Hypoxia in uterine fibroids: role in pathobiology and therapeutic opportunities.

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, TGFß, and Wnt/ß-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/ß-catenin inhibition, and TGFß cascade inhibitors as agents that may reduce fibroid development and growth through targeting hypoxia.

Predicting the Prognosis of HIFU Ablation of Uterine Fibroids Using a Deep Learning-Based 3D Super-Resolution DWI Radiomics Model: A Multicenter Study.

RATIONALE AND OBJECTIVES: 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. RESULT: 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. CONCLUSION: 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.

Common Beverage Consumption and Benign Gynecological Conditions.

The purpose of this article is to review the effects of four commonly consumed beverage types-sugar-sweetened beverages (SSBs), caffeinated beverages, green tea, and alcohol-on five common benign gynecological conditions: uterine fibroids, endometriosis, polycystic ovary syndrome (PCOS), anovulatory infertility, and primary dysmenorrhea (PD). Here we outline a plethora of research, highlighting studies that demonstrate possible associations between beverage intake and increased risk of certain gynecological conditions-such as SSBs and dysmenorrhea-as well as studies that demonstrate a possible protective effect of beverage against risk of gynecological condition-such as green tea and uterine fibroids. This review aims to help inform the diet choices of those with the aforementioned conditions and give those with uteruses autonomy over their lifestyle decisions.

Characterization of m6A Modifiers and RNA Modifications in Uterine Fibroids.

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.

Comprehensive Review of Uterine Leiomyosarcoma: Pathogenesis, Diagnosis, Prognosis, and Targeted Therapy.

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.

To Evaluate the Efficacy and Safety of Mifepristone in Reducing the Size & Symptoms of Uterine Leiomyoma/Fibroids.

Background and Study Objective: 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. Methodology: 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. Results: 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. Conclusion: 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.

Vaginal and rectal microbiome contribute to genital inflammation in chronic pelvic pain.

BACKGROUND: Chronic pelvic pain (CPP) is a multifactorial syndrome that can substantially affect a patient's quality of life. Endometriosis is one cause of CPP, and alterations of the immune and microbiome profiles have been observed in patients with endometriosis. The objective of this pilot study was to investigate differences in the vaginal and gastrointestinal microbiomes and cervicovaginal immune microenvironment in patients with CPP and endometriosis diagnosis compared to those with CPP without endometriosis and no CPP. METHODS: Vaginal swabs, rectal swabs, and cervicovaginal lavages (CVL) were collected among individuals undergoing gynecologic laparoscopy. Participants were grouped based on patients seeking care for chronic pain and/or pathology results: CPP and endometriosis (CPP-Endo) (n = 35), CPP without endometriosis (n = 23), or patients without CPP or endometriosis (controls) (n = 15). Sensitivity analyses were performed on CPP with endometriosis location, stage, and co-occurring gynecologic conditions (abnormal uterine bleeding, fibroids). 16S rRNA sequencing was performed to profile the microbiome, and a panel of soluble immune mediators was quantified using a multiplex assay. Statistical analysis was conducted with SAS, R, MicrobiomeAnalyst, MetaboAnalyst, and QIIME 2. RESULTS: Significant differences were observed between participants with CPP alone, CPP-Endo, and surgical controls for body mass index, ethnicity, diagnosis of ovarian cysts, and diagnosis of fibroids. In rectal microbiome analysis, both CPP alone and CPP-Endo exhibited lower alpha diversity than controls, and both CPP groups revealed enrichment of irritable bowel syndrome-associated bacteria. CPP-Endo exhibited an increased abundance of vaginal Streptococcus anginosus and rectal Ruminococcus. Patients with CPP and endometrioma (s) demonstrated increased vaginal Streptococcus, Lactobacillus, and Prevotella compared to other endometriosis sites. Further, abnormal uterine bleeding was associated with an increased abundance of bacterial vaginosis-associated bacteria. Immunoproteomic profiles were distinctly clustered by CPP alone and CPP-Endo compared to controls. CPP-Endo was enriched in TNF⍺, MDC, and IL-1⍺. CONCLUSIONS: Vaginal and rectal microbiomes were observed to differ between patients with CPP alone and CPP with endometriosis, which may be useful in personalized treatment for individuals with CPP and endometriosis from those with other causes of CPP. Further investigation is warranted in patients with additional co-occurring conditions, such as AUB/fibroids, which add additional complexity to these conditions and reveal the enrichment of distinct pathogenic bacteria in both mucosal sites. This study provides foundational microbiome-immunoproteomic knowledge related to chronic pelvic pain, endometriosis, and co-occurring gynecologic conditions that can help improve the treatment of patients seeking care for pain.

Appropriateness of Hysterectomy as Treatment for Benign Gynecological Conditions.

Objective: To assess the appropriateness of hysterectomies performed at a large tertiary health system using the 1997 RAND appropriateness classification system and an updated algorithm. Design: We abstracted structured and unstructured data from electronic medical records on patient demographics, primary indication(s) for hysterectomy, diagnosis codes associated with the hysterectomy, previous treatments, and laboratory results. Subjects: Patients aged 18-44 years. Exposure: Receipt of hysterectomy for benign and nonobstetric conditions from October 2014 to December 2017. Main Outcome Measures: Using these data, we provided a RAND-based (dichotomous: inappropriate/appropriate) and Wright-based (3-level: inappropriate/ambiguous/appropriate) appropriateness rating and characterized missing information patterns associated with inappropriate ratings. Results: We analyzed 1,829 hysterectomies across 30 nonmutually exclusive primary indications for surgery. Nearly a third (32.8%) of surgeries had only one primary indication for surgery. Using the RAND-based classifier, 31.3% of hysterectomies were rated as appropriate and 68.7% as inappropriate. Using the Wright-based algorithm, 58.1% of hysterectomies were rated as appropriate, 15.7% as ambiguous, and 26.2% as inappropriate. Missing information on diagnostic procedures was the most common characteristic related to both RAND-based (46.1%) and Wright-based (51.2%) inappropriate ratings. Conclusions: The 1997 RAND classification lacked guidance for several contemporary indications, including gender-affirming care. RAND also has an outdated requirement for diagnostic surgeries such as laparoscopies, which have decreased in practice as diagnostic imaging has improved. Sensitivity analyses suggest that inappropriate surgeries cannot all be attributed to bias from missing electronic medical record data. Accurately documenting care delivery for benign gynecological conditions is key to ensuring quality and equity in gynecological care.

Feasibility, safety and efficacy of high intensity focused ultrasound ablation as a preoperative treatment for challenging hysteroscopic myomectomy.

PURPOSE: To investigate the feasibility, safety and efficacy of high intensity focused ultrasound ablation (HIFU) as a preoperative treatment for challenging hysteroscopic myomectomies. MATERIALS AND METHODS: A total of 75 patients diagnosed with types 0-III of uterine fibroids were enrolled. Based on the Size, Topography, Extension of the base, Penetration and lateral Wall position (STEPW) classification scoring system, 25 cases with a score ≥ 5 points were treated with HIFU followed by hysteroscopic myomectomy (HIFU + HM group), whereas 50 cases with a score < 5 points were treated with hysteroscopic myomectomy (HM group). RESULTS: The median preoperative STEPW score was 7 in the HIFU + HM group and 2 in the HM group. The average non-perfused volume (NPV) ratio achieved in fibroids after HIFU was 86.87%. Patients in the HIFU + HM group underwent hysteroscopic myomectomy one to four days after HIFU, and downgrading was observed in 81.81% of fibroids. The operation time for patients in the HIFU + HM group was 73 min and the success rate of myomectomy in a single attempt was 60%. The volume of distention medium used during the operation was greater in the HIFU + HM group than in the HM group (15,500 ml vs. 7500 ml). No significant difference was observed between the two groups in terms of intraoperative blood loss, the incidence of intraoperative and postoperative complications, menstrual volume score, or uterine fibroid quality of life score. CONCLUSION: HIFU can be utilized as a preoperative treatment for large submucosal fibroids prior to hysteroscopic myomectomy. HIFU offers a novel approach in the management of this subset of patients.

Risk factors affecting long-term efficacy of ultrasound-guided high-intensity focused ultrasound treatment for multiple uterine fibroids.

OBJECTIVES: To investigate the long-term efficacy of ultrasound-guided high-intensity focused ultrasound (USgHIFU) for multiple uterine fibroids and the factors associated with recurrence. MATERIALS AND METHODS: Five hundred and forty-nine patients with multiple uterine fibroids treated with USgHIFU from June 2017 to June 2019 were retrospectively analyzed. The Pictorial Blood Loss Assessment Chart (PBAC) was used to assess menstrual blood loss. The patients were asked to undergo pre- and post-USgHIFU magnetic resonance imaging (MRI) and complete routine follow-up after USgHIFU. Cox regression analysis was used to investigate the risk factors associated with recurrence. RESULTS: The median number of fibroids per patient was 3 (interquartile range: 3-4), and a total of 1371 fibroids were treated. Among them, 446 patients completed 3 years follow-up. Recurrence, defined as PBAC score above or equal to 100 and/or the residual fibroid volume increased by 10%, was detected in 90 patients within 3 years after USgHIFU, with a cumulative recurrence rate of 20.2% (90/446). The multi-factor Cox analysis showed that age was a protective factor for recurrence. Younger patients have a greater chance of recurrence than older patients. Mixed hyperintensity of fibroids on T2WI and treatment intensity were risk factors for recurrence. Patients with hyperintense uterine fibroids and treated with lower treatment intensity were more likely to experience recurrence than other patients after USgHIFU. No major adverse effects occurred. CONCLUSIONS: USgHIFU can be used to treat multiple uterine fibroids safely and effectively. The age, T2WI signal intensity and treatment intensity are factors related to recurrence.

Changes in symptom burden and quality of life among women with uterine fibroids receiving relugolix combination therapy: a plain language summary.

WHAT IS THIS SUMMARY ABOUT?: 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. WHAT WERE THE RESULTS?: 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. WHAT DO THE RESULTS MEAN?: Relugolix combination therapy may lessen distress associated with uterine fibroid symptoms and improve health-related quality of life related to uterine fibroids.

Efficacy and safety of uterine artery embolization via the distal radial approach for uterine fibroids or adenomyosis: a single-center retrospective cohort study.

Background: The standard approach for transarterial embolization of uterine fibroids or adenomas is via the femoral artery, but this approach limits the patient's quality of life and increases the risk of deep vein thrombosis in the lower extremities. We applied the distal radial approach technique for the treatment of uterine artery embolization, and aimed to explore the feasibility and safety of uterine artery chemoembolization through the distal radial approach. Methods: We conducted a retrospective study at The First Hospital of Jilin University from January 1, 2021 to November 30, 2023. The main inclusion criteria were: (I) uterine fibroids and adenomyosis were confirmed by preoperative imaging examination; (II) able to accurately palpate the distal radial artery pulse, and the Allen test is negative. Exclusion criteria: patients with distal radial pulses that cannot be palpated, or who are palpable but have radial arteriotomy dialysis, have a tortuous angle on preoperative radial artery ultrasound, which is not conducive to guidewire catheter passage. The primary endpoint of this study was the success rate of distal radial artery puncture. The secondary endpoints included complications and the duration of the puncture. Results: Sixteen patients were enrolled in this study, of which 8 (50%) had uterine fibroids, 5 (31.25%) had uterine adenomas, and 3 (18.75%) had both. The puncture success rate was 93.75% (15/16) and one patient who failed to puncture the distal radial artery was changed to the radial artery approach. The mean time of puncture was 21±8.54 minutes. There were no complications, including bleeding, hematoma, arterial dissection, pseudoaneurysm formation, or distal radial artery occlusion, observed. Conclusions: Uterine artery embolization by the distal radial artery approach is safe and feasible, and should be widely promoted in uterine artery embolization.

Advancing women's health: The imperative for public health screening of uterine fibroids for personalized care.

Uterine fibroids represent the most prevalent genital tract tumours among women, with a disproportionately higher impact on ethnic minority groups, notably black women. These hormonally dependent monoclonal tumours, characterized by excessive extracellular matrix and influenced by genetic, epigenetic, and lifestyle factors, significantly affect women's quality of life and pose substantial economic burdens on healthcare systems. Recent advances in early detection and minimally invasive treatment options have shifted management paradigms towards personalized care, yet challenges in early diagnosis, education and access to treatment persist. This review synthesizes current knowledge on uterine fibroids, highlighting the impact of fibroids on women's health, risk factors, principles of screening, diagnostic tools, and treatment modalities. It emphasizes the importance of early screening and individualized management strategies in improving patient outcomes and reducing healthcare costs. The article also discusses the socio-economic and health disparities affecting the disease burden, underscoring the need for improved patient education, clinician training, and public health strategies to enhance fibroid management. This review proposes a pathway to not only ameliorate the quality of life for women with fibroids, but also to advance global women's health equity.

High-intensity Focused Ultrasound is a Better Choice for Women with Fertility Desire: A Systematic Review and Meta-analysis of the Comparison between High-intensity Focused Ultrasound and Laparoscopic Treatment of Uterine Fibroids.

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.

Associations of per- and polyfluoroalkyl substances with uterine leiomyomata incidence and growth: a prospective ultrasound study.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are endocrine-disrupting chemicals used in commercial and consumer products. OBJECTIVE: We evaluated PFAS exposure in relation to incidence and growth of uterine leiomyomata (UL), hormone-dependent neoplasms that are associated with severe gynecologic morbidity. METHODS: We studied 1158 participants in the Study of Environment, Lifestyle, and Fibroids, a Detroit-based prospective cohort study of Black females aged 23-35 years at enrollment (2010-2012). At enrollment and four subsequent visits during 10 years of follow-up, participants attended in-person clinic visits, completed questionnaires, provided non-fasting blood samples, and underwent ultrasound for UL detection. We quantified 7 PFAS in baseline plasma samples using mass spectrometry. We used Cox regression and probit Bayesian kernel machine regression to estimate individual and joint effects of PFAS on UL incidence. We fit linear mixed models to estimate effects of individual PFAS on UL growth. We stratified by parity, an important route of PFAS elimination and determinant of UL. RESULTS: In individual PFAS analyses, we observed inverse associations for perfluorodecanoate (PFDA; ≥0.3 vs. <0.2 ng/ml: hazard ratio [HR] = 0.74; 95% confidence interval [CI]: 0.54-1.00) and perfluoroundecanoate (detected vs. non-detected: HR = 0.78; 95% CI: 0.61-1.01) and a weak positive association for perfluorohexane sulfonate (≥1 vs. <0.6 ng/ml: HR = 1.17; 95% CI: 0.85-1.61), while perfluorooctane sulfonate, perfluorooctanoate, perfluorononanoate (PFNA), and 2-N-methyl-perfluorooctane sulfonamido acetate (MeFOSAA) showed little association with UL incidence. The PFAS mixture was inversely associated with UL incidence, a finding driven by MeFOSAA and PFDA; however, PFNA was positively associated with UL incidence. The inverse association for PFDA and positive association for PFNA were stronger among nulliparous participants. Most PFAS showed slight inverse associations with UL growth. IMPACT STATEMENT: In this prospective ultrasound study of 1158 Black females aged 23-35 years at enrollment, we conducted a mixtures analysis to account for co-pollutant confounding and interaction. MeFOSAA and PFDA concentrations were inversely associated with UL incidence, while PFNA concentrations were positively associated with UL incidence. Concentrations of most PFAS were associated with decreased UL growth. This study contributes data to the sparse literature on PFAS exposure and UL development.

Symptomatic Calcified Uterine Fibroids Refractory to Repeat Uterine Artery Embolization: A Case Report.

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.

Robotic Single-Site Plus One-Port Myomectomy versus Robotic Single-Site Plus Two-Port Myomectomy: A Propensity Score Matching Analysis.

PURPOSE: Robotic single-site plus one-port myomectomy (RSOM) was designed to reduce the number of incision sites for greater cosmetic satisfaction of patients while retaining the benefits of conventional robotic multi-site myomectomy (CRM). Robotic single-site plus two-port myomectomy (RSTM) eliminated one port relative to conventional CRM, and RSOM achieved the same advantage with respect to RSTM. This study aimed to compare RSOM with RSTM in terms of their respective methodologies and surgical outcomes. MATERIALS AND METHODS: The medical records of 230 patients who had undergone RSOM and 146 patients who had undergone RSTM were reviewed. The groups' surgical outcomes were compared using propensity score matching (PSM) analysis. RESULTS: In the total data, RSOM had a shorter operative time (135.1±57.4 min vs. 149.9±46.2 min, p=0.009) and a shorter hospital stay (5.2±0.5 days vs. 5.4±0.7 days, p=0.033) relative to RSTM. The PSM analysis showed that there were no statistically significant intergroup differences in the patients' baseline characteristics. Regarding the surgical outcomes, the RSOM group showed shorter operative time (129.2±49.3 min vs. 148.7±46.3 min, p=0.001) compared to the RSTM group. CONCLUSION: Compared with RSTM, RSOM was associated with shorter operative time. Additionally, more detailed comparative and prospective studies are needed to evaluate RSOM relative to RSTM.

Case report: Elective management of a bicornuate uterus with hematometra, incidentally found submucosal fibroids, rectus sheath hematoma, and hydronephrosis in a resource limited setting.

INTRODUCTION AND IMPORTANCE: Bicornuate uterus is a rare type of congenital mullerian anomaly, presenting as a diagnostic challenge. Metroplasty either via an open approach or laparoscopically can be performed to definitively diagnose and treat the defect. CASE PRESENTATION: A 26-year-old female, with no known comorbids and past surgical history of endometriotic cyst excision presented with acute symptoms of left lower abdominal pain, burning micturition, and relative constipation. After clinical and radiologic investigations, the diagnosis of bicornuate was suspected. An elective exploratory laparotomy was then performed due to limited resources and skilled surgical techniques. Intra-operatively it was found that she had a bicornuate uterus with a single cervix and vagina, with the left cornuate being non-communicating with fluid suggesting hematometra. Dense adhesions were reported with drainage of 150-200 ml of free fluid upon opening the rectus sheath. Postoperatively she remained vitally stable and was discharged home. CLINICAL DISCUSSION: We report a rare case of a bicornuate uterus with double horns along with submucosal fibroids, rectus sheath hematoma, and left sided hydronephrosis. Diagnosis of bicornuate uterus is associated with diagnostic uncertainty mainly due to its rarity and nonspecific presentation. CONCLUSION: Although bicornuate is rare, it may result in complications if not attended to timely. Early diagnosis and management are necessary to minimize associated morbidity and mortality that can occur as a consequence of associated unattended pressure symptoms.

Unlocking the potential of tranilast: Targeting fibrotic signaling pathways for therapeutic benefit.

Fibrosis is the excessive deposition of extracellular matrix in an organ or tissue that results from an impaired tissue repair in response to tissue injury or chronic inflammation. The progressive nature of fibrotic diseases and limited treatment options represent significant healthcare challenges. Despite the substantial progress in understanding the mechanisms of fibrosis, a gap persists translating this knowledge into effective therapeutics. Here, we discuss the critical mediators involved in fibrosis and the role of tranilast as a potential antifibrotic drug to treat fibrotic conditions. Tranilast, an antiallergy drug, is a derivative of tryptophan and has been studied for its role in various fibrotic diseases. These include scleroderma, keloid and hypertrophic scars, liver fibrosis, renal fibrosis, cardiac fibrosis, pulmonary fibrosis, and uterine fibroids. Tranilast exerts antifibrotic effects by suppressing fibrotic pathways, including TGF-ß, and MPAK. Because it disrupts fibrotic pathways and has demonstrated beneficial effects against keloid and hypertrophic scars, tranilast could be used to treat other conditions characterized by fibrosis.

Case report: A case of perineal prolapse of giant uterine fibroids complicated by multiple pulmonary embolisms and deep venous thrombosis.

A 43-year-old woman with a history of uterine fibroids, anemia, and deep vein thrombosis presented with a chief symptom of prolapse of tumor from the perineum, complicated by infection. The case was further complicated by bilateral pulmonary multiple embolism, deep vein thrombosis, acute cardiac insufficiency, acute renal insufficiency, and shock. The patient was treated with preoperative placement of an inferior vena cava filter, open hysterectomy, and perioperative anticoagulation with low-molecular-weight heparin. She smoothly navigated the perioperative period and recovered completely.