Residual Disease after Cytoreductive Surgery

The volume of residual disease after cytoreductive surgery has been strongly associated with survival. Optimal cytoreduction is defined as residual disease of less than 1 cm. The GOG reported 37- and 31-month median survival times for patients with residual disease less than 1 cm and 1 to 2 cm, respectively. In an analysis of patients presenting with stage IV disease median survival of optimally cytoreduced patients was 38.4 months compared with 10.3 months for patients with suboptimal residual...

Granulosa Stromal Cell Tumors

Granulosa-stromal cell tumors account for 70 of tumors in the sex cord-stromal group, and 2 to 5 of all ovarian tumors.40 They encompass GCTs, thecomas, and fibromas. Although GCTs are considered malignant, they grow slowly and do not behave as aggressively as their epithelial counterparts. However, if not detected at an early stage they do have the potential to metastasize and recur. Unlike epithelial-type ovarian tumors, there is no racial or ethnic predilection of GCTs. There is also no...

Followup

A number of approaches are used to detect recurrent disease after initial surgery and chemotherapy for ovarian cancer. These approaches include physical examination, determination of serum CA-125 levels, and imaging. CT, MRI, and PET all have been used to evaluate ovarian cancer recurrence.55 Recurrent ovarian malignancy may manifest as pelvic masses, peritoneal seeding, malignant ascites, and nodal recurrence (Fig. 5-12). Occasionally recurrent disease may present as pleuropulmonary lesions...

Combination Platinum Based Chemotherapy versus Single Agent Platinum

If a patient is to receive a platinum agent, the next question is Should the platinum drug be administered alone or in combination with a second non-platinum drug Figure 9-3. Up to 15 to 20 of women receiving a second-line platinum-based chemotherapy program will experience a toxic reaction. (Data from Markman M, Kennedy A, Webster K, et al Clinical features of hypersensitivity reactions to carboplatin. J Clin Oncol 17 1141, 1999, Table 1.) Figure 9-3. Up to 15 to 20 of women receiving a...

Mucinous Carcinoma

Morphologic transitions from mucinous cystadenoma to mucinous atypical proliferative tumor (borderline tumor), to mucinous intraepithelial carcinoma and invasive mucinous carcinoma have been recognized for some time, and an increasing frequency of KRAS mutations at codons 12 and 13 has been described in every stage of tumor progression.7,41-44 In addition, the same KRAS mutation has been detected in mucinous carcinoma and in the adjacent mucinous cystadenoma and borderline Table 2-5. Ovarian...

Definition of Recurrent versus Platinum Resistant Ovarian Cancer

It has long been recognized that ovarian cancer patients whose tumors exhibit objective evidence of a response to chemotherapy may respond a second time to the same (or a similar) treatment program.3,4 In fact, this observation is not unique to ovarian cancer, having been demonstrated relatively early in the development of modern chemotherapy in the management of hematologic malignancies.5 Because of the central role of the platinum agents in ovarian cancer,6 it should come as no surprise that...

Overexpression of Apolipoprotein E

Based on serial analysis of gene expression(SAGE), investigators have found apolip-rotein E (ApoE) overexpression in ovarian carcinoma. Besides the well-known role of ApoE in cholesterol transport and in the pathogenesis of atherosclerogenesis and Alzheimer's disease, ApoE may play a novel role in the development of human cancer. ApoE immunoreactivity has been detected in 66 of high-grade but only 12 of low-grade ovarian serous carcinomas, and not in normal ovarian surface epithelium, serous...

Diseasefree Interval

In many series, an important prognostic and therefore selection factor is the disease-free interval (DFI), defined as the interval from the completion of chemotherapy to the diagnosis of recurrence. The platinum-free interval is the interval of time between the last dose of platinum-based chemotherapy and the diagnosis of recurrence. Generally, the DFI and the platinum-free interval are the same, since almost all patients receive primary platinum-based chemotherapy. The importance of the DFI in...

Surgical Principles

A substantial number of patients with advanced-stage ovarian cancer present with bulky upper abdominal disease, malignant pleural effusions, or even intraparenchymal liver disease and may require diaphragmatic or intestinal procedures, splenectomy with or without a distal pancreatectomy, and peritoneal stripping to achieve an optimal cytoreduction. A survey of the Society of Gynecologic Oncologists (SGO) in 2000 revealed that up to 45 of patients deferred several procedures such as splenectomy...

Staging

Traditionally, ovarian cancer was staged surgically, based on the International Federation of Obstetrics and Gynecology (FIGO) classification system. However, current state-of-the-art imaging modalities have been shown to play a potential role in non-invasive preoperative staging. Intraperitoneal dissemination is the most common route of ovarian cancer spread, rather than solid organ parenchymal metastases in many malignancies. Peritoneal implants usually occur on the surfaces of the viscera...

Sex Cord Tumor with Annular Tubules

Sex cord tumors with annular tubules (SCTATs) were initially grouped with SLCTs, and some have proposed grouping them with GCTs. Correspondingly, these tumors possess characteristics of both, but they are recognized as a unique entity. Distinctive features include an association with Peutz-Jeghers syndrome in one third of cases, the potential to produce progesterone, and a higher penchant for lymph node metastasis than other sex cord-stromal tumors.84 The presentation of SCTATs differs based on...

Features and Risks of BRCA1 and BRCA2Related Cancers

Compared with the general population, BRCA1 2 mutation carriers have an increased risk of ovarian cancer. The lifetime risk of ovarian cancer in the general population Figure 3-3. Factors affecting penetrance. (From ASCO Curriculum Cancer Genetics and Cancer Predisposition Testing, 2nd ed, 2004, Slide 1-36.) Figure 3-3. Factors affecting penetrance. (From ASCO Curriculum Cancer Genetics and Cancer Predisposition Testing, 2nd ed, 2004, Slide 1-36.) 1 1 1 cnzi BRC repeats 1-8 Based on data from...

Choice of Chemotherapy and Duration of Treatment

Generally, choice of adjuvant chemotherapeutic agents for early-stage disease has been extrapolated from management of advanced-stage ovarian cancer. See the section on Advanced Ovarian Carcinoma, later in this chapter. Many of the investi-gational trials in early-stage ovarian cancer compared cisplatin-based combination chemotherapy to radiation therapy 18-20 (Table 8-5). Meta-analyses of these types of trials have shown no significant difference between chemotherapy and radiation therapy for...

New Combinations and Dose Schedules

GOG 182 ICON-5 is a large multicenter randomized trial, which closed to accrual in 2005 (Fig. 8-10). The aim of this study was to determine whether adding a third drug (topotecan, liposomal doxorubicin, or gemcitabine) and adjusting schedules Randomization Optimal and Suboptimal Stages III and IV Doxil triplet Carboplatin AUC 5 IV day 1 Paclitaxel 175 mg m2 IV day 1 Doxil 30 mg m2 IV every other day 1 Doxil triplet Carboplatin AUC 5 IV day 1 Paclitaxel 175 mg m2 IV day 1 Doxil 30 mg m2 IV every...

Sex Cord Stromal Tumors

Sex cord-stromal tumors consist of a pathologically diverse group of ovarian tumors originating from the sex cords and stroma of the ovary. Their exact histogenesis remains unclear. Collectively, they account for 5 to 8 of all ovarian tumors and can occur in women of any age group, but they are most commonly diagnosed in women in the fifth decade of life. Sex cord-stromal tumors are classified into granulosa cell tumors (GCTs), Sertoli-Leydig tumors, sex cord-stromal tumors with annular...

B

Peritoneal Tumors Mri

Common sex cord-stromal tumor of the ovary and is benign. It is composed of fibroblasts and collagen and is without estrogenic activity.71 It may be associated with ascites and Meigs syndrome. Ovarian fibromas are worth mentioning from an imaging standpoint because they have a relatively specific appearance on imaging that may suggest the diagnosis. The characteristic appearance of fibroma on ultrasound is a homogeneous hypoechoic mass with posterior acoustic shadowing.59 On CT, it has been...

Sertoli Leydig Cell Tumors Androblastomas

Sertoli-Leydig cell tumors (SLCTs) are rare, accounting for 0.2 of all ovarian tumors. Unlike granulosa-stromal cell tumors, they occur principally in women in the reproductive years with 75 occurring before age 40 and occurring less commonly during menopause or childhood. Similar to theca cells, SLCTs are usually hormonally active and secrete testosterone, thus resulting in androgen excess and potential virilization. The cause of SLCTs remains largely unknown because they originate from the...

General Population Screening Transvaginal Ultrasound

Transvaginal ultrasound (TVUS) has been evaluated for use in ovarian cancer screening in the general population. Because of the close proximity of the probe to the ovaries, TVUS offers excellent resolution of ovarian morphology. Volume, outline, papillations, and complexity of ovarian masses can be used to raise suspicion of cancer. Benign ovarian lesions are common, however, resulting in false-positives that may necessitate invasive surgery for asymptomatic women. In addition, TVUS as an...

References

Gershenson DM Clinical management of potential tumors of low malignancy. Best Pract Res Clin Obstet Gynaecol 16 513527, 2002. 2. Skirnisdottir I, Garmo H, Wilander E, et al Borderline ovarian tumors in Sweden 1960-2005 trends in incidence and age at diagnosis. Int J Cancer 15 123(8) 1897-1901, 2008. 3. Lu KH, Bell DA Borderline ovarian tumors. In Gershenson DM, McGuire WP, Gore M, et al (eds) Gynecologic Cancer Controversies in Management. Philadelphia Elsevier, 2004, pp 519-526. 4. Harlow BL,...

Prophylactic Surgery in the High Risk Population

When considering prophylactic procedure in the high-risk population, the surgeon needs to be cognizant of the risk of an occult malignancy. The patient needs to have signed consent forms for additional procedures including hysterectomy and full surgical staging, since there is a 4 chance of detecting an occult malignancy at the time of the procedure.21,22 Prophylactic bilateral salpingo-oophorectomy can be performed by laparotomy or laparoscopy (minimally invasive surgery). A methodical survey...

Histology

Dysgerminoma Tumor Ovary

Ovarian germ cell tumors comprise a number of different histologic types (Table 11-5). In terms of incidence, dysgerminomas are the most common malignant ovarian germ cell tumors (Fig. 11-8), followed by immature teratomas (Fig. 11-9) and endodermal sinus tumors (Fig. 11-10), although mixed varieties containing disparate tumor components also exist. Other histologic types such as embryonal carcinomas, nongestational choriocarcinomas, struma ovarii, and so on, are more rare. Surveillance,...

Detection and Characterization of Ovarian Tumors Role of Ultrasound

Bilateral Ovarian Solid Cystic Lesion

Ultrasound is considered the modality of choice for initial evaluation of an ovarian mass.19 It has been reported that in a setting similar to day-to-day clinical practice, in which the readers were given a brief clinical history of the patients (i.e., age, menstrual status, family history of ovarian cancer, previous pelvic surgery, and presenting symptoms), the experienced readers reached a prospective diagnostic accuracy of 92 , with excellent interobserver agreement (k 0.85). The less...

Tumor Biology

Various biologic factors have been associated with prognostic significance in ovarian cancer. The role of ploidy in predicting outcome in ovarian cancer remains controversial. In many studies, diploid tumors have been associated with better survival rates. Recurrence-free survival of patients with DNA-diploid primary ovarian cancer was significantly better compared with that of patients with DNA-aneuploid tumors in univariate analysis (47 versus 18 P .01). The tumor-dependent overall survival...

Mutation of BRAF and KRAS

Braf Und Kras

Several unique molecular changes characterize low-grade and high-grade serous carcinomas (Table 2-4 and Fig. 2-4). Among them, the most significant molecular genetic alterations are mutations in BRAF and KRAS oncogenes. The RAS, RAF, MEK, ERK, and MAP cascade is important for the transmission of growth signals Table 2-3. Summary of Clinicopathologic Features of the Prototypic Type I and Type II Tumors Type I Low-Grade Serous Carcinoma Type II High-Grade Serous Carcinoma 25 of serous carcinomas*...

Advanced Stage Epithelial Ovarian Cancer Principles of Surgical Cytoreduction

Advanced epithelial ovarian cancer typically presents with widely disseminated intraabdominal disease. The standard treatment of advanced epithelial ovarian cancer (EOC) includes primary cytoreductive or debulking surgery followed by adjuvant systemic chemotherapy. The goal of primary surgery for advanced epithelial ovarian cancer is to accurately establish a diagnosis and leave little or no residual disease. There are several potential benefits to the surgical removal of bulky tumor masses1,2...

Natural History of Untreated Early Ovarian Carcinoma

Pictures Stages Ovarian Cancer

Knowing the natural history of untreated early ovarian cancer should identify the need for adjuvant chemotherapy. Assessing an observation arm in randomized controlled trials RCTs should be an accurate means of determining the true rate of recurrent cancer after surgical resection. Table 8-1 lists five prominent randomized controlled trials comparing observation with a treatment arm. The rate of cancer recurrence in the observation arm varies from 9 to 35 owing to differences in substages and...

En bloc Pelvic Resection

Bladder Tumour Resection

Locally advanced ovarian cancer frequently distorts the pelvic anatomy encasing the adnexae, pelvic peritoneum, cul-de-sac, and rectosigmoid Fig. 7-5 . A retroperitoneal approach to the hysterectomy and bilateral salpingo-oophorectomy allows en bloc removal of the ovarian tumor and surrounding structures affected by confluent disease, including portions of the rectosigmoid and bladder.17 The procedure involves extending the peritoneal incisions along the paracolic gutters caudally Figure 7-5....