Archive for the Ovarian Cancer category.
Unfortunately, most patients with ovarian cancer are diagnosed after the disease has spread beyond the ovary. In these patients, symptoms may be abdominal pain or a bloated feeling, gastrointestinal or urinary tract disturbances, or in many cases, the onset of clinically detectable ascites. Some patients with advanced disease have menstrual irregularity or postmenopausal bleeding, but these symptoms occur infrequently. Occasionally, a patient may present with a palpable inguinal lymph node, tumor in a hernia sac, or pleural effusion. For patients with advanced disease, diagnosis is established by tissue obtained at exploratory laparotomy. In rare instances when a patient cannot undergo surgery because of medical problems, the histologic or cytologic diagnosis is established by needle biopsy.
Early ovarian cancer is diagnosed by the surgical evaluation of an adnexal mass. The decision to subject a patient to surgical exploration is difficult to make. Ultrasonographic evaluation of the adnexal mass has improved the ability to distinguish patients who should have surgical exploration from those who can be observed, but it has also resulted in an increasing number of patients who are found to have an asymptomatic ovarian cyst. This is of particular concern in the postmenopausal woman. Table 7 outlines the diagnostic criteria for surgical exploration of a patient with an adnexal mass. As with any diagnostic or therapeutic schema, the criteria for exploration cannot be absolute. For example, a patient with known endometriosis may meet the criteria for surgical exploration when it is not the best treatment option, or a postmenopausal patient with a 4-cm simple cyst may have risk factors for surgery that make observation a more reasonable option.
Cancer treatment
The use of tumor markers to assist in the evaluation of a patient with an adnexal mass is not inappropriate, but misinformation may result. Serum CA 125 is used most often and is the only serum marker available with the potential accuracy to be beneficial, but even this marker is less than optimal. Approximately half of early-stage ovarian cancer patients do not have elevated serum CA 125 levels. Also, a variety of nonmalignant and nonovarian malignant conditions can result in elevated serum CA 125 levels. These conditions are listed in Tables 8 and 9, page 43. A serum CA 125 elevation above 35 U may be helpful in deciding whether or not to recommend surgery in a postmenopausal patient with an ovarian mass, but a negative value is not helpful. Likewise, a serum CA 125 elevation in women of reproductive age with both an ovarian mass and leiomyomata or endometriosis may not be helpful.
TABLE 7. Management Schema for a Patient with an Adnexal Mass
Observe and Repeat Examination in 4-6 Weeks Surgical Exploration
Reproductive age Premenarchal or postmenopausal*
Mass <8 cm Mass >8 cm
Simple cysts on ultrasonography Complex cysts on ultrasonography
Decreasing size Increase in size or persistence through 2-3 menstrual cycles
Cystic and smooth Solid and irregular
Mobile Fixed
Unilateral Bilateral
Asymptomatic Pain or other symptoms of acute intraabdominal process
No ascites Ascites
*Simple cysts smaller than 3 cm may be followed closely with ultrasonography.
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Staging classification is made on the basis of surgical evaluation, and the removal of as much tumor as possible is the cornerstone of treatment. Despite the importance of surgery, some type of adjunctive treatment is almost always required. The proper surgical procedure and the appropriate choice of adjunctive therapy depend on the findings at initial exploration, the histologic type of the tumor, and the age and reproductive desires of the patient. There are few diseases encountered by the gynecologist that will demand as much knowledge and skill as the therapy of ovarian cancer.
Cancer
Staging
The FIGO staging classification scheme for ovarian cancer is outlined in the box, page 42. The staging of advanced disease (spread throughout the abdomen) may be obvious to most physicians, but it is important for a surgeon to be meticulous in the staging of early ovarian cancer. In one study it was found that one third of patients referred with stage I or stage II disease were actually found to have stage III disease when the appropriate staging operation was performed. Similar results have been reported by other researchers. Buy cheap levitra at Canadian Pharmacy
To perform a staging operation appropriately, the spread patterns of the cancer should be understood. The cancer can spread by direct infiltration of pelvic structures such as the pelvic peritoneum, bladder surface, rectal surface, fallopian tube, broad ligament, or uterus. Lymphatic spread occurs early in ovarian cancer, with nodal metastases occurring in 10-12% of patients with stage I cancer and 2025% of patients with stage II disease. In stage III and stage IV, the incidence of positive lymph nodes is 50-70%. By far, however, the most significant spread of ovarian cancer is exfoliation of clonogenic cells into the peritoneal cavity. These cells are swept up the right abdominal gutter to the diaphragm and omentum by the clockwise flow of peritoneal fluid in the abdomen. The cells implant, form tumor nodules, and in turn exfoliate more cells. The normal daily activities of the patient and normal peristalsis of the intestine result in spread of the disease throughout the abdominal cavity. Proper staging requires a generous lower and upper midline incision and meticulous exploration with multiple peritoneal and nodal biopsies.
In young patients who wish to bear children and have epithelial, germ cell, or stromal tumors confined to one ovary, conservation of the uterus and other ovary and fallopian tube is possible, provided that a full surgical staging procedure is performed. In these patients, it is particularly important to be meticulous in the evaluation of the entire abdomen.
Ovarian tumors are usually categorized by their tissue of origin: epithelial (from the coelomic epithelial cells that line the ovary), sex cord-stromal (from the mesenchymal tissue of the ovary), and germ cell (from the germinal epithelium). Epithelial tumors account for approximately 85% of ovarian cancers, germ cell cancers account for approximately 10%, and the remaining 5% of tumors are sex cord-stromal in origin. The World Health Organization’s classification system for ovarian tumors is shown in the box, pages 40-41.
Of the malignant epithelial ovarian cancers, 40-50% are serous tumors, 15-25% are endometrioid tumors, 6-16% are mucinous tumors, and 5-11% are clear cell tumors. Transitional cell (Brenner), mixed epithelial, and undifferentiated carcinomas are encountered less frequently. Epithelial tumors may be benign, have low malignant potential, or be frankly malignant. Tumors of low malignant potential (borderline tumors) have a much better prognosis than the frankly malignant cancers, but they are nevertheless malignant and can result in death. Malignant tumors are further subdivided by histologic grade either into three grades based on architecture (FIGO classification) or into four grades based on nuclear atypia (Broders’ index).
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The most common germ cell tumor is the mature cystic teratoma, a benign tumor. The most common malignant germ cell tumor is the dysgerminoma, followed in incidence by the endodermal sinus tumor and the immature teratoma. As can be seen in Figure 4, the germ cell tumors are most commonly seen in the first two decades of life.
The sex cord-stromal tumors are usually divided into the female type, characterized by the granulosa cell tumor, and the male type, characterized by the Sertoli-Leydig cell tumor. More than 90% of malignant stromal tumors are granulosa cell tumors. Although these tumors can occur at any age, they are more common before menopause.
One of the most significant ways to improve survival for patients with ovarian cancer would be to find a way to screen women for ovarian cancer and detect the disease before it spreads beyond the ovary. Currently available methods for screening for ovarian cancer are pelvic examination, serum CA 125 level measurements, and pelvic or transvaginal ultrasonography. To date, there is no evidence that routine pelvic examination is effective in the early diagnosis of ovarian cancer. Serum CA 125 levels have also shown to be ineffective because of the high false-negative rates. A review of the literature found that only about 50% of patients with stage I ovarian cancer have an abnormal serum CA 125 level. To substantiate this point further, the only study to look at CA 125 screening for ovarian cancer reported that in the six cancers of the ovary diagnosed by CA 125 screening, four had spread beyond the ovary. However, in three studies, pelvic or transvaginal ultrasonography screenings of 7,576 patients diagnosed 10 cancers, all stage I. Unfortunately, this technique has a high false-positive rate, and between 13 and 65 patients underwent surgical exploration for each cancer detected in these studies. If some additional test could be discovered that would allow determination of which patient with an enlarged ovary actually needs exploration, transvaginal ultrasonography might turn out to be an effective screening tool. Current research in this area centers around developing a more precise morphology index, a more specific color flow Doppler pattern, and more specific serum markers.
TABLE 6. Stage at Diagnosis and 5-Year Survival Rate of Gynecologic Cancers, United States 2006
Stage at Diagnosis (%) 5-Year Survival Rate (%)
Site Localized Regional Distant Localized Regional Distant
Endometrium 73 13 10 96 69 28
Cervix 51 33 8 92 52 10
Ovary 23 15 56 91 49 23
About 26,800 women are diagnosed with ovarian cancer each year in the United States. Of these women, approximately 14,200 will die of the disease. Ovarian cancer represents 55% of all deaths from gynecologic cancer. The risk of a woman developing ovarian cancer during her lifetime is 1-2%. The incidence varies with age and is 1.4 per 100,000 in women under age 40 years and 38 per 100,000 in women older than age 60 years. Figure 4 illustrates the prevalence of different types of ovarian cancer by age. Ovarian cancer is more common in Northern European and North American countries than in Asia, developing countries, or southern continents.
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The etiology of ovarian cancer is not known, but risk factors include infertility, low parity, or both; use of talc on the perineum; high-fat diet; lactose intolerance; history of breast or colon cancer; and a family history of ovarian cancer. Smoking, alcohol use, coffee consumption, estrogen replacement therapy, and viral infections (such as mumps) have not been associated with increased risk. Use of oral contraceptives, however, is protective for ovarian cancer, with an average relative risk of about 0.7 for women who have used oral contraceptives for 2 years and a 0.5 relative risk for women who have used oral contraceptives for 5 years or more. The protective effect of oral contraceptive use appears to be long term, with some studies indicating a lifetime risk reduction.
Table 6 illustrates the relative stage at diagnosis and the survival by stage for ovarian cancer in relation to other gynecologic cancers. The 5-year survival rate for ovarian cancer by stage is not significantly different from the 5-year survival rate for other gynecologic cancers; however, there is a significant difference in stages, with ovarian cancer usually having spread into the abdomen in about two thirds of patients at the time of diagnosis. It is clear from these data that the single most important factor in the large number of deaths from ovarian cancer is the failure to diagnosis the disease at an early stage. The reasons for this failure correspond to the growth and spread patterns of the disease. Because the ovary floats freely in the pelvic cavity, a tumor can grow for some time without producing symptoms associated with involvement of, or pressure on, other organs.