Surgical Outcomes and Predictive Factors in Patients With Detrusor Underactivity Undergoing Bladder Outlet Obstruction Surgery.

PURPOSE: This study was conducted to evaluate the efficacy of bladder outlet surgery in patients with detrusor underactivity (DU) and to identify factors associated with successful outcomes. METHODS: We conducted a retrospective review of men diagnosed with DU in urodynamic studies who underwent bladder outlet surgery for lower urinary tract symptoms between May 2018 and April 2023. The International Prostate Symptom Score (IPSS) questionnaire, uroflowmetry (UFM), and multichannel urodynamic studies were administered. Successful treatment outcomes were defined as either an IPSS improvement of at least 50% or the regaining of spontaneous voiding in patients urethral catheterization prior to surgery. RESULTS: The study included 93 male patients. Men diagnosed with significant or equivocal bladder outlet obstruction (BOO) experienced significant postoperative improvements in IPSS (from 20.6 to 6.0 and from 17.4 to 6.5, respectively), maximum urine flow rate (from 5.0 mL/sec to 14.4 mL/sec and from 8.8 mL/sec to 12.2 mL/sec, respectively) and voiding efficiency (from 48.8% to 86.0% and from 61.2% to 85.1%, respectively). However, in the group without obstruction, the improvements in IPSS and UFM results were not significant. The presence of detrusor overactivity (odds ratio [OR], 3.152; P=0.025) and preoperative urinary catheterization (OR, 2.756; P=0.040) were associated with favorable treatment outcomes. Conversely, an unobstructed bladder outlet was identified as a negative prognostic factor. CONCLUSION: In men with DU accompanied by equivocal or significant BOO, surgical intervention to alleviate the obstruction may enhance the IPSS, quality of life, and UFM results. However, those with DU and an unobstructed bladder outlet face a comparatively high risk of treatment failure. Preoperative detrusor overactivity and urinary catheterization are associated with more favorable surgical outcomes. Consequently, active deobstructive surgery should be considered for patients with DU who are experiencing urinary retention.

Therapeutic efficacy of 180-W GreenLight laser photoselective vaporization of the prostate for storage symptoms concomitant with benign prostatic obstruction and a search for outcome predictors.

PURPOSE: Benign prostatic obstruction (BPO) is the most common cause of lower urinary tract symptoms among men. GreenLight photoselective vaporization of the prostate (GL-PVP) using a 180-W Xcelerated performance system (XPS) laser is a well-established method for treating BPO-induced voiding symptoms. However, its therapeutic effects on storage symptoms remain unclear. This study aimed to analyze the storage outcomes in patients who underwent 180-W XPS GL-PVP for BPO and to identify outcome predictors. MATERIALS AND METHODS: Patients who underwent 180-W XPS GL-PVP for BPO between May 2018 and May 2021 were retrospectively reviewed. Data on clinical characteristics, prostate volume, preoperative and postoperative International Prostate Symptom Scores (IPSS), and preoperative urodynamic parameters were collected. A favorable storage outcome was defined as ≥50% reduction in the IPSS storage subscore. RESULTS: Ninety-nine male patients were included, with a mean age of 69.4 ± 9.6 years and a baseline prostatic volume of 75.9 ± 33.1 mL. The IPSS total, storage, and voiding subscores significantly decreased after GL-PVP (all p < 0.001). Seventy-two patients achieved favorable storage outcome at 6 months. Multivariate analysis revealed that detrusor underactivity was predictive of unfavorable storage outcomes (p = 0.022), while IPSS voiding-to-storage subscore ratio >1.25 and the presence of detrusor overactivity were predictive of favorable storage outcomes (p = 0.008 and 0.033, respectively). CONCLUSION: 180-W XPS GL-PVP provided excellent outcomes in both voiding and storage lower urinary tract symptoms concomitant with BPO. Preoperative IPSS and multichannel urodynamic parameters including detrusor overactivity and underactivity are valuable predictors of postoperative storage outcomes.

Aberrant trophoblastic differentiation in human cancer: An emerging novel therapeutic target (Review).

Various types of human cancer may develop aberrant trophoblastic differentiation, including histological changes and altered expression of ß­human chorionic gonadotropin (ß­hCG). Aberrant trophoblastic differentiation in epithelial cancer is usually associated with poor differentiation, tumor metastasis, unfavorable prognosis and treatment resistance. Since ß­hCG­targeting vaccines have failed in an early phase II trial, it is crucial to obtain a better understanding of the molecular pathogenesis of trophoblastic differentiation in human cancer. The present review summarizes the clinical and translational research on this topic with the aim of accelerating the development of an effective targeted therapy. Ectopic expression of ß­hCG promotes proliferation, migration, invasion, vasculogenesis and epithelial­mesenchymal transition (EMT) in vitro, and enhances metastatic and tumorigenic capabilities in vivo. Signaling cascades modulated by ß­hCG include the TGF­ß receptor pathway, EMT­related pathways, the c­MET receptor tyrosine kinase and mitogen­activated protein kinase/ERK pathways, and the SMAD2/4 pathway. Taken together, these findings indicated that TGF­ß receptors, c­MET and ERK1/2 are potential therapeutic targets. Nevertheless, further investigation on the molecular basis of aberrant trophoblastic differentiation is mandatory to improve the design of precision therapy for this aggressive type of human cancer.

Clinicopathologic Analysis of Micropapillary Urothelial Carcinoma of the Upper Urinary Tract: Implications for HER2-Targeted Therapy.

Introduction/Background To determine the clinical significance of micropapillary urothelial carcinoma (MPUC) of the upper urinary tract (UTUC) and a potential therapeutic strategy. Patients and Methods A retrospective cohort study was conducted to examine the incidence of micropapillary UTUC from 2010 to 2018 and its clinicopathological characteristics. Clinical outcomes and cancer-specific survival (CSS) were compared between MPUC and conventional UTUC matched by stage within a 6-month variation of receiving surgery. Results A total of 24 MPUC cases were identified out of 901 cases (2.7%) of urothelial carcinoma (UC) of the renal pelvis and ureter. MPUC was significantly smaller (<3 cm) and associated with nodal metastasis compared with conventional UTUC (P = .017 & 0.021, respectively); however, no significant difference was observed for lymphovascular invasion, distant metastasis, or CSS (P > 0.50, respectively) compared with match controls. Six MPUC patients (25%) developed metastasis to the liver, lymph nodes, and lung during follow-up. Patients with HER2-positive MPUC (3 of 4) had a significantly higher risk of metastasis compared with HER2-negative MPUC (3 of 20; P = 0.035). Conclusions MPUC is an aggressive variant of UTUC and usually presents as a small locally advanced disease. HER2 immunohistochemistry may identify the subset of patients with micropapillary UTUC that are candidates for targeted therapy.

Stem Cell Therapy in Spinal Cord Injury-Induced Neurogenic Lower Urinary Tract Dysfunction.

Spinal cord injury (SCI) is a devastating condition that enormously affects an individual's health and quality of life. Neurogenic lower urinary tract dysfunction (NLUTD) is one of the most important sequelae induced by SCI, causing complications including urinary tract infection, renal function deterioration, urinary incontinence, and voiding dysfunction. Current therapeutic methods for SCI-induced NLUTD mainly target on the urinary bladder, but the outcomes are still far from satisfactory. Stem cell therapy has gained increasing attention for years for its ability to rescue the injured spinal cord directly. Stem cell differentiation and their paracrine effects, including exosomes, are the proposed mechanisms to enhance the recovery from SCI. Several animal studies have demonstrated improvement in bladder function using mesenchymal stem cells (MSCs) and neural stem cells (NSCs). Human clinical trials also provide promising results in urodynamic parameters after MSC therapy. However, there is still uncertainty about the ideal treatment window and application protocol for stem cell therapy. Besides, data on the therapeutic effects regarding NSCs and stem cell-derived exosomes in SCI-related NLUTD are scarce. Therefore, there is a pressing need for further well-designed human clinical trials to translate the stem cell therapy into a formal therapeutic option for SCI-induced NLUTD.

Intravesical Injection of Botulinum Toxin Type A in Patients with Refractory Overactive Bladder-Results between Young and Elderly Populations, and Factors Associated with Unfavorable Outcomes.

Intravesical botulinum toxin type A (BoNT-A) injection has been recognized as the standard treatment for refractory overactive bladder (OAB). However, its therapeutic efficacy and safety have not been thoroughly reviewed in elderly patients. This study aims to provide treatment outcomes for patients aged ≥75 years, and to identify factors associated with unfavorable outcomes. Patients receiving intradetrusor injections of 100 U onabotulinumtoxinA for refractory OAB between 2011 and 2021 were retrospectively reviewed. Urodynamic parameters, underlying comorbidities, subjective success, and unfavorable outcomes were assessed. A total of 192 patients were included, and 65 of them were classified into the elderly group. For the elderly group, 60.0% experienced subjective dryness, and 84.6% remained subjective success at 6 months after the injections. The prevalence rates of common unfavorable outcomes, including urinary tract infections, large post-void residual urine volume, and urinary retention, were 9.2%, 27.7%, and 12.3%, respectively. Multivariate analysis revealed that female, baseline urodynamic parameters, and diabetes mellitus were associated with unfavorable outcomes in the elderly group. Intravesical BoNT-A injections provide comparable therapeutic efficacy and safety concerns in elderly patients with refractory OAB. A thorough consultation for treatment benefits and possible adverse events is mandatory before the procedure.

The feasibility of a multimodal exercise program for sedentary postmenopausal women with urinary incontinence: A pilot randomized controlled trial.

OBJECTIVES: The aim was to investigate the feasibility and effects of an eight-week multimodal exercise program in sedentary postmenopausal women with urinary incontinence (UI) compared with pelvic floor muscle training (PFMT) only. STUDY DESIGN: This was a pilot randomized controlled trial. The participants were randomly allocated to either the intervention group (IG), who received a multimodal exercise program that incorporated aerobic exercise, resistance exercise, and PFMT, or the control group (CG), who received PFMT only. The intervention was provided twice weekly for eight weeks. MAIN OUTCOME MEASURES: The primary outcome was feasibility in relation to consent rate, attendance, withdrawal rate, satisfaction with program, and adverse events. The secondary outcomes included pelvic floor muscle function (assessed using digital palpation and manometry), UI-specific quality of life (QoL) (rated on the International Consultation on Incontinence Questionnaire Lower Urinary Tract Symptoms Quality of Life [ICIQ-LUTSqol]), symptom severity (assessed using the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form [ICIQ-UI SF] and a bladder diary), and physical activity levels (rated on the International Physical Activity Questionnaire- short form [IPAQ]). RESULTS: Thirty-three of 63 eligible participants (52.4 %) consented to participate in the study and 26 completed it (IG n = 13, CG n = 13); the withdrawal rate was lower in the IG than in the CG (13.3 % vs 27.8 %). In both groups the attendance rate was 100 % and the satisfaction rate was 84.6 %. No adverse events were reported. The intention-to-treat analysis showed that UI-specific QoL (p = 0.011, mean difference: -5.62, 95 % CI: -9.67 to -1.57) and symptom severity measured using the ICIQ-UI SF (p = 0.001, mean difference: -3.23, 95 % CI: -4.93 to -1.54) were significantly improved in the IG after intervention, while no significant changes were found in the CG after intervention. The daytime frequency (p = 0.001) and number of leakages (p = 0.045) recorded in the bladder diary were significantly reduced in the CG after intervention. No significant differences between groups were found on any of the outcome measurements after intervention, except the daytime frequency from the bladder diary, which was significantly more reduced in the CG than in the IG (p = 0.003, mean difference: -0.28, 95 % CI: -2.25 to 1.67). CONCLUSION: An eight-week multimodal exercise program is feasible for sedentary postmenopausal women with UI, and the multimodal exercise program demonstrated potential benefits for improving UI-specific QoL and symptom severity in this population. The trial was registered at ClinicalTrials.gov (NCT04351750).

Predictive Factors for a Successful Treatment Outcome in Patients with Different Voiding Dysfunction Subtypes Who Received Urethral Sphincter Botulinum Injection.

Voiding dysfunction is a common but bothersome problem in both men and women. Urethral sphincter botulinum toxin A (BoNT-A) injections could serve as an option in refractory cases. This study analyzed the efficacy and outcome predictors of the injections in patients with functional, non-neurogenic voiding dysfunction. Patients who received urethral sphincter BoNT-A injection for refractory voiding dysfunction due to detrusor underactivity (DU) or urethral sphincter dysfunction were retrospectively reviewed. A successful outcome was defined as a marked improvement as reported in the global response assessment. The study evaluated the therapeutic efficacy of urethral sphincter BoNT-A injections and measured the changes in urodynamic parameters after the procedure in the patients. A total of 181 patients including 138 women and 43 men were included. The overall success rate was 64%. A lower success rate was noted in patients with DU compared to those with urethral sphincter dysfunction in both genders. In the multivariable analysis, recurrent urinary tract infection (UTI) and bladder voiding efficiency (BVE) were positive predictors for a successful outcome, while DU was a negative predictor. Urethral sphincter BoNT-A injection is an effective treatment for refractory non-neurogenic voiding dysfunction. Baseline BVE and history of recurrent UTI positively predict a successful outcome. DU is a negative outcome predictor.

Bladder Management Strategies for Urological Complications in Patients with Chronic Spinal Cord Injury.

Neurogenic lower urinary tract dysfunction, common in patients with chronic spinal cord injury, inevitably results in urological complications. To address neurogenic lower urinary tract dysfunction after spinal cord injury, proper and adequate bladder management is important in spinal cord injury rehabilitation, with the goal and priorities of the protection of upper urinary tract function, maintaining continence, preserving lower urinary tract function, improvement of SCI patients' quality of life, achieving compatibility with patients' lifestyles, and decreasing urological complications. This concise review aims to help urologists address neurogenic lower urinary tract dysfunction by focusing on the risks of long-term urological complications and the effects of different bladder management strategies on these complications based on scientifically supported knowledge.

Bladder Dysfunction in Older Adults: The Botulinum Toxin Option.

Bladder dysfunction, which involves inadequacies of urine storage or emptying, increases with age. Conventional medications may have insufficient efficacy for patients with refractory lower urinary tract symptoms, and their concomitant adverse events (AEs) may be intolerable for the older adult population. For decades, the botulinum toxin type A (BoNT-A) injection has been an option for managing urine frequency, urge incontinence, and voiding dysfunction in the general population refractory to conventional management. This review focuses on studies of BoNT-A application in the management of bladder dysfunction in older adult patients aged ≥ 65 years. In this target population, intravesical BoNT-A injections provide similar efficacy in idiopathic overactive bladder to that in younger adults. Good clinical response has also been demonstrated in older adult patients presenting with storage dysfunction and with various concomitant underlying neurological diseases. However, caution must be taken for the AEs that occur after intravesical BoNT-A injection, including increased post-void residual urine, acute urine retention, and urinary tract infection. Most evidence shows that age is not a major determinant of AEs after adjusting for other factors. In contrast to its application in storage dysfunction, evidence for voiding dysfunction in older adults is scarce. In general, BoNT-A may be a reasonable option for older adult patients with refractory storage dysfunction because of its promising clinical response without significant systemic AEs. Overall, clinicians should be aware of the balance between the therapeutic efficacy of BoNT-A and local AEs in vulnerable members of this population.

The significance of SMARCB1 in the pathogenesis of renal cell carcinoma with rhabdoid features.

BACKGROUND: Renal cell carcinoma with rhabdoid features (RCC-RF) is an aggressive histologic variant in the adults and is usually unresponsive to standard chemotherapy. METHODS: Expression of SMARCB1/INI1 was examined in primary RCC-RF (n = 5). Stable INI1 with/without prostaglandin E2 receptor 1 (EP1) knockdown cell lines were created in the ACHN and 786-O RCC cell lines and measured for epidermal growth factor receptor (EGFR)-related signaling pathways. Chemosensitivity to targeted drugs in vitro was tested after knocking down of INI1 in both cell lines. The outcome of co-targeting of INI1 and EP1 in RCC was examined using a tumorigenicity assay. RESULTS: Expression of INI1 was markedly reduced at both transcriptional and translational levels in primary RCC-RF. Immunohistochemical expression of INI1 protein was lost in the nuclei of rhabdoid cells compared with conventional RCC (n = 8). Using two cell lines with different genetic background, we showed that knocking down of INI1 activates the EGFR signaling with up-regulated AKT and ERK pathways and sensitizes cancer cells to Erlotinib treatment in vitro. However, cell-line dependent effects were also demonstrated with reference to impact of INI1 or EP1 on cell growth, migration and response to Gefitinib or Everolimus treatment in vitro. CONCLUSION: Inactivation of INI1 may play a role in the pathogenesis of RCC-RF. Erlotinib is recommended in the management of patients with INI1-related RCC.

Tumor Necrosis with Adjunction of Preoperative Monocyte-to-Lymphocyte Ratio as a New Risk Stratification Marker Can Independently Predict Poor Outcomes in Upper Tract Urothelial Carcinoma.

OBJECTIVES: This study aimed at investigating the prognostic impact of tumor necrosis and preoperative monocyte-to-lymphocyte ratio (MLR) in patients treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). METHODS: A total of 521 patients with UTUC treated with RNU from January 2008 to June 2019 at our institution were enrolled. Histological tumor necrosis was defined as the presence of microscopic coagulative necrosis. The optimal value of MLR was determined as 0.4 by receiver operating characteristic (ROC) analysis based on cancer-specific mortality. The Kaplan-Meier method with log-rank test and Cox proportional hazards regression models were performed to evaluate the impact of tumor necrosis and MLR on overall (OS), cancer-specific (CSS), and recurrence-free survival (RFS). Furthermore, ROC analysis was used to estimate the predictive ability of potential prognostic factors for oncological outcomes. RESULTS: Tumor necrosis was present in 106 patients (20%), which was significantly associated with tumor location, high pathological tumor stage, lymph node metastasis, high tumor grade, lymphovascular invasion, tumor size, and increased monocyte counts. On multivariate analysis, the combination of tumor necrosis and preoperative MLR was an independent prognosticator of OS, CSS, and RFS (all p < 0.05). Moreover, ROC analyses revealed the predictive accuracy of a combination of tumor necrosis and preoperative MLR for OS, CSS, and RFS with the area under the ROC curve of 0.745, 0.810, and 0.782, respectively (all p < 0.001). CONCLUSIONS: The combination of tumor necrosis and preoperative MLR can be used as an independent prognosticator in patients with UTUC after RNU. The identification of this combination could help physicians to recognize high-risk patients with unfavorable outcomes and devise more appropriate postoperative treatment plans.

Therapeutic Efficacy of Urethral Sphincteric Botulinum Toxin Injections for Female Sphincter Dysfunctions and a Search for Predictive Factors.

External urethral sphincter (EUS) dysfunction is a common, bothersome female voiding dysfunction. This study aims to analyze the characteristics of different types of female EUS dysfunction, as well as to determine the outcome predictors of sphincteric botulinum toxin A (BoNT-A) injection. Women receiving sphincteric BoNT-A injections for refractory EUS dysfunction were retrospectively reviewed. A comparison of the baseline clinical, urodynamic parameters and the treatment responses were made for patients with different EUS dysfunctions. A total of 106 females were included. Significantly increased detrusor overactivity, detrusor contracting pressure and the bladder outlet obstruction index with decreased urge sensation were noted in patients diagnosed with dysfunctional voiding or detrusor sphincter dyssynergia comparing to those diagnosed with poor relaxation of the external urethral sphincter. The average subjective improvement rate was 67% for the injection. The therapeutic effect was not affected by the type of EUS dysfunction. The multivariate analysis revealed that bladder neck narrowing and catheterization history were predictive of negative outcomes. There is a distinct urodynamic presentation for each type of female EUS dysfunction. Sphincteric BoNT-A injection provides a good therapeutic outcome for refractory EUS dysfunction. A narrowing bladder neck and a history of catheterization suggest poor therapeutic outcomes.

The Therapeutic Effects and Pathophysiology of Botulinum Toxin A on Voiding Dysfunction Due to Urethral Sphincter Dysfunction.

Neurogenic and non-neurogenic urethral sphincter dysfunction are common causes of voiding dysfunction. Injections of botulinum toxin A (BoNT-A) into the urethral sphincter have been used to treat urethral sphincter dysfunction (USD) refractory to conventional treatment. Since its first use for patients with detrusor sphincter dyssynergia in 1988, BoNT-A has been applied to various causes of USD, including dysfunctional voiding, Fowler's syndrome, and poor relaxation of the external urethral sphincter. BoNT-A is believed to decrease urethral resistance via paralysis of the striated sphincter muscle through inhibition of acetylcholine release in the neuromuscular junction. Recovery of detrusor function in patients with detrusor underactivity combined with a hyperactive sphincter also suggested the potential neuromodulation effect of sphincteric BoNT-A injection. A large proportion of patients with different causes of USD report significant improvement in voiding after sphincteric BoNT-A injections. However, patient satisfaction might not increase with an improvement in the symptoms because of concomitant side effects including exacerbated incontinence, urinary urgency, and over-expectation. Nonetheless, in terms of efficacy and safety, BoNT-A is still a reasonable option for refractory voiding function. To date, studies focusing on urethral sphincter BoNT-A injections have been limited to the heterogeneous etiologies of USD. Further well-designed studies are thus needed.

Long-term outcomes of total ureterectomy with ileal-ureteral substitution treatment for ureteral cancer: a single-center experience.

BACKGROUND: To explore the feasibility and long-term outcomes of renal preservation in a retrospective cohort of patients with ureteral urothelial carcinoma undergoing total ureterectomy with ileal-ureteral substitution. METHODS: A retrospective review of the data from patients treated with total ureterectomy with ileal-ureteral substitution from 1988 to 2016 was performed. The pre-operative oncological status, long-term oncological outcome, long-term renal functional outcome, early and late complications were analyzed. RESULTS: A total of eight patients with a median age of 70 years were included. The median follow-up time was 109 months. Six patients had multi-focal tumor involvement over the target ureter, and six patients had bilateral upper tract involvement. Only one patient encountered the upper-tract recurrence. The 2 and 5-year cancer-specific survival rates were 87.5 and 75.0%, respectively. The renal function was well-preserved in most patients, with only one patient needed life-long postoperative hemodialysis. Five patients experienced early complications and four patients experienced late complications. No perioperative mortality happened. CONCLUSIONS: A total ureterectomy with an ileal-ureteral substitution is feasible for treating ureteral urothelial carcinoma when a renal-sparing procedure is indicated. It provides good long-term oncological outcomes over the upper tract, and it also preserves the renal function.