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OBJECTIVE: To investigate presenting signs and symptoms of ovarian cancer and stage of tumor in a community cohort of women with the diagnosis of ovarian cancer. PATIENTS AND METHODS: We reviewed retrospectively the medical records of all women who sought primary and specialty care in Olmsted County, Minnesota, between January 1, 1985, and December 31, 1997, to evaluate presenting symptoms, time from first symptom to diagnosis of ovarian cancer, and stage of tumor at diagnosis. RESULTS: Of 107 women with a diagnosis of ovarian cancer, the most commonly documented presenting symptom was crampy abdominal pain. Urinary symptoms and abdominal pain were the most commonly documented presenting symptom in patients with stage I and II ovarian cancers, whereas abdominal pain and increased abdominal girth were the most commonly documented symptoms in patients with stage III and IV cancer. Approximately 15% of tumors (n = 15) were found during routine evaluations or during a procedure for another problem. Less than 25% of presenting symptoms (n = 24 women) related directly to the pelvis or were more traditional gynecologic symptoms. Delays in women seeking medical care, health care system issues, competing medical conditions, physicians' failure to follow up, and women not returning for follow-up were associated with longer time to diagnosis. CONCLUSION: Both stage I and II cancer are associated with symptoms, but few symptoms are directly related to the reproductive pelvic organs or unique to ovarian cancer. A longer interval from first sign or symptom to diagnosis of ovarian cancer is associated with both patient and health care system factors. [ABSTRACT FROM AUTHOR]

Objectives: The Gynecologic Cancer InterGroup aimed to provide an overview of uterine and ovarian leiomyosarcoma management., Methods: Published articles and author experience were used to draft management overview. The draft manuscript was circulated to international members of the Gynecologic Cancer InterGroup for review and comment, and appropriate revisions were made., Results: The approach to management of uterine and ovarian leiomyosarcoma management is reviewed., Conclusions: Uterine and ovarian leiomyosarcomas are rare and aggressive cancers that require specialized expertise for optimal management.

Objective: To estimate lower extremity lymphedema prevalence in patients surgically treated for endometrial cancer, identify predictors of lymphedema, and evaluate the effects of lymphedema on quality of life., Methods: One thousand forty-eight consecutive patients who were operated on between 1999 and 2008 at the Mayo Clinic were mailed a survey, which included our validated 13-item lymphedema screening questionnaire and two validated quality-of-life measures. Logistic regression models were fit to identify factors associated with prevalent lymphedema; a multivariable model was obtained using stepwise and backward variable selection methods. The relationship between lymphedema and obesity with each quality-of-life score was evaluated separate multivariable linear models., Results: There were 591 responders (56%) after exclusions. Our questionnaire revealed a previous self-reported lymphedema diagnosis in 103 (17%) patients and identified undiagnosed lymphedema in 175 (30%) (overall prevalence 47.0%, median 6.2 years follow-up). Lymphedema prevalence in patients treated with hysterectomy alone compared with lymphadenectomy was 36.1% and 52.3%, respectively (attributable risk 23%). Lymphedema risk was not associated with the number of nodes removed or the extent of lymphadenectomy after adjusting for other factors. On multivariable analysis, higher body mass index, congestive heart failure, performance of lymphadenectomy, and radiation therapy were associated with prevalent lymphedema. Multiple quality-of-life scores were worse in women with lymphedema., Conclusion: The attributable risk of developing lower extremity lymphedema was 23% for patients with endometrial cancer who underwent lymphadenectomy compared with hysterectomy alone with an overall prevalence of 47%. Lymphedema was associated with reductions in multiple quality-of-life domains., Level of Evidence: II.

Objective: We sought to estimate cytologically benign endometrial cell (CBEC)-associated endometrial hyperplasia and cancer rates, and describe clinical and histologic outcomes., Study Design: Medical records of women age >40 years with CBEC in 2005 through 2010 were reviewed for clinical characteristics; assessment with endometrial biopsy, ultrasound, or hysteroscopy; and consequent outcomes., Results: Of 658 women, 281 (42.7%) were assessed: 39.4% of 330 premenopausal, and 46.0% of 328 postmenopausal women. Among these, cancer rate was 3.6% and differed between premenopausal (0.8%) and postmenopausal (6.0%) women (P = .019). Hyperplasia rate was similar in premenopausal (3.9%) and postmenopausal (3.3%) women. Of 20 assessed women with endometrial pathology, 4 (1 premenopausal) women with cancer and 4 (2 premenopausal) women with hyperplasia had no abnormal bleeding., Conclusion: Cancer was more common in postmenopausal women with assessed CBEC while hyperplasia was comparably distributed between premenopausal and postmenopausal women. Findings support CBEC assessment regardless of menopausal status or abnormal bleeding., (Copyright © 2012 Mosby, Inc. All rights reserved.)

We designed a phase I clinical trial of escalating doses of topotecan with CY and carboplatin in combination with autologous hematopoietic SCT (AHSCT) for the treatment of relapsed or persistent platinum sensitive ovarian or primary peritoneal carcinoma. After stem cell collection, 16 patients received topotecan at 1.5, 2.5, 3.5, 4.5 or 6.0 mg/m(2)/d combined with CY 1.5 g/m(2)/d and carboplatin 200 mg/m(2)/d, all by 4-day continuous infusion. Steady state pharmacokinetics of topotecan and carboplatin were examined. Pre-treatment biopsies were examined for the expression of topoisomerase (topo) I, Ki67 and Bcl-2 family members by immunohistochemistry. One of six patients at a topotecan dose of 4.5 mg/m(2)/d and two of three patients at 6.0 mg/m(2)/d had dose-limiting toxicity of grade 3 stomatitis lasting >2 weeks. There was no treatment-related mortality. As topotecan clearance was constant over the dose range examined, topotecan steady state plasma concentrations increased with dose. Median progression-free survival and overall survival were 6.5 months and 2.7 years, respectively. Shorter progression-free survival was observed in tumors with low topo expression (P=0.04). Topotecan can safely be dose escalated to 4.5 mg/m(2)/d in combination with CY, carboplatin and AHSCT. This trial is registered at ClinicalTrials.gov as NCT00652691.

Edmonston vaccine strains of measles virus (MV) have shown significant antitumor activity in preclinical models of ovarian cancer. We engineered MV to express the marker peptide carcinoembryonic antigen (MV-CEA virus) to also permit real-time monitoring of viral gene expression in tumors in the clinical setting. Patients with Taxol and platinum-refractory recurrent ovarian cancer and normal CEA levels were eligible for this phase I trial. Twenty-one patients were treated with MV-CEA i.p. every 4 weeks for up to 6 cycles at seven different dose levels (10(3)-10(9) TCID(50)). We observed no dose-limiting toxicity, treatment-induced immunosuppression, development of anti-CEA antibodies, increase in anti-MV antibody titers, or virus shedding in urine or saliva. Dose-dependent CEA elevation in peritoneal fluid and serum was observed. Immunohistochemical analysis of patient tumor specimens revealed overexpression of measles receptor CD46 in 13 of 15 patients. Best objective response was dose-dependent disease stabilization in 14 of 21 patients with a median duration of 92.5 days (range, 54-277 days). Five patients had significant decreases in CA-125 levels. Median survival of patients on study was 12.15 months (range, 1.3-38.4 months), comparing favorably to an expected median survival of 6 months in this patient population. Our findings indicate that i.p. administration of MV-CEA is well tolerated and results in dose-dependent biological activity in a cohort of heavily pretreated recurrent ovarian cancer patients.

Background: Little information is available regarding long-term survival after pulmonary metastasectomy for gynecologic malignancies., Methods: All patients who underwent pulmonary resection for gynecologic malignancies at our institution between January 1985 and June 2001 were reviewed. Factors affecting long-term survival were analyzed., Results: There were 103 patients, 70 of whom had metastatic disease limited to the lungs. Median age of these 70 patients was 59.4 years (range, 31 to 80 years). The primary tumor originated in the uterine corpus in 37 patients, endometrium in 23, cervix in 7, ovaries in 2, and vagina in 1. Histopathology was leiomyosarcoma in 29 patients, adenocarcinoma in 23, other sarcoma in 11, squamous cell carcinoma in 5, and choriocarcinoma and endolymphatic stromal myosis in 1 each. The median time interval between the first gynecologic procedure and pulmonary resection was 24 months (range, 0 to 237 months). A wedge excision was performed in 44 patients, lobectomy in 14, bilobectomy in 2, pneumonectomy in 1, and a combination in 9. Five patients (7%) had an incomplete resection. Eighteen patients (25.7%) developed at least one complication and 1 died (operative mortality, 1.4%). At last follow-up, 35 had died, and the median follow-up among those who were still alive was 36 months (range, 6 months to 13 years). Five-year and 10-year survival was 46.8% (95% confidence interval, 34.2% to 63.0%) and 34.3% (95% confidence interval, 19.7% to 52.5%), respectively. Factors that adversely affected survival include a disease-free interval between the first gynecologic procedure and pulmonary resection of less than 24 months (p = 0.004) and a primary site located in the cervix (p < 0.001)., Conclusions: Pulmonary resection for metastatic gynecologic cancer in selected patients is safe and effective. Both a short disease-free interval between the primary gynecologic procedure and pulmonary metastasectomy, and a primary cervical tumor had an adverse effect on survival.

In summary, the EGF/ErbB family of receptor tyrosine kinases has been shown to play a key role in normal ovarian follicle development, and cell growth regulation of the ovarian surface epithelium. Disregulation of these normal growth regulatory pathways, including overexpression and/or mutation of EGFR/ErbB receptor family members, as well as elements of their downstream signalling pathways, have been shown to contribute to the etiology and progression of epithelial ovarian cancer. It is, therefore, not surprising that these gene products, and their related soluble receptor isoforms may have clinical utility as tumor and/or serum biomarkers of disease activity. Moreover, since several of these soluble receptor isoforms have potent growth inhibitory activity, and are naturally occurring in the circulation, they are ideal candidates for the development of novel therapeutics for the treatment of ovarian cancer patients.

Objective: To investigate the role of expression of p34cdc2 protein kinase in normal, benign, and malignant ovarian epithelium., Material and Methods: Tissue sections from 24 patients with epithelial ovarian carcinoma (EOC) along with 6 normal ovarian specimens and 12 benign cystadenomas were incubated with mouse IgG monoclonal antibody to human p34cdc2 protein kinase, followed by detection with use of a standard peroxidase-labeled streptavidin-biotin technique. Immunohistochemical staining was graded and compared. Clinical data were also reviewed., Results: Normal surface epithelium and 10 of 12 benign cystadenomas failed to stain for p34cdc2 protein kinase. Of the 24 EOC specimens, however, 19 (79%) stained positively. The staining pattern or intensity was not associated with the histologic grade or surgical stage., Conclusion: Expression of p34cdc2 protein kinase is strongly up-regulated in most cases of EOC but not in normal epithelial ovarian tissue or in most cases of benign epithelial tumors evaluated. Therefore, it may be associated with early events in carcinogenesis. Redundant overexpression of cyclin-dependent kinases such as p34cdc2 may contribute to deranged cell cycle progression and proliferation of EOC. Observation of overexpression of p34cdc2 protein kinase in other malignant lesions suggests a common mechanism.