Efficacy and Safety of Low-dose Oral Prednisolone for Patients with Refractory Hunner-type Interstitial Cystitis.

Background: Hunner-type interstitial cystitis (HIC) is an immunological, chronic inflammatory disease. The efficacy of corticosteroid as a treatment for HIC is unclear. Objective: To assess the efficacy and safety of low-dose oral prednisolone (PSL) treatment for patients with refractory HIC. Design setting and participants: This retrospective observational study reviewed the clinical outcomes of 31 patients with refractory HIC who received oral PSL daily (initial dose, 5.0 or 7.5 mg) for at least 12 mo between 2016 and 2023. The dose was tapered to the minimum that maintained symptom relief during follow-up. Outcome measurements and statistical analysis: Treatment outcomes were evaluated using a seven-graded global response assessment (scores ≥+2, moderately or markedly improved, were defined as treatment response), O'Leary and Sant symptom and problem indices (OSSI/OSPI), overactive bladder symptom score (OABSS), an 11-point pain intensity numerical rating scale, a quality of life (QOL) score, and frequency-volume chart variables. Related complications were also documented. Results and limitations: The mean follow-up period was 20.1 ± 14.6 mo. The overall response rates at 1, 3, 6, 9, and 12 mo at doses of 6.7, 6.7, 5.2, 4.0, and 3.0 mg were 38.7%, 48.4%, 54.8%, 61.3%, and 64.5%, respectively. Compared with baseline, OSSI/OSPI and pain intensity improved significantly from 1 mo after PSL induction. The OABSS, QOL score, urinary frequency, and voided volume improved significantly from 9 mo after PSL induction. No patients discontinued treatment due to adverse events, although hypertension and glucose intolerance occurred in two patients, but these were resolved by temporal medications. Conclusions: This study showed that low-dose oral PSL significantly improves bladder pain, urinary symptoms, and QOL in patients with HIC, without serious adverse events. Further prospective evaluation is warranted to verify the potential efficacy and safety of low-dose PSL for HIC. Patient summary: This retrospective observational study reviewed the clinical outcomes of 31 patients suffering from refractory Hunner-type interstitial cystitis treated with low-dose oral prednisolone. Low-dose prednisolone improved bladder pain, urinary symptoms, and quality of life significantly, without serious adverse events. The response rate of 64.5% at 12 mo was comparable with the rates reported in previous studies that used higher doses of prednisolone. This study provides a rationale for further prospective evaluation of low-dose prednisolone for this intractable disease.

Deep Learning Models for Cystoscopic Recognition of Hunner Lesion in Interstitial Cystitis.

Background: Accurate cystoscopic recognition of Hunner lesions (HLs) is indispensable for better treatment prognosis in managing patients with Hunner-type interstitial cystitis (HIC), but frequently challenging due to its varying appearance. Objective: To develop a deep learning (DL) system for cystoscopic recognition of a HL using artificial intelligence (AI). Design setting and participants: A total of 626 cystoscopic images collected from January 8, 2019 to December 24, 2020, consisting of 360 images of HLs from 41 patients with HIC and 266 images of flat reddish mucosal lesions resembling HLs from 41 control patients including those with bladder cancer and other chronic cystitis, were used to create a dataset with an 8:2 ratio of training images and test images for transfer learning and external validation, respectively. AI-based five DL models were constructed, using a pretrained convolutional neural network model that was retrained to output 1 for a HL and 0 for control. A five-fold cross-validation method was applied for internal validation. Outcome measurements and statistical analysis: True- and false-positive rates were plotted as a receiver operating curve when the threshold changed from 0 to 1. Accuracy, sensitivity, and specificity were evaluated at a threshold of 0.5. Diagnostic performance of the models was compared with that of urologists as a reader study. Results and limitations: The mean area under the curve of the models reached 0.919, with mean sensitivity of 81.9% and specificity of 85.2% in the test dataset. In the reader study, the mean accuracy, sensitivity, and specificity were, respectively, 83.0%, 80.4%, and 85.6% for the models, and 62.4%, 79.6%, and 45.2% for expert urologists. Limitations include the diagnostic nature of a HL as warranted assertibility. Conclusions: We constructed the first DL system that recognizes HLs with accuracy exceeding that of humans. This AI-driven system assists physicians with proper cystoscopic recognition of a HL. Patient summary: In this diagnostic study, we developed a deep learning system for cystoscopic recognition of Hunner lesions in patients with interstitial cystitis. The mean area under the curve of the constructed system reached 0.919 with mean sensitivity of 81.9% and specificity of 85.2%, demonstrating diagnostic accuracy exceeding that of human expert urologists in detecting Hunner lesions. This deep learning system assists physicians with proper diagnosis of a Hunner lesion.

Safety of Human Embryonic Stem Cell-derived Mesenchymal Stem Cells for Treating Interstitial Cystitis: A Phase I Study.

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.

A pilot study on oral cyclosporine A in association with fulguration for the treatment of interstitial cystitis with Hunner's lesions.

AIMS: To evaluate the efficacy and safety of lesion fulguration in combination with cyclosporine A (CyA) as a maintenance therapy in patients with interstitial cystitis/bladder pain syndrome (IC/BPS) with Hunner's lesion (HL). METHODS: Retrospective observational study of refractory patients with HL treated with daily 1.5 mg/kg or less of oral CyA following lesion fulguration. Pain severity, subjective improvement, urinary symptoms, and adverse events were used to assess long-term treatment efficiency and safety. RESULTS: Among the 22 patients, median follow-up under CyA was 27 months. Patients reported sustained significant reduction compared to pretreatment in pain (0/10 vs. 8/10; p < 0.001), urinary frequency per 24 h (9.5 vs. 20.8; p < 0.001), and nocturia (2.3 vs. 7.6; p < 0.001). Subjective improvement rate (SIR) and patient global impression of improvement were of 90% and 1 ("very much better"), respectively, including four patients who considered themselves cured (SIR: 100%). Three patients needed an additional procedure due to pain relapse. Minor increase in creatinine was observed and three patients developed or worsened their arterial hypertension. CyA dosage was decreased to 1.2 mg/kg or less for long-term relief (n = 8), creatinine increase (n = 5), and neutropenia (n = 1) with subsequent improvement in renal function without symptom deterioration. CONCLUSIONS: Oral CyA seems to allow a sustained long-term relief following HL fulguration by alleviating pain, decreasing urinary symptoms, and procuring great subjective improvement. The daily low dose of 1.5 mg/kg or less appears to have limited adverse events while preventing repeated procedures. Larger trials are warranted.

Reduction of Bladder Capacity Under Anesthesia Following Multiple Recurrences and Repeated Surgeries of Hunner Lesions in Patients With Interstitial Cystitis.

PURPOSE: To investigate the influence of multiple recurrences and repeated surgeries of Hunner lesions on bladder capacity under general anesthesia in patients with interstitial cystitis (IC). METHODS: We retrospectively reviewed the clinical records of Hunner-type IC (HIC) patients who underwent transurethral fulguration or resection of Hunner lesions combined with hydrodistension by a single surgeon between 2011 and 2020. Recurrence was defined as reappearance of uncontrolled urinary symptoms in association with new Hunner lesions identified by cystoscopy. Recurrent Hunner lesions were then treated by transurethral surgeries. The recurrence-free rate, potential predictive factors of recurrence, and changes in bladder capacity under anesthesia were examined at each surgical procedure. RESULTS: A total of 92 surgeries were performed in 47 HIC patients, 23 (49%) of whom required multiple procedures (range, 1-5 times). The mean recurrence-free time after the first surgery was 21.7 months. The recurrence-free rate was 53% at 24 months, and decreased to 32% at 48 months. There were no significant differences in age, sex, bladder capacity under anesthesia at the first surgery, duration from symptom onset to the first surgery, O'Leary-Sant questionnaire including symptom and problem indexes, visual analogue scale pain score, and the number of comorbidities between the cases with or without recurrence. Bladder capacity under anesthesia was gradually decreased as the number of surgeries was increased, and bladder capacity at the fourth procedure was significantly decreased to 80% of the capacity at the first surgery. CONCLUSION: These results suggest that multiple recurrences and repeated surgeries of Hunner lesions result in a reduction of bladder capacity under anesthesia in HIC patients although no predictive factors for recurrence of Hunner lesions were detected.

Identification of diagnostic serum biomarkers for Hunner-type interstitial cystitis.

OBJECTIVES: Diagnosis of Hunner-type interstitial cystitis (HIC) relies on the ability to identify Hunner lesions endoscopically, which can lead to storage symptom misdiagnosis. Here, we examined serum biomarkers for HIC and verified their utility. METHODS: Based on the previous definition of the Japanese guidelines, which did not distinguish HIC and non-HIC diseases, we searched for serum biomarkers in 25 patients with interstitial cystitis (IC) and 25 control participants using metabolomics during 2013-2014. In 2019, we conducted a validation study in HIC and control groups. Serum samples were analyzed using liquid chromatography-tandem mass spectrometry, and candidate biomarker concentrations were compared between the groups using Mann-Whitney test. RESULTS: Metabolomics targeted 678 metabolites and revealed that the levels of 14 lysolipids, seven γ-glutamyl amino acids, and two monoacylglycerols were significantly different between the IC and control groups. The following metabolites were selected from each metabolite category as candidates: 1-linoleoylglycerophosphocholine (1-linoleloyl-GPC [18:2]), γ-glutamylisoleucine (γ-Glu-Ile), and 1-arachidonylglycerol (1-AG). The serum concentrations of 1-linoleoyl-GPC (18:2) in the HIC and control groups were 27 920 ± 6261 and 40 360 ± 1514 ng/mL (P = 0.0003), respectively. The serum concentrations of γ-Glu-Ile and 1-AG were not significantly different between the groups. When the cut-off value of 1-linoleoyl-GPC (18:2) was set at 28 400 ng/mL, the sensitivity and specificity were 68% and 84%, respectively. CONCLUSIONS: Serum 1-linoleoyl-GPC (18:2) is a candidate diagnostic biomarker for HIC. Additional studies on whether this biomarker can distinguish HIC from other diseases with high urination frequency are required for its clinical use.

Integrated Analysis of Microarray Studies to Identify Novel Diagnostic Markers in Bladder Pain Syndrome/Interstitial Cystitis with Hunner Lesion.

Background: 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. Methods: 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. Results: 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 (p = 0.017), activated memory CD4+ T cells (p = 0.009), activated dendritic cells (p = 0.01), eosinophils (p = 0.004), and neutrophils (p = 0.03) were significantly higher in HIC than in normal samples, in contrast to resting mast cells (p = 0.022). A positive correlation existed between diagnostic markers and infiltrating immune cells. Conclusion: 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.

Bladder Microbiome in the Context of Urological Disorders-Is There a Biomarker Potential for Interstitial Cystitis?

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.

[EARLY EXPERIENCE OF INTRAVESICAL INSTILLATION OF DIMETHYL SULFOXIDE 50% SOLUTION FOR HUNNER TYPE INTERSTITIAL CYSTITIS IN A CLINIC].

(Objectives) To analyze the early observations in intravesical instillation of dimethyl sulfoxide (DMSO) 50% solution for Hunner-type interstitial cystitis (HIC) in our clinic and discuss possible factors affecting outcomes and future tasks. (Materials and methods) Seven patients who received DMSO therapy upon HIC relapse after transurethral resection of Hunner lesions with hydrodistension were enrolled for this study. For DMSO, 50 mL of 50% intravesical solution was administered six times every two weeks. Treatment evaluation was conducted using O'Leary & Sant Interstitial Cystitis Symptom and Problem Indexes (ICSI and ICPI), numerical rating scale (NRS) for bladder pain (0-10 points), and the post-treatment variations for which the pre-treatment values of the 24-hour urinary frequency, the average voided volume, and the maximum voided volume were used. The patient satisfaction survey was conducted with a questionnaire, and cystoscopy was conducted for all cases before and after treatment. (Results) All the patients were females with an average age of 58.3 years old. According to the Society of Interstitial cystitis of Japan Severity Criteria, 5 of the 7 cases showed a moderate level. No severe side effects were observed, and all the patients achieved six times administration. Changes in the points from the pre-treatment baseline values to the post-treatment values were -6.1, -9.1, and -10.0 for Pain NRS, ICSI, and ICPI, respectively. In addition, the 24-hour urinary frequency decreased by 5.34 times, while the average voided volume and the maximum voided volume increased to 60.3 mL and 75.7 mL, respectively. Subjective symptoms of all the patients improved, and cystoscopy revealed the disappearance or remission of Hunner lesions. (Conclusions) If Hunner lesions can be diagnosed, DMSO therapy could be used effectively and safely for HIC. The therapy is also promising for use as a future initial therapy. Therefore, the accurate diagnosis of Hunner lesions will be more important in the future.

The bacterial microbiota of Hunner lesion interstitial cystitis/bladder pain syndrome.

OBJECTIVE: To undertake the first comprehensive evaluation of the urinary microbiota associated with Hunner lesion (HL) interstitial cystitis/bladder pain syndrome (IC/BPS). Despite no previous identification of a distinct IC/BPS microbial urotype, HL IC/BPS, an inflammatory subtype of IC/BPS, was hypothesized most likely to be associated with a specific bacterial species or microbial pattern. PARTICIPANTS AND METHODS: The bacterial microbiota of midstream urine specimens from HL IC/BPS and age- and gender-matched IC/BPS patients without HL (non-HL IC/BPS) were examined using the pan-bacterial domain clinical-level molecular diagnostic Pacific Biosciences full-length 16S gene sequencing protocol, informatics pipeline and database. We characterized the differential presence, abundances, and diversity of species, as well as gender-specific differences between and among HL and non-HL IC/BPS patients. RESULTS: A total of 59 patients with IC/BPS were enrolled (29 HL, 30 non-HL; 43 women, 16 men) from a single centre and the microbiota in midstream urine specimens was available for comparison. The species abundance differentiation between the HL and non-HL groups (12 species) was not significantly different after Bonferroni adjustments for multiple comparisons. Similarly, the nine differentiating species noted between female HL and non-HL patients were not significantly different after similar statistical correction. However, four species abundances (out of the 10 species differences identified prior to correction) remained significantly different between male HL and non-HL subjects: Negativicoccus succinivorans, Porphyromonas somerae, Mobiluncus curtisii and Corynebacterium renale. Shannon diversity metrics showed significantly higher diversity among HL male patients than HL female patients (P = 0.045), but no significant diversity differences between HL and non-HL patients overall. CONCLUSIONS: We were not able to identify a unique pathogenic urinary microbiota that differentiates all HL from all non-HL IC/BPS. It is likely that the male-specific differences resulted from colonization/contamination remote from the bladder. We were not able to show that bacteria play an important role in patients with HL IC/BPS.

The O'Leary-Sant Interstitial Cystitis Symptom Index is a clinically useful indicator of treatment outcome in patients with interstitial cystitis/bladder pain syndrome with Hunner lesions: A post hoc analysis of the Japanese phase III trial of KRP-116D, 50% dimethyl sulfoxide solution.

OBJECTIVES: To evaluate the efficacy of intravesical KRP-116D, 50% dimethyl sulfoxide solution, in interstitial cystitis/bladder pain syndrome patients with Hunner lesions (Hunner-type interstitial cystitis), and to evaluate the correlations between efficacy variables and global response assessment to determine what constitutes a minimal clinically important change. METHODS: We performed a post hoc analysis of the Japanese phase III trial of KRP-116D. Changes at Week 12 from baseline in objective and subjective outcomes were compared between the KRP-116D and placebo groups in Hunner-type interstitial cystitis or non-Hunner-type interstitial cystitis patients. Correlations between efficacy variables at Week 12 and global response assessment were analyzed. Area under the receiver operating characteristic curve and the cut-off value of efficacy valuables were calculated to determine clinically meaningful changes. RESULTS: The effectiveness of intravesical treatment with KRP-116D was demonstrated in Hunner-type interstitial cystitis, but not in non-Hunner-type interstitial cystitis patients. Global response assessment was closely correlated with subjective outcomes including O'Leary-Sant Interstitial Cystitis Symptom Index, O'Leary-Sant Interstitial Cystitis Problem Index, and a numeric rating scale for bladder pain, but was less correlated with voiding variables including micturition frequency, voided volume, and maximum voided volume. In the receiver operating characteristic curve analyses, the cut-off value for the O'Leary-Sant Interstitial Cystitis Symptom Index was -5 (sensitivity 81.3%, specificity 83.3%). CONCLUSIONS: Clinical benefit of intravesical KRP-116D in Hunner-type interstitial cystitis patients was confirmed in this post hoc analysis. A five-point reduction in O'Leary-Sant Interstitial Cystitis Symptom Index is a clinically meaningful indicator for assessing patient satisfaction with KRP-116D treatment in patients with Hunner-type interstitial cystitis.

Current Understanding and Future Perspectives of Interstitial Cystitis/Bladder Pain Syndrome.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic disease characterized by suprapubic pain and lower urinary tract symptoms. Perhaps because of the heterogeneous nature of this disease and its multifactorial etiology, clinical trials in allinclusive populations of IC/BPS patients without phenotyping in the last decade have mainly failed to discover new therapeutic modalities of IC/BPS. Thus, phenotyping IC/BPS, aimed at identifying bladder-centric and/or bladder-beyond pathologies, including cystoscopic observation of Hunner or non-Hunner lesions of the bladder mucosa, is particularly important for the future of IC/BPS management. Based on recent discussions at international conferences, including the International Consultation on IC, Japan, it has been proposed that Hunner-lesion IC should be separated from other non-Hunner IC/BPS because of its distinct inflammatory profiles and epithelial denudation compared with non-Hunner IC/BPS. However, there are still no standard criteria for the diagnosis of Hunner lesions other than typical lesions, while conventional cystoscopic observations may miss atypical or small Hunner lesions. Furthermore, diagnosis of the bladder-centric phenotype of IC/BPS requires confirmation that identified mucosal lesions are truly a cause of bladder pain in IC/BPS patients. This review article discusses the current status of IC/BPS pathophysiology and diagnosis, as well as future directions of the proper diagnosis of bladder-centric IC/BPS, in which pathophysiological mechanisms other than those in inflammatory pathways, such as angiogenic and immunogenic abnormalities, could also be involved in both Hunner-lesion IC and non-Hunner IC/BPS. It is hoped that this new paradigm in the pathophysiological evaluation and diagnosis of IC/BPS could lead to pathology-based phenotyping and new treatments for this heterogeneous disease.

Comparison of deep phenotyping features of UCPPS with and without Hunner lesion: A MAPP-II Research Network Study.

OBJECTIVE: To use the phenotyping data from the MAPP-II Symptom Patterns Study (SPS) to compare the systemic features between urologic chronic pelvic pain syndrome (UCPPS) with Hunner lesion (HL) versus those without HL. METHODS: We performed chart review on 385 women and 193 men with UCPPS who enrolled in the MAPP-II SPS. 223 had cystoscopy and documentation of HL status. Among them, 12.5% had HL and 87.5% did not. RESULTS: UCPPS participants with HL were older, had increased nocturia, higher Interstitial Cystitis Symptom and Problem Indexes, and were more likely to report "painful urgency" compared with those without HL. On the other hand, UCPPS without HL reported more intense nonurologic pain, greater distribution of pain outside the pelvis, greater numbers of comorbid chronic overlapping pain conditions, higher fibromyalgia-like symptoms, and greater pain centralization, and were more likely to have migraine headache than those with HL. UCPPS without HL also had higher anxiety, perceived stress, and pain catastrophizing than those with HL. There were no differences in sex distribution, UCPPS symptom duration, intensity of urologic pain, distribution of genital pain, pelvic floor tenderness on pelvic examination, quality of life, depression, pain characteristics (nociceptive pain vs. neuropathic pain), mechanical hypersensitivity in the suprapubic area during quantitative sensory testing, and 3-year longitudinal pain outcome and urinary outcome between the two groups. CONCLUSIONS: UCPPS with HL displayed more bladder-centric symptom profiles, while UCPPS without HL displayed symptoms suggesting a more systemic pain syndrome. The MAPP-II SPS phenotyping data showed that Hunner lesion is a distinct phenotype from non-Hunner lesion.

Bladder pain syndrome/interstitial cystitis in contemporary UK practice: Outcomes of phenotype-directed management.

OBJECTIVES: Problem bladder pain syndrome/interstitial cystitis (BPS/IC) is a heterogeneous disorder with variation in management worldwide. Phenotyping aims to personalize therapy and optimize outcomes. The most well-described phenotype is Hunner lesion disease (HLD). The prevalence of HLD and outcome of phenotype-directed management in the UK is not well-studied. We describe the management of a contemporary cohort of patients with BPS/IC in the UK. METHODS: Retrospective analysis of all patients with BPS/IC from January 2015-November 2018. Outcomes of patients who underwent laser ablation to Hunner lesions were collected using the Global Response Assessment tool. RESULTS: One hundred and sixty-three patients (mean age of 43 years [20-85]) were included. 78% were female and patients had experienced symptoms for an average 6 years (1-30) prior to specialist assessment. Eighty-three percent of patients had pelvic imaging (44% ultrasound, 42% magnetic resonance imaging and 14% computed tomography), and a relevant abnormality was found in five (4%). Twenty-two patients (14%) had HLD (International Society for the Study of BPS [ESSIC] 3), with a mean bladder capacity of 373 mL (175-650 mL); 77% were ESSIC C on histopathology. All patients with HLD underwent laser ablation, with 55% experiencing a moderate/marked improvement in symptoms, with a mean duration of effect of 10 months (3-36); 27% of patients had a repeat treatment. CONCLUSIONS: The presence of HLD in patients with BPS/IC is not uncommon. Pelvic imaging rarely identifies any cause for pain and so cystoscopy under anesthesia is essential for accurate phenotyping. Phenotype-directed management with holmium laser ablation to Hunner lesions has good short-term efficacy in improving pain, but re-intervention is often required.

An adaptive randomized clinical trial in interstitial cystitis/bladder pain syndrome evaluating efficacy of ASP3652 and the relationship between disease characteristics and Hunner's lesions.

PURPOSE: The 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). METHODS: In 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. RESULTS: In 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]). CONCLUSION: ASP3652 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.

[Minimally invasive methods of treatment of interstitial cystitis/painful bladder syndrome].

Interstitial Cystitis (IC) or Painful Bladder Syndrome (PBS) is a heterogeneous disease which pathogenetic mode development is not fully studied. In the presented literature review IC/PBS is considered as urothelial dysfunction. The main issues discussed relate to IC/PBS diagnosis and minimally invasive methods of its treatment including intravesical instillations of therapeutic agents, botulinum toxin injections into bladder wall and hydrodistension. Efficacy of the above therapeutic methods is far from the desired what gives rise to search novel minimally invasive technologies and protocols to improve the outcomes of traditional treatment methods.

Presenting an atlas of Hunner lesions in interstitial cystitis which can be identified with office cystoscopy.

AIM: To assist clinicians in proper visual diagnosis of Hunner lesions by providing an atlas of representative images of the variability in Hunner lesion appearance. METHODS: Available cystoscopic images of Hunner lesions were reviewed from patients with interstitial cystitis or bladder pain syndrome (IC/BPS) treated by a single clinician between 2011 and 2020. For most patients, initial cystoscopy was performed in the office under local anesthesia. Images were categorized by variations in appearance. Data including Hunner lesion descriptions and patient demographics were retrospectively collected from the medical record. Only patients who had images available, received triamcinolone injection and/or fulguration of Hunner lesions, and reported improvement of their symptoms following treatment were included in the atlas. RESULTS: Thirty-one IC/BPS patients with Hunner lesions had cystoscopic images available for review. We created an atlas of representative images. Variations in appearance include classic lesions with or without a central coagulum, inflamed lesions, non-inflamed lesions, groupings of lesions, and lesions with a red waterfall bleeding appearance. CONCLUSION: There is variation in cystoscopic appearance of Hunner lesions. Most Hunner lesions can be identified during office visits using flexible cystoscopy and local anesthesia without hydrodistention or general anesthesia. Proper visual diagnosis of Hunner lesions is of upmost importance as these patients with IC/BPS respond greatly to endoscopic intervention. This atlas will serve as a reference for clinicians and researchers, so they are able to better identify and manage these patients.

Clinical Management of Bladder Pain Syndrome/Interstitial Cystitis: A Review on Current Recommendations and Emerging Treatment Options.

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.

Clinical efficacy of submucosal injection of triamcinolone acetonide in the treatment of type II/III interstitial cystitis/bladder pain syndrome.

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.

Hunner lesion disease differs in diagnosis, treatment and outcome from bladder pain syndrome: an ESSIC working group report.

Objectives: There is confusion about the terms of bladder pain syndrome (BPS) and Interstitial Cystitis (IC). The European Society for the Study of IC (ESSIC) classified these according to objective findings [9]. One phenotype, Hunner lesion disease (HLD or ESSIC 3C) differs markedly from other presentations. Therefore, the question was raised as to whether this is a separate condition or BPS subtype.Methods: An evaluation was made to explore if HLD differs from other BPS presentations regarding symptomatology, physical examination findings, laboratory tests, endoscopy, histopathology, natural history, epidemiology, prognosis and treatment outcomes.Results: Cystoscopy is the method of choice to identify Hunner lesions, histopathology the method to confirm it. You cannot distinguish between main forms of BPS by means of symptoms, physical examination or laboratory tests. Epidemiologic data are incomplete. HLD seems relatively uncommon, although more frequent in older patients than non-HLD. No indication has been presented of BPS and HLD as a continuum of conditions, one developing into the other.Conclusions: A paradigm shift in the understanding of BPS/IC is urgent. A highly topical issue is to separate HLD and BPS: treatment results and prognoses differ substantially. Since historically, IC was tantamount to Hunner lesions and interstitial inflammation in the bladder wall, still, a valid definition, the term IC should preferably be reserved for HLD patients. BPS is a symptom syndrome without specific objective findings and should be used for other patients fulfilling the ESSIC definitions.