Ovarian Cancer

Ovarian cancer has a high mortality rate because it is usually well advanced at the time of diagnosis. In the early stage symptoms are often missing completely and are nonspecific in advanced stages. The diagnosis usually comprises ultrasound, CT or MRI and the determination of the tumor marker (eg. B. CA 125). The diagnosis is made histologically, staging (staging) is done surgically. Treatment involves hysterectomy with bilateral Salpingoovarektomie and possible extensive resection of all affected tissue, followed by chemotherapy; it is because the cancer is localized.

In the US, ovarian cancer is the second most common gynecological cancer (about 1/70 patients) Regulations and the deadliest (about 1% of all women die from this disease); it is the fifth most common cause of cancer death in women; in 2013 it came in the US to about 22,200 new cases and 14,000 deaths. In industrialized countries, the incidence is higher.

Ovarian cancer has a high mortality rate because it is usually well advanced at the time of diagnosis. In the early stage symptoms are often missing completely and are nonspecific in advanced stages. The diagnosis usually comprises ultrasound, CT or MRI and the determination of the tumor marker (eg. B. CA 125). The diagnosis is made histologically, staging (staging) is done surgically. Treatment involves hysterectomy with bilateral Salpingoovarektomie and possible extensive resection of all affected tissue, followed by chemotherapy; it is because the cancer is localized. In the US, ovarian cancer is the second most common gynecological cancer (about 1/70 patients) Regulations and the deadliest (about 1% of all women die from this disease); it is the fifth most common cause of cancer death in women; in 2013 it came in the US to about 22,200 new cases and 14,000 deaths. In industrialized countries, the incidence is higher. Etiology Ovarian cancer affects mainly perimenopausal and postmenopausal women. Risks are higher for nulliparous Late primiparas Early menarche Late menopause Personal or familial pre-existing conditions to endometrial, breast or colon cancer, a decreased risk with oral contraceptives probably are 5-10% of all Ovarialkarzinomfälle related to mutations in autosomal dominant BRCA gene associated with a lifetime risk of ovarian cancer by 50-85%. Carriers of a mutation of the BRCA1 gene have a risk of 20 to 40% that they will develop ovarian cancer during his lifetime. The risk of women with BRCA2 mutations is less increased. The incidence of these mutations is higher than in the general population in Ashkenazi Jews. Mutations in several other genes, including TP53, PTEN, STK11 / LKB1, CDH1, CHEK2, ATM, MLH1 and MSH2, have also been implicated in hereditary breast and / or ovarian cancer. An XY gonadal dysgenesis predisposed to germ cell tumors of the ovary. Pathology ovarian cancers vary histologically (see table: Ovarialkarzinomtypen). At least 80% are of epithelial origin, of which 75% of serous cystadenocarcinomas and about 10% of invasive mucinous carcinomas. At the time of initial presentation almost 27% of the patients have with epithelial ovarian cancer in stage I mucinous histology, stage III or IV, this is only at <10% of cases. Approximately 20% of non-epithelial ovarian cancers originate primary germ cells of the ovaries or the gonadal (Keimstrang-) stroma or metastastische metastases to the ovary (most common tumors of the breast or of the gastrointestinal tract). Malignant germ cell tumors usually occur in women before age 30. Ovarialkarzinomtypen origin types epithelium Brenner Tumor clear cell carcinomas endometrioid carcinoma Mucinous carcinoma Serous cystadenocarcinomas (most common) transitional cell carcinoma Unclassified carcinoma Primary germ cells choriocarcinoma dysgerminomas embryonic carcinomas Endodermal sinus tumors Immature teratomas Polyembryome gonadal (Keimstrang-) stromal granulosa Sertoli Leydig cell tumors Metastatic breast cancer of the gastrointestinal tract, the spread of ovarian cancer occurs by direct growth, by exfoliation of cells into the peritoneal cavity (peritoneal seeding) and by lymphatic dissemination in the pelvis and along the aorta or rare hematogenous liver and lungs. Symptoms and signs Early cancer is usually asymptomatic. As chance find there is often a solitary, irregular, and fixed mass of the adnexa. Rectovaginal palpation and pelvic exam typically show a diffuse nodular surface. A few women have initially strongest abdominal pain, caused by a twist of the tumor (adnexal torsion). Most patients with advanced tumor disease at first diagnosis exhibit only nonspecific symptoms (eg. As dyspepsia, abdominal distension, early satiety, painful flatulence, back pain). Later often occur abdominal pain, anemia, cachexia and a distended by the tumor mass or ascites abdomen. Germ cell or stromal tumors can also have functional effects (eg. B. hyperthyroidism, Pseudopubertas praecox or virilization). (. Eg CA 125) Diagnostic ultrasound (in cases of suspected cancer in the early stages) or CT or MRI Intraoperative (in cases of suspected cancer at an advanced stage) tumor markers staging Suspicion of ovarian cancer is in women with the following characteristics: Unclear masses adnexal unclear bloating changes in bowel habits Unintentional weight loss vague abdominal pain A mass in the ovaries is probably malignant in older women. Benign functional cysts (benign ovarian tumors) may appear in young women as functional germ cell or sex cord tumors. A mass in the lower abdomen with ascites indicated generally indicate ovarian cancer, but can sometimes occur as part of a Meigs syndrome (benign fibroma with ascites and right-sided hydrothorax). Imaging methods in case of suspected carcinoma in the early stages, the first diagnostic method is an ultrasonic examination; following findings have a malignant disease through: A solid component Oberflächenausstülpungen size> 6 cm Irregular shape Low vascular resistance in the transvaginal Doppler sonography On suspicion of a carcinoma in advanced stages (eg due to ascites, bloated abdomen or nodularity or fixation. which was detected during the physical examination) is preoperatively usually a CT or MRI performed to the extent of the tumor disease to ermitteln.Tumormarker tumor markers, including the ?-chain of human chorionic gonadotropin (?-hCG), LDH, ?-fetoprotein, inhibin and CA 125, are (germ cell tumors, stromal tumors z. B.) determined mostly in young patients with an increased risk of nonepithelial tumors. In perimenopausal and postmenopausal women only CA 125 is measured, because in this age group, most ovarian cancers are epithelial tumors. CA 125 is elevated in 80% of advanced epithelial ovarian cancer, but may be slightly elevated in other conditions such as endometriosis, pelvic inflammatory disease, pregnancy, fibroids, peritoneal inflammation or infection of the peritoneum nichtovarialem tumor. In a mixed cystic-solid pelvic mass in postmenopausal women is suspected ovarian cancer, especially if the CA-125 value ist.Biopsie increased A biopsy is not routinely recommended, unless the patient is not eligible for operation in question , In these rare cases, a histological diagnosis of the lesion should be performed by needle biopsy or Asziteszytologie. With masses that appear benign on ultrasound, no histological analysis is required; after 6 weeks, the ultrasound examination is repeated. Benign appearing lesions are for. B. mature cystic teratoma (dermoid cysts), follicular cysts or Endometriome.Stadieneinteilung (staging) a suspected or confirmed ovarian cancer is intraoperatively divided into stages (see Table: Intra-operative staging of ovarian cancer). Intraoperative staging of ovarian cancer stage I tumor limited Description limited to ovaries IA tumor on one ovary. intact limited no tumor on the surface of the ovary, capsule IB tumor on both ovaries; no tumor on the surface of the ovary, capsule intact IC stage IA or IB, but with tumor on the surface of the ovary, with capsular or malignant cells in ascites or in the peritoneal * II tumor involvement of one or both ovaries with spreading / metastasis in the pelvis IIA spread to and / or metastasis in uterus, tubes or both IIB spread to other pelvic tissues IIC Stage IIA or IIB, but with malignant cells in the ascites or peritoneal washings in the * III tumor involvement of one or both ovaries with histologically confirmed peritoneal metastasis outside the pelvis IIIA microscopic peritoneal metastasis outside the pelvis detected; no lymph node involvement IIIB Macroscopic peritoneal metastasis outside the pelvis proven, ? 2 cm in diameter and no lymph node involvement IIIC Abdominal peritoneal metastases with spread across the pelvis out and> 2 cm in diameter and / or regional lymph node metastasis IV Distant metastases including parenchymal liver metastases; with pleural effusion IV cytologically malignant cells must be verified for the classification stage * Helpful in prognostic assessment for the stages IC and IIC have information on whether a capsular rupture occurred intraoperatively spontaneous or iatrogenic and whether malignant cells were detected in ascites or peritoneal washings. According to the staging systems of the International Federation of Gynecology and Obstetrics (FIGO) and the American Joint Committee on Cancer (AJCC), AJCC Cancer Staging Manual, 7th Edition New York, Springer, 2010. On suspicion of a carcinoma in the early stage staging by means laparoscopy or robot-guided laparoscopic surgery. Otherwise an abdominal midline incision is required that allows adequate access to the upper abdomen. All peritoneal surfaces diaphragm halves and the organs of the abdomen and pelvis are inspected and palpated. It is obtained lavage fluid from the pelvis (Douglas’scher space), the intra-abdominal gutters and paradiaphragmal, and multiple peritoneal be found in the central and lateral pelvis and abdomen. In early tumor stages the infrakolische omentum is resected and performed a pelvic and para-aortic lymphadenectomy. The tumors are located beyond histologically grade of 1 (least aggressive) to 3 (most aggressive). The recent classification distinguishes low-grade (grade 1) or high grade (grade 2 or 3) epithelial Ovarialkarzinome.Screening process In asymptomatic women at average risk a pelvic examination should be performed every 1 to 3 years between the ages of 18 and 40, from 40 years then annually. Although a high specificity (up to 99.9% in one study) was detected in large studies for CA 125, the sensitivity and positive predictive value is only moderate (71% in one study) is low; therefore CA 125 is not recommended for screening asymptomatic women at average risk. Although screening of asymptomatic women both by ultrasound and using the determination of CA 125 in serum can detect some cases of ovarian cancer, but not even applied for high-risk groups (including women with BRCA mutations) could be improved by overall survival. However, it should be tested for changes in the BRCA gene, when the family history of the following features: diagnosis of ovarian cancer at a 1st degree before age 40. diagnosing a breast or ovarian cancer in only a 1st degree, when the cancer was diagnosed before age 50 Two cases of ovarian cancer in relatives 1st and 2nd degree same line Two cases of breast cancer and one case of ovarian cancer in relatives 1st and 2nd degree same line One case of breast cancer and one case of ovarian cancer with relatives grade 1 and 2 the same line when the breast cancer was diagnosed before age 50 before age 40 or ovarian cancer Two cases of breast cancer in relatives grade 1 and 2 the same line if both cases before the 50 . age diagnostizie rt were two cases of breast cancer in relatives grade 1 and 2 the same line when a case was diagnosed before age 40. Even with Ashkenazi Jewish women with a family member with breast cancer, which was diagnosed before age 50, or ovarian cancer a test should be taken on mutation in the BRCA gene into consideration. Forecasters are treating the 5-year survival rates for stage I: 70 to 100% Stage II: 50-70% Stage III: 20-50% Stage IV: 10-20% A worse prognosis is in undifferentiated tumors surgically or if not all macroscopic tumor-affected tissue can be removed; In such cases, the best prognosis when the tumor-affected tissue can be ideally reduced to <1 cm in diameter or a microscopic residual amount. In the stages III and IV, the recurrence rate is 70%. Treatment Most hysterectomy and bilateral Salpingoovarektomie Mesit postoperative chemotherapy, usually with carboplatin and paclitaxel hysterectomy and bilateral Salpingoovarektomie are indexed with the exception of non-epithelial or low-grade and one ovary limited malignancies in stage I in young patients; In this case, fertility can be obtained by leaving the uterus and ovary unaffected. In patients with extensive tumor manifestation surgery is not indicated or can be deferred if one or more of the following findings are present: Multiple liver metastases lymphadenopathy in the hepatic portal Suprarenal para-aortic lymph nodes Diffuse mesenteric disease presence of pleural or parenchymal These patients are with neoadjuvant chemotherapy (z. B. with carboplatin plus paclitaxel) treated. An operation can be carried out occasionally after initial chemotherapy. If a hysterectomy and bilateral Salpingoovarektomie performed is - if possible - the entire affected tissue surgically removed. When complete resection is not possible, the broadest possible tumor mass reduction improves (cytoreductive surgery, often called "debulking") the effectiveness of other therapies. The operative tumor mass reduction typically includes a suprakolische Omentumresektion, sometimes with resection of the rectosigmoid (usually with a primary anastomosis system), radical peritonectomy, resection of the diaphragmatic peritoneum or splenectomy. The postoperative treatment depends on the stage and grade (see table: Postoperative treatment of ovarian cancer by stage and type) from. Postoperative treatment of ovarian cancer by stage and type stage and type of treatment Epithelial adenocarcinoma in stage IA or B / grade 1 No postoperative therapy carcinomas stage IA or B / grade 2 or 3 carcinoma stage II 6 courses chemotherapy (usually paclitaxel and carboplatin) carcinomas stage III cancer in stage IV 6 courses chemotherapy * as with stage IA or B / grade 2 or 3 Rarely, radiation therapy if necessary Although intraperitoneal cisplatin and paclitaxel germ cell tumors stromal tumors in stage II or III usually combination chemotherapy, usually bleomycin, cisplatin and etoposide * Intraperitoneal chemotherapy with cisplatin plus paclitaxel leads to longer survival than an i.v. Chemotherapy, however, may have a higher rate of complications. Intraperitoneal chemotherapy is not yet applied by default in ovarian cancer stage III or IV. Even if chemotherapy a complete clinical remission is achieved (d. H. Unobtrusive physical examination, normal CA-125 serum levels, inconspicuous abdominal and pelvic CT), about 50% of patients have with stage III or IV or remaining tumor. In persistent CA-125 increase from 90 to 95% of patients still have residual tumor. The rate of recurrence in patients with a clinically complete remission after initial chemotherapy (6 courses carboplatin and paclitaxel) is 60-70%. If a tumor recurrence or progression on to more effective chemotherapy, chemotherapy is resumed. Other potentially useful chemotherapeutic agents are topotecan, liposomal doxorubicin, docetaxel, paclitaxel, gemcitabine, bevacizumab, and a combination of cyclophosphamide plus bevacizumab or gemcitabine plus cisplatin. The targeted therapy with biologics are currently being investigated in studies. Prevention in patients with BRCA1 or BRCA2 gene mutations, the risk of ovarian cancer and, to a lesser extent, for breast cancer, when a bilateral prophylactic Salpingoovarektomie is performed after completion of family planning decreased. The cancer risk seems to be lower with this procedure than with the surveillance. Patients with BRCA1 or BRCA2 gene mutations should be referred to a gynecologic oncologist for a consultation. Other sources include the National Cancer Institute's Cancer Information Service (1-800-4-CANCER) and the Women's Cancer Network (www.wcn.org). Summary of ovarian cancer, especially post-menopausal and perimenopausal women are affected; Nulliparous, late primiparas, early menarche, late menopause and certain genetic markers increase the risk. The early signs (eg. As dyspepsia, abdominal distension, early satiety, painful flatulence, back pain) are non-specific. Is suspected carcinoma, ultrasound examination, determination of tumor markers (for. Example, CA 125) and intraoperative staging are indicated. Asymptomatic women are not screened by ultrasound and / or CA 125, unless there is a high risk for BRCA mutations before. Treatment usually consists of hysterectomy, bilateral Salpingoovarektomie and chemotherapy (z. B. carboplatin and paclitaxel).

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