New concept in urologic surgery: The total extended genital sparing radical cystectomy in women

Introduction and objectives: The aim of the study was to evaluate genital sparing radical cystectomy surgery in female patients from the point of view of both oncologic and functional outcomes (with emphasis on urinary and sexual outcomes) in a single high-volume center for the treatment of muscular invasive bladder cancer. Materials and methods: Between January 2014 and January 2018, 14 female patients underwent radical cystectomy with preservation of genital organs (the entire vagina, uterus, fallopian tubes, ovaries) and orthotopic urinary neobladder (Padua neobladder). Inclusion criteria were recurrent T1G3 tumors; refractory tumors after BCG therapy without associated carcinoma in situ (CIS); T2 or T3a tumors entirely resected at endoscopic transurethral resection of the bladder and not involving urethra/bladder trigone. Exclusion criteria were: T3b or higher bladder cancer, associated CIS and involvement of urethra or bladder trigone. Oncological and histopathological outcomes (Overall Survival - OS, Recurrence Free Survival - RFS), urinary outcomes (day and night incontinence, intermittent catheterization use, Sandvik Score) and sexual outcomes (Female Sexual Function Index 19 FSFI-19) were considered. The average follow-up time was 56 months. Results: Considering oncological outcomes, histologic examination reported urothelial carcinoma in 13/14 patients; 8/13 patients (61.5%) had high grade T1 stage, 3/13 patients (23%) had high grade T2 stage and finally 2/13 patients (15.5%) had high-grade T3 stage. One patient presented with embryonal rhabdomyosarcoma completely excised after surgery (PT2aN0M0). No patient developed local or metastatic recurrence (RFS 100%); OS was 100%. Considering urinary continence outcomes, 12/14 patients retained daytime and nighttime continence (85.5%); 2/14 (14.5%) complained of low stress urinary incontinence daily and nighttime urinary leakage. The Sandvik Score showed complete continence in 7/14 patients (50%); mild degree incontinence in 6/14 patients without use of incontinence devices (43%); moderate degree of incontinence in one patient (7%). The FSFI administered at 1 year from the surgery showed sexual desire in all patients (100%); subjective arousal, achievement of orgasm and sexual satisfaction in 12/14 patients (85.5%); sufficient lubrication in 11/14 patients (78.5%). Only one patient (7%) complained about dyspareunia during sexual intercourse. Conclusions: Our study aims to demonstrate that genital-sparing radical cystectomy is a safe surgery in terms of oncologic outcomes and, most importantly, that it is beneficial in terms of urinary and sexual function. Indeed, patients’ quality of life together with their psychological and emotional health should be put on the same level as oncological safety. However, it is a treatment reserved for selected patients who are strongly motivated to preserve fertility and sexual function and thoroughly informed about the benefits and complications of such a procedure

Long-term exposure of pancreatic β-cells to palmitate results in SREBP-1C-dependent decreases in GLP-1 receptor signaling via CREB and AKT and insulin secretory response

The effects of prolonged exposure of pancreatic β-cells to high saturated fatty acids on glucagonlike peptide-1 (GLP-1) action were investigated. Murine islets, human pancreatic 1.1B4 cells, and rat INS-1E cells were exposed to palmitate for 24 hours. mRNA and protein expression/phosphorylation were measured by real-time RT-PCR and immunoblotting, respectively. Specific short interfering RNAs were used to knockdown expression of the GLP-1 receptor (Glp1r) and Srebf1. Insulin release was assessed with a specific ELISA. Exposure of murine islets, as well as of human and INS-1E β-cells, to palmitate reduced the ability of exendin-4 to augment insulin mRNA levels, protein content, and release. In addition, palmitate blocked exendin-4-stimulated cAMP-response element-binding protein and v-akt murine thymoma viral oncogene homolog phosphorylation, whereas phosphorylation of MAPK-ERK kinase-1/2 and ERK-1/2 was not altered. Similarly, RNA interference-mediated suppression of Glp1r expression prevented exendin-4-induced cAMP-response element-binding protein and v-akt murine thymoma viral oncogene homolog phosphorylation, but did not impair exendin-4 stimulation of MAPK-ERK kinase-1/2 and ERK-1/2. Both islets from mice fed a high fat diet and human and INS-1E β-cells exposed to palmitate showed reduced GLP-1 receptor and pancreatic duodenal homeobox-1 (PDX-1) and increased sterol regulatory element-binding protein (SREBP-1C) mRNA and protein levels. Furthermore, suppression of SREBP-1C protein expression prevented the reduction of PDX-1 and GLP-1 receptor levels and restored exendin-4 signaling and action. Finally, treatment of INS-1E cells with metformin for 24 h resulted in inhibition of SREBP-1C expression, increased PDX-1 and GLP-1 receptor levels, consequently, enhancement of exendin-4-induced insulin release. Palmitate impairs exendin-4 effects on β-cells by reducing PDX-1 and GLP-1 receptor expression and signaling inaSREBP-1C-dependent manner. Metformin counteracts the impairment of GLP-1 receptor signaling induced by palmitate

Clinical Features, Cardiovascular Risk Profile, and Therapeutic Trajectories of Patients with Type 2 Diabetes Candidate for Oral Semaglutide Therapy in the Italian Specialist Care

Introduction: This study aimed to address therapeutic inertia in the management of type 2 diabetes (T2D) by investigating the potential of early treatment with oral semaglutide. Methods: A cross-sectional survey was conducted between October 2021 and April 2022 among specialists treating individuals with T2D. A scientific committee designed a data collection form covering demographics, cardiovascular risk, glucose control metrics, ongoing therapies, and physician judgments on treatment appropriateness. Participants completed anonymous patient questionnaires reflecting routine clinical encounters. The preferred therapeutic regimen for each patient was also identified. Results: The analysis was conducted on 4449 patients initiating oral semaglutide. The population had a relatively short disease duration (42%  60% of patients, and more often than sitagliptin or empagliflozin. Conclusion: The study supports the potential of early implementation of oral semaglutide as a strategy to overcome therapeutic inertia and enhance T2D management