The use of oral nomegestrol acetate/estradiol in rapid and random start preparation of endometrium before office hysteroscopic polypectomies: A multicenter, prospective, randomized controlled trial.

OBJECTIVE: To evaluate the use of oral nomegestrol acetate/estradiol in random start rapid preparation of endometrium before office hysteroscopic polypectomy. STUDY DESIGN: Multicenter, prospective, randomized controlled trial. SETTING: University hospitals. PARTICIPANTS: 80 adult women undergoing office hysteroscopic polypectomy between January 2023 and March 2024 were randomized to intervention (n = 40) or control (n = 40). Exclusion criteria included the presence of endouterine pathology other than endometrial polyps solely. METHODS: Subjects in the intervention group were treated with oral nomegestrol acetate/estradiol 1.5 mg/2.5 mg/day started taking the drug from an indefinite time in the menstrual cycle (random start) for 14 days. Subjects in the control group did not receive any pharmaceutical treatment and underwent polypectomy between days 8 and 11 of the menstrual cycle. RESULTS: On the day of the procedure, the difference in pre- and post-office hysteroscopic polypectomy endometrial ultrasound thickness was statistically significant between the two groups, with endometrial thickness in both measurements being thinner for the intervention group (p < 0.001). In the nomegestrol acetate/estradiol-treated group, compared with the control, there was also a statistically significant difference in the physician's assessment of the quality of endometrial preparation (p < 0.001), the quality of visualization of the uterine cavity (p < 0.001), and satisfaction with the performance of the procedure (p < 0.001). Finally, all surgical outcomes analyzed were better in the treatment group. CONCLUSION: Treatment with nomegestrol acetate/estradiol could provide rapid, satisfactory and low-cost preparation of the endometrium before office polypectomy, thus improving surgical performance and woman's compliance. TRIAL REGISTRATION: ClinicalTrials.gov NCT06316219.

Safety and efficacy of a class II medical device based on highly purified and standardized plant extracts in the management of post-menopausal patients with vulvar and vaginal atrophy: a single-center prospective observational study.

BACKGROUND: Despite the gold standard treatment for genitourinary syndrome of menopause (GSM) is based on the use of local or systemic estrogen-containing products, the typical long-term side effects of hormonal treatments and, most importantly, the contraindications in patients with history of breast and endometrial neoplasms do limit in some extent its use. As hyaluronic acid and some highly purified botanicals have clearly demonstrated their anti-inflammatory and mucosa-protecting properties, we have tested, in women with GSM, a class II vaginal medical device containing hyaluronate gel and a mucoadhesive active enriched with purified alkylamides from Zanthoxylum bungeanum, triterpenes from Centella asiatica and high molecular weight polysaccharides from Tamarindus indica. METHODS: Our single-center, open-label, prospective and observational study was conducted on 50 menopausal women enrolled at the Department of Maternal-Fetal Medicine at Umberto I Polyclinic Hospital in Rome, Italy. Gel administration lasted 150 days and was performed daily for the first 12 days and every 48 hours for the remaining 138 days. Clinical evaluations were performed at baseline and after 12, 57 and 150 days. Besides product safety, main outcomes of our study were: 1) vaginal health (by Vaginal Health Index score [VHI]); 2) sexual quality of life (by Female Sexual Distress Scale [FSDS]); and 3) percentage of women declaring regular sexual activity. RESULTS: The product was safe with no specific adverse events reported. It significantly improved VHI (about 5% after 57 days and 8% after 150 days), FSDS (about 7% after 57 days and 10% after 150 days), and sexual activity (about 20% after 150 days). It also reduced dryness, dyspareunia, burning, itching, and dysuria incidence, respectively by about 18%, 14%, 14%, 27% and 11% after 150 days. CONCLUSIONS: In women with GSM, the intravaginal administration of a hyaluronate-based gel enriched with purified botanical actives endowed with anti-inflammatory and mucosal-protecting properties, reduced painful sensation during sexual acts and increased regular sexual activity.

Primary neuroendocrine neoplasms of the vulva: A review of the MITO rare cancer group.

Gynecological neuroendocrine neoplasms are rare entities and can be divided into two groups: carcinoids and neuroendocrine carcinomas. Due to their rarity their management is not standardized. The aim of this work is to summarize and discuss the current literature evidence on this pathology. A scoping literature review was performed in multiple databases. Thirty-one studies were included: 30 case reports and one case series. Patients' age ranged between 28 and 92 years. Surgery was the most used treatment and the surgical approach included local excision (N = 16/31; 51.6%) with (N = 5/16; 31.25%) or without (N = 11/16; 68.75%) inguinal lymphadenectomy. Adjuvant radiotherapy was delivered in 12 (38.7%) cases; instead, platinum-based therapies were frequently used when chemotherapy was chosen for adjuvant treatment. The overall survival ranged between 20 days to 4 years. However, further research is needed; currently, multimodal approach including surgery, chemotherapy and radiotherapy appeared safe and feasible for the treatment of these rare and aggressive diseases.

HPV-related lesions after hysterectomy for high-grade cervical intraepithelial neoplasia and early-stage cervical cancer: A focus on the potential role of vaccination.

OBJECTIVE: To date, no data supports the execution of vaccination after hysterectomy for high-grade cervical intraepithelial neoplasia (CIN2+) and early-stage cervical cancer. We aim to evaluate the potential effect of vaccination after hysterectomy for high-grade cervical intraepithelial neoplasia and early-stage cervical cancer. METHODS: This is a multi-center retrospective study evaluating data of women who develop lower genital tract dysplasia (including anal, vulvar and vaginal intra-epithelial neoplasia) after having hysterectomy for CIN2+ and FIGO stage IA1- IB1 cervical cancer. RESULTS: Overall, charts for 77 patients who developed lower genital tract dysplasia were collected. The study population included 62 (80.5%) and 15 (19.5%) patients with CIN2+ and early-stage cervical cancer, respectively. The median (range) time between hysterectomy and diagnosis of develop lower genital tract dysplasia was 38 (range, 14-62) months. HPV types covered by the nonavalent HPV vaccination would potentially cover 94.8% of the development of lower genital tract dysplasia. Restricting the analysis to the 18 patients with available HPV data at the time of hysterectomy, the beneficial effect of nonvalent vaccination was 89%. However, considering that patients with persistent HPV types (with the same HPV types at the time of hysterectomy and who developed lower genital tract dysplasia) would not benefit from vaccination, we estimated the potential protective effect of vaccination to be 67% (12 out of 18 patients; four patients had a persistent infection for the same HPV type(s)). CONCLUSIONS: Our retrospective analysis supported the adoption of HPV vaccination in patients having treatment for HPV-related disease. Even in the absence of the uterine cervix, HPV vaccination would protect against develop lower genital tract dysplasia. Further prospective studies have to confirm our preliminary research.

Uterine sarcomas: A critical review of the literature.

This review aims to provide a comprehensive description of surgical approaches for the management of uterine sarcomas. Uterine sarcomas are rare uterine neoplasms. Frequently, diagnosis is made after hysterectomy or myomectomy scheduled for presumed benign leiomyomas. The gold standard for surgical treatment of uterine sarcomas is hysterectomy with bilateral salpingo-oophorectomy. It is possible to adopt a fertility-sparing approach for those patients who wish to maintain their fertility. The role of pelvic lymphadenectomy is controversial; in fact, removal of lymph nodes is only recommended in the case of radiological suspicion of nodal involvement. Use of a morcellator is associated with increased risk of total recurrence, intra-abdominal recurrence and death. Advanced disease management should be customized based on the patient's performance status given the uncertain role of adjuvant chemotherapy. Treatment of advanced or recurrent disease remains a subject of debate, but surgery is the best approach in terms of morbidity and mortality. There are few options for management of these uterine tumours, and further studies are needed to clarify the diagnostic and therapeutic pathways of patients with a first diagnosis of uterine sarcoma and patients with relapse of uterine sarcoma. No specific evidence supports the adoption of adjuvant therapy in uterine-confined disease, and molecular/genomic profiling may be useful to identify patients at risk of recurrence.

Hysterectomy Using Vaginal Natural Orifice Transluminal Endoscopic Surgery Compared with Classic Laparoscopic Hysterectomy: A New Advantageous Approach? A Systematic Review on Surgical Outcomes.

INTRODUCTION: Minimally invasive surgery aims to reduce surgical trauma and post-operative morbidity. Natural orifice transluminal endoscopic surgery is a safe and valid surgical option for hysterectomy. The present systematic review aims to compare hysterectomy by transvaginal natural orifice transluminal endoscopic surgery (vNOTES) with laparoscopic hysterectomy in terms of efficacy, surgical outcomes, complications, and cost. MATERIALS AND METHODS: This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. It includes randomized controlled trials, controlled clinical trials, prospective or retrospective cohorts, case-control studies, and previous systematic reviews. Inclusion criteria are as follows: female patients undergoing hysterectomy for benign pathologies by vNOTES or laparoscopic hysterectomy. The assessed outcomes were the following: conversion rate, mean uterus weight (g), operative time (mins), hospital stay (days), peri-operative complications, post-operative complications, peri-operative blood loss (mL), blood transfusion needs, post-operative day 1 hemoglobin (Hb) change (g/dL), post-operative pain level (VAS), and cost (USD) in both techniques. RESULTS: Seven studies were included. vNOTES hysterectomy was not inferior to laparoscopic hysterectomy regarding surgical outcomes, with a shorter operative time, shorter recovery time, less post-operative pain, and fewer post-operative complications. There was no significant difference in the rate of peri-operative complications and no differences in peri-operative blood loss, post-operative day 1 Hb change, and transfusions. Nevertheless, vNOTES hysterectomy was shown to be more expensive than its laparoscopic counterpart. CONCLUSIONS: While the feasibility and safety of the vNOTES hysterectomy were already established, this review also underlines the noninferiority of this technique when compared to laparoscopic hysterectomy in terms of surgical outcomes. In addition, vNOTES hysterectomy was associated with faster operating time, shorter hospital stay, and better post-operative pain scores compared with laparoscopic hysterectomy.

Magnetic resonance imaging-radiomics in endometrial cancer: a systematic review and meta-analysis.

OBJECTIVE: Endometrial carcinoma is the most common gynecological tumor in developed countries. Clinicopathological factors and molecular subtypes are used to stratify the risk of recurrence and to tailor adjuvant treatment. The present study aimed to assess the role of radiomics analysis in pre-operatively predicting molecular or clinicopathological prognostic factors in patients with endometrial carcinoma. METHODS: Literature was searched for publications reporting radiomics analysis in assessing diagnostic performance of MRI for different outcomes. Diagnostic accuracy performance of risk prediction models was pooled using the metandi command in Stata. RESULTS: A search of MEDLINE (PubMed) resulted in 153 relevant articles. Fifteen articles met the inclusion criteria, for a total of 3608 patients. MRI showed pooled sensitivity and specificity 0.785 and 0.814, respectively, in predicting high-grade endometrial carcinoma, deep myometrial invasion (pooled sensitivity and specificity 0.743 and 0.816, respectively), lymphovascular space invasion (pooled sensitivity and specificity 0.656 and 0.753, respectively), and nodal metastasis (pooled sensitivity and specificity 0.831 and 0.736, respectively). CONCLUSIONS: Pre-operative MRI-radiomics analyses in patients with endometrial carcinoma is a good predictor of tumor grading, deep myometrial invasion, lymphovascular space invasion, and nodal metastasis.

Outcomes of High-Grade Cervical Dysplasia with Positive Margins and HPV Persistence after Cervical Conization.

The objective of this work is to assess the 5-year outcomes of patients undergoing conization for high-grade cervical lesions that simultaneously present as risk factors in the persistence of HPV infection and the positivity of surgical resection margins. This is a retrospective study evaluating patients undergoing conization for high-grade cervical lesions. All patients included had both positive surgical margins and experienced HPV persistence at 6 months. Associations were evaluated with Cox proportional hazard regression and summarized using hazard ratio (HR). The charts of 2966 patients undergoing conization were reviewed. Among the whole population, 163 (5.5%) patients met the inclusion criteria, being at high risk due to the presence of positive surgical margins and experiencing HPV persistence. Of 163 patients included, 17 (10.4%) patients developed a CIN2+ recurrence during the 5-year follow-up. Via univariate analyses, diagnosis of CIN3 instead of CIN2 (HR: 4.88 (95%CI: 1.10, 12.41); p = 0.035) and positive endocervical instead of ectocervical margins (HR: 6.44 (95%CI: 2.80, 9.65); p < 0.001) were associated with increased risk of persistence/recurrence. Via multivariate analyses, only positive endocervical instead of ectocervical margins (HR: 4.56 (95%CI: 1.23, 7.95); p = 0.021) were associated with worse outcomes. In this high-risk group, positive endocervical margins is the main risk factor predicting 5-year recurrence.

Novel Insights into Molecular Mechanisms of Endometrial Diseases.

Endometrial diseases are the most common gynecological pathologies in Western Countries [...].

Role of Genomic and Molecular Biology in the Modulation of the Treatment of Endometrial Cancer: Narrative Review and Perspectives.

Endometrial cancer (EC) is one of the most common gynecological malignancies in Western countries. Traditionally, loco-reginal dissemination and histological characteristics are the main prognostic factors. Nowadays, molecular and genomic profiling showed exciting results in terms of prognostication. According to the data provided by The Cancer Genome Atlas and other studies, molecular and genomic profiling might be useful in identifying patients al low, intermediate, and high risk of recurrence. However, data regarding the therapeutic value are scant. Several prospective studies are ongoing to identify the most appropriate adjuvant strategy in EC patients, especially for those with positive nodes and low volume disease. The molecular classification has offered the possibility to improve the risk stratification and management of EC. The aim of this review is to focus on the evolution of molecular classification in EC and its impact on the research approach and on clinical management. Molecular and genomic profiling might be useful to tailor the most appropriate adjuvant strategies in apparent early-stage EC.

Radical Hysterectomy for Early Stage Cervical Cancer.

Radical hysterectomy and plus pelvic node dissection are the primary methods of treatment for patients with early stage cervical cancer. During the last decade, growing evidence has supported the adoption of a minimally invasive approach. Retrospective data suggested that minimally invasive surgery improves perioperative outcomes, without neglecting long-term oncologic outcomes. In 2018, the guidelines from the European Society of Gynaecological Oncology stated that a "minimally invasive approach is favored" in comparison with open surgery. However, the phase III, randomized Laparoscopic Approach to Cervical Cancer (LACC) trial questioned the safety of the minimally invasive approach. The LACC trial highlighted that the execution of minimally invasive radical hysterectomy correlates with an increased risk of recurrence and death. After its publication, other retrospective studies investigated this issue, with differing results. Recent evidence suggested that robotic-assisted surgery is not associated with an increased risk of worse oncologic outcomes. The phase III randomized Robotic-assisted Approach to Cervical Cancer (RACC) and the Robotic Versus Open Hysterectomy Surgery in Cervix Cancer (ROCC) trials will clarify the pros and cons of performing a robotic-assisted radical hysterectomy (with tumor containment before colpotomy) in early stage cervical cancer.

Assessing the role of low volume disease in endometrial cancer.

The role of retroperitoneal staging in endometrial cancer is still unclear. Although the prognostic value of lymphadenectomy has been demonstrated no data support the therapeutic value of nodal dissection. Sentinel node mapping represents an evolution of lymphadenectomy. Sentinel node mapping allows a more accurate identification of low-volume diseases (i.e., micrometastasis and isolated tumor cells) that are not always detectable via conventional histopathological evaluation. Adjuvant therapy might play a role in patients with low-volume disease. However, the presence of isolated tumor cells alone seems to not impact outcomes of endometrioid endometrial cancer patients. Hence, the choice to deliver adjuvant therapies has to be tailored based on uterine factors only. The introduction of molecular and genomic profiling would be useful in selecting appropriate surgical and adjuvant treatments. The molecular-integrated risk profile should be integrated in clinical practice to overcome the need of retroperitoneal staging (in case of non-bulky nodes) in patients at low risk.

Reducing the radicality of surgery for vulvar cancer: are smaller margins safer?

INTRODUCTION: Vulvar cancer accounts for ~4% of all gynecological malignancies and the majority of tumors (>90%) are squamous cell (keratinizing, ~60% and warty/basaloid, ~30%). Surgical excision forms the foundation of treatment, with resection margin status being the single most influential factor when predicting clinical outcome. There has been a paradigm shift concerning surgical approaches and radicality when managing vulvar cancer within recent times, largely owing to a desire to preserve vulvar structure and function without compromising oncological outcome. As such the safety of the size of resection margin has been called into question. In this narrative review we consider the current literature on the safety of resection margins for vulvar cancer. EVIDENCE ACQUISITION: PubMed, Medline and the Cochrane Database were searched for original peer-reviewed primary and review articles, from January 2005 to January 2020. The following search terms were used vulvar cancer surgery, vulvar squamous cell carcinoma, excision margins, adjuvant radiation. EVIDENCE SYNTHESIS: A pathological tumor margin of <8 mm has been widely considered to indicate "close" margins. This measurement after fixation of the tumor is considered comparable to a surgical resection margin of around 1cm, following an estimated 20% tissue shrinkage after formalin fixation and a 1-2cm clinical surgical margin in order to achieve the 8 mm final pathological margin. CONCLUSIONS: A surgical resection margin of 2-3mm does not appear to be associated with a higher rate of local recurrence than the widely used limit of 8 mm. As such the traditional practice of re-excision or adjuvant radiotherapy based on "close" surgical margins alone needs to be closely evaluated, since the attendant morbidity associated with these procedures may not be outweighed by oncological benefit.

Update on surgical treatment of female stress urinary incontinence.

INTRODUCTION: Urinary incontinence is a common condition that negatively impacts quality of life of millions of women. It is a result of a synergy between the structures of pelvic floor in particular levator ani muscle and pelvic connective tissues. Urinary incontinence, increasing with age, is associated with considerable personal and societal expenditure. EVIDENCE ACQUISITION: Systematic data search performed using PubMed/Medline database up to August 20, 2020. Focus was only for English language publications of original studies on urinary incontinence and in particular stress urinary incontinence. EVIDENCE SYNTHESIS: Given the basis of published evidence and the consensus of European experts, this study provides an updated overview on clinical applications and surgical procedures of urinary incontinence. CONCLUSIONS: Urinary incontinence is an underestimated health problem. Many surgical options exist for women with stress urinary incontinence. Nevertheless, new strategies need to be evaluated in order to improve quality of life of patients.