Hunner Lesions Research Articles

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

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

Clinical characterization of interstitial cystitis/bladder pain syndrome in women based on the presence or absence of Hunner lesions and glomerulations.

To compare the clinical characteristics of three groups of female patients with interstitial cystitis/bladder pain syndrome (IC/BPS) classified according to the presence or absence of Hunner lesions (HL) and glomerulations. The clinical records of 100 female patients with IC/BPS who underwent their first bladder hydrodistension at our institution were retrospectively reviewed. They were divided into patients having (HL-IC; n = 57) or lacking (BPS; n = 43) HL. BPS patients were further classified as those with (29) and without (14) glomerulations. Among these three subtypes, demographics, comorbidities, symptom parameters including a visual analog scale for pain scores, O'Leary and Sant Symptom and Problem (OSSI/OSPI) Indices, frequency volume chart variables, and bladder capacity at hydrodistension were compared. HL-IC patients were older and had higher OSSI/OSPI scores, greater daytime frequency and nocturia, reduced maximum and average voided volumes, and smaller bladder capacity at hydrodistension compared with BPS patients. Pain intensity and illness duration were comparable among the three groups. HL-IC patients had autoimmune disorders as comorbidities more often, but had psychiatric disorders and irritable bowel syndrome less often compared with BPS patients. No discernible differences in clinical characteristics of symptom severity and comorbid disorders were evident between BPS patients with and without glomerulations. The presence of HL is associated with distinctive clinical characteristics, while glomerulations are not in female patients with IC/BPS. The presence of HL, but not glomerulations, is a robust phenotypic feature of IC/BPS in women.

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

Bladder pain syndrome (BPS) is a chronic condition characterized by pelvic pain or pressure which is perceived to be originating from the bladder, accompanied by one or more urinary symptoms, including frequency, urgency and nocturia. The precise etiology of BPS is not fully understood. Chronic bacterial infection, defective glycosaminoglycan (GAG) layer of the bladder urothelium, inappropriate activation of mast cells in the suburothelial layer of the bladder, autoimmune-mediated mechanisms and autonomic nervous system dysfunction have all been implicated. Treatments targeted at each of these mechanisms have been developed with mixed outcomes. High-quality research into the treatment options is lacking and it is difficult to draw definite conclusions. The treatment approach is multimodal and should be patient specific, targeting the symptoms which they find most bothersome. Conservative treatment, including patient education, behavioural modification, dietary advice, stress relief and physical therapy is an essential initial management strategy for all patients. If no response is observed, oral treatments such as amitriptyline are likely to offer the greatest response. Cystoscopy is essential to phenotype patients, and Hunner lesion directed therapy with fulguration or resection can be performed at the same time. Intravesical instillation of DMSO or lidocaine, detrusor injections of botulinum toxin A and neuromodulation can be used if initial management fails to improve symptoms. Oral cyclosporin can be trialled in those experienced with its use; however, it is associated with significant adverse events and requires intense monitoring. Lastly, radical surgery should be reserved for those with severe, unremitting BPS, in which quality of life is severely affected and not improved by previously mentioned interventions. Future work investigating exact aetiological factors will help target the development of efficacious treatment options, and several promising oral and intravesical treatments are emerging.

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

The primary purpose of this study was to evaluate the effect of the fatty acid amide hydrolase (FAAH) inhibitor ASP3652 on efficacy and safety in patients with Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS). The secondary purpose was to evaluate phenotyping based on Hunner's lesions (HL). In this randomized trial, adult female patients with moderate/severe IC/BPS received 12weeks of treatment with an oral dose of ASP3652 (50, 150, or 300mg twice daily) or placebo. A Bayesian model was employed using accumulating data to adjust the randomization probability and to analyze the primary efficacy variable (change from baseline to end of treatment in Mean Daily Pain [MDP; range 0-10]). Study outcomes and patient characteristics of patients with and without HL (HL+ and HL-) were compared. In total, 287 patients were randomized. The 300mg dose group (n = 97) showed the largest effect, i.e., a mean change from baseline to end of treatment of -1.73 in MDP. However, the mean difference from placebo was 0.02. The probability that this dose was better than placebo was 13.5%. Adverse event incidence was low and similar between study groups. HL+ patients were older and had more severe symptoms than HL-. An association was suggested in HL+ patients between changes in micturition frequency and MDP (R = 0.41 [95% CI 0.18, 0.63]), which was not observed in HL- (R = 0.04 [95% CI -0.16, 0.29]). ASP3652 was safe and well tolerated, but did not show efficacy in IC/BPS. The observed differences between HL+ and HL- suggest that IC/BPS diagnosis and treatment may be approached differently in these two phenotypes. EudraCT number 2011-004555-39, date of registration: 2012-05-07.

284 - Comparative transcriptome analysis of interstitial cystitis/bladder pain syndrome with Hunner lesions and Bacillus Calmette-Guerin related cystitis by next-generation RNA-sequencing: Discovery of disease-specific genes and associated biological pathways

284 - Comparative transcriptome analysis of interstitial cystitis/bladder pain syndrome with Hunner lesions and Bacillus Calmette-Guerin related cystitis by next-generation RNA-sequencing: Discovery of disease-specific genes and associated biological pathways

IJU this issue

In this issue, a Guideline with Editorial Comment, a Review Article with Editorial Comment, five Original Articles with three Editorial Comments and a Urological Note were published in the International Journal of Urology. Interstitial cystitis/bladder pain syndrome (BPS) bothers both patients and urologists. Homma et al. (Tokyo, Japan) revised the previous guidelines completing articles identified by the PubMed database published from 2016 to 2019. In this article, the authors clearly defined Hunner-type interstitial cystitis (HIC) associated with Hunner’s ulceration and non-Hunner-type BPS featuring glomerulations or bladder bleeding after distension are different entities of disorder in terms of pathophysiology. Interestingly, HIC shows immunological inflammatory reaction accompanied by B-cell clonal expansion, which demonstrates HIC is genetically different from BPS. Urologists should keep in mind that patients should be treated differently based on the diagnosis of HIC or BPS, which requires cystoscopy to determine the presence or absence of Hunner lesions. Malignant ureteral obstruction, defined as either intrinsic or extrinsic compression caused by metastasis, lymphadenopathy or direct extension of the tumors, is an unfortunate finding that most urologists encounter in the daily practice. Tabib et al. (New York, USA) reviewed many types of ureteral stents, including tandem stents or metallic stents that aim for the resolution of malignant ureteral obstruction, and attempted to provide considerations regarding the treatment and management of malignant ureteral obstruction. Ochi et al. (Chiba, Japan) examined the anatomical relationship between the urinary system and perirenal fat using computed tomography images from 50 men, as well as macroscopic imaging in nine cadavers. They found that perirenal fat belongs to the connective tissue of the gonad and the adrenal gland. The urinary system is separated from perirenal fat, and is located on the dorsal side inside the renal fascia. The authors concluded that this anatomical finding might help aid in the isolation of periureteric fat from perinephric fat in retroperitoneoscopic donor nephrectomy. A substantial number of non-classic angiomyolipomas (AML), including fat-poor or epithelioid AML, are encountered in daily practice, and are occasionally difficult to discriminate from renal cell carcinoma. Kaneko et al. (Tokyo, Japan) retrospectively evaluated the incidence of epithelioid AML (17.9%) out of 39 renal tumors diagnosed as non-classical AML. They found that magnetic resonance imaging findings (apparent diffusion coefficient value) are potentially useful to differentiate between epithelioid and fat-poor AML. A recent trend for the treatment of metastatic castration-sensitive prostate cancer (CSPC) is upfront intensification therapy including androgen deprivation therapy (ADT) plus docetaxel, ADT plus abiraterone acetate, ADT plus enzalutamide and ADT plus apalutamide. However, indication is limited in high-risk (LATITUDE criteria) or high-volume (CHARRTED criteria) patients. Hatakeyama et al. (Hirosaki, Japan) retrospectively evaluated 679 patients with metastatic castration-sensitive prostate cancer. They found that the overall survival from the initiation of castration-resistant prostate cancer in patients with low-volume disease and those with high-volume disease was not significantly different, and concluded that upfront intensification therapy might be beneficial to patients with low-volume disease, because approximately half of patients with low-volume disease experienced metastatic castration-resistant prostate cancer progression in real-world practice. The Editorial Comment by Kato (Nagoya, Japan) is worthwhile to correctly evaluate this article. As most of the metastatic spread is reported to be in a hematogenous fashion in renal cell carcinoma, the impact of regional lymph node metastases on subsequent distant metastasis remains unknown. Yang et al. (Rochester, USA) retrospectively evaluated 1049 patients (135 pN1, 914 pN0/x) who were surgically treated at the Mayo Clinic. They found that pN1 nodal status in M0 patients treated with nephrectomy for renal cell carcinoma is associated with more frequent early metastasis to sites conferring poor prognosis when compared with pN0/x in the lung, bone and non-regional lymph nodes. Interestingly, pN1 status did not affect subsequent liver metastasis, one of the most hematogenous metastatic organs. Although this article involves several limitations, their finding might stimulate discussion of the predictive/therapeutic role of regional lymph node dissection during renal cancer surgery. None declared.

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.

Bioinformatics Approach for Identifying Novel Biomarkers and Their Signaling Pathways Involved in Interstitial Cystitis/Bladder Pain Syndrome with Hunner Lesion.

The complexity of interstitial cystitis/bladder pain syndrome (IC/BPS) has led to considerable uncertainty in terms of diagnosis and prevalence of the condition. Here, we try to identify the IC/BPS-associated genes through an integrated analysis of Gene Expression Omnibus (GEO) datasets and confirm experimentally to predict the pathologic diagnosis of IC/BPS. Data mining analysis of GEO datasets (GSE621, GSE11783, GSE28242, and GSE57560) revealed a total of 53 (51 upregulated and two downregulated) common differentially expressed genes (DEGs) in IC/BPS. A protein–protein interaction (PPI) network was then constructed with the 53 common DEGs using Cytoscape v3.7.2, and subsequently, six hub genes (CD5, CD38, ITGAL, IL7R, KLRB1, and IL7R) were identified using cytoHubba v0.1 that were upregulated in IC/BPS. Enrichment analysis of common DEGs revealed that hematopoietic cell lineage, immune system, and T-cell receptor (TCR) signaling in naïve CD4+ T cell signaling pathways were prominently involved with the common 51 upregulated DEGs. The two common downregulated DEGs may enrich linoleic acid metabolism and synthesis of epoxy (EET) and dihydroxyeicosatrienoic acid (DHET) signaling pathways in IC/BPS. Moreover, our RT-PCR data confirmed that the expression of the five hub genes (CD38, ITGAL, IL7R, KLRB1, and IL7R) was significantly augmented in IC/BPS patients’ samples when compared with their normal counterparts. In this study, we systematically predict the significant biomarkers and possible signaling pathways involved in IC/BPS, confirming the differential expression of the hub genes in tissue samples from patients with IC/BPS. Thus, the hub genes might be used as potential diagnostic biomarkers of IC/BPS.

Editorial Comment to Clinical guidelines for interstitial cystitis/bladder pain syndrome.

The former Japanese Clinical Guidelines for interstitial cystitis (IC) and related conditions was published in 2009 and 2016.1 Homma et al. revised the previous guidelines, completing articles identified by the PubMed database published from 2016 to 2019.2 In the current clinical guidelines, one of the characteristics is the categorization. IC/bladder pain syndrome (BPS) is utilized as a comprehensive term, and divided into Hunner-type IC (HIC) and BPS. Only HIC represents Hunner lesions, thus endoscopic findings are indispensable for the diagnosis. Hunner lesion is introduced as a reddish lesion associated with converging vessels, covering fibrin clots or scars, and in this guideline, multiple characteristic endoscopic pictures are shown for reference. The authors have first provided a histopathology section in this guideline, because a recent study showed the histological difference between HIC and BPS.3 It has been reported that HIC shows an immunological inflammatory reaction accompanied by B-cell clonal expansion and epithelial denudation, whereas BPS shows few changes. Treatments for IC/BPS were listed in the order of conservative, medical, intravesical instillation, endoscopy surgery, cystectomy and other treatments. Conservative treatment includes patient education, meditation and a strict dietary therapy. Medical treatments, including new evidence of pentosane polysulfate, cyclosporine A and antibacterial agents, have been added, and certolizumab and tacrolimus have been newly added. Dimethyl sulfoxide instillation therapy still requires information; however, a randomized study showed that efficacy favored HIC.4 Chondroitin sulfate, botulinum toxin and steroids instillation were also introduced. Endoscopic hydrodilation and transurethral fulguration are still effective. Cystectomy would be the last resort. The clinical algorithm shows how to care for IC/BPS patients. Electrostimulation, such as sacral nerve neuromodulation and acupuncture, are introduced in the other treatments section. The algorithm provides a useful approach in the treatment of patients. To validate the therapeutic effectiveness of the treatments, the patients should be specified to IC/BPS, HIC alone or BPS alone. Future clinical studies are still necessary; however, this clinical guideline would help open a new window in understanding the pathophysiology and provide better management for urologists in this field. None declared.

IJU this issue

This issue of International Journal of Urology contains one Guideline, three Review Articles, five Original Articles, two Urological Notes, five Editorial Comments and two Letters to the Editor. Miyakita et al. (Kanagawa, Japan) formulated and issued an algorithm to assist in the medical management of vesicoureteral reflux (VUR) consistent with clinical practice, and explained the epidemiology and the following elements: syndromes, diagnosis, treatment (medical and surgical), secondary VUR, long-term prognosis and reflux nephropathy. VUR is a major underlying precursor condition of urinary tract infection, and an important disorder in the field of pediatric urology. I am sure that the clinical algorithm for VUR should be helpful to your understanding and clinical practice. Akiyama et al. (Tokyo, Japan) reviewed recent evidence on interstitial cystitis/bladder pain syndrome (IC/BPS) categorization to describe the evolving taxonomy of IC/BPS, discussed the potential pathophysiologies and animal models, and suggested future strategies to achieve better clinical management and research progress of IC/BPS based on these emerging concepts. They emphasized the critical differences between IC/BPS with and without Hunner lesions, and suggested a tailored approach that targets Hunner lesions for better outcomes in clinical management and future research of IC/BPS. Ziegelmann et al. (Minnesota, USA) reviewed contemporary evaluation and management for Peyronie’s disease. Peyronie’s disease is a common, yet poorly understood, condition characterized by penile pain, curvature, sexual dysfunction and psychological bother. However, its prevalence is low in Japan. As Shiraishi (Yamaguchi, Japan) described in the Editorial Comment, there are distinct differences in the prevalence and patients’ dissatisfaction with their condition, goal for treatment, and satisfaction after treatment between USA and Japanese Peyronie’s disease patients. It should be elucidated in further investigations. Tsuchiya et al. (Kyoto, Japan) summarized recent advances in circadian clock emergence during ontogenesis, and discussed possible associations with cellular differentiation and carcinogenesis. It is desirable that the relationships between cancer development and circadian clock dysregulation could lead to identification of unrecognized prognostic markers and therapeutic targets for specific cancers. In the Original Articles, Laucirica et al. (Barcelona, Spain) reported the surgical technique of “muscle-sparing” laparoscopic radical prostatectomy as a simple technical variation. Urinary incontinence is an important complication, as well as erectile dysfunction, after radical prostatectomy. Various surgical techniques are implemented to improve urinary continence, and the fundamental principle of them is to preserve the normal anatomy and function of pelvic structures. The continence rate outcomes were excellent, with comparable cancer control evaluated by the positive surgical margin rate. However, the rationale for the benefit and utility of laparoscopic radical prostatectomy in the robotic era requires debate. I am sure that many fine pictorial essays should be helpful to your understanding. In the Urological Notes, Ohtake et al. (Yokohama, Japan) examined the effectiveness of the N-composite gel kidney tumor model – a tool for practicing laparoscopic partial nephrectomy. They compared the face validity (the realism of the model), content validity (its utility as a training tool) and construct validity (the surgical objective parameters) between laparoscopic novices and laparoscopic experts. Surgical simulation is an important adjunct in surgical education. There is growing interest in and provision of cadaveric simulation courses worldwide. However, it is important to develop surgical models that feel like real organs, and can be used daily without the cost implications and the ethical issues. Unfortunately, the limited space does not allow me to introduce all the articles. However, all the papers are very interesting and informative. Please enjoy this issue of International Journal of Urology. None declared.

Immunomodulatory Therapies for Interstitial Cystitis/Bladder Pain Syndrome

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic, debilitating condition of unknown etiology characterized by persistent pain perceived to be related to the urinary bladder and lower urinary tract symptoms. Evidence shows that immunological inflammatory responses underlie the pathophysiology of IC/BPS with Hunner lesions but not that of IC/BPS without Hunner lesions. Here, we review the current understanding of the immunological inflammatory nature of IC/BPS with Hunner lesions and the clinical outcomes of immunomodulatory therapies. Open trials show that steroids improve validated symptom scores and pain scale score markedly in patients with IC/BPS with Hunner lesions. Open trials and a randomized study show that cyclosporine A improves urinary frequency, pain intensity, and bladder capacity significantly in IC/BPS patients, showing therapeutic superiority in the Hunner lesion subtype. A randomized double-blind study showed that certolizumab pegol significantly improves patient-reported global response assessments of pain, urgency, and overall symptoms, and reduces the Interstitial Cystitis Symptom/Problem Index scores and pain scale score at 18 weeks. These results suggest that immunomodulatory therapy is more effective for IC/BPS patients with Hunner lesions than for IC/BPS without Hunner lesions. IC/BPS with Hunner lesions is associated specifically with immunological overreactions in the bladder; thus, immunomodulatory therapy could be a promising treatment option. Further studies focusing on the therapeutic responsiveness of IC/BPS subtypes are warranted to promote a tailored approach to clinical management of IC/BPS. To achieve this therapeutic strategy, clear and proper subtyping of IC/BPS is mandatory.

Clinical guidelines for interstitial cystitis/bladder pain syndrome

The clinical guidelines for interstitial cystitis and related symptomatic conditions were revised by updating our previous guidelines. The current guidelines define interstitial cystitis/bladder pain syndrome as a condition with chronic pelvic pain, pressure or discomfort perceived to be related to the urinary bladder accompanied by other urinary symptoms, such as persistent urge to void or urinary frequency in the absence of confusable diseases. The characteristic symptom complex is collectively referred as hypersensitive bladder symptoms. Interstitial cystitis/bladder pain syndrome is divided into Hunner-type interstitial cystitis and bladder pain syndrome; Hunner-type interstitial cystitis and bladder pain syndrome represent interstitial cystitis/bladder pain syndrome with Hunner lesions and interstitial cystitis/bladder pain syndrome without Hunner lesions, respectively. So-called non-Hunner-type interstitial cystitis featured by glomerulations or bladder bleeding after distension is included in bladder pain syndrome. The symptoms are virtually indistinguishable between Hunner-type interstitial cystitis and bladder pain syndrome; however, Hunner-type interstitial cystitis and bladder pain syndrome should be considered as a separate entity of disorder. Histopathology totally differs between Hunner-type interstitial cystitis and bladder pain syndrome; Hunner-type interstitial cystitis is associated with severe inflammation of the urinary bladder accompanied by lymphoplasmacytic infiltration and urothelial denudation, whereas bladder pain syndrome shows little pathological changes in the bladder. Pathophysiology would also differ between Hunner-type interstitial cystitis and bladder pain syndrome, involving interaction of multiple factors, such as inflammation, autoimmunity, infection, exogenous substances, urothelial dysfunction, neural hyperactivity and extrabladder disorders. The patients should be treated differently based on the diagnosis of Hunner-type interstitial cystitis or bladder pain syndrome, which requires cystoscopy to determine the presence or absence Hunner lesions. Clinical studies are to be designed to analyze outcomes separately for Hunner-type interstitial cystitis and bladder pain syndrome.

Interstitial cystitis/bladder pain syndrome: The evolving landscape, animal models and future perspectives.

Interstitial cystitis/bladder pain syndrome is a debilitating condition of unknown etiology characterized by persistent pelvic pain with lower urinary tract symptoms and comprises a wide variety of potentially clinically useful phenotypes with different possible etiologies. Current clinicopathological and genomic evidence suggests that interstitial cystitis/bladder pain syndrome should be categorized by the presence or absence of Hunner lesions, rather than by clinical phenotyping based on symptomatology. The Hunner lesion subtype is a distinct inflammatory disease with proven bladder etiology characterized by epithelial denudation and enhanced immune responses frequently accompanied by clonal expansion of infiltrating Bcells, with potential engagement of infection. Meanwhile, the non-Hunner lesion subtype is a non-inflammatory disorder with little evidence of bladder etiology. It is potentially associated with urothelial malfunction and neurophysiological dysfunction, and frequently presents with somatic and/or psychological symptoms, that commonly result in central nervous sensitization. Animal models of autoimmune cystitis and neurogenic sensitization might serve as disease models for the Hunner lesion and non-Hunner lesion subtypes, respectively. Here, we revisit the taxonomy of interstitial cystitis/bladder pain syndrome according to current research, and discuss its potential pathophysiology and representative animal models. Categorization of interstitial cystitis/bladder pain syndrome based on cystoscopy is mandatory to design optimized treatment and research strategies for each subtype. A tailored approach that specifically targets the characteristic inflammation and epithelial denudation for the Hunner lesion subtype, or the urothelial malfunction, sensitized/altered nervous system and psychosocial problems for the non-Hunner lesion subtype, is essential for better clinical management and research progress in this complex condition.

MP77-03 THE MICROBIOME OF HUNNER LESIONS IN INTERSTITIAL CYSTITIS/BLADDER PAIN SYNDROME (IC/BPS)

You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder II (MP77)1 Apr 2020MP77-03 THE MICROBIOME OF HUNNER LESIONS IN INTERSTITIAL CYSTITIS/BLADDER PAIN SYNDROME (IC/BPS) J. Curtis Nickel*, Garth Erhlich, R. Christopher Doiron, Kerri-Lynn Kelly, and Joshua Earl J. Curtis Nickel*J. Curtis Nickel* More articles by this author , Garth ErhlichGarth Erhlich More articles by this author , R. Christopher DoironR. Christopher Doiron More articles by this author , Kerri-Lynn KellyKerri-Lynn Kelly More articles by this author , and Joshua EarlJoshua Earl More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000963.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Hunner Lesions (HL) are distinct focal inflammatory areas in the bladder mucosa observed in a minority of patients diagnosed with IC/BPS. This is the first comprehensive evaluation of the microbiome of HL patients using a case-control design in an IC/BPS patient population. METHODS: The bacterial microbiota of mid-stream urine specimens from HL IC/BPS and age/gender matched IC/BPS subjects with no Hunner Lesions (NHL) were examined using state of the art next generation full-length 16S gene sequencing. The differential abundances and diversity of species were characterized and compared (R package DESeq2 v1.24.0) for HL and NHL as well as gender-specific HL and NHL subjects. RESULTS: IC/BPS subjects (total 59; 29 HL and 30 NHL; 43 female and 16 male) were analyzed as species grouped by HL/NHL and female/male designations. There were 10 (p < 0.05) significant species that differentiated HL from NHL urine specimens (though not significant after multiple testing correction). These included Streptococcus, Propionibacterium, Campylobacter, Atopobium, Anaerococcus, Actinomyces, Prevotella, Actinotignum, Gardnerella, and Peptoniphilus species. However, the difference between male and female subjects accounted for the majority of the variance observed in the total IC/BPS population. Similar findings were observed in respect to abundance analyses. In the female data set, there are 7 species abundances that significantly differ (p<0.05) between HL and NHL though only a single Lactobacillus species (L. crispatus) differed significantly after multiple testing correction. In the male subset, there were 11 species that were significantly different and the top 4 species were still significant after correction. The differences observed between HL and NHL species abundance appears to be driven, in part, by the male HL subjects. Diversity metrics (Shannon Diversity and Effective Number; see Figure) shows that both female HL and NHL are dominated by 5 different species and male HL by 10, while male NHL are less diverse at 6. CONCLUSIONS: There is a differential abundance of species in HL vs NHL, with the difference more pronounced in the male subset and much less clear between the female IC/BPS groups. Species differences between HL and NHL subjects are overshadowed by the strong differential clustering of species based on gender. Source of Funding: Canadian Research Chair Program © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e1163-e1164 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information J. Curtis Nickel* More articles by this author Garth Erhlich More articles by this author R. Christopher Doiron More articles by this author Kerri-Lynn Kelly More articles by this author Joshua Earl More articles by this author Expand All Advertisement PDF downloadLoading ...

MP07-03 COMPARISON OF DEEP PHENOTYPING FEATURES OF UCPPS PATIENTS WITH AND WITHOUT HUNNER LESION – A MAPP RESEARCH NETWORK STUDY

INTRODUCTION AND OBJECTIVE:It has been suggested that IC/BPS patients with Hunner lesion (also called “classic IC”, “ulcerative IC”, or ESSIC type 3C) might represent a distinct clinical phenotype ...

MP07-11 INTERSTITIAL CYSTITIS / BLADDER PAIN SYNDROME - DETRUSOR MAST CELL COUNT IS ASSOCIATED WITH HYDRODISTENTION CLINICAL RESPONSE

INTRODUCTION AND OBJECTIVE: Interstitial Cystitis / Bladder Pain Syndrome (IC/BPS) is, presumably, an umbrella term for several disorders, with hypothesized differences in pathomechanisms and response to treatment. Clinical guidelines are disputed whether bladder biopsies are indicated as a part of standard IC/BPS patient evaluation or only for ruling out differential diagnoses. Abnormal mast cell activation in the detrusor has long been suggested as a mechanism for IC/BPS symptoms, but their role in patient evaluation is unclear. Our aim was to find out if detrusor mastocytosis in bladder biopsies has clinical implications, specifically if it can predict clinical symptom improvement and its duration, following treatment with hydrodistention. METHODS: In a retrospective study, we examined bladder biopsies taken from patients with complaints concordant with IC/BPS during cystoscopy and hydrodistention under anesthesia. We correlated pathological findings with patient reported symptom improvement or resolution and its duration. We used t-test, chi-square, and multivariate linear regression to define the relations between detrusor mastocytosis (≥20 mast cells / mm2) and symptom improvement. RESULTS: 31 Patients, 27 female and 4 male, mean age 59±17.6 years, underwent cystoscopy under anesthesia for suspected IC/BPS between 2013 and 2019. For 24 patients (21 female, 3 male, mean age 59±17.5 years), bladder biopsies with mast cell count were available. Eight (33%) had detrusor mastocytosis. The median follow-up was 9.6 [range: 2.3-61.4] months. Mastocytosis was associated with symptom improvement (p=0.03) and patients with detrusor mastocytosis experienced an average additional 6.8 months (95% CI 1.6-12.1, p=0.014) of improvement, compared with patients without. In a univariate regression model, improvement duration was positively correlated with detrusor mastocytosis (p=0.005), age (p=0.047) and follow-up duration (0.002), but not with gender (p=0.25), Charlson comorbidity score (p=0.61), Hunner lesion presence (p=0.14) or bladder capacity under anesthesia (p=0.20). In a multivariate model, mastocytosis was the only factor correlated with improvement duration (p=0.025). CONCLUSIONS: Detrusor mastocytosis in bladder biopsies was associated with symptom improvement after hydrodistention in IC/BPS patients. This finding may improve disease phenotyping and treatment choice direction. Mast cell activity may be a target for future research on noninvasive test development for IC/BPS phenotyping. Source of Funding: none.

MP07-02 COMPARATIVE TRANSCRIPTOME ANALYSIS OF INTERSTITIAL CYSTITIS/BLADDER PAIN SYNDROME WITH HUNNER LESIONS AND BACILLUS CALMETTE-GUERIN RELATED CYSTITIS BY NEXT-GENERATION RNA-SEQUENCING: DISCOVERY OF DISEASE-SPECIFIC GENES AND ASSOCIATED BIOLOGICAL PATHWAYS

INTRODUCTION AND OBJECTIVE:Bacillus Calmette-Guerin related cystitis (BCG cystitis) shares similar clinicopathological features with Hunner lesion interstitial cystitis (HIC) such as hypersensitive...

Hunner Lesion Phenotype in Interstitial Cystitis/Bladder Pain Syndrome: A Systematic Review and Meta-Analysis.

We compared demographics, clinical presentation, comorbidities, urinary profiles, and treatment responses between patients with interstitial cystitis/bladder pain syndrome with and without Hunner lesions. We performed a systematic review of the literature in PubMed® in February 2019. Publications were included if they compared data between patients with interstitial cystitis/bladder pain syndrome with and without Hunner lesions, yielding 59 articles. Meta-analysis was performed on a subset of clinical characteristics. Meta-analysis showed that patients with interstitial cystitis/bladder pain syndrome with Hunner lesions were significantly older (MD 6.7 years, 95% CI 2.0-11.3, p=0.005), reported higher urinary frequency (MD 3.2 per day, 95% CI 1.1-5.4, p=0.003), nocturia (MD 1.0 per night, 95% CI 0.1-2.0, p=0.034) and Interstitial Cystitis Symptom Index (MD 2.2, 95% CI 1.4-3.0, p <0.001), but lower cystometric bladder capacity (MD -113 ml, 95% CI -164 to -61 ml, p <0.001) compared to those with interstitial cystitis/bladder pain syndrome without Hunner lesions. There were no differences in pain scores (p=0.105), symptom duration (p=0.2) or sex (p=0.83) between the 2 groups. While some studies reported higher rates of comorbid pain syndromes (eg fibromyalgia) among patients without Hunner lesions, overall results were conflicting. Patients with Hunner lesions had higher urinary levels of pro-inflammatory cytokines/chemokines (CXCL10, NGF, IL-6, IL-8, MIF), luminal nitric oxide and responded well to endoscopic treatment of the Hunner lesions (eg fulguration or triamcinolone injection). In comparative studies patients with interstitial cystitis/bladder pain syndrome with Hunner lesions responded better to oral cyclosporine A than those without Hunner lesions. Systematic review and meta-analysis demonstrated significant differences in demographics, clinical presentation, urinary marker profiles, and treatment responses between patients with and without Hunner lesions, suggesting that they may represent 2 distinct clinical phenotypes. Studies are needed to investigate their mechanistic differences.

Small Fiber Polyneuropathy in Hunner Lesion and Non-Hunner Lesion Interstitial Cystitis/Bladder Pain Syndrome.

This study aimed to determine whether small fiber polyneuropathy (SFPN) diagnosis differs between Hunner lesion interstitial cystitis/bladder pain syndrome (HL IC/BPS) and non-Hunner lesion IC/BPS (NHL IC/BPS). This was a pilot study of 20 women with IC/BPS. Results from baseline questionnaires, such as Genitourinary Pain Index, Interstitial Cystitis Symptom Index/Interstitial Cystitis Problem Index (ICSI/ICPI), Patient Health Questionnaire-2, were collected.Two punch biopsies were performed on each patient: distal leg and thigh. The samples were evaluated for intraepidermal nerve fiber density. One intraepidermal nerve fiber density less than the fifth percentile, regardless of site, indicated a positive SPFN diagnosis. Twenty patients were enrolled; 10 HL IC/BPS and 10 NHL IC/BPS. The HL IC/BPS group was found to be significantly older than the NHL IC/BPS group (63 vs 48 years, P = 0.007). No significant differences were found in employment or relationship statuses, or in levels of education or comorbidities between the 2 groups.Sixty percent (6/10) of patients had SFPN in the NHL IC/BPS group compared with 40% (4/10) in the HL IC/BPS group. No significant differences were seen in SFPN positivity (P = 0.3) or Genitourinary Pain Index, Patient Health Questionnaire-2, or Interstitial Cystitis Symptom Index/Interstitial Cystitis Problem Index scores between the NHL and HL IC/BPS groups. Similar to previously published studies, 60% of NHL IC/BPS patients in this cohort were positive for SFPN compared with only 40% of the HL IC/BPS patients. Larger studies may be needed to realize the full impact of SFPN in IC/BPS.

Comparison of the Efficacy Between Transurethral Coagulation and Transurethral Resection of Hunner Lesion in Interstitial Cystitis/Bladder Pain Syndrome Patients: A Prospective Randomized Controlled Trial

BackgroundInterstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic condition characterized by chronic pelvic pain related to the bladder with no effective treatment options. ObjectiveTo evaluate the efficacy and safety of transurethral resection (TUR) and transurethral coagulation (TUC) as treatments for Hunner lesion (HL) in IC/BPS. Design, setting, and participantsA single-center, prospective, randomized controlled trial involving 126 patients with HL in IC/BPS. InterventionTUR or TUC. Outcome measurements and statistical analysisPrimary outcome was recurrence-free time after surgery. Secondary outcomes included change of the number of frequency, nocturia, urgency episodes in voiding diaries, O’Leary-Sant Interstitial Cystitis Symptom Index (ICSI) and Interstitial Cystitis Problem Index (ICPI), pelvic pain and urgency/frequency (PUF) symptom scale, and visual analog scale (VAS) for pain and risk factors for recurrence. Results and limitationsThere were no differences in the recurrence-free time between treatment groups, a difference of 12.2 mo (95% confidence interval [CI], 11.1–17.6) for TUR, and a difference of 11.5 mo (95% CI, 9.03–16.1; p=0.735) for TUC. No difference was found in decreased mean daytime frequency, nocturia, urgency episodes, ICSI, ICPI, PUF symptom scale, and VAS for pain between both groups over 12 mo. Regardless of treatment types, there were significant improvements in all symptom questionnaires and pain compared with baseline (all, p < 0.05). Treatment type (TUR or TUC), age, sex, previous history of hydrodistension, and number of HLs did not affect recurrence. Incidence of bladder injury was higher in the TUR group (7.9%) than in the TUC group (3.4%). ConclusionsThere was no difference in the recurrence-free time and effect on urinary symptoms, including pain between TUC and TUR, for HL. Taking into account procedure-related complications, the surgeon can choose the method with which he/she is most familiar and comfortable. Patient summaryIn patients with bladder pain syndrome with Hunner lesions, both endoscopic resection and coagulation of the lesions are effective treatments.