RESUMEN

The narrative review article is focused on the strengths and limitations of modern imaging methods in the preoperative differential diagnosis of uterine mesenchymal tumours. In order to tailor the surgical procedures, imaging methods, namely ultrasound and magnetic resonance imaging (MRI), should be taken into account as well as clinical symptoms, age, and fertility plans. On ultrasound scans, uterine sarcomas have the appearance of large, usually solitary tumours of non-homogenous structure with irregular cysts, ill-defined outline borders (interrupted capsule), absence of calcifications with acoustic shadowing, and moderate to rich internal vascularisation. Rapid growth between follow-ups or atypical growth in peri- or post-menopause is also a sign of malignancy. On MRI, uterine sarcomas are characterized by irregular borders, hyperintense areas on T1-weighted and T2- weighted images, and central non-enhancing necrotic areas. On diffusion-weighted imaging (DWI/MRI), sarcomas exhibit markedly restricted diffusion but there is a significant overlap with some variants of fibroids. Core-needle or hysteroscopic biopsy can be used preoperatively if suspicious features are detected on ultrasound or MRI scans, particularly before myomectomy if fertility preservation is required or when conservative management is considered in asymptomatic women. Other imaging methods, such as positron emission tomography fused with CT (PET-CT) or computed tomography (CT) have limited role to distinguish uterine sarcomas from myomas and are suitable only for staging purposes. The importance of tumour markers including lactate dehydrogenase in preoperative work-up have not been verified yet. Conclusion: Uterine sarcomas can be distinguished from much more common myomas based on a combination of malignant features on ultrasound or MR imaging. In these suspicious cases the type and extent of surgery should be adjusted, avoiding intraperitoneal morcellation, which could lead to iatrogenic tumour spread and worsening of the patient's prognosis.

Asunto(s)

Sarcoma , Neoplasias Uterinas , Humanos , Femenino , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/diagnóstico por imagen , Neoplasias Uterinas/cirugía , Neoplasias Uterinas/patología , Sarcoma/diagnóstico , Sarcoma/diagnóstico por imagen , Sarcoma/cirugía , Diagnóstico Diferencial , Leiomioma/diagnóstico , Leiomioma/diagnóstico por imagen , Leiomioma/cirugía , Ultrasonografía/métodos , Imagen por Resonancia Magnética

RESUMEN

Background There are insufficient data comparing resorbable microspheres (RMs) with permanent trisacryl gelatin microspheres (TAGMs) for uterine artery embolization (UAE). Purpose To compare therapeutic efficacy and clinical outcomes in participants with symptomatic fibroids after UAE with RMs or TAGMs. Materials and Methods This randomized controlled trial included participants undergoing UAE for symptomatic fibroids at a single institution (from May 2021 to May 2023). Participants were randomized one-to-one to undergo UAE with either RMs or TAGMs. Numeric rating scale pain scores and cumulative fentanyl consumption were assessed for 24 hours after undergoing UAE. Anti-Mullerian hormone was measured to assess effects of UAE on ovarian function. MRI was performed before and 3 months after UAE to evaluate fibroid necrosis and uterine artery recanalization. Repeated variables such as pain were analyzed using Mann-Whitney U test with post hoc Bonferroni correction. Results Sixty female participants (mean age, 45.7 years ± 3.6 [SD]) completed the study, with 30 in each group. No evidence of a difference in pain scores was observed between groups (P > .99). Moreover, there was no evidence of a difference in the total fentanyl consumption at 24 hours after UAE between groups (median: RMs, 423 [IQR, 330-530] vs TAGMs, 562 [IQR, 437-780]; P = .15). Serum anti-Mullerian hormone 3 months after UAE showed no evidence of a difference between groups (RMs vs TAGMs, 0.71 ng/mL ± 0.73 vs 0.49 ng/mL ± 0.45, respectively; P = .09). No evidence of a difference in the rate of complete necrosis of the dominant fibroid was observed between groups (97% [29 of 30] for both groups; P > .99). The rate of uterine artery recanalization was higher in RM versus TAGM groups (70% [21 of 30] vs 17% [five of 30], respectively; P < .001). Conclusion UAE with RMs, compared with UAE with TAGMs, showed no evidence of a difference in terms of therapeutic effectiveness or postprocedural pain scores in participants with symptomatic fibroids. Clinical trial registration no. NCT05086770 © RSNA, 2024 See also the editorial by Spies in this issue.

Asunto(s)

Resinas Acrílicas , Gelatina , Leiomioma , Embolización de la Arteria Uterina , Humanos , Femenino , Embolización de la Arteria Uterina/métodos , Gelatina/uso terapéutico , Persona de Mediana Edad , Leiomioma/terapia , Leiomioma/diagnóstico por imagen , Resinas Acrílicas/uso terapéutico , Adulto , Microesferas , Neoplasias Uterinas/terapia , Neoplasias Uterinas/diagnóstico por imagen , Resultado del Tratamiento , Dimensión del Dolor

Asunto(s)

Embolización Terapéutica , Leiomioma , Neoplasias Uterinas , Leiomioma/terapia , Leiomioma/diagnóstico por imagen , Femenino , Humanos , Neoplasias Uterinas/terapia , Neoplasias Uterinas/diagnóstico por imagen , Embolización Terapéutica/métodos , Embolización Terapéutica/instrumentación , Implantes Absorbibles , Embolización de la Arteria Uterina/métodos , Gelatina/uso terapéutico

RESUMEN

High-Intensity Focused Ultrasound (HIFU) ablation represents a rapidly advancing non-invasive treatment modality that has achieved considerable success in addressing uterine fibroids, which constitute over 50% of benign gynecological tumors. Preoperative Magnetic Resonance Imaging (MRI) plays a pivotal role in the planning and guidance of HIFU surgery for uterine fibroids, wherein the segmentation of tumors holds critical significance. The segmentation process was previously manually executed by medical experts, entailing a time-consuming and labor-intensive procedure heavily reliant on clinical expertise. This study introduced deep learning-based nnU-Net models, offering a cost-effective approach for their application in the segmentation of uterine fibroids utilizing preoperative MRI images. Furthermore, 3D reconstruction of the segmented targets was implemented to guide HIFU surgery. The evaluation of segmentation and 3D reconstruction performance was conducted with a focus on enhancing the safety and effectiveness of HIFU surgery. Results demonstrated the nnU-Net's commendable performance in the segmentation of uterine fibroids and their surrounding organs. Specifically, 3D nnU-Net achieved Dice Similarity Coefficients (DSC) of 92.55% for the uterus, 95.63% for fibroids, 92.69% for the spine, 89.63% for the endometrium, 97.75% for the bladder, and 90.45% for the urethral orifice. Compared to other state-of-the-art methods such as HIFUNet, U-Net, R2U-Net, ConvUNeXt and 2D nnU-Net, 3D nnU-Net demonstrated significantly higher DSC values, highlighting its superior accuracy and robustness. In conclusion, the efficacy of the 3D nnU-Net model for automated segmentation of the uterus and its surrounding organs was robustly validated. When integrated with intra-operative ultrasound imaging, this segmentation method and 3D reconstruction hold substantial potential to enhance the safety and efficiency of HIFU surgery in the clinical treatment of uterine fibroids.

Asunto(s)

Ultrasonido Enfocado de Alta Intensidad de Ablación , Imagenología Tridimensional , Leiomioma , Imagen por Resonancia Magnética , Neoplasias Uterinas , Humanos , Leiomioma/diagnóstico por imagen , Leiomioma/cirugía , Femenino , Imagenología Tridimensional/métodos , Ultrasonido Enfocado de Alta Intensidad de Ablación/métodos , Imagen por Resonancia Magnética/métodos , Neoplasias Uterinas/diagnóstico por imagen , Neoplasias Uterinas/cirugía , Aprendizaje Profundo , Cirugía Asistida por Computador/métodos

RESUMEN

BACKGROUND: The addition of trabectedin to doxorubicin, followed by trabectedin maintenance, may have superior efficacy to doxorubicin alone as first-line treatment in patients with advanced leiomyosarcoma. METHODS: We conducted a phase 3 trial involving patients with metastatic or unresectable leiomyosarcoma who had not received chemotherapy previously. Patients were randomly assigned to receive either single-agent doxorubicin (six cycles) or doxorubicin plus trabectedin (six cycles), with continued trabectedin as maintenance therapy in patients in the doxorubicin-trabectedin group who did not have disease progression. Surgery to resect residual disease was allowed in each group after six cycles of therapy. Analyses of progression-free survival (primary end point) and overall survival (secondary end point) were adjusted for two stratification factors: tumor origin site (uterine vs. soft tissue) and disease stage (locally advanced vs. metastatic). The primary end-point results were reported previously. RESULTS: A total of 150 patients underwent randomization. At a median follow-up of 55 months (interquartile range, 49 to 63), a total of 107 patients had died (47 in the doxorubicin-trabectedin group and 60 in the doxorubicin group). The median overall survival was longer in the doxorubicin-trabectedin group (33 months; 95% confidence interval [CI], 26 to 48) than in the doxorubicin group (24 months; 95% CI, 19 to 31); the adjusted hazard ratio for death was 0.65 (95% CI, 0.44 to 0.95). In a finding consistent with earlier reports, progression-free survival was longer in the doxorubicin-trabectedin group (12 months; 95% CI, 10 to 16) than in the doxorubicin group (6 months; 95% CI, 4 to 7); the adjusted hazard ratio for progression or death was 0.37 (95% CI, 0.26 to 0.53). The incidence of adverse events and the percentage of patients with dose reductions were higher with doxorubicin plus trabectedin than with doxorubicin alone. CONCLUSIONS: Combination therapy with doxorubicin and trabectedin induction, followed by trabectedin maintenance, was associated with improved overall survival and progression-free survival, as compared with doxorubicin alone, among patients with metastatic or surgically unresectable uterine or soft-tissue leiomyosarcoma. (Funded by PharmaMar and others; LMS04 ClinicalTrials.gov number, NCT02997358.).

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica , Doxorrubicina , Leiomiosarcoma , Neoplasias de los Tejidos Blandos , Trabectedina , Neoplasias Uterinas , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Estimación de Kaplan-Meier , Leiomiosarcoma/tratamiento farmacológico , Leiomiosarcoma/mortalidad , Leiomiosarcoma/patología , Quimioterapia de Mantención , Supervivencia sin Progresión , Neoplasias de los Tejidos Blandos/tratamiento farmacológico , Neoplasias de los Tejidos Blandos/mortalidad , Neoplasias de los Tejidos Blandos/patología , Análisis de Supervivencia , Trabectedina/administración & dosificación , Trabectedina/efectos adversos , Neoplasias Uterinas/tratamiento farmacológico , Neoplasias Uterinas/mortalidad , Neoplasias Uterinas/patología , Estadificación de Neoplasias

RESUMEN

Emerging evidence suggests a tentative association between cathepsins and uterine leiomyoma (UL). Previous investigations have predominantly focused on the role of cathepsins in the metastasis and colonization of gynecological malignancies. Still, observational studies may lead to confounding and biases. We employed a bidirectional Mendelian randomization (MR) analysis to elucidate the causative links between various cathepsins and UL. Instrumental variables (IVs) of cathepsins and UL within the European cohort were from extant genome-wide association study datasets. Sensitivity assessments was executed, and the heterogeneity of the findings was meticulously dissected to affirm the solidity of the outcomes. Our findings reveal the association between cathepsin B (CTSB) and an elevated risk of developing UL (all cancers excluded) [Inverse Variance Weighted (IVW) method]: OR = 1.06, 95%CI [1.02, 1.11], P = 0.008895711. Although the association does not persist after multiple testing or Steiger filtering, this finding adds to our understanding of the causal relationship between CTSB of various cathepsins and UL (all cancers excluded) and may herald new therapeutic avenues for individuals affected by this condition.

Asunto(s)

Catepsina B , Catepsinas , Estudio de Asociación del Genoma Completo , Leiomioma , Análisis de la Aleatorización Mendeliana , Neoplasias Uterinas , Humanos , Femenino , Leiomioma/genética , Leiomioma/patología , Neoplasias Uterinas/genética , Neoplasias Uterinas/patología , Catepsina B/genética , Catepsina B/metabolismo , Catepsinas/genética , Catepsinas/metabolismo , Polimorfismo de Nucleótido Simple , Predisposición Genética a la Enfermedad

RESUMEN

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.

Asunto(s)

Leiomioma , Análisis de la Aleatorización Mendeliana , Neoplasias Uterinas , Humanos , Femenino , Leiomioma/genética , Leiomioma/epidemiología , Neoplasias Uterinas/genética , Neoplasias Uterinas/epidemiología , Predisposición Genética a la Enfermedad , Factores de Riesgo , Polimorfismo de Nucleótido Simple

RESUMEN

Over 70% of leiomyoma (LM) harbor MED12 mutations, primarily in exon 2 at c.130-131 (GG). Myometrial cells are the cell origin of leiomyoma, but the MED12 mutation status in non-neoplastic myometrial cells is unknown. In this study, we investigated the mutation burden of MED12 in myometrium. As traditional Sanger or even NGS sequencing may not be able to detect MED12 mutations that are lower than 0.1% in the testing sample, we used duplex deep sequencing analysis (DDS) to overcome this limitation. Tumor-free myometria (confirmed by pathology evaluation) were dissected, and genomic DNA from MED12 exon 2 (test) and TP53 exon 5 (control) were captured by customer-designed probe sets, followed by DDS. Notably, DDS demonstrated that myometrial cells harbored a high frequency of mutations in MED12 exon 2 and predominantly in code c.130-131. In contrast, the baseline mutations in other coding sequences of MED12 exon 2 as well as in the TP53 mutation hotspot, c.477-488 were comparably low in myometrial cells. This is the first report demonstrating a non-random accumulation of MED12 mutations at c.130-131 sites in non-neoplastic myometrial cells which provide molecular evidence of early somatic mutation events in myometrial cells. This early mutation may contribute to the cell origin for uterine LM development in women of reproductive age.

Asunto(s)

Complejo Mediador , Mutación , Miometrio , Humanos , Femenino , Miometrio/metabolismo , Miometrio/patología , Complejo Mediador/genética , Complejo Mediador/metabolismo , Mutación/genética , Exones/genética , Leiomioma/genética , Leiomioma/patología , Persona de Mediana Edad , Adulto , Neoplasias Uterinas/genética , Neoplasias Uterinas/patología , Secuenciación de Nucleótidos de Alto Rendimiento , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo

RESUMEN

Uterine leiomyosarcoma (uLMS) is the most common type of uterine sarcoma, associated with poor prognosis, high rates of recurrence, and metastasis. Currently, the molecular mechanism of the origin and development of uLMS is limited. Bromodomain and extra-terminal (BET) proteins are involved in both physiological and pathological events. However, the role of BET proteins in the pathogenesis of uLMS is unknown. Here, we show for the first time that BET protein family members, BRD2, BRD3, and BRD4, are aberrantly overexpressed in uLMS tissues compared to the myometrium, with a significant change by histochemical scoring assessment. Furthermore, inhibiting BET proteins with their small, potent inhibitors (JQ1 and I-BET 762) significantly inhibited the uLMS proliferation dose-dependently via cell cycle arrest. Notably, RNA-sequencing analysis revealed that the inhibition of BET proteins with JQ1 and I-BET 762 altered several critical pathways, including the hedgehog pathway, EMT, and transcription factor-driven pathways in uLMS. In addition, the targeted inhibition of BET proteins altered several other epigenetic regulators, including DNA methylases, histone modification, and m6A regulators. The connections between BET proteins and crucial biological pathways provide a fundamental structure to better understand uterine diseases, particularly uLMS pathogenesis. Accordingly, targeting the vulnerable epigenome may provide an additional regulatory mechanism for uterine cancer treatment.

Asunto(s)

Leiomiosarcoma , Factores de Transcripción , Neoplasias Uterinas , Humanos , Femenino , Leiomiosarcoma/metabolismo , Leiomiosarcoma/patología , Leiomiosarcoma/genética , Neoplasias Uterinas/metabolismo , Neoplasias Uterinas/patología , Neoplasias Uterinas/genética , Factores de Transcripción/metabolismo , Proliferación Celular , Azepinas/farmacología , Regulación Neoplásica de la Expresión Génica , Triazoles/farmacología , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Línea Celular Tumoral , Epigénesis Genética , Puntos de Control del Ciclo Celular/efectos de los fármacos , Puntos de Control del Ciclo Celular/genética , Persona de Mediana Edad , Proteínas que Contienen Bromodominio , Benzodiazepinas , Proteínas

RESUMEN

We aimed to find new therapeutic targets related to Cancer Stem Cell alterations in recurrent patients from two TCGA cohorts: Testicular Germ Cell Tumor (TGCT) and Uterine Corpus Endometrial Carcinoma (UCEC). Raw sequencing data were downloaded from the TCGA database. Datasets containing RNA expression and Methylation files were directly downloaded from cBioportal. Variant Call Format files (VCFs) were downloaded from the GDC portal. Gene enrichment analysis was performed using GSEA (Gene Set Enrichment Analysis) software. Transcriptome profiling, coexpression co-occurrence, networks, and survival analyses were performed using cBioportal tools, while mutational analysis of patients was processed using UNIX scripts. We found that cancer stem cell transcription factors were highly expressed in Testicular Germ Cell Tumor (TGCT) and Uterine Corpus Endometrial Carcinoma (UCEC) cohorts, compared to the other 29 cancer cohorts in TCGA. Patients presented a poorer diagnosis when the genes (POU5F1, NANOG, SOX2, SALL4, ABCB1, ABCC1, and ABCG2) were altered. In UCEC cohorts, recurrent patients showed the ABCG2 potentially phosphorylated by the PIM1 kinase. In the TGCT cohort, genes ABCB1 and ABCG2 only appeared in the phosphonetwork in recurrent patients potentially phosphorylated by the same kinase, PIM1, but also by PRKACA. Our data indicate that PRKACA and PIM1 may modulate POU5F1 phosphorylation.

Asunto(s)

Resistencia a Antineoplásicos , Neoplasias de Células Germinales y Embrionarias , Neoplasias Testiculares , Humanos , Femenino , Neoplasias Testiculares/genética , Neoplasias Testiculares/tratamiento farmacológico , Masculino , Neoplasias de Células Germinales y Embrionarias/genética , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Resistencia a Antineoplásicos/genética , Estudios de Cohortes , Neoplasias Uterinas/genética , Neoplasias Endometriales/genética , Neoplasias Endometriales/patología , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica/genética

RESUMEN

Choriocarcinoma is a malignant cancer that belongs to gestational trophoblastic neoplasia (GTN). Herein, serum metabolomic analysis was performed on 29 GTN patients and 30 healthy individuals to characterize the metabolic variations during GTN progression. Ultimately 24 differential metabolites (DMs) were identified, of which, Equol was down-regulated in GTN patients, whose VIP score is the 3rd highest among the 24 DMs. As an intestinal metabolite of daidzein, the anticancer potential of Equol has been demonstrated in multiple cancers, but not choriocarcinoma. Hence, human choriocarcinoma cell lines JEG-3 and Bewo were used and JEG-3-derived subcutaneous xenograft models were developed to assess the effect of Equol on choriocarcinoma. The results suggested that Equol treatment effectively suppressed choriocarcinoma cell proliferation, induced cell apoptosis, and reduced tumorigenesis. Label-free quantitative proteomics showed that 136 proteins were significantly affected by Equol and 20 proteins were enriched in Gene Ontology terms linked to protein degradation. Tripartite motif containing 21 (TRIM21), a E3 ubiquitin ligase, was up-regulated by Equol. Equol-induced effects on choriocarcinoma cells could be reversed by TRIM21 inhibition. Annexin A2 (ANXA2) interacted with TRIM21 and its ubiquitination was modulated by TRIM21. We found that TRIM21 was responsible for proteasome-mediated degradation of ANXA2 induced by Equol, and the inhibitory effects of Equol on the malignant behaviors of choriocarcinoma cells were realized by TRIM21-mediated down-regulation of ANXA2. Moreover, ß-catenin activation was inhibited by Equol, which also depended on TRIM21-mediated down-regulation of ANXA2. Taken together, Equol may be a novel candidate for the treatment for choriocarcinoma.

Asunto(s)

Anexina A2 , Coriocarcinoma , Equol , Ubiquitinación , Humanos , Femenino , Anexina A2/metabolismo , Anexina A2/genética , Coriocarcinoma/metabolismo , Coriocarcinoma/genética , Equol/farmacología , Línea Celular Tumoral , Ubiquitinación/efectos de los fármacos , Animales , Ratones , Proliferación Celular/efectos de los fármacos , Apoptosis/efectos de los fármacos , Antineoplásicos/farmacología , Embarazo , Ratones Desnudos , Neoplasias Uterinas/metabolismo , Neoplasias Uterinas/tratamiento farmacológico , Neoplasias Uterinas/genética , Ratones Endogámicos BALB C

RESUMEN

BACKGROUND: Despite being a highly debated issue, subtotal or supracervical hysterectomy (SCH) is still considered a safe and effective treatment for women with benign gynecological lesions. Benign and malignant cervical diseases have been reported after SCH, with fibroids being the most frequently diagnosed lesions in the excised cervical stump. Recurrence of cervical disease after SCH usually presents with vaginal bleeding, pelvic mass, or abdominal pain; moreover, it may necessitate reoperation and resection of the cervical stump or trachelectomy. Trachelectomy is known to be a difficult surgical procedure that may be associated with significant intra- and post-operative morbidity. CASE PRESENTATION: We presented here a case of a 41-year-old nulliparous woman with a pelvic mass related to the cervical stump presented 2 years after subtotal hysterectomy, performed due to interactable abnormal uterine bleeding, which was attributed to a multiple fibroid uterus. Six years ago, she complained of pelvic pain, excessive vaginal discharge, and spotting. A transvaginal sonography and magnetic resonance imaging with contrast were performed, which revealed a 10.2 × 7.6 × 6.5 cm heterogeneous pelvic mass with irregular borders and marked vascularity on color Doppler. Surgical exploration and resection of the mass with cervical stump excision were performed. Histopathology confirmed the diagnosis of cervical stump multiple benign leiomyomata with no atypical features. CONCLUSION: Recurrence or De novo development of leiomyomata and other cervical lesions might occur after supracervical or subtotal hysterectomy; thus, thorough pre-operative counseling for women requesting a SCH regarding the pros and cons of the procedure compared with total hysterectomy should be optimized. Meticulous follow-up, including the continuation of routine cervical cytological smears, is mandatory for patients with a retained cervix.

Asunto(s)

Histerectomía , Leiomioma , Humanos , Femenino , Adulto , Histerectomía/efectos adversos , Histerectomía/métodos , Leiomioma/cirugía , Cuello del Útero/cirugía , Cuello del Útero/patología , Neoplasias Uterinas/cirugía , Neoplasias del Cuello Uterino/cirugía

RESUMEN

OBJECTIVES: To investigate the clinicopathological characteristics and prognosis of patients with uterine sarcoma treated following surgery for presumed benign disease. METHODS: We identified all patients with uterine sarcoma found incidentally after primary surgery for presumed benign disease who presented to our institution and received re-exploration for completion surgery from January 1, 2004 to January 1, 2021. We analyzed the clinicopathological characteristics and prognosis. RESULTS: Overall, 95 patients were included in our study. For the initial surgery, myomectomy was performed in 50 (52.6%, 50/95) patients, hysterectomy was performed in 45 (47.4%, 45/95) patients. All patients were re-explored to complete the staging operation. The median time to the staging surgery was 40 days (range 15-90 days). There were 29 patients (30.5%, 29/95) had remnant sarcomas, with 17 patients (17/95, 17.9%) on the remaining uterus, 9 patients (9/95, 9.5%) had disseminated diseases, and 4 patients (4/95, 4.2%) had positive lymph nodes. About 40 patients (42.1%) received adjuvant chemotherapy, 55.2% (16/29) and 36.4% (24/66) patients with/without remnant diseases received adjuvant chemotherapy, respectively (P = 0.087). The median follow-up duration was 76.7 months (IQR: 34.8-118.1 months). And 17 patients (17.9%) had recurrence following re-exploration surgery. 5-year progression-free survival (PFS) and 5-year overall survival (OS) for the entire cohort was 81.7% and 92.1%, respectively. Patients with remnant sarcomas had a tendency towards a worse 5-year PFS and 5-year OS, compared with those without (5-year PFS: 75.6% vs. 84.5%, P = 0.224; 5-year OS: 85.5% vs. 95.1%, P = 0.217). Patients with disseminated diseases had a worse 5-year OS (62.5% vs. 95.1%, P = 0.007) and non-significantly worse 5-year PFS (64.8% vs. 83.4%, P = 0.153) compared with those without. CONCLUSIONS: Patients with uterine sarcoma treated following surgery for presumed benign disease have a favorable survival. Patients with disseminated diseases had a worse 5-year OS compared with those without. Surgical re-exploration may be valuable for removing remnant sarcomas and disseminated diseases.

Asunto(s)

Histerectomía , Sarcoma , Neoplasias Uterinas , Humanos , Femenino , Persona de Mediana Edad , Neoplasias Uterinas/cirugía , Neoplasias Uterinas/patología , Neoplasias Uterinas/mortalidad , Adulto , Sarcoma/cirugía , Sarcoma/mortalidad , Sarcoma/patología , Anciano , Pronóstico , Estudios Retrospectivos , Estadificación de Neoplasias , Quimioterapia Adyuvante , Miomectomía Uterina , Análisis de Supervivencia

RESUMEN

Selective progesterone receptor modulators (SPRMs) are synthetic steroid compounds that interact with the progesterone receptor, inducing various agonist, antagonist or mixed responses. First identified with mifepristone, they are now represented by ulipristal acetate (UPA), used for emergency contraception and uterine fibroids. Despite a few rare cases of severe hepatic insufficiency, SPRMs offer advantages in the treatment of uterine fibroids, reducing their volume without the hypoestrogenic side-effects of GnRH agonists, thus preserving patients' bone capital and quality of life. Despite temporary suspension of UPA administrated on a daily basis, research is exploring the potential of SPRMs in the management of endometriosis, adenomyosis and breast cancer. Despite certain concerns, SPRMs offer promising prospects in gynecological pathologies, opening up new therapeutic avenues to improve women's health and quality of life. This article describes the case of a patient with peritoneal leiomyomatosis for whom UPA significantly alleviated symptoms, reduced disease progression and improved quality of life, even allowing a pregnancy.

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Les modulateurs sélectifs des récepteurs de la progestérone (SPRMs) sont des composés stéroïdiens synthétiques qui interagissent via le récepteur de la progestérone, induisant diverses réponses, agonistes, antagonistes ou mixtes. Les SPRMs ont d'abord été représentés par la mifépristone, utilisée pour ses propriétés antagonistes dans la gestion de l'interruption de la grossesse, puis par l'acétate d'ulipristal, qui est indiqué en contraception d'urgence, mais aussi pour la gestion de myomes utérins symptomatiques. Les SPRMs permettent de réduire le volume des myomes utérins, sans induire les effets secondaires d'hypo-œstrogénie des agonistes de la GnRH, préservant ainsi le capital osseux et la qualité de vie des patientes. Néanmoins, quelques cas graves d'insuffisance hépatique ont conduit à la suspension temporaire de l'acétate d'ulipristal en traitement chronique. En dépit de certaines réserves, les SPRMs offrent des perspectives dans les affections gynécologiques, ouvrant de nouvelles voies thérapeutiques pour améliorer la santé et la qualité de vie des femmes. Des recherches explorent leur potentiel dans l'endométriose, l'adénomyose et la chimioprévention du cancer du sein. Nous décrivons ici le cas d'une patiente avec léiomyomatose péritonéale pour laquelle l'acétate d'ulipristal a significativement réduit les symptômes et l'évolution de la maladie, tout en améliorant la qualité de vie de la patiente, avec même l'obtention d'une grossesse menée à terme.

Asunto(s)

Leiomioma , Norpregnadienos , Receptores de Progesterona , Humanos , Femenino , Norpregnadienos/uso terapéutico , Receptores de Progesterona/metabolismo , Leiomioma/tratamiento farmacológico , Neoplasias Uterinas/tratamiento farmacológico , Adulto , Calidad de Vida

RESUMEN

A woman in her 30s presented to emergency with complaints of acute lower abdominal pain for 3 days, not associated with any menstrual, bowel or urinary symptoms. Examination revealed an abdominopelvic mass corresponding to an 18-week gravid uterus with diffuse tenderness and guarding over her lower abdomen. The patient was a follow-up case of subserosal fibroid uterus, chronic kidney disease stage 4 and rheumatic heart disease on anticoagulants. Fibroid degeneration or torsion was suspected. Ultrasound revealed a large posterior wall subserosal fibroid with free fluid in the pelvis. As findings did not suggest degeneration or pedunculated fibroid, noncontrast CT was done, which showed a similar mass with a pedicle arising from the uterine fundus with free fluid with no other evident cause of acute abdomen. The patient was taken up for emergency laparotomy. Intraoperatively, it was found to be a case of subserosal fibroid with greater omentum adhered to it and twisted around its axis about eight times. This case is being reported to highlight a rare cause of acute abdomen.

Asunto(s)

Abdomen Agudo , Leiomioma , Epiplón , Anomalía Torsional , Neoplasias Uterinas , Humanos , Abdomen Agudo/etiología , Femenino , Leiomioma/complicaciones , Leiomioma/cirugía , Leiomioma/diagnóstico por imagen , Epiplón/cirugía , Epiplón/patología , Anomalía Torsional/cirugía , Anomalía Torsional/diagnóstico por imagen , Anomalía Torsional/complicaciones , Anomalía Torsional/diagnóstico , Adulto , Neoplasias Uterinas/complicaciones , Neoplasias Uterinas/cirugía , Neoplasias Uterinas/diagnóstico por imagen , Laparotomía/métodos , Tomografía Computarizada por Rayos X , Enfermedades Peritoneales/cirugía , Enfermedades Peritoneales/complicaciones , Enfermedades Peritoneales/diagnóstico por imagen , Ultrasonografía

RESUMEN

Uterine fibroids (UFs), the most common tumors in women of reproductive age, are characterized by sex steroid-dependent growth and excessive deposition of extracellular matrix (ECM) surrounding UF smooth muscle cells. Women with symptomatic UFs experience heavy menstrual bleeding and consequent iron-deficiency anemia. They also have a risk of recurrent pregnancy loss, preterm birth, and cesarean delivery, indicating that UFs can negatively affect reproductive outcomes. Various types of immune cells, including innate and adaptive cells, are observed in UFs; however, the impact of these cells on the pathophysiology of UFs remains unclear. Inflammation may play important roles in the growth of UFs, and expression levels of proinflammatory and inflammatory cytokines, such as interleukin (IL)-1, IL-6, IL-10, TNF-α, and TGF-ß, are upregulated in UFs. These cytokines play important roles in the interaction between growth factors and ECM that is regulated by the sex steroids estrogen and progesterone. Furthermore, proinflammatory mediators are upregulated in females with UFs, with higher expression levels in the endometrium with submucosal and intramural UFs than in the endometrium without UFs, indicating that these proinflammatory cytokines may impair endometrial receptivity, leading to implantation failure in in vitro fertilization programs. Hormonal treatments using gonadotropin releasing hormone analogs and the selective progesterone receptor modulator ulipristal acetate significantly shrink UFs and improve UF-related symptoms. These compounds can regulate local inflammation in UFs and adjacent myometrium. Controlling and improving local inflammation caused by UFs may represent a novel therapeutic strategy for UFs and potentially improve reproductive outcomes in women with symptomatic UFs.

Asunto(s)

Inflamación , Leiomioma , Humanos , Femenino , Leiomioma/inmunología , Leiomioma/patología , Embarazo , Inflamación/inmunología , Citocinas/metabolismo , Neoplasias Uterinas/inmunología , Neoplasias Uterinas/patología , Endometrio/inmunología , Endometrio/patología , Mediadores de Inflamación/metabolismo

RESUMEN

BACKGROUND: Angioleiomyoma, a benign tumour composed of smooth muscle cells and thick-walled vessels, is expected to be very rare in the female genital tract. This study aimed to describe the clinicopathological features and treatment outcomes of angioleiomyoma in the female genital tract. METHODS: We retrospectively reviewed 89 women with angioleiomyoma in the genital tract who were treated at Third Xiangya Hospital of Central South University between July 2008 and October 2023. Symptom remission rate was the primary outcome of the study. RESULTS: Angioleiomyomas accounted for 0.6% of leiomyomas of the female genital tract. The average age of the 89 women was 41.8 ± 8.7 years. Seventy women (78.7%) had a history of uterine surgery, of whom two patients had removed uterine angioleiomyoma by laparoscopic myomectomy. The angioleiomyomas of 61 (68.5%) women were located in the uterine corpus, 17 (19.1%) in the broad ligament, 10 (11.2%) in the cervix and only 1 (1.1%) in the vagina. Abnormal uterine bleeding was the main clinical manifestation of angioleiomyomas located in the uterine corpus or cervix, whereas the main clinical manifestation of angioleiomyomas in the broad ligaments was pelvic mass. Of the 89 women, 59 underwent surgery to preserve the uterus, and 30 underwent total hysterectomy or subtotal hysterectomy. The intraoperative blood loss was more than 500 ml (700-4,500 ml) in six women. The symptom remission rate was 100% after surgery. Among the 59 women with preserved uterus, 8 showed multiple uterine leiomyomas during follow-up, but it was difficult to determine whether they were angioleiomyomas. Angioleiomyomas recurred in one women who underwent total hysterectomy. CONCLUSION: Angioleiomyoma is rare in the female reproductive tract, and patients may present with diverse symptoms, which are related to the location of the tumour. Hysterectomy and myomectomy are both effective treatment methods, but the risk of intraoperative bleeding should be recognised for multiple lesions and those with large diameters. Relapse may occur in some patients.

Asunto(s)

Angiomioma , Humanos , Femenino , Estudios Retrospectivos , Adulto , Angiomioma/cirugía , Angiomioma/patología , Persona de Mediana Edad , Resultado del Tratamiento , Neoplasias Uterinas/cirugía , Neoplasias Uterinas/patología , Neoplasias de los Genitales Femeninos/cirugía , Neoplasias de los Genitales Femeninos/patología , Estudios de Cohortes , Histerectomía/métodos , Histerectomía/estadística & datos numéricos

RESUMEN

PURPOSE: Uterine serous carcinoma (USC) is a highly aggressive and frequently recurring subtype of endometrial cancer with limited treatment options for advanced or recurrent stages. Sulindac, a classic non-steroidal anti-inflammatory drug, has demonstrated anti-tumor activity in several pre-clinical tumor models. This study aims to evaluate the effect of sulindac on cell proliferation and invasion in USC cells. METHODS: Human USC cell lines ARK-1 and SPEC2 were treated with different concentrations of sulindac. Cell proliferation was assessed using MTT and colony formation assays. ELISA assays measured cellular stress, cleaved caspase 3 activity, antioxidant ability, and adhesion. Cell cycle arrest was evaluated by Cellometer. The invasive capability was detected by wound healing assay. Western blotting was used to analyze the changes in protein expression induced by sulindac. RESULTS: Exposure to sulindac decreased cellular viability in a dose-dependent manner in ARK-1 and SPEC2 cells. Sulindac effectively inhibited cell cycle progression, increased cellular stress, caused apoptosis, and reduced cell adhesion and invasion in USC cells. Additionally, sulindac decreased the expression of COX-2 and blocked phosphorylation of NF-κB induced by TNF-α. CONCLUSION: Sulindac is a potential therapeutic agent for USC that deserves further exploration in pre-clinical studies and potentially future clinical trials.

Asunto(s)

Apoptosis , Proliferación Celular , Cistadenocarcinoma Seroso , Sulindac , Neoplasias Uterinas , Humanos , Femenino , Sulindac/farmacología , Proliferación Celular/efectos de los fármacos , Neoplasias Uterinas/tratamiento farmacológico , Neoplasias Uterinas/patología , Línea Celular Tumoral , Cistadenocarcinoma Seroso/tratamiento farmacológico , Cistadenocarcinoma Seroso/patología , Cistadenocarcinoma Seroso/metabolismo , Apoptosis/efectos de los fármacos , Invasividad Neoplásica , Adhesión Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos

RESUMEN

Gestational trophoblastic diseases (GTDs) encompass a spectrum of conditions characterized by abnormal trophoblastic cell growth, ranging from benign molar pregnancies to malignant trophoblastic neoplasms. This systematic review explores the molecular underpinnings of GTDs, focusing on genetic and epigenetic factors that influence disease progression and clinical outcomes. Based on 71 studies identified through systematic search and selection criteria, key findings include dysregulations in tumor suppressor genes such as p53, aberrant apoptotic pathways involving BCL-2 (B-cell lymphoma), and altered expression of growth factor receptors and microRNAs (micro-ribose nucleic acid). These molecular alterations not only differentiate molar pregnancies from normal placental development but also contribute to their clinical behavior, from benign moles to potentially malignant forms. The review synthesizes insights from immunohistochemical studies and molecular analyses to provide a comprehensive understanding of GTD pathogenesis and implications for personalized care strategies.

Asunto(s)

Mola Hidatiforme , Humanos , Mola Hidatiforme/genética , Mola Hidatiforme/patología , Mola Hidatiforme/metabolismo , Embarazo , Femenino , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias Uterinas/genética , Neoplasias Uterinas/patología , Neoplasias Uterinas/metabolismo , Epigénesis Genética

RESUMEN

BACKGROUND: This case describes chronic anemia of a late preterm infant secondary to maternal-fetal hemorrhage and subsequent findings of maternal choriocarcinoma. CLINICAL FINDINGS: This infant was born at 35 6/7 weeks gestational age via cesarean section for non-reassuring fetal heart tones. The mother presented with decreased fetal movement and the biophysical profile was 4/8. Following delivery, the infant did not require respiratory support, was vigorous with extreme pallor, and had a hemoglobin of less than 5 on cord gas. PRIMARY DIAGNOSIS: Chronic anemia secondary to fetomaternal hemorrhage. INTERVENTIONS: The infant's initial hemoglobin was 2.4 and hematocrit was 8.1. The mother's Kleihauer-Betke test was elevated at 7%. The infant required a partial exchange transfusion following admission to the neonatal intensive care unit. Following the partial exchange transfusion, the infant began to experience increasing respiratory distress and required respiratory support. An echocardiogram showed severe persistent pulmonary hypertension of the neonate. The mother was subsequently diagnosed with choriocarcinoma. OUTCOMES: The infant fully recovered from chronic anemia and persistent pulmonary hypertension of the neonate and was discharged home with the mother. The infant required follow-up testing for choriocarcinoma outpatient. PRACTICE RECOMMENDATIONS: Newborns diagnosed with early chronic anemia should be evaluated, the cause investigated, and appropriate treatment considered. If the cause of blood loss is unknown, a maternal Kleihauer-Betke test should be considered. In this case, a partial exchange transfusion was performed to avoid cardiovascular volume overload, but another course of treatment could include small aliquots of packed red blood cell transfusions.

Asunto(s)

Coriocarcinoma , Transfusión Fetomaterna , Humanos , Transfusión Fetomaterna/diagnóstico , Transfusión Fetomaterna/terapia , Transfusión Fetomaterna/complicaciones , Femenino , Recién Nacido , Embarazo , Coriocarcinoma/complicaciones , Coriocarcinoma/diagnóstico , Coriocarcinoma/terapia , Recambio Total de Sangre/métodos , Neoplasias Uterinas/complicaciones , Neoplasias Uterinas/terapia , Neoplasias Uterinas/diagnóstico , Recien Nacido Prematuro , Cesárea , Anemia/etiología , Anemia/terapia , Adulto