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.

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.

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.

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.