Chapter 093. Gynecologic Malignancies (Part 2)

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Screening In contrast to patients who present with advanced disease, patients with early ovarian cancers (stages I and II) are commonly curable with conventional therapy. Thus, effective screening procedures would improve the cure rate in this disease. Although pelvic examination and CA-125 can occasionally detect early disease, these are relatively insensitive screening procedures. Transvaginal sonography is often used, but significant false-positive results are noted, particularly in premenopausal women. Doppler flow imaging coupled with transvaginal ultrasound may improve accuracy and reduce the high rate of false positives. ...

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Chapter 093. Gynecologic Malignancies (Part 2) Screening In contrast to patients who present with advanced disease, patients with early ovarian cancers (stages I and II) are commonly curable with conventional therapy. Thus, effective screening procedures would improve the cure rate in this disease. Although pelvic examination and CA-125 can occasionally detect early disease, these are relatively insensitive screening procedures. Transvaginal sonography is often used, but significant false-positive results are noted, particularly in premenopausal women. Doppler flow imaging coupled with
transvaginal ultrasound may improve accuracy and reduce the high rate of false positives. CA-125 has significant limitations as a screening test. Half of women with stages I and II ovarian cancer have normal CA-125 levels. Attempts have been made to improve the sensitivity and specificity by combinations of procedures, commonly transvaginal ultrasound and CA-125. In a screening study of 22,000 women, 42 had a positive screen and 11 had ovarian cancer (seven with advanced disease). In addition, eight women with a negative screen developed ovarian cancer. Thus, the false-positive rate would lead to a large number of unnecessary (i.e., negative) laparotomies if each positive screen resulted in a surgical exploration. In the United Kingdom, a large collaborative screening trial is underway to prospectively compare various screening techniques with controls. Until the results of such trials are available, the National Institutes of Health Consensus Conference recommended against screening for ovarian cancer among the general population without known risk factors for the disease. Although no evidence shows that screening saves lives, many physicians use annual pelvic examinations, transvaginal ultrasound, and CA-125 to screen women with a family history of ovarian cancer, Lynch type II, or breast/ovarian cancer syndrome. Proteomic technologies have been used to identify patterns of proteins associated with early disease. Preliminary studies identified all 50 stage I patients with a sensitivity of 100%, a specificity of 95%, and a positive predictive value of
94%. However, difficulty in consistency of replicate samples, variability of results from different spectroscopy equipment, and the tendency of the artificial intelligence algorithms to overfit the data have limited its utility. Most proteins identified to date have been acute phase reactants, and extensive fractionation is necessary to identify unique cancer-specific proteins. Pathology Common epithelial tumors comprise most (85%) of the ovarian neoplasms. These may be benign (50%), malignant (33%), or tumors of low malignant potential (16%) (i.e., tumors of borderline malignancy). Epithelial tumors of low malignant potential have the cytologic features of malignancy but do not invade the ovarian stroma. More than 75% of borderline malignancies present in early stage and generally occur in the fourth or fifth decade of life. They usually have 10-year survival of 80–90%. There are five major subtypes of common epithelial tumors: serous (50%); mucinous (25%), endometrioid (15%); clear cell (5%); and Brenner tumors (1%), the latter derived from the urothelium. Benign common epithelial tumors are almost always serous or mucinous and develop in women ages 20–60. They are frequently large (20–30 cm), bilateral, and cystic. Malignant epithelial tumors are usually seen in women over 40.
Although most ovarian tumors are epithelial, two other ovarian tumor types, stromal and germ cell tumors, are distinct in their cell of origin, have different clinical presentations and natural histories, and require different management (see below). Metastasis to the ovary can occur from breast, colon, gastric, and pancreatic cancers. The Krukenberg tumor was classically described as bilateral ovarian masses from metastatic mucin-secreting gastrointestinal cancers. Staging and Prognostic Factors Laparotomy is the primary procedure used to establish the diagnosis and provide accurate staging. Less-invasive studies may help define the extent of spread, including chest x-rays, abdominal CT or MRI scans, and abdominal and pelvic sonography. Symptoms of bladder or renal dysfunction are evaluated by cystoscopy or intravenous pyelography. A careful staging laparotomy with a total abdominal hysterectomy and bilateral salpingo-oophorectomy will establish the stage and extent of disease and allow for the cytoreduction of tumor masses in patients with advanced disease. Proper laparotomy requires a vertical incision of sufficient length to ensure adequate examination of the abdominal contents. The presence, amount, and cytology of any ascitic fluid should be noted. The primary tumor should be evaluated for rupture, excrescences, or dense adherence. Careful visual and
manual inspection of the diaphragm and peritoneal surfaces is required. A partial omentectomy should be performed and the paracolic gutters inspected. Pelvic lymph nodes as well as para-aortic nodes in the region of the renal hilus should be biopsied. Since this surgical procedure defines stage, establishes prognosis, and determines the necessity for subsequent therapy, it should be performed by a surgeon with special expertise in ovarian cancer staging. Studies have shown that patients operated upon by gynecologic oncologists were properly staged 97% of the time, compared to 52 and 35% of cases staged by obstetricians/gynecologists and general surgeons, respectively. After staging, ~23% of women have stage I disease (cancer confined to the ovary or ovaries), 13% have stage II (disease confined to the true pelvis), 47% have stage III (disease spread into but confined to the abdomen), and 16% have stage IV disease (spread outside the pelvis and abdomen). The 5-year survival correlates with stage of disease: stage I, 90–95%; stage II, 70–80%; stage III, 25–50%; and stage IV, 1–5% (Table 93-1).