Faculty Bibliography

Ectopic human chorionic gonadotropin production has been described in a wide variety of non-germ cell tumors, particularly in epithelial tumors, but rarely in sarcomas. In this report, we describe the case of 49-year-old woman with a history of "uterine fibroids," who presented with vaginal bleeding and a positive urine pregnancy test. After pregnancy was ruled out by ultrasound, the patient underwent a laparotomy and hysterectomy for a presumptive diagnosis of "fibroids" and was found to have carcinomatosis at the time of the surgery. Therefore optimal debulking of tumors was performed. Two weeks later, the patient developed a small bowel obstruction, which apparently was due to rapid recurrence of tumors in the abdomen, and soon afterwards she died. Microscopically, the resected pelvic mass was composed of highly atypical and pleomorphic spindle cells admixed with many multinucleated giant cells. The tumor had a high mitotic rate along with areas of hemorrhage and necrosis. Immunohistochemically, the tumor cells were positive for vimentin, desmin, smooth muscle actin, and beta-human chorionic gonadotropin, and were negative for epithelial membrane antigen, keratin AE1/3, S-100, CD31, CD117, Ber-EP4, WT-1, estrogen and progesterone receptors. The majority of cells, including the multinucleated giant cells, were strongly immunoreactive for beta-human chorionic gonadotropin. Only three cases of leiomyosarcomas with beta/human chorionic gonadotropin production have been described in the literature, and all three cases had extrauterine origin. Our case, to the authors' best knowledge, is the first uterine leiomyosarcoma with prominent beta/human chorionic gonadotropin production.

The goal of this study was to determine whether patterns of expression profiles of p73 isoforms and of p53 mutational status are useful combinatorial biomarkers for predicting outcome in a gynecological cancer cohort. This is the first such study using matched tumor/normal tissue pairs from each patient. The median follow-up was over two years. The expression of all 5 N-terminal isoforms (TAp73, DeltaNp73, DeltaN'p73, Ex2p73 and Ex2/3p73) was measured by real-time RT-PCR and p53 status was analyzed by immunohistochemistry. TAp73, DeltaNp73 and DeltaN'p73 were significantly upregulated in tumors. Surprisingly, their range of overexpression was age-dependent, with the highest differences delta (tumor-normal) in the youngest age group. Correction of this age effect was important in further survival correlations. We used all 6 variables (five p73 isoform levels plus p53 status) as input into a principal component analysis with Varimax rotation (VrPCA) to filter out noise from non-disease related individual variability of p73 levels. Rationally selected and individually weighted principal components from each patient were then used to train a support vector machine (SVM) algorithm to predict clinical outcome. This SVM algorithm was able to predict correct outcome in 30 of the 35 patients. We use here a mathematical tool for pattern recognition that has been commonly used in e.g. microarray data mining and apply it for the first time in a prognostic model. We find that PCA/SVM is able to test a clinical hypothesis with robust statistics and show that p73 expression profiles and p53 status are useful prognostic biomarkers that differentiate patients with good vs. poor prognosis with gynecological cancers.

The aging population is the fastest growing segment of our population. Over the last century, the average life expectancy has increased by 25 years. The incidence of ovarian carcinoma, seen primarily in postmenopausal women, is, therefore, expected to increase. The current standard treatment of ovarian cancer has been determined on the basis of prospective, randomised clinical trials carried out by cooperative groups. Sixty-one percent of new cancer cases occur in women >65 years of age. Despite this fact, enrollment in clinical trials has been exceedingly low. In turn, this causes suboptimal treatment for a very fatal disease. The aetiology of this is multifactorial, and strategies for improvement are lacking. Elderly patients may be barred from participation based on physician biases alone. Elderly patients may have limited access to academic centres where clinical trials are conducted or be excluded on the basis of unrealistic inclusion criteria. As physicians, it is our duty to understand the elderly patient and the comorbidities in this age group that may influence the tolerability and toxicity of conventional therapies. Therefore, it is imperative that we make a conscious effort to examine ways in which we may improve enrollment of elderly women with ovarian cancer in clinical trials.

OBJECTIVE:This study was undertaken to report on the benign gynecologic conditions occurring among women with an intact uterus at enrollment in the Breast Cancer Prevention Trial of the National Surgical Adjuvant Breast and Bowel Project. STUDY DESIGN/METHODS:The incidence rates of several benign gynecologic conditions were determined and risks were compared among women receiving tamoxifen and those receiving placebo, based on risk ratios (RRs) with 95% CIs. Comparisons included stratification by menopausal status, body mass index, and history of estrogen use. RESULTS:Compared with women taking placebo, premenopausal women taking tamoxifen had a greater incidence of endometrial polyps (RR = 1.9, 95% CI = 1.55-2.41), leiomyomas (RR = 1.3, 95% CI = 1.14-1.55), endometriosis (RR = 1.9, 95% CI = 1.35-2.70), ovarian cysts (RR = 1.5, 95% CI = 1.20-1.78), and gynecologic surgical procedures, including hysterectomy (RR = 1.6, 95% CI = 1.29-1.88). Postmenopausal women taking tamoxifen also had an increased incidence of endometrial polyps (RR = 2.4, 95% CI = 1.76-3.24), leiomyomas (RR = 1.4, 95% CI = 1.04-1.80), endometriosis (RR = 1.9, 95% CI = 1.29-5.58), and gynecologic surgical procedures, including hysterectomy (RR = 2.2, 95% CI = 1.60-3.13), compared with women taking placebo. All women taking tamoxifen also had an increased incidence of simple endometrial hyperplasia without atypia (overall RR = 2.06, 95% CI = 1.64-2.60) compared with those taking placebo. CONCLUSIONS:Our results strongly support the estrogen agonist role of tamoxifen as the causative factor for the increased risk of endometrial polyps, leiomyomas, endometriosis, and endometrial hyperplasia among women taking this agent.

OBJECTIVE:Obstetrician/gynecologists' career satisfaction with certain work-related activities was examined among clinicians who perform deliveries and clinicians who do not. STUDY DESIGN/METHODS:A questionnaire was sent to 1500 member-fellows of the American College of Obstetricians and Gynecologists; 842 members (56%) responded. The questionnaire was designed to distinguish between obstetrician/gynecologists who perform deliveries and clinicians who do not in the areas of satisfaction with specific aspects of career and work-related activities. Data were examined initially by multivariate analysis of variance and subsequently by univariate analysis of variance if the multivariate test was found to be significant. RESULTS:Workload and personal control were the primary factors for which there was a significant difference in satisfaction between clinicians who perform deliveries and clinicians who do not (P<.001). Obstetrician/gynecologists who do not perform deliveries reported working significantly fewer hours per week (P<.001) and had more satisfaction with their work activities than the delivery group overall. Despite lowered satisfaction with certain career aspects among the delivery Group, the highest positive disposition ratings that was given by respondents were for surgery, vaginal delivery, and planned cesarean delivery, with gender differences observed in the level of disposition for these particular activities. The most negative rating was reported for on-call/in-hospital time. CONCLUSION/CONCLUSIONS:Although positive disposition is associated with the activity of vaginal and cesarean delivery overall, 2 primary contributing factors of dissatisfaction that were identified among obstetrician/gynecologists who perform deliveries were increased workload and decreased personal control.

This report summarizes our experience with the combination of mesna, doxorubicin, ifosfamide, and dacarbazine (MAID) for patients with gynecological sarcomas. We reviewed the records of all patients who had received the MAID regimen for a gynecological sarcoma between 1993 and 2000. The MAID regimen was administered intravenously every 4 weeks in the hospital as follows: (1) mesna 1500 mg/m2/day x 4 days; (2) doxorubicin 15 mg/m2/day x 3 days; (3) ifosfamide 1500 mg/m2/day x 3 days; (4) dacarbazine 250 mg/m2/day x 3 days. The results of treatment with MAID were disappointing. Overall, the response rate was 9% with one complete response and one partial response (both in patients with uterine leiomyosarcoma). We did not observe any responses among the patients with carcinosarcomas of either ovarian or uterine origin. The median progression-free interval and survival were 11 months and 29 months, respectively. This regimen was associated with substantial toxicity (including a death from neutropenic sepsis) as well as high cost and inconvenience due to the requirement for inpatient administration. Although our study contains a limited number of patients with a variety of gynecological sarcomas, our review has led us to discontinue using MAID. It remains to be established if any combination chemotherapy regimen is better than single agent treatment.

OBJECTIVE:To evaluate the safety and efficacy of early oral analgesia after intra-abdominal surgery in gynecologic oncology patients. METHODS:Over a 2.5-year period, 227 gynecologic oncology patients undergoing intra-abdominal surgery were enrolled in a randomized controlled trial of early oral versus traditional parenteral analgesia. All patients initially received parenteral morphine via a patient-controlled analgesia (PCA) pump with a basal dose of 0.5 mg/h and a PCA dose of 1 mg with a 10-minute lockout. On the first postoperative day, all patients began a clear liquid diet, which was advanced as tolerated. Patients allocated to early oral analgesia were switched from parenteral to oral morphine. They received a scheduled dose of 20 mg every 4 hours with an additional dose of 10 mg every 2 hours as needed for breakthrough pain. Patients allocated to traditional parenteral analgesia continued to receive parenteral morphine via a PCA pump with basal and PCA doses. On the second postoperative day, the scheduled oral and basal parenteral doses were discontinued. The oral and parenteral PCA doses were continued until 24 hours before discharge, at which time the patient was switched to oxycodone 5 mg/acetaminophen 325 mg. RESULTS:There were no significant differences among the groups in any demographic or clinical indices, including age, case distribution, surgery length, blood loss, time to return of bowel function, length of hospital stay, pain, sedation, and satisfaction scores, and incidence of nausea, vomiting, or major postoperative complications. CONCLUSIONS:Early oral analgesia in gynecologic oncology patients undergoing intra-abdominal surgery is safe and efficacious.

OBJECTIVE:This study was undertaken to compare the outcomes of patients with endometrial cancer who had primary surgery with gynecologic oncology involvement at university or community hospitals. METHODS:The study population consisted of all patients who had primary surgery for endometrial cancer with involvement of the attending physicians of the Division of Gynecologic Oncology. The patients were divided into two groups based on whether their surgery was performed at a university or community hospital. Demographic and clinical data were abstracted from the medical records. RESULTS:There were no significant differences between the two groups with regard to Quetelet index (kg/m(2)); intervals between biopsy and consultation, consultation and surgery, and biopsy and surgery; estimated blood loss; incidence of operative or hospital complications; frequency of appropriate surgical staging; stage distribution; histology or grade; and hospital stay. Patients at a university hospital were significantly older, had a higher severity index, were more likely to have had a vaginal hysterectomy, and participate in a research protocol. Both the Quetelet index and the severity index were significantly higher for patients who had vaginal hysterectomy than for those who had either laparoscopically assisted vaginal hysterectomy or total abdominal hysterectomy. When analyzed by surgical approach, the frequencies of pelvic and paraaortic lymph node sampling were comparable between the groups. Both the Quetelet and severity indices were significantly higher for patients who did not have lymph node sampling. CONCLUSION/CONCLUSIONS:Involvement of a gynecologic oncologist at the time of primary surgery for endometrial cancer was associated with comparable outcomes in both the university and community hospital setting.