Invasive and metastatic hydatidiform moles in Slovakia in 1993‒2022.

OBJECTIVE: A retrospective analysis of invasive and metastatic hydatidiform moles (HM) in the Slovak Republic (SR)‒epidemiology, patient characteristics and treatment outcomes. BACKROUND: Invasive and metastatic mole is a highly curable type of gestational trophoblastic neoplasia. Both invasive and metastatic HM may be cured by hysterectomy without adjuvant chemotherapy. METHODS: Nineteen cases of histopathologically confirmed HM (10 invasive and 9 metastatic) were treated in SR from 1993 to 2022. Patients were divided into two groups according to treatment modality (hysterectomy only ‒ 8; hysterectomy and chemotherapy ‒ 11). The parameters included in the analysis were patient age, antecedent pregnancy, human chorionic gonadotropin level, tumor size and time to remission. RESULTS: The incidence of invasive and metastatic HM in the SR was 1:121,253 pregnancies, or 1:86,589 live births. The overall cure rate was 100%, without recurrence. Hysterectomy was performed as first-line therapy in 14 patients, with a cure rate of 57.1%. 4 out of 8 patients (50%) with metastatic moles, who underwent first-line hysterectomy, were cured without chemotherapy. There was no statistically significant difference between the two groups in all selected parameters. CONCLUSION: First-line hysterectomy may lead to remission without adjuvant chemotherapy or reduce the number of chemotherapies in invasive and metastatic HM (Tab. 4, Fig. 2, Ref. 21).

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.

Advancements and Emerging Therapies in the Medical Management of Uterine Fibroids: A Comprehensive Scoping Review.

Uterine fibroids, benign tumors originating from uterine smooth muscle cells, vary in prevalence depending on patient ethnicity, hormonal exposure, and genetics. Due to their high incidence, these neoplasms pose a significant burden on healthcare systems. Current treatment strategies range from routine monitoring in asymptomatic cases to surgical procedures such as myomectomy or hysterectomy in symptomatic patients, with an increasing trend toward uterus-preserving or non-surgical alternatives. This review examines the existing medical treatments for uterine fibroids and delves into the potential of emerging therapies. A scoping review of the literature was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. Medical therapies are divided into hormonal and non-hormonal treatments; however, long-term, safe, and effective treatments in the treatment of uterine fibroids are limited. In addition to established therapies, there is an increasing number of studies investigating the effect of substances such as vitamin D or green tea extract on uterine fibroids. Some studies investigate acupuncture as a possible alternative therapy. While existing treatments offer symptomatic relief and preparation for surgery, our findings point to a significant need for further research into long-term solutions, especially owing to recent limitations in the use of ulipristal acetate due to risk of liver damage. Initial studies involving vitamin D and epigallocatechin gallate are encouraging; however, additional research is required to establish definitive therapeutic roles.

ACR Appropriateness Criteria® Management of Uterine Fibroids: 2023 Update.

Uterine fibroids are the most common benign tumor in women of reproductive age and can present with symptoms including bleeding, bulk related symptoms, and infertility. Several treatment options are available for the management of uterine fibroids, including medical management, minimally invasive therapies such as uterine artery embolization and MR-guided focused ultrasound ablation, and surgical interventions ranging from laparoscopic myomectomy to open hysterectomy. Given this wide range of therapeutic interventions, it is important to understand the data supporting these interventions and to be able to apply it in different clinical settings. This document provides a summary of recent trials supporting various therapies for uterine fibroids, including recent evidence for MR-guided focused ultrasound ablation and a detailed discussion of fertility outcomes in myomectomy and uterine fibroid embolization. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

Currently Available Treatment Modalities for Uterine Fibroids.

Uterine fibroids (leiomyomas and myomas) are the most common benign gynecological condition in patients presenting with abnormal uterine bleeding, pelvic masses causing pressure or pain, infertility and obstetric complications. Almost a third of women with fibroids need treatment due to symptoms. OBJECTIVES: In this review we present all currently available treatment modalities for uterine fibroids. METHODS: An extensive search for the available data regarding surgical, medical and other treatment options for uterine fibroids was conducted. REVIEW: Nowadays, treatment for fibroids is intended to control symptoms while preserving future fertility. The choice of treatment depends on the patient's age and fertility and the number, size and location of the fibroids. Current management strategies mainly involve surgical interventions (hysterectomy and myomectomy hysteroscopy, laparoscopy or laparotomy). Other surgical and non-surgical minimally invasive techniques include interventions performed under radiologic or ultrasound guidance (uterine artery embolization and occlusion, myolysis, magnetic resonance-guided focused ultrasound surgery, radiofrequency ablation of fibroids and endometrial ablation). Medical treatment options for fibroids are still restricted and available medications (progestogens, combined oral contraceptives andgonadotropin-releasing hormone agonists and antagonists) are generally used for short-term treatment of fibroid-induced bleeding. Recently, it was shown that SPRMs could be administered intermittently long-term with good results on bleeding and fibroid size reduction. Novel medical treatments are still under investigation but with promising results. CONCLUSIONS: Treatment of fibroids must be individualized based on the presence and severity of symptoms and the patient's desire for definitive treatment or fertility preservation.

Choriocarcinoma in neonates and infants: A severe but curable disease.

Choriocarcinoma in neonates and infants (N-CC) is an extremely rare, but aggressive cancer, frequently observed with concomitant maternal disease. A retrospective, bi-national study of patients treated in France and Poland for infantile choriocarcinoma analysed eight cases of N-CC, median age of 6 weeks. All tumours were diffuse. Six patients received a platinum-based regimen, and five had delayed surgery on residual distant tumour sites. At the end of follow-up, four patients were in complete remission and four had died of the disease. In all but two cases, mothers had simultaneous metastatic choriocarcinoma. Even if the outcome remains poor, patients could be cured with multimodal therapy.

Pilot Study on Boiling Histotripsy Treatment of Human Leiomyoma Ex Vivo.

OBJECTIVE: As an alternative to surgical excision and magnetic resonance-guided thermal high-intensity focused ultrasound ablation of uterine leiomyoma, this work was aimed at pilot feasibility demonstration of use of ultrasound-guided boiling histotripsy for non-invasive non-thermal fractionation of human uterine leiomyoma ex vivo. METHODS: A custom-made sector ultrasound transducer of 1.5-MHz operating frequency and nominal f-number F# = 0.75 was used to produce a volumetric lesion (two layers of 5 × 5 foci with a 1 mm step) in surgically resected human leiomyoma ex vivo. A sequence of 10 ms pulses (P+/P-/As = 157/-25/170 MPa in situ) with 1% duty cycle was delivered N = 30 times per focus under B-mode guidance. The treatment outcome was evaluated via B-mode imaging and histologically with hematoxylin and eosin and Masson's trichrome staining. RESULTS: The treatment was successfully performed in less than 30 min and resulted in formation of a rectangular lesion visualized on B-mode images during the sonication as an echogenic region, which sustained for about 10 min post-treatment. Histology revealed loss of cellular structure, necrotic debris and globules of degenerated collagen in the target volume surrounded by injured smooth muscle cells. CONCLUSION: The pilot experiment described here indicates that boiling histotripsy is feasible for non-invasive mechanical disintegration of human uterine leiomyoma ex vivo under B-mode guidance, encouraging further investigation and optimization of this potential clinical application of boiling histotripsy.

Genetic Mechanisms Driving Uterine Leiomyoma Pathobiology, Epidemiology, and Treatment.

Uterine leiomyomas (ULs) are the most common benign tumor of the uterus. They can be associated with symptoms including abnormal uterine bleeding, pelvic pain, urinary frequency, and pregnancy complications. Despite the high prevalence of UL, its underlying pathophysiology mechanisms have historically been poorly understood. Several mechanisms of pathogenesis have been suggested, implicating various genes, growth factors, cytokines, chemokines, and microRNA aberrations. The purpose of this study is to summarize the current research on the relationship of genetics with UL. Specifically, we performed a literature review of published studies to identify how genetic aberrations drive pathophysiology, epidemiology, and therapeutic approaches of UL. With regards to pathophysiology, research has identified MED12 mutations, HMGA2 overexpression, fumarate hydratase deficiency, and cytogenetic abnormalities as contributors to the development of UL. Additionally, epigenetic modifications, such as histone acetylation and DNA methylation, have been identified as contributing to UL tumorigenesis. Specifically, UL stem cells have been found to contain a unique DNA methylation pattern compared to more differentiated UL cells, suggesting that DNA methylation has a role in tumorigenesis. On a population level, genome-wide association studies (GWASs) and epidemiologic analyses have identified 23 genetic loci associated with younger age at menarche and UL growth. Additionally, various GWASs have investigated genetic loci as potential drivers of racial disparities in UL incidence. For example, decreased expression of Cytohesin 4 in African Americans has been associated with increased UL risk. Recent studies have investigated various therapeutic options, including ten-eleven translocation proteins mediating DNA methylation, adenovirus vectors for drug delivery, and "suicide gene therapy" to induce apoptosis. Overall, improved understanding of the genetic and epigenetic drivers of UL on an individual and population level can propel the discovery of novel therapeutic options.

The modern management of uterine fibroids-related abnormal uterine bleeding.

Uterine fibroids (UFs) are the most common female benign pelvic tumors, affecting >60% of patients aged 30-44 years. Uterine fibroids are asymptomatic in a large percentage of cases and may be identified incidentally using a transvaginal ultrasound or a magnetic resonance imaging scan. However, in approximately 30% of cases, UFs affect the quality of life and women's health, with abnormal uterine bleeding and heavy menstrual bleeding being the most common complaints, along with iron deficiency (ID) and ID anemia. Medical treatments used for UFs-related abnormal uterine bleeding include symptomatic agents, such as nonsteroidal antiinflammatory drugs and tranexamic acid, and hormonal therapies, including combined oral contraceptives, gonadotropin-releasing hormone agonists or antagonists, levonorgestrel intrauterine systems, selective progesterone receptor modulators, and aromatase inhibitors. Nevertheless, few drugs are approved specifically for UF treatment, and most of them manage the symptoms. Surgical options include fertility-sparing treatments, such as myomectomy, or nonconservative options, such as hysterectomy, especially in perimenopausal women who are not responding to any treatment. Radiologic interventions are also available: uterine artery embolization, high-intensity focused ultrasound or magnetic resonance-guided focused ultrasound, and radiofrequency ablation. Furthermore, the management of ID and ID anemia, as a consequence of acute and chronic bleeding, should be taken into account with the use of iron replacement therapy both during medical treatment and before and after a surgical procedure. In the case of symptomatic UFs, the location, size, multiple UFs, or coexistent adenomyosis should guide the choice with a shared decision-making process, considering long- and short-term treatment goals expected by the patient, including pregnancy desire or wish to preserve the uterus independently of reproductive goals.

Targeting the long non-coding RNA MIAT for the treatment of fibroids in an animal model.

Our previous studies indicated that there is overexpression of MIAT in fibroids and MIAT is a sponge for the miR-29 family in these tumors. The objective of the present study was to determine if the knockdown of MIAT in fibroid xenografts will increase miR-29 levels and reduce the expression of genes targeted by this miRNA such as collagen and cell cycle regulatory proteins in a mouse model for fibroids. Ovariectomized CB-17 SCID/Beige mice bearing estrogen/progesterone pellets were implanted subcutaneously in the flank with equal weight of fibroid explants which had been transduced by lentivirus for either control (empty vector) or MIAT knockdown for four weeks (n=7). Knockdown of MIAT in fibroid xenografts resulted in a 30% reduction of tumor weight and a marked increase in miR-29a, -b, and -c levels in the xenografts. There was reduced cell proliferation and expression of cell cycle regulatory genes CCND1, CDK2, and E2F1 and no significant changes in apoptosis. The xenografts with MIAT knockdown expressed lower mRNA and protein levels of FN1, COL3A1, and TGF-ß3, and total collagen protein. Targeting MIAT, which sponges the pro-fibrotic miR-29 family, is an effective therapy for fibroids by reducing cell proliferation and thereby, tumor growth and accumulation of ECM, which is a hallmark of these benign gynecologic tumors.

Top advances of the year: Uterine cancer.

Endometrial cancer continues to be the only gynecologic malignancy with a rising incidence and mortality, with both regional and global implications. Combination carboplatin and paclitaxel has been the recognized chemotherapy backbone for the treatment of advanced-stage or recurrent disease, with modest clinical outcomes. Over the last year, significant advances were achieved in improving oncologic outcomes by capitalizing on the molecular characterization of this heterogenous disease. These advances include incorporation of immunotherapy, identification of effective hormonal approaches, the evolution of antibody drug conjugates, and utilization of alternate targeted therapies. PLAIN LANGUAGE SUMMARY: The molecular characterization of endometrial cancer has been critical in informing novel treatment strategies. Over the past year, significant gains have been made via the incorporation of immunotherapy, hormonal combinations as well as antibody drug conjugates.

Patient Experiences With a Multidisciplinary Fibroid Program.

STUDY OBJECTIVE: Although medical, interventional, and surgical treatment options for fibroids have expanded over the last decade, many patients are not thoroughly counseled about all available therapies. Patients desire a more comprehensive approach with shared decision-making tailored to their health goals. The aim of this study is to assess patient knowledge regarding treatment options before and after consultation with a multidisciplinary fibroid center. DESIGN: Prospective survey study. SETTING: Academic medical center in New York, NY. PATIENTS AND PARTICIPANTS: Patients who presented for initial consultation with a multidisciplinary fibroid program from July 2021 through January 2022. INTERVENTIONS: Patients were offered same-day office consultation with a minimally invasive gynecologic surgeon (MIGS) followed by a telemedicine visit with an interventional radiologist (IR) within 3 weeks of the appointment request. Collaborative discussions were held between providers regarding patient care. Patients were asked to complete the survey following both appointments. Data was collected regarding demographics, prior evaluation of fibroids, knowledge about treatment options, and overall experience. RESULTS: A total of 102 patients completed the survey (response rate 77%). A majority (55.9%) had known about their fibroids for at least 2 years. Most patients sought out the fibroid program for a 2nd (28.4%), 3rd (22.5%) or 4th (7.8%) opinion. Notably, 35.3% of patients who had previously been seen by an obstetrician-gynecologist (OB/GYN) were not offered any treatment. Of those who had been offered treatment, 24.5% were counseled on medical management with oral contraceptives, 28.4% on surgical options, and 5.9% on uterine artery embolization. Nearly all patients (86.3%) endorsed that they would not have sought 2 separate consultations had it not been for the program. Patients were overall well-informed after their experience, with 95.1% reporting they were more knowledgeable about their options and none reporting the 2 separate consults created more confusion for them. CONCLUSION: Many patients with symptomatic fibroids seeking secondary opinions have not been adequately counseled on fibroid management options. A collaborative approach to fibroid management better educates patients, provides an opportunity to be thoroughly counseled by the specialists performing either surgical or interventional procedures, and increases patient knowledge about fibroid treatment options.

Uterine Fibroids.

This JAMA Insights in the Women's Health series discusses the incidence, diagnosis, and treatment of uterine fibroids.

Uterine fibroid-related infertility: mechanisms and management.

Fibroids are a common pathology and increasingly observed in women seeking medical treatment for infertility. The longer reproductive horizon because of improvements in medical care and current trend for women to postpone childbearing are making fibroid-related infertility increasingly common. This review aimed to critically analyze the association between uterine fibroids and infertility, mechanisms by which uterine fibroids may impair fertility, and management of myoma-related infertility. The association of fibroids with infertility is a source of controversy. As the focus of this review is infertility, it is crucial to analyze the mechanisms by which fertility may be impaired by the presence of fibroids. Current management strategies involve mainly surgical interventions, including myomectomy by hysteroscopy, laparotomy, or laparoscopy, and nonsurgical approaches, such as uterine artery embolization and focused ultrasound performed under radiologic or echographic guidance. The risks and benefits of each option should be discussed with patients, and several factors need to be considered, including the skills of surgeons and availability of different resources in various centers. Concerning the efficacy of oral gonadotropin-releasing hormone antagonists (i.e., elagolix, relugolix, and linzagolix), they were shown to have a rapid impact on heavy menstrual bleeding (HMB) in >70% of women. When used without add-back therapy, these drugs cause a significant reduction in fibroid volume, namely, approximately 50% from baseline to week 24. Further studies are required to determine the best protocol and optimal dosage if a reduction in myoma volume is the main goal, as in case of myoma-related infertility.

Long-Term Risk of Reintervention After Surgical Leiomyoma Treatment in an Integrated Health Care System.

OBJECTIVE: To compare long-term risk of reintervention across four uterus-preserving surgical treatments for leiomyomas and to assess effect modification by sociodemographic factors in a prospective cohort study in an integrated health care delivery system. METHODS: We studied a cohort of 10,324 patients aged 18-50 (19.9% Asian, 21.2% Black, 21.3% Hispanic, 32.5% White, 5.2% additional races and ethnicities) who had a first uterus-preserving procedure (abdominal, laparoscopic, or vaginal myomectomy [referred to as myomectomy]; hysteroscopic myomectomy; endometrial ablation; uterine artery embolization) after leiomyoma diagnosis in the 2009-2021 electronic health records of Kaiser Permanente Northern California. We followed up patients until reintervention (second uterus-preserving procedure or hysterectomy) or censoring. We used a Kaplan-Meier estimator to calculate the cumulative incidence of reintervention and Cox regression models to estimate hazard ratios and 95% CIs comparing rates of reintervention across procedures, adjusting for age, parity, race and ethnicity, body mass index (BMI), Neighborhood Deprivation Index, and year. We also assessed effect modification by demographic characteristics. RESULTS: Median follow-up was 3.8 years (interquartile range 1.8-7.4 years). Index procedures were 18.0% (1,857) hysteroscopic myomectomies, 16.2% (1,669) uterine artery embolizations, 21.4% (2,211) endometrial ablations, and 44.4% (4,587) myomectomies. Accounting for censoring, the 7-year reintervention risk was 20.6% for myomectomy, 26.0% for uterine artery embolization, 35.5% for endometrial ablation, and 37.0% for hysteroscopic myomectomy; 63.2% of reinterventions were hysterectomies. Within each procedure type, reintervention rates did not vary by BMI, race and ethnicity, or Neighborhood Deprivation Index. However, rates of reintervention after uterine artery embolization, endometrial ablation, and hysteroscopic myomectomy decreased with age, and reintervention rates for hysteroscopic myomectomy were higher for parous than nulliparous patients. CONCLUSION: Long-term reintervention risks for uterine artery embolization, endometrial ablation, and hysteroscopic myomectomy are greater than for myomectomy, with potential variation by patient age and parity but not BMI, race and ethnicity, or Neighborhood Deprivation Index.