Endoscopic management of upper tract urothelial cancer in a highly endemic area: A Taiwan nationwide collaborative study.

BACKGROUND: Endoscopic management of upper tract urothelial cancer (UTUC) is an important treatment option for low risk UTUC. Although Taiwan is an endemic area for UTUC, endoscopic treatment outcomes in Taiwan are frequently under- reported. METHODS: This study retrospectively reviewed the treatment outcomes of endoscopic management for clinically localized UTUC. Patients with biopsy or washing cytology confirmed UTUC who underwent endoscopic or percutaneous management with a curative intent were retrospectively reviewed for eligibility of analysis. Those cases without pre-intervention confirmed UTUC, and metastatic or nodal disease at diagnosis were excluded. RESULTS: In total, 307 patients who underwent endoscopic management were reviewed and 279 cases were eligible for final analysis. With a median follow-up of 44.3 months (inter-quartile range (IQR): 23.4-76.4 months), 117 cases (46.4%) were endoscopic cured after median one session (range:1-8; IQR:1-2) of endoscopic treatment. Those endoscopic cured UTUC was associated with more small-sized tumor, more low-grade biopsied-histology, less concomitant bladder UC and less pre-operative hydronephrosis. In addition, 201(79.7%) cases among 252 cases with confirmed oncological outcome were free of UTUC at the end of follow-up and only 43 (17%) patients had a UTUC related mortality. Salvage RNU offered a better tumor free survival rate (92% vs. 77.5%) than those without salvage RNU in those UTUC refractory to endoscopic management. In multivariable analyses, pre-operative hydronephrosis was the independent risk factor for OS. Multiplicity and concomitant bladder UC were independent risk factors for DFS. CONCLUSIONS: We confirmed the consistent safety and efficacy of endoscopic management of clinical localized UTUC in a highly UTUC endemic area like Taiwan. Early salvage RNU is mandatory in those UTUC refractory to endoscopic management in prevention of UTUC related death.

Impact of pathological response on oncological outcomes in patients with upper tract urothelial cancer receiving neo-adjuvant chemotherapy.

PURPOSE: The purpose of this study is to evaluate the rates of pathological complete response (ypT0N0/X) and pathological response (ypT1N0/X or less) in patients with upper tract urothelial cancer who were treated with neo-adjuvant chemotherapy and to examine their impact on oncological outcomes. METHODS: This study is a multi-institutional retrospective analysis of patients with high-risk upper tract urothelial cancer who underwent neoadjuvant chemotherapy and radical nephroureterectomy between 2002 and 2021. Logistic regression analyses were used to investigate all clinical parameters for response after neoadjuvant chemotherapy. Cox proportional hazard models were performed to assess the effect of the response on the oncological outcomes. RESULTS: A total of 84 patients with UTUC who received neo-adjuvant chemotherapy were identified. Among them, 44 (52.4%) patients received cisplatin-based chemotherapy, and 22 (26.2%) patients had a carboplatin-based regimen. The pathological complete response rate was 11.6% (n = 10), and the pathological response rate was 42.9% (n = 36). Multifocal tumors or tumors larger than 3 cm significantly reduced the odds of pathological response. In the multivariable Cox proportional hazard model, pathological response was independently associated with better overall survival (HR 0.38, p = 0.024), cancer-specific survival (HR 0.24, p = 0.033), and recurrence-free survival (HR 0.17, p = 0.001), but it was not associated with bladder recurrence-free survival (HR 0.84, p = 0.69). CONCLUSION: Pathological response after neo-adjuvant chemotherapy and radical nephroureterectomy is strongly associated with patient survival and recurrence, and it might be a good surrogate for evaluating the efficacy of neo-adjuvant chemotherapy in the future.

Effectiveness of Platelet-Rich Plasma Injections as Prophylaxis for Recurrent Urinary Tract Infection in Women.

PURPOSE: To investigate the therapeutic efficacy of intravesical platelet-rich plasma (PRP) injections as prophylaxis for adult women with recurrent urinary tract infection (rUTI). METHODS: This proof-of-concept study enrolled 63 women with rUTI in PRP treatment and control groups after achieving control of the most recent urinary tract infection (UTI) episode. The treatment group included 34 women who received 4 monthly intravesical PRP injections. The control group was made up of 30 women who received continuous antibiotic treatment for 3 months. After the completion of PRP or antibiotic treatment, outpatient follow-up was continued for up to 12 months. Treatment was considered successful if ≤2 UTI episodes occurred during a period of 12 months or ≤1 UTI episode within 6 months; otherwise, the outcome was considered a treatment failure. The frequency of symptomatic UTI episodes before and after PRP treatment was compared with that of the controls. Regression analysis was used to determine the association between potential predictors for a failed treatment outcome. RESULTS: At the study endpoint, 33 PRP and 25 control group patients were available for analysis. After four PRP injections, the frequency of rUTI episodes per month was significantly decreased compared with baseline (0.46 ± 0.27 vs. 0.28 ± 0.30, p = 0.047). The PRP treatment success rate was 51.5% (17 of 33) for the PRP group versus 48% (12 of 25) for the control group. The PRP treatment success group had significantly higher voided volume, lower post-void residual volume, and higher voiding efficiency than the PRP treatment failure group. A higher baseline voiding efficacy ≥0.71 was significantly associated with a successful outcome (OR 16.56; p = 0.049). CONCLUSIONS: The study results revealed that repeat intravesical PRP injections decreased the recurrence rate of UTI within 1 year in women with rUTI. The treatment success rate with intravesical PRP injections for rUTI was about 51.5%, whereas for women with prolonged antibiotic treatment, it was 48.0%. A baseline VE ≥ 0.71 was associated with a better treatment outcome with PRP injections.

Oncological and functional outcomes of high-risk and very high-risk prostate cancer patients after robot-assisted radical prostatectomy.

PURPOSE: This study investigated the oncological and functional outcomes of robot-assisted radical prostatectomy (RaRP) in high-risk and very high-risk prostate cancer patients. MATERIALS AND METHODS: One hundred localized prostate cancer patients receiving RaRP from August 2015 to December 2020 were retrospectively enrolled. According to NCCN risk classification, patients were classified into two groups, below high-risk group, and high-risk/very high-risk group, to analyze continence outcome within postoperative year one and biochemical recurrence-free survival. RESULTS: The mean age of the cohort was 69.7 ± 7.4 years with a median follow-up of 26.4 (range 3.3-71.3) months. Among them, 53%, and 47% patients were below high-risk group, and high-risk/very high-risk group, respectively. The median biochemical recurrence-free survival of the entire cohort was 53.1 months. The high-risk/very high-risk group without adjuvant treatment had significantly worse biochemical recurrence-free survival than the high-risk/very high-risk group with adjuvant treatment (19.6 vs. 60.5 months, p = 0.029). Rates of postoperative stress urinary incontinence at 1 week, 1 month, and 12 months were 50.7%, 43.7%, and 8.5%, respectively. High-risk/very high-risk patients had significantly higher rates of stress urinary incontinence at postoperative week 1 (75.8% vs. 28.9%) and month 1 (63.6% vs. 26.3%) than the below high-risk group (both p < 0.01). Rates of stress urinary incontinence after RaRP did not differ between two groups from postoperative 3 months to 12 months. The factor of high-risk / very high-risk group was a predictor of immediate but not for long-term postoperative stress urinary incontinence. CONCLUSIONS: High-risk and very high-risk prostate cancer patients receiving a combination of RaRP and adjuvant treatment had comparable biochemical recurrence-free survival to below high-risk prostate cancer patients. The high-risk/very high-risk factor impeded early but not long-term postoperative recovery of continence. RaRP can be considered a safe and feasible option for high-risk and very high-risk prostate cancer patients.

Preoperative hydronephrosis is an independent protective factor of renal function decline after nephroureterectomy for upper tract urothelial carcinoma.

Objectives: To evaluate the predictive role of pre-nephroureterectomy (NU) hydronephrosis on post-NU renal function (RF) change and preserved eligibility rate for adjuvant therapy in patients with upper tract urothelial carcinoma (UTUC). Patients and methods: This retrospective study collected data of 1018 patients from the Taiwan UTUC Collaboration Group registry of 26 institutions. The patients were divided into two groups based on the absence or presence of pre-NU hydronephrosis. Estimated glomerular filtration rate (eGFR) was calculated pre- and post-NU respectively. The one month post-NU RF change, chronic kidney disease (CKD) progression, and the preserved eligibility rate for adjuvant therapy were compared for each CKD stage. Results: 404 (39.2%) patients without and 614 (60.8%) patients with pre-NU hydronephrosis were enrolled. The median post-NU change in the eGFR was significantly lower in the hydronephrosis group (-3.84 versus -12.88, p<0.001). Pre-NU hydronephrosis was associated with a lower post-NU CKD progression rate (33.1% versus 50.7%, p< 0.001) and was an independent protective factor for RF decline after covariate adjustment (OR=0.46, p<0.001). Patients with pre-NU hydronephrosis had a higher preserved eligibility rate for either adjuvant cisplatin-based chemotherapy (OR=3.09, 95%CI 1.95-4.69) or immune-oncology therapy (OR=2.31, 95%CI 1.23-4.34). Conclusion: Pre-NU hydronephrosis is an independent protective predictor for post-NU RF decline, CKD progression, and eligibility for adjuvant therapy. With cautious selection for those unfavorably prognostic, non-metastatic UTUC patients with preoperative hydronephrosis, adjuvant rather than neoadjuvant therapy could be considered due to higher chance of preserving eligibility.

Satisfaction with Urinary Incontinence Treatments in Patients with Chronic Spinal Cord Injury.

Purpose: To investigate the long-term satisfaction and complications in chronic spinal cord injury (SCI) patients after various bladder management strategies and surgical procedures for the treatment of urinary incontinence. Methods: Patients at a single institution with chronic SCI who received bladder management treatment or surgical procedure to improve urinary continence were retrospectively assessed. Thorough urological examinations and videourodynamic studies were performed. Patients were treated either through conservative approaches including medical treatment, clean intermittent catheterization (CIC), cystostomy, and indwelling urethral catheter, or through surgical procedures including detrusor botulinum toxin (Botox) injections, augmentation, ileal conduit, Kock pouch diversion, continent cystostomy, suburethral sling, and artificial urethral sphincter (AUS) implantation. The patients' satisfaction with urinary continence improvement, causes of dissatisfaction, long-term complications, and overall satisfaction with bladder and voiding condition were assessed. Results: A total of 700 consecutive patients were enrolled in this study. High satisfaction rates were noted after detrusor Botox injection (81.1%), augmentation enterocystoplasty (91.4%), autoaugmentation (80%), Kock pouch diversion, and continent cystostomy (all 100%). Fair satisfaction rates were noted after ileal conduit diversion (66.7%), suburethral sling (64.3%), and AUS implantation (66.7%). Patients who received conservative treatment with medicines, CIC, cystostomy, or an indwelling urethral catheter all had less-satisfactory outcomes (all < 40%). Conclusion: Overall satisfaction with surgical procedures aimed to improve urinary continence in chronic SCI patients was higher than with conservative bladder management (35.4%). Appropriate surgical procedures for chronic SCI patients with neurogenic lower urinary tract dysfunction (NLUTD) and urological complications yielded satisfaction with both urinary continence improvement and with overall bladder and voiding condition.

Is Lymph Node Dissection Necessary During Radical Nephroureterectomy for Clinically Node-Negative Upper Tract Urothelial Carcinoma? A Multi-Institutional Study.

Purpose: This study aimed to compare the oncological outcomes of patients with upper tract urothelial carcinoma (UTUC) without clinical lymph node metastasis (cN0) undergoing lymph node dissection (LND) during radical nephroureterectomy (NU). Methods: From the updated data of the Taiwan UTUC Collaboration Group, a total of 2726 UTUC patients were identified. We only include patients with ≥ pT2 stage and enrolled 658 patients. The Kaplan-Meier estimator and Cox proportional hazards model were used to analyze overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), and bladder recurrence-free survival (BRFS) in LND (+) and LND (-) groups. Results: A total of 658 patients were included and 463 patients without receiving LND and 195 patients receiving LND. From both univariate and multivariate survival analysis, there are no significant difference between LND (+) and LND (-) group in survival rate. In LND (+) group, 18.5% patients have pathological LN metastasis. After analyzing pN+ subgroup, it revealed worse CSS (p = 0.010) and DFS (p < 0.001) compared with pN0 patients. Conclusions: We found no significant survival benefit related to LND in cN0 stage, ≥ pT2 stage UTUC, irrespective of the number of LNs removed, although pN+ affected cancer prognosis. However, from the result of pN (+) subgroup of LND (+) cohort analysis, it may be reasonable to not perform LND in patients with cT2N0 stage due to low positive predictive value of pN (+). In addition, performing LND may be considered for ureter cancer, which tends to cause lymphatic and hematogenous tumor spreading. Further large prospective studies are needed to validate our findings.

Impact of Adjuvant Chemotherapy on Variant Histology of Upper Tract Urothelial Carcinoma: A Propensity Score-Matched Cohort Analysis.

Background: The advantage of adjuvant chemotherapy for upper urinary tract urothelial cancer (UTUC) has been reported, whereas its impact on upper tract cancer with variant histology remains unclear. We aimed to answer the abovementioned question with our real-world data. Design Setting and Participants: Patients who underwent radical nephroureterectomy (RNU) and were confirmed to have variant UTUC were retrospectively evaluated for eligibility of analysis. In the Taiwan UTUC Collaboration database, we identified 245 patients with variant UTUC among 3,109 patients with UTUC who underwent RNU after excluding patients with missing clinicopathological information. Intervention: Those patients with variant UTUC were grouped based on their history of receiving adjuvant chemotherapy or not. Outcome Measurements and Statistical Analysis: Propensity score matching was used to reduce the treatment assignment bias. Multivariable Cox regression model was used for the analysis of overall, cancer-specific, and disease-free survival. Results and Limitations: For the patients with variant UTUC who underwent adjuvant chemotherapy compared with those without chemotherapy, survival benefit was identified in overall survival in univariate analysis (hazard ratio (HR), 0.527; 95% confidence interval (CI), 0.285-0.973; p = 0.041). In addition, in multivariate analysis, patients with adjuvant chemotherapy demonstrated significant survival benefits in cancer-specific survival (OS; HR, 0.454; CI, 0.208-0.988; p = 0.047), and disease-free survival (DFS; HR, 0.324; 95% CI, 0.155-0.677; (p = 0.003). The main limitations of the current study were its retrospective design and limited case number. Conclusions: Adjuvant chemotherapy following RNU significantly improved cancer-related survivals in patients with UTUC with variant histology.

Changes in the Ultrastructure of the Bladder Urothelium in Patients with Interstitial Cystitis after Intravesical Injections of Platelet-Rich Plasma.

Urothelial dysfunction is considered a key pathological mechanism of interstitial cystitis/bladder pain syndrome (IC/BPS). Intravesical platelet-rich plasma (PRP) injections might be effective for treating IC/BPS. This prospective study investigated the changes in electron microscopic findings among IC/BPS patients after intravesical PRP injections. Twenty-six patients with refractory non-ulcer IC/BPS underwent monthly intravesical PRP injections for 4 months. Changes in clinical symptom scores and video urodynamic study parameters were assessed from baseline to after the PRP injections. A post-treatment Global Response Assessment (GRA) score ≥ 2 was considered a successful outcome. The mean GRA score was significantly higher after 4 PRP injections than at baseline. Approximately 42% of patients experienced successful outcomes after PRP treatment. Urothelial ultrastructural defects showed no significant differences between baseline and after the PRP injections. However, patients showed variable improvements in different urothelial defects (grade improvements: urothelium cell layers, 31%; umbrella cell integrity, 42%; umbrella cell surface uroplakin plaque, 54%; tight junctions between adjacent umbrella cells, 46%; lysed organelles, 58%; inflammatory cell infiltration, 31%). Patients with successful treatment outcomes showed significant improvements in urothelial tight junction defects. Repeated intravesical PRP injections are effective for improving IC/BPS symptoms as they promote urothelial ultrastructural defect recovery.

Clinical Efficacy of Adjuvant Chemotherapy in Advanced Upper Tract Urothelial Carcinoma (pT3-T4): Real-World Data from the Taiwan Upper Tract Urothelial Carcinoma Collaboration Group.

The clinical efficacy of adjuvant chemotherapy in upper tract urothelial carcinoma (UTUC) is unclear. We aimed to assess the therapeutic outcomes of adjuvant chemotherapy in patients with advanced UTUC (pT3-T4) after radical nephroureterectomy (RNU). We retrospectively reviewed the data of 2108 patients from the Taiwan UTUC Collaboration Group between 1988 and 2018. Comprehensive clinical features, pathological characteristics, and survival outcomes were recorded. Univariate and multivariate Cox proportional hazards models were used to evaluate overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS). Of the 533 patients with advanced UTUC included, 161 (30.2%) received adjuvant chemotherapy. In the multivariate analysis, adjuvant chemotherapy was significantly associated with a reduced risk of overall death (hazard ratio (HR), 0.599; 95% confidence interval (CI), 0.419-0.857; p = 0.005), cancer-specific mortality (HR, 0.598; 95% CI, 0.391-0.914; p = 0.018), and cancer recurrence (HR, 0.456; 95% CI, 0.310-0.673; p < 0.001). The Kaplan-Meier survival analysis revealed that patients receiving adjuvant chemotherapy had significantly better five-year OS (64% vs. 50%, p = 0.002), CSS (70% vs. 62%, p = 0.043), and DFS (60% vs. 48%, p = 0.002) rates compared to those who did not receive adjuvant chemotherapy. In conclusion, adjuvant chemotherapy after RNU had significant therapeutic benefits on OS, CSS, and DFS in advanced UTUC.

Low-Energy Shock Wave Plus Intravesical Instillation of Botulinum Toxin A for Interstitial Cystitis/Bladder Pain Syndrome: Pathophysiology and Preliminary Result of a Novel Minimally Invasive Treatment.

Low-energy shock wave (LESW) therapy is known to facilitate tissue regeneration with analgesic and anti-inflammatory effects. LESW treatment has been demonstrated to be effective in treating chronic prostatitis and pelvic pain syndrome as well as overactive bladder, and it has a potential effect on interstitial cystitis/bladder pain syndrome (IC/BPS) in humans. LESW reduces pain behavior, downregulates nerve growth factor expression, and suppresses bladder overactivity by decreasing the expression of inflammatory proteins. Previous rat IC models have shown that LESW can increase urothelial permeability, facilitate intravesical delivery of botulinum toxin A (BoNT-A), and block acetic acid-induced hyperactive bladder, suggesting that LESW might be a potential therapeutic module for relieving bladder inflammatory conditions, such as bladder oversensitivity, IC/BPS, and overactive bladder. A recent clinical trial showed that LESW monotherapy was associated with a significant reduction in pain scores and IC symptoms. BoNT-A detrusor injection or liposome-encapsulated BoNT-A instillation could also inhibit inflammation and improve IC symptoms. However, BoNT-A injection requires anesthesia and certain complications might occur. Our preliminary study using LESW plus intravesical BoNT-A instillation every week demonstrated an improvement in global response assessment without any adverse events. Moreover, an immunohistochemistry study revealed the presence of cleaved SNAP25 protein in the suburothelium of IC bladder tissue, indicating that BoNT-A could penetrate across the urothelial barrier after application of LESW. These results provide evidence for the efficacy and safety of this novel IC/BPS treatment by LESW plus BoNT-A instillation, without anesthesia, and no bladder injection. This article reviews the current evidence on LESW and LESW plus intravesical therapeutic agents on bladder disorders and the pathophysiology and pharmacological mechanism of this novel, minimally invasive treatment model for IC/BPS.

Oncologic impact of delay between diagnosis and radical nephroureterectomy.

Purpose: This study aimed to evaluate the oncological outcome of delayed surgical wait time from the diagnosis of upper tract urothelial carcinoma (UTUC) to radical nephroureterectomy (RNU). Methods: In this multicenter retrospective study, medical records were collected between 1988 and 2021 from 18 participating Taiwanese hospitals under the Taiwan UTUC Collaboration Group. Patients were dichotomized into the early (≤90 days) and late (>90 days) surgical wait-time groups. Overall survival, disease-free survival, and bladder recurrence-free survival were calculated using the Kaplan-Meier method and multivariate Cox regression analysis. Multivariate analysis was performed using stepwise linear regression. Results: Of the 1251 patients, 1181 (94.4%) were classifed into the early surgical wait-time group and 70 (5.6%) into the late surgical wait-time group. The median surgical wait time was 21 days, and the median follow-up was 59.5 months. Our study showed delay-time more than 90 days appeared to be associated with worse overall survival (hazard ratio [HR] 1.974, 95% confidence interval [CI] 1.166-3.343, p = 0.011), and disease-free survival (HR 1.997, 95% CI 1.137-3.507, p = 0.016). This remained as an independent prognostic factor after other confounding factors were adjusted. Age, ECOG performance status, Charlson Comorbidity Index (CCI), surgical margin, tumor location and adjuvant systemic therapy were independent prognostic factors for overall survival. Tumor location and adjuvant systemic therapy were also independent prognostic factors for disease-free survival. Conclusions: For patients with UTUC undergoing RNU, the surgical wait time should be minimized to less than 90 days. Prolonged delay times may be associated with poor overall and disease-free survival.

Impact of Pathology Review in Adverse Histological Characteristics and pT Stages of Upper Tract Urothelial Cancer in a Multicenter Study.

PURPOSE: Pathology reviews for upper urinary tract cancer (UTUC) remained scarce in the literature. Here, we reported the interobserver variation among the review and local pathologies of featured histologic characteristics for UTUC. METHODS: Patients who underwent definitive surgical treatments for UTUC were retrospectively reviewed for eligibility of pathology review. In the Taiwan UTUC Collaboration cohort, 212 cases were reviewed, of which 154 cases were eligible for pathology review. Agreement between original pathology and review pathology was measured by the total percentage of agreement and by simple kappa statistics. The prognostic impact was analyzed by the Cox regression model with the estimation of hazard ratios (HR) and 95% confidence intervals. RESULTS: There were 80 women and 74 men enrolled in this study, and the median age at treatment was 71.7 years. The agreement is moderate agreement for surgical margin status (87.7%; κ = 0.61), tumor grade (82.5%; κ = 0.43), tumor invasiveness (76.6%; κ = 0.45), lymphovascular invasion (70.8%; κ = 0.42) and T stage (67.5%; κ = 0.52). The interobserver agreements for perineural invasion and variant histology identification were slight. Kaplan-Meier analysis for disease-free survival revealed comparable results in local and review pathology for localized (Tis, Ta, T1-2) or advanced T stage (T3-4). CONCLUSIONS: Pathology review of UTUC had minimal impact on clinical practice based on current available disease treatment guidelines. However, significant interobserver variations were observed in featured adverse histopathological characters.

Difference in electron microscopic findings among interstitial cystitis/bladder pain syndrome with distinct clinical and cystoscopic characteristics.

Urothelial dysfunction may be a key pathomechanism underlying interstitial cystitis/bladder pain syndrome (IC/BPS). We therefore examined if clinical severity is associated with the extent of urothelial damage as revealed by electron microscopic (EM) analysis of biopsy tissue. One hundred IC/BPS patients were enrolled and 24 patients with stress urinary incontinence served as controls. Clinical symptoms were evaluated by visual analog scale pain score and O'Leary-Sant Symptom score. Bladder biopsies were obtained following cystoscopic hydrodistention. The presence of Hunner's lesions and glomerulation grade after hydrodistention were recorded and patients classified as Hunner-type IC (HIC) or non-Hunner-type IC (NHIC). HIC patients exhibited more severe defects in urothelium cell layers, including greater loss of umbrella cells, umbrella cell surface uroplakin plaque, and tight junctions between adjacent umbrella cells, compared to control and NHIC groups (all p < 0.05). Both NHIC and HIC groups demonstrated more severe lamina propria inflammatory cell infiltration than controls (p = 0.011, p < 0.001, respectively). O'Leary-Sant Symptom scores were significantly higher among patients with more severe urothelial defects (p = 0.030). Thus, urothelium cell layer defects on EM are associated with greater clinical symptom severity.

Endoscopic management versus radical nephroureterectomy for localized upper tract urothelial carcinoma in a high endemic region.

Our aim was to analyze the clinical and survival differences among patients who underwent the two main treatment modalities, endoscopic ablation and radical nephroureterectomy. This study examined all patients who had undergone endoscopic management and RNU between Jul. 1988 and Mar. 2019 from the Taiwan UTUC registry. The inclusion criteria were low stage UTUC in RNU and all cases in endoscopic managed UTUC with a curative intent. The demographic and clinical characteristics were included for analysis. In total, 84 cases in the endoscopic group and 272 cases in the RNU group were enrolled for final analysis. The median follow-up period were 33.5 and 42.0 months in endoscopic and RNU group, respectively (p = 0.082). Comparison of Kaplan-Meier estimated survival curves between groups, the endoscopic group was associated with similar overall survival (OS), cancer specific survival (CSS), and intravesical recurrence free survival (IVRS) but demonstrated inferior disease free survival (DFS) (p = 0.188 for OS, p = 0.493 for CSS and p < 0.001 for DFS). Endoscopic management of UTUC was as safe as RNU in UTUC endemic region.

Factors Predicting Oncological Outcomes of Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma in Taiwan.

BACKGROUND: Taiwan is one of the endemic regions where upper tract urothelial carcinoma (UTUC) accounts for approximately a third of all urothelial tumors. Owing to its high prevalence, extensive experience has been accumulated in minimally invasive radical nephroureterectomy (RNU). Although a variety of predictive factors have been explored in numerous studies, most of them were on a single-center or limited institutional basis and data from a domestic cohort are lacking. OBJECTIVE: This study aims to identify significant predicting factors of oncological outcomes, including overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), and intravesical recurrence-free survival (IVRFS), following RNU for UTUC in Taiwan. METHODS: A multicenter registry database, Taiwan UTUC Collaboration Group, was utilized to analyze oncological outcomes of 3,333 patients undergoing RNU from 1988 to 2021 among various hospitals in Taiwan. Clinicopathological parameters were recorded according to the principles established by consensus meetings. The Kaplan-Meier estimator was utilized to estimate the survival rates, and the curves were compared using the stratified log-rank test. Univariate and multivariate analyses were performed with the Cox proportional hazard model to explore potential predicting factors. RESULTS: With a median follow-up of 41.8 months in 1,808 patients with complete information, the 5-year IVRFS, DFS, CSS, and OS probabilities were 66%, 72%, 81%, and 70%, respectively. In total, 482 patients experienced intravesical recurrence, 307 died of UTUC, and 583 died of any cause. Gender predominance was female (57%). A total of 1,531 patients (84.7%) had high-grade tumors; preoperative hydronephrosis presented in 1,094 patients (60.5%). Synchronous bladder UC was identified in 292 patients (16.2%). Minimally invasive procedures accounted for 78.8% of all surgeries, including 768 hand-assisted laparoscopic (42.5%) and 494 laparoscopic (27.3%) approaches. Synchronous bladder UC was the dominant adverse predicting factor for all survival outcomes. Other independent predicting factors for OS, CSS, and DFS included age ≧70, presence of preoperative hydronephrosis, positive surgical margin, LVI, pathological T and N staging, and laparoscopic RNU. CONCLUSION: Synchronous UC of the urinary bladder is an independent adverse prognostic factor for survival in UTUC. The presence of preoperative hydronephrosis was also corroborated as a disadvantageous prognostic factor. Our multivariate analysis suggested that laparoscopic RNU might provide better oncological control.

Prognostic Significance of Primary Tumor Location in Upper Tract Urothelial Carcinoma Treated with Nephroureterectomy: A Retrospective, Multi-Center Cohort Study in Taiwan.

We sought to examine the effect of tumor location on the prognosis of patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). This retrospective study came from the Taiwan UTUC Collaboration Group, which consisted of 2658 patients at 15 institutions in Taiwan from 1988 to 2019. Patients with kidney-sparing management, both renal pelvic and ureteral tumors, as well as patients lacking complete data were excluded; the remaining 1436 patients were divided into two groups: renal pelvic tumor (RPT) and ureteral tumor (UT), with 842 and 594 patients, respectively. RPT was associated with more aggressive pathological features, including higher pathological T stage (p < 0.001) and the presence of lymphovascular invasion (p = 0.002), whereas patients with UT often had synchronous bladder tumor (p < 0.001), and were more likely to bear multiple lesions (p = 0.001). Our multivariate analysis revealed that UT was a worse prognostic factor compared with RPT (overall survival: HR 1.408, 95% CI 1.121-1.767, p = 0.003; cancer-specific survival: HR 1.562, 95% CI 1.169-2.085, p = 0.003; disease-free survival: HR 1.363, 95% CI 1.095-1.697, p = 0.006; bladder-recurrence-free survival: HR 1.411, 95% CI 1.141-1.747, p = 0.002, respectively). Based on our findings, UT appeared to be more malignant and had a worse prognosis than RPT.

Therapeutic Effects of Botulinum Toxin A, via Urethral Sphincter Injection on Voiding Dysfunction Due to Different Bladder and Urethral Sphincter Dysfunctions.

Botulinum toxin A (BoNT-A) urethral sphincter injections have been applied in treating voiding dysfunction but the treatment outcome is not consistent. This study analyzed treatment outcomes between patients with different bladder and urethral sphincter dysfunctions. Patients with refractory voiding dysfunction due to neurogenic or non-neurogenic etiology were treated with urethral sphincter 100 U BoNT-A injections. The treatment outcomes were assessed by a global response assessment one month after treatment. The bladder neck opening and urodynamic parameters in preoperative videourodynamic study were compared between successful and failed treatment groups. A total of 80 non-neurogenic and 75 neurogenic patients were included. A successful outcome was noted in 92 (59.4%) patients and a failed outcome in 63 (40.6%). The treatment outcome was not affected by the gender, voiding dysfunction subtype, bladder dysfunction, or sphincter dysfunction subtypes. Except an open bladder neck and higher maximum flow rate, no significant difference was noted in the other variables between groups. Non-neurogenic patients with successful outcomes had a significantly higher detrusor pressure, and patients with neurogenic voiding dysfunction with successful results had higher maximum flow rates and smaller post-void residuals than those who failed the treatment. However, increased urinary incontinence was reported in 12 (13%) patients. BoNT-A urethral sphincter injection is effective in about 60% of either neurogenic or non-neurogenic patients with voiding dysfunction. An open bladder neck during voiding and a higher maximum flow rate indicate a successful treatment outcome.

Safety and therapeutic efficacy of mirabegron 25 mg in older patients with overactive bladder and multiple comorbidities.

AIM: The present study assessed the therapeutic efficacy and safety of mirabegron 25 mg in older patients aged ≥80 years with overactive bladder and multiple comorbidities. METHODS: Patients with overactive bladder were prospectively treated with 25 mg of mirabegron once daily. The patients were divided into a younger group (aged 40-60 years) and an older group (aged ≥80 years), and their underlying comorbidities were recorded. The primary efficacy end-point was the change in symptom score from baseline to the third month. Safety assessments included adverse events and post-void residual urine volume. RESULTS: A total of 217 patients (younger, n = 62; older, n = 155) were included. The older patients had more comorbidities than the younger patients. Statistically significant improvements in the Quality of Life index and Patient Perception of Bladder Condition were noted in the younger patients from 1 month after treatment, whereas the International Prostate Symptom Score-Voiding subscore, International Prostate Symptom Score-Total, Quality of Life index, post-void residual urine volume and Patient Perception of Bladder Condition were all significantly decreased in the older patients after 3 months of treatment. The mean changes in the International Prostate Symptom Score-Voiding subscore, maximal flow rate, post-void residual urine volume, nocturia and Urgency Severity Score were significantly different between the two groups. The younger patients experienced more minor adverse events than the older patients (41.94% vs 24.62%) during treatment. Nevertheless, the adverse event rate was acceptably low in both groups. CONCLUSIONS: Mirabegron 25 mg once daily is a safe and effective treatment for older patients with overactive bladder. Geriatr Gerontol Int 2018; 18: 1330-1333.

Clinical Outcome of Augmentation Enterocystoplasty for Patients with Ketamine-induced Cystitis.

BACKGROUND: Ketamine abuse has become a global phenomenon in recent years. Ketamine-induced cystitis (KC) is a new clinical syndrome which can result in severely inflamed bladder and intractable bladder pain. Currently there is no guideline for managing patients with KC. OBJECTIVES: To analyze the clinical outcome of patients with KC managed with augmentation enterocystoplasty (AE). STUDY DESIGN: Retrospective interventional study. SETTING: A tertiary teaching hospital, Hualien Tzu Chi Hospital. METHODS: We retrospectively collected and analyzed the medical records and video-urodynamic (VUD) test results of 26 patients who underwent AE as treatment for refractory KC during the period 2009 - 2014. All of these patients abused ketamine with nasal snorting, at least 3 grams per dose, twice per week for 6 months. Data from VUD studies performed before AE and 3 - 6 months after surgery that were analyzed in this study included cystometric bladder capacity (CBC), post-void residual (PVR) urine volume, maximum urinary flow rate (Qmax), voided volume, and bladder compliance. A self-report questionnaire was used to assess patient satisfaction with AE. RESULTS: Patients included 14 women and 12 men aged 20 - 43 years (mean age, 28.5 years) with an average duration of ketamine abuse of 4.7 years (range, 1 - 10 years). All patients had contracted bladder, 9 had hydronephrosis, and 10 had vesicoureteral reflux (VUR). There was significant improvement in CBC (52.7 ± 29.7 v 327 ± 69.4 mL, P < 0.0001), Qmax (6.94 ± 4.32 v 13.7 ± 4.96 mL/s, P < 0.0001), PVR (8.08 ± 19.2 v 82.6 ± 91.5 mL, P < 0.0001), voided volume (44.1 ± 28.3 v 250.7 ± 133.4 mL, P < 0.0001), and bladder compliance (11.1 ± 11.9 v 54 ± 43, P < 0.0001) after AE. Hydronephrosis resolved in 7 patients after AE and VUR resolved in all patients who underwent AE with ureteral reimplantation. All patients who stopped using ketamine were free of bladder pain postoperatively. However, 10 patients who reused ketamine had recurrent bladder pain and recurrent urinary tract infection. LIMITATIONS: Small number of patients limits scope of study. CONCLUSIONS: AE is effective at treating KC-induced bladder pain and restoring normal lower urinary tract function. However, absolute cessation of ketamine is the key to success in KC treatment.Key words: Ketamine-induced cystitis, augmentation enterocystoplasty, bladder pain, contracted bladder, inflammation, surgery.