Cytolysis of Eutopic and Ectopic Endometrial Cells by Peripheral Blood Monocytes and Peritoneal Macrophages in Women with Endometriosis

Objective: To compare the ability of peripheral blood monocytes (PBM) and peritoneal macrophages (PM) to mediate the in vitro cytolysis of endometrial cells from eutopic and ectopic endometrium in women with endometriosis.

Design: Prospective study of immune function.

Setting: Institute for the Study and Treatment of Endometriosis and university-based research laboratories.

Patient(s): Twenty-four women with endometriosis (15 in stage I/II, 9 in stage III/IV) and 4 patients treated with GnRH agonists.

Intervention(s): Peritoneal fluid and peripheral blood were sampled and eutopic and ectopic endometrium were biopsied during diagnostic laparoscopy.

Main Outcome Measure(s): Lysis of autologous endometrial cells.

Result(s): Peripheral blood monocytes were significantly more cytolytic than peritoneal macrophages against autologous uterine endometrial cells. However, PBM and PM displayed a similar degree of cytolysis against a hepatoma cell line. Ectopic endometrial cells were significantly more resistant to cytolysis by autologous PBMC than were matched eutopic endometrial cells, and were completely resistant to cytolysis by autologous PM.

Conclusion(s): The reduced capacity of PM from women with endometriosis to mediate the destruction of endometrial cells coupled with the increased resistance of ectopic endometrial cells to macrophage-mediated cytolysis may facilitate the survival of these cells within the peritoneal cavity of women with endometriosis.     

IL-2 enhances standard IFNgamma/LPS activation of macrophage cytotoxicity to human ovarian carcinoma in vitro: a potential for adoptive cellular immunotherapy.

OBJECTIVE: The objective was to evaluate the enhancement of human peritoneal macrophage cytotoxic in vitro activity by the addition of interleukin-2 (IL-2) to the standard interferon gama (IFNgamma) and lipopolysaccharide (LPS) activation procedure used for cellular adoptive immunotherapy in a human ovarian cancer system. This cytotoxic effect of these activated macrophages was tested on cells from ovarian cancers of various stages, histology type, and grade, both prior to chemotherapy and at recurrence, in ovarian carcinoma cells lines and normal cells. Increased activation of the macrophage may make it a better candidate for intraperitoneal cellular adoptive immunotherapy as a component of ovarian cancer therapy. This was not a study of the mechanism of macrophage killing. METHODS: Ascites specimens were collected from 24 ovarian cancer patients at the time of surgery or by paracentesis. The mononuclear cell fraction was isolated by discontinuous density gradient centrifugation and used as a cellular source of peritoneal macrophages (PMs) and primary cultured ovarian cancer cells. PMs were separated by 1-h adhesion followed by intensive washing to remove floating cells. The floating cells were cultured for 24 h which left the cancer cells attached after unattached cells were removed by washing. These cells formed a monolayer of cancer cells, which could be subcultured in 22 patients. The cells from the third to fifth passages were used as target cells without coculture with other cells. PMs were identified by latex ingestion, and their purity after isolation by adhesion culture was tested by flow cytometry and immunofluorescence. PMs were activated by culturing in the presence of IFNgamma, with or without IL-2, for 18 h followed by the addition of LPS 6 h prior to use as effector cells in cytotoxicity assays. Ovarian cancer cells of both established cell lines and primary cultures were labeled with (51)Cr and utilized as target cells to quantitatively measure PM-mediated cytotoxicity. Ovarian cancer cells were also cocultured with PMs for morphologic observations to provide supporting evidence to the cytotoxicity assays. RESULTS: IL-2 enhances the cytotoxicity of the standard IFNgamma/LPS macrophage activation in this system. Peritoneal macrophages so activated are cytotoxic to autologous and allogenic primary cultured ovarian tumors and to ovarian carcinoma cell lines. The macrophages are cytotoxic to cells both prior to treatment and at recurrence, but the data from the few recurrent patients did reach statistical significance. This cytotoxicity is not MHC associated. Normal cells are minimally affected. CONCLUSIONS: IL-2 augmented the standard IFNgamma/LPS method of activating peritoneal macrophage cell killing of human ovarian cancer cells in this in vitro system. The cell killing occurred with autologous and allogenic tumor cells from patients with primary and possibly recurrent tumors. Activated PMs minimally affected the normal cells tested. This enhanced activation may improve the disappointing results of previous adoptive cellular immunotherapy human trials and should be considered for ovarian cancer clinical trials.     

Cisplatin, adriamycin and ifosfamide-based combination chemotherapy for gynecological cancers derived from the extended müllerian system.

Their histogenetic similarity suggests that a group of malignant tumors may have a common sensitivity to a cytotoxic chemotherapy. Seventy patients with a variety of gynecological cancers arising from the uterine cervix, endometrium, ovary and pelvic peritoneum were treated with a combination of cisplatin, adriamycin and ifosfamide (PAI). As schedule modifications, PAI plus bleomycin for cancers containing squamous components and PAI plus etoposide for nonepithelial malignancies were recommended. In twenty-five evaluable cases, including 12 recurrent tumors after previous radiation therapy or PAC (cisplatin, adriamycin and cyclophosphamide) chemotherapy, the total response rate was 95% for epithelial cancers (vaginal cancer: 1/1, cervical: 9/10, endometrial: 2/2, ovarian: 6/6 and peritoneal: 2/2), and 100% for nonepithelial malignancies including one uterine leiomyosarcoma, one uterine mixed Müllerian tumor and one extragonadal mixed Müllerian tumor. The survival rates of patients with non measurable lesion were 100% for cervical cancer (the observation period: 65-879 days), 92.9% for endometrial cancer (96-975 days) and 88.9% for ovarian cancer (148-976 days). The hematological toxicity of this treatment was severe but acceptable. The results obtained indicate that a wide range of gynecological cancers originating in the primary and secondary Müllerian tissues (extended Müllerian system) must have a similar sensitivity to cytotoxic treatment with a PAI-based combination chemotherapy.     

Monocyte chemotaxis in patients with cervical or ovarian cancer

The chemotactic response of peripheral blood monocytes to untreated, complement activated and inactivated autologous serum was determined in patients receiving therapy for cervical or ovarian cancer. A significant reduction in monocyte chemotaxis, based on the number of migrating monocytes, in complement activated autologous serum, was observed in the cervical cancer group relative to the healthy subjects (controls). However, this reduction in response was not reflected in the monocyte chemotactic response index (response in treated serum/untreated serum). No significant difference in monocyte chemotaxis was found between the ovarian cancer group and the controls.     

Serum vascular endothelial growth factor C (VEGF-C) as a specific biomarker for advanced cervical cancer: Relationship to insulin-like growth factor II (IGF-II), IGF binding protein 3 (IGF-BP3) and VEGF-A [corrected

OBJECTIVES: An early non-invasive diagnosis of cervical cancer and its metastasis can save lives. We have shown that serum IGF-II levels can be effectively used for a specific early diagnosis of cervical cancer. Here, we shall determine if serum levels of vascular endothelial growth factors B and C (VEGF-A [corrected] VEGF-C) associated with vasculogenic and lymphogenic metastasis may be used for an early diagnosis of advanced metastatic cervical cancer and compare these levels with those of the serum IGF-II and IGF-binding protein 3 (IGF-BP3). MATERIAL AND METHODS: (a) Serum levels of IGF-II, IGF-BP3, VEGF-A [corrected] (VEGF(165)) and VEGF-C (ELISA kits) were determined in: 82 controls with normal Pap smears; 29 women with atypical squamous cells of undetermined significance (ASCUS) and normal cervical biopsy; 46 ASCUS and cervical intraepithelial neoplasia (CIN) on biopsy; 8 pre-therapy CIN-I; 23 successfully treated CIN-I; 75 persistent CIN-I; 14 CIN-II/III pre-therapy; 14 successfully treated CIN-II/III; 70 persistent CIN-II/III; 86 pre-therapy cervical cancer; 26 in early grades of cervical cancer; 21 in late grades of cervical cancer; 22 cervical cancer patients in remission; 50 persistent cervical cancer; 18 with ovarian cancer; and 57 with endometrial cancer. (b) Serial serum samples collected over 5 years in 5 women with progressing cervical cancer were also tested. (c) Serum and tissue VEGF-C were enumerated in 20 matched serum (ELISA) and tissue (semi-quantitative immunofluorescent antibody assay) samples from controls, early cervical cancer, late cervical cancer, ovarian cancer and endometrial cancer patients. Student's t test, chi-square analysis and linear regression analysis were used. RESULTS: (a) As anticipated, serum IGF-II levels were elevated as early as ASCUS with CIN on biopsy and continued to be elevated in CIN (all grades; pre-therapy and persistent) and cervical cancer (pre-therapy, early, late and persistent). Serum IGF-II levels were normal in ASCUS with normal biopsy, successfully treated CIN-I, II/III, cervical cancer as well as pre-therapy ovarian and endometrial cancers (therapy efficacy: P < 0.0001 by chi-square analysis). Serum IGF-BP3 showed a significant decrease with advancing disease. Serum VEGF-A [corrected] levels were the highest in pre-therapy, early, advanced and persistent cervical cancer, as well as in ovarian and endometrial cancers. Serum VEGF-C levels, on the other hand, were the highest in late and persistent cervical cancers, but not in ovarian or endometrial cancers. (b) In the 5 women with serial samples, the serum levels of the growth factors showed similar trends. (c) VEGF-C levels in serum and tissue were elevated in cervical cancers especially in advanced grades, while they were normal in serum and tissue from the controls and women with ovarian and endometrial cancers. There was a highly significant positive correlation between VEGF-C and IGF-II and a negative correlation between IGF-BP3 and VEGF-C (P < 0.0001). CONCLUSION: Serum IGF-II up-regulation is specific to cervical cancer and helps in the early diagnosis of malignant proliferation, while serum VEGF-C up-regulation appears to be a unique marker for an early diagnosis of cervical cancer metastasis. VEGF-C and IGF-II systems appear to be interrelated in cervical cancer, contributing to the early malignant cell proliferation and lympho-vascular metastasis. Serum IGF-BP3 and VEGF-A [corrected] appear to be common markers for all gynecological cancers.     

Occurrence of CA 125 and CA 19-9 tumor-associated antigens in sera of patients with gynecologic, trophoblastic, and colorectal tumors

The present study was undertaken to test the parallel detectability of ovarian cancer antigen CA 125 and gastrointestinal cancer antigen CA 19-9 in the sera of patients with malignant ovarian tumors, benign ovarian tumors, endometrial cancers, cervical cancers, colorectal cancers, and trophoblastic tumors and in early 1st-trimester pregnant as well as in healthy nonpregnant controls. In all kinds of gynecologic and colorectal tumors raised concentrations of both antigens were found with the exception of malignant nonepithelial ovarian tumors where neither of the antigens showed positive reaction. The most positive cases were found in the group with epithelial ovarian cancers. Of the two antigens CA 125 was the more responsive. No positive cases were found with either of the antigens in nonpregnant healthy controls or in patients with benign ovarian tumors. The parallel determination of the two antigens gives us a better opportunity to recognize pelvic tumors and further may enable us to distinguish ovarian and colorectal tumors.     

Microsatellite instability in mitochondrial genome of common female cancers

Abstract.   Wang Y, Liu VWS, Tsang PCK, Chiu PM, Cheung ANY, Khoo US, Nagley P, Ngan HYS. Microsatellite instability in mitochondrial genome of common female cancers. Int J Gynecol Cancer 2006; 16(Suppl. 1): 259–266.
To investigate the occurrence of mitochondrial genome instability in primary cervical, endometrial, ovarian, and breast carcinomas, we analyzed 12 microsatellite regions in mitochondrial DNA (mtDNA) of tumor tissues and their matched normal controls. Four of the 12 microsatellite markers starting at nucleotide position (np) 303, 514, 956, and 16184, respectively, exhibited instability as indicated by the change in length of short base-repetitive sequences of mtDNA in cancer tissue relative to that in control normal tissue from the same patient. About 25.4% of cervical cancers, 48.4% of endometrial cancers, 21.9% of ovarian cancers, and 29.4% of breast cancers carried one or more mitochondrial microsatellite instability (mtMSI). mtMSI was frequently detected in the D-loop region but rarely occurred in the coding region. A relatively long C tract interrupted by a T residue is the mtMSI hot spot in all four types of cancer studied. Different tumors have different mtMSI profiles. In particular, the frequency of mtMSI in endometrial cancer was significantly higher than in the other three types of cancer. Furthermore, carriers of a germ-line T to C polymorphism at np 16189 could be more susceptible to breast cancer development in light of the higher frequency detected in cancer patients than in normal individuals.     

Sex hormone-binding globulin and estrogen receptor in endometrial and cervical cancer

Estrogen receptors (ER) were estimated in tissue of endometrial and cervical cancers. At the same time sex hormone-binding globulin (SHBG) was measured in the blood of the patients and in normal pre- and postmenopausal controls. The average SHBG level was significantly higher in postmenopausal patients with ER-positive endometrial or cervical cancers than in patients with ER-negative cancers. There was no correlation between the SHBG levels in plasma and the receptor levels in tissue in either ER-positive or ER-negative tissues. The average SHBG value in postmenopausal patients with ER-positive endometrial cancer was similar to the average value found in normal premenopausal women. In premenopausal patients with cervical cancer there was no difference in SHBG values between ER-positive and ER-negative cancers.     

Gynaecological cancers in Umbria (Italy): trends of incidence, mortality and survival, 1978-1998

OBJECTIVE: For the period 1978-1998 incidence, mortality and survival from gynaecological cancers in the Umbria region (Central Italy) were examined. STUDY DESIGN: Mortality data were derived from the National Institute of Statistics while incidence and survival data were provided by an ad hoc survey carried out over the period 1978-1982 and by the Umbrian Population-Based Cancer Registry operating since 1994. Age-standardised mortality and incidence rates were calculated. Survival was assessed using the Estève method. Mortality trends were analysed by joinpoint regression model. RESULTS: In the Umbria Region, over the period 1978-1998, the incidence rate of cervical cancer decreased, while those for endometrial and ovarian cancers rose. By contrast, the mortality rates from ovarian and endometrial cancers decreased, while that for cervical cancer rose slightly. Comparing relative survival rates, at 5 years an increase in survival was reported for ovarian cancer, cervical cancer remained constant and endometrial cancer slightly decreased; at 1 year only the ovarian cancer survival improved. Nevertheless, age-standardised survival rates showed that survival improved in all examined sites. CONCLUSIONS: The improvement in diagnosis and in data coding could have determined an increase in endometrial and ovarian cancer incidence, while the dramatic decrease in cervical cancer incidence is probably due to the effectiveness of cervical screening.     

Shortcomings and deficits in surgical treatment of gynecological cancers: a German problem only?

OBJECTIVES: The objective of this study was to assess the quality of preoperative diagnostic, primary surgical, and postoperative treatment of ovarian, endometrial, and cervical cancers in women in Hesse, Germany, in relation to current international recommendations. METHODS: Data on all diagnostic, surgical, and postoperative gynecological procedures undertaken in Hesse in 1997-2001 were collected in a standardized form and validated for clinical quality. Databases were generated for cases of endometrial, ovarian, and cervical cancer, and details of treatment were analyzed. RESULTS: There were 1119 cases of endometrial, 824 cases of ovarian, and 472 cases of cervical cancer. The malignancy remained undiagnosed until after surgery in 17.8% (199/1119) of endometrial cancers, 28.5% (245/824) of ovarian cancers, and 15.5% (73/472) of cervical cancers. There was evidence of suboptimal surgical treatment. Lymphadenectomy rates were low in endometrial and ovarian cancers (about 32%), and omentectomy rates in were low in ovarian cancer (about 50%). Furthermore, 10.7% (31/289) of patients with cervical cancer diagnosed before hospital admission did not undergo radical surgery. CONCLUSION: Discrepancies between guidelines and treatment of gynecological cancers in Hesse were striking, particularly for endometrial and ovarian cancer, and this situation may be mirrored internationally. The fact that many guidelines are not supported by results from clinical studies may be a factor in this apparently suboptimal treatment. Clinical collaborative trials are needed to provide the necessary evidence to support current recommendations and benchmarks of survey are required to facilitate future quality assessment.     

Estradiol, androstenedione, testosterone, and dehydroepiandrosterone sulfate in the ovarian and peripheral blood of postmenopausal patients with and without endometrial cancer

Estradiol (E), androstenedione (A), testosterone (T), and dehydroepinadrosterone sulfate (DHEAS) were determined in the plasma taken from the ovarian and cubital vein in endometrial cancer patients and controls. All the cases and controls experienced their menopause more than 4 years before the study. The patients were matched for weight and height. No difference was found for T, A, and DHEAS in the peripheral blood between cases and controls. Nevertheless a statistically significant difference was observed for T and A, higher in the cases than in the controls: 4.38 ± 1.32 vs 1.38 ± 0.51, for T and 5.69 ± 1.65 vs 2.57 ± 0.12 for A. Estradiol was higher in peripheral and ovarian blood of cancer cases when compared with the controls but the difference is not statistically significant.     

The Significance of Peritoneal Cytology in Uterine Cervix and Endometrial Cancer

Objective.The purpose of this study was to determine the incidence of positive peritoneal cytology and to elucidate the prognostic value of peritoneal cytology in patients with uterine cervix and endometrial cancer.Materials and methods.The incidence of positive peritoneal cytology was investigated in 642 patients including 339 uterine cervix and 303 endometrial cancers. Survival was estimated by the Kaplan–Meier method in a subgroup of 116 stage II cervix and 199 stage I endometrial cancers, and multivariate analysis using Cox's proportional hazards model was used to identify an independent prognostic factor.Results.The incidence of positive peritoneal cytology was found to be 9% in uterine cervix cancer and 15% in endometrial cancer. The incidence was higher in patients with some clinicopathologic status such as advanced stage, lymph node metastasis, ovarian metastasis, and deeper myometrial invasion. The 5-year survival rate for patients with positive or negative peritoneal cytology was 44 or 80% in stage II cervix cancers and 80 or 92% in clinical stage I endometrial cancers, respectively. Multivariate analysis revealed that independent prognostic determinants were pelvic and paraaortic lymph node metastasis and peritoneal cytology in stage II cervix cancer and peritoneal cytology in stage I endometrial cancer. Proper treatment protocol should be scheduled for patients with positive peritoneal cytology.     

Soluble urokinase plasminogen activator receptor in preoperatively obtained plasma from patients with gynecological cancer or benign gynecological diseases

OBJECTIVE: The present study was planned to measure preoperative levels of soluble urokinase plasminogen activator receptor (suPAR) in plasma from patients with gynecological diseases, and to test for a relationship to clinical and biochemical patient characteristics. METHODS: Using a specific and sensitive kinetic ELISA, suPAR levels were determined in preoperative citrate plasma samples from 53 ovarian, 34 endometrial, and 30 cervical cancer patients, 17 patients with benign ovarian tumors, and 28 patients with benign endometrial diseases. In addition, suPAR was measured in citrate samples from 31 female blood donors. RESULTS: suPAR was measurable in all samples. No significant difference was found between plasma suPAR in the blood donors and the patients with benign diseases (P = 0.58). The groups of cancer patients had suPAR levels that were significantly higher than those found in the blood donors (P < 0.0001, P < 0.0001, and P = 0.001 for patients with ovarian, endometrial, and cervical cancer, respectively). In all groups of cancer patients a trend toward increasing suPAR levels with increasing FIGO stage was noted (P = 0.0003, P = 0.02, and P = 0.01 for patients with ovarian, endometrial, and cervical cancer, respectively). Using the median suPAR level to dichotomize the ovarian cancer patients, FIGO stages I-III, a significantly increased risk of progression/relapse was found for patients with high suPAR levels (Hazard ratio (HR) = 3.1, 95% CI: 1.1-8.8, P = 0.03). A multivariate analysis was performed, including suPAR, FIGO stage, and CA-125. Only FIGO stage III compared with FIGO stage I was significant (HR = 15, 95% CI: 1.8-129, P = 0.01). Survival analyses were not performed in the endometrial or cervical cancer patients due to few progressions/relapses during the follow-up period. CONCLUSION: This study concludes that patients with gynecological cancers have elevated plasma suPAR levels as compared with healthy female blood donors and patients with benign gynecological diseases. In addition, high preoperative plasma levels of suPAR are significantly associated with poor outcome of ovarian cancer patients. However, additional studies are needed to further validate the clinical usefulness of plasma suPAR measurements in the management of ovarian cancer patients.     

Stimulation of ovarian tumor cell proliferation with monocyte products including interleukin-1, interleukin-6, and tumor necrosis factor-alpha.

OBJECTIVE: We investigated whether monocyte-derived factors could stimulate the growth of ovarian cancer cells. STUDY DESIGN: Human peripheral blood monocytes or human monocyte-like cell lines THP-1 and U-937 were cultured with or without macrophage colony-stimulating factor, lipopolysaccharide, or phorbol myristate acetate. Culture supernatants or recombinant cytokines were assayed for growth stimulation of ovarian cancer cell lines by tritium-thymidine incorporation and direct cell counts followed by statistical analysis with Student t test. RESULTS: Conditioned medium from peripheral blood monocytes or from THP-1 or U-937 cells stimulated ovarian cancer cell growth. Interleukin-1 alpha, tumor necrosis factor-alpha, and interleukin-6 also stimulated ovarian cancer cell growth, whereas macrophage, granulocyte, and granulocyte-macrophage colony-stimulating factor did not. Concentrations of tumor necrosis factor, interleukin-1, and interleukin-6 in conditioned medium could not account for all the growth stimulation, and activity remained after neutralization of tumor necrosis factor, interleukin-1, and interleukin-6 with antibodies. CONCLUSIONS: Interleukin-1, interleukin-6, tumor necrosis factor, and additional monocyte factor(s) could provide paracrine growth stimulation when monocytes are attracted to ovarian cancers that produce macrophage colony-stimulating factor.     

Elevation of serum interleukin-1 receptor antagonist levels in women with gynaecological cancers

This study included 15 patients with gynaecological cancers (7 with cervical cancer, 6 with endometrial cancer, and 12 with ovarian cancer); 7 with benign gynaecological disorders (5 with benign ovarian tumour and 2 with uterine myoma); and 10 healthy women as a control group. Serum interleukin-1 receptor antagonist (IL-1 ra) levels in patients with gynaecological cancer were significantly higher than those in patients with benign gynaecological disorders (P = 0.04) and in healthy controls (P = 0.0009). IL-1 ra may play an important role in host immune responses in local and general environments against gynaecological cancers.     

Fertility-preserving surgical procedures, techniques

As a result of the trend toward late childbearing, fertility preservation has become a major issue in young women with gynaecological cancer. Fertility-sparing treatments have been successfully attempted in selected cases of cervical, endometrial and ovarian cancer, and gynaecologists should be familiar with fertility-preserving options in women with gynaecological malignancies. Options to preserve fertility include shielding to reduce radiation damage, fertility preservation when undergoing cytotoxic treatments, cryopreservation, assisted reproduction techniques, and fertility-sparing surgical procedures. Radical vaginal trachelectomy with laparoscopic lymphadenectomy is an oncologically safe, fertility-preserving procedure. It has been accepted worldwide as a surgical treatment of small early stage cervical cancers. Selected cases of early stage ovarian cancer can be treated by unilateral salpingo-ophorectomy and surgical staging. Hysteroscopic resection and progesterone treatment are used in young women who have endometrial cancer to maintain fertility and avoid surgical menopause. Appropriate patient selection, and careful oncologic, psychologic, reproductive and obstetric counselling, is mandatory.     

Synchronous primary neoplasms of the female reproductive tract

A histopathologic review of synchronous primary neoplasms of the female reproductive tract is presented. During a 30-year period, 3863 patients with female genital malignancies were accessioned to the UCLA Tumor Registry: 958 had ovarian cancer, 776 endometrial cancer, 1556 cervical cancer, and 573 other gynecologic malignancies. Twenty-six (0.7%) patients with invasive synchronous primary cancers were identified. The most frequent synchronous genital lesions were ovarian and endometrial cancers in 11 patients (0.3%). No association was documented between genital and extragenital cancers. Patients with synchronous ovarian and endometrial cancers each were low stage and low grade, and the prognosis was excellent. Their detection in a relatively early stage suggests diagnosis may be facilitated by early symptoms from the endometrial carcinoma, and that these lesions are biologically of relatively low grade. These data support the conclusion that there is an association between low-stage epithelial carcinoma of the ovary and endometrial carcinoma.     

Release of tumor necrosis factor alpha by human peritoneal macrophages in response to toxic shock syndrome toxin-1

We examined the release in vitro of tumor necrosis factor-alpha (TNF-alpha) by peritoneal macrophages and peripheral blood monocytes following incubation with toxic shock syndrome toxin-1 (TSST-1). We obtained peritoneal macrophages from 22 women at laparoscopy and peripheral blood monocytes from four healthy women during both the midfollicular and midluteal phases of the menstrual cycle. The samples were incubated for 24 hours at 37 C with 10(-2)-10(4) ng/mL of TSST-1 or 10(4) ng/mL of bacterial endotoxin. Tumor necrosis factor-alpha activity was determined with a bioassay using an actinomycin D-sensitized WEHI-164 murine fibrosarcoma cell line. Twenty-four-hour incubation with TSST-1 resulted in a dose-dependent release of TNF-alpha by both peritoneal macrophages (maximal response 554 +/- 97 U of activity) and peripheral blood monocytes (maximal response 478 +/- 81 U of activity). We observed enhanced TNF-alpha release by peritoneal macrophages from women with endometriosis, compared with those without endometriosis, at a concentration of 10(4) ng/mL of TSST-1 (704 +/- 134 versus 354 +/- 103 U of activity; P less than .05). These data support the theory that the metabolic and physiologic derangements of perimenstrual toxic shock syndrome may be partially mediated by TNF-alpha released by peritoneal macrophages as a result of exposure to TSST-1.     

Serum vitamins A and E and carotene in patients with gynecologic cancer

Summary Serum concentrations of vitamin A (retinol), vitamin E (alphatocopherol) and total carotene were measured in 88 women with gynecologic cancer (9 vulvar, 15 cervical, 36 endometrial and 28 ovarian carcinomas) and 31 healthy controls. No significant differences were found in the serum levels of the vitamins and carotene in patients with vulvar, cervical or endometrial cancer compared to the controls. The patients with ovarian cancer had a significantly (P<0.01) lower mean serum level of vitamin A than the controls, while carotene and vitamin E level were similar in both groups. The results indicate that vitamin A may have a role in the metabolism of patients with advanced ovarian cancer.     

Fertility-sparing Surgery for Patients with Cervical,Endometrial, and Ovarian Cancers

ObjectiveNearly 10% of the 1.3 million women living with a gynecologic cancer are aged <50 years. For these women, although their cancer treatment can be lifesaving, it's also life-altering because traditional surgical procedures can cause infertility and, in many cases, induce surgical menopause. For appropriately selected patients, fertility-sparing options can reduce the reproductive impact of lifesaving cancer treatments. This review will highlight existing recommendations as well as innovative research for fertility-sparing treatment in the 3 major gynecologic cancers.Tabulation, Integration, and ResultsFor early-stage cervical cancers, fertility-sparing surgeries include cold knife conization, simple hysterectomy with ovarian preservation, or radical trachelectomy with placement of a permanent cerclage. In locally advanced cervical cancer, ovarian transposition before radiation therapy can help preserve ovarian function. For endometrial cancers, fertility-sparing treatment includes progestin therapy with endometrial sampling every 3 to 6 months. After cancer regression, progestin therapy can be halted to allow attempts to conceive. Hysterectomy with ovarian preservation can also be considered, allowing for fertility using assisted reproductive technology and a gestational carrier. For ovarian cancers, fertility-sparing surgery includes unilateral salpingo-oophorectomy or bilateral salpingo-oophorectomy (with lymphadenectomy and staging depending on tumor histology). With higher-risk histology or higher early-stage disease, adjuvant chemotherapy is recommended—however, this carries a 3% to 10% risk of ovarian failure. Use of oocyte or embryo cryopreservation in patients with early-stage ovarian malignancy remains an area of ongoing research.ConclusionOverall, fertility-sparing management of gynecologic cancers is associated with acceptable rates of progression-free survival and overall survival and is less life-altering than more radical surgical approaches.