Risk of endometrial malignancy in women treated for breast cancer: the BLUSH prediction model - evidence from a comprehensive multicentric retrospective cohort study.

OBJECTIVE: This study aimed to evaluate characteristics of endometrial surveillance in women treated for breast cancer to build a clinical prediction model. DESIGN: A multicentric retrospective cohort study was conducted at two tertiary-care university hospitals from January 2020 to June 2023. Perimenopausal and postmenopausal women treated for breast cancer were categorized into two groups: patients with and without diagnosis of endometrial malignancy (endometrial carcinoma) or premalignancy (atypical endometrial hyperplasia). Characteristics of breast cancer and ultrasonographic and hysteroscopic examinations were compared. A prediction model for endometrial malignancy was built using logistic regression. Predictive accuracy was assessed using the receiver operating characteristic (ROC) curve and goodness of fit using the Hosmer-Lemeshow test. RESULTS: One hundred and thirty-two (28 with premalignancy or malignancy and 104 without malignancy) women were analyzed. A nomogram was produced for prediction model development utilizing the presence and duration in months of abnormal uterine (BL)eeding, ultrasound (US) vascular pattern and echogenicity and (H)ysteroscopic appearance of endometrium (BLUSH) as determined by logistic regression. Sensitivity and specificity were 79.17% and 95.19%, respectively, with an area under ROC curve of 0.965, indicating good accuracy. Good goodness of fit and prediction stability were indicated by the calibration curve and Hosmer-Lemeshow test (χ2 = 26.36; p = 0.999). CONCLUSIONS: Breast cancer survivors undergoing endometrial surveillance might benefit from a potentially useful prediction model based on hysteroscopic appearance, ultrasonographic uniformity of endometrium, Doppler flow and presence of abnormal uterine bleeding.

The association between fetal Doppler and uterine artery blood volume flow in term pregnancies: a pilot study.

PURPOSE: To investigate the relationship between uterine artery blood volume flow and fetal Doppler indices in term pregnancies. MATERIALS AND METHODS: A prospective observational study in a tertiary-care university hospital was performed between December 2021 and May 2022. We included only term pregnancies that received accurate ultrasound scans until a week before the birth. The uterine artery (UtA) diameter and UtA volume blood flow were estimated and recorded. The volume of each artery was summed to obtain the total uterine artery volume blood flow (QUtA). The following fetal Doppler indices were evaluated: Umbilical artery (UA), middle cerebral artery (MCA), ductus venosus (DV), and cerebroplacental ratio (CPR). Linear regression analysis was performed to investigate the relationship between the QUtA and the fetal Doppler indices. RESULTS: 49 pregnancies were included. The UA pulsatility index (PI) analysis showed a significant association with QUtA (r2=0.40, p=0.01), demonstrating a decrease of the UA PI when the QUtA increased. The same relationship was noted between the UtA mean PI and QUtA (r2=0.41, p=0.005). A weak correlation between the newborn weight and the QUtA was also noted (r2=0.31, p=0.048), with an elevated newborn weight when the QUtA was high. CONCLUSION: This study showed that UA, UtA PI, and birth weight seem to be linked to QUtA. QUtA had an inverse correlation with UA and UtA PI. In addition, increasing the QUtA showed a linear increase in fetal birth weight. These findings could be helpful in high-risk pregnancy management, but additional research is needed to identify how QUtA in the third trimester impacts labor and fetal outcomes.

Stable Ozonides plus Vitamin E Acetate (Ozoile) for Treatment of Genitourinary Syndrome.

Background and Objectives: Genitourinary syndrome, previously defined as vulvovaginal atrophy, manifests with signs and symptoms deriving from estrogen diminution in the female genitourinary tract. Stable ozonides are derivatives of artemisinin found to be stable against strong basic and acidic conditions. Vitamin E is an important antioxidant diminishing the output of reactive oxygen species in the oxidation of fats and the emanation of free radicals, reducing cellular injury and aging. The primary aim of the present study was to assess the positive effects of an ozonide plus a vitamin E acetate-based compound (Ozoile) on genitourinary syndrome symptom relief after a maximum of 20 days of treatment. Materials and Methods: The inclusion criteria for patients' enrollment were women of child-bearing age or in menopause reporting genitourinary syndrome's related symptoms, such as pain, burning, a bad smell, dyspareunia, dryness, itching, bleeding, and nervousness. The exclusion criteria were Sjogren's syndrome and patients administered retinoic acid, an agent that causes mucosal dryness. Participants completed a questionnaire before and after 20 days of treatment. Results: The incidence of pain decreased from 16.7% to 11.8% (p-value < 0.0001). In addition, the mean symptom intensity decreased from 2.10 to 0.87 (p-value < 0.0001). Dryness was the most frequent pre-treatment symptom and decreased from 85.5% to 53.8% (p-value < 0.0001) (mean: 2.21 vs. 0.90; p-value < 0.0001). Conclusions: Ozoile was effective in reducing most gynecologic symptoms related to genitourinary syndrome. However, further studies are needed to compare its effect with other standards of care.

MicroRNA Expression in Endometrial Cancer: Current Knowledge and Therapeutic Implications.

Background and Objectives: An extracellular vesicle is part of a class of submicron particles derived from cells, mediating cellular crosstalk through microRNA (miRNA). MiRNA is a group of RNA molecules, each of which consists of 15-22 nucleotides and post-transcriptionally modulates gene expression. The complementary mRNAs-onto which the miRNAs hybridize-are involved in processes such as implantation, tumor suppression, proliferation, angiogenesis, and metastasis that define the entire tumor microenvironment. The endometrial biopsy is a standard technique used to recognize cellular atypia, but other non-invasive markers may reduce patient discomfort during the use of invasive methods. The present study aims to examine the distribution and the regulation of the differentially expressed miRNAs (DEMs) and EV-derived substances in women with endometrial cancer. Materials and Methods: We systematically searched the PubMed, EMBASE, Scopus, Cochrane Library, and ScienceDirect databases in April 2023, adopted the string "Endometrial Neoplasms AND Exosomes", and followed the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We selected all the studies that included patients with endometrial cancer and that described the regulation of miRNA molecules in that context. The differences in molecule expression between patients and controls were evaluated as significant when the proteins had a fold change of ±1.5. Results: Seventeen records fulfilled the inclusion criteria: a total of 371 patients and 273 controls were analyzed. The upregulated molecules that had the widest delta between endometrial cancer patients and controls-relative expression ≥ 1 > 3 log2(ratio)-were miR-20b-5p, miR-204-5p, miR-15a-5p, and miR-320a. In particular, miR-20b-5p and miR-204-5p were extracted from both serum and endometrial specimens, whereas miR-15a-5p was only isolated from plasma, and miR-320a was only extracted from the endometrial specimens. In parallel, the most downregulated miRNA in the endometrial cancer patients compared to the healthy subjects was miR-320a, which was found in the endometrial specimens. Conclusions: Although their epigenetic regulation remains unknown, these upregulated molecules derived from EVs are feasible markers for the early detection of endometrial cancer. The modulation of these miRNA molecules should be assessed during different treatments or if recurrence develops in response to a targeted treatment modality.

Fertility-Sparing Treatment for Early-Stage Cervical Cancer ≥ 2 cm: Can One Still Effectively Become a Mother? A Systematic Review of Fertility Outcomes.

BACKGROUND: Fertility-sparing treatments (FSTs) have played a crucial role in the management of early-stage cervical cancer (ECC); however, there is currently no standard of care for women with ECC ≥ 2 cm who wish to preserve their fertility. The current orientation of the scientific community comprises upfront surgical techniques and neoadjuvant chemotherapy (NACT) followed by minor surgery such us conization. However these approaches are not standardized. This systematic review aimed to collect the evidence in the literature regarding the obstetric outcomes of the different techniques for applying FSTs in ECC ≥ 2 cm. METHODS: A systematic review was performed in September 2022 using the Pubmed and Scopus databases, from the date of the first publication. We included all studies containing data regarding pregnancy, birth, and preterm rates. RESULTS: Fifteen studies fulfilled the inclusion criteria, and 352 patients were analyzed regarding fertility outcomes. Surgery-based FST showed the pregnancy rate (22%), birth rate (11%), and preterm rate (10%). Papers regarding FST using the NACT approach showed a pregnancy rate of 44%, with a birth rate of 45% in patients who managed to get pregnant. The preterm rate amounted to 44%, and pregnancy rates and birth rates were significantly different between the two groups (p < 0.001). CONCLUSION: Fertility preservation in patients with ECC > 2 cm is challenging. The endpoint for evaluating the best treatment should include oncological and fertility outcomes together. From this prospective, NACT followed by less radical surgery could be a reasonable compromise.

Two clinical case reports of embryonic mosaicism identified with PGT-A persisting during pregnancy as true fetal mosaicism.

The health risks associated with transferring embryos classified as mosaic by preimplantation genetic testing for aneuploidies (PGT-A) are currently unknown. Such embryos produce PGT-A results indicating the presence of both euploid and aneuploid cells and have historically been deselected from transfer and grouped with uniformly aneuploid embryos as 'abnormal'. In recent years, numerous groups have reported the intentional transfer of mosaic embryos in the absence of uniformly euploid embryos, largely observing births of seemingly healthy babies. However, it remains to be understood whether the embryonic mosaicism invariably becomes resolved during the ensuing pregnancy, or whether the placenta and/or fetal tissues retain aneuploid cells, and if so to what potential clinical effect. Here, we report two cases of mosaicism persisting from the embryonic stage to the established pregnancy. Case 1 involved an embryonic low-level segmental mosaic loss in Chromosome (Chr) 1, which was confirmed in amniocentesis as well as in brain tissue of the products of conception. This pregnancy was terminated due to the chromosomal pathologies associated with 1p36 deletion syndrome, such as severe intellectual disability. Case 2 involved a low-level mosaic Chr 21 trisomy, which was confirmed with chorionic villus sampling and amniocentesis. The ensuing pregnancy was terminated after ultrasound identification of severe abnormalities in the placenta and fetus. Together, these two cases should be taken into account for risk-benefit assessments of prospective mosaic embryo transfers.

Consensus on the Gemelli terminology of surgical anatomy for radical hysterectomy.

OBJECTIVES: To report on a consensus survey of experts on a recently proposed simplified nomenclature of surgical anatomy of the female pelvis for radical hysterectomy. The aim was to standardize surgical reports in clinical practice and understanding of the techniques in future surgical literature. METHODS: The anatomical definitions were included in 12 original images taken at the time of cadaver dissections. Denomination of the corresponding anatomical structures was based on the nomenclature recently proposed by the same team. A three step modified Delphi method was used to establish consensus. After a first round of online survey, the legends of the images were amended to respond to the comments of the experts. Second and third rounds were performed. Consensus was defined as a yes vote to each question regarding the images provided, and 75% was defined as the cut-off for agreement. Comments justifying the no votes were taken into account to amend the set of images and legends. RESULTS: A group of 32 international experts from all continents was convened. Consensus exceeded 90% for all five images documenting the surgical spaces. Consensus ranged between 81.3% and 96.9% for the six images documenting the ligamentous structures surrounding the cervix. Finally, consensus was lowest (75%) for the most recently defined denomination of the broad ligament (lymphovascular parauterine tissue or upper lymphatic pathway). CONCLUSION: Simplified anatomic nomenclature is a robust tool to describe the surgical spaces of the female pelvis. The simplified definition of ligamentous structures reached a high level of consensus, even if the terms paracervix (instead of lateral parametrium), uterosacral ligament (replaced by rectovaginal ligament), vesicovaginal ligament, and lymphovascular parauterine tissue remain matters of debate.

Liquid Biopsy in Endometriosis: A Systematic Review.

Despite laparoscopy being a standardized option to diagnose pelvic endometriotic implants, non-invasive biomarkers are necessary to avoid the discomfort of invasive procedures. Recent evidence suggests a potential role of microRNAs (miRNAs) as feasible biomarkers for the early diagnosis of endometriosis. Following the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, we systematically searched PubMed, EMBASE, Scopus, Cochrane Library, and Science Direct in January 2023. We provided no restriction on the country and year of publication, and considered English published articles. We selected studies including patients with endometriosis and describing miRNA regulation in the context of endometriosis. Overall, 45 studies fulfilled the inclusion criteria, and 2045 patients with endometriosis and 1587 controls were screened. Patients were analyzed concerning miRNAs expression and sources, stage of disease, and symptoms, and compared to controls. Among DEMs, the ones with the widest delta between endometriosis patients and controls-Relative Expression ≥ 4 Log2(ratio)-were miR-145, miR-191, miR-195, miR-21-5p, miR-106b-5p, miR-195-5p, miR-451a, miR-200c, miR-20a-5p, and miR-15a-5p. Although the epigenetic regulation is partially unclear, miRNAs are valid biomarkers to diagnose endometriotic lesions in symptomatic and non-symptomatic women. MiRNAs modulation should be clarified, especially during therapies or relapse, to plan targeted management protocols.

Robotic Single-Site Hysterectomy in Gynecologic Benign Pathology: A Systematic Review of the Literature.

Background and objectives: Total hysterectomy is one of the most common gynecologic surgical procedures and it is mainly performed for benign pathologies. The introduction of robotic single-site surgery (RSS) as an acceptable alternative to laparoendoscopic surgery combines the advantages of robotics with the aesthetic result of a single incision. This study aims to review the existing literature on a single-site robotic hysterectomy in patients with benign pathologies and verify its safety and feasibility. Materials and Methods: Following the recommendations in the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement, FP and AR systematically screened the PubMed, Embase, and Scopus databases. No temporal or geographical limitation was discriminatory. Studies containing data about feasibility and safety were included. Results: From 219, only eight studies met the inclusion criteria, and a total of 212 patients were included with a mean patient age of 45.42 years old (range 28-49.5 years old) and a mean BMI of 25.74 kg/m2 (range 22-28.5 kg/m2). The mean presurgical time, including port placement and docking time, was 15.56 (range 3-30) minutes. Mean console time was reported in six studies and is 83.21 min (range 25-180 min). The mean operative time is 136.6 min (range 60-294 min) and the mean blood loss is 43.68 mL (range 15-300 mL). Only two patients in the total analyzed had intraoperative complications and no conversion to LPT occurred. The median hospital stay was 1.71 days (range 0.96-3.5 days). The postoperative complication rate was estimated at 1.4% (vaginal bleeding). Conclusions: Our review supports the safety and feasibility of robotic single-site hysterectomy for benign gynecological diseases.

Mininvasive Cytoreduction Surgery plus HIPEC for Epithelial Ovarian Cancer: A Systematic Review.

Background and objectives: The Gold-Standard treatment for Advanced Epithelial Ovarian Cancer remains cytoreductive surgery followed by systemic chemotherapy. Surgery can be performed either by an open or minimally invasive approach (MIS), although the former remains the most widely used approach. Recently, Van Driel et al. proved that adding 100 mg/m2 of Cisplatin in Hyperthermic Intraperitoneal Chemotherapy (HIPEC) at Interval Debulking Surgery (IDS) gives a disease-free survival (DFS) advantage. Similarly, Gueli-Alletti et al. demonstrated how the MIS approach is feasible and safe in IDS. Moreover, Petrillo et al. reported pharmacokinetic profiles with a higher chemotherapy concentration in patients undergoing HIPEC after MIS compared with the open approach. Therefore, the following review investigates the oncological and clinical safety consequences of the association between MIS and HIPEC. Methods: Following the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, we systematically searched the PubMed and Scopus databases in April 2022. Studies containing data about oncological and safety outcomes were included. We registered the Review to the PROSPERO site for meta-analysis with protocol number CRD42022329503. Results: Five studies fulfilled inclusion criteria. 42 patients were included in the review from three different Gynecological Oncological referral centers. The systematic review highlighted a Recurrence Rate ranging between 0 and 100%, with a 3-year Platinum-Free Survival between 10 and 70%. The most common HIPEC drug was Cisplatin, used at concentrations between 75 and 100 mg/m2 and at an average temperature of 42 °C, for 60 to 90 min. Only 1 Acute Kidney Insufficiency has been reported. Conclusions: The scarcity of clinical trials focusing on a direct comparison between MIS and the open approach followed by HIPEC in EOC treatment does not make it possible to identify an oncological advantage between these two techniques. However, the safety profiles shown are highly reassuring.

Tertiary Cytoreduction for Isolated Lymphnode Recurrence (ILNR) Ovarian Cancer in a BRCA2 Mutated Patient: Our Experience and Prevalence of BRCA 1 or 2 Genes Mutational Status in ILNR.

We report the case of a tertiary cytoreductive surgery for isolated lymph-node recurrence (ILNR) in a 54-years old Brest cancer 2 (BRCA 2) mutated patients, with a personal history of ovarian cancer previously treated elsewhere. She was admitted to our department for a suspected isolated lymph-nodal pelvic recurrence. A positron emission tomography acquisition with contrast enhanced computed tomography (PET-CT) scan revealed an increased node at the level of the right external iliac (SUV 6.9) in correspondence with the obturator nerve, which was confirmed by transvaginal ultrasound. Since the recurrence was in a single site and the patient had previously undergone three lines of chemotherapy and maintenance with Poly(ADP-ribose) polymerase (PARP) inhibitors, we decided to perform tertiary cytoreductive surgery by minimally invasive laparoscopic approach. After gradual and careful isolation of the obturator nerve, lumbo-sacral trunk and venous vessels afferent to the external and internal iliac vein, the suspected node has been removed. No intra- and postoperative complications occurred. The patient was discharged three days after procedure. We decided to quarterly follow-up; actually, after 16 months no recurrence was detected. Several studies have reported ILNR as a unique clinical disease with low growth rate and less chemosensitivity; this can lead to considered ILNR more susceptible to take advantage of surgical treatment, even in case of second or third recurrence. The BRCA mutational status seems to play a role in the decision-making process in the approach to patients with platinum sensitive relapse of ovarian cancer or in specific isolated forms of recurrence such as the hepatic one. However, data on frequency and prognostic impact of BRCA gene mutation in ILNR are very limited. In this article we investigated the role of BRCA 1 or 2 mutational status in this rare pattern of recurrence according to more recent advances in literature.

Correlations between Gut Microbial Composition, Pathophysiological and Surgical Aspects in Endometriosis: A Review of the Literature.

Background and Objectives: Endometriosis is an estrogen-dependent, inflammatory, gynecological disorder represented by the migration of endometrial tissue outside the uterus. It can manifest through gynecological and gastrointestinal (GI) signs. Given the hormonal imbalances in endometriosis and the effect of microbiota on immune dysfunction, it has been thought that the human microbiome may play a role in its pathogenesis, acting differently before and after laparotomy. The aim of this review is to establish whether there is an interaction between endometriosis and gut microbial composition. Materials and Methods: We aimed to review available literature by systematically searching five databases: PubMed, EMBASE, Scopus, Cochrane Library, and ScienceDirect. We included records describing gut microbiota in the context of endometriosis-observing PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines-to recognize the presence of disease by the expression of bacterial taxa-based on 16S ribosomal RNA gene sequencing analysis. Results: Among 10 studies selected, there were four review articles and six clinical trials. The latter identified significant differences at a genus level in increased Prevotella, Blautia, and Bifidobacterium and decreased Paraprevotella, Ruminococcus, and Lachnospira (p < 0.05). In patients undergoing abdominal hysterectomy, Proteobacteria phylum increased from 34.36% before surgery to 54.04% after surgery (p < 0.05). Conclusions: Although scientific literature reports different characterizations of intestinal microbiota in endometriotic patients, further evidence is needed to develop new diagnostic-therapeutic strategies, for example, administration with probiotics before surgery.

The Efficiency of Sclerotherapy for the Management of Endometrioma: A Systematic Review and Meta-Analysis of Clinical and Fertility Outcomes.

Background and Objectives: The most common sites of implantation of endometriotic tissue are the ovaries. Endometriomas are present in most cases of endometriosis (up to 45%). Although laparoscopic cystectomy is the standard of care in endometrioma, new strategies have been set up to minimize iatrogenic injuries to ovarian tissue. Sclerotherapy consists of injecting alcohol into the endometrioma to denature the amino acidic components of its pseudocapsule. The aim of this systematic review and meta-analysis is to compare clinical and pregnancy outcomes in surgery and sclerotherapy. Materials and Methods: Following the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, we systematically searched PubMed, EMBASE, Scopus, Google Scholar, Clinical-trials.gov, and the Cochrane Central Register of Controlled Trials databases in January 2023, adopting the string "Endometriosis and sclerotherapy". We made no limitations on the country and year of publication. We included the studies containing Success Rate (SR), Recurrence Rate (RR), Pregnancy Rate (PR) before and after the procedure. We used comparative studies for meta-analysis. Results: A total of 29 studies fulfilled inclusion criteria, 7 retrospective observational studies and 22 prospective studies. Eight comparative studies were enrolled in meta-analysis. Patients were analyzed concerning the number of recurrences and pregnancies in surgery, and compared with sclerotherapy. Four studies showed SR > 80.0%, and only two had SR < 80.0%, of which one consisted of tetracycline instillation. Only 1 study had 100% PR, the other 14 reported PR > 30.0%, whereas six had PR < 30.0%, of which one showed 0.0% PR with ethanol injection at two-thirds of the cyst fluid volume. Meta-analysis highlighted a non-significant lower incidence of recurrence in the surgery group compared to the sclerotherapy group (p = 0.87). In parallel, the surgery group showed a non-significant better PR than the sclerotherapy group (p = 0.08). Conclusions: Despite sclerotherapy having a minor incidence of postoperative complications compared to surgery, the latter is associated with a lower RR and better PR. However, those data assert the importance of a targeted therapy according to preoperative conditions and reproductive potential.

Meigs Syndrome and Elevated CA-125: Case Report and Literature Review of an Unusual Presentation Mimicking Ovarian Cancer.

Background and Objectives: Meigs syndrome is represented by a benign adnexal tumor, ascites, and hydrothorax. Even though the ovarian mass is often characterized by a fibroma-like origin, cancer antigen-125 (CA-125) serum levels could be elevated as in the development of ovarian cancer. Here, we present the case of a patient with Meigs syndrome and increased CA-125. Materials and Methods: We performed systematic research for articles including similar cases in PubMed, EMBASE, and Scopus in February 2023, adopting the string of idioms: "Meigs syndrome AND Cancer antigen 125", and following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Results: Eligible records were 25. Hydrothorax was right-sided in 10 cases over 25; left-sided in two patients over 25. Concerning ascites, two patients showed more than 6 L of ascitic fluid, whereas three patients had 6 L or less. CA-125 elevation ranged from 149 IU/mL to 3803 IU/mL. Adnexal mass histotypes were: struma ovarii (12 cases), thecomas (two cases), fibrothecomas (five cases), fibromas (five cases), and one sclerosing stromal tumor (SST). Conclusions: In postmenopausal women with elevated CA-125 serum levels and an adnexal mass suspicious for malignancy at ultrasound (US), ascites and pleural effusion, surgery, and histopathological examination are necessary. MS is a diagnostic option, with an excellent prognosis after exeresis of the mass.

Exploring Surgical Strategies for Uterine Fibroid Treatment: A Comprehensive Review of Literature on Open and Minimally Invasive Approaches.

Background and Objectives: Uterine myomas represent one of the most prevalent pathologies affecting the female population. These benign neoplasms originate from the smooth muscular cells of the uterus, and they can be either single or multiple. Often associated with debilitating symptoms such as pelvic heaviness, pain, constipation, and urinary dysfunctions, the surgical management of myomectomy exhibits considerable variability. This diversity in approaches is influenced by factors such as the number and size of myomas, the patient's age, and overall clinical conditions. This study aims to elucidate and compare the advantages and disadvantages of different surgical approaches, specifically endoscopic procedures versus open surgery, providing valuable insights for clinical decision making. Materials and Methods: A comprehensive bibliographic search spanning from 2013 to 2023 was systematically conducted across databases including Medline, Embase, the Cochrane Database of Systematic Reviews, and ClinicalTrials.gov. The search utilized keywords such as "myomectomy laparoscopic and open", "myomectomy open and minimally invasive", "myomectomy open and laparoscopic", and "myomectomy open vs. laparoscopic." The research methodology, along with predetermined inclusion and exclusion criteria, was established prior to the search, ensuring a systematic and rigorous approach. Subsequently, data analysis was carried out. Results: Following the study selection process, 25 articles met the eligibility criteria for inclusion in this analysis. The average numbers of myomas were 3.7 (ranging from 1 to 13.7) and 5.4 (ranging from 1 to 13.5) for the minimally invasive surgery and open surgery groups, respectively. In terms of myoma size, the total averages across studies were 7 cm (ranging from 4.8 to 14) for the minimally invasive group and 8 cm (ranging from 3.9 to 11.2) for the open surgery group. The average pregnancy and delivery rates were 29.7% (ranging from 1.8 to 100) for the minimally invasive group and 28.5% (ranging from 1.8 to 100) for the open surgery group. Regarding complications, the average rate was 14.2% (ranging from 0 to 50) for the endoscopic group and 22.3% (ranging from 0 to 60.3) for the laparotomic group. Conclusions: In conclusion, a critical factor influencing the choice of surgical approach is primarily the size and quantity of fibroids. The mini-laparotomic approach emerges as a viable alternative to endoscopy, demonstrating favorable surgical outcomes and aesthetic results. Interestingly, the type of surgical procedure appears to have no significant impact on the pregnancy rate.

Fertility-Sparing Treatment for Early-Stage Cervical Cancer ≥ 2 cm: A Problem with a Thousand Nuances-A Systematic Review of Oncological Outcomes.

BACKGROUND: Fertility-sparing treatments (FSTs) have played a crucial role in the management of early-stage cervical cancer (ECC). The guidelines have recognized various approaches, depending on the tumor stage and other risk factors such as histotype and lymphovascular positivity. Much more debate has centered around the boundary within which these treatments should be considered. Indeed, these are methods to be reserved for ECC, but tumor size may represent the most significant limitation. In particular, there is no consensus on the strategy to be adopted in the case of ECC ≥ 2 cm. Therefore, this systematic review was to collect the literature evidence regarding the management of these patients. METHODS: Following the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, we systematically searched the Pubmed and Scopus databases was conducted in April 2022, from the date of the first publication. We made no limitation on the country. We included all studies containing data on disease-free survival, overall survival, recurrence rate (RR), or complete response rate (CRR) to chemotherapy. RESULTS: Twenty-six studies fulfilled the inclusion criteria, and 691 patients were analyzed regarding FST. Surgery-based FST showed an RR of between 0 and 42.9%, which drops to 12.9% after excluding the vaginal or minimally invasive approaches. Furthermore, papers regarding FST based on the neoadjuvant chemotherapy (NACT) approach showed a CRR of between 21.4 and 84.5%, and an RR of between 0 and 22.2% CONCLUSION: This paper focused on the significant heterogeneity present in the clinical management of FST of ECC ≥ 2 cm. Nevertheless, from an oncological point of view, approaches limited to the minimally invasive or vaginal techniques showed the highest RR. Vice versa, the lack of standardization of NACT schemes and the wealth of confounders to be attributed to the histological features of the tumor make it difficult, if not impossible, to set a standard of treatment.

Laparo-assisted vaginal radical hysterectomy as a safe option for minimal invasive surgery in early stage cervical cancer: A systematic review and meta-analysis.

BACKGROUND: Radical hysterectomy and pelvic lymphadenectomy are considered the standard treatment for early-stage cervical cancer (ECC). Minimal Invasive approach to this surgery has been debated after the publication of a recent prospective randomized trial (Laparoscopic Approach to Cervical Cancer, LACC trial). It demonstrated poorer oncological outcomes for Minimal Invasive Surgery in ECC. However, the reasons are still an open debate. Laparo-Assisted Vaginal Hysterectomy (LAVRH) seems to be a logical option to Abdominal Radical Hysterectomy (ARH). This meta-analysis has the aim to prove it. METHODS: Following the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, the Pubmed database and Scopus database were systematically searched in January 2022 since early first publications. No limitation of the country was made. Only English article were considered. The studies containing data about Disease-free Survival (DFS) and/or Overall Survival (OS) and/or Recurrence Rate (RcR) were included. RESULTS: 18 studies fulfilled inclusion criteria. 8 comparative studies were enrolled in meta-analysis. Patients were analyzed concerning surgical approach (Laparo-Assisted Vaginal Radical Hysterectomy) and compared with ARH Oncological outcomes such as DFS and OS were considered. 3033 patiets were included. Meta-analysis highlighted a non-statistic significant difference between LARVH and ARH (RR 0.82 [95% CI 0.55-1.23] p = 0.34; I2 = 0%; p = 0.96). OS was feasible only for 3 studies (RR 1.14 [95% CI 0.28-4.67] p = 0.43; I2 = 0 p = 0.86). Data about the type of recurrences (loco-regional vs distant) were collected. CONCLUSION: LARVH does not appear to affect DFS and OS in ECC patients. The proposed results seem to be comparable with the open approach group of the LACC trial, which today represents the reference standard for the treatment of this pathology. More studies will be needed to test the safety and efficacy of LARVH in the ECC.

Laparo-assisted vaginal radical hysterectomy as a safe option for Minimal Invasive Surgery in early stage cervical cancer: A systematic review and meta-analysis.

BACKGROUND: Radical hysterectomy and pelvic lymphadenectomy are considered the standard treatment for early-stage cervical cancer (ECC). Minimal Invasive approach to this surgery has been debated after the publication of a recent prospective randomized trial (Laparoscopic Approach to Cervical Cancer, LACC trial). It demonstrated poorer oncological outcomes for Minimal Invasive Surgery in ECC. However, the reasons are still an open debate. Laparo-Assisted Vaginal Hysterectomy (LAVRH) seems to be a logical option to Abdominal Radical Hysterectomy (ARH). This meta-analysis has the aim to prove it. METHODS: Following the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, the Pubmed database and Scopus database were systematically searched in January 2022 since early first publications. No limitation of the country was made. Only English article were considered. The studies containing data about Disease-free Survival (DFS) and/or Overall Survival (OS) and/or Recurrence Rate (RcR) were included. RESULTS: 19 studies fulfilled inclusion criteria. 9 comparative studies were enrolled in meta-analysis. Patients were analyzed concerning surgical approach (Laparo-Assisted Vaginal Radical Hysterectomy) and compared with ARH Oncological outcomes such as DFS and OS were considered. 3196 patiets were included for the review. Meta-analysis of 1988 0f them highlighted a non-statistic significant difference between LARVH and ARH (RR 0.8 [95% CI 0.55-1.16] p = 0.24; I2 = 0%; p = 0.98). OS was feasible only for 4 studies (RR 0.84 [95% CI 0.23-3.02] p = 0.79; I2 = 0 p = 0.44). Sub-analysis for tumor with a maximum diameter greater than 2 cm was performed. Data about the type of recurrences (loco-regional vs distant) were collected. CONCLUSION: LARVH does not appear to affect DFS and OS in ECC patients. The proposed results seem to be comparable with the open approach group of the LACC trial, which today represents the reference standard for the treatment of this pathology. More studies will be needed to test the safety and efficacy of LARVH in the ECC.

The Oncological Implication of Sentinel Lymph Node in Early Cervical Cancer: A Meta-Analysis of Oncological Outcomes and Type of Recurrences.

Background and Objectives: Pelvic lymphadenectomy has been associated with radical hysterectomy for the treatment of early Cervical Cancer (ECC) since 1905. However, some complications are related to this technique, such as lymphedema and nerve damage. In addition, its clinical role is controversial. For this reason, the sentinel lymph node (SLN) has found increasing use in clinical practice over time. Oncologic safety, however, is debated, and there is no clear evidence in the literature regarding this. Therefore, our meta-analysis aims to schematically analyze the current scientific evidence to investigate the non-inferiority of SLN versus PLND regarding oncologic outcomes. Materials and Methods: Following the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, we systematically searched the PubMed and Scopus databases in June 2022 since their early first publications. We made no restrictions on the country. We considered only studies entirely published in English. We included studies containing Disease-Free Survival (DFS), Overall Survival (OS), Recurrence Rate (RR), and site of recurrence data. We used comparative studies for meta-analysis. We registered this meta-analysis to the PROSPERO site for meta-analysis with protocol number CRD42022316650. Results: Twelve studies fulfilled inclusion criteria. The four comparative studies were enrolled in meta-analysis. Patients were analyzed concerning Sentinel Lymph Node Biopsy (SLN) and compared with Bilateral Pelvic Systematic Lymphadenectomy (PLND) in early-stage Cervical Cancer (ECC). Meta-analysis highlighted no differences in oncological safety between these two techniques, both in DFS and OS. Moreover, most of the sites of recurrences in the SLN group seemed not to be correlated with missed lymphadenectomy. Conclusions: Data in the literature do not seem to show clear oncologic inferiority of SLN over PLND. On the contrary, the higher detection rate of positive lymph nodes and the predominance of no lymph node recurrences give hope that this technique may equal PLND in oncologic terms, improving its morbidity profile.

Ovarian Drilling: Back to the Future.

Polycystic ovary syndrome (PCOS) is the leading cause of anovulatory infertility. The complex metabolic dysregulation at the base of this syndrome often renders infertility management challenging. Many pharmacological strategies have been applied for the induction of ovulation with a non-negligible rate of severe complications such as ovarian hyperstimulation syndrome and multiple pregnancies. Ovarian drilling (OD) is currently being adopted as a second-line treatment, to be performed in case of medical therapy. Laparoscopic ovarian drilling (LOD), the contemporary version of ovarian wedge resection, is considered effective for gonadotropins in terms of live birth rates, but without the risks of iatrogenic complications in gonadotropin therapy. Its endocrinal effects are longer lasting and, after the accomplishment of this procedure, ovarian responsiveness to successive ovulation induction agents is enhanced. Traditional LOD, however, is burdened by the potential risks of iatrogenic adhesions and decreased ovarian reserve and, therefore, should only be considered in selected cases. To overcome these limits, novel tailored and mini-invasive approaches, which are still waiting for wide acceptance, have been introduced, although their role is still not well-clarified and none of them have provided enough evidence in terms of efficacy and safety.