Symptomatic Leiomyomas Research Articles

O-226 Effects of preventive uterine artery occlusion during laparoscopic myomectomy on ovarian reserve markers: a randomized controlled trial

Abstract Study question Does definitive occlusion of uterine arteries have a short or long term impact on anti-Müllerian hormone (AMH) levels in reproductive age women undergoing laparoscopic myomectomy? Summary answer Preventive uterine artery occlusion during laparoscopic myomectomy does not impact AMH levels in reproductive age women. What is known already Uterine leiomyoma are the most common benign tumours in women of reproductive age. For symptomatic women willing to retain their uterus, especially for a future pregnancy, the current gold standard is the myomectomy for subserous/intramural leiomyoma. Temporary or definitive occlusion of uterine arteries can be performed to control bleeding during surgery but its impact on ovarian reserve markers is still unknown. A single randomized trial with a one-year follow-up demonstrated that temporary bilateral uterine artery occlusion during laparoscopic myomectomy slightly decreased AMH levels at day-2 after surgery but has no impact thereafter 3, 6 and 12 months postoperatively. Study design, size, duration We conducted a randomized controlled trial with a two-year follow-up evaluating the effect of definitive occlusion of uterine arteries on ovarian reserve via sequential measures of anti-Müllerian hormone (AMH) levels. Fifty-eight women with symptomatic leiomyoma type FIGO 3-6 scheduled for laparoscopic myomectomy at were included between July 2015 and October 2021. Participants/materials, setting, methods Patients were randomized into: the intervention group (laparoscopic myomectomy with preventive occlusion of uterine arteries) and the control group (laparoscopic myomectomy without occlusion of uterine arteries) ). AMH evaluated at T0 and followed at 1 month (T1), 3 months (T3), 6 months (T6), 12 months (T12) and 24 months (T24) after surgery. Intraoperative blood loss, leiomyoma recurrence and adenomyosis occurrence were also evaluated comparing pre- and post-operative findings. Finally, pregnancies and live births were monitored. Main results and the role of chance Women in both groups did not differ in their baseline characteristics in terms of age, body mass index, ethnicity, parity, wish to become pregnant, hormonal treatment, leiomyoma number and size, baseline haemoglobin levels, bleeding symptoms baseline AMH levels and antral follicular count (AFC). The mean operative time was similar in between both groups. Mean blood loss during surgery was on average 138 (±104)ml in the intervention group versus 436 (±498)ml in controls (p < 0.001). The difference in haemoglobin between before and after surgery was significantly higher in the control group 21.8 (±12.7)g/l compared with the intervention group 14.8 (±8.9)g/l (p = 0.02). Regarding clinical symptoms, most patients had decreased menstrual flow at the last follow-up visit (24 months) compared to baseline in both group improvement of dysmenorrhea followed the same trend with a reduction in pain levels in both groups. Risk of leiomyoma recurrence was found similar between both groups. Most importantly, AMH levels were similar between groups at all times (T1, T3, T6, T12 and T24) and non-inferiority of preventive occlusion was demonstrated with a non-inferiority margin of -3.5pmol/L (0.5 ng/ml). The pregnancy rate was not different between groups. Limitations, reasons for caution Our sample size was calculated to detect a clinically relevant difference of at least two-third of the standard deviation in AMH levels, but we cannot exclude a smaller impact on AMH with a different sample size. Wider implications of the findings Preventive uterine artery occlusion during laparoscopic myomectomy does not impact ovarian reserve markers and can be safely used to control perioperative bleeding. Trial registration number NCT02563392

Outcomes of transvaginal radiofrequency ablation for symptomatic leiomyomas

ObjectiveDescribe the effect of transvaginal radiofrequency ablation for leiomyoma in symptomatic patients and post procedure follow-up. Material and methodsA retrospective forward-looking observational study was performed including 63 patients who underwent transvaginal radiofrequency ablation between January 2016 and December 2022 at San Cecilio University Hospital in Granada, Spain. The variables registered were: age, parity, the clinical features that lead to the medical visit and pre-surgical treatment. Prior to the procedure, leiomyoma location and volume were determined by transvaginal ultrasound. Follow-ups were scheduled at 6 and 12 months to evaluate symptom improvement, adverse outcomes, leiomyoma volume and if any necessary post-surgical treatment was required. ResultsMean leiomyoma volume at baseline, 6 months and 12 months was 83.3 (24.9–130.7), 42.4 (4.7–89.0) and 19.2 (1.9–80.4) cm3, respectively (p < .001). Significant differences were found between the baseline and 12 month visits (p < .001). At the annual follow-up, the mean rate of volume reduction was 79.5 %, being higher in women who reported symptom improvement compared to those who reported no change in symptom intensity from baseline (84.6% vs. 30.8 %). Patients with a lower initial volume and age over 40 were more likely to have treatment efficacy. 8 pregnancies were registered post procedure. ConclusionRadiofrequency is well tolerated, allowing for same-day discharge, rapid recovery and a safe approach for women who want to preserve their reproductive potential. Initial volume and age over 40 appear to be factors that should be considered in patient selection. Further studies are needed to continue evaluating the outcomes and identifying predictive factors.

An Unusually Large Symptomatic Leiomyoma of the Renal Capsule

Leiomyoma of the renal capsule is an extremely rare tumor. Diagnosis is usually made by histopathological examination of surgically removed specimen by partial or radical nephrectomy. We present the case of a 57-year-old female who presented with low backache and right leg pain and on evaluation leiomyoma of renal capsule. It was detected to have unusually large right renal mass mimicking renal cell carcinoma. Radical nephrectomy was done due to large tumor size and histopathology confirmed leiomyoma of the renal capsule.

Oxytocin Infusion versus Vaginal Misoprostol in Reducing Blood Loss during Abdominal Myomectomy: A Randomized Controlled Trial

Background Uterine myomas are most prevalent benign tumors in reproductive-aged women. Myomectomy is an alternative to hysterectomy for women who wish to retain their uterus but it is associated with higher risk of blood loss, greater operative time and need for blood transfusion. Knowledge of the effectiveness of the interventions to reduce bleeding during myomectomy is essential to enable evidence-based clinical decisions. Aim of the Work The aim of the study is to compare between the efficacy of intraoperative oxytocin infusion and preoperative vaginal misoprostol in reducing blood loss during abdominal myomectomies. Methods In a prospective randomized controlled trial which was conducted at Ain shams maternity Hospital in Cairo from July 2017 to May 2021.100 women who had abdominal myomectomy for symptomatic leiomyomas were enrolled. Patients were randomly assigned to 2 groups. Group O (Oxytocin group) patients (n = 50) received 30 U oxytocin in 500 ml normal saline infusion intraoperative and Group M (Misoprostol group) An hour before the operation, patients (n = 50) received a single dose of vaginal misoprostol (400 μg). The primary outcome was the operative blood loss. The secondary outcomes were the need for blood transfusion, change in hemoglobin (Hb) and hematocrit (Hct) levels 24 h after operation, conversion to hysterectomy, hospitalization and the prevalence of side effects. Results Intra-operative blood loss was significantly lower in those women randomized to receive vaginal misoprostol versus the oxytocin infusion group (458.5 ± 115.4 mL vs 618.8 ± 115.1 ml {P = &amp;lt; 0.001}). Misoprostol group showed lower mean blood loss by – 160.3 ml (95% CI -206.0 to -114.6) and reduced need for blood transfusion (RR 0.22, 95% CI 0.005 to 0.98) {P = 0.025}. Additionally, there was a highly significant statistical difference between Misoprostol group and Oxytocin group as regards the postoperative hemoglobin, hematocrit concentration, operative time as Misoprostol group showed a higher postoperative hemoglobin and hematocrit concentration, and less operative time. There was no difference in the patient demographics, intraoperative characteristics, postoperative stay, complications, and the side effects between the two groups. Conclusion As evident from the current study, pre-operative misoprostol in abdominal myomectomy is a safe and reliable method that offers some practical advantages, such as reducing intra-operative blood loss and blood transfusion needs

Frequency of Diseases Requiring Hysterectomy: A Cross Sectional Study at Tertiary Care Hospitals in Peshawar

Hysterectomy, after cesarean section is the most common performed major surgical procedures all over the world. In the united states, 5.5/1000 women underwent hysterectomy in the years 2001 to 2005. Objective: To estimate the frequencies of different diseases that needs hysterectomy at Peshawar Medical College and its affiliate hospitals. Methods: This cross-sectional study was carried out from 3rd Oct, 2020 to 3rd Oct, 2021 at the Department of Obstetrics and Gynecology, Peshawar Medical College and its affiliated hospitals. Consecutive sampling was done and a sample size of 104 patients was obtained. Those patients who recently underwent abdominal or vaginal hysterectomies aged 25-60 years with history of any parity were included. Patients with co-morbid conditions such ischemic heart disease, chronic kidney disease, malignancies and other obstetric complications such as emergency cesarean hysterectomies were excluded. Results: Mean age with standard deviation was 48.55 ± 8.53. Mean and standard deviation for weight was 73.20 ± 6.103. Of total patients, 44 (42.3%) patients had symptomatic fibroid uterus, 29 (27.9%) patients had uterovaginal prolapse while 31 (29.8%) patients had abnormal uterine bleeding as indication for hysterectomy. Among these patients, 66 (63.5%) were subjected to abdominal hysterectomy while 38 (36.5%) went through vaginal hysterectomy. Conclusions: The most common disease that needs hysterectomy in our study was symptomatic leiomyomas of uterus followed by abnormal uterine bleeding due to other causes and uterovaginal prolapse.

Racial differences in transcriptomics and reactive oxygen species burden in myometrium and leiomyoma.

Are there differences in Mediator Complex Subunit 12 mutations (MED12) mutation, transcriptomics, and protein expression in uterine myometrium and leiomyomas of Black and White women? RNA sequencing, tissue microarray, and immunohistochemistry data revealed that Black and White women have significant differences in their myometrium and leiomyoma profiles. Black women develop uterine leiomyoma earlier than White women, and are more likely to be anemic, have multiple tumors, undergo hysterectomy at an earlier age, have a higher uterine weight, and report very severe pelvic pain. Uterine tissues were collected from premenopausal women undergoing hysterectomy or myomectomy at Northwestern University Prentice Women's Hospital (Chicago, IL) from 2010 to 2021. Tissues were collected from a total of 309 women, including from 136 Black women, 135 White women, and 38 women from other racial groups. A total of 529 uterine leiomyomas (290 from Black women, 184 from White women, and 55 from women of other racial groups) were subjected to molecular analysis. Leiomyoma and matched myometrium from a total of 118 cases including 60 Black women and 58 White women, were used for tissue microarrays, along with 34 samples of myometrium without leiomyoma from White women. Tissues from the above patient cohorts were analyzed by tissue microarray, immunohistochemistry, RNA sequencing, and mutation analysis. The results indicated that leiomyoma from Black women have a higher rate of MED12 mutations (79.0%) than those from White women (68.5%) (*P ≤ 0.05). RNA-sequencing analysis in myometrium revealed differentially expressed genes (270 upregulated, 374 downregulated) dependent on race, wherein reactive oxygen species, hypoxia, and oxidative phosphorylation pathways were positively correlated with samples derived from Black patients. The levels of proteins associated with oxidative DNA damage and repair, 8-hydroxyguanosine (8-OHdG), 8-oxoguanine glycosylase (OGG1), heme oxygenase-1 (HO-1), and kelch-like ECH-associated protein 1 (KEAP1), were higher in leiomyoma and matched myometrium, particularly those from Black patients, compared to the control myometrium (with leiomyoma) (***P ≤ 0.001). The datasets are available in the NCBI (The BioProject number: PRJNA859428). Myometrium without leiomyoma derived from White patients was used as a control in the tissue microarray analysis, as myometrium without leiomyoma from Black patients was not accessible in large numbers. The RNA sequencing was performed on myometrium tissue with leiomyoma present from 10 White and 10 Black women. However, one sample from a Black woman yielded low-quality RNA-sequencing data and was excluded from further analysis. Women with symptomatic leiomyomas have a considerable loss in their quality of life. This study provides information on underlying genetic and molecular defects that may be necessary for future therapeutics targeted at leiomyomas. This work was supported by grants from NCI (R01CA254367) and NICHD (P01HD057877). The authors declare no conflict of interest.

Deep learning enables automated MRI-based estimation of uterine volume also in patients with uterine fibroids undergoing high-intensity focused ultrasound therapy

BackgroundHigh-intensity focused ultrasound (HIFU) is used for the treatment of symptomatic leiomyomas. We aim to automate uterine volumetry for tracking changes after therapy with a 3D deep learning approach.MethodsA 3D nnU-Net model in the default setting and in a modified version including convolutional block attention modules (CBAMs) was developed on 3D T2-weighted MRI scans. Uterine segmentation was performed in 44 patients with routine pelvic MRI (standard group) and 56 patients with uterine fibroids undergoing ultrasound-guided HIFU therapy (HIFU group). Here, preHIFU scans (n = 56), postHIFU imaging maximum one day after HIFU (n = 54), and the last available follow-up examination (n = 53, days after HIFU: 420 ± 377) were included. The training was performed on 80% of the data with fivefold cross-validation. The remaining data were used as a hold-out test set. Ground truth was generated by a board-certified radiologist and a radiology resident. For the assessment of inter-reader agreement, all preHIFU examinations were segmented independently by both.ResultsHigh segmentation performance was already observed for the default 3D nnU-Net (mean Dice score = 0.95 ± 0.05) on the validation sets. Since the CBAM nnU-Net showed no significant benefit, the less complex default model was applied to the hold-out test set, which resulted in accurate uterus segmentation (Dice scores: standard group 0.92 ± 0.07; HIFU group 0.96 ± 0.02), which was comparable to the agreement between the two readers.ConclusionsThis study presents a method for automatic uterus segmentation which allows a fast and consistent assessment of uterine volume. Therefore, this method could be used in the clinical setting for objective assessment of therapeutic response to HIFU therapy.

Epidemiologic and Therapeutic Aspect of Urogenital Fistula Following Obstetric and Gynecologic Surgeries Repaired at the Nkwen Baptist Hospital

Introduction: Urogenital fistula is an abnormal communication between the urinary and the genital systems. It may occur following vaginal deliveries or following pelvic surgeries. Data concerning urogenital fistula post-surgery is limited and we have noticed in recent years in Sub-Saharan Africa, an increase in the burden of iatrogenic urogenital fistula. Objective: The aim of this study was to assess the epidemiology, clinical profiles and therapeutic aspects of urogenital fistula following obstetric and gynaecologic surgeries repaired at the Nkwen Baptist Hospital Bamenda. Materials/Methods: This was a longitudinal descriptive study with a retrospective and prospective phase carried out at the Nkwen Baptist Hospital for 5 months. However the complete duration of the study was about 17 months. Data was collected using a pretested questionnaire containing socio-demographic information, clinical features, and therapeutic methods used. We used the statistical software SPSS (Social Package for Statistical Sciences) V 26.0 for data analysis. Results: The number of participants in the study was 40. The mean age was 43.5 years (+/- 13.3) ranging from 16 - 74 years. The prevalence of urogenital fistula post obstetric and gynecologic surgeries at the Nkwen Baptist hospital was 64.6%. The most common symptom was urine leakage and the most common surgery that exposed the patient to the urogenital fistula was total abdominal hysterectomy (60%) followed by caesarean section (35%). The different indications for these surgeries were mostly symptomatic leiomyoma (70.8 %) and prolonged labor (64.2%) respectively. The different types of fistula encountered were Vesicovaginal fistula (55%), Ureterovaginal fistula 40% and Vesicoutetrine fistula 5%. The different treatment modalities used were trans abdominal (77.5%) and transvaginal repair (22.5%). The overall repair success rate after one month was 85%. Conclusion: There is high burden of urogenital fistula post surgeries in our setting. Having more specialists trained in obstetric and gynaecologic procedures may help in the prevention of such an event.

New local ganirelix sustained release therapy for uterine leiomyoma. Evaluation in a preclinical organ model

Currently, there is a limited number of treatment options available for patients with symptomatic leiomyomas, and surgical removal is by far the most frequent procedure. Previous studies found that GnRH agonists and antagonists acting through GnRH receptors led to cell death and decreased extracellular synthesis in cultured leiomyoma cells. In this study, we encapsulated the GnRH antagonist ganirelix in PLGA microspheres contained in an alginate scaffold that also supports a leiomyoma ex vivo tissue explant. Microspheres maintained ganirelix concentration stably during six days of culture, inducing significant cell death in 50–55% of tumor cells. Although no changes were observed in the expression of extracellular matrix genes, a decreased expression of the Nuclear Factor of Activated T cells 5, a transcription factor involved in osmotic stress and tumor size. Interestingly, all tumors analyzed experienced apoptosis independently of the original driver mutation. These data indicate that local therapy of ganirelix would induce tumor reduction in a wide range of uterine leiomyomas.

The impact of anemia on treatment management and clinical outcomes of women hospitalized for uterine leiomyomas.

Uterine leiomyomas are the most common benign gynecological tumors. Symptomatic leiomyomas represent a major cause of hospitalization, particularly those associated with abnormal uterine bleeding (AUB) and anemia. The aim of this study was to identify predictors of anemia in women hospitalized due to uterine leiomyomas and evaluate its impact on treatment management and clinical outcomes. Population-based retrospective study of women hospitalized for uterine fibroids in public hospitals in mainland Portugal between 2010 and 2015. Data were extracted from the national database of the Central Administration of the Portuguese Health System. Comparative and multivariable logistic regression analysis was performed to assess outcomes. A total of 36 295 patients were hospitalized due to uterine leiomyomas during this period. Of those, 11.5% presented with anemia. Age, obesity, intramural type of leiomyoma and AUB are independent predictors of anemia (p < 0.001, AUC 0.7056). Anemia was associated with a high risk of inpatient hospitalization (OR: 5.161, 95% CI: 4.376-6.085), urgent admission (OR: 1.953, 95% CI: 1.797-2.121), radical surgical approach (OR: 2.559, 95% CI: 2.298-2.849), laparoscopic hysterectomy (OR: 1.575, 95% CI: 1.393-1.780) and intra- and post-operative complications (OR: 5.285, 95% CI: 4.332-6.448). It was also associated with longer hospital stays (p < 0.001). These outcomes were more pronounced in acute anemic patients. Anemia has a significant impact on treatment approaches and clinical outcomes of women hospitalized for uterine leiomyomas. Age, obesity, intramural leiomyomas and AUB are some predictors of anemia that could represent a risk-stratification opportunity, allowing for its prompt identification and correction, therefore improving patient care.

MRI Evaluation of Uterine Masses for Risk of Leiomyosarcoma: A Consensus Statement.

Laparoscopic myomectomy, a common gynecologic operation in premenopausal women, has become heavily regulated since 2014 following the dissemination of unsuspected uterine leiomyosarcoma (LMS) throughout the pelvis of a physician treated for symptomatic leiomyoma. Research since that time suggests a higher prevalence than previously suspected of uterine LMS in resected masses presumed to represent leiomyoma, as high as one in 770 women (0.13%). Though rare, the dissemination of an aggressive malignant neoplasm due to noncontained electromechanical morcellation in laparoscopic myomectomy is a devastating outcome. Gynecologic surgeons' desire for an evidence-based, noninvasive evaluation for LMS is driven by a clear need to avoid such harms while maintaining the availability of minimally invasive surgery for symptomatic leiomyoma. Laparoscopic gynecologists could rely upon the distinction of higher-risk uterine masses preoperatively to plan oncologic surgery (ie, potential hysterectomy) for patients with elevated risk for LMS and, conversely, to safely offer women with no or minimal indicators of elevated risk the fertility-preserving laparoscopic myomectomy. MRI evaluation for LMS may potentially serve this purpose in symptomatic women with leiomyomas. This evidence review and consensus statement defines imaging and disease-related terms to allow more uniform and reliable interpretation and identifies the highest priorities for future research on LMS evaluation.

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.

Short-Term Health-Related Quality of Life After Hysterectomy Compared With Myomectomy for Symptomatic Leiomyomas.

Short-Term Health-Related Quality of Life After Hysterectomy Compared With Myomectomy for Symptomatic Leiomyomas.

Laparoscopic in-bag morcellation - a comparison of two tissue extraction systems.

Morcellation is an integral part of laparoscopic procedures related to uterine fibroids, which consist of the mechanical fragmentation of the tumor and its extraction outside the abdominal cavity. To avoid the risk of tissue dissemination, special extraction systems have been developed, which allow morcellation of the specimen under visual control and its removal without contact with the abdominal organs. The aim of the paper is to compare the two systems for laparoscopic morcellation. The study included 33 premenopausal women with symptomatic leiomyomas or adenomyosis, who were qualified for laparoscopic surgery with contained power morcellation. Patients were allocated alternately to a different tissue extraction system's group. According to the study protocol, selected operative parameters were prospectively recorded. Finally, an assessment of bag use was performed. The data was statistically analyzed. There were significant differences between the two tested systems in terms of introducing and positioning the bag, its removal from the peritoneal cavity, as well as optic trocar insertion and establishing the pseudo-peritoneum. Despite the minor design differences and some ergonomic aspects, both presented systems proved to be safe and feasible tools for laparoscopic contained morcellation. This technique both reduces the risk of tissue dissemination and preserves the advantages of minimal invasiveness.

The True Fibroid Map: Correlating Preoperative MRI and Intraoperative Findings

Study Objective To evaluate and compare the accuracy of Magnetic Resonance Imaging (MRI) in myoma diagnosis and mapping and its correlation with intraoperative findings. Design All patients with symptomatic leiomyoma attending the centre of study (Centre for minimally invasive Gynaecology, Obstetrics and ART, Paras Hospital, India) from August 2018-June 2020 underwent MRI and were subsequently operated at the same centre were considered for inclusion. The MRI was reviewed for number of fibroids, size, location, type and FIGO class of the largest fibroid and the same was correlated with intraoperative findings. Setting N/A. Patients or Participants 42 women with a diagnosis of symptomatic leiomyoma and meeting the inclusion criteria were enrolled. Interventions Laparoscopic myomectomy, Hysteroscopic myomectomy, Total laparoscopic hysterectomy, Abdominal myomectomy. Measurements and Main Results Of 42 patients enrolled, the number of fibroids predicted by MRI corroborated with intraoperative findings in 26 patients, 15 patients had greater number of fibroids during surgery and 1 had less than that predicted (median fibroid on MRI=2.0, median number in surgery=2.0, p=0.001). Location of largest fibroid predicted by MRI correlated with intraoperative findings in 77.8% anterior wall, 90% posterior wall, 83.3% left lateral wall and in 81.8% of fundal fibroids (k=0.757, p<0.001). MRI could accurately predict the type of fibroid in 80% submucosal, 87.5% intramural and 66.7% subserosal variants (k=0.642, p<0.001). FIGO class of largest fibroid denoted by MRI showed good correlation with intraoperative findings (k=0.670, p<0.001). Size of largest fibroid predicted by MRI (median=58.5cm2) correlated well with size measured during surgery (median= 60cm2, k=0.819). Conclusion MRI is an efficient tool for mapping of fibroid location, type and FIGO class but falls short in identifying the exact number of fibroids that can be encountered during surgery particulary in patients with larger uteri (> 12-week size) or multiple myomas (>5 in number). To evaluate and compare the accuracy of Magnetic Resonance Imaging (MRI) in myoma diagnosis and mapping and its correlation with intraoperative findings. All patients with symptomatic leiomyoma attending the centre of study (Centre for minimally invasive Gynaecology, Obstetrics and ART, Paras Hospital, India) from August 2018-June 2020 underwent MRI and were subsequently operated at the same centre were considered for inclusion. The MRI was reviewed for number of fibroids, size, location, type and FIGO class of the largest fibroid and the same was correlated with intraoperative findings. N/A. 42 women with a diagnosis of symptomatic leiomyoma and meeting the inclusion criteria were enrolled. Laparoscopic myomectomy, Hysteroscopic myomectomy, Total laparoscopic hysterectomy, Abdominal myomectomy. Of 42 patients enrolled, the number of fibroids predicted by MRI corroborated with intraoperative findings in 26 patients, 15 patients had greater number of fibroids during surgery and 1 had less than that predicted (median fibroid on MRI=2.0, median number in surgery=2.0, p=0.001). Location of largest fibroid predicted by MRI correlated with intraoperative findings in 77.8% anterior wall, 90% posterior wall, 83.3% left lateral wall and in 81.8% of fundal fibroids (k=0.757, p<0.001). MRI could accurately predict the type of fibroid in 80% submucosal, 87.5% intramural and 66.7% subserosal variants (k=0.642, p<0.001). FIGO class of largest fibroid denoted by MRI showed good correlation with intraoperative findings (k=0.670, p<0.001). Size of largest fibroid predicted by MRI (median=58.5cm2) correlated well with size measured during surgery (median= 60cm2, k=0.819). MRI is an efficient tool for mapping of fibroid location, type and FIGO class but falls short in identifying the exact number of fibroids that can be encountered during surgery particulary in patients with larger uteri (> 12-week size) or multiple myomas (>5 in number).

Simvastatin Inhibits Wnt/β-Catenin Pathway in Uterine Leiomyoma.

The Wnt/β-catenin pathway is upregulated in uterine leiomyomas, the most common benign tumors in the female reproductive tract. Simvastatin is an antihyperlipidemic drug, and previous in vitro and in vivo reports showed that it may have therapeutic effects in treating leiomyomas. The objective of this study was to examine the effects of simvastatin on the Wnt/β-catenin signaling pathway in leiomyoma. We treated primary and immortalized human leiomyoma cells with simvastatin and examined its effects using quantitative real-time polymerase chain reaction, Western blotting, and immunocytochemistry. We also examined the effects using human leiomyoma tissues from an ongoing randomized controlled trial in which women with symptomatic leiomyoma received simvastatin (40 mg) or placebo for 3 months prior to their surgery. The results of this study revealed that simvastatin significantly reduced the expression of Wnt4 and its co-receptor LRP5. After simvastatin treatment, levels of total β-catenin and its active form, nonphosphorylated β-catenin, were reduced in both cell types. Additionally, simvastatin reduced the expression of Wnt4 and total β-catenin, as well as nonphosphorylated β-catenin protein expression in response to estrogen and progesterone. Simvastatin also inhibited the expression of c-Myc, a downstream target of the Wnt/β-catenin pathway. The effect of simvastatin on nonphosphorylated-β-catenin, the key regulator of the Wnt/β-catenin pathway, was recapitulated in human leiomyoma tissue. These results suggest that simvastatin may have a beneficial effect on uterine leiomyoma through suppressing the overactive Wnt/β-catenin pathway.

UTERINE ARTERY EMBOLIZATION AS AN EFFICACIOUS STAND-ALONE TECHNIQUE IN MANAGEMENT OF SYMPTOMATIC UTERINE LEIOMYOMATA

Background: Uterine artery embolization is now evolving to be the first-line therapy for symptomatic uterine leiomyoma alongside elder conventional alternatives comprising hysterectomy and myomectomy whether surgical or endoscopic. Many clinical trials have confronted UAE and surgical therapies as regard safety and efficacy in treatment of symptomatic leiomyomas where UAE exhibited comparable short and mid-term clinical outcomes, encompassing symptomatic amelioration, better quality of life and psychological satisfaction benefiting from uterine preservation.Aim of the Work: to emphasize the role of the trans-catheter uterine artery embolization as an effective stand-alone technique in treating the symptoms attributable to uterine leiomyomata.Patients and Methods: This study included 30 patients with uterine fibroids referred from gynecology clinic to interventional radiology unit to be counseled for UAE.Results: Follow-up symptomatic assessment was done for all patients at 1 and 3 months. Most patients confirmed symptomatic amelioration at 1 months persisting or continue at 3-month follow-up visit. Among 21 patients presented with bleeding, 90.5% of patients reported symptomatic improvement at 1 month post-procedurally continued to increase to reach 95.2% at 3 months follow-up visit, however, no significant symptomatic change was noted between 3, 6 months follow up. Fourteen patients complained from pressure symptoms. At 1-month follow-up, 71.44% of patients stated improvement, 14.29% had stationary course with similar percentage exhibited slightly worse response. Contrariwise, 85.71% of patients reported symptomatic amelioration at 3 month and 14.3% had no change. Indifferent from bleeding, a highly statistically significant time improvement between 1, 3 months follow up is notable. Of 13 patients admitted with pelvic pain, 53.9% get improved, 30.77% showed no change, 15.38 % gave slightly worse response in comparison to 84.7%, 7.69%, 7.69% at 1, 3 months follow-up clinical assessment visits. There is clinical reduction of pain between 1, 3 months however it didn’t reach clinical significance. Among three patients presented with infertility, one gets pregnant at 3 months follow up with no significant change between 1, 3 months follow up. On MRI, the mean uterine volume was reduced by 30% 6 months after treatment. Similarly, mean dominant leiomyoma volume was reduced by 44 % after 6 months. There was highly statistically reduction of volume between 1 and 6 months follow up. Conclusion: Although limited by small sample size however we might conclude that UAE is associated with considerable cumulative reduction of leiomyoma volume that parallels patients’ symptomatic amelioration and psychological satisfaction and should be considered among first lines of management of symptomatic leiomyoma particularly in child-bearing age.

Single-Incision versus Multiport Robotic Myomectomy: A Propensity Score Matched Analysis of Surgical Outcomes and Surgical Tips.

We aimed to compare the perioperative outcomes of single-incision robotic myomectomy (SIRM) and multiport robotic myomectomy (MPRM) and provide surgical tips. We retrospectively analyzed the medical records of 462 patients with symptomatic leiomyoma who underwent MPRM or SIRM between March 2019 and April 2021. Demographic characteristics and surgical outcomes, including the total operative time (OT), estimated blood loss (EBL), and surgical complication rate, were compared between the two groups. Patients in the SIRM group had lower a body mass index and rate of previous pelvic surgery and were younger than those in the MPRM group. The myoma type was not different between groups; however, the MPRM group had larger, and more myomas than the SIRM group. After propensity score matching, these variables were not significantly different between the groups. The total OT, EBL, difference in hemoglobin levels, transfusion rate, and postoperative fever were not different between the groups. No postoperative complications occurred in the SIRM group. In the MPRM group, one patient needed conversion to laparotomy, and two patients had postoperative complications (umbilical incisional hernia and acute kidney injury). In conclusion, both MPRM and SIRM are feasible and effective surgical options for symptomatic myomas with cosmetic benefits and minimal risk of laparotomy conversion.

P–543 Inhibition of cell proliferation and extracellular matrix formation in human uterine leiomyomas by 5-aza–2’-deoxycitidine via Wnt/ β-catenin pathway

Abstract Study question Is DNA methylation reversion through DNA methyltransferases (DNMT) inhibitors, such as 5-aza–2’-deoxycitidine, a potential therapeutic option for treatment of patients with uterine leiomyomas (UL)? Summary answer 5-aza–2’-deoxycitidine reduces proliferation and extracellular matrix (ECM) formation by inhibition of Wnt/ β-catenin pathway on UL cells, suggesting DNMT inhibitors as an option to treat UL. What is known already: UL is a multifactorial disease with an unclear pathogenesis and inaccurate treatment. Aberrant DNA methylation have been found in UL compared to myometrium (MM) tissue, showing hypermethylation of tumor suppressor genes, which contributes to the development of this tumor. The use of DNMT inhibitors, such as 5-aza–2’-deoxycytidine (5-aza-CdR), has been suggested to treat tumors in which altered methylation pattern is related to tumor progression, as occurs in UL. Based on this, we aimed to evaluate whether DNA methylation reversion through 5-aza-CdR reduces cell proliferation and ECM formation in UL cells, being a potential option for UL medical treatment. Study design, size, duration Prospective study comparing UL versus MM tissue and human uterine leiomyoma primary (HULP) cells treated with/without 5-aza-CdR at 0 µM (control), 2 µM, 5 µM and 10 µM for 72 hours. UL and MM tissue were collected from women without any hormonal treatment for the last 3 months (n = 16) undergoing myomectomy or hysterectomy due to symptomatic leiomyoma pathology. Participants were recruited between January 2019 and February 2020 at Hospital Universitario y Politecnico La Fe (Spain). Participants/materials, setting, methods Samples were collected from Caucasian premenopausal women aged 31–48 years, with a body mass index of &amp;lt; 30 and without hormonal treatment. DNMT1 gene expression was analysed in UL vs MM tissue by qRT-PCR and activity of DNMT was measured in UL and MM tissue and cells by ELISA. 5-aza-CdR effect on proliferation was assessed by CellTiter test and Western blot (WB), apoptosis and ECM analyzed by WB and Wnt/ β-catenin pathway by qRT-PCR and WB. Main results and the role of chance: DNMT1 gene expression was increased in UL compared to MM tissue (fold change [FC]=2.49, p-value [p]=0.0295). Similarly, DNMT activity was increased in both UL compared to MM tissue and HULP cells versus MM cells (6.50 vs 3.76 OD/h/mg, p = 0.026; 211.30 vs 63.67 OD/h/mg, p = 0.284, respectively). After 5-aza-CdR treatment, cell viability of HULP cells was reduced in a dose dependent manner, being statistically significant at 10 µM (85.25%, p = 0.0001). Accordantly, PCNA protein expression was significantly decreased at 10 µM in HULP cells (FC = 0.695, p = 0.034), demonstrating cell proliferation inhibition. Additionally, 5-aza-CdR inhibited ECM protein expression in HULP cells in a dose-dependent manner being statistically significant at 10 µM for COLLAGEN I (FC = 0.654, p = 0.023) and PAI–1 (FC = 0.654, p = 0.023), and at 2 µM and 10 µM for FIBRONECTIN (FC = 0.812, p = 0.020; FC = 0.733, p = 0.035; respectively). Final targets of Wnt/ β-catenin pathway were decreased after 5-aza-CdR treatment, protein expression of WISP1 was significantly inhibited at 10 µM (FC = 0.699, p = 0.026), while expression levels of Wnt/ β-catenin target genes C-MYC (FC = 0.745, p = 0.028 at 2 µM; FC = 0.728, p = 0.019 at 10 µM) and MMP7 (FC = 0.520, p = 0.003 at 5 µM, FC = 0.577, p = 0.007 at 10 µM) were also significantly downregulated in HULP-treated cells vs untreated cells. Limitations, reasons for caution: This study has strict inclusion criteria to diminish epigenetic variability, thereby we should be cautious extrapolating our results to general population. Besides, this is a proof of concept with the inherent cell culture limitations. Further studies are necessary to determine 5-aza-CdR dose and adverse effects on UL in vivo. Wider implications of the findings: 5-aza-CdR treatment reduces cell proliferation and ECM formation through Wnt/ β-catenin pathway inhibition, suggesting that inhibition of DNA methylation could be a promising new therapeutic approach to treat UL. Trial registration number Not applicable

Comparison of 1.5 T and 3 T non-contrast-enhanced MR angiography for visualization of uterine and ovarian arteries before uterine artery embolization.

This study aimed to compare the performance of non-contrast-enhanced magnetic resonance angiography (NCE-MRA) at 1.5 T and 3 T for the visualization of uterine and ovarian arteries (OAs) before uterine artery embolization (UAE). Preprocedural pelvic NCE-MRA images of 85 symptomatic patients undergoing UAE for the treatment of uterine leiomyomas were reviewed by two specialists in pelvic MRI. Left and right uterine arteries (UAs) were judged separately and scored on a 5-point scale. Score 5 was the highest, in which the UA could be visualized inside the musculature, forming a peritumoral plexus. Score 1 was the lowest, where visualization was limited to the descending segment. The detection of enlarged OAs was also compared. The Mann-Whitney U and Fisher exact tests were used for statistical analysis. p < 0.05 was considered to be statistically significant. Of the 170 UAs, 110 were classified at 1.5 T and 60 were classified at 3 T. Median (interquartile range [IQR]) score was 3 (IQR: 2-4) for visualization at 1.5 T vs 5 (IQR: 4-5) for 3 T. The scores for UA visualization were significantly higher at 3 T (p < 0.05). For enlarged OAs, NCE-MRA at 1.5 T and 3 T visualized 7 and 5 enlarged OAs, respectively; there was no significant difference between the two field strengths (p = 0.36). NCE-MRA performed at 3 T can visualize UAs over a greater range than at 1.5 T. No difference was found regarding the detection of enlarged OAs. • Preprocedural MRA can provide interventional radiologists with valuable information, including the origin and course of the uterine arteries and the existence of collateral feeders to the tumor. • This study demonstrates the superiority of non-contrast-enhanced MRA performed at 3 T over that performed at 1.5 T in the visualization of the uterine arteries in patients undergoing uterine artery embolization for the treatment of uterine leiomyomas. • Non-contrast-enhanced MRA is a useful imaging modality for patients with symptomatic leiomyoma undergoing uterine artery embolization in whom contrast administration is unfeasible. If available, it is preferable to perform the examination with a 3 T MR unit rather than a 1.5 T MR unit.