Ovarian cancer is a malignant tumor (a kind of neoplasm) located on an ovary. Although many ovarian tumors are benign, most have the potential to become malignant unless treated.

Causes

 Ovarian cancer is the fifth leading cause of cancer death in women, the leading cause of death from gynecological malignancy, and the second most commonly diagnosed gynecologic malignancy.

 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. 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 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 ages 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.

 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 providing conclusive evidence for such a link.  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 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. Patients with a personal history of breast cancer or a family history of breast and/or ovarian cancer, especially if 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 child-bearing.

 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."  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.

 

 Classification

 Ovarian tumors can be classified by their presumed cell of origin. The main categories are:

     * surface epithelial-stromal tumours

    * sex cord-stromal tumours (ICD-O 8590)

    * germ cell tumours (ICD-O 9060-9090)

    * secondary or metastatic tumours

 

Histology

 Ovarian cancer is classified according to the histology of the tumor (ICD-O codes). Histology dictates many aspects of clincal treatment, management, and prognosis.

 * Surface epithelial-stromal tumours are the most common type of ovarian cancers. They are thought to originate from the ovarian surface lining, and include serous cystadenocarcinoma (8441/3), and mucinous cystadenocarcinoma (8470/3). The abdominal cavity is lined with the same cells that make up the ovarian surface lining, and it is possible to have cancer begin there, in which case, it is called primary peritoneal cancer. Treatment, however, is basically the same as treatment for ovarian cancer.

    * Sex cord-stromal tumors (8590) include lesions that are hormonally active such as the estrogen-producing granulosa cell tumor (8620/3) and the virilizing Sertoli-Leydig cell tumor or arrhenoblastoma.

    * Germ cell tumors (9060-9090) of the ovary originate from germ cells and tend to occur in young women and girls. These tumors represent approximately 5% of ovarian cancers.[citation needed] They tend to be well encapsulated and many are benign, and therefore have a better prognosis than other ovarian tumors.

    * mixed tumors

    * secondary or metastatic tumors

Natural history

Ovarian cancer often is primary, but can also be secondary, the result of metastasis from primary cancers elsewhere in the body. For example, from breast cancer, or from gastrointestinal cancer (in which case the ovarian cancer is a Krukenberg cancer).

 

Symptoms

Studies on the 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. The smaller, second study found that women with ovarian cancer had pelvic/abdominal pain, increased abdominal size/bloating, and difficulty eating/feeling full. The latter study created a symptom index that was considered positive if any of the 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%.

 

  Ovarian Cancer Symptoms 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.

Historically ovarian cancer was called the “silent killer” because symptoms were not thought to develop until the chance of cure was poor. However, recent studies have shown this term is untrue and that 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

    * Difficulty eating or feeling full quickly

    * Urinary symptoms (urgency or frequency)

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.

 

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 due to the fact that 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, a serum 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.

The blood test called CA-125 is useful in differential diagnosis and in follow up of the disease, but it has not been shown to be an effective method to screen for early-stage ovarian cancer and is currently not recommended for this use.

Current research is looking at ways to combine tumor markers 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 unacceptable numbers of false positive results (i.e. performing surgical procedures in which cancer is not found intra-operatively). This is exemplified by the recent discovery of proteomic predictors that showed 100% sensitivity and 95% specificity.

A pelvic examination, including CT scan, trans-vaginal ultrasound, is also of utility. 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 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.

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, and pelvic (peritoneal) washings for cytology. The AJCC stage is the same as the FIGO stage.

    * Stage I - limited to one or both ovaries

          o IA - involves one ovary; capsule intact; no tumor on ovarian surface; no malignant cells in ascites or peritoneal washings

          o IB - involves both ovaries; capsule intact; no tumor on ovarian surface; negative washings

          o IC - tumor limited to ovaries with any of the following: capsule ruptured, tumor on ovarian surface, positive washings

    * Stage II - pelvic extension or implants

          o IIA - extension or implants onto uterus or fallopian tube; negative washings

          o IIB - extension or implants onto other pelvic structures; negative washings

          o 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

          o IIIA - microscopic peritoneal metastases beyond pelvis

          o IIIB - macroscopic peritoneal metastases beyond pelvis less than 2 cm in size

          o IIIC - peritoneal metastases beyond pelvis > 2 cm or lymph node metastases

    * Stage IV - distant metastases--in the liver, or outside the peritoneal cavity

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

 

 

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