Explore the vast range of titles available.

Bladder pain syndrome (BPS) is a chronic condition characterized by pelvic pain or pressure which is perceived to be originating from the bladder, accompanied by one or more urinary symptoms, including frequency, urgency and nocturia. The precise etiology of BPS is not fully understood. Chronic bacterial infection, defective glycosaminoglycan (GAG) layer of the bladder urothelium, inappropriate activation of mast cells in the suburothelial layer of the bladder, autoimmune-mediated mechanisms and autonomic nervous system dysfunction have all been implicated. Treatments targeted at each of these mechanisms have been developed with mixed outcomes. High-quality research into the treatment options is lacking and it is difficult to draw definite conclusions. The treatment approach is multimodal and should be patient specific, targeting the symptoms which they find most bothersome. Conservative treatment, including patient education, behavioural modification, dietary advice, stress relief and physical therapy is an essential initial management strategy for all patients. If no response is observed, oral treatments such as amitriptyline are likely to offer the greatest response. Cystoscopy is essential to phenotype patients, and Hunner lesion directed therapy with fulguration or resection can be performed at the same time. Intravesical instillation of DMSO or lidocaine, detrusor injections of botulinum toxin A and neuromodulation can be used if initial management fails to improve symptoms. Oral cyclosporin can be trialled in those experienced with its use; however, it is associated with significant adverse events and requires intense monitoring. Lastly, radical surgery should be reserved for those with severe, unremitting BPS, in which quality of life is severely affected and not improved by previously mentioned interventions. Future work investigating exact aetiological factors will help target the development of efficacious treatment options, and several promising oral and intravesical treatments are emerging.

Background To evaluate the efficacy of submucosal injection of triamcinolone acetonide for the treatment of type II/III interstitial cystitis/bladder pain syndrome. Methods A retrospective analysis of the clinical data of type II/III interstitial cystitis/bladder pain syndrome patients treated in our department from April 2016 to August 2018 was conducted, and changes in International Prostate Symptom Scores and the Pelvic Pain and Urgency/Frequency symptom scale after surgery were evaluated to explore factors that may affect patient outcomes. Results A total of 27 female patients and 8 male patients were enrolled, with type II patients accounting for 62.9% of the sample, and the median follow-up duration was 31 months (range: 12–40 months). Twenty-two patients (74.3%) had significantly improved questionnaire scores at 4 weeks postoperatively. Treatment efficacy was sustained for at least 1 year in 15 patients, and persistent effectiveness was noted in 10 (28.6%) patients. Patients with an advanced age ( p  = 0.015), high pain scores ( p  = 0.040), and higher International Prostate Symptom Scores ( p  = 0.037) and Pelvic Pain and Urgency/Frequency symptom scale scores ( p  = 0.020) were more likely to benefit from submucosal injection of triamcinolone acetonide. Gender, disease duration, and the presence of Hunner’s lesions had no predictive value for treatment outcomes. Conclusion Submucosal injection of triamcinolone acetonide can improve the clinical symptoms and quality of life in both men and women with type II/III interstitial cystitis/bladder pain syndrome. Patients with an advanced age and more severe interstitial cystitis/bladder pain syndrome related symptoms may benefit more from triamcinolone acetonide injection.

Abstract There are still no definite treatment modalities for interstitial cystitis (IC). Meanwhile, stem cell therapy is rising as potential alternative for various chronic diseases. This study aimed to investigate the safety of the clinical-grade mesenchymal stem cells (MSCs) derived from human embryonic stem cells (hESCs), code name MR-MC-01 (SNU42-MMSCs), in IC patients. Three female IC patients with (1) symptom duration >6 months, (2) visual pain analog scale (VAS) ≥4, and (3) one or two Hunner lesions <2 cm in-office cystoscopy within 1 month were included. Under general anesthesia, participants received cystoscopic submucosal injection of SNU42-MMSCs (2.0 × 107/5 mL) at the center or margin of Hunner lesions and other parts of the bladder wall except trigone with each injection volume of 1 mL. Follow-up was 1, 3, 6, 9, and 12 months postoperatively. Patients underwent scheduled follow-ups, and symptoms were evaluated with validated questionnaires at each visit. No SNU42-MMSCs-related adverse events including immune reaction and abnormalities on laboratory tests and image examinations were reported up to 12-month follow-up. VAS pain was temporarily improved in all subjects. No de novo Hunner lesions were observed and one lesion of the first subject was not identifiable on 12-month cystoscopy. This study reports the first clinical application of transurethral hESC-derived MSC injection in three patients with IC. hESC-based therapeutics was safe and proved to have potential therapeutic efficacy in IC patients. Stem cell therapy could be a potential therapeutic option for treating IC. Graphical Abstract The current manuscript describes the clinical trials of human embryonic stem cell (hESC)-derived multipotent mesenchymal stem cells (MMSCs) for patients with interstitial cystitis (IC). We provide the clinical importance and advance that cystoscopic submucosal injection of the hESC-derived MMSC was safe and exhibited potential therapeutic efficacy in human subjects, without no adverse events.

This study aimed to elucidate distinct cellular and immunological characteristics associated with chronic inflammatory conditions of the urinary bladder, including Hunner-type interstitial cystitis (HIC), bacillus Calmette–Guérin (BCG)-related cystitis, follicular cystitis (FC), and chronic bacterial cystitis (CBC). Transcriptomic analyses using next-generation RNA sequencing, along with quantitative polymerase chain reaction, were performed on mucosal bladder biopsies to assess the whole transcriptional and immune-response profiles. Furthermore, digital immunohistochemical quantification evaluated urothelial denudation and the densities of infiltrating immune cells, including T-lymphocytes, B-lymphocytes, mast cells, and plasma cells. HIC specimens exhibited a markedly distinct transcriptional profile, with 3,566 differentially expressed genes and enrichment of 116 biological processes particularly associated with microbial response and heightened autoimmunity with Th1/Th17 axis polarization. Histologically, HIC bladders demonstrated significant epithelial denudation, elevated IL-17-positive cell density, and increased plasma cell ratios compared to other cystitis types. No significant differences were observed in overall lymphoplasmacytic or mast cell densities, nor in B cell ratios among the groups. These findings underscore a unique immunopathological signature in HIC, characterized by plasma cell predominance within a Th1/17-polarized immune environment and epithelial denudation, offering new insights into its pathogenesis and therapeutic targeting.

This study investigated the safety and efficacy of MR-MC-01, a mesenchymal stem cell therapy derived from human embryonic stem cells, in patients with interstitial cystitis (IC), particularly those with Hunner lesions unresponsive to pentosan polysulfate sodium (PPS). Conducted as a prospective, randomized, double-blind, placebo-controlled phase I/IIa clinical trial, it enrolled 22 patients, with six completing phase I and 16 participating in phase IIa. Phase I tested 2 doses (2.0 × 107 and 5.0 × 107 cells) to determine the maximum tolerated dose (MTD), revealing no dose-limiting toxicities and only mild adverse events such as transient hemorrhage and bladder pain. In phase IIa, 12 participants received the MTD of 5.0 × 107 cells, and 4 received placebo. Significant reductions in interstitial cystitis questionnaire (ICQ) and pain urgency frequency (PUF) scores were observed in the treatment group. Improvements were noted in nocturnal voiding frequency and Hunner lesion size, with 8 patients showing either a reduction or complete resolution of lesions after 6 months. The global response assessment (GRA) reported moderate to marked improvement in 41.67% of treated patients versus 25% in the placebo group. MR-MC-01 demonstrated no serious drug-related adverse events, highlighting its favorable safety profile. These findings suggest that MR-MC-01 not only alleviates symptoms but also promotes structural recovery in IC, making it a promising treatment option. Further large-scale, long-term studies are warranted to confirm these results and optimize therapeutic protocols. (Identifier: NCT04610359)

Introduction and hypothesisWe investigated the effects of locally administered human multilineage-differentiating stress enduring (Muse) cells, nontumorigenic pluripotent-like endogenous stem cells, on bladder tissues, function, and nociceptive behavior in a chemically induced Hunner-type interstitial cystitis (HIC)-like rat model without immunosuppressant.MethodsChemical cystitis was induced by intravesical instillation of 0.2 N hydrochloride (HCl) for 15 min in female F344 rats. SSEA-3+ Muse cells, SSEA-3− non-Muse cells or Hanks' balanced salt solution (HBSS; vehicle) were injected into the anterior and posterior bladder wall at each 1×104 cells/10 μl 6 h after HCl application. The sham group received HBSS without HCl instillation. Urinary frequency was assessed using metabolic cages, cystometrograms, nociceptive behavior, and histological analysis of the bladder and L6 spinal cord.ResultsIncreases in urinary frequency and decreases in bladder capacity compared with the sham group were observed in the vehicle and non-Muse groups, but not in the Muse group, at 1 week. Significant increases in nociceptive behavior compared with the sham group and the expression of TNFα in the bladder and c-Fos in the bilateral dorsal horns of L6 spinal cord were also observed in the vehicle and non-Muse groups, whereas these changes were not seen in the Muse group at 1 week. Histological analysis exhibited a higher proportion of injected Muse cells remaining in the urothelial basal layer and lamina propria of the bladder than non-Muse cells until 4 weeks.ConclusionsMuse cell therapy could be a promising modality for treating HIC.

Since the development of modern cultivation and sequencing techniques, the human microbiome has increasingly become the focus of scientific attention. Even in the bladder, long considered to be a sterile niche, a highly variable and complex microbial colonization has now been demonstrated. Especially in the context of diseases such as interstitial cystitis, whose etiopathogenesis is largely unknown, and whose diagnosis is based on a process of exclusion of confusable diseases, science hopes to gain far-reaching insights for etiology and diagnosis, including the identification of potential biomarkers. While for functional disorders such as urge urinary incontinence and overactive bladder syndrome, initial associations have been demonstrated between reduced microbial diversity and increased symptomatology, as well as shifts in the abundance of specific microorganisms such as Lactobacillus or Proteus, studies in interstitial cystitis show conflicting results and have failed to identify a putative organism or urotype that clearly distinguishes the urinary microbiome of patients with IC/BPS from that of healthy controls. At the present time, therefore, the new insights into the bladder microbiome and its potential influence on urologic disease cannot yet be used in the context of elucidating possible etiopathogenetic causes, as well as in the use of a biomarker for diagnostic or prognostic purposes. Further studies should focus primarily on uniform procedures and detection methods to achieve better comparability of results and increase the likelihood of detecting hidden patterns.

Introduction and hypothesis Cystoscopy has been routinely performed in patients suspected to be suffering from bladder pain syndrome/interstitial cystitis (BPS/IC) across the globe. The methodology reported by various guidelines appears to have differences in the techniques and hence there is a need for a review of all those techniques in order to arrive at a consensus. The aim was to review the literature describing the prevalent techniques of cystoscopy for patients of BPS/IC and try to evolve a consensus. Methods The group the Global Interstitial Cystitis, Bladder Pain Society (GIBS) has worked collectively to systematically review the literature using the key words, “Cystoscopy in Hunner’s lesions, bladder pain syndrome, painful bladder syndrome and interstitial cystitis” in the PubMed, COCHRANE, and SCOPUS databases. A total of 3,857 abstracts were studied and 96 articles referring to some part of technique of cystoscopy were short-listed for review as full-length articles. Finally, six articles with a description of a technique of cystoscopy were included for final tabulation and comparison. The group went on to arrive at a consensus for a stepwise technique of diagnostic and therapeutic cystoscopy in cases of BPS/IC. This technique has been compared with the previously described techniques and may serve to be a useful practical guide for treating physicians. Conclusion It is important to have a uniform standardized technique for performing a diagnostic and therapeutic cystoscopy in patients with BPS/IC. Consensus on one such a technique has been arrived at and described in the present article.

PurposeThe primary purpose of this study was to evaluate the effect of the fatty acid amide hydrolase (FAAH) inhibitor ASP3652 on efficacy and safety in patients with Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS). The secondary purpose was to evaluate phenotyping based on Hunner’s lesions (HL).MethodsIn this randomized trial, adult female patients with moderate/severe IC/BPS received 12 weeks of treatment with an oral dose of ASP3652 (50, 150, or 300 mg twice daily) or placebo. A Bayesian model was employed using accumulating data to adjust the randomization probability and to analyze the primary efficacy variable (change from baseline to end of treatment in Mean Daily Pain [MDP; range 0–10]). Study outcomes and patient characteristics of patients with and without HL (HL+ and HL−) were compared.ResultsIn total, 287 patients were randomized. The 300 mg dose group (n = 97) showed the largest effect, i.e., a mean change from baseline to end of treatment of −1.73 in MDP. However, the mean difference from placebo was 0.02. The probability that this dose was better than placebo was 13.5%. Adverse event incidence was low and similar between study groups. HL+ patients were older and had more severe symptoms than HL−. An association was suggested in HL+ patients between changes in micturition frequency and MDP (R = 0.41 [95% CI 0.18, 0.63]), which was not observed in HL− (R = 0.04 [95% CI −0.16, 0.29]).ConclusionASP3652 was safe and well tolerated, but did not show efficacy in IC/BPS. The observed differences between HL+ and HL− suggest that IC/BPS diagnosis and treatment may be approached differently in these two phenotypes.Trial registration: EudraCT number 2011-004555-39, date of registration: 2012-05-07.

The aim of this study was to identify novel genetic features of Hunner's lesion interstitial cystitis (HIC) via comprehensive analysis of the Gene Expression Omnibus (GEO) database. The GSE11783 and GSE28242 datasets were downloaded from GEO for further analysis. Differentially expressed genes (DEGs) were identified and analyzed for functional annotation. The diagnostic markers for HIC were screened and validated using the least absolute shrinkage and selection operator (LASSO) logistic regression and support vector machine recursive feature elimination (SVM-RFE) algorithms. Finally, the cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) algorithm was adopted to investigate the correlation between immune cell infiltration and diagnostic markers in HIC. A total of 7837 DEGs were identified in GSE11783 and 1583 DEGs in GSE28242. Venn diagrams were used to obtain 16 overlapping upregulated and 67 overlapping downregulated DEGs separately. The LASSO logistic model and SVM-RFE algorithm were used to identify 6 genes including KRT20, SLFN11, CD86, ITGA4, PLAC8, and BTN3A3 from DEGs as diagnostic markers for HIC. Their diagnostic potential in HIC and bladder pain syndrome/interstitial cystitis (BPS/IC) were acceptable. PLAC8 exhibited the best diagnostic performance in BPS/IC with an area under the curve of 0.916. The results of immune infiltration involving GSE11783 revealed that the plasma cell ratio ( = 0.017), activated memory CD4+ T cells ( = 0.009), activated dendritic cells ( = 0.01), eosinophils ( = 0.004), and neutrophils ( = 0.03) were significantly higher in HIC than in normal samples, in contrast to resting mast cells ( = 0.022). A positive correlation existed between diagnostic markers and infiltrating immune cells. KRT20, SLFN11, CD86, ITGA4, PLAC8, and BTN3A3 represent novel and potent diagnostic markers for HIC. They also exhibit certain diagnostic potential in BPS/IC. Immune cell infiltration might play a key role in the pathogenesis and progression of BPS/IC.