Estetrol Inhibits Endometriosis Development in an In Vivo Murine Model.

Endometriosis is characterized by the growth of endometrial-like tissue outside the uterus, and it is associated with alterations in the expression of hormone receptors and inflammation. Estetrol (E4) is a weak estrogen that recently has been approved for contraception. We evaluated the effect of E4 on the growth of endometriotic-like lesions and the expression of TNF-α, estrogen receptors (ERs), and progesterone receptors (PRs) in an in vivo murine model. Endometriosis was induced surgically in female C57BL/6 mice. E4 was delivered via Alzet pump (3 mg/kg/day) from the 15th postoperative day for 4 weeks. E4 significantly reduced the volume (p < 0.001) and weight (p < 0.05) of ectopic lesions. Histologically, E4 did not affect cell proliferation (PCNA immunohistochemistry) but it did increase cell apoptosis (TUNEL assay) (p < 0.05). Furthermore, it modulated oxidative stress (SOD, CAT, and GPX activity, p < 0.05) and increased lipid peroxidation (TBARS/MDA, p < 0.01). Molecular analysis showed mRNA (RT-qPCR) and protein (ELISA) expression of TNF-α decreased (p < 0.05) and mRNA expression of Esr2 reduced (p < 0.05), in contrast with the increased expression of Esr1 (p < 0.01) and Pgr (p < 0.05). The present study demonstrates for the first time that E4 limited the development and progression of endometriosis in vivo.

Targeting BRAF pathway in low-grade serous ovarian cancer.

Mutations in genes encoding for proteins along the RAS-RAF-MEK-ERK pathway have been detected in a variety of tumor entities including ovarian carcinomas. In the recent years, several inhibitors of this pathway have been developed, whose antitumor potential is currently being assessed in different clinical trials. Low grade serous ovarian carcinoma, is a rare gynecological tumor which shows favorable overall survival, compared to the general ovarian cancer population, but worrying resistance to conventional chemotherapies. The clinical behavior of low grade serous ovarian carcinoma reflects the different gene profile compared to high-grade serous carcinoma: KRAS/BRAF mutations. BRAF inhibitors as single agents were approved for the treatment of BRAF mutated tumors. Nevertheless, many patients face progressive disease. The understanding of the mechanisms of resistance to BRAF inhibitors therapy and preclinical studies showing that BRAF and mitogen-activated protein kinase kinase (MEK) inhibitors combined therapy delays the onset of resistance compared to BRAF inhibitor single agent, led to the clinical investigation of combined therapy. The aim of this paper is to review the efficacy and safety of the combination of BRAF plus MEK inhibitors on ovarian carcinomas, in particularly focusing on low grade serous ovarian carcinoma.

Effect of maternal age and BMI on induction of labor using oral misoprostol in late-term pregnancies: a retrospective cross-sectional study.

OBJECTIVES: To evaluate the effect of maternal age and body mass index (BMI) on oral misoprostol induction of labor for late-term pregnancies. DESIGN: Retrospective cross-sectional study (ClinicalTrial iD: NCT06184139), including only late-term pregnancies in healthy nulliparous women and single cephalic fetus with normal birthweight. Specify the type of study (randomized, prospective cohort, case-control, other) and include the number of study subjects (cases/controls), treatment type and duration, sampling procedures if applicable. PARTICIPANTS/MATERIALS, SETTING, METHODS: One-hundred-and-four pregnant women underwent induction of labor with oral misoprostol for late-term pregnancy on the 290th day of gestation. Study population was divided in two groups based on age (<35 and ≥35 years) and obesity (BMI <30 and ≥30). Statistical analysis was performed using SPSS V.21.0 (IBM Corporation, Armonk, NY). The inclusion of 51 women from each of the two arms achieved 80% power with an alpha error of 0.05. Continuous variables were expressed as the mean and standard deviation (SD). Categorical variables are expressed as frequencies and percentages. Results No statistically significant differences were recorded between younger and older women. Obese women reported a longer time between the last dose of misoprostol and cervical dilation of 6 cm (p=0.01), a longer time between the last dose of misoprostol and delivery (p=0.04), and a higher rate of grade II vaginal lacerations (p=0.02). Limitations While this study contributes novel insights into cervical ripening and labor induction using oral misoprostol for late-term pregnancies, its scope is limited by the retrospective study design, inherently carrying biases compared to prospective approaches, and the limited sample size within the study cohort. Conclusions Maternal BMI is a factor negatively influencing the efficacy of oral misoprostol for induction of labor in late-term pregnancy.

The great debate: Surgical outcomes of laparoscopic versus laparotomic myomectomy. A meta-analysis to critically evaluate current evidence and look over the horizon.

Myomectomy is one of the most common surgical procedure in the field of gynecology. However, the role of laparoscopic myomectomy is still debated for many factors, including surgical considerations, safety and fertility concerns, long-term outcomes, and cost-related issues. The aim of this study is to evaluate the surgical peri- and post-operative outcomes of laparoscopic and abdominal myomectomy. A systematic search for studies was performed up to June 2023 through MEDLINE, Pubmed, Embase. Studies reporting the comparison of surgical and obstetrical outcomes in laparoscopic versus laparotomic myomectomy were included for the following outcomes: time of surgery, estimated blood loss, decrease of postoperative hemoglobin, hospital stay, intra-operative complication rates, postoperative complications rates, postoperative analgesic use, postoperative pain at 24 h and pregnancy rate. The meta-analysis was performed using the Cochrane Review software. Fifty-six relevant articles were retrieved through the process of evidence acquisition. Eleven articles met inclusion criteria, for a total of 2,133 patients undergoing laparoscopic or laparotomic myomectomy. The estimated blood loss [standard mean differences (SMD) 0.72, IC 95 % 0.22 to 1.22], the hospital stays [SMD 3.12, IC 95 % 0.57 to 4.28], were significantly lower in laparoscopic than in open group. No statistically significant difference in intra-operative and post-operative complication rates, in pregnancy rate and others obstetrical outcomes between two surgical approaches were found. The findings of present metanalysis suggest that laparoscopic myomectomy offers multiple benefits, including reduced blood loss, shorter hospital stays, and less postoperative analgesic need, without a significant increase in complication rates and similar results in obstetrical outcomes when compared to abdominal myomectomy. However, the presence of few randomized studies on selected population may limit the generalizability of the findings to the entire population. Therefore, more well-designed studies or large population programdata to draw definitive conclusions are therefore warranted.

Reproductive Outcomes in Young Women with Early-Stage Cervical Cancer Greater than 2 cm Undergoing Fertility-Sparing Treatment: A Systematic Review.

Background and Objectives: Despite advancements in detection and treatment, cervical cancer remains a significant health concern, particularly among young women of reproductive age. Limited data exists in the literature regarding fertility-sparing treatment (FST) of cervical cancers with tumor sizes greater than 2 cm. The objective of this systematic review was to evaluate the reproductive outcomes of women diagnosed with cervical cancer greater than 2 cm who underwent FST. Materials and Methods: A comprehensive search of the literature was carried out on the following databases: MEDLINE, EMBASE, Global Health, The Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Cochrane Methodology Register), the Health Technology Assessment Database, and Web of Science. Only original studies (retrospective or prospective) that reported reproductive outcomes of patients with cervical cancer >2 cm were considered eligible for inclusion in this systematic review (CRD42024521964). Studies describing only the oncologic outcomes, involving FST for cervical cancers less than 2 cm in size, and case reports were excluded. Results: Seventeen papers that met the abovementioned inclusion criteria were included in the present systematic review. In total, 443 patients with a cervical cancer larger than 2 cm were included in this systematic review. Eighty pregnancies occurred, with 24 miscarriages and 54 live births. Conclusions: FST appears to be a viable option for women of childbearing age diagnosed with cervical cancer larger than 2 cm. However, careful consideration is advised in interpreting these encouraging results, as they are subject to limitations, such as variability in study designs and potential biases. In addition, reproductive outcomes should be further cross-referenced with oncologic outcomes to clarify the potential risk-benefit ratio. It is critical to conduct further research using standardized approaches and larger participant groups to strengthen the validity of the conclusions drawn.

Approaches to prevention of gynecological malignancies.

Gynecological malignancies represent one of the prevalent diseases in the female sex and prevention is essential to limit their incidence and mortality. Nowadays, not all malignancies benefit from adequate screening methods for this reason new biomarkers and methods are being developed to undertake timely and effective therapies.

Hormone replacement therapy in gynecological cancer survivors and BRCA mutation carriers: a MITO group survey.

OBJECTIVE: Early iatrogenic menopause in gynecological cancer survivors and BRCA mutation (BRCAm) carriers undergoing risk-reducing salpingo-oophorectomy (RRSO) is a major health concern. Hormone replacement therapy (HRT) is the most effective remedy, but remains underused in clinical practice. The Multicenter Italian Trials in Ovarian cancer and gynecologic malignancies (MITO) group promoted a national survey to investigate the knowledge and attitudes of healthcare professionals regarding the prescription of HRT. METHODS: The survey consisted of a self-administered, multiple-choice 45-item questionnaire, available online to all MITO members for 2 months starting from January 2022. RESULTS: A total of 61 participants completed the questionnaire (47 out of 180 MITO centers; compliance: 26.1%). Most respondents were female (73.8%), younger than 50 years (65.6%), and gynecologic oncologists (55.7%), working in public general hospitals (49.2%). An 84.4% of specialists actively discuss HRT with patients and 51.0% of patients ask the specialist for an opinion on HRT. The rate of specialists globally in favor of prescribing HRT was 22.9% for ovarian cancer, 49.1% for cervical cancer, and 8.2% for endometrial cancer patients. Most respondents (70.5%) believe HRT is safe for BRCA-mutated patients after RRSO. Nearly 70% of physicians prescribe systemic HRT, while 23.8% prefer local HRT. Most specialists recommend HRT for as long as there is a benefit and generally for up to 5 years. CONCLUSION: Real-world data suggest that many healthcare professionals still do not easily prescribe HRT for gynecological cancer survivors and BRCA mutation carriers after RRSO. Further efforts are required to implement the use of HRT in clinical practice and to support both clinicians in recommending HRT and patients in accepting it.

Health-related quality of life after hysterectomy for endometrial cancer: the impact of enhanced recovery after surgery (ERAS) shifting paradigm.

OBJECTIVES: Enhanced recovery after surgery (ERAS) protocols provide well-known benefits in the immediate recovery with a shorter length of stay (LOS) also in gynecological surgery. However, the impact of ERAS has not been clearly showed yet regarding long-term consequences and health-related quality of life (HRQL). The aim of this study is to investigate the impact of ERAS on HRQL after hysterectomy for endometrial cancer. DESIGN: Observational retrospective study with propensity score matching (PSM). Participants We administered the SF-36 validated questionnaire to women underwent hysterectomy and lymph nodal staging before and after introducing ERAS protocol, getting, respectively, a standard practice (SP) and ERAS group Settings Academic hospital Methods We collected demographic, clinical, surgical and postoperative data and performed a PSM of the baseline coufouders. We administered the questionnaire four weeks after the surgery. The SF-36 measures HRQL using eight scales: physical functioning (PF), role physical (RLP), bodily pain (BP), general health (GH), vitality (Vt), social functioning (SF), role emotional (RLE) and mental health (MH). Results After PSM, we enrolled a total of 154 patients, 77 in each group (SP and ERA). The two groups were similar in terms of age, BMI, anaesthesiologic risk, Charlson comorbidity index (CCI) and surgical technique (minimally invasive versus open access). Median LOS was shorter for ERAS group (5 versus 3 days; p = 0.02), while no significant differences were registered in the rates of postoperative complications (16.9% versus 17.4%; p = 0.66). Response rates to SF-36 questionnaire were 89% and 92%, respectively, in SP and ERAS group. At multivariate analyzes, the mean scores of SF-36 questionnaire, registered at 28 days weeks after surgery (range 26-32 days), were significantly higher in ERAS group for PF (73.3 vs 91.6; p < 0.00), RLP (median 58.3 vs 81.2; p = 0.02) and SF (37.5 versus 58.3; p = 0.01) domains, when compared to SP patients. Limitations Further follow-up was not possible due to the anonymized data derived from clinical audit. Conclusions ERAS significantly increases HRQL of women underwent surgery for endometrial cancer. HRQL assessment should be routinary implemented in the ERAS protocol.

Sentinel node mapping in high-intermediate and high-risk endometrial cancer: Analysis of 5-year oncologic outcomes.

OBJECTIVE: To assess 5-year oncologic outcomes of apparent early-stage high-intermediate and high-risk endometrial cancer undergoing sentinel node mapping versus systematic lymphadenectomy. METHODS: This is a multi-institutional retrospective, propensity-matched study evaluating data of high-intermediate and high-risk endometrial cancer (according to ESGO/ESTRO/ESP guidelines) undergoing sentinel node mapping versus systematic pelvic lymphadenectomy (with and without para-aortic lymphadenectomy). Survival outcomes were assessed using Kaplan-Meier and Cox proportional hazard methods. RESULTS: Overall, the charts of 242 patients with high-intermediate and high-risk endometrial cancer were retrieved. Data on 73 (30.1%) patients undergoing hysterectomy plus sentinel node mapping were analyzed. Forty-two (57.5%) and 31 (42.5%) patients were classified in the high-intermediate and high-risk groups, respectively. Unilateral sentinel node mapping was achieved in all patients. Bilateral mapping was achieved in 67 (91.7%) patients. Three (4.1%) patients had site-specific lymphadenectomy (two pelvic areas only and one pelvic plus para-aortic area), while adjunctive nodal dissection was omitted in the hemipelvis of the other three (4.1%) patients. Sentinel nodes were detected in the para-aortic area in eight (10.9%) patients. Twenty-four (32.8%) patients were diagnosed with nodal disease. A propensity-score matching was used to compare the aforementioned group of patients undergoing sentinel node mapping with a group of patients undergoing lymphadenectomy. Seventy patient pairs were selected (70 having sentinel node mapping vs. 70 having lymphadenectomy). Patients undergoing sentinel node mapping experienced similar 5-year disease-free survival (HR: 1.233; 95%CI: 0.6217 to 2.444; p = 0.547, log-rank test) and 5-year overall survival (HR: 1.505; 95%CI: 0.6752 to 3.355; p = 0.256, log-rank test) than patients undergoing lymphadenectomy. CONCLUSIONS: Sentinel node mapping does not negatively impact 5-year outcomes of high-intermediate and high-risk endometrial cancer. Further prospective studies are warranted.

Deciphering the "David Sign": Intersections in esthetic surgery and renaissance sculpture.

Spotlighting a 500-year-old detail in Michelangelo's "David," this paper delves into the intricate connection between technique and art in the medical field, especially in esthetic surgery. With rapid technological advancement, medical specialties are becoming increasingly segmented, leading to potential oversights in holistic human examination. Drawing from ancient Greek concepts, "Techne," "Ars," and "Episteme" are explored as symbolic representations of the convergence of skill and knowledge. Art, defined as a reflection of human creativity and emotion, was historically intertwined with science, as symbolized by the nine Muses. The Renaissance period, exemplified by works like "David," underlines the profound relationship between art and anatomy. Dr. Gelfman's observations on the "David sign" serve as a testament to the continuous dance between medical science and artistic representation. This paper underscores the timeless value of a comprehensive approach in medical practice, urging professionals to amalgamate technical precision with an artistic understanding of the human form. LEVEL OF EVIDENCE: Level V, opinion expert.

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.

Placentation and complications of ART pregnancy. An update on the different possible etiopathogenic mechanisms involved in the development of obstetric complications.

INTRODUCTION: Infertile couples' percentage is increasing all over the world, especially in Italy, with high number of children born in our country through assisted reproductive techniques (ART). However, pregnancies obtained by ART have increased potential obstetrical risks which could be caused by fetus-placenta unit development, most of all due to placentation's evolution. These can be reassumed into miscarriage, chromosomal abnormalities, preterm delivery, multiple pregnancy, IUGR, placenta previa, abruptio placentae, preeclampsia and hypertensive disorders, postpartum hemorrhage. METHODS: The aim of this article is to evaluate hypothetic mechanism involved in placentation process and in the etiopathology of ART pregnancies disorders, giving an updating overview of different etiopathogenetic pathways and features. On this scenario, we create an updated review about the etiopathogenesis of abnormal placentation in ART pregnancies. RESULTS: Several features and different etiopathogenetic characteristic might impact differently such as advanced maternal age, poor ovarian reserve, oocyte quality and causes of subfertility themselves, and the ART techniques itself, as hormonal medical treatments and laboratory techniques such as gamete and embryo laboratory culture, cryopreservation versus fresh ET, number of embryos transferred. CONCLUSION: To further explore the molecular mechanisms behind placentation in ART pregnancies, further studies are necessary to gain a better understanding of the various aspects involved, particularly those which are not fully comprehended. This could prove beneficial to clinicians in both ART care and obstetric care, as it could help to stratify obstetrical risk and decrease complications in women undergoing ART, as well as perinatal disorders in their children. Correct placentation is essential for a successful pregnancy for both mother and baby.

Counseling in menopausal women: How to address the benefits and risks of menopause hormone therapy. A FIGO position paper.

Menopause marks the end of menstrual cyclicity and, depending on individual vulnerability, has several consequences related to gonadal steroid deprivation, especially if it is premature. Menopause may be more burdensome for some women than for others. Individual factors, such as personal history, socioeconomic status, ethnicity, and current health conditions, affect symptomatology and, thereby, the menopausal experience. In addition, some menopausal symptoms, such as severe hot flashes, sleep disorders, and depression, are markers of future health risks. Counseling is a fundamental part of health care in the peri- and postmenopause periods. It must include an assessment of the patient's symptoms, needs, desires, and risk profile to address the benefits and risks of menopausal hormone therapy (MHT) on an individual basis and promote a healthy lifestyle. Indeed, healthcare practitioners can and must protect the health and lives of mid-life women by increasing awareness of menopausal symptoms and ensuring healthcare options, especially MHT. The type and duration of MHT should be tailored based on the patient's history, menopausal age, physical characteristics, and current health status so that the benefits always outweigh the risks. This FIGO position paper focuses on the benefits and risks of MHT on health domains, target organs, and systems, and on systemic and vaginal MHT regimens, to provide indications that can be used in the clinical practice for menopausal counseling. Moreover, it offers insights into what FIGO considers the mainstay for the healthcare management of women in peri- and postmenopause, worldwide.

Polycystic Ovary Syndrome and Alteration of Vocal Function: A Systematic Review and Meta-Analysis.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a common hormonal disorder among young women, correlated with hyperandrogenism. Among the symptoms of PCOS, vocal alterations are quite unknown. Dysphonia may be related to hyperandrogenism, and there is no consensus about its prevalence and the severity of vocal disorders, which can cause noticeable discomfort. METHODS: A systematic review of the literature was conducted. Four studies on PCOS that evaluated the phonatory system were included for a total of 174 patients (96 PCOS, 78 controls), and a meta-analysis on comparable data was performed. RESULTS: Four studies evaluated parameters related to vocal symptomatology, altered audiometric examination, and findings at the laryngoscopy in patients affected by PCOS versus controls. Although the individual studies showed increased incidence of alterations and a tendency to develop speech fatigue in women with PCOS, when the results of studies were pulled in meta-analysis, the overall difference was not statistically significant. The studies themselves were very different from each other; therefore, it is hard to draw any firm conclusions. DISCUSSION: The aim of this study was to assess the prevalence of vocal alterations, the correlation with hyperandrogenism, the quality of life, and the voice changes after starting a therapy for PCOS. The present meta-analysis failed to find any difference in terms of PCOS and control cohort. However, the lack of high-quality studies makes it difficult to draw firm conclusions. New and larger studies or big population program data are therefore warranted.

Sentinel node mapping in endometrial cancer.

Nodal status is one of the most important prognostic factors for patients with apparent early stage endometrial cancer. The role of retroperitoneal staging in endometrial cancer is controversial. Nodal status provides useful prognostic data, and allows to tailor the need of postoperative treatments. However, two independent randomized trials showed that the execution of (pelvic) lymphadenectomy increases the risk of having surgery-related complication without improving patients' outcomes. Sentinel node mapping aims to achieve data regarding nodal status without increasing morbidity. Sentinel node mapping is the removal of first (clinically negative) lymph nodes draining the uterus. Several studies suggested that sentinel node mapping is not inferior to lymphadenectomy in identifying patients with nodal disease. More importantly, thorough ultrastaging sentinel node mapping allows the detection of low volume disease (micrometastases and isolated tumor cells), that are not always detectable via conventional pathological examination. Therefore, the adoption of sentinel node mapping guarantees a higher identification of patients with nodal disease than lymphadenectomy. Further evidence is needed to assess the value of various adjuvant strategies in patients with low volume disease and to tailor those treatments also on the basis of the molecular and genomic characterization of endometrial tumors.

The role of L1CAM as predictor of poor prognosis in stage I endometrial cancer: a systematic review and meta-analysis.

INTRODUCTION: Molecular and genomic profiling in endometrial cancer is increasing popularity. L1 cell adhesion molecule (L1CAM) is frequently mutated in endometrial cancer. In this paper, we aim to evaluate the prognostic role of L1CAM in patients with stage I endometrial cancer. METHODS: We performed a systematic review and meta-analysis searching in PubMed (MEDLINE), EMBASE, and Web of Science database to identify studies reporting the expression of L1CAM in endometrial cancer. The primary endpoint measure was to assess and evaluate the impact of L1CAM on survival outcomes. This study was performed according to the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) statement. RESULTS: Five studies were included. The pooled results suggested that L1CAM expression influences survival outcomes in stage I endometrial cancer. High L1CAM expression correlated with worse disease-free survival (HR 4.11, 95% CI 1.02-16.59, p = 0.047) and overall survival (HR 3.62, 95% CI 1.32-9.31, p = 0.012). High L1CAM level was also associated with a more aggressive FIGO grade and with older age. CONCLUSION: This systematic review supported that L1CAM have a prognostic role in stage I endometrial cancer, thus providing a potential useful tool for tailoring the need of adjuvant therapy.

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.

Pharmacotherapy for the treatment of recurrent cervical cancer: an update of the literature.

INTRODUCTION: Cervical cancer is the fourth most common cause of cancer-related death worldwide. High-risk locally advanced or recurrent/metastatic cervical cancers have a poor prognosis with routine treatments. The objective of this study is to analyze the data available in the literature on therapies and molecules currently in use to improve the prognosis of recurrent cervical cancer. AREAS COVERED: An extensive literature search was conducted by authors to identify relevant trials on various databases. Articles in English published until September 2023 that investigate different pharmacotherapy strategies for the treatment of recurrent cervical cancer, were included. Results of various pharmacological regimens including different combinations of chemotherapy, immune checkpoint inhibitors, DNA damage repair inhibitors and antibody-drug conjugates were analyzed. EXPERT OPINION: In recent years, there have been significant improvements in the outcomes of recurrent/metastatic cervical cancer. However, these improvements do not address the unmet need in terms of oncological outcomes. The introduction of immunotherapy and targeted therapies showed advantages in cervical cancer patients. New therapies and combination strategies must be implemented. Centralization of care and enrollment in clinical trials are of paramount importance. Primary and secondary prevention remains the fundamental goal to reduce the burden of cervical cancer.

Spotlight on Compounded Bioidentical Hormones.

BACKGROUND: The role of hormonal replacement therapy in menopause is under debate. The premature closure of the Women's Health Initiative (WHI) study in 2002 is still a source of concern among treating physicians. OBJECTIVES: The interest in alternatives to conventional hormone therapy has significantly increased. The adoption of personalized steroid hormone galenic preparations, formulated by compounding pharmacies, has recently spread. METHODS: In June 2023, an extensive literature search was conducted by different authors to identify relevant studies in various databases (MEDLINE, Embase, PubMed, and Cochrane). The studies that met the inclusion and exclusion criteria were further analyzed, and relevant data were extracted and analyzed for each paper. Any discrepancies between the investigators were resolved through a consensus approach. OUTCOMES: The primary outcomes observed included the clinical utility of CBHT. This study reviewed the current evidence on the utility of compounded bioidentical hormones, concluding that improving knowledge and awareness of bioidentical hormones is necessary to consider their use in clinical practice. CONCLUSION AND OUTLOOK: These formulations might provide effective options to best tailor therapies to each patient.