Catechol-O-Methyltransferase Expression and 2-Methoxyestradiol Affect Microtubule Dynamics and Modify Steroid Receptor Signaling in Leiomyoma Cells

CONTEXT: Development of optimal medicinal treatments of uterine leiomyomas represents a significant challenge. 2-Methoxyestradiol (2ME) is an endogenous estrogen metabolite formed by sequential action of CYP450s and catechol-O-methyltransferase (COMT). Our previous study demonstrated that 2ME is a potent antiproliferative, proapoptotic, antiangiogenic, and collagen synthesis inhibitor in human leiomyomas cells (huLM). OBJECTIVES: Our objectives were to investigate whether COMT expression, by the virtue of 2ME formation, affects the growth of huLM, and to explore the cellular and molecular mechanisms whereby COMT expression or treatment with 2ME affect these cells. RESULTS: Our data demonstrated that E(2)-induced proliferation was less pronounced in cells over-expressing COMT or treated with 2ME (500 nM). This effect on cell proliferation was associated with microtubules stabilization and diminution of estrogen receptor alpha (ERalpha) and progesterone receptor (PR) transcriptional activities, due to shifts in their subcellular localization and sequestration in the cytoplasm. In addition, COMT over expression or treatment with 2ME reduced the expression of hypoxia-inducible factor -1alpha (HIF-1 alpha) and the basal level as well as TNF-alpha-induced aromatase (CYP19) expression. CONCLUSIONS: COMT over expression or treatment with 2ME stabilize microtubules, ameliorates E(2)-induced proliferation, inhibits ERalpha and PR signaling, and reduces HIF-1 alpha and CYP19 expression in human uterine leiomyoma cells. Thus, microtubules are a candidate target for treatment of uterine leiomyomas. In addition, the naturally occurring microtubule-targeting agent 2ME represents a potential new therapeutic for uterine leiomyomas

Disseminated Intravascular Coagulation, Hemoperitoneum, and Reversible Ischemic Neurological Deficit Complicating Anaphylaxis to Prophylactic Antibiotics during Cesarean Delivery: A Case Report and Review of Literature

Routine use of prophylactic antibiotics reduces the risk of postcesarean fever and infections by over 50% in both nonelective and elective (scheduled) procedures. Although anaphylaxis to prophylactic antibiotics is rare, potentially fatal complications might occur. Herein, we present a case where disseminated intravascular coagulation and reversible ischemic neurological deficit complicated anaphylactic reactions to prophylactic antibiotics administered during cesarean delivery. A 27-year-old gravida 9, para 7 at 392/7 weeks underwent elective repeat cesarean delivery and bilateral tubal ligation. Her surgery was complicated by intraoperative hypotension, generalized itching, and urticarial skin rash consistent with anaphylactic reaction upon administering prophylactic cefazolin. In the recovery room, she continued to be hemodynamically unstable despite energetic resuscitation. Hemoperitoneum was suspected, and laboratory evaluation indicated disseminated intravascular coagulation. Abdominal exploration revealed massive hemoperitoneum, but there was no source of active bleeding noted. The postoperative course was complicated by reversible ischemic neurological deficit, which resolved on expectant management. Disseminated intravascular coagulation and reversible ischemic neurological deficit may complicate anaphylactic reaction to prophylactic antibiotics administered during cesarean delivery. Immediate recognition and intervention is crucial for a successful outcome

Initial Experience with Robotic Retropubic Urethropexy Compared to Open Retropubic Urethropexy

Study Objective. To compare the clinical outcomes of robotic retropubic urethropexy versus open retropubic urethropexy. Design. Retrospective case-control study (II-2). Setting. University Hospital. Patients. All patients who underwent robotic retropubic urethropexy from 1/1/12 to 6/1/12 by a single gynecologic surgeon were included in the case series. The control cases consisted of the last five consecutive open retropubic urethropexies performed by the same surgeon. Main Results. A total of 10 patients (5 robotic cases and 5 open cases) were included in this study. Both groups were similar with respect to age, BMI, and obstetrical history. Mean hospital stay length and mean EBL were overall less for robotic cases than for open cases (1.2 days versus 2.6 days; 169 mL versus 300 mL). One of the 5 patients who underwent the open approach and 2 of the 5 patients who underwent the robotic approach sustained a minor intraoperative complication. All but one patient from each group experienced resolution of incontinence after the procedure. Two of the patients who underwent the open approach had postoperative complications. Conclusions. Robotic retropubic urethropexy may be a feasible alternative to open retropubic urethropexy. A larger study is necessary to support our observations

Clinical Study Initial Experience with Robotic Retropubic Urethropexy Compared to Open Retropubic Urethropexy

. Study Objective. To compare the clinical outcomes of robotic retropubic urethropexy versus open retropubic urethropexy. Design. Retrospective case-control study (II-2). Setting. University Hospital. Patients. All patients who underwent robotic retropubic urethropexy from 1/1/12 to 6/1/12 by a single gynecologic surgeon were included in the case series. The control cases consisted of the last five consecutive open retropubic urethropexies performed by the same surgeon. Main Results. A total of 10 patients (5 robotic cases and 5 open cases) were included in this study. Both groups were similar with respect to age, BMI, and obstetrical history. Mean hospital stay length and mean EBL were overall less for robotic cases than for open cases (1.2 days versus 2.6 days; 169 mL versus 300 mL). One of the 5 patients who underwent the open approach and 2 of the 5 patients who underwent the robotic approach sustained a minor intraoperative complication. All but one patient from each group experienced resolution of incontinence after the procedure. Two of the patients who underwent the open approach had postoperative complications. Conclusions. Robotic retropubic urethropexy may be a feasible alternative to open retropubic urethropexy. A larger study is necessary to support our observations

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 statement What 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

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 statement What 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