Search Results (168)

Uterine leiomyoma (uterine fibroids, UF) are benign myometrium tumors that affect up to 70% of the female population and may lead to severe clinical symptoms. Despite the high prevalence, pathogenesis of UF is not understood and involves cytokines, steroid hormones, and growth factors. Additionally, an increased deposition and remodelling of the extracellular matrix is characteristic for UF. Vitamin D seems to play a new role in UF. Interestingly, hypovitaminosis D correlates with a higher prevalence of myomas and the severity of the myomas. Administration of vitamin D in women with insufficiency (serum level <30 ng/mL) restored the vitamin D status and reduced the mild symptoms of myomas. In addition, inflammatory processes may play a role. In the past years, it has become clear that cessation of inflammation is an active process driven by a class of lipid mediator molecules called specialized pro-resolving mediators (SPM). Inadequate resolution of inflammation is related to several chronic inflammatory diseases and several studies have proven the crucial role of SPMs in improving these diseases. In this review, we will give an overview on processes involved in UF growth and will give an overview on the modern view regarding the concept of inflammation and the role of SPMs in resolution of inflammation, especially in chronic inflammatory diseases. Full article

Background: This study was designed to evaluate and contrast the surgical outcomes between coaxial robotic single-site myomectomy (RSSM) performed using the da Vinci Xi system and da Vinci SP system. Methods: A retrospective review was conducted on 81 women who underwent coaxial RSSM and 108 women who underwent myomectomy with the da Vinci SP system between October 2020 and January 2024. Propensity score matching was performed based on myoma count, the dominant myoma’s maximum diameter, and the myoma type according to the International Federation of Gynecology and Obstetrics (FIGO) classification. Patient characteristics and surgical outcomes were evaluated and compared between the two groups. Results: Compared to the SP group, the coaxial RSSM group showed significantly lower estimated blood loss (102.33 ± 61.01 vs. 203.98 ± 163.15 mL, p < 0.001), shorter operative time (91.22 ± 18.25 vs. 148.69 ± 45.62 min, p < 0.001), and smaller hemoglobin decrement (1.69 ± 0.93 vs. 2.85 ± 1.30, p < 0.001). However, hospital stay was shorter in the SP group than in the coaxial group (2.06 ± 0.24 vs. 4.07 ± 0.76 days, p < 0.001). There were no statistically significant differences in postoperative complications, including ileus, fever, or wound dehiscence. Additional comparisons using cases performed by four different surgeons yielded results consistent with the one-to-one surgeon comparison. Conclusions: Coaxial RSSM was associated with a shorter operative time and lower blood loss compared to SP myomectomy. A prospective study is warranted to validate and further compare the surgical outcomes of the two techniques. Full article

Uterine fibroids (leiomyomas) are benign tumors whose growth is influenced by estrogen and progesterone. This study aimed to compare the profiles of differentially expressed long non-coding RNAs (lncRNAs) in fibroids from postmenopausal and premenopausal women to identify hormone-responsive lncRNAs. RNA sequencing was performed on six pairs of fibroid (Fib) and adjacent myometrium (Myo) tissues from postmenopausal women. Out of 7876 normalized lncRNAs, 3684 were differentially expressed (≥1.5-fold), with 1702 upregulated and 1982 downregulated in Fib. Comparative analysis with a previously published premenopausal dataset identified 741 lncRNAs that were altered based on their menopausal status, including 62 lncRNAs that were uniquely dysregulated in postmenopausal samples. Overall, 9 lncRNAs were selected for validation by PCR in an expanded cohort of 31 postmenopausal and 84 premenopausal paired samples. Several lncRNAs, including LINC02433, LINC01449, SNHG12, H19, and HOTTIP, were upregulated in premenopausal Fib but not in postmenopausal ones, while ZEB2-AS1 displayed the opposite pattern. CASC15 and MIAT were elevated in Fib from both groups, although the increase was less pronounced in the postmenopausal group. LINC01117 was significantly downregulated in postmenopausal Fib, with no change observed in premenopausal samples. Additionally, analysis based on MED12 mutation status revealed that lncRNAs such as LINC01449, CASC15, and MIAT showed limited or reduced differential expression (mutation-positive vs. mutation-negative) in postmenopausal patients compared to the premenopausal group. These findings indicate that lncRNA expression in fibroids is modulated by menopausal status, likely reflecting hormonal influence. Hormone-responsive lncRNAs may play key roles in fibroid pathogenesis and represent potential targets for therapeutic intervention. Full article

Objectives: CA19-9 elevation in non-gastrointestinal tumor patients may be influenced by various non-tumor factors, which poses challenges for clinical diagnosis. This study aims to assess the consistency between initial elevated CA19-9 levels detected by the ARCHITECT/Alinity i system (Abbott Diagnostics) and subsequent retesting using the Elecsys CA19-9 assay (Roche Diagnostics) in 5372 non-gastrointestinal tumor patients, and to explore potential factors contributing to CA19-9 non-specific elevation. Methods: Bland-Altman and Passing-Bablok analyses were used to assess the agreement between the two assays. Nonparametric Spearman and Pearson’s chi-square tests were used to assess the correlation between CA19-9 and different clinical comorbidities/antigen concentration strata and to compare the categorization by age/disease, respectively. Results: Bland–Altman and Passing–Bablok regression analyses revealed that the CA19-9 test results from Abbott and Roche platforms show significant systematic bias and weak correlation, making the two methods not directly interchangeable. After excluding common confounders, the study focused on heterophilic antibodies (HAs) as target. Blood samples were treated with a commercial blocking agent demonstrated alignment with baseline Elecsys CA19-9 results but differed significantly from initial ARCHITECT/Alinity i measurements. Furthermore, non-specific CA19-9 elevation was also associated with comorbidities such as diabetes mellitus, pulmonary infections, breast nodules, uterine leiomyoma, and its incidence increased with age. Conclusions: The study highlights the need to consider potential interferences and underlying disorders when results conflict with clinical diagnoses. Method-specific validation and comprehensive clinical correlation are crucial for accurate interpretation of CA19-9 levels to prevent misdiagnosis and ensure appropriate patient management. Full article

Background and Clinical Significance: Uterine fibroids affect up to 25% of women of reproductive age and can lead to significant symptoms or impact fertility, often requiring surgical management. While hysteroscopic myomectomy is suitable for intracavitary fibroids, intramural and subserosal fibroids typically necessitate open or minimally invasive surgery (MIS). Laparoscopic approaches offer notable advantages, including reduced postoperative pain and faster recovery. However, MIS is frequently avoided in cases of very large fibroids due to technical difficulty and concerns about safe tissue extraction. Power morcellation, previously used for specimen removal, has fallen out of favor due to the risk of disseminating occult malignancies, especially in women over 35. Therefore, establishing the feasibility of MIS without morcellation in such cases is essential. Case Presentation: A woman of reproductive age presented with a symptomatic uterine fibroid measuring approximately 4 kg (1500 cm³). Laparoscopic myomectomy was performed using a modified trocar entry technique and contained tissue fragmentation, avoiding morcellation. The operation was completed successfully without complications. Postoperative recovery was uneventful, and the patient was discharged on postoperative day two. Histopathological examination confirmed a benign leiomyoma. Conclusions: This case highlights the feasibility of laparoscopic removal of an exceptionally large uterine fibroid without morcellation. Through careful patient selection, strategic trocar placement, and controlled tissue fragmentation, MIS can be safely performed in select high-volume cases. These findings support reconsidering the size limitations of laparoscopic myomectomy when conducted by experienced surgeons using appropriate techniques. Full article

Background: Ectopic pregnancy (EP) is defined as the implantation of an embryo outside the uterine cavity, which can lead to high morbidity and mortality if not diagnosed and treated promptly. A rare form of EP is myomectomy scar pregnancy (MSP), where the embryo implants in a scar from a prior myomectomy. Due to its rarity, MSP presents unique diagnostic and therapeutic challenges. This scoping review aims to map the existing literature on MSP to better understand the diagnostic strategies, management options, and clinical outcomes associated with this condition, and to identify gaps in current research. Methods: We conducted a scoping review by searching databases such as PubMed, Scopus, Web of Science, and MEDLINE for studies published between 2003 and 2023. Keywords used in combination included “myomectomy scar pregnancy”, “scar pregnancy”, “leiomyoma”, “uterine myomectomy”, “PAS disorders”, “placenta previa”, and “placenta accreta”. Studies were screened for relevance and eligibility by two independent reviewers. Data were extracted from case reports, retrospective studies, and reviews discussing MSP. Results: From an initial set of 111 studies, 28 papers met the inclusion criteria, comprising 4 retrospective studies and 24 case reports. A total of 44 cases of MSP were analyzed. The majority of diagnoses were made through ultrasound, with magnetic resonance imaging (MRI) used in more complex cases. Surgical interventions, primarily cesarean sections and myometrial repairs, were the most common treatments, while medical therapy with methotrexate was less frequently applied. Conclusions: This scoping review highlights the challenges of diagnosing and managing MSP due to its rarity. Although surgical management remains the primary approach, there is a lack of consensus on the optimal treatment for different clinical scenarios. Further research is needed to establish standardized diagnostic and therapeutic protocols for MSP and to evaluate the long-term outcomes of affected patients. Full article

Background: Serum biomarkers such as Carcinoma Antigen 125 (CA125) and Human Epididymis Protein 4 (HE4) are widely used in the diagnosis and prognosis of gynecological malignancies. Serum biomarkers such as CA125 and HE4 represent essential tools in improving early detection, risk stratification, and therapeutic decision-making for gynecological malignancies. However, their role in identifying uterine sarcomas remains debated. This systematic review and case series aims to examine the diagnostic and prognostic significance of CA125 and HE4 in uterine sarcomas. Methods: A systematic review was performed on studies investigating serum CA125 and HE4 levels in uterine sarcomas. A case series of all uterine sarcomas treated at the Campus Bio-Medico Gynecology Unit of Rome from 2010 to 2020 was analyzed. Results: The analysis of the 11 selected studies allowed us to investigate the role of CA125 in uterine sarcomas. No studies analyzing the role of HE4 in monitoring the disease were found. A total of 16 patients with confirmed uterine leiomyosarcoma were included in our case series. Conclusions: Neither CA125 nor HE4 can currently be considered definitive biomarkers for the diagnosis of uterine leiomyosarcomas. However, they may serve as useful adjuncts in the differential diagnosis between leiomyomas and leiomyosarcomas, particularly in reproductive-age patients. Full article

Background and Clinical Significance: This study presents a case of a 43-year-old female with a long history of infertility, treated for uterine leiomyoma and endometrial hyperplasia, over a total observation period of 42 months. Case Presentation: Levonorgestrel intrauterine device (LNG-IUD) therapy, as a first and subsequent line of treatment, was introduced. The patient also received medroxyprogesterone acetate oral treatment. Finally, she underwent surgery for an ovarian tumor that appeared to be an ovarian adenocarcinoma concurrent with endometrial cancer. After the removal of the reproductive organ, the patient was diagnosed with synchronous low-grade endometrioid adenocarcinoma in the endometrium and a concurrent grade 2 (G2) endometrioid adenocarcinoma in the left ovary. Conclusions: The prognosis and further management largely depend on whether these are two individual neoplasms or one metastatic tumor. Considering the young age of the patients, an early disease stage, a low grade of both cancers, and favorable prognosis, most synchronous endometrial and ovarian cancers are identified as two independent primary tumors. The diagnosis of a multi-focal neoplasm is important, as in patients with endometrial cancer and ovarian metastasis, the 5-year survival rate is 30–40%, whereas in the case of individual neoplasms, it is 75–80%. Full article

Background/Objectives: We have previously identified let-7f-5p, miR-10b-5p, miR-34a-5p, miR-181b-5p, and miR-181d-5p as differentially expressed between uterine leiomyoma (LM) and leiomyosarcoma (LMS) tissue samples. The present study aimed to characterize these miRNA expression profiles and to assess the functional role of miR-34a and miR-181b in uterine LM and LMS cells. Methods: All the selected miRNAs showed downregulation in LMS cells compared to LM cells, but only miR-34a and miR-181b expression patterns matched those of patient samples. Therefore, these two miRs were selected for further analyses. Results: Loss of function analysis demonstrated that miR-34a and miR-181b silencing inhibited LM cell proliferation and migration. MiR-34a silencing induced CCND1 and MDM4 expression and inhibited KMT2D, BCL2, and NOTCH2 in LM. Silencing of miR-181b promotes TIMP3 and FGFR1 expression in LM and diminishes BCL2, NOTCH2, ATM, IRS1, and PRLR. Gain of function analysis revealed that the introduction of miR-34a and miR-181b mimics suppressed proliferation and migration in malignant LMS cells. Additionally, transfection with a miR-34a mimic downregulated NOTCH2 and BCL2 expression and enhanced the expression of CCND1, KMT2D, and TP53 in LMS cells. Moreover, miR-181b overexpression decreased TIMP3, NOTCH2, ATM, and IRS1 expression and increased the expression of FGFR1 in this cell. Importantly, the single introduction of either a miR-34a or miR-181b mimic was able to decrease the invasion capacity of LMS cells. Conclusions: Our studies demonstrated that miR-34a or miR-181b may play an anti-oncogenic role in uterine tumors; further studies are needed to better understand the role and regulatory mechanism of these miRNAs in LMS cancer development, which will help provide prognostic and therapeutic options for patients with LMS. Full article

Uterine tumors resembling ovarian sex-cord tumors (UTROSCTs) are among the rarest types of uterine tumors. Diagnosis of a UTROSCT is often challenging. Imaging techniques such as ultrasound and MRI are limited in distinguishing UTROSCTs as their appearance is usually suggestive of uterine leiomyoma or adenomyosis. Additionally, the value of a preoperative biopsy remains uncertain due to the heterogeneous composition of the tumor and the inadequacy of limited samplings. We present a rare case of UTROSCT in a 59-year-old woman and we have performed a narrative review of the literature on PubMed, Scopus, and Web of Science from 2000 to June 2024, identifying 133 cases. According to our review, at histological exam UTROSCTs are mainly composed of cells resembling ovarian sex-cord elements which are arranged in cords or trabeculae, typically with a mild cytologic atypia. The most expressed sex-cord differentiation markers include inhibin, calretinin, melan A, CD56, CD99, SF1, WT1, CD10, and FOXL2. For women who have completed their reproductive plans, a total hysterectomy with adnexectomy is an adequate treatment for tumors confined to the uterus. For younger patients who wish to preserve fertility, tumorectomy via hysteroscopy or laparoscopy is the preferred treatment option and the recurrence rates range from 5% to 30%. Treatments for recurrent disease include surgery, chemotherapy, and radiation therapy, often used in combination. Advancements in molecular profiling and immunohistochemistry will improve our ability to diagnose and manage this tumor. Such investigations will enhance prognostic stratification, facilitating more accurate predictions of biological behavior and recurrence risk. Full article

We performed next-generation sequencing (NGS) on RNA from 19 paired leiomyoma (Lyo) and myometrium (Myo) specimens, stratified by race/ethnicity (White: n = 7; Black: n = 12) and mediator complex subunit 12 (MED12) mutation status (mutated: n = 10; non-mutated: n = 9). Analysis identified 2,189 small non-coding RNAs (sncRNAs) with altered expression in Lyo compared to paired Myo (≥1.5-fold change), including small nuclear RNAs (snRNAs), small nucleolar RNAs (snoRNAs), microRNAs (miRNAs), and PIWI-interacting RNAs (piRNAs). Among these, 17 sncRNAs showed differential expression in the MED12-mutated group versus Myo, while minimal changes were observed in the non-mutated group. Additionally, 31 sncRNAs displayed differential expression in Black women compared to White women. For validation, five novel miRNAs (miR-19a-3p, miR-99a-5p, miR-3196, miR-499a-5p, and miR-30d-3p) and five piRNAs (piR-009295, piR-020326, piR-020365, piR-006426, and piR-020485) were analyzed in 51 paired Lyo samples using qRT-PCR. Reduced expression of the selected sncRNAs was confirmed in Lyo versus Myo, with miR-19a-3p, miR-3196, miR-30d-3p, piR-006426, and piR-020485 linked to MED12 status, while miR-499a-5p and miR-30d-3p were associated with race/ethnicity. These findings suggest that sncRNA dysregulation contributes to altered gene expression in Lyo, influenced by MED12 mutation and racial background. Full article

Fumarate hydratase (FH) deficiency is a rare, yet impactful metabolic disorder caused by mutations in the FH gene, affecting the Krebs cycle, leading to the accumulation of fumarate and pseudohypoxic states. This metabolic shift promotes cell signaling alterations that can drive tumorigenesis, as heterozygous germline mutations in the FH gene, resulting in hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome. FH-deficient uterine leiomyomas show peculiar histological features that may lead to misdiagnosis STUMP (smooth muscle tumor of uncertain malignant potential) and uLMS (uterine leiomyosarcoma). Definitive diagnosis involves clinical evaluation, imaging, and histopathological examination, with immunohistochemistry for FH protein being a key diagnostic tool. Management of FH-deficient leiomyomas may involve conventional treatments like surgery and hormonal therapy but also requires careful monitoring and genetic counseling for associated malignancies. High-intensity focused ultrasound (HIFU) has emerged as a promising treatment option for fibroids, although long-term efficacy remains a concern also because of its inability to obtain tissue for a pathological diagnosis. Fumarate hydratase deficiency (FHD) represents a significant challenge in gynecologic oncology due to its association with an increased risk of hereditary leiomyomatosis and renal cell carcinoma. Nevertheless, to the best of our knowledge, there is a lack of studies demonstrating the potential role of FH deficiency in increased risk of leiomyosarcomatosus transformation. Early detection, genetic screening, and personalized treatment approaches are critical for improving patient outcomes. The aim of this review is to develop a narrative overview of the implications of FHD in gynecological diseases and its correlation with cancer risk. For the first time, this review offers an overview of the necessity for studies to address the possible correlation between FH deficiency and the risk of developing leiomyosarcoma, focusing on new perspectives that can be explored in the field of better FH deficiency knowledge and cancer risk. Full article

Licochalcone A (LicoA) possesses anti-tumor properties. However, the potential therapeutic effect of LicoA on uterine leiomyomas (ULs) remains unknown. In this study, the effects of LicoA on the proliferation of ULs and its underlying mechanism were explored. LicoA treatment significantly decreased the viability of uterine smooth muscle cells (UtSMCs) and ELT3 cells in a dose-dependent manner. The induction of ELT3 cell apoptosis by LicoA was accompanied by the increased generation of reactive oxygen species (ROS), elevated endoplasmic reticulum (ER) stress (GRP78/IRE1α/ATF6/CHOP), and the increased expression of proapoptotic proteins (c-caspase-3, c-caspase-9, and c-PARP). The ability of Z-VAD-FMK (a caspase inhibitor) and n-acetylcysteine (NAC; a cell membrane permeable antioxidant) to reverse LicoA-induced ROS-mediated ER stress pathways also observed. Furthermore, GRP78 or JNK knockdown was involved in LicoA-induced ROS-mediated ER stress and apoptosis in ELT3 cells. In immunodeficient mice, LicoA significantly suppressed the growth of ELT3 tumor cells, without toxicity. This study is the first to show that LicoA exerts anti-leiomyoma effects via the modulation of ROS-mediated ER stress-induced apoptosis through the JNK/GRP78/NRF2 signaling pathway. Full article

Disruptions in uterine tissue function contribute to disorders such as endometriosis, adenomyosis, endometrial cancer, and fibroids, which all significantly impact health and fertility. Advances in transcriptomics, particularly single-cell RNA sequencing, have revolutionized uterine biological research by revealing the cellular heterogeneity and molecular mechanisms underlying disease states. Single-cell RNA sequencing and spatial transcriptomics have mapped endometrial and myometrial cellular landscapes, which helped to identify critical cell types, signaling pathways, and phase-specific dynamics. Said transcriptomic technologies also identified stromal and immune cell dysfunctions, such as fibroblast-to-myofibroblast transitions and impaired macrophage activity, which drive fibrosis, chronic inflammation, and lesion persistence in endometriosis. For endometrial cancer, scRNA-seq uncovered tumor microenvironmental complexities, identifying cancer-associated fibroblast subtypes and immune cell profiles contributing to progression and therapeutic resistance. Similarly, studies on adenomyosis highlighted disrupted signaling pathways, including Wnt and VEGF, and novel progenitor cell populations linked to tissue invasion and neuroinflammation, while single-cell approaches characterized smooth muscle and fibroblast subpopulations in uterine fibroids, elucidating their roles in extracellular matrix remodeling and signaling pathways like ERK and mTOR. Despite challenges such as scalability and reproducibility, single-cell transcriptomic approaches may have potential applications in biomarker discovery, therapeutic target identification, and personalized medicine in gynecological disorders. Full article

Background/Objectives: Uterine leiomyomas are the most common benign gynecological tumors in women of reproductive age and are often associated with localized symptoms. However, emerging evidence suggests a link between uterine leiomyomas and systemic conditions such as cardiovascular disease (CVD), particularly myocardial infarction (MI) and ischemic stroke (IS). This study aimed to investigate the relationship between uterine leiomyomas and the risk of CVD events in young women aged 20–39 years using a large, nationwide, population-based cohort. Methods: This retrospective cohort study analyzed data from the National Health Insurance Service database of South Korea of 2,581,700 women aged 20–39 years who underwent health screening between 2009 and 2012. Uterine leiomyomas were identified using International Code of Disease, 10th Edition codes. CVD events (MI and IS) were defined according to hospital claims and radiological data. Multivariate hazard ratios (HRs) were calculated to evaluate the association between leiomyomas and CVD after adjusting for confounders (age, lifestyle factors, comorbidities, and body mass index). Results: In all, 58,812 were diagnosed with uterine leiomyomas, and 25,063 underwent surgical treatment. During the follow-up period, MI occurred in 115 women (0.21%) and IS in 82 women (0.15%) in the leiomyoma group, compared with 3107 cases of MI (0.12%) and 2240 cases of IS (0.09%) in the non-leiomyoma group. The leiomyoma group demonstrated a higher incidence rate of CVD (IR: 0.63 vs. 0.39 per 1000 person-years). After adjusting for confounding factors such as age, lifestyle, comorbidities, and body mass index (BMI), the hazard ratio (HR) for MI was 1.32, indicating a statistically significant increase in cardiovascular risk. The risk of CVD was lower in women who underwent surgical treatment; however, when specifically analyzing the occurrence of MI and IS, no statistically significant differences were observed between the two groups. Conclusions: Uterine leiomyomas are associated with an increased risk of MI and IS in young women. Surgical treatment itself may be associated with additional cardiovascular risks. Further research is needed to develop strategies to mitigate these risks and elucidate the underlying mechanisms. Full article