Background: Ion channels play a crucial role in many physiological processes. Several subtypes are expressed in the endometrium. Endometriosis is strictly correlated to estrogens and it is evident that expression and functionality of different ion channels are estrogen-dependent, fluctuating between the menstrual phases. However, their relationship with endometriosis is still unclear. Objective: To summarize the available literature data about the role of ion channels in the etiopathogenesis of endometriosis. Methods: A search on PubMed and Medline databases was performed from inception to November 2019. Results: Cystic fibrosis transmembrane conductance regulator (CFTR), transient receptor potentials (TRPs), aquaporins (AQPs), and chloride channel (ClC)-3 expression and activity were analyzed. CFTR expression changed during the menstrual phases and was enhanced in endometriosis samples; its overexpression promoted endometrial cell proliferation, migration, and invasion throughout nuclear factor kappa-light-chain-enhancer of activated B cells-urokinase plasminogen activator receptor (NFκB-uPAR) signaling pathway. No connection between TRPs and the pathogenesis of endometriosis was found. AQP5 activity was estrogen-increased and, through phosphatidylinositol-3-kinase and protein kinase B (PI3K/AKT), helped in vivo implantation of ectopic endometrium. In vitro, AQP9 participated in extracellular signal-regulated kinases/p38 mitogen-activated protein kinase (ERK/p38 MAPK) pathway and helped migration and invasion stimulating matrix metalloproteinase (MMP)2 and MMP9. ClC-3 was also overexpressed in ectopic endometrium and upregulated MMP9. Conclusion: Available evidence suggests a pivotal role of CFTR, AQPs, and ClC-3 in endometriosis etiopathogenesis. However, data obtained are not sufficient to establish a direct role of ion channels in the etiology of the disease. Further studies are needed to clarify this relationship.

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.

The goal of this paper is to assess the concordance between the clinical diagnosis of Endometrial Hyperplasia (EH), suspected by senior gynecologists throughout outpatient office hysteroscopy, and the results from histopathological examination, in order to evaluate hysteroscopic accuracy for EH. A prospective cohort study was done at a Tertiary University Hospital. From January to December 2018, we enrolled women with the following criteria: abnormal uterine bleeding in post-menopause and endometrial thickening in pre-or post-menopause. Patients underwent office hysteroscopy with a 5 mm continuous-flow hysteroscope, and endometrial biopsies were taken using miniaturized instruments. Senior operators had to foresee histopathological diagnosis using a questionnaire. Histopathological examination was conducted to confirm the diagnosis. This study was approved by the local ethical and registered in the ClinicalTrials.gov registry (ID no. NCT03917147). In 424 cases, 283 clinical diagnoses of EH were determined by senior surgeons. A histopathological diagnosis was then confirmed in 165 cases (58.3%; p = 0.0001). Furthermore, 14 endometrial carcinoma and atypical hyperplasia were found. The sensitivity, positive predictive value, and negative predictive values for EH were, respectively, 90.4, 58.4, and 86.6%. Subdivided by clinical indication, the sensitivity was higher in patients with post-menopause endometrial thickening. The diagnostic accuracy of office hysteroscopy in the diagnosis and prediction of endometrial hyperplasia was high. Senior operators could foresee EHs in more than half the cases.

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.

Titanium dioxide nanoparticles (NPs-TiO₂ or TiO₂-NPs) have been employed in many commercial products such as medicines, foods and cosmetics. TiO₂-NPs are able to carry antibiotics to target cells enhancing the antimicrobial efficiency; so that these nanoparticles are generally used in antibiotic capsules, like lincomycin, added as a dye. Lincomycin is usually used to treat pregnancy bacterial vaginosis and its combination with TiO₂-NPs arises questions on the potential effects on fetus health. This study investigated the potential impact of TiO₂-NPs and lincomycin co-exposure on human amniocytes in vitro. Cytotoxicity was evaluated with trypan blue vitality test, while genotoxic damage was performed by Comet Test, Diffusion Assay and RAPD-PCR for 48 and 72 exposure hours. Lincomycin exposure produced no genotoxic effects on amniotic cells, instead, the TiO₂-NPs exposure induced genotoxicity. TiO₂-NPs and lincomycin co-exposure caused significant increase of DNA fragmentation, apoptosis and DNA damage in amniocytes starting from 48 exposure hours. These results contribute to monitor the use of TiO₂-NPs combined with drugs in medical application. The potential impact of antibiotics with TiO₂-NPs during pregnancy could be associated with adverse effects on embryo DNA. The use of nanomaterials in drugs formulation should be strictly controlled in order to minimize risks.

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.