Simvastatin-loaded liposome nanoparticles treatment for uterine leiomyoma in a patient-derived xenograft mouse model: a pilot study.

Uterine leiomyomas are complex tumours with limited medical treatment options. Simvastatin is used to treat hypercholesterolaemia and has shown promising effects as a treatment option for leiomyomas. Previously, our group demonstrated a promising effect of simvastatin treatment in a patient-derived xenograft mouse model. Here, we tested the efficacy of simvastatin liposomal nanoparticles (NPs). After bilateral leiomyoma xenograft implantation, mice (N = 12) were divided into three treatment arms: control, simvastatin and simvastatin-loaded liposome NPs (simvastatin-NPs). Treatment with simvastatin significantly reduced tumour volume and inhibited the Ki67 expression when compared to the control group. There was a trend of reduced tumour volume and Ki67 expression after treatment with simvastatin-NP; however, the results were not significant. Due to low bioavailability and short half-life of simvastatin, liposomal NPs have the potential to enhance drug delivery, however, in this study NP did not provide improvement over simvastatin, but did demonstrate their potential for the delivery of simvastatin.Impact statementWhat is already known on this subject? Simvastatin treatment in a patient-derived xenograft mouse model reduced tumour growth and decreased proliferation.What do the results of this study add? Treatment with simvastatin significantly reduced tumour volume and inhibited the Ki67 expression when compared to the control group. There was a trend of reduced tumour volume and Ki67 expression after treatment with simvastatin-NP, however, it did not improve the efficacy of simvastatin at reducing tumour growth and proliferation.What are the implications of these findings for clinical practice and/or further research? More studies are needed to optimise the formulation of NPs to further enhance the sustainable delivery of simvastatin.

Safety and efficacy of robotic-assisted Burch for pure stress urinary incontinence: a large case series.

Burch urethropexy is one of the earliest and most effective surgeries for stress urinary incontinence. Minimally invasive robotic surgery is becoming more popular in the field of urogynecology. Herein, we present the safety and efficacy of a large case series of robotic-assisted Burch urethropexy. A retrospective chart review was performed on robotic-assisted Burch urethropexy cases performed between 2013 and 2019. Patient characteristics, perioperative data and follow-up outcomes were collected at a single teaching institution. A total of 76 women underwent robotic-assisted Burch urethropexy for pure stress urinary incontinence. Fifty of them had concomitant robotic procedures at the time of the Burch. We performed the robotic-assisted Burch urethropexy alone on 26 patients. The mean age was 55 years old. The overall treatment success rate was 85% with a mean follow-up time of 134 (±157.8) days. Complications included cystotomy (3%), urinary tract infection (16%) and postoperative voiding dysfunction (10%). Our study reveals that robotic-assisted Burch urethropexy is a feasible option in the treatment of stress urinary incontinence in terms of operative outcomes and short-term efficacy.Impact statementWhat is already known on this subject? Minimally invasive robotic surgery is becoming more popular in the field of urogynecology. Surgical repairs for stress urinary incontinence will likely increase in the coming years secondary to an aging population. Burch urethropexy is one of the earliest and most effective surgeries for stress urinary incontinence and can be performed abdominally, laparoscopically and now, using robotic assistance.What do the results of this study add? This study reveals that robotic-assisted Burch urethropexy is a feasible option in the treatment of stress urinary incontinence in terms of intraoperative outcomes with good short-term efficacy.What are the implications of these findings for clinical practice and/or further research? Lately, interest in colposuspension procedures has been rekindled as physicians seek alternative stress urinary incontinence treatment options. Robotic-assisted Burch urethropexy will continue to gain popularity with its efficacy and safety.

Medicolegal Review of Methotrexate Administration to Viable Intrauterine Pregnancies.

Objective: To examine 3 legal cases in which physicians prescribed methotrexate to women with a viable intrauterine pregnancy, presumed to be ectopic, resulting in adverse fetal outcomes. Study Design: We conducted an electronic literature search for legal cases using the keywords "methotrexate" and "pregnancy" in the LexisNexis legal research engine as well as an Internet-wide search using the additional keyword "verdict." We manually searched the resultant list of identified cases and categorized the studies identified in the search by verdict, award amount, and outcome of the embryo exposed to methotrexate. Results: The monetary awards are typically greater when the embryo exposed to methotrexate lives and requires continuous medical and custodial care as compared to when the fetus dies in utero or shortly after birth. Conclusion: Physicians who, with all good intentions, prescribe methotrexate to women with a viable pregnancy, presumed to be ectopic, could find them-selves liable for an adverse fetal outcome. For the benefit of patients, their unborn offspring, and the liability exposure of the physician, it is important to be very cautious when prescribing methotrexate.

Statin use and uterine fibroid risk in hyperlipidemia patients: a nested case-control study.

BACKGROUND: Statins are 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors primarily used for treatment of hyperlipidemia. Recently, they have been shown to inhibit proliferation of uterine fibroid cells and inhibit tumor growth in fibroid animal models. OBJECTIVE: We sought to examine the association between statin use and the risk of uterine fibroids and fibroid-related symptoms in a nationally representative sample of commercially insured women diagnosed with hyperlipidemia. STUDY DESIGN: We performed a nested case-control study of >190,000 women enrolled in one of the nation's largest commercial health insurance programs. From a cohort of women aged 18-65 years diagnosed with hyperlipidemia from January 2004 through March 2011, we identified 47,713 cases (women diagnosed with uterine fibroids) and 143,139 controls (women without uterine fibroids) matched at a 1:3 ratio on event/index date (month and year) and age (±1 year). We used conditional and unconditional logistic regression to calculate odds ratios and 95% confidence intervals for the risk of uterine fibroids and fibroid-related symptoms associated with prior use of statins. RESULTS: Exposure to statins within 2 years before the event/index date was associated with a decreased risk of uterine fibroids (odds ratio, 0.85; 95% confidence interval, 0.83-0.87). In a separate subanalysis restricted to cases, statin users had a lower likelihood of having menorrhagia (odds ratio, 0.88; 95% confidence interval, 0.84-0.91), anemia (odds ratio, 0.84; 95% confidence interval, 0.79-0.88), or pelvic pain (odds ratio, 0.85; 95% confidence interval, 0.81-0.91) and of undergoing myomectomy (odds ratio, 0.76; 95% confidence interval, 0.66-0.87) compared to nonusers. CONCLUSION: The use of statins was associated with a lower risk of uterine fibroids and fibroid-related symptoms. Further studies, including randomized controlled trials, may be warranted.

Simvastatin potently induces calcium-dependent apoptosis of human leiomyoma cells.

Statins are drugs commonly used for the treatment of high plasma cholesterol levels. Beyond these well known lipid-lowering properties, they possess broad-reaching effects in vivo, including antitumor effects. Statins inhibit the growth of multiple tumors. However, the mechanisms remain incompletely understood. Here we show that simvastatin inhibits the proliferation of human leiomyoma cells. This was associated with decreased mitogen-activated protein kinase signaling and multiple changes in cell cycle progression. Simvastatin potently stimulated leiomyoma cell apoptosis in a manner mechanistically dependent upon apoptotic calcium release from voltage-gated calcium channels. Therefore, simvastatin possesses antitumor effects that are dependent upon the apoptotic calcium release machinery.

Signaling Pathways in Leiomyoma: Understanding Pathobiology and Implications for Therapy.

Uterine leiomyomas are the most common tumors of the female genital tract, affecting 50% to 70% of females by the age of 50. Despite their prevalence and enormous medical and economic impact, no effective medical treatment is currently available. This is, in part, due to the poor understanding of their underlying pathobiology. Although they are thought to start as a clonal proliferation of a single myometrial smooth muscle cell, these early cytogenetic alterations are considered insufficient for tumor development and additional complex signaling pathway alterations are crucial. These include steroids, growth factors, transforming growth factor-beta (TGF-ß)/Smad; wingless-type (Wnt)/ß-catenin, retinoic acid, vitamin D, and peroxisome proliferator-activated receptor γ (PPARγ). An important finding is that several of these pathways converge in a summative way. For example, mitogen-activated protein kinase (MAPK) and Akt pathways seem to act as signal integrators, incorporating input from several signaling pathways, including growth factors, estrogen and vitamin D. This underlines the multifactorial origin and complex nature of these tumors. In this review, we aim to dissect these pathways and discuss their interconnections, aberrations and role in leiomyoma pathobiology. We also aim to identify potential targets for development of novel therapeutics.

Novel effects of simvastatin on uterine fibroid tumors: in vitro and patient-derived xenograft mouse model study.

OBJECTIVE: Uterine leiomyomas represent a common gynecologic problem with no satisfactory long-term medical treatment. The purpose of this study is to examine the effects of simvastatin on uterine leiomyoma, both in vitro and in vivo. STUDY DESIGN: This is a laboratory-based experimental study. For in vitro studies, we used human and rat leiomyoma cells. For in vivo studies, we used immunodeficient mice supplemented with estrogen/progesterone pellets xenografted with human leiomyoma tissue explant. RESULTS: For in vitro studies, cells were treated with different concentrations of simvastatin for 48 hours. Simvastatin induced dose-dependent apoptosis in leiomyoma cells as measured by a fluorometric caspase-3 activity assay, and inhibited proliferation as demonstrated by an (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay (both were significant at 5 and 10 µM). In addition, simvastatin decreased Akt signaling pathway phosphorylation as examined using Western blot analysis. For in vivo studies, animals were treated for 28 days with simvastatin (20 µg/gm body weight/day) vs vehicle control. The treatment inhibited tumor growth as measured weekly using calipers and/ or ultrasound (P < .01). Finally, simvastatin decreased expression of the proliferation marker Ki67 in xenograft tumor tissue as examined by immunohistochemistry (P = .02). CONCLUSION: Simvastatin can be a promising treatment for uterine leiomyoma. Further studies, including pharmacokinetic and drug delivery studies, are required.

A medical-legal review of power morcellation in the face of the recent FDA warning and litigation.

Minimally invasive gynecologic surgeons who perform laparoscopic intraperitoneal morcellation should be aware of the recent US Food and Drug Administration (FDA) warning and litigation arising from use of morcellation devices with claims of intraperitoneal dissemination of cancerous cells. On November 24, 2014, the FDA issued a statement warning against using laparoscopic power morcellators in the majority of women undergoing hysterectomy or myomectomy for uterine fibroids. Despite the best intentions in regards to their patients, gynecologists who continue to use power morcellation devices expose themselves to liability. This article is not meant to further deter gynecologists from using laparoscopic power morcellators, but rather to provide an interpretation of the FDA statement as to the patients for whom the use of power morcellation may still be permitted under the FDA guidelines. This article also offers protective measures from a legal perspective for those who choose to continue to use power morcellation in the face of the recent FDA warning and litigation.

Trends in the national distribution of laparoscopic hysterectomies from 2003 to 2010.

STUDY OBJECTIVE: The purpose of this analysis was to compare the trends in undergoing laparoscopic hysterectomy (versus abdominal or vaginal hysterectomy) based on patient age, race, median income and insurance type, from 2003 to 2010. DESIGN: Retrospective study (Canadian Task Force classification II-3). SETTING: National sample of hospital admissions after hysterectomy. PATIENTS: Health Cost and Utilization Project-Nationwide Inpatient Sample database was used to review records of women who underwent hysterectomy for either menorrhagia or leiomyoma from 2003-2010. INTERVENTION: The predicted probability of undergoing laparoscopic hysterectomy was determined for each year according to patient age, race, median income, and insurance type. The slopes of these values (i.e. the trend) was compared for each subgroup (i.e. black, white, Asian, etc.) in these categories. MAIN RESULTS: A total of 530, 154 cases were included in this study. Total number of hysterectomies decreased by 39% from 60,364 to 36,835 from 2003 to 2010. The percent of hysterectomies that were laparoscopic increased from 11% in 2003 to 29% in 2010. All groups analyzed experienced an increase in predicted probability of undergoing a laparoscopic hysterectomy. Of all women undergoing hysterectomy, the probability of undergoing a laparoscopic hysterectomy remained highest for women who were less than 35 years old, white, with the highest median income, and with private insurance from 2003-2010. The slope was significantly greater for (1) white females versus all other races analyzed (p<0.01), (2) females in the highest income quartile versus females in the lowest income quartile (p<0.01) and (3) females with private insurance versus females with Medicaid (p<0.01) or Medicare (p<0.01). CONCLUSIONS: There remains a gap in distribution of laparoscopic hysterectomies with regards to age, race, median income and insurance type that does not seem to be closing, despite the increased availability of laparoscopic hysterectomies.

Disparities in use of laparoscopic hysterectomies: a nationwide analysis.

STUDY OBJECTIVE: To determine patient and hospital characteristics that were associated with undergoing laparoscopic hysterectomy compared with abdominal hysterectomy. DESIGN: Canadian Task Force Classification II-3. METHODS: In this retrospective cohort study, we analyzed the 2010 Healthcare Cost and Utilization Project Nationwide Inpatient Sample database. All women who underwent laparoscopic or abdominal hysterectomy for either menorrhagia or leiomyoma were included based on International Classification of Diseases, Ninth Revision coding. A linear model with binomial distribution and logit link function was used to determine patient and hospital characteristics associated with hysterectomy approach. MAIN RESULTS: A total of 32 436 patients were included in this study. Of these, 32% patients underwent laparoscopic hysterectomies, and 67% underwent abdominal hysterectomies. With regard to patient characteristics, women younger than 35 years old were more likely to undergo laparoscopic hysterectomy when compared with each of the other age categories (p < .001). White women were more likely to undergo laparoscopic hysterectomy than black women, Hispanic women, or women classified as "other" races (p < .001 for all comparisons). With regard to median income, patients from the lowest national quartile were less likely to undergo laparoscopic hysterectomy when compared with each of the other 3 national quartiles for income (p = .01, p < .001, p = .001, respectively). Payment by private insurance was associated with laparoscopic hysterectomy when compared with payment by Medicare or payment by insurance category "other" (p < .001 for both). With regard to hospital characteristics, hospitals in the Northeast were more likely to have laparoscopic hysterectomies than hospitals in the Midwest or South (p < .001 for both comparisons); urban hospitals were more likely than rural hospitals (p < .001); teaching hospitals were more likely than nonteaching hospitals (p < .001); and government-owned hospitals were less likely than private, nonprofit or private, investor owned (p < .001 for both comparisons). CONCLUSIONS: Despite the increased popularity of and training in laparoscopic hysterectomies, there remains an obvious disparity in its delivery with regard to patient and hospital characteristics. Further investigation is needed on the etiology of this disparity and interventions that may alleviate it.

Robotic-assisted, ultrasound-guided abdominal cerclage during pregnancy: overcoming minimally invasive surgery limitations?

Herein, we report robotic abdominal cerclage placement under ultrasound guidance. The da Vinci Si system (Intuitive Surgical, Sunnyvale, CA) allows a simultaneous display of the operative field and transvaginal ultrasound images. Additionally, the vaginal ultrasound probe assisted in the manipulation of the uterus to improve visualization without placing excessive pressure on the gravid uterus. Ultrasound guidance improves needle placement accuracy and reduces potential for injuries.

Modular comparison of laparoscopic and robotic simulation platforms in residency training: a randomized trial.

STUDY OBJECTIVE: To compare minimally invasive surgery (MIS) skills acquired using laparoscopic and robotic simulation training platforms. DESIGN: Randomized trial (Canadian Task Force classification I). SETTING: University residency training program. SUBJECTS: PGY1 and PGY2 resident physicians in Obstetrics and Gynecology. INTERVENTIONS: All residents completed prestudy questionnaires (demographic data and previous experience in MIS) followed by simulation pretesting to assess baseline laparoscopic and robotic skills. Residents were then randomized to laparoscopic or robotic training cohorts in which they completed proctored training of 4 basic laparoscopic or 4 matching robotic modules (1 hour per module, 4 hours total). Thereafter, residents repeated the timed assessment of all skills. Finally, they completed poststudy questionnaires about the training experience. The primary outcome measure was the percentage of improvement in skill completion time. Secondary outcome measures were answers to poststudy questionnaires. MEASUREMENTS AND MAIN RESULTS: Sixteen residents completed the study. The laparoscopic and robotic training groups did not differ substantially on demographic measures, previous experience in MIS, or baseline laparoscopic and robotic completion times. Median improvement for individual laparoscopic modules was, respectively, 37.76%, 46.43%, 53.29%, and 66.48% in the laparoscopic cohort vs 21.84%, 21.80%, 38.15%, and 32.98% in the robotic cohort. Median improvement for individual robotic modules was, respectively, 35.42%, 26.08%, 22.33%, and 47.48% in the laparoscopic cohort vs 52.70%, 62.02%, 67.64%, and 71.62% in the robotic cohort. Median improvement in combined laparoscopic, robotic, and overall skills was, respectively, 50.56%, 34.83%, and 45.52% in the laparoscopic group vs 36.18%, 64.12%, and 49.86% in the robotic group. Residents predicted greater comfort performing surgical procedures using the platform in which they trained; however, the robotic training cohort liked their training more. CONCLUSIONS: Laparoscopic and robotic simulation platforms each demonstrated improved performance in the same and other platform. The robotic platform seems to have an edge over the laparoscopic platform. Larger studies are required in addition to studies to compare the effectiveness of both platforms in more advanced skills and to compare their effect on proficiency in the operating room.

Analysis of tubal patency after essure placement.

STUDY OBJECTIVE: To evaluate tubal patency after hysteroscopic sterilization using the Essure microinsert (Conceptus Inc, San Carlos, CA). DESIGN: A retrospective longitudinal cohort study. DESIGN CLASSIFICATION: II-3. SETTING: Patients undergoing hysteroscopic sterilization in the outpatient clinic of a university-based hospital in Southeast Texas from July 2009 to November 2011. PATIENTS: Two hundred twenty-nine women (ages 21-44 yrs, 71% Hispanic) desiring sterilization with a history of regular menses, demonstrated prior fertility (≥1 live birth), and the ability to use an alternative contraceptive method for at least 90 days after coil placement were included. Twenty six patients in this cohort were excluded because of failure to perform a hysterosalpingogram (HSG), tubal perforation, severe dyspareunia, a history of ectopic pregnancy, tubal surgery, or cervical intraepithelial neoplasia. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: HSGs were assessed for microinsert location and tubal occlusion. Two hundred three patients were included for analysis. After the successful bilateral hysteroscopic placement of Essure microinserts in fallopian tubes, all patients returned for the first follow-up HSG a mean of 103 ± 38 days after the procedure. Patients with fallopian tube patency at the initial HSG returned for second and/or third HSGs as needed at 192 ± 45 and 291 ± 97 days, respectively. Correct device placement was confirmed in 100% of cases at the first HSG. The tubal patency rates at the 90-day and 180-day HSGs were 16.1% (95% confidence interval, 7.4%-31.7%) and 5.8% (95% CI, 1.2%-24.4%), respectively. These rates were estimated by the accelerated failure time model with log normal distribution and interval censored time to event. The 16.1% 90-day tubal patency rate is significantly different from the 8% rate reported by Cooper et al in the 2003 multicenter phase III pivotal trial (p <.001). CONCLUSION: Our data indicate that hysteroscopic sterilization with Essure results in a higher initial tubal patency rate than previously reported. Multivariate analyses are needed to identify factors associated with an increased risk of postprocedure tubal patency.

Intraocular pressure and steep Trendelenburg during minimally invasive gynecologic surgery: is there a risk?

STUDY OBJECTIVE: Steep Trendelenburg position is frequently used during gynecologic minimally invasive surgery (MIS). However, little attention has been given to the potential impact of this nonphysiologic positioning on patients, specifically intraocular pressure (IOP). The purpose of our study was to evaluate IOP changes during laparoscopic or robotic hysterectomy conducted in the steep Trendelenburg position. DESIGN: Prospective cohort study (Canadian Task Force classification II-2). SETTING: John Sealy Hospital at the University of Texas Medical Branch, Galveston, TX. PATIENTS: Female patients with no history of ocular pathology who underwent elective robotic or laparoscopic hysterectomy. INTERVENTIONS: The anesthesia protocol was standardized for all study patients. IOP and mean arterial pressure (MAP) were obtained before anesthesia, after general anesthesia and intubation were achieved, after 1 hour of steep Trendelenburg positioning, after 2 hours of steep Trendelenburg positioning, and after the patient was returned to the supine position. Ocular perfusion pressure (OPP) was calculated using the following equation: OPP = MAP - IOP. MAIN RESULTS: A total of 10 patients were included in this prospective study. A significant increase in IOP from baseline was observed after 1 hour and 2 hours of steep Trendelenburg positioning (p = .005 and .002, respectively). There was a statistically significant trend of increasing the IOP from baseline to the second hour of steep Trendelenburg positioning (p < .001). The IOP remained significantly elevated once the patient was returned to the supine position when compared with the baseline IOP (p = .006). OPP significantly decreased from baseline after 2 hours of steep Trendelenburg positioning (p = .03). CONCLUSIONS: IOP increases significantly when patients are placed in the steep Trendelenburg position. Although further studies are needed to better characterize this process, given the aging population of our MIS patients in whom risk for glaucoma is significant, preoperative ocular health assessment should be considered in certain cases.

Cumulative Effects of Comorbid Burden and Overactive Bladder Symptoms on Fall Risk Among Older Women Seeking Treatment for Urogynecologic Conditions.

IMPORTANCE: Overactive bladder (OAB) syndrome and urinary incontinence, age, and comorbid burden are strong risk factors for falls in women. Less is known about their cumulative effects on fall risk in a urogynecologic population. OBJECTIVE: The purpose of this study was to investigate the effects of coexisting OAB, older age, and comorbidities on risk of falling among treatment seeking women with pelvic floor disorders. STUDY DESIGN: We conducted a retrospective medical records review of 348 consecutive women presenting to a urogynecology clinic over 6 months. Fall risk was determined by the Centers for Disease Control and Prevention's, Stopping Elderly Accidents, Deaths, and Injuries screening tool. Clinical and sociodemographic measures were abstracted from the electronic medical record. Odds of screening positive for high fall risk based on different patient profiles were calculated. We then used a classification and regression tree analysis to determine the relative importance of the different variables on fall risk within the homogeneous subgroups. RESULTS: Of the 348 women (mean age, 58.7 ± 15.8 years) who completed the fall risk screen, 124 (36%) screened positive for increased fall risk. Overactive bladder symptoms increased the likelihood of a positive fall risk screen across all combinations of age and comorbid burden. The patient profile of ≥3 OAB symptoms, ≥4 comorbid conditions, and age 65 years or older increased the odds of screening positive for high fall risk more than 6-fold (odds ratio, 6.4; 95% confidence interval, 3.1-12.9). In the following order of importance, the combination of high comorbid burden, OAB, and older age identified approximately 3 in 4 patients (73.3%) at high risk of falling. CONCLUSION: The presence of 3 easily identifiable patient characteristics is strongly associated with a risk of falls in women seeking care for pelvic floor disorders.

Prevalence and Predictors of Increased Fall Risk Among Women Presenting to an Outpatient Urogynecology and Pelvic Health Center.

OBJECTIVES: The objective of this study was to determine the prevalence of increased fall risk among women presenting to a large pelvic health center using a screening method compatible with the busy clinic environment and to identify factors associated with increased risk. METHODS: A retrospective medical records review was conducted on consecutive treatment-seeking women presenting to a Urogynecology & Pelvic Health Center over 6 months. The Centers for Disease Control and Prevention, Stopping Elderly Accidents, Deaths, and Injuries fall risk screening tool was included among the intake questionnaires all patients completed before their scheduled appointments. Relevant sociodemographic and clinical measures were abstracted from the electronic medical record. RESULTS: Three hundred and forty-eight women completed the fall screen. One hundred and twenty-four (36%) screened positive for increased fall risk. Mean age was 58.7 ± 15.8 years. An age threshold of 68 years best discriminated between those who were and were not identified as at risk. There was a gradient of association between number of urinary symptoms and prevalence of increased fall risk. Patients with 3 or more urinary symptoms were most likely to screen positive (1: odds ratio [OR], 1.51 [0.86-2.66]; 2: OR, 1.62 [0.99-2.64]; 3 or more: OR, 1.84 [1.07-3.17]) after adjusting for other know fall risk factors. CONCLUSIONS: The prevalence of increased fall risk in this patient population is high and highest in women with multiple urinary symptoms. The Stopping Elderly Accidents, Deaths, and Injuries screening tool was a feasible and nonintrusive screening method for identifying increased fall risk during routine patient care. Fall risk and concern about falling should be taken into consideration when deciding management strategies for urinary problems.

Predictors of same-day discharge after minimally invasive hysterectomy for benign indications.

OBJECTIVE: To identify predictors of same-day discharge after benign minimally invasive hysterectomy. METHODS: In this retrospective cohort study, we identified women (n = 1084) undergoing benign minimally invasive hysterectomy from 2009 to 2016. Multivariate logistic regression was used to examine demographic, operative, and surgeon factors associated with discharge on postoperative day 0. RESULTS: In our study population, 238 women (22%) were discharged on the same day. Robotic hysterectomy (risk ratio [RR] 2.24; 95% confidence interval [CI] 1.13-4.44), shorter operative time (lowest quartile; RR 5.28; 95% CI 2.66-10.46), and minimal blood loss (lowest quartile; RR 3.01; 95% CI 1.68-6.23) were associated with higher same-day discharge likelihood whereas later procedure start time (2-5 pm; RR 0.38; 95% CI 0.17-0.85) and postoperative complications (RR 0.19; 95% CI 0.06-0.55) significantly decreased its likelihood. The strongest predictor was surgeon's number of years in practice, with recently graduated surgeons more likely to discharge their patients on the same day (RR 3.15; 95% CI 2.09-4.77). CONCLUSION: Same-day discharge after minimally invasive hysterectomy is determined by several patient, operative, and surgeon factors that can be incorporated into an implementation plan to promote earlier discharge. Most especially, scheduling patients based on perceived case complexity and targeted surgeon education can qualify a larger cohort for same-day discharge.

Medicolegal review of liability risks for gynecologists stemming from lack of training in robot-assisted surgery.

The advances in robot-assisted surgery in gynecology evolved after most practicing gynecologists had already completed residency training. Postgraduate training in new technology for gynecologists in practice is limited. Therefore, gynecologists with insufficient training who perform robot-assisted surgery may potentially be at risk for liability. In addition to the traditional medical negligence claims, plaintiff attorneys are seeking causes of actions for lack of informed consent and negligent credentialing. Thus, it is essential that gynecologists be aware of these potential liability claims that arise in a robot-assisted malpractice suit. This commentary provides an overview of the current medicolegal liability risks originating from lack of training in robotic surgery and seeks to raise awareness of the implications involved in these claims. A better understanding of the doctrine of informed consent and seeking assistance of proctors or experienced co-surgeons early in robotics training are likely to reduce the liability risks for gynecologic surgeons.

Predictors of the cost of hysterectomy for benign indications.

INTRODUCTION: Hysterectomy is a commonly performed procedure with widely variable costs. As gynecologists divert from invasive to minimally invasive approaches, many factors come into play in determining hysterectomy cost and efforts should be sought to minimize it. Our objective was to identify the predictors of hysterectomy cost. MATERIALS AND METHODS: This was a retrospective cohort study where women who underwent hysterectomy for benign conditions at the University of Texas Medical Branch from 2009 to 2016 were identified. We obtained and analyzed demographic, operative, and financial data from electronic medical records and the hospital finance department. RESULTS: We identified 1,847 women. Open hysterectomy was the most frequently practiced (35.8 %), followed by vaginal (23.7 %), laparoscopic (23.6 %), and robotic (16.9 %) approaches. Multivariate regression demonstrated that hysterectomy charges can be significantly predicted from surgical approach, patient's age, operating room (OR) time, length of stay (LOS), estimated blood loss, insurance type, fiscal year, and concomitant procedures. Charges increased by $3,723.57 for each day increase in LOS (P <0.001), by $76.02 for each minute increase in OR time (P <0.001), and by $48.21 for each one-year increase in age (P 0.037). Adjusting for LOS and OR time remarkably decreased the cost of open and robotic hysterectomy, respectively when compared with the vaginal approach. CONCLUSION: Multiple demographic and operative factors can predict the cost of hysterectomy. Healthcare providers, including gynecologists, are required to pursue additional roles in proper resource management and be acquainted with the cost drivers of therapeutic interventions. Future efforts and policies should target modifiable factors to minimize cost and promote value-based practices.

Liposomal 2-Methoxyestradiol Nanoparticles for Treatment of Uterine Leiomyoma in a Patient-Derived Xenograft Mouse Model.

Uterine leiomyomas represent a challenging problem with limited medical treatment options. The anti-tumor agent 2-methoxyestradiol (2-ME) shows promising results but its efficacy is limited by inadequate pharmacokinetics. We previously demonstrated that 2-ME nanoparticles can be successfully formulated and that they show improved in vitro anti-leiomyoma cell activity. Here, we examined the effects of the in vivo delivery of 2-ME nanoparticles in a patient-derived xenograft (PDX) leiomyoma mouse model. Patient-derived leiomyoma tumor tissues were xenografted subcutaneously in estrogen/progesterone pretreated immunodeficient NOG mice. Animals (n = 12) were treated with liposomal 2-ME nanoparticles by intra-peritoneal (IP) injection (50 mg/kg/dose, three times weekly) or control for 28 days. Tumor volume was measured weekly by calipers and prior to sacrifice by ultrasound. In addition, the expression of the cell proliferation marker Ki67 and the apoptosis marker cleaved caspase-3 in tumor tissues after treatment were measured by immunohistochemistry. Liposomal 2-ME treatment was associated with a significant tumor growth inhibition (30.5% less than controls as early as 2 weeks, p = 0.025). In addition, injections of liposomal 2-ME inhibited the expression of the proliferation marker Ki67 (55.8% reduction, p < 0.001). Furthermore, liposomal 2-ME treatment was associated with a 67.5% increase of cleaved caspase-3 expression of increase (p = 0.048). Our findings suggest that liposomal nanoparticle formulation can successfully deliver 2-ME and can be a promising therapeutic strategy for uterine leiomyoma. Further characterization of the liposomal-2ME, including pharmacokinetics, maximal tolerated dose, and safety, is needed in preclinical models prior to clinical trials.