Durability of the Blood Pressure Effects of Renal Pelvis Denervation in Patients with Hypertension During a 12-Month Observation.

INTRODUCTION: We previously completed a trial of renal pelvic denervation for treating hypertension that reduced blood pressure by the 2-month primary endpoint. However, information on the durability of effectiveness is a critical requirement for device therapy and we now report data up to 12 months. METHODS: This was an open label single-arm feasibility study in patients with increased blood pressure despite taking an average of 2.7 medications. The key endpoint reported here was ambulatory blood pressure at 12 months following renal pelvic denervation. RESULTS: In the 17 patients (mean age 56) studied, there was a reduction from the baseline of 148 + 8.7 mmHg in the primary endpoint of mean daytime systolic blood pressure at 12 months of 19.1 (26.7, 11.6) mmHg, P<0.001, as compared with the 2-month result of 19.4 (24.9, 14.0) mmHg. The 24-hour systolic blood pressure fell by 19.3 (26.7, 11.9), P<0.001, and nighttime systolic fell by 18.7 (27.5, 9.8), P<0.001, mmHg at 12 months. Diastolic pressures also fell significantly from baseline at 12 months. As well, automated office systolic blood pressure was reduced from the baseline of 156.5 + 12.3 by 24.8 (33.2. 16.8) mmHg, P<0.001, at 12 months as compared with 22.4 (31.5, 13.3) at 2-months. . All blood pressure changes at 12 months were not different from those at 2 months, thus confirming the durability of the procedure. There were no serious procedural, clinical or laboratory adverse events related to the intervention. Serum creatinine fell from 1.03 + 0.22 to 0.82 + 0.16 mg/dl and estimated glomerular filtration rate rose from 79.6 + 17.8 to 96.3 + 16.4 ml/min/1.73m2 by 12 months, again sustaining effects seen at 2 months. DISCUSSION/CONCLUSION: These findings provide evidence that the significant blood pressure-lowering effects of renal pelvis denervation are durable and safe for at least one year and provide the basis for a pivotal randomized blinded trial to further define the safety and effectiveness of this procedure.

Transurethral Renal Pelvic Denervation: A Feasibility Trial in Patients with Uncontrolled Hypertension.

BACKGROUND: Endovascular renal denervation reduces blood pressure (BP). We explored an alternative approach to renal denervation using radiofrequency energy delivered across the renal pelvis utilizing the natural orifice of the urethra and the ureters. METHODS: This open-label, single-arm feasibility study enrolled patients with uncontrolled hypertension despite antihypertensive drug therapy. The primary effectiveness endpoint was the change in ambulatory daytime systolic BP (SBP) 2 months following renal pelvic denervation. RESULTS: The 18 patients (mean age 56±12 years) enrolled were taking an average of 2.7 antihypertensive drugs daily. Renal pelvic denervation reduced mean daytime SBP by 19.4 mm Hg (95% CI, -24.9 to -14.0, P<0.001) from its baseline of 148.4±8.7 mm Hg. Mean nighttime (-21.4 mm Hg [95% CI, -29.5 to -13.3]) and 24-hour (-20.3 mm Hg [95% CI, -26.2 to -14.5]) SBP each fell significantly (P<0.001) as did the corresponding diastolic BPs (P<0.001). Office SBP decreased from 156.5±12.3 mm Hg by 22.4 mm Hg (95% CI, -31.5 to -13.3, P<0.001) by 2 months. Office SBP decreased over time (P=0.001 by linear trend test) starting by day 1 with a decrease of 8.3 mm Hg (95% CI, -16.9 to 0.3, P=0.057). There were no serious adverse events. Mild transitory back pain followed the procedure. Serum creatinine decreased by 0.08 mg/dL (P=0.02) and estimated glomerular filtration rate increased by 7.2 mL/min/1.73m2 (P=0.03) 2 months following ablation procedure. CONCLUSIONS: Based on these initial findings, a well-powered, sham-controlled trial of renal pelvic denervation to more fully establish its safety and effectiveness is now justified in patients with uncontrolled hypertension despite drug therapy. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT05440513.

Expression of p27((Kip1)), cyclin D3 and Ki67 in BPH, prostate cancer and hormone-treated prostate cancer cells.

p27((Kip1)), cyclin D3 and Ki67 are the markers of DNA damage and cell proliferation. The goal of the current study was to analyze expression of the markers in benign and malignant prostate cancer tissues. Activity of p27((Kip1)), cyclin D3 and Ki67 was immunohistochemically evaluated in different cells of BPH, prostate cancer (PCa) and hormonally treated prostate cancer (HTPCa) tissues. The tissue samples were derived by means of TURP or radical prostatectomy. Intensity of the expression was compared between the groups, and association was sought with clinical parameters. Total expression of p27((Kip1)) was significantly higher in BPH as compared with PCa. Epithelial marker expression was higher in HTPCa than in PCa. Intensity of the expression in epithelial, vascular and ductal cells was negatively associated with the tumor stage and Gleason grades. Total Ki67 activity was positively correlated with patient age and serum PSA level. There was significantly higher expression in PCa and hormone-escaped PCa (HEPCa) as compared with BPH. Epithelial and vascular marker expression was positively associated with tumor stage and Gleason grades. There was a positive correlation between cyclin D3 and serum PSA level. With the increase of Gleason grades, cyclin D3 expression increased significantly. Expression of p27((Kip1)) negatively correlated with Ki67 and cyclin D3, while the latter two markers correlated positively. p27((Kip1)) is down-regulated, whereas Ki67 and cyclin D3 are up-regulated in PCa. Intensity of the markers' expression is associated with tumor stage and grades. Hormonotherapy of PCa causes activation of p27((Kip1)). HEPCa is characterized by increased Ki67 expression.

Loss of p27(Kip1) CDKI is a predictor of poor recurrence-free and cancer-specific survival in patients with renal cancer.

The importance of cyclin-dependent kinase inhibitors (CDKI) in benign and malignant urological diseases is a subject of intense ongoing investigation. The goal of the current study was to analyze the expression of p27((Kip1))CDKI in benign and malignant renal cells and assess their possible association with different clinical parameters. Expression of p27((Kip1)) was evaluated and compared in 24 normal human kidneys and in 52 renal cell carcinoma (RCC) tissue samples. Intensity of the expression was compared between the groups and association was analyzed with cancer clinical parameters. The expression of the marker was significantly higher in normal than in RCC samples (P = 0.0045). Intensity of p27((Kip1)) expression in RCC was negatively correlated with tumor size (Rho = -0.438, P = 0.0051) and associated with pathological stage and grade (P = 0.0488 and < 0.0001, respectively). The patients with symptomatic disease had significantly less marker expression than incidentally discovered tumors (P = 0.0301). Loss of p27((Kip1)) expression, pathological stage, grade and tumor size were the risk-factors for disease recurrence (P = 0.0072, 0.0011, 0.0467 and < 0.0001, respectively) and patient survival (P = 0.0021, 0.0106, 0.0151 and 0.0021, respectively). With Cox multivariate analysis loss of p27((Kip1)) expression (hazard ratio 9.3, P = 0.002) and tumor size (hazard ratio 5.9, P = 0.015) were the predictors of cancer-specific survival. Expression of p27((Kip1)) is significantly decreased in RCC as compared with normal kidney tissue. Intensity of the expression is associated with clinical parameters: tumor size, stage, grade and disease presentation. Loss of p27((Kip1)) expression is a risk-factor for disease recurrence and the strongest predictor of cancer-specific survival.

Retroperitoneoscopic Partial Nephrectomy for a Horseshoe Kidney Tumor.

Horseshoe kidney is the most common renal fusion anomaly found in about 0.15% to 0.25% of the population. Renal cell carcinoma associated with a horseshoe kidney has been described in fewer than 200 cases. Its incidence and prognosis seems to be not different from those of the general population, but surgical management may be challenging due to unique anatomic features of horseshoe kidneys, such as highly variable vasculature. We report a case of a 69-year-old male with an incidental 48-mm solid mass in the left moiety of a horseshoe kidney, successfully treated by retroperitoneoscopic partial nephrectomy.

Influence of bladder neck suspension stitches on early continence after radical prostatectomy: a prospective randomized study of 180 patients.

Several techniques have been introduced to improve early postoperative continence. In this study, we evaluated the impact of bladder neck (vesicourethral anastomosis) suspension on the outcome of extraperitoneal endoscopic radical prostatectomy (EERPE). In this research, a total of 180 patients underwent EERPE. Group 1 included patients who underwent nerve-sparing EERPE (nsEERPE) (n=45), and Group 2 included patients who underwent nsEERPE with bladder neck suspension (BNS, n=45). Groups 3 (n=45) and 4 (n=45) included patients who received EERPE and EERPE with BNS, respectively. Patients were randomly assigned to receive BNS with their nsEERPE or EERPE procedure. Perioperative parameters were recorded, and continence was evaluated by determining the number and weight of absorbent pads (pad weighing test) on the second day after catheter removal and by a questionnaire 3 months postoperatively. Two days after catheter removal, 11.1% of Group 1, 11.1% of Group 2, 4.4% of Group 3 and 8.9% of Group 4 were continent. The average urine loss was 80.4, 70.1, 325.0 and 291.3 g for the each of these groups, respectively. At 3 months, 76.5% of Group 1 and 81.3% of Group 2 were continent. The continence figures for Group 3 and 4 were 48.5% and 43.8%, respectively. Similar overall rates were observed in all groups. In conclusion, although there are controversial reports in the literature, early continence was never observed to be significantly higher in the BNS groups when compared with the non-BNS groups, regardless of the EERPE technique performed.

Immunoreactivity of p27(Kip1), cyclin D3, and Ki67 in conventional renal cell carcinoma.

The goal of the study was to evaluate expression of the cell-cycle regulatory proteins (p27(Kip1) and cyclin D3) and proliferation marker Ki67 in normal human kidneys and renal cell carcinoma (RCC) tissues. Intensity of the markers' expression was prospectively studied and compared between normal and RCC tissue samples. Association was analyzed with cancer clinical parameters. p27(Kip1) was significantly upregulated in normal compared with in RCC samples. Immunoreactivity of the protein negatively correlated with tumor size and was associated with pathological stage and grade. Patients with symptomatic disease had significantly less marker expression than those with incidentally discovered tumors. Intensity of Ki67 staining positively correlated with primary tumor size and associated with disease stage and grade. Cyclin D3 immunoreactivity positively correlated with tumor size. Loss of p27(Kip1) expression, pathological stage, grade, and tumor size were risk factors for disease recurrence (P = 0.0072, 0.0011, and 0.0467, and P < 0.0001, respectively) and patient death (P = 0.0021, 0.0106, 0.0151, and 0.0021, respectively). With Cox multivariate analysis loss of p27(Kip1) expression (hazard ratio 9.3, P = 0.002) and tumor size (hazard ratio 5.9, P = 0.015) were the predictors of cancer-specific survival. In conclusion, intensity of the markers' expression in RCC is associated with tumour clinical parameters (size, stage, grade, and disease presentation type). Loss of p27(Kip1) expression is a risk factor for the disease recurrence and cancer-related patient death.