[Estrogen, estrogen receptor and miR-21 in adenomyosis: their pathogenic roles and regulatory interactions].

OBJECTIVE: To explore the pathogenic roles of miR-21, estrogen (E2), and estrogen receptor (ER) in adenomyosis. METHODS: We examined the expression levels of miR-21 in specimens of adenomyotic tissue and benign cervical lesions using qRT-PCR. In primary cultures of cells isolated from the adenomyosis lesions, the effect of ICI82780 (an ER inhibitor) on miR-21 expression levels prior to E2 activation or after E2 deprivation were examined with qRT-PCR. We further assessed the effects of a miR-21 mimic or an inhibitor on proliferation, apoptosis, migration and autophagy of the cells. RESULTS: The expression level of miR-21 was significantly higher in adenomyosis tissues than in normal myometrium (P < 0.05). In the cells isolated from adenomyosis lesions, miR-21 expression level was significantly higher in E2 activation group than in ER inhibition + E2 activation group and the control group (P < 0.05); miR-21 expression level was significantly lower in cells in E2 deprivation+ER inhibition group than in E2 deprivation group and the control group (P < 0.05). The adenomyosis cells transfected with miR-21 inhibitor showed inhibited proliferation and migration, expansion of mitochondrial endoplasmic reticulum, increased lysosomes, presence of autophagosomes, and increased cell apoptosis, while transfection of the cells with the miR-21 mimic produced the opposite effects. CONCLUSION: MiR-21 plays an important role in promoting proliferation, migration, and antiapoptosis in adenomyosis cells by altering the cell ultrastructure, which may contribute to early pathogenesis of the disease. In addition to binding with E2, ER can also regulate miR-21 through other pathways to participate in the pathogenesis of adenomyosis, thus having a stronger regulatory effect on miR-21 than E2.

Macrophage polarization in adenomyosis: A review.

Adenomyosis (AM) is a common gynecological disorder characterized by the presence of endometrial glands and stroma within the uterine myometrium. It is associated with abnormal uterine bleeding (AUB), dysmenorrhea, and infertility. Although several mechanisms have been proposed to elucidate AM, the exact cause and development of the condition remain unclear. Recent studies have highlighted the significance of macrophage polarization in the microenvironment, which plays a crucial role in AM initiation and progression. However, a comprehensive review regarding the role and regulatory mechanism of macrophage polarization in AM is currently lacking. Therefore, this review aims to summarize the phenotype and function of macrophage polarization and the phenomenon of the polarization of adenomyosis-associated macrophages (AAMs). It also elaborates on the role and regulatory mechanism of AAM polarization in invasion/migration, fibrosis, angiogenesis, dysmenorrhea, and infertility. Furthermore, this review explores the underlying molecular mechanisms of AAM polarization and suggests future research directions. In conclusion, this review provides a new perspective on understanding the pathogenesis of AM and provides a theoretical foundation for developing targeted drugs through the regulation of AAM polarization.

Risk assessment of extra-uterine involvement and prognosis in young type I endometrial carcinoma with high or moderate differentiation and less than 1/2 myometrial invasion.

PURPOSE: The aim of this study was to investigate whether young patients with endometrial carcinoma can preserve adnexa and lymph nodes to improve their quality of life without compromising their prognosis. METHODS: A total of 319 patients with type I endometrial carcinoma (high or moderate differentiation and less than 1/2 myometrial invasion) hospitalized in the First Affiliated Hospital of Zhengzhou University from May 2012 to July 2021 were included. The patients were divided into four groups: high differentiation without myometrial invasion group (G1MI-), high differentiation with superficial myometrial invasion group (G1MI+), moderate differentiation without myometrial invasion group (G2MI-), and moderate differentiation with superficial myometrial invasion group (G2MI+). Logistic regression analysis was conducted to identify risk factors for extra-uterine involvement. Kaplan-Meier method was used to draw the survival curve to compare the prognosis in subgroups and rates of extra-uterine involvement were also compared using Chi-square test or Fisher's exact test. RESULTS: Multivariable logistic regression revealed that differentiation (HR = 14.590, 95%CI = 1.778-119.754, p = 0.013) and myometrial invasion (HR = 10.732, 95%CI = 0.912-92.780, p = 0.037) were the independent risk factors for extra-uterine involvement. The overall difference was statistically significant (p < 0.001). In the subgroups analysis, both adnexal metastasis and lymph node metastasis were statistically significant in the G2MI+ group compared with G1MI- (p = 0.007, p = 0.008). There were no significant differences in the overall survival (OS) rate and progression free survival (PFS) rate among the four subgroups (p > 0.05). CONCLUSIONS: Surgery with adnexal preservation and without systematic lymphadenectomy could be employed for the patients who are high differentiation with less than 1/2 myometrial invasion or moderate differentiation without myometrial invasion, but not recommended to the patients with moderate differentiation and superficial myometrial invasion.

FOXO3a deregulation in uterine smooth muscle tumors.

OBJECTIVE: The present study aimed to investigate FOXO3a deregulation in Uterine Smooth Muscle Tumors (USMT) and its potential association with cancer development and prognosis. METHODS: The authors analyzed gene and protein expression profiles of FOXO3a in 56 uterine Leiomyosarcomas (LMS), 119 leiomyomas (comprising conventional and unusual leiomyomas), and 20 Myometrium (MM) samples. The authors used techniques such as Immunohistochemistry (IHC), FISH/CISH, and qRT-PCR for the present analyses. Additionally, the authors conducted an in-silico analysis to understand the interaction network involving FOXO3a and its correlated genes. RESULTS: This investigation revealed distinct expression patterns of the FOXO3a gene and protein, including both normal and phosphorylated forms. Expression levels were notably elevated in LMS, and Unusual Leiomyomas (ULM) compared to conventional Leiomyomas (LM) and Myometrium (MM) samples. This upregulation was significantly associated with metastasis and Overall Survival (OS) in LMS patients. Intriguingly, FOXO3a deregulation did not seem to be influenced by EGF/HER-2 signaling, as there were minimal levels of EGF and VEGF expression detected, and HER-2 and EGFR were negative in the analyzed samples. In the examination of miRNAs, the authors observed upregulation of miR-96-5p and miR-155-5p, which are known negative regulators of FOXO3a, in LMS samples. Conversely, the tumor suppressor miR-let7c-5p was downregulated. CONCLUSIONS: In summary, the outcomes of the present study suggest that the imbalance in FOXO3a within Uterine Smooth Muscle Tumors might arise from both protein phosphorylation and miRNA activity. FOXO3a could emerge as a promising therapeutic target for individuals with Unusual Leiomyomas and Leiomyosarcomas (ULM and LMS), offering novel directions for treatment strategies.

Accuracy of MRI in predicting deep myometrial invasion in endometrial cancer and the influence of leiomyoma, adenomyosis and the microcystic elongated and fragmented tumour pattern.

INTRODUCTION: The most common form of endometrial cancer is Type 1 endometrioid adenocarcinoma. Depth of myometrial invasion is the most important prognostic factor correlating with overall patient survival. The objective was to investigate how accurate magnetic resonance imaging (MRI) is in predicting the depth of myometrial invasion in preoperative assessment, and the influence of leiomyoma and/or adenomyosis, or microcystic, elongated and fragmented (MELF) pattern of invasion on MRI diagnostic performance. METHOD: Retrospective audit of 235 endometrial cancer patients from the regional Gynaecology Oncology multidisciplinary meeting at Auckland City Hospital, between January 2020 and January 2021. Radiologist assigned stage was compared to histopathology. Presence of leiomyoma, adenomyosis and MELF pattern evaluated followed by analysis under a Biostatistician's supervision. RESULTS: Overall MRI diagnostic accuracy for depth of myometrial invasion was 86%. For deep myometrial invasion, MRI had a sensitivity of 72% and specificity 91%. Out of the misreported 32/235 cases, 16 demonstrated fibroids and/or adenomyosis leading to a sensitivity of 57% and specificity 93% for deep invasion, compared with 94% and 74% respectively in the population without, demonstrating statistical significance. Thirty seven cases with MELF pattern of invasion showed a sensitivity of 81% and specificity 80% for deep invasion, compared with 63% and 92% respectively in the group without, demonstrating no statistical significance. CONCLUSION: MRI assessment of the depth of myometrial invasion in endometrial cancer has high accuracy. In the presence of background uterine fibroids/adenomyosis, pre-operative MRI accuracy of evaluating deep invasion shows a statistically significant reduction.

Repair of a chronic myometrial defect with successful pregnancy outcome.

OBJECTIVE: To surgically demonstrate preconceptional laparoscopic repair of a chronic myometrial defect with mesh reinforcement, resulting in a successful pregnancy outcome. DESIGN: Video case report. The Institutional Ethical Committee was consulted, and the requirement for approval was waived because the video describes a modified surgical technique. The patient included in this video gave consent for publication of the video and posting of the video online, including on social media, the journal website, scientific literature websites (such as PubMed, ScienceDirect, Scopus, and others), and other applicable sites. SETTING: A referral advanced gynecological endoscopy center. PATIENT: A 27-year-old woman (P0A1) was diagnosed with myomas during pregnancy, resulting in miscarriage at 22 weeks. Laparotomy and myomectomy were performed 2 months later, and three 8-cm myomas were removed. The endometrial cavity opened posteriorly during surgery, and retained products of conceptions were removed. Periconceptional imaging done after two years showed few intramural myomas and a deficient myometrium in the posterior fundal region. Laparoscopy revealed a defect in the posterior fundal aspect of the uterus with leakage of dye, which was converted to laparotomy and myomectomy with the repair of the myometrial defect. After 1 year, follow-up magnetic resonance imaging showed thinned-out posterior myometrium with a focal area of absent myometrium in the midline and endometrial prolapse. The patient was advised on surrogacy, but she wanted to repair the defect again and try for pregnancy, so she was referred to our center. With the background of a few case reports using mesh to reinforce myometrial repair (1, 2), we counseled the patient about the myometrial repair with the additional use of mesh as an off-label use. INTERVENTION: The risk of uterine rupture after myomectomy is rare (<1%) (3), but it is a severe complication. High-risk cases, like significant myometrial defects or previous ruptures, may require surgical correction. Native repair may not achieve optimal results in all cases. Alternative approaches, like the additional use of mesh or biological materials, have been reported (4). In this case, we demonstrate the use of dual mesh for scar repair. Synthetic mesh over the uterus is used in laparoscopic procedures like sacrohysteropexy and cerclage. We used Parietex (Covidien, New Haven, CT, USA) mesh, a composite macroporous polyester mesh usually used for ventral hernia repair. It has an outer hydrophilic, absorbable collagen barrier that reduces adhesion formation. Laparoscopically, after adhesiolysis, a significant defect was demonstrated on the posterior wall of the uterus (Fig. 1). A complete resection of the fibrotic tissue along the edges of the scar defect was done to expose healthy myometrium. Myometrium was repaired in two layers, excluding the endometrium, with a V-Loc (Covidien, Dublin, Ireland) No. 1-0 suture. Parietex mesh was sutured over the repaired posterior myometrium to reinforce it (Fig. 2). MAIN OUTCOME MEASURES: The postoperative myometrial thickness on imaging and pregnancy outcome. RESULTS: Postoperative ultrasound scan after 6 weeks demonstrated restoration of posterior wall myometrial thickness of 14 mm. The patient was conceived through in vitro fertilization techniques 4 months after surgery. Antenatal follow-up was uneventful except for suspicion of posterior placenta accreta. She underwent an elective cesarean section with uterine artery embolization at 34 weeks and delivered a healthy infant weighing 1,950 g. Placental removal was uneventful. On inspection, the posterior surface of the uterus was intact without dehiscence, meshing in situ with minimal adhesions (Fig. 3). CONCLUSION: Myometrial scar defects can cause potential obstetric complications. Native repair of scar defects may not achieve optimal results, as in our case. Mesh repair of myomectomy scar defects can be used as an alternative approach, as exemplified in this case. However, further studies are required to establish the safety and efficacy of this approach.

Smooth muscle tumours of the uterus: MR imaging malignant predictive features-a 12-year analysis in a referral hospital in Portugal.

PURPOSE: To evaluate the magnetic resonance imaging (MRI) features that may help distinguish leiomyosarcomas from atypical leiomyomas (those presenting hyperintensity on T2-W images equal or superior to 50% compared to the myometrium). MATERIALS AND METHODS: The authors conducted a retrospective single-centre study that included a total of 57 women diagnosed with smooth muscle tumour of the uterus, who were evaluated with pelvic MRI, between January 2009 and March 2020. All cases had a histologically proven diagnosis (31 Atypical Leiomyomas-ALM; 26 Leiomyosarcomas-LMS). The MRI features evaluated in this study included: age at presentation, dimension, contours, intra-tumoral haemorrhagic areas, T2-WI heterogeneity, T2-WI dark areas, flow voids, cyst areas, necrosis, restriction on diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) values, signal intensity and heterogeneity after contrast administration in T1-WI, presence and location of unenhanced areas. The association between the MRI characteristics and the histological subtype was evaluated using Chi-Square and ANOVA tests. RESULTS: The MRI parameters that showed a statistically significance correlation with malignant histology and thus most strongly associated with LMS were found to be: irregular contours (p < 0.001), intra-tumoral haemorrhagic areas (p = 0.028), T2-WI dark areas (p = 0.016), high signal intensity after contrast administration (p = 0.005), necrosis (p = 0.001), central location for unenhanced areas (p = 0.026), and ADC value lower than 0.88 × 10-3 mm2/s (p = 0.002). CONCLUSION: With our work, we demonstrate the presence of seven MRI features that are statistically significant in differentiating between LMS and ALM.

The effect of uterine closure technique on cesarean scar niche development after multiple cesarean deliveries.

OBJECTIVES: To use saline infusion sonohysterography (SIS) to evaluate the effect of uterine closure technique on niche formation after multiple cesarean deliveries (CDs). METHODS: Patients with at least one prior CD were evaluated for niche via SIS. Subgroups of any number repeat CD (>1 prior), lower-order CD (<4 prior), and higher-order CD (≥4 prior) were analyzed, stratifying by hysterotomy closure technique at last cesarean preceding imaging; techniques included Technique A (endometrium-free double-layer closure) and Technique B (single- or double-layer routine endo-myometrial closure). Niche defects were quantified (depth, length, width, and residual myometrial thickness). The primary outcome was clinically significant niche, defined as depth >2 mm. Statistical analysis was performed using chi-square, ANOVA, t-test, Kruskal-Wallis, and multiple logistic regression, with p-values of <0.05 were statistically significant. RESULTS: A total of 172 post-cesarean SIS studies were reviewed: 105 after repeat CDs, 131 after lower-order CDs, and 41 after higher-order CDs. Technique A was associated with a shorter interval to imaging and more double-layer closures. Technique B was associated with more clinically significant niches across all subgroups, and these niches were significantly longer and deeper when present. Multiple logistic regression demonstrated a 5.6, 8.1, and 11-fold increased adjusted odds of clinically significant niche following Technique B closure in the repeat CD (p<0.01), lower-order CD (p<0.001), and higher-order CD (p=0.04) groups, respectively. CONCLUSIONS: While multiple CDs are known to increase risk for niche defects and their sequelae, hysterotomy closure technique may help to reduce niche development and severity.

Understanding Ultrasound Features that Predict Symptom Severity in Patients with Adenomyosis: a Systematic Review.

Adenomyosis is associated with pelvic pain, abnormal uterine bleeding, and infertility. Several ultrasound-based classifications have been reported, but it is not clear which criteria reflect the severity of symptoms. The aim of this review is to summarize the ultrasound features that correlate with clinical manifestations of adenomyosis and to discuss diagnostic methods for predicting disease severity. A literature search of PubMed and Google Scholar published up to March 2022 was performed. A consensus-based classification was determined primarily by defining the mapping or topography of the lesion. Ultrasound features can be classified into direct (i.e., the presence of ectopic endometrial tissue within the myometrium) and indirect findings (i.e., changes in the myometrial structure and translesional vascularity secondary to myometrial invasion). There are some reports that symptoms are positively correlated with the location and spread of the disease. Indeed, the lesion thickness, diffuse or internal adenomyosis, and focal adenomyosis may be associated with increased risks of dysmenorrhea, abnormal uterine bleeding, and infertility, respectively. Two ultrasound markers (i.e., the presence of heterogeneous myometrium and myometrial cysts) appear to be the criteria most clinicians focus on. However, decision-making on treatment necessity is determined by symptom severity rather than the topography of the lesions. There is currently no consensus that symptom severity can be predicted based on ultrasound features, but the ultrasound-based criteria may be helpful in diagnosing adenomyosis.

Mmp2 Deficiency Leads to Defective Parturition and High Dystocia Rates in Mice.

Parturition is the final and essential step for mammalian reproduction. While the uterus is quiescent during pregnancy, fundamental changes arise in the myometrial contractility, inducing fetal expulsion. Extracellular matrix (ECM) remodeling is fundamental for these events. The gelatinases subgroup of matrix metalloproteinases (MMPs), MMP2 and MMP9, participate in uterine ECM remodeling throughout pregnancy and parturition. However, their loss-of-function effect is unknown. Here, we determined the result of eliminating Mmp2 and/or Mmp9 on parturition in vivo, using single- and double-knockout (dKO) mice. The dystocia rates were measured in each genotype, and uterine tissue was collected from nulliparous synchronized females at the ages of 2, 4, 9 and 12 months. Very high percentages of dystocia (40-55%) were found in the Mmp2-/- and dKO females, contrary to the Mmp9-/- and wild-type females. The histological analysis of the uterus and cervix revealed that Mmp2-/- tissues undergo marked structural alterations, including highly enlarged myometrial, endometrial and luminal cavity. Increased collagen deposition was also demonstrated, suggesting a mechanism of extensive fibrosis in the Mmp2-/- myometrium, which may result in dystocia. Overall, this study describes a new role for MMP2 in myometrium remodeling during mammalian parturition process, highlighting a novel cause for dystocia due to a loss in MMP2 activity in the uterine tissue.

Reproductive outcomes after laparoscopic resection of symptomatic niches in uterine cesarean scars: Long-term follow-up on the prospective LAPNICHE study.

INTRODUCTION: After incomplete healing of the uterine cesarean section scar, a niche can be observed; 24% of the women develop large niches with a residual myometrial thickness <3 mm. In these cases a laparoscopic resection is possible. The effect of this new treatment on fertility outcome is not known yet. This paper describes reproductive outcomes 2 years after a laparoscopic niche resection and compares women with or without secondary infertility at baseline. MATERIAL AND METHODS: A prospective cohort study was performed, with consecutive inclusion of women between 2011 and 2019. Women with a niche in the uterine cesarean scar, with a residual myometrial thickness of <3 mm and with a desire to become pregnant, were scheduled to undergo a laparoscopic niche resection because of one or more of the following problems (1) postmenstrual spotting; (2) midcycle intrauterine fluid accumulation diagnosed during the fertility workup or (3) difficulties with a previous embryo transfer and preferring a surgical therapy. The study is registered in the ISRCTN register (ref. no. ISRCTN02271575) on April 23, 2013. RESULTS: There were 133 (62%) women included with a desire to become pregnant, 88 with secondary infertility. In all, 83 had an ongoing pregnancy at the 2-year follow-up. The ongoing pregnancy rate in patients with previous fertility problems was 60.2% compared with 66.7% in patients without infertility (odds ratio [OR] 0.68, 95% confidence interval [CI] 0.32-1.7). The OR for live births was 0.57 (95% CI 0.02-1.2). Overall, 8.3% of the pregnancies resulted in miscarriages by the 2-year follow-up. CONCLUSIONS: The reproductive outcomes in women with and without previous fertility problems undergoing resection of a large niche are very promising and quite comparable in both groups. These results suggest, but do not prove, a beneficial effect of this therapy for these indications. The results support the design of future randomized controlled trials to evaluate the effect of niche resection vs expectant management to assess its additional value in women with or without fertility problems who desire pregnancy.

Abnormal Uterine Involution May Lead to Atony and Postpartum Hemorrhage: A Hypothesis, With Review of the Evidence.

Uterine involution has 2 major components-(1) involution of vessels; and (2) involution of myometrium. Involution of vessels was addressed by Rutherford and Hertig in 1945; however, involution of myometrium has received little attention in the modern literature. We suggest that the pathophysiology of myometrial involution may lead to uterine atony and postpartum hemorrhage. The myometrium dramatically enlarges due to gestational hyperplasia and hypertrophy of myocytes, caused by hormonal influences of the fetal adrenal cortex and the placenta. After delivery, uterine weight drops rapidly, with physiologic involution of myometrium associated with massive destruction of myometrial tissue. The resulting histopathology, supported by scientific evidence, may be termed "postpartum metropathy," and may explain the delay of postpartum menstrual periods until the completion of involution. When uterine atony causes uncontrolled hemorrhage, postpartum hysterectomy examination may be the responsibility of the perinatal pathologist.Postpartum metropathy may be initiated when delivery of the baby terminates exposure to the hormonal influence of the fetal adrenal cortex, and may be accelerated when placental delivery terminates exposure to human chorionic gonadotrophin (HCG). This hypothesis may explain why a prolonged third stage of labor, and delays in management, are risk factors for severe hemorrhage due to uterine atony.

Diagnosis and Management of an Intramyometrial Ectopic Pregnancy Within a Septate Uterus.

BACKGROUND: An intramyometrial pregnancy is a rare form of ectopic pregnancy, making up an estimated 1% of all ectopic pregnancies. Previously described management options have included surgical excision in the emergency setting. CASE: A 32-year-old woman, gravida 4 para 0, at 6 0/7 weeks of gestation by last menstrual period, was noted to have a gestational sac implanted entirely within the uterine myometrium. Ultrasonography and magnetic resonance imaging confirmed the presence of an intramyometrial ectopic pregnancy within a septate uterus. The patient's abnormal pregnancy was successfully treated with multidose methotrexate. CONCLUSION: Intramyometrial pregnancy is a rare entity that should be considered when it is suggested by ultrasonography or if an intrauterine pregnancy is surgically inaccessible from the endometrial cavity. In a stable patient, multidose systemic methotrexate may be a feasible management strategy.

Placenta previa percreta with surrounding organ involvement: a proposal for management.

Placenta accreta spectrum encompasses cases where the placenta is morbidly adherent to the myometrium. Placenta percreta, the most severe form of placenta accreta spectrum (grade 3E), occurs when the placenta invades through the myometrium and possibly into surrounding structures next to the uterine corpus. Maternal morbidity of placenta percreta is high, including severe maternal morbidity in 82.1% and mortality in 1.4% in the recent nationwide U.S. statistics. Although cesarean hysterectomy is commonly performed for patients with placenta accreta spectrum, conservative management is becoming more popular because of reduced morbidity in select cases. Treatment of grade 3E disease involving the urinary bladder, uterine cervix, or parametria is surgically complicated due to the location of the invasive placenta deep in the maternal pelvis. Cesarean hysterectomy in this setting has the potential for catastrophic hemorrhage and significant damage to surrounding organs. We propose a step-by-step schema to evaluate cases of grade 3E disease and determine whether immediate hysterectomy or conservative management, including planned delayed hysterectomy, is the most appropriate treatment option. The approach includes evaluation in the antenatal period with ultrasound and magnetic resonance imaging to determine suspicion for placenta previa percreta with surrounding organ involvement, planned cesarean delivery with a multidisciplinary team including experienced pelvic surgeons such as a gynecologic oncologist, intra-operative assessment including gross surgical field exposure and examination, cystoscopy, and consideration of careful intra-operative transvaginal ultrasound to determine the extent of placental invasion into surrounding organs. This evaluation helps decide the safety of primary cesarean hysterectomy. If safely resectable, additional considerations include intra-operative use of uterine artery embolization combined with tranexamic acid injection in cases at high risk for pelvic hemorrhage and ureteral stent placement. Availability of resuscitative endovascular balloon occlusion of the aorta is ideal. If safe resection is concerned, conservative management including planned delayed hysterectomy at around 4 weeks from cesarean delivery in stable patients is recommended.

ROLE OF STROMAL MICROENVIRONMENT IN THE FORMATION OF INVASIVE, ANGIOGENIC, AND METASTATIC POTENTIAL OF ENDOMETRIOID CARCINOMA OF ENDOMETRIUM.

The aim of the study was to determine the association of indicators of the progression of endometrioid carcinoma of the endometrium (ECE) with the type of stromal microenvironment, the counts of CXCL12+ fibroblasts and CD163+ macrophages, and the expression of the chemokine CXCL12 and its receptor CXCR4 in tumor cells. MATERIALS AND METHODS: Histological preparations of ECE samples (n = 51) were analyzed. Expression of CXCL2 and CXCR4 antigens in tumor cells, the content of CXCL12+ fibroblasts and CD163+ macrophages, and the density of microvessels were determined by the immunohistochemical method. RESULTS: Groups of ECE with desmoplastic and inflammatory stromal reactions were delineated. The majority (80.0%) of tumors with desmoplasia were of low differentiation grade, deeply invading the myometrium; 65.0% of patients with these tumors were at stage III of the disease. In ECE cases of stages I-II, 77.4% of ECE showed an inflammatory type of stroma. The high angiogenic and invasive potential of EC of stages I-II was associated with an inflammatory stromal type, high counts of CD163+ macrophages and CXCL12+ fibroblasts in the tumor microenvironment, high expression of the chemokine receptor CXCR4, and reduced expression of its ligand CXCL12 in tumor cells. In the majority of EC of stage III, the increase in angiogenic, invasive, and metastatic potential was accompanied by the presence of desmoplastic stroma, increased expression of CXCR4 in tumor cells, and a high count of CXCL12+ fibroblasts. CONCLUSIONS: The obtained results showed that the morphological architecture of the stromal ECE component is related to the molecular features of its constituents and tumor cells. Their interaction modulates the phenotypic characteristics of ECE associated with the degree of malignancy.

Enhanced myometrial vascularity and AVM: A review on diagnosis and management.

Uterine Arteriovenous malformations (AVM) are vascular disorders characterized by complex high-flow tangles of abnormal vessels connecting arteries and veins with bypassing capillaries. Recently, the terminology applied to describe uterine AVMs has been modified. Most AVMs are acquired. The term enhanced myometrial vascularity (EMV) is used to describe any condition in which any uterine pathology may lead to increased myometrial vascularity regardless of the absence or presence of residual tissue of gestation.

Transvaginal ultrasound versus magnetic resonance imaging for preoperative assessment of myometrial infiltration in patients with low-grade endometrioid endometrial cancer: A systematic review and head-to-head meta-analysis.

PURPOSE: We aimed to compare the diagnostic performance of magnetic resonance imaging (MRI) and transvaginal ultrasound (TVS) for detecting myometrial invasion (MI) in patients with low-grade endometrioid endometrial carcinoma. METHODS: A comprehensive search of MEDLINE (Pubmed), Web of Science, Embase and Scopus (from January 1990 to December 2022) was performed for articles comparing TVS and MRI in the evaluation of myometrial infiltration in low-grade (grade 1 or 2) endometrioid endometrial carcinoma in the same group of patients. We used QUADAS-2 tool for assessing the risk of bias of studies. RESULTS: We found 104 citations in our extensive research. Four articles were ultimately included in the meta-analysis, after excluding 100 reports. All articles were considered low risk of bias in most of the domains assessed in QUADAS-2. We observed that pooled sensitivity and specificity for detecting deep MI were 65% (95% confidence interval [CI] = 54%-75%) and 85% (95% CI = 79%-89%) for MRI, and 71% (95% CI = 63%-78%) and 76% (95% CI = 67%-83%) for TVS, respectively. No statistical differences were found between both imaging techniques (p > 0.05). We observed low heterogeneity for sensitivity and high for specificity regarding TVS; and moderate for both sensitivity and specificity in case of MRI. CONCLUSIONS: The diagnostic performance of TVS and MRI for the evaluation of deep MI in women with low-grade endometrioid endometrial cancer is similar. However, further research is needed as the number of studies is scanty.

Adenomyosis at a Glance: An Integrated Review of Transvaginal Ultrasound and MR Imaging Findings.

Adenomyosis is a benign uterine disorder increasingly recognized in premenopausal women. Given its significant clinical burden, an accurate noninvasive diagnosis is paramount. Both transvaginal ultrasound (TVUS) and magnetic resonance (MR) provide an adequate assessment of adenomyosis, the former being recommended for first-line imaging evaluation and the latter being mainly used as a problem-solving technique. In this article, the authors review the TVUS and MR imaging findings of adenomyosis while referring to their histopathological background. Whereas direct signs correlate directly to ectopic endometrial tissue and are highly specific to adenomyosis, indirect signs result from myometrial hypertrophy and increase diagnostic sensitivity. Potential pitfalls, differential diagnoses, and frequently associated estrogen-dependent conditions are also discussed.