Background: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a condition causing bladder inflammation. Urinary biomarkers have been assessed as suitable for the diagnosis and treatment. This study aimed at investigating the role of urinary biomarkers in identifying bladder conditions and predicting the treatment outcome of IC/BPS. Methods: A total of 309 patients with IC/BPS and 30 controls were enrolled in this study. All patients underwent a comprehensive urological workup of symptoms, pain severity, and cystoscopic hydrodistention findings including maximal bladder capacity (MBC) and glomerulation grade. Urine samples were collected to investigate the levels of urinary cytokines and chemokines. According to MBC and glomerulation grade, patients with IC/BPS were further classified into the Hunner’s IC (HIC) and non-HIC groups. The urinary biomarkers between IC/BPS and control groups and HIC and non-HIC groups were compared. Moreover, the treatment response was graded according to global response assessment (GRA) scores, and urinary biomarker levels were analyzed based on different GRAs. Results: Patients with IC/BPS had significantly high urinary monocyte chemoattractant protein-1, eotaxin, tumor necrosis factor -alpha (TNF-α), and prostaglandin E2 levels. Significantly higher levels of urinary interleukin-8, C-X-C motif chemokine ligand 10 (CXCL 10), brain-derived neurotrophic factor, eotaxin, and regulated-on-activation, normal T-cell expressed and secreted (RANTES) were noted in HIC than those with non-HIC and controls. Among all biomarkers, TNF-α had the best sensitivity, specificity, positive predictive value, and negative predictive value. There was a significant correlation between biomarker levels and GRA. Conclusions: Significantly higher urine cytokines and chemokine levels were found in patients with IC/BPS. Most urinary biomarkers were significantly associated with MBC, glomerulation grade, and treatment outcome.

Diabetes mellitus (DM) is an independent risk factor for overactive bladder (OAB). The pathophysiology of DM-associated OAB is multifactorial and time-dependent. Diabetic bladder dysfunction is highly associated with diabetic complications, mainly including diabetic neuropathy and atherosclerosis. Chronic systemic inflammation and bladder urothelial inflammation may contribute to the onset of OAB. Intravesical botulinum toxin A (BoNT-A) injection has proved to be a successful treatment for idiopathic and neurogenic OAB. BoNT-A can inhibit the efferent pathways of the bladder as well as the chronic inflammation and hypersensitivity via the afferent pathways. We conducted a review of the published literature in Pubmed using a combination of two keywords, namely “botulinum toxin A” (BoNT-A) and “overactive bladder”, with or without the additional keywords “detrusor overactivity”, “diabetes mellitus”, “inflammation”, and “urodynamic study”. We also reviewed the experience of our research teams, who have published several studies of the association between DM and OAB. Since limited data support the effectiveness and safety of BoNT-A for treating patients with DM-associated OAB, a comprehensive evaluation of diabetic complications and urodynamic study is needed before treatment. In the future, it is imperative to explore the clinical characteristics and inflammatory biomarkers of diabetes as determining predictors of the treatment efficacy.

Underactive bladder is frequently encountered in elderly patients. It may result from detrusor underactivity (DU) or low detrusor contractility due to a urethral sphincter inhibitory effect. This study analyzed the video-urodynamic study (VUDS) characteristics of patients with underactive bladder in a large cohort of men with lower urinary tract symptoms (LUTS). Male patients with LUTS who had failed the initial treatment were consecutively enrolled. All patients underwent detailed urological investigations including prostate measurement, free uroflowmetry, post-void residual volume (PVR) measurement, cystoscopy and VUDS. The VUDS characteristics of the men with underactive bladder were analyzed and compared with those of men with bladder outlet obstruction and normal tracing. A total of 1329 men who underwent VUDS were included in this retrospective analysis. After VUDS, the final diagnosis was DU in 165 patients, poor relaxation of external sphincter (PRES) in 525, bladder outlet obstruction in 501, and normal tracing in 138. VUDS findings in DU patients showed a slowly increased detrusor pressure, intermittent detrusor contractions, or early decline of detrusor contraction, resulting in a low maximum flow rate (Qmax), and large PVR. In comparison with the PRES groups, DU patients were older, had reduced bladder sensation, lower detrusor pressure (Pdet), lower Qmax, larger PVR volume, and lower voiding efficiency. Patients with urodynamic PRES also had low-pressure–low-flow tracings, but their bladder sensation was similar to that with normal tracing. DU patients with very low Pdet also had low detrusor tonicity, and more medical co-morbidities than the other groups did. Idiopathic underactive bladder in elderly men could be attributed to urodynamic DU and PRES. DU is associated with old age, reduced bladder sensation, low voiding efficiency, and medical co-morbidities.

Low-energy shock wave (LESW) therapy is known to facilitate tissue regeneration with analgesic and anti-inflammatory effects. LESW treatment has been demonstrated to be effective in treating chronic prostatitis and pelvic pain syndrome as well as overactive bladder, and it has a potential effect on interstitial cystitis/bladder pain syndrome (IC/BPS) in humans. LESW reduces pain behavior, downregulates nerve growth factor expression, and suppresses bladder overactivity by decreasing the expression of inflammatory proteins. Previous rat IC models have shown that LESW can increase urothelial permeability, facilitate intravesical delivery of botulinum toxin A (BoNT-A), and block acetic acid-induced hyperactive bladder, suggesting that LESW might be a potential therapeutic module for relieving bladder inflammatory conditions, such as bladder oversensitivity, IC/BPS, and overactive bladder. A recent clinical trial showed that LESW monotherapy was associated with a significant reduction in pain scores and IC symptoms. BoNT-A detrusor injection or liposome-encapsulated BoNT-A instillation could also inhibit inflammation and improve IC symptoms. However, BoNT-A injection requires anesthesia and certain complications might occur. Our preliminary study using LESW plus intravesical BoNT-A instillation every week demonstrated an improvement in global response assessment without any adverse events. Moreover, an immunohistochemistry study revealed the presence of cleaved SNAP25 protein in the suburothelium of IC bladder tissue, indicating that BoNT-A could penetrate across the urothelial barrier after application of LESW. These results provide evidence for the efficacy and safety of this novel IC/BPS treatment by LESW plus BoNT-A instillation, without anesthesia, and no bladder injection. This article reviews the current evidence on LESW and LESW plus intravesical therapeutic agents on bladder disorders and the pathophysiology and pharmacological mechanism of this novel, minimally invasive treatment model for IC/BPS.

Purpose: This study aimed to investigate improvement in voiding condition after the initial botulinum toxin A (BoNT-A) injection into the urethral sphincter among patients with chronic spinal cord injury (SCI) and voiding dysfunction. Moreover, subsequent surgical procedures and bladder management were evaluated. Materials and Methods: From 2011 to 2020, 118 patients with SCI and dysuria who wanted to void spontaneously received their first BoNT-A injection at a dose of 100 U into the urethral sphincter. Improvement in voiding and bladder conditions after BoNT-A treatment were assessed. Next, patients were encouraged to continually receive BoNT-A injections into the urethral sphincter, convert to other bladder managements, or undergo surgery. After undergoing bladder management and surgical procedures, the patients were requested to report improvement in voiding condition and overall satisfaction to bladder conditions. Then, data were compared. Results: In total, 94 male and 24 female participants were included in this analysis. Among them, 51 presented with cervical, 43 with thoracic, and 24 with lumbosacral SCI. After BoNT-A injections into the urethral sphincter, 71 (60.2%) patients, including 18 (15.3%) with excellent, and 53 (44.9%) with moderate improvement, had significant improvement in voiding condition. Patients with cervical SCI (66.6%), detrusor overactivity and detrusor sphincter dyssynergia (72.0%), partial hand function (80.0%), and incomplete SCI (68.4%) had a better improvement rate than the other subgroups. Only 42 (35.6%) patients continually received treatment with BoNT-A injections into the urethral sphincter. Meanwhile, more than 60% of patients who converted their treatment to augmentation enterocystoplasty (n = 5), bladder outlet surgery (n = 25), BoNT-A injections into the detrusor muscle (n = 20), and medical treatment (n = 55) had moderate and marked improvement in voiding dysfunction and overall satisfaction. Discussion: Although BoNT-A injections into the urethral sphincter could improve voiding condition, only patients with SCI who presented with voiding dysfunction were commonly satisfied. Those whose treatments were converted to other bladder managements, which can promote urinary continence, or to surgical procedures, which can facilitate spontaneous voiding, had favorable treatment outcomes.

Overactive bladder (OAB) symptoms increase with age and involve several comorbidities. OnabotulinumtoxinA (BoNT-A) intravesical injection is a treatment choice for patients who are intolerant of or refractory to antimuscarinics. However, the increased risk of urinary tract infection and elevated post-void residual (PVR) volume post-treatment require resolution. Male sex, baseline PVR > 100 mL, and comorbidities are independent risk factors of adverse events (AEs) such as acute urinary retention (AUR). Intravesical BoNT-A injection is safe and effective for OAB patients with frailty, medical comorbidities such as Parkinson’s disease (PD), chronic cerebrovascular accidents (CVA), dementia, or diabetes, or a history of prior lower urinary tract surgery (prostate or transvaginal sling surgery). Post-treatment, 60% of frail elderly patients had a PVR volume > 150 mL and 11% had AUR. Although intravesical BoNT-A injection is safe for PD patients, CVA patients had higher strain voiding rates. Diabetic patients were at increased risk of large PVR urine volume and general weakness post-treatment. Treatment results were similar between patients with and without a history of prostate or transvaginal sling surgery. Possible AEs and bladder management strategies should be conveyed to patients before treatment. Careful patient selection is important, and therapeutic safety and efficacy should be carefully balanced.