Ovarian cancer

Definition

Ovarian cancer is cancer of the ovaries, the eggreleasing and hormone-producing organs of the female reproductive tract. Cancerous, or malignant, cells divide and multiply in an abnormal fashion.

Description

The ovaries are small, almond-shaped organs, located in the pelvic region, one on either side of the uterus. When a woman is in her childbearing years, the ovaries alternate to produce and release an egg each month during the menstrual cycle. The released egg is picked up by the adjacent fallopian tube, and continues down toward the uterus. The ovaries also produce and secrete the female hormones estrogen and progesterone, which regulate the menstrual cycle and pregnancy, as well as support the development of the secondary female sexual characteristics (breasts, body shape, and body hair). During pregnancy and when women take certain medications, such as oral contraceptives, the ovaries are given a rest from their usual monthly duties.

Ninety percent of all ovarian cancers develop in the cells lining the surface, or epithelium, of the ovaries and so are called epithelial cell tumors. About 15% of epithelial cancers are considered low malignant potential or LMP tumors. These tumors occur more often in younger women, and are more likely to be caught early, so prognosis is good.

Germ cell tumors develop in the egg-producing cells of the ovary, and comprise about 5% of ovarian tumors. These tumors are usually found in teenage girls or young women. The prognosis is good if found early, but as with other ovarian cancers, early detection is difficult.

Primary peritoneal carcinoma (PPC) is a cancer of the peritoneum, the lining of the abdominal cavity where the internal organs are located. Although it is a distinct disease, it is linked with ovarian cancer. This is because the ovarian and peritoneal cells have the same embryonic origin. This means that the very early cells of the embryo that will ultimately develop into the ovaries and the peritoneum share a common origin. The term "primary" means that the cancer started first in the peritoneum, as opposed to the cancer starting in the ovary and then moving, or metastasizing, into the peritoneum.

Ovarian cancer can develop at any age, but is most likely to occur in women who are 50 years or older. More than half the cases are among women who are aged 65 years and older. Industrialized countries have the highest incidence of ovarian cancer. Caucasian women, especially of Ashkenazi Jewish descent, are at somewhat higher risk; African-American and Asian women are at a slightly lower risk. The risk of developing the disease increases with age. Ovarian cancer is the fifth most common cancer among women in the United States, and the second most common gynecologic cancer. It accounts for 4% of all cancers in women. However, because of poor early detection, the death rate for ovarian cancer is higher than for that of any other cancer among women. The American Cancer Society estimates about 24,000 new cases of ovarian cancer in 2000 in the United States, and about 14,000 deaths.

Only 50% of the women who are diagnosed with ovarian cancer will survive five years after initial diagnosis. This is due to the cancer being at an advanced stage at the time of diagnosis. With early detection, however, survival at five years post diagnosis may be 95%.

— Esther Csapo Rastegari, R.N., B.S.N., Ed.M.

For more information on ovarian cancer, visit Britannica.com.

Key Terms: Biomarker, Gynecologic oncologist, Kallikrein, Lymphatic system.

Definition

Ovarian cancer is cancer of the ovaries, the eggreleasing and hormone-producing organs of the female reproductive tract. Cancerous, or malignant, cells divide and multiply in an abnormal fashion.

Description

The ovaries are small, almond-shaped organs, located in the pelvic region, one on either side of the uterus. When a woman is in her childbearing years, the ovaries alternate to produce and release an egg each month during the menstrual cycle. The released egg is picked up by the adjacent fallopian tube, and continues down towards the uterus. The ovaries also produce and secrete the female hormones estrogen and progesterone, which regulate the menstrual cycle and pregnancy, as well as support the development of the secondary female sexual characteristics (breasts, body shape, and body hair). During pregnancy and when women take certain medications, such as oral contraceptives, the ovaries are given a rest from their usual monthly duties.

Types of Ovarian Cancers

Ninety percent of all ovarian cancers develop in the cells lining the surface, or epithelium, of the ovaries and so are called epithelial cell tumors. About 15% of epithelial cancers are considered low malignant potential or LMP tumors. These tumors occur more often in younger women, and are more likely to be caught early, so prognosis is good.

Germ cell tumors develop in the egg-producing cells of the ovary, and comprise about five percent of ovarian tumors. These tumors are usually found in teenage girls or young women. The prognosis is good if found early, but as with other ovarian cancers, early detection is difficult.

Primary peritoneal carcinoma (PPC) is a cancer of the peritoneum, the lining of the abdominal cavity where the internal organs are located. Although it is a distinct disease, it is linked with ovarian cancer. This is because the ovarian and peritoneal cells have the same embryonic origin. This means that the very early cells of the embryo that will ultimately develop into the ovaries and the peritoneum share a common origin. The term primary means that the cancer started first in the peritoneum, as opposed to the cancer starting in the ovary and then moving, or metastasizing, into the peritoneum.

Demographics

Ovarian cancer can develop at any age, but is most likely to occur in women who are 50 years or older. More than half the cases are among women who are aged 65 years and older. Industrialized countries have the highest incidence of ovarian cancer. Caucasian women, especially of Ashkenazi Jewish descent, are at somewhat higher risk; African-American and Asian women are at a slightly lower risk. The risk of developing the disease increases with age. Ovarian cancer is the fourth most common cancer among women in the United States, and the second most common gynecologic cancer. It accounts for 4% of all cancers in women. However, because of poor early detection, the death rate for ovarian cancer is higher than for that of any other cancer among women. About 1 in 70 American women will develop ovarian cancer during her lifetime, and 1 in 100 will die from it. The American Cancer Society estimates about 26,000 new cases of ovarian cancer in 2004 in the United States, and about 16,000 deaths.

Only 50% of the women who are diagnosed with ovarian cancer will survive five years after initial diagnosis. This is due to the cancer being at an advanced stage at the time of diagnosis. With early detection, however, survival at five years post diagnosis may be 95%.

Causes and Symptoms

Causes

The actual cause of ovarian cancer remains unknown, but several factors are known to increase one's chances of developing the disease. These are called risk factors. Women at a higher risk than average of developing ovarian cancer include women who:

• have never been pregnant or had children
• are Caucasian, especially of Northern European or Askenazi Jewish descent
• are over 50. Half of all diagnosed cases are in women over 65.
• have a family history of breast, ovarian, endometrial (uterine), prostate or colon cancer
• have had breast cancer
• have a first-degree relative (mother, daughter, sister) who has had ovarian cancer. (The risk is greater if two or more first-degree relatives had the disease. Having a grandmother, aunt or cousin with ovarian cancer also puts a woman at higher-than-average risk.)
• have the genetic mutation BRCA1 or BRCA2. (Not all women with these genetic breast cancer mutations will develop ovarian cancer. By age 70, a woman who has the BRCA1 mutation carries about a 40–60% risk of developing ovarian cancer. Women with the genetic mutation BRCA2 have a 15% increased risk of developing ovarian cancer. However, heredity only plays a role in about 5–10% of cases of ovarian cancer.) Women who have a strong familial history may benefit from genetic counseling to better understand their risk factors.

In addition to the above risk factors, the following factors appear to play a role in affecting a women's chances of developing ovarian cancer.

Reproduction and Hormones

Early menstruation (before age 12) and late menopause seem to put women at a higher risk for ovarian cancer. This appears to be because the longer, or more often, a woman ovulates, the higher her risk for ovarian cancer. As mentioned above, women who were never pregnant have a higher risk of developing the disease than women with one or more pregnancies. It is not yet clear from research studies whether a pregnancy that ends in miscarriage or stillbirth lowers the risk factor to the same degree as the number of term pregnancies. The use of post-menopausal estrogen supplementation for 10 years or more may double a woman's risk of ovarian cancer. Short-term use does not seem to alter one's risk factor.

Infertility Drug-Stimulated Ovulation

Research studies have reported mixed findings on this issue. It appears that women who take medications to stimulate ovulation, yet do not become pregnant, are at higher risk of developing ovarian cancer. Women who do become pregnant after taking fertility drugs do not appear to be at higher risk. One study reported that the use of the fertility drug clomiphene citrate for more than a year increased the risk of developing LMP tumors. LMP tumors respond better to treatment than other ovarian tumors.

Talc

The use of talcum powder in the genital area has been implicated in ovarian cancer in many studies. It may be because talc contains particles of asbestos, a known carcinogen. Female workers exposed to asbestos had a higher-than-normal risk of developing ovarian cancer. Genital deodorant sprays may also present an increased risk. Not all studies have brought consistent results.

Fat

A high-fat diet has been reported in some studies to increase the risk of developing ovarian cancer. In one study the risk level increased with every 10 grams of saturated fat added to the diet. This may be because of its effect on estrogen production.

Symptoms

Most of the literature on ovarian cancer states that there are usually no early warning symptoms for the disease. Ovarian cancer is often referred to as a silent killer, because women either are unaware of having it, or have symptoms that are not accurately diagnosed until the disease is in an advanced state. However, a November 2000 study reported in the medical journal Cancer analyzed more than 1,700 questionnaires completed by women with stage III and stage IV ovarian cancer. The researchers found that 95% of the women reported having had early symptoms that they brought to their doctors. Most symptoms were somewhat vague and either abdominal or gastrointestinal in nature, and consequently were either not properly diagnosed or were recognized as being ovarian in nature only after a significant length of time had passed.

The following symptoms are warning signs of ovarian cancer, but could also be due to other causes. Symptoms that persist for two to three weeks, or symptoms that are unusual for the particular woman should be evaluated by a doctor right away.

• digestive symptoms, such as gas, indigestion, constipation, or a feeling of fullness after a light meal
• bloating, distention or cramping
• abdominal or low-back discomfort
• pelvic pressure or frequent urination
• unexplained changes in bowel habits
• nausea or vomiting
• pain or swelling in the abdomen
• loss of appetite (anorexia)
• fatigue
• unexplained weight gain or loss
• pain during intercourse
• vaginal bleeding in post-menopausal women

Diagnosis

In the best-case scenario a woman is diagnosed with ovarian cancer while it is still contained in just one ovary. Early detection can bring five-year survival to near 95%. Unfortunately, about 75% of women (3 out of 4) have advanced ovarian cancer at the time of diagnosis. (Advanced cancer is at stage III or stage IV when it has already spread to other organs.) Five-year survival for women with stage IV ovarian cancer may be less than 5%.

Diagnostic Tests and Techniques

If ovarian cancer is suspected, several of the following tests and examinations will be necessary to make a diagnosis.

• a complete medical history to assess all the risk factors
• a thorough bi-manual pelvic examination
• CA-125 assay
• one or more various imaging procedures
• a lower GI series, or barium enema
• diagnostic laparoscopy

Bi-Manual Pelvic Examination

The exam should include feeling the following organs for any abnormalities in shape or size: the ovaries, fallopian tubes, uterus, vagina, bladder, and rectum. Because the ovaries are located deep within the pelvic area, it is unlikely that a manual exam will pick up an abnormality while the cancer is still localized. However, a full examination provides the practitioner with a more complete picture. An enlarged ovary does not confirm cancer, as the ovary may be large because of a cyst or endometriosis. While women should have an annual Pap test, this test screens for cervical cancer. Cancerous ovarian cells, however, might be detected on the slide. Effectiveness of using Pap smears for ovarian cancer detection is about 10-30%.

Ca-125 Assay

This is a blood test to determine the level of CA-125, a biomarker or tumor marker. A tumor marker is a measurable protein-based substance given off by the tumor. A series of CA-125 tests may be done to see if the amount of the marker in the blood is staying stable, increasing or decreasing. A rising CA-125 level usually indicates cancer, while a stable or declining value is more characteristic of a cyst. The CA-125 level should never be used alone to diagnose ovarian cancer. It is elevated in about 80% of women with ovarian cancer, but in 20% of cases is not. In addition, it could be elevated because of a non-ovarian cancer, or it can be elevated with non-malignant gynecologic conditions, such as endometriosis or ectopic pregnancy. During menstruation the CA-125 level may be elevated, so the test is best done when the woman is not having her menstrual period.

Imaging

There are several different imaging techniques used in ovarian cancer evaluation. A fluid-filled structure such as a cyst creates a different image than does a solid structure, such as a tumor. An ultrasound uses high-frequency sound waves that create a visual pattern of echoes of the structures at which they are aimed. It is painless, and is the same technique used to check the developing fetus in the womb. Ultrasound may be done externally through the abdomen and lower pelvic area, or with a transvaginal probe.

Other painless imaging techniques are computed tomography (CT) and magnetic resonance imaging (MRI). Color Doppler analysis provides additional contrast and accuracy in distinguishing masses. It remains unclear whether Doppler is effective in reducing the high number of false-positives with transvaginal ultrasonography. These imaging techniques allow better visualization of the internal organs and can detect abnormalities without having to perform surgery.

Lower Gi Series

A lower GI series, or barium enema, uses a series of x rays to highlight the colon and rectum. To provide contrast, the patient drinks a chalky liquid containing barium. This test might be done to see if the cancer had spread to these areas.

Diagnostic Laparoscopy

This technique uses a thin hollow lighted instrument inserted through a small incision in the skin near the belly button to visualize the organs inside of the abdominal cavity. If the ovary is believed to be malignant, the entire ovary is removed (oophorectomy) and its tissue sent for evaluation to the pathologist, even though only a small piece of the tissue is needed for evaluation. If cancer is present, great care must be taken not to cause the rupture of the malignant tumor, as this would cause spreading of the cancer to adjacent organs. If the cancer is completely contained in the ovary, its removal functions also as the treatment. If the cancer has spread or is suspected to have spread, then a saline solution may be instilled into the cavity and then drawn out again. This technique is called peritoneal lavage. The aspirated fluid will be evaluated for the presence of cancer cells. If peritoneal fluid is present, called ascites, a sample of this will also be drawn and examined for malignant cells. If cancer cells are present in the peritoneum, then treatment will be directed at the abdominal cavity as well.

Research and New Diagnostic Tests

Many cancer researchers recognize the urgency of developing a new diagnostic test for ovarian cancer that is both sensitive and reliable. Some experts in the field look to proteomics, which is the large-scale identification and analysis of all the proteins in an organism or organ, to lead eventually to the development of a useful new test for ovarian cancer.

A group of researchers in Canada reported in 2003 that human kallikrein gene 14 (KLK14) might serve as a new biomarker for ovarian cancer. Kallikreins are a group of compounds that help to split up complex protein molecules into smaller units; prostate-specific antigen, or PSA, is a kallikrein. Early results of tests for KLK14 indicate that about 65% of women known to have ovarian cancer have elevated levels of this kallikrein.

Treatment Team

A woman's treatment team may consist of her primary care physician, her gynecologist/surgeon, a medical oncologist, a gynecologic oncologist, and a radiation oncologist. Professionals to address her psychological needs may also be part of the team, such as a medical social worker or a psychiatric nurse specializing in oncology. A case coordinator may also participate, as may individuals to address her spiritual and/or mind/body needs. The purpose of the team, versus seeing the various specialists independently, is to coordinate the care, treatments and appointments between the different team members. This allows all team members to know what everyone is doing, to coordinate appointments to minimize fatigue, and to make sure the physical, psychological, and spiritual needs of the patient are being addressed to the fullest degree possible.

Clinical Staging, Treatment, and Prognosis

Clinical Staging

Staging is the term used to determine if the cancer is localized or has spread, and if so, how far and to where. Staging helps define the cancer, and will determine the course of suggested treatment. Staging involves examining any tissue samples that have been taken from the ovary, nearby lymph nodes, as well as from any nearby organs or structures where metastasis was suspected. This may include the diaphragm, lungs, stomach, intestines and omentum (the tissue covering internal organs), and any fluid as described above.

The National Cancer Institute Stages for ovarian cancer are:

• Stage I: Cancer is confined to one or both ovaries.
• Stage II: Cancer is found in one or both ovaries and/or has spread to the uterus, fallopian tubes, and/or other body parts within the pelvic cavity.
• Stage III: Cancer is found in one or both ovaries and has spread to lymph nodes or other body parts within the cavity, such as the surfaces of the liver or intestines.
• Stage IV: Cancer is found in one or both ovaries and has spread to other organs such as the liver or lung.

The individual stages are also further broken down in detail, such as Ia, Ib, etc. Accurate staging is important for several reasons. Treatment plans are based on staging, in part because of trying to duplicate the best results achieved in prior research trials. When staging is inconsistent, it becomes more difficult to know how different research studies compare, so the results themselves cannot be relied upon.

Treatment

Treatment offered will primarily depend on the stage of the cancer and the woman's age. It is always appropriate to consider getting a second opinion, especially when treatment involves surgery, chemotherapy, and possible radiation. Before the patient makes her decision as to which course of treatment to take, she should feel that she has the information necessary with which to make an informed decision. The diagnostic tools mentioned above are used to determine the course of treatment. However, the treatment plan may need to be revised if the surgeon sees that the tumor has spread beyond the scope of what was seen during diagnostic tests.

Surgery

Surgery is done to remove as much of the tumor as possible (called tissue debulking), utilizing chemotherapy and/or radiation to target cancer cells that have remained in the body, without jeopardizing the woman's health. This can be hard to balance once the cancer has spread. Removal of the ovary is called oophorectomy, and removal of both ovaries is called bilateral oophorectomy. Unless it is very clear that the cancer has not spread, the fallopian tubes are usually removed as well (salpingo-oophorectomy). Removal of the uterus is called hysterectomy.

If the woman is very young, all attempts will be made to spare the uterus. It is crucial that a woman discuss with her surgeon her childbearing plans prior to surgery. Unfortunately, ovarian cancer spreads easily and often swiftly throughout the reproductive tract. It may be necessary to remove all reproductive organs as well as part of the lining of the peritoneum to provide the woman with the best possible chance of long-term survival. Fertility-sparing surgery can be successful if the ovarian cancer is caught very early.

Side effects of the surgery will depend on the extent of the surgery, but may include pain and temporary difficulty with bladder and bowel function, as well as reaction to the loss of hormones produced by the organs removed. A hormone replacement patch may be applied to the woman's skin in the recovery room to help with the transition. An emotional side effect may be the feeling of loss stemming from the removal of reproductive organs.

Chemotherapy

Chemotherapy is used to target cells that have traveled to other organs, and throughout the body via the lymphatic system or the blood stream. Chemotherapy drugs are designed to kill cancer cells, but may also be harmful to healthy cells as well. Chemotherapy may be administered through a vein in the arm (intravenous, IV), may be taken in tablet form, and/or may be given through a thin tube called a catheter directly into the abdominal cavity (intraperitoneal). IV and oral chemotherapy drugs travel throughout the body; intraperitoneal chemotherapy is localized in the abdominal cavity.

Side effects of chemotherapy can vary greatly depending on the drugs used. Currently, chemotherapy drugs are often used in combinations to treat advanced ovarian cancer, and usually the combination includes a platinum-based drug (such as cisplatin) with a taxol agent, such as paclitaxel. Some of the combinations used or being studied include: carboplatin/paclitaxel, cisplatin/paclitaxel, cisplatin/topotecan, and cisplatin/carboplatin. As new drugs are evaluated and developed, the goal is always for maximum effectiveness with minimum of side effects. Side effects include nausea and vomiting, diarrhea, decreased appetite and resulting weight loss, fatigue, headaches, loss of hair, and numbness and tingling in the hands or feet. Managing these side effects is an important part of cancer treatment.

After the full course of chemotherapy has been given, the surgeon may perform a "second look" surgery to examine the abdominal cavity again to evaluate the success of treatment.

Radiation

Radiation uses high-energy, highly focused x rays to target very specific areas of cancer. This is done using a machine that generates an external beam. Very careful measurements are taken so that the targeted area can be as focused and small as possible. Another form of radiation uses a radioactive liquid that is administered into the abdominal cavity in the same fashion as intraperitoneal chemotherapy. Radiation is usually given on a daily Monday though Friday schedule and for several weeks continuously. Radiation is not painful, but side effects can include skin damage at the area exposed to the external beam, and extreme fatigue. The fatigue may hit suddenly in the third week or so of treatment, and may take a while to recover even after treatments have terminated. Other side effects may include nausea, vomiting, diarrhea, loss of appetite, weight loss and urinary difficulties. For patients with incurable ovarian cancer, radiation may be used to shrink tumor masses to provide pain relief and improve quality of life.

Once the full course of treatment has been undertaken, it is important to have regular follow-up care to monitor for any long-term side effects as well as for future relapse or metastases.

Alternative and Complementary Therapies

The term alternative therapy refers to therapy utilized instead of conventional treatment. By definition, these treatments have not been scientifically proven or investigated as thoroughly and by the same standards as conventional treatments. The terms complementary or integrative therapies denote practices used in conjunction with conventional treatment. Regardless of the therapies chosen, it is key for patients to inform their doctors of any alternative or complementary therapies being used or considered. (Some alternative and complementary therapies adversely affect the effectiveness of conventional treatments.) Some common complementary and alternative medicine techniques and therapies include:

• prayer and faith healing
• meditation
• mind/body techniques such as support groups, visualization, guided imagery and hypnosis
• energy work such as Therapeutic Touch and Reiki
• acupuncture and Chinese herbal medicine
• body work such as yoga, massage and t'ai chi
• vitamins and herbal supplements
• diets such as vegetarianism and macrobiotic

Mind/body techniques along with meditation, prayer, yoga, t'ai chi, and acupuncture have been shown to reduce stress levels, and the relaxation provided may help boost the body's immune system. The effectiveness of other complementary and alternative treatments is being studied by the National Institutes of Health's National Center for Complementary and Alternative Medicine (NCCAM). For a current list of the research studies occurring, results of recent studies, or publications available, patients can visit the NCCAM web site or call at (888) 644-6226.

Prognosis

Prognosis for ovarian cancer depends largely on the stage at which it is first diagnosed. While stage I cancer may have a 95% success rate, stages III and IV may have a survival rate of 17-30% at five years post-diagnosis. Early detection remains an elusive, yet hopeful, goal of research. Also, clinical trials are addressing new drug and treatment combinations to prolong survival in women with more advanced disease. Learning one's family history may assist in early detection, and genetic studies may clarify who is at greater risk for the disease.

Coping With Cancer Treatment

While the cancer may only be in part of the body, it is very much a full mind/body experience. Strategies for coping with the treatment need to address the entire range of the experience. Each woman will have different needs. She might want to create a personal support team of friends. They can provide support by:

• Finding helpful information in the library or on the Internet about clinical trials, new therapies or treatments, different treatment centers, etc.
• Providing transportation to and from appointments. A diagnosis of cancer can be overwhelming. In such a stressful and distracted state it is often hard to remember what a doctor has said, or even to remember the questions to be asked. Having a second set of ears during this stressful time can be helpful.
• Helping with household duties so that the woman can rest after treatments and have more energy to devote to her family.
• Assisting with child care. Children are very much affected by a parent's cancer diagnosis, whether they have been fully informed or not of what is taking place. For a child to go to a friend's house can provide a sense of normalcy and security.
• Being available to participate in activities and conversations not centering on the cancer. While in the midst of cancer treatments, it is important to talk about non-cancer issues as well, and to maintain social relationships and activities. It is important for the cancer patient to keep at least some of the social outlets she had before the diagnosis.

A woman may wish to join a support group of women with ovarian cancer. This group can provide the environment to talk about the diagnosis, the treatments, the side effects and the impact the diagnosis has on her life with others who can empathize. If there is no support group nearby, she may be able to start one, or use one on the Internet. Studies examining support groups for children of a parent with cancer have shown these groups to be helpful for the child as well.

Clinical Trials

Clinical trials are human research studies. Their goal is to evaluate the effectiveness of new ways to treat cancer. There are many different designs, and they target different aspects of care. For example, some may investigate the response of different chemotherapy drugs, while another study may compare different types of treatment/chemotherapy combinations. The Cancer Information Service (CIS) is a division of the National Cancer Institute, the United States government agency for cancer research. Their web site contains information on all ongoing research trials, the areas being researched, and whether or not individuals can still participate.

Questions to Ask the Doctor

• What tests will be used to look for and diagnose my cancer?
• How should I prepare for the tests?
• What will take place during the test? Will it be painful? What can I do to decrease the pain?
• When will I learn the results?
• Once the results are in: What do these results mean?
• What type and stage is my cancer?
• What are my treatment options?
• Who will be involved in my care?
• What clinical trials would benefit me?
• What changes in my ability to work or perform my daily functions should I expect during treatment?
• How long will my treatment last?
• What side effects should I expect from treatment?
• Are there any conventional or alternative therapies that can diminish these side effects?
• How soon after treatment will I be able to resume my regular activities?
• What is the plan for my follow-up care?

Research studies are usually designed to compare a new treatment method against the standard method, or the effectiveness of a drug against a placebo (an inert substance that would be expected to have no effect on the outcome). Since the research is experimental in nature, there are no guarantees about the outcome. New drugs being used may have harmful, unknown side effects. Some people participate to help further knowledge about their disease. For others, the study may provide a possible treatment that is not yet available otherwise. If one participates in a study and is in the group receiving the standard care or the placebo, and the treatment group gets clear benefit, it may be possible to receive the experimental treatment once one's original participation role is over. Participants will have to meet certain criteria before being admitted into the study. It is important to fully understand one's role in the study, and weigh the potential risks versus benefits when deciding whether or not to participate.

As of late 2004, the National Cancer Institute (NCI) had nearly 150 clinical trials related to ovarian cancer in its database. Most of these trials are devoted to combination chemotherapy or chemotherapy administered after surgery, but they also include studies of stem cell transplantation, newer drugs like amifostine, pain management and supportive care for advanced ovarian cancer, and cancer vaccines.

Prevention

Since the cause of ovarian cancer is not known, it is not possible to fully prevent the disease. However, there are ways to reduce one's risks of developing the disease.

Decrease Ovulation

Pregnancy gives a break from ovulation, and multiple pregnancies appear to further reduce the risk of ovarian cancer. The research is not clear as to whether the pregnancy must result in a term delivery to have full benefit. Women who breast-feed their children also have a lower risk of developing the disease. Since oral contraceptives suppress ovulation, women who take birth control pills (BCPs), even for as little as 3 to 6 months have a lower incidence of the disease. It appears that the longer a woman takes BCPs, the lower her risk for ovarian cancer. Also, this benefit may last for up to 15 years after a woman has stopped taking them. However, since BCPs alter a woman's hormonal status, her risk for other hormonally related cancers may change. For this reason it is very important to discuss all the risks and benefits with one's health care provider.

GENETIC TESTING. Genetic testing is available which can help to determine whether a woman who has a family history of breast, endometrial, or ovarian cancer has inherited the mutated BRCA gene that predisposes her to these cancers. If the woman tests positive for the mutation, then she may be able to choose to have her ovaries removed. Even without testing for the mutated gene, some women with strong family histories of ovarian cancer may consider having their ovaries removed as a preventative measure (prophylactic oophorectomy). This procedure diminishes but does not completely remove the risk of cancer, as some women may still develop primary peritoneal carcinoma after oophorectomy.

Surgery

Procedures such as tubal ligation (in which the fallopian tubes are blocked or cut off) and hysterectomy (in which the uterus is removed) appear to reduce the risk of ovarian cancer. However, any removal of the reproductive tract organs has surgical as well as hormonal side effects.

Screening

There are no definitive tests or screening procedures as of early 2005 to detect ovarian cancer in its early stages. Women at high risk should consult with their physicians about regular screenings, which may include transvaginal ultrasound and the blood test for the CA-125 protein.

The American Cancer Society recommends annual pelvic examinations for all women after age 40, in order to increase the chances of early detection of ovarian cancer.

Special Concerns

Early detection remains the key focal point because the more ovarian cancer has spread, the poorer the chance for survival past a few years. As women and practitioners become more aware of the vague early warning signs, and seek out more accurate family histories, earlier screening can begin to lead to earlier detection and improved treatment success.

Resources

Books

Beers, Mark H., MD, and Robert Berkow, MD, editors. "Ovarian Cancer." Section 18, Chapter 241 In The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2004.

Runowicz, Carolyn D., Jeanne A. Petrek and Ted S. Gansler. American Cancer Society: Women and Cancer. New York: Villard Books/Random House, 1999.

Teeley, Peter and Philip Bashe. The Complete Cancer Survival Guide. New York: Doubleday, 2000.

Periodicals

Almadrones, L. A. "Treatment Advances in Ovarian Cancer." Cancer Nursing 26, Supplement 6 (December 2003): 16S–20S.

Borgono, C. A., L. Grass, A. Soosaipillai, et al. "Human Kallikrein 14: A New Potential Biomarker for Ovarian and Breast Cancer." Cancer Research 63 (December 15, 2003): 9032–9041.

Kohn, E. C., G. B. Mills, and L. Liotta. "Promising Directions for the Diagnosis and Management of Gynecological Cancers." International Journal of Gynaecology and Obstetrics 83, Supplement 1 (October 2003): 203–209.

McCorkle, R., J. Pasacreta, and S. T. Tang. "The Silent Killer: Psychological Issues in Ovarian Cancer." Holistic Nursing Practice 17 (November-December 2003): 300–308.

See, H. T., J. J. Kavanagh, W. Hu, and R. C. Bast. "Targeted Therapy for Epithelial Ovarian Cancer: Current Status and Future Prospects." International Journal of Gynecological Cancer 13 (November-December 2003): 701–734.

Organizations

American Cancer Society. (800) ACS-2345. .

Cancer Research Institute. 681 Fifth Avenue, New York, NY 10022. (800) 992-2623. .

Gilda Radner Familial Ovarian Cancer Registry. Roswell Park Cancer Institute. Elm and Carlton Streets. Buffalo, NY 14263-0001. (800) OVARIAN. (800) 682-7426.

National Cancer Institute. Building 31, Room 10A31, 31 Center Drive, MSC 2580, Bethesda, MD 20892-2580. (301) 435-3848. .

National Center for Complementary and Alternative Medicine. NCCAM Clearinghouse, P.O. Box 8218, Silver Spring, MD 20907-8218. (888) 644-6226. .

Oncolink at the University of Pennsylvania. .

Women's Cancer Network. c/o Gynecologic Cancer Foundation, 401 N. Michigan Avenue, Chicago, IL 60611. (312) 644-6610. .

Other

"Ovarian Cancer: New Treatments in the Pipeline." National Cancer Institute Cancer Trials. 3 [cited July 30, 2005]. .

"Ovarian Cancer." OncoLink:University of Pennsylvania Cancer Center. [cited July 6, 2005]. .

—Esther Csapo Rastegari, R.N., B.S.N., Ed.M.; Rebecca J. Frey, Ph.D.

Definition

Ovarian cancer is a disease in which the cells in the ovaries become abnormal, start to grow uncontrollably, and form tumors. Ninety percent of all ovarian cancers develop in the cells that line the surface of the ovaries and are called epithelial cell tumors.

Description

The ovaries are a pair of almond-shaped organs that lie in the pelvis on either side of the uterus. The fallopian tubes connect the ovaries to the uterus. The ovaries produce and release usually one egg each month during the menstrual cycle. Along with the adrenal gland, the ovaries also produce the female hormones estrogen and progesterone, which regulate and maintain the secondary female sexual characteristics.

Ovarian cancer is the fifth most common cancer among women in the United States. It accounts for 4% of all cancers in women. However, the death rate due to this cancer is higher than that of any other cancer among women. About 1 in 70 women in the United States will eventually develop ovarian cancer, and 1 in 100 will die from it. The National Cancer Institute (NCI) estimates that 25,400 new cases of ovarian cancer will be diagnosed in the United States in 2003, and that 14,300 women will die from the disease.

Ovarian cancer can develop at any age, but more than half the cases occur among women who are 65 years old or older. The incidence of the disease is highest among Native American women, followed by Caucasian, Vietnamese, Hispanic, and Hawaiian women. Only 50% of the women who are diagnosed with ovarian cancer will survive five years after initial diagnosis. This low survival rate is because at the time of initial diagnosis, the cancer is usually in an advanced stage. It is difficult to diagnose ovarian cancer early because often there are no warning symptoms and the disease spreads relatively quickly. In addition, the ovaries are situated deep in the pelvis and small tumors can't be detected easily during a routine physical examination.

Causes & Symptoms

The actual cause of ovarian cancer is not known, but several factors are known to increase a woman's chances of developing the disease. These are called risk factors. The major risk factors for cancer in general are tobacco, alcohol, diet, sexual and reproductive behavior, infectious agents, family history, occupation, environment, and pollution. There are several risk factors particularly associated with ovarian cancer.

• Age. The incidence of the disease increases with age. Half of all cases are diagnosed after age 65.
• Race. The incidence of the disease is highest among Native American women and lowest among Korean and Chinese women.
• High-fat diet. When Asian women move to the more affluent Western countries and adopt a diet that is rich in fat, the incidence of ovarian cancer among them rises. Furthermore, ovarian cancer is highest in those countries with the highest consumption of dairy foods (Switzerland, Denmark, and Sweden) and lowest in those countries with the lowest dairy intake (Japan, Hong Kong, Singapore). Ovarian cancer is also linked to high socioeconomic status in women.
• Family history. Women who have even one close relative with the disease increase their risk threefold. In addition, if a woman has had breast cancer, she is at an increased risk for ovarian cancer.
• Early menstruation/late menopause. Menstruating early (before age 12) and experiencing menopause late seem to put women at a higher risk for ovarian cancer. It is believed that the longer a woman ovulates, the higher her risk of ovarian cancer (some researchers think exposure to estrogen during the monthly cycles is the cause). Since ovulation occurs only during the childbearing years, the longer she menstruates, the greater her risk. Pregnancy gives a break from ovulation and exposure to estrogen for nine months. Hence, multiple pregnancies actually appear to reduce the risk of ovarian cancer. Similarly, since oral contraceptives suppress ovulation and reduce exposure to estrogen, women who take birth control pills have a lower incidence of the disease.
• Fertility drugs. One study has shown that prolonged use of certain fertility drugs, such as clomiphene citrate, may increase a woman's risk of developing ovarian tumors.
• Talcum powder. Some studies have suggested that the use of talcum powder in the genital area may double a woman's risk of getting the cancer. The incidence of ovarian cancer is higher than normal among female workers exposed to asbestos. Since talc contains particles of asbestos, some researchers believe that is what accounts for the increased risk.

Ovarian cancer has no specific signs or symptoms in the early stages of the disease. There may be some vague, nonspecific symptoms that are often ignored. However, if any of the symptoms persist, it is essential to have them evaluated by a doctor immediately. Only a doctor can determine whether the symptoms are an indication of early ovarian cancer; however, the presence of two or more of the following symptoms is reason for concern. The patient may experience:

• pain or swelling in the abdomen
• bloating, and a general feeling of abdominal discomfort
• constipation, nausea, or vomiting
• loss of appetite, fatigue
• unexplained weight gain (generally due to an accumulation of fluid in the abdomen)
• vaginal bleeding in postmenopausal women.

Diagnosis

If ovarian cancer is suspected, the doctor typically begins the diagnosis by taking a complete medical history to assess all the risk factors. A thorough pelvic examination is conducted. Blood tests to determine the level of a particular blood protein, CA125, may be ordered. This protein is usually elevated when a woman has ovarian cancer. However, it is not a definitive test because the levels may also rise in other gynecologic conditions, such as endometriosis and ectopic pregnancy. Recently, researchers have found another biological marker, a protein called prostasin, that appears to be specific to ovarian cancer. While prostasin should not be used as the only blood test for ovarian cancer, assessment of prostasin levels together with CA125 levels improves the likelihood of early detection. Ultrasound is almost always used to check the size of the ovaries. Standard imaging techniques such as computed tomography scans (CT scans) and magnetic resonance imaging (MRI) may be used to determine the condition of the ovaries and if the disease has spread to other parts of the body.

A new noninvasive technique for early detection of ovarian cancer involves a genetically altered virus. Researchers at the University of Alabama engineered a common cold virus to infect ovarian cancer cells with a green fluorescent protein that reveals the cancer cells. The technique can also be used to monitor the effectiveness of therapy.

Other new tests for the early detection of ovarian cancer are still undergoing development. One of the most promising is a blood test for asymptomatic earlystage ovarian cancer.

In order to determine if the tumor is benign or cancerous, surgery is necessary. If the tumor appears to be small from the imaging tests, then a procedure known as laparoscopy may be used. A tiny incision is made in the abdomen and a slender, hollow, lighted instrument is inserted through it. This lets the doctor view the ovary more closely and to obtain a piece of tissue for microscopic examination. If the tumor appears large, a laparotomy is performed under general anesthesia. This procedure combines both diagnosis and treatment for ovarian cancer because the tumor is often completely removed at this time. A piece of the tissue that is removed will be examined under a microscope to determine whether the tumor was benign or malignant.

Surgery confirms the diagnosis, but ovarian cancer is often strongly suspected before surgery based on symptoms and ultrasound. The goal of surgery is to completely remove the cancer, but often this is not possible.

Diagnosis in alternative treatment uses mainstream diagnostic techniques and supplements them with thorough physical and psychological examinations. Considerations such as lifestyle, relationships, and emotional and psychological histories are used to complete an overall portrait of a patient's health in order to develop holistic strategies for healing.

Treatment

There are many alternative treatments available to help with ovarian cancer. Alternative treatments can be used in conjunction with, or separate from, surgery, chemotherapy, and radiation therapy. When used with conventional treatment, alternative treatments have been shown to decrease pain and side effects, aid in the recovery process, and improve the quality of life of cancer patients.

Alternative treatment of cancer is complicated, and there are many choices in therapies and alternative practitioners. Consumers should consult as many trained healthcare practitioners as possible when choosing alternative therapies. If consumers are willing to ask questions and thoroughly research their options, they can increase their chances of getting the best possible alternative support for the difficult task of treating cancer.

Alternative medicine generally views cancer as a holistic problem. That is, cancer represents a problem with the body's overall health and immunity. As such, treatment is holistic as well, striving to strengthen and heal the physical, mental, and emotional aspects of patients. Alternative cancer treatments may emphasize different basic approaches, which include traditional medicines, mind/body approaches, physical approaches, nutritional and dietary approaches, integrated approaches, and experimental programs.

Traditional Medicines

Traditional Chinese medicine uses acupuncture, acupressure massage, herbal remedies, and movement therapies like t'ai chi and qigong to treat cancer. Traditional Chinese herbal remedies have already contributed a significant number of anticancer drugs, and studies have shown their anticancer properties. Acupuncture has been shown to reduce some tumors, significantly reduce pain, and support and improve immune system activity.

Ayurvedic medicine uses detoxification, herbal remedies, massage, exercise, yoga, breathing techniques, and meditation as part of its cancer treatment. Panchakarma is an extensive detoxification and strengthening program that is recommended for cancer patients and those undergoing chemotherapy and radiation. Panchakarma uses fasting, special vegetarian diets, enemas, massage, herbal medicines, and other techniques to rid the body of excess toxins (believed to contribute to chronic diseases like cancer) and to strengthen the immune system. Some ayurvedic herbs may also have significant anticancer properties.

Naturopathy and homeopathy are traditional Western healing systems using herbal medicines and other techniques to strengthen the immune system and reduce the pain of cancer treatment. Western herbalism is also beginning to compile studies of many herbs that have potential anticancer and immune strengthening properties (like mistletoe).

Mind/Body Approaches

Mind/body treatments seek to help patients with the mental and spiritual challenges posed by cancer and try to mobilize the body's own defenses and immune system. Some of these therapies include psychotherapy, support groups, guided imagery, visualization techniques, meditation, biofeedback, hypnosis, breathing techniques, and yoga. Mind/body approaches work with the idea that the mind and emotions can profoundly influence the health of the body. These techniques help patients manage the stress and anxiety that accompany cancer. Mind/body techniques have also been shown to stimulate the immune system and to reduce the pain of symptoms and conventional treatments.

Physical Approaches

Physical approaches to cancer include exercise; massage therapies; movement therapies including yoga, t'ai chi, and qigong; breathing techniques; and relaxation techniques. These therapies strive to increase immune system response, promote relaxation and stress reduction, and reduce side effects (like pain, nausea, weakness, and physical immobility) of conventional treatments.

Nutritional and Dietary Approaches

Cancer patients have heightened needs for diets free of toxic chemicals and full of cancer-fighting nutrients. Diet and nutrition may improve both a cancer patient's chances for recovery and the patient's quality of life during treatment. In laboratory studies, vitamins such as A, C and E, as well as compounds such as isothiocyanates and dithiolthiones found in broccoli, cauliflower, and cabbage, and beta-carotene found in carrots, tomatoes, and salad greens, have been shown to protect against cancer. The minerals selenium and zinc are also important nutrients in the ovarian cancer diet. Omega-3 essential fatty acids such as flaxseed oil or evening primrose oil are recommended as well.

Dietary approaches for ovarian cancer include vegetarianism, the raw food diet, and macrobiotics. Cancer diets generally emphasize raw and fresh fruits, vegetables, whole grains, beans, and peas. These diets also restrict or eliminate intake of fat, meat, dairy products, sugar, hydrogenated oils, processed foods, and foods with additives and artificial ingredients. Caffeine and alcohol are generally prohibited, and overeating is strongly discouraged.

Many herbs have been shown to have anticancer, immune enhancing, and symptom reducing properties. Some of the herbs used for ovarian problems include burdock, mullein, yarrow, vitex, dandelion, black cohosh, St. John's wort, red raspberry, nettles, and Siberian ginseng. Chinese herbs include astragalus, ginger, dong quai, cinnamon, rehmannia root, and scrophularia root. Patients should consult a competent herbalist or naturopathic doctor for individualized herbal support for ovarian cancer.

A review of medical literature done in early 2003 found that five plant extracts and 69 compounds isolated from plants have been shown to have antitumor activity against ovarian cancers. Some recent additions to the list include triterpenes isolated from Manihot esculenta, a plant found in the Surinam rain forest, and from Ligulariopsis shichuana, a plant used in traditional Chinese medicine to bring down inflammation.

Integrated Approaches

Keith Block, M.D., is a conventional doctor and oncologist (cancer specialist) who is integrating many alternative practices into his cancer treatment center affiliated with the Chicago Medical School. His program seeks to provide individualized cancer treatment using both conventional therapies while integrating alternative healing techniques. Block advocates a special diet (based on vegetarianism and macrobiotics), exercise, psychological support, and herbal and nutritional supplements. Block's program has received acclaim for both treatment success and satisfaction of patients.

As of early 2003, the University of Kansas Medical Center is conducting a study of the effectiveness of adding four well-known antioxidants (vitamins A, C, E, and beta-carotene) to conventional chemotherapy for ovarian cancer.

Experimental Programs

Antineoplaston therapy was developed by Stanislaw Burzynski, a Polish doctor, who began practicing in Houston, Texas. Burzynski has isolated a chemical, deficient in those with cancer, that he believes stops cancer growth, and his treatment has shown some promise.

Dr. Joseph Gold, the director of the Syracuse Cancer Research Institute, discovered that the chemical hydrazine sulfate has many positive effects in cancer patients, including stopping weight loss, shrinking tumors, and increasing survival rates.

The Livingston therapy was developed by the late Virginia Livingston, an American doctor. She asserted that cancer is caused by certain bacteria that she claimed are present in all tumors. She advocated a detoxification program and special diet that emphasized raw or lightly cooked, primarily vegetarian foods, with special vitamin and nutritional supplements.

The Gerson therapy has been the best known nutritional therapy for cancer. It is available in two clinics in California and Mexico. It consists of a basic vegetarian diet low in salt and fat, with high dosages of particular nutrients using raw fruit and vegetable juices. The Gerson therapy also requires patients to drink raw calf's liver juice, believed to aid the liver, and advocates frequent coffee enemas (thought to help the body evacuate toxins).

Allopathic Treatment

The cornerstone of allopathic treatment for ovarian cancer is surgery. The goal is to remove as much of the cancer as possible. Chemotherapy, which involves the use of anticancer drugs to kill the cancer cells, is usually administered after the surgery to destroy any remaining cancer. New drugs to treat ovarian cancer are in the clinical trial stage, including monoclonal antibody treatment for advanced ovarian cancer. Radiation therapy is not routinely used for ovarian cancer.

The type of surgery depends on the extent of the disease. In most procedures, the ovaries, uterus, and fallopian tubes are completely removed. In rare cases, if the cancer is not very aggressive and the woman is young and has not had children, a more conservative approach may be adopted. Only one ovary may be removed, and, if possible, the fallopian tubes and the uterus may be left intact. Occasionally, in addition to the female reproductive organs, the appendix may also be removed. The liver and the intestine will be examined for signs of cancer and may be biopsied. Ovarian cancer spreads contiguously, which means that it moves to the organs that are next to it. In some cases, extensive surgery may be needed to remove as much of the cancer as possible.

If the patient's cancer is advanced, she may be treated with radiation therapy, chemotherapy, or both. Chemotherapy may be either systemic or intraperitoneal (IP), which means that the drugs are injected into the abdomen. The most common drug used is paclitaxel (Taxol), combined with either cisplatin or carboplatin. Cancers that do not respond to these combinations may be treated with topotecan (Hycamtin) or with a a combination of paclitaxel and epirubicin (Ellence).

Expected Results

Most often ovarian cancer is not diagnosed until it is in an advanced stage, making it the most deadly of the female reproductive cancers. More than 50% of the women who are diagnosed with the disease die within five years. If ovarian cancer is diagnosed while it is still localized to the ovary, more than 90% of the patients will survive five years or more. However, only 24% of all cancers are found at this early stage.

Alternative medicine rarely claims to be able to cure cancer on a regular basis, but many treatments have been shown to help improve symptoms, control the pain and side effects of conventional treatments, speed healing, and increase the quality of life for cancer patients. Alternative therapies have also shown some unexpected results and cures. Some alternative therapies may be strongest as preventative measures, before major problems like cancer occur in the body, and as supportive measures, used with allopathic medicine.

Prevention

There are ways to reduce one's risks of developing ovarian cancer. Currently, genetic tests are available that can help to determine whether a woman who has a family history of breast, endometrial, or ovarian cancer has inherited the mutated gene that predisposes her to these cancers. (However, this mutation affects only a few women.) If the woman tests positive for the mutation, then she may opt to have her ovaries removed (a procedure called an oophorectomy). Allopathic medicine often recommends removing the ovaries as prevention even when a clear genetic component is not found, and this procedure is called a prophylactic oophorectomy.

Having one or more children, preferably having the first before age 30, and breast-feeding may decrease a woman's risk of developing the disease. High-risk women are advised to undergo periodic screening with transvaginal ultrasound or a blood test for CA125 protein. The American Cancer Society recommends annual pelvic examinations for all women after age 40, in order to increase the chances of early detection of ovarian cancer.

Alternative medicine stresses preventative measures that avoid removing the ovaries, unless a clear genetic risk has been established. Some studies have shown that removal of the ovaries does not necessarily reduce the risk of cancer, and does not necessarily increase longevity rates in women.

Having sound physical and mental health can significantly reduce the chances of getting cancer of any type. The following guidelines are generally recommended by doctors, nutritionists, and alternative practitioners for cancer prevention and recovery.

• Do not smoke.
• Do not drink alcohol excessively.
• Exercise regularly, at least 20 minutes per day. It is better to exercise outdoors in the fresh air. In a 1987 study at Harvard, Dr. Rose Frisch surveyed more than 5,398 women of all age groups. Those women in all groups who performed regular exercise had less risk for uterine, breast, cervical, ovarian, and vaginal cancers. For breast cancer, the risk was cut in half.
• Avoid exposure to radiation. This includes avoiding unnecessary x rays, not residing near sources of natural or man-made radiation, and avoiding occupational exposure to radiation.
• Avoid exposure to harmful chemicals, in food, the home, and the workplace.
• Maintain proper body weight and avoid obesity.
• Practice safe sex.
• Protect the skin from overexposure to sunlight. People should avoid direct exposure to sunlight between 11 A.M. and 3 P.M., and take other necessary precautions against sunburn.
• Eat a healthy diet. People should become educated on and practice dietary principles that reduce the risk of cancer. These principles include eating plenty of raw and fresh fruits, vegetables, beans, and whole grains. People should consume organically grown foods when possible, minimize overeating, reduced the intake of meat and dairy products, increase fiber, avoid processed and artificial foods. They should also avoid canned foods including soft drinks, avoid sugar and refined starch products such as white flour, reduce the intake of fat, avoid hydrogenated vegetable oils such as margarine and shortening, and drink filtered or spring water.
• Strive to maintain sound mental and emotional health. It is helpful to learn a technique like yoga, t'ai chi, or meditation to reduce stress and promote relaxation. People should maintain healthy relationships and social support systems.

Resources

Books

Northrup, Christiane, M.D. Women's Bodies, Women's Wisdom. New York: Bantam, 1994.

"Ovarian Cancer." Section 18, Chapter 241 in The Merck Manual of Diagnosis and Therapy, edited by Mark H. Beers, MD, and Robert Berkow, MD. Whitehouse Station, NJ: Merck Research Laboratories, 1999.

Pelletier, Kenneth R., MD. The Best Alternative Medicine, Part II, "CAM Therapies for Specific Conditions: Cancer." New York: Simon & Schuster, 2002.

Weil, Andrew, M.D. Natural Health, Natural Medicine. New York: Houghton Mifflin, 1995.

Yance, Donald R. Herbal Medicine, Healing and Cancer. Chicago: Keats Publishing, 1999.

Periodicals

Balat, O., and M. G. Ugur. "Prolonged Stabilization of Platinum/Paclitaxel-Refractory Ovarian Cancer with Topotecan: A Case Report and Review of the Literature." Clinical and Experimental Obstetrics and Gynecology 30 (February 2003): 151–152.

Chaturvedula, V. S., J. K. Schilling, S. Malone, et al. "New Cytotoxic Triterpene Acids from Aboveground Parts of Manihot esculenta from the Suriname Rainforest." Planta Medica 69 (March 2003): 271–274.

Drisko, J. A., J. Chapman, and V. J. Hunter. "The Use of Antioxidant Therapies During Chemotherapy." Gynecologic Oncology 88 (March 2003): 434–439.

"Genta's Decoy Program Suppresses Key Cancer Genes in Breast and Ovarian Cancer." Drug Week (November 9, 2001): 13.

Mok, Samuel C., Julie Chao, Steven Skates, et al. "Prostasin, a Potential Serum Marker for Ovarian Cancer: Identification Through Microarray Technology." Journal of the American Cancer Institute 93 (October 2001): 1458.

O'Rourke, J., and S. M. Mahon. "A Comprehensive Look at the Early Detection of Ovarian Cancer." Clinical Journal of Oncology Nursing 7 (January-February 2003): 41–47.

Ray-Coquard, I., T. Bachelot, J. P. Guastalla, et al. "Epirubicin and Paclitaxel (EPI-TAX Regimen) for Advanced Ovarian Cancer After Failure of Platinum-Containing Regimens." Gynecologic Oncology 88 (March 2003): 351–357.

"Researchers Develop Noninvasive Method of Detecting Disease." Medical Devices & Surgical Technology Week (October 21, 2001): 29.

Silva, J. S., M. D. Moura, R. A. Oliveira, et al. "Natural Product Inhibitors of Ovarian Neoplasia." Phytomedicine 10 (March 2003): 221–232.

Wang, W. S., K. Gao, C. M. Wang, and Z. J. Jia. "Cytotoxic Triterpenes from Ligulariopsis shichuana." Pharmazie 58 (February 2003): 148–150.

Organizations

The Alliance for Alternative Medicine. PO Box 59, Liberty Lake, WA 99019.

American Cancer Society (National Headquarters).1599 Clifton Rd., N.E., Atlanta, GA 30329. (800) 227-2345. http://www.cancer.org.

The Health Resource. 209 Katherine Dr., Conway, AR 72032. (501) 329-5272.

National Cancer Institute (NCI). Public Inquiries Office, Suite 3036A, 6116 Executive Blvd., MSC 8322, Bethesda, MD 20892-8322. (800) 4-CANCER. .

Women's Cancer Resource Center. 3023 Shattuck Ave., Berkeley, CA 94705. (510) 548-9272.

Other

Cancer Nutrition Center. http://www.cancernutrition.com.

Cancer Prevention Coalition. http://www.preventcancer.com.

Cancer Support and Education Center. http://www.cs-ec.org.

Ovarian Cancer Home Page, National Cancer Institute. .

[Article by: Douglas Dupler; Rebecca J. Frey, PhD]

Ovarian cancer affects 12 out of every 1,000 women in the United States over the age of forty, and only two or three of these women will ultimately be cured of their disease. The average age of onset is sixty-four. Approximately 25,500 new cases are diagnosed each year, and 14,500 women die of the disease annually. The etiology of epithelial ovarian cancer is unknown, and it is usually asymptomatic until presenting as advanced staged disease. The majority of ovarian cancers are believed to arise sporadically, however three discrete hereditary syndromes are currently recognized.

(SEE ALSO: Cancer; Carcinogenesis)

Bibliography

Lynch, H. T., and Lynch, J. F. (1989). "Hereditary Ovarian Cancer." Hematol Oncol Clin North Am 6:783.

Wingo, P. A.; Tong, T.; and Bodden, S. (1992). "Cancer Statistics." CA: A Cancer Journal for Clinicians 45:8.

Young, R. C.; Fuks, Z.; and Hoskins, W. J. (1989). "Cancer of the Ovary." In Cancer: Principles and Practices of Oncology, 3rd edition, eds. V. T. DeVita, Jr.,S. Hellman, and S. A. Rosenberg. Philadelphia, PA: Lippincott.

— THOMAS J. RUTHERFORD

This article's tone or style may not be appropriate for Wikipedia. Specific concerns may be found on the talk page. See Wikipedia's guide to writing better articles for suggestions. (December 2007)

This article needs additional citations for verification. Please help improve this article by adding reliable references. Unsourced material may be challenged and removed. (September 2008)

Ovarian cancer (human)
Classification and external resources
Micrograph of a low malignant potential mucinous ovarian tumour. H&E stain.
ICD-10	C56., D27.
ICD-9	183, 220
ICD-O:	varied
DiseasesDB	9418
MedlinePlus	000889
eMedicine	med/1698
MeSH	D010051

Ovarian cancer is a cancerous growth arising from different parts of the ovary.

The most common form of ovarian cancer (≥80%) arises from the outer lining (epithelium) of the ovary.^[1]. However, recent evidence shows cells that line the Fallopian tube (epithelium) also to be prone to develop into the same kind of cancer as seen in the ovaries. Since the ovaries and tubes are closely related to each other, it is hypothesized that these cells can mimic ovarian cancer.^[2]. Other forms arise from the egg cells (germ cell tumor).

In 2004, in the United States, 25,580 new cases were diagnosed and 16,090 women died of ovarian cancer. The risk increases with age and decreases with pregnancy. Lifetime risk is about 1.6%, but women with affected first-degree relatives have a 5% risk. Women with a mutated BRCA1 or BRCA2 gene carry a risk between 25% and 60% depending on the specific mutation.^[3] Ovarian cancer is the fifth leading cause of death from cancer in women and the leading cause of death from gynecological cancer.^[4]

In early stages ovarian cancer is associated with abdominal distension.^[5]

10-year relative survival ranges from 84.1% in stage IA to 10.4% in stage IIIC.^[6]

Ovarian cancer causes non-specific symptoms.^[7] Early diagnosis would result in better survival, on the assumption that stage I and II cancers progress to stage III and IV cancers (but this has not been proven). Most women with ovarian cancer report one or more symptoms such as abdominal pain or discomfort, an abdominal mass, bloating, back pain, urinary urgency, constipation, tiredness and a range of other non-specific symptoms, as well as more specific symptoms such as pelvic pain, abnormal vaginal bleeding or involuntary weight loss.^[8][9][10] There can be a build-up of fluid (ascites) in the abdominal cavity.

Diagnosis of ovarian cancer starts with a physical examination (including a pelvic examination), a blood test (for CA-125 and sometimes other markers), and transvaginal ultrasound. The diagnosis must be confirmed with surgery to inspect the abdominal cavity, take biopsies (tissue samples for microscopic analysis) and look for cancer cells in the abdominal fluid. Treatment usually involves chemotherapy and surgery, and sometimes radiotherapy.^[11]

In most cases, the cause of ovarian cancer remains unknown. Older women, and in those who have a first or second degree relative with the disease, have an increased risk. Hereditary forms of ovarian cancer can be caused by mutations in specific genes (most notably BRCA1 and BRCA2, but also in genes for hereditary nonpolyposis colorectal cancer). Infertile women and those with a condition called endometriosis, those who have never been pregnant and those who use postmenopausal estrogen replacement therapy are at increased risk. Use of combined oral contraceptive pills is a protective factor. The risk is also lower in women who have had their uterine tubes blocked surgically (tubal ligation).^[12][13]

Contents 1 Classification 1.1 Staging 2 Symptoms 2.1 Accuracy of symptoms 2.2 Consensus statement 3 Cause 3.1 Hormones 3.2 Genetics 3.3 Alcohol 3.4 Other 4 Diagnosis 5 Prevention 6 Screening 7 Management 8 Prognosis 8.1 Complications 9 Epidemiology 10 In other animals 11 See also 12 References 13 External links

Classification

A benign tumor of the ovary, discovered during a C-section; this is a 4 cm teratoma

Ovarian cancer is classified according to the histology of the tumor, obtained in a pathology report. Histology dictates many aspects of clinical treatment, management, and prognosis.

• Surface epithelial-stromal tumour, also known as ovarian epithelial carcinoma, is the most common type of ovarian cancer. It includes serous tumour, endometrioid tumor and mucinous cystadenocarcinoma.
• Sex cord-stromal tumor, including estrogen-producing granulosa cell tumor and virilizing Sertoli-Leydig cell tumor or arrhenoblastoma, accounts for 8% of ovarian cancers.
• Germ cell tumor accounts for approximately 30% of ovarian tumors but only 5% of ovarian cancers, because most germ cell tumors are teratomas and most teratomas are benign (see Teratoma). Germ cell tumor tends to occur in young women and girls. The prognosis depends on the specific histology of germ cell tumor, but overall is favorable.
• Mixed tumors, containing elements of more than one of the above classes of tumor histology.

According to SEER, types of ovarian cancers in women age 20+ are as follows:^[6]

Percent of ovarian cancers in women age 20+		Histology	5 year RSR
89.7		Surface epithelial-stromal tumor (Adenocarcinoma)	54.4
	26.4	Papillary serous cystadenocarcinoma	21.0
	15.9	"Borderline" adenocarcinoma (underestimated b/c short data collection interval)	98.2
	12.6	Adenocarcinoma, not otherwise specified	18.3
	9.8	Endometrioid tumor	70.9
	5.8	Serous cystadenocarcinoma	44.2
	5.5	Papillary	21.0
	4.2	Mucinous cystadenocarcinoma	77.7
	4.0	Clear-cell ovarian tumor	61.5
	3.4	Mucinous adenocarcinoma	49.1
	1.3	Cystadenocarcinoma	50.7
5.5		Carcinoma
	4.1	Carcinoma not otherwise specified	26.8
	1.1	Sex cord-stromal tumour	87.8
	0.3	Other carcinomas, specified	37.3
1.7		Mullerian tumor	29.8
1.5		Germ cell tumor	91.0
	0.8	Teratoma	89.1
	0.5	Dysgerminoma	96.8
	0.3	Other, specified	85.1
0.6		Not otherwise specified	23.0
0.5		Epidermoid (Squamous cell carcinoma)	51.3
0.2		Brenner tumor	67.9
0.2		Other, specified	71.7

Ovarian cancer can also be a secondary cancer, the result of metastasis from a primary cancer elsewhere in the body. 7% of ovarian cancers are due to metastases while the rest are primary cancers. Common primary cancers are breast cancer and gastrointestinal cancer (A common mistake is to name all peritoneal metastases from any gastrointestinal cancer as Krukenberg cancer^{[citation needed]}, but this is only the case if it originates from primary gastric cancer). Surface epithelial-stromal tumor can originate in the peritoneum (the lining of the abdominal cavity), in which case the ovarian cancer is secondary to primary peritoneal cancer, but treatment is basically the same as for primary surface epithelial-stromal tumor involving the peritoneum.^{[citation needed]}

Staging

Ovarian cancer staging is by the FIGO staging system and uses information obtained after surgery, which can include a total abdominal hysterectomy, removal of (usually) both ovaries and fallopian tubes, (usually) the omentum ^{[disambiguation needed]}, and pelvic (peritoneal) washings for cytopathology. The AJCC stage is the same as the FIGO stage.

• Stage I - limited to one or both ovaries
  • IA - involves one ovary; capsule ^{[disambiguation needed]} intact; no tumor on ovarian surface; no malignant cells in ascites or peritoneal washings
  • IB - involves both ovaries; capsule intact; no tumor on ovarian surface; negative washings
  • IC - tumor limited to ovaries with any of the following: capsule ruptured, tumor on ovarian surface, positive washings
• Stage II - pelvic extension or implants
  • IIA - extension or implants onto uterus or fallopian tube; negative washings
  • IIB - extension or implants onto other pelvic structures; negative washings
  • IIC - pelvic extension or implants with positive peritoneal washings
• Stage III - microscopic peritoneal implants outside of the pelvis; or limited to the pelvis with extension to the small bowel or omentum
  • IIIA - microscopic peritoneal metastases beyond pelvis
  • IIIB - macroscopic peritoneal metastases beyond pelvis less than 2 cm in size
  • IIIC - peritoneal metastases beyond pelvis > 2 cm or lymph node metastases
• Stage IV - distant metastases to the liver or outside the peritoneal cavity

Para-aortic lymph node metastases are considered regional lymph nodes (Stage IIIC).

Symptoms

Accuracy of symptoms

Two case-control studies, both subject to results being inflated by spectrum bias, have been reported. The first found that women with ovarian cancer had symptoms of increased abdominal size, bloating, urge to pass urine and pelvic pain.^[10] The smaller, second study found that women with ovarian cancer had pelvic/abdominal pain, increased abdominal size/bloating, and difficulty eating/feeling full.^[14] The latter study created a symptom index that was considered positive if any of the six (6) symptoms "occurred >12 times per month but were present for <1 year".They reported a sensitivity of 57% for early-stage disease and specificity 87% to 90%.

Consensus statement

In 2007, the Gynecologic Cancer Foundation, Society of Gynecologic Oncologists and American Cancer Society originated the following consensus statement regarding the symptoms of ovarian cancer.^[15]

Ovarian cancer is called a “silent killer” because symptoms were not thought to develop until the disease had advanced and the chance of cure or remission poor. However, the following symptoms are much more likely to occur in women with ovarian cancer than women in the general population. These symptoms include:

• Bloating
• Pelvic or abdominal pain
• Pain in the back or legs
• Diarrhea, gas, nausea, constipation, indigestion
• Difficulty eating or feeling full quickly
• Urinary symptoms (urgency or frequency)
• Pain during sex
• Abnormal vaginal bleeding
• Trouble breathing

Women with ovarian cancer report that symptoms are persistent and represent a change from normal for their bodies. The frequency and/or number of such symptoms are key factors in the diagnosis of ovarian cancer. Several studies show that even early stage ovarian cancer can produce these symptoms. Women who have these symptoms almost daily for more than a few weeks should see their doctor, preferably a gynecologist. Prompt medical evaluation may lead to detection at the earliest possible stage of the disease. Early stage diagnosis is associated with an improved prognosis.

Several other symptoms have been commonly reported by women with ovarian cancer. These symptoms include fatigue, indigestion, back pain, pain with intercourse, constipation and menstrual irregularities. However, these other symptoms are not as useful in identifying ovarian cancer because they are also found in equal frequency in women in the general population who do not have ovarian cancer.^{[citation needed]}

Cause

The exact cause is usually unknown. The risk of developing ovarian cancer appears to be affected by several factors. The more children a woman has, the lower her risk of ovarian cancer. Early age at first pregnancy, older age of final pregnancy and the use of low dose hormonal contraception have also been shown to have a protective effect. Ovarian cancer is reduced in women after tubal ligation.^{[citation needed]}

Hormones

The relationship between use of oral contraceptives and ovarian cancer was shown in a summary of results of 45 case-control and prospective studies. Cumulatively these studies show a protective effect for ovarian cancers. Women who used oral contraceptives for 10 years had about a 60% reduction in risk of ovarian cancer. (risk ratio .42 with statistical significant confidence intervals given the large study size, not unexpected). This means that if 250 women took oral contraceptives for 10 years, 1 ovarian cancer would be prevented. This is by far the largest epidemiological study to date on this subject (45 studies, over 20,000 women with ovarian cancer and about 80,000 controls).^[16]

The link to the use of fertility medication, such as Clomiphene citrate, has been controversial. An analysis in 1991 raised the possibility that use of drugs may increase the risk of ovarian cancer. Several cohort studies and case-control studies have been conducted since then without demonstrating conclusive evidence for such a link. ^[17] It will remain a complex topic to study as the infertile population differs in parity from the "normal" population.

Genetics

There is good evidence that in some women genetic factors are important. Carriers of certain mutations of the BRCA1 or the BRCA2 gene are notably at risk. The BRCA1 and BRCA2 genes account for 5%-13% of ovarian cancers^[18] and certain populations (e.g. Ashkenazi Jewish women) are at a higher risk of both breast cancer and ovarian cancer, often at an earlier age than the general population.^{[citation needed]} Patients with a personal history of breast cancer or a family history of breast and/or ovarian cancer, especially if diagnosed at a young age, may have an elevated risk.

A strong family history of uterine cancer, colon cancer, or other gastrointestinal cancers may indicate the presence of a syndrome known as hereditary nonpolyposis colorectal cancer (HNPCC, also known as Lynch II syndrome), which confers a higher risk for developing ovarian cancer. Patients with strong genetic risk for ovarian cancer may consider the use of prophylactic, i.e. preventative, oophorectomy after completion of childbearing.^{[citation needed]}

Alcohol

A pooled analysis of ten (10) prospective cohort studies conducted in a number of countries and including 529,638 women found that neither total alcohol consumption nor alcohol from drinking beer, wine or spirits was associated with ovarian cancer risk."^[19] The results of a case-control study in the region of Milan, Italy, "suggests that relatively elevated alcohol intake (of the order of 40 g per day or more) may cause a modest increase of epithelial ovarian cancer risk"^[20]. "Associations were also found between alcohol consumption and cancers of the ovary and prostate, but only for 50 g and 100 g a day."^[21] "Statistically significant increases in risk also existed for cancers of the stomach, colon, rectum, liver, female breast, and ovaries."^[22]

Other

A Swedish study, which followed more than 61,000 women for 13 years, has found a significant link between milk consumption and ovarian cancer. According to the BBC, "[Researchers] found that milk had the strongest link with ovarian cancer—those women who drank two or more glasses a day were at double the risk of those who did not consume it at all, or only in small amounts." ^[23] Recent studies have shown that women in sunnier countries have a lower rate of ovarian cancer, which may have some kind of connection with exposure to Vitamin D.^{[citation needed]}

Other factors that have been investigated, such as talc use, asbestos exposure, high dietary fat content, and childhood mumps infection, are controversial and have not been definitively proven.

Diagnosis

Ovarian cancer at its early stages(I/II) is difficult to diagnose until it spreads and advances to later stages (III/IV). This is because most of the common symptoms are non-specific.

When an ovarian malignancy is included in the list of diagnostic possibilities, a limited number of laboratory tests are indicated. A complete blood count (CBC) and serum electrolyte test should be obtained in all patients.

The serum BHCG level should be measured in any female in whom pregnancy is a possibility. In addition, serum alpha-fetoprotein (AFP) and lactate dehydrogenase (LDH) should be measured in young girls and adolescents with suspected ovarian tumors because the younger the patient, the greater the likelihood of a malignant germ cell tumor.

A blood test called CA-125 is useful in differential diagnosis and in follow up of the disease, but it by itself has not been shown to be an effective method to screen for early-stage ovarian cancer due to its unacceptable low sensitivity and specificity. However, this is the only widely-used marker currently available.

Current research is looking at ways to combine tumor markers proteomics along with other indicators of disease (i.e. radiology and/or symptoms) to improve accuracy. The challenge in such an approach is that the very low population prevalence of ovarian cancer means that even testing with very high sensitivity and specificity will still lead to a number of false positive results (i.e. performing surgical procedures in which cancer is not found intra-operatively). However, the contributions of proteomics are still in the early stages and require further refining. Current studies on proteomics mark the beginning of a paradigm shift towards individually tailored therapy.^{[citation needed]}

A pelvic examination and imaging including CT scan^{[citation needed]} and trans-vaginal ultrasound are essential. Physical examination may reveal increased abdominal girth and/or ascites (fluid within the abdominal cavity). Pelvic examination may reveal an ovarian or abdominal mass. The pelvic examination can include a rectovaginal component for better palpation of the ovaries. For very young patients, magnetic resonance imaging may be preferred to rectal and vaginal examination.

To definitively diagnose ovarian cancer, a surgical procedure to take a look into the abdomen is required. This can be an open procedure (laparotomy, incision through the abdominal wall) or keyhole surgery (laparoscopy). During this procedure, suspicious areas will be removed and sent for microscopic analysis. Fluid from the abdominal cavity can also be analysed for cancerous cells. If there is cancer, this procedure can also determine its spread (which is a form of tumor staging).

Prevention

There are a number of ways to reduce or eliminate the risk of ovaran cancer. Pregnancy before the age of 25 as well as breastfeeding provides some reduction in risk. Tubal ligation and hysterectomy reduce the risk and removal of both ovaries (bilateral oophorectomy) nearly eliminates the risk. The use of oral contraceptives (birth control pills) for five years or more decreases the risk of ovarian cancer in later life by 50%.^[24]

Screening

Routine screening of the general population is not recommended by any professional society. This includes the U.S. Preventitive Services Task Force, the American Cancer Society, the American College of Obstetricians and Gynecologists, and the National Comprehensive Cancer Network. ^[25]

No trial has shown improved survival for women undergoing screening.^[25]

Screening tests include the CA-125 marker, transvaginal ultrasound, and combinations of markers such as OvaSure (LabCorp). A definitive diagnosis requires surgical excision of the ovaries and fallopian tubes, so a positive screening test must be followed up by surgery.^[25]

The purpose of screening is to discover ovarian cancer in early stages, when it is more curable, on the hypothesis that early-stage cancer develops into later-stage cancer. However, it is not known whether early stage ovarian cancer evolves to later stage cancer, or whether stage III (peritoneal cavity involvement) arises as a diffuse process.^[25]

The goal of ovarian cancer screening is to detect ovarian cancer at stage I.^[26]Several large studies are ongoing, but none have recommended screening.^[27] In 2009, however, Menon et al. reported from the UKCTOCS that utilizing mutimodal screening, in essence first performing annual CA 125 testing, followed by ultrasound imaging on the secondary level, the positive predictive value was 35.1% for primary invasive epithelial ovarian and tubal carcinoma, making such screening feasible.^[28] However, it remains to be seen if such screening is effective to reduce mortality.

Management

This article may require cleanup to meet Wikipedia's quality standards. Please improve this article if you can. (January 2008)

Surgical treatment may be sufficient for malignant tumors that are well-differentiated and confined to the ovary. Addition of chemotherapy may be required for more aggressive tumors that are confined to the ovary. For patients with advanced disease a combination of surgical reduction with a combination chemotherapy regimen is standard. Borderline tumors, even following spread outside of the ovary, are managed well with surgery, and chemotherapy is not seen as useful.

Surgery is the preferred treatment and is frequently necessary to obtain a tissue specimen for differential diagnosis via its histology. Surgery performed by a specialist in gynecologic oncology usually results in an improved result.^{[citation needed]} Improved survival is attributed to more accurate staging of the disease and a higher rate of aggressive surgical excision of tumor in the abdomen by gynecologic oncologists as opposed to general gynecologists and general surgeons.

The type of surgery depends upon how widespread the cancer is when diagnosed (the cancer stage), as well as the presumed type and grade of cancer. The surgeon may remove one (unilateral oophorectomy) or both ovaries (bilateral oophorectomy), the fallopian tubes (salpingectomy), and the uterus (hysterectomy). For some very early tumors (stage 1, low grade or low-risk disease), only the involved ovary and fallopian tube will be removed (called a "unilateral salpingo-oophorectomy," USO), especially in young females who wish to preserve their fertility.

In advanced malignancy, where complete resection is not feasible, as much tumor as possible is removed (debulking surgery). In cases where this type of surgery is successful (i.e. < 1 cm in diameter of tumor is left behind ["optimal debulking"]), the prognosis is improved compared to patients where large tumor masses (> 1 cm in diameter) are left behind. Minimally invasive surgical techniques may facilitate the safe removal of very large (greater than 10 cm) tumors with fewer complications of surgery.^[29]

Chemotherapy has been a general standard of care for ovarian cancer for decades, although with highly variable protocols.^[30] Chemotherapy is used after surgery to treat any residual disease, if appropriate. This depends on the histology of the tumor; some kinds of tumor (particularly teratoma) are not sensitive to chemotherapy. In some cases, there may be reason to perform chemotherapy first, followed by surgery.

For patients with stage IIIC epithelial ovarian adenocarcinomas who have undergone successful optimal debulking, a recent clinical trial demonstrated that median survival time is significantly longer for patient receiving intraperitoneal (IP) chemotherapy. ^[31] Patients in this clinical trial reported less compliance with IP chemotherapy and fewer than half of the patients received all six cycles of IP chemotherapy. Despite this high "drop-out" rate, the group as a whole (including the patients that didn't complete IP chemotherapy treatment) survived longer on average than patients who received intravenous chemotherapy alone.

Some specialists believe the toxicities and other complications of IP chemotherapy will be unnecessary with improved IV chemotherapy drugs currently being developed.

Although IP chemotherapy has been recommended as a standard of care for the first-line treatment of ovarian cancer, the basis for this recommendation has been challenged.^[32]

Radiation therapy is not effective for advanced stages because when vital organs are in the radiation field, a high dose cannot be safely delivered.

Prognosis

Ovarian cancer usually has a poor prognosis. It is disproportionately deadly because it lacks any clear early detection or screening test, meaning that most cases are not diagnosed until they have reached advanced stages. More than 60% of patients presenting with this cancer already have stage III or stage IV cancer, when it has already spread beyond the ovaries. Ovarian cancers shed cells into the naturally occurring fluid within the abdominal cavity. These cells can implant on other abdominal (peritoneal) structures, included the uterus, urinary bladder, bowel and the lining of the bowel wall (omentum ^{[disambiguation needed]}). These cells can begin forming new tumor growths before cancer is even suspected.

The five-year survival rate for all stages of ovarian cancer is 45.5%. For cases where a diagnosis is made early in the disease, when the cancer is still confined to the primary site, the five-year survival rate is 92.7%. ^[33]

Germ cell tumors of the ovary have a much better prognosis than other ovarian cancers, in part because they tend to grow rapidly to a very large size, hence they are detected sooner.^{[citation needed]}

Complications

• Spread of the cancer to other organs
• Progressive function loss of various organs
• Ascites (fluid in the abdomen)
• Intestinal obstructions

These cells can implant on other abdominal (peritoneal) structures, including the uterus, urinary bladder, bowel, lining of the bowel wall (omentum) and, less frequently, to the lungs.

Epidemiology

Age-standardized death from ovarian cancer per 100,000 inhabitants in 2004.^[34]

     no data      less than 0.6      0.6-1.2      1.2-1.8      1.8-2.4      2.4-3      3-3.6      3.6-4.2      4.2-4.8      4.8-5.4      5.4-6      6-7      more than 7

The exact cause is usually unknown. The disease is more common in industrialized nations, with the exception of Japan. In the United States, females have a 1.4% to 2.5% (1 out of 40-60 women) lifetime chance of developing ovarian cancer. Older women are at highest risk.^{[citation needed]} More than half of the deaths from ovarian cancer occur in women between 55 and 74 years of age and approximately one quarter of ovarian cancer deaths occur in women between 35 and 54 years of age.

In other animals

Ovarian tumors have been reported in mares. Reported tumor types include teratoma,^[35][36] cystadenocarcinoma,^[37] and particularly granulosa cell tumor.^{[38][39][40][41][42]}

See also

• List of women with ovarian cancer
• Germ cell tumor
• Desmoplastic small round cell tumor
• Ovarian cyst

References

1. ^ EBSCO database verified by URAC; accessed from Mount Sinai Hospital, New York
2. ^ [1]accessed from VU University medical center, Amsterdam http://dare.ubvu.vu.nl/handle/1871/9013
3. ^ Robert C. Young (2005). "Ch. 83, Gynecologic Malignancies". in Jameson JN, Kasper DL, Harrison TR, Braunwald E, Fauci AS, Hauser SL, Longo DL. Harrison's principles of internal medicine (16th ed.). New York: McGraw-Hill Medical Publishing Division. ISBN 0-07-140235-7. http://highered.mcgraw-hill.com/sites/0071402357/information_center_view0/. 
4. ^ Gynecologic Neoplasms at Merck Manual of Diagnosis and Therapy Professional Edition
5. ^ Hamilton, W.; Round, A.; Sharp, D. (Jul 2009). "Not a silent killer". BMJ 339: b2719. doi:10.1136/bmj.b2719. ISSN 0959-8138. PMID 19581327.  edit
6. ^ ^{a b} Kosary, Carol L. (2007), "Chapter 16: Cancers of the Ovary", in Ries, LAG; Young, JL; Keel, GE et al., SEER Survival Monograph: Cancer Survival Among Adults: US SEER Program, 1988-2001, Patient and Tumor Characteristics, SEER Program, NIH Pub. No. 07-6215, Bethesda, MD: National Cancer Institute, pp. 133–144, http://seer.cancer.gov/publications/survival/surv_ovary.pdf 
7. ^ Goff BA, Mandel L, Muntz HG, Melancon CH (November 2000). "Ovarian carcinoma diagnosis". Cancer 89 (10): 2068–75. doi:10.1002/1097-0142(20001115)89:10<2068::AID-CNCR6>3.0.CO;2-Z. PMID 11066047. 
8. ^ Bankhead CR, Kehoe ST, Austoker J (July 2005). "Symptoms associated with diagnosis of ovarian cancer: a systematic review". BJOG 112 (7): 857–65. doi:10.1111/j.1471-0528.2005.00572.x. PMID 15957984. 
9. ^ Ryerson AB, Eheman C, Burton J, et al. (May 2007). "Symptoms, diagnoses, and time to key diagnostic procedures among older U.S. women with ovarian cancer". Obstet Gynecol 109 (5): 1053–61. doi:10.1097/01.AOG.0000260392.70365.5e (inactive 2009-03-01). PMID 17470582. http://journals.lww.com/greenjournal/pages/articleviewer.aspx?year=2007&issue=05000&article=00008&type=abstract. 
10. ^ ^{a b} Goff BA, Mandel LS, Melancon CH, Muntz HG (June 2004). "Frequency of symptoms of ovarian cancer in women presenting to primary care clinics". JAMA 291 (22): 2705–12. doi:10.1001/jama.291.22.2705. PMID 15187051. http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=15187051. 
11. ^ Chobanian N, Dietrich CS (April 2008). "Ovarian cancer". Surg. Clin. North Am. 88 (2): 285–99, vi. doi:10.1016/j.suc.2007.12.002. PMID 18381114. http://linkinghub.elsevier.com/retrieve/pii/S0039-6109(07)00180-6. 
12. ^ Vo C, Carney ME (December 2007). "Ovarian cancer hormonal and environmental risk effect". Obstet. Gynecol. Clin. North Am. 34 (4): 687–700, viii. doi:10.1016/j.ogc.2007.09.008. PMID 18061864. http://linkinghub.elsevier.com/retrieve/pii/S0889-8545(07)00090-3. 
13. ^ Bandera CA (June 2005). "Advances in the understanding of risk factors for ovarian cancer". J Reprod Med 50 (6): 399–406. PMID 16050564. 
14. ^ Goff BA, Mandel LS, Drescher CW, et al. (2007). "Development of an ovarian cancer symptom index: possibilities for earlier detection". Cancer 109 (2): 221–7. doi:10.1002/cncr.22371. PMID 17154394. 
15. ^ "Ovarian Cancer Symptoms Consensus Statement" (pdf). http://www.sgo.org/publications/OvarianCancerSymptoms.pdf. Retrieved 2007-07-19. 
16. ^ Collaborative Group on Epidemiological Studies of Ovarian Cancer, Beral V, Doll R, Hermon C, Peto R, Reeves G (January 2008). "Ovarian cancer and oral contraceptives: collaborative reanalysis of data from 45 epidemiological studies including 23,257 women with ovarian cancer and 87,303 controls". Lancet 371 (9609): 303–14. doi:10.1016/S0140-6736(08)60167-1. PMID 18294997. 
17. ^ Brinton, L.A., Moghissi, K.S., Scoccia, B., Westhoff, C.L., Lamb, E.J. (2005). "Ovulation induction and cancer risk". Fertil. Steril. 83 (2): 261–74; quiz 525–6. doi:10.1016/j.fertnstert.2004.09.016. PMID 15705362. 
18. ^ Lakhani SR, Manek S, Penault-Llorca F, et al. (April 2004). "Pathology of ovarian cancers in BRCA1 and BRCA2 carriers". Clin. Cancer Res. 10 (7): 2473–81. PMID 15073127. http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=15073127. 
19. ^ Genkinger JM, Hunter DJ, Spiegelman D, et al. (March 2006). "Alcohol intake and ovarian cancer risk: a pooled analysis of 10 cohort studies". British Journal of Cancer 94 (5): 757–62. doi:10.1038/sj.bjc.6603020. PMID 16495916. 
20. ^ La Vecchia C, Negri E, Franceschi S, Parazzini F, Gentile A, Fasoli M (September 1992). "Alcohol and epithelial ovarian cancer". Journal of Clinical Epidemiology 45 (9): 1025–30. doi:10.1016/0895-4356(92)90119-8. PMID 1432017. 
21. ^ "Alcohol consumption and cancer risk". Bandolier. 2007-04-01. http://www.jr2.ox.ac.uk/bandolier/booth/hliving/alccan.html. 
22. ^ Bagnardi V, Blangiardo M, La Vecchia C, Corrao G (2001). "Alcohol consumption and the risk of cancer: a meta-analysis". Alcohol Research & Health 25 (4): 263–70. PMID 11910703. http://pubs.niaaa.nih.gov/publications/arh25-4/263-270.htm. 
23. ^ BBC News Milk link to ovarian cancer risk 29 November 2004
24. ^ Bast RC, Brewer M, Zou C, et al. (2007). "Prevention and early detection of ovarian cancer: mission impossible?". Recent Results Cancer Res. 174: 91–100. PMID 17302189. 
25. ^ ^{a b c d} Screening for Ovarian Cancer Daniel L. Clarke-Pearson, N Engl J Med, 361:170, July 9, 2009
26. ^ Kurman RJ, Visvanathan K, Roden R, Wu TC, Shih IeM (April 2008). "Early detection and treatment of ovarian cancer: shifting from early stage to minimal volume of disease based on a new model of carcinogenesis". Am. J. Obstet. Gynecol. 198 (4): 351–6. doi:10.1016/j.ajog.2008.01.005. PMID 18395030. PMC 2532696. http://linkinghub.elsevier.com/retrieve/pii/S0002-9378(08)00020-3. 
27. ^ Partridge E, Kreimer AR, Greenlee RT, et al. (April 2009). "Results from four rounds of ovarian cancer screening in a randomized trial". Obstet Gynecol 113 (4): 775–82. doi:10.1097/AOG.0b013e31819cda77. http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0029-7844&volume=113&issue=4&spage=775. 
28. ^ Menon U, Gentry-Maharaj A, Hallett R, et al. (April 2009). "Sensitivity and specificity of multimodal and ultrasound screening for ovarian cancer, and stage distribution of detected cancers: results of the prevalence screen of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS)". Lancet Oncol. 10 (4): 327–40. doi:10.1016/S1470-2045(09)70026-9. PMID 19282241. http://linkinghub.elsevier.com/retrieve/pii/S1470-2045(09)70026-9. 
29. ^ Ehrlich, P.F., Teitelbaum, D.H., Hirschl, R.B., Rescorla, F. (2007). "Excision of large cystic ovarian tumors: combining minimal invasive surgery techniques and cancer surgery—the best of both worlds". J. Pediatr. Surg. 42 (5): 890–3. doi:10.1016/j.jpedsurg.2006.12.069. PMID 17502206. 
30. ^ McGuire WP, Markman M (December 2003). "Primary ovarian cancer chemotherapy: current standards of care". Br. J. Cancer 89 (Suppl 3): S3–8. doi:10.1038/sj.bjc.6601494. PMID 14661040. 
31. ^ Armstrong DK, Bundy B, Wenzel L, Huang HQ, et al. (January 2006). "Intraperitoneal Cisplatin and Paclitaxel in Ovarian Cancer". NEJM 354 (1): 34–43. doi:10.1056/NEJMoa052985. PMID 16394300. http://content.nejm.org/cgi/content/full/354/1/34. 
32. ^ Swart AM, Burdett S, Ledermann J, Mook P, Parmar MK (April 2008). "Why i.p. therapy cannot yet be considered as a standard of care for the first-line treatment of ovarian cancer: a systematic review". Ann. Oncol. 19 (4): 688–95. doi:10.1093/annonc/mdm518. PMID 18006894. http://annonc.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=18006894. 
33. ^ Survival rates based on SEER incidence and NCHS mortality statistics, as cited by the National Cancer Institute in SEER Stat Fact Sheets - Cancer of the Ovary
34. ^ "WHO Disease and injury country estimates". World Health Organization. 2009. http://www.who.int/healthinfo/global_burden_disease/estimates_country/en/index.html. Retrieved Nov. 11, 2009. 
35. ^ Catone G, Marino G, Mancuso R, Zanghì A (April 2004). "Clinicopathological features of an equine ovarian teratoma". Reprod. Domest. Anim. 39 (2): 65–9. doi:10.1111/j.1439-0531.2003.00476.x. PMID 15065985. 
36. ^ Lefebvre R, Theoret C, Doré M, Girard C, Laverty S, Vaillancourt D (November 2005). "Ovarian teratoma and endometritis in a mare". Can. Vet. J. 46 (11): 1029–33. PMID 16363331. 
37. ^ Son YS, Lee CS, Jeong WI, Hong IH, Park SJ, Kim TH, Cho EM, Park TI, Jeong KS (May 2005). "Cystadenocarcinoma in the ovary of a Thoroughbred mare". Aust. Vet. J. 83 (5): 283–4. doi:10.1111/j.1751-0813.2005.tb12740.x. PMID 15957389. 
38. ^ Frederico LM, Gerard MP, Pinto CR, Gradil CM (May 2007). "Bilateral occurrence of granulosa-theca cell tumors in an Arabian mare". Can. Vet. J. 48 (5): 502–5. PMID 17542368. 
39. ^ Hoque S, Derar RI, Osawa T, Taya K, Watanabe G, Miyake Y (June 2003). "Spontaneous repair of the atrophic contralateral ovary without ovariectomy in the case of a granulosa theca cell tumor (GTCT) affected mare" (^{[dead link]} – ^{Scholar search}). J. Vet. Med. Sci. 65 (6): 749–51. doi:10.1292/jvms.65.749. PMID 12867740. http://joi.jlc.jst.go.jp/JST.JSTAGE/jvms/65.749?from=PubMed. 
40. ^ Sedrish SA, McClure JR, Pinto C, Oliver J, Burba DJ (November 1997). "Ovarian torsion associated with granulosa-theca cell tumor in a mare". J. Am. Vet. Med. Assoc. 211 (9): 1152–4. PMID 9364230. 
41. ^ Moll HD, Slone DE, Juzwiak JS, Garrett PD (1987). "Diagonal paramedian approach for removal of ovarian tumors in the mare". Vet Surg 16 (6): 456–8. doi:10.1111/j.1532-950X.1987.tb00987.x. PMID 3507181. http://www3.interscience.wiley.com/journal/119849124/abstract. 
42. ^ Doran R, Allen D, Gordon B (January 1988). "Use of stapling instruments to aid in the removal of ovarian tumours in mares". Equine Vet. J. 20 (1): 37–40. PMID 2835223. 

v • d • e Tumors: urogenital neoplasia · genital neoplasia (C51-C63/D25-29, 179-187/218-222) Female Ovaries Glandular and epithelial Clear cell adenocarcinoma · Endometrioid tumor CMS: Krukenberg tumor · Serous cystadenoma/Mucinous cystadenoma · Cystadenocarcinoma/Papillary serous cystadenocarcinoma Sex cord-gonadal stromal Leydig cell tumour · Sertoli cell tumour · Sertoli-Leydig cell tumour · Thecoma · Granulosa cell tumour · Luteoma Connective tissue Fibroma (Meigs syndrome) · Surface epithelial-stromal tumor (Brenner tumour) Germ cell Dysgerminoma · Embryonal carcinoma · Gonadoblastoma · Teratoma · Choriocarcinoma Fallopian tube Adenomatoid tumor Uterus Uterine sarcoma · Leiomyosarcoma Endometrium (Endometrioid tumor), (Uterine papillary serous carcinoma), (Clear cell carcinoma) Adenomyoma Cervix (SCC, Cervical intraepithelial neoplasia) Vagina SCC · Botryoid rhabdomyosarcoma · Adenocarcinoma/Clear cell adenocarcinoma Vulva Papillary hidradenoma · Extramammary Paget's disease Placenta Choriocarcinoma Male Testicles Sex cord-gonadal stromal Sertoli-Leydig cell tumour (Sertoli cell tumor, Leydig cell tumor) Germ cell G Seminoma (Spermatocytic seminoma) · Intratubular germ cell neoplasia NG Embryonal carcinoma · Endodermal sinus tumor · Gonadoblastoma · Teratoma · Choriocarcinoma · Embryoma Prostate Adenocarcinoma · Prostatic intraepithelial neoplasia (HGPIN) · Small cell carcinoma · Transitional cell carcinoma Penis Carcinoma (Extramammary Paget's disease) · Bowen's disease · Bowenoid papulosis · Erythroplasia of Queyrat reproductive system navs: anat female,male/physio/dev, noncongen/congen/neoplasia, symptoms+signs/eponymous, proc

External links

• Ovarian Cancer at American Cancer Society
• Ovarian Cancer From Cancer Management: A Multidisciplinary Approach
• Recognizing the Signs-Sandra O.Goodman
• WebMD: Ovarian Cancer Health Center
• Medical Encyclopedia MayoClinc: Ovarian Cancer
• Interactive Health Tutorials Medline Plus: Ovarian cancer Using animated graphics and you can also listen to the tutorial
• Cancer of the Ovary, Stephen A. Cannistra, New England Journal of Medicine, 351:2519-2529, December 9, 2004
• Ovarian cancer at the Open Directory Project
• Ovarian cancer at the Yahoo! Directory
• The latest news and medical research on ovarian cancer at MedWorm

This entry is from Wikipedia, the leading user-contributed encyclopedia. It may not have been reviewed by professional editors (see full disclaimer)