Clinical relevance of silent red blood cell autoantibodies.

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Serum anti‐müllerian hormone levels and risk of premature ovarian insufficiency in female childhood cancer survivors: Systematic review and network meta‐analysis

Background: Female childhood cancer survivors (CCS) might have impaired ovarian reserves, especially after alkylating agents or radiotherapy. The purpose of this systematic review and network meta‐analysis is to evaluate the role of serum anti‐Müllerian hormone (AMH) for ovarian reserve screening and the risk of premature ovarian insufficiency (POI) according to the subtype of childhood cancer. (2) Methods: PRISMA‐NMA guidelines were followed. We carried out a network meta‐analysis based on a random effects model for mixed multiple treatment comparisons to rank childhood cancers effects on fertility by surface under the cumulative ranking curve (SUCRA). Studies were selected only if they had an age‐matched control group. Quality assessment was performed using Newcastle–Ottawa Scale. The co‐primary outcomes were mean AMH levels and the incidence of POI. (3) Results: A total of 8 studies (1303 participants) were included. Women treated for a neuroblastoma during infancy were more likely to be ranked first for impaired AMH levels (SUCRA = 65.4%), followed by mixed CCS (SUCRA = 29.6%). The greatest rates of POI were found in neuroblastoma survivors (SUCRA = 42.5%), followed by acute lymphoid leukemia (SUCRA = 26.3%) or any other neoplasia (SUCR A= 20.5%). (4) Conclusions: AMH represents a trustworthy approach for ovarian reserve screening. Direct and indirect comparisons found no differences in mean AMH levels and POI risk between subtypes of CCS and healthy controls. SUCRA analysis showed that female neuroblastoma survivors were more at risk for reduced serum AMH levels and increased risk of POI

Assessment of Salvage Surgery in Persistent Cervical Cancer after Definitive Radiochemotherapy: A Systematic Review

Background and Objectives: The standard treatment approach in locally advanced cervical cancer (LACC) is exclusive concurrent chemoradiation therapy (RTCT). The risk of local residual disease after six months from RTCT is about 20–30%. It is directly related to relapse risk and poor survival, such as in patients with recurrent cervical cancer. This systematic review aims to describe studies investigating salvage surgery’s role in persistent/recurrent disease in LACC patients who underwent definitive RTCT. Materials and Methods: Studies were eligible for inclusion when patients had LACC with radiologically suspected or histologically confirmed residual disease after definitive RTCT, diagnosed with post-treatment radiological workup or biopsy. Information on complications after salvage surgery and survival outcomes had to be reported. The methodological quality of the articles was independently assessed by two researchers with the Newcastle–Ottawa scale. Following the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, we systematically searched the PubMed, Scopus, Cochrane, Medline, and Medscape databases in May 2022. We applied no language or geographical restrictions but considered only English studies. We included studies containing data about postoperative complications and survival outcomes. Results: Eleven studies fulfilled the inclusion criteria and all were retrospective observational studies. A total of 601 patients were analyzed concerning the salvage surgery in LACC patients for persistent/recurrent disease after RTCT treatment. Overall, 369 (61.4%) and 232 (38.6%) patients underwent a salvage hysterectomy (extrafascial or radical) and pelvic exenteration (anterior, posterior, or total), respectively. Four hundred and thirty-nine (73%) patients had histologically confirmed the residual disease in the salvage surgical specimen, and 109 patients had positive margins (overall range 0–43% of the patients). The risk of severe (grade ≥ 3) postoperative complications after salvage surgery is 29.8% (range 5–57.5%). After a median follow-up of 38 months, the overall RR was about 32% with an overall death rate of 40% after hysterectomy or pelvic exenteration with or without lymphadenectomy. Conclusions: There is heterogeneity between the studies both in their design and results, therefore the effect of salvage surgery on survival and recurrence cannot be adequately estimated. Future homogeneous studies with an appropriately selected population are needed to analyze the safety and efficacy of salvage hysterectomy or pelvic exenteration in patients with residual tumors after definitive RTCT

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

Hyperthermic intraperitoneal chemotherapy (HIPEC) for ovarian cancer recurrence: systematic review and meta-analysis.

Background: Ovarian cancer is the first cause of death among gynecological malignancies with a high incidence of recurrence. Different treatment options are suitable to prolong the survival rate of these patients. Over the last years, one of the most intriguing methods, adopted in different oncologic centers worldwide, is the hyperthermic intraperitoneal chemotherapy (HIPEC). Methods: A meta-analysis was performed to value the role of HIPEC for ovarian cancer recurrence. Search strategy was conducted with a combination of the following keywords: "ovarian recurrence, ovarian cancer recurrence, peritoneal cancer recurrence, ovarian recurrence AND HIPEC, secondary cytoreduction HIPEC". Seven studies were selected for analysis. Results: In women with recurrent ovarian cancer (ROC), the use of HIPEC in addition to cytoreductive surgery and chemotherapy significantly improved 1-year overall survival (OS) when compared to protocols without HIPEC (OR 2.42; 95% CI, 1.06-5.56; P=0.04; I2=4%). The improvement in OS was maintained significant also after 2, 3 and 5 years respectively (OR 3.33; 95% CI, 1.81-6.10; P&lt;0.01; I2=0%), (OR 4.22; 95% CI, 2.07-8.60; P&lt;0.01; I2=52%), (OR 5.17; 95% CI, 1.40-19.09; P=0.01; I2=82%). Conclusions: HIPEC seems to have an effective role to prolong survival in patients affected by ROC

Hysteroscopy in the management of endometrial hyperplasia and cancer in reproductive aged women: new developments and current perspectives

Over the last twenty years, the incidence of early endometrial cancer (EC) and atypical endometrial hyperplasia (AEH) among women of reproductive age is increasing rapidly, likely due to a combination of factors including increased prevalence of obesity and delayed of childbirths. Regarding preoperative diagnosis of endometrial neoplasia, it is still debated which is the most accurate and reliable method to obtain endometrial histopathological samples with fractional dilatation and curettage (D&amp;C) having been considered, for a long time, as the method of choice. Nowadays, the advent of in-office endometrial biopsy with or without hysteroscopy has radically changed the approach, giving the opportunity to perform the endometrial biopsy under direct visualization. However, the lack of agreement about its diagnostic accuracy is still relevant. Since a significant number of women with AEH and/or EC are of childbearing age, a fertility-sparing diagnostic and therapeutic approach should be considered in all cases. The feasibility, safety and efficacy of fertility-sparing strategies involving hysteroscopic focal resections in conjunction with hormonal therapies have been evaluated and beneficial effects have been confirmed in several studies and one meta-analysis. Both local and systemic administration of hormonal therapies are currently used. Oral progestin, including medroxyprogesterone acetate (MPA) and megestrol acetate, are the most commonly used therapies. Nowadays, new therapeutic approaches, such as levonorgestrel intrauterine systems (LNG-IUS), gonadotropin-releasing hormone (GnRH) agonists, combined megestrol acetate and metformin, and other combinations of therapies are also used as first line therapies or after the hysteroscopic resection of the lesion. However, it is still unclear which approach provides higher clinical response with lower relapse rate, in addition to preserving fertility in women desiring to conceive. The aim of this narrative review is to summarize the available evidence regarding the evaluation and management with fertility-sparing treatments options of women with AEC and EC

Ion channels in the pathogenesis of endometriosis: A cutting-edge point of view

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

Microbiome and PCOS: State-of-art and future aspects

Polycystic ovary syndrome (PCOS) is a complex and heterogeneous endocrine disease. The hypothesis that alterations in the microbiome are involved in the genesis of PCOS has been postulated. Aim of this review is to summarize the available literature data about the relationship between microbiome and PCOS. A search on PubMed and Medline databases was performed from inception to November 20Most of evidence has focused on the connection of intestinal bacteria with sex hormones and insulin-resistance: while in the first case, a relationship with hyperandrogenism has been described, although it is still unclear, in the second one, chronic low-grade inflammation by activating the immune system, with increased production of proinflammatory cytokines which interfere with insulin receptor function, causing IR (Insulin Resistance)/hyperinsulinemia has been described, as well as the role of gastrointestinal hormones like Ghrelin and peptide YY (PYY), bile acids, interleukin-22 and Bacteroides vulgatus have been highlighted. The lower genital tract mi-crobiome would be affected by changes in PCOS patients too. The therapeutic opportunities include probiotic, prebiotics and synbiotics, as well as fecal microbiota transplantation and the use of IL-22, to date only in animal models, as a possible future drug. Current evidence has shown the involvement of the gut microbiome in PCOS, seen how humanized mice receiving a fecal transplant from women with PCOS develop ovarian dysfunction, immune changes and insulin resistance and how it is capable of disrupting the secondary bile acid biosynthesis. A future therapeutic approach for PCOS may involve the human administration of IL-22 and bile acid glycodeoxycholic acid