Advances in Urinary Diversion: From Cutaneous Ureterostomy to Orthotopic Neobladder Reconstruction-A Comprehensive Review.

Bladder cancer ranks as the 10th most prevalent cancer globally with an increasing incidence. Radical cystectomy combined with urinary diversion represents the standard treatment for muscle-invasive bladder cancer, offering a range of techniques tailored to patient factors. Overall, urinary diversions are divided into non-continent and continent. Among the first category, cutaneous ureterostomy and ileal conduit represent the most common procedures while in the second category, it could be possible to describe another subclassification which includes ureterosigmoidostomy, continent diversions requiring catheterization and orthotopic voiding pouches and neobladders. In this comprehensive review, urinary diversions are described in their technical aspects, providing a summary of almost all alternatives to urinary diversion post-radical cystectomy.

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.

The Role of ß1 Integrin/CD29 as a Potential Prognostic Factor for the Risk of Progression to Cervical Carcinoma in HPV-Associated Lesions.

Background and Objectives: Available evidence reports the overexpression of ß1 integrin in dysplastic rather than normal cervical tissue. We aimed to evaluate the involvement of ß1 (CD29) integrin in the progressive pathogenesis of cervical intraepithelial neoplasia (CIN). Materials and Methods: From January 2019 to December 2021, we prospectively enrolled women undergoing a colposcopy with a cervical biopsy for abnormal cervical cytology and/or undefined cytology with a positive HPV DNA test and women with relapsing cervical inflammatory disorders. Based on the histopathological results, women were divided into four groups: group A (CIN1), group B (CIN2), group C (CIN3), and group D (no CIN diagnosis) as a control group. Subsequently, cytofluorimetry and immunohistochemical analysis (based on the identified positive cell ratios as follows: ≤10%, negative; 10-25%, 1+ (weak); 25-50%, 2+ (medium); ≥50%, and 3+ (high)) for ß1 integrin were carried out. Results: In total, 154 women were included. The average fluorescence intensity in the four groups was 2.35 ± 1.37, 2.73 ± 1.56, 3.09 ± 1.56, and 2.13 ± 1.25 UA from groups A to D, respectively; this figure was significantly different for CIN3 (group C) women relative to the other groups (p = 0.0132). Higher ß1 integrin/CD29 concentrations in the CIN groups with HR-HPV 16 and 18 were also detected (p = 0.0292, 0.0367, and 0.0357 respectively for CIN3, CIN2, and CIN1). Immunohistochemistry analysis showed higher results for the CIN3 group compared to controls and all the other groups (p < 0.001). Conclusions: ß1/CD29 integrin expression increased with CIN grade, and it was significantly higher in CIN3 lesions. This could be used as a promising screening tool to identify women prone to developing high-grade cervical lesions. However, additional evidence is needed to strengthen these findings.

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.

Changes in Circulating Acylated Ghrelin and Neutrophil Elastase in Diabetic Retinopathy.

Background and Objectives: The role and the levels of ghrelin in diabetes-induced retinal damage have not yet been explored. The present study aimed to measure the serum levels of total ghrelin (TG), and its acylated (AG) and des-acylated (DAG) forms in patients with the two stages of diabetic retinopathy (DR), non-proliferative (NPDR) and proliferative (PDR). Moreover, the correlation between serum ghrelin and neutrophil elastase (NE) levels was investigated. Materials and Methods: The serum markers were determined via enzyme-linked immunosorbent assays in 12 non-diabetic subjects (CTRL), 15 diabetic patients without DR (Diabetic), 15 patients with NPDR, and 15 patients with PDR. Results: TG and AG serum levels were significantly decreased in Diabetic (respectively, p < 0.05 and p < 0.01 vs. CTRL), NPDR (p < 0.01 vs. Diabetic), and in PDR patients (p < 0.01 vs. NPDR). AG serum levels were inversely associated with DR abnormalities (microhemorrhages, microaneurysms, and exudates) progression (r = -0.83, p < 0.01), serum neutrophil percentage (r = -0.74, p < 0.01), and serum NE levels (r = -0.73, p < 0.01). The latter were significantly increased in the Diabetic (p < 0.05 vs. CTRL), NPDR (p < 0.01 vs. Diabetic), and PDR (p < 0.01 vs. PDR) groups. Conclusions: The two DR stages were characterized by decreased AG and increased NE levels. In particular, serum AG levels were lower in PDR compared to NPDR patients, and serum NE levels were higher in the PDR vs. the NPDR group. Together with the greater presence of retinal abnormalities, this could underline a distinctive role of AG in PDR compared to NPDR.

Efficacy of a Novel Rigenase® and Polyhexanide (Fitostimoline® Septagel) Hydrogel Device for the Treatment of Vulvovaginitis Symptoms: Cross-Sectional Analysis of a National Survey and Prospective Observational Study.

Background and Objectives: Signs and symptoms of vulvovaginitis, especially when recurrent, have a significant impact on a woman's quality of life. The aim of this study was to survey gynecologists about their habits regarding the treatments of the pathology and to evaluate the efficacy of a novel vaginal hydrogel composed of wheat extracts and polyhexanide aimed at reducing vulvovaginitis symptomatology. Materials and Methods: A cross-sectional analysis of a national survey using 155 Italian gynecologists and a prospective, open-label, observational study were carried out in 75 outpatient clinics across Italy. Pre- and postmenopausal women with suspicion of vulvovaginitis due to at least four of the following symptoms (leucoxanthorrhea, bad odor from genitalia, vulvovaginal dryness, petechiae, burning, and pruritus) while waiting for microbiological swab analysis were included and treated with one hydrogel application every 3 days for 1 week. Primary endpoint was the complete resolution of symptomatology. Results: The pre-study survey reported that, for most clinicians, local or oral treatment (65.7% and 82.8%, respectively) with antibiotics or antifungals is used very often. Therefore, we proceeded to carry out an observational study. Overall, 615 (362 of fertile age and 253 in postmenopause) women were included in this study. At the 28th follow-up examination, complete resolution of symptomatology was achieved in 578/615 (94.1%; p < 0.001) within 12.72 ± 6.55 and 13.22 ± 6.33 days for those of fertile age and in postmenopause, respectively (p = 0.342). All of the evaluated symptoms were significantly reduced after treatment (p = 0.001) without differences according to the patient's menopausal status. A slightly significant reduction in Gardnerella Vaginalis (p = 0.040) and Candida Albicans (p = 0.049) was found after treatment. No patient reported side effects, adverse reactions, or discontinued therapy. Conclusions: This pilot study showed that a hydrogel based on Rigenase® (wheat extract) and polyhexanide could be a promising treatment for the relief of vulvovaginitis symptoms. However, these results are limited by the absence of a control group. Additional comparative and randomized controlled trials between the hydrogel and other non-antibiotic devices as well as local antibiotic therapy should be performed to increase the validity of the findings.

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.

Critical Overview of Serous Endometrial Intraepithelial Cancer Treatment: Systematic Review of Adjuvant Options.

SEIC is a non-invasive lesion of the endometrial epithelium considered to be the precursor to uterine serous carcinoma (USC) and is just as aggressive as USC. Currently, there are no reliable data about the behavior and prognosis of SEIC; therefore, the therapeutic management approach is not clear. Method: A systematic search of the Pubmed, Scopus and Embase databases was conducted, following the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Results: Of the 296 studies that matched the search criteria, only 9 met the inclusion criteria, covering a total of 81 patients. The main disease-presenting pattern was AUB (abnormal uterine bleeding). In 31 cases, SEIC was associated with extrauterine disease. All patients underwent hysterectomy and salpingo-oophorectomy, while only 15 of the 81 patients received adjuvant treatments. In the patients receiving adjuvant therapy, the RR was 42.67%, the DFS was 35.71% and the OS was 57.13%. In patients subjected to follow-up alone, the RR was only 28.78%, the DFS was 59.1% and the OS was 66.6%. Conclusions: The presence of an extrauterine disease significantly worsens outcomes, regardless of adjuvant treatment. In cases of disease confined to the uterine mucosa alone, the prognosis is good and follow-up allows a good control of the disease; however, adjuvant therapy could further increase survival rates and reduce relapse rates.

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.

Laparoscopic uterosacral ligament suspension: a systematic review and meta-analysis of safety and durability.

Introduction: Pelvic organ prolapse (POP) is a widespread condition affecting from 40% to 60% of women. Reconstructive vaginal surgeries are the most commonly performed procedures to treat POP. Among those, uterosacral ligament suspension (USLS), which is usually performed transvaginally, preserves pelvic statics and dynamics and appears to be an effective method. Laparoscopic USLS is a valid alternative to vaginal approach, and the aim of our review is to confirm its safety and feasibility and to compare clinical outcomes among the procedures. 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 December 2022. We made no restriction on the publication year nor on the country. Data about POP-Q recurrence rate (RR), intraoperative and postoperative complications (graded according to Clavien-Dindo classification), readmission rate, and reoperation rate were collected and analyzed. We used comparative studies for meta-analysis. Results: A total of nine studies fulfilled inclusion criteria: two articles were non-comparative retrospective observational studies, three more articles were comparative studies where laparoscopic USLS was confronted with other surgical techniques (only data of laparoscopic USLS were analyzed), and four were comparative retrospective cohort studies between laparoscopic and vaginal USLS procedures. The comparative studies were enrolled in meta-analysis. Patients were analyzed concerning perioperative risks and the risk of recurrence. The meta-analysis highlighted that there was no clear inferiority of one technique over the other. Discussion: Laparoscopic USLS is a technique with a low complication rate and low recurrence rate. Indeed, laparoscopic procedure allows better identification of anatomical landmarks and access to retroperitoneum. Moreover, efficacy over time and durability of Laparoscopic (LPS) USLS was also observed. However, these data should be weighed in light of the length of follow-up, which was in a very short range. Further, focused and prospective studies will be necessary to confirm this finding.

Pelvic Organ Prolapse Syndrome and Lower Urinary Tract Symptom Update: What's New?

(1) Background: This narrative review aimed to analyze the epidemiological, clinical, surgical, prognostic, and instrumental aspects of the link between pelvic organ prolapse (POP) and lower urinary tract symptoms (LUTS), collecting the most recent evidence from the scientific literature. (2) Methods: We matched the terms "pelvic organ prolapse" (POP) and "lower urinary tract symptoms" (LUTS) on the following databases: Pubmed, Embase, Scopus, Google scholar, and Cochrane. We excluded case reports, systematic reviews, articles published in a language other than English, and studies focusing only on a surgical technique. (3) Results: There is a link between POP and LUTS. Bladder outlet obstruction (BOO) would increase variation in bladder structure and function, which could lead to an overactive bladder (OAB). There is no connection between the POP stage and LUTS. Prolapse surgery could modify the symptoms of OAB with improvement or healing. Post-surgical predictive factors of non-improvement of OAB or de novo onset include high BMI, neurological pathologies, age > 65 years, and the severity of symptoms; predictors of emptying disorders are neurological pathologies, BOO, perineal dysfunctions, severity of pre-surgery symptoms, and severe anterior prolapse. Urodynamics should be performed on a specific subset of patients (i.e., stress urinary incontinence, correct surgery planning), (4) Conclusions: Correction of prolapse is the primary treatment for detrusor underactivity and for patients with both POP and OAB.

Risk of Premature Ovarian Insufficiency after Human Papilloma Virus Vaccination: A PRISMA Systematic Review and Meta-Analysis of Current Evidence.

(1) Background: Premature ovarian insufficiency (POI) has been linked to human papilloma virus (HPV) vaccination in small case-reports. The aim of this meta-analysis was to evaluate the risk of POI after HPV vaccination. (2) Methods: Electronic searches in MEDLINE Scopus, LILACS, ClinicalTrials.gov, EMBASE, PROSPERO, Cochrane CENTRAL and other registries were searched from inception to September 2022. Inclusion criteria were cohort studies of female children or adolescents vaccinated with quadrivalent (4vHPV), bivalent (2vHPV) or 9-valent (9vHPV) vaccine and compared to unvaccinated, other HPV vaccine, or vaccinated with other childhood vaccine girls. Primary outcome was risk of POI after vaccination. (3) Results: Four studies, including 1,253,758 patients, were included. Overall, there was no significant risk for POI between 4vHPV and controls (unvaccinated or other vaccines) (RR 0.47 (95% CI 0.14 to 1.59) I2 = 75%), or unvaccinated only controls (RR 0.75 (95% CI 0.22 to 2.49) I2 = 26%). One study reported a significant reduction of POI risk for 4vHPV relative to the other childhood vaccinations (RR 0.03 (95% CI 0.00 to 0.21)); meanwhile, one study showed no increased risk with 4vHPV relative to 2vHPV and 9vHPV (RR 0.93 (95% CI 0.33 to 2.64)). (4) Conclusions: 4vHPV vaccination does not seem to increase risk of POI relative to unvaccinated people or other childhood vaccines. No difference was seen with 4vHPV vaccine relative to 2vHPV and 9vHPV. Moreover, the risk of POI after HPV vaccination is relatable to worldwide incidence, giving reassurance about safety.