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Objectives: Blood products are scarce but essential medical resources. Initially transfusions showed increased perioperative complications, prolonged hospitalizations, and higher mortality. Recently developed restrictive transfusion policies have not shown those adverse affects in critically ill patients. Hospitals adopted these policies to guide blood product administration. The objective of this study is to determine compliance with a restrictive transfusion policy in gynecologic oncology patients., Methods: A retrospective chart review of gynecologic oncology patients undergoing transfusion with packed red blood cells (pRBCs) from 12/2008 to 9/2011 was performed. Cancer type and stage, surgical procedure, hemoglobin values, pRBC transfusions, intraoperative blood loss, and postoperative complications were collected. Each transfusion was classified as compliant or noncompliant., Results: A total of 582 patients requiring 2,276 blood transfusions were identified. The mean age was 55.9 years. Ovarian and endometrial cancers were the most common malignancies. Gynecologic oncologists were 81.1% compliant with the restrictive transfusion policy; 59.0% of transfusions were secondary to exceptions. Noncompliant transfusions were commonly given on the day of surgery when intraoperative blood loss was < 1500 cc and for asymptomatic anemia. Only 64.7% of the transfusions were ordered in single unit increments. There was no significant difference in postoperative infections, thrombotic events, and mortality between compliant and noncompliant transfusions., Conclusion: The majority of gynecologic oncology patients receive transfusions compliant with the restrictive transfusion policy. Morbidity and mortality are not increased with a restrictive transfusion policy. Efforts to improve compliance should focus on limiting transfusions when the hemoglobin is ≥ 7 g/dL and transfusing in single pRBCs unit increments.

Objective: Ovarian cancer is the deadliest gynecologic malignancy and the fifth leading cause of death from cancer in women in the U.S. Since overall survival remains poor, there is a need for new therapeutic paradigms. This paper will review the Wnt/β-catenin pathway as it relates to epithelial ovarian cancer, specifically its role in chemoresistance and its potential role as a target for chemosensitization., Methods: A PubMed search was performed for articles published pertaining to Wnt/β-catenin pathway specific to ovarian cancer. Wnt/β-catenin signaling pathways play an active role in cancer stem cells (CSCs) and carcinogenesis of all ovarian cancer subtypes. Studies also have shown that ovarian CSCs are involved in chemoresistance, metastasis, and tumor recurrence., Results: Wnt/β-catenin target genes regulate cell proliferation and apoptosis, thereby mediating cancer initiation and progression. The Wnt/β-catenin pathway is one of the major signaling pathways thought to be involved in epithelial-to-mesenchymal transition (EMT). Alterations affecting Wnt pathway proteins on the cell membrane, in the cytoplasm, and in the nucleus have been shown to play important roles in the tumorigenesis of ovarian cancer., Conclusions: Wnt signaling is activated in epithelial ovarian cancer. Given the role of the Wnt/β-catenin pathway in carcinogenesis, more pre-clinical studies are warranted to further investigate other Wnt inhibitors in ovarian cancer. The Wnt pathway should also be investigated as a potential target in the development of new drugs for ovarian cancer as a single agent and in combination with chemotherapy or other targeted agents., (© 2013.)

Purpose: Ovarian serous carcinoma is an aggressive cancer that often presents with metastatic disease. Although primary tumor and established metastatic foci in the omentum are generally compared to identify proteins involved in drug resistance, we investigated a potential bridge, the malignant cells from ascites, as facilitator of drug resistance and recurrence., Methods: We evaluated the expression of drug resistance markers P-glycoprotein (P-gp), canalicular multispecific organic anion transporter (MRP2), and lung resistance-related protein (LRP) in malignant cells from ascites and matched omental metastasis from 25 patients with advanced-stage ovarian serous carcinoma who were chemotherapeutic naïve and undergoing initial cytoreductive surgery. Cell viability in vitro, patient response to chemotherapy, and patient survival were correlated with these biomarkers., Results: Of the 25 patients evaluated for a correlation of LRP to 1-year recurrence, we correctly predicted the 1-year recurrence of 24 patients based solely on the presence of LRP in ascitic tumor cells (p=0.01). P-gp and MRP2 were not expressed in malignant cells of ascites or omental metastases. Malignant cells from ascites had higher expression of LRP and were found to be more resistant to carboplatin treatment than cells from omental metastasis (p=0.00375) by in vitro assay. LRP expression in the malignant cells of ascites correlated with carboplatin resistance (p=0.001) by in vitro assay and recurrence at 1 year (p=0.0125)., Conclusions: LRP expression in malignant cells of ascites is a promising marker to predict response to first-line chemotherapy in patients with advanced ovarian serous carcinoma.

Objective: To compare the operative data and complications of radical hysterectomy performed on pregnant women versus nonpregnant women., Study Design: Following institutional review board approval, we reviewed our surgical databases to identify pregnant women who had undergone a radical hysterectomy for cervical carcinoma from 1992-2005 (n = 7). A nonpregnant control group (n = 35) of women undergoing radical hysterectomy during the study interval were identified and matched for age, year of surgery, and surgeon. Pertinent operative and outcome data were abstracted and compared., Results: Of the 7 women who had undergone a radical hysterectomy during pregnancy, 4 had a cesarean radical hysterectomy at a mean gestational age of 35.4 weeks (range, 32.3-38 weeks) and 3 had a radical hysterectomy with a previable fetus in situ at a mean gestational age of 14.2 weeks. Demographics were similar between groups. Transfusion rates were significantly higher among pregnant women (57%) as compared to nonpregnant controls (9%) (p = 0.0009). The overall incidence of operative complications was similar between the pregnant women (43%) and nonpregnant controls (40%) (p = NS)., Conclusion: Radical hysterectomy performed in pregnant women was associated with higher blood loss and increased need for transfusion as compared to nonpregnant controls. No differences were observed in regards to other operative surgical complications between the two groups.

Objective: To review the clinical trial experience with chemotherapy for patients with primary Stage IVB, persistent and recurrent cervical cancer., Methods: PubMed and cooperative group website search was performed and included clinical trials until September 2012. Emphasis was placed on the phase II and III clinical trial experience of the Gynecologic Oncology Group., Results: Experience and trial results with single agents and combination agents in phase II settings are reviewed. Cisplatin has been considered as the most effective agent for metastatic cervical cancer. Most patients who develop metastatic disease have received cisplatin with concurrent radiation and may no longer be sensitive to single-agent therapy. Therefore, cisplatin-based combination chemotherapy regimens have been extensively studied and eight sentinel phase III trials are discussed in this review., Conclusion: Based on phase III results, the combination of cisplatin and paclitaxel remains the standard of care; however, alternative combination therapies including cisplatin/topotecan and cisplatin/gemcitabine may be acceptable considerations for patients when considering potential toxicities. Further research is necessary to determine the optimal therapy for this group of patients. Final data from GOG 240 and JCOG 0505 will likely contribute to the design of future clinical trials in this disease setting., (Copyright © 2012 Elsevier Inc. All rights reserved.)

A number of members of the B7 superfamily of ligands have been implicated in tumor immunogenicity and cancer development. Two of these recently characterized ligands, B7-H4 and B7-H3, have been linked to ovarian tumors. B7-H4 is consistently overexpressed in ovarian tumor specimens, and its tissue and serum levels have been found to be a potential biomarker for ovarian cancer, either alone or in combination with CA125. More recently, B7-H3 has been found to be overexpressed in a large series of ovarian cancer tumor specimens and similar to other types of carcinomas, B7-H3 overexpression has been correlated with poor survival. On the basis of the results obtained by knocking down B7-H3 protein using siRNA, researchers have suggested that blocking the action of B7-H3 could reduce tumor growth, metastatic potential, and improve survival. Because siRNA knock-down is not an ideal clinical therapeutic vehicle, additional studies using antibody-mediated suppression of the B7-H3 protein are necessary to fully evaluate the clinical potential of this molecule as a therapeutic target., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Palliative and supportive care services provide excellent care to patients near the end of life. It is estimated that enrollment in such services can reduce end-of-life costs; however, there is limited data available regarding the impact of palliative services in end-of-life care in gynecologic oncology patients. We examined the use of palliative services in gynecologic oncology patients during the last six months of life., Methods: After IRB approval, a retrospective chart review of patients with a diagnosis of a gynecologic malignancy who died between June 2007 and June 2010 was performed. Abstracted data included demographics, admission and procedural history, use of anti-cancer therapy, and palliative care utilization during the last six months of life., Results: 268 patients were identified. Most patients were white (76.9%) and had ovarian cancer (56.7%). During the last six months of life, 155 (57.8%) patients underwent anti-cancer therapy with chemotherapy, 19 (7.1%) patients were treated with radiation therapy, and 17 patients (6.3%) underwent treatment with both. 218 patients (81.3%) had at least one admission during this time (range 0-14). The most common reason for admission was gastrointestinal complaints (37.1%), followed by admissions for procedures (18.3%). The median time between the last admission and death was 32 days. 157 patients (58.6%) underwent at least one procedure during the last six months of life (range 0-11). The most common procedure performed was paracentesis (22.6%). 198 (73.9%) patients died at home or in a palliative care unit. 189 (70.5%) patients were referred to hospice or palliative care. 3.2% underwent a procedure or treatment with chemotherapy or radiation after hospice enrollment. The median time between hospice enrollment and death was 22 days. 55% of patients were enrolled in hospice less than 30 days before death. Of the 79 patients not referred to hospice, only 16.5% had documentation of refusing hospice services., Conclusions: During the last six months of life, the majority of gynecologic oncology patients receive anticancer therapy and many have repeated hospital admissions. While the majority of patients are referred for palliative care, it appears that most patients spend less than 30 days on hospice. Earlier referral could decrease the number of hospital admissions and procedures while providing invaluable support during this end of life transition., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: To develop a cost-minimization analysis of a multivariate index assay (MIA) used for women with complex pelvic masses., Methods: A decision analysis model was used to evaluate 81,000 hypothetical patients with a complex pelvic mass requiring surgery. Three strategies were evaluated: (1) referral to a gynecologic oncologist (GO) based on clinical assessment including physical exam, ultrasonography, and CA125 (CLINICAL); (2) utilization of a multivariate index assay (MIA); or (3) referral of all patients to a GO (REFER ALL). Various reoperation rates were evaluated with sensitivity analyses. Actual payer costs were compared between each strategy., Results: The CLINICAL strategy cost $933.9 million (M) and resulted in 72% of patients receiving appropriate initial surgical staging. The REFER ALL strategy cost $939.7 M and all patients were appropriately staged. The MIA strategy cost $976.7 M and resulted in 91% of patients having appropriate initial staging. Using conservative reoperation rates (10-20%), 461 patients required reoperation using CLINICAL strategy compared to 142 patients in MIA strategy. Using aggressive reoperation rates (40-50%), 1715 patients required reoperation using CLINICAL strategy resulting in an incremental cost of $15.2M compared to 529 patients at $4.7 M in MIA strategy. The increased costs associated with an aggressive reoperation rate resulted in the REFER ALL strategy being the least expensive alternative, with the highest rates of appropriate initial surgery., Conclusions: Utilizing an MIA resulted in more ovarian cancer patients receiving appropriate initial surgery, but at increased costs. Referring all patients with complex masses avoids the most reoperations at reduced cost compared to using an MIA., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: Debate continues about optimal management of patients with node-positive stage I cervical cancer. Our objective was to determine if patient outcomes are affected by radical hysterectomy in the modern era of adjuvant chemoradiation., Methods: Cervical cancer patients diagnosed from 2000 to 2008 were identified. Demographics, therapy, clinicopathologic data, progression free survival (PFS), overall survival (OS), total radiation exposure, and grade 3-4 complications were analyzed by student t, Mann-Whitney, Fisher's exact, Kaplan-Meier, and log rank tests., Results: This single-institution review evaluated forty-one of 334 (13.4%) patients scheduled to undergo radical hysterectomy that had gross nodal disease diagnosed intraoperatively. 15 underwent aborted radical hysterectomy following lymphadenectomy; the remaining 26 underwent radical hysterectomy and lymphadenectomy. Eleven patients undergoing radical hysterectomy underwent whole pelvic radiation therapy (WPRT) while 8 (30.7%) patients underwent WPRT and postoperative vaginal brachytherapy (BT) for local treatment secondary to close margins. All patients undergoing aborted radical hysterectomy underwent WPRT and BT. With mean follow-up of 42.3 months, there were no significant differences in urinary, gastrointestinal, or hematologic complications between groups. When comparing those undergoing radical hysterectomy to aborted radical hysterectomy, there were no significant differences in local recurrence (11.5% vs 26.7%, p=0.39) or distant recurrence (19.2% vs. 33.3%, p=0.45), PFS (74.9 months vs 46.8 months, p=0.106), or OS (91.8 months vs 69.4 months, p=0.886)., Conclusions: Treatment of patients with early stage cervical cancer and nodal metastasis may be tailored intraoperatively. Completion of radical hysterectomy and lymphadenectomy decreases radiation exposure without apparently compromising safety or outcome in the era of adjuvant chemoradiation., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objectives: We evaluated the indications and outcomes of patients with known gynecologic malignancies that underwent video-assisted thoracoscopic surgery (VATS) and pleurodesis for malignant pleural effusion., Methods: After IRB approval was obtained, a retrospective study of patients with gynecologic malignancies who underwent planned VATS/pleurodesis between 1/2000 and 7/2010 was performed. Abstracted data included demographics, diagnosis, disease status, treatment history, indication for VATS, complications, and outcomes., Results: Forty-two patients with a gynecologic malignancy underwent VATS/pleurodesis. Median age was 63 years. Twenty-nine patients (69%) had ovarian cancer. Fifty-seven percent had recurrent disease at the time of VATS and 57% were undergoing chemotherapy at the time of VATS. Eight patients (19%) underwent perioperative VATS to improve pulmonary status. Seven patients (17%) underwent a palliative VATS. The median length of stay was 7 days (range 1-53). Sixty-two percent had gross disease noted at the time of VATS. A mean of 1650 cc of fluid was drained at time of surgery (range 300-4500), and the majority (88%) of patients had a talc pleurodesis performed. Seven patients (17%) were readmitted within 30 days; 6 were for complications unrelated to their VATS. One patient was readmitted with hospital-acquired pneumonia and died during readmission. Median time to death after VATS was 104 days (range 4-1062). Patients who underwent a perioperative VATS had the longest survival (845 days)., Conclusion: Patients with gynecologic malignancies may require a VATS/pleurodesis for symptomatic pleural effusions. This procedure appears to be safe and effective in this patient population., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: Retinoids are important modulators of cell growth, differentiation, and proliferation. 9cUAB30, 9cUAB124, and 9cUAB130 are three novel retinoid compounds that show cytotoxic effects in other malignancies. We evaluated these novel retinoids in combination with chemotherapy against ovarian cancer stem cells (CSCs) in vitro and in an ex vivo model., Methods: A2780 cells were plated in 96-well plates and treated with retinoid, carboplatin, or combination therapy. Cell viability was evaluated using ATPLite assay. The A2780 cell line was also analyzed for CSCs by evaluating ALDH activity using flow cytometry. A2780 cells treated ex vivo with retinoids and chemotherapy were injected into the flank of athymic nude mice in order to evaluate subsequent tumor initiating capacity., Results: A2780 cells were sensitive to treatment with retinoids and carboplatin. The best treatment resulted from the combination of retinoid 9cUAB130 and carboplatin. Untreated A2780 cells demonstrated ALDH activity in 3.3% of the cell population. Carboplatin treatment enriched ALDH activity to 27.3%, while 9cUAB130±carboplatin maintained the ALDH positive levels similar to untreated controls (2.3% and 6.7%, respectively). Similar results were found in tumorsphere-forming conditions. Flank injections of ex vivo treated A2780 cells resulted in 4/4 mice developing tumors at 40 days in the untreated group, while 0/4 tumors developed in the 9cUAB130 and carboplatin treated group., Conclusion: Combination treatment with carboplatin and retinoids reduced cell-viability, reduced CSC marker expression, and inhibited tumorigenicity, making it a more effective treatment when compared with carboplatin alone., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: The purpose of this study was to investigate the incidence of mechanical complications associated with low-profile subcutaneous implantable venous access devices in gynecologic oncology patients., Methods: Gynecologic oncology patients with low-profile Port-a-Caths implanted between March 2005 and July 2006 were identified into a computerized database. Patient demographics, operative complications, number of chemotherapy cycles, duration of implantation, and mechanical complications were collected. Primary outcomes included port leakage, catheter fracture, and catheter embolization., Results: 112 patients underwent 115 Port-a-Cath placements with low profile single-lumen plastic ports with Groshong-valved catheters. Mean Port-a-Cath indwelling duration was 197 days (range: 4-395) with a mean number of 12 chemotherapy cycles (range 0-64). The cumulative complication rate necessitating removal or replacement was 15%. Of the 14 Port-a-Caths removed, ten (8.7%) were secondary to mechanical malfunction: one for leakage at the port site, two for catheter fracture, and seven for fracture with catheter embolization to the heart or pulmonary vasculature-most commonly the right ventricle. Patients with embolization were asymptomatic and all embolized catheters were successfully retrieved by interventional radiology without complications., Conclusions: The rates of catheter fracture and embolization have previously been reported to be low in patients with subcutaneous Port-a-Caths, and have not been studied in patients receiving low-profile subcutaneous Port-a-Caths. This study suggests that catheter fracture may be more common (8.7%) and must be considered in patients with malfunctioning low-profile Port-a-Caths. Embolized catheters can be removed by interventional radiology without significant adverse affects., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: Relative dose intensity (RDI) is the ratio of delivered dose intensity of chemotherapy to standard dose intensity. In this study, we sought to determine the prognostic significance of RDI in patients with epithelial ovarian cancer (EOC)., Methods: A retrospective analysis of chemotherapy naïve patients treated between 2001 and 2008 with intravenous taxane and platinum was performed. RDI was calculated as the delivered dose intensity (total dose delivered/total time of therapy) divided by standard dose intensity calculated for each regimen and compared to progression-free survival (PFS). Multivariate recursive partitioning survival analysis was utilized., Results: 138 EOC patients completed initial taxane/platinum-based chemotherapy following surgical cytoreduction. The most common reasons for dose delays and reductions were thrombocytopenia (38%) and neutropenia (31%). 24% of treatment delays were due to social reasons such as transportation constraints or scheduling conflicts. The average RDI was 90% (range, 24-126%). The mean PFS was 31 months (range, 3-117). Patients that achieved an RDI between 70% and 110% had a mean PFS of 32 months compared to 20 months in patients with an RDI of <70% or >110% (p=0.046). 14 patients (10%) had a RDI of <70%., Conclusions: RDI is a significant predictor of survival in patients with EOC. Effort should be made to achieve an RDI of at least 70%. Dose reductions and treatment delays could be minimized by utilizing prophylactic colony stimulating factors and educating patients about the importance of adhering to their treatment schedule., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mediates apoptosis via binding to death receptors and enhances the anti-tumor effect of conventional cancer therapies. We evaluated the efficacy of TRA-8, an agonistic antibody to DR5, combined with docetaxel and carboplatin in vitro in an intraperitoneal (IP) ovarian cancer model., Methods: Luciferase positive ES2 cells (ES2H) were treated in 96 well plates with TRA-8, carboplatin, docetaxel, and combination therapy. Cell viability was assessed using ATP-lite assay. Apoptosis was confirmed via Western blot analysis. ES2H cells were injected IP into female athymic nude mice. Animals were sorted based on bioluminescent signal with the following treatments: 1) untreated; 2) TRA-8 alone; 3) docetaxel+carboplatin; and 4) docetaxel+carboplatin+TRA-8. Animals receiving TRA-8 antibody were injected IP with 200 μg of TRA-8 twice weekly until death. Animals receiving docetaxel+carboplatin were injected IP with 5mg/kg and 15 mg/kg respectively every 3 weeks until death. Animals were assessed for tumor burden using bioluminescence imaging and overall survival., Results: Combination therapy reduced viability of ES2H cells in vitro over single agent therapy. Tumor burden was lowest in the chemotherapy+TRA-8 group at days 23 (p<0.001) and 30 (p = 0.04). Mean survival was greatest in the chemotherapy+TRA-8 group (41 days) compared to the chemotherapy only group (34 days) and control group (27 days) as determined by Kaplan-Meier analysis (p<0.001)., Conclusion: Conventional chemotherapy combined with TRA-8 reduced cell-viability via activation of apoptotic pathways, reduced tumor burden and improved survival in this ovarian cancer model., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background: The objective of this study was to evaluate the impact of a weekly tumor board conference on the management of patients with gynecologic malignancies., Methods: The medical records of consecutive patients referred to a multidisciplinary gynecologic oncology tumor board were reviewed. Patient demographics were abstracted from medical records and tumor board minutes. An evaluation was made whether the pathological or radiological findings were changed by the tumor board consultants. If a discrepancy existed, it was determined whether the change impacted clinical management., Results: From January 2004 to December 2006, 741 patients presented at the tumor board were evaluable. Seventy-one percent of the patients were presented for pathology review and 29% for radiology review. The most common diagnoses were ovarian cancer (29%), endometrial cancer (26%), and cervical cancer (12%). Of the 526 pathology reviews, 27% had a change in diagnosis; this discrepancy altered clinical management 74% of the time (20% of all reviews). Of the 215 radiology presentations, 89% were reviewed to confirm recurrent or persistent disease; malignant disease was confirmed 74% of the time. Review of imaging studies resulted in a new diagnosis or upstaging 10% of the time., Conclusions: A multidisciplinary tumor board allows a wide range of gynecologic diagnoses and clinical scenarios to be discussed. Careful review of pathology results in a change in the clinical management of 20% of patients presented at the tumor board. The majority of radiology reviews are presented to confirm persistent or recurrent cancer before recommending further therapy.

Objective: Ovarian cancer, the deadliest of the gynecologic malignancies, poses a therapeutic challenge because of the 70% recurrence rate among patients treated with taxane/platinum-based chemotherapy. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anti-cancer therapy due to its ability to selectively induce apoptosis in cancer cells with little toxicity to normal cells. Despite initially promising results from early TRAIL studies in ovarian cancer, reports of significant TRAIL resistance soon followed. The current study reviews strategies to overcome TRAIL resistance in ovarian cancer., Methods: PubMed was searched for published literature in English using key words "TRAIL," "ovarian," "death receptor" and "resistance". The references of identified articles were then searched for further related literature., Results: A number of mechanisms underlying TRAIL resistance have been proposed, including absence of death receptor expression and genetic alterations, leading to silencing of the downstream effects of ligand binding. Numerous strategies to overcome these mechanisms have been investigated, including combination treatment with cytotoxic chemotherapy, retinoids, proteasome inhibitors, demethylating agents, Akt inhibitors and EGFR inhibitors. Many of the combination treatments have demonstrated success at restoring TRAIL sensitivity in preclinical studies., Conclusion: Continued efforts with combination therapy designed to target multiple steps in apoptotic pathways may not only improve the efficacy of TRAIL-mediated therapies, but may also improve quality of life for ovarian cancer patients by reducing toxicity associated with cancer therapy., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Objective: The 2006 American Society for Colposcopy and Cervical Pathology Consensus guidelines state that it is acceptable to defer colposcopy until 6 weeks postpartum in pregnant patients with atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesion (LSIL) cytology. Therefore, we sought to determine the incidence of cervical intraepithelial neoplasia (CIN) 2,3 in pregnant patients referred to a university colposcopy clinic., Materials and Methods: A retrospective study identified all pregnant women with abnormal cytology referred to the University of Alabama at Birmingham colposcopy clinic between May 2005 and September 2007. After an institutional review board approval was obtained, demographic information, referral cytology, and histologic data were collected. The colposcopic impression was also obtained from the records., Results: Six hundred twenty-five pregnant patients were identified. The mean age was 23 years (range, 14-44 years), the mean parity was 1 (range, 0-7), and the mean gestational age was 24 weeks (range, 4-39 weeks). The most common referral cytology was LSIL (41.0%), followed by ASC-US (34.1%), and high-grade squamous intraepithelial lesion (13.6%). One hundred thirty-eight patients (22%) underwent cervical biopsy at the time of initial colposcopy. Forty-three patients had CIN 1, 28 patients had CIN 2, and 23 patients had CIN 3. Forty-four patients (32%) had no evidence of CIN on biopsy. There were no cases of invasive cervical cancer identified. Of the 469 patients with ASC-US and LSIL cytology, 20 of 78 patients who had a cervical biopsy were diagnosed with CIN 2,3. Of the 128 patients with high-grade intraepithelial lesion or high-grade squamous intraepithelial lesion cytology, 31 of 60 patients who had a cervical biopsy were diagnosed with CIN 2,3. Repeat colposcopy in the third trimester was performed on 47 patients. Only 3 of 13 patients with a repeat biopsy had CIN 2,3., Conclusions: Pregnant patients with ASC-US or LSIL cytology rarely have colposcopically suspected CIN 2,3 at their initial colposcopy that warrants a cervical biopsy; therefore, it is reasonable to defer the initial colposcopy in patients with ASC-US and LSIL until at least 6 weeks postpartum.

Background: To develop a standardized protocol for management of postoperative fever in gynecology patients to decrease unnecessary diagnostic workups and empiric use of antibiotics., Study Design: A prospective analysis of postoperative gynecology patients identified those who experienced fever (maximum temperature [T(max)] > 100.4 degrees F). Patients were triaged into low- and high-risk groups. High-risk patients were managed independent of the protocol. High-risk criteria included bowel operation, preoperative infection, immunodeficiency, indwelling vascular access, mechanical heart valves, and intensive care unit admissions. Low-risk patients were treated with observation and antipyretics. Patients with persistent or high fever, defined as T(max) > 101 degrees F for > 48 hours, were evaluated and treated based on physical examination findings., Results: We evaluated 292 postoperative patients. Forty-seven percent of patients had a final diagnosis of malignancy. Sixty-four patients were high-risk and 33% of these patients experienced fever. Using the standardized protocol, 228 low-risk patients were managed. Thirty-seven of the 228 patients (16%) had fever postoperatively. Nineteen patients had low-grade fever (100.4 to 101 degrees F); none of these patients required antibiotics. Seventeen patients had fever (101.1 to 102 degrees F) and one patient had fever > 102 degrees F. Using the protocol, 6 of 37 patients (16%) were treated with antibiotics for an infectious diagnosis., Conclusions: Although postoperative fever is common in gynecologic patients, the incidence of infection is low (3%). A standardized postoperative fever protocol in low-risk gynecology patients decreases use of empiric antibiotics without compromising morbidity.

Objective: The relationship between the apoptotic pathway and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising area of scientific interest for cancer researchers. TRAIL-receptor-activating agents have demonstrated favorable in vitro and in vivo activity for the treatment of several malignancies including breast and gynecologic cancers., Methods: This article reviews the available peer-reviewed literature and our own institution's experience with specific TRAIL-receptor-activating agents. Emphasis was placed on the apoptotic/TRAIL mechanism, preclinical evaluation, and phase I studies in various malignancies., Results: Preclinical and early phase I studies indicate that these novel agents are safe with enhanced target specificity for malignancy. When these targeted agents are combined with conventional chemotherapy drugs or radiation therapy, they appear to increase cell death over single-agent modalities., Conclusions: TRAIL-receptor-activating agents represent an exciting new class of targeted therapies that hold promise to improve the treatment of women with breast and gynecologic malignancies.

Objective: To assess the potential effectiveness and costs of 4 commonly used strategies to manage abnormal early pregnancies (AEPs)., Study Design: A decision analysis model was constructed to compare 4 strategies to manage AEPs: (1) observation, (2) medical management, (3) manual vacuum aspiration (MVA), and (4) dilation and curettage (D&C)., Results: MVA was the most cost-effective strategy, at dollar 793 per cure, for a total cost of dollar 377 million per 500,000 women and a cure rate of 95%. D&C was more effective than MVA, with a cure rate of 99%, but was more expensive (dollar 2,333 per cure, for a total cost of dollar 1.2 billion). D&C cured 20,000 more patients than MVA; however, at a substantial cost of dollar 38,925 per additional cure. With other estimates at baseline, MVA remained more cost-effective than D&C until the efficacy of MVA was < 82% or the cost of D&C was < dollar 240., Conclusion: MVA is the most cost-effective strategy for managing AEP and would be appropriate in settings in which resources are limited. D&C remains a reasonable strategy; however, one must spend dollar 38,925 per additional cure. In the United States, MVA would save dollar 779 million per year relative to D&C.

Objective: To evaluate the incidence of c-kit expression in uterine sarcomas., Study Design: Immunohistochemical evaluation for expression of c-kit was performed on specimens from 11 patients with pathologically documented uterine sarcomas. Histologic subtypes included 5 carcinosarcomas, 3 leiomyosarcomas and 3 endometrial stromal sarcomas. Histologic sections of formalin-fixed, paraffin-embedded hysterectomy specimens from patients with uterine sarcomas were immunostained with c-kit (CD117) antibody. Overall staining intensity was graded as strong, intermediate or weak., Results: In all 11 patients with uterine sarcoma, c-kit immunostaining was positive. Four specimens demonstrated stronger staining intensity than did the gastrointestinal stromal tumor control. Five specimens demonstrated intermediate staining intensity. Two specimens demonstrated weak staining intensity. Furthermore, in the carcinosarcoma specimens both the epithelial and sarcomatous elements were positive for c-kit staining., Conclusion: In this case series, c-kit expression was demonstrated in all sarcomas of the uterus regardless of histologic type. These results suggest that such drugs as imatinib mesylate, which inhibit the c-kit tyrosine kinase, should be investigated for these mesenchymal neoplasms.

Objectives: To assess the morbidity and efficacy of radical parametrectomy (RP) performed following extrafascial hysterectomy in patients with occult cervical carcinoma., Methods: An IRB approved retrospective chart review identified 23 patients that underwent RP with pelvic and/or para-aortic lymphadenectomy and upper vaginectomy. Data were collected on demographics, tumor stage, grade, histology, indication for hysterectomy, surgical findings, complications, recurrence, and survival., Results: Of the 23 patients, 2 patients had a stage IA(2) lesion while 21 patients had a stage IB(1) lesion. There were 5 patients with a grade 1 tumor, 10 with grade 2, 4 with grade 3, and 4 with unknown grade. Median age was 41 years (range 27-59). The most common indication (48%) for extrafascial hysterectomy was CIS of the cervix. Four patients (17%) had metastasis to pelvic nodes or evidence of tumor at the margin at the time of RP. Three of these 4 patients with a positive specimen received adjuvant radiation and all are alive (mean follow-up 66 months). One patient declined radiation and is alive at 42 months. There were 7 (30%) operative complications: Most notably 4 patients received blood transfusions. Two of 19 patients (11%) with no residual tumor in RP specimen recurred and 1 patient was salvaged with radiation (follow-up 103 months). With a median follow-up of 61 months (range 9-103), overall 5-year survival is 96%., Conclusions: RP is an acceptable option for patients diagnosed with an occult cervical carcinoma at the time of extrafascial hysterectomy. Careful selection of RP for patients unlikely to have residual tumor will obviate the need for radiation in most instances.

Objective: Our aim was to determine the outcomes of Stage I uterine papillary serous carcinoma (UPSC) patients with and without adjuvant therapy after comprehensive surgical staging., Methods: Patients with FIGO Stage I UPSC diagnosed from 1987 to 2000 were identified from tumor registry databases at four institutions. A retrospective chart review identified 60 women who underwent comprehensive surgical staging, including a total hysterectomy, bilateral salpingo-oophorectomy, pelvic/para-aortic lymphadenectomy, and peritoneal cytology. Fisher's exact, chi(2), and log-rank tests were used for the statistical analyses., Results: Of the 60 Stage I patients, 40 (66%) patients received no adjuvant therapy, 12 (20%) received adjuvant radiation therapy (XRT), 7 (12%) received adjuvant chemotherapy (CHM), and 1 (2%) received both XRT and CHM. There were seven recurrences in the observation group versus two recurrences in the XRT group (17% vs 16%, P = 0.9). No recurrences or deaths were observed in the CHM group. The mean disease-free survival rates for the observation and the XRT groups were 31 and 41 months, respectively. The mean overall survival rates for the observation and XRT groups were 39 and 40 months, respectively. The 5-year disease-free survival rates for the observation and XRT groups were 65 and 60%, respectively; the 5-year overall survival rates for observation and XRT groups were 66 and 59%. There was no statistical difference in overall survival among the three groups., Conclusion: In this largest reported series of surgical Stage I UPSC patients, recurrence rates were lower than those published in previous studies, suggesting a potential benefit of comprehensive surgical staging in these patients. The risk of recurrence and the mean overall survival were similar between surgical Stage I UPSC patients who were managed conservatively and those treated with adjuvant radiation therapy. These data question the benefit of radiation therapy in UPSC patients with disease confined to the uterus. Finally, given the absence of recurrences and disease-related deaths for adjuvant chemotherapy in these patients, a Phase II/III trial evaluating adjuvant chemotherapy in surgical Stage I UPSC patients should be considered.

Objective: The purpose of this study was to evaluate the complication rates associated with indwelling venous access devices in patients with gynecologic malignancies., Methods: Following IRB approval, a computerized database identified women that had indwelling access devices placed for chemotherapy from March 1999 to June 2001. A retrospective chart review identified 116 venous access devices that were placed in 104 patients. All devices were silicone and had a closed tip design with a three-position valve. Data were collected on patient demographics, clinicopathologic features, type of venous device, and complications. The chi(2) test was used for statistical analysis., Results: Of the 104 patients, 79 had ovarian cancer, 11 had uterine cancer, 10 had cervical cancer, 2 had fallopian tube cancer, and 2 had vaginal cancer. The median age was 61 years. There were a total of 116 venous devices placed: 65 external catheters (EC) and 51 subcutaneous ports (SP). Seventy-nine percent of the patients were administered low-dose coumadin (1 mg/day) for catheter clot prophylaxis. There were three operative complications in the EC group and two in the SP group (P = NS). The most common postoperative complications were infection and thrombosis. Nineteen patients in the EC group experienced a catheter-related infection versus 5 in the SP group (P = 0.025). In the EC group, there were 11 cases of site infection and 8 cases of line sepsis. In contrast, there were 3 cases of exit site infection and 2 cases of line sepsis in the SP group. Deep vein thrombosis occurred in 5 patients with EC and 3 patients with SP (P = NS). Twenty-seven patients with EC had the device removed for catheter-related complications versus 2 patients with SP (P = 0.001). Six patients inadvertently removed their EC., Conclusion: There is a significantly higher postoperative complication rate in gynecologic oncology patients with external catheters versus subcutaneous ports. Infection and catheter-related malfunction are more common in patients with external catheters. We recommend the use of subcutaneous ports in the majority of patients with gynecologic malignancies.

Objective: The goal of this study was to determine the outcomes of stage IC endometrial carcinoma patients who are managed with and without adjuvant radiation therapy after comprehensive surgical staging., Methods: Patients with FIGO stage IC adenocarcinoma of the endometrium diagnosed from 1988 to 1999 were identified from tumor registry databases at four institutions. A retrospective chart review identified 220 women who underwent comprehensive surgical staging including a total hysterectomy, bilateral salpingo-oophorectomy, pelvic/paraaortic lymphadenectomy, and peritoneal cytology., Results: Of the 220 stage IC patients, 56 (25%) patients received adjuvant brachytherapy (BT), 19 (9%) received whole-pelvis radiation (WPRT), and 24 (11%) received both WPRT and BT. One hundred twenty-one patients (55%) did not receive adjuvant radiation. There were 6 recurrences (6%) in the radiated group and 14 (12%) in the observation group (P = 0.20). Seven of fourteen recurrences in the observation group were local, and all local recurrences were salvaged with radiation therapy. Two of seven distant recurrences in this group were also salvaged with surgery and chemotherapy. The overall salvage rate for the observation group was 64%. There was a statistical difference in 5-year disease-free survival between the radiated and observation groups (93% vs 75%, P = 0.013). However, the 5-year overall survival was similar in the two groups (92% vs 90%, P = 0.717)., Conclusion: Adjuvant radiation therapy improves disease-free survival in surgical stage IC patients; however, overall survival is not improved with adjuvant radiation therapy since the majority of local recurrences in conservatively managed patients can be salvaged with radiation therapy.

Objective: The aim of this study was to determine the outcomes of Stage I endometrial carcinoma patients who are managed without adjuvant radiation after comprehensive surgical staging., Methods: A computerized hospital database identified women diagnosed with adenocarcinoma of the endometrium from 1993 to 1998. A chart review identified 864 women as having primary surgery for adenocarcinoma of the endometrium. A total of 670 of 864 patients (78%) underwent comprehensive surgical staging with total hysterectomy, bilateral salpingo-oophorectomy, pelvic/para-aortic lymphadenectomy, and peritoneal cytology. After 57 patients with high-risk histologic subtypes were excluded, 613 patients remained for analysis., Results: A total of 321 of 325 Stage IB patients (99%) did not receive adjuvant radiation. Fifteen of 321 patients (5%) recurred; 9 recurred in the pelvis or vagina. All 9 local recurrences were salvaged with whole pelvic radiation (XRT) and brachytherapy (BT). Seventy-seven patients were diagnosed with Stage IC disease; 53 (69%) received no adjuvant therapy. Four patients (8%) recurred, of which 2 recurred in the vagina. Three of 4 patients (75%) were salvaged, 2 with XRT/BT and 1 with surgery and chemotherapy. For all Stage I patients, the 5-year disease-free survival was 93% and the 5-year overall survival was 98%., Conclusions: Surgically staged patients with endometrial carcinoma confined to the uterine corpus have a small risk of recurrence and the majority of these recurrences can be salvaged with radiation therapy. Conservative management of Stage I endometrial carcinoma patients is an effective treatment strategy., (©2001 Elsevier Science.)