Ovarian

According to the National Cancer Institute, a woman without family history of ovarian cancer has a 1 in 55 lifetime chance of developing ovarian cancer. The risk increases 10-fold when known family history exist. 1 Carcinoma of the ovary is a disease of older women, with a peak incidence in the fifth to seventh decade, it is rarely seen before menarche. 2 Ovarian cancer is the fourth most frequent cause of cancer death and the most lethal of all gynecologic tumors in women from North America and northern and western Europe. 3 ||
 * **Epidemiolgy:** || Jenn
 * **Etiology:** || Jenn

The precise cause of ovarian cancer is unknown, but there are several risk factors. Some of these include: age, family history of ovarian cancer, and women who have never given birth. Hereditary forms of ovarian cancer can be caused by mutations and specific genes known as BRCA1 and BRCA2. 3 || The most common malignant ovarian tumors have a histology of epithelial cells, which arise from the germinal epithelium surface of the ovary. 5 This epithelial histology accounts for roughly 85% to 90% of all ovarian tumors. 5 Of all the epithelial malignant tumors, serous cystadenocarcinomas are the most common. 5 The other 10% to 15% ovarian tumors include: primary germ cell, sex cord, and stomal tumors. 5 || The primary lymphatic drainage site for ovarian cancer are the periaortic lymph nodes at the level of the renal veins. 5 From the periaortic nodes, the external iliac nodes an inguinal nodes may be involved due to retrograde lymphatic flow. 5 || The epidemic of metastatic ovarian cancer continues to be of concern in the US. Over 17,000 women have some metastatic spread at the time of their diagnosis and the number continues to grow. 6 This type of cancer is known to primarily metastasize to abdominal organs, tissues and lymph nodes. Lymphatic spread most often includes the pelvis and para-aortic nodes. 6 In rare cases, ovarian cancer can metastasize to the supraclavicular lymph nodes as well. 6 Other sites include visceral and parietal peritoneal surfaces as well as, omentum, gastrointestinal tract, bladder, liver and spleen. 6 Bone, lung, parenchyma and brain metastases are extremely rare but are considered the most severe with a poor prognosis. 6 The image below demonstrates metastatic spread from epithelial ovarian cancer.
 * **Signs & Symptoms:** || Rachel
 * Pelvic pain, pelvic mass, and serosanguinous vaginal discharge. 4
 * Colicky lower abdominal pain, followed with a release of sporadic, yellowish watery vaginal discharge.
 * Early gastrointestinal symptoms are nonspecific. Women present with early-stage disease only 15% to 25% of the time.
 * Detection of early-stage disease usually only happens by palpation of an asymptomatic adnexal mass on a routine examination.
 * Diagnosis usually happens after the disease has spread beyond the pelvis and presents as abdominal pain or discomfort with increased abdominal girth due to ascites or large intraabdominal masses. ||
 * **Diagnostic Procedures:** || Rachel
 * A patient suspected of having an ovarian malignancy should have an evaluation of her full history and a physical assessment, including bimanual pelvic examinations. 4
 * Transvaginal ultrasonography is a sensitive tool for the assessment of adnexal masses, especially when combined with color flow Doppler.
 * Computed Tomography is the modality of choice for the detection of upper abdominal and retroperitoneal disease.
 * Laboratory studies should include a complete blood count, blood urea nitrogen, creatinine, liver enzymes, and CA 125 level.
 * CA 19-9, along with carcinoembryonic antigen, has shown to be useful in monitoring patients with mucinous subtypes of ovarian cancer.
 * Human chorionic gonadotropin and alpha-fetoprotein have shown to be the most useful markers for monitoring patients with germ cell type tumors. ||
 * **Histology:** || Brandon
 * **Lymph node drainage:** || Brandon
 * **Metastatic spread:** || Ashley

|| Grade and stage are two very important indicators of a patient’s prognosis when diagnosed with ovarian cancer. The stage refers to tumor size, lymph node involvement and metastatic spread. In any case, there can be several combinations of the staging criteria and differ from patient to patient. Tumor grading refers to cell differentiation. When a suspicious ovarian lesion is detected, a biopsy of the site is taken to learn more about the cancer and the best way to treat the patient. The biopsy sample is analyzed microscopically and given a grade based on how the cells are behaving. Grade I ovarian cancer contains cells that have few abnormalities compared to normal cells. 8 These cancers are generally early stage and are easier to treat. Grade III cancer cells are almost unrecognizable compared to normal cells and indicates the cancer is aggressive. 8 Grade II ovarian cancer is in between grades I and III and is moderately aggressive. 8 The image below shows cell differentiation with descriptive characteristics for each grade.
 * **Grading:** || Ashley

|| The TNM and International Federation of Gynecology and Obstetrics (FIGO) classification for staging ovarian cancer is as follows: 10 || Common side effects from treatment include: 11,12 - Short term side effects: - Long term side effects: -Major prognostic factors: tumor stage, volume of post-operative residual disease, and tumor grade. 13 -Overall 5 year survival rates: Stage I = 90%, Stage II = 80%, Stage III = 15-20%, and Stage IV = < 5%. -Histologic grade is an important factor for early stage disease: Stage I patients with grade I, II and III disease have survival rates of 97%, 78% and 62%, respectively. -Degree of differentiation, presence of dense adhesions between tumor and pelvic organs, and presence of ascites are predictive for high probability of relapse following complete tumor removal in patients with Stage I disease. -When these factors were considered, bilateral tumor, capsular penetration, tumor size, cyst rupture, patient age, histologic subtype, or type of post-operative therapy were found to be insignificant. -Other studies found tumor ploidy to be significant. Aneuploid tumors are more aggressive than diploid tumors and usually of higher stage at presentation. These tumors are also associated with a shorter median survival time. || -**Surgery** 13 -tumor debulking or cytoreductive surgery -primary cytoreduction: before adjuvant therapy -interventional cytoreduction: done after a few cycles of chemo -secondary cytoreduction: after completion of chemo -2nd look laparotomy: surgical exploration done after a patient has finished a course of treatment -__Treatment options after a 2nd look laparotomy:__ -External Beam Radiation Therapy -intraperitoneal radioactive organic phosphate -monoclonal antibodies -chemotherapy -**Adjuvant therapy for epithelial ovarian carcinoma**: -Radiation Therapy: role is controversial; whole abdomen treatment may be curative in some patients; Phosphorus 32 is a radioisotope used and its use is limited to patients with little or no residual disease post surgery -Chemotherapy: usually given after surgery; 6 cycles is standard -Hormonal: no benefit from primary hormonal or chemohormonal therapy; option for patients with recurrences when chemo is not an option -**Dysgerminoma: (very radiosensitive)** -Stage IA: unilateral salpingo-oophorectomy and inspection of entire peritoneal cavity -post operative RT to periaortic and ipsilateral hemipelvic nodes -Beyond stage IA: total abdominal hysterectomy and bilateral salpingo-oophorectomy -Radiation Therapy: 25-30 Gy; well-tolerated but patients left sterilized -most recurrences are treated with chemo; RT may be used too -studies suggest that high stage or recurrent tumors should be treated with platinum-based chemo -Intraperitoneal Instillation: Phosphorus 32 used for post op microscopic residual disease; -15-20 mCi used -estimated surface dose from 10 mCi of Phosphate 32 is about 30 Gy -EBRT: open field to treat entire peritoneal cavity including periaortic, pelvic, and mesenteric nodes, and the entire diaphragm -doses: 22.5-30 Gy to abdomen, 45-50 Gy to pelvis -anterior blocks used after 18 Gy for kidneys and posterior block after 25 Gy for liver || TD 5/% Table for OAR in the abdomen-pelvic portal. 14  ||
 * **Staging:** || Amanuel
 * **Radiation side effects:** || Amanuel
 * Diarrhea
 * Irritable bladder/ radiation cystitis
 * Nausea
 * Fatigue
 * Vaginal Irritation, sometimes with discharge
 * Bowel changes
 * Frequent urination ||
 * **Prognosis:** || Lindsey
 * **Treatments:** || Lindsey
 * **TD 5/5:** || Kevin
 * **References:** || # Medscape Today. Epidemiological and Genetic Factors Associated With Ovarian Cancer. Avaiable at: []. Accessed June 27, 2013.
 * 1) Chaos KS, Perez CA, Brady LW. Radiation Oncology Management Decisions. 3rd ed. Philadelphia, PA: Lippincott, Williams and Wilkins; 2011: 59.
 * 2) American Association for Cancer Research. Cancers Epidemiology Biomarkers & Prevention. Available at: []. Accessed June 27, 2013.
 * 3) Chaos KS, Perez CA, Brady LW. Radiation Oncology Management Decisions. 3rd ed. Philadelphia, PA: Lippincott, Williams and Wilkins; 2011: 593-594.
 * 4) Chao KS, Perez CA, Brady LW. //Radiation Oncology Management Decisions//. 2nd ed. Philadelphia, PA: Lippincott, Williams, and Wilkins; 2002: 519-523.
 * 5) Metastatic Ovarian Cancer. Medscape Education Web site. []. Updated 2013. Accessed June 24, 2013.
 * 6) Cancer, Health and Medical Glossary. Treatment Options Web site.[]. Accessed June 24, 2013.
 * 7) Vasilev, S. Ovarian Cancer Grade and Stage: Two Critical Factors. Ovarian Cancer Web site. []. Updated February 7, 2008. Accessed June 24, 2013.
 * 8) Naniwa J, Itamochi H, Kigawa J. Implication of Clear Cell and Mucinous Histology. In: Diaz-Padilla. //Ovarian Cancer- A Clinical and Translational Update.// Shanghai, China: InTech; 2013: 175-179.
 * 9) Mohaghegh P, Rockall AG. Imaging Strategy for Early Ovarian Cancer: Characterization of Adnexal Masses with Conventional and Advanced Imaging Techniques. RadioGraphics. 32, 1751-1773
 * 10) <span style="color: #ff7100; font-family: Arial,Helvetica,sans-serif;">Radiation therapy for ovarian cancer. American Cancer Society. http://www.cancer.org/cancer/ovariancancer/detailedguide/ovarian-cancer-treating-radiation-therapy. Accessed June 25, 2013.
 * 11) <span style="color: #ff7100; font-family: Arial,Helvetica,sans-serif;">Radiation therapy for ovarian cancer. Cancer Research UK. http://www.cancerresearchuk.org/cancer-help/type/ovarian-cancer/treatment/radiotherapy-for-ovarian-cancer. Accessed June 25. 2013.
 * 12) Chao KS, Perez CA, Brady LW. //Radiation Oncology Management Decisions//. 3rd ed. Philadelphia, PA: Lippincott, Williams, and Wilkins; 2011: 594-602.
 * 13) Emami B, Lyman J, Brown A, et al. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys. 1991; 21: 109-122.

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