different effects in men than in women. Of some concern is one study reporting more mental decline in men who consume greater amounts of tofu.)
Spinach and other dark green leafy vegetables	Zeaxanthin, Beta carotene	Vitamin C, folate, vitamin A (converted from carotenoids)	Protects lungs and brain.
Tea (Both black and green tea are beneficial. Best results associated with green tea.)	Flavonoids (primarily catechins)		Cancer fighting properties, particularly in green tea, which may be especially beneficial for smokers. Both black and green tea may protect against heart disease and stroke, although studies are mixed. Tea drinking also may help with weight control and help prevent osteoporosis.
Tomatoes	Lycopene, Flavonoids	Vitamin C, biotin, minerals	Studies link to reductions in prostate and other cancers. Infection fighters.
Note on Organic versus Inorganic Products. There is some evidence that organic produce has higher levels of antioxidants and that some agricultural chemicals may destroy flavonoids. Nevertheless, organic produce is expensive, and fruits and vegetables, no matter how they are grown, are still filled with healthful nutrients.

Dietary Health Benefits

The benefits of any dietary factors are very difficult to prove, and, to date, there is little evidence that most dietary supplements protect against major diseases in otherwise healthy people with normal eating habits. An exception is lutein, which is known to reduce the risk of macular degeneration. However, a diet naturally high in vitamins and minerals can be the best defense against many diseases. Fresh fruits and vegetables and whole grains are the primary sources of vitamins, carotenoids, and vitamins, as well as of fiber and important minerals.

Description of Oxygen-Free Radicals (Oxidants). Currently, the most important benefit claimed for vitamins A, C, E, and many of the carotenoids and phytochemicals is their role as antioxidants, which are scavengers of particles known as oxygen-free radicals (also sometimes called oxidants). These chemically active particles are by-products of many of the body's normal chemical processes. Their numbers are increased by environmental assaults, such as smoking, chemicals, toxins, and stress. In higher levels, oxidants can be very harmful in the following way:

They can damage cell membranes and interact with genetic material, possibly contributing to the development of a number of disorders including cancer, heart disease, cataracts, and even the aging process itself.
Oxygen-free radicals can also enhance the dangerous properties of low-density lipoprotein (LDL) cholesterol, a major player in the development of atherosclerosis.

Description of Antioxidants and Warnings on High-Dose Supplements. Antioxidant vitamins (A, C, and E), carotenoids, and many phytochemicals can neutralize free radicals. Unfortunately, although it is clear that vitamins are required to prevent deficiency diseases, high doses of vitamin C, vitamin E, and beta carotene supplements may also have pro-oxidant effects, which can be harmful in patients with cancer. In these people, high doses of antioxidant vitamins may actually protect cancer cells just as they do healthy cells.

The strongest evidence on negative effects to date comes from studies reporting 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. One study also reported a higher risk for cancer in male smokers who took multivitamins plus A, C, or E.

Some evidence also indicates that high doses of vitamin C may speed up atherosclerosis, or hardening of the arteries. In one study, women with heart disease who took antioxidant vitamins had a higher risk for heart attack or death than those who didn't take one.

Another study also reported a higher incidence and greater severity of respiratory infections in older adults who took 200 mg of vitamin E daily. Some researchers speculate that certain immune factors generate oxidants to fight bacteria. This antioxidant vitamin, then, may block that action. Research published in 2005 suggests that those who take large amounts of vitamin E (1,500 IU/day) may slightly increase their risk for heart failure and death, but this evidence is not considered conclusive. Further study is necessary.

Vitamins and Heart Protection.

Antioxidant Vitamins A, C, and E. Deficiencies in vitamins A, C, E, and beta carotene have been linked to heart disease. All of these nutrients have antioxidant effects and other properties that should benefit the heart. A study in patients with heart failure has shown that vitamin C can work with dobutamine, a powerful intravenous medication, to strengthen the heart’s ability to contract following a heart attack. In fact, a 2005 study has found that taking high doses of vitamin E is associated with an increased risk of heart failure. In 2007, the Women’s Antioxidant Cardiovascular Study failed to find that vitamins C, E, and beta carotene could reduce the risk of heart attack, stroke, need for revascularization, or cardiovascular death in women. According to the U.S. Preventive Service Task Force, evidence is insufficient to confirm or refute the benefits of supplements of any of these vitamins in protecting against heart disease.
Folate and B12 Vitamins. Deficiencies in the B vitamins folate (known also as folic acid) and B12 have been associated with elevated blood levels of homocysteine, an amino acid that has been associated with a higher risk for heart disease, stroke, and heart failure. One study, reported lower failure rates after heart surgery in patients who took folic acid and vitamins B12 and B6. And a major 2002 study suggested that lowering homocysteine levels with folic acid would reduce the risk for heart disease by 16% and stroke by 24%. However, a 2007 trial in adults with stable coronary artery disease found that lowering homocysteine levels 33% with B vitamins and folic acid had no effect on arterial inflammation, meaning that lower levels were unlikely to offer protection against heart attack or stroke. More evidence is needed to determine whether homocysteine plays a causal role in cardiovascular disease and whether the B vitamins are protective. Folate improves blood flow through the arteries, which may be important for the heart, regardless of its effect on homocysteine. Although people with high levels of homocysteine are prone to damaging blood clots in their arteries and veins, a 2007 study found that lowering homocysteine with folic acid and other B vitamins does not reduce the incidence of blood clots in the peripheral veins (deep venous thrombosis).
Niacin. Niacin (vitamin B3) is used for lowering unhealthy cholesterol levels. Although vitamin B3 is available over the counter, it can have significant side effects. A physician should prescribe niacin in order to ensure its safety and effectiveness. [See In-Depth Report #23, Cholesterol.]

Carotenoids and Heart Protection. Studies have reported that a diet high in fruits and vegetables containing beta carotene, lycopene, and other carotenoids may reduce the risk of heart attack. A small Finish study found that a diet high in tomatoes reduced total cholesterol and LDL ("bad") cholesterol. Diets low in lycopene (particularly from tomatoes) were associated with a significantly higher risk of heart disease and stroke.

Atherosclerosis is a disease of the arteries in which fatty material is deposited in the vessel wall, resulting in narrowing and eventual impairment of blood flow. Severely restricted blood flow in the arteries to the heart muscle leads to symptoms such as chest pain. Atherosclerosis shows no symptoms until a complication occurs.

Phytochemicals and Heart Protection. Several phytochemicals are associated with heart protection.

Flavonoids. Certain flavonoids, found in both black and green tea, dark chocolate, onions, red wine or red grape juice, and apples, appear to be strongly heart protective. In one study, people who consumed the most flavonoids in foods had a 20% lower risk for heart disease than those with low consumption. Flavonoids may protect against damage done by cholesterol and help prevent blood clots. A number of studies have now reported heart protection from the flavonoid catechin, which is found in both black and green tea. The flavonoid resveratrol, which is found in grape skin, appears to be responsible for the well-known heart protective effects in red wine and purple grape juice.
Organosulfurs. Organosulfurs found in onions and garlic have been under investigation for possible beneficial effects on cholesterol levels. One study reported an association between taking garlic capsules and significantly lower cholesterol-build up in the arteries of older women but not in older men. In the study, daily garlic supplements dramatically reduced the build-up of newly formed plaque in the arteries, while having much less effect on older, harder plaque deposits. Garlic supplements for cardiovascular disease may be most beneficial when used during earlier years among men and later years among women.
Isoflavones. Soy protein is the most studied source of isoflavones (known as phytoestrogens, or plant estrogens). Not all studies are consistent, but the majority has shown an improvement in at least one of the cholesterol components in people who consumed at least 25 grams of soy protein. A 2007 meta-analysis of all soy protein studies performed from 1990 - 2006 found that soy protein significantly decreased total cholesterol and LDL cholesterol, but had no effect on HDL or triglycerides. The effect was particularly evident in people with hypercholesterolemia. A 2007 study found that 12 weeks of soy supplement lowered total cholesterol and LDL levels in both Caucasian and African-American postmenopausal women. Soy may also reduce other heart risk factors, at least in certain populations. For example, in one 2002 study, soy was beneficial for controlling blood sugar and lowering LDL in postmenopausal women with type 2 diabetes. In a 2007 study of overweight men and postmenopausal women, soy protein reduced blood pressure and arterial stiffness. In another study, soy protein was associated with lower systolic blood pressure in men. The best sources are soy products (tofu, soy milk) or whole soy protein. Powdered soy protein that contains at least 60 mg of isoflavones may provide similar benefits.
Sterols. The plant sterols, including sitosterol, are also proving to be potent cholesterol fighters by blocking the absorption of cholesterol in the intestine. Sitostanol, a derivative of sitosterol, is being used in new margarine products to lower cholesterol levels. Sterols and stanols are now found in breads, cereals, yogurt, and fruit juices.

A healthy diet rich in fruits and vegetables and low in salt and saturated fats may significantly lower the risk for a first stroke, perhaps by helping to protect against high blood pressure -- a major risk factor for stroke.

Vitamins and Stroke Protection. The effects of antioxidant vitamins and carotenoids on stroke, dementia, or both are being studied. Studies are conflicting, however. A 2007 study of 8,171 women with cardiovascular disease reported that vitamins C, E, and beta carotene offered no protection against heart attack and stroke.

The B vitamin folate (usually in the form of folic acid) may protect against stroke. However, exactly which people benefit from this therapy has yet to be determined. Studies have suggested that people who have higher blood levels of folate have a lower than average risk for stroke. Its primary benefit in this case appears to be to reduce levels of homocysteine, an amino acid that has been strongly linked to an increased risk of coronary artery disease, stroke, and Alzheimer's disease. A 2007 meta-analysis of 8 trials found that folate supplements decreased homocysteine 20% and lowered stroke risk 18%. Interestingly, lowering homocysteine with folic acid and B vitamins had no effect on heart attack, strokes, amputations, need for dialysis, or death in patients with chronic or end-stage kidney disease.

Carotenoids and Stroke Protection. Some, but not all, studies have reported a lower risk of stroke from carotenoids, including beta carotene and lycopene.

Many fresh fruits and vegetables contain chemicals that may fight many cancers, including lung, breast, colon, and prostate cancers. Examples of important cancer fighting foods include the following:

Cruciferous vegetables (such as cabbage, Brussels sprouts, and broccoli)
Tomatoes (which contain lycopene)
Carrots (which contain alpha carotene)

Some evidence suggests that antioxidants may enhance the anticancer effects of chemotherapy. In multiple studies, patients who maintained their antioxidant levels were better able to withstand the high stress caused by chemotherapy or radiation therapy compared to those with low antioxidant levels. Antioxidant nutrients that may help reduce the side effects of chemotherapy include vitamins E and C, beta carotene, genistein and daidzein (isoflavones found in soy), and quercetin (found in red wine an purple grape juice).

Any protective effects of vitamins or specific phytochemical against cancer, however, appear to depend on the cooperative effort among them. Individual supplements of any vitamin or food chemical have not as yet shown any benefits.

Additionally, certain supplements may actually encourage tumor growth, particularly when taken in large amounts. Two 2007 studies found a connection between folate supplements and colorectal cancer. In one study, which was designed to evaluate the benefits of folic acid in patients who had previous colorectal adenomas (precancerous polyps), the researchers instead found that folic acid was associated with a higher risk of having 3 or more adenomas and noncolorectal cancers. In another study, it was noted that the downward trend in colorectal cancer diagnoses abruptly started to rise in 1996 when mandatory folate enrichment of grains within the U.S. and Canada began. Rates continue to exceed pre-1996 levels. Additionally, a large 2007 National Cancer Institute/AARP study found an increased risk of advanced and fatal prostate cancer in men who took more than 7 multivitamins a week, but no association between multivitamin use and localized prostate cancer.

High consumption of cruciferous vegetables (at least once per week) was associated with lower risk of kidney cancer, and low consumption (less than once per month) of cruciferous vegetables was associated with higher risk of kidney cancer in a multinational 2007 European study. Cruciferous vegetables also appear to offer protection against head and neck cancer resulting from chemical toxins found in cigarettes and alcohol, for example.

Vitamins and Cancer Protection. Because many cancers are thought to be initiated by the effects of oxygen-free radicals on DNA, the antioxidants A, C, and E and beta carotene have been intensively studied. A major study found that men who took selenium for 6 or 7 years reduced their risk of prostate cancer by 52%. Nevertheless, most individual supplements have not been proven to protect against cancer, and high doses may be dangerous.

A 2007 review of the diets of men exposed to asbestos found a decreased risk of prostate cancer associated with increasing intakes of vitamin C-rich vegetables, but not fruits and vegetables high in vitamin A. The chemopreventive role of silymarin (Silybum marianum), found in milk thistle extract, has been extensively studied and has shown anticancer efficacy against various cancers, especially prostate and skin, by inhibiting UVB radiation.

A review of 13 cancer registries found 416,134 cases of skin cancer and 3,776,501 cases of non-skin cancer as a first cancer. Rates from cancer registries in sunny countries (such as Australia and Spain) and less sunny countries (such as Canada and Iceland) were compared. The researchers concluded that vitamin D production in the skin decreases the risk of several solid cancers, especially stomach, colorectal, liver and gallbladder, pancreas, lung, female breast, prostate, bladder, and kidney cancers. The apparently protective effect of sun exposure against second primary cancer is more pronounced after non-melanoma skin cancers than melanoma.

Consumption of aflatoxins, a common fungus-related toxin infecting cereal grains, oil seeds, spices, tree nuts, and the milk of animals fed contaminated feed, is known to cause hepatocellular carcinoma, a deadly form of liver cancer. Rodent studies have shown that phenolic antioxidants, dithiolethiones, isothiocyanates, and triterpenoids may act as chemopreventive agents, dispersing aflatoxins and protecting against hepatocellular carcinoma. Human trials are planned. A similar study found that several isothiocyanates, diallyl sulfide, and polyphenolic compounds can prevent esophageal dysplasia from progressing to squamous cell carcinoma.

A review of all articles on vitamins and cancer published through February 2007 found that multivitamin/mineral supplement use may prevent cancer in individuals with poor or suboptimal nutritional status. One trial on poorly nourished Chinese showed supplementation with combined Beta-carotene, vitamin E and selenium reduced gastric cancer incidence and mortality, and overall cancer mortality. In a French trial, combined vitamin C, vitamin E, beta-carotene, selenium, and zinc reduced cancer risk in men but not in women. With few exceptions, neither beta-carotene nor vitamin E had benefits for preventing cancer. Beta-carotene supplementation increased lung cancer risk in smokers and persons exposed to asbestos.

A 2007 study of nearly 82,000 men and women in Sweden found that high intake of methionine was associated with reduced risk of pancreatic cancer. The same relationship was not seen with vitamin B6 or folate.

Vitamin A, C, and E. Although some studies have reported an association between low blood levels of these antioxidant vitamins and a higher risk for cancer, supplements of vitamins A, C, and E appear to have few advantages in most cases. And there are some studies finding higher cancer risks with high intakes of antioxidants. For example, a 2003 study reported a higher risk in melanoma in people with vitamin-C rich diets. Another study also reported a higher risk for cancer in male smokers who took multivitamins plus A, C, or E. (Vitamin E may be protective against bladder cancer and ovarian cancer.)
Vitamin D. Some studies have suggested that certain vitamin D compounds may inhibit certain cancer cells, specifically prostate cancer, from proliferating. More research is needed. In 2007, the National Cancer Institute confirmed that ultraviolet (UV) radiation exposure may reduce the risk of developing non-Hodgkin lymphoma (NHL), but only in patients with certain variations in the D vitamin receptor gene. A second 2007 study found that variations in this gene increase the risk of diffuse large B-cell lymphoma. A 2007 prospective analysis of 31,500 women in the Women’s Health Study evaluated calcium and vitamin D intake. The researchers found a moderately lower risk of premenopausal, but not postmenopausal, breast cancer with higher intakes of total calcium and vitamin D. A 2007 review of breast cancer cases reported in Ontario, Canada, found reduced breast cancer risks were associated with increasing sun exposure in women ages 10 - 19, less evidence for associations in women ages 20 - 29, and no evidence for ages 45 - 54. Researchers concluded that sun exposure earlier in life, particularly during breast development, may be key in the connection between vitamin D exposure and breast cancer risk.
Folic acid and B12. These B vitamins convert the amino acid homocysteine to methionine, a substance that helps prevent cells from becoming malignant. Folic acid may provide some protection against cervical and colon cancer. One small study showed a reduction of lung cancer cells in smokers taking folic acid and vitamin B12, but the study was very small, of short duration, and other factors might have biased the results. Still another study reported that folic acid may reduce the risk for breast cancer among women who regularly drink alcohol. (In the study, folic acid had no other effect on breast cancer.)

In 2006, a study for the National Institutes of Health reviewed randomized trials evaluating the effectiveness and safety of multivitamin and mineral supplements in preventing cancer and chronic disease. The studies had mixed results, and some supplements reduced cancer rates in certain populations. However, the reviewers concluded that current evidence is not sufficient to determine whether multivitamin and mineral supplements may prevent cancer and chronic disease.

Carotenoids and Cancer Protection. A number of studies have reported that fruits and vegetables rich in carotenoids are associated with protection against many cancers. Lycopene, found in tomatoes, may have particular value in protection against prostate, colon, lung, and bladder cancer. A 2005 study found that in one out of four men with genetic variations that cause them to be more sensitive to oxidative stress, supplementation with selenium, vitamin E, and lycopene significantly reduces the risk of prostate cancer. Individual supplements, however, do not offer any advantage. In fact, evidence now strongly suggests that beta carotene supplements increase the risk for lung cancer in smokers and people exposed to asbestos

Phytochemicals and Cancer Protection. The following phytochemicals appear to have cancer-protecting properties.

Isothiocyanates. Isothiocyanates and sulforaphane, found in cruciferous vegetables, may block the effects of carcinogens and suppress tumor growth. In one study, for example, women with the highest consumption of cruciferous vegetables had a 24% lower risk of breast cancer than women with the lowest consumption.
Isoflavones. Isoflavones, found in soy beans and flax seed, behave like estrogen in some ways and not in others. Researchers are very interested, then, in their effects on hormone-related cancers, including breast and prostate cancers. Much research has focused on soy. In general, a number of Asian studies have reported an association between a higher intake of soy and a lower incidence of reproductive and breast cancers. The effects of phytoestrogens, however, in all women are far from settled. Some evidence suggests the genistein in soy may have properties that are protective against lung cancer. Nonfermented soy products (tofu, soy milk) also may protect against stomach cancer, while fermented soy products (miso, soy paste) appears to increase the risk.
Organosulfurs. The organosulfur compounds found in the onion and garlic family may have very potent properties in suppressing or blocking carcinogenic substances. A 2007 study found that synthetic organosulfur compounds act as selective inhibitors of growth in breast cancer cells. Studies indicate that people who regularly consume fresh or cooked garlic have about half the risk of developing stomach cancer and two thirds the risk of colorectal cancer as people who eat little or no garlic. One possible explanation for garlic's anti-cancer effect in the stomach is its antibacterial action against H. pylori, which can promote stomach cancer. Taking garlic supplements, however, did not offer these benefits.

It should be noted that studies on the health benefits of vitamins and minerals have some important limitations. Some are held to rigorous standards, while others are not. In most cases, the results of existing research are complex, as they can easily be complicated by factors such as diet, exercise, the presence of healthy or unhealthy lifestyle behaviors, environmental factors, and more.


Disease or Condition	Vitamins	Carotenoids, Phytochemicals, and Healthy Foods
Alzheimer's Disease	Vitamin E. Some reports, including a large 2002 population study, have suggested that vitamin E intake, from food or supplements, may protect against mental decline. (One study suggested that the vitamin protected only those who carried the apoE4 gene. No strong evidence to date has found any protection from antioxidant supplements.) Some studies performed since 2002 challenge this finding, while others agree with it. B Vitamins. Some studies suggest that deficiencies of the B vitamins B6, B12, and folate may be a risk factor for Alzheimer' diseases, possibly because deficiencies elevate homocysteine levels, which some research now associated with a higher risk for Alzheimer's disease. Of these, folates may offer the best protection. In 2007, researchers at Tufts-New England Medical Center reviewed all human studies on folate, vitamin B-6, vitamin B-12, and cognitive function in the elderly conducted between 1966 and November 2006. Six of 10 folate studies reported a significant association between low baseline blood folate concentrations and poor cognitive test performance; 4 of 9 folate studies found associations between low blood folate concentrations and increased prevalence of Alzheimer's disease. No association between vitamin B-6 and vitamin B-12 blood concentrations and cognitive-test performance or Alzheimer's disease was seen, and B-vitamin dietary intake was not associated with cognitive function. Although the majority of studies indicated that low blood folate concentrations predicted poorer cognitive function, data are not solid, due to variations in the way the studies were conducted and lack of agreement on what constitutes a low B-vitamin status.	According to several studies, eating plenty of darkly colored fruits and vegetables may slow brain aging. The estrogen-like properties in isoflavones are of interest in the study of Alzheimer's disease. Animal studies suggest that soy might be protective against AD, particularly in postmenopausal women. Of some concern, however, were one population and a few animal studies suggesting that soy intake may pose a risk for greater mental decline among older men. More research is needed to confirm the effects of soy on the aging brain and to determine if there are gender differences.
Infectious Disease	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. A review of all studies on vitamin C and pneumonia prevention found only 1 placebo-controlled, randomized trial conducted in an English boarding school during World War II. The trial found a statistically significant (80% or greater) reduction in pneumonia incidence among boys consuming vitamin C. Two less-well-constructed trials arrived at the same conclusion. Therapeutic trials were even scarcer. Only one randomized, double-blind, placebo-controlled study of vitamin C for treatment of pneumonia was found. In this trial, elderly patients given vitamin C had lower mortality and respiratory symptom scores. However, the benefits were restricted to the sickest patients. One other trial of adults in the former Soviet Union found a dose-dependent reduction in the time to recover with two vitamin C doses. One 2007 study on vitamin D found that a single dose by mouth of this vitamin might prevent healthy individuals from activating the bacterium that causes tuberculosis in patients who harbor the infection. Studies on vitamin E specifically have been mixed. 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. However, a 2004 clinical trial conducted among elderly nursing home residents found that daily supplementation with 200 IU of vitamin E did provide protection from upper respiratory infections, especially the common cold. At present, there is not enough evidence to recommend vitamin E for infection prevention. Diarrhea is a worldwide problem, particularly in developing countries and those with poor sanitation. Taking supplements with B-complex vitamins, vitamin C, vitamin E, and selenium may reduce the risk of diarrhea, depending upon the organism that causes the disease. Meanwhile, iron supplements appear to increase the risk of infection from organisms that cause diarrhea. Vitamin A has not been shown to prevent diarrhea. Urinary tract infections (UTIs) may affect as many as 25% of pregnant women. A 2007 study found that women who took vitamin C (100 mg) for 3 months had significantly fewer UTIs than women who did not take vitamin C supplements. Rotavirus is a common cause of acute gastric pain in children under age 5. A 2007 study showed that the high amount of isoflavones found in soy-based infant formula can help prevent rotavirus infection.	Lycopene, found in tomatoes, appears to have properties that protect infection-fighting white blood cells. Saponins extracted from ginseng and allicin (found in garlic) have properties that boost the immune system. Both ginseng and garlic have long been traditionally used for their health benefits.
Asthma	Vitamin C from diet has been associated with lower risk for asthma. In one study, some people with exercise-induced asthma benefited from taking vitamin C one hour before strenuous physical activity. In a 2007 study, taking 1,500 mg supplements of vitamin C for 2 weeks helped prevent exercise-induced airway narrowing in patients with asthma.	Flavonoids found in apples and red wine may help lower the risk for asthma. Some evidence indicates that a low dietary intake of antioxidant nutrients could increase the risk for lung damage. Such nutrients should be obtained from fresh, deep green and yellow-orange fruits and vegetables. A 2007 study found low blood lycopene levels in people with asthma. Increasing lycopene- and vitamin A-rich foods may help raise lycopene levels.
Eye Disorder	Cataracts and Macular Degeneration. Oxygen-free radicals play a role in cataract formation and age related macular degeneration, the most common cause of irreversible blindness in the elderly. Bilberry (Vaccinium myrtillis), which contains powerful anthocyanins, is widely used to prevent macular degeneration. Low levels of vitamin C in the lens of the eye have been particularly strong predictors of cataracts. People with cataracts are frequently deficient in vitamin A, the carotenes, lutein, and zeaxanthin. Studies on protection against cataracts using antioxidant supplements have been mixed, including two identically conducted studies that reported opposite results. Vitamin C currently has the strongest evidence for protection, but even with this antioxidant studies are not consistent. A combination of zinc and antioxidants, including vitamin C and E, may slow the progression of macular degeneration. (Vitamin E alone does not appear to be protective.) Glaucoma. Although no evidence exists that antioxidants will prevent glaucoma, some studies reported an association between vitamin E and improved visual fields in patients with glaucoma.	Several studies report that the consumption of antioxidant-rich foods is associated with a decreased risk for cataracts. Carotenoids, especially lutein, lycopene, and zeaxanthin, are especially eye-protective and may help prevent cataracts and macular degeneration. The National Eye Institute in 2007 suggested that people with intermediate- or advanced macular degeneration in one eye may want to take a vitamin formula shown to reduce the risk of macular degeneration in the other eye by 25%. The formula contains vitamin C, vitamin E, beta-carotene, and zinc. They also suggest that a diet high in lutein and zeaxanthin may help reduce the risk of advanced age-related macular degeneration. Several studies report that the consumption of antioxidant-rich foods is associated with a decreased risk for cataracts. Carotenoids, especially lutein lycopene, and zeaxanthin are especially eye-protective and may help prevent cataracts and macular degeneration.
Skin Disorders and Wrinkles	Topical vitamin A (retinol) has been shown to improve fine wrinkles due to aging, by increasing glycosaminoglycan, which retains water, and increasing collagen production. One small study found that taking a combination of vitamins oral C and E supplements may help reduce sunburn reactions, although the protection is much less than from sunscreens. Taking the vitamins singly did not have any effect. In fact, a 2002 study reported that oral vitamin C had no effect on sunburn reaction. Of concern, in the same study some natural antioxidants in the body were reduced in people who took the vitamin. Also of concern are studies reporting no benefits and possibly harm from topical vitamin C in the form of ascorbyl palmitate, which is soluble in fat. One study reported that older adults had fewer wrinkles if they ate whole grains, fresh fruits and vegetables, and the use of healthy oils (such as olive oil). Diet played a role in improving skin regardless of whether the people in the study smoked or lived in sunny countries.	The following foods and phytochemicals may be especially skin protective: Both green tea and ginger appear to have properties that may provide some protection against skin cancer. Green tea skin care products are now available. The substance silymarin, found in the milk thistle family (which includes artichokes), may inhibit UVB-promoted cancers in animals. In one interesting study, eating garlic protected animals very effectively against UVB damage by interfering with urocanic acid in the skin. Whether these results may apply to humans (and what quantities of garlic might be beneficial) is still unknown.
Osteoporosis	Vitamin D. Vitamin D is the essential companion to calcium in maintaining strong bones. Supplements may be needed for people who have poor exposure to sunlight. It should be noted that diet supplies most people's need and high amounts of vitamin D can be toxic. Of interest: Taking vitamin D supplements does not prevent bone loss in post-menopausal African American women, according to research published in 2005. Further study will be needed to determine whether vitamin D prevents bone loss in women from other ethnic groups. Vitamin K. Studies suggest that vitamin K has properties that protect bone and prevent fracture. Vitamin K2 (menatetrenone), a form of vitamin K, is proving to prevent fractures in people with osteoporosis. Vitamin K affects blood clotting, and supplements are not recommended without specific physician instruction. Vitamin B12. One study reported that in people with osteoporosis and pernicious anemia, taking vitamin B12 (which is used to treat the anemia) also increased bone density. Vitamin C and E. There has been some indication of a positive association between vitamin C and E intake and bone density, although evidence proving actual benefits is weak. Note on Vitamin A. High amounts of dietary vitamin A reduces bone density and may even increase the risk for fracture in both postmenopausal women and men. (A form of vitamin A, retinoic acid, has been found to stimulate bone break down.) Beta carotene does not appear to increase risk. Studies suggest that diets rich in fresh fruits and vegetables (which include those high in potassium and magnesium) reduce elimination of calcium from the body and help preserve bones.	Studies suggest that diets rich in fresh fruits and vegetables (which include those high in potassium and magnesium) reduce elimination of calcium from the body and help preserve bones. Studies are suggesting that isoflavones-rich soy products may actually improve bone density in postmenopausal women. A 2007 study of postmenopausal women in Italy found that 24 months of treatment with genistein plus calcium and vitamin D increased bone density, while women who took calcium and D alone lost bone density. Flavonoids and other compounds in tea may protect the bones.
Menstrual Disorders	Vitamin B6. Limited clinical evidence suggests that vitamin B6 may be beneficial in reducing premenstrual symptoms, including depression. Typically, women take 100 mg per day, although one study suggested that a lower dose (50 mg) may have the same effect. Other preliminary research indicates that women who receive the equivalent of 1,200 mg of calcium and 400 IU of vitamin D per day (through food or supplements) have a significantly lower incidence of premenstrual symptoms than women who did not. Vitamin B1. One study reported relief from menstrual pain using vitamin B1 (thiamin). Vitamin E. Several randomized controlled trials have shown that vitamin E significantly improves both physical and emotional premenstrual symptoms. One study reported that high doses of vitamin E helped reduce menstrual cramps. The doses were much higher than those recommended and could possibly increase the risk for bleeding. Although anecdotal evidence reports that vitamin E helps reduce the frequency of hot flashes for menopausal women, there is no clinical evidence to support this claim.

Resources

http://fnic.nal.usda.gov -- The Food and Nutrition Information Center
http://dietary-supplements.info.nih.gov -- Office of Dietary Supplements, National Institutes of Health
www.ars.usda.gov/ba/bhnrc/ndl -- Nutrient Data Laboratory
www.fda.gov -- Food and Drug Administration
www.eatright.org -- The American Dietetic Association
www.acsh.org -- American Council on Science and Health
www.aicr.org -- American Institute for Cancer Research
www.nutritiondata.com -- Information on vitamins and nutrients in foods
www.consumerlab.com -- Independent testing of nutritional supplements' contents and quality
www.usp.org -- US Pharmacopeia
www.herbs.org -- Herb Research Foundation

References

Age-Related Eye Disease Study Research Group, SanGiovanni JP, Chew EY, Clemons TE, Ferris FL 3rd, Gensler G, Lindblad AS, Milton RC, Seddon JM, Sperduto RD. The relationship of dietary carotenoid and vitamin A, E, and C intake with age-related macular degeneration in a case-control study: AREDS Report No. 22. Arch Ophthalmol. 2007;125(9):1225-1232.

Ambrosini GL, de Klerk NH, Fritschi L, Mackerras D, Musk B. Fruit, vegetable, vitamin A intakes, and prostate cancer risk. Prostate Cancer Prostatic Dis. 2007 May 22; [Epub ahead of print]

Aubertin-Leheudre M, Lord C, Khalil A, Dionne IJ. Six months of isoflavone supplement increases fat-free mass in obese-sarcopenic postmenopausal women: a randomized double-blind controlled trial. Eur J Clin Nutr. 2007 Feb 21; [Epub ahead of print]

Bermudez Y, Ahmadi S, Lowell NE, Kruk PA. Vitamin E suppresses telomerase activity in ovarian cancer cells. Cancer Detect Prev. 2007;31(2):119-28. Epub 2007 Feb 28.

Bodnar LM, Catov JM, Simhan HN, Holick MF, Powers RW, Roberts JM. Maternal vitamin d deficiency increases the risk of preeclampsia. J Clin Endocrinol Metab. 2007 ;92(9):3517-22. Epub 2007 May 29.

Clements RH, Katasani VG, Palepu R, Leeth RR, Leath TD, Roy BP, Vickers SM. Incidence of vitamin deficiency after laparoscopic Roux-en-Y gastric bypass in a university hospital setting. Am Surg. 2006;72(12):1196-202.

Coull DB, Tait RC, Anderson JH, McKee RF, Finlay IG. Vitamin B12 deficiency following restorative proctocolectomy. Colorectal Dis. 2007;9(6):562-566.

Dietary Guidelines for Americans 2005. Dept of Health and Human Services, US Dept of Agriculture. Accessed 10/3/2007.

Fischer Walker CL, Black RE. Micronutrients and diarrheal disease. Clin Infect Dis. 2007;45 Suppl 1:S73-S77.

Glynn RJ, Ridker PM, Goldhaber SZ, Zee RY, Buring JE. Effects of random allocation to vitamin E supplementation on the occurrence of venous thromboembolism: report from the Women's Health Study. Circulation. 2007;116(13):1497-503.

Headstrom PD, Rulyak SJ, Lee SD. Prevalence of and risk factors for vitamin B(12) deficiency in patients with Crohn's disease. Inflamm Bowel Dis. 2007 Sep 20; [Epub ahead of print]

Inderjeeth CA, Glennon D, Petta A, Soderstrom J, Boyatzis I, Tapper J.Vitamin D and muscle strength in patients with previous fractures. N Z Med J. 2007;120(1262):U2730.

Ishihara J, Otani T, Inoue M, Iwasaki M, Sasazuki S, Tsugane S; Japan Public Health Center-based Prospective Study Group. Low intake of vitamin B-6 is associated with increased risk of colorectal cancer in Japanese men. J Nutr. 2007;137(7):1808-1814.

J.G. Ray, C. Kearon, Q. Yi, P. Sheridan, and E. Lonn, for the Heart Outcomes Prevention Evaluation 2 (HOPE-2) Investigators. Randomized Trial of Homocysteine-Lowering Therapy and Risk for Venous Thromboembolism. Ann Intern Med. 2007;146(11):761-767.

Kitchin B, Morgan SL. Not just calcium and vitamin D: other nutritional considerations in osteoporosis. Curr Rheumatol Rep. 2007;9(1):85-92.

Kune G, Watson L. Colorectal cancer protective effects and the dietary micronutrients folate, methionine, vitamins B6, B12, C, E, selenium, and lycopene. Nutr Cancer. 2006;56(1):11-21.

Lim MR, Huang RC, Wu A, Girardi FP, Cammisa FP Jr. Evaluation of the elderly patient with an abnormal gait. J Am Acad Orthop Surg. 2007;15(2):107-117.

Martin H, Lindblad B, Norman M. Endothelial function in newborn infants is related to folate levels and birth weight. Pediatrics. 2007;119(6):1152-1158.

Mason JB, Dickstein A, Jacques PF, Haggarty P, Selhub J, Dallal G, Rosenberg IH. A temporal association between folic acid fortification and an increase in colorectal cancer rates may be illuminating important biological principles: a hypothesis. Cancer Epidemiol Biomarkers Prev. 2007;16(7):1325-1329.

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Ochoa-Brust GJ, Fernández AR, Villanueva-Ruiz GJ, Velasco R, Trujillo-Hernández B, Vásquez. Daily intake of 100 mg ascorbic acid as urinary tract infection prophylactic agent during pregnancy. Acta Obstet Gynecol Scand. 2007;86(7):783-787.

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Review Date:
10/29/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

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Pancreatic carcinoma

admin — Wed, 03 Sep 2008 17:48:17 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Definition

Pancreatic carcinoma is cancer of the pancreas.

Alternative Names

Pancreatic cancer; Cancer - pancreas

Causes, incidence, and risk factors

Pancreatic cancer is the fourth leading cause of death from cancer in the United States. The disease is slightly more common in men than in women, and risk increases with age.

The cause is unknown, but it is more common in smokers and in obese individuals. Almost a third of cases of pancreatic cancer are due to cigarette smoking. There is controversy as to whether type 2 diabetes is a risk factor for pancreatic cancer. A small number of cases are known to be related to syndromes that are passed down through families.

Symptoms

Weight loss
Abdominal pain
Loss of appetite
Jaundice
Nausea and vomiting
Weakness
Fatigue
Diarrhea
Indigestion
Back pain
Clay-colored stools
Paleness
Depression

Signs and tests

This disease may also alter the results of the following tests:

Treatment

At the time of diagnosis, only about 20% of pancreatic tumors can be removed by surgery. The standard procedure is called a pancreaticoduodenectomy (Whipple procedure).

This surgery for pancreatic cancer should be done at centers that perform the procedure frequently. Some studies suggest that surgery is best performed at hospitals that perform at least 9 of these surgeries per year.

When the tumor is confined to the pancreas but cannot be removed, a combination of radiation therapy and chemotherapy may be recommended. When the tumor has spread (metastasized) to other organs such as the liver, chemotherapy alone is usually used. The standard chemotherapy agent is gemcitabine, but other drugs may be used. Gemcitabine provides clinical improvement in approximately 25% of patients.

For patients who have biliary obstruction (blockage of the vessels that transport bile) and the tumor cannot be totally removed, the obstruction must be relieved. There are generally two approaches to this -- surgery and placement of a biliary stent (similar to stents placed in the arteries of the heart to relieve blockages) during ERCP.

Management of pain and other symptoms is an important part of the treatment of advanced pancreatic cancer. Hospice can be very helpful to patients for both pain and symptom management and psychological support for the patient and the family during the course of the illness.

Support Groups

The stress of illness can often be eased by joining a support group with members who share common experiences and problems. See cancer - support group. Also see the discussion of hospice in the treatment section above.

Expectations (prognosis)

Some patients with pancreatic cancer that is resectable (can be surgically removed) are cured. However, cure rates are significantly less than 50%.

Chemotherapy and radiation are often given after surgery to attempt to increase the cure rate. For pancreatic cancer that cannot be removed completely with surgery, or cancer that has spread beyond the pancreas, cure is not currently possible and the average survival is usually less than 1 year. Such patients might consider enrollment in a clinical trial (a medical research study to determine the best treatment).

Complications

Pancreatic cancer may result in weight loss, blood clots, liver dysfunction, infections, pain, and depression. Symptoms such as pain can usually be controlled with aggressive pain management.

Calling your health care provider

Call for an appointment with your health care provider if you have persistent abdominal pain, loss of appetite, fatigue, back pain, or other symptoms suggestive of this disorder.

Prevention

If you smoke, stop smoking. Eat a diet high in fruits, vegetables, and whole grains, and exercise regularly.

Review Date: 9/11/2006

Reviewed By: Rita Nanda, M.D., Department of Medicine, Section of Hematology/Oncology, University of Chicago Medical Center, Chicago, IL. Review provided by VeriMed Healthcare Network.

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