Evaluation of Uterine Fibroid Vascularity Using Contrast-Enhanced Ultrasound in Comparison with Contrast-Enhanced Magnetic Resonance Imaging.

OBJECTIVE: The aim of the work described here was to assess uterine fibroid vascularity using contrast-enhanced ultrasound (CEUS) as compared with magnetic resonance imaging (MRI). METHODS: Forty women diagnosed with symptomatic uterine fibroids scheduled for uterine artery embolization (UAE) were enrolled in this institutional review board-approved study. Before UAE, participants underwent CEUS examination with an Aplio i800 scanner (Canon Medical Systems, Tustin, CA, USA) with curvilinear array (8C1). CEUS was performed using 2.0 mL of the ultrasound contrast agent Lumason (Bracco, Milan, Italy) administered intravenously. Digital CEUS clips were acquired and randomized offline, and fibroids were characterized as hyper- or hypovascular. MRI was used as reference standard for fibroid vascularity and compared with CEUS. Results were analyzed using McNemar's test. RESULTS: Forty participants were enrolled in the trial. One patient did not proceed with the UAE procedure and one patient refused pre-procedure MRI because of claustrophobia. Therefore, 38 participants underwent CEUS and MRI examinations before UAE. Hypervascular fibroids were seen on MRI and CEUS in 24 and 26 participants, respectively. Hypovascular fibroids were seen with MRI and CEUS in 14 and 12 participants, respectively. Fibroids characterized as hypovascular in two participants by MRI were characterized as hypervascular by CEUS. CEUS and MRI findings were similar in 36 of 38 participants, corresponding to an accuracy of 95% (p = 0.62). CONCLUSION: Contrast-enhanced ultrasound can accurately assess uterine fibroid vascularity, serving as a potential alternative to MRI in determination of the vascularity of uterine fibroids.

Preoperative Endovascular Embolization of Orbital Solitary Fibrous Tumor With 500-700 Micron Tris-Acryl Gelatin Microspheres.

The reported experience with preoperative embolization of solid orbital tumors is scarce. Herein, we present a case of a large and hypervascular orbital solitary fibrous tumor (SFT) in which 500-700 µm tris-acryl gelatin microspheres (TAGM) were used for preoperative embolization. A 41-year-old man presented with severe proptosis, palpable mass, restrictive myopathy, exposure keratopathy, and compressive optic neuropathy in the right orbit. Magnetic resonance imaging showed a 65x35x35 mm, diffusely contrast-enhanced tumor in the superior orbit, extending to the apex, and multiple intratumoral vascular flow voids. A diagnosis of SFT was made by incisional biopsy. Endovascular tumor embolization was performed with 500-700 µm TAGM. Two days later, the tumor was entirely removed with minimal bleeding. No embolization- or surgery-related complications and tumor recurrence or metastasis developed during the 42-month postoperative follow-up.

The assessment of the relationship between the vascularity of FIGO Type 4-7 leiomyomas and abnormal uterine bleeding.

The current study aimed to analyse and compare the vascularity of FIGO Type 4-7 leiomyoma specimens obtained from women with or without abnormal uterine bleeding (AUB). The records of 31 women who underwent myomectomy for FIGO Type 4-7 leiomyomas in a university hospital setting were analysed. Group I (n = 16) was composed of women that were symptomatic for AUB and group II (n = 15) consisted of asymptomatic cases. The myomectomy material(s) of each case were processed with CD34 staining and evaluated by Image J® software (Image J 1.52a, Wayne Rasband National Institutes of Health, Bethesda, MD). There was no statistically significant difference between the rates of vascular areas in the specimens of the two groups (p>.05). Although areas with large vessels were higher in group I compared to group II, the difference did not reach statistical significance (p>.05). AUB caused by FIGO Type 4-7 leiomyomas seems to be related to factors other than vascular density.Impact StatementWhat is already known on this subject? Uterine leiomyomas are the most common benign gynaecologic neoplasms with a prevalence of approximately 40% in women of reproductive age. They are most often asymptomatic but when symptomatic, abnormal uterine bleeding (AUB) is one of the most commonly observed symptoms. Although there are some hypothetical explanations, the exact pathogenesis underlying leiomyoma-associated AUB has not yet been elucidated. Almost a century ago, the vascular abnormalities of fibroids were hypothesised as one of the etiopathological factors correlated with clinical symptoms, such as AUB, and current data suggest that the vascular map of leiomyomas consists of an avascular core surrounded by a vascularised capsule. To our knowledge, there are no studies in the literature comparing the histopathological evaluation of the vascularity scores of FIGO Type 4-7 leiomyomas in symptomatic (with AUB) and asymptomatic (without AUB) women.What the results of this study add? The study revealed that there was no statistically significant difference between the vascularity scores of FIGO Type 4-7 leiomyomas excised from the symptomatic and asymptomatic women. Large vessel densities also did not statistically significantly differ between the two groups.What the implications are of these findings for clinical practice and/or further research? This study revealed that AUB caused by FIGO Type 4-7 leiomyomas was related to factors other than vascular density.

Intravenous leiomyomatosis is inclined to a solid entity different from uterine leiomyoma based on RNA-seq analysis with RT-qPCR validation.

INTRODUCTION: Intravenous leiomyomatosis (IVL) is currently regarded as a special variant of the common uterine leiomyoma (LM). Though IVL shows a similar histological morphology to LM, IVL is characterized by unique intravenous growth patterns and low-grade malignant potential, which are quite different from LM. There are currently few studies underlying the molecular alterations of IVL, though this information is important for understanding the pathogenesis of the disease, and for identifying potential biomarkers. METHOD: We carried out a high-throughput whole transcriptome sequencing of tumor and normal tissue samples from five IVL patients and five LM patients and compared the differentially expressed genes (DEGs) between IVL and leiomyoma. We performed multiple different enrichment and target analyses, and the expression of selected DEGs was validated using RT-qPCR in formalin-fixed samples. RESULTS: Our study identified substantial different genes and pathways between IVL and LM, and functional enrichment analyses found several important pathways, such as angiogenesis and antiapoptosis pathways, as well as important related genes, including SH2D2A, VASH2, ADAM8, GATA2, TNF, and the lncRNA GATA6-AS1, as being significantly different between IVL and LM (P = .0024, P = .0195, P = .0212, P = .0435, P = .0401, and P = .0246, respectively). CXCL8, LIF, CDKN2A, BCL2A1, COL2A1, IGF1, and HMGA2 were also differently expressed between IVL and LM groups, but showed no statistical difference (P = .2409, P = .1773, P = .0596, P = .2737, P = .1553, P = .1045, and P = .1847, respectively) due to the large differences among individuals. Furthermore, RT-qPCR results for five selected DEGs in IVL tissues and adjacent nontumor tissues were mainly consistent with our sequencing results. CONCLUSION: Our results indicated that IVL may be a solid entity that is unique and different from LM, proving consistent with previous studies. Furthermore, we identified DEGs, particularly within angiogenesis and antiapoptosis pathway-related genes that may play crucial roles in the development and pathogenesis of IVL and may be potential specific biomarkers.

Forskolin promotes vasculogenic mimicry and invasion via Notch­1­activated epithelial­to­mesenchymal transition in syncytiolization of trophoblast cells in choriocarcinoma.

Choriocarcinoma (CC) is characterized by earlier blood metastasis compared with other female genital tumors and a high incidence of massive hemorrhage. Vasculogenic mimicry (VM) is highly associated with metastasis, and syncytiotrophoblast is involved in the formation of VM in CC. Forskolin is a typical activator of the cAMP pathway, which is involved in the syncytiolization of trophoblastic cells. In the present study, to determine the effects and mechanism of forskolin on cell invasion and VM during syncytiolization in vitro and in vivo, JEG­3 and JAR cell lines were treated with 100 µM forskolin for 48 h, and wound healing and invasion assays were used to verify cell migratory and invasive capacities. A 3D culture and tube formation assays were established to detect VM. Variation of morphology and markers of the epithelial­to­mesenchymal transition (EMT) were assessed, and the role of the Notch signaling pathway was investigated in CC cells treated with forskolin. The results of the present study demonstrated that 100 µM forskolin induced syncytiolization of trophoblastic cells and enhanced the migratory and invasive abilities of JEG­3 and JAR cell lines. In addition, the capacity of VM was significantly increased, whereas tube formation ability was decreased by forskolin in vitro and in vivo compared with the respective control groups. The cellular morphology exhibited EMT during the syncytiolization process, which was further supported by the changes in EMT marker expression, including downregulation of E­cadherin and cytokeratin and upregulation of N­cadherin, vimentin and zinc finger E­box­binding homeobox 1. The Notch­1 signaling pathway was activated to induce EMT in forskolin­induced VM process in CC cells, and VM and EMT could be reversed by using the γ­secretase inhibitor DAPT to block the Notch­1 pathway. Overall, the results of the present study demonstrated that forskolin enhanced the capacity of VM formation and metastasis through Notch­1­activated EMT in the syncytiolization of trophoblastic cells.

Differences in fibroid vascularity after three months of pre-treatment with leuprolide acetate or ulipristal acetate: A pilot study.

OBJECTIVES: To investigate differences in volume and fibroid vascularity expressed in vascular index after three months of (pre-)treatment with leuprolide acetate (LPA) or ulipristal acetate (UPA). STUDY DESIGN: Prospective pilot study of 23 premenopausal women with uterine fibroids. Patients who started with LPA or UPA and had at least one fibroid with a size between 3 and 12 cm, were included consecutively. Per patient one fibroid was evaluated. The ultrasound was performed at baseline and after three months using LPA or UPA using a standardized protocol. 3D scans were evaluated using VOCAL software to calculate outcomes of volume, vascular index (VI) without shell ("shell off") and of the inner shell. RESULTS: Four patients in the LPA group were additionally excluded from analyses due to insufficient quality of 3D scans. In the ten remaining patients (pre-)treated with LPA both volume and vascular indices of the fibroid reduced significantly after three months from a median of 224.3 cm3 (IQR 338.0) to 124.8 cm3 (IQR 186.1) (p = 0,05); median VI fibroid (shell off) reduced from 4.30 (IQR 4.72) to 0.93 (IQR 1.54) (p = 0,05); and VI inner capsule from 6.34 (IQR 7.51) to 1.28 (IQR 2.13) (p = 0,05). After UPA (n = 9) changes in fibroid volume and vascular indices did not reach statistical significance. Volume reduced from 248.5 cm3 (IQR 271.9) to 140.7 cm3 (IQR 209.4) (p > 0,05); median VI fibroid (shell off) from 2.97 (IQR 3.81) to 2.90 (IQR 4.82) (p > 0,05); and VI inner capsule from 2.56 (IQR 7.48) to 2.89 (IQR 4.83) (p > 0,05). A strong positive correlation was found between the VI of the fibroid (shell off) at baseline with the volume change after three months of LPA use (LPA r = 0.636, p = 0.048, 95% CI = -0.03 - 1.00). CONCLUSION: In this pilot study we observed a consistent and statistically significant decrease in VI and fibroid volume after three months of LPA treatment in patients with uterine fibroids. The decrease in fibroid volume and VI was less consistent after UPA use. The strong correlation between the VI at baseline and volume reduction, may in theory be used to predict the volume reduction after LPA.

Disappearance of the blood supply to a giant uterine myoma due to childbirth: A CARE-compliant article.

RATIONALE: Giant uterine myomas may be life-threatening due to pressure effects on the lungs and other contiguous organs. PATIENT CONCERNS: A 32-year-old pregnant Asian woman was admitted to our hospital early in her pregnancy with a pre-pregnancy history of multiple uterine myomas. DIAGNOSIS: She was diagnosed with multiple giant uterine myomas in pregnancy. INTERVENTIONS: No intervention was performed on the woman. OUTCOMES: A reduction in tumor size and disappearance of tumor blood supply were seen on conventional and contrast-enhanced ultrasounds (CEUS) on postpartum day 34. Mass volume gradually decreased and no blood flow signals were seen on CEUS during postpartum follow-up. LESSONS: Childbirth can block the blood supply of giant uterine myomas and reduce mass size. In such cases, childbirth may be considered therapeutic.

Insufficient Leiomyoma Infarction in Uterine Artery Embolization: Relationship with Tumor Location.

PURPOSE: To evaluate which leiomyoma location in the uterus predicts insufficient tumor infarction after uterine artery embolization (UAE). MATERIALS AND METHODS: In this single-institution retrospective study, 45 patients (mean age, 43.4 y ± 4.1) underwent UAE for leiomyomas using trisacryl gelatin microspheres alone with "pruned-tree" endpoint performed by qualified interventional radiologists between October 2015 and July 2017. Technical outcomes and complications were assessed. All patients underwent unenhanced and enhanced MR imaging before and after UAE. A total of 476 tumors of ≥ 1 cm observed in all patients were evaluated. Multivariate generalized linear mixed model analysis was performed to investigate relationships between insufficient tumor infarction (< 90%) on contrast-enhanced MR imaging after UAE and baseline factors, including tumor location in the long-axis, front-back, and inner-outer directions and tumor size. RESULTS: All patients successfully underwent UAE with no major complications. Multivariate analysis revealed that there was a higher likelihood of insufficient infarction of tumors at the cervix (odds ratio [OR] 80.45; 95% confidence interval [CI] 9.97, 649.09; P < .001) and lower body (OR 4.31; 95% CI 2.52, 7.38; P < .001) than at the upper body and of tumors at the front than at the back wall (OR 2.20; 95% CI 1.32, 3.67; P = .002). Tumor size (OR 0.71; 95% CI 0.61, 0.82; P < .001) was a significant factor, whereas tumor location in the inner-outer direction was not. CONCLUSIONS: Insufficient leiomyoma infarction after UAE was more likely to involve tumors at the cervix, lower body, or front wall of the uterus or smaller tumors.

The Role of Non-Contrast Cone Beam CT in Identifying Incomplete Treatment during Uterine Artery Embolization.

PURPOSE: To describe the utility of post-procedure noncontrast cone-beam computed tomography (CT) in identifying cases of incomplete treatment and the need to search for additional vascular supply during uterine artery embolization (UAE). MATERIALS AND METHODS: From June 2013 to June 2018, 427 patients (age, 45 ± 5 years) underwent 430 consecutive UAEs with post-embolization noncontrast cone-beam CT. If noncontrast cone-beam CT showed an area of the uterus lacking contrast retention, aortography was performed to search for collateral supply. Procedures were characterized as suspected complete bilateral UAEs or suspected incomplete UAEs, such as in cases of a unilateral uterine artery or diminutive uterine arteries. Rates of inadequate contrast retention on noncontrast cone-beam CT and discovered collateral artery supply were calculated. In 10 consecutive cases in which both noncontrast cone-beam CT and aortography were performed, dose-area product radiation exposure from noncontrast cone-beam CT and aortography was compared using a 2-sided paired-sample t-test. RESULTS: Of the 411 suspected complete bilateral UAEs, noncontrast cone-beam CT showed an area of the uterus lacking contrast retention in 38 (9.2%) cases. Of the 19 suspected incomplete UAEs, noncontrast cone-beam CT demonstrated incomplete treatment in 6 (31.6%) patients. Aortography was performed in 40 of the 44 cases of incomplete treatment on noncontrast cone-beam CT, and collateral supply was found in 28 (70.0%) cases. In 22 of these cases (5.2% of the 427 patients studied), noncontrast cone-beam CT led to the discovery of significant collateral supply requiring further embolization. Dose-area product radiation exposure from noncontrast cone-beam CT was less than from aortography (P = .007). CONCLUSIONS: Post-UAE noncontrast cone-beam CT can be used to select a subset of patients with a higher likelihood of collateral supply who may benefit from post-embolization aortography.

Predictive Value of Quantitative Uterine Fibroid Perfusion Parameters From Contrast-Enhanced Ultrasound for the Therapeutic Effect of High-Intensity Focused Ultrasound Ablation.

OBJECTIVES: To assess the predictive significance of quantitative perfusion parameters from contrast-enhanced ultrasound (CEUS) for the therapeutic response to high-intensity focused ultrasound (HIFU) ablation in patients with uterine fibroids. METHODS: A total of 263 patients with single uterine fibroids were treated with HIFU ablation under ultrasound guidance. The arrival time, peak time, enhancement time, enhancement intensity, and enhancement rate were evaluated with pretreatment CEUS. According to a nonperfused volume ratio evaluation by posttreatment magnetic resonance imaging, all patients were assigned to groups with volume ratios of 70% or higher and lower than 70%. Then the predictive performances of different parameters for ablation efficacy were studied. RESULTS: The arrival time, peak time, and enhancement time in the group with a nonperfused volume ratio of 70% or higher were longer than those in the group with a volume ratio lower than 70% (mean ± SD, 16.7 ± 3.5, 26.5 ± 4.9, and 10.2 ± 2.6 seconds, respectively, versus 13.3 ± 4.2, 20.8 ± 5.4, and 7.6 ± 2.3 seconds), whereas patients with a volume ratio of 70% or higher had a lower mean enhancement intensity and enhancement rate than those with a volume ratio lower than 70% (29.7 ± 16.7 dB and 3.2 ± 1.5 dB/s versus 63.2 ± 26.3 dB and 8.6 ± 4.3 dB/s; P < .05). The nonperfused volume ratio was negatively correlated with the enhancement intensity and enhancement rate (r = -0.631 and -0.712) but positively correlated with the arrival time, peak time, and enhancement time (r = 0.322, 0.456, and 0.477; P < .05). The areas under the receiver operating characteristic curve for the enhancement time, enhancement intensity, and enhancement rate were 0.73, 0.79, and 0.81 (P < .05). CONCLUSIONS: Quantitative parameters from CEUS are potentially useful for evaluating the therapeutic effect of HIFU ablation for uterine fibroids.

The Enlarged Fibroid Uterus: Aberrant Arterial Supply via the Omental Artery.

Uterine artery embolization is considered a first-line therapy for symptomatic fibroids and is occasionally required to mitigate operative risk prior to total abdominal hysterectomy or myomectomy. We present a pictorial review of parasitized omental artery supply to the enlarged fibroid uterus in three patients undergoing preoperative uterine artery embolization. A detailed understanding of variant uterine blood supplies is crucial when performing fibroid embolization. Although omental artery supply to the fibroid uterus is an unusual finding, aortography to include mesenteric arteries may be necessary when anomalous blood supply to the enlarged fibroid uterus is suspected.

Temporary simultaneous two-arterial occlusion for reducing operative blood loss during laparoscopic myomectomy: a randomized controlled trial.

BACKGROUND: To evaluate the efficacy and safety of temporary simultaneous two-arterial occlusions (TESTO) in terms of operative blood loss during laparoscopic myomectomy. METHODS: A total of 62 patients with symptomatic myomas were randomly assigned to either the experimental group or the control group. In the experimental group, the uterine arteries and utero-ovarian arteries were temporarily occluded with laparoscopic bulldog clamps. The primary outcome measures were operative blood loss and change in hemoglobin. RESULTS: There were no differences in baseline demographics between the two groups. The amounts of operative blood loss (56.3 ± 42.8 mL vs. 138.2 ± 48.8 mL, p < 0.001) and change in hemoglobin (1.0 ± 0.5 g/dL vs. 1.7 ± 1.1 g/dL, p = 0.002) were significantly lower in the experimental group than that in the control group. The total operative time was not significantly different between the two groups. However, it took less time for myoma enucleation (13.1 ± 14.6 min vs. 17.6 ± 10.4 min, p = 0.006) and for uterine suturing (19.5 ± 10.7 min vs. 24.6 ± 8.8 min, p = 0.006) in the experimental group than that in the control group. None of patients in both groups developed operative complications. CONCLUSION: The use of the TESTO procedure is effective in reducing operative blood loss and hemoglobin loss without causing morbidity during laparoscopic myomectomy.

Transdifferentiations and heterogeneity in the stromal niches of uterine leiomyomas.

Uterine leiomyomas, also known as uterine fibroids (UFs), are benign smooth muscle cells tumors, the most frequent tumors in women. Even though UFs are monoclonal tumors, they contain a heterogeneous and versatile cells population. There are scarce proofs about the processes of transdifferentiation that might occur in UFs, modify the tumor microenvironment and support blood and lymph vessels formation. The stromal niches of the UFs harbor cells with angiogenic∕lymphangiogenic, as well as with vasculogenic∕lymphvasculogenic potential, which belong to a phenotypic continuum between the endothelial and mesenchymal lineages. Within these niches, the expressions of CD44 and podoplanin were less investigated and regarded as markers of such processes of transdifferentiation.

[MODERN VIEW ON ETIOPATHOGENESIS AND NEW OPPORTUNITIES FOR DIAGNOSIS OF UTERINE FIBROIDS].

Uterine fibroids remain a burning issue for modern gynecology and cause suffering to women, significantly worsening their quality of life. This article includes the latest information about etiology, risk factors, pathobiochemical, genetic and immunological features of pathogenesis, clinical findings, early detection of fibroids and sarcoma differential diagnostic criteria by ultrasonography and MRI. Foreign publications form the basis of the given article, as well as domestic ones.

Use of Contrast-Enhanced Ultrasound in the Assessment of Uterine Fibroids: A Feasibility Study.

Contrast-enhanced ultrasound (CEUS) is an innovative ultrasound technique capable of visualizing both the macro- and microvasculature of tissues. In this prospective pilot study, we evaluated the feasibility of using CEUS to visualize the microvasculature of uterine fibroids and compared CEUS with conventional ultrasound. Four women with fibroids underwent gray-scale ultrasound, sonoelastography and power/color Doppler scans followed by CEUS examination. Analysis of CEUS images revealed initial perfusion of the peripheral rim, that is, a pseudo-capsule, followed by enhancement of the entire lesion through vessels traveling from the exterior to the interior of the fibroid. The pseudo-capsules exhibited slight hyper-enhancement, making a clear delineation of the fibroids possible. The centers of three fibroids exhibited areas lacking vascularization, information not obtainable with the other imaging techniques. CEUS is a feasible technique for imaging and quantifying the microvasculature of fibroids. In comparison with conventional ultrasound imaging modalities, CEUS can provide additional diagnostic information based on the microvasculature.