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Background: The purpose of this article was to relate preoperative serum CA 125 to risk of nodal metastases in women with Grade 1 endometrial cancer that were fully surgically staged. Materials and Methods: Charts were reviewed to determine all patients with preoperative Grade 1 endometrial carcinoma and a serum CA 125 undergoing complete surgical staging. Charts were also reviewed for final stage, grade, and site of metastases. All serum CA 125s were drawn within four weeks ofdefinitive surgery. Results: Analysis was completed on 737 patients with Grade 1 endometrial cancer. The mean age of the population was 61.9 years (95% CI 61.3-62.4). Extrauterine disease was found in 14.7% of patients and nodal disease in 12.6%. A significant difference in BMI was seen between those not having lymph node metastases (mean 38.7 kg/m²; 95% CI 38.1, 39.3) and those having positive nodes (mean 35.3 kg/m²; 95% CI 34.336.3) (p < 0.001). The mean CA 125 for the cohort was 25.6 mIU/ml (95% CI 22.0-29.2). No patients with preoperative Grade 1 disease and a CA 125 < 15 mIU/ml (0/239) had nodal disease at surgical staging while 18.7% (93/498) with a CA 125 ≥ 15 mIU/ml had nodal metastases (p < 0.001). Conclusion: In patients with Grade 1 endometrial adenocarcinomas, CA 125 can be used to determine who needs full surgical staging with minimal risk of missing nodal positive patients. [ABSTRACT FROM AUTHOR]

Purpose of investigation: Randomized trials have demonstrated improvements in overall survival when using platinum doublets compared to single agent platinum in the treatment of women with advanced or recurrent cervical cancer. The authors sought to evaluate the cost effectiveness of these regimens. Methods: A decision model was developed based on Gynecologic Oncology Group (GOG) protocols 179 and 204. Cisplatin alone was compared to cisplatin/paclitaxel (CP), cisplatin/topotecan (CT), cisplatin/gemcitabine (GC), cisplatin/vinorelbine (CV), and a hypothetical novel agent. Parameters included overall survival (OS), cost, and complications. One way sensitivity analyses were performed. In further sensitivity analysis, a hypothetical agent that added 3.7 months survival to CP's survival was studied. Results: The chemotherapy drug costs for six cycles of cisplatin was 89 USD while for cisplatin/paclitaxel it was 489 USD. The highest chemotherapy cost was for GC at 18,306 USD. The average total cost of six cycles CP was 13,250 USD while the average cost of cisplatin alone was 14,573 USD. The highest average cost for six cycles was for GC at 33,559 USD. With cisplatin/paclitaxel being the most effective, the cost effectiveness analysis showed that cisplatin, CT, GC, and VC were all dominated by CP. Because of the regimens being dominated, no baseline ICERs compared to CP were calculable. Sensitivity analyses demonstrate that even all of the chemotherapies were given for free, CP would still be the regimen of choice. Conclusions: In this model, CP is the most cost effective regimen for the treatment of these patients with an average cost of 13,250 USD. With the fact that GOG 204 also showed statistically significantly improved survival for CP, CP should be considered the regimen of choice. [ABSTRACT FROM AUTHOR]

Background: DNA promoter methylation serves as an alternative to gene mutation in silencing genes. The progesterone receptor, a target for cancer therapy, has been shown to be silenced in this manner. The object of the study was to determine if patients taking hydralazine as a global demethylating agent would have tumor stabilization or response from using sequential megestrol acetate and secondarily whether the tumor would show changes consistent with the demethylation. Materials and Methods: Heavily pretreated women with gynecologic adenocarcinomas were enrolled on an institutional review approved study. Results: Five patients were enrolled on this initial study. Three patients continued therapy beyond the first four week cycle. These patients had progression free intervals of six, seven, and nine months, respectively. All of the evaluable patients had negative staining for progesterone receptor prior to study. All three patients who finished at least one cycle of therapy had repeat biopsies that demonstrated their tumors stained positively for progesterone receptor. Conclusions: In this pilot study, three patients had progression free intervals of ≥ six months and their tumors which previously stained negatively for progesterone receptor stained positively for progesterone receptor after treatment with hydralazine. [ABSTRACT FROM AUTHOR]

Objective: To determine how often adnexal remnants are found surgically after documented bilateral salpingo-oophorectomy. Materials and Methods: Retrospective chart review of all referrals to gynecologic oncology service. Patients undergoing surgery on the gynecologic oncology service after previous hysterectomy and bilateral salpingo-oophorectomy were analyzed. Results: Seventy-two patients met the inclusion criteria including having obtainable operative reports. Dysfunctional bleeding was the most common indication for the surgery involving bilateral salpingo-oophorectomy, while a suspicious pelvic mass was the most common indication for referral to the gynecologic oncology service. Twenty-nine patients (40.3%) were found to have residual ovarian tissue. Residual fallopian tube tissue was found in seven patients. No specific diagnosis was statistically more likely to lead to remnant tissue (p = 0.7). Conclusion: Although the majority of patients undergoing bilateral salpingo-oophorectomy had no residual ovarian or adnexal tissue, over 40% of patients were found to have residual ovarian tissue after a previous bilateral salpingo-oophorectomy. [ABSTRACT FROM AUTHOR]

Objective: There are numerous explanations behind the presence of post-operative fever that patients may experience. The aim of this study was to determine if temperatures = 38.0°C were more common in patients undergoing open or robotic surgery for endometrial cancer. Materials and Methods: 150 women were retrospectively analyzed; half underwent robotic hysterectomy and the other half underwent an open approach. A febrile episode was a single temperature of = 38.3°C or a sustained temperature of = 38.0°C for more than one hour. Temperatures were recorded and compared for 48 hours postoperatively. Results: Febrile episodes of 38.0-38.3°C were seen in 33.3% of patients undergoing an open approach and 12% of patients undergoing robotic surgery (p = 0.003) within two days of surgery. Temperatures of = 38.3°C were only seen in three patients in the open arm and one in the robotic arm (4% vs. 1.3%, p = 0.3). Those few who experienced temperatures = 38.3°C were all found to have infections. Conclusions: There is a significantly decreased incidence of a post-operative fever in a patient who undergoes a robotic hysterectomy instead of an open abdominal hysterectomy for the treatment of endometrial cancer. [ABSTRACT FROM AUTHOR]

The article presents a study which reexamines the complications, indications and procedure associated with total colectomy with ileorectal anastamosis (IRA) in women undergoing primary ovarian cytoreduction. It determines that total colectomy can be performed in select patients with primary ovarian cancer. It also mentions that the complete removal of visible or palpable disease is the goal of primary ovarian cytoreduction.

Purpose of investigation: Vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX 2) are markers of angiogenesis and potential therapeutic targets. Previous studies demonstrate that VEGF is upregulated in some ovarian cancers. The purpose of this study was to determine the correlation of VEGF and COX 2 staining with survival in ovarian cancer patients. Materials and Methods: One hundred forty-three consecutive patients with ovarian carcinoma underwent primary staging or cytoreduction prior to platinumbased chemotherapy. Their tumors were immunohistochemically stained for expression of VEGF and COX 2. FIGO stage, grade, cytoreduction status, and histology were also analyzed as prognostic factors. Results: Twenty-seven patients had Stage I tumors, three Stage II, 87 Stage III, and 26 Stage IV. Median follow-up was 74 months (mean 79 months). One hundred nineteen patients (83.2%) had tumors that were positive for VEGF and 110 patients (76.9%) had tumors that were positive for COX 2. Patients with tumors staining positive for both VEGF and COX 2 (68.5%) had a significantly increased risk of dying from their ovarian cancer (Chi-square p = 0.011, Log rank p = 0.037). Multivariate logistic regression analysis revealed FIGO stage, grade, cytoreduction status, and VEGF/COX 2 expression to be independent prognostic indicators of survival. Conclusion: VEGF and COX 2 staining are frequently positive in ovarian cancer. Patients whose tumors are positive for both VEGF and COX 2 have a decreased survival. These patients may benefit from antiangiogenesis targeted therapy. [ABSTRACT FROM AUTHOR]

Objective: Upregulation of cyclin E and cyclin D1-6 accelerates the transition from G1 to S phase. The objective of this study was to determine if cyclin D1 and E are prognostic indicators in endometrial cancer. Materials and Methods: Surgically-treated patients with endometrial carcinoma had their tumors stained for nuclear expression of cyclin D1 and E. Quantification of staining and measurement of growth phase fraction were performed using image analysis. FIGO stage, grade, and histology were also analyzed. Results: Cyclin D1 and E expression was unrelated to DNA index (p = 0.93). While cyclin D1 expression did not correlate with S+G2M phase fraction (p = 0.69), increased cyclin E expression was directly correlated with increased S+G2M phase fraction (p = 0.002). Cyclin E expression was highest in clear cell carcinomas (p = 0.042) while cyclin D1 expression was highest in adenosquamous carcinomas (p = 0.028). Patients dying from cancer had significantly higher expression of cyclin D1 (p = 0.042) and E (p = 0.02) as compared to patients surviving their disease. Multivariate logistic regression revealed FIGO stage, grade, and lack of cyclin E overexpression to be independent prognostic indicators of survival. Conclusion: Cyclin E expression is related to increased growth fraction, clear cell histology, and decreased survival in patients with endometrial cancer. [ABSTRACT FROM AUTHOR]

Natalie Klag, Adam C Walter, Kristen M Sheely, Kelly J Manahan, John P Geisler Division of Gynecologic Oncology, Cancer Treatment Centers of America Newnan, Georgia, USA Background: New chemotherapy combinations are being tested for the treatment of women with advanced, persistent or recurrent cervical cancer. We sought to evaluate the cost effectiveness of some newer combination therapies in cervical cancer. Patients and methods: A cost effectiveness decision model was used to analyze Gynecologic Oncology Group 240. All regimens were modeled for seven cycles. The regimens studied are as follows: regimen 1, cisplatin/paclitaxel (CP); regimen 2, CP with bevacizumab (CP+B); regimen 3, paclitaxel/topotecan (PT); and regimen 4, PT with bevacizumab (PT+B). Overall survival, cost, and complications were studied. Sensitivity analyses were performed. Results: Mean chemotherapy costs over mean total costs for seven cycles of each follows: CP $571/$32,966; CP+B $61,671/$96,842; PT $9,211/$71,620; and PT+B $70,312/$109,211. Incremental cost-effectiveness ratio (ICER) for CP+B was $133,559/quality adjusted life year (QALY). ICER for PT+B was $124,576/QALY. To achieve an incremental ICER for CP+B:CP of 10 years for PT and 4.1 years for PT+B. Treating 1,000 women with cervical cancer with CP+B would cost almost double the cost of treating >18,000 women with ovarian cancer annually (carboplatin/paclitaxel). Conclusion: CP is the most cost effective regimen. A 12-month increase in overall survival will not even make the newer combinations cost effective. Currently, the use of bevacizumab is not sustainable at today's costs. Keywords: cervical cancer, chemotherapy, bevacizumab, cost-effectiveness

Objectives: Partial upper vaginectomy consists of removal of the vaginal apex and is indicated for the diagnosis and treatment of vaginal intraepithelial neoplasia and recurrent cancer. We present a novel surgical approach to partial upper vaginectomy by use of the loop electrosurgical excision procedure.Study Design: A total of 15 consecutive patients with abnormal vaginal cytologic results were treated by the loop electrosurgical excision procedure for partial upper vaginectomy. After submucosal injection of local anesthetic, the loop electrode was used to resect the upper third of the vagina. An iodoform vaginal pack was placed for 24 hours. All patients with high-grade vaginal intraepithelial neoplasia received intravaginal 5-fluorouracil cream postoperatively.Results: The mean blood loss was 0 mL, and the mean surgical time was 30 minutes. A complication developed in 1 patient (7%). One case of invasive carcinoma was diagnosed. No recurrences have developed in any patients with vaginal intraepithelial neoplasia after hysterectomy.Conclusions: The loop electrosurgical excision procedure for partial upper vaginectomy can be performed quickly, with minimal blood loss, minimal complications, and minimal recurrence of neoplasia, and it provides a histologic specimen for evaluation. [ABSTRACT FROM AUTHOR]

The article presents case studies involving the application of robotically-assisted laparoscopic radical parametrectomy and vaginectomy. It mentions the cases of women who have squamous cell carcinoma in the cervix and vaginal cancer respectively and were offered surgery and chemoradiation. It also notes that both treatment procedures are technically feasible due to efficiency.

Background and Objectives: This is a case report of a 5-mm trocar-site large bowel herniation following laparoscopic tubal sterilization. During laparoscopic sterilization, the 5-mm port site was closed initially. Large bowel herniation was recognized at the end of the case and managed immediately by laparoscopically reducing the hernia and closing the port site without any short- or long-term complications. Trocar-site bowel hernia is a rare complication after laparoscopic surgery. It is usually associated with trocar size > 10 mm. We describe a case of bowel herniation through a 5-mm trocar site, which was managed after laparoscopic surgery., Case Report: A 36-year-old multigravid patient underwent a laparoscopic tubal fulguration. Two 5-mm ports were used for the procedure. At the end of the procedure, the lateral trocar site was found to have fat protrusion that looked like appendices epiploicae. A laparoscopic camera was reintroduced into the abdominal cavity that showed a large bowel herniation through the 5-mm lateral port site. The hernia was reduced laparoscopically, and the fascial defect was repaired., Conclusion: Bowel herniation can occur through a 5-mm port. All port sites should be closed to avoid such complications.

Objective: The purpose of this study was to analyze estrogen receptor alpha and beta (ERalpha, ERbeta) expression in a stage and grade matched cohort of patients with serous and endometrioid adenocarcinoma of the ovary., Methods: Forty-two patients from 1991 to the present were found to have the diagnosis of endometrioid adenocarcinoma of the ovary and have tissue available for analysis. Of these 42, ten were selected for analysis. These were stage and grade matched with ten patients having serous adenocarcinoma of the ovary during the same time period. ERalpha and ERbeta mRNA was detected by a multiplex RT-PCR and amplification of random hexamer generated cDNA using a housekeeping gene (G3PD) as a control for mRNA quality and quantity. Methylation specific PCR (MS-PCR) was used to correlate methylation of the ERalpha and ERbeta CpG islands with mRNA expression status., Results: ERalpha expression was present in ten of ten endometrioid adenocarcinomas but in only five of ten serous carcinomas (chi2, p = 0.01). ERbeta expression was present in six of ten endometrioid adenocarcinomas and in four of ten serous caricinomas (chi2, p = 0.65). Methylation of the ERalpha and ERbeta CpG islands was found in tumors without mRNA expression but not in the tumors with mRNA expression (p = 0.005)., Conclusions: ERalpha expression, but not ERbeta expression, is significantly more common in endometrioid than serous adenocarcinomas of the ovary when controlled for stage and grade. The role of methylation in ER silencing may lead to potential therapeutic interventions.

Purpose: To determine the difference in the immediate complication rate between placement of long-term central venous catheters (LTCVCs) by the percutaneous versus jugular venous cutdown method., Method: Case lists were examined to determine the number of LTCVCs placed during the designated time period. Medical records, operative reports, and chest roentgenograms were examined to extract pertinent information. Immediate complications included complications occurring in the operating room until 30 days postoperatively. Complications included misplacement of the catheter requiring an adjustment or a repeat procedure, pneumothorax, hydrothorax, or hemothorax, operative site or tunnel infection, and line migration requiring removal., Results: Five hundred and one patients had LTCVCs placed during the period of this study. This included 399 totally implantable venous access devices (TIVADs) and 102 free access venous access devices (FAVADs) with 163 placed percutaneously into subclavian veins and 338 placed by cutdown into jugular veins. There was a significant increased risk in the overall immediate complication rate for the percutaneous placement compared to venous cutdown (p < 0.001). Also, pneumothorax was more common with the percutaneous approach compared to the venous cutdown approach (p < 0.001)., Conclusions: Immediate complications, especially pneumothorax, were more common when placing catheters by the percutaneous approach as compared to the venous cutdown approach.

Background: The purpose is to determine the rate of lymph node metastases in women with endometrioid adenocarcinoma of the endometrium (EAE) undergoing systematic lymphadenectomy., Methods: Patients (349) underwent a complete pelvic and para-aortic lymphadenectomy from caudal to the median circumflex to the level of the renal vessels., Results: Grade 1 tumors accounted for 32.7% of the tumors and 31.0% of the positive nodes, grade 2 accounted for 47.3% of the tumors (37.9% of positive nodes), and grade 3 accounted for 20.1% of the tumors and 31.0% of the positive nodes (P>0.05). Positive nodes were found in 15.8% of grade 1 tumors, 13.3% of grade 2 tumors and 25.7% of grade 3 tumors (P>0.05). Isolated para-aortic involvement without pelvic nodal involvement occurred in 29% of patients with positive nodes., Conclusions: When complete lymphadenectomies are performed in EAE, positive lymph nodes (including isolated para-aortic lymph nodes) are common in all grades.

A 31-year-old female was found to have FIGO Stage IIB squamous cell carcinoma of the cervix. The patient began her prescribed radiation therapy and 5-fluorouracil radio-sensitizing chemotherapy. During the first day of infusion, she began having severe shortness of breath. Cardiac evaluation revealed acute congestive heart failure with a cardiac ejection fraction of 19%. Radiation was continued without chemotherapy. Four years later, the patient is alive and well with an ejection fraction of 53%.

Although cytoreductive surgery is the most influential factor in treatment for ovarian cancer, chemotherapy is needed for almost all patients diagnosed with this disease. The mainstay of chemotherapy is platinum. Different platinum compounds are used for different histologies, and different combinations are used for different histologies also. We will present the data so that each reader can understand the knowledge behind chemotherapy decisions.

Purpose: Since its discovery 50 years ago, DNA methylation has been found to be an important part of gene regulation. Newer methods of analysis over the last decade have helped further the understanding of this epigenetic phenomenon. The purpose of this article is to describe current methods of analysis and discuss advantages and disadvantages of each and their possible roles in gynecologic malignancies., Results: The methods for analysis of DNA methylation are divided into two major categories: 1) methods which utilize chemical methods or restriction enzymes to differentially cleave at cytosine versus 5-methylcytosine sites, 2) methods which utilize sodium bisulfite (NaHSO3) to specifically convert unmethylated cytosines to uracil (thymine after PCR). This recently developed method appears to be more sensitive and allows the investigator to specifically delineate the study site(s)., Conclusion: DNA methylation is important in the human genome. Its role in tumorigenesis is just beginning to be understood. While relying upon newly designed methods of analysis, further understanding of this epigenetic phenomenon and its role in gene expression and tumorigenesis will be forthcoming.

Background: Although not fully understood, heat shock proteins (HSP) are well known stress response proteins. The purpose of this analysis was to determine whether staining for HSP27 was different between placentas from pregnancies complicated by severe pre-eclampsia with intrauterine growth restriction (IUGR) as compared to controls., Methods: Sterile placental tissue was collected from ten women whose pregnancies were complicated by severe preeclampsia with IUGR and from ten women with uncomplicated by severe pre-eclampsia with IUGR and from ten women with uncomplicated term pregnancies. The tissue was then stained for HSP27., Results: The median age of the patients was 27 years (mean 27, range 17-37). The median estimated gestational age at delivery was 38 weeks (mean 37, range 29-41). Overall 12 of 20 placentas stained positively for HSP27 (nuclear and/or cytoplasmic). Eight of ten placentas from women with pre-eclampsia and IUGR stained positively for HSP27 (p = 0.046)., Conclusion: HSP27 staining of the placenta is twice as common in patients with severe preeclampsia as compared to patients with normal term gestations. These preliminary results warrant the inauguration of a similar but larger study to examine the significance of these findings.

Objective: Heat shock protein 27 (HSP27) is produced in response to pathophysiologic stress in animal cells. The authors have previously shown that HSP27 is an independent prognostic indicator in patients with ovarian carcinoma. The present study was performed to see whether HSP27 remained an independent prognostic indicator with longer follow-up., Methods: One hundred and three consecutive patients with epithelial ovarian carcinoma were studied. Slides were prepared from fresh tissue. HPS27 staining was performed as previously described. Patient records were examined for FIGO stage, grade, histology, level of cytoreduction and survival., Results: One hundred and three patients were followed for a mean of 60 months. Twenty patients had FIGO Stage I disease, four Stage II, 59 Stage III, and 20 Stage IV. Immunohistochemical (IHC) staining for HSP27 was not related to histologic grade, level of cytoreduction or histologic subtype. A statistically significant decrease in HSP27 staining was found to correlate with increased FIGO stage (p = 0.008). Using cox-regression analysis, HSP27 staining (p = 0.025), stage (p = 0.0012), and level of cytoreduction (p < 0.0001) were independent predictors of survival in these patients., Conclusion: Cox-regression analysis found HSP27 to be an independent indicator of prognosis and survival in patients with ovarian carcinoma who had longer follow-up. Decreased HSP27 staining was related to decreased survival. This study confirms the authors' earlier report on the importance of HSP27 as a prognostic indicator in ovarian carcinoma.

This case illustrates that methylation of one BRCA1 allele may serve as the second hit in a patient with a diploid locus and missense mutation on the other allele.

We analyzed clonal populations of ovarian cancer cells for heterogeneity in p53 mutations (exons 4-9) and chemosensitivity. UL-3A cells were developed from a patient with stage IIIC ovarian adenocarcinoma. Heterogeneity in p53 mutations was demonstrated, ranging from point mutations to deletions in exons 4, 6 and 7. UL-3A cells contained two point mutations, in codon 248 of exon 7 and in codon 76 of exon 4. Five groups of clones were identified according to the p53 mutations. UL-3A clones with low p53 levels were more sensitive to CDDP (LD50 <8.0 microg/ml). Heterogeneity of p53 mutations may provide growth advantage during disease progression or chemotherapy.

Introduction: Our objective was to review our experience with vulvar cancer treated with modified radical vulvectomy without lymphadenectomy under local anesthesia and sedation., Methods: A retrospective review of surgical case lists revealed five patients who underwent modified radical vulvectomy without lymphadenectomy under local anesthesia with sedation. All patients had significant medical diseases which precluded regional or general anesthesia. Modified radical vulvectomy was performed in standard fashion under sedation and local anesthesia. Inguinal lymphadenectomy was not performed., Results: Median operative time was 1.5 h and median blood loss was 100 cc. Median diameter of tissue resected was 5 cm and median depth was 5 cm. Median length of hospital stay was 4 days. No patient complained of pain during the operative procedure. At a median follow-up of 2.5 years, there has been one local recurrence., Conclusion: Five patients with symptomatic vulvar cancer who were not candidates for regional or general anesthesia underwent modified radical vulvectomy without lymphadenectomy under local anesthesia with sedation. The procedure was well-tolerated and produced minimal morbidity and adequate short-term local control., (Copyright 1997 Academic Press.)