Editorial Comment on Long-Term Clinical Outcome of Transurethral Resection of Hunner Lesions Combined With Bladder Hydrodistention for Patients With Interstitial Cystitis at a Tertiary Center in Japan.

Interstitial cystitis/bladder pain syndrome (IC/BPS) with Hunner Lesions (Hunner Type Interstitial Cystitis or HIC) is characterized by lesions on the bladder wall. Previous work on these lesions identified B cells and monocytes within the lesion. However, the overall role of the adaptive immune system in the disorder remains uncertain. In this study, we performed HLA sequencing on 12 IC/BPS patients with HIC and 7 Non Hunner Type IC (NHIC) patients, and identified HLA-DQB1*02:02 and HLA-DRB1*07:01:01 have a significant association with HIC. This pilot study provides genetic evidence supporting a potential autoimmune component in HIC and may help define the pathogenesis of at least one subtype of IC/BPS, and lay the groundwork for identifying the etiology of IC/BPS as a disease complex. Identifying the mechanisms can also open new approaches to treatment. Identifying an HLA haplotype associated with HIC would indicate that it is autoimmune.

Management algorithms for Bladder Pain Syndrome (BPS) have remained stagnant over the past 20 years. Lack of high level evidence has hindered progress. Contributors to this have been the use of confusing and inconsistent terminology and failure to adequately phenotype participants entering clinical trials. At the International Consultation on Incontinence Research Society (ICI-RS) meeting in 2025 a Think Tank addressed the question of "How can we make progress in the management of Bladder Pain Syndrome," focussing on the non-Hunner lesion group. The Think Tank conducted a literature review and expert consensus meeting focusing on the current limitations in terminology and phenotyping, how we can improve identification of bladder-centric BPS, and how we can improve assessment of psychological comorbidity. Terminology needs to be standardised to enable more homogenous recruitment to clinical trials. Use of the term "interstitial cystitis" may be misleading, and the term is often inappropriately used. Classification based on the European Association of Urology guidelines should be favoured, using the term Primary Bladder Pain Syndrome. Participants entering clinical trials need to undergo thorough investigation to enable accurate phenotyping. The non-Hunner lesion BPS group need to be the focus of future research. Tools to aid identification of a bladder-centric phenotype (through biopsy and other techniques) need to be studied, including investigating the roles of inflammation, ischaemia and oxidative stress in this condition. A psychological assessment tool specific for BPS should be created to ensure earlier psychological intervention for those who would benefit most. The use of accurate terminology in describing this condition is the first step toward improving the quality of future research. The Think Tank overwhelmingly recommended that the term "Interstitial Cystitis" should not be used. Future studies should be focussed on understanding the BPS group, excluding those with Hunner lesion disease. Studying inflammation, ischaemia and oxidative stress will help to identify a bladder-centric phenotype, whereas improving our understanding of psychological mechanisms will help to direct psychological therapies more effectively.

BPS symptom load during pentosane polysulfate sodium treatment in real life in France.

Chronic bladder pain syndrome (CBPS) is a debilitating condition with limited treatment efficacy. This meta-analysis evaluates the effectiveness of sacral nerve stimulation (SNS) in the management of pain, urinary symptoms, and quality of life (QoL) in patients with CBPS. A systematic review was conducted across EMBASE, PubMed, and the Cochrane Library, adhering to Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Studies involving adult patients with bladder pain symptoms treated with SNS and reported pain scores were included. Pain scores were the primary outcome measure of interest. Secondary outcome measures included Interstitial Cystitis Problem Index (ICPI)/Interstitial Cystitis Symptom Index (ICSI), urinary frequency, nocturia, and QoL. Risk of bias was assessed using Risk Of Bias In Non-randomized Studies-of Interventions, and pooled effect estimates were calculated using random-effects meta-analysis models. A total of 15 studies (N = 494) were included in the meta-analysis. SNS was associated with a statistically significant reduction in pain scores (mean difference: -2.27 on a 0-10 scale, 95% CI: -2.94 to -1.60, p < 0.001), ICSI (-2.18, 95% CI: -2.99 to -1.37, p < 0.001), urinary frequency (-1.71 voids/d, 95% CI: -2.29 to -1.12), and nocturia (-1.49 episodes/night, 95% CI: -2.35 to -0.63). Changes in ICPI and QoL were not statistically significant. Complication rates ranged from 0% to 40.6%, and explantation rates from 0% to 18%. This meta-analysis suggests that SNS may offer clinically meaningful pain and urinary symptom relief in patients with CBPS. However, substantial methodological heterogeneity, moderate-to-high risk of bias, and the absence of randomized control trials limit the strength of conclusions. Larger, high-quality trials with standardized diagnostic criteria and outcome measures are essential to establish SNS as a validated treatment option for CBPS.

ABSTRACT Introduction: This study analyzes clinical associations of pain in young men presenting with a primary complaint of a lower urinary tract symptom (LUTS). Methods: A secondary analysis of the SciCOM 3 study examining young men presenting with LUTS was performed. Bladder pain was recorded by Q4 of the Interstitial Cystitis Symptom Score, while nonbladder pain was captured by the Visual Analog Scale. LUTS, sexual dysfunction, stool consistency, perception of problems related to the bladder, and general well-being were captured by questionnaires. Results: A total of 448 young men (18–40 years; median 30 years, interquartile range: 25–35 years) were studied across 16 centers. Eighty-seven (19.8%) reported no pain (Group 1), 143 (32.6%) bladder pain alone (Group 2), 39 (8.9%) only nonbladder pain (Group 3), and 170 (38.7%) both bladder and nonbladder pain (Group 4). Men in Group 4 were more likely to report reduced strength of stream (odds ratio [OR] 1.95; 95% confidence interval [CI]: 1.27 and 3.01), need to stop and start (OR 1.81; 95% CI: 1.19 and 2.74), sense of incomplete evacuation (OR: 2.64; 95% CI: 1.58 and 4.40), and urgency (OR: 1.73; 95% CI: 1.16 and 2.59), while men in Group 2 were more likely to report urine leak for no apparent reason (OR: 1.85; 95% CI: 1.17 and 2.90). Group 1 was the least likely to report an abnormal sense of well-being. Conclusions: Pain is commonly reported by young men presenting with LUTS. The pattern of pain in LUTS is associated with a distinct clinical epidemiology, including both storage and voiding LUTS, with an impact on bother and quality of life. It is important to assess pain in young men presenting with LUTS.

Interstitial cystitis (IC) is a chronic pelvic condition in the absence of other pathology leading to significant morbidity with limited available treatment options. Cystoscopic hydrodistension (HD) remains an offered intervention for diagnosis and management, providing temporary relief in some patients. There is no overall consensus regarding the optimal duration of HD. This systematic review aims to comprehensively assess the existing literature to identify if there is a relationship between HD time and treatment efficacy. A systematic search in MEDLINE, Embase, and PubMed between January 1969 to April 2024 was performed to identify relevant articles investigating the efficacy of HD as a sole treatment for IC. Two independent reviewers screened abstracts and full texts, and a third resolved conflicts. Quality assessment was performed by two independent blinded authors using The Risk Of Bias In Non-randomized Studies - of Interventions (ROBINS-I) assessment tool. Data regarding population characteristics, duration of HD, treatment number and method, outcome measurements and values were extracted. Included articles were subcategorized into standard (< 15 min) and prolonged (> 15 min) HD durations. A total of 1404 patients in 14 studies were included. Ten studies were prospective or retrospective cohort studies, and four were randomized controlled trials. Nine trials investigated the effect of HD for 15 min or less. Of these, four demonstrated no statistically significant differences in preoperative and post operative symptoms and voiding function between 1 month and 6 months. Four trials found significant improvement in subjective patient symptom scores. Of these, one study investigated two groups of different HD times via different surgeons, and found significant improvements in pain scores for patients in those undergoing HD for 2 min (Pre: 2.4 vs. Post: 5.5) and over 5 min (Pre: 1.3 vs. Post: 3.6). A final study found a time to therapeutic failure post 3 min HD of 25.2 months. Five trials performed prolonged HD between 30 min to 2 h in a total of 152 patients. All were older studies (1977-2003) and performed HD under spinal or local anesthetic. These studies demonstrated long term symptomatic improvement in included participants (32.3%-67.3%) with follow up durations of 7 months to 3.2 years. Overall risk of bias across domains was assessed as high between included studies. HD remains a contentious treatment option for IC, with limited long-term results in the literature. Our study suggests longer HD times may result in improved efficacy and duration of symptom relief but in the setting of potentially increased risks of severe complications including bladder perforation. Risk of bias, observational study designs, heterogeneity, and lack direct comparisons in durations of HD limits our conclusions. This review underscores the need for larger, prospective trials determining the effects of HD duration on treatment efficacy.

Research on female patients with bladder pain syndrome/interstitial cystitis (BPS/IC) who have urethral, vaginal, perineal, or anal pain (pelvic-perineal pain, PPP) remains limited. This retrospective study characterized their clinical features and treatment outcomes. From 2013 to 2023, a total of 130 female patients with BPS/IC were enrolled. Treatments included hydrodistension with Hunner lesion resection (when present), oral/intravesical medications, and pudendal nerve block for significant PPP. Recurrences were managed with repeat therapy or advanced options (platelet-rich plasma, botulinum toxin, sacral neuromodulation), with urinary diversion as the last resort. Among the cohort, 24 patients (18.46%) were identified as having PPP. These patients were significantly older and had higher symptom scores than those without PPP (all p < 0.05). The PPP group exhibited a higher prevalence of cystoscopic grade 4 lesions and a smaller anesthetic bladder capacity. Furthermore, within the PPP cohort, the presence of grade 4 lesions and a bladder capacity ≤ 400ml were significant predictors of poor treatment outcome. Over a median follow-up of 74.8months, although overall improvement was not statistically different from a severity-matched control group, treatment failure necessitating urinary diversion occurred exclusively in the PPP group (12.5% vs 0%, p = 0.013). Furthermore, the PPP group required significantly more therapeutic interventions per patient (1.96 vs 1.17, p = 0.001). A subset of female patients with BPS/IC presents who had concomitant PPP, which identifies a more severe disease phenotype characterized by objective markers of severity and a higher risk of treatment failure. The assessment of PPP serves as a straightforward and valuable prognostic marker in clinical practice.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic inflammatory bladder disorder characterized by pelvic pain and urinary symptoms, yet effective therapeutic options remain limited. Baicalin (BA), a bioactive flavonoid derived from Scutellaria baicalensis, exhibits anti-inflammatory and antioxidant properties, though its role in IC/BPS has not been fully elucidated. This study demonstrates that BA significantly ameliorates cyclophosphamide-induced urination frequency and bladder tissue damage and reduces serum levels of pro-inflammatory cytokines, including TNF-α, IL-6, and IL-1β, in a rat model of IC/BPS. Integrated analysis of network pharmacology, metabolomics, molecular docking, and experimental validation elucidated the potential mechanism by which BA treats IC/BPS through regulation of the TLR4/NF-κB signaling pathway.Network pharmacological analysis identified 13 core targets, and both KEGG pathway enrichment and metabolomics results indicated significant enrichment of the NF-κB signaling pathway. Molecular docking confirmed strong binding affinities between BA and TLR4, MYD88, and NF-κB p65, with binding energies below - 7.0kcal/mol. Western blot analysis further verified that BA treatment downregulated the expression of these key signaling molecules. These results indicate that BA alleviates IC/BPS primarily by suppressing the TLR4/NF-κB pathway, thereby attenuating inflammation and restoring metabolic balance. Our findings provide a mechanistic basis for the application of BA in IC/BPS treatment and support its potential for clinical translation.

While many patients with lower urinary tract symptoms (LUTS) improve by treating peripheral causes, a substantial proportion continue to experience symptoms despite apparently successful interventions. Central nervous system (CNS) mechanisms could potentially contribute to persisting symptoms after the initial peripheral cause has been treated. The aim of this paper is to explore how maladaptive CNS processes may underlie refractory LUTS and to consider the therapeutic and research implications. The manuscript summarizes discussions from a proposal hosted at the 2025 International Consultation on Incontinence-Research Society (ICI-RS) meeting. Research priorities were formulated into consensus questions. Evidence indicates that central sensitization and neuroplasticity may sustain urgency, increased frequency, or pain even after resolution of peripheral triggers. Neuroimaging demonstrates structural and functional brain changes in bladder pain syndrome and spinal cord injury, while preclinical studies implicate neurotrophin and nitric oxide pathways in LUT dysfunction. Nerve stimulation, intravesical agents, and behavioral strategies can benefit selected patients, though with variable outcomes. Priority questions focus on causality versus consequence of CNS changes, the development of biomarkers for patient stratification, and the evaluation of novel therapeutic targets. Refractory LUTS potentially involve peripheral and/or central maladaptation. Advancing diagnosis and treatment will require improved tools to assess LUT-CNS interactions, refined translational models, and multidisciplinary strategies to enable individualized, mechanism-based therapies.

Imaging Mass Cytometry Immune Profiling of Hunner Lesions in a Convenience Sample of Patients With Interstitial Cystitis/Bladder Pain Syndrome.

BACKGROUND: Bladder pain syndrome / interstitial cystitis is a chronic condition characterized by bladder pain and dysuria in the absence of identifiable local abnormalities. Despite its clinical and social significance, data on long-term efficacy of treatment remain limited. AIM: The work aimed to evaluate the long-term efficacy of minimally invasive surgical treatment in women with bladder pain syndrome. METHODS: A total of 29 women with bladder pain syndrome refractory to standard conservative therapy were followed up for at least 5 years. Patients were divided into two groups: Group 1 included 20 patients without Hunner’s lesions, and Group 2 included 9 patients with Hunner’s lesions. All patients initially underwent cystoscopy with bladder hydrodistension; in the presence of Hunner’s lesions, laser ablation was performed. Subsequent endoscopic procedures were carried out upon symptom recurrence. Patients without Hunner’s lesions underwent hydrodistension combined with intravesical botulinum therapy, whereas in patients with Hunner’s lesions, these interventions were supplemented by laser ablation. RESULTS: Treatment efficacy was assessed by analyzing the time intervals between repeated surgical procedures performed in response to worsening bladder pain syndrome symptoms. The mean time interval between interventions in Group 1 was significantly longer than in Group 2 (9.4 ± 1.2 months vs. 6.9 ± 1.0 months). Significant intergroup differences were observed beginning with the time interval between the second and third procedures. Group 1 demonstrated a progressive increase in the duration of these time intervals. No such trend was observed in Group 2. During the long-term 5-year follow-up period, no significant changes in maximum bladder capacity were detected in either group. CONCLUSION: Minimally invasive surgical treatment for bladder pain syndrome has a high long-term efficacy rate, with no tendency of worsening outcomes. Therapeutic modalities, their sequence, and frequency should be selected on a case-by-case basis.

Overactive bladder (OAB) and primary bladder pain syndrome (PBPS) are among the most common lower urinary tract dysfunctions. The authors note the similarities between many aspects of OAB and PBPS, particularly their pathogenesis, symptoms, and clinical course. Thus, similar infectious and non-infectious factors may play a role in the development of these conditions. The authors’ assertion that the insufficient effectiveness of standard therapy in patients with OAB and PBPS may be due to its limited effect on the afferent signaling system responsible for bladder hypersensitivity, chronic bladder wall inflammation, which maintains high levels of afferent activity, and central sensitization, which makes pharmacotherapy acting at the bladder level ineffective. The authors proposed the concept of hypersensory bladder disease, which combines the hypersensory phenotypes of OAB and PBPS. This concept is not without controversy, but it deserves close attention and further study, as it will allow for individualized treatment and tailored therapy based on the pathogenetic and clinical characteristics of these conditions.

Integrative Diagnostic Model Combining Urinary Biomarkers and Clinical Parameters to Improve Diagnostic Performance in Interstitial Cystitis/Bladder Pain Syndrome

We aimed to assess the effects of intravesical cocktail instillation on the outcomes and serum pain factors of patients with bladder pain syndrome (BPS). The clinical data of 86 female BPS patients hospitalized between March 2017 and March 2024 were collected for retrospective analysis. All patients were treated with oral medication (amitriptyline) + local intravesical instillation of drugs, and then assigned to a control group (sodium hyaluronate intravesical instillation) and a research group [intravesical instillation of dimethyl sulfoxide (DMSO) + chondroitin sulfate (CS) + low-molecular-weight heparin (LMWH) cocktail]. The research group (n=43) had lower urination frequency in 24 h, Pelvic Pain and Urgency/Frequency Patient Symptom Scale score, and O'Leary-Sant interstitial cystitis symptom index and interstitial cystitis problem index, as well as larger single urination volume than those of the control group (n=43) after 3 and 6 months of treatment (P<0.05). In the serum, the levels of substance P (SP), 5-hydroxytryptamine (5-HT), prostaglandin E2 (PGE2), neuropeptide Y (NPY), β-endorphin (β-EP), and dopamine (DA) declined in the two groups after 1 month of treatment in comparison to the pre-treatment levels. The levels of SP, 5-HT, PGE2, and NPY were lower, while the levels of β-EP and DA were higher in the research group than those in the control group (P<0.05). The intravesical instillation of DMSO + CS + LMWH cocktail is superior in long-term outcomes. It is more conducive to improving the levels of serum pain factors, with a good safety profile and without increasing adverse reactions.

Evaluate current knowledge of the physiological and clinical consequences of oxidative stress on the development of lower urinary tract dysfunction (LUTD), identify clinically relevant biomarkers and potential therapeutics. This review summarizes topics discussed during Proposal #7 at the International Consultation on Incontinence Research Society 2025 meeting and derives a consensus of future research directions. Pelvic ischemia/hypoxia can result in LUTD including detrusor over-/underactivity, bladder pain syndrome and nocturia. Major causes of bladder ischemia include aging, atherosclerosis and bladder outlet obstruction. The bladder wall undergoes physiological cycles of ischemia and reperfusion with normal filling and emptying: thus, infrequent voiding habits, co-morbidities and some medications can exacerbate LUTD. Ischemia can lead to oxidative stress which is an increase in reactive oxygen species (ROS), superoxide and the hydroxyl radical, over enzymatic antioxidants, superoxide dismutase and glutathione peroxidase. ROS can be generated by monoamine, xanthine and nicotinamide adenine dinucleotide phosphate oxidases, but the main source is dysfunctional mitochondria. Biomarkers of oxidative stress such as 8-hydroxydeoxyguanosine, indicative of DNA damage, can be measured in plasma and urine. Soluble guanylate cyclase activators have been recently demonstrated to have beneficial actions in several LUTD by ameliorating prostatic hyperplasia, bladder overactivity, cellular senescence and fibrosis. Many LUTD were identified as having links to oxidative stress. There are still questions regarding correlation of the severity of oxidative stress to LUTD symptomology, the selectivity of biomarkers and the most efficacious druggable target. These were considered key research directions for future studies.

Interstitial cystitis is a complex, highly challenging chronic inflammatory condition that is most predominant in women. It is characterised by persistent pain in the bladder and pelvis area and an urgent and frequent need to urinate during the day and at night. Despite the chronic and burdensome nature of interstitial cystitis, the lived experiences of women suffering from it have been inadequately explored. We sought to acquire in-depth knowledge and insights into the experiences of Norwegian women living with interstitial cystitis. A qualitative approach was used with an exploratory descriptive design, using the participants' own written stories of living with interstitial cystitis. The data were analysed using a reflective thematic analytic method. Three main themes came to the fore: (1) interstitial cystitis impacts every aspect of life, (2) struggling to be believed and heard, and (3) struggling to access personalised treatment for symptom alleviation. Interstitial cystitis is a complex condition that negatively impacts women's physical, mental, and sexual health. Women with interstitial cystitis may face disbelief and medical gaslighting compounded by a lack of awareness about the condition, which hinders their access to tailored treatment and care. The findings emphasise the need for competence and empathy among healthcare professionals and underscore the importance of an increased focus on conditions predominantly affecting women.

The standard questionnaire for evaluated patients with bladder pain syndrome/interstitial cystitis (BPS/IC) is the O'Leary-Sant questionnaire, of which there is no validated Italian version. The objective of this study was to translate the O'Leary-Sant and validate it for Italian patients. We enrolled BPS/IC patients (aged over 18years) alongside an age-matched control group without BPS/IC (healthy-volunteers). Inclusion criteria for BPS/IC patients: diagnosis of BPS/IC-according to the definition of the International Society for the study of bladder pain syndrome, ESSIC-and no specific treatment for BPS/IC. The study was approved by our institutional review board. We translated the questionnaire following the common guidelines for this process. All the enrolled women then answered the translated questionnaire at baseline and 2 weeks later. Cronbach's alpha; interclass correlation coefficient; Fisher-Freeman-Halton's exact test or Student's t-test when appropriate; Pearson's r. Between February 2022 and March 2023, we enrolled 102 BPS/IC patients and 51 healthy volunteers controls. Data analysis demonstrated: internal consistency between the two versions of the questionnaire; reproducibility for total scores and all single items in both indexes of O'Leary-Sant; discriminatory ability of the questionnaire between patients' mean scores and controls in both indexes and in single items; highly significant direct correlations between scores in the same domain and with the other domain (construct validity). Our study demonstrates that our Italian version of the O'Leary-Sant questionnaire is a reliable, consistent, and valid instrument to evaluate symptoms of Italian speakers with BPS/IC.

To develop a drug-releasing intravesical floating technology (DRIFT) device for controlled sequential delivery of gemcitabine and docetaxel (Gem/Doce) to optimise the treatment of non-muscle-invasive bladder cancer (NMIBC) while enabling patient mobility and self-removal, as sequential intravesical Gem/Doce has been increasingly utilised but has logistical limitations requiring prolonged clinic visits and patient immobilisation. The DRIFT device features a three-dimensional printed perforated tube with latex sleeve, dissolvable polyvinyl acetate and polyvinylpyrrolidone end cap with adjustable fluorinated polymer (FluoroPel) coating, and patient-removal suture. A 14-F catheter is placed and intravesical gemcitabine is instilled. The deflated DRIFT device is inserted via catheter and inflated with docetaxel and air. The catheter is removed, allowing gemcitabine to dwell temporarily and be voided by the patient. The DRIFT device remains in the bladder and subsequently releases docetaxel in a controlled, delayed fashion, followed by patient removal. Its flexible, buoyant design supports patient mobility and maintains unimpeded urinary flow. Dissolution kinetics were evaluated using methylene blue, device performance was assessed in Merino sheep, and docetaxel tissue penetration was evaluated in rabbit bladder tissue using high-performance liquid chromatography analysis. The DRIFT device demonstrated adaptable drug release through FluoroPel coating optimisation, with dissolution times extending significantly from zero to three coatings (P < 0.001). Docetaxel release kinetics plateaued between 2.0 and 3.0 mL volumes. Sheep studies revealed similar timed drug release as in vitro testing. Escalating gemcitabine concentrations enhanced docetaxel tissue penetration, with peak concentrations reaching 0.45 vs 0.08 mg/mL in controls. Extended gemcitabine dwell time (up to 4 h) further improved docetaxel delivery, achieving significant enhancement in deep tissue penetration (P < 0.001). The DRIFT enables controlled sequential delivery of Gem/Doce, reliably maintaining docetaxel containment for up to 120 min during gemcitabine pre-treatment. Future in vivo validation will establish safety and therapeutic potential. This platform has broader applications beyond NMIBC, including urinary tract infections and interstitial cystitis.

Injectable pentosan polysulfate: A novel cause of heparin-induced thrombocytopenia and stroke