Abstract:A clinical guideline and algorism for interstitial cystitis and hypersensitive bladder syndrome has been developed by a group of East Asian urologists as a revised form of the Japanese guideline for interstitial cystitis. The guideline defines interstitial cystitis (IC) as a disease of the urinary bladder diagnosed by 3 requirements; 1) a characteristic complex of lower urinary tract symptoms, 2) bladder pathology such as Hunner's ulcer and bladder bleeding after overdistension, and 3) exclusions of confusable diseases. The characteristic symptom complex is termed as hypersensitive bladder syndrome (HBS), which is defined as bladder hypersensitivity, usually associated with urinary frequency, with or without bladder pain. For the definite diagnosis of IC, cytoscopy or hydrodistension is crutial; HBS is the diagnosis when IC is suspected but not confirmed by the 3 requirements. Numerous therapeutic options are available; however, most of them lack in high level of evidence, leaving a few as recommended therapies. Etiology of IC are multifactorial; the interaction among nervous, immune and endocrine factors forms a vicious cycle, provocating and maintaining inflammatory reactions in the bladder. The inclusion and efficacy criteria for clinical trials should be standardized to enhance the clinical research for this disabling disease, which has proved to be more prevalent than previously believed.

OBJECTIVE 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). PATIENTS AND METHODS A prospective, randomized study was performed in a urological referral centre. In all, 67 patients with IC/PBS who had failed conventional treatments were enrolled. Of these, 44 patients received suburothelial injection with 200 U (15) or 100 U (29) of BoNT‐A followed by cystoscopic HD 2 weeks later (BoNT‐A groups). The control group (23 patients) received the identical HD procedure with no BoNT‐A injection. All patients remained on baseline medications of pentosan polysulphate throughout the study. Bladder pain visual analogue scale (VAS), O’Leary‐Sant symptom and problem indexes, functional bladder capacity (FBC) and urodynamic variables were measured at baseline and after treatment. Global response assessment was used to evaluate successful treatment response. RESULTS The IC/PBS symptom score significantly decreased in all three groups, but VAS reduction, FBC and cystometric bladder capacity increases were significant only in the BoNT‐A groups at 3 months. Of the 44 patients in the BoNT‐A group 31 (71%) had a successful result at 6 months. A successful result at 12 and 24 months was reported in 24 (55%) and 13 (30%) patients in BoNT‐A group, respectively, compared with only six (26%) and four (17%) in the control group (P = 0.002). CONCLUSION Intravesical injections of BoNT‐A followed by HD produced significantly better clinical results than HD alone in patients with IC/PBS.

No abstract

No abstract

No abstract

What’s known on the subject? and What does the study add? Interstitial cystitis/painful bladder syndrome (IC/PBS) is considered to result from long‐standing inflammation of the bladder. Urothelial dysfunction and increased urothelial permeability are known to result in clinical symptoms such as pain and urgency, however the actual pathophysiology remains unclear. This study demonstrated increased cell apoptosis, decreased cell proliferation, increased mast cell activation, and impaired expression of E‐cadherin were significant in IC/PBS bladders. There was a significant correlation between mast cell activation and urothelial cell apoptosis and the reduced E‐cadherin expression was significantly correlated with clinical pain VAS scale, suggesting the barrier defect of the bladder wall may lead to increasing bladder sensitivity and pain. OBJECTIVE • To investigate the relationships between suburothelial inflammation and urothelial dysfunction in interstitial cystitis/painful bladder syndrome (IC/PBlS). MATERIALS AND METHODS • Immunofluorescence staining of ki‐67 (to assess cell proliferation), junction protein E‐cadherin, tryptase (to assess mast cell activation) and TUNEL (to assess urothelial apoptosis) were performed in bladder tissues from 20 patients with IC/PBlS and from 6 control patients. • The fluorescence intensity of E‐cadherin was measured using the ImageJ method. • The percentage of apoptotic cells, proliferated cells and activated mast cells were measured and quantified as positive cells (±SD) per area unit (4 µm2). RESULTS • The ratio of ki‐67‐positive cells in the bladder tissue of the patients with IC/PBlS was significantly down‐regulated compared with that of the control patients (0.559 ± 0.658 vs. 1.23 ± 1.28, P= 0.001). • TUNEL staining revealed a significantly higher number of apoptotic cells in the IC/PBlS bladder tissue compared with control bladder tissue (2.26 ± 2.04 v 0.051 ± 0.124, P= 0.000). • The tryptase signal was significantly stronger in the IC/PBlS bladder tissue compared with that of control patients (6.16 ± 4.35 v 1.15 ± 0.436, P= 0.000). • The apoptotic cell number in IC/PBlS bladder tissue correlated significantly with mast cell activation (P= 0.021). • Immunofluorescence also showed a significantly lower distribution of E‐cadherin in IC/PBlS bladder tissue compared with that of control patients (8.50 ± 6.83 v 17.2 ± 11.9, P= 0.000). • Lower expression of E‐cadherin in IC/PBlS bladder tissue was significantly correlated with higher visual analogue pain scores in patients with IC/PBlS (P= 0.008). CONCLUSIONS • The results of the present study suggest that urothelial homeostasis in IC/PBlS bladders was impaired, and abnormal urothelial function was significantly associated with chronic inflammation. • The junctions between urothelial cells in IC/PBlS bladders were abnormal, which was associated with the patient’s self‐report pain scales.

Botulinum A toxin urethral injections at doses of 50 or 100 units were effective in decreasing urethral sphincter resistance in patients with various types of lower urinary tract dysfunction.

Ketamine-related cystitis is characterized by ketamine-induced urinary frequency and bladder pain. It has become a serious problem in recent years. The most typical grossly pathological bladder change with ketamine related cystitis is a contracted bladder and bladder wall thickening. Ulcerative cystitis with an easily bleeding mucosa is a common cystoscopic finding. Microscopically, the urothelium is denuded and is infiltrated by inflammatory cells, such as mast cells and eosinophils. The pathogenesis of ketamine-related cystitis is complicated and involves many different pathways. Past evidence suggests a direct toxic effect, bladder barrier dysfunction, neurogenic inflammation, immunoglobulin-E-mediated inflammation, overexpression of carcinogenic genes, abnormal apoptosis and nitric oxide synthase-mediated inflammation contribute to the pathogenesis of ketamine-related cystitis. The first step to managing ketaminerelated cystitis is always asking patients to cease ketamine. Medical treatment might be helpful in patients with early ketamine-related cystitis and abstinence from ketamine. Several case studies showed that the intravesical installation of hyaluronic acid and intravesical injection of botulinum toxin type A were effective for symptom relief in selected patients. For patients with irreversible pathological change, such as contracted bladder, augmentation enterocystoplasty might be the only solution to increase bladder capacity and relieve intractable bladder pain.