Uterine leiomyosarcoma (uLMS) is the most common subtype of uterine sarcomas. They have a poor prognosis with high rates of recurrence and metastasis. The five-year survival for uLMS patients is between 25 and 76%, with survival rates approaching 10-15% for patients with metastatic disease at the initial diagnosis. Accumulating evidence suggests that several biological pathways are involved in uLMS pathogenesis. Notably, drugs that block abnormal functions of these pathways remarkably improve survival in uLMS patients. However, due to chemotherapy resistance, there remains a need for novel drugs that can target these pathways effectively. In this review article, we provide an overview of the recent progress in ascertaining the biological functions and regulatory mechanisms in uLMS from the perspective of aberrant biological pathways, including DNA repair, immune checkpoint blockade, protein kinase and intracellular signaling pathways, and the hedgehog pathway. We review the emerging role of epigenetics and epitranscriptome in the pathogenesis of uLMS. In addition, we discuss serum markers, artificial intelligence (AI) combined with machine learning, shear wave elastography, current management and medical treatment options, and ongoing clinical trials for patients with uLMS. Comprehensive, integrated, and deeper insights into the pathobiology and underlying molecular mechanisms of uLMS will help develop novel strategies to treat patients with this aggressive tumor.

UNASSIGNED: Uterine leiomyomas, or fibroids, are prevalent benign gynecological tumors affecting many women during their reproductive years. While surgical excision has long been the gold standard for fibroid treatment, the pharmacological management, including progesterone receptor modulators like mifepristone (RU 486), has garnered attention due to the reduced surgical approaches. However, there is a notable paucity of research on the effectiveness of mifepristone, on the same. This study seeks to evaluate the safety and efficacy of mifepristone in reducing uterine leiomyoma size and alleviating associated symptoms.
UNASSIGNED: Conducted prospectively, the study enrolled 20 pre-menopausal women, aged 18 years or older, from Nanavati Max Super Speciality Hospital Mumbai, Maharashtra, India. Participants were selected based on specific inclusion criteria, including the presence of at least one uterine myoma with a minimum diameter of 2.5 cm as confirmed by ultrasound. Participants had an average age of 39.75 years and an average BMI of 27.58 kg/m2.
UNASSIGNED: The study found that mifepristone significantly reduced uterine volume by 75%, with hemoglobin levels substantially improving from 9 gm/dL initially to 12.51 gm/dL after six months. Pain intensity, assessed using the Visual Analog Scale (VAS) score, gradually decreased from baseline to three-month, with all 20 patients reporting the complete absence of pelvic pain by six months.
UNASSIGNED: This prospective study highlights mifepristone\'s promise as a non-surgical approach to effectively reduce uterine fibroid volume, improve hemoglobin levels, and mitigate uterine blood loss in patients.

UNASSIGNED: Uterine fibroids locations and sizes, have significant influences on the quality of life of women especially pregnant women and on live birth rate.
UNASSIGNED: To determine the anatomical locations and sizes of uterine fibroids and assess any possible associations with age groups.
UNASSIGNED: This retrospective study reviewed the locations and sizes of a total of 3,542 patients who were ultrasonographically diagnosed with uterine fibroids from January 2019 to December 2021. The obtained data were analysed using GNU PSPP, and Python on Jupyter Notebook with statistical significance level set at p≤0.05.
UNASSIGNED: The overall average diameter of uterine myoma was 5.50±2.60cm (95%CI=5.41-5.58, range=1.00cm-19.10cm) and the respective mean diameter of intramural, subserosal and submucosal fibroids were 5.53±2.60cm (95%CI=5.44-5.62), 5.50±2.27cm (95%CI=5.27-5.74) and 5.82±2.77cm (95%CI=5.49-6.14). Most of the fibroid nodules were small (48.36%, n=1713) and only 5.84% (n=207) were large (>10cm). Posterofundal fibroids and lower anterior myomas were mostly seen in the 35-44 years age class.
UNASSIGNED: The majority of the uterine fibroids were intramural and were mostly at the anterior uterine wall. The submucosal fibroids, even though the rarest, were averagely larger than the other types of uterine myomas. The diameter of uterine fibroids increased with age.

OBJECTIVE: To assess the feasibility and efficacy of a deep learning-based three-dimensional (3D) super-resolution diffusion-weighted imaging (DWI) radiomics model in predicting the prognosis of high-intensity focused ultrasound (HIFU) ablation of uterine fibroids.
METHODS: This retrospective study included 360 patients with uterine fibroids who received HIFU treatment, including Center A (training set: N = 240; internal testing set: N = 60) and Center B (external testing set: N = 60) and were classified as having a favorable or unfavorable prognosis based on the postoperative non-perfusion volume ratio. A deep transfer learning approach was used to construct super-resolution DWI (SR-DWI) based on conventional high-resolution DWI (HR-DWI), and 1198 radiomics features were extracted from manually segmented regions of interest in both image types. Following data preprocessing and feature selection, radiomics models were constructed for HR-DWI and SR-DWI using Support Vector Machine (SVM), Random Forest (RF), and Light Gradient Boosting Machine (LightGBM) algorithms, with performance evaluated using area under the curve (AUC) and decision curves.
RESULTS: All DWI radiomics models demonstrated superior AUC in predicting HIFU ablated uterine fibroids prognosis compared to expert radiologists (AUC: 0.706, 95% CI: 0.647-0.748). When utilizing different machine learning algorithms, the HR-DWI model achieved AUC values of 0.805 (95% CI: 0.679-0.931) with SVM, 0.797 (95% CI: 0.672-0.921) with RF, and 0.770 (95% CI: 0.631-0.908) with LightGBM. Meanwhile, the SR-DWI model outperformed the HR-DWI model (P < 0.05) across all algorithms, with AUC values of 0.868 (95% CI: 0.775-0.960) with SVM, 0.824 (95% CI: 0.715-0.934) with RF, and 0.821 (95% CI: 0.709-0.933) with LightGBM. And decision curve analysis further confirmed the good clinical value of the models.
CONCLUSIONS: Deep learning-based 3D SR-DWI radiomics model demonstrated favorable feasibility and effectiveness in predicting the prognosis of HIFU ablated uterine fibroids, which was superior to HR-DWI model and assessment by expert radiologists.

Uterine fibroids are the most common tumors in females affecting up to 70% of women world-wide, yet targeted therapeutic options are limited. Oxidative stress has recently surfaced as a key driver of fibroid pathogenesis and provides insights into hypoxia-induced cell transformation, extracellular matrix pathophysiology, hypoxic cell signaling cascades, and uterine biology. Hypoxia drives fibroid tumorigenesis through (1) promoting myometrial stem cell proliferation, (2) causing DNA damage propelling transformation of stem cells to tumor initiating cells, and (3) driving excess extracellular matrix (ECM) production. Common fibroid-associated DNA mutations include MED12 mutations, HMGA2 overexpression, and Fumarate hydratase loss of function. Evidence suggests an interaction between hypoxia signaling and these mutations. Fibroid development and growth are promoted by hypoxia-triggered cell signaling via various pathways including HIF-1, TGFβ, and Wnt/β-catenin. Fibroid-associated hypoxia persists due to antioxidant imbalance, ECM accumulation, and growth beyond adequate vascular supply. Current clinically available fibroid treatments do not take advantage of hypoxia-targeting therapies. Growing pre-clinical and clinical studies identify ROS inhibitors, anti-HIF-1 agents, Wnt/β-catenin inhibition, and TGFβ cascade inhibitors as agents that may reduce fibroid development and growth through targeting hypoxia.

Uterine leiomyoma or fibroids are prevalent noncancerous tumors of the uterine muscle layer, yet their origin and development remain poorly understood. We analyzed RNA expression profiles of 15 epigenetic mediators in uterine fibroids compared to myometrium using publicly available RNA sequencing (RNA-seq) data. To validate our findings, we performed RT-qPCR on a separate cohort of uterine fibroids targeting these modifiers confirming our RNA-seq data. We then examined protein profiles of key N6-methyladenosine (m6A) modifiers in fibroids and their matched myometrium, showing no significant differences in concordance with our RNA expression profiles. To determine RNA modification abundance, mRNA and small RNA from fibroids and matched myometrium were analyzed by ultra-high performance liquid chromatography-mass spectrometry identifying prevalent m6A and 11 other known modifiers. However, no aberrant expression in fibroids was detected. We then mined a previously published dataset and identified differential expression of m6A modifiers that were specific to fibroid genetic subtype. Our analysis also identified m6A consensus motifs on genes previously identified to be dysregulated in uterine fibroids. Overall, using state-of-the-art mass spectrometry, RNA expression, and protein profiles, we characterized and identified differentially expressed m6A modifiers in relation to driver mutations. Despite the use of several different approaches, we identified limited differential expression of RNA modifiers and associated modifications in uterine fibroids. However, considering the highly heterogenous genomic and cellular nature of fibroids, and the possible contribution of single molecule m6A modifications to fibroid pathology, there is a need for greater in-depth characterization of m6A marks and modifiers in a larger and diverse patient cohort.

OBJECTIVE: To evaluate the safety and efficacy of myomectomy for recurrent uterine fibroids (UFs) after high-intensity focused ultrasound (HIFU) ablation.
METHODS: This was a retrospective study. Patients who underwent abdominal myomectomy (AM) and laparoscopic myomectomy (LM) from January 2018 to December 2021 at the Three Gorges Hospital of Chongqing University were included. Among them, 73 had undergone prior HIFU ablation (Group 1), while 120 had not undergone HIFU (Group 2). Outcome measures included operating time, estimated blood loss (EBL), blood transfusion, postoperative activity times (PAT), duration of hospital stay (DOHS), and complications.
RESULTS: The operating time was 90.0 min (70.5, 115.0) for Group 1 and 110.0 min (81.5, 130.0) for Group 2 (P < 0.05). During all AM pathways, there were no significant differences observed between the two groups in EBL, blood transfusion, PAT, DOHS, and complications; however, operating time was shorter in Group 1. The operating time, EBL, blood transfusion, PAT, DOHS, and complications were similar in both groups during LM pathway. During the follow-up 40 (range: 24-53) months, the rate of relief, recurrence, and reintervention in Groups 1 and 2 was 78.1% versus 74.1%, 14.6% versus 16.4%, and 3.7% versus 2.6%, respectively (P > 0.05).
CONCLUSIONS: Myomectomy is a safe and effective surgical method for treating recurrent UFs after HIFU. Myomectomy for treating recurrent UFs resulted in a shorter operative and hospital stay, reduced blood loss, faster postoperative recovery, and fewer complications, better symptom relief rates, and lower risk of recurrence or reintervention. These findings indicate that previous HIFU ablation does not worsen the outcomes of the subsequent myomectomy.

UNASSIGNED: This is a summary of findings from two research studies (known as clinical trials). The studies looked at how well a medicine called relugolix combination therapy worked in women with heavy menstrual bleeding (heavy bleeding during a period) with uterine fibroids (noncancerous or benign growths in the uterus). In this analysis of the studies, researchers looked at how patients self-reported their uterine fibroid symptoms before and after taking relugolix combination therapy. Researchers also looked at how patients self-reported the impact of uterine fibroids on their health-related quality of life before and after taking relugolix combination therapy.
UNASSIGNED: Women took either relugolix combination therapy or placebo (a pill that contains no medicine) by mouth once daily for 24 weeks. Women completed the Uterine Fibroid Symptom and Quality of Life questionnaire (where \"quality of life\" refers to the women\'s health-related quality of life related to uterine fibroids) before, during, and after treatment. The questionnaire let researchers see if the women felt that relugolix combination therapy decreased the burden of uterine fibroid symptoms and improved the women\'s health-related quality of life related to uterine fibroids. More women said that they felt less distress due to their uterine fibroid symptoms and that their health-related quality of life related to uterine fibroids was better after taking relugolix combination therapy compared with women who took placebo.
UNASSIGNED: Relugolix combination therapy may lessen distress associated with uterine fibroid symptoms and improve health-related quality of life related to uterine fibroids.

Uterine leiomyomas, also known as uterine fibroids, are a commonly encountered condition with a diverse clinical presentation. Uterine fibroids are benign, smooth muscle tumors of the uterus arising from a single myometrial cell. The presentation can vary from asymptomatic incidental findings to causing a wide array of gynecological symptoms, including abnormal uterine bleeding, infertility, chronic pelvic pain, and bulk-related symptoms. There are several management approaches depending on the patient\'s clinical manifestations and goals. This is a unique case of a patient with symptomatic calcified uterine fibroids refractory to medical management and two uterine artery embolizations presenting with persistent abnormal uterine bleeding and chronic pelvic pain. Preservation of the uterus was desired, so an open myomectomy was subsequently performed. The patient was asymptomatic at two weeks follow-up, and further follow-up was unable to be obtained.  When considering interventions for symptomatic uterine fibroids, it is essential to consider the patient\'s preference for uterine-sparing methods and desire to preserve fertility. It is necessary that all modes of treatment and their potential future implications be discussed so that patients can make well-informed decisions regarding all aspects of their care. Further studies are needed comparing the outcomes of uterine-sparing interventions for symptomatic uterine fibroids so that the best possible shared decision-making can take place.

High-intensity focused ultrasound (HIFU) is commonly used to treat uterine fibroids and adenomyosis, but there is no evidence using metadata to compare fertility outcomes between conventional laparoscopic procedures and HIFU. The purpose of this study analysis is that evidence-based fertility outcomes may provide better treatment options for clinicians and patients considering fertility. The literature on fertility data for HIFU surgery versus laparoscopic myomectomy was searched in seven English language databases from January 1, 2010, to November 23, 2022. A total of 1375 articles were received in the literature, 14 of which were selected. We found that women who underwent HIFU surgery had higher rates of spontaneous pregnancy, higher rates of spontaneous delivery, and higher rates of full-term delivery but may have higher rates of miscarriage or postpartum complications than women who underwent laparoscopic myomectomy. Looking forward to future studies, it is hoped that the literature will examine endometrial differences in women who undergo HIFU and laparoscopic myomectomy to demonstrate the ability of endometrial repair. The location of fibroids in the sample should also be counted to allow for attribution statistics on the cause of miscarriage.