Oncologic impact of delay between diagnosis and radical nephroureterectomy

PurposeThis 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).MethodsIn 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.ResultsOf 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.ConclusionsFor 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

Adipose-Derived Stem Cells and Their Derived Microvesicles Ameliorate Detrusor Overactivity Secondary to Bilateral Partial Iliac Arterial Occlusion-Induced Bladder Ischemia

(1) Background: We established a new bladder ischemia rat model through bilateral partial iliac arterial occlusion (BPAO) and investigated the therapeutic effect of adipose-derived stem cells (ADSCs) and ADSC-derived microvesicles (MVs); (2) Methods: The study included four groups: (1) sham, (2) BPAO, (3) BPAO + ADSCs, and (4) BPAO + ADSC-derived MVs. Female Wistar rats with BPAO were injected with ADSCs or ADSC-derived MVs through the femoral artery. Doppler flowmetry and real-time laser speckle contrast imaging were performed to quantify blood flow in the common iliac arteries and bladder microcirculation. A 24-h behavior study and transcystometrogram were conducted after 2 weeks. Bladder histology, immunostaining, and lipid peroxidation assay were performed. The expressions of P2X2, P2X3, M2, and M3 receptors and nerve growth factor (NGF) were evaluated; (3) Results: BPAO significantly reduced bladder microcirculation, intercontraction interval (ICI), and bladder volume and increased the amplitude of nonvoiding contraction, neutrophil infiltration, and malondialdehyde and NGF levels. ADSCs and ADSC-derived MVs significantly ameliorated these effects. The results of Western blot showed that the BPAO group exhibited the highest expression of M3 and P2X2 receptors. ADSCs significantly attenuated the expressions of M2 and P2X2 receptors. ADSC-derived MVs significantly attenuated the expressions of M3 and P2X2 receptors; (4) Conclusions: ADSCs and ADSC-derived MVs ameliorated the adverse effects of BPAO including bladder overactivity, bladder ischemia, and oxidative stress. Inflammation, muscarinic signaling, purinergic signaling, and NGF might be involved in the therapeutic mechanism

Significant intravesical prostatic protrusion and prostatic calcification predict unfavorable outcomes of medical treatment for male lower urinary tract symptoms

Objective: To evaluate the impact of intravesical prostatic protrusion (IPP) and prostatic calcification on medical treatment for male lower urinary tract symptoms (LUTS). Materials and methods: Men over the age of 40 years with total International Prostate Symptom Score (IPSS) ≥ 8 were recruited from January to August 2013. The maximal flow rate, postvoiding residual (PVR) urine volume, total prostate volume (TPV), transitional zone volume (TZV), transitional zone index (TZI), and grades of IPP and prostate calcification were recorded. All patients received α-blocker monotherapy, and Global Response Assessment (GRA) was used to determine treatment response 1 month after the treatment. The primary end point was to compare the treatment results in patients with and without significant IPP or prostate calcification. Univariate and multivariate logistic regression analyses were performed to determine whether IPP and prostatic calcification are predictors of improved outcome (GRA ≥ 1). Results: We enrolled 112 men with a mean age of 65.5 (range, 42–89) years. IPP was significantly positively correlated with TPV, TZV, TZI, and PVR. Prostatic calcification was significantly negatively correlated with total IPSS, IPSS Voiding, and IPSS Storage. After 1-month treatment with α-blockers, the average total IPSS decreased from 18.2 ± 7.4 to 13.1 ± 4.5. Sixty-nine patients (61.6%) reported improved outcomes. Patients with large prostate volumes (TPV ≥ 40 mL) and small prostate volumes (TPV < 40 mL) had similar improved outcome rates (56.5% and 65.1%, respectively). Patients with significant IPP (Grades II and III) had significantly lower improved outcome rates (36.8%) than those without significant IPP (74.3%). Patients with prostatic calcification also had a significantly lower rate of improved outcome (47.9%) than those who did not (71.9%). Multivariate logistic regression analyses showed that IPP and prostatic calcification are predictors of unfavorable outcome (GRA < 1) after adjusting for age, TPV, and total IPSS. Conclusion: Significant IPP and prostatic calcification are unfavorable predictors of successful α-blocker treatment for benign prostatic hyperplasia-induced male LUTS

Can Botulinum Toxin A Still Have a Role in Treatment of Lower Urinary Tract Symptoms/Benign Prostatic Hyperplasia Through Inhibition of Chronic Prostatic Inflammation?

Patients with benign prostatic hyperplasia (BPH) can exhibit various lower urinary tract symptoms (LUTS) owing to bladder outlet obstruction (BOO), prostatic inflammation, and bladder response to BOO. The pathogenesis of BPH involves an imbalance of internal hormones and chronic prostatic inflammation, possibly triggered by prostatic infection, autoimmune responses, neurogenic inflammation, oxidative stress, and autonomic dysfunction. Botulinum toxin A (BoNT-A) is well recognized for its ability to block acetylcholine release at the neuromuscular junction by cleaving synaptosomal-associated proteins. Although current large clinical trials have shown no clinical benefits of BoNT-A for the management of LUTS due to BPH, BoNT-A has demonstrated beneficial effects in certain subsets of BPH patients with LUTS, especially in males with concomitant chronic prostatitis/chronic pelvic pain syndrome and smaller prostate. We conducted a review of published literature in Pubmed, using Botulinum toxin, BPH, BOO, inflammation, LUTS, and prostatitis as the key words. This article reviewed the mechanisms of BPH pathogenesis and anti-inflammatory effects of BoNT-A. The results suggested that to achieve effectiveness, the treatment of BPH with BoNT-A should be tailored according to more detailed clinical information and reliable biomarkers

Urothelial Calcium-Sensing Receptor Modulates Micturition Function via Mediating Detrusor Activity and Ameliorates Bladder Hyperactivity in Rats

The urothelium displays mechano- and chemosensory functions via numerous receptors and channels. The calcium-sensing receptor (CaSR) detects extracellular calcium and modulates several physiological functions. Nonetheless, information about the expression and the role of CaSR in lower urinary tract has been absent. We aimed to determine the existence of urothelial CaSR in urinary bladder and its effect on micturition function. We utilized Western blot to confirm the expression of CaSR in bladder and used immunofluorescence to verify the location of the CaSR in the bladder urothelium via colocalization with uroplakin III A. The activation of urothelial CaSR via the CaSR agonist, AC-265347 (AC), decreased urinary bladder smooth muscle (detrusor) activity, whereas its inhibition via the CaSR antagonist, NPS-2143 hydrochloride (NPS), increased detrusor activity in in vitro myography experiments. Cystometry, bladder nerve activities recording, and bladder surface microcirculation detection were conducted to evaluate the effects of the urothelial CaSR via intravesical administrations. Intravesical AC inhibited micturition reflex, bladder afferent and efferent nerve activities, and reversed cystitis-induced bladder hyperactivity. The urothelial CaSR demonstrated a chemosensory function, and modulated micturition reflex via regulating detrusor activity. This study provided further evidence of how the urothelial CaSR mediated micturition and implicated the urothelial CaSR as a potential pharmacotherapeutic target in the intervention of bladder disorders

The efficacy of extracorporeal shockwave lithotripsy for symptomatic ureteral stones: Predictors of treatment failure without the assistance of computed tomography

<div><p>Objectives</p><p>Non-contrast computed tomography (NCCT) is not always performed clinically if the diagnosis of ureteral calculi has been confirmed using other radiographic imaging modalities. The aim of this study was to identify predictors of successful extracorporeal shockwave lithotripsy (ESWL) without assistance of NCCT.</p><p>Methods</p><p>We retrospectively reviewed the medical records of patients with symptomatic solitary ureteral stones who underwent ESWL between November 2015 and January 2016. Abdominal plain radiography or intravenous urography were performed before ESWL for localization. The exclusion criteria were repeated sessions of ESWL for the target stone and congenital genitourinary tract anomalies. The demographic characteristics, clinical history, medical charges, or imaging features of the stones were recorded. Successful treatment was defined as no fragments detected on radiography or ultrasonography in 4 weeks. For radiolucent calculi, successful treatment was regarded as cases without hydronephrosis, symptoms, or hematuria. Patients experiencing intractable pain and undergoing subsequent auxiliary surgeries were regarded as having ESWL treatment failure.</p><p>Results</p><p>Age (odds ratio [OR], 1.042; 95% confidence interval [CI], 1.007–1.078), history of ipsilateral renal or ureteral calculi episodes (OR, 2.669; 95% CI, 1.281–5.687), stone burden (OR, 3.499; 95% CI, 1.284–9.530), and radiopaque stone (OR, 2.351; 95% CI, 1.049–5.267) were significant predictors of ESWL failure in all patients.</p><p>Conclusions</p><p>For treating symptomatic ureteral stones, those with smaller size, radiolucency, and without a history of ipsilateral renal or ureteral calculi could be considered for first-line therapy with ESWL.</p></div

Demographics of all the patients, successful and failure treatment groups.

<p>Demographics of all the patients, successful and failure treatment groups.</p