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Objective. Dramatic shifts in prescription practices during the last 30 years have left physicians confused and uncertain about the use of hormone replacement therapy (HRT) in endometrial cancer survivors. Materials and Methods. This article reviews the published literature concerning both the safety of prescribing HRT to endometrial cancer survivors and the therapy s potential risks and benefits. Results. Prescribing HRT to endometrial cancer survivors does not seem to be contraindicated and may even confer modest protection, depending on the doses and the specific drugs used. The potential benefits of HRT are more conflicting. Although the medical community agrees on the positive effects for bone density and relief of vasomotor symptoms, the results of our review offer no clear consensus in regard to HRT's effects on coronary heart disease, health-related quality of life, cognitive functioning, and cancer incidence. Conclusions. Until the medical community can concur on the proper prescription practices in endometrial cancer survivors, an individualized patient-based approach must be taken.

The purpose of the present study is evaluation of the long-term efficacy of sequential abdominopelvic radiotherapy and melphalan in the management of ovarian carcinoma.From 1970 to 1976, 94 women with stages I-III epithelial ovarian carcinoma enrolled in a prospective nonrandomized clinical trial were prescribed 20 Gy to the upper abdomen and 50 Gy to the pelvis followed by courses of melphalan (1 mg/kg/course). Primary endpoints were survival, recurrence, and toxicity.There were 19 stage I, 25 stage II, and 50 stage III patients. For all stages, overall survival was 42% at 5 years, 30% at 10 years, and 17% at 25 years. Median follow-up of the survivors was 24 years. Disease-free survival was 48% at 5 years and remained at 45% from 10 to 25 years. All but two recurrences occurred within the first 27 months. No recurrence or treatment-related death occurred after 8 years. No recurrence was salvaged. All but one initial recurrence was within the peritoneal cavity. Of the 31 patients undergoing a second-look surgical procedure, 84% were free of tumor. Only 8% of patients recurred after a negative second look. Stage and the presence of palpable postoperative disease were significant prognostic factors. Disease-free survivals were 95% from 5 to 25 years for stage I, 70% at 5 years and 60% at 25 years for stage II, and 20% from 5 to 25 years for stage III (P0.0001). Although no patient with postoperative palpable tumor was cured, 25% lived beyond 2 years. Stage III patients without postoperative palpable tumor achieved a 47% 25-year disease-free survival. Acute toxicity was acceptable, and 98% of patients completed radiation therapy. Chronic toxicity included a 12% small bowel obstruction rate and a 3% fatal second malignancy/hematological toxicity rate (two cases of acute myelocytic leukemia, one case of thrombocytopenia).The long-term disease-free survival obtained with abdominopelvic radiotherapy followed by single alkylating agent chemotherapy has not been exceeded by three subsequent decades of multiagent chemotherapy trials. Abdominal radiotherapy may be useful to consolidate complete responses following therapy multiagent chemotherapy, particularly with the upper abdominal dose escalation provided by intensity modulated radiation therapy and possibly in conjunction with chemotherapy.

Objective: To assess whether circulating insulin-like growth factor-1 (IGF-1), IGF-2, insulin-like growth factor-binding protein-1 (IGFBP-1), or IGFBP-3 were associated with endometrial cancer in postmenopausal women. Study Design: Between 1987 and 1990, we conducted a case-control study of 405 women with endometrial cancer and 297 matched population-based controls. This analysis included 174 postmenopausal cases and 136 controls. Results: In logistic regression models adjusted for potential confounders, higher IGF-1 levels were not positively associated with endometrial cancer: odds ratio (OR) for the highest tertile versus the lowest tertile = 0.63, 95% confidence interval (CI) = 0.30–1.32. Endometrial cancer was inversely associated with IGF-2 (OR for the highest tertile = 0.35, 95% CI = 0.18–0.69) and IGFBP-3 (OR for the highest tertile = 0.40, 95% CI = 0.21–0.77), and not associated with IGFBP-1. Conclusion: Serum IGF-1, IGF-2, and IGFBP-3, but not IGFBP-1, were inversely associated with endometrial cancer in postmenopausal women. These associations and the potential role of the IGF system in endometrial proliferation and carcinogenesis warrant further research.

Objective: The study was undertaken to provide consensus guidelines for the management of women with histologically confirmed cervical intraepithelial neoplasia (CIN) that can act as a precursor to invasive cervical cancer and represents one of the most common significant gynecologic diseases of women of reproductive age. Participants: An independent panel of 121 experts in various aspects of the diagnosis and management of cervical cancer precursors, including representatives from 29 participating professional organizations, federal agencies, national and international health organizations, and others were invited by the American Society for Colposcopy and Cervical Pathology (ASCCP). Consensus Process: Guidelines for the management of women with CIN were developed through a multistep process. Draft management guidelines were developed by working groups who performed formal literature reviews and obtained input from the professional community at large by way of an interactive internet-based bulletin board. At the ASCCP Consensus Conference, September 6 through 8, 2001, in Bethesda, Md, all guidelines were discussed, revised, and adopted by formal vote. Conclusion: Evidence-based guidelines have been developed for the management of women with biopsy-confirmed CIN. (Am J Obstet Gynecol 2003;189:295-304.)

BACKGROUND: The presence of extragenital malignant cells in cervicovaginal smears is a rare and usually late event in a patient with a long history of cancer. This, to the best of our knowledge, is the first case of breast cancer initially diagnosed on a Pap smear. CASE: A 50-year-old woman presented with abdominal distension and weight gain. A Pap smear showed numerous signet ring cells and was diagnosed as signet ring cell adenocarcinoma, most likely metastatic from the breast or stomach. Subsequent evaluation revealed bilateral adnexal masses and inguinal lymphadenopathy, leading to hysterectomy and bilateral salpingo-oophorectomy. The ovaries, corpus and cervix were involved by signet ring cell carcinoma. The metastatic tumor proved to be positive for CK7, CEA, estrogen receptor and progesterone receptors and negative for CK20. Despite the absence of a discrete palpable breast mass, a mammogram was recommended based on these results, and an ensuing breast biopsy showed the presence of an infiltrating lobular carcinoma. CONCLUSION: Lobular carcinoma of the breast may present in a cervicovaginal smear. Correct interpretation of signet ring cells as metastatic, most likely from the breast or stomach, is helpful in guiding management.

BACKGROUND The routine use of extraperitoneal surgical staging prior to radiation therapy in patients with bulky or locally advanced cervical carcinoma remains controversial. METHODS A review was performed of 266 patients with cervical carcinoma who underwent extraperitoneal pelvic and paraaortic lymphadenectomy prior to receiving radiotherapy. Patients were divided into groups based on their lymph node status. Group A had negative lymph nodes; Group B had resected, microscopic lymph node metastases; Group C had macroscopically positive lymph nodes that were resectable at the time of surgery; and Group D had unresectable lymph nodes. All patients received standard radiotherapy utilizing external beam and brachytherapy. Patients with lymph node metastases received extended field irradiation. Survival probabilities were computed by the Kaplan-Meier product limits method with statistical significance determined by the Mantel-Cox log rank test. RESULTS Lymph node metastases were detected in 49% of patients. Five- and 10-year disease free survival rates were similar for all patients in Groups B and C. All patients in Group D recurred. There was a 10.5% incidence of severe radiation-related morbidity and a 1.1% incidence of treatment-related deaths. CONCLUSIONS Pretreatment extraperitoneal staging of patients with bulky or locally advanced cervical carcinoma may afford a survival benefit via the debulking of macroscopically positive lymph nodes without significantly increasing treatment-related morbidity or mortality. Cancer 1998;82:2241-2248. © 1998 American Cancer Society.

Vascular endothelial growth factor (VEGF) expression and microvessel density were studied in cases of advanced epithelial ovarian carcinoma to evaluate their usefulness as prognostic variables. Tumor samples from 18 patients with advanced stage serous epithelial ovarian cancer were evaluated for VEGF expression by reverse-transcriptase polymerase chain reaction (RT-PCR) analysis. Immunohistochemical study of corresponding archival tissues with an antibody to von Willebrand factor (vWF; FVIII-RA) was used for tumor microvessel count determinations. The correlation of VEGF expression and mean microvessel counts was determined by an unpaired t-test. Survival analysis for known prognostic factors and VEGF expression was performed. Survival distributions were calculated by the product limit of Kaplan and Meier and significant differences between distributions were analyzed with a log rank test. From the RT-PCR analysis of tumor VEGF expression, 12 samples were found to be strongly positive, whereas six samples had low/negative VEGF expression. The median survival was 60 months for the VEGF-low/negative group and 28 months for the VEGF-positive group (P = 0.058). Other prognostic variables had minimal impact on survival, i.e. age < 65 years (P = 0.873), FIGO stage (P = 0.06), grade (P = 0.236) and debulking status (P = 0.842). Fourteen of 18 tumor specimens were suitable for microvessel counting. The mean microvessel counts of the VEGF-positive group and the VEGF-negative group were 27/hpf and 35/hpf, respectively (P = 0.16). In this preliminary analysis, high VEGF expression in epithelial ovarian carcinomas was associated with poor overall survival. Further study will be necessary to elucidate the lack of association of VEGF expression and tumor microvessel counts.

BACKGROUND Although the ascites of patients with ovarian carcinoma has been reported to contain immunosuppressive factors, the identity and source of this activity has not been fully elucidated. The objective of this study was to describe the purification of a single immunosuppressive protein, α-1 acid glycoprotein, from ovarian carcinoma ascites, identify its site of production, and describe a possible mechanism by which it inhibits lymphocytes. METHODS Ascites from proteins from five patients with epithelial ovarian carcinoma first were differentially precipitated by size with different concentrations of polyethylene glycol and then separated on the basis of isoelectric focusing. The protein factions then were placed in a lymphocyte proliferation assay to determine immunosuppressive activity. Western blot analysis was used to identify α-1 acid glycoprotein as an immunosuppressive protein in ascites. Total RNA was extracted from ovarian and hepatic cell lines as well as primary and recurrent ovarian tumor samples. Reverse-transcriptase polymerase chain reaction then was utilized to identify the site of production of this protein. Purified α-1 acid glycoprotein was placed in lymphocyte culture and its effects on lymphocyte interleukin-2 (IL-2) production were measured by enzyme-linked immunoadsorbent assay. RESULTS Addition of purified α-1 acid glycoprotein to the lymphocyte assay resulted in a 60% decrease in lymphocyte proliferation (P < 0.05). α-1 acid glycoprotein transcript was not identified in ovarian tumor cells. The addition of purified α-1 acid glycoprotein to the lymphocyte culture resulted in a 65% decrease in IL-2 secretion into the media (P < 0.05). CONCLUSIONS α-1 acid glycoprotein is an immunosuppressive protein purified from ovarian carcinoma ascites. It is not expressed primarily by ovarian carcinoma cells. It appears to inhibit IL-2 secretion by lymphocytes. Cancer 1997; 80:1448-56. © 1997 American Cancer Society.

BACKGROUND Tumor angiogenesis is essential for solid tumor growth. Yet, the importance of any particular factor in neoplastic proliferation is poorly defined. This study examines the clinical significance of increased expression of one of the angiogenic factors, vascular endothelial growth factor (VEGF), in early stage ovarian carcinoma. METHODS Tumor specimens from 68 patients with International Federation of Gynecology and Obstetrics Stage I and II ovarian carcinoma were evaluated for VEGF expression. Antisense and corresponding sense (control) RNA probes were transcribed from the pCR™II construct (Invitrogen, San Diego, CA), which contained human VEGF cDNA. The antisense probe was designed to include a highly conserved region of the VEGF coding sequence and thus detect all known variants. After in situ hybridization, sections were assessed for overexpression of VEGF. RESULTS Twenty-nine of the tumor samples overexpressed VEGF, whereas 39 specimens did not. In patients whose tumors demonstrated elevated VEGF expression, 25% were without evidence of disease recurrence at last follow-up. In contrast, 75% of the patients whose tumors did not overexpress VEGF were without evidence of disease at last follow-up (P 108 months for the VEGF negative group (P 120 months for the VEGF negative group (P 0.05). Assignment to a high risk group, as defined by the Gynecologic Oncology Group of the National Cancer Institute, was somewhat predictive of a shorter relapse free interval (P = 0.056). In a multivariate analysis, however, only elevated VEGF expression was associated with poorer survival. CONCLUSIONS In this analysis, patients with early stage ovarian carcinoma with increased VEGF expression had a poorer prognosis. Further study of VEGF may ultimately lead to identification of patients with high risk lesions whose tumor biology portends a worse prognosis and who therefore may benefit from aggressive adjuvant therapy. Cancer 1997; 80:98-106. © 1997 American Cancer Society.

In spite of extensive research, the behavior of granulosa cell ovarian tumors remains unpredictable and is complicated by the lack of prognostic factors in early-stage disease. Forty patients with granulosa cell tumors were identified from tumor registries and data were analyzed for patient outcome. Mitotic count and nuclear atypia were determined at time of histological review. Paraffin-embedded archival tumor tissues from 32 of 40 patients were available, and immunohistochemical testing for Ki-67, c-myc, p21-ras, c-erbB2, and p53 was performed on archival tissues. Results were correlated with patients' outcome. Mitotic count and Ki-67 were found to be negatively associated with survival in granulosa cell tumors. Nuclear atypia, c-myc, p21-ras, c-erbB2, and p53 were not found to be of prognostic significance.

Home infusion therapy began in response to the medi cal needs of the patients. In the traditional model, prod ucts and services were delivered in the home on a physi cian's prescription. Limitations related to medical quality management and cost were recognized in this model. Because of these limitations, the changes that continue to occur in health care delivery and the in crease in number and acuity of patients requiring non- hospital services, a managed care model was conceived and implemented at the University of Minnesota Medi cal School and Hospital. This model emphasizes physi cian-based case management, total quality management, a point of contact medical information system, out comes assessment and management, and research and education activities designed to evaluate and improve home infusion therapies. The model was implemented through a public-private partnership. This application of managed care to home infusion therapies is described in this communication.

Patients with gynecologic malignancies may develop stenosis of the large pelvic veins as a result of their disease or its treatment. The percutaneous insertion of a stainless steel vascular stent is a novel approach to the management of an extrinsically compressed vein. The objective of this study was to review the results of treating lower extremity edema secondary to a pelvic venous stenosis through the percutaneous insertion of a stainless steel vascular stent. A retrospective review was performed on gynecologic oncology patients who presented with an edematous lower extremity and underwent an evaluation to diagnose proximal venous stenosis. The evaluation included sonography, venography, and balloon angioplasty prior to the percutaneous insertion of a stainless steel vascular stent. If a venous thrombosis was documented, thrombolysis with urokinase was performed prior to evaluation for venous stenosis. Records were reviewed for the etiology of the venous stenosis, the location and type of stent inserted, and the ability of the stent to maintain patency and provide symptomatic relief. Patency was evaluated at 1-week and then at 1-, 3-, and 6-month intervals. The probability of vascular stent patency was calculated using life table analysis. Ten patients with cervical (n = 4), corpus (n = 3), ovarian (n = 1), vulvar (n = 1), and vaginal (n = 1) cancer had one or more vascular stents inserted for the treatment of a stenosed pelvic vein. The etiologies of venous stenosis were radiation fibrosis and surgery (n = 5), postoperative fibrosis (n = 3), and metastatic tumor (n = 2). The stented vessels were the left common (n = 5) or left external (n = 4) iliac veins, the right common (n = 1) or right external (n = 3) iliac veins, and the right common femoral vein (n = 1). The median follow-up was 21 months. All patients had subjective resolution of their edematous extremity while the stents were patent. The interval probability of patency of stented veins was greater than 85% at each evaluation interval. Patency was 100% for patients beyond 6 months of follow-up. There were no major complications. The percutaneous intravascular insertion of a stainless steel stent was safe and subjectively effective in the management of venous stenosis associated with a gynecologic cancer. A prospective trial with objective endpoints may be warranted.

The American Cancer Society (ACS) recommends that asymptomatic women, age 50 and over, undergo sigmoidoscopy every 3 to 5 years, after two negative yearly exams. Epidemiologic evidence suggests that women with gynecologic or breast cancers have an increased risk of developing colon cancer. It is unclear whether the ACS guidelines are applicable for women with a new diagnosis of gynecologic malignancy. This retrospective study was undertaken to assess the usefulness of preoperative colonoscopy in our gynecologic oncology patient population. Patients undergoing evaluation for a major operative procedure for known or suspected gynecologic malignancies were referred for colonoscopy at the discretion of their attending surgeon. Five hundred patients' charts were reviewed to identify 212 patients in whom preoperative colonoscopy was performed (the study group). In this group, 17 cases of colonic polyps, 5 cases of synchronous colon cancer, and 2 cases of cancer metastatic to the colon were discovered, representing 11% of the study group. Whereas 23% of the patients screened were less than 50 years of age, only two cases of polyps occurred in this age group, and no cases of cancer. Patients aged 70 or greater made up 28% of the study group, but accounted for 41% of the cases of polyps and 40% of the colon cancers. Twenty-nine percent of the study group had adenocarcinoma of the endometrium, representing 7 of 17 cases of polyps, 1 of 5 colon cancers, and 1 of 2 metastatic cancers. Although this retrospective study involved colonoscopy, the locations of the observed lesions were within the theoretic reach of a flexible sigmoidscope in 75% of cases. We conclude that in the preoperative workup of gynecologic oncology patients, no colon screening is needed in the asymptomatic patient less than 50 years of age. ACS guidelines are appropriate for patients aged 50-70, but for those 70 or greater we would consider full colonoscopy.

Transvaginal Doppler ultrasound was applied to 85 patients to determine whether pelvic malignancy could be predicted by pulsatility (PI) and resistive indices (RI) of intratu-moral, ovarian, and uterine vessels. Thirty-five of the patients in the study were confirmed to have malignant tumors of the cervix, uterus, or ovary. The mean intratu-moral PI and RI from malignant tumors were 0.81 (SD 0.24; range 0.3-1.2) and 0.54 (SD 0.10; range 0.27-0.62), respectively. They were significantly lower than those of the benign group (both with P < 0.05, Student's t test). Thresholds of intratumoral PI < 1.0 and RI < 0.6, which differentiate malignant from benign tumors, were determined by using two receiver operating characteristic (ROC) curves. These gave a sensitivity of 94% and specificity of 63% for PI and a sensitivity of 71% and specificity of 63% for RI. The mean PI and RI from individual ovarian and uterine vessels were also significantly lower for the malignant group than those for the benign group. The authors conclude that PIs and RIs from intratumoral, ovarian, and uterine vessels are all useful in differentiating malignant tumors from benign ones, but universal thresh-olds for this purpose are far from determined. Also, comparison of intratumoral PI and RI showed that neither PI nor RI was statistically better than the other in malignancy prediction, because the areas under the two ROC curves were not statistically different (P > 0.2, chi-square method).

The purpose of this study was to review the clinical outcomes and cost of administration of a prophylactic antibiotic compared to G-CSF for the prevention of neutropenic morbidity associated with taxol. The study group was composed of 62 patients with ovarian cancer who received a 24-h infusion of a taxol-based regimen at doses less than or equal to 175 mg/m2 between June 1992 and April 1994. The records were retrospectively reviewed and the patients were grouped and analyzed according to the management of their myelosuppression. Group I patients (n = 29) were observed until their absolute neutrophil count (ANC) was less than 500/microliters and then were placed on ciprofloxacin 500 mg orally twice a day until their ANC was 1,000/microliters. Group II patients (n = 15) received G-CSF from Day 2 until the ANC was greater than 10,000/microliters beginning with their first cycle. Group III patients (n = 18) received their taxol regimen without either ciprofloxacin or G-CSF. Two hundred eighty-two taxol-based chemotherapy cycles were administered to these 62 patients. There was no statistically significant difference between the groups concerning disease status as measured by age, stage, performance status, dose intensity, or number of previous regimens. There were two episodes of febrile neutropenia in Group I and three episodes in Group II. Group III had 15 episodes of febrile neutropenia. The estimated cost of the different prophylactic regimens was $5,215.00 for Group I versus $104,000.00 for G-CSF in Group II. Within the three groups, there were 27 patients with an episode of febrile neutropenia (n = 20) or prolonged myelosuppression (n = 7) that were followed for an additional 104 taxol cycles. Twenty-four of these patients received G-CSF prophylaxis with intermittent ciprofloxacin and three received only ciprofloxacin. There were eight more episodes of febrile neutropenia in the patients receiving G-CSF. There were no additional febrile episodes on cycles prophylaxed with ciprofloxacin. There was no septic mortality. For patients receiving a 24 h infusion of taxol at doses less than 175 mg/m2, ciprofloxacin given through the ANC nadir may be effective in preventing febrile morbidity. A prospective randomized trial is underway to evaluate this approach.

The aim of this study was to investigate gray scale and color flow characteristics of a group of patients with a suspected uterine pathologic condition. One hundred and twenty-two consecutive patients at the Women's Cancer Center, University of Minnesota, undergoing transvaginal sonography and color flow Doppler imaging for suspected uterine corpus abnormality made up the study group. After gray scale morphologic assessment, color flow Doppler imaging of the tumor and uterus was performed, including the ipsilateral uterine artery. Malignant tumors were confirmed pathologically in all 35 patients who had them. In comparing patients with benign versus malignant tumors, gray scale morphologic assessment confirmed that malignant uterine tumors (31 endometrial cancers and four sarcomas) were more likely to have a thickened echoic endometrium (P = < 0.0001), be enlarged (P = 0.004), to be retroverted (P = 0.02), and to lack a subendometrial halo (P < 0.0001). Patients with four benign and 13 malignant tumors demonstrated increased flow when assessed by CFD. The calculated sensitivity of increased color flow in predicting malignancy was 39%, with a specificity of 92%, a positive predictive value of 77%, and a negative predictive value of 71%. No difference existed between the benign and malignant groups for the systolic, diastolic, and mean velocities and for the calculated pulsatility index and resistive index in both sampled uterine and intramyometrial or tumor vessels.(ABSTRACT TRUNCATED AT 250 WORDS)

Purpose: Anemia during radiation therapy independently predicts poor outcome in patients with cervical cancer. Despite a randomized trial demonstrating red cell transfusions improve local control and survival, many patients are not transfused due to toxicity concerns. This study evaluates the efficacy of recombinant human erythropoietin (r-HuEPO) in reversing anemia in patients undergoing radiation therapy. Methods and Materials: Twenty patients with criteria of anemia (Hgb n = 7), IIA ( n = 1), IIB ( n = 9), and IIIB ( n = 3), ranging in ages from 23–75 years (median 43), were included in this Phase I/II study. Fifteen were treated with r-HuEPO (200 U/kg/day) and ferrous sulfate 5–10 days prior to initiation of external beam radiation therapy, continuing until Hgb was ≤ 14 g/dL or completion of radiation therapy. Five patients were treated with ferrous sulfate alone. An additional 61 historical controls meeting eligibility criteria were analyzed. All received external beam radiation therapy and two intracavitary cesium applications. Cisplatinum chemotherapy (20 mg/m 2 /week) was given as a radiosensitizer in 14 r-HuEPO patients, 4 concurrent controls, and 17 historical controls. Results: A marked reticulocytosis was seen in the r-HuEPO group, but not the study controls. In the r-HuEPO group, the mean ± SD serum Hgb rose +30% over the course of radiation therapy from a baseline of 10.3 ± 1.04 g/dL to 13.2 ± 1.7 g/dL. Average increase in Hgb was 0.5 g/dL per week. Average Hgb during RT was 13.4 g/dL. In study and historical controls, mean initial Hgb levels were 10.7 ± 1.04 g/dL and 11.1 ± 1.3g/dL, respectively, remaining unchanged over the course of radiation therapy. Average Hgb levels during radiation therapy were 11.1 g/dL in study controls and 11.4 g/dL in historical controls, significantly lower than r-HuFP0 patients ( p = 0.0001). Erythropoietin was well tolerated. There were no significant differences in white blood counts ( p = 0.6) or platelet counts ( p = 0.4) between r-HuEPO patients and both control groups. No patients had blood pressure changes during r-HuEPO therapy. The only possible side effect was deep venous thrombosis, occurring in two patients who were withdrawn from r-HuFP0 therapy. Two additional patients developed deep venous thrombosis 9 and 10 days after radiation therapy and r-HuFP0 were completed. Conclusion: Erythropoietin appears to be both safe and effective at raising Hgb levels in anemic cervical cancer patients receiving radiation therapy and chemotherapy.

Recent improvements in parenteral nutrition and home care delivery systems have made home parenteral nutrition (HPN) a reality for patients with gynecologic malignancies. The records of 61 patients with gynecologic cancers who received HPN between 1981 and 1990 were retrospectively reviewed for outcome, complications, survival, and quality of life. Indications for HPN included mechanical bowel obstruction, short bowel syndrome, malnutrition during cancer therapy, or complications of cancer therapy. Ninety-two percent of patients had disease present at initiation of HPN. Fifty-six percent of patients had ovarian cancer; the remainder had other gynecologic malignancies. The vast majority of patients had prior surgery, radiotherapy, or chemotherapy before receiving HPN. Sixty-four percent of patients underwent cancer treatment (chemotherapy, surgery, or radiation) during HPN. Median survival for ovarian cancer patients on HPN was 72 days and 52.5 days for nonovarian patients (not statistically significant, P = 0.95). Minimal complications were noted from HPN with 9% of hospitalizations due to HPN. Nutritional parameters initially improved in most patients on HPN but then decreased prior to death. Quality of life parameters improved significantly in patients on HPN as compared to pre-HPN status (P < 0.05). In conclusion, HPN is a viable option in gynecologic cancer patients and offers improved quality of life even during the terminal phase of their illness.

Reconstructive procedures are being performed with increasing frequency in conjunction with pelvic exenterations and other radical gynecologic surgeries. The most common reconstructive procedures include continent urinary diversion, rectosigmoid anastomosis, and vaginal reconstruction. Historically, the gracilis myocutaneous flap has been the procedure of choice for vaginal reconstruction. However, the gracilis myocutaneous flap has a history of partial to severe necrosis, a propensity to prolapse, and leaves ipsilateral donor scars on the thigh. In contrast, neovaginal reconstruction using a relatively new procedure, the distally based rectus abdominis myocutaneous flaps, has the advantage of using a large, single flap that can be incorporated into the primary incision. This flap is mobilized on a long vascular pedicle, the rectus muscle. In relation to the underlying rectus muscle, the orientation of the cutaneous portion of this flap may be customized to accommodate the pelvic defect or the surgeon's preference. Depending on their primary orientation, they are referred to as either a vertical or transverse rectus abdominis myocutaneous flap. The versatility and reliability of the rectus flap is demonstrated here through the presentation of a small pilot series of seven patients. The technique was used for vaginal reconstruction, primarily in conjunction with pelvic exenteration. The flaps were mobilized from the supraumbilical area and had a flap viability of 100% for the 2 years that they have been followed. There were no postoperative incisional or flap infections. There was one infraumbilical fascial dehiscence. The advantages of primary pelvic reconstruction along with the description of the operative techniques are presented.

Purpose : This study ascertains the benefit and detriment of cis-platinum-based regimes for advanced cervical cancer using standard response parameters as well as a methodology to separate potential effects of radiosensitization and effects of control of occult systemic metastases. Materials and Methods : In addition to conventional response criteria used to analyze three recently published randomized studies, the efficacy of neoadjuvant chemotherapy is measured with a statistical model to calculate potential improvement in survival offered by perfect local and distant control. Results : Neoadjuvant chemotherapy either did not affect or it impaired survival in the three trials. Evidence of altered failure patterns was obtained. In particular, local control was compromised by neoadjuvant chemotherapy. Conclusion : Failure patterns are altered by treatment as well as by standard prognostic factors. Neoadjuvant chemotherapy may decrease survival. Possible reasons include the limited efficacy of cis-platinum alone and in combination with other therapeutic agents, accelerated repopulation caused by neoadjuvant therapy, delay in initiation of radiotherapy by neoadjuvant chemotherapy, low statistical power of published studies, and tumor heterogeneity. Curative modalities such as surgery and radiotherapy must not be compromised by neoadjuvant chemotherapy.

BACKGROUND Recent studies have shown that multiple cytokines are secreted by ovarian epithelial cancer cells. Previous studies have shown that the cancer cell lines secrete macrophage colony-stimulating factor (M-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-1 (IL-1), interleukin-6 (IL-6), and transforming growth factor-alpha (TGF-alpha). Concomitantly, the serum levels of one of the growth factors (M-CSF) was found to be significantly elevated in patients with primary ovarian cancer and in second-look patients. The authors evaluated the serum levels of IL-1 alpha, IL-1 beta, IL-6, and tumor necrosis factor-alpha (TNF-alpha) in patients with primary ovarian epithelial cancer. These levels were then compared with cytokine concentration found in normal peritoneal fluid. METHODS Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of cytokines in normal peritoneal fluid, ascites, and serum. RESULTS In serum, TNF-alpha and IL-6 were significantly increased in primary ovarian cancer patients when compared with control subjects (P < 0.0001 for both cytokines). TNF-alpha and IL-6 were also significantly higher than the levels found in second-look patients (P < 0.007 for TNF-alpha, and P = 0.0002 for IL-6). The levels of IL-1 alpha and beta were not elevated in ovarian cancer. TNF-alpha in the ascites was higher when compared with normal peritoneal fluid and was statistically significantly different when a cut-off point between 71-110 pg was selected (P < 0.005). The levels of IL-6 in ascites from patients with primary ovarian cancer also showed a marked increase (P < 0.0001) when compared with peritoneal fluid from control subjects. CONCLUSIONS Levels of IL-1, IL-6, and TNF-alpha were determined in normal peritoneal fluid, ovarian malignant ascites, normal serum, and serum from patients with ovarian cancer. This study showed that the patients with ovarian cancer have elevated levels of IL-6 and TNF-alpha in serum and ascitic fluid. A larger study would help in evaluating the potential use of cytokines as tumor markers in ovarian cancer.

Background. Haptoglobin is an acute-phase reactant protein involved in immune regulation. It has been isolated from malignant ovarian ascites and has been shown to be capable of mediating nonspecific immune suppression in vitro in humans and in vivo in experimental animals. The range of concentrations under which such a nonspecific suppression is observed lies well within concentrations of haptoglobin observed in vivo. This immune suppression could adversely affect patient outcome. Methods. Based on this information, ascites haptoglobin levels of 21 consecutive patients with ovarian cancer who underwent initial surgical debulking were determined. After the patients received chemotherapy, they were divided into those having a positive and those have a negative second-look operation. Results. Seventeen patients with positive pathology at second look had an initial mean ascites haptoglobin level of 99 ± 49 mg/dl. The mean haptoglobin level in the four patients with negative findings was 67 ± 42 mg/dl. The difference in these mean haptoglobin levels is not statistically significant (P > 0.05). Conclusion. Although the number of patients in this study is small, the wide range of values documented in both groups make it doubtful that an initial absolute ascites haptoglobin level will prove clinically prognostic of eventual disease status at the time of second look laparotomy.

A case-control study involving 405 cases of epithelial endometrial carcinoma (newly diagnosed between 1987 and 1990 in five US areas) and 297 population controls enabled evaluation of risk in relation to detailed smoking characteristics. Cigarette smokers were at a reduced risk of disease, with the effect primarily restricted to women whose diseases were detected postmenopausally (relative risk (RR) = 0.6, 95% confidence interval 0.4-0.9). Among postmenopausal women, current smokers showed the greatest reduction in risk (RR = 0.4, 95% confidence interval 0.2-0.7), with former smokers, including those who had recently stopped, being less affected (RR = 0.8). Other measures of smoking were highly correlated with currency of smoking, but there were no clear patterns of risk with either duration or intensity of smoking. Smoking appeared to reduce risk to the greatest extent in subjects who were multiparous, obese, or nonusers of exogenous hormones, but none of these relations was statistically significant. The results support the notion that smoking reduces the risk of endometrial cancer through extraovarian endogenous hormonal mechanisms, but further studies are needed to clarify why reduced risks are most pronounced among postmenopausal women and those currently exposed to cigarette smoke.

Tumor lysis syndrome (TLS) is an extremely rare complication of solid tumors and is more frequently observed in patients with hematologic malignancies. This report describes a novel approach to the management of a rare case of TLS in metastatic gestational trophoblastic neoplasia (GTN).A 17-year-old female presented 8 weeks postpartum with severe anemia, thyrotoxicosis, and elevated serum beta-human chorionic gonadotropin (beta-hCG). Imaging studies confirmed metastatic GTN to the lungs. The patient developed grade 4 TLS after the first cycle of etoposide, methotrexate, dactinomycin, cyclophosphamide, and vincristine (EMA-CO). She did not respond to standard treatment of aggressive hydration and allupurinol and continued to be in renal failure with elevated uric acid. A single dose of recombinant urate oxidase, rasburicase, rendered the uric acid level undetectable in 3 days and completely reversed the renal failure, avoiding hemodialysis. Three more cycles of EMA-CO were then administered. Subsequently, the patient developed congestive heart failure and was switched to single-agent actinomycin-D. Beta-hCG became negative after 5 cycles, and her ejection fraction returned to baseline.This is a rare case of TLS in the setting of metastatic GTN. To our knowledge this is the first reported case of utilizing rasburicase for the management of TLS in GTN.

Objective: The purpose of this study was to evaluate the prognostic significance of macrophage colony-stimulating factor serum levels in patients with ovarian cancer undergoing second-look laparotomy. Study design: The presurgical serum levels of macrophage colony-stimulating factor from 33 consecutive patients with ovarian cancer undergoing second-look laparotomy were determined and compared with those of 50 healthy control subjects. Mean differences in groups were evaluated with the Student f test. Results: Sixteen of 33 patients had a positive result at second look and a mean serum macrophage colony-stimulating factor level of 2.31 ± 1.45 ng/ml. Seventeen of 33 patients had a negative result at second look and a mean macrophage colony-stimulating factor level of 1.90 ± 0.86 ng/ml ( p > 0.05). The mean macrophage colony-stimulating factor level in the control group was 1.20 ± 0.51 ng/ml. This was statistically lower than the mean level found in patients with a negative second-look result ( p Conclusion: Regardless of tumor status, serum macrophage colony-stimulating factor levels tend to be elevated at the time of second-look laparotomy.

Background. With the pharmacokinetic advantages of intraperitoneal chemotherapy delivery and the increased popularity of immunotherapy and gene therapy, intraperitoneal catheters have moved to the forefront as a delivery system in cancer treatment. This delivery system, however, carries with it an intrinsic morbidity warranting attention in the often prolonged chemotherapy regimens demanded by cancer patients. Case. In reviewing the literature of intraperitoneal catheter complications, there is no other cited case of a peritoneal catheter erosion into intestine presenting as an enterovaginal fistula. Our patient, diagnosed with persistent ovarian carcinoma, had a peritoneal Tenckoff catheter placed for chemotherapy. Many months after termination of the chemotherapy and 15 months after placement, she presented with bowel contents per vagina. A CT scan revealed an abdominopelvic abscess encompassing the detached catheter which embedded in the rectosigmoid colon, allowing direct communication to the upper vagina. The catheter was removed and the abscess was drained. Conclusion. Intraperitoneal catheters have a morbidity that persists after nonuse. Therefore, intraperitoneal catheters should be removed if they are not being used.

Pseudomyxoma peritonei is an uncommon clinical entity. It is characterized by massive abdominal distension by gelatinous material. It is produced by mucous-secreting peritoneal implants which are secondary, usually, to an ovarian or appendiceal neoplasm. Although remaining localized to the peritoneal cavity and hence thought to be a benign process, the clinical course of the disease, the association, in the majority of cases, with a malignant primary tumor, and the report of a small number of cases with extraperitoneal spread lends support to the belief that this is a malignant disease. Five-year survival is 68% with ten-year survival at 52%. Despite the utilization of numerous adjuvant therapies, the mainstay of treatment remains complete surgical debulking at initial presentation followed by palliative debulking for symptomatic relief.

Because the use of cisplatin-based chemotherapy for ovarian carcinoma has not significantly improved 5-year survival rates compared with either whole-abdominal radiation (WAR) or single-agent chemotherapy, a pilot study was begun to assess the feasibility of concomitant radiation and chemotherapy. Eleven previously untreated patients with Stages III and IV ovarian carcinoma were treated concomitantly with 2000 cGy of WAR and intraperitoneal (IP) cisplatin followed by additional IP cisplatin after debulking surgery. Toxicity was moderate to severe. Sixty-four percent of patients had Grades 3 to 4 hematologic toxicity, and 36% required hospitalization for sepsis during WAR/IP cisplatin. Hematologic toxicity was less pronounced during IP cisplatin alone. All patients experienced moderate gastrointestinal toxicity. The average percentage of total body weight lost was 13.5%. Fifty-five percent of all patients demonstrated a complete clinical response to therapy, and patients with minimal postoperative residual disease fared better. One patient with persistent disease had acute nonlymphocytic leukemia (ANLL) 24 months after initial diagnosis. No patients with residual disease greater than 20 mm survived, while 50% of patients with less than 20 mm are clinically free of disease. Toxicity appears to be additive with the combination of WAR and IP cisplatin. Therapeutic efficacy was comparable with standard chemotherapy regimens, but no therapeutic or survival advantages were demonstrated with the use of this treatment protocol.

From 1978 to 1986, 183 women with cervical cancer received definitive radiation therapy after extraperitoneal surgical staging. Relapse-free rates were strong functions of pelvic lymph node metastases and cervical size. the recurrence distribution consisted of 4% isolated local, 13% isolated distant, and 17% combined local and distant failures. With the assumption of independent local and distant failure probabilities, Suit et al.'s method was extended to assess potential improvement in cure attainable with perfect local and distant control, yielding local (LSA) and distant (DSA) survival advantages of 17% and 28%. Various subsets of clinical stage, cervical size, pelvic node metastases, periaortic metastases, and peritoneal metastases had LSA from 12% to 27% and DSA from 12% to 71%. For any prognostic group, LSA never exceeded DSA, showing that effective systemic therapy would have a greater impact on improving survival than would advances in local and regional tumor control. Therapeutic implications and limitations of the extended LSA-DSA model are discussed. This form of analysis can be used to guide the intensity of local and distant treatment to maximize the cure of the patient with cancer.

We retrospectively analyzed clinicopathological findings in 10 cases of primary malignant melanoma of the vagina. The main presenting symptoms were vaginal bleeding, vaginal discharge, and feeling of a mass. The tumors were predominantly located in the lowest one-third and in the anterolateral aspect of the vagina. Patients underwent various surgical procedures, radiation therapy, and chemotherapeutic modalities. The mean survival time and the recurrence time from the time of diagnosis were 15 and 8 months, respectively. The tumors were examined for histological characteristics of cell type, presence of melanin pigment, depth of invasion, vascular invasion, intraepithelial spread, junctional activity, and mitotic count. Of all these histological variables, the mean survival time had a significant correlation to mitotic count (P less than 0.04). We concluded that patients with lower mitotic counts (less than 6 per 10 HPF) had better survival (21 months) compared to patients with mitotic counts greater than 6 per 10 HPF who had a mean survival of only 7 months.

Objective The study was undertaken to provide consensus guidelines for the management of women with a cytologic interpretation of high-grade squamous intraepithelial lesion (HSIL) on cytologic examination. This review article presents relevant literature supporting the proposed guidelines. Participants An independent panel of 121 experts in various aspects of the diagnosis and management of cervical cancer precursors, including representatives from 29 participating professional organizations, federal agencies, national and international health organizations, and others were invited by the American Society for Colposcopy and Cervical Pathology. Consensus process Guidelines for the management of women with HSIL cytologic results were developed through a multistep process. Draft management guidelines were developed by the HSIL working group after formal literature reviews and obtained input from the professional community at large by way of an interactive internet-based bulletin board. At the American Society for Colposcopy and Cervical Pathology Consensus Conference, September 6 through 8, 2001, in Bethesda, Maryland, the guidelines were discussed, revised, and adopted by formal vote. Conclusions Evidence-based guidelines have been developed for the management of women with HSIL cytologic results.

OBJECTIVE: The Home Study Course is intended for the practicing colposcopist or practitioner who is seeking to develop or enhance his or her colposcopic skills. The goal of the course is to present colposcopic cases that are unusual or instructive in terms of appearance, presentation, or management or that demonstrate new and important knowledge in the area of colposcopy or pathology. Participants may benefit from reading and studying the material or from testing their knowledge by answering the questions. ACCME ACCREDITATION: The American Society for Colposcopy and Cervical Pathology (ASCCP) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to sponsor continuing medical education for physicians. The ASCCP designates this continuing medical education activity for 1 credit hour Category I of the Physician's Recognition Award of the American Medical Association. Credit is available for those who choose to apply. The Home Study Course is planned and produced in accordance with the ACCME's Essential Areas and Elements.

Patients with advanced or recurrent endometrial cancer of any cell type having measurable disease have been entered into this study to determine the effectiveness and toxicity of circadian-timed doxorubicin-cisplatin chemotherapy. This Phase II study involved no randomization with treatment initiated with doxorubicin 60 mg/m2 over 30 minutes at 6:00 a.m., followed by cisplatin 60 mg/m2 over 30 minutes at 6:00 p.m. every 28 days. Treatment was continued for eight cycles or to a maximum tolerable doxorubicin dose of 480 mg/m2 for patients without progression. Thereafter, responders continued on cisplatin alone. A review of 30 evaluable patients showed 6 (20%) complete responses, 12 (40%) partial responses, and 7 (23%) with stable disease. The number of treatment courses ranged from 2 to 14 with a median of 6.5. the median white blood cell nadir for the 27 patients experiencing leukopenia was 1,600/mm3 (range: 300–3,600/mm3). For the 16 patients experiencing thrombocytopenia the median nadir was 48,500/mm3 (range: 8,000–138,000/mm3). There were no treatment-related deaths. Circadian-timed delivery of doxorubicin-cisplatin chemotherapy was reasonably well tolerated and demonstrated notable response rates in patients with advanced or recurrent endometrial carcinoma.

Objective. Surgical sterilization is a common method of contraception among U.S. women. Most surgical sterilizations are tubal ligations, but few studies have investigated their potential impact on endometrial cancer risk. Methods. A case–control study included 405 women diagnosed with endometrial cancer at 5 U.S. medical centers between 1987 and 1990 and 297 age-, race-, and location-matched controls who were identified by random-digit-dialing. Questionnaires ascertained information on tubal sterilization, and logistic regression models generated odds ratios (ORs) to estimate relative risk. Results. The OR and 95% confidence interval for tubal sterilization, which was reported by 47 cases and 40 controls, was 0.9 (0.6–1.4) before adjustment and 1.4 (0.8–2.4) after adjustment for age, parity, and oral contraceptive use. Age at surgery, years since surgery, or calendar years of surgery were not associated with endometrial cancer, and associations did not vary according to parity or stage of disease at diagnosis. Conclusions. Tubal sterilization is not substantially associated with endometrial cancer.

Objective. Complement system plays an important role in host defense mechanisms against microorganisms and tumor cells. To protect themselves from autologous complement-mediated damage, normal host tissues express cell membrane-associated complement regulatory proteins (CRPs). To investigate whether neoplastic endometrial tissues overexpress these proteins to escape complement damage, we examined the distribution of complement receptor type 1 (CR1, CD35), membrane cofactor protein (MCP, CD46), decay-accelerating factor (DAF, CD55), and protectin (MACIF, CD59) on frozen endometrial tissue samples. Methods. A total of 54 endometrial tissue samples were collected. Cryosections were obtained of 31 benign and 23 malignant tissue specimens. Tissue sections were stained by immunohistochemical staining procedure using specific antibodies and employing the avidin–biotin technique. Quantitation of the protein content of these CRPs was determined using the Samba 4000 image analysis system. Results. For all four of the CRPs studied, a statistically significant difference in protein expression between the benign and malignant endometrial tissue specimens ( P Conclusions. Overexpression of all the CRPs studied (CD35, CD46, CD55, CD59) was observed in the malignant as compared with the benign endometrial tissues. The upregulation of these CRPs may promote resistance of the endometrial malignant tissue to complement-mediated damage, thereby allowing the tumor cells to escape from cytolysis and thus promoting carcinogenesis.

Gestational trophoblastic disease refers to a spectrum of rare benign and malignant gynecologic disorders whose pathogenesis is not well understood. Recent studies from China and the United States have raised the hypothesis that long-term use of oral contraceptives before conception may increase the risk of gestational trophoblastic tumors. A multicenter case-control study of gestational trophoblastic tumors was undertaken to test this hypothesis.Telephone interviews were conducted with 235 case patients, including 50 with gestational choriocarcinoma, and 413 control subjects matched on recentness of pregnancy, age at pregnancy, and area of residence. Relative risks (odds ratios) were computed by conditional logistic regression. Reported P values are two-sided.The relative risk estimate for ever having used oral contraceptives before the index pregnancy was 1.9 (95% confidence interval [CI] = 1.2-3.0), and the risk increased with duration of use (P for trend = .05). The estimate was highest for women who used oral contraceptives during the cycle in which they became pregnant (relative risk = 4.0; 95% CI=1.6-10), but there was no consistent pattern according to the time interval since last use. Separate analyses of choriocarcinoma and persistent mole yielded similar results, i.e., the relative risk estimates for oral contraceptive use were 2.2 (95% CI=0.8-6.4) and 1.8 (95% CI=1.0-3.0), respectively. Control for the number of sexual partners, which was independently associated with risk (P for trend = .05), did not materially change the results.This study, the largest to date, indicates that long duration of oral contraceptive use before conception increases the risk of gestational trophoblastic tumors. These findings may provide clues to the pathogenesis of this rare disease. Changes in use of oral contraceptives are not warranted, however, because the incidence attributable to oral contraceptive use is very low.Recent studies in the US and China have suggested that long-term use of oral contraceptives (OCs) before conception increases the risk of gestational trophoblastic tumors. This association was investigated further in a study conducted at 8 US medical centers that specialize in the treatment of this gynecologic disorder. 235 cases, including 50 women with gestational choriocarcinoma, were matched with 413 controls on recentness of pregnancy, age at pregnancy, and area of residence. The relative risk estimate for ever-use of OCs before the index pregnancy was 1.9 (95% confidence interval [CI], 1.2-3.0) and the risk increased with duration of OC use. The relative risk was highest (4.0; 95% CI, 1.6-10.0) for women who used OCs during the cycle in which they became pregnant, but there was no consistent pattern according to the time interval since last OC use. The relative risks for choriocarcinoma and persistent mole associated with OC use were 2.2 (95% CI, 0.8-6.4) and 1.8 (95% CI, 1.0-3.0), respectively. This study, the largest to date, suggests that a long duration of OC use before conception does, indeed, increase the risk of gestational trophoblastic tumors.

A variety of cytokines have been identified to play a role in ovarian cancer. In this pilot study, we sought to determine whether transforming growth factor-alpha (TGF-alpha) was detectable in the serum and ascites of women with advanced stage epithelial ovarian cancer. TGF-alpha was measured using an enzyme-linked immunosorbent assay and was present in 18 of 25 control sera. Prior to treatment for stage III or IV epithelial ovarian cancer, 18 patients had undetectable serum levels of TGF-alpha, while 18 had values ranging from 10.6 to 531.7 pg/ml. The group with undetectable levels had a 6-month greater median survival; detectable TGF-alpha might be a negative prognostic indicator. In a separate group undergoing second-look laparotomy, differences in median TGF-alpha values versus controls and the primary study group approached significance. TGF-alpha was detected in significantly more control peritoneal fluid samples than in patient ascites. A larger study is warranted.