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.

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.

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.

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.

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.

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 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.

[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.

Patterns and predictors of Hunner lesion recurrence in patients with interstitial cystitis.

AIMS: To evaluate the patterns and predictive factors associated with Hunner lesions (HLs) recurrence in patients with interstitial cystitis (IC). METHODS: This study was a retrospective analysis of data from patients with IC who underwent transurethral resection and cauterization (TUR-C) of HLs between October 2011 and December 2017. Symptoms were evaluated using the Pelvic Pain and Urgency/Frequency Patient Symptom Scale (PUF), O'Leary-Sant Interstitial Cystitis Symptom Index, and Visual Analogue Scale (VAS). Patients attended follow-up visits every 3 months; cystoscopy was performed immediately in patients with aggravated symptoms. Recurrence was defined as a VAS score greater than or equal to 4 and HLs recurrence on cystoscopy. RESULTS: A total of 91 patients were enrolled (25 male, 66 female): median follow-up was 30.6 months. HLs recurrence occurred in 101 sites (53 patients), 21.8% in the previous TUR-C site, 18.8% de novo, and 59.4% at both previous and de novo sites. The recurrence rate was approximately 12.7%, 40%, and 55.2% at 6, 12, and 18 months, respectively. A higher PUF bother score was the only predictive factor of recurrence (odds ratio: 1.142, 95% confidence interval: 1.016-1.284, P = 0.026), with a cut-off value of 7.5 (sensitivity: 67.9%, specificity: 62.5%). In case of late recurrence (>18 months), there was no predictive factor. CONCLUSIONS: The HLs recurrence pattern was unpredictable, involving both previous TUR-C and de novo areas. More accurately defining the HLs resection margin may lead to better surgical outcomes but this remains to be proven.

Hunner lesion versus non-Hunner lesion interstitial cystitis/bladder pain syndrome.

BACKGROUND: Global consensus on the standardization of terminology for interstitial cystitis/bladder pain syndrome is lacking and is in the formative stages. The Workshop on Hunner lesion versus non-Hunner lesion at the 2018 International Consultation on Interstitial Cystitis Japan discussed prevalence, performance and outcome of endoscopy, the role of histopathology, and markers. METHODS: A panel of experts reviewed the literature regarding Hunner lesion vs. non-Hunner lesion interstitial cystitis/bladder pain syndrome. RESULTS: The prevalence of Hunner lesion has been reported to be 5-57%. Older age and smaller anatomic bladder capacity were associated with Hunner lesions. Cystoscopy using local anesthesia is not adequate in diagnosing interstitial cystitis but is needed to rule out confusable diseases. Cystoscopy with hydrodistention and redistention of the bladder is considered standard. A Hunner lesion is visualized as a quite typical inflammatory reaction: a reddened mucosal area with small vessels radiating towards a central scar, splitting at distension, usually associated with a waterfall bleeding pattern. Biopsies from the inflamed area show inflammatory infiltrates, granulation tissue, detrusor mastocytosis, and fibrin deposits. Ablation of Hunner lesions includes transurethral resection of lesions, fulguration, laser ablation, and cortical steroid injections. Mast cell density is a somewhat controversial matter, described differently in different studies: marked increase in Hunner lesion vs. non-Hunner lesion in the majority of studies, no difference in a few. Nitric oxide appears to be a definitive marker in distinguishing Hunner lesion vs. non-Hunner lesion disease. Macrophage migration inhibitory factor is elevated in Hunner lesion patients. Increased level of urinary proinflammatory genes expression has also been found in Hunner lesion subjects. CONCLUSIONS: Hunner lesion patients are clinically and pathologically distinct from non-Hunner lesion bladder pain syndrome patients.

Low bladder capacity is an important predictor for comorbidity of interstitial cystitis with Hunner's lesion in patients with refractory chronic prostatitis/chronic pelvic pain syndrome.

OBJECTIVE: To evaluate the predictive factors for comorbidity of Hunner-type interstitial cystitis in patients with chronic prostatitis/chronic pelvic pain syndrome using urethrocystoscopy. METHODS: Thirty-two male patients were included in this study. Between April 2012 and April 2016; they were diagnosed with chronic prostatitis/chronic pelvic pain syndrome according to the National Institutes of Health classification. Their symptoms were not improved by 3 months of behavioral and pharmacological therapies. They all underwent narrow band imaging-assisted urethrocystoscopy to assess whether the presence of Hunner's lesions correlated with other variables. RESULTS: Thirteen out of 32 patients (41%) had Hunner's lesions. Of the variables, maximal voided volume per micturition (106 ± 29 mL vs 171 ± 61 mL) and bladder capacity (267 ± 121 mL vs 407 ± 137 mL) were significantly smaller in patients with Hunner's lesions compared to those without. Other variables, apart from age, were not significantly different. Furthermore, patients with voided volume less than 150 mL were more likely to have Hunner's lesions than those with voided volume exceeding 150 mL. CONCLUSIONS: Hunner-type interstitial cystitis is a common comorbidity among patients with refractory chronic prostatitis/chronic pelvic pain syndrome. In cases where voided volume is small, performing narrow band imaging-assisted urethrocystoscopy would be very helpful for detecting bladder mucosal changes such as Hunner's lesions.

Comparison of urologic and non-urologic presentation in interstitial cystitis/bladder pain syndrome patients with and without Hunner lesions.

AIMS: To compare severity and characteristics of urologic pain, other urinary symptoms, sexual pain, psychosocial health, and the distribution and intensity of non-urologic pain between men and women with and without Hunner lesions. METHODS: All cystoscopies were performed and documented by the same clinician to ensure uniform recognition of Hunner lesions. Intensity of urologic and sexual pain, nocturia, frequency, urgency, and bladder hypersensitivity features were assessed using validated questionnaires and numeric rating scales. The distribution and intensity of non-urologic pain was assessed using self-reported history, a body map diagram, and numeric rating scales. Somatic symptom burden, depression, and anxiety were compared. RESULTS: Among the 150 participants, 27% (n = 41) had Hunner lesions (36% of men, 25% of women). Participants with Hunner lesions were significantly older (median age 58 vs 41, P < 0.001). They reported less intense urologic pain (5 vs 7, P = 0.024) and more nocturia (ICSI nocturia symptom score: 4 vs 3, P = 0.007). They also were less likely to have a history of irritable bowel syndrome (15% vs 36%, P = 0.013) and anxiety attacks (22% vs 44%, P = 0.013). Close to half of Hunner IC patients had non-urologic pain outside the pelvis. There were no differences in bladder hypersensitivity features (eg, painful bladder filling) between the two groups. CONCLUSIONS: Hunner lesions can be identified in both men and women. There are significant overlaps in terms of their urologic and non-urologic presentation. Further investigation is needed on phenotypic and biological distinction between IC/BPS with and without Hunner lesions.

Extent of Hunner lesions: The relationships with symptom severity and clinical parameters in Hunner type interstitial cystitis patients.

AIMS: To assess the clinical impact of Hunner lesions in patients with Hunner type interstitial cystitis (HIC). METHODS: The clinical records of 94 HIC patients who underwent their first hydrodistension (with lesion fulguration) were retrospectively reviewed. At surgery, the extent of each lesion was classified in terms of the relative involvement for the whole-bladder luminal surface; we defined four grades of involvement: <10%, 10-24%, 25-49%, and ≥50%; and two grades of severity: <25% (focal) and ≥25% (extensive). We examined the relationships between the extent of the lesions and all demographic characteristics, symptom scores, voiding symptoms, and bladder capacity. Factors predictive of the need for repeat hydrodistension were also explored. RESULTS: Symptom severity worsened as the lesional extent rose. Those with extensive lesions scored higher on the O'Leary and Sant Symptom (P = 0.004) and Problem Index scales (P < 0.001), the pain visual analog scale (P = 0.011), the International Prostate Symptom Score scale (P = 0.012), and a quality-of-life index (P = 0.020); and exhibited greater daytime urinary frequency (P = 0.040), more nocturia (P = 0.041), and a smaller bladder capacity (P = 0.007) than the focal group. No symptomatic or clinical parameters predicted the need for repeat hydrodistension. CONCLUSIONS: The extent of Hunner lesions was associated with both symptom severity and bladder capacity but not with other clinical parameters, including the need for repeat hydrodistension, in patients with HIC.

Histopathological characteristics of interstitial cystitis/bladder pain syndrome without Hunner lesion.

AIMS: To assess the distinct histopathological characteristics and their clinical significance between non-Hunner-type and Hunner-type interstitial cystitis (IC)/bladder pain syndrome (BPS). METHODS AND RESULTS: We prospectively enrolled and classified IC/BPS patients, on the basis of cystoscopic findings, as having non-Hunner-type IC and Hunner-type IC. Specimens obtained from the posterior wall in non-Hunner-type IC cases during hydrodistension or from Hunner/non-Hunner lesions in Hunner-type IC cases during transurethral resection were evaluated. Stress urinary incontinence patients with microscopic haematuria were selected as controls. Biopsy specimens were obtained from 15 non-Hunner-type IC, 15 Hunner-type IC and 5 non-IC patients. Severe and moderate fibrosis was more frequently observed in non-Hunner-type IC than in Hunner-type IC and non-IC cases. However, severe and moderate inflammation was more frequently observed in Hunner-type IC than in non-Hunner-type IC cases. The remnant urothelium was significantly decreased in Hunner-type IC cases as compared with non-Hunner-type IC and non-IC cases (P < 0.05), and non-Hunner-type IC cases showed a higher number of mast cells than Hunner-type IC and non-IC cases (P = 0.035). Accordingly, several fibrosis-promoting genes were highly expressed in bladder tissues of non-Hunner-type IC, as compared with Hunner-type IC. Patients with severe fibrosis showed significantly higher urinary frequency and smaller bladder capacity than those with moderate and mild fibrosis (all P < 0.05). CONCLUSIONS: Non-Hunner-type IC is characterized by severe fibrosis and increased mast cell infiltration, whereas Hunner-type IC is characterized by severe inflammation and urothelial denudation in the entire bladder. Fibrosis in the bladder of IC/BPS patients was correlated with increased urinary frequency and decreased bladder capacity.

A standard for terminology in chronic pelvic pain syndromes: A report from the chronic pelvic pain working group of the international continence society.

AIMS: Terms used in the field of chronic pelvic pain (CPP) are poorly defined and often confusing. An International Continence Society (ICS) Standard for Terminology in chronic pelvic pain syndromes (CPPS) has been developed with the aim of improving diagnosis and treatment of patients affected by chronic pelvic pain syndromes. The standard aims to facilitate research, enhance therapy development and support healthcare delivery, for healthcare providers, and patients. This document looks at the whole person and all the domains (organ systems) in a systematic way. METHODS: A dedicated working group (WG) was instituted by the ICS Standardisation Steering Committee according to published procedures. The WG extracted information from existing relevant guidelines, consensus documents, and scientific publications. Medline and other databases were searched in relation to each chronic pelvic pain domain from 1980 to 2014. Existing ICS Standards for terminology were utilized where appropriate to ensure transparency, accessibility, flexibility, and evolution. Consensus was based on majority agreement. RESULTS: The multidisciplinary CPPS Standard reports updated consensus terminology in nine domains; lower urinary tract, female genital, male genital, gastrointestinal, musculoskeletal, neurological aspects, psychological aspects, sexual aspects, and comorbidities. Each is described in terms of symptoms, signs and further evaluation. CONCLUSION: The document presents preferred terms and definitions for symptoms, signs, and evaluation (diagnostic work-up) of female and male patients with chronic pelvic pain syndromes, serving as a platform for ongoing development in this field. Neurourol. Urodynam. 36:984-1008, 2017. © 2016 Wiley Periodicals, Inc.

Correlation of cystoscopically confirmed periureterally located hunner lesion with vesicoureteral reflux: preliminary study in patients with interstitial cystitis.

OBJECTIVE: The purpose of this study is to evaluate the incidence of vesicoureteral reflux (VUR) in patients with interstitial cystitis (IC) and to explore the correlation between periureterally located Hunner lesions and ipsilateral VUR. MATERIALS AND METHODS: We evaluated 344 patients with IC who underwent cystoscopy (March 2012 to July 2013). Among these patients, 25 underwent voiding cystourethrography (VCUG) to check for the presence of VUR. We reviewed the cystoscopy findings (grade and location of Hunner lesions) and the results of VCUG (presence and grade of VUR). The relationship between VUR and periureterally located Hunner lesions and the association between cystoscopic grading of IC and VUR were evaluated. RESULTS: Of the 25 patients with IC, seven (28%) had VUR (two bilateral and five unilateral). Among nine separate ureters with VUR, seven (78%) had associated periureterally located Hunner lesions, as evaluated cystoscopically. The median bladder capacity was 200 mL for patients with VUR and 230 mL for patients without VUR, with no statistically significant difference between the two groups (p>0.05). There was a strong correlation between the presence of VUR and ipsilateral periureterally located Hunner lesions (p<0.05). However, there was no association between the severity of cystoscopy grading and the presence of VUR (p>0.05). CONCLUSION: According to our study, VUR is not an uncommon complication in patients with IC, and there is a statistically significant correlation between VUR and periureterally located Hunner lesions. We assume that, along with the decrease in bladder capacity, a periureterally located Hunner lesion may be an important factor in the development of VUR.

Interstitial cystitis is bladder pain syndrome with Hunner's lesion.

The contents and understanding of the term, interstitial cystitis, have undergone major changes during the past 100 years, moving from a chronic, true inflammatory bladder disorder to an extensive syndrome with lower urinary tract pain. Comments on this development are presented. From examples in the literature, some important features of classic interstitial cystitis are outlined. The more inclusive attitude of later decades has drawn desirable attention to the entire spectrum of disorders resulting in bladder pain. The wish to include all of them into one handy entity has unfortunately resulted in much scientific and clinical confusion, though. It is noted that originally interstitial cystitis represented the Hunner type of disease. Today, there is agreement that the classic type of interstitial cystitis with Hunner's lesions, bladder pain syndrome type 3C according to current terminology, stands out as a well-defined phenotype; it has to evaluated separately in clinical studies and practice, as treatment requirements differ importantly between this and other phenotypes.

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.

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.