Hann-Chorng Kuo

Urinary Nerve Growth Factor Levels are Elevated in Patients with Detrusor Overactivity and Decreased in Responders to Detrusor Botulinum Toxin-A Injection

BACKGROUND Increased nerve growth factor (NGF) levels have been reported in the bladder tissue and urine of patients with overactive bladder and detrusor overactivity (DO). Determination of urinary NGF level could serve as a valuable biomarker for the diagnosis and monitoring of disease progression of DO. OBJECTIVE To investigate NGF levels in patients with DO and after treatment including detrusor botulinum toxin A (BoNT-A) injections. DESIGN, SETTING, AND PARTICIPANTS A cross-sectional study was performed in a referred center. Participants included 143 patients with idiopathic DO (IDO) and 100 with neurogenic DO (NDO) who were untreated, well-treated, and failed-treated with antimuscarinics. Thirty-eight subjects without lower urinary tract symptoms served as controls. Detrusor injection of BoNT-A (100 U for IDO, 200 U for NDO) was given to 24 patients with IDO and 19 with NDO who had failed antimuscarinic treatment. MEASUREMENTS Urine samples were obtained from controls and patients. Urinary NGF levels were measured by ELISA and normalized by urine creatinine level (NGF/Cr). The urinary NGF/Cr levels in controls and patients with DO at baseline and 3 mo after BoNT-A injection were compared. RESULTS AND LIMITATIONS The mean urinary NGF/Cr levels were significantly higher in 66 patients with untreated IDO (mean+/-standard deviation, 1.44+/-2.66, p=0.000) and 59 with untreated NDO (0.62+/-1.22, p=0.000) compared to controls (0.005+/-0.019). Patients with well-treated IDO or NDO had reduced NGF/Cr levels, whereas those with failed-treated IDO or NDO did not. Patients who responded to BoNT-A treatment had significantly reduced urinary NGF/Cr levels in both the IDO (0.07+/-0.12, p=0.025) and NDO (0.096+/-0.17, p=0.033) groups compared to baseline levels. However, the NGF levels remained significantly higher at 3 mo in 7 IDO (1.01+/-1.25) and 5 NDO (1.64+/-2.39) patients who failed BoNT-A treatment. The major limitation of this study is the wide deviation of the urinary NGF levels and lack of age controls. CONCLUSIONS Urinary NGF level is a sensitive biomarker for the diagnosis of IDO and NDO and can be used as a tool to evaluate the therapeutic effect of detrusor BoNT-A injection.

Comparison of intravesical botulinum toxin type A injections plus hydrodistention with hydrodistention alone for the treatment of refractory interstitial cystitis/painful bladder syndrome

To compare the clinical effectiveness of botulinum toxin type A (BoNT‐A) injections followed by hydrodistention (HD) with HD alone in patients with interstitial cystitis/painful bladder syndrome (IC/PBS).

Urinary nerve growth factor level is increased in patients with interstitial cystitis/bladder pain syndrome and decreased in responders to treatment

To measure urinary nerve growth factor (NGF) levels in patients with interstitial cystitis/bladder pain syndrome (IC/BPS), and to evaluate the role of urinary NGF in predicting the response to treatment, as the clinical diagnosis of IC/BPS is based on subjective symptoms and recent investigations suggest that urinary NGF is increased in patients with IC/BPS.

Urinary nerve growth factor but not prostaglandin E2 increases in patients with interstitial cystitis/bladder pain syndrome and detrusor overactivity

Study Type – Aetiology (case series)
Level of Evidence 4

Decrease of urinary nerve growth factor levels after antimuscarinic therapy in patients with overactive bladder

To determine urinary nerve growth factor (NGF) levels in patients with overactive bladder (OAB) and after treatment with antimuscarinics.

Adverse Events of Intravesical Botulinum Toxin A Injections for Idiopathic Detrusor Overactivity: Risk Factors and Influence on Treatment Outcome

BACKGROUND Intravesical injection of botulinum toxin type A (BoNTA) provides effective treatment for detrusor overactivity and overactive bladder (OAB). However, the high rates of treatment-related adverse events (AEs) prevent its more widespread use. OBJECTIVE To investigate the risk factors of increasing AEs after BoNTA injection for idiopathic detrusor overactivity (IDO). DESIGN, SETTING, AND PARTICIPANTS This study included a total of 217 patients receiving their first intravesical BoNTA injection for refractory IDO in a tertiary university hospital from 2004 to 2009. MEASUREMENTS AE incidence was analyzed according to gender, age, comorbidities, prostate condition in men, OAB subtype, BoNTA dose, injection site, and baseline urodynamic parameters. Successful outcome was determined based on patient perception of improvement of bladder condition at 3 mo. RESULTS AND LIMITATIONS Successful outcomes were reported by 144 (66.3%) patients. By multivariable analysis, male gender (p=0.013) and baseline postvoid residual (PVR) ≥100ml (p=0.003) were independent predictors of acute urinary retention (AUR). Baseline PVR ≥100ml (p=0.007) and receiving >100 U BoNTA (p=0.029) were predictors of straining to void. The incidence of large PVR after treatment was associated with comorbidity (p=0.011). Urinary tract infection occurred more frequently in women (p=0.003) and in men with retaining prostate (p=0.008). No AUR developed after bladder base/trigonal injection. Nevertheless, the occurrence of AUR or large PVR did not affect therapeutic outcome. This study is limited by nonconsecutive enrollment of patients. CONCLUSIONS Male gender, baseline PVR ≥100ml, comorbidity, and BoNTA dose >100 U are risk factors for increasing incidence of AEs after intravesical BoNTA injection for IDO.

Higher levels of cell apoptosis and abnormal E-cadherin expression in the urothelium are associated with inflammation in patients with interstitial cystitis/painful bladder syndrome

What’s known on the subject? and What does the study add?

Bladder base/trigone injection is safe and as effective as bladder body injection of onabotulinumtoxinA for idiopathic detrusor overactivity refractory to antimuscarinics†‡

The purpose of this study was to evaluate the efficacy and safety of onabotulinumtoxinA injections at bladder base/trigone and compare with injections at bladder body or bladder body/trigone for the treatment of idiopathic detrusor overactivity (IDO) refractory to antimuscarinics.

Pilot Study of Liposome-encapsulated OnabotulinumtoxinA for Patients with Overactive Bladder: A Single-center Study

BACKGROUND Intradetrusor onabotulinumtoxinA (BoNT-A) injection benefits overactive bladder (OAB) patients, but increased postvoid residual (PVR) urine volume and urinary tract infection (UTI) remain risks. Intravesical instillation of liposomal BoNT-A instead of injection could prevent such adverse events. OBJECTIVE To evaluate instillation of liquid liposomal BoNT-A (Lipotoxin) for the treatment of OAB and to determine its mechanism of action. DESIGN, SETTING, AND PARTICIPANTS A double-blind randomized parallel controlled pilot trial in 24 OAB patients at a single tertiary center. INTERVENTION Patients were randomly assigned to intravesical instillation of Lipotoxin containing 80 mg liposomes and 200 U BoNT-A or normal saline (N/S). Patients were retreated with Lipotoxin 1 mo later if they failed the first treatment. OUTCOME MEASUREMENT AND STATISTICAL ANALYSIS Voiding diaries, OAB symptom scores, urodynamic studies, and adverse events were monitored. The primary end point was change of total urinary frequency per 3 d at 1 mo after treatment. Immunohistochemistry and Western blotting for synaptic vesicle glycoprotein 2A (SV2A) and synaptosomal-associated protein, 25 kDa (SNAP25) were performed at baseline and 3 mo after treatment. The Wilcoxon rank sum test and Wilcoxon signed rank test were used for statistical analysis. RESULTS AND LIMITATIONS At 1 mo after treatment, the change of urinary frequency per 3 d significantly improved in the Lipotoxin group (n=12; median: -6.50; interquartile range [IQR]: -18.3 to -0.25; p=0.008) but not in the N/S group. (n=12.0; IQR: -7.75 to 8.0; p=0.792). Urgency episodes also showed a significant decrease in the Lipotoxin group (-12.0; IQR: -20.3 to -2.75; p=0.012) but not in the N/S group (-1.0; IQR: -11.0 to 2.5; p=0.196). SV2A and SNAP25 were expressed in urothelial cells and suburothelial tissues. However, the protein expression did not significantly differ between responders and nonresponders at 3 mo after treatment. CONCLUSIONS Intravesical Lipotoxin instillation effectively reduced frequency episodes 1 mo after treatment in OAB patients without any increase in PVR or risk of UTI. PATIENT SUMMARY We demonstrated that intravesical Lipotoxin instillation reduced frequency episodes at 1 mo in overactive bladder patients. This procedure is safe, without an increase in postvoid residual or the risk of urinary tract infection.

Urinary Nerve Growth Factor is a Better Biomarker than Detrusor Wall Thickness for the Assessment of Overactive Bladder with Incontinence

To compare the differences in urinary nerve growth factor (NGF) and detrusor wall thickness (DWT) between patients with overactive bladder (OAB) and controls to evaluate their suitability as biomarkers in OAB.