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Ovarian cancer

From Academic Kids

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

Contents

Causes

Ovarian cancer is the fourth leading cause of cancer death in women, the leading cause of death from gynecologic malignancies and the second most commonly diagnosed gynecologic malignancy [1] (http://www.merck.com/mrkshared/mmanual/section18/chapter241/241b.jsp). While the exact cause is unknown (i.e., idiopathic), the disease is more common in industrialized nations, with the exception of Japan. In the United States, females have a 1.4 percent to 2.5 percent (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 some 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 that stimulate ovulation 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.1 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. Carrier of mutations of the BRCA1 or the BRCA2 gene are at higher risk of both breast cancer and ovarian cancer already at a younger age. 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, colon, 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 prophyllactic oophorectomy after completion of their reproductive goal.

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 American Cancer Society conducted at the H. Lee Moffitt Cancer Center of the University of South Florida has found a correlation between high levels of lysophospholipids (http://cancerweb.ncl.ac.uk/cgi-bin/omd?query=lysophospholipids&action=Search+OMD) (a type of fatty acid) with ovarian cancer patients and low levels of lysophospholipids with healthy women. This potential biomarker (http://dictionary.reference.com/search?q=biomarker) can be detected by a simple blood test. The blood test was 93 percent accurate as predictor of ovarian cancer with less than 4 percent false positives of the 117 women studied. Other indicators of ovarian cancer could be used to increase accuracy to 100 percent. 2


Symptoms

  • sense of pelvic heaviness
  • vague lower abdominal discomfort
  • vaginal bleeding
  • weight gain or loss
  • abnormal menstrual cycles
  • unexplained back pain that worsens over time
  • increased abdominal girth
  • non specific gastrointestinal symptoms:
    • 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

Note: There may be no symptoms until late in the disease.

Women experiencing these symptoms should insist on having a blood test called CA-125 done. While this test is far from perfect, and is generally not regarded as useful for large scale screening by the medical community, a high value will immediately signal the need for further testing. Normal values range from 0 to 35. Values can be temporarily elevated due to a number of non-cancerous causes.

CA-125 stands for Cancer Antigen 125. The CA-125 test looks for the presence of a protein on the surface of cells from the ovary. Elevated levels of this protein have been associated with other types of cancer, but it is considered a biomarker for ovarian cancer.3

Further screening may involve CT scans, trans-vaginal ultrasounds, or retesting of the CA-125 value at a later date.

Signs

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.

Classification

Ovarian cancer is classified according to the histology of the tumor. Lesions differ significantly in clinical features, management, and prognosis:

  • Epithelial ovarian tumors are the most common and prototypic ovarian cancers. They are thought to originate from the ovarian surface lining, including the serous cystadenocarcinoma, and the mucinous cystadenocarcinoma.
  • Stromal ovarian cancer includes lesions that are hormonally active such as the estrogen-producing granulosa cell tumor and the virilizing arrhenoblastoma.
  • Germ cell cancer originates from dysplastic germ material and tends to occur in young women and girls. Lesions include the dysgerminoma, a form of the choriocarcinoma, and the malignant form of the teratoma.
  • 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 2cm in size
    • IIIC - peritoneal metastases beyond pelvis > 2 cm or lymph node metastases
  • Stage IV - distant metastases

Paraaortic 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 results in a higher rate of cure. Chemotherapy is used as after surgery to treat any residual disease. Chemotherapy can also be used to treat women who have a recurrence. Radiation therapy is rarely used in ovarian cancer in the United States.

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.

Also, ovarian cancers shed malignant cells that frequently implant on the uterus, 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 percent 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 percent to 38 percent. If, however, diagnosis is made early in the disease, five-year survival rates can reach 90 percent to 98 percent. 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: ie, they can only look into past results. Therefore they cannot take into account the benefits on 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

References

1Brinton LA et al. Ovulation induction and cancer risk. Fertil Steril 2005;83:261-74.

2The study is published in the July 7, 2004 journal of Cancer Epidemiology, Biomarkers & Prevention (http://cebp.aacrjournals.org).

3American Association for Clinical Chemistry (2002). CA-125 At a Glance (http://www.labtestsonline.org/understanding/analytes/ca125/glance.html) at Lab Tests Online (http://www.labtestsonline.org/index.html). Retrieved 2005-03-01.

See also

External links

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