Background: No conceptually new drugs for the safe and successful cure of endometriosis are likely to become available soon. Hormonal modulation of ovarian function and suppression of menstruation remain the pillars of disease control. However, existing drugs may be used following novel modalities to limit the consequences of endometriosis progression.
Objectives: To propose a pharmacological approach aimed at limiting the potential detrimental effects of the recent dramatic increase in postmenarcheal repetitive ovulatory menses and to define the type of hormones and the routes of administration that can be used to maximize safety and tolerability in the medical treatment of endometriosis.
Methods: For this narrative review, we selected the best quality evidence, prioritizing RCTs, systematic reviews, meta-analyses, network meta-analyses, and international guidelines, preferably published in the last decade.
Outcome: Medical treatment of endometriosis should be included into all aspects of prevention. Very-low-dose combined oral contraceptives can be used for years to counteract the increased risk of ovarian cancer observed in patients with endometriosis. This primary prevention measure saves lives and can effectively integrate targeted risk-reducing surgery. Secondary pharmacological prevention, based on a working diagnosis of early-onset adenomyosis-endometriosis selectively in adolescents with severe dysmenorrhea and heavy menstrual bleeding, can potentially impede the development of advanced disease forms, and reduce the need for management of complications due to a delay in diagnosis and treatment. Tertiary prevention, i.e., medical therapy of established disease, is based initially on the safest available estrogen-progestogen combinations and progestogen monotherapies. Whenever possible, ethinyl estradiol and cyproterone acetate should be avoided because of thromboembolic and meningioma risks, respectively. Estradiol can be administered transdermally. Switching to GnRH agonists and antagonists should not be delayed when first-line agents fail.
Conclusions and outlook: Two-thirds of symptomatic endometriosis patients can be managed satisfactorily for many years using, with the right modality, the existing safe, effective, and well-tolerated medications. Despite the constant plea for new drugs, this already appears to be an excellent clinical outcome, unsurpassed in managing other human chronic inflammatory diseases. Cohort studies are needed to verify whether turning off the recurrent inflammation caused by repeated ovulation and menstruation could also affect the risk of systemic conditions associated with endometriosis.
Objectives: To report the first cases of surgical staging for apparently early-stage endometrial cancer performed using the Versius® next-generation robotic surgical system (Cambridge Medical Robots [CMR] Surgical, Cambridge, UK).
Design: Prospective case series. Participants/Materials: Women who underwent surgical staging, including total hysterectomy, bilateral adnexectomy, and sentinel lymph node (SLN) biopsy, for apparently early-stage endometrial cancer using the Versius® next-generation robotic surgical system (CMR Surgical, Cambridge, UK).
Setting: Gynecologic oncology referral center.
Methods: We prospectively recorded data of all consecutive women who underwent the investigated surgical procedure.
Results: Fourteen endometrial cancer patients were treated between March and August 2024 at the Azienda Ospedaliera Universitaria Integrata of Verona. The mean age was 69.4 ± 8.7 years, and the average body mass index was 27.2 ± 4.8. SLN biopsy was performed in all patients: 5 patients had unilateral and 9 bilateral successful SLN detection; 6 women underwent systematic pelvic lymphadenectomy in the unmapped areas. The median operative time was 122 (min-max, 77-185) minutes, and the median hysterectomy time was 34 (min-max, 18-68) minutes. None of the surgical procedures required conversion to conventional laparoscopic or open surgery for technical reasons, and no intraoperative complications were recorded. No readmissions, reoperations, or deaths were observed during the follow-up (median 102 days, min-max 39-249).
Limitations: First experience in a limited study population and use of methylene blue for SLN mapping.
Conclusions: Our preliminary results with the Versius® platform appear encouraging regarding surgical time, blood loss, rate of completion of the robotic procedures, and complications risk. Further studies will confirm the indications, feasibility, and safety of the Versius® surgical robot system for treating apparently early-stage endometrial cancer.
Objective: Abnormal expression of circular RNA (circRNA) leads to the occurrence and development of endometriosis (EM), but its underlying mechanisms are largely unknown.
Methods: Abnormally expressed circRNAs were screened in EM and normal tissues. A series of gain-of-function or loss-of-function experiments were conducted to evaluate the biological behavior of circ_0008927 in EM cells. The role of circ_0008927 in the proliferation, migration, and invasion of EM cells was investigated. The downstream mechanisms of circ_0008927 were studied through bioinformatics analysis and RNA sequencing, and this was confirmed through RNA immunoprecipitation and dual-luciferase reporter assays.
Results: circ_0008927 is highly expressed in EM tissues. From a biological perspective, silencing circ_0008927 can inhibit the proliferation, migration, and invasion of EMS cells in vitro. Mechanistically, circ_0008927 can interact with miR-608 through a competitive endogenous RNA mechanism, upregulating prominin2(PROM2) and inhibiting ferroptosis in EM, thereby exacerbating the progression of EM.
Conclusions: Our research results not only reveal the key role of circ_0008927 in regulating the progression of EM but also advocate for attenuating the circ_0008927/miR-608/PROM2 regulatory axis to combat EM.
Introduction Uterine fibroids (UFs), also known as leiomyomas, are the most common benign gynecological tumors. Currently, morcellation is discouraged owing to the risk of disseminating undetected malignancies. This study aims to update the prevalence data on occult malignancies in surgeries for suspected benign uterine lesions and analyze the impact of treatment strategies on survival outcomes in patients with occult malignancies. Methods Five English-language literature databases were systematically searched up to July 25, 2024, for studies reporting the incidence of occult malignancies in patients with suspected UFs and their survival outcomes. The study was preregistered on PROSPERO(CRD42024580233). Results A total of 34 studies were included in the analysis. The pooled incidence of occult malignancies, calculated via a random effects model, was 2.88 (2.10-3.94) per 1,000 individuals. Significant regional variations were observed in the subgroup comparisons (p<0.01). Moreover, morcellation did not significantly affect progression-free survival (PFS) (hazard ratio [HR]: 1.26, 95% CI: 0.86 - 1.84, p = 0.240) or overall survival (OS) (HR: 1.13, 95% CI: 0.70 - 1.82, p = 0.614). Pooled HR analysis revealed that chemotherapy significantly improved PFS (HR: 0.49; 95% CI: 0.32-0.77; p = 0.002) and OS (HR: 0.49; 95% CI: 0.28-0.87; p = 0.015). Conclusions The incidence of occult malignancies in women undergoing hysterectomy or myomectomy for benign conditions is approximately 2.88 per 1,000 individuals. Morcellation does not impact survival outcomes, whereas adjuvant chemotherapy provides a survival benefit. Further well-designed clinical trials are needed to validate these findings.
Objective: This study aimed to determine the prevalence of polycystic ovarian morphology (PCOM) in healthy postmenarcheal girls and assess whether it represents a crucial physiological phase in gynecological development. Additionally, it evaluated if an elevated stromal-to-surface area (S/A) ratio could identify individuals at risk of developing polycystic ovarian syndrome (PCOS).
Design: This is an observational cross-sectional study.
Participants: A total of 302 healthy postmenarcheal girls aged 14-18 were included in the study.
Setting: The study was conducted at the Pediatric and Adolescent Gynecology Service of the University Hospital Duilio Casula, Monserrato, University of Cagliari, from 2020 to 2023.
Methods: Participants were divided into three groups: normal ovarian morphology (NOM), PCOM with normal S/A ratio (PCOM-NS), and PCOM with increased S/A ratio (PCOM-IS). Anthropometric, clinical, hormonal, and ultrasound (US) characteristics were analyzed.
Results: The overall prevalence of PCOM was 43% (95% CI: 0.37-0.49). Among 302 subjects, 171 (57%) exhibited NOM, 90 (30%) showed PCOM-NS, and 41 (13%) had PCOM-IS. The age and years of postmenarcheal life were significantly lower in the PCOM-NS group than in the NOM group. PCOM-NS exhibited a higher waist-to-hip ratio, hirsutism prevalence, and follicle count per ovarian section. PCOM-IS was associated with elevated androgen levels. A significant reduction in the PCOM pattern was observed after the third postmenarcheal year, while the NOM pattern increased significantly beyond 5 years postmenarche.
Limitations: The study is limited by its cross-sectional design, which precludes establishing causality. Additionally, the exclusion of certain participants due to technical limitations in US evaluation may introduce selection bias.
Conclusions: PCOM may represent a normal physiological phase in ovarian development during early adolescence, predominantly observed in the first 1-3 years postmenarche. An increased S/A ratio could help identify adolescents who may benefit from monitoring for potential PCOS development.
Background: Pelvic floor dysfunctions (PFDs) have a complex, multifactorial pathophysiology that impacts women's health and must be identified to provide the most appropriate care and treatment. Therefore, symptom and quality of life (QoL) questionnaires, briefly identified as patient-reported outcomes (PROs), have been developed. Despite the large number of questionnaires available for the assessment of PFDs and QoL-related issues in English, few of them have been validated for the Italian language.
Objectives: The aim of this article is to systematically review the literature on Italian-language validated PROs for PFDs assessment, along with practical information on literature references and suggestions on how to obtain each individual questionnaire.
Methods: A systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement was performed up to 1 March 2024. PubMed/MEDLINE databases and websites were used to identify validated questionnaires in Italian language for PFDs. Once identified, the possibility of obtaining a copy of the questionnaire was checked, and the steps to obtain one are given in the text.
Outcome: Thirty-five Italian-validated questionnaires were included: 17 out of 35 (48.6%) questionnaires focused on Lower urinary tract symptoms, 1 (2.8%) on genital prolapse symptoms, 8 (22.8%) on sexuality, 3 (8.6%) on bowel symptoms and 6 (17.2%) on pelvic dysfunctions. The literature search turned up seven more Italian PRO validation papers than the previous review. Specifically, the newly validated PROs include: Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12), Sexual Desire and Erotic Fantasies (SDEF) Questionnaire, Sexual Inhibition/Sexual Excitation Scales (SIS/SES), 12-Item Sexual Distress Scale (SDS) and 5-Item Sexual Distress Scale-Short Form (SDS-SF), Vaizey and Wexner and fecal incontinence severity index (FISI) questionnaires, Pelvic Floor Distress Inventory (PFDI-20) questionnaire, Intermittent Catheterization Acceptance Test (I-CAT).
Conclusions and outlook: This systematic review is intended to be a tool to promote the adoption of appropriate PROs when studying PFDs in Italian patients.
Objective: This retrospective cohort study aimed to investigate postoperative pain levels and analgesic drug requirements in women who underwent general anesthesia (GA) or spinal anesthesia (SA) during vaginal pelvic floor surgeries.
Design: This was a retrospective cohort study.
Participants/materials, setting, methods: Women aged 18 or above who underwent vaginal pelvic floor surgery between 2019 and 2021 were included in the study. Univariate and multivariate analyses were performed separately for vaginal wall repair and stress urinary incontinence surgery.
Results: During the study period, 101 women underwent surgery under SA, and 99 women underwent surgery under GA. Intravenous analgesia administration rates were significantly lower under SA for both vaginal wall repair (20.2% vs. 38.9%, p = 0.017) and mid-urethral sling placement (20.2% vs. 37.8%, p = 0.007). Multivariate analysis revealed that intravenous analgesia requirement was significantly lower in the SA group than in the GA group after controlling for patient's age, concurrent hysterectomy, and mesh placement for vaginal wall repair (aOR = 0.33, p = 0.008) and mid-urethral sling placement (aOR = 0.37, p = 0.004).
Limitations: This is a retrospective study, thus the choice of anesthesia may be biased.
Conclusion: SA is associated with less postoperative pain and intravenous analgesia requirement in women who undergo vaginal pelvic floor surgeries. However, further research is needed to determine the preferred anesthesia method for specific types of pelvic floor surgeries.
Objective: The increasing rate of cesarean sections (CSs) raises concerns over severe intra-abdominal adhesions, which are associated with numerous complications. We aimed to identify risk factors and predictive tools for severe adhesions.
Design: A prospective study was conducted. Participants/Materials: Women with at least one prior CS were evaluated.
Setting: The study was conducted at a tertiary medical center from January to July 2021.
Methods: Surgeons assessed adhesions at four anatomical sites, scoring them from 0 (none) to 2 (dense), with a total possible score of 0-8. Severe adhesions were defined as a score of ≥5. Risk factors were analyzed using logistic regression to create a prediction model.
Results: Overall, 341 women were included in the study. Significant predictors included the number of previous CS, maternal body mass index, maternal morbidity at the time of the previous CS, and operation time. The model predicted severe adhesions with 79.1% accuracy, a positive predictive value of 68.4%, and a negative predictive value of 79.5%.
Limitations: Few risk factors, such as surgical history beyond cesarean sections, endometriosis, and pelvic inflammatory disease were not available. Additionally, the sample size of 341 women, while substantial, may limit the identification of further risk factors and the precision of the predictive model.
Conclusion: The severity of most cases of post-CS adhesions can be predicted by a model which considers common risk factors.
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