Modified Botulinum Toxin Type A Injections Improve Symptoms Associated With Interstitial Cystitis/Bladder Pain Syndrome in Women: A Retrospective Cohort Study.

OBJECTIVE: To investigate the efficacy and safety of modified botulinum toxin type A (BoNT-A) injections (with additional periurethral injection [PUI] of BoNT-A) for the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS). METHODS: This single-center, retrospective cohort study included 52 adult female patients with IC/BPS, with 24 patients receiving conventional BoNT-A injections and 28 receiving modified BoNT-A injections. The primary outcome measure was patient-reported global response assessment. Secondary outcomes included daytime frequency, nocturia, number of urinary urgency episodes in the voiding diary, pain visual analog score, O'Leary-Sant interstitial cystitis symptom index and interstitial cystitis problem index, pelvic pain and urgency/frequency scores, risk factors for recurrence, and postoperative recurrence-free time. RESULTS: The median duration of follow-up was 16.0 months (interquartile range 11.75-21 months). Patients who underwent modified BoNT-A injections showed significant improvement in postoperative global response assessment, symptom questionnaires, and pain assessment compared with those who underwent conventional surgery. A statistically significant difference was observed between the 2 groups in terms of recurrence-free time (12.5 vs 18.0 months, P = .02). Subgroup analysis suggested that additional PUI of BoNT-A was more effective in patients with combined severe periurethral pain. No serious complications occurred in both groups, and all minor postoperative complications were temporary. CONCLUSION: Modified BoNT-A injection is an effective treatment for IC/BPS that significantly reduces pain and improves voiding symptoms. It is particularly effective in patients with combined periurethral pain. In such patients, PUI of BoNT-A should be added to the routine intravesical injection of BoNT-A.

Effect of lower urinary tract conditions on surgical outcomes of different suburethral sling procedures for female stress urinary incontinence.

PURPOSE: The suburethral sling procedure has been widely used as the first-line treatment for female stress urinary incontinence (SUI). This study retrospectively compared the long-term surgical outcomes and complications between retropubic and transobturator suburethral sling procedures. METHODS: From 2010 to 2022, a total of 533 women with SUI underwent retropubic pubovaginal sling (PVS) or transobturator tape (TOT) procedures using a synthetic polypropylene mesh with or without concomitant anterior colporrhaphy. All patients underwent preoperative videourodynamic studies, Valsalva leak point pressure (VLPP), and voiding efficiency (VE). The success rate, postoperative complications, overactive bladder symptoms, transvaginal urethrolysis, and repeat procedures were compared among different surgical procedures. RESULTS: Among the patients, PVS was performed in 251 (47.1%) patients and with colporrhaphy in 58 (10.9%), TOT in 174 (32.6%) and with colporrhaphy in 50 (9.4%). The success rate was 87.4% in the PVS group and 75.4% in the TOT group, with or without colporrhaphy (p = 0.001). Urethrolysis was performed in 4.7% of the patients, and repeat suburethral sling procedures were performed in 8.3%. The overall success rate was significantly lower in TOT group, either with high or low VLPP, or with high or low VE. The rate of persistent OAB was significantly higher in TOT group regardless of VLPP or VE, whereas patients with VE < 90% at baseline had a significantly higher rate of postoperative dysuria. CONCLUSION: TOT procedures had an inferior long-term success rate than PVS procedures for female SUI. Additionally, no differences in the success rate were observed between patients with different bladder functions, high or low VLPP, and high or low VE.

Urine biomarker could be a useful tool for differential diagnosis of a lower urinary tract dysfunction.

A precision diagnosis of lower urinary tract dysfunctions (LUTD) such as bladder outlet obstruction, detrusor overactivity (DO), interstitial cystitis/bladder pain syndrome (IC/BPS), dysfunctional voiding (DV), or detrusor underactivity (DU) needs invasive videourodynamic study. Exploring non-invasive tools to help screening LUTD is necessary for clinicians in their daily practice. This article reviews recently clinical studies of using urinary inflammatory proteins and oxidative stress biomarkers in the identification of specific LUTD among men and women with lower urinary tract symptoms (LUTS). Some important findings have been reported: (1) Using urine chemokines CXCL-1 and interleukin-8 (IL-8), we may discriminate overactive bladder (OAB) symptoms in women between DO and urinary tract infection. (2) Urinary levels of oxidative stress biomarkers such as 8-hydroxydeoxyguanosine (8-OHdG) and 8-isoprostane have a potential being used as a tool to identify women with mixed DO and stress urinary incontinence. (3) Urine levels of total antioxidant capacity (TAC), and prostaglandin E2 (PGE2) are positively correlated with voiding detrusor pressure in patients with DU. (4) Urine levels of brain-derived neurotrophic factor (BDNF) and PGE2 were significantly higher in the DU patients with detrusor function recovery. (5) Women with DV had higher urinary levels of tumor necrosis factor-alpha (TNF-α) and 8-OHdG, and urinary IL-2 level was significantly lower. (6) Urine level of 8-isoprostane was higher in the patients with idiopathic DO and neurogenic DO. (7) Higher urine cytokine levels of monocyte chemoattractant protein-1 (MCP-1), regulated on activation, normal T-cell expressed and secreted (RANTES), CXCL-10, IL-7, and eotaxin-1 in patients with IC/BPS than controls. (8) The urine levels of IL-8, CXCL-10, BDNF, IL-6, and RANTES were significantly higher in patients with Hunner's IC than non-Hunner's IC. (9) Male patients with IC/BPS had a significantly higher level of eotaxin, MCP-1, TNF-α, 8-OHdG, and TAC. Combining a higher eotaxin and a higher TNF-α can provide a satisfactory diagnostic value in discriminating IC/BPS from other LUTD in men. These studies provide evidence that measurement of cluster of urine biomarkers could be used as a diagnostic tool to differentiate different LUTD in patients with similar LUTS.

Implementation of antibody-drug conjugates in HER2-positive solid cancers: Recent advances and future directions.

In recent decades, there has been a surge in the approval of monoclonal antibodies for treating a wide range of hematological and solid malignancies. These antibodies exhibit exceptional precision in targeting the surface antigens of tumors, heralding a groundbreaking approach to cancer therapy. Nevertheless, monoclonal antibodies alone do not show sufficient lethality against cancerous cells compared to chemotherapy. Consequently, a new class of anti-tumor medications, known as antibody-drug conjugates (ADCs), has been developed to bridge the divide between monoclonal antibodies and cytotoxic drugs, enhancing their therapeutic potential. ADCs are chemically synthesized by binding tumor-targeting monoclonal antibodies with cytotoxic payloads through linkers that are susceptible to cleavage by intracellular proteases. They combined the accurate targeting of monoclonal antibodies with the potent efficacy of cytotoxic chemotherapy drugs while circumventing systemic toxicity and boasting superior lethality over standalone targeted drugs. The human epidermal growth factor receptor (HER) family, which encompasses HER1 (also known as EGFR), HER2, HER3, and HER4, plays a key role in regulating cellular proliferation, survival, differentiation, and migration. HER2 overexpression in various tumors is one of the most frequently targeted antigens for ADC therapy in HER2-positive cancers. HER2-directed ADCs have emerged as highly promising treatment modalities for patients with HER2-positive cancers. This review focuses on three approved anti-HER2 ADCs (T-DM1, DS-8201a, and RC48) and reviews ongoing clinical trials and failed trials based on anti-HER2 ADCs. Finally, we address the notable challenges linked to ADC development and underscore potential future avenues for tackling these hurdles.

Hypermethylation Loci of ZNF671, IRF8, and OTX1 as Potential Urine-Based Predictive Biomarkers for Bladder Cancer.

Bladder cancer (BCa) is a significant health issue and poses a healthcare burden on patients, highlighting the importance of an effective detection method. Here, we developed a urine DNA methylation diagnostic panel for distinguishing between BCa and non-BCa. In the discovery stage, an analysis of the TCGA database was conducted to identify BCa-specific DNA hypermethylation markers. In the validation phase, DNA methylation levels of urine samples were measured with real-time quantitative methylation-specific PCR (qMSP). Comparative analysis of the methylation levels between BCa and non-BCa, along with the receiver operating characteristic (ROC) analyses with machine learning algorithms (logistic regression and decision tree methods) were conducted to develop practical diagnostic panels. The performance evaluation of the panel shows that the individual biomarkers of ZNF671, OTX1, and IRF8 achieved AUCs of 0.86, 0.82, and 0.81, respectively, while the combined yielded an AUC of 0.91. The diagnostic panel using the decision tree algorithm attained an accuracy, sensitivity, and specificity of 82.6%, 75.0%, and 90.9%, respectively. Our results show that the urine-based DNA methylation diagnostic panel provides a sensitive and specific method for detecting and stratifying BCa, showing promise as a standard test that could enhance the diagnosis and prognosis of BCa in clinical settings.

Automatic recognition of white blood cell images with memory efficient superpixel metric GNN: SMGNN.

An automatic recognizing system of white blood cells can assist hematologists in the diagnosis of many diseases, where accuracy and efficiency are paramount for computer-based systems. In this paper, we presented a new image processing system to recognize the five types of white blood cells in peripheral blood with marked improvement in efficiency when juxtaposed against mainstream methods. The prevailing deep learning segmentation solutions often utilize millions of parameters to extract high-level image features and neglect the incorporation of prior domain knowledge, which consequently consumes substantial computational resources and increases the risk of overfitting, especially when limited medical image samples are available for training. To address these challenges, we proposed a novel memory-efficient strategy that exploits graph structures derived from the images. Specifically, we introduced a lightweight superpixel-based graph neural network (GNN) and broke new ground by introducing superpixel metric learning to segment nucleus and cytoplasm. Remarkably, our proposed segmentation model superpixel metric graph neural network (SMGNN) achieved state of the art segmentation performance while utilizing at most 10000$ \times $ less than the parameters compared to existing approaches. The subsequent segmentation-based cell type classification processes showed satisfactory results that such automatic recognizing algorithms are accurate and efficient to execeute in hematological laboratories. Our code is publicly available at https://github.com/jyh6681/SPXL-GNN.

Real-Life Treatment Outcome of Botulinum Toxin A Injection on Overactive Bladder and Voiding Dysfunction in Patients with Central Nervous System Lesions.

PURPOSE: Neurogenic lower urinary tract dysfunction (NLUTD) is common in patients with neurological lesions in the central nervous system (CNS). Medical treatment usually cannot adequately relieve NLUTD. This study reported the real-life treatment outcome of botulinum toxin A (BoNT-A) for overactive bladders (OAB) and voiding dysfunction in patients with CNS lesions. METHODS: We retrospectively analyzed the first-time treatment outcome of 74 patients who received detrusor 100 U BoNT-A for OAB and 45 patients who received a urethral sphincter 100 U BoNT-A injection for voiding dysfunction. The treatment outcome, therapeutic duration, and adverse events (AE) after BoNT-A were compared among different CNS lesions and among patients with different urodynamic characteristics. RESULTS: The study included 74 patients receiving detrusor injections for OAB (36 with cerebrovascular accidents, 13 with Parkinson's disease, and 25 with dementia) and 45 patients receiving a urethral sphincter injection for voiding dysfunction (26 with cerebrovascular accidents, 7 with Parkinson's disease, and 12 with dementia). After detrusor BoNT-A treatment, urinary continence was achieved in 28.4% of patients with neurogenic OAB, postoperative difficult urination in 59.5%, acute urinary retention (AUR) in 9.5%, and urinary tract infection (UTI) in 14.9%, with a therapeutic duration of 6.43 months. There were no differences among subgroups or between patients with detrusor overactivity (DO) and DO with detrusor underactivity (DU) in terms of treatment outcomes and AEs. The improvement rate of urethral sphincter BoNT-A injections was 75.6% without any difference among subgroups. After treatment, 24.4% of the patients had exacerbated urinary incontinence, 33.3% had persistent difficult urination, and 15.6% had UTI. Patients with dementia had higher rates of difficult urination and UTI, higher postvoid residual volume, and a shorter therapeutic duration. Patients with DU and those without urethral sphincter dyssynergia had less favorable outcomes after their urethral sphincter BoNT-A injection. CONCLUSIONS: The therapeutic efficacy of detrusor BoNT-A injection for OAB due to CNS lesions is limited, with high rates of difficult urination, AUR, and UTI. Although urethral sphincter BoNT-A injection is effective in treating voiding dysfunction; however, exacerbated urinary incontinence and persistent difficult urination remain a problem, particularly in patients with dementia.

Urinary Viral Spectrum in Patients with Interstitial Cystitis/Bladder Pain Syndrome and the Clinical Efficacy of Valacyclovir Treatment.

Our previous study showed that the Epstein-Barr virus (EBV) may be the etiology for some patients with interstitial cystitis/bladder pain syndrome (IC/BPS); hence, the current study aimed to investigate the urinary viral spectrum in patients with IC/BPS and the clinical efficacy of valacyclovir. Twenty-eight patients were prospectively enrolled for valacyclovir 500 mg twice a day for 4 weeks. Urine samples were collected from IC/BPS patients and 30 controls. The primary outcome was the difference in the visual analog scale (VAS) pain score, and secondary outcomes included changes in the urinary viral spectrum and urinary inflammatory cytokine level (ClinicalTrials.gov Identifier: NCT05094414). Urinary EBV was detected in 14.2% IC/BPS patients but not in the controls. Urinary John Cunningham virus and BK virus were detected in 18 (64.3%) and 2 (7.1%) patients with IC/BPS, respectively, with similar prevalences noted for the controls. No cytomegalovirus, varicella-zoster virus, or herpes simplex virus was detected in the urine samples. The VAS pain score in patients with IC/BPS significantly decreased after 4 weeks (from 7.5 [5.52-9.0] to 5 [1.5-6.0], p = 0.0003). Urinary EBV was undetectable in any sample after valacyclovir treatment, and the decreases in urinary interleukin (IL)-1ß (from 0.66 [0.55-0.82] pg/mL to 0.58 [0.55-0.64] pg/mL, p = 0.0034), IL-8 (from 6.81 [2.38 to 29.1] pg/mL to 4.33 [1.53-11.04] pg/mL, p = 0.0361), IL-10 (from 1.06 [0.94-1.18] pg/mL to 0.92 [0.88-1.02], p = 0.0086), and tumor necrosis factor-α (from 1.61 [1.50-1.72] pg/mL to 1.50 [1.44-1.55] pg/mL, p = 0.0079) were significant. Valacyclovir could relieve bladder pain, eliminate urinary EBV, and reduce bladder inflammation.

Cystoscopic characteristic findings of interstitial cystitis and clinical implications.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic inflammatory bladder disease of unknown etiology, characterized by bladder pain and frequency urgency symptoms. Based on the cystoscopic findings after hydrodistention under anesthesia, the phenotype of IC/BPS includes no glamerulation, characteristic glomerulation, and with Hunner's lesion. IC is specifically defined if there are characteristic Hunner's lesion appeared in cystoscopy or after hydrodistention. If there are glomerulations without Hunner's lesion, BPS should be considered. The definition of Hunner's lesion and glomerulations differs based on different definition and observations. Currently, there has been no clear description and grading of the glomerulations and Hunner's lesion. Because the classification of IC/BPS has an impact on the treatment strategy and associated with therapeutic outcome, it is unmet to have a clear definition and consensus on the characteristic cystoscopic findings of IC/BPS. This article reviews the literature and presents the figures of Hunner's lesions and description of different mucosal lesions after cystoscopic hydrodistention.

Safety and efficacy of an α1 -blocker plus mirabegron compared with an α1 -blocker plus antimuscarinic in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia and overactive bladder: A systematic review and network meta-analysis.

AIM: Antimuscarinics and the ß3-adrenoreceptor agonist, mirabegron, are commonly used for treating patients with overactive bladder (OAB) and α1 -adrenoreceptor antagonists (α1 -blockers) are the main pharmacological agents used for treating lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). As these conditions commonly occur together, the aim of this systematic review was to identify publications that compared the use of an α1 -blocker plus mirabegron with an α1 -blocker plus antimuscarinic in men with LUTS secondary to BPH and OAB. A meta-analysis was subsequently conducted to explore the safety and efficacy of these combinations. METHODS: Included records had to be from a parallel-group, randomized clinical trial that was ≥8 weeks in duration. Participants were male with LUTS secondary to BPH and OAB. The indirect analyses that were identified compared an α1 -blocker plus OAB agent with an α1 -blocker plus placebo. The PubMed/Medical Literature Analysis and Retrieval System Online, the Excerpta Medica Database, the Cochrane Central Register of Controlled Trials, and the ClinicalTrials.gov registry were searched for relevant records up until March 5, 2020. Safety outcomes included incidences of overall treatment-emergent adverse events (TEAEs) and urinary retention, postvoid residual volume, and maximum urinary flow (Qmax ). Primary efficacy outcomes were micturitions/day, incontinence episodes/day, and urgency episodes/day, and secondary outcomes were Overactive Bladder Symptom Score and International Prostate Symptom Score. A Bayesian network meta-analysis approach was used for the meta-analysis. RESULTS: Out of a total of 1039 records identified, 24 were eligible for inclusion in the meta-analysis. There were no statistically significant differences between the α1 -blocker plus mirabegron and α1 -blocker plus antimuscarinic groups in terms of the comparisons identified for all the safety and efficacy analyses conducted. Numerically superior results were frequently observed for the α1 -blocker plus mirabegron group compared with the α1 -blocker plus antimuscarinic group for the safety parameters, including TEAEs, urinary retention, and Qmax . For some of the efficacy parameters, most notably micturitions/day, numerically superior results were noted for the α1 -blocker plus antimuscarinic group. Inconsistency in reporting and study variability were noted in the included records, which hindered data interpretation. CONCLUSION: This systematic review and meta-analysis showed that an α1 -blocker plus mirabegron and an α1 -blocker plus antimuscarinic have similar safety and efficacy profiles in male patients with LUTS secondary to BPH and OAB. Patients may, therefore, benefit from the use of either combination within the clinical setting.

Prognostic factors of intravesical recurrence after radical nephroureterectomy for upper tract urothelial carcinoma.

PURPOSE: To evaluate predictive factors of increasing intravesical recurrence (IVR) rate in patients with upper tract urothelial carcinoma (UTUC) after receiving radical nephroureterectomy (RNUx) with bladder cuff excision (BCE). MATERIALS AND METHODS: A total of 2114 patients were included from the updated data of the Taiwan UTUC Collaboration Group. It was divided into two groups: IVR-free and IVR after RNUx, with 1527 and 587 patients, respectively. To determine the factors affecting IVR, TNM stage, the usage of pre-operative ureteroscopy, and pathological outcomes were evaluated. The Kaplan-Meier estimator was used to estimate the rates of prognostic outcomes in overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), and bladder recurrence-free survival (BRFS), and the survival curves were compared using the stratified log-rank test. RESULTS: Based on our research, ureter tumor, female, smoking history, age (< 70 years old), multifocal tumor, history of bladder cancer were determined to increase the risk of IVR after univariate analysis. The multivariable analysis revealed that female (BRFS for male: HR 0.566, 95% CI 0.469-0.681, p < 0.001), ureter tumor (BRFS: HR 1.359, 95% CI 1.133-1.631, p = 0.001), multifocal (BRFS: HR 1.200, 95% CI 1.001-1.439, p = 0.049), history of bladder cancer (BRFS: HR 1.480, 95% CI 1.118-1.959, p = 0.006) were the prognostic factors for IVR. Patients who ever received ureterorenoscopy (URS) did not increase the risk of IVR. CONCLUSION: Patients with ureter tumor and previous bladder UC history are important factors to increase the risk of IVR after RNUx. Pre-operative URS manipulation is not associated with higher risk of IVR and diagnostic URS is feasible especially for insufficient information of image study. More frequent surveillance regimen may be needed for these patients.

Efficacy of single and repeated transurethral bladder neck incisions for female voiding dysfunction.

OBJECTIVE: This study aimed to assess the efficacy of single and repeat transurethral bladder neck incision (TUI-BN) for female voiding dysfunction caused by bladder outlet obstruction (BNO). Further, the predictive factors associated with better treatment outcomes were identified. METHODS: Women with voiding difficulty due to BNO who underwent TUI-BN were included in this research. All patients underwent videourodynamics study at baseline and after TUI-BN. Successful outcome was defined as a voiding efficiency of ≥ 66.7% and a global response assessment score of ≥ 2 after treatment. Repeat TUI-BN was considered for patients with insufficient improvement. The outcomes of repeat surgery, surgical complications, and predictive factors of successful outcomes were evaluated. RESULTS: In total 158 cases, the success rates were 61.4% and 45.2% after the first and second TUI-BN, respectively, with an overall cumulative rate of 70.3%. The success rates were comparable between patients with detrusor underactivity (DU) and those without (54.9% vs. 68.4%). The absence of a previous history of suburethral sling and a high baseline corrected maximum flow rate were a significant predictor of favorable outcomes. The cumulative rate of regaining self-voiding function was 95.1%. The incidence rates of vesico-vaginal fistula and de novo stress urinary incontinence requiring surgery were 1.2% and 2.5%, respectively. CONCLUSIONS: Regardless of the presence of DU, TUI-BN is effective against female voiding dysfunction caused by BNO. Repeat procedures are beneficial and can improve self-voiding function. A high corrected maximum flow rate and the absence of a previous history of suburethral sling can contribute to greater success rates.

Current optimal pharmacologic therapies for overactive bladder.

INTRODUCTION: Overactive bladder (OAB) is a common syndrome in adults. Current pharmacologic treatment includes antimuscarinic agents and ß-3 adrenoceptor agonists. For non-responders to oral medication, intravesical injection of botulinum toxin A (BoNT-A) is an effective option. However, these treatments have potential adverse events and should be cautiously selected for appropriate patients. This review presents the recently published results of clinical trials and studies for patients with OAB and the underlying pathophysiology of OAB. Appropriate medical therapy based on pathophysiology of OAB is also presented. AREAS COVERED: Literature search from Pubmed from 2001 to 2023 including clinical background, pharmacology, and clinical studies for OAB medications. EXPERT OPINION: Treatment of OAB syndrome with any antimuscarinic or ß-3 adrenoceptor agonist is feasible as a first-line approach. For patients with suboptimal therapeutic effect to full-dose antimuscarinics or mirabegron, combination with both drugs can improve efficacy. Intravesical BoNT-A 100-U injection provides therapeutic effects for refractory OAB. Patients who are refractory to initial pharmacotherapies should be investigated for the underlying pathophysiology; then an appropriate medication can be added, such as an α1-blocker or anti-inflammatory agents. Patient education about behavioral modification and therapies should always be provided with oral medication or BoNT-A injection for OAB patients.

Overactive bladder (OAB) causes urgency, frequency, and nocturia, and greatly impacts quality of life. Pharmacological treatment with antimuscarinics, beta-3 adrenoceptor agonists, or in combination can effective improve OAB symptoms. In cases of treatment failure, searching for underlying causes and switching to the other treatment modalities such as Botox injection are also feasible to relieve the bothersome bladder symptoms.

Novel agents and clinical trials in castration-resistant prostate cancer: latest updates from 2023 ASCO-GU Cancers Symposium.

Numerous novel and effective therapeutic agents and clinical trials addressing castration-resistant prostate cancer (CRPC) were reported during the 2023 American Society of Clinical Oncology-Genitourinary (ASCO-GU) Cancers Symposium. Notably, radionuclide drug conjugates (RDC), specifically 177Lu/111In-J591 and 225Ac-J591, exhibited enhanced therapeutic efficacy in treating patients with CRPC. Furthermore, promising treatment approaches for CRPC included dual anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and anti-programmed death-1 (PD-1) blockade in rare tumors (DART)-Lorigerlimab, prostate stem cell antigen (PSCA)-directed chimeric antigen receptor (CAR)-T cell immunotherapy-BPX-601, and protein kinase inhibitor (AKTi)-CAPltello-280. We have summarized the latest CRPC treatment strategies presented at the 2023 ASCO-GU Cancers Symposium, along with recent advances in CRPC clinical trials.

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.

Use of Urinary Biomarkers in Discriminating Interstitial Cystitis/Bladder Pain Syndrome from Male Lower Urinary Tract Dysfunctions.

To analyze the urinary biomarkers in men with lower urinary-tract symptoms (LUTS) and identify interstitial cystitis/bladder pain syndrome (IC/BPS) from the other lower urinary-tract dysfunctions (LUTDs) by the levels of characteristic urinary biomarkers. In total, 198 men with LUTS were prospectively enrolled and urine samples were collected before intervention or medical treatment. Videourodynamic studies were routinely performed and the LUTDs were diagnosed as having bladder-outlet obstruction (BOO) such as bladder-neck dysfunction, benign prostatic obstruction, or poor relaxation of external sphincter (PRES); and bladder dysfunction such as detrusor overactivity (DO), hypersensitive bladder (HSB), and IC/BPS. Patients suspicious of IC/BPS were further confirmed by cystoscopic hydrodistention under anesthesia. The urine samples were investigated for 11 urinary inflammatory biomarkers including eotaxin, IL-6, IL-8, CXCL10, MCP-1, MIP-1ß, RANTES, TNF-α, NGF, BDNF, and PGE2; and 3 oxidative stress biomarkers 8-OHdG, 8-isoprostane, and TAC. The urinary biomarker levels were analyzed between LUTD subgroups and IC/BPS patients. The results of this study revealed that among the patients, IC/BPS was diagnosed in 48, BOO in 66, DO in 25, HSB in 27, PRES in 15, and normal in 17. Patients with BOO had a higher detrusor pressure and BOO index than IC/BPS, whereas patients with IC/BPS, BOO, and DO had a smaller cystometric bladder capacity than the PRES and normal subgroups. Among the urinary biomarkers, patients with IC/BPS had significantly higher levels of eotaxin, MCP-1, TNF-α, 8-OHdG, and TAC than all other LUTD subgroups. By a combination of different characteristic urinary biomarkers, TNF-α, and eotaxin, either alone or in combination, had the highest sensitivity, specificity, positive predictive value, and negative predictive value to discriminate IC/BPS from patients of all other LUTD subgroups, BOO, DO, or HSB subgroups. Inflammatory biomarker MCP-1 and oxidative stress biomarkers 8-OHdG and TAC, although significantly higher in IC/BPS than normal and PRES subgroups, did not have a diagnostic value between male patients with IC/BPS and the BOO, DO, or HSB subgroups. The study concluded that using urinary TNF-α and eotaxin levels, either alone or in combination, can be used as biomarkers to discriminate patients with IC/BPS from the other LUTD subgroups in men with LUTS.

Novel ADCs and combination therapy in urothelial carcinoma: latest updates from the 2023 ASCO-GU Cancers Symposium.

Antibody-drug conjugates (ADCs) combine the cytotoxicity of small-molecule drugs with antibody targeting. Due to their precise and powerful effect, they have become a new hotspot and an important trend in the research and development of anti-tumor antibody drugs. Every year, exciting new developments and innovations in the treatment of urological tumors are introduced at the American Society of Clinical Oncology-Genitourinary (ASCO-GU) Cancers Symposium. In this article, we summarize some of the most impressive advances in new clinical trials and clinical data on ADCs in the 2023 ASCO-GU Cancers Symposium for the treatment of urothelial carcinoma.

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.

Changes of lower urinary tract function after robot-assisted radical prostatectomy: An urodynamic follow-up within 1 year.

Objectives: This study investigated the changes of lower urinary tract function after robot-assisted radical prostatectomy (RaRP) with 1-year urodynamic follow-up. Materials and Methods: Clinically localized prostate cancer patients receiving RaRP were prospectively enrolled. We analyzed their clinical symptoms, stress urinary incontinence (SUI) and urge urinary incontinence (UUI) status, and videourodynamic studies (VUDSs) during the postoperative 1st year. Results: In total, 74 patients were enrolled with a mean age of 69.4 ± 8.1 years, a mean total prostate volume of 34.7 ± 15.9 mL, a ≥pT3 stage proportion of 37.8%, and a positive surgical margin rate of 18.9%. The International Prostate Symptom Score significantly reduced from 7.3 ± 6.0 before surgery to 4.1 ± 4.1 at postoperative 1 year. Significantly increased full sensation, reduced detrusor voiding pressure, increased maximal urinary flow rate, and decreased bladder outlet obstruction index were noted at 1-year VUDS follow-up. The changes of VUDS parameters were significantly different between the patients with and without preoperative bladder outlet obstruction. At postoperative 1 year, 8.1% and 6.8% of patients experienced SUI and UUI, respectively. In multivariate analysis, the factors of T stage ≥3, preoperative detrusor overactivity (DO), and positive surgical margin were the independent predictors of immediate SUI and SUI at 3 and 12 months, respectively. Conclusion: During the 1st year after RaRP, patients experienced significant changes of lower urinary tract function demonstrated in VUDS with the improvement in clinical symptoms. Factors of T stage ≥3, preoperative DO, and positive surgical margin were the predictors of postoperative SUI.

Liquid biopsy in urothelial carcinoma: Detection techniques and clinical applications.

The types of urothelial carcinoma (UC) include urothelial bladder cancer and upper tract urothelial carcinoma. Current diagnostic techniques cannot meet the needs of patients. Liquid biopsy is an accurate method of determining the molecular profile of UC and is a cutting-edge and popular technique that is expected to complement existing detection techniques and benefit patients with UC. Circulating tumor cells, cell-free DNA, cell-free RNA, extracellular vesicles, proteins, and metabolites can be found in the blood, urine, or other bodily fluids and are examined during liquid biopsies. This article focuses on the components of liquid biopsies and their clinical applications in UC. Liquid biopsies have tremendous potential in multiple aspects of precision oncology, from early diagnosis and treatment monitoring to predicting prognoses. They may therefore play an important role in the management of UC and precision medicine.