The implementation of critical pathways in gynecologic oncology in a managed care setting: a cost analysis.

OBJECTIVES: The aim of the study is to determine whether critical pathways can be implemented at an academic institution to limit cost, without compromising patient satisfaction and quality of care. PATIENTS AND METHODS: Patients undergoing a hysterectomy with either cervical or endometrial cancer were placed on specific critical pathways consecutively for an 18-month study period. Preoperative teaching was intensified to educate the patient regarding expectations during the postoperative period. All patients were started on early feeding and patients were also placed on separate care pathways addressing pain and deep vein thrombosis prophylaxis. Total direct costs and patient satisfaction were obtained throughout the study period. During the year prior to care pathway implementation, patient data and direct costs were obtained for the preintervention group utilized for comparison. Postintervention groups were summarized every 6 months during the study period. RESULTS: From January 1997 through June 1998, 63 patients with cervical carcinoma undergoing a radical hysterectomy (DRG 353) and 21 patients with endometrial cancer who underwent a hysterectomy and lymph node sampling (DRG 355) were utilized as the preintervention group. During the 18-month study period (July 1998-December 1999), 42 patients (DRG 353) and 25 patients (DRG 355) were accrued. The average length of stay was reduced from 5.2 (DRG 353) and 4.7 days (DRG 355) prior to implementation of pathways to 3.4 days in both groups. In addition, total direct costs were reduced by 29 (DRG 353) and 32% (DRG 355) after implementation of care pathways. Patient satisfaction data recorded during the study did not demonstrate any change throughout the study period nor were there any higher rates of readmission after implementation of the care pathways. CONCLUSIONS: Critical pathways in gynecologic oncology can be implemented in a managed care environment in order to maintain high quality of care, maintain outcomes, and help reduce costs.

Tubal sterilization and risk of cancer of the endometrium.

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.

Signet ring cell lobular carcinoma of the breast presenting in a cervicovaginal smear. A case report.

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.

Erosion of an intraperitoneal chemotherapy catheter resulting in an enterovaginal fistula.

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.

Expression of complement regulatory proteins-CD 35, CD 46, CD 55, and CD 59-in benign and malignant endometrial tissue.

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 < 0.0001) was observed. 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.

Cardiac metastasis of cloacagenic carcinoma of the vagina: a case and review of gynecologic malignancies with cardiac metastasis.

We report of a case of a 44-year-old woman with a vaginal cloacagenic carcinoma who initially presented with a hymenal lesion that metastasized first to the perihilar lymph nodes and then consequently to the right ventricle. The embryological tumor is rare with only a few cases of vaginal or vulvar involvement. We present the first case of cloacagenic cancer of the vagina with metastasis to the heart. The lesion was surgically resected after completion of neoadjuvant therapy. Herein we present this unique case and the clinical manifestations of intracardiac and pericardial lesions from gynecologic malignancies.

Paclitaxel, carboplatin, and hexamethyl-melamine (taxchex) as first-line therapy for ovarian cancer.

BACKGROUND: The addition of hexamethylmelamine to therapy with cisplatin, cyclophosphamide, and doxorubicin significantly enhanced outcomes of patients with advanced ovarian cancer. Hexamethylmelamine, also known as altretamine, has potent antineoplastic activity when used as a single agent in patients who have failed to respond to both platinum-based and paclitaxel therapy. We have conducted a pilot study to evaluate the efficacy and safety of adding this drug to the popular ovarian cancer regimen of paclitaxel plus carboplatin. METHODS: Patients with advanced ovarian, fallopian tube, or primary peritoneal cancer (International Federation of Gynecology and Obstetrics stages IIA, IIIC, and IV) were prospectively enrolled to receive six cycles, repeated every 4 weeks, of paclitaxel (150 mg/m2 i.v., day 1), carboplatin (AUC 5.0 i.v., day 1), and hexamethylmelamine (150 mg/m2 p.o., days 2-15). Colony stimulating factors were prohibited. Response and toxicity were monitored by use of Eastern Cooperative Oncology Group criteria. RESULTS: Twenty patients were enrolled, 18 with ovarian cancer, one with fallopian tube cancer, and one with peritoneal cancer; 17 of these patients were evaluable for response and toxicity. At a median follow-up of 6.5 months, 13 of the patients had a complete response (76%), and four had progressive disease. Three of those with a complete response had a recurrence within 1 year of completing treatment. Toxicity was acceptable, with myelosuppression the most severe adverse effect; one patient had grade 3 anemia, one patient had grade 4 thrombocytopenia, and 12 patients had grade 4 neutropenia. Quality of life showed improvement over the course of therapy, particularly in the physical well-being subscale. CONCLUSION: The addition of hexamethylmelamine to paclitaxel and carboplatin is a well-tolerated multidrug combination for women with advanced ovarian cancer that deserves further testing in a phase III study.

Oral contraceptive use and risk of gestational trophoblastic tumors.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

PIP: 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.

Transforming growth factor-alpha levels in the serum and ascites of patients with advanced epithelial ovarian cancer.

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.

Metastatic placental site trophoblastic tumor.

Since our publication, which first defined the malignant potential of placental site trophoblastic tumor (PSTT), we have had a keen interest in this rare, unique entity. This histologic entity is noted by its monomorphic population of trophoblast-like cells which are classified as originating in the intermediate trophoblast. These cells contain hymman placental lactogen (HPL). This is in contrast to cytotrophoblastic and syncytiotrophblastic tissues as the histologic, cytologic and immunohistochemical stain characteristics are disparate. Its rarity and the wide spectrum of clinical behavior combined with the lack of sensitivity of serum levels of beta hCG in predicting disease recurrence and spread have lead to anecdotal reports outlining clinical management. Most discerning to the clinician is the high mortality of metastatic placental site trophoblastic tumor. At our institution, we have treated two patients with a metastatic disease with a successful conclusion. The durability of responses is 3 and 8 years. This report will present these patients in detail and define the important characteristics of successful treatment. The use of dose-intensive, multi-agent chemotherapy, early intervention when metastatic disease is discovered, imaging techniques to define disease spread, surgery for localized disease and the use of growth factors, most notably granulocyte colony-stimulating factor (G-CSF), are the fundamentals of clinical care of placental site trophoblastic tumor in patients with metastatic placental site trophoblastic tumor.

Evidence for a common etiology for endometrial carcinomas and malignant mixed mullerian tumors.

OBJECTIVE: To elucidate factors linked to the development of malignant mixed mullerian tumors (MMMT) and determine whether the risk factor profile for these tumors corresponds with that for the more common endometrial carcinomas. METHODS: A multicenter case-control study of 424 women diagnosed with endometrial carcinoma, 29 women diagnosed with MMMT, and 320 community controls was conducted. Review of pathological reports and slides was performed to classify cases by histological type. All participants were asked to respond to a questionnaire which ascertained information on exposure to factors postulated to be linked to the development of uterine tumors. RESULTS: Women with endometrial carcinomas and MMMTs were similar with respect to age and educational attainment. Women diagnosed with MMMTs were more likely than those diagnosed with carcinomas to be of African-American descent (28% vs 4%; P = 0.001). Weight, exogenous estrogen use, and nulliparity were related to risk of both tumor types. Marked obesity was associated with a 4.8-fold (95% CI = 3.0,7.6) increase in risk of carcinoma and a 3.2-fold (95% CI = 1.1,9.1) increase in risk of MMMT development. Use of exogenous estrogens increased the odds of developing carcinomas by 2-fold (95% CI = 1.3,3.2) and that of developing MMMTs by 1.8-fold (95% CI = 0.57,5.5). Nulliparity was associated with a 2.9-fold (95% CI = 1.9,4.8) increase in risk of carcinomas and a 1.7-fold (95% CI = 0.53,5.6) increase in risk of MMMTs. Oral contraceptive use protected against the development of both carcinomas (OR = 0.39; 95% CI = 0.26,0.58) and MMMTs (OR = 0.76; 95% CI = 0.25,2.3). Current smokers were at a reduced risk of developing endometrial carcinomas (OR = 0.34; 95% CI = 0.21,0.55) and MMMTs (OR = 0.57; 95% CI = 0.15,2.3), while former smokers were at an increased risk of MMMT (OR = 2.7; 95% CI = 1.1,6.8) but not carcinoma development (OR = 0.81; 95% CI = 0.56,1.2). CONCLUSION: Results from this study suggest that MMMTs and carcinomas have a similar risk factor profile. This observation is compatible with the hypothesis that the pathogenesis of these two histological types of uterine tumors is similar.

Pretreatment surgical staging of patients with cervical carcinoma: the case for lymph node debulking.

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 brachy-therapy. 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 50% 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.

Analysis of histopathological features of endometrioid uterine carcinomas and epidemiologic risk factors.

A large case-control study was performed to determine whether risk factors for endometrioid carcinoma, the most common type of endometrial cancer, vary according to the histological features of the tumor. Study subjects consisted of 328 women with newly diagnosed endometrioid adenocarcinoma and 320 population-based control subjects. Variables studied included age at menarche, menopausal estrogen use, weight, parity, cigarette smoking, and oral contraceptive use. The risk factor profile for endometrioid carcinomas with and without squamous differentiation was very similar. No striking differences in risk factors were observed between endometrioid cancers with and without adjacent endometrial hyperplasia. Finally, none of the risk factors varied substantially between early-stage and late-stage tumors or low-grade and high-grade tumors. In summary, this study indicates that risk factors for endometrioid carcinomas are not related to the morphological features of the tumor.

Metastatic placental site trophoblastic tumor.

Since our publication, which first defined the malignant potential of placental site trophoblastic tumor (PSTT), we have had a keen interest in this rare, unique entity. This histologic entity is noted by its monomorphic population of trophoblast-like cells which are classified as originating in the intermediate trophoblast. These cells contain hymman placental lactogen (HPL). This is in contrast to cytotrophoblastic and syncytiotrophblastic tissues as the histologic, cytologic and immunohistochemical stain characteristics are disparate. Its rarity and the wide spectrum of clinical behavior combined with the lack of sensitivity of serum levels of beta hCG in predicting disease recurrence and spread have lead to anecdotal reports outlining clinical management. Most discerning to the clinician is the high mortality of metastatic placental site trophoblastic tumor. At our institution, we have treated two patients with a metastatic disease with a successful conclusion. The durability of responses is 3 and 8 years. This report will present these patients in detail and define the important characteristics of successful treatment. The use of dose-intensive, multi-agent chemotherapy, early intervention when metastatic disease is discovered, imaging techniques to define disease spread, surgery for localized disease and the use of growth factors, most notably granulocyte colony-stimulating factor (G-CSF), are the fundamentals of clinical care of placental site trophoblastic tumor in patients with metastatic placental site trophoblastic tumor.

Phase I trial of taxol as a radiation sensitizer with cisplatin in advanced cervical cancer.

OBJECTIVE: The aim of this study was to determine tolerable doses and potential toxicities of taxol, administered weekly, with concomitant cisplatin and radiation therapy in advanced cervical cancer. METHODS: Patients with cervical cancer, either with evidence of distant metastatic disease at presentation or otherwise at high risk for recurrent disease, were eligible for this phase I study. Taxol was administered weekly as a 3-hr intravenous infusion in addition to the prescribed radiation therapy. The starting dose was 10 mg/m2/week and escalated at 10 mg/m2/week increments if tolerated by successive cohorts of three new patients. Cisplatin was given every 3 weeks at 50 mg/m2. Chemotherapy was continued until radiation was completed. For each patient quality of life was assessed weekly during therapy. RESULTS: Sixteen patients, undergoing a total of 102 cycles, have been enrolled. Dose escalation of taxol from 10 mg/m2/week to 50 mg/m2/week was well tolerated, with no significant change in quality of life during therapy. Two radiation fractions (0.5%) were delayed due to toxicity from this chemotherapy regimen. Of 102 cycles, 6 resulted in grade 2 and 1 in grade 3 neutropenia, and no patient developed >grade 2 anemia or thrombocytopenia. Three patients developed GI-related toxicities and 1 patient presented with urosepsis during treatment. There was a 93% response rate to this regimen, with 10 patients (63%) presently having no evidence of disease. CONCLUSIONS: This study has demonstrated that up to 50 mg/m2/week of taxol is well tolerated in patients undergoing radiation therapy for advanced cervical cancer. A phase II trial will assist in determining the efficacy of taxol as a radiation sensitizer in these patients.

Risk factors and hormone levels in patients with serous and endometrioid uterine carcinomas.

We performed a multi-institutional, incident case-control study of 328 endometrioid and 26 serous carcinomas to assess whether risk factors and circulating hormone levels in women with serous carcinoma differ from the expected profile for endometrial carcinoma We also evaluated exposures potentially related to endometrial cancer risk, anthropometric measurements, and circulating levels of sex hormones and related carrier proteins. Histopathologic specimens were reviewed without knowledge of the other data. As expected, a statistically significant association was observed for high body mass index (BMI) (relative risk, 3.5) and use of menopausal estrogens (relative risk, 2.4) in the endometrioid carcinoma cases, whereas serous carcinomas were not strongly associated with these factors. Smoking and oral contraceptive use decreased risk for both tumor types. For five of six sex hormones tested, age-adjusted mean serum levels in patients with serous carcinoma were significantly lower than those in women with endometrioid carcinoma. After adjustment for BMI, these differences were narrowed, but levels of albumin-bound estradiol and estrone remained significantly lower in the serous cases. Age and BMI-adjusted levels of sex hormone-binding globulin were significantly higher in patients with serous carcinoma than in women with endometrioid carcinomas. In conclusion, risk factors and sex hormone levels in patients with uterine serous carcinoma seem to differ from those in women with endometrioid carcinoma, suggesting that there may be at least two different pathways of endometrial carcinogenesis.

Alpha-1 acid glycoprotein is an immunosuppressive factor found in ascites from ovaria carcinoma.

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, alpha-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 alpha-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 alpha-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 alpha-1 acid glycoprotein to the lymphocyte assay resulted in a 60% decrease in lymphocyte proliferation (P < 0.05). Alpha-1 acid glycoprotein transcript was not identified in ovarian tumor cells. The addition of purified alpha-1 acid glycoprotein to the lymphocyte culture resulted in a 65% decrease in IL-2 secretion into the media (P < 0.05). CONCLUSIONS: Alpha-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.

Vascular endothelial growth factor expression in early stage ovarian carcinoma.

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 pCRII 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 < 0.001). Median disease free survival for the VEGF positive group was 22 months, compared with > 108 months for the VEGF negative group (P < 0.001). When borderline tumors were excluded from the survival analysis, median disease free survival for the VEGF positive group was 18 months, compared with >120 months for the VEGF negative group (P < 0.001). Other possible prognostic variables had minimal impact on survival; these included age, stage, grade, cytology, and tumor size (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.

Intrauterine device use and endometrial cancer risk.

BACKGROUND: Because intrauterine devices (IUD) invoke acute and chronic inflammatory responses in the endometrium, it is possible that prolonged insertion of an IUD could induce endometrial cancer. METHODS: We examined the relation between use of an IUD and endometrial cancer risk using data from a multicentre case-control study involving 405 endometrial cancer cases and 297 population controls. RESULTS: A total of 20 (4.9%) cases and 34 (11.4%) controls reported any use of an IUD. After adjustment for potential confounders, IUD use was not associated with an increased risk of endometrial cancer (RR = 0.56 for ever use; 95% CI: 0.3-1.0). Little reduction in risk was observed among women who last used an IUD within 10 years of the index date (RR = 0.84; 95% CI: 0.3-2.4) but risk was decreased among women who used an IUD in the more distant past (RR = 0.45; 95% CI: 0.2-1.0). Risk did not vary consistently with number of years of IUD use or with years since first use. Risk was not increased among women who used inert devices (RR = 0.46; 95% CI: 0.3-3.6) or those who used devices containing copper (RR = 1.08; 95% CI: 0.1-3.6). CONCLUSION: These data are reassuring in that they do not provide any evidence of an increased risk of endometrial cancer among women who have used IUD.

PIP: IUDs invoke acute and chronic inflammatory responses in the endometrium. The authors therefore explored whether the prolonged insertion of an IUD increases one's risk of developing endometrial cancer. The relation between the use of an IUD and endometrial cancer risk was examined using data from a multicenter case-control study involving 405 endometrial cancer cases and 297 population controls. 20 cases and 34 controls reported using an IUD. After adjusting for potential confounders, IUD use was not associated with an increased risk of endometrial cancer. A small reduction in risk was observed among women who last used an IUD within 10 years of the index date, with the risk further reduced among women who last used an IUD more than 10 years ago. Risk did not vary consistently with the number of years of IUD use or with years since first use. Furthermore, the level of risk was not increased among women who used inert devices or those who used copper-containing devices.

The effect of prolonged cycles of chemotherapy on quality of life in gynaecologic cancer patients.

OBJECTIVE: The aim of this study was to determine if the prescription of prolonged cycles of chemotherapy to patients with a variety of gynaecologic cancers has an adverse effect on quality of life (QOL). METHODS: Patients attending a single gynaecologic oncology clinic who received greater than 6 cycles of chemotherapy were identified. Prior to each chemotherapy cycle, patients were asked to complete a modified Functional Assessment Cancer Therapy-General (FACT-G) quality of life form. QOL scores were compared to their baseline or pretreatment score (cycle 1 score), as well as to their score representing the completion of primary therapy (cycle 6 score). RESULTS: Seventeen patients were identified as having received greater than 6 cycles of systemic cytotoxic chemotherapy. The total number of chemotherapy cycles analyzed was 95. Comparing QOL scores for cycle 1 and 6 to cycles 7-16, we found no significant alteration (improvement or deterioration) in the following subscale scores: physical well being (PWB), social well being (SWB), and functional well being (FWB). Similarly, overall QOL as represented by the summed individual scores was also not affected by the prescription of up to 16 cycles of chemotherapy. Analysis of the emotional well being (EWB) subscale scores revealed a significant downward trend after the 12th cycle of therapy as compared to the 6th cycle (p = 0.04), however this trend was not significant when compared to the pretreatment or cycle 1 scores (p = 0.16). There was however a statistically significant progressive deterioration in the subscale score of the relationship with the doctor (RWD). This was most marked after the 10th cycle of therapy (p < 0.0001). When split by disease status, we again found no statistically significant alteration in PWB, SWB, RWD, EWB, FWB and overall QOL for cycle 1 and 6 as compared to cycles 7-17. However, those patients who were able to attain a complete clinical response (CCR) disease status, achieved a higher SWB (p = 0.003), RWD (p = 0.02), EWB (p = 0.03), and overall QOL scores (p = 0.04) while their PWB scores were not statistically different from patients with stable (p = 0.7) or progressive disease (p = 0.6). CONCLUSION: In conclusion, the prescription of prolonged cycles of chemotherapy to patients with gynaecologic cancers does not result in an overall deterioration of QOL. Further more an improvement in subscale and overall QOL was demonstrated in those patients able to attain a complete clinical response (CCR).