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cell types that compose the organ. Epithelial Nearly 90% of ovarian malignancies are classified as epithelial ovarian carcinom as. These cancers arise from the germinal epithelium lining the ovary. Epithelia l ovarian cancer can be further subdivided into several histologic cell types: s erous, mucinous, endometrioid, clear cell, transitional, and undifferentiated ca rcinomas. The risk of epithelial ovarian cancer increases with age and is found predominantly in postmenopausal women. Epithelial tumors of low malignant potent ial (borderline ovarian carcinoma) are a histologic variant that is less aggress ive than their invasive epithelial counterparts, are found in younger women, and are often confined to the ovary at diagnosis. Germ Cell Germ cell tumors account for approximately 5% of all ovarian cancers and recapit ulate the developing embryo or placental structures. Histologic subtypes include dysgerminoma (most common), endodermal sinus tumor, immature teratoma, chorioca rcinoma, and embryonal carcinoma. Germ cell ovarian cancer can occur in women of any age, but approximately 80% of these are diagnosed in women younger than 30 years. Sex Cord Stromal Sex cord stromal tumors, which account for approximately 5% of all ovarian cancers , develop in the connective tissue and supporting ovarian stroma. These tumors a re generally less aggressive and often produce steroid hormones, including estro gen, progesterone, and testosterone. Some patients with hormone-producing tumors present with signs and symptoms of steroid excess, such as vaginal bleeding or hyperandrogenism. Prevalence According to the American Cancer Society, there were more than 23,000 new cases of ovarian cancer and 14,000 deaths from the disease in the United States in 200 1. It is estimated that a woman has a 1% to 2% lifetime risk for developing ovar ian cancer. Ovarian carcinoma is the fifth most frequent cause of cancer death i n women, and one half of all cases occur in women older than 65 years. Pathophysiology The cause of ovarian cancer is poorly understood; however, risk factors and mode of spread have been well described. Risk Factors The most significant risk factor for ovarian cancer is a positive family history . When two or more first-degree relatives have or have had ovarian cancer, a wom an's lifetime risk for developing this cancer is 7%. If a heritable cancer syndr ome is identified, this lifetime risk can increase 17- to 50-fold. Three dominan tly inherited mutations are known to be associated with the development of appro ximately 10% of all ovarian carcinomas: breast-ovarian cancer syndrome, which is associated with mutations in BRCA-1 and BRCA-2 genes; site-specific ovarian car cinoma; and hereditary nonpolyposis colorectal cancer (Lynch syndrome II), which is associated with mutations in mismatch repair genes. Advanced age is also ass ociated with increased risk, whereas high parity, oral contraceptive use, tubal ligation, and hysterectomy decrease one's risk. Mode of Spread Ovarian cancer usually spreads via cellular shedding into the peritoneal cavity followed by implantation on the peritoneal surface. Local invasion of the bowel
nausea. or ascites. The distended abdomen is dull to percussion and an omental cake may be palpated in the upper abdomen. allowing improved morphologic characterization. Chest x-ray might indicate pleural effusion . Signs and Symptoms Unfortunately. Furthermore. vomit ing. These masses are occasionally detected during the screening pelvic examination. Diagnosis A complete physical examination is the first step in the diagnosis of ovarian ca ncer. The addition of color flow Doppl er can further characterize the mass. Manifesting symptoms usua lly relate to an increasing intra-abdominal tumor burden and ascites and are oft en vague. but its usefulness as a diagnostic tool is hindered by poor sensitivity and specificity. early satiety. carcinomatosis. and associated symptoms may be related to their large size. CA 125 is a high-molecular-weight glycoprotein that is expressed b y more than 80% of nonmucinous epithelial ovarian cancers.and bladder is common in advanced cases. colonoscopy. or ascites. carcinomatosis. Serum Tumor Markers Serum tumor markers can assist in preoperative evaluation. These include sigmoidoscopy. or barium enema. and intravenous pyelogram. bloati ng or a feeling of fullness. shortness of breath. such as nausea. Tumor cells also may block diaphragmati c lymphatics. Imaging Studies Transvaginal ultrasound uses higher-frequency sound waves to image the ovaries. a pelvic mass can often be palpated on examinatio n in symptomatic patients. an elevated CA 125 is not specific for ovarian cancer. Although elevated in most women with advanced ovarian cancer. On the other hand. Although pelvic examination is notoriously inefficient at detecting presym ptomatic early ovarian cancer. borderline. Many nongynecologic and benign gynecologic conditions also are associat . They may be quite large at present ation. unexplained weight lo ss or gain. patients feel the mass themselves or present with symptoms of acute abdomen du e to torsion of the adnexa or rupture of the tumor. More commonly . CT scans of the abdom en and pelvis with intravenous and oral contrast characterize tumor burden and a ssist in evaluating other causes of adnexal mass. Abdo minal distention due to ascites is another common finding. and indigestion. Ot her studies may be performed based on a patient's risk factors and symptoms at p resentation. which is common in patients with ovarian carcinomatosis. and sex cord stromal tumors are often co nfined to the ovary at the time of diagnosis. Serum testing is essential to monitoring treatment response for ovarian can cer. however. only 50% of patients with early-stage d isease have an elevated CA 125. most patients with epithelial ovarian cancer experience few or no symptoms until the disease has widely metastatasized. and constipation or obstipation. The finding of a unilateral or bilateral nonmobile (f ixed) mass is characteristic of epithelial ovarian carcinoma. and mucinous epithelial ovarian cancers express this antigen poorly. Symptoms include fatigue. The resulting impairment of lymphatic drainage of the peritoneum i s believed to play a role in development of ascites in ovarian cancer. change in bowel habits. Impingement of the rectum an d compromise of lumen diameter can also be appreciated on this examination. such as gas. Cul-de-sac masses may also be palpated with rectovaginal examination. A vascular mass with low resistive indices supports a diagnosis of malignancy. Further diagnostic workup is necessary to establish extent of disease and exclu de other causes of an adnexal mass. abdominal swelling or pain. their limita tions must be understood so they are not misinterpreted or obtained inappropriat ely. frequency or urgency of urination. and obstructive symptoms. upper ga strointestinal endoscopy. vague bu t persistent gastrointestinal complaints. mimicking other more common diseases. germ cell. Transdiap hragmatic spread and seeding of the pleura with pleural effusion are also common in advanced cases.
diagnostic testing. I n addition. carcinomatosis related to an extraovarian primary t umor does not necessarily benefit from such measures. consultation wit h a gynecologic oncologist is essential to ensure appropriate preoperative couns eling and preparation. Limitations in the sensitivity and specificity of the se tests must be understood so they can be interpreted appropriately for each pa tient. and differentiating the site of tumor origin is rarely possible on c ytologic examination. may be use ful for palliation of symptoms of abdominal distention and associated respirator y compromise due to diaphragmatic elevation. Surgical Staging Accurate staging determines both treatment and prognosis. fertility-sparing surg ery may be an option in select ovarian malignancies. If metastatic colo n or pancreatic carcinoma is suspected. however. other tumor markers may be useful to assist in diagnosis. Table 3: FIGO Staging for Ovarian Cancer Stage Definition I Growth limited to the ovaries II Growth involves one or both ovaries with pelvic extension III Tumor with peritoneal implants outside the pelvis. human chorionic gonadotropin. although tumor debulking appears to have survival benefit in patient s with ovarian malignancies. Consultation If a reasonably high probability for ovarian malignancy exists. operative management. or positive retroperi toneal or inguinal nodes. International Federation of Gynecology and Obstetrics. or both IV Tumor involves one or both ovaries with distant metastasis FIGO. serum carcinoembryonic antigen and CA 19 -9 might also be elevated. FIGO staging criteria are described in Table 3. and lac tic dehydrogenase may be expressed by germ cell malignancies. Cytoreduction . However. Inadequate surgical st aging is a common problem in patients with presumed early-stage disease when the operating surgeon does not perform the necessary procedures for adequate stagin g. Alpha fetoprotein. If nonepithelial ovarian cancer is suspected. Treatment Ovarian cancer is initially managed with exploratory laparotomy to confirm the d iagnosis and determine the extent of disease (surgical staging) and for tumor cy toreduction. and postoperative care. diagnostic par acentesis is not necessary for most patients if they have already been deemed ap propriate for exploratory surgery and operative management. Paracentesis Malignant ascites is common in patients with metastatic epithelial ovarian carci noma. if necessary. a negat ive cytology from preoperative paracentesis does not exclude the possibility of malignancy. such as germ cell tumors. For example. Although paracentesis may be performed for cytologic examination. Furthermore.ed with elevations in this serum antigen. it is imperative that the operating surgeon is familiar with stagi ng criteria and has the surgical skills necessary to perform all the necessary s teps of the staging procedure. ascites due to other conditions such as congestive heart failure and cirrhosis must be ruled out by careful history and. Therefore. Histologic Identification The availability of reliable intraoperative frozen section is essential for opti mal surgical decision making and management. Large-volume therapeutic paracentesis.
total omentum. small bowel. Although not documented by any randomized clinical trial. although some regimens are given over a period of sev eral days. For epithelial ovarian cancer. Aggressive resection of tumor does not appear to have any clinical advantage unl ess all metastatic implants also can be optimally reduced. surgical techniques suc h as en bloc hysterectomy with resection of the rectosigmoid. spleen. Although its impact on overall survival is uncertain. platinum-based therapy-either cisplatin or carbop latin-in combination with paclitaxel has demonstrated the highest activity of al l agents studied. suggests that continuation of si ngle-agent paclitaxel for 12 courses is associated with an improved disease-free survival.Metastatic implants of ovarian cancer typically involve the peritoneal surfaces and are often amenable to resection along with the primary tumor mass. ovarian cancer patients require adjuvant chemotherapy after s urgery. The importance of adequate surgical staging is evident when making decis ions regarding adjuvant therapy in stage I disease.3 To achieve these goals. but not all.4 These agents are generally given intravenously every 3 weeks for a total of six courses. optimal tumor cytoreduction (de fined as removal of the primary tumor and all gross metastatic implants to less than 1 cm residual in largest diameter) is believed to improve chemotherapy resp onse and disease-free survival. . requiring hospitalization. Most chemotherapy can be giv en on an outpatient basis. however. Adjuvant Treatment Most. these findings have the potential to significantly affect recommended adjuvant therapy for this disease. and possibly more may be necessary. The operating surgeon must exercise judgment as to whether optimal tumor reduction is possible and ca n be safely achieved without incurring significant complications that would dela y chemotherapy. One study.
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