Hunner's Ulcer Research Articles

LACTOFERRIN IN THE TREATMENT OF INTERSTITIAL CYSTITIS: A RETROSPECTIVE PILOT STUDY.

Interstitial cystitis (IC), defined as a painful bladder syndrome (PBS), is a chronic condition that manifests itself as a suprapubic pain associated with an enhancing of frequency/urgency of urination, and for which there is no cure. Here, we present a retrospective pilot study on women affected from IC/PBS and treated with bovine lactoferrin (bLf). A total of 31 women, affected (20) or unaffected (11) from hereditary thrombophilia (HT), presented the median of 6 episodes of IC/PBS during the 6 months before the study. Treatment consisted of 17 weeks of orally administered Valpalf® capsules, containing bLf plus sodium bicarbonate and citrate. Out of 31 patients, only 3 women had one episode of IC/PBS during the follow-up period, while no episode was observed in 28 women. In the HT group, a significant decrease in both serum IL-6 and D-dimers was found after Valpalf® treatment. Moreover, in Valpalf®-treated women, cystoscopy revealed a global improvement in the appearance of the bladder, especially in term of inflammation/irritation and presence of Hunner ulcers. Even if our results must be corroborated by randomized double-blinded controlled trials on a larger number of patients, our observations indicate that bLf treatment is efficient in relieving IC/PBS symptoms, without side effects.

Outcomes of Cystodistension for Bladder Pain Syndrome: A Monocentric Analysis

Introduction: Bladder pain syndrome (BPS) is a chronic condition characterized by pelvic pain and urinary urgency/frequency. While the exact cause of BPS is unknown, various treatment options exist. This study aimed to evaluate bladder hydrodistension's short- and long-term efficacy in BPS patients. Methods: A retrospective analysis of four female BPS patients treated with bladder hydrodistension over 10 years was conducted. Symptoms, cystoscopy findings, and treatment outcomes were reviewed. Results: The average patient age was 40 years. All patients reported pain, with an average of 13 daytime and 3 nighttime urinary voids per day. Hydrodistension improved symptoms in 75% of patients, reducing daytime frequency and nocturia. Cystoscopy after hydrodistension revealed Hunner's ulcers in one patient and petechiae in three. One patient required a second hydrodistension. Transient worsening of symptoms and hematuria occurred in one patient each. Discussion: Bladder hydrodistension appears to be a safe and effective treatment for BPS, improving symptoms in most patients in our study. The findings are consistent with previous reports suggesting. Our study adds to the growing body of evidence supporting hydrodistension as a valuable tool in managing BPS. Conclusion: Bladder hydrodistension is a simple and minimally invasive technique that has proven its efficacy with a low complication rate. Our findings support the existing literature on the benefits of hydrodistension for BPS.

Local immune response in patients with classic and nonulcer type of interstitial cystitis/bladder pain syndrome

Several hypotheses regarding the pathophysiology of interstitial cystitis/bladder pain syndrome (IC/BPS) have been put forward, but no consensus has yet been reached. It is suggested that cytokines are involved in IC/BPS, as well as in inflammatory autoimmune diseases. Examining various biomarkers of bladder tissue, including mast cells is underway. However, few reports on a consistent immune activity profile are available. The aim of the study was to assess the cytokine profile, counts of mast cells and plasma cells as well as their relationship in patients with IC/BPS with and without Hunner’s lesions. 44 women with Hunner’s lesions (group I) and 82 women with non-ulcer type (group II) were examined. Patients were questioned on the Pelvic Pain Symptom Scale, Urinary Frequency Scale (PUF), Visual Analogue Scale (VAS) and O’Leary–Santa Interstitial Cystitis Symptom Index (ICSI). Cystoscopy and hydrodistension of the bladder were performed under general anesthesia. In biopsies of the bladder wall, the number of plasma cells and mast cells was assessed, in urine — IL-1β, IL-6, IL-8, TNFα. Statistical processing of the results was carried out using the Statistica 6 software (StatSoft, USA). The Student’s t-test, Spearman’s correlation coefficient were calculated. In patients with Hunner's ulcer, there was an insignificant increase in the scale indices and decreased magnitude for average volume, urination frequency, and maximum emptying volume. The maximum bladder capacity during hydrodistension was lowered by 42.01% (p 0.001). The level of IL-8 in group I was higher on average by 28.57% (p = 0.434) as compared with that in group II, IL-6 — by 13.46% (p = 0.638), TNFα — by 9.09% (p = 0.244) and IL-1β — by 4.13% (p = 0.859). The number of mast cells in patients of group I vs. group II was higher by 40.65% (p 0.05). In group I, a marked relationship was found between count of mast cells and plasma cells (r = –0.555, p 0.05), as well as between count of plasma cells and IL-6 level (r = –0.639, p 0.05). In group II, a significant connection was found between count of mast cells and TNFα level (r = +0.562, p 0.05). Patients with Hunner’s IC/BPS are characterized by severe inflammation, wherein mast cells are involved in induction. Determination of cytokines in urine can provide a non-invasive division of IC/BPS into ulcerative and non-ulcerative groups.

The diagnostic and therapeutic efficacy of cystoscopy with hydrodistension and random biopsies in clinically suspected interstitial cystitis/bladder pain syndrome

ObjectiveWe aimed to explore the diagnostic and therapeutic efficacy of cystoscopy with hydrodistension and random biopsies for clinically suspected interstitial cystitis/bladder pain syndrome (IC/BPS). Study designWe reviewed the data of fifty-five clinically suspected IC/BPS patients underwent cystoscopy with hydrodistension and random biopsies. Global Response Assessment was used to evaluate the efficacy. Disease severity was assessed by thorough history, physical examination, 3-day frequency volume chart, visual analog scale of pain, Interstitial Cystitis Symptom Index (ICSI) and clinical phenotype system (UPOINT). ResultsAccording to the pathologic outcomes from random biopsies, three out of the 55 clinically suspected IC/BPS were diagnosed as bladder carcinoma. Among the 52 IC/BPS patients, thirty-six patients (69.2%) had initial chief complaints of urinary frequency and urgency. Under cystoscopy, twenty-nine patients and 23 patients were classified as Hunner ulcer type and diffuse global mucosal bleeding (grade III glomerulation). The median functional bladder capacity of the 52 IC/BPS patients was 100 ml. Hydrodistension was effective in 28 patients (53.8%) at postoperative 3 months, which decreased to 25% at post-hydrodistension 6 months and to 13.5% at 12 months. For the 28 hydrodistension-effective patients, the remission degrees of daytime frequency, nocturia, VAS bladder pain and ICSI score were 50.3%, 49.4%, 68.1% and 48%, which were significantly higher than the 16.9% (daytime frequency, P < 0.001), 20.5% (nocturia, P = 0.021), 7.4% (VAS pain score, P < 0.001) and 6.1% (ICSI, P < 0.001) in the hydrodistension-negative group. According to the UPOINT system, the hydrodistension-effective cases had significantly higher rates of symptom remission in U (P = 0.002), P (P = 0.026), O (P < 0.001), and T (P < 0.001) domains than the corresponding negative cases. In effective group, the O domain had the most remission rate (26 out of 28, 92.9%, P < 0.001), followed by the U domain (12 out of 28, 42.9%, P < 0.001) and T domain (12 out of 28, 42.9%, P < 0.001). ConclusionHistopathological analysis from random biopsies could distinguish bladder carcinoma from clinically suspected IC/BPS. Hydrodistension is more likely to be effective when chronic pelvic pain is obviously alleviated. The efficacy of hydrodistension could act in a certain period of time.

How can we improve the diagnosis and management of bladder pain syndrome? Part 1: ICI-RS 2018.

This paper summarizes the discussion in a think tank at the ICI-RS 2018 about the diagnosis of bladder pain syndrome (BPS). To review the guidelines, investigations and subtypes of BPS. Review of literature in the light of the think tank discussion. All guidelines recommend completing history, physical examination, urine analysis, urine culture, and urine cytology to define the BPS phenotype but there are differences on further investigations. In those guidelines which recommend cystoscopy, the identification of Hunner's lesions (HLs) is recommended as this changes the treatment plan and outcome. We propose that the differentiation of Hunner's ulcers is an important step in the assessment of these patients. Further suggestions for research are suggested.

Re: Therapeutic Effects of Endoscopic Ablation in Patients with Hunner Type Interstitial Cystitis.

No AccessJournal of UrologyUrological Survey1 Jul 2019Re: Therapeutic Effects of Endoscopic Ablation in Patients with Hunner Type Interstitial Cystitis Alan J. WeinMD, PhD (hon) Alan J. WeinAlan J. Wein More articles by this author View All Author Informationhttps://doi.org/10.1097/01.JU.0000557758.04284.9fAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Re: Therapeutic Effects of Endoscopic Ablation in Patients with Hunner Type Interstitial Cystitis." The Journal of Urology, 202(1), pp. 38–39 Suggested Reading : Fulguration for Hunner ulcers: long-term clinical outcomes. J Urol 2012; 188: 2238. Link, Google Scholar : Conservative management of chronic interstitial cystitis: transcutaneous electrical nerve stimulation and transurethral resection. J Urol 1985; 133: 774. Link, Google Scholar : Diagnosis and treatment of interstitial cystitis/bladder pain syndrome: AUA guideline amendment. J Urol 2015; 193: 1545. Link, Google Scholar : Toward a precise definition of interstitial cystitis: further evidence of differences in classic and nonulcer disease. J Urol 2002; 167: 2470. Link, Google Scholar © 2019 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 202Issue 1July 2019Page: 38-39 Advertisement Copyright & Permissions© 2019 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alan J. Wein More articles by this author Expand All Advertisement Loading ...

Analysis of key genes and micro-RNA-mRNA regulatory networks in women with ulcerative interstitial cystitis/pain bladder syndrome.

This aim of this study was to better understand ulcerative interstitial cystitis/painful bladder syndrome (IC/PBS) at the molecular level and provide new clues related to diagnosis and treatment. The microarray data set GSE11783, including the mRNA and miRNA profiles of bladder tissue obtained at cystoscopic biopsy from patients with ulcerative IC/PBS (presence of at least one Hunner's ulcer) and normal controls, was downloaded from the GEO (Gene Expression Omnibus) database (National Center for Biotechnology Information). These were evaluated using Greenspring GX and Ingenuity Pathway Analysis (IPA) software. The differentially expressed genes (DEGs) and miRNAs (DEMs) in these two groups were identified. Subsequently, the DEGs were subjected to functional analysis, and a protein-protein interaction (PPI) network was constructed. Finally, the miRNA-mRNA regulatory network was visualized using Cystoscope software. Four DEMs and 1521 DEGs were identified between the ulcerative IC/PBS and control groups. The PPI network of the DEGs was constructed by STRING, which was composed of 393 nodes and 1039 edges, including 221 upregulated genes and 172 downregulated genes. Moreover, 27 genes in the PPI network were identified as hub genes in the IC/PBS group, e.g., PNOC, SSTR1, FPR3, GPR18 and APLNR. Subsequently, 27 clusters were selected from the PPI network using MCODE. It was shown that the most significant cluster consisted of 22 nodes and 231 edges. Moreover, miR-21 was the most significantly upregulated miRNA and was predicted to target one upregulated gene (RASGRP1) and two downregulated genes (KLF5 and SC5D). The results of this data mining and integration provide further information on the possible molecular basis of IC/PBS pathogenesis as well as potential biomarkers and therapeutic targets for ulcerative IC/PBS diagnosis and treatment.

Expression of programmed death ligand-1 on bladder tissues is detected in a clinically and histologically well-defined interstitial cystitis cohort.

To investigate the expression of programmed death ligand-1 (PD-L1) in interstitial cystitis (IC). We reviewed the data of IC patients underwent hydrodistension plus bladder biopsy. Follow-ups were performed. We assessed the degree of inflammation of the bladder wall on slides stained with hematoxylin and eosin (H&E). We performed immunohistochemistry for PD-L1 expression detection and for counting T lymphocytes and B lymphocytes. The present study included eight men and 32 women. With H&E staining, we detected 13, 15, and 12 patients with mild, moderate, and severe inflammation. The degree of inflammation was negatively correlated with disease course (P = 0.018) and positively correlated with bladder pain (P < 0.001). Hydrodistension was found effective at postoperative 3-month for 19 patients. Overall, 17, 15, 7, and 1 subject had no, mild, moderate, and high PD-L1 expression, that correlated positively with the degree of inflammation. Compared with patients with no and mild PD-L1 expression, patients with moderate and high PD-L1 expression tended to have more effective hydrodistension outcomes (12 of 32 vs 7 of 8; P = 0.017). In the subset of 12 patients with severe inflammation, there were five of six patients (83.3%) with moderate or high PD-L1 expression and one of six patients (16.7%) with no and mild PD-L1 expression with an effective hydrodistension outcome. Expression of PD-L1 on bladder is detected in a cohort of IC patients presented with diffuse global glomerulation or Hunner ulcer. PD-L1 expression is more common in IC patients with severe bladder inflammation.

What are the diagnostic criteria for interstitial cystitis?

EVIDENCE-BASED ANSWER Interstitial cystitis may be diagnosed by the more restrictive criteria of the National Institute of Diabetes, Digestive, and Kidney (NIDDK), which requires bladder pain or urinary urgency for 9 months, the presence of glomerulations or Hunner's ulcer on cystoscopy, and urodynamic evaluation. The NIDDK criteria exclude more than 50% of patients who clinicians suspect have interstitial cystitis based on the more inclusive criteria of urinary frequency (≥7 times per day), urgency, or bladder pain for at least 6 months with no other clear etiologies (SOR: B, cross-sectional study). The most common symptoms of interstitial cystitis include urgency, frequency, nocturia, pain in the bladder, pain in the urethra, and pain in the vagina (SOR: B, systematic review of cross-sectional studies). Experts characterize interstitial cystitis as an unpleasant sensation (pain, pressure, discomfort) thought to be related to the urinary bladder and associated with lower urinary tract symptoms of more than 6 weeks’ duration, in the absence of infection or other identifiable causes (SOR: C, expert opinion).

Development of an interstitial cystitis risk score for bladder permeability.

BackgroundInterstitial cystitis/bladder pain syndrome (IC) is a multifactorial syndrome of severe pelvic and genitalia pain and compromised urinary function; a subset of IC patients present with Hunner’s lesions or ulcers on their bladder walls (UIC). UIC is diagnosed by cystoscopy, which may be quite painful. The objective of this study was to determine if a calculated Bladder Permeability Defect Risk Score (BP-RS) based on non-invasive urinary cytokines could discriminate UIC patients from controls and IC patients without Hunner’s ulcers.MethodsA national crowdsourcing effort targeted IC patients and age-matched controls to provide urine samples. Urinary cytokine levels for GRO, IL-6, and IL-8 were determined using a Luminex assay.ResultsWe collected 448 urine samples from 46 states consisting of 153 IC patients (147 female, 6 male), of which 54 UIC patients (50 females, 4 male), 159 female controls, and 136 male controls. A defined BP-RS was calculated to classify UIC, or a bladder permeability defect etiology, with 89% validity.ConclusionsThe BP-RS Score quantifies UIC risk, indicative of a bladder permeability defect etiology in a subset of IC patients. The Bladder Permeability Defect Risk Score is the first validated urine biomarker assay for interstitial cystitis/bladder pain syndrome.

MP29-16 IMPROVING THE UTILITY OF CLINICAL PHENOTYPING IN INTERSTITIAL CYSTITIS/PAINFUL BLADDER SYNDROME: FROM UPOINT TO INPUT

You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis II1 Apr 2017MP29-16 IMPROVING THE UTILITY OF CLINICAL PHENOTYPING IN INTERSTITIAL CYSTITIS/PAINFUL BLADDER SYNDROME: FROM UPOINT TO INPUT Alice Crane, Jessica Lloyd, and Daniel Shoskes Alice CraneAlice Crane More articles by this author , Jessica LloydJessica Lloyd More articles by this author , and Daniel ShoskesDaniel Shoskes More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.928AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES 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 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 vs 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. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e386-e387 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Alice Crane More articles by this author Jessica Lloyd More articles by this author Daniel Shoskes More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

MP29-07 DEVELOPMENT OF THE ULCERATIVE INTERSTITIAL CYSTITIS RISK SCORE (ICUS): A URINE-BASED MULTIPLE PROTEIN ASSAY TO PREDICT ULCERATIVE INTERSTITIAL CYSTITIS

You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis II1 Apr 2017MP29-07 DEVELOPMENT OF THE ULCERATIVE INTERSTITIAL CYSTITIS RISK SCORE (ICUS): A URINE-BASED MULTIPLE PROTEIN ASSAY TO PREDICT ULCERATIVE INTERSTITIAL CYSTITIS Laura Lamb, Joseph Janicki, Sarah Bartolone, Interstitial Cystitis Association, Bernadette Zwaans, Kenneth Peters, and Michael Chancellor Laura LambLaura Lamb More articles by this author , Joseph JanickiJoseph Janicki More articles by this author , Sarah BartoloneSarah Bartolone More articles by this author , Interstitial Cystitis AssociationInterstitial Cystitis Association More articles by this author , Bernadette ZwaansBernadette Zwaans More articles by this author , Kenneth PetersKenneth Peters More articles by this author , and Michael ChancellorMichael Chancellor More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.919AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Interstitial cystitis/bladder pain syndrome (IC/BPS) is a multifactorial syndrome of severe pelvic and genitalia pain and compromised urinary function. A fraction of IC patients who are the most severe present with Hunner's ulcers or patches on their bladder walls, termed ulcerative IC (UIC). UIC is diagnosed by cystoscopy, however this is a painful and expensive procedure. The objective of this study was to determine if a calculated Interstitial Cystitis Ulcerative Risk Score (ICUS) based on non-invasive urinary cytokines could discriminate UIC patients from controls and non-ulcerative IC patients. METHODS A national crowdsourcing effort targeting IC/BPS patients resulted in 442 urine samples consisting of 153 IC patients (146 female, 7 male), 155 female controls, and 134 male controls were collected. Controls were age-matched. This consisted of 52 UIC patients (48 females, 4 male). Urinary cytokine levels were determined using Luminex assay. A predictive classification model was generated from this data using the scikit-learn machine learning library and the Python programming language. It provides a probability of ulcerative IC when the algorithm is supplied with the levels of three different proteins found in the urine. RESULTS A defined ICUS Score of 0 to 1 was calculated to predict UIC, or a bladder permeability defect etiology (Figure 1). If the ICUS is ≥ 0.5, then there is an 87% chance that the patient has ulcerative IC. If the ICUS is <0.5, there is an 87% chance that the patient does not have ulcerative IC. The three protein levels combined provide a much better prediction model versus any of the individual protein levels alone. CONCLUSIONS The ICUS Score quantifies UIC risk, indicative of a bladder permeability defect etiology, in a subset of IC patients. This provides a new clinical tool to improve diagnosing patients with suspected IC symptoms. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e382 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Laura Lamb More articles by this author Joseph Janicki More articles by this author Sarah Bartolone More articles by this author Interstitial Cystitis Association More articles by this author Bernadette Zwaans More articles by this author Kenneth Peters More articles by this author Michael Chancellor More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Management of Bladder Pain Syndrome: Green-top Guideline No. 70.

Management of Bladder Pain Syndrome: Green-top Guideline No. 70.

Pain relief after triamcinolone infiltration in patients with bladder pain syndrome with Hunner's ulcers.

Bladder pain syndrome (BPS) is a chronic condition with severe implications in the patient's quality of life with no definitive treatment. Our objective was to assess pain relief after triamcinolone injection in patients with BPS with Hunner's ulcers (HU). Retrospective study of 20 consecutive patients with BPS treated at the Hospital Clinic of Barcelona with triamcinolone injection with flexible cystoscope between 2015 and 2016. Pain was assessed according to the visual analog scale (VAS) (0-10) before and after treatment. Outcomes were compared using Student's t test for paired samples. Twenty-seven procedures were performed in 20 patients, who were followed up for a median of 7months (range 1-15). Median age was 75years (52-86), and median time from diagnosis to treatment was 4.5years (1-7). Fifteen (75%) patients had received treatment with corticoid injection for BPS before entering the study. Pre- and postreatment VAS was 8 and 2.5 (p < 0.001), respectively. Pre -and postreatment VAS in those with muscular pain was 8 and 5 (p = 0.012), respectively and in those without muscular pain was 8 and 2 (p < 0.001), respectively. Three (15%) patients required retreatment due to nonresponse and 5 (25%) patients for pain recurrence after 4months (3.5-8). Four of them (50%) were performed with triamcinolone injection again. Seven of ten patients (70%) followed for ≥8months required at least one retreatment. Triamcinolone injection for HU in patients with BPS is associated with significant pain reduction. However, most patients will require retreatment.

MP72-15 GENE EXPRESSION IN THE BLOOD OF INTERSTITIAL CYSTITIS PATIENTS AND CONTROLS DISTINGUISHES PATHWAYS ASSOCIATED WITH INTERSTITIAL CYSTITIS AND PREDICTS CLINICAL RESPONSE TO CYCLOSPORINE THERAPY

You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis1 Apr 2016MP72-15 GENE EXPRESSION IN THE BLOOD OF INTERSTITIAL CYSTITIS PATIENTS AND CONTROLS DISTINGUISHES PATHWAYS ASSOCIATED WITH INTERSTITIAL CYSTITIS AND PREDICTS CLINICAL RESPONSE TO CYCLOSPORINE THERAPY Daniel Shoskes, Karen Keslar, Barbara Tucky, and Robert Fairchild Daniel ShoskesDaniel Shoskes More articles by this author , Karen KeslarKaren Keslar More articles by this author , Barbara TuckyBarbara Tucky More articles by this author , and Robert FairchildRobert Fairchild More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1628AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Interstitial cystitis (IC) is a heterogeneous condition with urinary and systemic symptoms. Clinically relevant phenotyping has been a challenge, but some patients, especially those with Hunner's Ulcers, have evidence for immune activation. We hypothesize that gene expression signatures can be used as a biomarker to phenotype patients with IC and predict response to specific therapies. METHODS As part of a clinical trial of oral cyclosporine A (CyA), blood was collected from 26 IC patients prior to treatment and after 3 months of CyA at 3 mg/kg/d as well as from 20 asymptomatic controls. A training set of 6 controls and 6 IC patients including those who did or did not respond to CyA was initially run. RNA was isolated from whole blood (Tempus tubes) and analyzed using Illumina HT-12 v4 BeadChip arrays. PANTHER pathway analysis and DAVID functional classification were used for annotation and grouping of differently expressed genes. RESULTS Using the criteria of fold-changes less than 0.5 or greater than 2 and p<.05, we found 155 unique genes that were differently expressed in the blood of IC patients vs controls representing 55 pathways including inflammation mediated by chemokines and cytokines, T cell activation, integrin signaling, angiogenesis, and apoptosis. Comparing patients who subsequently had significant clinical improvement with CyA therapy to those who didn't improve, there were 37 genes with at least two fold differential expression. Using DAVID functional annotation clustering, these genes represented responses in inflammation, wound healing, and innate immunity. Finally, following CyA therapy, interleukin signaling changed in all patients but other pathways that changed were distinct between responders and non-responders. In CyA responders, the altered gene expression pathways were related to matrix remodeling (plasminogen activating cascade) and pain modulation (cannabinoid and dopamine receptor signaling). CONCLUSIONS Gene expression signatures in whole blood distinguished between IC patients and controls as well as between patients who would subsequently improve with CyA therapy. Pathways altered following CyA therapy in the responders could serve as potential targets for new drug development. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e958 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Daniel Shoskes More articles by this author Karen Keslar More articles by this author Barbara Tucky More articles by this author Robert Fairchild More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Increased bladder permeability in interstitial cystitis/painful bladder syndrome.

The definition of interstitial cystitis (IC) has evolved over the years from being a well-defined entity characterized by diagnostic lesion (Hunner’s ulcer) in the urothelium to a clinical diagnosis by exclusion [painful bladder syndrome (PBS)]. Although the etiology is unknown, a central theme has been an association with increased permeability of the bladder. This article reviews the evidence for increased permeability being important to the symptoms of interstitial cystitis/painful bladder syndrome (IC/PBS) and in treating the disorder. Recent work showing cross-communication among visceral organs is also reviewed to provide a basis for understanding IC/PBS as a systemic disorder of a complex, interconnected system consisting of the bladder, bowel and other organs, nerves, cytokine-responding cells and the nervous system.

Electrosurgical management of Hunner ulcers in a referral center's interstitial cystitis population.

To characterize electrocautery (EC) as a valid treatment option in interstitial cystitis (IC) patients with Hunner ulcers (HUs). From 1997 to 2013, a single urologist's IC population was retrospectively reviewed to identify HU patients as well as their demographics, operative characteristics, and response to a 2-page questionnaire evaluating parameters of their experience with EC. Descriptive statistics, Pearson chi-square test, Student t test, and Pearson coefficient were used. Two hundred fourteen EC procedures were performed in 76 patients (87% women; mean age, 66 ± 1.67 years). Fifty-one patients (69%) who underwent multiple EC had mean initial bladder capacity of 438.62 ± 27.90 mL and final bladder capacity of 422.40 ± 30.10 mL. Mean number of EC procedures was 2.98 ± 0.25 (range, 1-11). Mean time between sessions was 14.52 ± 1.34 months (range, 1-121 months). Fifty-two patients (68%) completed our questionnaire, with 13.54 ± 1.28 years of symptoms and 10.66 ± 0.96 years since diagnosis. Ranking IC treatments, 37 patients (84%) reported EC most beneficial. On a 0-10 (none to worst possible) scale before and after EC, frequency improved from 9.04 ± 1.30 to 3.65 ± 2.75 (P <.001), urgency from 8.40 ± 2.38 to 3.28 ± 2.71 (P <.001), and pain from 8.62 ± 2.36 to 2.68 ± 2.55 (P <.001). Overall, 89.6% of patients noted some degree of symptom improvement after EC; 56.3% of patients had marked improvement. A total of 98% of patients would undergo EC again. EC of HU is an effective and safe procedure with high patient satisfaction that does not diminish bladder capacity.

468 Elimination of Hunner's ulcers by fulguration in patients with interstitial cystitis: Is it effective and long lasting?

468 Elimination of Hunner's ulcers by fulguration in patients with interstitial cystitis: Is it effective and long lasting?

Pretreatment features to influence effectiveness of intravesical hyaluronic Acid instillation in refractory interstitial cystitis/painful bladder syndrome.

PurposeTo determine the efficacy of intravesical hyaluronic acid (HA) instillation in treating patients with refractory interstitial cystitis/painful bladder syndrome (IC/PBS) and to identify any related factors that influence its therapeutic effect.MethodsThirty-three female IC/PBS patients who demonstrated poor or unsatisfactory responses to previous treatments between December 2010 and October 2012 were enrolled. Despite previous treatments, the enrolled patients had visual analogue scale (VAS) pain scores ≥4 and total scores (symptom and bother scores) ≥13 on the pelvic pain and urgency/frequency (PUF) questionnaire and ≥12 on the O'Leary-Sant interstitial cystitis symptoms index (ICSI)/problems index (ICPI). All patients received once weekly intravesical instillations of 40-mg HA diluted in 50-mL saline for 4 weeks. The efficacy of the HA instillation was evaluated by comparing the mean changes in the scores of the VAS and questionnaires from baseline to 4 weeks after treatment. Improvement was defined as a ≥2 decrease in the VAS. Moreover, we investigated the effects of the presence of Hunner's ulcer and previous treatment modalities on the therapeutic outcome of HA instillation.ResultsThe mean age was 57.0±1.8 years (range, 28-75 years). The VAS score significantly decreased from baseline to 4 weeks after treatment (-2.5, P<0.001). The mean changes in the PUF, ICSI, and ICPI from baseline to 4 weeks after the treatment were -3.8 (P<0.001), -2.3 (P<0.001), and -2.7 (P<0.001), respectively. Twenty patients (61%) showed improvements. Previous treatment modalities did not affect the efficacy of HA instillation and the presence of Hunner's ulcer was unrelated to outcomes. No complications were observed.ConclusionsThese results show that intravesical HA instillation is an effective and safe treatment for patients with refractory IC/PBS. Previous treatment modalities and presence of Hunner's ulcer do not affect the efficacy of HA instillation.

Interstitial cystitis in urology clinic: current status and problems

We examined the complications in the diagnosis and treatment of interstitial cystitis in daily clinical practice. The study included 82 patients who were suspected of having interstitial cystitis at our hospital from March 2002 to April 2013. All hydrodistention procedures were performed with the aid of an anesthesiologist, as recommended by the Ministry of Health, Labour, and Welfare since April 2010. Of the 82, 20 patients were male and 62 were female, (mean age at diagnosis 53 years.) Six of the suspected cases did not have interstitial cystitis. Of the 67 patients diagnosed with interstitial cystitis during hydrodistention, 29 (43%) did not experience pain. The time taken to diagnose these asymptomatic patients was longer than that taken for those who experienced pain. Twenty-eight patients (42%) discontinued treatment because it was ineffective. Interstitial cystitis has been widely recognized, but general physicians are unable to provide a diagnosis and suggest aggressive treatment because of difficulty associated in the treatment and diagnosis. To resolve these issues, physicians should be keep in mind that interstitial cystitis involves a hypersensitive bladder, and that some patients may not experience pain. Further, knowledge about Hunner's ulcer is essential. We believe that the most important points are improving health insurance about facility criteria of hydrodistention, and evaluating behavioral modification and dietary manipulation.