Association between uterine leiomyoma and fragmented QRS waves: a prospective case-control study.

OBJECTIVE: The aim of this study was to evaluate the relationship between uterine leiomyoma and fragmented QRS, a non-invasive indicator of cardiovascular risk and myocardial ischemia, in women with uterine leiomyoma. METHODS: In this prospective case-control study, a total of 47 patients diagnosed with uterine leiomyoma (case group) and 47 healthy individuals without uterine leiomyoma (control group) who had undergone bilateral tubal ligation surgery were included. Various demographic, clinical, and laboratory parameters and the presence of fragmented QRS were recorded. RESULTS: The leiomyoma group showed significantly higher body mass index (27.46±2.18 vs. 25.9±2.87 kg/m2, p=0.005) and waist circumference (91.34±9.30 vs. 84.97±9.3 cm, p=0.001) compared with the control group. Uterine volumes were also significantly higher in the leiomyoma group (235.75±323.48 vs. 53.24±12.81 mm3, p<0.001). The presence of fragmented QRS was detected in 18.1% of the patients. Multiple regression analysis identified age, fasting blood glucose value, and the presence of fragmented QRS as independent risk factors for the presence of leiomyoma. CONCLUSION: This study provides valuable insights into the relationship between uterine leiomyoma and fragmented QRS. The presence of fragmented QRS was identified as an independent risk factor for the presence of leiomyoma. Further research is needed to better understand the underlying mechanisms connecting uterine leiomyoma and cardiovascular health.

Giant uterine tumor and miscarriage: how to proceed?

Expanding uterine masses can be the cause of pregnancy loss and add technical difficulties to uterus evacuation due to the intense anatomical distortion of the endocervical canal and uterine cavity. The literature is scarce in the peculiarities of the management of missed abortions in uterus with important distorted anatomies. We report a case of a primigravida patient who presented a rapid and expressive increase of abdominal volume due to a giant uterine mass, evolving to miscarriage. Ultrasound can be a useful tool, allowing visualization of the endocervical path and uterine cavity, helping to perform uterine evacuation in the presence of anatomical distortion without compromising the reproductive future. To the best of our knowledge, no such case has been previously reported.

The influence of uterine fibroids on adverse outcomes in pregnant women: a meta-analysis.

OBJECTIVE: The objective of the meta-analysis was to determine the influence of uterine fibroids on adverse outcomes, with specific emphasis on multiple or large (≥ 5 cm in diameter) fibroids. MATERIALS AND METHODS: We searched PubMed, Embase, Web of Science, ClinicalTrials.gov, China National Knowledge Infrastructure (CNKI), and SinoMed databases for eligible studies that investigated the influence of uterine fibroids on adverse outcomes in pregnancy. The pooled risk ratio (RR) of the variables was estimated with fixed effect or random effect models. RESULTS: Twenty-four studies with 237 509 participants were included. The pooled results showed that fibroids elevated the risk of adverse outcomes, including preterm birth, cesarean delivery, placenta previa, miscarriage, preterm premature rupture of membranes (PPROM), placental abruption, postpartum hemorrhage (PPH), fetal distress, malposition, intrauterine fetal death, low birth weight, breech presentation, and preeclampsia. However, after adjusting for the potential factors, negative effects were only seen for preterm birth, cesarean delivery, placenta previa, placental abruption, PPH, intrauterine fetal death, breech presentation, and preeclampsia. Subgroup analysis showed an association between larger fibroids and significantly elevated risks of breech presentation, PPH, and placenta previa in comparison with small fibroids. Multiple fibroids did not increase the risk of breech presentation, placental abruption, cesarean delivery, PPH, placenta previa, PPROM, preterm birth, and intrauterine growth restriction. Meta-regression analyses indicated that maternal age only affected the relationship between uterine fibroids and preterm birth, and BMI influenced the relationship between uterine fibroids and intrauterine fetal death. Other potential confounding factors had no impact on malposition, fetal distress, PPROM, miscarriage, placenta previa, placental abruption, and PPH. CONCLUSION: The presence of uterine fibroids poses increased risks of adverse pregnancy and obstetric outcomes. Fibroid size influenced the risk of breech presentation, PPH, and placenta previa, while fibroid numbers had no impact on the risk of these outcomes.

PI3K/mTOR inhibition induces tumour microenvironment remodelling and sensitises pS6high uterine leiomyosarcoma to PD-1 blockade.

BACKGROUND: Uterine leiomyosarcomas (uLMS) are aggressive tumours with poor prognosis and limited treatment options. Although immune checkpoint blockade (ICB) has proven effective in some 'challenging-to-treat' cancers, clinical trials showed that uLMS do not respond to ICB. Emerging evidence suggests that aberrant PI3K/mTOR signalling can drive resistance to ICB. We therefore explored the relevance of the PI3K/mTOR pathway for ICB treatment in uLMS and explored pharmacological inhibition of this pathway to sensitise these tumours to ICB. METHODS: We performed an integrated multiomics analysis based on TCGA data to explore the correlation between PI3K/mTOR dysregulation and immune infiltration in 101 LMS. We assessed response to PI3K/mTOR inhibitors in immunodeficient and humanized uLMS patient-derived xenografts (PDXs) by evaluating tumour microenvironment modulation using multiplex immunofluorescence. We explored response to single-agent and a combination of PI3K/mTOR inhibitors with PD-1 blockade in humanized uLMS PDXs. We mapped intratumoural dynamics using single-cell RNA/TCR sequencing of serially collected biopsies. RESULTS: PI3K/mTOR over-activation (pS6high) associated with lymphocyte depletion and wound healing immune landscapes in (u)LMS, suggesting it contributes to immune evasion. In contrast, PI3K/mTOR inhibition induced profound tumour microenvironment remodelling in an ICB-resistant humanized uLMS PDX model, fostering adaptive anti-tumour immune responses. Indeed, PI3K/mTOR inhibition induced macrophage repolarisation towards an anti-tumourigenic phenotype and increased antigen presentation on dendritic and tumour cells, but also promoted infiltration of PD-1+ T cells displaying an exhausted phenotype. When combined with anti-PD-1, PI3K/mTOR inhibition led to partial or complete tumour responses, whereas no response to single-agent anti-PD-1 was observed. Combination therapy reinvigorated exhausted T cells and induced clonal hyper-expansion of a cytotoxic CD8+ T-cell population supported by a CD4+ Th1 niche. CONCLUSIONS: Our findings indicate that aberrant PI3K/mTOR pathway activation contributes to immune escape in uLMS and provides a rationale for combining PI3K/mTOR inhibition with ICB for the treatment of this patient population.

'Just Get A Hysterectomy'.

An African American woman with uterine fibroids is advised to get a hysterectomy, despite the availability of less life-altering options.

Metrics of uterine myomatosis symptomatology in clinical practice.

AIM: A review of diagnostic options and standardized methods for specifying clinical symptoms associated with uterine myomatosis. METHODS: A literature search of databases aimed at finding validated metrics for assessing myomas symptomatology. RESULTS: Summary of obligatory and optional examination methods in the diagnosis of uterine fibroids and methods of examination of reproductive parameters of the couple in relation to myomatosis. Defining the metrics of bleeding manifestations of myomatosis with emphasis on the "Pictorial Bleeding Assessment Chart". Reviewing metrics of algic manifestations of myomatosis and quality of life with emphasis on the "Quality of Life Questionnaire - Myomatosis - Severity Symptom Scale". CONCLUSION: The purpose of the applicable metrics, which summarize objective findings and subjective complaints of patients, is to describe and evaluate possible correlations and dynamics of changes in the health status, depending on the chosen therapy.

Use of natural language processing to uncover racial bias in obstetrical documentation.

Natural Language Processing (NLP), a form of Artificial Intelligence, allows free-text based clinical documentation to be integrated in ways that facilitate data analysis, data interpretation and formation of individualized medical and obstetrical care. In this cross-sectional study, we identified all births during the study period carrying the radiology-confirmed diagnosis of fibroid uterus in pregnancy (defined as size of largest diameter of >5 cm) by using an NLP platform and compared it to non-NLP derived data using ICD10 codes of the same diagnosis. We then compared the two sets of data and stratified documentation gaps by race. Using fibroid uterus in pregnancy as a marker, we found that Black patients were more likely to have the diagnosis entered late into the patient's chart or had missing documentation of the diagnosis. With appropriate algorithm definitions, cross referencing and thorough validation steps, NLP can contribute to identifying areas of documentation gaps and improve quality of care.

Cesarean Myomectomy: Reflections on Clinical and Surgical Controversies between a New Trans-Decidual Technique vs. Traditional Method.

Up to 70-80% of women of reproductive age may be affected with the most common uterine tumors, known as fibroids or myomas. These benign tumors are the second most prevalent cause of surgery among premenopausal women. Predictions show that the occurrence of myomas in pregnancy will increase, and that the risk of having myomas during pregnancy increases with advanced maternal age. Although most women with fibroids do not experience any symptoms during pregnancy, up to 30% of women experience problems during pregnancy, childbirth, and the puerperium. The viability of myoma excision during cesarean surgery (CS) is a contentious issue raised by the rising incidence of myomas in pregnancy and CS rates. A new surgical procedure for removing fibroids using a trans-endometrial approach, which involves making an incision through the decidua itself, has put into doubt the long-standing practice of cesarean myomectomy (CM) with a trans-serosal approach. Some authors have recently advocated for this last approach, highlighting its advantages and potential uses in real-world situations. The purpose of this paper is to critique the present approach to cesarean myomectomy by analyzing the clinical and surgical distinctions between the two approaches and providing illustrations of the CM methods.

Partial Molar Ectopic Pregnancy: A diagnostic challenge.

Here, we present a rare case of a primigravida who presented to us with symptoms and signs suggestive of an ectopic gestation, which turned out to be a partial mole in histopathological examination. Since it is a very rare occurrence, we would like to publish the case details in this case report.

Uterine Fibroids.

This JAMA Insights in the Women's Health series discusses the incidence, diagnosis, and treatment of uterine fibroids.

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.

Advancements in the application of uterine ultrasound elastography.

PURPOSE OF REVIEW: This article reviews recent advances in ultrasound elastography in diagnosing and evaluating the normal nongravid uterus and the infertile uterus in the gynecologic patient. RECENT FINDINGS: Focusing on the most recent primary literature, studies have demonstrated new findings among a breadth of gynecologic clinical settings. Studies in the nongravid uterus have found that menopausal status, age, and menstrual phase have not been associated with changes in uterine tissue stiffness. Focusing on myometrial disease, there have been conflicting data regarding the ability to distinguish uterine fibroids from adenomyosis. One area of expanding research surrounding uterine elastography includes the infertile population, where ongoing studies attempt to provide a predictive model using shear wave elastography (SWE) in patients undergoing in-vitro fertilization. SUMMARY: Ultrasound elastography has become an increasingly studied and utilized tool in assessing physiologic and pathologic processes in the field of gynecology. Evaluating tissue stiffness through strain and SWE can serve to improve diagnosis of various uterine and cervical lesions, as well as prognosticate outcomes after fertility treatments. This growing area of research will continue to establish the role and application of ultrasound elastography into clinical practice.

Germline and Somatic Fumarate Hydratase Testing in Atypical Uterine Leiomyomata.

Women with germline pathogenic variants (PV) in the fumarate hydratase (FH) gene develop cutaneous and uterine leiomyomata and have an increased risk of developing aggressive renal cell carcinomas. Many of these women are unaware of their cancer predisposition until an atypical uterine leiomyoma is diagnosed during a myomectomy or hysterectomy, making a streamlined genetic counseling process after a pathology-based atypical uterine leiomyoma diagnosis critical. However, the prevalence of germline pathogenic/likely PVs in FH among atypical uterine leiomyomata cases is unknown. To better understand FH germline PV prevalence and current patterns of genetic counseling and germline genetic testing, we undertook a retrospective review of atypical uterine leiomyomata cases at a single large center. We compared clinical characteristics between the FH PV, FH wild-type (WT), and unknown genetic testing cohorts. Of the 144 cases with atypical uterine leiomyomata with evaluable clinical data, only 49 (34%) had documented genetic test results, and 12 (8.3%) had a germline FH PV. There were 48 IHC-defined FH-deficient cases, of which 41 (85%) had FH testing and nine had a germline FH PV, representing 22% of the tested cohort and 18.8% of the FH-deficient cohort. Germline FH PVs were present in 8.3% of evaluable patients, representing 24.5% of the cohort that completed genetic testing. These data highlight the disconnect between pathology and genetic counseling, and help to refine risk estimates that can be used when counseling patients with atypical uterine leiomyomata. PREVENTION RELEVANCE: Women diagnosed with fumarate hydratase (FH)-deficient uterine leiomyomata are at increased risk of renal cancer. This work suggests a more standardized pathology-genetic counseling referral pathway for these patients, and that research on underlying causes of FH-deficient uterine leiomyomata in the absence of germline FH pathogenic/likely pathogenic variants is needed.

Non-persistent endocrine disrupting chemical mixtures and uterine leiomyomata in the study of environment, lifestyle and fibroids (SELF).

BACKGROUND: Results of studies investigating associations between individual endocrine-disrupting chemicals (EDCs) and incidence of uterine leiomyomata (UL), a hormone-dependent gynecological condition, have been inconsistent. However, few studies have evaluated simultaneous exposure to a mixture of EDCs with UL incidence. METHODS: We conducted a case-cohort analysis (n = 708) of data from the Study of the Environment, Lifestyle and Fibroids (SELF), a prospective cohort study. Participants were aged 23-35 years at enrollment, had an intact uterus, and identified as Black or African American. We measured biomarker concentrations of 21 non-persistent EDCs, including phthalates, phenols, parabens, and triclocarban, in urine collected at baseline, 20-month, and 40-month clinic visits. We ascertained UL incidence and characteristics using ultrasounds at baseline and approximately every 20 months through 60 months. We used probit Bayesian Kernel Machine Regression (BKMR-P) to evaluate joint associations between EDC mixtures with cumulative UL incidence. We estimated the mean difference in the probit of UL incidence over the study period, adjusting for baseline age, education, years since last birth, parity, smoking status and body mass index. We converted probit estimates to odds ratios for ease of interpretation. RESULTS: We observed that urinary concentrations of the overall EDC mixture were inversely associated with UL incidence in the overall mixtures model, with the strongest inverse associations at the 70th percentile of all biomarkers compared with their 50th percentile (odds ratio = 0.59; 95% confidence interval: 0.36, 0.96). Strongest contributors to the joint association for the mixture were bisphenol S (BPS), ethyl paraben (EPB), bisphenol F (BPF) and mono (2-ethyl-5-carboxypentyl) phthalate (MECPP), which each demonstrated inverse associations except for MECPP. There was suggestive evidence of an interaction between MECPP and EPB. CONCLUSION: In this prospective ultrasound study, we observed evidence of an inverse association between the overall mixture of urinary biomarker concentrations of non-persistent EDCs with UL incidence.

A case report of uterine leiomyosarcoma: unusual clinical presentation with unilateral hydronephrosis and importance of an appropriate diagnosis.

Uterine leiomyosarcoma is a rare malignant gynecologic tumor that arises from the myometrial or endometrial stromal precursor cells. This tumor has the highest prevalence in the pre- and post-is more frequent between 40 and 60 years old. It has a very unfavorable prognosis: only early-stage tumors have an acceptable prognosis; unfortunately, it is often diagnosed accidentally, typically on an advanced stage, when hematological metastases have already spread. Surgery is the main treatment strategy, while systemic treatment and radiotherapy are not recommended due to the lack of results. Since metastatization is mainly hematological, lymphadenectomy is not recommended. Recent progresses have been achieved in advanced and recurrent disease, often inoperable, thanks to new chemotherapies, target therapies and immunotherapies. We reported the case of a 51-year-old woman evaluated for lumbar pain in the right region compatible with renal colic. The ultrasound evaluation revealed right hydronephrosis and the presence of a paraovarian or intraligamentary mass compatible with fibroma. The abdominal CT confirmed the presence of a mass with heterogeneous vascularization. Therefore, the patient underwent laparoscopic surgery to remove the lesion which resulted to be a leiomyosarcoma G2. During the following week the patient underwent a laparoscopic hysterectomy. The first step for differential diagnosis consists in the evaluation of clinicopathological features, followed by the analysis of preoperative imaging. Pelvic MRI represents the gold standard, while CT is used to detect metastases. The main issue is that imaging shows limited ability in differential diagnosis between benign and malign smooth muscle tumor. The definitive diagnosis is confirmed by histological analysis; this implies the necessity of improved attentions on the surgical procedure, which is often performed by steps with prolongation of the treatment pathway. To distinguish which fibroids presents a major risk to be misdiagnosed, some risk scores were developed (rPRESS in 2014 and pLMS in 2019), though actually they are not applied in clinical practice. Uterine leiomyosarcoma (uLMS) is rare but causes several deaths in perimenopausal women due to lack of effective treatments, although target therapies represent a future hope. Furthermore, clinical practice needs support through the development and improvement of diagnostic risk scores and their integration into guidelines.

A vocal cord palsy caused by the uterine cancer metastatic tumor in the mediastinum revealed in a patient with a thyroid lesion: a case report and review of the literature.

BACKGROUND: The main cause of vocal cord palsy (VCP) is idiopathic impairment of the recurrent laryngeal nerve (RLN). However, solid tumors along the pathway of the RLN can also impact the nerve's function. We presented a patient with a thyroid lesion and VCP due to a bulky metastatic mass (uterine cancer) on the aortic arch field in the mediastinum. The report aims to show the significance of comorbid tumors in thyroid pathology and the importance of additional diagnostic methods in avoiding unnecessary surgeries. A patient's lifetime and the outcome of the disease were also presented. CASE PRESENTATION: A 58-year-old Ukrainian woman with a hoarse voice, intermittent dry cough, and weakness was presented to an endocrine surgeon. Thyroid pathology included signs of hypothyroidism treated with Thyroxine 112.5 µg and a nodule in the left lobe. The lesion is located on the posterior aspect of the lobe, which could probably be a cause of RLN involvement. Fine needle aspiration biopsy (FNAB) was performed twice with Bethesda category 2 result. Fibrolaryngoscopy (FLS) revealed the median position of the left vocal cord. Idiopathic, laryngeal, and thyroid causes of the VCP were excluded. Additionally, the patient displayed her anamnesis of the endometrial clear cell carcinoma following hysterectomy, external beam radiation therapy, and chemotherapy. The mediastinal metastasis was revealed sixteen years later. A chest computed tomography (CT) with intravenous contrast was done. A bulky tumor was found right under the aortic arch. Subsequently, the voice complaints reduced significantly after 4 chemotherapy courses. Cancer progression had led to the appearance of lymph node metastases on the supraclavicular region. Following six months the 60-year-old patient had passed away. CONCLUSION: A history of the disease should always be kept in mind when assessing a patient's complaints. VCP in case of thyroid pathology and previous secondary malignancy may be caused by metastatic tumor anywhere along the RLN pathway. Such a rare case shows the importance of additional methods of examination which may avoid unnecessary thyroid surgeries.

Sarcoma of the uterine cervix: experience of a single center.

OBJECTIVES: To investigate the clinicopathological characteristics and prognosis of patients with primary sarcoma of the uterine cervix. METHODS: We identified all patients with primary cervical sarcomas treated at our institution from 2002 to 2020 and analyzed the clinicopathological characteristics and prognosis. RESULTS: 34 patients were identified, 7 (20.6%) patients had leiomyosarcoma, 6 (17.6%) had carcinosarcoma, 5 (14.7%) had Ewing sarcoma, 4 (11.8%) had rhabdomyosarcoma, 4 (11.8%) had undifferentiated sarcoma, 2 (5.9%) had adenosarcoma, 2 (5.9%) had endometrial stromal sarcoma, 1 (2.9%) had dermatofibrosarcoma protuberans, 1 (2.9%) had alveolar soft tissue sarcoma and 2 (5.9%) had sarcoma not otherwise specified. The median age of the whole patients was 43.5 years (range, 13-63). The median age of patients with Ewing sarcoma or rhabdomyosarcoma was 22 years (range, 13-39) and 17 years (range, 13-36 years), respectively. The distribution by stage was: stage I in 21 (61.8%) patients, stage II in 4 (11.8%), stage III in 6 (17.6%) and stage IV in 3 (8.8%). Overall, 30 patients (88.2%) received surgical treatment. The median follow-up was 33.3 months (range 3.6-187.3 months). 11 patients died within 2 years after diagnosis, most of them were patients with carcinosarcoma or undifferentiated sarcoma (45.5%, 5/11). In the entire cohort, 2- and 5-year OS were 67.2% and 56.9%, respectively. 5-year OS was 25.0% for undifferentiated sarcoma, 50.0% for rhabdomyosarcoma, 50.0% for carcinosarcoma, 53.3% for Ewing sarcoma, 57.1% for leiomyosarcoma. CONCLUSION: Cervical sarcomas are rare neoplasms with multiple histological subtypes and follow an aggressive course. Prognosis may be associated with tumor histology and stage.