Jia-Fong Jhang

Down regulation of vascular endothelial growth factor is associated with decreased inflammation after intravesical OnabotulinumtoxinA injections combined with hydrodistention for patients with interstitial cystitis--clinical results and immunohistochemistry analysis.

OBJECTIVEnTo measure the expression of vascular endothelial growth factor (VEGF) in bladder tissue and improvement of clinical symptoms and inflammatory biomarkers after repeated onabotulinumtoxinA injections in patients with interstitial cystitis/bladder pain syndrome (IC/BPS).nnnMETHODSnTwenty-one patients with IC/BPS received 4 sets of intravesical 100-U onabotulinumtoxinA injections combined with hydrodistention. Assessments at baseline and 6 months after each treatment included OLeary-Sant Symptom Score, bladder pain visual analog scale, functional bladder capacity (FBC), grade of glomerulations under cystoscopic hydrodistention, and urodynamic parameters. The bladder specimens at baseline and at the fourth treatment were investigated by western blotting for the expression of VEGF, Bcl-2-associated X protein (Bax), and phospho-p38 (p-p38), and immunohistochemistry staining for apoptotic and mast cell activity. Six women with genuine stress urinary incontinence served as controls for comparison.nnnRESULTSnThe measured immunohistochemical parameters were significantly higher in patients with IC/BPS than the controls. Statistically significant decrease in the expression of VEGF was noted in patients treated with repeated onabotulinumtoxinA injections compared with baseline (0.83 ± 0.28 vs 1.00; P = .016). The apoptotic cell count (0.86 ± 1.00 vs 1.76 ± 1.69; P = .026) and mast cell activity (1.81 ± 2.29 vs 5.82 ± 4.97; P = .009) were also reduced. Significant increases in FBC and global response assessment score were also observed after onabotulinumtoxinA treatment; however, except for mast cell activity, VEGF expression and apoptotic cell count were still significantly higher than the controls.nnnCONCLUSIONnIncreased VEGF was associated with bladder inflammation and smaller FBC in patients with IC/BPS and decreased after repeated onabotulinumtoxinA injections and hydrodistention, suggesting VEGF plays an important role in the pathogenesis of IC/BPS.

Urothelial Functional Protein and Sensory Receptors in Patients With Interstitial Cystitis/Bladder Pain Syndrome With and Without Hunner's Lesion

OBJECTIVEnTo investigate the urothelium function and sensory receptors difference between interstitial cystitis/bladder pain syndrome (IC/BPS) patients with or without Hunners lesion.nnnMETHODSnFourteen female IC/BPS patients with Hunners lesion (Hunner IC) and 14 age-matched IC/BPS patients without Hunners lesions (non-Hunner IC) were enrolled. Bladder mucosa biopsies were obtained. Bladder inflammation, eosinophil infiltration, and urothelial denudation were graded on a 4-point scale after staining with hematoxylin and eosin. Adhesive protein E-cadherin, tryptase, and zonula occuldens-1 in the bladder tissues were assessed with immunofluorescence staining. Urothelial muscarinic receptors M2, M3, endothelial nitric oxide synthase (eNOS), and purinergic receptor P2X3 were evaluated by Western blotting.nnnRESULTSnHunner IC patients had a significantly higher mean visual analog scale pain score and smaller cystometric bladder capacity than non-Hunner IC patients. The Hunner IC bladder specimens showed more severe or moderate eosinophilic infiltration and urothelial denudation than the non-Hunner IC bladder specimens did. The E-cadherin expression was significantly lower, and eNOS expression was significantly higher in the Hunner IC bladder samples than in the non-Hunner IC samples. The other functional proteins or sensory receptors did not differ between groups.nnnCONCLUSIONnBladder inflammation and urothelial cell adhesion defects were more severe in the Hunner IC than that in the non-Hunner IC patients. eNOS was significantly higher in the Hunner IC than in the non-Hunner IC bladder samples, suggesting that eNOS expression difference may implicate different pathogenesis in 2 types of IC.

Therapeutic effect of urethral sphincter onabotulinumtoxinA injection for urethral sphincter hyperactivity

Urethral sphincter hyperactivity resulting in voiding dysfunction is frequently encountered. Medical treatment might not achieve a satisfactory result. OnabotlinumtoxinA urethral sphincter injection relaxes sphincter tonicity and possibly resumes efficient voiding. This study analyzed the treatment outcomes and predictor for successful onabotulinumtoxinA treatment on these patients.

Epstein-Barr Virus as a Potential Etiology of Persistent Bladder Inflammation in Human Interstitial Cystitis/Bladder Pain Syndrome

Purpose: Interstitial cystitis/bladder pain syndrome is characterized by bladder inflammation without bacterial infection. Although viral infection is a potential etiological cause, few studies have been reported. Materials and Methods: Bladder specimens were obtained from patients with interstitial cystitis/bladder pain syndrome and from patients with stress urinary incontinence as controls. Bladder specimens were tested for Epstein‐Barr encoded RNAs by in situ hybridization and for Epstein‐Barr DNA by quantitative real‐time polymerase chain reaction, serology and immunohistochemical staining. Results: Enrolled in study were 16 patients with interstitial cystitis/bladder pain syndrome and Hunner lesions, 23 without interstitial cystitis/bladder pain syndrome or Hunner lesions and 10 controls. The positive rate of Epstein‐Barr encoded RNA on in situ hybridization in bladder specimens from patients with vs without interstitial cystitis/bladder pain syndrome and Hunner lesions was 50% vs 8.6%. No Epstein‐Barr encoded RNA was found in control specimens. On quantitative real‐time polymerase chain reaction Epstein‐Barr DNA was detected in 68.8% vs 16.7% of bladder specimens in patients with vs without interstitial cystitis/bladder pain syndrome and Hunner lesions. The median viral load was 1,836 copies per ml (range 216 to 75,144). Only 1 control specimen was Epstein‐Barr positive on quantitative real‐time polymerase chain reaction. All serum samples from patients with interstitial cystitis/bladder pain syndrome showed past Epstein‐Barr viral infection. Epstein‐Barr infection was present in 87.5% vs 17.4% of bladder specimens from patients with vs without interstitial cystitis/bladder pain syndrome and Hunner lesions for a total of 46.2% with interstitial cystitis/bladder pain syndrome. Immunohistochemical staining of CD3 and CD20 revealed that Epstein‐Barr infection was mainly restricted to T lymphocytes in bladders showing interstitial cystitis/bladder pain syndrome. Conclusions: Bladder Epstein‐Barr infection in T cells may be linked to the pathogenesis of persistent inflammation in patients with interstitial cystitis/bladder pain syndrome.

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.

Vascular fibrinoid necrosis in the urinary bladder of ketamine abusers: A new finding that may provide a clue to the pathogenesis of ketamine-induced vesicopathy

Two 31‐year‐old women who had abused ketamine, 1 for 8 years and 1 for 5 years, presented with ketamine‐induced vesicopathy with urinary frequency, decreased bladder capacity, and detrusor overactivity. An enterocystoplasty was performed in both cases. The pathology of the urinary bladders in both women showed ulcerative cystitis and fibrinoid necrosis of vessels; the latter was confirmed by Masson trichrome staining. Fibrinoid necrosis of vessels is a kind of immune complex‐mediated vasculitis that induces the release of inflammatory mediators, with subsequent thrombosis, ischemic injury, and eventual tissue necrosis in localized areas, the so‐called Arthus reaction. The new finding of fibrinoid necrosis in the urinary bladders of ketamine abusers may provide a new clue to the pathogenesis of ketamine‐induced vesicopathy.