European Society For The Study Of Interstitial Cystitis Research Articles

Effectiveness of hydrodistention procedure under local anesthesia in the treatment of bladder pain syndrome/interstitial cystitis

Objective: We aimed to indicate the effectiveness of local anesthesia in the treatment of hydrodistention in women with Bladder Pain Syndrome/interstitial Cystitis (BPS/IC) in our study.
 Material and Method: The data of a total of 77 female patients who underwent hydrodistention treatment for BPS/IC in our clinic between January 2015 and July 2021 were analyzed retrospectively. The patients were divided into two groups as local anesthesia (LA, n=41) and spinal anesthesia (SA, n=36) groups according to the type of anesthesia applied. The groups were compared by determining the preoperative and postoperative O'Leary symptom index (SI) and problem index (PI), minimum voiding volume (MinVV), maximum voiding volume (MaxVV), average voiding volume (AvgVV) and daily frequency. 
 Results: The mean age of the patients was 48.97±11.09 years in the LA group and 45.19±14.35 years in the SA group (p=0.197). There was no significant difference between the groups in terms of the preoperative European Society for the Study of Interstitial Cystitis (ESSIC) group (p=0.999). During the postoperative period, a median (IQR) improvement of 11.0 (2.0) points was observed in the SI of the LA group, while a median improvement of 11.0 (2.0) points were observed in the SA group (p=0.437). The median improvement in PI score was 8.4 (4.0) points in the SA group, while it was 7.0 (3.0) points in the LA group (p=0.415). There was no significant difference between the groups in terms of improvements in minVV, maxVV, avgVV and daily frequency (p=0.480, p=0.460, p=0.614 and p=0.910, respectively).
 Conclusion: Hydrodistention treatment in women with BPS/IC can be performed safely and with high success rate under local anesthesia and it is well tolerated by the patients. Local anesthesia offers a minimally invasive treatment option as well as the advantage of avoiding possible complications of spinal, epidural or general anesthesia.

PD01-04 ANTIMICROBIAL PEPTIDE, BETA-DEFENSIN 2 (BD2), IS A NOVEL BIOMARKER ON ULCERATIVE INTERSTITIAL CYSTITIS; CAN BD2 SUSPECT THE DYSBIOSIS OF URINE MICROBIOTA?

You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis (PD01)1 Sep 2021PD01-04 ANTIMICROBIAL PEPTIDE, BETA-DEFENSIN 2 (BD2), IS A NOVEL BIOMARKER ON ULCERATIVE INTERSTITIAL CYSTITIS; CAN BD2 SUSPECT THE DYSBIOSIS OF URINE MICROBIOTA? Sang Wook Lee, Woong Bin Kim, Si Hyun Kim, Ji Kang Yun, and Young Ho Kim Sang Wook LeeSang Wook Lee More articles by this author , Woong Bin KimWoong Bin Kim More articles by this author , Si Hyun KimSi Hyun Kim More articles by this author , Ji Kang YunJi Kang Yun More articles by this author , and Young Ho KimYoung Ho Kim More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001965.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Since urine is not sterile, inflammatory reactions caused by dysbiosis of urinary microbiota may induce interstitial cystitis. A study was conducted to find out whether BD2, one of antimicrobial peptides in urine, could be used as a novel diagnostic marker for ulcerative interstitial cystitis (IC), compared to macrophage migration inhibitory factor (MIF). METHODS: Urine samples were assayed for BD2 and MIF by enzyme-linked immunosorbent assays (ELISA). Urine samples from three female groups were examined: healthy controls (N=34, Group I), non-ulcerative IC (N=40, Group II), and ulcerative IC (N=68, Group III). Urine samples were collected via transurethral catheter all patients with IC. Cystoscopy with diagnostic and therapeutic hydrodistention was applied a to Group II & III patients. The National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) criteria were applied to the patients with endoscopic clinical diagnosis of Painful bladder syndrome/IC. The mast cell counts criteria proposed by the European Society for the Study of Interstitial Cystitis (ESSIC) were contrasted and results were compared. RESULTS: Based on urinary specimens from a total of 142 patients, BD2 expressed 18-fold higher in patients with ulcerative IC than in patients with non-ulcerative IC. MIF levels were 31-fold higher in patients with ulcerative IC than in patients with non-ulcerative IC. The enhanced secretion of BD-2 exhibited a strong correlation with the increased mast cell counts associated with bladder IC pathology. CONCLUSIONS: Enhanced urinary secretion of BD2 from ulcerative IC patients demonstrated relatively robust levels to be used as potential biomarkers, and associated with clinical phenotypes. Moreover, the increased urinary level of anti-microbial peptide BD2 may suggest a new possibility of diagnosis caused by dysbiosis of urinary microbiota in ulcerative IC. Source of Funding: This work was supported by the “Soonchunhyang University Research Fund” © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e31-e32 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Sang Wook Lee More articles by this author Woong Bin Kim More articles by this author Si Hyun Kim More articles by this author Ji Kang Yun More articles by this author Young Ho Kim More articles by this author Expand All Advertisement Loading ...

Clinical Relevance of Bladder Histopathological Findings and Their Impact on Treatment Outcomes among Patients with Interstitial Cystitis/Bladder Pain Syndrome: An Investigation of the European Society for the Study of Interstitial Cystitis Histopathological Classification.

We investigate the clinical significance of European Society for the Study of Interstitial Cystitis (ESSIC) bladder histopathological classification and its impact on treatment outcomes among patients with interstitial cystitis/bladder pain syndrome. Bladder biopsy specimens obtained from severe, treatment refractory interstitial cystitis/bladder pain syndrome cases were analyzed by a single pathologist blinded to clinical data. Inflammatory cell infiltration and urothelium denudation, eosinophil infiltration, plasma cell infiltration, lamina propria hemorrhage and granulation in specimens were evaluated separately. Patients with at least 1 histopathological finding were classified as ESSIC type C, with the rest being classified as ESSIC type A. Current overall treatment outcomes were determined via telephone interview. Bladder specimens were obtained from 352 patients with interstitial cystitis/bladder pain syndrome. Bladder inflammation, urothelium denudation, eosinophil and plasma cell infiltration, lamina propria hemorrhage and granulation were present in 69.6%, 44.6%, 9.1%, 15.3%, 4.8% and 5.1% of the bladder specimens, respectively. Approximately 78.7% of the patients included were ESSIC type C and had a smaller cystometric bladder capacity and higher bladder pain compared to ESSIC type A. Although individual histopathological findings were not associated with treatment outcome, a higher proportion of ESSIC type A patients had worse, unchanged or less than 25% improvement outcomes compared to ESSIC type C (43.1% vs 25.8%, p=0.025). Bladder histopathological findings were associated with clinical parameters and differences in patient reported treatment outcomes. Accordingly, patients with interstitial cystitis/bladder pain syndrome who had no remarkable bladder histopathological findings had less favorable treatment outcomes compared to those who did.

Relevance of the Endoscopic Evaluation in the Diagnosis of Bladder Pain Syndrome/Interstitial Cystitis

ObjectiveTo assess the relevance of the endoscopic evaluation in clinically suspected cases of Bladder Pain Syndrome/Interstitial Cystitis (BPS/IC), using ESSIC criteria, established in 2008 by the European Society for the Study of Interstitial Cystitis (ESSIC). MethodsWe included all patients who underwent endoscopic evaluation between January 01, 2015 and October 31, 2019 for clinical suspicion of BPS/IC. Collected data included demographic and baseline clinical features, endoscopic appearance (prior and after hydrodistension), and bladder wall biopsy results, both defined according to ESSIC criteria. Data were cross tabulated to define ESSIC phenotypes, while subgroups and multivariate analyses were carried out to assess the influence of clinical variables on ESSIC phenotypes. ResultsFifty-two subjects were included, mainly women (92%). Median age at evaluation was 45 (32.9-58.2) years. At hydrodistension, 21 patients (42%) had positive and 29 (58%) had negative findings. Grade 2-3 glomerulations were found in 18 patients, while Hunner lesions were reported only in 1 patient. Positive results at biopsy were found in 24 pts (51.1%), while negative in 23 (48.9%). Overall, the positive and negative concordance between hydrodistension and biopsy results was 78%. No significant differences in ESSIC subtypes were found after stratification based on clinical features and at multivariate analysis. Retrospective design is the main limitation. ConclusionCystoscopy with hydrodistension and biopsy do have a role in the diagnostic pathway of BPS/IC. However, results should be considered in the clinical context of the individual patient.

Urine cytokines as biomarkers for diagnosing interstitial cystitis/bladder pain syndrome and mapping its clinical characteristics.

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

Classic Interstitial Cystitis: Unrelated to BPS

When first recognized, more than one hundred years ago, the term interstitial cystitis (IC) was reserved for subjects with a special type of deep inflammation of the bladder wall. Later, the scope of IC widened, including all kinds of bladder pain syndromes (BPS), giving rise to a lot of confusion and difficulties in research as well as in clinical practice. Herein, recent progress in the understanding of the BPS/IC complex will be discussed, emphasizing the fact that the classic Hunner disease (BPS type 3C according to the European Society for the Study of Interstitial Cystitis (ESSIC) classification) is a well-defined condition that fulfills the requirements of the denomination interstitial cystitis. The paper will also discuss recent research on diagnostics, markers, genetics, and various types of remedies for classic IC. For the benefit of our patients, in BPS/IC, it is time for a final separation of the concepts BPS and IC. Classic IC is a well-defined entity with multiple unique characteristics, those characteristics having a potential for development of a specific rational, pharmacological, and surgical treatment algorithm if further investigated. BPS, on the other hand, seems to include a heterogenic composition of conditions calling for broad attempts to be more closely explored.

Effect of amitriptyline in treatment interstitial cystitis or bladder pain syndrome according to two criteria: Does ESSIC criteria change the response rate?

The European Society for the Study of Interstitial Cystitis (ESSIC) recommended that interstitial cystitis (IC) should be replaced by bladder pain syndrome (BPS), which focused more attention on the painful or discomfort feeling related to bladder and weakened the importance of cystoscopy in diagnosis process. Our study aimed to explore whether this alteration changed the treatment outcomes of amitriptyline and whether cystoscopy was meaningful for the treatment of this disease. We conducted a retrospective study including 25 IC patients fulfilled the National Institute of Diabetes and Digestive and Kidney Disease (NIDDK) criteria and 42 BPS patients diagnosed according to ESSIC criteria. All the patients received amitriptyline with a self-uptitration protocol. We compared the response rates of two groups by a patient reported global response assessment after 3 months and reclassified all the 67 patients according to ESSIC criteria, the response rates of different BPS types were also assessed. There was no significant difference of response rate between IC patients (12/25, 48%) and BPS patients (19/42, 45.2%) according to different criteria (P = 0.337). The response rate of BPS type 1 (13/30, 43.3%) was similar to that of type 2 or 3 (18/37, 48.6%) (P = 0.664). ESSIC criteria did not decrease the response rate of amitriptyline treatment for BPS patients compared to IC patients with complaint of bladder pain or discomfort. Cystoscopy showed no predictive effect for the treatment outcome of amitriptyline.

Local immune response in bladder pain syndrome/interstitial cystitis ESSIC type 3C

Introduction and hypothesisBladder pain syndrome/interstitial cystitis (BPS/IC) is identified based on subjective symptoms which lead to heterogeneous patient populations. Previous studies using gene expression arrays for BPS/IC with Hunner’s lesions [European Society for the Study of Interstitial Cystitis (ESSIC) type 3C], a subtype of the condition discernible by cystoscopy, have revealed characteristic immune responses and urothelial abnormalities. This current study aimed to further characterize this subtype using a gene expression panel. We hypothesized that B-cell activation with high levels of urinary antibody concentration would be found.MethodsCold-cup bladder biopsies, catheterized urine and blood were collected from 15 BPS/IC ESSIC type 3C patients, 11 non-inflammatory overactive bladder (OAB) patients and eight healthy controls. Gene expression in biopsies was quantified by real-time quantitative polymerase chain reaction (RT-qPCR), immunohistochemistry was performed on bladder tissue and urinary immunoglobulins G and A were quantified by enzyme-linked immunosorbent assay. Statistical analyses included the Kruskal-Wallis test for non-parametric data and post hoc tests identified differences between groups.ResultsHigh expression of T- and B-cell markers (CTLA4, CD20, CD79A, IGH@), low expression of urothelial markers (KRT20, UPK1B, UPK3A), focal lymphoid aggregates in the submucosa and high immunoglobulin concentration in urine were found exclusively in BPS/IC ESSIC type 3C patients. Results for OAB were in intermediate ranges between the other two groups and UPK1B even reached significantly lower expression when compared to healthy controls.ConclusionsBPS/IC ESSIC type 3C is characterized by a local adaptive immune response with elevated urinary antibody concentrations. Quantification of urinary immunoglobulin levels could be used for a non-invasive diagnosis of BPS/IC ESSIC type 3C.

Clinical characteristics differ considerably between phenotypes of bladder pain syndrome/interstitial cystitis

Bladder pain syndrome/interstitial cystitis (BPS/IC) is one of the most bothersome conditions in urological practice. This syndrome includes a heterogeneous collection of underlying pathological conditions. Compared to the classic IC with a Hunner lesion, now denominated European Society for the Study of Interstitial Cystitis (ESSIC) type 3C, the non-Hunner type of BPS/IC appears different concerning demographic, endoscopic and histological findings, as well as the response to all forms of treatment. The objective of this study was to determine whether there are additional dissimilarities in clinical presentation between the main phenotypes of BPS/IC. In total, 393 BPS/IC patients (210 type 3C and 183 non-Hunner), diagnosed according to National Institute of Diabetes and Digestive and Kidney Diseases and ESSIC criteria, were studied by surveying the clinical records including micturition diaries. In this clinical material, BPS/IC ESSIC type 3C accounted for 55% of cases. Patients with non-Hunner disease were on average 20 years younger at the time of diagnosis. Furthermore, there was a marked and significant difference in bladder capacity under general anaesthesia (p < 0.0001). The findings in the present series, together with previously published reports by this group and by others, confirm the striking differences between the main forms of BPS/IC and underline the indispensability of adequate subtyping in clinical studies.

YKL‐40 and mast cells are associated with detrusor fibrosis in patients diagnosed with bladder pain syndrome/interstitial cystitis according to the 2008 criteria of the European Society for the Study of Interstitial Cystitis

Bladder pain syndrome/interstitial cystitis (BPS/IC), diagnosed according to the new 2008 criteria of the European Society for the Study of Interstitial Cystitis (ESSIC), may lead to detrusor fibrosis. In some inflammatory diseases, fibrosis is related to YKL-40. The aims were to examine YKL-40 antigenic expression in bladder tissue and levels in serum and urine in BPS/IC and to evaluate whether YKL-40 could be a non-invasive, prognostic biomarker for bladder fibrogenesis and treatment intensity. Immunohistochemistry, immunoelectron microscopy and enzyme-linked immunosorbent assay (ELISA) analyses in 45 patients showed YKL-40 expression in detrusor mast cell granules and submucosal macrophages, and elevated YKL-40 levels in serum and urine compared to healthy individuals (median 72 versus 7 μg/l, P < 0.001). Clinicopathological parameters showed associations of detrusor fibrosis with YKL-40-positive cells (P = 0.001), mast cells (P = 0.014) and urine YKL-40 (P = 0.009). Bladder capacity correlated inversely with YKL-40-positive cells (P < 0.001) and mast cells (P = 0.029). Treatment intensity was not associated with YKL-40. Serum and urine levels of YKL-40 may be used as non-invasive biomarkers in BPS/IC for the evaluation of bladder fibrogenesis.

Neue Erkenntnisse zur Differenzialdiagnostik des Bladder-Pain-Syndroms

The diagnosis of bladder pain syndrome/interstitial cystitis (BPS/IC) is challenging, since pathogenetic mechanisms and the definition of clinical relevant parameters are still under lively discussion. The criteria recently proposed by the European Society for the Study of Interstitial Cystitis (ESSIC) define a collective of patients based on the cardinal symptom of bladder pain which is heterogeneous, and therefore cannot receive standardised consistent therapy. Thus an extended diagnosis based on molecular markers seems to be indicated to render individual pharmacotherapy possible, and to contribute to elucidation of BPS/IC pathogenesis. For this purpose we feel the vital need for taking a bladder biopsy. The diagnosis of BPS/IC should rely on 3 "columns": (1) clinical diagnostics; (2) histopathology; (3) molecular diagnostics/protein expression. Since a significant contribution of the 3 functional units of the bladder to the pathophysiology is most evident, the examinations should ideally include urothelium, lamina propria, and detrusor musculature. Generation of receptor profiles of the detrusor muscle represents a first attempt to define a diagnostic tool for the individualisation of BPS/IC pharmacotherapy. Other factors, e.g., beta-hCG expression in the urothelium, need further evaluation. Extended BPS/IC diagnostics could be realistically integrated into routine patient care within a clinic/laboratory network.

Bladder pain syndrome/interstitial cystitis in a Danish population: a study using the 2008 criteria of the European Society for the Study of Interstitial Cystitis

To characterize and evaluate a Danish patient population with bladder pain syndrome/interstitial cystitis (BPS/IC), using a working definition for BPS/IC incorporating six variables, and a set of criteria defined by the European Society for the Study of Interstitial Cystitis (ESSIC); to describe the clinical course and treatment intensity in relation to these variables. Clinical data were obtained retrospectively from medical records for 349 consecutive patients with IC referred to the Department of Urology, Copenhagen University Hospital Herlev, Denmark between 1966 and 2008. The median (range) age at diagnosis was 53 (16-88) years; 64% were followed for at least 2 years. The outcome was expressed in terms of treatment intensity and was correlated with clinical data (pain, nocturnal frequency, bladder capacity, mucosal glomerulations, detrusor mastocytosis, detrusor intrafascicular fibrosis, IFF). All patients had pain and 75% had nocturia at least twice. The bladder capacity estimated under general anaesthesia was <500 mL in 42%; 53% presented with detrusor mastocytosis (> or =28 mast cells/mm(2)) and 50% with IFF. The detrusor mast cell count (P < 0.001), IFF (P = 0.004) and nocturnal frequency (P = 0.043) had statistically significant prognostic value for treatment intensity, whereas bladder capacity and glomerulations were not significant. Nocturia, detrusor mastocytosis and IFF are associated with multiple treatments and presumed failure of standard urological therapy in patients with BPS/IC, while bladder capacity and glomerulations are not. Valid conclusions cannot be drawn because of numerous limitations to the study.