Treatment Of Uterine Leiomyomas Research Articles

Evaluating for Racial Disparities in the Utilization of Minimally Invasive Hysterectomy for the Treatment of Uterine Leiomyoma

Introduction: Minimally invasive hysterectomy (MIH) for benign gynecologic indications has many patient advantages over traditional abdominal hysterectomy (AH) including decreased hospital stay, decreased mortality, and faster recovery. Although MIH has been shown to improve outcomes as compared with abdominal hysterectomy, racial and socioeconomic disparities can impact patient access to the minimally invasive procedure. Previous studies have demonstrated that Black and Hispanic-identifying patients are significantly less likely to receive a MIH when compared to White patients. One proposed contributor to this finding is the higher rate and delayed diagnosis of uterine leiomyoma in Black patients compared to White patients. This disparity could delay diagnosis, and cause a larger leiomyoma necessitating use of abdominal hysterectomy. Another explanation in disparity is the physician training at hospitals in underserved areas. This study aims to investigate if race impacts access to MIH for leiomyoma at Carle Foundation Hospital in Urbana, Illinois. Methods: This retrospective analysis studied patients from 2011-2020 who received a hysterectomy at Carle Foundation Hospital for a primary diagnosis of leiomyoma. MIH included laparoscopic, vaginal, and robotic-assisted. Hysterectomies for malignancy were excluded. The demographic data included age, race, body mass index (BMI), type of hysterectomy, insurance, history of previous obstetric and abdominal surgeries, and uterine weight. The race categories included White, Black, and Others. Hispanic and Asian patients were placed into the other category due to the limited sample size. Descriptive statistics were used to evaluate the demographic data. Odd ratios were calculated to determine if a patient received a MIH over an AH based on race. An adjusted odds ratio was calculated to account for BMI, uterine weight, history of cesarean section, and previous abdominal surgery. Results: A total of 324 hysterectomies from 2011-2020 were performed for leiomyoma. Abdominal hysterectomies accounted for 32.1% and MIH accounted for 68.9%, with 7.4% being laparoscopic, 5.6% being vaginal, and 55.9% being robotic-assisted. The average age of White patients was 46.7 years old, and was higher than Black patients, 43.6 years old (p<.01). The average BMI of Black patients was 34.6 kg/m2, and was higher than White patients, 30.3 34.6 kg/m2 (p<.01). More White patients had commercial insurance at 83.5% compared to Black patients at 48.1% (p<.01). More Black patients had Medicaid or Medicare at 50.6% compared to White patients at 14.8% (p<.01). Black patients had an average uterine weight at 579.8g compared to White patients at 438.6g (p<.05). The majority (73.7%) of White patients received a MIH, with 26.3% receiving an AH. Forty five percent of Black patients received an AH while 54.5% received a MIH. Conclusion: At Carle Foundation Hospital during the years 2011-2020, a lower percentage of African American patients, compared to white patients, received a minimally invasive hysterectomy in the treatment of uterine leiomyoma. Further analysis will investigate for the odds ratios of each group receiving a MIH and will adjust for BMI, uterine weight, obstetric and abdominal surgical history.

Surgical Treatment of Uterine Leiomyomas from 2016-2022 in the Republic of Kazakhstan

Background: Due to the transition to a mandatory health insurance system (MHIS) and also taking into account the impact of the COVID-19 pandemic, the purpose of this study was to evaluate the surgical treatment of uterine leiomyoma in Kazakhstan in recent years, taking into account the ratio of uterine-preserving surgery (UPS) and hysterectomy. Methods and Results: This epidemiological study was carried out upon the request of the Republican E-Health Center (RCEZ) to assess the dynamics of surgical treatment of uterine leiomyomas (UL) in Almaty at the expense of the Republican budget from 2016 to 2022. Since 2016, by 2022 there was a decrease in the total number of treated cases of UL at the expense of the Republican budget (from 1,478 to 1,063). From 2016 to 2019, there were statistically significantly more hysterectomies, whereas from 2020 to 2022 the number of uterine-preserving surgeries increased statistically significantly. The number of laparoscopic myomectomy and hysteroscopic myomectomy for treating submucous leiomyomas increased statistically significantly from 2016 to 2019. However, there were no statistical differences in the number of treated cases with this technique from 2020 to 2022. Conclusion: Although high-tech fibroid surgery has been performed more frequently in recent years, these numbers are insufficient today, which justifies the need to train more specialists in advanced technologies.

Long-term Efficacy of Fibroid Devascularization with Ultrasound-Guided High-Intensity Focused Ultrasound

High-intensity focused ultrasound (HIFU) has been increasingly used for treatment of uterine leiomyoma. The superiority of HIFU therapy targeting uterine leiomyoma blood vessels, however, still needs to be further explored. This study aims to evaluate the long-term efficacy of fibroid devascularization with ultrasound-guided HIFU (USgHIFU) and the effects of treatment on the ovarian reserve and endometrial injury. Fibroid devascularization was assessed with the Adler grade obtained by color Doppler flow imagingand power Doppler imaging (PDI). The targeted vessels were covered and then sonicated by HIFU focal spots. The patients were followed up at 1 month, 3 months, 6 months, 1 year, 2 years and 3 years after treatment. Adverse effects and complications were recorded. The non-perfusion volume rate (NPVR), fibroid volume shrinkage rate (FVSR), Adler Grade, symptom severity score (SSS) and uterine fibroid symptom and quality of life (UFS-QOL) were evaluated. Adverse events (AEs)were recorded. In Center 1, the enrolled patients completed the anti-Müllerian hormone (AMH) test before and at 6 months after treatment. A total of 117 eligible patients were consecutively enrolled to receive interventions and follow-up evaluations of the three centers from January 2019 to May 2023. The 1-month and 6-monthNPVRs were 66.60%±33.14% and 51.12%±39.84%, respectively. The mean FVSRs at 1 month and 6 months after treatment were 38.20% and 43.89%, respectively. No significant difference was observed in AMH levels before and after treatment (p>0.05). No irreversible endometrial injury was observed in MR images after HIFU treatment. No significant difference was observed in both 1-month and 6-monthFVSRs among Center 1, 2 and 3 (p>0.05). No severe AEs occurred. For long-term outcomes, significant differences were observed in Adler grade, FV, FVSR, SSS, reduction in SSSand UFS-QOL before and after treatment (p<0.001) whereas no significant difference was observed in Adler grade among 3 months, 1 year, 2 years and 3 years after treatment (p>0.05). The SSSs were reduced by 33.42% at 1 year, 42.32% at 2 years and 52.46% at 3 years after treatment. For patients with uterine fibroids, USgHIFU-induced devascularization is a safe and effective treatment option. It has little effect on ovarian function and the endometrial injury is reversible, which could be attractive for patients who plan to become pregnant.

Ulipristal acetate, a selective progesterone receptor modulator, induces cell death via inhibition of STAT3/CCL2 signaling pathway in uterine sarcoma

Ulipristal acetate (UPA) is a selective progesterone receptor modulator and is used for the treatment of uterine leiomyoma (a benign tumor). Uterine sarcoma which is highly malignant cancer with a poor prognosis is clinically resembled with uterine leiomyoma. There has been no experimental research on the effect of UPA on uterine sarcoma. In this study, we examined the efficacy of UPA in uterine sarcoma with in vitro and in vivo animal models. Cytotoxicity of UPA was determined in uterine sarcoma cell lines (MES-SA, SK-UT-1, and SK-LMS-1). Apoptotic genes and signaling pathways affected by UPA were analyzed by complementary DNA (cDNA) microarray of uterine sarcoma cell lines and western blot, respectively. An in vivo efficacy of UPA was examined with uterine sarcoma cell line- and patient-derived xenograft (PDX) mice models. UPA inhibited cell growth in uterine sarcoma cell lines and primary culture cells from a PDX mouse (PDX-C). cDNA microarray analysis revealed that CCL2 was highly down-regulated by UPA. Phosphorylation and the total expression of STAT3 were inhibited by UPA. UPA also inhibited CCL2 and STAT3 in PDX-C. The inhibitory effect of UPA had not changed in the overexpression of PR and treatment of progesterone. In vivo efficacy studies with cell line-derived xenografts and a PDX model with leiomyosarcoma, a typical uterine sarcoma, demonstrated that UPA significantly decreased tumor growth. UPA had significant anti-tumor effects in uterine sarcoma through the inhibition of STAT3/CCL2 signaling pathway and might be a potential therapeutic agent to treat this disease.

Combined Treatment of Uterine Leiomyoma and Ovarian Endometrioma: Transvaginal Ultrasound-Guided Radiofrequency Ablations in Five Steps

Combined Treatment of Uterine Leiomyoma and Ovarian Endometrioma: Transvaginal Ultrasound-Guided Radiofrequency Ablations in Five Steps

PEGylated Polymeric Nanoparticles Loaded with 2-Methoxyestradiol for the Treatment of Uterine Leiomyoma in a Patient-Derived Xenograft Mouse Model

Leiomyomas, the most common benign neoplasms of the female reproductive tract, currently have limited medical treatment options. Drugs targeting estrogen/progesterone signaling are used, but side effects and limited efficacy in many cases are major limitation of their clinical use. Previous studies from our laboratory and others demonstrated that 2-methoxyestradiol (2-ME) is promising treatment for uterine fibroids. However, its poor bioavailability and rapid degradation hinder its development for clinical use. The objective of this study is to evaluate the in vivo effect of biodegradable and biocompatible 2-ME-loaded polymeric nanoparticles in a patient-derived leiomyoma xenograft mouse model. PEGylated poly(lactide-co-glycolide) (PEG-PLGA) nanoparticles loaded with 2-ME were prepared by nanoprecipitation. Female 6-week age immunodeficient NOG (NOD/Shi-scid/IL-2Rγnull) mice were used. Estrogen-progesterone pellets were implanted subcutaneously. Five days later, patient-derived human fibroid tumors were xenografted bilaterally subcutaneously. Engrafted mice were treated with 2-ME-loaded or blank (control) PEGylated nanoparticles. Nanoparticles were injected intraperitoneally and after 28 days of treatment, tumor volume was measured by caliper following hair removal, and tumors were removed and weighed. Up to 99.1% encapsulation efficiency was achieved, and the in vitro release profile showed minimal burst release, thus confirming the high encapsulation efficiency. In vivo administration of the 2-ME-loaded nanoparticles led to 51% growth inhibition of xenografted tumors compared to controls (P < 0.01). Thus, 2-ME-loaded nanoparticles may represent a novel approach for the treatment of uterine fibroids.

Papillary Histiocytic and Mesothelial Hyperplasia of the Ovary Related to a Huge Uterus: A Case Report

Nodular histiocytic/mesothelial hyperplasia (NHMH) is a very rare condition. It is generally thought to be associated with repeated mechanical or chemical stimulation. This study reported NHMH with papillary growth pattern in the ovary following high-intensity focused ultrasound (HIFU) treatment for uterine leiomyoma and adenomyosis. A 48-year-old female, who had a history of undergoing HIFU treatment 7 times for adenomyosis and leiomyoma of the uterus 6 months ago, was referred to the hospital. After the hysterectomy and right salpingo-oophorectomy, the patient was confirmedly diagnosed with nodular histiocytic and mesothelial hyperplasia with the papillary growth pattern of the right ovary. This benign reactive inflammatory lesion of the mesothelium mimicking malignancy must be kept in mind to avoid unnecessary treatment.

Ultrasound-guided microwave, radiofrequency, and high intensity focused ultrasound (HIFU) ablation in treating uterine leiomyoma: A systemic review and meta-analysis of retrospective studies

ABSTRACT To retrospectively evaluate the efficacy and safety of ultrasound-guided microwave (MWA), radiofrequency (RF), and high-intensity focused ultrasound (HIFU) ablation in the treatment of uterine leiomyoma and to provide a suggestion for the selection of clinical treatment of uterine leiomyoma. The retrospective cohort studies on the efficacy of high-intensity focused ultrasound in treating uterine leiomyoma was collected through a literature search in Pubmed, Embase, Cochrane library, Scopus, and Web of Science, and selected according to the specified inclusion criteria and exclusion criteria. Evaluate the study quality, extract relevant data, and RevMan 5.4.1 was used to conduct this meta-analysis. Compared with HIFU therapy, the complete or partial ablation rate and recurrence rate of uterine leiomyoma treated with RFA/MWA were statistically different (P < 0.05). Compared with RF, the overall efficacy of HIFU in treating uterine leiomyoma was not as good as that of RF. There was no significant difference between the RFA therapy and the MWA. HIFU still has mild and short-term complications, such as abdominal pain, bloody vaginal discharge, sacral pain, and fever. Although myomectomy is usually the first choice for uterine preservation, RFA/MWA and HIFU have also been shown to relieve clinical symptoms significantly, shorten treatment time, reduce complications, and improve prognosis.

Oral Gonadotropin-Releasing Hormone Antagonists for the Treatment of Uterine Leiomyomas.

Uterine leiomyomas are common hormone-responsive neoplasms that frequently cause heavy menstrual bleeding, anemia, pelvic pressure, pain, and adverse reproductive outcomes. In this overview, the efficacy and safety of oral gonadotropin-releasing hormone (GnRH) antagonists, co-administered with menopausal replacement-level steroid hormones or used at doses to avoid complete hypothalamic suppression, are reviewed for the management of uterine leiomyomas. Oral GnRH antagonists provide rapid suppression of sex steroids and avoid the initial steroidal flare and resultant temporary worsening of symptoms typically seen with parenteral GnRH agonists. Oral GnRH antagonists are effective in reducing leiomyoma-associated heavy menstrual bleeding, with high rates of amenorrhea and improved anemia and leiomyoma-associated pain, and providing modest reduction in uterine volume when used in combination with menopausal replacement-level steroid hormones. This add-back therapy can reduce hypogonadal side effects, including hot flushes and bone mineral density loss, close to levels seen with placebo therapy. Currently, both elagolix 300 mg twice daily with once-daily estradiol (1 mg) and norethindrone (0.5 mg) and relugolix 40 mg once daily with estradiol (1 mg) and norethindrone (0.5 mg) combination therapy are approved for leiomyoma treatment by the U.S. Food and Drug Administration. Linzagolix is under investigation in the United States but approved at two does with and without steroid hormones in the European Union. The efficacy of these agents appears to be robust over a wide spectrum of clinical presentations, demonstrating that worse disease parameters at baseline do not appear to inhibit efficacy. Across clinical trials, participants largely reflected the population of individuals affected by uterine leiomyomas.

Pivotal Role of Ubiquitin Carboxyl-Terminal Hydrolase L1 (UCHL1) in Uterine Leiomyoma.

Uterine leiomyomas are smooth-muscle tumors originating in the myometrium and are the most common pelvic tumors in women of reproductive age. Symptomatic tumors may result in abnormal uterine bleeding, bladder dysfunction, pelvic discomfort, and reproductive issues, such as infertility and miscarriage. There are currently few non-invasive treatments for leiomyoma, but there are no practical early intervention or preventive methods. In this study, human uterine leiomyoma and myometrial tissues were used to detect the protein and mRNA expression levels of UCHL1. To explore the effects of UCHL1 knockdown and inhibition in leiomyoma and myometrial cells, we determined the mRNA expressions of COL1A1 and COL3A1. Collagen gel contraction and wound-healing assays were performed on myometrial and leiomyoma cells. We found that UCHL1 expression was considerably higher in uterine leiomyomas than in the myometrium. COL1A1 and COL3A1 expression levels were downregulated after inhibition of UCHL1 in human leiomyoma cells. Furthermore, the elimination of UCHL1 significantly decreased the migration and contractility of leiomyoma cells. In conclusion, these results indicate that UCHL1 is involved in the growth of leiomyoma in humans. For the treatment of uterine leiomyoma, targeting UCHL1 activity may be a unique and possible therapeutic strategy.

Curcumin inhibits human leiomyoma xenograft tumor growth and induces dissolution of the extracellular matrix

To determine whether a curcumin-supplemented diet would prevent and/or treat uterine leiomyoma growth in our mouse xenograft model. Animal study. Laboratory study. N/A. Curcumin-supplemented diet. Dietary intake, blood concentrations, tumor size, extracellular matrix protein concentrations, apoptosis markers. We found that curcumin was well tolerated as a dietary supplement, free curcumin and its metabolites were detected in the serum, and exposure resulted in approximately 60% less leiomyoma xenograft growth as well as dissolution of the peripheral extracellular matrix architecture of the xenografts. The production of matrix proteins, including collagens, decreased, whereas the number of apoptotic cells in the xenografts increased. Additionally, when xenografts were placed in a uterine intramural location, we found a significantly increased apoptotic response to curcumin in the diet. Mice on a diet supplemented with curcumin could achieve serum concentrations sufficient to regulate human leiomyoma xenograft growth, and curcumin could play both preventive and curative roles in the treatment of uterine leiomyoma as an oral nutritional supplement.

In Silico Analysis of Plant-Based Bioactive Compounds Targeting Progesterone Receptors for the Treatment of Uterine Leiomyoma

Uterine leiomyomas are the most common benign gynaecological tumours that affect 50% - 60% of females belonging to reproductive age. The role of progesterone in the growth and development of leiomyomas is evident. Progesterone is regulated by progesterone receptors and it acts by activating PI3K/AKT pathway, by increasing proliferating cell nuclear antigen (PCNA) levels and Bcl-2 expression. Thus, modulating the receptor can help in the treatment of leiomyomas. The current study involves testing the efficiency of the various plant-based bioactive compounds to bind to the progesterone receptors, which may possess inhibitory or modulatory effects on or against progesterone receptors. These compounds can be further experimented with using other in vivo and in vitro methods to produce phytomedicine based on drugs for the treatment of uterine leiomyomas. This study is an in silico analysis performed using various bioinformatics databases and software. The receptor and ligand structures were retrieved from PDB and PubChem databases. Their pharmacokinetics and pharmacodynamics properties were analyzed using various databases. AutoDock4.2.6 was used for molecular docking, and the results were visualized using LigPlot+. Among 15 compounds selected, 8 compounds had higher binding energies than the control drug Ulipristal acetate i.e., -8.21Kcal/mol. Of which Ursolic acid, Vitamin-D2, and Betulinic acid had binding energies above -9.0 Kcal/mol. This concludes that these compounds can modulate the progesterone receptors, thus decreasing the proliferation and growth of uterine leiomyomas. Further studies can bring out the potential therapeutic effects of these bioactive compounds and they can act as a potential lead compound in the design of novel drug targets for the treatment of uterine leiomyoma.

Alport syndrome with pelvic leiomyomatosis: The role of hormonal suppression

Introduction: Alport syndrome with diffuse pelvic leiomyomatosis is a complex combination for which the course of treatment is not well described. This case describes the outcomes of a trial with gonadotropin-releasing hormone analogues as an alternative to extensive surgery. Case Report: A 47-year-old female patient, known with Alport syndrome associated with diffuse leiomyomatosis, was referred to our gynecological service because of a pelvic mass. The patient complained of obstipation and pain in the right hypochondrium. Magnetic resonance imaging showed a diffuse multi-lobulated leiomyomatosis from the vulvar to the perineal area. As the removal of the mass would imply very extensive surgery, conservative treatment options were searched for, in analogy with the medical treatment of uterine leiomyomas. A few trials used gonadotropin-releasing hormone analogues in the treatment of diffuse pelvic leiomyomatosis but follow-up data of these articles are lacking. For this patient, who was close to menopausal age, a trial therapy with gonadotropin-releasing hormone analogues was followed by an adnexectomy for total hormonal suppression. The patient’s follow-up showed stabilization of the mass and decrease of the pain complaints. Conclusion: This case demonstrates that hormonal suppression can be a successful alternative to complex surgery in a case combining Alport syndrome and diffuse pelvic leiomyomatosis.

Importance of Fibrosis in the Pathogenesis of Uterine Leiomyoma and the Promising Anti-fibrotic Effects of Dipeptidyl Peptidase-4 and Fibroblast Activation Protein Inhibitors in the Treatment of Uterine Leiomyoma.

Uterine fibroid or leiomyoma is the most common benign uterus tumor. The tumor is primarily composed of smooth muscle (fibroid) cells, myofibroblast, and a significant amount of extracellular matrix components. It mainly affects women of reproductive age. They are uncommon before menarche and usually disappear after menopause. The fibroids have excessive extracellular matrix components secreted by activated fibroblast cells (myofibroblast). Myofibroblast has the characteristics of fibroblast and smooth muscle cells. These cells possess contractile capability due to the expression of contractile proteins which are normally found only in muscle tissues. The rigid nature of the tumor is responsible for many side effects associated with uterine fibroids. The current drug treatment strategies are primarily hormone-driven and not anti-fibrotic. This paper emphasizes the fibrotic background of uterine fibroids and the mechanisms behind the deposition of excessive extracellular matrix components. The transforming growth factor-β, hippo, and focal adhesion kinase-mediated signaling pathways activate the fibroblast cells and deposit excessive extracellular matrix materials. We also exemplify how dipeptidyl peptidase-4 and fibroblast activation protein inhibitors could be beneficial in reducing the fibrotic process in leiomyoma. Dipeptidyl peptidase-4 and fibroblast activation protein inhibitors prevent the fibrotic process in organs such as the kidneys, lungs, liver, and heart. These inhibitors are proven to inhibit the signaling pathways mentioned above at various stages of their activation. Based on literature evidence, we constructed a narrative review on the mechanisms that support the beneficial effects of dipeptidyl peptidase-4 and fibroblast activation protein inhibitors for treating uterine fibroids.

Impact of Uterine Size on Outcomes of Total Laparoscopic Hysterectomy for Uterine Leiomyomas

Background: Given that total laparoscopic hysterectomy (TLH) is less invasive than open surgery, its popularity has increased in Japan. The aim of the present study was to determine the most appropriate uterine size for the safe completion of TLH for the treatment of uterine leiomyomas. Methods: This retrospective study included 505 patients who underwent TLH for uterine leiomyomas. Patients were divided into three groups according to the weight of the excised uterus (&lt;500 g, n = 347; 500–1000 g, n = 125; &gt;1000 g, n = 33). TLH procedures were performed by a resident physician under the supervision of an attending physician. Clinical outcomes including blood loss and duration of surgery were collected from patients’ electronic medical records and compared according to uterine size. Magnetic resonance imaging (MRI) was performed prior to TLH for detection, localization, and measurement of the myoma. Results: Mean operation times were shortest (&lt;500 g: 163 min; 500–1000 g: 190 min; &gt;1000 g: 209 min) and the mean volume of blood lost was lowest (&lt;500 g: 116 mL; 500–1000 g: 208 mL; &gt;1000 g: 402 mL) in patients with a uterus weighing less than 500 g. There were no significant differences in operation time or bleeding between those with a uterine weight of 500–1000 g or &gt;1000 g. MRI revealed that myomas tended to be restricted within the sacral promontory in patients with uterine weights &lt;500 g, whereas those in the other two groups tended to extend beyond this region. Conclusions: TLH outcomes are best when the uterine weight is &lt;500 g. The use of MRI prior to TLH may provide insights into uterine size and/or mass and thus allow for improved surgical planning.

Histotripsy for the Treatment of Uterine Leiomyomas: A Feasibility Study in Ex Vivo Uterine Fibroids.

Uterine fibroids (leiomyomas), the most common benign tumors in women of reproductive age, are a frequent cause of abnormal vaginal bleeding and other reproductive complaints among women. This study investigates the feasibility of using histotripsy, a non-invasive, non-thermal focused ultrasound ablation method, to ablate uterine fibroids. Human fibroid samples (n=16) were harvested after hysterectomy or myomectomy procedures at Carilion Memorial Hospital. Histotripsy was applied to ex vivo fibroids in two sets of experiments using a 700-kHz clinical transducer to apply multicycle histotripsy pulses and a prototype 500-kHz transducer to apply single-cycle histotripsy pulses. Ultrasound imaging was used for real-time treatment monitoring, and post-treatment ablation was quantified histologically using hematoxylin and eosin and Masson trichrome stains. Results revealed that multicycle histotripsy generated diffuse cavitation in targeted fibroids, with minimal cellular ablative changes after treatment with 2000 pulses/point. Single-cycle pulsing generated well-confined bubble clouds with evidence of early coagulative necrosis on histological assessment in samples treated with 2000 pulses/point, near-complete ablation in samples treated with 4000 pulses/point and complete tissue destruction in samples treated with 10,000 pulses/point. This study illustrates that histotripsy is capable of fibroid ablation under certain pulsing parameters and warrants further investigation as an improved non-invasive ablation method for the treatment of leiomyomas.

Radiofrequency ablation methods for uterine sparing fibroid treatment.

This article provides a clinical review of radiofrequency ablation (RFA) for the treatment of uterine leiomyomas. RFA is an effective and durable treatment for fibroids with sustained improvements in fibroid volume, bleeding, and patient reported outcomes with low reintervention rates. Although fertility data is limited, it is overall positive and may represent a uterine conserving and fertility preserving treatment modality. RFA is a safe and effective uterine preserving treatment option for symptomatic leiomyomas.

Ulipristal-temozolomide-hydroxyurea combination for glioblastoma: in-vitro studies.

Glioblastoma multiforme (GBM) is a brain malignancy with worst survival. Low dose progesterone stimulates GBM growth, while progesterone receptor (PR)-antagonist mifepristone was shown to reduce growth and to enhance temozolomide sensitivity in GBM cells. Mifepristone is not available in all countries due to ethical reasons and may cause adrenal insufficiency and pelvic infections. Ulipristal is also a PR-antagonist used in treatment of uterine leiomyomas with higher biosafety. Ulipristal is demonstrated to suppress growth of breast cancer, yet it is not tested as yet whether it can also block growth and sensitize to temozolomide in glioblastoma as it was previously shown with mifepristone. Our first aim was to detect whether ulipristal exerts antiproliferative and chemotherapy-sensitizing effects in glioblastoma. Hydroxyurea inhibits DNA replication via blocking ribonucleotide reductase (RR) and it was demonstrated to increase temozolomide antineoplasticity in GBM. Progesterone receptor-activation in the uterus enhances RR transcription. Hence, we have hypothesized that PR-inactivation with ulipristal would further enhance hydroxyurea antineoplasticity by shutting down DNA synthesis mechanisms through further suppression of RR. Lastly, there exists no study as yet whether ulipristal, hydroxyurea and temozolomide could exert ternary antineoplastic efficacy, which was our last aim to define. To reveal interactions between ulipristal, hydroxyurea and temozolomide, we treated human U251 GBM cell line with these agents alone and in combination and measured cell proliferation, total antioxidant capacity (TAC) and total oxidant status (TOS) in conditioned medium and cellular cytokine gene expressions. All agents significantly reduced cell proliferation significantly, yet the most significant decrease of GBM cells occured with the triple drug combination at the 96th hour. All agents significantly decreased TAC and increased TOS in culture media, which was mostly relevant for the triple combination at the 96th hour. All these 3 agents tend to reduce the expression of immunosuppressive and/or GBM-growth stimulating cytokines TGFβ, IL-10 and IL-17 while increasing the expression of GBM-growth suppressing cytokine IL-23. Repurposal of these agents in treatment of GBM would be a plausible approach if future studies prove their efficacy.

Abstract No. 134 Histotripsy for the treatment of uterine leiomyomas: a feasibility study in ex vivo uterine fibroids

Uterine fibroids (leiomyomas), the most common benign tumors experienced by women of reproductive age, are a leading cause of morbidity and reproductive complication among women. Here, we investigate the feasibility of using histotripsy, a non-invasive and non-thermal focused ultrasound ablation method, for the treatment of uterine fibroids.

Effect of the enhanced recovery after surgery protocol on recovery after laparoscopic myomectomy: a systematic review and meta-analysis

Surgery is the recommended treatment for uterine leiomyoma but it still has issues like postoperative complications and slow recovery. The enhanced recovery after surgery (ERAS) protocol could probably reduce traumatic stress and promote the rapid postoperative recovery of patients, but there are controversies for the results of different studies. This meta-analysis was performed to resolve the controversies and provide evidence for the application of ERAS in gynecology. The PubMed, Embase, Ovid, CNKI (China), Wanfang Data (China), and Google Scholar databases were searched to recruit all studies on the application of ERAS in laparoscopic myomectomy up to November 2021. The inclusion criteria of studies was established according to the PICOS principles. the Cochrane RoB 2.0 and Newcastle-Ottawa Scale (NOS) scale were used to assess the bias of the studies, RevMan 5.3 software was used for meta-analysis. Ten studies that met the criteria were finally included with 1,441 participants. Eight of them were randomized controlled trials (RCTs) and two were cohort studies, all of them were with low level of bias. Meta-analysis showed that ERAS protocol after laparoscopic myomectomy could significantly shorten the first time getting out of bed after surgery [mean difference (MD) =-4.85; 95% confidence interval (CI): (-7.35, -2.36); P=0.0001], the first defecation time after surgery [MD =-4.69; 95% CI: (-5.68, -3.69); P<0.00001], and the postoperative hospital stay [MD =-1.32, 95% CI: (-2.08, -0.56); P=0.0007]. It could also markedly reduce the patient readmission rate [odds ratio (OR) =0.42; 95% CI: (0.23, 0.76); P=0.004], and notably reduced the incidence of complications [OR =0.37; 95% CI: (0.22, 0.61); Z=3.82; P=0.0001]. Yet, the cost of the ERAS protocol was not significantly different from that of routine care [MD =-127.76, 95% CI: (-997.19, 741.66); P=0.77]. The application of ERAS protocol after gynecological laparoscopic myomectomy can shorten the first defecation time, first time out of bed, hospital stay, and reduce the readmission rate as well as the incidence of postoperative complications, without additional costs. But still there was heterogeneity among the studies, the topic still deserved further exploration.