Current Surgical Treatment for Neurogenic Lower Urinary Tract Dysfunction in Patients with Chronic Spinal Cord Injury.

This study aimed to present a comprehensive literature review of the efforts of a spinal cord injury workgroup in Taiwan regarding urologic surgery for neurogenic lower urinary tract dysfunction (NLUTD) in patients with chronic spinal cord injury (SCI). Surgical procedures should be viewed as a final option for managing patients with SCI who have persistent symptoms and complications that cannot be resolved by other means. Surgeries can be grouped according to their purpose: reducing bladder pressures, reducing urethra resistance, increasing urethra resistance, and urinary diversion. The choice of surgery depends on the type of LUTD based on urodynamic tests. Additionally, cognitive function, hand motility, comorbidities, efficacy of surgery, and related complications should be considered.

Prospective, Randomized, Double-blind, Placebo-controlled, Pilot Study of Extracorporeal Shock Wave Therapy for Detrusor Underactivity/Underactive Bladder.

BACKGROUND: Detrusor underactivity/underactive bladder (DU/UAB) is a disease with great unmet needs and no current approved drug treatment. Extracorporeal shock wave therapy (ESWT) has been shown to improve regeneration of tissue and increase detrusor contractility in preclinical studies of DU/UAB. OBJECTIVE: To assess ESWT as a treatment of DU/UAB. DESIGN, SETTING, AND PARTICIPANTS: Patients with DU/UAB were enrolled in this phase 2 randomized, double-blind, placebo-controlled, physician-initiated study. INTERVENTION: The patients were assigned to ESWT (N = 6, 2500 shocks, frequency of four pulses per second, and maximum total energy flow density of 0.25 mJ/mm2) once a week for 6 wk at the suprapubic bladder area or to placebo (N = 5, shock wave setting without energy transmission). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was the average changes in postvoid residual urine (PVR) from baseline to 4 wk after treatment. Other endpoints included the average changes in 3-d voiding diary, global response assessment of patient satisfaction, Underactive Bladder Questionnaire (UAB-Q) score, and urodynamic evaluation. RESULTS AND LIMITATIONS: The difference in improvement in PVR was -157.8 ml (95% confidence interval [CI]: -380.1, 64.4) versus -6.6 ml (95% CI: -178.1, 164.9) and -77.5 ml (95% CI: -242.1, 87.1) versus 81.8 ml (95% CI: -137.2, 300.7) for ESWT versus placebo (p = 0.116 and 0.056) at 4 and 12 wk, respectively. The ESWT group exhibited a significant reduction in the UAB-Q score (-4.3; 95% CI: -9.1, 0.4) compared with the placebo group (-0.4; 95% CI: -1.8, 1.0) at 4 wk after treatment (p = 0.025), and the effects were decreased at 12 wk (p = 0.091). This study was limited by small sample size. CONCLUSIONS: ESWT was well tolerated with a statistically significant decrease of DU/UAB symptoms and a trend to decrease PVR versus placebo. These results indicate that ESWT may be a promising treatment for DU/UAB and multicenter studies are needed. PATIENT SUMMARY: Bladder shock wave therapy was studied in this randomized, double-blind, placebo-controlled study in patients with inadequate bladder emptying (underactive bladder). Bladder shock wave therapy was found to be well tolerated with an improvement in bladder emptying. These results indicate that bladder shock wave therapy may be a promising treatment for patients who cannot empty their bladder adequately.

Totally X-ray-Free Ultrasound-Guided Mini-Percutaneous Nephrolithotomy in Galdakao-Modified Supine Valdivia Position: A Novel Combined Surgery.

We introduced a novel surgery that combines ultrasound guidance, miniaturization and Galdakao-modified supine Valdivia (GMSV) position in percutaneous nephrolithotomy (PCNL) and evaluated the safety and efficacy. This retrospective, single-center study retrospectively reviewed 150 patients who underwent ultrasound-guided mini-PCNL in the GMSV position from November 2019 to March 2022. All perioperative parameters were collected. Stone-free status was defined as no residual stones or clinically insignificant residual fragments (CIRF) <0.4 cm on postoperative day one. Among the 150 patients, the mean age was 56.96 years. The mean stone size was 3.19 cm (427 mm2). The mean S.T.O.N.E. score was 7.61, including 36 patients (24%) with scores ≥9. The mean operative time was 66.22 min, and the success rate of renal access creation in the first attempt was 88.7%. One hundred and forty (93.3%) patients were stone free. The mean decrease in Hemoglobin was 1.04 g/dL, and no patient needed a blood transfusion. Complications included transient hematuria (n = 13, 8.7%), bladder blood clot retention (n = 2, 1.3%), fever (n = 15, 10%) and sepsis (n = 2, 1.3%). Totally X-ray-free ultrasound-guided mini-PCNL in the GMSV position is feasible, safe and effective for patients with upper urinary tract stones, indicating the synergistic and complementary effects of the three novel techniques.

MiR-26a-5p as a useful therapeutic target for upper tract urothelial carcinoma by regulating WNT5A/ß-catenin signaling.

The role of miRNAs in cancer and their possible function as therapeutic agents are interesting and needed further investigation. The miR-26a-5p had been demonstrated as a tumor suppressor in various cancers. However, the importance of miR-26a-5p regulation in upper tract urothelial carcinoma (UTUC) remains unclear. Here, we aimed to explore the miR-26a-5p expression in UTUC tissues and to identify its regulatory targets and signal network involved in UTUC tumorigenesis. The miR-26a-5p expression was validated by quantitative real-time polymerase chain reaction (qPCR) using renal pelvis tissue samples from 22 patients who were diagnosed with UTUC and 64 cases of renal pelvis tissue microarray using in situ hybridization staining. BFTC-909 UTUC cells were used to examine the effects of miR-26a-5p genetic delivery on proliferation, migration and expression of epithelial-to-mesenchymal transition (EMT) markers. MiR-26a-5p was significantly down-regulated in UTUC tumors compared to adjacent normal tissue and was decreased with histological grades. Moreover, restoration of miR-26a-5p showed inhibition effects on proliferation and migration of BFTC-909 cells. In addition, miR-26a-5p delivery regulated the EMT marker expression and inhibited WNT5A/ß-catenin signaling and expression of downstream molecules including NF-κB and MMP-9 in BFTC-909 cells. This study demonstrated that miR-26a-5p restoration may reverse EMT process and regulate WNT5A/ß-catenin signaling in UTUC cells. Further studies warranted to explore the potential roles in biomarkers for diagnostics and prognosis, as well as novel therapeutics targets for UTUC treatment.

The Prognostic Impact of Tumor Location in pT3N0M0 Upper Urinary Tract Urothelial Carcinoma: A Retrospective Cohort Study.

Background: We aimed to evaluate the impact of tumor location on cancer outcomes in patients with pT3N0M0 upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU) with bladder cuff excision. Materials and Methods: We retrospectively reviewed 302 patients with pT3N0M0 UTUC who underwent RNU with bladder cuff excision at our institution between 2005 and 2019, including 191 renal pelvis tumors and 111 ureteral tumors. Clinicopathologic characteristics were compared between renal pelvis and ureter urothelial carcinomas. Multivariate Cox proportional hazard regression was used to assess the association between outcomes and clinical factors. Outcomes of interest included intravesical recurrence-free survival (IVRFS), local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and cancer-specific survival (CSS), which were measured using the Kaplan-Meier curve with a log-rank test. Results: A total of 302 patients underwent RNU with bladder cuff excision. During the median follow-up of 42.7 months, 70 (23.2%), 95 (31.5%), and 99 (32.8%) patients experienced intravesical recurrence, local recurrence, and distant metastasis, respectively. Seventy (23.2%) patients died from UTUC. Multivariate Cox regression analysis showed that tumor location was an independent predictor of local recurrence (HR = 2.05, p = 0.001), with borderline independent significance in intravesical recurrence (HR = 1.54, p = 0.074) and distant metastasis (HR = 1.45, p = 0.08). Kaplan-Meier analysis showed that ureter tumors had a worse 5-year local recurrence (log-rank p < 0.001) and borderline worse 5-year intravesical recurrence (log-rank p = 0.055) and 5-year distant metastasis (log-rank p = 0.073). Conclusion: Ureter tumors seem to be associated with worse oncological outcomes, especially with local recurrence in UTUC. Further large and long-term studies are warranted for investigating biological differences based on tumor location.

Improves symptoms and urinary biomarkers in refractory interstitial cystitis/bladder pain syndrome patients randomized to extracorporeal shock wave therapy versus placebo.

Extracorporeal shock wave therapy (ESWT) has been shown to improve symptoms in patients with interstitial cystitis/bladder pain syndrome (IC/BPS); however, there is a lack of objective evidence. We measured change of urinary biomarker levels in 25 patients with IC/BPS received ESWT or placebo once a week for 4 weeks. Urines were collected from participants at baseline, 4 and 12 weeks post treatment. A representative 41 inflammatory growth factors, cytokines, and chemokines in urine were measured using a MILLIPLEX immunoassay kit. Symptom bother was assessed by O'Leary-Sant symptom scores (OSS), and visual analog scale (VAS) for pain. The ESWT group exhibited a significant reduction in the OSS and VAS compared to the placebo group 4 weeks post-treatment (P < 0.05), and the effects were persistent at 12 weeks. The difference in urinary markers change in ESWT versus placebo was P = 0.054 for IL4, P = 0.013 for VEGF, and P = 0.039 for IL9 at 4 weeks. The change of urine biomarker was not significant in other biomarkers or all the measured proteins at 12 weeks. The current data suggest that IL4, IL9, and VEGF mediation may be involved in its pathophysiologic mechanisms and response to LESW treatment.

The role of intravesical prostatic protrusion in the evaluation of overactive bladder in male patients with LUTS.

PURPOSE: To evaluate the association of intravesical prostatic protrusion (IPP) and overactive bladder (OAB) in male patients with lower urinary tract symptoms (LUTS). IPP has been suggested to correlate with storage symptoms in addition to bladder outlet obstruction. METHODS: This was an open-labeled, single-center, prospective study involving 128 men older than 40 years presenting with LUTS. We analyzed the relationship of IPP with age, prostate volume, uroflowmetry, post-void residual urine volume (PVR), International Prostate Symptom Score (IPSS), urgency severity scale (USS), and OAB symptom score (OABSS). The patients with an urgency score of ≥ 2 (OABSS question 2) and sum score of ≥ 3 were considered to have OAB. IPP was measured in the mid-sagittal section using transrectal ultrasound. The degree of IPP was classified as grade 1 (≤ 5 mm), grade 2 (> 5-10 mm), and grade 3 (> 10 mm). RESULTS: The mean age of the patients was 64.9 ± 9.2 years, and 101 patients were diagnosed with OAB (79%). Mean IPPs were 2.4 ± 1.4 mm (grade 1, n = 77), 7.6 ± 1.4 mm (grade 2, n = 27), and 14.8 ± 4.4 mm (grade 3, n = 24). IPP was positively correlated with age, prostate size, PSA, PVR, and OABSS nocturia subscore, but not correlated with the presence or severity of OAB. Areas under the receiver-operating characteristic (ROC) curves for the diagnosis of OAB were 0.807 and 0.604 for IPSS-storage subscore and IPP, respectively. CONCLUSION: IPP is not a good predictor of OAB in men presenting with LUTS. However, grade 3 IPP indicates higher frequency of nocturia.

Modest dose anti-thymocyte globulin administered intraoperatively is safe and effective in kidney transplantations: a retrospective study.

BACKGROUND: Anti-thymocyte globulin (ATG) as induction therapy in renal transplantation is facing the dilemma of reducing the incidence of acute rejection (AR) and delayed graft function (DGF) or increasing risks of infection and malignancy. The purpose of this study was to delineate the safety and efficiency of the optimal ATG dosage. METHODS: We retrospectively evaluated 91 deceased donor kidney transplant recipients (KTRs) in our institution between March 2011 and January 2019. The patients were classified into three groups based on induction therapy: (1) Group 1: modest-dose ATG (three mg/kg) intraoperatively (N = 21); (2) Group 2: low-dose ATG (1-1.5 mg/kg) intraoperatively (N = 23); (3) Group 3: basiliximab 20 mg both on day 0 and 4 (N = 47). In Groups 1 and 2, all patients received a daily low-dose program (1-1.5 mg/kg each day) with target dosage of six mg/kg. Induction therapy was combined with standard immunosuppressive regimen consisting of calcineurin inhibitors, mycophenolate/the mammalian target of rapamycin inhibitors and corticosteroids. RESULTS: There was no significant difference in patient characteristics among groups. The outcomes of infection rate, biopsy-proven acute rejection, post-transplant diabetes mellitus, graft survival, and patient survival were similar among groups. Compared to the daily low-dose ATG regimen, the intraoperative modest-dose regimen did not cause more dose interruption and hence was more likely to reach the target ATG dosage. The intraoperative modest-dose regimen also seemed to reduce the rate of DGF. DISCUSSION: In recent years, a trend of using a "lower" dose of ATG has seemed to emerge. Our results suggest intraoperative modest-dose ATG followed by daily low-dose ATG regimen was safe and effective in cadaveric renal transplantations for preventing DGF, AR, and graft loss.

Efficacy of switching therapy of luteinizing hormone-releasing hormone analogue for advanced prostate cancer.

This study was conducted to determine the efficacy of switching therapy with a second-line luteinizing hormone-releasing hormone (LHRH) analogue after prostate-specific antigen (PSA) progression for advanced prostate cancer. We enrolled 200 patients, from December 2005 to September 2013, with nodal positive, metastatic prostate cancer or disease progression after definite treatment receiving continuous LHRH analogue therapy with monthly depot leuprorelin(sc) acetate 3.75 mg/vial (LA) or goserelin acetate(sc) 3.6 mg/vial (GA). If the patients had castration-resistant prostate cancer, the treatment choice of switching therapy (from LA to GA or from GA to LA) prior to starting chemotherapy was given. The LH, testosterone level, and PSA change were recorded. The records showed that there were 127 patients receiving LA as initial ADT therapy, whereas the other 73 patients were in GA therapy. A total of 92 patients received LHRH analogue switching therapy (54 patients switched from LA to GA and 38 switched from GA to LA). The effect of LH and testosterone reduction prior to and after switching therapy was comparable between the two groups, and increased PSA level after 3 months of treatment was seen in both groups (median PSA: 15.7-67.7 ng/mL in the LA to GA group; 15.2-71.4 ng/mL in the GA to LA group). This study concluded that switching therapy for patients with PSA progression after ADT has no efficacy of further PSA response.

Determine of the optimal number of cycles of docetaxel in the treatment of metastatic castration-resistant prostate cancer.

To determine the optimal number of cycles of docetaxel for metastatic castration-resistant prostate cancer, we retrospectively collected 73 patients receiving varying numbers of docetaxel plus prednisolone and analyzed the clinical outcomes including overall survival, prostate-specific antigen (PSA) response, and adverse events. The study included 33 patients receiving ≤ 10 cycles of docetaxel and 40 patients receiving > 10 cycles. Patients receiving > 10 cycles were younger than those who received ≤ 10 cycles. There was no statistical significant difference in overall survival between the two groups (log-rank test, p = 0.75). Adverse effects were more common among patients receiving ≥ 10 cycles of treatment. A PSA flare-up was observed among six patients (8.2%); the median duration of the PSA surge was 3 weeks (range, 3-12 weeks). The overall survival rates in patients with PSA flare-up were comparable with the patients having PSA response. We concluded that at least four cycles of docetaxel should be administered in metastatic castration-resistant prostate cancer patients in order not to cease treatment prematurely from potentially beneficial chemotherapy. However, administering > 10 cycles does not result in any further improvement in survival and is associated with more adverse effects.

The experience of artificial urinary sphincter implantation by a single surgeon in 15 years.

Artificial urinary sphincter (AUS) is the gold standard treatment for urinary incontinence owing to sphincter incompetence. We reviewed our experience in AUS implantation. From 1995 to 2009, 19 patients underwent 25 AUS implantations performed by a single surgeon. The cause of incontinence was sphincter incompetence, which was secondary to prostate surgery, neurogenic bladder, radiation, and post-traumatic urethral lesion. Twenty-three prostheses were placed in the bulbar urethra for male patients: 11 AUS cuffs were placed through the perineal approach and 12 through the penoscrotal approach. Two procedures were applied over the bladder neck for the female patients. Through a retrospective review of charts, continence and complications were analyzed. The mean follow-up time was 50.0 ± 42.9 months (range: 2-146 months). There were 16 successful surgeries (64%), and these patients were free from the need for a pad. In eight surgeries (32%), the devices were removed due to infection, while one implantation (4%) was unsuccessful due to perforation into the bulbar urethra. There was a statistically significant difference (p = 0.024) in failure rates between patients who received radiotherapy (100%) and other patients (22.7%). There was no statistically significant difference in dry and revision rates (p > 0.05) between the perineal and penoscrotal approach. Accordingly, over half of the patients with total incontinence benefitted from AUS implantation. In consideration of the high failure rate for patients receiving radiotherapy, caution should be exercised in the use of implantation. Secondary implantation has a satisfactory success rate in selected patients. The same success rate was noted for both perineal and penoscrotal approaches.

Application of resonance metallic stents for ureteral obstruction.

OBJECTIVE: • To determine the effectiveness of the Resonance ureteral stent and clarify the risk factors that lead to stent failure. In the present study, we review our clinical experiences using Resonance stent in treating malignant and benign ureteral obstruction. PATIENTS AND METHODS: • Nineteen patients with extrinsic malignant ureteral obstruction (n= 15) and benign stricture (n= 4) were retrospectively evaluated. • All patients had received Resonance stent insertion through antegrade or cystoscopic retrograde approaches. The pre-insertion and follow-up interventions included image studies and biochemical tests. The insertion success rate, obstruction patency rate and complications were reviewed. • For categorical variables, the chi-square test and Fisher's exact test were carried out to determine associations between variables. RESULTS: • The technical success rate of stent insertion was 84.6%. The mean follow-up was 5 months (range 1-10.5 months). • Five stents failed to alleviate the obstruction, and the patency rate was 77.3% (17/22). • Patients who had had previous radiation therapy had a lower ureter patency rate in comparison with non-radiation patients (50% vs 92.3% respectively, P= 0.039). • The 6- and 9-month patency rates were 81.0% with 11 stents and 27.0% with 3 stents, respectively. CONCLUSIONS: • The results of the present study demonstrated that malignant or benign ureteral obstruction could be treated safely and sufficiently with the Resonance metallic stent. • Careful patient selection is critical to achieve successful results. • For malignant ureteral obstruction, previous radiation therapy is a risk factor for stent failure.