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.

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.

PCOS and vitamin D: a clinical appraisal.

PURPOSE: Polycystic ovary syndrome (PCOS) is the most common endocrine-reproductive disease linked not just to infertility but also to serious comorbidities. There is a reported association between low vitamin D levels and multiple health conditions including PCOS. This narrative review aims to analyze the role of vitamin D in PCOS development, use of the vitamin D in the treatment of PCOS, and the molecular basis of these observations. METHODS: A Medline and PubMed research was performed, during the years 1990-2023, using a combination of keywords on such topic. According to the author's evaluation and target, papers were identified and included for a narrative review. RESULTS: There are associations between lower levels of vitamin D and PCOS, as well as with insulin resistance, metabolic syndrome, hyperandrogenemia, metabolic and endocrine disorders as well as the onset of oxidative stress and pro-inflammatory milieu, in PCOS women. CONCLUSION: Vitamin D has a role in pathologic changes linked to PCOS. Molecular and clinical investigations which give new information about the role of vitamin D in the development of PCOS and related endocrine and metabolic disturbance are further needed.

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.

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.

Obstructed Hemivagina and Ipsilateral Renal Anomaly Syndrome: A Systematic Review about Diagnosis and Surgical Management.

Obstructed hemivagina and ipsilateral renal agenesis (OHVIRA) syndrome is a rare congenital defect of the Müllerian ducts characterized by uterus didelphys, unilateral obstructed hemivagina, and ipsilateral renal agenesis. The aim of this systematic review is to summarize the main symptoms and presentation of the OHVIRA syndrome, as well as the different types of management, fertility, and obstetrical outcomes. A comprehensive search was performed in PubMed, EMBASE, SCOPUS, and Web of Science databases since inception to May 1, 2022, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. After duplicate records removed, the search strategy retrieved 103 articles. The full texts of 73 articles further were assessed for eligibility, and 44 studies were finally included in the systematic review. The mainstay surgical treatment of OHVIRA syndrome is usually a minimally invasive vaginal approach to remove the septum. Ultrasound-guided hysteroscopic resection and laparoscopic resection of the septum have been described as alternatives. Considering the feasibility of minimally invasive approach for the management of the syndrome, laparotomy should be avoided as much as possible and considered only in selected cases.

Patterns of recurrence in FIGO stage IB1-IB2 cervical cancer: Comparison between minimally invasive and abdominal radical hysterectomy.

OBJECTIVE: Aim of our study was to evaluate whether the different laparotomic (ARH) or minimally invasive (laparoscopic and robotic) approaches (MIS) in FIGO stage IB1-IB2 cervical cancer, present different patterns of recurrence of the disease. The secondary endpoint of the study was the evaluation of the variables most involved with the risk of relapse and therefore lower DFS and OS. MATERIAL AND METHODS: The study enrolled patients with definitive histological diagnosis of squamous or adenocarcinoma stage IB1-IB2 cervical cancer who underwent minimally invasive or abdominal radical hysterectomy from 2001 to 2018. RESULTS: The study enrolled 360 patients and 59 patients (16.4 %) reported a disease relapse. The data showed that ARH group was not associated with different recurrence patterns than MIS group (p = 0.14). Moreover, there was no statistically significant difference regarding DFS (p = 0.52) and OS (p = 0.29) between the ARH group and the MIS group. CONCLUSIONS: MIS, in FIGO stage IB1-IB2 cervical cancer, is not associated with different relapse patterns compared to ARH, nor with a higher risk of distance metastasis and finally, without significant difference in term of DFS and OS. More studies are needed to determine the factors that modify the site of relapse.

Smooth Muscle Tumor of Uncertain Malignant Potential (STUMP): A Comprehensive Multidisciplinary Update.

Background and Objectives: The uterine smooth muscle tumors of uncertain malignant potential (STUMP) are tumors with pathological characteristics similar to leiomyosarcoma, but that do not satisfy histological criteria for leiomyoma. These are problematic lesions with intermediate morphologic features; thus, diagnosis and treatment are difficult. This narrative review aims to review data in the literature about STUMPs, particularly focusing on management and therapeutic options and strategies for women who desire to preserve fertility. Material and Methods: authors searched for "uterine smooth muscle tumor of uncertain malignant potential" in PubMed and Scopus databases, from 2000 to March 2023. Pertinent articles were obtained in full-text format and screened for additional references. Only articles in English language were included. Studies including full case description of patients with histopathological diagnosis of STUMP in accordance with Stanford criteria were included. Results: The median age was 43 years old. Symptoms are similar to those of leiomyomas, with a mean diameter of 8.0 cm. Total hysterectomy with or without bilateral salpingo-oophorectomy is the standard care for women if fertility desire is satisfied. Myomectomy alone can be considered for young patients. Although these tumors have not a high malignant potential, several studies described recurrence and metastases. Conclusions: STUMPs are complex uterine smooth muscle tumors, with a rare but reasoned clinical-diagnostic management. Considering the high clinical and histological complexity of these tumors, high level of expertise is mandatory.

PARP Inhibitors in Newly Diagnosed and Recurrent Ovarian Cancer.

Ovarian cancer is the most lethal gynecologic malignancy, characterized by a high death-to-incidence ratio. Platinum-based chemotherapy is the mainstay of treatment for newly diagnosed and platinum-sensitive recurrent ovarian cancer. Poly (ADP-ribose) polymerase inhibitors (PARP inhibitors) have been incorporated into the treatment strategy for ovarian cancer. PARP inhibitors showed particular benefit for patients harboring defects in DNA repair pathways. Accumulating evidence showed that PARP inhibitors provide a benefit in newly diagnosed advanced ovarian cancer, even in the absence of BRCA mutation, as reported in the PRIMA, PRIME, and ATHENA-mono trials. Interestingly, the PAOLA-1 study provides another important finding, supporting the adoption of olaparib plus bevacizumab in patients with homologous recombination deficiency. Although those results are exciting, several patients develop resistance to PARP inhibitors. Hence, new combinations are under investigation to identify new treatment strategies to overcome this resistance. Currently, researchers are focused on the possibility to adopt PARP inhibitors even in the setting of platinum-resistant disease. The present critical review aims to report the current landscape and further perspective for strengthening PARP inhibitors' effectiveness in newly diagnosed and recurrent ovarian cancer.

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.

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.

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.

Laparoscopic Management of Rudimentary Uterine Horns in Patients with Unicornuate Uterus: A Systematic Review.

INTRODUCTION: Unicornuate uterus is a rare Müllerian anomaly. Its potential association with a rudimentary uterine horn can cause a diagnostic delay. The most common consequences are pelvic pain, hematometra, and endometriosis. Diagnosis of a unicornuate uterus is usually done by imaging combining ultrasound and magnetic resonance imaging. The aim of this systematic review is to assess the role of laparoscopic approach in the management of this rare condition. METHODS: A comprehensive search was performed in PubMed, EMBASE, SCOPUS, and Web of Science databases prior to 1 May 2022 according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA). The inclusion criteria were: cases of rudimentary horn managed through laparoscopy only; laparoscopic treatment of communicating or noncommunicating uterine horn. RESULTS: The search strategy identified 45 articles. After this first screening, 37 studies were evaluated. The full text of remaining articles was examined. 35 studies were finally included in this article. All included studies were case reports, due to the rarity of this condition. Rudimentary horns were noncommunicating in all cases. CONCLUSION: The laparoscopic removal of a rudimentary uterine horn could be considered a feasible therapeutic option. An accurate preoperative evaluation is mandatory to assess anatomic variants and to select the optimal and tailored surgical approach, based also on the symptoms complained by the patient.

Radiomics and Molecular Classification in Endometrial Cancer (The ROME Study): A Step Forward to a Simplified Precision Medicine.

Molecular/genomic profiling is the most accurate method to assess prognosis of endometrial cancer patients. Radiomic profiling allows for the extraction of mineable high-dimensional data from clinical radiological images, thus providing noteworthy information regarding tumor tissues. Interestingly, the adoption of radiomics shows important results for screening, diagnosis and prognosis, across various radiological systems and oncologic specialties. The central hypothesis of the prospective trial is that combining radiomic features with molecular features might allow for the identification of various classes of risks for endometrial cancer, e.g., predicting unfavorable molecular/genomic profiling. The rationale for the proposed research is that once validated, radiomics applied to ultrasonographic images would be an effective, innovative and inexpensive method for tailoring operative and postoperative treatment modalities in endometrial cancer. Patients with newly diagnosed endometrial cancer will have ultrasonographic evaluation and radiomic analysis of the ultrasonographic images. We will correlate radiomic features with molecular/genomic profiling to classify prognosis.

Hysterectomy: Let's Step Up the Ladder of Evidence to Look Over the Horizon.

Hysterectomy is one of the most common non-obstetric gynecological surgical procedures carried out in Western countries [...].

Fibroid Removal after Myomectomy: An Overview on the Problems of Power Morcellation.

The authors reviewed uterine fibroid (UF) morcellation and its potential consequences, notably a hypothetical spread and dissemination of occult uterine leiomyosarcoma (LMS) tissue, evaluating the effect of laparoscopic versus open myomectomies with and without morcellation on patients' outcomes, as well as related medical-legal issues. MEDLINE and PubMed search was performed for the years 1990-2021, using a combination of keywords on this topic. Relevant articles were identified and included in this narrative review. There is an individual risk, for all patients, for LMS diagnosis after myomectomy. However, the risk for occult LMS diagnosis during a laparoscopic myomectomy is generally reduced when the guidelines of scientific societies are followed, with an overall benefit from the laparoscopic approach with morcellation in appropriate cases. Gynecological societies do not ban morcellation and laparoscopic hysterectomy/myomectomy per se, but recommend their use on the basis of the patients' clinical characteristics. It is suggested for gynecologists to provide detailed information to patients when obtaining an informed consent for open or laparoscopic hysterectomy/myomectomy. A detailed preoperative assessment of patients and the risk benefit ratio of laparoscopic morcellation of uterine mass could overcome the "a priori" banning of the morcellation technique.

Advances on Prevention and Screening of Gynecologic Tumors: Are We Stepping Forward?

According to 2020 comprehensive global cancer statistics published by the International Agency for Research on Cancer, gynecologic malignancies accounted overall for 16 [...].

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.

Fractional Co2 laser for vulvo-vaginal atrophy in gynecologic cancer patients: A valid therapeutic choice? A systematic review.

INTRODUCTION: One of the most common adverse events reported by gynecological cancer survivors with spontaneous or iatrogenic menopause is vulvo-vaginal atrophy (VVA). An increasing number of women have this kind of discomfort related to the menopause induced by different cancer therapies. In this regard, fractional CO2 laser may be a valid therapeutic choice for these patients. METHODS: We performed a literature search of PubMed, EMBASE, SCOPUS and Web of Science databases with search terms of laser CO2 treatment of vulvovaginal atrophy and gynecologic cancer survivors and reviewed major US Society Guidelines to create this narrative review of this topic. Breast, ovarian endometrial and cervical cancers were included. RESULTS: Nine studies were included. Fractional CO2 laser improves clinical symptoms and sexual function, in terms of VHI (vaginal health index) and FSFI (female sexual function index). Non severe adverse event occurred. CONCLUSION: According to the best evidence available, fractional CO2 laser treatment for VVA is an effective and safe therapeutic option for gynecological cancer survivors, improving sexual life and quality of life (QoL).

Age-Adjusted Charlson Comorbidity Index Predicts Survival in Endometrial Cancer Patients.

OBJECTIVE: Comorbidity scores are increasingly used to reduce potential confounding in oncologic research. This is of paramount importance in endometrial cancer (EC) since it is characterized by quite indolent behavior. Here, we aim to evaluate the impact of various comorbidities and concurrent medications used on survival outcomes, adopting the age-adjusted Charlson comorbidity index (A-CCI). DESIGN: This is an observational study. Charts of 257 EC patients were retrieved. METHODS: We retrospectively evaluated data of patients who underwent surgical treatment for EC. A-CCI was calculated by summing the weighted comorbidities and age of each patient. A binomial value was assigned to different comorbidities and different drugs. Oncologic outcomes were evaluated using Cox proportional hazard models adjusted for age. RESULTS: A-CCI ≥3 correlated with more aggressive tumor features (47.6% vs. 26.8%, p = 0.001), higher risk of recurrence (29.7% vs. 11.6%, p = 0.001), death (20.7% vs. 7.1%, p = 0.002), and death due to disease (16.6% vs. 6.3%, p = 0.012). Considering comorbidities and drugs at parsimonious multivariable analysis model: cardiac disease, liver disease, and proton pump inhibitors (PPIs) use were independent predictors of disease-free survival. Cardiac disease, autoimmune disease, and PPIs use were independent predictors of overall survival. Diabetes was the only independent predictor for cause-specific survival. LIMITATIONS: The major limitation of the present study is its retrospective nature and the relatively small sample size that limit the possibility to have firm conclusions. CONCLUSION: Patients with EC are characterized by a high burden of comorbidities. Comorbidities are associated directly with survival outcomes. Further attention is needed to improve the active management of comorbidities soon after EC treatments. Interventional studies are needed to improve patients' outcomes.