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1.
Front Oncol ; 14: 1461092, 2024.
Article in English | MEDLINE | ID: mdl-39372869

ABSTRACT

Objective: Uterine inflammatory myofibroblastic tumor (UIMT) is a rare tumor of the female reproductive tract with uncertain malignant potential. Previous case series reports have limited our understanding of its diagnosis and treatment. Therefore, we conducted a retrospective analysis of patient files at West China Second University Hospital, Sichuan University to contribute valuable clinical insights to future treatment strategies for this disease. Method: We comprehensively reviewed patient files of individuals diagnosed with UIMT from January 1st, 2013 to May 1st, 2023. Results: We included twenty-seven cases of uterine inflammatory myofibroblastic tumor in our study. Of these, 51.85% (14 cases) were diagnosed with abnormal uterine bleeding, 2 cases had dysmenorrhea, and 12 were unexpectedly diagnosed with suspected uterine fibroids. Ten cases performed total hysterectomy, and 17 cases underwent lesion resection. The positive rate of anaplastic lymphoma kinase (ALK) immunohistochemistry reached 96.3%. After a median of 8 months follow-up time, all patients were disease-free and had survived. Conclusion: Uterine inflammatory myofibroblastic tumor is easily misdiagnosed, making its diagnosis challenging. Histological features, immunohistochemical results, and molecular confirmation using fluorescence in situ hybridization (FISH) or Next-generation sequencing should be used to confirm the diagnosis. Positive ALK immunohistochemistry, ALK rearrangement, ALK fusion are helpful in diagnosis and ALK inhibitor therapy. Total hysterectomy is often performed for women who do not require fertility, while lesion resection and close follow-up may be considered for those who require fertility preservation.

2.
Mol Genet Genomics ; 299(1): 93, 2024 Oct 05.
Article in English | MEDLINE | ID: mdl-39368016

ABSTRACT

Visceral obesity (VO), characterized by excess fat around internal organs, is a recognized risk factor for gynecological tumors, including benign uterine leiomyoma (ULM) and malignant uterine leiomyosarcoma (ULS). Despite this association, the shared molecular mechanisms remain underexplored. This study utilizes an integrated bioinformatics approach to elucidate common molecular pathways and identify potential therapeutic targets linking VO, ULM, and ULS. We analyzed gene expression datasets from the Gene Expression Omnibus (GEO) to identify differentially expressed genes (DEGs) in each condition. We found 101, 145, and 18 DEGs in VO, ULM, and ULS, respectively, with 37 genes overlapping across all three conditions. Functional enrichment analysis revealed that these overlapping DEGs were significantly enriched in pathways related to cell proliferation, immune response, and transcriptional regulation, suggesting shared biological processes. Protein-protein interaction network analysis identified 14 hub genes, of which TOP2A, APOE, and TYMS showed significant differential expression across all three conditions. Drug-gene interaction analysis identified 26 FDA-approved drugs targeting these hub genes, highlighting potential therapeutic opportunities. In conclusion, this study uncovers shared molecular pathways and actionable drug targets across VO, ULM, and ULS. These findings deepen our understanding of disease etiology and offer promising avenues for drug repurposing. Experimental validation is needed to translate these insights into clinical applications and innovative treatments.


Subject(s)
Computational Biology , Gene Expression Regulation, Neoplastic , Gene Regulatory Networks , Leiomyoma , Obesity, Abdominal , Protein Interaction Maps , Uterine Neoplasms , Female , Humans , Uterine Neoplasms/genetics , Uterine Neoplasms/pathology , Computational Biology/methods , Leiomyoma/genetics , Leiomyoma/pathology , Protein Interaction Maps/genetics , Obesity, Abdominal/genetics , Leiomyosarcoma/genetics , Leiomyosarcoma/pathology , Gene Expression Profiling/methods , DNA Topoisomerases, Type II/genetics , Apolipoproteins E/genetics , Databases, Genetic , Poly-ADP-Ribose Binding Proteins
3.
J Belg Soc Radiol ; 108(1): 79, 2024.
Article in English | MEDLINE | ID: mdl-39282017

ABSTRACT

In hereditary leiomyomatosis and renal cell carcinoma syndrome, fumarate hydratase-deficient renal cell carcinomas typically present as aggressive, unilateral, often cystic masses with heterogeneous enhancement. These tumors can metastasize early, making appropriate imaging and staging critical for diagnosis and management. Teaching point: When a renal lesion suspected of RCC is identified in a patient with cutaneous and uterine leiomyomas, HLRCC should be evaluated, which is important for future genetic counseling.

5.
Cureus ; 16(8): e68193, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39221293

ABSTRACT

Introduction Uterine leiomyoma is a benign smooth muscle tumor. It does not necessarily require curative treatment, but if conservative management is chosen, it is important to rule out uterine leiomyosarcoma. When a size increase is observed, one must consider malignancy, and thus objective and cost-effective measurement of uterine size is important, especially for early detection of malignant change. Although MRI imaging is thought to be the gold standard for the diagnosis of uterine leiomyosarcoma, frequent MRI is impractical because of the incidence of uterine leiomyoma and the economic burden in real-world clinical practice. On the other hand, ultrasonography (US) is considered the most useful device in the observation of size changes. So this study aimed to examine the accuracy of the measurement of transabdominal US compared to MRI imaging. Materials and methods This retrospective study included 92 patients with uterine myoma ≥ 50 mm who undertook an MRI within 30 days after the transabdominal US. The longest diameter of the largest myoma (a), the longest diameter perpendicular to a in the sagittal image (b), and the longest diameter perpendicular to a and b in the axial image (c) were measured by US and MRI, and these were used to calculate the volume. Results were analyzed by intraclass correlation coefficient (ICC) 3.1. Results The ICC for the volume and major axis of the largest myoma by US and MRI were 0.87 and 0.90, respectively. The 95% confidence intervals (CI) were 0.82-0.91 and 0.87-0.93, respectively. Both reliability levels ranged from good to excellent. ICC was 0.54 (95%CI 0.15-0.78) in myomas with a volume of >500 cm3, and the concordant rate between US and MRI was poor to good. On the other hand, ICC was 0.82 (95%CI 0.57-0.93) even though all myomas with major axes greater than 120 mm had a volume >500 cm3, and the concordant rate between US and MRI measurements was moderate to excellent. In the evaluation by major axis, ICC was 0.60 (95%CI -0.41-0.95) for myomas larger than 160 mm, indicating a lower concordant rate. Conclusion Transabdominal US is an appropriate modality as well as MRI for follow-up of uterine myoma size if the nodules are 160 mm or smaller. Measurement of the major axis is easier and more useful than volume.

6.
Ecotoxicol Environ Saf ; 285: 117069, 2024 Sep 18.
Article in English | MEDLINE | ID: mdl-39299212

ABSTRACT

BACKGROUND: There is evidence that exposure to phthalate in women may increase the risk of uterine leiomyomas. Whereas, the association between exposure to phthalate and the incidence of uterine leiomyoma remained inconclusive. METHODS: A meta-analysis was performed to evaluate their relationship. Literature eligible for inclusion was found in PubMed, EMBASE, Web of Science, and WanFang Medical Database. Pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated to assess the risk for effect estimate for each phthalate. RESULTS: A total of fourteen observational studies with 5777 subjects of adult women were included in this study. In the pooled analysis, we found an elevated risk of uterine leiomyoma among women who were exposed to higher levels of di-2-ethylhexyl phthalate (DEHP) (OR 1.61, 95 % CI: 1.18-2.20), as estimated indirectly from the molar summation of its urinary metabolite concentrations. In addition, a positive association was observed between the occurrence of uterine leiomyoma and exposure to low molecular weight phthalate mixture (OR 1.08, 95 % CI: 1.00-1.15), as well as high molecular weight phthalate mixture (OR 1.08, 95 % CI: 1.01-1.15), as quantified by integrating the effect estimates of individual metabolite from each study. Urinary levels of DEHP metabolites, monobenzyl phthalate, mono-(3-carboxypropyl) phthalate, mono-isobutyl phthalate, mono-n-butyl phthalate, monoethyl phthalate, and monomethyl phthalate were not appreciably correlated with the risk of uterine leiomyoma. CONCLUSION: Our results indicated that exposure to DEHP, and co-exposure to high or low molecular weight phthalate mixture might be potential risk factors for uterine leiomyoma in adult women. Owing to the indirect estimation of association, when interpreting these findings, cautions should be taken.

7.
Urol Case Rep ; 56: 102792, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39263218

ABSTRACT

We present a case of acute urinary retention (AUR) with hyper-angulation of the urinary bladder neck secondary to uterine leiomyoma. Our patient is a 45-year-old female who presented with AUR and suprapubic pain requiring catheterization. CT images highlight the level of obstruction secondary to suspension of the urinary bladder rather than direct urethral compression. This case highlights this unique manifestation of AUR demonstrating the necessity for understanding its different mechanisms. Clinicians should maintain a high index of suspicion for AUR in patients with leiomyoma and lower urinary tract symptoms. Heightened awareness and timely intervention are crucial in preventing potential complications.

8.
Article in English | MEDLINE | ID: mdl-39257183

ABSTRACT

BACKGROUND: Fibroids are non-cancerous uterine tumors potentially associated with cardiovascular risk factors. We examined prospectively associations of glucose, insulin, sex hormone binding globulin (SHBG), and diabetes with incidence of fibroid diagnoses in midlife. METHODS: Participants in the Study of Women's Health Across the Nation (SWAN) cohort (n=2570) reported fibroid diagnoses at enrollment (1996-1997) and 13 follow-up visits (1996-2013). At all visits, we measured glucose, insulin, and SHBG in fasting blood samples and calculated homeostatic model assessment for insulin resistance (HOMA-IR). Diabetes was defined using glucose levels, self-reported diabetes, or diabetes medication use. We used discrete-time survival models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations of time-varying biomarkers and diabetes with incident fibroid diagnoses, adjusted for demographics and healthcare utilization. We also evaluated effect modification by menopausal status. RESULTS: At baseline, 2.7% of participants (n=70) were using diabetes medication. Time-varying glucose, insulin, HOMA-IR, and SHBG were not associated with fibroid diagnosis. However, diabetes was associated with a 28% lower incidence of fibroid diagnosis (adjusted HR: 0.72, 95% CI: 0.44, 1.17), driven by participants using metformin (adjusted HR: 0.49, 95% CI: 0.21, 1.12), though precision was limited. After stratification by menopausal status, higher HOMA-IR and insulin were associated with greater incidence of fibroid diagnosis during premenopause but not perimenopause, while the inverse association between diabetes and fibroids was strongest during perimenopause. CONCLUSION: The effect of diabetes and biomarkers on fibroids may vary by menopausal status. Fibroid risk may increase with insulin resistance and decrease with diabetes treatment.

9.
Front Endocrinol (Lausanne) ; 15: 1429165, 2024.
Article in English | MEDLINE | ID: mdl-39268242

ABSTRACT

Purpose: Studies have demonstrated that hormonal imbalance, such as elevated level of estrogen or reduced level of progesterone, was the main inducing factor of uterine leiomyoma (UL) development and some cancers. UL has been reported to be associated with several cancers in observational studies. However, the causal associations between UL and cancers remain unclear. Methods: A two-sample Mendelian randomization (MR) analysis was conducted to investigate the causal associations between UL and 16 site-specific cancers using the public databases. Four methods, namely, the inverse variance weighting (IVW), MR-Egger, weighted median, and weighted mode, were applied in our MR analysis. Sensitivity tests were also performed to evaluate the robustness of these causal associations. Results: The IVW analysis indicated that genetically predicted UL increased the risk of low malignant potential ovarian cancer [odds ratio (OR) = 1.22, 95% confidence interval (CI): 1.06-1.40, p = 0.004], serous ovarian cancer (OR = 1.29, 95% CI: 1.10-1.52, p = 0.002), invasive mucinous ovarian cancer (OR = 1.24, 95% CI: 1.08-1.44, p = 0.003), clear cell ovarian cancer (OR = 1.25, 95% CI: 1.03-1.51, p = 0.023), breast cancer (OR = 1.07, 95% CI: 1.02-1.11, p = 0.002), and brain tumor (OR = 1.23, 95% CI: 1.06-1.42, p = 0.007). Conversely, genetically predicted UL reduced the risk of gastric cancer (OR = 0.91, 95% CI: 0.85-0.98, p = 0.008). The causal effects were consistent in the sensitivity analysis. Conclusions: Our results demonstrated that UL exhibits a causal relationship with high risk of several cancers. We suggest reinforcing the cancer screening in UL patients to enable the early detection of cancers.


Subject(s)
Leiomyoma , Mendelian Randomization Analysis , Uterine Neoplasms , Humans , Female , Leiomyoma/genetics , Leiomyoma/epidemiology , Uterine Neoplasms/genetics , Uterine Neoplasms/epidemiology , Genetic Predisposition to Disease , Risk Factors , Polymorphism, Single Nucleotide
10.
Cardiovasc Pathol ; 73: 107685, 2024.
Article in English | MEDLINE | ID: mdl-39142442

ABSTRACT

BACKGROUND: To report the diagnosis and treatment of a rare disease of intravenous leiomyomatosis (IVL) originating from the uterus, growing in the inferior vena cava (IVC) and extending into the right atrium (RA) associated with a pelvic arteriovenous fistula (AVF). This is the first reported case of IVL in the IVC and RA with pulmonary benign metastasizing leiomyoma (PBML) secondary to a pelvic AVF despite the use of GnRH agonists in a nonmenopausal woman. CASE PRESENTATION: The patient was a 50-year-old premenopausal woman with a history of surgical resection for and antiestrogen conservative drug for pulmonary benign metastasizing leiomyoma (PBML) 5 years. The patient nevertheless developed IVL in the IVC, internal iliac vein and RA accompanied by AVF. Vaginal ultrasound combined with echocardiography and computerized tomographic venography imaging assists in the diagnosis of IVL combined with AVF, with histopathology and immunohistochemistry ultimately confirming the diagnosis. The patient ultimately was performed with a combination of hysterectomy, bilateral adnexectomy, and resection of tumors in the IVC and RA without cardiopulmonary bypass and sternotomy. CONCLUSION: BML may be difficult to control with incomplete removal of the uterus and ovaries even with the use of antiestrogenic medications, and medically induced AVF resulting from fibroid surgery may accelerate this process and the development of IVL.


Subject(s)
Arteriovenous Fistula , Heart Atria , Leiomyomatosis , Lung Neoplasms , Uterine Neoplasms , Vascular Neoplasms , Vena Cava, Inferior , Humans , Female , Vena Cava, Inferior/pathology , Vena Cava, Inferior/surgery , Vena Cava, Inferior/diagnostic imaging , Middle Aged , Uterine Neoplasms/pathology , Uterine Neoplasms/surgery , Arteriovenous Fistula/surgery , Arteriovenous Fistula/etiology , Arteriovenous Fistula/diagnostic imaging , Arteriovenous Fistula/pathology , Heart Atria/pathology , Heart Atria/surgery , Heart Atria/diagnostic imaging , Leiomyomatosis/pathology , Leiomyomatosis/surgery , Leiomyomatosis/diagnostic imaging , Lung Neoplasms/secondary , Lung Neoplasms/pathology , Vascular Neoplasms/pathology , Vascular Neoplasms/surgery , Vascular Neoplasms/diagnostic imaging , Heart Neoplasms/secondary , Heart Neoplasms/pathology , Heart Neoplasms/surgery , Heart Neoplasms/complications , Treatment Outcome , Hysterectomy , Iliac Vein/pathology , Iliac Vein/diagnostic imaging
11.
Ultrasound Obstet Gynecol ; 64(4): 463-469, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39177335

ABSTRACT

OBJECTIVE: Uterine fibroids are monoclonal tumors, which are often genetically abnormal and associated with false-positive genome-wide cell-free DNA (cfDNA) screening results, particularly when large. It is plausible that fibroids may also increase the risk of cfDNA failure by affecting fetal fraction or due to their genetic anomalies confounding cfDNA algorithms. We aimed to investigate a possible association between fibroids and cfDNA non-informative results. METHODS: This was a retrospective cohort study of women undergoing cfDNA screening for fetal chromosomal abnormalities between 2013 and 2020, comparing pregnancies with vs without uterine fibroids recorded on any obstetric ultrasound before 24 weeks' gestation. Univariable and multivariable logistic regression models were used to investigate the association between fibroids and cfDNA failure, adjusting for gestational age, maternal age, weight and height at blood sampling, mode of conception, multiple gestation and test platform (chromosome-selective or genome-wide). Analyses were stratified according to the number of fibroids and total fibroid volume. The impact of fibroids on fetal fraction was assessed using linear regression, adjusting for the same covariates. RESULTS: Among 19 818 pregnancies undergoing cfDNA screening, fibroids were reported in 2038 (10.28%) and cfDNA failure at the first screening attempt occurred in 228 (1.15%) pregnancies. Non-informative results occurred in 1.96% of pregnancies with fibroids and 1.06% of pregnancies without fibroids (adjusted odds ratio (aOR), 2.40 (95% CI, 1.65-3.48)). The risk of failure in the first screening attempt increased progressively with the number of fibroids (aOR, 5.05 (95% CI, 2.29-11.13) in women with four or more fibroids) and total fibroid volume, with greater than a 5-fold and 14-fold increase in risk among women with fibroid volumes of 100.1-400 mL (aOR, 5.52 (95% CI, 2.30-13.25)) and > 400 mL (aOR, 14.80 (95% CI, 4.50-48.69)), respectively. Although test failure was more common with chromosome-selective than genome-wide screening, fibroids similarly increased the risk of failure of both screening platforms. Compared to pregnancies without fibroids, those with fibroids had a fetal fraction on average 0.61% lower (adjusted mean difference, -0.61% (95% CI, -0.77% to -0.45%)). CONCLUSION: Uterine fibroids are associated with lower fetal fraction and an increased risk of cfDNA screening failure. The strength of this association increases with increasing fibroid number and volume. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.


Subject(s)
Cell-Free Nucleic Acids , Leiomyoma , Uterine Neoplasms , Humans , Female , Leiomyoma/genetics , Leiomyoma/diagnostic imaging , Leiomyoma/diagnosis , Leiomyoma/blood , Pregnancy , Cell-Free Nucleic Acids/blood , Retrospective Studies , Adult , Uterine Neoplasms/genetics , Uterine Neoplasms/diagnostic imaging , Uterine Neoplasms/diagnosis , Uterine Neoplasms/blood , Noninvasive Prenatal Testing/statistics & numerical data , Noninvasive Prenatal Testing/methods , Ultrasonography, Prenatal , Pregnancy Complications, Neoplastic/genetics , Pregnancy Complications, Neoplastic/diagnosis , Pregnancy Complications, Neoplastic/diagnostic imaging , Pregnancy Complications, Neoplastic/blood , Gestational Age
12.
Eur J Obstet Gynecol Reprod Biol ; 301: 142-146, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39137592

ABSTRACT

OBJECTIVE: Molecular status of uterine leiomyomas has been shown to affect both tumor characteristics and treatment response. Mutations in mediator complex subunit 12 (MED12), the most prevalent alterations in leiomyomas, are associated with tumor size and number of leiomyomas. Myomectomy can be performed by laparoscopy or by open abdominal surgery, depending on the size and number of leiomyomas removed. The aim of this study was to examine the association between MED12 mutation status and surgical approach of myomectomy. We also evaluated myomectomy patients' quality of life after laparoscopic or abdominal surgery and according to the MED12 mutation status. STUDY DESIGN: The prospective cohort study included 104 women who underwent laparoscopic or abdominal myomectomy at the Helsinki University Hospital during 2015-2019. Patients filled in the validated Uterine Fibroid Symptom and Quality of Life (UFS-QOL) questionnaire before the operation and 6 and 12 months after the operation. Medical records were reviewed to collect clinical data. Leiomyoma tissue samples were collected and screened for MED12 mutations. RESULTS: Patients undergoing abdominal myomectomy had larger and more numerous leiomyomas compared to patients with laparoscopic myomectomy (10 cm vs 7.4 cm, p < 0.001 and 3 vs 1 leiomyomas, p < 0.001, respectively). A mean change of over 20 points was seen in UFS-QOL scores at 6 months after both laparoscopic and abdominal myomectomy (p < 0.001). MED12 mutations were detected in 178/242 (74 %) of leiomyomas. Of the patients, 45/97 (46 %) had only MED12 positive leiomyomas, while 39/97 (40 %) had only MED12 wild type leiomyomas. The number of leiomyomas removed was higher among patients with MED12 positive leiomyomas than in patients with MED12 wild type tumors (p < 0.001). Laparoscopic approach was equally common in both groups (62 % and 64 %), and there was no statistically significant difference in the UFS-QOL scores. CONCLUSION: Both laparoscopic and abdominal myomectomy significantly improved the quality of life. While MED12 mutations were related with multiple leiomyomas and therefore potentially generated a greater leiomyoma burden, they were not associated with the surgical approach. Pre- and postoperative quality of life was comparable between patients regardless of MED12 status.


Subject(s)
Laparoscopy , Leiomyoma , Mediator Complex , Mutation , Quality of Life , Uterine Myomectomy , Uterine Neoplasms , Humans , Female , Uterine Myomectomy/methods , Uterine Neoplasms/surgery , Uterine Neoplasms/genetics , Uterine Neoplasms/psychology , Adult , Mediator Complex/genetics , Leiomyoma/surgery , Leiomyoma/genetics , Leiomyoma/psychology , Middle Aged , Prospective Studies
13.
Int J Hyperthermia ; 41(1): 2384459, 2024.
Article in English | MEDLINE | ID: mdl-39074841

ABSTRACT

OBJECTIVE: This study aimed to explore the efficacy and safety of high-intensity focused ultrasound (HIFU) ablation for treating fumarate hydratase (FH)-deficient uterine leiomyomas. METHOD: Ten patients with FH-deficient uterine leiomyomas treated with HIFU ablation at the Third Xiangya Hospital from July 2017 to January 2023 were enrolled in this study. The effectiveness and adverse effects of HIFU were analyzed. RESULTS: The median age of the patients who received HIFU was 32.0 years (range: 28-41 years). Only 2 patients had solitary uterine leiomyomas, whereas the remaining 8 patients had multiple uterine leiomyomas. The median diameter of the largest myoma was 56 mm (range: 41-99 mm). Magnetic resonance imaging showed that the FH-deficient uterine leiomyomas of 8 patients presented as mixed intensity on T2WI, that of one patient was hypointense, and that of another patient was hyperintense on T2WI. All patients successfully underwent HIFU ablation in one session without severe adverse effects. The median nonperfusion volume ratio (NPVR) was 40% (30.0%-78.0%) after HIFU treatment. Four patients had NPVR ≥70%. At 3-month follow-up after HIFU ablation, the clinical symptoms of 5 of the 8 patients with symptoms before treatment were relieved. Six months after treatment, 4 of the 8 patients with symptoms were still in remission. All patients received reintervention by March 2024. The reintervention rates were 20%, 70%, and 90% at 12, 24, and 36 months, respectively, after HIFU ablation. CONCLUSION: HIFU is a safe and feasible treatment for FH-deficient uterine leiomyomas, and most patients show effective results in the short term after treatment. However, the reintervention rates are high, and the long-term effects are limited.


Subject(s)
Fumarate Hydratase , High-Intensity Focused Ultrasound Ablation , Leiomyoma , Humans , Female , High-Intensity Focused Ultrasound Ablation/methods , Adult , Leiomyoma/surgery , Leiomyoma/therapy , Fumarate Hydratase/genetics , Uterine Neoplasms/surgery , Uterine Neoplasms/therapy
15.
Risk Manag Healthc Policy ; 17: 1669-1685, 2024.
Article in English | MEDLINE | ID: mdl-38919406

ABSTRACT

Purpose: The aim of this study was to investigate the risk factors of postmenopausal special uterine leiomyoma pathological types or leiomyosarcoma and to develop a nomogram for clinical risk assessment, ultimately to reduce unnecessary surgical interventions and corresponding economic expenses. Methods: A total of 707 patients with complete information were enrolled from 1 August 2012 to 1 August 2022. Univariate and multivariate logistic regression models were used to analyse the association between variables and special uterine leiomyoma pathological types or leiomyosarcoma in postmenopausal patients. A nomogram for special uterine leiomyoma pathological types or leiomyosarcoma in postmenopausal patients was developed and validated by bootstrap resampling. The calibration curve was used to assess the accuracy of the model and receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were compared with the clinical experience model. Results: The increasing trend after menopause, the diameter of the largest uterine fibroid, serum carcinoembryonic antigen 125 concentration, Serum neutrophil to lymphocyte ratio, and Serum phosphorus ion concentration were independent risk factors for special uterine leiomyoma pathological types or leiomyosarcoma in postmenopausal patients. We developed a user-friendly nomogram which showed good diagnostic performance (AUC=0.724). The model was consistent and the calibration curve of our cohort was close to the ideal diagonal line. DCA indicated that the model has potential value for clinical application. Furthermore, our model was superior to the previous clinical experience model in terms of ROC and DCA. Conclusion: We have developed a prediction nomogram for special uterine leiomyoma pathological types or leiomyosarcoma in postmenopausal patients. This nomogram could serve as an important warning signal and evaluation method for special uterine leiomyoma pathological types or leiomyosarcoma in postmenopausal patients.

16.
Reprod Sci ; 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38858328

ABSTRACT

Bromodomain (BRD)-containing proteins are evolutionarily conserved protein-protein interaction modules involved in many biological processes. BRDs selectively recognize and bind to acetylated lysine residues, particularly in histones, and thereby have a crucial role in the regulation of gene expression. BRD protein dysfunction has been linked to many diseases, including tumorigenesis. Previously, we reported the critical role of BRD-containing protein 9 (BRD9) in the pathogenesis of UFs. The present study aimed to extend our previous finding and further understand the role of the BRD9 in UFs. Our studies demonstrated that targeted inhibition of BRD9 with its potent inhibitor TP-472 inhibited the pathogenesis of UF through increased apoptosis and proliferation arrest and decreased extracellular matrix deposition in UF cells. High-throughput transcriptomic analysis further and extensively demonstrated that targeted inhibition of BRD9 by TP-472 impacted the biological pathways, including cell cycle progression, inflammatory response, E2F targets, ECM deposition, and m6A reprogramming. Compared with the previous study, we identified common enriched pathways induced by two BRD9 inhibitors, I-BRD9 and TP-472. Taken together, our studies further revealed the critical role of BRD9 in UF cells. We characterized the link between BRD9 and other vital pathways, as well as the connection between epigenetic and epitranscriptome involved in UF progression. Targeted inhibition of BRD proteins might provide a non-hormonal treatment strategy for this most common benign tumor in women of reproductive age.

17.
Front Endocrinol (Lausanne) ; 15: 1373724, 2024.
Article in English | MEDLINE | ID: mdl-38800482

ABSTRACT

Objectives: Hypertension and hypertensive disorders of pregnancy (HDP) are common diseases in women at different stages, which affect women's physical and mental health, and the impact of the latter on the offspring cannot not be ignored. Observational studies have investigated the correlation between uterine leiomyoma (UL) and the above conditions, but the relationship remains unclear. In this study, we employed two-sample Mendelian randomization (MR) analysis to assess the association between UL and hypertension, HDP, as well as blood pressure. Methods: We collected genetic association data of UL (35,474 cases), hypertension (129,909 cases), HDP (gestational hypertension with 8,502 cases, pre-eclampsia with 6,663 cases and eclampsia with 452cases), systolic blood pressure (SBP) and diastolic blood pressure (DBP) (both 757,601 participants) from published available genome-wide association studies (GWAS). The single nucleotide polymorphisms (SNPs) associated with UL phenotype were used as instrumental variables, and hypertension, three sub-types of HDP, SBP and DBP were used as outcomes. The inverse-variance weighted (IVW) method was employed as the primary method of causal inference. Heterogeneity was assessed using Cochran's Q test, and sensitivity analyses were conducted using MR-Egger regression and MR pleiotropy residual sum and outlier (MR-PRESSO) tests to evaluate the pleiotropy of instrumental variables. PhenoScanner search was used to remove confounding SNP. Robustness and reliability of the results were assessed using methods such as the weighted median and weighted mode. Results: The IVW analysis revealed a positive correlation between genetically predicted UL and SBP [odds ratio (OR)= 1.67, 95% confidence interval (CI):1.24~2.25, P = 0.0007], and no statistical association was found between UL and hypertension, HDP, or DBP. The MR-Egger regression suggested that the above causal relationships were not affected by horizontal pleiotropy. The weighted median method and weighted model produced similar results to the IVW. Conclusion: Based on large-scale population GWAS data, our MR analysis suggested a causal relationship between UL and SBP. Therefore, women with UL, especially pregnant women, should pay attention to monitoring their blood pressure levels. For patients with hypertension who already have UL, interventions for UL may serve as potential therapeutic methods for managing blood pressure.


Subject(s)
Blood Pressure , Genome-Wide Association Study , Hypertension , Leiomyoma , Mendelian Randomization Analysis , Polymorphism, Single Nucleotide , Uterine Neoplasms , Humans , Female , Leiomyoma/genetics , Uterine Neoplasms/genetics , Blood Pressure/genetics , Pregnancy , Hypertension/genetics , Hypertension/epidemiology , Hypertension, Pregnancy-Induced/genetics
18.
Molecules ; 29(9)2024 May 01.
Article in English | MEDLINE | ID: mdl-38731586

ABSTRACT

Nanomedicine has revolutionized drug delivery in the last two decades. Nanoparticles appear to be a promising drug delivery platform in the treatment of various gynecological disorders including uterine leiomyoma, endometriosis, polycystic ovarian syndrome (PCOS), and menopause. Nanoparticles are tiny (mean size < 1000 nm), biodegradable, biocompatible, non-toxic, safe, and relatively inexpensive materials commonly used in imaging and the drug delivery of various therapeutics, such as chemotherapeutics, small molecule inhibitors, immune mediators, protein peptides and non-coding RNA. We performed a literature review of published studies to examine the role of nanoparticles in treating uterine leiomyoma, endometriosis, PCOS, and menopause. In uterine leiomyoma, nanoparticles containing 2-methoxyestradiole and simvastatin, promising uterine fibroid treatments, have been effective in significantly inhibiting tumor growth compared to controls in in vivo mouse models with patient-derived leiomyoma xenografts. Nanoparticles have also shown efficacy in delivering magnetic hyperthermia to ablate endometriotic tissue. Moreover, nanoparticles can be used to deliver hormones and have shown efficacy as a mechanism for transdermal hormone replacement therapy in individuals with menopause. In this review, we aim to summarize research findings and report the efficacy of nanoparticles and nanotherapeutics in the treatment of various benign gynecologic conditions.


Subject(s)
Genital Diseases, Female , Nanomedicine , Nanoparticles , Humans , Female , Nanomedicine/methods , Nanoparticles/chemistry , Animals , Genital Diseases, Female/drug therapy , Drug Delivery Systems , Leiomyoma/drug therapy , Endometriosis/drug therapy , Polycystic Ovary Syndrome/drug therapy
19.
Int J Med Sci ; 21(7): 1227-1240, 2024.
Article in English | MEDLINE | ID: mdl-38818470

ABSTRACT

Uterine leiomyomas (ULM) are the most common benign tumors of the female genitalia, while uterine leiomyosarcomas (ULMS) are rare. The sarcoma is diffuse growth, prone to hematogenous metastasis, and has a poor prognosis. Due to their similar clinical symptoms and morphological features, it is sometimes difficult to distinguish them, and the final diagnosis depends on histological diagnosis. Misdiagnosis of ULM as ULMS will lead to more invasive and extensive surgery when it is not needed, while misdiagnosis of ULMS as ULM may lead to delayed treatment and poor prognosis. This review searched and studied the published articles on ULM and ULMS, and summarized the potential markers for the differential diagnosis of ULMS. These markers will facilitate differential diagnosis and personalized treatment, providing timely diagnosis and potentially better prognosis for patients.


Subject(s)
Biomarkers, Tumor , Leiomyoma , Leiomyosarcoma , Uterine Neoplasms , Humans , Female , Leiomyoma/diagnosis , Leiomyoma/pathology , Uterine Neoplasms/diagnosis , Uterine Neoplasms/pathology , Diagnosis, Differential , Leiomyosarcoma/diagnosis , Leiomyosarcoma/pathology , Prognosis
20.
Gynecol Oncol Rep ; 53: 101415, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38798949

ABSTRACT

Background: Uterine leiomyomas are benign tumors characterized by pelvic pain and abnormal bleeding. Their evolution can lead to degenerative changes, occasionally mimicking malignancies on imaging, presenting diagnostic challenges. Case presentation: A 31-year-old nulliparous woman presented with symptoms of bloating, cramping, and abdominal distension. Imaging suggested an advanced ovarian malignancy, showing a complex adnexal mass and elevated CA-125 levels. During exploratory laparotomy, what was suspected to be ovarian cancer was instead identified as a large uterine mass on pathologic evaluation revealing a benign leiomyoma with extensive hydropic change. Conclusion: This case highlights the diagnostic intricacies associated with large complex adnexal masses and illustrates how benign conditions like leiomyomas with hydropic degeneration can mimic ovarian cancer. This emphasizes the importance of comprehensive preoperative and intraoperative assessments to tailor management and avoid unindicated radical procedures.

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