Association of metabolic syndrome conditions with risk of second primary uterine cancer in breast cancer survivors.

PURPOSE: Uterine cancer risk is high in breast cancer survivors. Although breast cancer and uterine cancer share some common epidemiological risk factors, association of metabolic syndrome with incident uterine cancer in breast cancer survivors is under-studied. We evaluated the association of metabolic syndrome conditions with second primary uterine cancer in breast cancer survivors. METHODS: In this retrospective cohort study, 37,303 breast cancer patients diagnosed between 2008 and 2020 at Kaiser Permanente Southern California, an integrated healthcare system, were included. Data on cancer-related variables, sociodemographic, and clinical variables were extracted from KPSC's Surveillance, Epidemiology, and End Results (SEER)-affiliated cancer registry and electronic health records, as appropriate. Patients were followed from breast cancer diagnosis until 12/31/2021 for incident uterine cancer. Proportional hazards regression was used to report association [HR (95% CI)] between metabolic conditions and uterine cancer. RESULTS: More than half (53.1%) of the breast cancer survivors had 1-2 metabolic conditions; 19.4% had 3 + , while 27. 5% had no metabolic conditions. Median time to follow-up was 5.33 years and 185 (0.5%) patients developed second primary uterine cancer. Obesity was associated with an elevated uterine cancer risk in the adjusted model [HR (95% CI) 1.64 (1.20-2.25)]. Having 1-2 metabolic conditions (versus none) was not associated with increased uterine cancer risk [adjusted HR (95% CI) 1.24 (0.85-1.82)]; however, there was an increased uterine cancer risk with 3 + metabolic conditions [adjusted HR (95% CI) 1.82 (1.16-2.87)]. CONCLUSION: Although not statistically significant, we found a trend demonstrating greater uterine cancer risk by increasing numbers of metabolic syndrome conditions in breast cancer survivors.

Soy-Based Infant Formula Feeding and Uterine Fibroid Development in a Prospective Ultrasound Study of Black/African-American Women.

BACKGROUND: Uterine fibroids are highly prevalent, benign tumors. They are the leading indication for hysterectomy, and Black women are disproportionally burdened. Soy-based infant formula contains phytoestrogens, and exposure during sensitive developmental windows may adversely affect the developing uterus; early phytoestrogen treatment in rodent studies led to detrimental uterine effects, including increased fibroid risk in Eker rats. Limited epidemiological studies also have suggested increased fibroid development with soy formula infant feeding. OBJECTIVE: The goal of this study was to examine the association between soy formula feeding in infancy and fibroid development in adulthood. METHODS: We evaluated this association among 1,610 Black/African-American women age 23-35 y in the Study of Environment, Lifestyle & Fibroids (SELF). Soy formula feeding data was gathered directly from the participants' mothers (89%). A standardized ultrasound examination was conducted during 4 clinic visits over 5 y to detect fibroids ≥0.5cm in diameter. We used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between soy formula feeding and incident fibroids adjusted for early-life and adult factors. Fibroid growth was calculated as change in log-volume for fibroids matched at successive visits. RESULTS: Of 1,121 fibroid-free participants at baseline, 150 (13%) were ever fed soy formula as infants, and 269 (24%) developed incident fibroids. We did not observe an association between ever being fed soy formula and incident fibroid risk (HR=1.08; 95% CI: 0.75, 1.54). However, participants fed soy formula within 2 months of birth and for >6 months (n=53) had an elevated risk of fibroid incidence in comparison with those never fed soy formula (HR=1.56; 95% CI: 0.92, 2.65). Fibroid growth rates did not differ. DISCUSSION: Adding support to limited human data, this prospective fibroid study found that soy-based formula feeding during infancy was associated with a suggestive increase in risk of ultrasound-identified incident fibroids in adulthood. https://doi.org/10.1289/EHP11089.

Vitamin D and uterine fibroid growth, incidence, and loss: a prospective ultrasound study.

OBJECTIVE: Fibroid treatments that have few side-effects and can preserve fertility are a clinical priority. We studied the association between serum vitamin D and uterine fibroid growth, incidence, and loss. DESIGN: A prospective community cohort study (enrollment 2010-2012) with 4 study visits over 5 years to conduct standardized ultrasounds, measure 25-hydroxyvitamin D (25(OH)D), and update covariates. SETTING: Detroit, Michigan area. PATIENTS: Self-identified African American or Black women aged 23-35 at enrollment without previous clinical diagnosis of fibroids. INTERVENTION(S): Serum 25(OH)D measured using immunoassay or liquid chromatography-tandem mass spectrometry. MAIN OUTCOME MEASURE(S): The primary outcomes were fibroid growth, as measured by change in log volume per 18 months, and fibroid incidence (first detection of fibroid in previously fibroid-free uterus). Adjusted growth estimates from linear mixed models were converted to estimated difference in volume for high vs. low 25(OH)D. Incidence differences were estimated as hazard ratios from age-specific Cox regression. A secondary outcome fibroid loss (reduction in fibroid number between visits), was modeled using Poisson regression. Covariates (reproductive and hormonal variables, demographics, body mass index, current smoking) and 25(OH)D were modeled as time-varying factors. RESULT(S): At enrollment among 1,610 participants with ≥1 follow-up ultrasound, mean age was 29.2 years, 73% had deficient vitamin D (<20ng/mL), and only 7% had sufficient vitamin D (≥30ng/mL). Serum 25(OH)D ≥20ng/mL compared with <20ng/mL was associated with an estimated 9.7% reduction in fibroid growth (95% confidence interval [CI]: -17.3%, -1.3%), similar to the minimally adjusted estimate -8.4% (95% CI: -16.4, 0.3). Serum 25(OH)D ≥30ng/mL compared with <30ng/mL was associated with an imprecise 22% reduction in incidence (adjusted hazard ratio=0.78; 95% CI: 0.47, 1.30), similar to the unadjusted estimate of 0.84 (95% CI: 0.51, 1.39). The >30ng/mL group also had a 32% increase in fibroid loss (adjusted risk ratio=1.32; 95% CI: 0.95, 1.83). CONCLUSION(S): Our data support the hypothesis that high concentrations of vitamin D decrease fibroid development but are limited by the few participants with serum 25(OH)D ≥30ng/mL. Interventional trials that raise and maintain 25(OH)D concentrations >30ng/mL and then prospectively monitor fibroid development are needed to further assess supplemental vitamin D efficacy and determine optimal treatment protocols.

Association between serum vitamin D level and uterine fibroid in premenopausal women in Indian population.

We aim to evaluate the association between serum 25-hydroxyvitamin D3 levels and total number, volume and location of uterine fibroids (UFs) in premenopausal women in North Indian population. This case control study was undertaken in 310 women between 18 years and 45 years of age. Cases comprised of 102 women with fibroid lesion and the control group included 208 women with normal uterine morphology on ultrasonography. Blood samples were taken for measuring 25-hydroxyvitamin D3 levels. The mean serum 25-hydroxyvitamin D3 level in the study and control group was 14.52 ± 7.89 ng/mL and 26.6 ± 14.36 ng/mL respectively (p < 0.05). There was significant inverse correlation between serum 25-hydroxyvitamin D3 levels and total volume of fibroids (p = 0.000) while none between 25-hydroxyvitamin D3 levels with location, number of fibroids. 25-hydroxyvitamin D3 deficiency was more common in the study group (54.90%) compared to healthy controls (6.7%) while sufficiency was more common among controls (67.8% vs. 27.45) (p < 0.05). Women with deficient 25-hydroxyvitamin D3 levels have an odds of 18.36 for developing uterine fibroid. Women with low parity, those belonging to higher socioeconomic status and having less than 1-hour sun exposure per day were independently found to have high risk for development of UFs. Vitamin D may have a role in growth of UFs. Women not able to get adequate sun exposure due to indoor working conditions may need evaluation and supplementation as prophylaxis for development of fibroid.

Minimally invasive myomectomy: practice trends and differences between Black and non-Black women within a large integrated healthcare system.

BACKGROUND: Although multiple professional organizations encourage minimally invasive surgical approaches whenever feasible, nationally, fewer than half of myomectomies are performed via minimally invasive routes. Black women are less likely than their non-Black counterparts to have minimally invasive surgery. OBJECTIVE: This study aimed to assess the trends in surgical approach among women who underwent minimally invasive myomectomies for uterine leiomyomas within a large integrated healthcare system as initiatives were implemented to encourage minimally invasive surgery, particularly evaluating differences in the proportion of minimally invasive surgery performed in Black vs non-Black women. STUDY DESIGN: We conducted a retrospective cohort study of women, aged ≥18 years, who underwent a myomectomy for a uterine leiomyoma within Kaiser Permanente Northern California between 2009 and 2019. Generalized estimating equations and Cochran-Armitage testing were used to assess myomectomy incidence and linear trend in the proportions of myomectomy by surgical route-abdominal myomectomy and minimally invasive myomectomy. Multivariable logistic regression analyses were used to assess the associations between surgical route and (1) race and ethnicity and (2) complications, controlling for patient demographic, clinical, and surgical characteristics. RESULTS: A total of 4033 adult women underwent a myomectomy during the study period. Myomectomy incidence doubled from 0.12 (95% confidence interval, 0.12-0.13) per 1000 women in 2009 to 0.25 (95% confidence interval, 0.24-0.25) per 1000 women in 2019 (P<.001). During the 11-year study period, the proportion of minimally invasive myomectomy increased from 6.0% to 89.5% (a 15-fold increase). The proportion of minimally invasive myomectomy in Black women remained lower than in non-Black women (54.5% vs 64.7%; P<.001). Black women undergoing myomectomy were younger (36.4±5.6 vs 37.4±5.8 years; P<.001), had a higher mean fibroid weight (436.0±505.0 vs 324.7±346.1 g; P<.001), and had a higher mean body mass index (30.8±7.3 vs 26.6±5.9 kg/m2; P<.001) than their non-Black counterparts. In addition to patient race, surgery performed between 2016 and 2019 compared with surgery performed between 2009 and 2012 and higher surgeon volume compared with low surgeon volume were associated with an increased proportion of minimally invasive myomectomy (adjusted relative risks, 12.58 [95% confidence interval, 9.96-15.90] and 6.63 [95% confidence interval, 5.35-8.21], respectively). Black race and fibroid weight of >500 g each independently conferred lower rates of minimally invasive myomectomy. In addition, there was an interaction between race and fibroid weight such that Black women with a fibroid weight of ≤500 g or >500 g were both less likely to have minimally invasive myomectomy than non-Black women with a fibroid weight of ≤500 g (adjusted relative risks, 0.74 [95% confidence interval, 0.58-0.95] and 0.26 [95% confidence interval, 0.18-0.36], respectively). Operative, perioperative, and medical complications were low during the 11-year study period. In regression analyses, after controlling for race, age, fibroid weight, parity, low-income residence, body mass index, surgeon volume, and year of myomectomy, the risk of complications was not markedly different comparing abdominal myomectomy with minimally invasive myomectomy. Similar results were found comparing laparoscopic minimally invasive myomectomy with robotic-assisted minimally invasive myomectomy except for women who underwent laparoscopic minimally invasive myomectomy had a lower risk of experiencing any medical complications than those who underwent robotic-assisted minimally invasive myomectomy (adjusted relative risk, 0.27; 95% confidence interval, 0.09-0.83; P=.02). CONCLUSION: Within an integrated healthcare delivery system, although initiatives to encourage minimally invasive surgery were associated with a marked increase in the proportion of minimally invasive myomectomy, Black women continued to be less likely to undergo minimally invasive myomectomy than their non-Black counterparts. Race and fibroid weight alone did not explain the disparities in minimally invasive myomectomy.

Surveillance for gestational trophoblastic neoplasia following molar pregnancy: a cost-effectiveness analysis.

BACKGROUND: Historically, published guidelines for care after molar pregnancy recommended monitoring human chorionic gonadotropin levels for the development of gestational trophoblastic neoplasia until normal and then for 6 months after the first normal human chorionic gonadotropin. However, there are little data underlying such recommendations, and recent evidence has demonstrated that gestational trophoblastic neoplasia diagnosis after human chorionic gonadotropin normalization is rare. OBJECTIVE: We sought to estimate the cost-effectiveness of alternative strategies for surveillance for gestational trophoblastic neoplasia after human chorionic gonadotropin normalization after complete and partial molar pregnancy. STUDY DESIGN: A Markov-based cost-effectiveness model, using monthly cycles and terminating after 36 months/cycles, was constructed to compare alternative strategies for asymptomatic human chorionic gonadotropin surveillance after the first normal (none; monthly testing for 1, 3, 6, and 12 months; or every 3-month testing for 3, 6, and 12 months) for both complete and partial molar pregnancy. The risk of reduced surveillance was modeled by increasing the probability of high-risk disease at diagnosis. Probabilities, costs, and utilities were estimated from peer-reviewed literature, with all cost data applicable to the United States and adjusted to 2020 US dollars. The primary outcome was cost per quality-adjusted life year ($/quality-adjusted life year) with a $100,000/quality-adjusted life year willingness-to-pay threshold. RESULTS: Under base-case assumptions, we found no further surveillance after the first normal human chorionic gonadotropin to be the dominant strategy from both the healthcare system and societal perspectives, for both complete and partial molar pregnancy. After complete mole, this strategy had the lowest average cost (healthcare system, $144 vs maximum $283; societal, $152 vs maximum $443) and highest effectiveness (2.711 vs minimum 2.682 quality-adjusted life years). This strategy led to a slightly higher rate of death from gestational trophoblastic neoplasia (0.013% vs minimum 0.009%), although with high costs per gestational trophoblastic neoplasia death avoided (range, $214,000 to >$4 million). Societal perspective costs of lost wages had a greater impact on frequent surveillance costs than rare gestational trophoblastic neoplasia treatment costs, and no further surveillance was more favorable from this perspective in otherwise identical analyses. No further surveillance remained dominant or preferred with incremental cost-effectiveness ratio of <$100,000 in all analyses for partial mole, and most sensitivity analyses for complete mole. Under the assumption of no disutility from surveillance, surveillance strategies were more effective (by quality-adjusted life year) than no further surveillance, and a single human chorionic gonadotropin test at 3 months was found to be cost-effective after complete mole with incremental cost-effectiveness ratio of $53,261 from the healthcare perspective, but not from the societal perspective (incremental cost-effectiveness ratio, $288,783). CONCLUSION: Largely owing to the rare incidence of gestational trophoblastic neoplasia after human chorionic gonadotropin normalization after molar pregnancy, prolonged surveillance is not cost-effective under most assumptions. It would be reasonable to reduce, and potentially eliminate, current recommendations for surveillance after human chorionic gonadotropin normalization after molar pregnancy, particularly among partial moles. With any reduction in surveillance, patients should be counseled on symptoms of gestational trophoblastic neoplasia and established in routine gynecologic care.

Vitamin D: Mechanism of Action and Biological Effects in Uterine Fibroids.

Uterine fibroids (UFs) are the most common benign gynecological tumors. It was estimated that fifty percent of women presenting with UFs has symptomatology that negatively influences their quality of life. Pharmacological and/or surgical treatments are frequently required, depending on the woman's desire to preserve fertility, with a high impact on healthcare costs. Generally, the use of currently available pharmacological treatments may lead to side effects. Therefore, there is a growing interest in a natural and safe approach for UFs. In recent years, epidemiological studies reported a vitamin D deficiency in patients with UFs raised interest in the potential biological effects of vitamin D supplementation. In vitro studies proved vitamin D efficacy in inhibiting UFs growth by targeting pathways involved in the regulation of various biological processes, including proliferation, extracellular matrix (ECM) remodeling, DNA repair, signaling and apoptosis. However, clinical studies supported only in part the beneficial effects of vitamin D supplementation in reducing UFs growth and tumor volume. Randomized controlled trials and large population studies are mandatory as the potential clinical benefits are likely to be substantial.

Intake of Lycopene and other Carotenoids and Incidence of Uterine Leiomyomata: A Prospective Ultrasound Study.

BACKGROUND: Uterine leiomyomata (UL) are the leading indication for hysterectomy in the United States. Dietary supplementation with lycopene was associated with reduced size and incidence of oviduct leiomyoma in the Japanese quail. Two US prospective cohort studies of women reported little association between intake of lycopene, or other carotenoids, and UL incidence. However, these studies relied on self-reported physician-diagnosed UL, which is prone to misclassification. OBJECTIVE: This study examines the association between dietary intake of carotenoids and UL incidence. DESIGN: Data were derived from the Study of the Environment, Lifestyle, and Fibroids, a prospective cohort study. Women completed self-administered baseline questionnaires on demographic characteristics, reproductive history, and lifestyle, including a 110-item validated food frequency questionnaire, from which dietary intakes of carotenoids-including alpha carotene, beta carotene, cryptoxanthin, lutein-zeaxanthin, and lycopene-and vitamin A were estimated. PARTICIPANTS/SETTING: One thousand two hundred thirty Black women aged 23 to 35 years who did not have a previous diagnosis of UL, cancer, or autoimmune disease were eligible for enrollment (2010-2012). Participants were residents of the Detroit, MI, metropolitan area. MAIN OUTCOME MEASURES: Transvaginal ultrasound was used to assess UL at baseline and 20, 40, and 60 months of follow-up. STATISTICAL ANALYSES PERFORMED: Cox regression was used to estimate hazard ratios and 95% CIs, adjusted for energy intake, age at menarche, education, body mass index, parity, age at first birth, years since last birth, current use of oral contraceptives or progestin-only injectables, alcohol intake, and cigarette smoking. RESULTS: Among 1,230 women without prevalent UL at baseline, 301 incident UL cases during follow-up were identified. Intakes of lycopene, other carotenoids, and vitamin A were not appreciably associated with UL incidence. Hazard ratios comparing quartiles 2 (2,376 to 3,397 µg/day), 3 (3,398 to 4,817 µg/day), and 4 (≥4,818 µg/day) with quartile 1 (<2,376 µg/day) of lycopene intake were 1.03 (95% CI 0.72 to 1.47), 1.22 (95% CI 0.86 to 1.72), and 0.95 (95% CI 0.67 to 1.36), respectively. CONCLUSIONS: Study findings do not support the hypothesis that greater carotenoid intake is associated with reduced UL incidence.

Increasing Awareness of Uterine Cancer Risks and Symptoms by Using Campaign Materials from Inside Knowledge: Get the Facts About Gynecologic Cancer.

Uterine cancer is the fourth most commonly diagnosed cancer among women in the USA. To increase knowledge among women and healthcare providers about uterine cancer, the Centers for Disease Control and Prevention's National Comprehensive Cancer Control Program (NCCCP) partnered with the Inside Knowledge: Get The Facts About Gynecologic Cancer campaign to present facilitated discussions about uterine cancer with women and providers. After standardized training, local NCCCP grantees developed and led community-based, tailored, facilitated discussions for public participants and providers. Pre- and post-session surveys were administered to assess knowledge of risk factors, symptoms, testing, and diagnostic options for uterine cancer. Following the facilitated sessions, significantly, more public respondents identified uterine cancer risk factors (e.g., advanced age, post-menopausal status). However, they also equally identified factors not associated with uterine cancer (e.g., smoking, HPV). Non-OB/GYN provider knowledge increased, significantly for some risks and symptoms, and their confidence with relaying uterine cancer information to patients significantly increased from 51.4 to 91.0% (P < 0.0001). Relatively low proportions of OB/GYNs (19.3%), other primary care providers (46.2%), and public participants (51.8%) knew post-session that genetic testing for Lynch syndrome can help stratify women for uterine cancer risk. Participant knowledge significantly increased for some risk factors and symptoms following Inside Knowledge educational sessions; however, some knowledge gaps remained. Overall, the Inside Knowledge materials are effective for increasing uterine cancer awareness among providers and women. Additional provider education could include specific resources related to uterine cancer genetic associations, as advancements in genetic testing for all uterine cancers are currently being made.

Radiofrequency Thermal Ablation for Uterine Myomas: Long-term Clinical Outcomes and Reinterventions.

STUDY OBJECTIVE: To assess the long-term efficacy and rate of reintervention after ultrasound-guided radiofrequency thermal ablation (RFA) for uterine myomas. DESIGN: A retrospective follow-up, cohort study (Canadian Task Force classification II-2). SETTING: University hospitals and private clinics. PATIENTS: Between November 1, 2007, and February 26, 2010, 66 consecutive women underwent ultrasound-guided RFA. INTERVENTIONS: Patients underwent abdominal or vaginal ultrasound-guided RFA and were contacted for a long-term follow-up to complete the Uterine Fibroid Symptom and Quality of Life Score (UFS-QOL) questionnaire and optional ultrasound and examination. MEASUREMENTS AND MAIN RESULTS: Sixty-six consecutive patients (mean age 45 ± 7 years) with type 2 to 5 symptomatic myomas per the International Federation of Gynecology and Obstetrics (median size = 122.5 cm3 [range, 24-675]) were included. Forty of 62 patients recruited for follow-up underwent no/minor hysteroscopic reinterventions; 35 patients from this group completed the UFS-QOL questionnaire and showed sustained and improved symptom severity scores (100-point scale) from baseline (57.2 ± 16.6) to long-term follow-up (23.8 ± 20.8, p < .001). Twenty-two patients (35%) had major reinterventions (15 hysterectomies and 7 myomectomies). Six of the 22 patients underwent major reinterventions for reasons other than myoma-related complaints. The estimated major reintervention rate because of myoma-related symptoms determined by the Kaplan-Meier method was 13.5% (95% confidence interval [CI], 7%-25%) after 2 years and 29.1% (95% CI, 19%-43%) after 5 years. Women ≥45 years of age had a major reintervention rate of 12% (95% CI, 5%-26%) after 2 years and 19% (95% CI, 10%-35%) after 5 years, and women <45 years had a major reintervention rate of 35.0% (95% CI, 19%-60%) and 73.8% (95% CI, 52%-92%) after 2 and 5 years, respectively. Fewer major reinterventions occurred in women with only 1 RFA-treated myoma (volume ≤180 cm3, diameter <7 cm) than women with more than 1 RFA-treated myoma (>180 cm3, p < .01). The Kaplan-Meier estimates for reintervention in women with only 1 RFA-treated myoma with a volume ≤180 cm3 were 13% (95% CI, 6-28%) and 26% (95% CI, 14%-45%) after 2 and 5 years, respectively. No patients with morphologic myoma characteristics underwent reinterventions. CONCLUSION: Ultrasound-guided RFA for uterine myomas is an alternative treatment option especially for women ≥45 years of age with only 1 myoma (volume ≤180 cm3) and warrants further evaluation.

Minilaparotomy Versus Laparoscopic Myomectomy After Cessation of Power Morcellation: Rate of Wound Complications.

STUDY OBJECTIVE: After the US Food and Drug Administration statement warning against electronic morcellation devices, gynecologic surgeons are performing laparoscopic and robotic myomectomies with minilaparotomy incisions for tissue morcellation and removal. No data exist that focus on the superficial wound complications as a result of these larger incisions. The objective of this study is to compare the rate of wound complications for myomectomy via minilaparotomy versus laparoscopic or robotic myomectomy. DESIGN: Retrospective cohort study (Canadian Task Force classification II-2). SETTING: Kaiser Permanente Northern California, a large integrated healthcare delivery system. PATIENTS: Women > 18 years of age who underwent a myomectomy from either complete laparoscopic or robotic approach (LR) were compared with minilaparotomy myomectomy (MM), comprising complete minilaparotomy (ML) and laparoscopic or robotic assisted by a minilaparotomy for morcellation purposes only (LRM) from January 2011 through December 2014. INTERVENTION: Myomectomy via LR, complete ML, and LRM. MEASUREMENTS AND MAIN RESULTS: Medical records were reviewed for outcomes of interest, including superficial wound complications and surgical and demographic data. After exclusion criteria were met, 405 cases were included in the study; 270 cases were classified as MM, which included ML (n = 224), or LRM (n = 46). One hundred thirty-five cases were classified as LR. Parametric and nonparametric analyses were used to compare the 2 groups. There was no significant difference between the groups insofar as patient morbidity, including the primary outcome of wound complications and other postoperative complications; emergency visits; or readmissions. There were 2 (1.5%) wound complications in the LR group and 7 (2.6%) in the MM group (p = .72). Similarly, there were no significant differences in the subcategories of wound complications, including cellulitis, seroma, hematoma, skin separation, wound infection, or postprocedure wound complication. The distribution of estimated blood loss was significantly different between LR and MM groups with an interquartile range of 50 to 150 mL in the LR group versus 50 to 300 mL in the MM group (p < .01). The MM group experienced a shorter procedure time with a median procedure time of 125 minutes compared with 169.5 minutes in LR surgeries (p < .01). The LR group demonstrated a significantly shorter median length of hospital stay (LR 5.0 hours vs MM 23 hours; p < .01). CONCLUSION: Compared with MM, LR is associated with a shorter length of hospital stay and longer operating time but no reduction in wound complication or other patient morbidity.

Occult Uterine Sarcoma and Leiomyosarcoma: Incidence of and Survival Associated With Morcellation.

OBJECTIVE: To estimate the incidence of occult uterine sarcoma and leiomyosarcoma in hysterectomies for leiomyomas and the risk associated with their morcellation. METHODS: We conducted a population-based cohort study. All uterine sarcomas from 2006-2013 in an integrated health care system were identified. Age- and race-specific incidences of occult uterine sarcoma were calculated. Kaplan-Meier survival analysis was performed. Crude and adjusted risk ratios of recurrence and death associated with morcellation at 1, 2, and 3 years were estimated using Poisson regression with inverse probability weighting. RESULTS: There were 125 hysterectomies with occult uterine sarcomas identified among 34,728 hysterectomies performed for leiomyomas. The incidence of occult uterine sarcoma and leiomyosarcoma was 1 of 278 or 3.60 (95% confidence interval [CI] 2.97-4.23) and 1 of 429 or 2.33 (95% CI 1.83-2.84) per 1,000 hysterectomies. For stage I leiomyosarcoma (n=111), eight (7.2%) were power and 27 (24.3%) nonpower-morcellated. The unadjusted 3-year probability of disease-free survival for no morcellation, power and nonpower morcellation was 0.54, 0.19, and 0.51, respectively (P=.15); overall survival was 0.64, 0.75, and 0.68, respectively (P=.97). None of the adjusted risk ratios for recurrence or death were significant except for death at 1 year for power and nonpower morcellation groups combined (6/33) compared with no morcellation (4/76) (5.12, 95% CI 1.33-19.76, P=.02). We had inadequate power to infer differences for all other comparisons including 3-year survival and power morcellation. CONCLUSION: Morcellation is associated with decreased early survival of women with occult leiomyosarcomas. We could not accurately assess associations between power morcellation and 3-year survival as a result of small numbers.

Urinary isoflavone and lignan phytoestrogen levels and risk of uterine fibroid in Jamaican women.

BACKGROUND: Isoflavones and lignans are phytoestrogens, and therefore, are able to bind to and activate estrogen receptors. The resultant estrogenic or antiestrogenic effect is dependent on the concentration of these phytoestrogens relative to endogenous estrogens and the site of their action, among others. Thus, isoflavones and lignans act as selective estrogen receptor modulators; having a beneficial effect in some tissues while simultaneously causing deleterious changes in others. OBJECTIVE: This case-control study investigates the relationship between urinary concentrations of genistein, daidzein, equol, and enterolactone, and the presence of uterine leiomyomas (fibroids) in Jamaican women. DESIGN: Phytoestrogen concentration in spot urine samples from 157 uterine fibroid cases and 171 fibroid-free controls diagnosed by ultrasonography, were assessed by Time-resolved Fluoroimmnoassay. Statistical evaluations were performed using SPSS 12.0. RESULTS: The median concentration of urinary enterolactone was significantly different between uterine fibroid cases and controls (p=0.029). However, this was not observed to affect risk of uterine fibroid, as trends across quartiles of urine enterolactone did not differ significantly between cases and controls. Median urinary genistein (p=0.510), daidzein (p=0.838), equol (p=0.621), total isoflavones (0.510) and total phytoestrogens (p=0.084) were similar for both groups. Binary logistic regression analysis of quartiles of urine genistein, daidzein, equol, enterolactone, total isoflavones, and total phytoestrogens showed no association with uterine fibroid. CONCLUSIONS: Uterine fibroid cases had a higher median urine concentration of enterolactone compared with controls. However, this was not observed to affect ones risk of fibroid. Neither was urine genistein, daidzein, equol total isoflavones, and total phytoestrogens observed to be associated with risk of uterine fibroid.

Higher risk for meningioma in women with uterine myoma: a nationwide population-based retrospective cohort study.

OBJECT: Evidence suggests that hormones play a role in modifying both uterine myoma (UM) and meningioma. A number of studies have observed the positive association between these diseases. The aim of the current population-based study was to determine if women with UM are at a higher risk for meningioma. METHODS: The authors used data from the National Health Insurance system of Taiwan for the study. The UM cohort contained 281,244 women. Each woman was randomly frequency-matched with 4 women without UM, based on age, index year of diagnosis, occupation, urbanization (urbanization level was categorized by the population density of the residential area into 4 levels, with Level 1 as the most urbanized and Level 4 as the least urbanized), and comorbidity, to form the control cohort. Cox's proportional hazard regression analysis was conducted to estimate the influence of UM on the meningioma risk. RESULTS: Among women with UM, the risk of developing meningioma was significantly higher (45%) than among women without UM (95% CI 1.23-1.70). The same phenomenon was observed among most age groups, but a significant difference was only seen in the middle-age range. For women with UM, further analysis did not show a significant change after myomectomy. The cumulative incidence of meningioma between groups with and without UM differed over time. CONCLUSIONS: The nationwide population-based cohort study found that Taiwanese women with UM are at higher risk for developing meningioma.

Survey among German gynecologists on the clinical management of patients with sarcomas of the uterus.

AIM: To gain more information about the knowledge of the clinical management of uterine sarcoma. MATERIALS AND METHODS: This survey was performed among members of the North-Eastern German Society of Gynecological Oncology (NOGGO) and the German Society of Psychosomatic Medicine in Gynecology and Obstetrics (DGPFG) on the treatment of uterine sarcomas. RESULTS: Altogether, 374 gynecologists took part. When asked about the surgical therapy of leiomyosarcoma, 64% indicated hysterectomy with bilateral adenectomy and lymph node dissection. Answers on the extent of lymphadenectomy in leiomyosarcoma differed widely. When asked about the preferred chemotherapy regimen for metastatic uterine sarcoma, more than 60% of all gynecologists would not apply any chemotherapy. Almost 40% recommended any kind of radiotherapy in this situation. CONCLUSION: There is a great uncertainty about the standard treatment of uterine sarcoma, even among specialists of gynecological oncology. It is time for organized efforts to improve the treatment of uterine sarcoma.

Clinical epidemiology and management of gestational trophoblastic neoplasia in Hungary in the past 34 years.

OBJECTIVE: To review our clinical experience in the treatment of patients with gestational trophoblastic neoplasia (GTN) over the past 34 years in our national trophoblastic disease center. STUDY DESIGN: Between January 1, 1977, and December 31, 2010, 331 patients with low-risk GTN and 174 patients with high-risk GTN (altogether 505) were treated. The patients were directed to the national trophoblastic disease center from all parts of Hungary. The patients were between 14 and 54 years of age, with an average age of 28.7 years. Primary chemotherapy was selected based upon the patient's stage and prognostic score of GTN. RESULTS: Among 237 low-risk patients, 228 (96.2%) achieved remission as a result of primary methotrexate (MTX) therapy. Out of 94 low-risk patients 90 (95.7%) achieved remission as a result of primary actinomycin-D (Act-D) therapy. MTX, Act-D and cyclophosphamide (MAC) as a primary therapy was used in 118 high-risk cases, and 110 (93.2%) patients achieved complete remission. A total of 32 high-risk patients were treated with the etoposide, high-dose MTX/folinic acid, Act-D, cyclophosphamide and vincristine (EMA-CO) regimen, and of 26 primary therapies complete remission was achieved in 21 (80.8%) cases. Primary cisplatin, etoposide and bleomycin (CEB) therapy was successful in 16 of 17 high-risk cases (94.1%). Metastases were found in 47.3% (239/505) of the patients. Hysterectomy was performed in 68 of 505 (13.5%) cases. Chemotherapy, surgical intervention or other supplementary treatments resulted in 100% remission in cases of nonmetastatic and metastatic low-risk disease. Comparison of mean prognostic scores resulted in significant differences between CEB and MAC, CEB and EMA-CO, and MAC and EMA-CO. CONCLUSION: Our data indicate that MTX/folinic acid or Act-D should be the primary treatment in patients with nonmetastatic or metastatic low-risk GTN. Patients with high-risk metastatic GTN should be treated primarily with combination chemotherapy. Our data support the effectiveness of MAC, EMA-CO and CEB regimens. Results also show that patient care under the direction of experienced clinicians serves to optimize the opportunity for cure and minimize morbidity.

Validation of the aging hen (Gallus gallus domesticus) as an animal model for uterine leiomyomas.

Uterine leiomyomas, or fibroids, are the most frequent gynecological tumors in premenopausal women with as many as 65% of women becoming clinically symptomatic. Uterine fibroids are benign myometrial tumors that produce large quantities of extracellular matrix proteins. Despite its high morbidity, the molecular basis underlying the development of uterine leiomyomas is not well understood. Domestic hens of Gallus gallus domesticus develop oviductal leiomyomas similar to those found in humans. We investigated the natural history of chicken leiomyomas, in vivo expression of protein biomarkers, and in vitro expression of ovarian steroid receptors. Based on the analysis of 263 hens, tumor prevalence, tumor number per hen, and tumor size increased as the hens aged. Immunohistochemistry for alpha-smooth muscle actin (SMA) and desmin confirmed the smooth muscle phenotype of the chicken leiomyomas. Intense collagen expression was detected in these oviductal leiomyomas by Mason's trichrome, and the tumors also showed increased expression of TGFB3 and collagen type I mRNAs. Consistent with human leiomyomas, chicken fibroids displayed increased BCL2 and estrogen (E) and progesterone (P) receptor expression. Chicken leiomyomas were dissociated for in vitro culture. Cells from explants were positive for SMA, desmin, and E and P receptors until the fourth passage. These cells also displayed a response similar to human cells when challenged with halofuginone, an antifibrotic agent. Our findings indicate that the chicken is an excellent complementary model for studies involving the pathophysiology of human uterine leiomyomas.

Molecular pathways: digoxin use and estrogen-sensitive cancers--risks and possible therapeutic implications.

Digoxin, a phyto-estrogen, binds with estrogen receptors (ER) and can cause gynecomastia. Among women currently using digoxin, breast and uterus cancer incidences are significantly increased (approximate risk ratios, 1.3-1.5). Both cancers are often estrogen sensitive. In contrast, ovary and cervix cancers are relatively estrogen insensitive, and incidence is unaffected by digoxin exposure. When digoxin use stops, incidence rapidly reverts to that in nonusers. These patterns parallel those of estrogen, suggesting that digoxin works via ER-stimulated proliferation of ductal and/or acinar cells, accelerating the growth of nascent cancers. Also consistent with an estrogenic effect, men using digoxin have a small but significant reduction in prostate cancer (risk ratio, 0.76). Other estrogen-like drugs, particularly spironolactone, should be investigated for similar effects. The effect of digoxin use in women being treated for breast cancer or in survivors is unknown. Women with estrogen-sensitive cancers on adjuvant therapy may take tamoxifen, which blocks ERs. However, postmenopausal patients may use aromatase inhibitors, which block estrogen production while leaving ERs susceptible to digoxin. If adverse effects are found, tamoxifen may be preferred over aromatase inhibitors in patients receiving estrogen-mimicking drugs. Alternatively, other cardiotropic drugs might be considered in women with or at high risk of developing estrogen-sensitive cancers.

Intake of fruit, vegetables, and carotenoids in relation to risk of uterine leiomyomata.

BACKGROUND: US black women have higher rates of uterine leiomyomata (UL) and lower intakes of fruit and vegetables than do white women. Whether fruit and vegetable intake is associated with UL in black women has not been studied. OBJECTIVE: We assessed the association of dietary intake of fruit, vegetables, carotenoids, folate, fiber, and vitamins A, C, and E with UL in the Black Women's Health Study. DESIGN: In this prospective cohort study, we followed 22,583 premenopausal women for incident UL (1997-2009). Diet was estimated by using food-frequency questionnaires in 1995 and 2001. Cox regression was used to derive incidence rate ratios (IRRs) and 95% CIs for the association between each dietary variable (in quintiles) and UL. RESULTS: There were 6627 incident cases of UL diagnosed by ultrasonography (n = 4346) or surgery (n = 2281). Fruit and vegetable intake was inversely associated with UL (≥4 compared with <1 serving/d; IRR: 0.90; 95% CI: 0.82, 0.98; P-trend = 0.03). The association was stronger for fruit (≥2 servings/d compared with <2 servings/wk; IRR: 0.89; 95% CI: 0.81, 0.98; P-trend = 0.07) than for vegetables (≥2 servings/d compared with <4 servings/wk: IRR: 0.97; 95% CI: 0.89, 1.05; P-trend = 0.51). Citrus fruit intake was inversely associated with UL (≥3 servings/wk compared with <1 serving/mo: IRR: 0.92; 95% CI: 0.86, 1.00; P-trend = 0.01). The inverse association for dietary vitamin A (upper compared with lower quintiles: IRR: 0.89; 95% CI: 0.83, 0.97; P-trend = 0.01) appeared to be driven by preformed vitamin A (animal sources), not provitamin A (fruit and vegetable sources). UL was not materially associated with dietary intake of vitamins C and E, folate, fiber, or any of the carotenoids, including lycopene. CONCLUSION: These data suggest a reduced risk of UL among women with a greater dietary intake of fruit and preformed vitamin A.

[Predisposing factors of hysteromyoma and effect of hualiu recipe on it].

OBJECTIVE: To observe the clinical efficacy of hualiu recipe (HLR) in treating hysteromyoma, and to explore the correlation between the predisposing factors and the tumor volume as well as the therapeutic efficacy. METHODS: One hundred and ten outpatients with hysteromyoma of qi deficiency blood stasis syndrome were enrolled, who were outpatients of Department of Gynecology, Shanghai Yueyang Hospital of Integrative Medicine from September 2005 to September 2007. Their predisposing factors were collected by questionnaire. They were randomly assigned to two groups. The eighty patients in the treatment group were treated with HLR, while the thirty patients in the control group were treated with Guizhi Fuling Capsule. The clinical efficacy and changes of uterus and tumor volumes before and after treatment, improvement of Chinese syndrome, and the correlation between the therapeutic efficacy and predisposing factors were observed. RESULTS: The total effective rate in the treatment group was 85.0% (68/80), while that in the control group was 66.7% (20/30), showing statistical significance (P < 0.05). The therapeutic efficacy of patients with predisposing factors was better in the treatment group than in the control group, showing significant difference (P < 0.05). The tumor volume was observed to be positively correlated with the delivery age, the disease course, and the emotional stress. The clinical efficacy was negatively correlated with the disease course, the emotional stress, and the hyperplasia of mammary glands. CONCLUSION: HLR could effectively reduce the tumor volume of hysteromyoma, and obviously improve clinical symptoms and accompanied disease. The therapeutic efficacy could be improved by prevention and treatment of predisposing factors.