The Role of Adjuvant Therapy for the Treatment of Micrometastases in Endometrial Cancer: A Systematic Review and Meta-Analysis.

Endometrial cancer is the most incident gynecological cancer. Lymph node dissemination is one of the most important factors for the patient's prognosis. Pelvic lymph nodes are the primary site of extra-uterine dissemination in endometrial cancer (EC), setting the 5-year survival to 44-52%. It is standard practice for radiation therapy (RT) and/or chemotherapy (CTX) to be given as adjuvant treatments to prevent the progression of micrometastases. Also, administration of EC patients with RT and/or CTX regimens before surgery may decrease micrometastases, hence the need for lymphadenectomy. The primary aim of the systematic review and meta-analysis is to assess whether adjuvant RT and/or CTX improve oncological outcomes through the management of micrometastases and nodal recurrence. We performed systematic research using the string "Endometrial Neoplasms" [Mesh] AND "Lymphatic Metastasis/therapy" [Mesh]. The methods for this study were specified a priori based on the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Outcomes were 5-year overall survival, progression-free survival, recurrence rate, and complications rate. We assessed the quality of studies using the Newcastle-Ottawa Scale (NOS). A total of 1682 patients with stage I-to-IV EC were included. Adjuvant treatment protocols involved external-beam RT, brachytherapy, and CTX either alone or in combination. The no-treatment group showed a non-statistically significant higher recurrence risk than any adjuvant treatment group (OR 1.39 [95% CI 0.68-2.85] p = 0.36). The no-treatment group documented a non-statistically significant higher risk of death than those who underwent any adjuvant treatment (RR 1.47 [95% CI 0.44-4.89] p = 0.53; I2 = 55% p = 0.000001). Despite the fact that early-stage EC may show micrometastases, adjuvant treatment is not significantly associated with better survival outcomes, and the combination of EBRT and CTX is the most valid option in the early stages.

The Role of ß1 Integrin/CD29 as a Potential Prognostic Factor for the Risk of Progression to Cervical Carcinoma in HPV-Associated Lesions.

Background and Objectives: Available evidence reports the overexpression of ß1 integrin in dysplastic rather than normal cervical tissue. We aimed to evaluate the involvement of ß1 (CD29) integrin in the progressive pathogenesis of cervical intraepithelial neoplasia (CIN). Materials and Methods: From January 2019 to December 2021, we prospectively enrolled women undergoing a colposcopy with a cervical biopsy for abnormal cervical cytology and/or undefined cytology with a positive HPV DNA test and women with relapsing cervical inflammatory disorders. Based on the histopathological results, women were divided into four groups: group A (CIN1), group B (CIN2), group C (CIN3), and group D (no CIN diagnosis) as a control group. Subsequently, cytofluorimetry and immunohistochemical analysis (based on the identified positive cell ratios as follows: ≤10%, negative; 10-25%, 1+ (weak); 25-50%, 2+ (medium); ≥50%, and 3+ (high)) for ß1 integrin were carried out. Results: In total, 154 women were included. The average fluorescence intensity in the four groups was 2.35 ± 1.37, 2.73 ± 1.56, 3.09 ± 1.56, and 2.13 ± 1.25 UA from groups A to D, respectively; this figure was significantly different for CIN3 (group C) women relative to the other groups (p = 0.0132). Higher ß1 integrin/CD29 concentrations in the CIN groups with HR-HPV 16 and 18 were also detected (p = 0.0292, 0.0367, and 0.0357 respectively for CIN3, CIN2, and CIN1). Immunohistochemistry analysis showed higher results for the CIN3 group compared to controls and all the other groups (p < 0.001). Conclusions: ß1/CD29 integrin expression increased with CIN grade, and it was significantly higher in CIN3 lesions. This could be used as a promising screening tool to identify women prone to developing high-grade cervical lesions. However, additional evidence is needed to strengthen these findings.

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.

Hyperthermic Intraperitoneal Chemotherapy (HIPEC): New Approaches and Controversies on the Treatment of Advanced Epithelial Ovarian Cancer-Systematic Review and Meta-Analysis.

BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery has been extensively studied in patients with peritoneal carcinomatosis, and it holds promise as a therapeutic strategy, but its role remains elusive. The aim of this study was to assess the existing evidence for the use or not of HIPEC in primary debulking surgery (PDS), interval debulking surgery (IDS), and recurrent ovarian cancer (ROC), evaluated in terms of survival rates and post-surgical morbidity. METHODS: Medline, Pubmed, Cochrane, and Medscape were systematically searched for any article comparing the use of HIPEC treatment with any other therapy in patients with ovarian cancer in PDS, IDS, and ROC. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines were followed. We only considered English-language published studies. RESULTS: We included 14 studies, including two RCTs with a total of 1813 women, published between 2003 and 2023 with a recruitment period between 1998 and 2020. In PDS, there were no differences in progression-free survival (PFS) between HIPEC and controls [MD -5.53 months [95% CI -19.91 to 8.84 months]; I2 = 96%]. Conversely, in patients treated with NACT, pooled results showed a significant survival advantage in terms of progression-free survival (PFS) and overall survival (OS) in the combined HIPEC plus IDS group rather than surgery alone [PFS: MD 4.68 months (95% CI 3.49 to 5.86 months, I2 = 95%); OS: MD 11.81 months (95% CI 9.34 to 14.27 months); I2 = 97%]. Concerning ROC patients, pooled MD did not show either a significant PFS difference between intervention and controls [MD 2.68 months (95% CI 433 to 9.70 months); I2 = 95%], and OS significant difference (MD 6.69 months [95% CI -9.09 to 22.47 months]; I2 = 98%). Severe post-operative complications (≥grade 3) were available in 10 studies, accounting for 1108 women. Overall, there was a slightly but significantly increased risk with the combined approach compared to controls [RR 1.26 (95% CI 1.02 to 1.55); I2 = 0%]. CONCLUSIONS: The combination of HIPEC with cytoreductive surgery prolongs OS and PFS in advanced epithelial ovarian cancer after NACT with acceptable morbidity. However, additional trials are still needed to determine the effectiveness of HIPEC in primary and recurrence settings. In the era of personalized medicine, the correlation between the efficacy of HIPEC and biological and molecular findings represents a challenge for the future of ovarian cancer.

Efficacy of Hysteroscopy in Improving Fertility Outcomes in Women Undergoing Assisted Reproductive Technique: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Usefulness of hysteroscopy before assisted reproductive technique (ART) was considered debatable. However, over the last decade, several new trials have been added to available literature. We aimed to assess the impact of diagnostic and operative hysteroscopy on reproductive outcomes of infertile women with and without intrauterine abnormalities. MATERIALS AND METHODS: MEDLINE, Scopus, SciELO, Embase, Cochrane Library at CENTRAL, PROSPERO, CINAHL, grey literature, conference proceedings, and international controlled trials registries were searched without temporal, geographical, or language restrictions. Randomized controlled trials (RCTs) of infertile women comparing hysteroscopy versus no hysteroscopy prior to the first ART or after at least one failed attempt were included. RCTs of infertile women with intrauterine pathology comparing diagnostic versus operative hysteroscopy were included in separate analysis. Random-effect meta-analysis was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Grading of Recommendations, Assessment, Development and Evaluation and Cochrane criteria were used for quality of evidence and risk of bias assessment. Primary outcome was live birth rate (LBR). Secondary outcomes were clinical pregnancy (CPR) and pregnancy loss rate. RESULTS: Fifteen studies (5,038 women) were included. Compared to no hysteroscopy before first or after failed ART attempts, moderate-quality evidence showed that hysteroscopy increased the LBR (relative risk [RR] 1.24, 95% confidence interval [CI] 1.09-1.43, I2 = 21%), confirmed by subgroup analysis for women with failure after one or more ART cycles (RR 1.43, 95% CI: 1.19-1.72, I2 = 0%) but not before the first ART. Moderate-quality evidence showed that it increased the CPR (RR 1.36, 95% CI: 1.18-1.57; I2 = 51%), confirmed in subgroup analysis for both implantation failure (RR 1.40, 95% CI: 1.12-1.74, I2 = 52%) and before first ART (RR 1.32, 95% CI: 1.11-1.57, I2 = 42%). Low-quality data suggest that operative hysteroscopy increases CPR when used to treat intrauterine pathologies (RR 2.13, 95% CI: 1.56-2.92, I2 = 0%). CONCLUSIONS: Although moderate-quality evidence supports performing hysteroscopy before ART in women with history of implantation failure, hysteroscopic evaluation of uterine cavity should be considered a first-line technique in all infertile women undergoing ART. Additional high-quality RCTs are still needed, particularly to assess yield during couple's initial evaluation even before ART is considered.

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.

Critical Overview of Serous Endometrial Intraepithelial Cancer Treatment: Systematic Review of Adjuvant Options.

SEIC is a non-invasive lesion of the endometrial epithelium considered to be the precursor to uterine serous carcinoma (USC) and is just as aggressive as USC. Currently, there are no reliable data about the behavior and prognosis of SEIC; therefore, the therapeutic management approach is not clear. Method: A systematic search of the Pubmed, Scopus and Embase databases was conducted, following the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Results: Of the 296 studies that matched the search criteria, only 9 met the inclusion criteria, covering a total of 81 patients. The main disease-presenting pattern was AUB (abnormal uterine bleeding). In 31 cases, SEIC was associated with extrauterine disease. All patients underwent hysterectomy and salpingo-oophorectomy, while only 15 of the 81 patients received adjuvant treatments. In the patients receiving adjuvant therapy, the RR was 42.67%, the DFS was 35.71% and the OS was 57.13%. In patients subjected to follow-up alone, the RR was only 28.78%, the DFS was 59.1% and the OS was 66.6%. Conclusions: The presence of an extrauterine disease significantly worsens outcomes, regardless of adjuvant treatment. In cases of disease confined to the uterine mucosa alone, the prognosis is good and follow-up allows a good control of the disease; however, adjuvant therapy could further increase survival rates and reduce relapse rates.

Minimally Invasive Staging of Early-Stage Epithelial Ovarian Cancer versus Open Surgery in Terms of Feasibility and Safety: A Systematic Review and Meta-Analysis.

Epithelial ovarian cancer is women's fourth most common oncological cause of death. One of the main prognostic factors in ovarian cancer is the tumor stage. For instance, surgical staging of the disease is focal when choosing the best therapeutic option for each case. Although open surgery is the prevalent approach for staging and treating ovarian cancer, the use of minimally invasive surgery (MIS) has found recent application in staging or restaging cases of early disease. Our work compares oncological outcomes after MIS staging for FIGO I epithelial ovarian cancer with the laparotomic approach. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement recommendations, we systematically searched the Pub Med and Scopus databases in February 2023. No temporal nor geographical limitation was made. We included the articles containing data about Disease-Free Survival (DFS) and Overall Survival (OS), Recurrence Rates (RR), and Upstaging Rates (UpR). We used comparative studies for the meta-analysis. After the database search and article selection, 19 works matched the inclusion criteria for the systematic review. Eleven of these were comparative studies between MIS and Open Surgical Staging (OSS) approaches for ovarian cancer staging and were included in the meta-analysis. The meta-analysis did not show a statistically significant difference between the MIS and the OSS group concerning DFS, OS, and RR. Only Upstaging Rate ≥ FIGO Stage II was statistically significative higher in the OSS group. Likewise, MIS is confirmed to be an approach with a lower profile of surgical complications. In conclusion, our study did not show one approach to be safer than the other. However, the lack of dedicated studies limits the evidence of our study. For instance, we recommend adequately selecting the specimen, minimizing the risk of spillage, and optimizing surgical staging.

Radiotherapy and Chemotherapy Features in the Treatment for Locoregional Recurrence of Endometrial Cancer: A Systematic Review.

Radiation therapy (RT) is the standard of care in patients with locoregional or isolated vaginal recurrence who never underwent irradiation. It is often associated with brachytherapy (BT), whereas chemotherapy (CT) is a rare treatment option. We systematically searched the PubMed and Scopus databases in February 2023. We included patients with relapsed endometrial cancer, describing the treatment of locoregional recurrence, and reporting at least one outcome of interest-disease-free survival (DFS), overall survival (OS), recurrence rate (RR), site of recurrence, and major complications. A total of 15 studies fulfilled the inclusion criteria. Overall, 11 evaluated RT only, 3 evaluated CT, and 1 analyzed oncological outcomes after administration with a combination of CT and RT. In total, 4.5-year OS ranged from 16% to 96%, and DFS ranged from 36.3% to 100% at 4.5 years. RR ranged from 3.7% to 98.2% during a median follow-up of 51.5 months. Overall, RT showed a 4.5-year DFS from 40% to 100%. CT revealed 36.3% DFS at 4.5 years. RT showed a 4.5-year OS ranging from 16% to 96%, whereas CT revealed a 27.7% OS rate. It would be appropriate to test multi-modality regimens to evaluate outcomes and toxicity. EBRT and BT are the most employed options to treat vaginal recurrences.

Endometrial biopsy: Indications, techniques and recommendations. An evidence-based guideline for clinical practice.

This practice guideline provides updated evidence for the gynecologist who performs endometrial biopsy (EB) in gynecologic clinical practice. An international committee of gynecology experts developed the recommendations according to AGREE Reporting Guideline. An adequate tissue sampling is mandatory when performing an EB. Blind methods should not be first choice in patients with suspected endometrial malignancy. Hysteroscopy is the targeted-biopsy method with highest diagnostic accuracy and cost-effectiveness. Blind suction techniques are not reliable for the diagnosis of endometrial polyps. In low resources settings, and in absence of the capacity to perform office hysteroscopy, blind techniques could be used for EB. Hysteroscopic punch biopsy allows to collect only limited amount of endometrial tissue. grasp biopsy technique should be considered first choice in reproductive aged women, bipolar electrode chip biopsy should be preferred with hypotrophic or atrophic endometrium. EB is required for the final diagnosis of chronic endometritis. There is no consensus regarding which endometrial thickness cut-off should be used for recommending EB in asymptomatic postmenopausal women. EB should be offered to young women with abnormal uterine bleeding and risk factors for endometrial carcinoma. Endometrial pathology should be excluded with EB in nonobese women with unopposed hyperestrogenism. Hysteroscopy with EB is useful in patients with abnormal bleeding even without sonographic evidence of pathology. EB has high sensitivity for detecting intrauterine pathologies. In postmenopausal women with uterine bleeding, EB is recommended. Women with sonographic endometrial thickness > 4 mm using tamoxifen should undergo hysteroscopic EB.

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.

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.

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.

Impact of the hemostatic approach after laparoscopic endometrioma excision on ovarian reserve: Systematic review and network meta-analysis of randomized controlled trials.

BACKGROUND: Laparoscopic excision of endometrioma and subsequent hemostasis have detrimental effects on ovarian reserve. OBJECTIVES: To evaluate which hemostatic approach after stripping cystectomy shows less damage on ovarian reserve. SEARCH STRATEGY: Embase, MEDLINE, Scopus, Scielo.br, LILACS, Cochrane Library at the CENTRAL Register of Controlled Trials, Clinicaltrials.gov, CINAHL, conference abstracts, and International Clinical Trials Registry Platform were searched from inception until April 2022. SELECTION CRITERIA: Randomized controlled trials of women undergoing laparoscopic endometrioma excision that compared at least two hemostatic approaches. DATA COLLECTION AND ANALYSIS: Relevant data were extracted and tabulated. Network meta-analysis based on random-effects model for mixed multiple treatment to rank hemostatic strategies using the surface under the cumulative ranking curve area (SUCRA) was performed. Quality assessment was performed using Cochrane criteria. The primary outcome was serum antimullerian hormone levels 3 months after surgery. MAIN RESULTS: Ten studies, including 748 women, were selected. Suturing the ovary with barbed suture (SUCRA, 82.80%) seem the most effective strategy to avoid antimullerian hormone reduction. Similarly, for ultrasonographic antral follicular count, barbed (SUCRA, 30.70%) and simple suture (SUCRA, 30.70%) were ranked the best choices. Ovarian suturing with simple suture demonstrated lower follicle-stimulating hormone levels (SUCRA, 88.70%). CONCLUSIONS: Suturing the ovary, with simple or barbed suture, seems the most effective approach to keep ovarian reserve higher.

Surgical management of endocervical and decidual polyps during pregnancy: systematic review and meta-analysis.

PURPOSE: To evaluate the impact of endocervical and decidual polypectomy on obstetrical outcomes of pregnant women. METHODS: MEDLINE, Scopus, ClinicalTrials.gov, Scielo, EMBASE, Cochrane Library at the CENTRAL Register of Controlled Trials, and LILACS were searched from inception to April 2021. No language or geographical restrictions were applied. Inclusion criteria regarded observational studies concerning pregnant women with a cervical lesion who underwent cervical polypectomy. Co-primary outcomes were incidence of late pregnancy loss and preterm birth in women with endocervical or decidual polypectomy as well as polypectomy versus expectant management. Random effect meta-analyses to calculate risk ratio (RR) with 95% confidence interval (CI) were performed. Quality assessment of included papers was performed using Newcastle-Ottawa Scale criteria. RESULTS: Three studies, with data provided for 3097 women, were included in quantitative analysis, with comparisons between endocervical and decidual polyps extracted from two studies and 156 patients. After a first trimester endocervical or decidual polypectomy, no significant differences were found for late pregnancy losses (RR 0.29 [95% CI 0.05, 1.80], I2 = 11%). Risk for preterm birth was significantly higher for decidual polyps' removal (RR 6.13 [95% CI 2.57, 14.59], I2 = 0%). One paper compared cervical polypectomy vs expectant management, with increased incidence of late pregnancy loss (4/142 vs 5/2799; p < 0.001) and preterm birth (19/142 vs 115/2799; p < 0.001) in women subjected to polypectomy. CONCLUSIONS: Evidence regarding the removal of cervical polyps in pregnancy is extremely limited. However, the removal of either decidual or endocervical polyps seems associated with increased risk of pregnancy loss and preterm birth, with increased preterm birth risk following endocervical rather than decidual polypectomy.

Risk of endometrial cancer in asymptomatic postmenopausal women in relation to ultrasonographic endometrial thickness: systematic review and diagnostic test accuracy meta-analysis.

OBJECTIVE: This study aimed to evaluate the risk of endometrial carcinoma and atypical endometrial hyperplasia in asymptomatic postmenopausal women concerning the endometrial thickness measured by stratified threshold categories used for performing subsequent endometrial sampling and histologic evaluation. DATA SOURCES: MEDLINE, Scopus, ClinicalTrials.gov, SciELO, Embase, the Cochrane Central Register of Controlled Trials, LILACS, conference proceedings, and international controlled trials registries were searched without temporal, geographic, or language restrictions. STUDY ELIGIBILITY CRITERIA: Studies were selected if they had a crossover design evaluating the risk of atypical endometrial hyperplasia and endometrial carcinoma in postmenopausal asymptomatic women and calculated the diagnostic accuracy of transvaginal ultrasonography thresholds (at least 3.0 mm) confirmed by histopathologic diagnosis. METHODS: This was a systematic review and diagnostic test accuracy meta-analysis according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Diagnostic Test Accuracy and Synthesizing Evidence from Diagnostic Accuracy Tests guidelines. Endometrial thickness thresholds were grouped as follows: from 3.0 to 5.9 mm; between 6.0 and 9.9 mm; between 10.0 and 13.9 mm; and ≥14.0 mm. Quality assessment was performed using the Quality Assessment Tool for Diagnostic Accuracy Studies 2 tool. Publication bias was quantified using the Deek funnel plot test. Coprimary outcomes were the risk of atypical endometrial hyperplasia or endometrial carcinoma according to the endometrial thickness and diagnostic accuracy of each threshold group. RESULTS: A total of 18 studies provided the data of 10,334 women who were all included in the final analysis. Overall, at an endometrial thickness threshold of at least 3.0 mm, the risk of atypical endometrial hyperplasia or endometrial carcinoma was increased 3-fold relative to women below the cutoff (relative risk, 3.77; 95% confidence interval, 2.26-6.32; I2=74%). Similar degrees of risk were reported for thresholds between 3.0 and 5.9 mm (relative risk, 5.08; 95% confidence interval, 2.26-11.41; I2=0%), 6.0 and 9.9 mm (relative risk, 4.34; 95% confidence interval, 1.68-11.23; I2=0%), 10.0 and 13.9 mm (relative risk, 4.11; 95% confidence interval, 1.55-10.87; I2=86%), and ≥14.0 mm (relative risk, 2.53; 95% confidence interval, 1.04-6.16; I2=78%) with no significant difference among subgroups (P=.885). Regarding diagnostic accuracy, the pooled sensitivity decreased from thresholds below 5.9 mm (relative risk, 0.81; 95% confidence interval, 0.49-0.85) to above 14.0 mm (relative risk, 0.28; 95% confidence interval, 0.18-0.40). Furthermore, the specificity increased from 0.70 (95% confidence interval, 0.61-0.78) for endometrial thickness between 3.0 and 5.9 mm to 0.86 (95% confidence interval, 0.71-0.94) when the endometrial thickness is ≥14.0 mm. For 3.0 to 5.9 mm and 10.0 to 13.9 mm thresholds, the highest diagnostic odds ratios of 10 (95% confidence interval, 3-41) and 11 (95% confidence interval, 2-49), with areas under the curve of 0.81 (95% confidence interval, 0.77-0.84) and 0.82 (95% confidence interval, 0.79-0.86), respectively, were retrieved. The summary point analysis revealed that the 3.0 to 5.9 mm cutoff point was placed higher in the summary receiver operator curve space than the other subgroups, indicating increased endometrial carcinoma or atypical endometrial hyperplasia diagnosis using these cutoffs. CONCLUSION: Both low and high endometrial thickness thresholds in postmenopausal asymptomatic women seem equally effective in detecting endometrial carcinoma and atypical endometrial hyperplasia. However, although using a 3.0 to 5.9 mm cutoff results in a lower specificity, the offsetting improvement in sensitivity may justify using this cutoff for further endometrial evaluation in patients with suspected endometrial malignancy.

Quality of Life, Anxiety and Depression in Women Treated with Hysteroscopic Endometrial Resection or Ablation for Heavy Menstrual Bleeding: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background and Objectives: Hysteroscopic endometrial resection (ER) or global endometrial ablation (GEA) are feasible methods to treat heavy menstrual bleeding (HMB). The aim of this systematic review and meta-analysis of randomized controlled trials (RCTs) was to assess patient's quality of life (QoL) in women treated with ER/GEA compared to hysterectomy. Materials and Methods: Electronic searches in MEDLINE Scopus, ClinicalTrials.gov, EMBASE, PROSPERO and Cochrane CENTRAL were conducted from their inception to July 2022. Inclusion criteria were RCTs of premenopausal women with HMB randomized to conservative surgical treatment (ER/GEA) or hysterectomy. The primary outcome was the evaluation of QoL using the SF-36 score. Results: Twelve RCTs (2773 women) were included in the analysis. Women treated with hysteroscopic ER/GEA showed significantly lower scores for the SF-36 general health perception (mean difference (MD) -8.56 [95% CI -11.75 to -5.36]; I2 = 0%), social function (MD -12.90 [95% CI -23.90 to -1.68]; I2 = 91%), emotional role limitation (MD -4.64 [95% CI -8.43 to -0.85]; I2 = 0%) and vitality (MD -8.01 [95% CI -14.73 to -1.30]; I2 = 74%) domains relative to hysterectomy. Anxiety, depression scores and complication rates were similar between treatments. Relative to uterine balloon therapy, amenorrhea was more common with EA/GER (relative risk 1.51 [95% CI 1.03 to 1.20] I2 = 28%), but posttreatment satisfaction was similar. Conclusions: Women's perception of QoL might be seen to be less improved after hysteroscopic ER/GEA rather than hysterectomy. However, such findings need to be confirmed by additional trials due to the high number of outdated studies and recent improvements in hysteroscopic instrumentation and techniques.

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.

Oncological outcomes in fertility-sparing treatment in stage IA-G2 endometrial cancer.

Background: The gold standard treatment for early-stage endometrial cancer (EC) is hysterectomy with bilateral salpingo-oophorectomy (BSO) with lymphadenectomy. In selected patients desiring pregnancy, fertility-sparing treatment (FST) can be adopted. Our review aims to collect the most incisive studies about the possibility of conservative management for patients with grade 2, stage IA EC. Different approaches can be considered beyond demolition surgery, such as local treatment with levonorgestrel-releasing intra-uterine device (LNG-IUD) plus systemic therapy with progestins. Study design: Our systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. PubMed, EMBASE, and Scopus databases were consulted, and five studies were chosen based on the following criteria: patients with a histological diagnosis of EC stage IA G2 in reproductive age desiring pregnancy and at least one oncological outcome evaluated. Search imputes were "endometrial cancer" AND "fertility sparing" AND "oncologic outcomes" AND "G2 or stage IA". Results: A total of 103 patients were included and treated with a combination of LNG-IUD plus megestrol acetate (MA) or medroxyprogesterone acetate (MPA), gonadotrophin-releasing hormone (GnRH) plus MPA/MA, hysteroscopic resectoscope (HR), and dilation and curettage (D&C). There is evidence of 70% to 85% complete response after second-round therapy prolongation to 12 months. Conclusions: Conservative measures must be considered temporary to allow pregnancy and subsequently perform specific counseling to adopt surgery. Fertility-sparing management is not the current standard of care for young women with EC. It can be employed for patients with early-stage diseases motivated to maintain reproductive function. Indeed, the results are encouraging, but the sample size must be increased.

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.