Proteomic analysis of bladder biopsies from interstitial cystitis/bladder pain syndrome patients with and without Hunner's lesions reveals differences in expression of inflammatory and structural proteins.

BACKGROUND: Interstitial cystitis/bladder pain syndrome is a bladder disease usually characterized by pain, urgency, and frequency. Interstitial cystitis is currently classified into two subtypes, with and without Hunner's lesions. However, the underlying etiology of interstitial cystitis and its subtypes are largely unknown. METHODS: To better understand the biological changes in the bladder of interstitial cystitis/bladder pain syndrome patients, we directly analyzed bladder tissue of interstitial cystitis patients, both those with Hunner's lesions and those without. Proteins in the bladder biopsies were analyzed using nanoscale high-performance liquid chromatography-tandem mass spectrometry. Disease subgroups were compared and significantly expressed proteins were mapped using STRING to determine protein associations and functions. RESULTS: We found that patients with Hunner's lesions had significant increases in inflammatory and endoplasmic reticulum stress proteins, with a decrease in cellular adhesive proteins, compared to patients without Hunner's lesions. These patients also exhibited a decrease in proteins associated with the Rap1 signaling pathway, which regulates cell proliferation and wound healing. When comparing diseased and non-disease-apparent tissue in patients with Hunner's lesions, diseased tissue exhibited a decrease in ubiquitination proteins. CONCLUSIONS: In summary, there are significant differences in protein expression found in the bladders of interstitial cystitis patients with and without Hunner's lesions, indicating a disturbance in proteins associated with cellular adhesion, proliferation, protein processing, and wound healing.

Molecular Taxonomy of Interstitial Cystitis/Bladder Pain Syndrome Based on Whole Transcriptome Profiling by Next-Generation RNA Sequencing of Bladder Mucosal Biopsies.

PURPOSE: We systematically characterized gene expression, inflammation and neovascularization in patients with interstitial cystitis/bladder pain syndrome to obtain biological evidence supporting diagnosis and classification. MATERIALS AND METHODS: We sequenced RNA obtained from bladder mucosal biopsies of 33 patients with 3 subtypes of interstitial cystitis/bladder pain syndrome, including Hunner lesions in 12, no Hunner lesions in 11 but with glomerulations and neither Hunner lesions nor glomerulations in 10, and 9 controls. Differentially expressed genes of each subtype were searched to identify subtype specific biological pathways and candidate genes important for pathogenesis. Candidate genes were validated by quantitative polymerase chain reaction and immunohistochemistry. Digital immunohistochemical quantification was performed to assess subepithelial lymphoplasmacytic cell and microvessel density. Relationships between candidate gene over expression and symptom severity were explored. RESULTS: Patients with Hunner lesions showed a distinct gene expression profile associated with significant up-regulation of biological processes involving immune responses and infection, and an increase in subepithelial lymphoplasmacytic cell and microvessel density. Over expression of 2 candidate genes, VEGF and BAFF, correlated with symptom severity. Meanwhile, the gene expression profiles of patients with the 2 subtypes without Hunner lesions were similar to those of controls. No difference in biological pathways or subepithelial lymphoplasmacytic cell and microvessel density were detected between these 2 subtypes and controls. CONCLUSIONS: Interstitial cystitis/bladder pain syndrome with Hunner lesions shows distinct genomic and histological features associated with immune responses and infection. In addition, VEGF and BAFF are potential disease biomarkers and therapeutic targets. This subtype should be considered separate from the syndrome.

Histological evidence supports low anesthetic bladder capacity as a marker of a bladder-centric disease subtype in interstitial cystitis/bladder pain syndrome.

INTRODUCTION AND HYPOTHESIS: Low anesthetic bladder capacity has been shown to be a biomarker for bladder-centric interstitial cystitis/bladder pain syndrome (IC/BPS). The goal of this study was to determine if histopathological evidence from bladder biopsies supports anesthetic bladder capacity (BC) as a marker to distinguish a bladder-centric IC/BPS subtype. METHODS: From a review of our large IC/BPS cohort of patients undergoing hydrodistention, we identified a total of 41 patients with low BC (≤ 400 ml); an additional 41 consecutive patients with BC > 400 ml were selected as the comparator group. The original bladder mucosal biopsy pathology slides were re-reviewed by a single pathologist (blinded to patient information) using a standardized grading scale developed for this study. RESULTS: Histologically, the low BC subjects exhibited higher levels of acute inflammation (p = 0.0299), chronic inflammation (p = 0.0139), and erosion on microscopy (p = 0.0155); however, there was no significant difference in mast cell count between groups (p = 0.4431). There was no significant gender difference between the groups; female patients were the majority in both groups (low BC: 94.12%, non-low BC: 100%; p = 0.1246). Individuals in the low BC group were older (p < 0.0001), had a higher incidence of Hunner's lesions on cystoscopy (p < 0.0001), and had significantly higher scores, i.e., more bother symptoms, on two IC/BPS questionnaires (ICPI, p = 0.0154; ICSI, p = 0.0005). CONCLUSIONS: IC/BPS patients with low anesthetic bladder capacity have histological evidence of significantly more acute and chronic inflammation compared with patients with a non-low bladder capacity. These data provide additional evidence to support low bladder capacity as a marker of a distinct bladder-centric IC/BPS phenotype.

Interstitial cystitis, bladder pain syndrome, hypersensitive bladder, and interstitial cystitis/bladder pain syndrome - clarification of definitions and relationships.

Interstitial cystitis and interstitial cystitis-related conditions such as bladder pain syndrome and hypersensitive bladder have a similar symptomatic profile but probably different etiologies. A meaningful classification of these diseases/conditions is mandatory for clinical and investigational progress. The condition with Hunner lesions (Hunner type interstitial cystitis) is distinct from other categories in terms of histopathology, gene expression, and clinical management. Classification should clearly differentiate the presence or absence of Hunner lesions. The term covering patients as a whole should contain interstitial cystitis, since interstitial cystitis is historically a well-known name and used for insurance reimbursement. The proposed taxonomy features an umbrella term (interstitial cystitis/bladder pain syndrome) and two subgroups, Hunner type interstitial cystitis (with Hunner lesions) and bladder pain syndrome (without Hunner lesions). Interstitial cystitis/bladder pain syndrome is convenient for initial management, and subgroups can categorize the patients for specific management. The characteristic symptom profile is to be collectively termed as hypersensitive bladder symptoms.

Improving the utility of clinical phenotyping in interstitial cystitis/painful bladder syndrome: from UPOINT to INPUT.

INTRODUCTION: The phenotyping system UPOINT has proven effective in classifying patients with Urologic Pelvic Pain Syndromes in a clinically meaningful way and to guide therapy. While highly successful in men with chronic pelvic pain syndrome (CPPS), UPOINT is more limited in patients with interstitial cystitis/painful bladder syndrome (IC/PBS) since by definition all patients have the urinary and organ specific phenotype. Furthermore, AUA guidelines recommend a sequential tiered approach to therapy rather than the multimodal UPOINT scheme. We sought to modify UPOINT to be more practical and efficacious for IC/PBS. MATERIALS AND METHODS: We developed a new phenotype by removing the urinary and organ specific domains from UPOINT and adding a Hunner's ulcers (U) domain, since these patients benefit from phenotype specific therapies (fulguration, cyclosporine). This yields 'INPUT': infection, neurologic/systemic, psychosocial, ulcers and tenderness of muscles. We applied this system retrospectively to our previously validated upointmd.com IC/PBS database. Symptoms were measured by the Genitourinary Pain Index (GUPI) (valid for men and women). The database was searched for patients with complete data to assess the INPUT domains and include GUPI. Men were included if they reported pain relieved by voiding and/or presence of Hunner's ulcers. Groups were compared with ANOVA, Mann-Whitney, t test or chi squared when appropriate and correlated with Spearman r. RESULTS: There were 239 patients, 154 female (64%) with age range 18-79 (mean 41.8). Incidence of domains was infection 11%, neurologic/systemic 51%, psychosocial 81%, ulcers 18% and tenderness 85%. Mean total domains was 2.46 (range 0-5) and 65% had 2 or 3 positive domains while only 5% had none. There was a stepwise increase in GUPI score with increasing number of positive INPUT domains (ANOVA for differences between groups p < 0.0001. Correlation by Spearman r = 0.355 p < 0.0001). Presence of Hunner's ulcers increased mean symptom score (25.7 versus 29.7, p = 0.004) and indeed each of the domains significantly increased total GUPI score except for Infection. CONCLUSIONS: The INPUT phenotype in IC/PBS appears to replicate the validity and potential clinical utility of UPOINT in CPPS. Patients have a diversity of phenotypes and more positive domains correlate with more severe symptoms. Since 95% of patients have at least 1 positive domain it may benefit patients to receive multimodal therapy up front for these extra domains (eg. pelvic floor physical therapy, fulguration of ulcers) rather than relying on a sequential tiered approach.

Painful Bladder Filling and Painful Urgency are Distinct Characteristics in Men and Women with Urological Chronic Pelvic Pain Syndromes: A MAPP Research Network Study.

PURPOSE: We describe bladder associated symptoms in patients with urological chronic pelvic pain syndromes. We correlated these symptoms with urological, nonurological, psychosocial and quality of life measures. MATERIALS AND METHODS: Study participants included 233 women and 191 men with interstitial cystitis/bladder pain syndrome or chronic prostatitis/chronic pelvic pain syndrome in a multicenter study. They completed a battery of measures, including items asking whether pain worsened with bladder filling (painful filling) or whether the urge to urinate was due to pain, pressure or discomfort (painful urgency). Participants were categorized into 3 groups, including group 1-painful filling and painful urgency (both), 2-painful filling or painful urgency (either) and 3-no painful filling or painful urgency (neither). RESULTS: Of the men 75% and of the women 88% were categorized as both or either. These bladder characteristics were associated with more severe urological symptoms (increased pain, frequency and urgency), a higher somatic symptom burden, depression and worse quality of life (3-group trend test each p<0.01). A gradient effect was observed across the groups (both>either>neither). Compared to those in the neither group men categorized as both or either reported more frequent urological chronic pelvic pain syndrome symptom flares, catastrophizing and irritable bowel syndrome, and women categorized as both or either were more likely to have a negative affect and chronic fatigue syndrome. CONCLUSIONS: Men and women with bladder symptoms characterized as painful filling or painful urgency had more severe urological symptoms, more generalized symptoms and worse quality of life than participants who reported neither characteristic, suggesting that these symptom characteristics might represent important subsets of patients with urological chronic pelvic pain syndromes.

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

AIMS: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Inflammation characteristics in bladder pain syndrome ESSIC type 3C/classic interstitial cystitis.

OBJECTIVES: Interstitial cystitis is regarded as a heterogenous syndrome with two distinguishable forms: the non-ulcer and the classic form of interstitial cystitis, the latter with Hunner's lesions; or bladder pain syndrome type 3C and non-Hunner bladder pain syndrome, respectively. METHODS: A cohort of 379 patients diagnosed with interstitial cystitis was studied. Nitric oxide release from the bladder was measured using a chemiluminescence nitric oxide analyzer. Bladder biopsies from the patients and healthy controls were analyzed by routine histopathological examination. Biopsies from a subset of patients and controls were also analyzed by immunohistochemistry and cytokine gene expression by real-time polymerase chain reaction. RESULTS: Patients with bladder pain syndrome type 3C/classic interstitial cystitis had considerably higher levels of nitric oxide as compared with non-Hunner bladder pain syndrome/non-ulcer interstitial cystitis patients and healthy individuals, and showed histologically a chronic inflammation in the bladder mucosa, with abundant mast cell infiltration in all layers of the bladder wall. No inflammation was noted in non-Hunner bladder pain syndrome/non-ulcer interstitial cystitis patients. The isoenzymes inducible nitric oxide synthase, the catalyst in the nitric oxide production, was strongly expressed in the inflammatory cells in the bladder mucosa of bladder pain syndrome type 3C/classic interstitial cystitis patients. In addition, the expression of the pro-inflammatory cytokines interleukin-6 and interleukin-17A messenger ribonucleic acid, and of anti-inflammatory interleukin-10 messenger ribonucleic acid showed significantly increased levels in bladder pain syndrome type 3C/classic interstitial cystitis compared with healthy controls. CONCLUSION: Bladder pain syndrome type 3C/classic interstitial cystitis is a distinct inflammatory disease and in many aspects shares features of inflammatory autoimmune diseases. These findings could open up novel research avenues with expectations for new targets for pharmacological treatment.

Risk Classification for Interstitial Cystitis/Bladder Pain Syndrome Using Machine Learning Based Predictions.

OBJECTIVE: To improve diagnosis of interstitial cystitis (IC)/bladder pain syndrome(IC) we hereby developed an improved IC risk classification using machine learning algorithms. METHODS: A national crowdsourcing resulted in 1264 urine samples consisting of 536 IC (513 female, 21 male, 2 unspecified), and 728 age-matched controls (318 female, 402 male, 8 unspecified) with corresponding patient-reported outcome (PRO) pain and symptom scores. In addition, 296 urine samples were collected at three academic centers: 78 IC (71 female, 7 male) and 218 controls (148 female, 68 male, 2 unspecified). Urinary cytokine biomarker levels were determined using Luminex assay. A machine learning predictive classification model, termed the Interstitial Cystitis Personalized Inflammation Symptom (IC-PIS) Score, that utilizes PRO and cytokine levels, was generated and compared to a challenger model. RESULTS: The top-performing model using biomarker measurements and PROs (area under the curve [AUC]=0.87) was a support vector classifier, which scored better at predicting IC than PROs alone (AUC=0.83). While biomarkers alone (AUC=0.58) did not exhibit strong predictive performance, their combination with PROs produced an improved predictive effect. CONCLUSION: IC-PIS represents a novel classification model designed to enhance the diagnostic accuracy of IC/bladder pain syndrome by integrating PROs and urine biomarkers. The innovative approach to sample collection logistics, coupled with one of the largest crowdsourced biomarker development studies utilizing ambient shipping methods across the US, underscores the robustness and scalability of our findings.

Clinical phenotyping of urologic pain patients.

PURPOSE OF REVIEW: Urologic pain conditions such as chronic prostatitis/chronic pelvic pain syndrome, interstitial cystitis/bladder pain syndrome and chronic orchialgia are common, yet diagnosis and treatment are challenging. Current therapies often fail to show efficacy in randomized controlled studies. Lack of efficacy may be due to multifactorial causes and heterogeneity of patient presentation. Efforts have been made to map different phenotypes in patients with urologic pain conditions to tailor more effective therapies. This review will look at current literature on phenotype classification in urologic pain patients and their use in providing effective therapy. RECENT FINDINGS: There has been validation of the 'UPOINT' system (urinary symptoms, psychosocial dysfunction, organ specific findings, infection, neurologic/systemic and tenderness of muscle) to better categorize male chronic prostatitis/chronic pelvic pain syndrome and interstitial cystitis/bladder pain syndrome. Refinement of domain systems and recent cluster analysis has suggested possible central processes involved in urologic pain conditions similar to systemic pain syndromes such as fibromyalgia, chronic fatigue and irritable bowel syndrome. SUMMARY: Domain characterization of urologic pain conditions via phenotype mapping can be used to better understand causes of chronic pain and hopefully provide more effective, targeted and multimodal therapy.

Chronic pelvic pain syndrome/bladder pain syndrome: taking stock, looking ahead: ICI-RS 2011.

This review reflects the presentations and subsequent discussions at the International consultation on Incontinence Research Society's annual meeting. It updates the current definitions and diagnostic and treatment algorithms for bladder pain syndrome and chronic pelvic pain syndrome (non-bacterial prostatitis), highlights some specific basic research findings from discussion participants, looks at what we can hope to eventually learn from a large multicenter National Institutes of Health study, reviews future research pathways as articulated by the National Urologic Research Agenda of the American Urological Association and others, discusses recent therapeutic efforts, and concludes with discussion points from the ICI-RS meeting.

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

OBJECTIVE: 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. MATERIAL AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Anesthetic Bladder Capacity is a Clinical Biomarker for Interstitial Cystitis/Bladder Pain Syndrome Subtypes.

OBJECTIVE: To further examine anesthetic bladder capacity as a biomarker for interstitial cystitis/bladder pain syndrome (IC/BPS) patient subtypes, we evaluated demographic and clinical characteristics in a large and heterogeneous female patient cohort. MATERIAL AND METHODS: This is a retrospective review of data from women (n = 257) diagnosed with IC/BPS who were undergoing therapeutic bladder hydrodistention (HOD). Assessments included medical history and physical examination, validated questionnaire scores, and anesthetic BC. Linear regression analyses were computed to model the relationship between anesthetic BC and patient demographic data, symptoms, and diagnoses. Variables exhibiting suggestive correlations (P ≤ .1) were candidates for a multiple linear regression analysis and were retained if significant (P ≤ .05). RESULTS: Multiple regression analysis identified a positive correlation between BC and endometriosis (P = .028) as well as negative correlations between BC and both ICSI score (P < .001) and the presence of Hunner's lesions (P < .001). There were higher average numbers of pelvic pain syndrome (PPS) diagnoses (P = .006) and neurologic, autoimmune, or systemic pain (NASP) diagnoses (P = .003) in IC/BPS patients with a non-low BC, but no statistical difference in the duration of diagnosis between patients with low and non-low BC (P = .118). CONCLUSION: These data, generated from a large IC/BPS patient cohort, provide additional evidence that higher BC correlates with higher numbers of non-bladder-centric syndromes while lower BC correlates more closely with bladder-specific pathology. Taken together, the results support the concept of clinical subgroups in IC/BPS.

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.

Clinical phenotyping of women with interstitial cystitis/painful bladder syndrome: a key to classification and potentially improved management.

PURPOSE: We have proposed a clinical phenotype system (UPOINT) to classify patients with urological pelvic pain to improve the understanding of etiology and guide therapy. We examined the relationship between UPOINT and symptoms in patients with interstitial cystitis/painful bladder syndrome. MATERIALS AND METHODS: Patients with interstitial cystitis/painful bladder syndrome were classified in each domain of UPOINT, that is urinary, psychosocial, organ specific, infection, neurological/systemic and tenderness. Symptoms were assessed using the Interstitial Cystitis Symptom Index, Pain/Urgency/Frequency score and visual analogue scale for pain/urgency/frequency. Clinically relevant associations were calculated. RESULTS: The mean age of 100 consecutive patients with interstitial cystitis/painful bladder syndrome was 48 years, median symptom duration was 7 years and median Interstitial Cystitis Symptom Index score was 12.8. The percent positive for each domain was urinary 100%, psychosocial 34%, organ specific 96%, infection 38%, neurological/systemic 45% and tenderness 48%. All patients were included in at least 2 domains, with 2 domains for 13%, 3 domains--35%, 4 domains--34%, 5 domains--13% and 6 domains--5%. The number of domains was associated with greater symptom duration (p = 0.014) but not age. The number of domains was also associated with poorer general interstitial cystitis and pain symptoms (Interstitial Cystitis Symptom Index p = 0.012, pain p = 0.036) but not with frequency or urgency. The psychosocial domain was associated with increased pain, urgency and frequency, while tenderness was associated with increased Interstitial Cystitis Symptom Index score, pain/urgency/frequency score and urgency. The neurological/systemic domain was associated with increased Interstitial Cystitis Symptom Index score while the infection domain was not associated with any increased symptoms. CONCLUSIONS: The UPOINT phenotyping system can classify patients with interstitial cystitis according to clinically relevant domains. Increased symptom duration leads to a greater number of domains, and domains that function outside of the bladder (psychosocial, neurological, tenderness) predict a significant impact on symptoms. We hypothesize that the UPOINT system can direct multimodal therapy and improve outcomes.

Pathology and terminology of interstitial cystitis/bladder pain syndrome: A review.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is an umbrella term of chronic debilitating conditions of unknown etiology characterized by symptoms of lower urinary tract hypersensitivity such as bladder pain/discomfort, urgency, and urinary frequency. The pathological features of IC/BPS have been generally reported as non-specific chronic inflammatory changes, with mast cell infiltration as a potential key finding. However, growing evidence reveals a histological distinction between IC/BPS with Hunner lesions and IC/BPS without Hunner lesions, and also sheds doubt on the diagnostic value of the mast cell count. Specifically, IC/BPS with Hunner lesions is an inflammatory disorder characterized by pancystitis with B cell abnormalities and epithelial denudation, while IC/BPS without Hunner lesions shows minimal histological changes. The umbrella term "IC/BPS" connects totally distinct clinical entities. Pathological evaluation thus plays an important role in the precise subtyping and clinical management of IC/BPS. In addition, terminology should be developed to refer separately to IC/BPS with Hunner lesions and IC/BPS without Hunner lesions.

Stratification of Patients With Interstitial Cystitis/Bladder Pain Syndrome According to the Anatomical Bladder Capacity.

OBJECTIVE: To compare the data of score symptoms (Interstitial Cystitis Problem Index, Interstitial Cystitis Symptom Index, Pelvic Pain and Urgency/Frequency Patient Symptom Scale and SF-36quality of life), voiding diaries, urodynamic studies, and cystoscopy under general anesthesia according to the anatomical bladder capacity for patients with interstitial cystitis/bladder pain syndrome (IC/BPS). MATERIAL AND METHOD: Single-centre descriptive observational epidemiological study based on retrospective review of 134 patients managed for IC/BPS between January 2010 and December 2016. Patients were stratified into 2 groups according to anatomical bladder capacity measured under general anesthesia: ≤400 mL (n = 40) and >400 mL (n = 94). RESULTS: Patients with an anatomical bladder capacity less than 400 of mL presented significantly different results for voiding diary data: higher total frequency (P = .0023) especially at night (P = .0008), lower functional bladder capacity (P = .0082) and lower maximum bladder capacity (P = .0001); urodynamic data: earlier onset of painful urge during bladder filling (P = .0002), lower maximum bladder filling capacity (P = .0001) and lower compliance (P = .0067); and the findings of cystoscopy under general anesthesia: more Hunner's lesions (P = .00013). These patients presented poorer Pelvic Pain and Urgency/Frequency Patient Symptom Scale symptom scores (P = .0176) but associated with better overall quality of life as assessed by SF-36 (P = .0295). CONCLUSION: The anatomical bladder capacity, measured under general anesthesia, can be used objectively to define 2 distinct groups of patients with symptoms of IC/BPS.

Re-imagining interstitial cystitis.

Since the postulation of an "antiproliferative factor" in 1998 and a description, six years later, of this putative central protein in the etiologic pathway of the painful bladder syndrome/interstitial cystitis, there have been no dramatic breakthroughs in the field. Although much potentially exciting work is in progress with regard to epidemiology, etiology, and clinical treatment, many clinicians and researchers have used this hiatus to take another look at what exactly is being studied and how the syndrome should be approached. This article explores some of the current "hot-button" issues of definition and nomenclature that have formed the basis of many international meetings in the last 5 years.

Interstitial cystitis and systemic autoimmune diseases.

The cause of interstitial cystitis, a chronic disease that affects the bladder, is unknown. Autoantibodies, such as those against nuclear and bladder epithelium antigens, have been found in patients with interstitial cystitis, but these are likely to be secondary to the disease. No data support a direct causal role of autoimmune reactivity in the pathogenesis of interstitial cystitis. Indirect evidence, however, does support a possible autoimmune nature of interstitial cystitis, such as the strong female preponderance and the clinical association between interstitial cystitis and other known autoimmune diseases within patients and families. The strongest association occurs between interstitial cystitis and Sjögren's syndrome. Increasing evidence suggests a possible role of autoantibodies to the muscarinic M3 receptor in Sjögren's syndrome. The M3 receptor is also located on the detrusor muscle cells of the bladder and mediates cholinergic contraction of the urinary bladder and other smooth muscle tissues. Autoantibodies to the M3 receptor might be important in both the early noninflammatory and the late inflammatory features of interstitial cystitis.