Cheng-Ling Lee

Increased apoptosis and suburothelial inflammation in patients with ketamine-related cystitis: a comparison with non-ulcerative interstitial cystitis and controls

To investigate the suburothelial inflammation and urothelial dysfunction that occurs with ketamine‐related cystitis (KC) and interstitial cystitis/bladder pain syndrome (IC/BPS).

Urothelial Dysfunction, Suburothelial Inflammation and Altered Sensory Protein Expression in Men with Bladder Outlet Obstruction and Various Bladder Dysfunctions: Correlation with Urodynamics

PURPOSE We investigated urothelial integrity, suburothelial inflammation and the expression of sensory proteins in the bladder urothelium of male patients with bladder outlet obstruction and various bladder dysfunctions. MATERIALS AND METHODS We prospectively enrolled 33 men with urodynamically proven bladder outlet obstruction as the study group. Bladder biopsies were obtained from all study patients and 10 control patients. The expression of E-cadherin, zonula occludens-1, tryptase, apoptosis, TRPV (transient receptor potential vanilloid) 1 and 4, β3 adrenoreceptor, M2 and M3 muscarinic receptors, P2X3 receptor, and inducible/epithelial nitric oxide synthase were compared between study and control patients. RESULTS Study patients had significantly lower expression of E-cadherin, and a higher number of suburothelial mast and apoptotic cells than controls. Additionally, higher expression of P2X3 and M2 muscarinic receptors, and lower expression of M3 muscarinic receptor were detected in study patients. The detrusor underactivity subgroup was characterized by significantly higher expression of β3 adrenoreceptors and lower expression of inducible nitric oxide synthase than in controls. In study patients a significantly positive correlation was noted between voided volume and E-cadherin expression (r = 0.372), volume at first sensation of filling and β3 adrenoreceptor expression (r = 0.386), and detrusor pressure and M2 muscarinic receptor expression (r = 0.496) in the bladder urothelium (each p <0.05). CONCLUSIONS Urothelial dysfunction, suburothelial inflammation, cellular apoptosis and alterations in sensory proteins are prominent in bladder dysfunction secondary to bladder outlet obstruction. Impaired urothelial signaling and sensory transduction pathways appear to reflect the pathophysiology of bladder dysfunction and detrusor underactivity in patients with bladder outlet obstruction.

Current pharmacological and surgical treatment of underactive bladder

Underactive bladder (UAB) or detrusor underactivity (DU) is a common yet still poorly understood urological problem. In addition to true detrusor failure and neuropathy, the inhibitory effects of detrusor contraction by the striated urethral sphincter and the bladder neck through alpha-adrenergic activity may also play a role in the development of UAB or DU. Treatment of UAB or DU aims to reduce the postvoid residual (PVR) urine volume and increase voiding efficiency, either by spontaneous voiding or abdominal straining. Pharmacotherapy with parasympathomimetics or cholinesterase inhibitors might be tried, and benefits can be achieved in combination with alpha-blockers. Bladder outlet surgeries, including urethral onabotulinumtoxinA injection, transurethral incision of the bladder neck, and transurethral incision or resection of the prostate can effectively improve voiding efficiency and decrease the PVR in most patients with DU. The mechanisms have not been well elucidated. It is likely that ablation of the bladder neck or prostatic urethra might not only decrease bladder outlet resistance but also abolish the sympathetic hyperactivity which inhibits detrusor contractility in patients with idiopathic UAB or DU.

PD59-06 TAILORING MEDICATION FOR LOWER URINARY TRACT SYMPTOMS IN MEN BASED ON INTERNATIONAL PROSTATE SYMPTOM SCORE VOIDING TO STORAGE RATIO

OBJECTIVE To investigate therapeutic results of tailoring medication for lower urinary tract symptoms (LUTS) in men according to initial treatment results and International Prostate Symptom Score (IPSS)-voiding to storage subscore (V/S) ratio. METHODS Men with mild-to-moderate LUTS were initially treated for 1 month with doxazosin 4 mg daily for IPSS-V/S >1 or tolterodine 4 mg daily for IPSS-V/S ≤1. They then underwent the Global Response Assessment (GRA) to tailor their medication by changes in IPSS-V/S, uroflow, and GRA, which were compared at baseline, 1, and 3 months post-treatment. RESULTS Upon baseline, 162/374 men had IPSS-V/S ≤1, and 212/374 had an IPSS-V/S >1. Both groups had significant improvement in IPSS-T, IPSS-S, and IPSS-V/S 1 month post-treatment. Of the 162 men initially receiving tolterodine, 102 (63.0%) continued monotherapy; 20 (12.3%) had IPSS-V/S >1.5 and were shifted to doxazosin monotherapy, and 40 (24.7%) had IPSS-V/S >1 but ≤1.5 and added doxazosin. Among the 212 men initially receiving doxazosin, 171 (80.7%) continued monotherapy; 9 with IPSS-V/S <1.5 were switched to tolterodine, and 32 had IPSS-V/S <2 but >1.5 and added tolterodine. Improvement in GRA was remarkable in all subgroups with tailoring the medication to patient symptomatology. CONCLUSION This study reveals that treatment customization according to IPSS-V/S after initial medical therapy provided satisfactory outcomes for men with mild-to-moderate LUTS.

Electron microscopic characteristics of interstitial cystitis/bladder pain syndrome and their association with clinical condition

Background Electron microscopy (EM) characteristics of the urothelium in interstitial cystitis/bladder pain syndrome (IC/BPS) and their association with clinical condition are unclear. Methods Ten IC/BPS patients who were admitted for hydrodistention and 5 patients with stress urinary incontinence (control patients) were enrolled. All patients provided detailed clinical histories and underwent urodynamic studies. Cystoscopic bladder biopsies were obtained and processed for transmission EM (TEM) and scanning EM (SEM). The severity of the urothelium findings was graded on a 4-point scale (0: none, 1: mild, 2: moderate, and 3: severe). The EM findings between IC/BPS and control patients were compared; the results were analyzed using the chi-square test. Results Compared with the urothelium of control patients, the urothelium of IC/BPS patients had more severe defects of the urothelial cell layers and integrity of umbrella cells in TEM (p = 0.045 and 0.01, respectively). In SEM, umbrella cell pleomorphism increased and microplicae of the cell membrane decreased in the IC/BPS group, and both were more severe than in the control group (p = 0.022 and 0.007, respectively). The patients with moderate to severe defects of umbrella cell integrity had more severe bladder pain and smaller maximal bladder capacity (MBC) (both p = 0.010). Patients with moderate to severe defects in microplicae of the cell membrane had smaller cystometric bladder capacity and MBC (p = 0.037 and 0.047, respectively). Conclusions The results revealed significant urothelium defects in IC/BPS, especially in the umbrella cells. Defects of umbrella cells may play an important role in the pathogenesis of IC/BPS.

Histopathological characteristics of ketamine-associated uropathy and their clinical association

To investigate the histopathological findings in ketamine‐associated uropathy (KU) and their clinical association.

Comparative study of efficacy and safety between bladder body and trigonal intravesical onabotulinumtoxina injection in the treatment of interstitial cystitis refractory to conventional treatment-A prospective, randomized, clinical trial

Intravesical onabotulinumtoxinA (BoNT‐A) injection can relieve symptoms of interstitial cystitis/bladder pain syndrome (IC/BPS). However, the therapeutic efficacy of different injection sites is not well known. This study compared therapeutic efficacy and safety between bladder body and trigonal BoNT‐A injection.

Changes in sensory proteins in the bladder urothelium of patients with chronic kidney disease and end-stage renal disease

Patients with chronic kidney disease (CKD) or end‐stage renal disease (ESRD) frequently have lower urinary tract symptoms, such as frequency, urgency, or bladder pain. This study evaluated sensory protein expression in the bladder urothelium of patients with CKD or ESRD.

Pathophysiology of benign prostate enlargement and lower urinary tract symptoms: Current concepts

Lower urinary tract symptoms (LUTS) are highly prevalent in the aging population, particularly in men. Historically, prostate enlargement was thought to be responsible for most cases of male LUTS. Several risk factors for the development of benign prostate enlargement/hyperplasia (BPE/BPH) have been identified, including age, genetics, hormones, growth factors, inflammation, and lifestyle factors. However, as our knowledge continues to evolve, male LUTS are no longer managed entirely in a prostate-centric fashion. In this article, we review current concepts in the epidemiology, etiology, and pathophysiology of BPE/BPH and male LUTS.