Body mass index as a prognostic factor in endometrioid adenocarcinoma of the endometrium.

OBJECTIVE: To determine if body mass index (BMI) influences tumor expression of HER-2/neu, estrogen and progesterone receptors (ER/PR), and survival in women with endometrial adenocarcinoma. METHODS: Patients diagnosed between January 1992 and December 2001 with endometrioid adenocarcinoma of the uterus were identified. Clinical and pathologic data were retrospectively collected. HER-2/neu, estrogen and progesterone receptor expression were determined by immunohistochemistry. Differences in these variables and other prognostic factors were analyzed and correlated with effect on survival. RESULTS: One-hundred-sixty-five patients were included in this analysis. Lower BMI was associated with high stage (p=0.04) and HER-2/neu expression (p=0.04). Black race, high grade, high stage and lack of ER/PR expression were all associated with decreased survival. Despite having better prognostic factors, women with a BMI >25 had a lower survival than women with a BMI <25 (p=0.36). When five-year survival rates were calculated for BMI category and stratified by prognostic factors, for almost every high risk factor, survival was lower in overweight patients. CONCLUSION: In patients with endometrioid adenocarcinoma, low BMI is associated with high stage and tumor expression of HER-2/neu. Despite better prognostic factors, overweight women experience poorer survival.

Mesonephric adenocarcinoma of the cervix: a case report and review of the literature.

BACKGROUND: Malignant mesonephric tumor arising in the uterine cervix is an exceedingly uncommon variant of cervical adenocarcinoma with only 30 well-documented cases in the literature. CASE: We present a case of a 54-year-old woman with postmenopausal vaginal bleeding who was found to have a stage IB mesonephric adenocarcinoma of the cervix. CONCLUSION: At present there is no consensus on a standardized treatment protocol for malignant mesonephric tumors of the cervix. The present case suggests that a favorable outcome may be achieved for patients with stage IB tumors with aggressive initial therapy.

Racial and ethnic disparities in cancers of the uterine corpus.

Survival after diagnosis of cancer of the uterine corpus is significantly worse in black women as compared with white women. The etiology of the racial and ethnic disparities that exist in endometrial cancer incidence and outcome is multifactorial and complex. Potential explanations include cancer biology, differences in access to care, sociodemographic characteristics, response to treatment and comorbid factors. In this article, a review was performed to assess the magnitude and reasons for the observed disparity in endometrial cancer mortality. Strategies and recommendations to reduce or eliminate differences in endometrial cancer outcome are explored. These include advocacy for more research to clarify the underlying causes of cancer disparities at all levels, including the molecular basis of disparate outcomes, improving access to quality healthcare services, establishing culturally competent models of healthcare delivery, and developing novel cost-effective screening and early prevention methods.

Innovations in fertility preservation for patients with gynecologic cancers.

OBJECTIVE: To review options for fertility preservation in women with gynecologic cancers. DESIGN: Literature review. RESULT(S): We discuss the data regarding cancer treatment and fertility outcomes and current controversies for women with gynecologic cancers. CONCLUSION(S): Gynecologic cancers represent 12%-15% of cancers affecting women, and 21% of these are diagnosed in women of reproductive age. Current advances in our understanding of these diseases, along with improved multimodality treatment, allow for consideration of fertility options. For some women with gynecologic cancers, fertility-sparing treatment might be appropriate.

Intraoperative radiation therapy in recurrent ovarian cancer.

PURPOSE: To evaluate disease outcomes and complications in patients with recurrent ovarian cancer treated with cytoreductive surgery and intraoperative radiation therapy (IORT). METHODS AND MATERIALS: A retrospective study of 24 consecutive patients with ovarian carcinoma who underwent secondary cytoreduction and intraoperative radiation therapy at our institution between 1994 and 2002 was conducted. After optimal cytoreductive surgery, IORT was delivered with orthovoltage X-rays (200 kVp) using individually sized and beveled cone applications. Outcomes measures were local control of disease, progression-free interval, overall survival, and treatment-related complications. RESULTS: Of these 24 patients, 22 were available for follow-up analysis. Additional treatment at the time of and after IORT included whole abdominopelvic radiation, 9; pelvic or locoregional radiation, 5; chemotherapy, 6; and no adjuvant treatment, 2. IORT doses ranged from 9-14 Gy (median, 12 Gy). The anatomic sites treated were pelvis (sidewalls, vaginal cuff, presacral area, anterior pubis), para-aortic and paracaval lymph node beds, inguinal region, or porta hepatitis. At a median follow-up of 24 months, 5 patients remain free of disease, whereas 17 patients have recurred, of whom 4 are alive with disease and 13 died from disease. Five patients recurred within the radiation fields for a locoregional relapse rate of 32% and 12 patients recurred at distant sites with a median time to recurrence of 13.7 months. Five-year overall survival was 22% with a median survival of 26 months from time of IORT. Nine patients (41%) experienced Grade 3 toxicities from their treatments. CONCLUSION: In carefully selected patients with locally recurrent ovarian cancer, combined IORT and tumor reductive surgery is reasonably tolerated and may contribute to achieving local control and disease palliation.

Maternal and neonatal outcomes after uterine rupture in labor.

OBJECTIVE: There is significant controversy about the risks related to attempted vaginal birth after cesarean and the implications for informed consent of the patient. Recent data suggest that women who deliver in hospitals with high attempted vaginal birth after cesarean rates are more likely to experience successful vaginal birth after cesarean, as well as uterine ruptures. We conducted a study to evaluate maternal and neonatal morbidity and mortality after uterine rupture at a tertiary care center. STUDY DESIGN: We performed a retrospective chart review of cases of uterine rupture from 1976 to 1998. All women who had a history of uterine rupture were identified with International Classification of Diseases, Ninth Revision, identifiers with hospital discharge data cross-referenced with a separate obstetric database. We abstracted demographic information, fetal heart rate patterns, maternal pain and bleeding patterns, umbilical cord gas values, and Apgar scores from the medical record. Outcome variables were uterine rupture events and major and minor maternal and neonatal complications. RESULTS: During the study period there were 38,027 deliveries. The attempted vaginal birth after cesarean rate was 61.3%, of which 65.3% were successful. We identified 21 cases of uterine rupture or scar dehiscence. Seventeen women had prior cesarean deliveries (10 with primary low transverse cesarean delivery, 3 with unknown scars, 1 with classic cesarean delivery, 2 with two prior cesarean deliveries, and 1 with four prior cesarean deliveries). Of the 4 women who had no history of previous uterine surgery, one had a bicornuate uterus whereas the others had no factors increasing the risk for uterine rupture. We confirmed uterine rupture and scar dehiscence in 19 women. Specific details were not available for 2 patients. Uterine rupture or scar dehiscence was clinically suspected in 16 women with 3 cases identified at delivery or after delivery. Sixteen women had symptoms of increased abdominal pain, vaginal bleeding, or altered hemodynamic status. There were 2 patients who required hysterectomies and 3 women who received blood transfusions; there were no maternal deaths related to uterine rupture. The fetal heart rate pattern in 13 cases showed bradycardia and repetitive variable or late decelerations. Thirteen neonates had umbilical artery pH >7.0. Two cases of fetal or neonatal death occurred, one in a 23-week-old fetus whose mother had presented to an outlying hospital and the second in a 25-week-old fetus with Potter's syndrome. All live-born infants were without evidence of neurologic abnormalities at the time of discharge. CONCLUSION: Our data confirm the relatively small risk of uterine rupture during vaginal birth after cesarean that has been demonstrated in previous studies. In an institution that has in-house obstetric, anesthesia, and surgical staff in which close monitoring of fetal and maternal well-being is available, uterine rupture does not result in major maternal morbidity and mortality or in neonatal mortality.

Symptomatic vasospasm after resection of a suprasellar pilocytic astrocytoma: case report and possible pathogenesis.

BACKGROUND: Cerebral vasospasm from pathology other than subarachnoid hemorrhage is uncommon. A case of severe vasospasm after resection of a suprasellar pilocytic astrocytoma is reported. METHODS: A 45-year-old male presented with headache, left facial numbness, bilateral visual loss, and ataxia. Evaluation revealed a large suprasellar tumor, which was resected. Pathologic examination showed pilocytic astrocytoma. The patient developed hemiparesis and aphasia on the fifth postoperative day. Vascular spasm was documented on angiography and by transcranial Doppler. RESULTS: Intraarterial papaverine resulted in moderate angiographic improvement. Attempts to open middle cerebral artery branches with angioplasty were unsuccessful. The patient subsequently developed a left middle cerebral artery infarct. CONCLUSIONS: To our knowledge, this is the first description of vasospasm after resection of an astrocytoma. Possible mechanisms contributing to this unusual complication after resection of tumors are discussed.

Growth factor regulation of insulin-like growth factor binding protein secretion by cultured human granulosa-luteal cells.

OBJECTIVE: To examine the effects of epidermal growth factor (EGF), transforming growth factor-beta (TGF-beta), and fibroblast growth factor (FGF) on insulin-like growth factor binding protein (IGFBP) secretion by cultured human granulosa-luteal cells. DESIGN: Granulosa-luteal cells obtained at the time of oocyte harvest for IVF were cultured in serum-free medium in the presence or absence of EGF, TGF-beta, or FGF. Conditioned medium then was analyzed by Western ligand blot and immunoradiometric assays. SETTING: An academic medical center. PATIENT(S): Women undergoing IVF. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): IGFBP-1 secretion. RESULT(S): By Western ligand blot analysis, IGFBP-1 levels were 1.4-fold to 7.4-fold higher in conditioned medium from cells cultured in the presence of EGF than in control medium. By immunoradiometric assay, IGFBP-1 levels increased from 1.6 to 9.9 times over control. The TGF-beta had no apparent effect, and FGF did not consistently stimulate IGFBP-1 secretion. CONCLUSION(S): The EGF may decrease intrafollicular bioavailable IGF levels by increasing inhibitory IGFBPs, thereby leading to arrest of follicular development. Interactions between the EGF and IGF systems may be involved in the processes governing human ovarian follicle maturation and atresia.

Insulin-like growth factors and insulin-like growth factor binding proteins in androgen-dominant ovarian follicles from testosterone-treated female-to-male trans-sexuals.

OBJECTIVE: To determine insulin-like growth factor (IGF)-I and IGF-II levels, IGF binding protein (IGFBP) profile, and IGFBP-4 protease activity in androgen-dominant follicular fluid (FF) from female-to-male trans-sexuals and to compare with those in follicles from normocycling women. DESIGN: Follicular fluid samples were obtained from four female-to-male trans-sexuals and 15 women with normo-ovulatory cycles at the Dijkzigt Academic Hospital. Western ligand blot analysis and protease assays were used to determine IGFBP profile, and immunoradiometric assays were used to detect IGF levels. SETTING: The study was performed in two academic medical centers. PATIENT(S): Female-to-male trans-sexuals and women with normo-ovulatory cycles. INTERVENTIONS: None. MAIN OUTCOME MEASURE(S): Determination of IGF levels and IGFBP profile. RESULT(S): Insulin-like growth factor I levels in FF from female-to-male trans-sexuals were not significantly different compared with levels in androgen-dominant FF and estrogen-dominant FF. Significantly lower levels of IGF-II were observed in FF from female-to-male trans-sexuals than in estrogen-dominant FF, whereas IGF-II levels in FF from female-to-male trans-sexuals were not significantly different than those in androgen-dominant FF. Similar IGFBP profiles from FF from female-to-male trans-sexuals and androgen-dominant FF were noted, with markedly elevated levels of the 31- and 24-kd IGFBPs and a 28-kd IGFBP, compared with estrogen-dominant FF. An IGFBP-4-specific metalloserine protease that is active in estrogen-dominant FF likewise was undetected in FF from female-to-male trans-sexuals. CONCLUSION(S): Follicles developing under the influence of exogenous androgens in ovaries in female-to-male trans-sexuals appear to be similar to androgen-dominant follicles in normo-ovulatory women with regard to IGF-I and IGF-II levels, IGFBP profile, and the absence of IGFBP-4 protease activity.

Serum and follicular fluid levels of insulin-like growth factor I (IGF-I), IGF-II, and IGF-binding protein-1 and -3 during the normal menstrual cycle.

Insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) have important regulatory functions in ovarian follicular development. Although most studies have investigated the IGF system in ovarian cells in vitro, investigation of the IGF system in the peripheral circulation and in follicles of varying sizes throughout the menstrual cycle in large numbers of subjects has been lacking. In the current study we performed daily IGF-I, IGF-II, IGFBP-1, and IGFBP-3 measurements in 9 healthy regularly cycling volunteers throughout the menstrual cycle. In addition, we investigated IGF-I, IGF-II, IGFBP-1, and IGFBP-3 levels in 13 samples of androgen-dominant follicular fluid [FFa androstenedione to estradiol (AD:E2) ratio, > 4] and 19 samples of estrogen-dominant follicular fluid (FFe; AD:E2 ratio, 4) obtained from 21 regularly cycling subjects and in 18 samples of fluid from luteinizing follicles obtained from patients undergoing in vitro fertilization (IVF) treatment (FFivf). IGF-I, IGF-II, IGFBP-1, and IGFBP-3 were measured using two-site immunoradiometric assays. No significant day to day differences were observed in IGF-I, IGF-II, IGFBP-1, and IGFBP-3 levels across the menstrual cycle. Median IGF-II levels in FFe (630 ng/mL; range, 212-1000) were significantly higher compared to those in FFa (474 ng/mL; range, 272-603; P = 0.002). Median IGFBP-3 levels in FFe (2955 ng/mL; range, 388-3448) were also significantly higher than those in FFa (2352 ng/mL; range, 756-2604; P = 0.003). Median IGF-I (192 ng/mL; range, 29-256) and IGFBP-1 (12 ng/mL; range, 2-281) levels in FFe were not significantly different from those in FFa [149 (range, 22-232) and 21 (range, 5-32) ng/mL, respectively). In contrast, significantly lower IGFBP-1 levels were found in FFe compared to FFivf (79 ng/mL; range, 57-234; P = 0.002), whereas there was no significant difference between FFe and FFivfe IGF-I, IGF-II, or IGFBP-3 levels, respectively. IGF-II levels were correlated with follicle diameter (r = 0.52; P = 0.002), cycle day (r = 0.47; P = 0.0065), E2 levels (r = 0.53; P = 0.003), AD:E2 ratio (r = -0.58; P = 0.001), and P concentrations (r = 0.60; P = 0.001) in all follicles, whereas no such correlations were found with IGF-I. In conclusion, as circulating levels of IGF-I, IGF-II, IGFBP-1, and IGFBP-3 are not menstrual cycle dependent, it is unlikely that these growth factors and these binding proteins play an endocrine role in cyclic ovarian follicle development, although both cycle-dependent delivery to the ovary and modification of their actions locally within the ovary cannot be excluded. With regard to FF1 the findings that IGF-II levels in FF1 are elevated compared to those in FFa and correlate with follicular functional status support a role for IGF-II during development of the dominant follicle. In addition, as IGFBP-3 in estrogen-dominant follicles mirrors the rise of IGF-II, this IGFBP may be a primary regulator of IGF-II action within the estrogen-dominant follicle. Finally, the finding of elevated levels of IGFBP-1 in luteinizing (IVF) follicles suggests an important role for this peptide in corpus luteum regulation.

Circulating and ovarian IGF binding proteins: potential roles in normo-ovulatory cycles and in polycystic ovarian syndrome.

IGFs function as co-gonadotropins in the ovary, facilitating steroidogenesis and follicle growth. IGFBP-1 to -5 are expressed in human ovary and mostly inhibit IGF action in in vitro ovarian cell culture systems. In the clinical disorder of polycystic ovarian syndrome (PCOS), which is characterized by hyperandrogenemia, polycystic ovaries and anovulation, follicles have a higher androgen: estradiol (A : E2) content and growth is arrested at the small antral stage. In the PCOS follicle, follicle stimulating hormone (FSH) and IGF levels are in the physiologic range, and even in the face of abundant androstenedione (AD) substrate, aromatase activity and E2 production are low. When PCOS granulosa are removed from their ovarian environment, they respond normally or hyperrespond to FSH. It has been postulated that an inhibitor of IGF's synergistic actions with FSH on aromatase activity may be one (or more) of the IGFBPs, which contributes to the arrested state of follicular development commonly observed in this disorder. High levels of IGFBP-2 and IGFBP-4 are present in follicular fluid (FF) from androgen-dominant follicles (FFa) from normally cycling women and in women with PCOS. This is in marked contrast to the near absence of these IGFBPs in estrogen-dominant FF (FFe), determined by Western ligand blotting. Regulation of granulosa-derived IGFBPs is effected by gonadotropins and insulin-like peptides. In addition, an IGFBP-4 metallo-serine protease is present in FFe, but not in FFa in ovaries from normally cycling women and those with PCOS, although the IGFBP-4 protease is present in PCOS follicles hyperstimulated for in vitro fertilization. Recent studies demonstrate that IGF-II in FFe is higher than in FFa' whereas IGF-I, IGFBP-3 and IGFBP-1 levels do not differ, underscoring the importance of local IGF-II production by the granulosa and the importance of IGFBP-4 and IGFBP-2 in regulation of IGF-II action within the follicle during its developmental pathway as an E2- or A-dominant follicle. In the androgen-treated female-to-male transsexual (TSX) model for PCOS, IGF-I, IGF-II, IGFBP-3 and IGFBP-1 levels do not differ.