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.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a heterogeneous syndrome which is usually characterized by urinary frequency, nocturia, and bladder pain. Several pathomechanisms have been proposed, including uroepithelial dysfunction, mast cell activation, neurogenic inflammation, autoimmunity, and occult urinary tract infections. It is possible that an inflammatory process alters regulation of urothelial homeostasis and results in dysfunction of the bladder epithelium. Different phenotypes of IC/BPS have been explored including Hunner and non-Hunner type IC, hypersensitive bladder, and bladder pain both with and without functional somatic syndrome. Different gene expressions have also been found in different IC phenotypes. Abnormal expressions of uroplakin, chondroitin sulfate and adhesive protein E-cadherin, tight junction protein zonula occludens-1 in IC/BPS bladder suggest abnormal epithelial differentiation in this bladder disease. Analysis of inflammatory proteins, or cytokines in the urine or serum provides another diagnostic foundation forIC/BPS subtypes. The involvement of IC/BPS in systemic functional somatic syndrome and other pelvic organ diseases might also subdivide subtypes of IC/BPS. Chronic inflammation, increased urothelial apoptosis, and abnormal urothelial function are closely associated in IC bladders. This article reviews recent research on the pathomechanisms of IC, which might help us in mapping the heterogeneity of the disease.

Aims Current treatments for interstitial cystitis/bladder pain syndrome (IC/BPS) are usually unsuccessful in achieving long‐term bladder pain relief and irritable symptom improvement. This study investigated the clinical efficacy of platelet‐rich plasma (PRP) intravesical injections on IC/BPS patients refractory to conventional therapies. Methods Forty patients received four monthly intravesical injections of 10 mL PRP extracted from 50 mL of whole blood. The primary end‐point was Global Response Assessment (GRA) at 3 months after the 4th PRP injection. Secondary endpoints included changes in O'Leary‐Sant symptom score (OSS), visual analog scale (VAS) of pain, daily frequency, nocturia, functional bladder capacity (FBC), maximum flow rate, voided volume, post‐void residual volume (PVR) from baseline to 3 months after the 4th PRP injection. Results All 40 patients (37 women and 3 men, aged 55.5 ± 11.1 years) completed the four injections and follow‐up visits. GRA improved after the 1st PRP injection and the satisfaction persists till the primary end‐point. The success rate was 45%, 52%, 70%, 70%, and 67.5% after the 1st, 2nd, 3rd, 4th, and 3 months after the 4th PRP injection, respectively. OSS and VAS also significantly decreased. The PVR did not change after repeated PRP injections, FBC increased, frequency, and nocturia were decreased after PRP injections. All patients were free of urinary tract infection or difficulty urinating. Conclusion The study demonstrated that repeated intravesical injections of autologous PRP can increase bladder capacity and provide IC symptom improvement in patients with IC/BPS refractory to conventional therapy. Autologous PRP injection is safe and effective in selected patients.

This study aimed to investigate the diagnostic values of urine cytokines in interstitial cystitis/bladder pain syndrome (IC/BPS) and overactive bladder (OAB) patients, and to develop a novel diagnostic algorithm. Urine samples were collected from 40 IC/BPS, 40 OAB patients, and 30 controls. Commercially available multiplex immunoassays were used to analyze 31 targeted cytokines. Urine cytokine profiles were significantly different among study groups and controls. MIP-1β showed the highest sensitivity (92.2%) for identifying diseased study patients from controls. The cytokines with high diagnostic values for distinguishing between IC and OAB included IL-10, RANTES, eotaxin, CXCL10, IL-12p70, NGF, IL-6, IL-17A, MCP-1, and IL-1RA. The diagnostic algorithm was subsequently developed according to the diagnostic values obtained. MIP-1β was selected for the initial screening test to diagnose diseased patients and controls with diagnostic rates of 81.6% and 68.4%, respectively. As confirmation tests for IC/BPS, the diagnostic rates of eotaxin, CXCL10, and RANTES were 73.3%, 72.7%, and 69.7%, respectively. As the confirmation test for OAB, the diagnostic rate of IL-10 was 60%. Urine cytokine profiles of IC/BPS and OAB patients differed from those of controls and might be useful as biomarkers for diagnosis. A novel pilot diagnostic algorithm was developed based on these profiles.

The objective of the present study was to investigate the diagnostic values of urine cytokines in patients with interstitial cystitis/bladder pain syndrome (IC/BPS) and to identify their correlations with clinical characteristics. Urine samples were collected from 127 patients with IC/BPS [European Society for the Study of Interstitial Cystitis (ESSIC) types 1 and 2] and 28 controls. Commercially available multiplex immunoassays (MILLIPLEX map kits) were used to analyze 31 targeted cytokines. Cytokine levels between patients with IC/BPS and controls were analyzed using ANOVA. Receiver-operating characteristic curves of each cytokine to distinguish IC/BPS from controls were generated for calculation of the area under the curve. Patients with IC/BPS had urine cytokine profiles that differed from those of controls. Between patients with ESSIC type 1 and 2 IC/BPS, urine cytokine profiles were also different. Among cytokines with high diagnostic values (i.e., area under the curve > 0.7) with respect to distinguish patients with ESSIC type 2 IC/BPS from controls, regulated upon activation, normal T cell expressed and presumably secreted (RANTES), macrophage inflammatory protein (MIP)-1β, and IL-8 were of higher sensitivity, whereas macrophage chemoattractant protein (MCP)-1, chemokine (C-X-C motif) ligand 10 (CXCL10), and eotaxin-1 were of higher specificity. In multivariate logistic regression models controlling for age, sex, body mass index, and diabetes mellitus, the urine cytokines with high diagnostic values (MCP-1, RANTES, CXCL10, IL-7, and eotaxin-1) remained statistically significant in differentiating IC/BPS and controls. MCP-1, CXCL10, eotaxin-1, and RANTES were positively correlated with glomerulation grade and negatively correlated with maximal bladder capacity. In conclusion, patients with IC/BPS had urine cytokine profiles that clearly differed from those of controls. Urine cytokines might be useful as biomarkers for diagnosing IC/BPS and mapping its clinical characteristics.

Patients with ketamine cystitis had higher serum IgE than patients with interstitial cystitis/bladder pain syndrome or acute bacterial cystitis, or controls. Serum IgE and the severity of eosinophil infiltration were associated with bladder pain severity and small maximal bladder capacity.

BackgroundElectron microscopy (EM) characteristics of the urothelium in interstitial cystitis/bladder pain syndrome (IC/BPS) and their association with clinical condition are unclear.MethodsTen 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.ResultsCompared 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).ConclusionsThe 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.

Repeated intravesical injections of autologous platelet-rich plasma (PRP) have been shown to improve symptoms in patients with interstitial cystitis/bladder pain syndrome (IC/BPS); however, there is a paucity of objective evidence of the effectiveness of this therapy. In this study, we investigated the changes in urinary markers after PRP treatment. Forty patients with IC/BPS who were refractory to conventional therapy received four injections of PRP at monthly intervals; 10 mL PRP solution with 2.5 times the peripheral blood platelet concentration was used. Urine levels of thirteen functional proteins, growth factors, and cytokines were assessed at baseline and at the 4th PRP injection. The clinical parameters included visual analog scale (VAS) pain score, daily urinary frequency, nocturia episodes, functional bladder capacity, and global response assessment (GRA). The GRA and symptom score significantly decreased post-treatment. In patients with GRA ≥ 2, the success rates at 1 month and at 3 months after the 4th PRP injection were 70.6% and 76.7%, respectively. The VAS pain score, frequency, and nocturia showed a significant decrease (all p < 0.05). Urinary levels of nerve growth factor, matrix metalloproteinase-13, and vascular endothelial growth factor significantly decreased post-treatment (p = 0.043, p = 0.02, and p = 0.000, respectively); platelet-derived growth factor-AB showed a significant increase (p = 0.004) at the 4th PRP treatment compared with baseline. In this study, repeated intravesical PRP injections provided significant symptom improvement in IC/BPS patients with concomitant changes in the related biomarker levels. Trial registration: ClinicalTrial.gov: NCT03104361; IRB: TCGH 105-48-A.