Epigallocatechin Gallate for the Treatment of Benign and Malignant Gynecological Diseases-Focus on Epigenetic Mechanisms.

The most common malignant gynecologic diseases are cervical, uterine, ovarian, vaginal, and vulvar cancer. Among them, ovarian cancer causes more deaths than any other cancer of the female reproductive system. A great number of women suffer from endometriosis, uterine fibroids (UFs), adenomyosis, dysmenorrhea, and polycystic ovary syndrome (PCOS), which are widespread benign health problems causing troublesome and painful symptoms and significantly impairing the quality of life of affected women, and they are some of the main causes of infertility. In addition to the available surgical and pharmacological options, the effects of supporting standard treatment with naturally occurring compounds, mainly polyphenols, are being studied. Catechins are responsible for the majority of potential health benefits attributed to green tea consumption. Epigallocatechin gallate (EGCG) is considered a non-toxic, natural compound with potential anticancer properties. Antioxidant action is its most common function, but attention is also drawn to its participation in cell division inhibition, apoptosis stimulation and epigenetic regulation. In this narrative review, we describe the role of EGCG consumption in preventing the development of benign reproductive disorders such as UF, endometriosis, and PCOS, as well as malignant gynecologic conditions. We discuss possible epigenetic mechanisms that may be related to the action of EGCG.

Occurrence and Risk Factors for Perioperative Treatment Discontinuation during Magnetic Resonance-Guided High-Intensity Focused Ultrasound (MR-HIFU) Therapy in Symptomatic Uterine Fibroids-A Retrospective Case-Control Study.

BACKGROUND: The main aim of our study involves the analysis of reasons and risk factors for perioperative treatment discontinuation in patients with symptomatic uterine fibroids (UFs) who were qualified for magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) and in whom the procedure was discontinued. METHODS: The presented research included 372 women who were primarily eligible for MR-HIFU, but the procedure was interrupted. The reasons and risk factors for treatment discontinuation were analyzed. A statistical comparison of two cohorts (patients in whom the treatment was discontinued and completed) was conducted based on epidemiological factors, UF characteristics and the implementation of uterotonics. RESULTS: The mean discontinuation rate was 18.28% (n = 68). The main reason was the malposition of the intestines (52.94% of all cases). The thermoablation of subserosal UFs was a statistically significant risk factor of perioperative treatment discontinuation (OR 4.62, CI 95% 2.04-10.56), while the therapy of intramural UFs considerably decreased the risk (OR 0.21, CI 95% 0.08-0.51). The volume of the targeted UF was negatively correlated with the risk of discontinuation (OR 0.991, CI 95% 0.986-0.996). Augmentation with oxytocin, but not misoprostol, during the procedure significantly decreased the risk of potential discontinuation (OR 0.15, CI 95% 0.045-0.387, p < 0.001). CONCLUSION: Although the discontinuation rate seems to be relatively low, further prospective randomized trials are needed to confirm our results. The establishment of particular eligibility criteria for the treatment is a crucial issue in this area. Resigning from the procedure in cases at a high risk of discontinuation might increase patient safety and shorten the time to introduce the most appropriate therapy.

GnRH agonists and antagonists in therapy of symptomatic uterine fibroids - current roles and future perspectives.

INTRODUCTION: Uterine fibroids are the most common noncancerous tumors in women of childbearing age. This review was developed to evaluate the current role of gonadotropin-releasing hormone (GnRH) agonists and antagonists in the therapy of symptomatic uterine fibroids. AREAS COVERED: There is a great need for alternative methods for surgical treatment of uterine fibroids. Hormonal therapy remains the first-line treatment option for most patients. GnRH analogs (agonists and antagonists) modulate the pulsatile release of GnRH. This review summarizes the available literature concerning pharmacologic principles underlying the mechanism of action of GnRH and its analogs, as well as individual therapeutic applications to which these drugs have been applied. EXPERT OPINION: In many cases, it is possible to try to treat uterine fibroids pharmacologically. Both groups of GnRH analogs are used in therapy, agonists instead as a preparation for surgery, and antagonists as a drug for long-term use. It is essential to develop this path further and look for at least long-term-release systems or new methods of administering these drugs. It is also important from the patient's perspective to search for possible drugs that may have an additive effect of decreasing side effects when combined with GnRH analogs.

Occurrence of adverse events after magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) therapy in symptomatic uterine fibroids-a retrospective case-control study.

OBJECTIVES: Our study aims at the comprehensive analysis of adverse events (AEs) in patients with symptomatic uterine fibroids (UFs) who underwent magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) in the last 6 years in one of the major Polish centers performing this type of therapy. METHODS: The presented retrospective case-control study was conducted in the Department of Obstetrics and Gynecology, Pro-Familia Hospital, Rzeszów in cooperation with the Second Department of Obstetrics and Gynecology, Center of Postgraduate Medical Education, Warsaw. The study enrolled 372 women with symptomatic UFs who underwent MR-HIFU and reported AEs during or after the procedure. The occurrence of particular AEs was analyzed. Statistical comparison of two cohorts (patients with and without AEs) was conducted based on epidemiological factors, UF characteristics, fat layer thickness, the presence of abdominal scars and technical parameters of the procedure. RESULTS: The overall mean occurrence rate of AEs was 8.9% (n = 33). No major AEs were reported. The only statistically significant risk factor of AEs was the treatment of type II UFs according to Funaki (OR 2.12, CI 95%, p = 0.043). Other investigated factors did not have a statistically significant influence on AE occurrence. Abdominal pain was the most common AE. CONCLUSION: Our data showed that MR-HIFU seemed to be a safe procedure. The AE rate after the treatment is relatively low. According to the obtained data it seems that the occurrence of AEs does not depend on the technical parameters of the procedure and the volume, position and location of UFs. Further prospective, randomized studies and with long follow-up are necessary to confirm the final conclusions.

Performance of IOTA Simple Rules Risks, ADNEX Model, Subjective Assessment Compared to CA125 and HE4 with ROMA Algorithm in Discriminating between Benign, Borderline and Stage I Malignant Adnexal Lesions.

BACKGROUND: Borderline ovarian tumors (BOTs) and early clinical stage malignant adnexal masses can make sonographic diagnosis challenging, while the clinical utility of tumor markers, e.g., CA125 and HE4, or the ROMA algorithm, remains controversial in such cases. OBJECTIVE: To compare the IOTA group Simple Rules Risk (SRR), the ADNEX model and the subjective assessment (SA) with serum CA125, HE4 and the ROMA algorithm in the preoperative discrimination between benign tumors, BOTs and stage I malignant ovarian lesions (MOLs). METHODS: A multicenter retrospective study was conducted with lesions classified prospectively using subjective assessment and tumor markers with the ROMA. The SRR assessment and ADNEX risk estimation were applied retrospectively. The sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-) were calculated for all tests. RESULTS: In total, 108 patients (the median age: 48 yrs, 44 postmenopausal) with 62 (79.6%) benign masses, 26 (24.1%) BOTs and 20 (18.5%) stage I MOLs were included. When comparing benign masses with combined BOTs and stage I MOLs, SA correctly identified 76% of benign masses, 69% of BOTs and 80% of stage I MOLs. Significant differences were found for the presence and size of the largest solid component (p = 0.0006), the number of papillary projections (p = 0.01), papillation contour (p = 0.008) and IOTA color score (p = 0.0009). The SRR and ADNEX models were characterized by the highest sensitivity (80% and 70%, respectively), whereas the highest specificity was found for SA (94%). The corresponding likelihood ratios were as follows: LR+ = 3.59 and LR- = 0.43 for the ADNEX; LR+ = 6.40 and LR- = 0.63 for SA and LR+ = 1.85 with LR- = 0.35 for the SRR. The sensitivity and specificity of the ROMA test were 50% and 85%, respectively, with LR+ = 3.44 and LR- = 0.58. Of all the tests, the ADNEX model had the highest diagnostic accuracy of 76%. CONCLUSIONS: This study demonstrates the limited value of diagnostics based on CA125 and HE4 serum tumor markers and the ROMA algorithm as independent modalities for the detection of BOTs and early stage adnexal malignant tumors in women. SA and IOTA methods based on ultrasound examination may present superior value over tumor marker assessment.

Adverse events and complications after magnetic resonance-guided focused ultrasound (MRgFUS) therapy in uterine fibroids - a systematic review and future perspectives.

OBJECTIVES: The aim of this review was to analyze and summarize the most common adverse events (AEs) and complications after magnetic resonance-guided focused ultrasound (MRgFUS) therapy in uterine fibroids (UFs) and to establish the risk factors of their occurrence. METHODS: We searched for original research studies evaluating MRgFUS therapy in UFs with outcomes containing AEs and/or complications in different databases (PubMed/MEDLINE, SCOPUS, COCHRANE) until March 2022. Reviews, editorials, opinions or letters, case studies, conference papers and abstracts were excluded from the analysis. The systematic literature search identified 446 articles, 43 of which were analyzed. RESULTS: According to available evidence, the overall incidence of serious complications in MRgFUS therapy is relatively low. No AEs/complications were reported in 11 out of 43 analyzed studies. The mean occurrence of all AEs in the analyzed material was 24.67%. The most commonly described AEs included pain, skin burns, urinary tract infections and sciatic neuropraxia. Major AEs, such as skin ulcerations or deep vein thrombosis, occurred in 0.41% of cases in the analyzed material. CONCLUSION: MRgFUS seems to be safe in UF therapy. The occurrence of AEs, especially major ones, is relatively low in comparison with other methods. The new devices and more experience of their users seem to reduce AE rate. The lack of unification in AE reporting and missing data are the main issues in this area. More prospective, randomized studies with unified reporting and long follow-up are needed to determine the safety in a long-term perspective.

The Approach of Pregnant Women to Vaccination Based on a COVID-19 Systematic Review.

Background and Objectives: Pregnant women are more likely to develop a more severe course of COVID-19 than their non-pregnant peers. There are many arguments for the safety and efficacy of COVID-19 vaccines in pregnant women. The aim of this study is to conduct a systematic review concerning the approach of pregnant women towards vaccination against COVID-19, with particular regard to determinants of vaccination acceptance. Materials and Methods: Articles were reviewed in which the aim was to evaluate-via a survey or questionnaire-the acceptance and decision to undergo vaccination against COVID-19. The articles were subjected to review according to recommendations of Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement (PRISMA). Results: In various studies, the percentage of pregnant women accepting the COVID-19 vaccine was between 29.7% and 77.4%. The strongest factors co-existing with the acceptance of the COVID-19 vaccination in pregnancy were trust in the importance and effectiveness of the vaccine, explicit communication about the safety of COVID-19 vaccines for pregnant women, acceptance of other vaccinations such as those for influenza, belief in the importance of vaccines/mass vaccination in one's own country, anxiety about COVID-19, trust in public health agencies/health science, as well as compliance to mask guidelines. The remaining factors were older age, higher education, and socioeconomic status. Conclusions: This review allowed us to show that geographic factors (Asian, South American countries) and pandemic factors (different threats and risks from infection) significantly influence the acceptance of vaccines. The most significant factors affecting acceptance are those related to public awareness of the risk of infection, vaccine safety, and the way in which reliable information about the need and safety of vaccines is provided. Professional and reliable patient information by obstetricians and qualified medical personnel would significantly increase the level of confidence in vaccination against COVID-19.

Risk Assessment of Endometrial Hyperplasia or Endometrial Cancer with Simplified Ultrasound-Based Scoring Systems.

BACKGROUND: Abnormal uterine bleeding (AUB) represents a common diagnostic challenge, as it might be related to both benign and malignant conditions. Endometrial cancer may not be detected with blind uterine cavity sampling by dilatation and curettage or suction devices. Several scoring systems using different ultrasound image characteristics were recently proposed to estimate the risk of endometrial cancer (EC) in women with AUB. AIM: The aim of the present study was to externally validate the predictive value of the recently proposed scoring systems including the Risk of Endometrial Cancer scoring model (REC) for EC risk stratification. MATERIAL AND METHODS: It was a retrospective cohort study of women with postmenopausal bleeding. From June 2012 to June 2020 we studied a group of 394 women who underwent standard transvaginal ultrasound examination followed by power Doppler intrauterine vascularity assessment. Selected ultrasound features of endometrial lesions were assessed in each patient. RESULTS: The median age was 60.3 years (range ± 10.7). The median body mass index (BMI) was 30.4 (range ± 6.0). Histological examination revealed 158 cases of endometrial hyperplasia (EH) and 236 cases of EC. Of the studied ultrasound endometrial features, the highest areas under the curve (AUCs) were found for endometrial thickness (ET) (AUC = 0.76; 95% CI: 0.71-0.81) and for interrupted endomyometrial junction (AUC = 0.70, 95% CI: 0.65-0.75). Selected scoring systems presented moderate to good predictive performance in differentiating EC and EH. The highest AUC was found for REC model (AUC = 0.75, 95% CI: 0.70-0.79) and for the basic model that included ET, Doppler score and interrupted endometrial junction (AUC = 0.77, 95% CI: 0.73-0.82). REC model was more accurate than other scoring systems and selected single features for differentiating benign hyperplasia from EC at early stages, regardless of menopausal status. CONCLUSIONS: New scoring systems, including the REC model may be used in women with AUB for more efficient differentiation between benign and malignant conditions.

Magnetic resonance-guided high-intensity ultrasound (MR-HIFU) in the treatment of symptomatic uterine fibroids - five-year experience.

OBJECTIVES: Uterine fibroids (UF) are the most common benign tumors of the female reproductive organ. It is crucial to recognize that the appropriate treatment of UFs requires an individualized approach. The present paper aimed at the presentation of the five-year experience of our center in the treatment of UFs with the use of magnetic resonance-guided high-intensity ultrasound (MR-HIFU) therapy. MATERIAL AND METHODS: The study enrolled a total of 1284 patients with symptomatic UFs. The Sonalleve MR-HIFU system (Philips Ingenia 3.0T System) was used for magnetic resonance imaging (MRI) qualification and treatment. RESULTS: The group of patients qualified for thermal ablation included 356 (28%) women. No significant differences were observed between the group undergoing thermal ablation and patients who were disqualified. A complete procedure was performed in 22.6% of patients who presented at the center. Non-perfused volume (NPV) is one of the most important parameters assessed during MR-HIFU procedures. The mean NPV value in the present study was 71%. The average UF volumes decreased by 27% at three-month follow-up ultrasound, by 34% after six months and by 39% as shown by MRI measurements performed 6 months post-treatment. CONCLUSIONS: According to our data, MR-HIFU therapy is associated with good clinical outcomes in patients with symptomatic UFs. The method facilitates a marked symptom reduction and, in many cases, diminishing tumor volume. The presented five-year outcomes as regards our experience in the MR-HIFU therapy of patients with symptomatic UFs indicate that the method offers an attractive alternative to the traditional methods of UF treatment in selected cases.

Magnetic Resonance-Guided High-Intensity Focused Ultrasound Ablation of Uterine Fibroids-Efficiency Assessment with the Use of Dynamic Contrast-Enhanced Magnetic Resonance Imaging and the Potential Role of the Administration of Uterotonic Drugs.

OBJECTIVE: The assessment of the usefulness of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) when qualifying patients with uterine fibroids (UFs) for magnetic resonance-guided high-intensity ultrasound (MR-HIFU). MATERIAL AND METHODS: This retrospective, single center study included 283 women who underwent DCE-MRI and were treated with MR-HIFU. The patients were divided according to non-perfused volume (NPV) as well as by the type of curve for patients with a washout curve in the DCE-MRI study and patients without a washout curve. The studied women were assessed in three groups according to the type of uterotonics administered. Group A (57 patients) received one dose of misoprostol/diclofenac transvaginally and group B (71 patients) received oxytocin intravenously prior to the MR-HIFU procedure. The remaining 155 women (group C) were treated with the traditional non-drug enhanced MR-HIFU procedure. RESULTS: The average NPV value was higher in no washout group, and depended on the uterotonics used. CONCLUSIONS: We demonstrated a correlation between dynamic contrast enhancement curve types and the therapeutic efficacy of MR-HIFU. Our results suggest that DCE-MRI has the potential to assess treatment outcomes among patients with UFs, and patients with UFs that present with a washout curve may benefit from the use of uterotonic drugs. More studies are required to draw final conclusions.

Sonographic Assessment of Complex Ultrasound Morphology Adnexal Tumors in Pregnant Women with the Use of IOTA Simple Rules Risk and ADNEX Scoring Systems

BACKGROUND: To evaluate the accuracy of subjective assessment (SA), the International Ovarian Tumor Analysis (IOTA) group Simple Rules Risk (SRR) and the Assessment of Different NEoplasias in the adneXa (ADNEX) model for the preoperative differentiation of adnexal masses in pregnant women. METHODS: The study population comprised 36 pregnant women (median age: 28.5 years old, range: 20-42 years old) with a mean gestation age of 13.5 (range: 8-31) weeks at diagnosis. Tumors were prospectively classified by local sonographers as probably benign or probably malignant using SA. Final tumor histological diagnosis was used as the reference standard in all cases. Logistic regression SRR and ADNEX models were used to obtain a risk score for every case. Serum CA125 and human epidydimis protein 4 (HE4) concentrations were also retrieved and the Risk of Ovarian Malignancy Algorithm (ROMA) value was calculated. The calculated predictive values included positive and negative likelihood ratios of ultrasound and biochemical tests. RESULTS: Final histology confirmed 27 benign and 9 malignant (including 2 borderline) masses. The highest sensitivity (89%) and specificity (70%) were found for the subjective tumor assessment. Although no malignancy was classified as benign using the SRR criteria (sensitivity = 100%), the specificity of this scoring system was only 37%. At the cut-off risk level of >20%, the ADNEX model had a sensitivity of 78% and a specificity of 70%. Serum levels of CA125, HE4 and the ROMA risk model correctly identified adnexal malignant tumors with a sensitivity of 67%, 25% and 25%, respectively. Corresponding specificities were 72%, 100% and 100%, respectively. The highest positive and negative likelihood ratios were found for SA (LR+ = 3.0 and LR- = 0.16, respectively). Overall diagnostic accuracy of all predictive methods used in this study were similar (range: 70-75%) except for SRR (53%). CONCLUSION: Subjective assessment remains the best predictive method in complex adnexal masses found at prenatal ultrasound in pregnant women. For less experienced sonographers, both the SRR and ADNEX scoring systems may be also used for the characterization of such tumors, while serum tumor markers CA125 and HE4, along with the ROMA algorithm appear to be less accurate.

Oxytocin and Misoprostol With Diclofenac in the Preparation for Magnetic Resonance-Guided High-Intensity Ultrasound Treatment of Symptomatic Uterine Fibroids: A Prospective Cohort Study.

Uterine fibroids (UFs) are very common benign tumors of the female reproductive tract. According to recent reports, magnetic resonance-guided high-intensity ultrasound (MR-HIFU) appears to be a well-tolerated and efficient treatment option for UFs. However, MR-HIFU still presents several limitations. The treatment is rarely associated with achieving complete non-perfused volume (NPV). Not all patients are qualified for a final procedure, and selected women obtain very good results in such treatment. The primary objective of this experimental study was to assess the effect of transvaginal misoprostol and intravenous oxytocin preparation on UF volume change, sonication time and NPV after MR-HIFU procedure in women of reproductive age with symptomatic UFs. Secondary outcomes included the effect on the peri-procedural effectiveness of misoprostol and oxytocin. This study enrolled 247 women with symptomatic UFs; based on gynecologic examinations and magnetic resonance imaging (MRI) scans, 128 women qualified for MR-HIFU without pharmacologic treatment, 57 women qualified for the misoprostol/diclofenac group and 62 women qualified for the oxytocin group. Pharmacologic pre-treatment improved NPV compared with non-pharmacologic treatment (average NPV: controls 61.9% ± 25.8%; oxytocin 76.8% ± 20.7%; misoprostol/diclofenac 85.2% ± 15.1%; average sonication time: controls 120 min ± 56.4%; oxytocin 111 min ± 45.4%; misoprostol/diclofenac 80 min ± 47.7%). Statistical analysis did not reveal significant intergroup differences in UF volume changes after 6 mo (controls: n = 40, 37.4% ± 27.5%; oxytocin n = 25, 45.8% ± 31%; misoprostol/diclofenac n = 19, 33.4% ± 23.2%). The misoprostol/diclofenac group, which achieved the highest NPV immediately after the MR-HIFU procedure, was characterized by the lowest UF volume change percentages 6 mo later. The administration of vasoconstrictor drugs (oxytocin and misoprostol/diclofenac) to support MR-HIFU in UF treatment is a new issue that may improve the total effectiveness of this method. Randomized controlled trials are necessary to estimate the real effect of vasoconstrictors on MR-HIFU.

Tumor budding index and microvessel density assessment in patients with endometrial cancer: A pilot study.

The present study aimed to analyze the association between tumor budding index (TBI) and microvessel density (MVD) and selected clinicopathological features in female patients with endometrial cancer (EC). The present study included 137 patients, of whom 117 had endometrial endometrioid cancer and 3 had non-endometrioid EC (NEEC). Additionally, 8 cases of simple endometrial hyperplasia and 9 cases of atypical endometrial hyperplasia were included in the present study. Patient age, menopausal status, tumor histological type, grade and International Federation of Gynecologists and Obstetricians (FIGO) clinical stage were investigated. Immunohistochemistry was utilized to detect MVD using a CD34 antibody, and a laminin-5γ2 antibody was used for TBI assessment. In nonmalignant endometrial lesions, the TBI was significantly lower than that in patients with EC and NEEC (P=0.002). Significant differences in median TBI (MD-TBI) were also observed between patients with low-grade EC (MD-TBI, 4.5) and high-grade EC (MD-TBI, 16.2; P=0.01). Age, body mass index and tumor FIGO stage were not indicated to be associated with the MD-TBI. Premenopausal patients with EC had lower MD-TBI values than postmenopausal patients (0.3 vs. 11.1; P<0.005). The median MVD-CD34 in the study group was 19 (range, 13-29). Significant differences in MVD-CD34 were observed between malignant and nonmalignant endometrial lesions (P=0.01). Histological grade was markedly associated with tumor MVD-CD34 (P=0.001). The MVD was higher in high-grade cancer (G3; MVD-CD34, 24.9) than in grade G1 and G2 lesions (MVD-CD34, 14 and 18.6, respectively; P=0.01). FIGO clinical stage was not associated with MVD-CD34 in low and high stage lesions (MD, 18.4 for FIGO stage I/II; MD, 17.6 for FIGO stage III/IV; P=0.2). High MVD was markedly associated with high MD-TBI (P=0.0002). In conclusion, TBI could be a valuable indicator of tumor aggressiveness in patients with EC. The presence of the tumor budding phenomenon with increased MVD may have the potential to further refine clinical management decisions when endometrial malignancy is detected.

The role of magnetic resonance-guided focused ultrasound in fertility-sparing treatment of uterine fibroids-current perspectives.

Uterine fibroids (UFs) are the most common benign tumours of the female reproductive system and the most frequent reason for hysterectomy worldwide. UFs are reported in 20%-70% of women of reproductive age depending on a study group. Although most women with UFs are asymptomatic, over 30% of them will present with different symptoms. Abnormal uterine bleeding, pain, pressure and infertility are the most common. Lesions that cause these kinds of symptoms may require medical intervention. Trends in UF treatment change along with patient awareness and the introduction of new methods and techniques. Selecting an appropriate treatment option should be individualised and adjusted to the patient's expectations as much as possible. This choice will mostly depend on the patient's age, UF location, the size and number of lesions, severity of symptoms and, most importantly, the patient's expectations concerning the preservation of fertility. Observations made for the past few years showed an increasing number of pre- and perimenopausal women who wish to preserve their uterus or decline surgery. In line with current trends and demands in medicine, great importance is attached to the development and upgrade of new minimally invasive or noninvasive procedures in UF therapy. Magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) is not associated with severe destruction of the uterine cavity and walls. For this reason, this method may be considered as a kind of hope in fertility-sparing UF therapy and the data about its use in this indication raises future hope. In this review, we summarise the available data on the use of MR-HIFU as a fertility-sparing method in the treatment of UFs. We also indicate how it could evolve in the future. According to the available data, MR-HIFU is a relatively safe noninvasive method which seems not to deteriorate fertility compared to the pre-treatment status. MR-HIFU may constitute an alternative solution and be chosen in patients who meet the qualification criteria and deny other methods, which also facilitates the use of other treatment options in case the procedure is ineffective. Further randomised studies are necessary to confirm the above information.

The Role of miRNA and Related Pathways in Pathophysiology of Uterine Fibroids-From Bench to Bedside.

Uterine fibroids (UFs) are the most common benign tumors of the female genital tract. Their prevalence usually is estimated at 30-40%, but may reach up to 70-80% in predisposed groups of women. UFs may cause various clinical issues which might constitute the major reason of the overall deterioration of the quality of life. The mechanisms leading to UFs formation and growth still remain poorly understood. The transformation of smooth muscle cells of the uterus into abnormal, immortal cells, capable of clonal division, is thought to be a starting point of all pathways leading to UF formation. Micro-ribonucleic acids (miRNAs) are non-coding single-stranded RNAs about 22 nucleotides in length, that regulate gene expression. One of recent advances in this field is the comprehension of the role of miRNAs in tumorigenesis. Alterations in the levels of miRNAs are related to the formation and growth of several tumors which show a distinct miRNA signature. The aim of this review is to summarize the current data about the role of miRNAs in the pathophysiology of UFs. We also discuss future directions in the miRNA research area with an emphasis on novel diagnostic opportunities or patient-tailored therapies. In our opinion data concerning the regulation of miRNA and its gene targets in the UFs are still insufficient in comparison with gynecological malignancies. The potential translational use of miRNA and derived technologies in the clinical care is at the early phase and needs far more evidence. However, it is one of the main areas of interest for the future as the use of miRNAs in the diagnostics and treatment of UFs is a new and exciting opportunity.

Obesity as a risk factor of in-hospital outcomes in patients with endometrial cancer treated with traditional surgical mode.

OBJECTIVES: Abdominal obesity is a risk factor for endometrial cancer. The negative impact of individual parameters of obesity on the procedural effects of endometrial cancer surgical treatment has been suggested. The aim of the current study was to estimate the relationship of particular parameters of obesity and in-hospital outcomes in patients treated surgically due to endometrial cancer. MATERIAL AND METHODS: The study included 70 women treated surgically for endometrial cancer. Pre-operatively, mass, body mass index (BMI), waist circumference, waist-hip ratio and selected anatomical indices were measured. The duration of surgery, hospitalisation, and the loss of haemoglobin served as parameters of in-hospital procedure success. Also, procedural-related complications were estimated. RESULTS: There were 37 (52.8%) obese females in the current study. They were obese patients presenting more advanced clinical stages of endometrial cancer before operation. The duration of operation (94.9 ± 21.6 min. vs. 76.1 ± 13.5 min., p < 0.0001), hospitalisation (12.4 ± 3.4 days vs. 10 ± 2.3 days, p = 0.0009) and haemoglobin loss (2.5 ± 0.9 g/dL vs. 1.9 ± 0.8 g/dL, p = 0.004) were significantly greater in obese patients. Multivariate analysis, among the independent predictors of the duration of operation, has confirmed the correlation between BMI, waist circumference and weight and the duration of hospitalisation. Waist and hip circumference and BMI coupled with external conjugate dimension and intertrochanteric distance have been linked with haemoglobin loss. The strongest correlation for the duration of operation, hospitalisation and haemoglobin loss was noticed for waist circumference (r = 0.7, r = 0.57 and r = 0.59). CONCLUSIONS: Waist circumference and BMI are strong predictors of in-hospital outcomes among patients with endometrial cancer treated via traditional surgical operation.

The outcome of magnetic resonance-guided high-intensity ultrasound for clinically symptomatic submucosal uterine fibroid performed accidentally in very early pregnancy: a case report.

This is a report of an unintended application of MR-HIFU therapy of uterine fibroids (UFs) in a woman in early pregnancy and should be treated as the first description of such an event. A 37-year-old nullipara with confirmed UFs, who suffered from excessive uterine bleeding and dysmenorrhea, was qualified for MR-HIFU therapy to reduce UF-related symptoms. The procedure took place 2 months later. No complications occurred and the patient was discharged home in good overall condition. About 5 weeks after the procedure the patient was diagnosed with viable intrauterine pregnancy. Basing on early pregnancy ultrasound it was calculated that at the time of MR-HIFU procedure the patient was about 10 (+/- 3 days) days after the conception. Later, the pregnancy was uncomplicated and she gave birth to a healthy neonate. Physical examinations did not reveal any abnormalities in her child. Symptoms associated with UFs significantly decreased after the therapy and pregnancy. Despite the fact that the pregnancy being subjected to MR-HIFU treatment had further uncomplicated course, the presented case indicates that counseling/management in women at reproductive age should be standardized to avoid unknown consequences of such unrecommended procedures for the fetus. According to current standards MR-HIFU procedures to treat UFs should never be performed without a negative pregnancy test.

The effect of high-intensity focused ultrasound guided by magnetic resonance therapy on obstetrical outcomes in patients with uterine fibroids - experiences from the main Polish center and a review of current data.

Introduction: Uterine fibroids (UFs) are benign tumors of female genital tract. Clinically symptomatic UFs may be a cause of serious health problems for many women worldwide. The optimal choice of a treatment method should fit a patient's specific life situation or expectancies (especially fertility) as much as possible. In line with the general current trend in medicine and surgery, great importance is attached to the development of minimally invasive radiological procedures e.g., magnetic resonance guided focused ultrasound (MRgFUS). Materials and methods: Single-center retrospective cohort study conducted at the Department of Obstetrics and Gynecology of Pro-Familia Hospital in Rzeszów, Poland. The study group consisted of 276 patients suffering from UFs and treated with MR-HIFU over the period from April 2015 to May 2018. Results: In our group 20 out of 276 patients conceived after the MR-HIFU therapy (7.25%). A general improvement and alleviation of symptoms of the disease after MRgFUS/MR-HIFU procedure were observed in 80% (n = 16) of study participants that conceived. 15% (n = 3) did not report any changes in disease severity. Out of 11 patients who already gave birth - 63.64% (n = 7) underwent cesarean section. Conclusions: MRgFUS/MR-HIFU seems to be an interesting minimally invasive alternative for women with UFs who wish to conceive and deliver after the procedure. This method does not increase the rate of spontaneous abortions or pregnancy complications. In our opinion, it is important to take off an unjustified badge stating that MRgFUS/MR-HIFU method is contraindicated in women with UFs who wish to conceive.

The Usefulness of Immunohistochemistry in the Differential Diagnosis of Lesions Originating from the Myometrium.

Uterine leiomyomas (LMs), currently the most common gynecological complaint around the world, are a serious medical, social and economic problem. Accurate diagnosis is the necessary prerequisite of the diagnostic-therapeutic process. Statistically, mistakes may occur more often in case of disease entities with high prevalence rates. Histopathology, based on increasingly advanced immunohistochemistry methods, is routinely used in the diagnosis of neoplastic diseases. Markers of the highest sensitivity and specificity profiles are used in the process. As far as LMs are concerned, the crux of the matter is to identify patients with seemingly benign lesions which turn out to be suspicious (e.g., atypical LM) or malignant (e.g., leiomyosarcoma (LMS)), which is not uncommon. In this study, we present the current state of knowledge about the use of immunohistochemical markers in the differential diagnosis of LM, atypical LM, smooth muscle tumors of uncertain malignant potential (STUMP), and LMS, as well as their clinical predictive value.

The Role of Tumor Necrosis Factor α in the Biology of Uterine Fibroids and the Related Symptoms.

Uterine fibroids (UFs) are the most common benign tumors of the female genital tract. The incidence of UFs has been estimated at 25⁻80% depending on selected population. The pathophysiology of UFs remains poorly understood. The transformation of smooth muscle cells of the uterus into abnormal, immortal cells, capable of clonal division, is the main component of all pathways leading to UF tumor formation and tumor necrosis factor α (TNF-α) is believed to be one of the key factors in this field. TNF-α is a cell signaling protein involved in systemic inflammation and is one of the cytokines responsible for the acute phase reaction. This publication presents current data about the role of tumor necrosis factor α in the biology of UFs and the related symptoms. TNF-α is an extremely important cytokine associated with the biology of UFs, UF-related symptoms and complaints. Its concentration has been proven to be elevated in women with clinically symptomatic UFs. The presented data suggest the presence of an "inflammation-like" state in women with UFs where TNF-α is a potent inflammation inducer. The origin of numerous symptoms reported by women with UFs can be traced back to the TNF-α influence. Nevertheless, our knowledge on this subject remains limited and TNF-α dependent pathways in UF pathophysiology should be investigated further.