Ovarian cancer

Ovarian cancer is a malignant ovarian neoplasm (an abnormal growth located on the ovaries).

Causes
Ovarian cancer is the fifth leading cause of cancer death in women (after lung, breast, colon and pancreas), the leading cause of death from gynecologic malignancies and the second most commonly diagnosed gynecologic malignancy. It is idiopathic, meaning that 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) lifelong chance of developing ovarian cancer.

Older women are at highest risk. 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.

The risk for 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 ages of final pregnancy and the use of low dose oral contraceptive pills have also been shown to have a protective effect. Ovarian cancer is reduced in women after tubal ligation.

The link to the use of fertility medication has been controversial. An analysis in 1991 raised the possibility that use of drugs may increase the risk for ovarian cancer. Several cohort studies and case-control studies have been conducted since then without providing conclusive evidence for such a link with the possible exception that prolonged use (> 1 year) of clomiphene citrate should be avoided. It will remain a complex topic to study as the infertile population differs in parity from the "normal" population.

There is good evidence that in some women genetic factors are important. Carriers of certain mutations of the BRCA1 or the BRCA2 gene (especially Ashkenazi Jewish women) are at a higher risk of both breast cancer and ovarian cancer, often at an earlier age than the general population. Patients with a personal history of breast cancer, or a family history of breast and/or ovarian cancer, 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 non-polyposis colon cancer (HNPCC), which confers a higher risk for developing ovarian cancer. Patients with strong genetic risk for ovarian cancer may consider the use of prophylactic oophorectomy after completion of child-bearing.

A recent 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." See http://news.bbc.co.uk/2/hi/health/4051331.stm for more.

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.

A study funded by the American Cancer Society conducted at the H. Lee Moffitt Cancer Center & Research Institute has found a correlation between high levels of lysophospholipids (a type of fatty acid) with ovarian cancer patients and low levels of lysophospholipids with healthy women. This potential biomarker can be detected by a simple blood test. The blood test was 93 % accurate as predictor of ovarian cancer with less than 4 % false positives of the 117 women studied. Other indicators of ovarian cancer could be used to increase accuracy to 100 %.

"Associations were also found between alcohol consumption and cancers of the ovary and prostate, but only for 50 g and 100 g a day."

Symptoms
Note: There may be no symptoms until late in the disease.
 * sense of pelvic heaviness
 * vaginal bleeding
 * weight gain or weight loss
 * abnormal menstrual cycles
 * unexplained back pain that worsens over time
 * increased abdominal girth
 * non specific gastrointestinal symptoms:
 * vague lower abdominal discomfort
 * increased gas
 * indigestion
 * lack of appetite
 * nausea and vomiting
 * inability to ingest usual volumes of food
 * bloating
 * Additional symptoms that may be associated with this disease:
 * increased urinary frequency/urgency
 * excessive hair growth

In particular, women should watch for symptoms occurring in groups and lasting two weeks or more.

Diagnosis
Women experiencing these symptoms should request a blood test called CA-125, along with a complete pelvic examination. While this test is not generally regarded as useful for large scale screening by the medical community, a high value may be an indication that the woman should receive further diagnostic screening or treatment. Normal values range from 0 to 35. Elevated levels in post-menopausal women are usually an indication that further screening is necessary. In pre-menopausal women, the test is less reliable as values are often elevated due to a number of non-cancerous causes, and a value above 35 is not necessarily a cause for concern.

Further screening may involve CT scans, trans-vaginal ultrasounds, or retesting of the CA-125 value at a later date (to see if the value is normalising, or increasing).

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 exam should include a rectovaginal component for better palpation of the ovaries.

However, ovarian cancer at its early stages(I/II) is difficult to be diagnosed until it spreads and advances to later stages(III/IV). It is due to the fact that most of the common symptoms are non-specific.

Classification
Ovarian cancer is classified according to the histology of the tumor. Lesions differ significantly in clinical features, management, and prognosis (ICD-O codes provided where available):
 * Surface epithelial-stromal tumours are the most common and prototypic ovarian cancers. They are thought to originate from the ovarian surface lining, and include serous cystadenocarcinoma (8441/3), and mucinous cystadenocarcinoma (8470/3).
 * Sex cord-stromal tumors include lesions that are hormonally active such as the estrogen-producing granulosa cell tumor (8620/3) and the virilizing arrhenoblastoma.
 * Germ cell tumors originate from dysplastic germ material and tend to occur in young women and girls. Lesions include the dysgerminoma (9060/3), a form of the choriocarcinoma (9100/3), and the malignant form of the teratoma (9083/3).
 * Other lesions include metastasis to the ovary, for instance from breast cancer. Krukenberg cancer is ovarian cancer originating from gastrointestinal cancer.

Staging
Ovarian cancer staging is by the FIGO staging system and uses information obtained after surgery, which should include a total abdominal hysterectomy, removal of (usually) both ovaries and fallopian tubes, (usually) the omentum, and pelvic (peritoneal) washings for cytology. The AJCC stage is the same as the FIGO stage.


 * Stage I - limited to one or both ovaries
 * IA - involves one ovary; capsule 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

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

Treatment
Surgery is the preferred treatment and is frequently necessary for diagnosis. Studies have shown that surgery performed by a specialist in gynecologic oncology usually result in a higher rate of cure. Chemotherapy is used as after surgery to treat any residual disease. Until recently, intravenous chemotherapy was used in treating patients with advanced ovarian cancer. A recent study has shown that women with advanced ovarian cancer live longer if chemotherapy is given into the abdomen. Now doctors are recommending chemotherapy delivered to the abdomen as a preferred method of treating advanced ovarian cancer. This treatment is referred to as intraperitoneal chemoperfusion. Chemotherapy can also be used to treat women who have a recurrence. Radiation therapy is rarely used in ovarian cancer in the United States.

Chemosensitivity testing is being done by laboratories in the USA, Europe, and Asia. These labs use a variety of methods to attempt to identify chemotherapy agents that will work with an individual's cancer. It is impossible to perfectly model cancer chemotherapy in a laboratory test. Nonetheless, more than a dozen peer-reviewed studies have shown that drugs active in the laboratory are more likely to work than drugs that are inactive in the laboratory. The tests remain controversial because clinical trials have not been performed to prove that basing treatment on test results improves clinical outcomes. In other words, the tests have been validated for accuracy but not for efficacy. On the other hand, all other laboratory tests used as an aid for drug selection in cancer have also been validated only for accuracy and not for efficacy. The procedure often requires that the patient contact a lab offering this service, which then ships containers ahead of surgery, so that the surgeon can send tumor samples in for testing. Costs are often not covered by insurance.

Surgery is usually the first treatment for ovarian cancer. The type of surgery depends upon how widespread the cancer is when diagnosed (the cancer stage), as well as the type and grade of cancer. The surgeon may remove one (unilateral) or both ovaries (bilateral), 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 and have children.

Expectations (prognosis)
Ovarian cancer is disproportionately deadly for a number of reasons. First, symptoms are vague and non-specific, so women and their physicians frequently attribute them to more common conditions. By the time the cancer is diagnosed, the tumor has often spread beyond the ovaries. More than 60% of patients presenting with this disease already have stage III status.

Also, ovarian cancers shed malignant cells into the naturally occurring fluid within the abdominal cavity. These cells then have the potential to float in this fluid and frequently implant on other abdominal (peritoneal) structures includind the uterus, urinary bladder, bowel, and lining of the bowel wall (omentum). These cells can begin forming new tumor growths before cancer is even suspected.

Second, because no cost-effective screening test for ovarian cancer exists, more than 50 % of women with ovarian cancer are diagnosed in the advanced stages of the disease.

Ovarian cancer is rarely diagnosed in its early stages; it is usually quite advanced by the time diagnosis is made. The outcome is often poor. The five-year survival rate for all stages is only 35 % to 38 %. If, however, diagnosis is made early in the disease, five-year survival rates can reach 90 % to 98 %. Germ Cell Ovarian Cancer has a much better prognosis, but is rarer.

Despite this poor prognosis, patients should keep in mind that all such studies are retrospective in nature: i.e., they can only look into past results. Therefore they cannot take into account the benefits to survival that newer therapies may provide.

Complications

 * spread of the cancer to other organs
 * progressive function loss of various organs
 * ascites (fluid in the abdomen)
 * blockage of the intestines

Victims of ovarian cancer

 * Evelyn Ankers, actress (died at age 67); (see )
 * Raelene Boyle, Australian athlete; surviving
 * Laurie Beechman, actress/singer (died at age 43)
 * Clare Boylan, Irish writer (died at age 58)
 * Jill Chaifetz, American lawyer and childen's right advocate (died at age 41)
 * Carol Channing, actress/entertainer; surviving
 * Caitlin Clarke, actress (died at age 52)
 * Helen Cresswell, British writer and author (died at age 71)
 * U.S. Congresswoman Rosa DeLauro, surviving (see )
 * Mildred Dean, mother of American actor James Dean; she died when Dean was 9 years old (see).
 * Sandy Dennis, Oscar-winning actress (died at age 54)
 * Rosalind Franklin, British physical chemist and crystallographer (died at age 37)
 * Diana Dors, actress, also known as Diana d'Ors (died at age 52)
 * Robert Eads, American female to male transsexual who was refused medical treatment for the cancer in the state of Georgia (died at age 53)
 * Susan Fleetwood, British actress (died at age 51)
 * Ella Grasso, former Connecticut governor, and the first woman ever to be elected governor in her own right (died at age 61)
 * Cassandra Harris, Australian actress/wife of Pierce Brosnan (died at age 43)
 * Dolly Haas, actress/singer; wife of Al Hirschfeld (died at age 84)
 * Joan Hackett, actress (died at age 49)
 * Madeline Kahn, actress, singer and comedienne (died at age 57)
 * Coretta Scott King, wife of civil rights activist Rev. Martin Luther King, Jr. (died at age 78)
 * Dixie Lee, actress/singer; converted to marry Bing Crosby (died at age 40)
 * Janet Margolin, actress (died at age 50)
 * Mary I of England, neé Mary Tudor; British Queen Mary I (died either of uterine cancer or ovarian cancer at the age of 42)
 * Mary Millar, British actress, most famous as "Rose" from Keeping Up Appearances (died at age 62)
 * Helen Simpson Morosini, Mother of Dana Reeve, who was wife of Christopher Reeve (died at age 71)
 * Bess Myerson, surviving
 * Laura Nyro, singer (died at age 49; her own mother, Gilda Nigro, also died of ovarian cancer and at the same age as Nyro)
 * Alice Pearce, actress (died at age 48)
 * Gilda Radner, actress/comedienne/Saturday Night Live alumna (died at age 42)
 * Patsy Ramsey, mother of the late JonBenét Ramsey (died at age 49)
 * Janet Sandell, South African social activist (died at age 70)
 * Dinah Shore, actress/singer (died at age 77)
 * Linda Smith, comedienne, actress; head of the British Humanists' Association (died at age 48)
 * Jessica Tandy, actress (died at age 85)
 * Elizabeth Tilberis, Harper's Bazaar Editor-in-Chief (died at age 51)
 * Loretta Young, Oscar-winning actress (died at age 87)