Dietary Supplementation of Myo-Inositol, Cocoa Polyphenols, and Soy Isoflavones Improves Vasomotor Symptoms and Metabolic Profile in Menopausal Women with Metabolic Syndrome: A Retrospective Clinical Study.

Background and Objectives: Hormonal changes physiologically occurring in menopausal women may increase the risk of developing metabolic and vasomotor disturbances, which contribute to increase the risk of developing other concomitant pathologies, such as metabolic syndrome (MetS). Materials and Methods: Retrospective data from 200 menopausal women with MetS and vasomotor symptoms taking one sachet per day of the dietary supplement INOFOLIC® NRT (Farmares srl, Rome, Italy) were collected. Each sachet consisted of myo-Inositol (2000 mg), cocoa polyphenols (30 mg), and soy isoflavones (80 mg, of which 50 mg is genistin). Patients recorded their symptoms through a medical questionnaire at the beginning of the administration (T0) and after 6 months (T1). Results: We observed an improvement in both the frequency and the severity of hot flushes: increased percentage of 2-3 hot flushes (28 at T0 vs. 65% at T1, p value < 0.001) and decreased percentage of 4-9 hot flushes (54% at T0 vs. 18% at T1, p value < 0.001). Moreover, symptoms of depression improved after supplementation (87% at T0 vs. 56% at T1 of patients reported moderate depression symptoms, p value < 0.001). Regarding metabolic profile, women improved body mass index and waist circumference with a reduction in the percentage of overweight and obesity women (88% at T0 vs. 51% at T1, p value = 0.01; 14% at T0 vs. 9% at T1, p value = 0.04). In addition, the number of women suffering from non-insulin dependent diabetes reduced (26% at T0 vs. 16% at T1, p value = 0.04). Conclusions: These data corroborate previously observed beneficial effects of the oral administration of myo-Inositol, cocoa polyphenols, and soy isoflavones against menopausal symptoms in the study population. Considering the promising results of the present study, further prospective controlled clinical trials are needed to deeply understand and support the efficacy of these natural compounds for the management of menopausal symptoms.

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.

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.

Meigs Syndrome and Elevated CA-125: Case Report and Literature Review of an Unusual Presentation Mimicking Ovarian Cancer.

Background and Objectives: Meigs syndrome is represented by a benign adnexal tumor, ascites, and hydrothorax. Even though the ovarian mass is often characterized by a fibroma-like origin, cancer antigen-125 (CA-125) serum levels could be elevated as in the development of ovarian cancer. Here, we present the case of a patient with Meigs syndrome and increased CA-125. Materials and Methods: We performed systematic research for articles including similar cases in PubMed, EMBASE, and Scopus in February 2023, adopting the string of idioms: "Meigs syndrome AND Cancer antigen 125", and following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Results: Eligible records were 25. Hydrothorax was right-sided in 10 cases over 25; left-sided in two patients over 25. Concerning ascites, two patients showed more than 6 L of ascitic fluid, whereas three patients had 6 L or less. CA-125 elevation ranged from 149 IU/mL to 3803 IU/mL. Adnexal mass histotypes were: struma ovarii (12 cases), thecomas (two cases), fibrothecomas (five cases), fibromas (five cases), and one sclerosing stromal tumor (SST). Conclusions: In postmenopausal women with elevated CA-125 serum levels and an adnexal mass suspicious for malignancy at ultrasound (US), ascites and pleural effusion, surgery, and histopathological examination are necessary. MS is a diagnostic option, with an excellent prognosis after exeresis of the mass.

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.

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.

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.

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.

A Rare Complication during Vaginal Delivery, Hamman's Syndrome: A Case Report and Systematic Review of Case Reports.

BACKGROUND: Spontaneous pneumomediastinum (SPM) during pregnancy or labor is a rare event. We presented a case report and a systematic review of the literature to provide comprehensive symptoms, treatments, and complications analysis in the pregnant population affected by SPM. METHODS: We conducted a comprehensive search of four databases for published papers in all languages from the beginning to 1 September 2021; Results: We included 76 papers with a total of 80 patients. A total of 76% patients were young primiparous, with a median age of 24 ± 5.4 years. The median gestational age was 40 ± 2.4 weeks, with a median duration of labor of 7.4 ± 4.2 h. In 86%, the ethnic origin was not specified. SPM develops in 55% of cases during the second stage of labor. Subcutaneous swelling and subcutaneous emphysema were present in 91.4%. Chest pain and dyspnea were present in 51.4% and 50% of the patients, respectively. We found that 32.9% patients had crepitus, and less common symptoms were dysphonia and tachycardia (14.3% and 14.3%, respectively). Oxygen and bronchodilators were used in 37.7% of the cases. Analgesics or sedatives were administered in 27.1%. Conservative management or the observation was performed in 21.4% and 28.6%, respectively. Antibiotics treatment was offered in 14.3%, whereas invasive procedures such as chest-tube drainage were used in just 5.7% of patients. There were no complications documented in most SPM (70.0%). We found that 16.7% of the SPM developed a pneumothorax and 5% developed a pneumopericardium.; Conclusions: In pregnancy, SPM occurs as subcutaneous swelling or emphysema during the second stage of labor. The treatment is usually conservative, with oxygen and bronchodilators and a low sequela rate. A universal consensus on therapy of spontaneous pneumomediastinum in pregnancy is necessary to reduce the risk of complications.

Incidence of gestational diabetes mellitus before and after the Covid-19 lockdown: A retrospective cohort study.

AIM: To evaluate whether the first Covid-19 lockdown for Italian citizens (March to July 2021) might have altered the incidence of gestational diabetes mellitus (GDM). METHODS: A retrospective single-center study in a tertiary referral center. Primary outcome was the incidence of GDM among pregnant women. GDM incidence, from June 11, 2019 to December 4, 2020, was compared by dividing the study time as follows: from the beginning of the study to before Covid-19 lockdown (from June 11, 2019, to March 9, 2020) and lockdown period (from March 10, 2020, to December 4, 2020). GDM was diagnosed with a 75-g, 2-h oral glucose tolerance test (OGTT) at 24-28 gestational weeks. RESULTS: Concerning 1295 women, GDM incidence increased during the lockdown period (9.3% vs. 3.4%, p < 0.001). Higher pregnancy weight gain with an increased body mass index (BMI) at the delivery was reported during the lockdown (31.3 vs. 28.4 kg/m2 , p = 0.02 and mean weight gain of 9.3 vs. 6.6 kg, p = 0.007). There was no difference in other comorbidity incidence and OGTT values between the two groups. CONCLUSIONS: Pregnant women during the Covid-19 lockdown might have experienced higher BMI and pregnancy weight gain with increased GDM diagnoses. This may be related to physical limitations and emotional distress experienced during the lockdown. However, evidence is limited due to restricted study duration and random variations of outcomes across time. More studies are needed to understand the dietary patterns and the physical activity changes during the Covid-19 lockdown and its impact on fetal outcomes.

The gut-brain axis in irritable bowel syndrome and inflammatory bowel disease.

Research increasingly demonstrates the bidirectional communication between gut microbiota and the brain, enhancing the role of gut microbiota modulation in the treatment of central nervous system (CNS) disorders. The first five years of life are extremely important as it affects the development of gut microbiota, immune system and, consequently, the onset of psychometric alterations, particularly in genetically predisposed individuals. In this review, we focus on the link between specific microbial genera, gastrointestinal (GI) disorders, anxiety and depression and on the effects of different therapeutic strategies for mood disorders on gut microbiota.