Intravesical Instillations of Hyaluronic Acid as First-Line Treatment in Patients with Interstitial Cystitis/Bladder Pain Syndrome: Use, Efficacy and Effects on Quality of Life.

The efficacy of hyaluronic acid instillations as therapy for patients with Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) has been demonstrated in some clinical studies, with response rates up to 70%. The aim of the study is to investigate the change in symptoms and quality of life in female patients with IC/BPS after intravesical instillations of hyaluronic acid used as first-line treatment. A retrospective single-center cohort study was conducted. Female patients, whose symptoms were compatible with the diagnosis of IC/BPS as defined by the International Continence Society, were treated with a variable number of intravesical instillations of a hyaluronic acid-based drug. Three validated questionnaires were administered by telephone to all patients, before the beginning of the treatment and 6 months after the last administration of the drug. A total of 50 patients with symptoms compatible with the diagnosis of IC/BPS were included in the study. The median number of instillations performed is 4. For all questionnaires, the median value was significantly reduced following treatment with intravesical instillations (p = 0.000). The present study has shown that intravesical hyaluronic acid treatment results in both statistically and clinically significant symptomatic improvement, thereby improving the quality of life of patients with IC/BPS.

Bloodless Gynecological Surgery in Blood Products Refusing Patients: Experience of a Single Institution.

Propose: This pilot study aimed to apply the central tenets of bloodless surgery and to analyze the effectiveness of specific preoperative, intraoperative, and postoperative strategies to minimize the risk for blood transfusion after gynecological surgery in a specific group of patients who refused blood products. Methods: A total of 83 patients undergoing gynecological surgery were included in the study. Forty-two patients received preoperatively oral iron, acid folic, and vitamin B12 supplementation in the 30 days before surgery, and 41 patients did not receive therapy. Results: No significant differences were found when comparing the two study groups. The implementation of all procedures to maintain a bloodless surgery has been helpful, in association with the other available procedures, in achieving optimal management and maintenance of hemoglobin levels, even in the most critical situations. Conclusion: In conclusion, implementing the bloodless approach as much as possible could guarantee the patient better and safer clinical and care management. Furthermore, well-designed research is required to clarify further the effects of bloodless surgery in gynecological patients.

The great debate: Surgical outcomes of laparoscopic versus laparotomic myomectomy. A meta-analysis to critically evaluate current evidence and look over the horizon.

Myomectomy is one of the most common surgical procedure in the field of gynecology. However, the role of laparoscopic myomectomy is still debated for many factors, including surgical considerations, safety and fertility concerns, long-term outcomes, and cost-related issues. The aim of this study is to evaluate the surgical peri- and post-operative outcomes of laparoscopic and abdominal myomectomy. A systematic search for studies was performed up to June 2023 through MEDLINE, Pubmed, Embase. Studies reporting the comparison of surgical and obstetrical outcomes in laparoscopic versus laparotomic myomectomy were included for the following outcomes: time of surgery, estimated blood loss, decrease of postoperative hemoglobin, hospital stay, intra-operative complication rates, postoperative complications rates, postoperative analgesic use, postoperative pain at 24 h and pregnancy rate. The meta-analysis was performed using the Cochrane Review software. Fifty-six relevant articles were retrieved through the process of evidence acquisition. Eleven articles met inclusion criteria, for a total of 2,133 patients undergoing laparoscopic or laparotomic myomectomy. The estimated blood loss [standard mean differences (SMD) 0.72, IC 95 % 0.22 to 1.22], the hospital stays [SMD 3.12, IC 95 % 0.57 to 4.28], were significantly lower in laparoscopic than in open group. No statistically significant difference in intra-operative and post-operative complication rates, in pregnancy rate and others obstetrical outcomes between two surgical approaches were found. The findings of present metanalysis suggest that laparoscopic myomectomy offers multiple benefits, including reduced blood loss, shorter hospital stays, and less postoperative analgesic need, without a significant increase in complication rates and similar results in obstetrical outcomes when compared to abdominal myomectomy. However, the presence of few randomized studies on selected population may limit the generalizability of the findings to the entire population. Therefore, more well-designed studies or large population programdata to draw definitive conclusions are therefore warranted.

Efficacy and safety of follitropin delta for ovarian stimulation in vitro fertilization/ intracytoplasmic sperm injection cycles: a systematic review with meta-analysis.

BACKGROUND: Follitropin delta is a novel recombinant follicle stimulating hormone preparation uniquely expressed in a human fetal retinal cell line by recombinant DNA technology. To date, no systematic review was available about the safety and the efficacy of the follitropin delta. The objective of this study was systematically reviewing the available literature and to provide updated evidence regarding the efficacy-safety profile of follitropin delta when compared to other gonadotropin formulations for ovarian stimulation in in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycles. METHODS: An extensive search was performed to identify phase 1, phase 2 and phase 3 RCTs in humans focused on follitropin delta use for ovarian stimulation in IVF/ICSI cycles. The risk of bias and the overall quality of the evidence was analyzed. All data were extracted and analyzed using the intention-to-treat principle and expressed per woman randomized. RESULTS: A total of 7 RCTs (1 phase 1 RCT, 2 phase 2 RCTs and 4 phase 3 RCTs) were included in the qualitative analysis, whereas data of three phase 3 RCTs were meta-analyzed. All trials compared personalized recombinant follitropin delta treatment versus conventional recombinant follitropin alfa/beta administration in potentially normo-responder patients who receive ovarian stimulation in GnRH antagonist IVF/ICSI cycles. No difference between two regimens was detected for clinical pregnancy rate [odds ratio (OR) 1.06; 95% confidence intervals (CI): 0.90, 1.24; P = 0.49; I2 = 26%], ongoing pregnancy rate (OR 1.15; 95%CI: 0.90, 1.46; P = 0.27; I2 = 40%), and live birth rate (OR 1.18; 95%CI: 0.89, 1.55; P = 0.25; I2 = 55%). No data were available regarding cumulative success rates. The rate of adoption of strategies to prevent ovarian hyperstimulation syndrome (OHSS) development (OR 0.45; 95%CI: 0.30, 0.66; P < 0.0001; I2 = 0%), and the rate of both early OHSS (OR 0.62; 95%CI: 0.43, 0.88; P = 0.008; I2 = 0%) and all forms of OHSS (OR 0.61; 95%CI: 0.44, 0.84; P = 0.003; I2 = 0%) were significantly lower in the group of patients treated with personalized follitropin delta treatment compared to those treated with conventional follitropin alfa/beta administration. CONCLUSION: Personalized follitropin delta treatment is associated with a lower risk of OHSS compared to conventional follitropin alfa/beta administration in potentially normo-responder patients who receive ovarian stimulation in GnRH antagonist IVF/ICSI cycles. The absence of cumulative data does not allow definitive conclusions to be drawn regarding the comparison of the effectiveness of the two treatments. PROTOCOL STUDY REGISTRATION: CRD42023470352 (available at http://www.crd.york.ac.uk/PROSPERO ).

The role of L1CAM as predictor of poor prognosis in stage I endometrial cancer: a systematic review and meta-analysis.

INTRODUCTION: Molecular and genomic profiling in endometrial cancer is increasing popularity. L1 cell adhesion molecule (L1CAM) is frequently mutated in endometrial cancer. In this paper, we aim to evaluate the prognostic role of L1CAM in patients with stage I endometrial cancer. METHODS: We performed a systematic review and meta-analysis searching in PubMed (MEDLINE), EMBASE, and Web of Science database to identify studies reporting the expression of L1CAM in endometrial cancer. The primary endpoint measure was to assess and evaluate the impact of L1CAM on survival outcomes. This study was performed according to the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) statement. RESULTS: Five studies were included. The pooled results suggested that L1CAM expression influences survival outcomes in stage I endometrial cancer. High L1CAM expression correlated with worse disease-free survival (HR 4.11, 95% CI 1.02-16.59, p = 0.047) and overall survival (HR 3.62, 95% CI 1.32-9.31, p = 0.012). High L1CAM level was also associated with a more aggressive FIGO grade and with older age. CONCLUSION: This systematic review supported that L1CAM have a prognostic role in stage I endometrial cancer, thus providing a potential useful tool for tailoring the need of adjuvant therapy.

Pharmacotherapy for the treatment of recurrent cervical cancer: an update of the literature.

INTRODUCTION: Cervical cancer is the fourth most common cause of cancer-related death worldwide. High-risk locally advanced or recurrent/metastatic cervical cancers have a poor prognosis with routine treatments. The objective of this study is to analyze the data available in the literature on therapies and molecules currently in use to improve the prognosis of recurrent cervical cancer. AREAS COVERED: An extensive literature search was conducted by authors to identify relevant trials on various databases. Articles in English published until September 2023 that investigate different pharmacotherapy strategies for the treatment of recurrent cervical cancer, were included. Results of various pharmacological regimens including different combinations of chemotherapy, immune checkpoint inhibitors, DNA damage repair inhibitors and antibody-drug conjugates were analyzed. EXPERT OPINION: In recent years, there have been significant improvements in the outcomes of recurrent/metastatic cervical cancer. However, these improvements do not address the unmet need in terms of oncological outcomes. The introduction of immunotherapy and targeted therapies showed advantages in cervical cancer patients. New therapies and combination strategies must be implemented. Centralization of care and enrollment in clinical trials are of paramount importance. Primary and secondary prevention remains the fundamental goal to reduce the burden of cervical cancer.

Beyond the Umbrella: A Systematic Review of the Interventions for the Prevention of and Reduction in the Incidence and Severity of Ovarian Hyperstimulation Syndrome in Patients Who Undergo In Vitro Fertilization Treatments.

Ovarian hyperstimulation syndrome (OHSS) is the main severe complication of ovarian stimulation for in vitro fertilization (IVF) cycles. The aim of the current study was to identify the interventions for the prevention of and reduction in the incidence and severity of OHSS in patients who undergo IVF not included in systematic reviews with meta-analyses of randomized controlled trials (RCTs) and assess and grade their efficacy and evidence base. The best available evidence for each specific intervention was identified, analyzed in terms of safety/efficacy ratio and risk of bias, and graded using the Oxford Centre for Evidence-Based Medicine (CEBM) hierarchy of evidence. A total of 15 interventions to prevent OHSS were included in the final analysis. In the IVF population not at a high risk for OHSS, follitropin delta for ovarian stimulation may reduce the incidence of early OHSS and/or preventive interventions for early OHSS. In high-risk patients, inositol pretreatment, ovulation triggering with low doses of urinary hCG, and the luteal phase administration of a GnRH antagonist may reduce OHSS risk. In conclusion, even if not supported by systematic reviews with homogeneity of the RCTs, several treatments/strategies to reduce the incidence and severity of OHSS have been shown to be promising.

Polycystic ovary syndrome and thyroid disorder: a comprehensive narrative review of the literature.

Background: Published data on the relationship between polycystic ovary syndrome (PCOS) and thyroid dysfunction are sparse and confusing. Objective: To comprehensively review data available in the literature regarding the relationship between PCOS and the thyroid function, and its abnormalities. Methods: Nine main areas of interest were identified and analyzed according to the available evidence: 1) Evaluation of thyroid function for PCOS diagnosis; 2) Epidemiology data on thyroid function/disorders in patients with PCOS, and vice versa; 3) Experimental data supporting the relationship between thyroid function/disorders and PCOS; 4) Effects of thyroid function/disorders on PCOS features, and vice versa; 5) Effect of thyroid alterations on the cardiometabolic risk in women with PCOS; 6) Effect of thyroid abnormalities on reproductive outcomes in women with PCOS; 7) Relationship between thyroid function/abnormalities in patients with PCOS who are undergoing fertility treatment; 8) Effect of treatments for thyroid diseases on PCOS; and 9) Effect of treatments for PCOS on thyroid function. An extensive literature search for specific keywords was performed for articles published from 1970 to March 2023 using PubMed and Web of Science. Data were reported in a narrative fashion. Results: PCOS is a diagnosis of exclusion for which diagnosis is possible only after excluding disorders that mimic the PCOS phenotype, including thyroid dysfunctions. However, the tests and the cutoff values used for this are not specified. Many experimental and clinical data suggest a relationship between perturbations of the thyroid function and PCOS. Direct and unequivocal evidence on the effects of thyroid function/disorders on PCOS features are lacking. High thyroid-stimulating hormone levels and subclinical hypothyroidism may be associated with significant worsening of several intermediate endpoints of cardiometabolic risk in women with PCOS. Thyroid abnormalities may worsen reproductive outcomes, especially in patients undergoing fertility treatment. To date, there are no data demonstrating the efficacy of thyroid medications on fertility and cardiometabolic risk in women with PCOS. Lifestyle modification changes, metformin, and vitamin D seem to improve thyroid function in the general population. Conclusion: PCOS and thyroid disorders are closely related, and their coexistence may identify patients with a higher reproductive and metabolic risk. Regular screening for thyroid function and thyroid-specific autoantibodies in women with PCOS, particularly before and during pregnancy, is highly recommended.

Interventions to prevent or reduce the incidence and severity of ovarian hyperstimulation syndrome: a systematic umbrella review of the best clinical evidence.

Ovarian hyperstimulation syndrome (OHSS) is a potentially life-threating iatrogenic complication of the early luteal phase and/or early pregnancy after in vitro fertilization (IVF) treatment. The aim of the current study was to identify the most effective methods for preventing of and reducing the incidence and severity of OHSS in IVF patients. A systematic review of systematic reviews of randomized controlled trials (RCTs) with meta-analysis was used to assess each potential intervention (PROSPERO website, CRD 268626) and only studies with the highest quality were included in the qualitative analysis. Primary outcomes included prevention and reduction of OHSS incidence and severity. Secondary outcomes were maternal death, incidence of hospital admission, days of hospitalization, and reproductive outcomes, such as incidence of live-births, clinical pregnancies, pregnancy rate, ongoing pregnancy, miscarriages, and oocytes retrieved. A total of specific interventions related to OHSS were analyzed in 28 systematic reviews of RCTs with meta-analyses. The quality assessment of the included studies was high, moderate, and low for 23, 2, and 3 studies, respectively. The certainty of evidence (CoE) for interventions was reported for 37 specific situations/populations and resulted high, moderate, and low-to-very low for one, 5, and 26 cases, respectively, while it was not reported in 5 cases. Considering the effective interventions without deleterious reproductive effects, GnRH-ant co-treatment (36 RCTs; OR 0.61, 95% C 0.51 to 0.72, n = 7,944; I2 = 31%) and GnRH agonist triggering (8 RCTs; OR 0.15, 95% CI 0.05 to 0.47, n = 989; I2 = 42%) emerged as the most effective interventions for preventing OHSS with a moderate CoE, even though elective embryo cryopreservation exhibited a low CoE. Furthermore, the use of mild ovarian stimulation (9 RCTs; RR 0.26, CI 0.14 to 0.49, n = 1,925; I2 = 0%), and dopaminergic agonists (10 RCTs; OR 0.32, 95% CI 0.23 to 0.44, n = 1,202; I2 = 13%) coadministration proved effective and safe with a moderate CoE. In conclusion, the current study demonstrates that only a few interventions currently can be considered effective to reduce the incidence of OHSS and its severity with high/moderate CoE despite the numerous published studies on the topic. Further well-designed RCTs are needed, particularly for GnRH-a down-regulated IVF cycles.

Fertility specialists' views, behavior, and attitudes towards the use of endometrial scratching in Italy.

BACKGROUND: Endometrial scratching (ES) or injury is intentional damage to the endometrium performed to improve reproductive outcomes for infertile women desiring pregnancy. Moreover, recent systematic reviews with meta-analyses and randomized controlled trials demonstrated that ES is not effective, data on the safety are limited, and it should not be recommended in clinical practice. The aim of the current study was to assess the view and behavior towards ES among fertility specialists throughout infertility centers in Italy, and the relationship between these views and the attitudes towards the use of ES as an add-on in their commercial setting. METHODS: Online survey among infertility centers, affiliated to Italian Society of Human Reproduction (SIRU), was performed using a detailed questionnaire including 45 questions with the possibility to give "closed" multi-choice answers for 41 items and "open" answers for 4 items. Online data from the websites of the infertility centers resulting in affiliation with the specialists were also recorded and analyzed. The quality of information about ES given on infertility centers websites was assessed using a scoring matrix including 10 specific questions (scored from 0 to 2 points), and the possible scores ranged from 0 to 13 points ('excellent' if the score was 9 points or more, 'moderate' if the score was between 5 and 8, and 'poor' if it was 4 points or less). RESULTS: The response rate was of 60.6% (43 questionnaires / 71 infertility SIRU-affiliated centers). All included questionnaires were completed in their entirety. Most physicians (~ 70%) reported to offer ES to less than 10% of their patients. The procedure is mainly performed in the secretory phase (69.2%) using pipelle (61.5%), and usually in medical ambulatory (56.4%) before IVF cycles to improve implantation (71.8%) without drugs administration (e.g., pain drugs, antibiotics, anti-hemorrhagics, or others) before (76.8%) or after (64.1%) the procedure. Only a little proportion of infertility centers included in the analysis proposes formally the ES as an add-on procedure (9.3%), even if, when proposed, the full description of the indications, efficacy, safety, and costs is never addressed. However, the overall information quality of the websites was generally "poor" ranging from 3 to 8 and having a low total score (4.7 ± 1.6; mean ± standard deviation). CONCLUSIONS: In Italy, ES is a procedure still performed among fertility specialists for improving the implantation rate in IVF patients. Moreover, they have a poor attitude in proposing ES as an add-on in the commercial setting.

Endometrial Scratching for Improving Endometrial Receptivity: a Critical Review of Old and New Clinical Evidence.

Endometrial scratching is intentional injury of the endometrium intended to improve the reproductive outcomes of infertile women who seek pregnancy. In recent years, several randomized controlled trials, systematic reviews, and meta-analyses of trials have been published, reporting controversial results. Some authors have recommended against endometrial scratching in clinical practice, while others have recommended its application to specific categories of patients. This article aimed to provide a critical analysis of the old and new available evidence, to assist physicians interpreting the published data, and to generate insights for future research on the topic.

Is endometrial receptivity impaired in women with polycystic ovary syndrome?

Women with polycystic ovary syndrome (PCOS) seem to have impaired reproductive performances. It is generally considered that an altered ovulatory function is the main cause of infertility in the affected women. However, other factors may play a role in the pathogenesis of the PCOS-related infertility. During the last years, more and more importance has been given to endometrium as contributor of the PCOS-related subfertility. In the present narrative review, the main and recent experimental and clinical data will discuss in order to clarify the role played by the endometrium in the PCOS-related subfertility. The overall analysis of available data suggests that, in women with PCOS, the endometrium is primarily affected, and closely and deeply influenced by the several hormonal, metabolic, clinical alterations related to the syndrome.

Advances on Prevention and Screening of Gynecologic Tumors: Are We Stepping Forward?

According to 2020 comprehensive global cancer statistics published by the International Agency for Research on Cancer, gynecologic malignancies accounted overall for 16 [...].

Fractional Co2 laser for vulvo-vaginal atrophy in gynecologic cancer patients: A valid therapeutic choice? A systematic review.

INTRODUCTION: One of the most common adverse events reported by gynecological cancer survivors with spontaneous or iatrogenic menopause is vulvo-vaginal atrophy (VVA). An increasing number of women have this kind of discomfort related to the menopause induced by different cancer therapies. In this regard, fractional CO2 laser may be a valid therapeutic choice for these patients. METHODS: We performed a literature search of PubMed, EMBASE, SCOPUS and Web of Science databases with search terms of laser CO2 treatment of vulvovaginal atrophy and gynecologic cancer survivors and reviewed major US Society Guidelines to create this narrative review of this topic. Breast, ovarian endometrial and cervical cancers were included. RESULTS: Nine studies were included. Fractional CO2 laser improves clinical symptoms and sexual function, in terms of VHI (vaginal health index) and FSFI (female sexual function index). Non severe adverse event occurred. CONCLUSION: According to the best evidence available, fractional CO2 laser treatment for VVA is an effective and safe therapeutic option for gynecological cancer survivors, improving sexual life and quality of life (QoL).

Endocrine Disruptors and Endometrial Cancer: Molecular Mechanisms of Action and Clinical Implications, a Systematic Review.

It has been widely demonstrated that endocrine disruptors play a central role in various physiopathological processes of human health. In the literature, various carcinogenic processes have been associated with endocrine disruptors. A review of the molecular mechanisms underlying the interaction between endocrine disruptors and the endometrial cancer has been poorly developed. A systematic review was performed using PubMed®/MEDLINE. A total of 25 in vivo and in vitro works were selected. Numerous endocrine disruptors were analyzed. The most relevant results showed how Bisphenol A (BPA) interacts with the carcinogenesis process on several levels. It has been demonstrated how BPA can interact with hormonal receptors and with different transcription proliferative and antiproliferative factors. Furthermore, the effect of Polycyclic aromatic hydrocarbons on Aryl hydrocarbon receptors was investigated, and the role of flame retardants in promoting proliferation and metastasis was confirmed. The results obtained demonstrate how the mechanisms of action of endocrine disruptors are manifold in the pathophysiology of endometrial cancer, acting on different levels of the cancerogenesis process.

Female fertility preservation: Impact of cancer on ovarian function and oocyte quality.

OBJECTIVE: To evaluate the influence of cancer on ovarian response and oocyte quality in controlled ovarian hyperstimulation (COH). METHODS: This prospective study conducted at the Physiopathology of Reproduction and Andrology Unit of Sandro Pertini Hospital enrolled 82 cancer patients undergoing controlled ovarian stimulation (COH) cycles for fertility preservation, and age- and date-matched controls undergoing COH for in vitro fertilization for male-factor infertility from June 2016 to November 2019. The interventions performed were COH, oocyte retrieval, and quality evaluation. Main outcome measures were maximal estradiol levels on the day of human chorionic gonadotropin administration, duration of stimulation, total amount of gonadotropins administered, number of oocytes retrieved, and rates of metaphase 2 oocytes and abnormal oocytes. All data were analyzed using the Statistical Package for the Social Sciences (IBM Corp., Armonk, NY, USA) 22.0. RESULTS: Intergroup comparisons (82 cancer patients and 180 patients in control group) showed a significant difference in ovarian response, especially for a significant higher number of abnormal oocytes in cancer patients (P < 0.0001). Regression analysis to assess the influence of the neoplastic process, regardless of the type, on ovarian response showed an effect on the main outcome measured due to cancer itself. CONCLUSION: Cancer influences the ovarian response, particularly the oocyte quality, during COH performed for fertility preservation.

Effects of Endocrine-Disrupting Chemicals on Endometrial Receptivity and Embryo Implantation: A Systematic Review of 34 Mouse Model Studies.

Several available studies have already analyzed the systemic effects of endocrine-disrupting chemicals (EDCs) on fertile woman and neonatal outcomes, but little is still known in humans about the precise mechanisms of interference of these compounds with the endometrial receptivity. There is consistent evidence that continuous and prolonged exposure to EDCs is a risk factor for reduced fertility and fecundity in women. Preliminary studies on mammalian models provide robust evidence about this issue and could help gynecologists worldwide to prevent long term injury caused by EDCs on human fertility. In this systematic review, we aimed to systematically summarize all available data about EDC effects on blastocyst endometrial implantation. We performed a systematic review using PubMed®/MEDLINE® to summarize all in vivo studies, carried out on mice models, analyzing the molecular consequences of the prolonged exposure of EDC on the implantation process. 34 studies carried out on mouse models were included. Primary effects of EDC were a reduction of the number of implantation sites and pregnancy rates, particularly after BPA and phthalate exposure. Furthermore, the endometrial expression of estrogen (ER) and progesterone receptors (PR), as well as their activation pathways, is compromised after EDC exposure. Finally, the expression of the primary endometrial markers of receptivity (such as MUC1, HOXA10, Inn and E-cadherin) after EDC contact was analyzed. In conclusion EDC deeply affect blastocyst implantation in mouse model. Several players of the implantation mechanism are strongly influenced by the exposure to different categories of EDC.

Fibrin Sealants and Axillary Lymphatic Morbidity: A Systematic Review and Meta-Analysis of 23 Clinical Randomized Trials.

BACKGROUND: use of fibrin sealants following pelvic, paraaortic, and inguinal lymphadenectomy may reduce lymphatic morbidity. The aim of this meta-analysis is to evaluate if this finding applies to the axillary lymphadenectomy. METHODS: randomized trials evaluating the efficacy of fibrin sealants in reducing axillary lymphatic complications were included. Lymphocele, drainage output, surgical-site complications, and hospital stay were considered as outcomes. RESULTS: twenty-three randomized studies, including patients undergoing axillary lymphadenectomy for breast cancer, melanoma, and Hodgkin's disease, were included. Fibrin sealants did not affect axillary lymphocele incidence nor the surgical site complications. Drainage output, days with drainage, and hospital stay were reduced when fibrin sealants were applied (p < 0.0001, p < 0.005, p = 0.008). CONCLUSION: fibrin sealants after axillary dissection reduce the total axillary drainage output, the duration of drainage, and the hospital stay. No effects on the incidence of postoperative lymphocele and surgical site complications rate are found.

The Clinical and Pathological Profile of BRCA1 Gene Methylated Breast Cancer Women: A Meta-Analysis.

BACKGROUND: DNA aberrant hypermethylation is the major cause of transcriptional silencing of the breast cancer gene 1 (BRCA1) gene in sporadic breast cancer patients. The aim of the present meta-analysis was to analyze all available studies reporting clinical characteristics of BRCA1 gene hypermethylated breast cancer in women, and to pool the results to provide a unique clinical profile of this cancer population. METHODS: On September 2020, a systematic literature search was performed. Data were retrieved from PubMed, MEDLINE, and Scopus by searching the terms: "BRCA*" AND "methyl*" AND "breast". All studies evaluating the association between BRCA1 methylation status and breast cancer patients' clinicopathological features were considered for inclusion. RESULTS: 465 studies were retrieved. Thirty (6.4%) studies including 3985 patients met all selection criteria. The pooled analysis data revealed a significant correlation between BRCA1 gene hypermethylation and advanced breast cancer disease stage (OR = 0.75: 95% CI: 0.58-0.97; p = 0.03, fixed effects model), lymph nodes involvement (OR = 1.22: 95% CI: 1.01-1.48; p = 0.04, fixed effects model), and pre-menopausal status (OR = 1.34: 95% CI: 1.08-1.66; p = 0.008, fixed effects model). No association could be found between BRCA1 hypermethylation and tumor histology (OR = 0.78: 95% CI: 0.59-1.03; p = 0.08, fixed effects model), tumor grading (OR = 0.78: 95% CI :0.46-1.32; p = 0.36, fixed effects model), and breast cancer molecular classification (OR = 1.59: 95% CI: 0.68-3.72; p = 0.29, random effects model). CONCLUSIONS: hypermethylation of the BRCA1 gene significantly correlates with advanced breast cancer disease, lymph nodes involvement, and pre-menopausal cancer onset.