Cisplatin eligibility in the neoadjuvant setting of patients with muscle-invasive bladder cancer undergoing radical cystectomy.

BACKGROUND: To examine the agreement of different calculated estimated glomerular filtration rate (eGFR) formulas and measured creatinine clearance (CrCI) at the primary diagnosis of muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: We performed a multicenter analysis of patients with MIBC, treated with cisplatin-based neoadjuvant chemotherapy (NAC) and radical cystectomy (RC), or with RC alone, between 2011 and 2021. Baseline eGFR was computed using 4 calculated serum equations including Cockcroft-Gault (CG), MDRD, CKD-EPI 2009, and race-free CKD-EPI 2021. To examine the association between calculated eGFR and measured CrCI, subgroup analyses were performed among patients in whom measured 24-hour urine CrCl was determined. Cisplatin-ineligibility was defined as CrCI and/or eGFR < 60 mL/minute per 1.73 m2. RESULTS: Of 956 patients, 30.0%, 33.3%, 31.9%, and 27.7% were found to be cisplatin-ineligible by the CG, MDRD, CKD-EPI, and race-free CKD-EPI equations (P = .052). The concordance between calculated eGFR formulas was rated substantial (Cohen's kappa (k): 0.66-0.95). Among the subgroup (n = 245) with measured CrCl, 37 (15.1%) patients had a CrCI less than 60 mL/minute. Concordance between measured CrCl and calculated eGFR was poor (ĸ: 0.29-0.40). All calculated eGFR formulas markedly underestimated the measured CrCI. Specifically, 78%-87.5% of patients with a calculated eGFR between 40 and 59 mL/minute exhibited a measured CrCI ≥ 60 mL/minute. CONCLUSIONS: Comparing calculated eGFR formulas, similar percentages of patients with MIBC were deemed cisplatin-ineligible. However, a significant number of patients could be upgraded by being cisplatin-fit based on measured CrCI, particularly when the calculated eGFR was falling within the gray range of 40-59 mL/minute.

Assessing Functional Outcomes of Partial Versus Radical Nephrectomy for T1b-T2 Renal Masses: Results from a Multi-institutional Collaboration.

BACKGROUND: Deterioration of renal function is associated with increased all-cause mortality. In renal masses larger than 4 cm, whether partial versus radical nephrectomy (PN vs. RN) might affect long-term functional outcomes is unknown. This study tested the association between PN versus RN and postoperative acute kidney injury (AKI), recovery of at least 90% of the preoperative estimated glomerular filtration rate (eGFR) at 1 year, upstaging of chronic kidney disease (CKD) one stage or more at 1 year, and eGFR decline of 45 ml/min/1.73 m2 or less at 1 year. METHODS: Data from 23 high-volume institutions were used. The study included only surgically treated patients with single, unilateral, localized, clinical T1b-2 renal masses. Multivariable logistic regression analyses were performed. RESULTS: Overall, 968 PN patients and 325 RN patients were identified. The rate of AKI was lower in the PN versus the RN patients (17% vs. 58%; p < 0.001). At 1 year after surgery, for the PN versus the RN patients, the rate for recovery of at least 90% of baseline eGFR was 51% versus 16%, the rate of CKD progression of ≥ 1 stage was 38% versus 65%, and the rate of eGFR decline of 45 ml/min/1.73 m2 or less was 10% versus 23% (all p < 0.001). Radical nephrectomy independently predicted AKI (odds ratio [OR], 7.61), 1-year ≥ 90% eGFR recovery (OR, 0.30), 1-year CKD upstaging (OR, 1.78), and 1-year eGFR decline of 45 ml/min/1.73 m2 or less (OR, 2.36) (all p ≤ 0.002). CONCLUSIONS: For cT1b-2 masses, RN portends worse immediate and 1-year functional outcomes. When technically feasible and oncologically safe, efforts should be made to spare the kidney in case of large renal masses to avoid the hazard of glomerular function loss-related mortality.

The optimal number of induction chemotherapy cycles in clinically lymph node-positive bladder cancer.

OBJECTIVE: To investigate the optimal number of induction chemotherapy cycles needed to achieve a pathological response in patients with clinically lymph node-positive (cN+) bladder cancer (BCa) who received three or four cycles of induction chemotherapy followed by consolidative radical cystectomy (RC) with pelvic lymph node dissection. PATIENTS AND METHODS: We included 388 patients who received three or four cycles of cisplatin/gemcitabine or (dose-dense) methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC), followed by consolidative RC for cTanyN1-3M0 BCa. We compared pathological complete (pCR = ypT0N0) and objective response (pOR = yp ≤T1N0) between treatment groups. Predictors of pCR and/or pOR were assessed using uni- and multivariable logistic regression analysis. The secondary endpoints were overall (OS) and cancer-specific survival (CSS). We evaluated the association between the number of induction chemotherapy cycles administered and survival outcomes on multivariable Cox regression. RESULTS: Overall, 101 and 287 patients received three or four cycles of induction chemotherapy, respectively. Of these, 72 (19%) and 128 (33%) achieved pCR and pOR response, respectively. The pCR (20%, 18%) and pOR (40%, 31%) rates did not differ significantly between patients receiving three or four cycles (P > 0.05). The number of cycles was not associated with pCR or pOR on multivariable logistic regression analyses. The 2-year OS estimates were 63% (95% confidence interval [CI] 0.53-0.74) and 63% (95% CI 0.58-0.7) for patients receiving three or four cycles, respectively. Receiving three vs four cycles was not associated with OS and CSS on uni- or multivariable Cox regression analyses. CONCLUSION: Pathological response and survival outcomes did not differ between administering three or four induction chemotherapy cycles in patients with cN+ BCa. A fewer cycles (minimum three) may be oncologically sufficient in patients with cN+ BCa, while decreasing the wait for definitive local therapy in those patients who end up without a response to chemotherapy. This warrants further validation.

Thromboprophylaxis during neoadjuvant chemotherapy for bladder cancer reduces thromboembolism and bleeding.

OBJECTIVES: To assess the risk of venous thromboembolic events (VTEs) and bleeding with or without thromboprophylaxis during neoadjuvant chemotherapy in bladder cancer patients scheduled for radical cystectomy. MATERIALS AND METHODS: We conducted a retrospective cohort study in 4886 patients with non-metastatic bladder cancer undergoing cystectomy across 28 centres in 13 countries between 1990 and 2021. Inverse probability weighting analyses were performed to estimate the effect of thromboprophylaxis on VTE and bleeding. RESULTS: In 147 patients (3%) VTEs were recorded within the first year. These occurred a median (interquartile range [IQR]) of 127 (82-198) days after bladder cancer diagnosis. Bleeding events occurred in 131 patients (3%) within the first year. These occurred a median (IQR) of 101 (83-171) days after cancer diagnosis. In inverse probability weighting analyses, compared to patients without thromboprophylaxis during chemotherapy, patients with thromboprophylaxis had not only a lower risk of VTE (hazard ratio [HR] 0.32, 95% confidence interval [CI] 0.12-0.81; P = 0.016) but also a lower bleeding risk (HR 0.03, 95% CI 0.09-0.12; P <0.0001). The retrospective nature of the study was its main limitation. CONCLUSIONS: In this retrospective analysis, the benefit of thromboprophylaxis during neoadjuvant chemotherapy before cystectomy is in line with data from randomised trials in other malignancies. Our data suggest thromboprophylaxis is protective against VTEs and should be the standard of care during neoadjuvant chemotherapy.

Three-dimensional virtual model for robot-assisted partial nephrectomy: a propensity-score matching analysis with a contemporary control group.

PURPOSE: To compare two cohorts of patients submitted to robot-assisted partial nephrectomy (RAPN) with vs without the use of three-dimensional virtual models (3DVMs). METHODS: We screened a prospective consecutive cohort of 152 patients submitted to RAPN with 3DVM and 1264 patients submitted to RAPN without 3DVM between 2019 and 2022. Propensity score matching analysis (PSMA) was applied. Primary endpoint was to evaluate whereas RAPNs with 3DVM were superior in terms of functional outcomes at 12-month. Secondary endopoints were to compare perioperative and oncological outcomes. Multivariable logistic regression analyses (MVA) tested the associations of clinically significant eGFR drop and 3DVMs. Subgroups analysis was performed for PAUDA-risk categories. RESULTS: 100 patients for each group were analyzed after PSMA. RAPN with 3DVM presented a higher rate of selective/no clamping procedure (32% vs 16%, p = 0.03) and a higher enucleation rate (40% vs 29%, p = 0.04). As concern to primary endopoint, 12-month functional preservation performed better within 3DVM group in terms of creatinine serum level (median 1.2 [IQR 1.1-1.4] vs 1.6 [IQR 1.1-1.8], p = 0.03) and eGFR (median 64.6 [IQR 56.2-74.1] vs 52.3 [IQR 49.2-74.1], p = 0.03). However, this result was confirmed only in the PADUA ≥ 10 renal masses. Regarding secondary endpoints, no significative difference emerged between the two cohorts. MVA confirmed 3DVM as a protective factor for clinically significant eGFR drop only in high-risk (PADUA ≥ 10) masses. CONCLUSIONS: RAPN performed with the use of 3DVM assistance resulted in lower incidence of global ischemia and higher rate of enucleations. The positive impact of such technology was found at 12-month only in high-risk renal masses.

Low-Dose Sulfonylurea Plus DPP4 Inhibitor Lower Blood Glucose and Enhance Beta-Cell Function Without Hypoglycemia.

CONTEXT: Low-dose sulfonylureas (SUs) have been found to augment the classical incretin effect, increase glucose sensitivity and late phase incretin potentiation. OBJECTIVE: To evaluate potential synergy between low-dose SU plus a dipeptidyl peptidase 4 (DPP4) inhibitor. METHODS: Unblinded randomized crossover study at the Clinical Research Centre, University of Dundee. Thirty participants with T2DM (HbA1c < 64 mmol/mol) were treated with diet or metformin. Participants completed 4, 14-day blocks in a random order: control, gliclazide 20 mg (SU), sitagliptin 100 mg (DPP4 inhibitor [DPP4i]), or combination (SUDPP4i). A mixed meal test was conducted after each intervention. The primary outcome was the effect of treatment on beta-cell glucose sensitivity. Secondary outcomes included frequency of glucose <3 mmol/L on continuous glucose monitoring, subanalyses by genotype (KNCJ11 E23K), gender, and body mass index. RESULTS: SU combination with DPP4i showed additive effect on glucose lowering: mean glucose area under the curve (mean 95% CI) (mmol/L) was control 11.5 (10.7-12.3), DPP4i 10.2 (9.4-11.1), SU 9.7 (8.9-10.5), SUDPP4i 8.7 (7.9-9.5) (P < .001). Glucose sensitivity mirrored the additive effect (pmol min-1 m-2 mM-1): control 71.5 (51.1-91.9), DPP4i 75.9 (55.7-96.0), SU 86.3 (66.1-106.4), SUDPP4i 94.1 (73.9-114.3) (P = .04). The additive effect was seen in men but not women. Glucose time in range <3 mmol/L on continuous glucose monitoring (%) was unaffected: control 1 (2-4), DPP4i 2 (3-6), SU 1 (0-4), SUDPP4i 3 (2-7) (P = .65). CONCLUSION: Low-dose sulfonylurea plus DPP4i has a potent glucose-lowering effect through augmentation of beta-cell function. A double-blind randomized controlled trial would formalize efficacy and safety of this combination, which may avoid negative aspects of SU.

Isomaltulose Enhances GLP-1 and PYY Secretion to a Mixed Meal in People With or Without Type 2 Diabetes as Compared to Saccharose.

SCOPE: Secretion of the gut hormones glucagon-like peptide (GLP-1) and peptide YY (PYY) are induced by nutrients reaching the lower small intestine which regulate insulin and glucagon release, inhibit appetite, and may improve ß-cell regeneration. The aim is to test the effect of a slowly digested isomaltulose (ISO) compared to the rapidly digested saccharose (SAC) as a snack given 1 h before a standardized mixed meal test (MMT) on GLP-1, PYY, glucose-dependent insulinotropic peptide (GIP), and metabolic responses in participants with or without type 2 diabetes (T2DM). METHODS AND RESULTS: Fifteen healthy volunteers and 15 patients with T2DM consumed either 50 g ISO or SAC 1 h preload of MMT on nonconsecutive days. Clinical parameters and incretin hormones are measured throughout the whole course of MMT. Administration of 50 g ISO as compared to SAC induced a significant increase in GLP-1, GIP, and PYY responses over 2 h after intake of a typical lunch in healthy controls. Patients with T2DM showed reduced overall responses of GLP-1 and delayed insulin release compared to controls while ISO significantly enhanced the GIP and almost tripled the PYY response compared to SAC. CONCLUSION: A snack containing ISO markedly enhances the release of the metabolically advantageous gut hormones PYY and GLP-1 and enhances GIP release in response to a subsequent complex meal.

Effects of hypertriglyceridemia with or without NEFA elevation on ß-cell function and insulin clearance and sensitivity.

AIMS: Hypertriglyceridemia is a risk factor for developing type 2 diabetes (T2D) and might contribute to its pathogenesis either directly or through elevation of non-esterified fatty acids (NEFAs). This study aimed at comparing the glucometabolic effects of acute hypertriglyceridemia alone or combined with NEFA elevation in non-diabetic subjects. METHODS: Twenty-two healthy lean volunteers underwent two 5-h intravenous infusions of either saline or Intralipid, without (n=12) or with heparin (I+H; n=10) to activate the release of NEFAs. Oral glucose tolerance tests (OGTTs) were performed during the last 3h of infusion. Insulin sensitivity, insulin secretion rate (ISR), model-derived ß-cell function, and insulin clearance were measured after 2h of lipid infusion and during the OGTTs. RESULTS: In fasting conditions, both lipid infusions increased plasma insulin and ISR and reduced insulin clearance, without affecting plasma glucose and insulin sensitivity. These effects on insulin and ISR were more pronounced for I+H than Intralipid alone. During the OGTT, the lipid infusions markedly impaired glucose tolerance, increased plasma insulin and ISR, and decreased insulin sensitivity and clearance, without significant group differences. Intralipid alone inhibited glucose-stimulated insulin secretion (i.e. ß-cell glucose sensitivity) and increased ß-cell potentiation, whereas I+H had neutral effects on these ß-cell functions. CONCLUSION: In healthy non-obese subjects, mild acute hypertriglyceridemia directly reduces glucose tolerance, insulin sensitivity and clearance, and has selective and opposite effects on ß-cell function that are neutralized by NEFAs. These findings provide new insight into plausible biological signals that generate and sustain insulin resistance and chronic hyperinsulinemia in the development of T2D.

3D virtual model for robot-assisted partial nephrectomy in highly-complex cases (PADUA ⩾ 10).

PURPOSE: To compare two cohorts of patients submitted to robot-assisted partial nephrectomy (RAPN) for highly-complex renal masses (PADUA ⩾ 10) with versus without the use of 3DVMs. MATERIALS AND METHODS: We screened a prospective consecutive cohort of 152 patients submitted to RAPN with 3DVM and 1264 patients submitted to RAPN without 3DVM between 2019 and 2022. Only PADUA ⩾ 10 cases were considered eligible for analysis. Propensity score matching (PSM) analysis was applied. Primary endpoint was to evaluate whereas RAPNs with 3DVM were superior in terms of functional outcomes at 12-month. Secondary outcomes were to compare perioperative and oncological outcomes. Multivariable logistic regression analyses (MVA) tested the associations of clinically significant eGFR drop and 3DVMs. Subgroups analysis was performed for PAUDA-risk categories. RESULTS: Thirty seven patients for each group were analyzed after PSM. RAPN with 3DVM presented a higher rate of selective/no clamping procedure (32.5% vs 16.2%, p = 0.03) and a higher enucleation rate (43.2% vs 29.8%, p = 0.04). Twelve-month functional preservation performed better within 3DVM group in terms of creatinine serum level (median 1.2 [IQR 1.1-1.4] vs 1.6 [IQR 1.1-1.8], p = 0.03) and eGFR (median 64.6 [IQR 56.2-74.1] vs 52.3 [IQR 49.2-74.1], p = 0.03). MVA confirmed 3DVM as a protective factor for clinically significant eGFR drop in this subgroup of patients. CONCLUSIONS: RAPN performed with the use of 3DVM assistance for PADUA ⩾ 10 cases resulted in lower incidence of global ischemia and higher rate of enucleations. The positive impact of such technology was found at 12-month follow-up.

Is it safe to defer prostate cancer treatment? Assessing the impact of surgical delay on the risk of pathological upstaging after robot-assisted radical prostatectomy.

INTRODUCTION: We sought to investigate whether surgical delay may be associated with pathological upstaging in patients treated with robot assisted radical prostatectomy (RARP) for localized and locally advanced prostate cancer (PCa). MATERIALS AND METHODS: Consecutive firstly-diagnosed PCa patients starting from March 2020 have been enrolled. All the patients were categorized according to EAU risk categories for PCa risk. Uni- and multivariate analysis were fitted to explore clinical and surgical predictors of pathological upstaging to locally advanced disease (pT3/pT4 - pN1 disease). RESULTS: Overall 2017 patients entered the study. Median age at surgery was 68 (IQR 63-73) years. Overall low risk, intermediate risk, localized high risk and locally advanced disease were recorded in 368 (18.2 %), 1071 (53.1 %), 388 (19.2 %) and 190 (9.4 %), respectively. Median time from to diagnosis to treatment was 51 (IQR 29-70) days. Time to surgery was 56 (IQR 32-75), 52 (IQR 30-70), 45 (IQR 24-60) and 41 (IQR 22-57) days for localized low, intermediate and high risk and locally advanced disease, respectively. Considering 1827 patients with localized PCa, at multivariate analysis ISUP grade group ≥4 on prostate biopsy (HR: 1.30; 95 % CI 1.07-1.86; p = 0.02) and surgical delay only in localized high-risk disease (HR: 1.02; 95 % CI 1.01-1.54; p = 0.02) were confirmed as independent predictors of pathological upstaging to pT3-T4/pN1 disease at final histopathological examination. CONCLUSIONS: In localized high-risk disease surgical delay could be associated with a higher risk of adverse pathologic findings.

Effects of Tirzepatide vs Semaglutide on ß-cell Function, Insulin Sensitivity, and Glucose Control During a Meal Test.

CONTEXT: In a clinical study, tirzepatide, a glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonist (GIP/GLP-1RA), provided superior glycemic control vs the GLP-1RA semaglutide. The physiologic mechanisms are incompletely understood. OBJECTIVE: To evaluate treatment effects by model-based analyses of mixed-meal tolerance test (MMTT) data. DESIGN: A 28-week double-blind, randomized, placebo-controlled trial. SETTING: Two clinical research centers in Germany. PATIENTS: Patients with type 2 diabetes treated with metformin. INTERVENTIONS: Tirzepatide 15 mg, semaglutide 1 mg, placebo. MAIN OUTCOME MEASURES: Glycemic control, model-derived ß-cell function indices including insulin secretion rate (ISR) at 7.2-mmol/L glucose (ISR7.2), ß-cell glucose (ß-CG) sensitivity, insulin sensitivity, and estimated hepatic insulin-to-glucagon ratio. RESULTS: Tirzepatide significantly reduced fasting glucose and MMTT total glucose area under the curve (AUC) vs semaglutide (P < 0.01). Incremental glucose AUC did not differ significantly between treatments; therefore, greater total glucose AUC reduction with tirzepatide was mainly attributable to greater suppression of fasting glucose. A greater reduction in total ISR AUC was achieved with tirzepatide vs semaglutide (P < 0.01), in the context of greater improvement in insulin sensitivity with tirzepatide (P < 0.01). ISR7.2 was significantly increased with tirzepatide vs semaglutide (P < 0.05), showing improved ß-CG responsiveness. MMTT-derived ß-CG sensitivity was increased but not significantly different between treatments. Both treatments reduced fasting glucagon and total glucagon AUC, with glucagon AUC significantly reduced with tirzepatide vs semaglutide (P < 0.01). The estimated hepatic insulin-to-glucagon ratio did not change substantially with either treatment. CONCLUSIONS: These results suggest that the greater glycemic control observed for tirzepatide manifests as improved fasting glucose and glucose excursion control, due to improvements in ISR, insulin sensitivity, and glucagon suppression.

Variation in Follow-Up after Radical Cystectomy for Bladder Cancer-An Inventory Roundtable and Literature Review.

Background: Follow-up after radical cystectomy (RC) for bladder cancer can be divided into oncological and functional surveillance. It remains unclear how follow-up after RC should ideally be scheduled. The aim of this report was to gain insight into the organization of follow-up after RC in Europe, for which we conducted a roundtable inventory within the EAU Young Academic Urologists Urothelial Cancer working group. Methods: An inventory semi-structured survey was performed among urologists of the EAU Young Academic Urologists Urothelial Cancer working group to describe the organization of follow-up. The surveys were analyzed using a deductive approach. Similarities and differences in follow-up after RC for bladder cancer were described. Results: The survey included 11 urologists from six different European countries. An institutional follow-up scheme was used by six (55%); three (27%) used a national or international guideline, and two (18%) indicated that there was no defined follow-up scheme. Major divergent aspects included the time points of follow-up, the frequency, and the end of follow-up. Six centers (55%) adopted a risk-adapted follow-up approach tailored to (varying) patient and tumor characteristics. Laboratory tests and CT scans were used in all cases; however, the intensity and frequency varied. Functional follow-up overlapped with oncological follow-up in terms of frequency and duration. Patient-reported outcome measures were only used by two (18%) urologists. Conclusions: Substantial variability exists across European centers regarding the follow-up after RC for bladder cancer. This highlights the need for an international analysis focusing on its organization and content as well as on opportunities to improve patients' needs during follow-up after RC.

Beta-cell function and glucose metabolism in patients with chronic pancreatitis.

AIMS: Chronic pancreatitis (CP) is - along with acute pancreatitis - the most frequent cause of diabetes of the exocrine pancreas (DEP). Although insulin deficiency is widely accepted as the major feature of DEP, it is still unclear whether diabetes associated with CP is characterized by additional or different functional defects of the insulin secretory machinery. To identify possible functional defects specifically induced by CP, we performed a cross-sectional study in individuals with normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and diabetes mellitus (DM) comparing patients with and without CP (CP vs. NCP). METHODS: We administered an oral glucose tolerance test (OGTT) to all participants and, according to their glucose tolerance, classified them as NGT, IGT and DM. Insulin sensitivity and beta-cell functional parameters were derived from OGTT, hyperglycemic clamp and hyperinsulinemic euglycemic clamp. RESULTS: Studying 146 subjects, we found that beta-cell function and insulin secretion were significantly lower in CP compared to NCP patients. However, when we classified the subjects according to OGTT-derived glucose tolerance, we found no differences in beta-cell function or in insulin sensitivity between CP and NCP with the same glucose tolerance status. Of note, we found that arginine-stimulated insulin secretion is reduced only in subjects with CP and DM compared to NCP subjects with DM. CONCLUSIONS: Patients with CP had no specific alterations in insulin secretion and beta-cell function. However, in patients diagnosed with diabetes, we found a lower arginine-stimulated insulin secretion, a marker of reduced functional mass.

Step by step technique of Stentless Florence Robotic Intracorporeal Neobladder (FloRIN), does the ureteral management influence functional outcomes?

INTRODUCTION: Benefits and harms of avoid the sent placement during IntraCorporeal Neobladder configuration are still debated. Our objective was to describe the step-by-step technique of Florence intracorporeal neobladder (FloRIN) configuration performed with stentless procedure focusing on perioperative and mid-term functional outcomes. MATERIALS AND METHODS: In this single institution prospective randomized 1:1 series all consecutive patients underwent Robot-Assisted Radical Cystectomy (RARC) and FloRIN reconfiguration from January 2021 to March 2021 were enrolled. Functional perioperative and mid-term outcomes were gathered. Postoperative complications were graded according to Clavien-Dindo classification and divided in early (<30 days from discharge) and delayed (>30 days). RESULTS: Overall, 10 patients were included in the analysis. Of these, the 50.0% was treated with Stentless FloRIN. In terms of baseline features, no differences were recorded between the two groups. Median age was 65 and 66 years while median BMI was 27 and 25 in the stentless and in the stent group, respectively. Concerning intraoperative variables, no intraoperative complications as well as open conversion occurred among both groups. As regard introperative features, a shorter console time was associated with stentless procedure (331 min vs 365 min). In terms of perioperative outcomes, canalization and time to drainage removal didn't differ between groups while length of hospital stay was significantly lower in stentless group 10 days versus 14 days. Early and delayed postoperative complication rate was not influenced by the ureteral management at a preliminary assessment with comparable rates of Clavien Dindo ⩾ 3a between the two groups. Mid-term functional outcomes did not differ between groups in terms of kidney function loss. CONCLUSIONS: FloRIN with Stentless technique showed functional and perioperative preliminary outcomes comparable with the standard ureteral management strategy. Further series with longer functional follow-up assessment will be needed to confirm our preliminary results.

Outcomes and Techniques of Robotic-Assisted Partial Nephrectomy (RAPN) for Renal Hilar Masses: A Comprehensive Systematic Review.

Background: Robot-assisted partial nephrectomy (RAPN) is increasingly being employed in the management of renal cell carcinoma (RCC) and it is expanding in the field of complex renal tumors. The aim of this systematic review was to consolidate and assess the results of RAPN when dealing with entirely central hilar masses and to examine the various methods used to address the surgical difficulties associated with them. Methods: A thorough literature search in September 2023 across various databases focused on RAPN for renal hilar masses, adhering to PRISMA guidelines. The primary goal was to evaluate RAPN's surgical and functional outcomes, with a secondary aim of examining different surgical techniques. Out of 1250 records, 13 full-text manuscripts were reviewed. Results: Evidence is growing in favor of RAPN for renal hilar masses. Despite a predominance of retrospective studies and a lack of long-term data, RAPN shows positive surgical outcomes and preserves renal function without compromising cancer treatment effectiveness. Innovative suturing and clamping methods are emerging in surgical management. Conclusions: RAPN is a promising technique for managing renal hilar masses in RCC, offering effective surgical outcomes and renal function preservation. The study highlights the need for more long-term data and prospective studies to further validate these findings.

Treating BCG-Induced Cystitis with Combined Chondroitin and Hyaluronic Acid Instillations in Bladder Cancer.

In non-muscle invasive bladder cancer, Bacillus Calmette-Guérin (BCG) responders benefit from strong Th1-type inflammatory and T cell responses mediating tumor rejection. However, the corresponding lack of anti-inflammatory Th2-type immunity impairs tissue repair in the bladder wall and facilitates the development of cystitis, causing urinary pain, urgency, incontinence, and frequency. Mechanistically, the leakage of the glycosaminoglycan (GAG) layer enables an influx of potassium ions, bacteria, and urine solutes towards the underlying bladder tissue, promoting chronic inflammation. Treatments directed towards re-establishing this mucopolysaccharide-based protective barrier are urgently needed. We discuss the pathomechanisms, as well as the therapeutic rationale of how chondroitin and hyaluronic acid instillations can reduce or prevent BCG-induced irritative bladder symptoms. Moreover, we present a case series of five patients with refractory BCG-induced cystitis successfully treated with combined chondroitin and hyaluronic acid instillations.

Application of the ERAS guidelines in pediatric urological surgery: a systematic review.

INTRODUCTION: Consensus for Enhanced Recovery After Surgery (ERAS) in pediatrics has been achieved in neonatal intestinal surgery, yet it is not widely utilized in pediatric urology. We investigated the application of ERAS guidelines in pediatric urology, and determined its effects given the available level of evidence supporting the ERAS protocol in children. EVIDENCE ACQUISITION: A systematic literature review including series providing adoption of fast-track recovery protocols for pediatric urology procedures was carried out. Main outcome measures were study characteristics, adherence to the 19 ERAS items, complication rates and length of hospital stay. Sub-group analysis by surgery type (hypospadias versus major surgery) was performed. EVIDENCE SYNTHESIS: Nine series with data from 1272 surgical pediatric cases were included. An enhanced recovery pathway was applied in 67.3% of the reports. Two series included patients undergoing hypospadias repair and ERAS items were insufficiently reported. Studies including children undergoing major procedures mentioned a median of 15 ERAS items, yet applied a median of 11 items. Median compliance rate was 88.9% (range 50-100). More ERAS guideline items were reported (applied or mentioned) in the most recently published studies. CONCLUSIONS: There is limited reporting and use of the ERAS guidelines in urologic surgery particularly in hypospadias repair; whilst in major surgery in children, adherence and compliance rates vary widely. In more recent series there was an increase in ERAS items that have been mentioned and applied. Future research is needed to identify barriers and to overcome them in order to fully adopt and benefit from the ERAS pathway.

A systematic review and meta-analysis to evaluate the diagnostic accuracy of PSMA PET/CT in the initial staging of prostate cancer.

BACKGROUND: Positron Emission Tomography-Computed Tomography using Prostate-Specific Membrane Antigen (PSMA PET/CT) is notable for its superior sensitivity and specificity in detecting recurrent PCa and is under investigation for its potential in pre-treatment staging. Despite its established efficacy in nodal and metastasis staging in trial setting, its role in primary staging awaits fuller validation due to limited evidence on oncologic outcomes. This systematic review and meta-analysis aims to appraise the diagnostic accuracy of PSMA PET/CT compared to CI for comprehensive PCa staging. METHODS: Medline, Scopus and Web of science databases were searched till March 2023. Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines were followed to identify eligible studies. Primary outcomes were specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) of PSMA PET/CT for local, nodal and metastatic staging in PCa patients. Due to the unavailability of data, a meta-analysis was feasible only for detection of seminal vesicles invasion (SVI) and LNI. RESULTS: A total of 49 studies, comprising 3876 patients, were included. Of these, 6 investigated accuracy of PSMA PET/CT in detection of SVI. Pooled sensitivity, specificity, PPV and NPV were 42.29% (95%CI: 29.85-55.78%), 87.59% (95%CI: 77.10%-93.67%), 93.39% (95%CI: 74.95%-98.52%) and 86.60% (95%CI: 58.83%-96.69%), respectively. Heterogeneity analysis revealed significant variability for PPV and NPV. 18 studies investigated PSMA PET/CT accuracy in detection of LNI. Aggregate sensitivity, specificity, PPV and NPV were 43.63% (95%CI: 34.19-53.56%), 85.55% (95%CI: 75.95%-91.74%), 67.47% (95%CI: 52.42%-79.6%) and 83.61% (95%CI: 79.19%-87.24%). No significant heterogeneity was found between studies. CONCLUSIONS: The present systematic review and meta-analysis highlights PSMA PET-CT effectiveness in detecting SVI and its good accuracy in LNI compared to CI. Nonetheless, it also reveals a lack of high-quality research on its performance in clinical T staging, extraprostatic extension and distant metastasis evaluation, emphasizing the need for further rigorous studies.

SUCNR1 regulates insulin secretion and glucose elevates the succinate response in people with prediabetes.

Pancreatic ß-cell dysfunction is a key feature of type 2 diabetes, and novel regulators of insulin secretion are desirable. Here we report that the succinate receptor (SUCNR1) is expressed in ß-cells and is up-regulated in hyperglycemic states in mice and humans. We found that succinate acts as a hormone-like metabolite and stimulates insulin secretion via a SUCNR1-Gq-PKC-dependent mechanism in human ß-cells. Mice with ß-cell-specific Sucnr1 deficiency exhibit impaired glucose tolerance and insulin secretion on a high-fat diet, indicating that SUCNR1 is essential for preserving insulin secretion in diet-induced insulin resistance. Patients with impaired glucose tolerance show an enhanced nutritional-related succinate response, which correlates with the potentiation of insulin secretion during intravenous glucose administration. These data demonstrate that the succinate/SUCNR1 axis is activated by high glucose and identify a GPCR-mediated amplifying pathway for insulin secretion relevant to the hyperinsulinemia of prediabetic states.