Hunner Type Interstitial Cystitis Research Articles

Relationship between the frequency of electrocautery of Hunner lesions and changes in bladder capacity in patients with Hunner type interstitial cystitis

Electrocautery is a promising treatment option for patients with Hunner type interstitial cystitis (HIC), but frequently requires multiple sessions due to recurrence of the lesions. In the present study, we assessed the relationship between the frequency of electrocautery of Hunner lesions and changes in maximum bladder capacity (MBC) at hydrodistension in a large cohort of 118 HIC patients. Three mixed-effect linear regression analyses were conducted for MBC against (1) the number of sessions; (2) the number of sessions and the time between each session and the first session; and (3) other relevant clinical parameters in addition to the Model (2). The mean number of sessions was 2.8 times. MBC decreased approximately 50 mL for each additional electrocautery session, but this loss was offset by 10 mL for each year the subsequent session was postponed. MBC of < 400 mL at the first session was a significant risk factor for MBC loss with further sessions. No other clinical parameters were associated with MBC over time. This study demonstrates a significant relationship between the frequency of electrocautery of Hunner lesions and MBC changes in HIC patients. Low MBC at the first session is a poor prognostic marker for MBC loss over multiple sessions.

Autoimmunity to urothelial antigen causes bladder inflammation, pelvic pain, and voiding dysfunction: a novel animal model for Hunner-type interstitial cystitis.

Recent evidence revealed that Hunner-type interstitial cystitis (HIC) is a robust inflammatory disease potentially associated with enhanced immune responses and histologically characterized by epithelial denudation and lymphoplasmacytic infiltration with frequent clonal expansion of infiltrating B cells. To date, few animal models that reproduce the histological and clinical correlates of HIC have yet been established. In the present study, we aimed to develop a novel animal model for HIC via autoimmunity to the bladder urothelium using the transgenic mouse model (URO-OVA) that expresses the membrane form of the model antigen ovalbumin (OVA) as a self-antigen on the bladder urothelium. OVA-specific lymphocytes (splenocytes) were generated by immunization of C57BL/6 mice with OVA protein and injected intravenously into URO-OVA mice. The splenocytes from OVA-immunized C57BL/6 mice showed increased interferon (IFN)-γ production in response to OVA stimulation in vitro. URO-OVA mice adoptively transferred with OVA-primed splenocytes developed cystitis exhibiting histological chronic inflammatory changes such as remarkable mononuclear cell infiltration predominantly composed of T and B lymphocytes, increased vascularity, and mucosal hyperemia in the bladder at days 7-28 with a peak at day 21 tested. No systemic inflammation was found in cystitis-induced URO-OVA mice, nor was any inflammation found in wild-type C57BL/6 mice adoptively transferred with OVA-primed splenocytes. Along with bladder inflammation, URO-OVA mice demonstrated significantly increased pelvic nociceptive responses, voiding dysfunction, and upregulated mRNA expression levels for IFN-γ, tumor necrosis factor-α (TNF-α), and substance P precursor in the bladder. This model reproduces the histological and clinical features of human HIC, providing a novel model for HIC research.

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.

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.

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.

Therapeutic Endoscopic Treatment Plus Maintenance Dimethyl Sulfoxide Therapy Prolongs Recurrence-Free Time in Patients With Hunner Type Interstitial Cystitis: A Pilot Study.

PurposeTo evaluate whether hydrodistention with fulguration of Hunner lesions (HD/FUL) plus maintenance dimethyl sulfoxide (DMSO) therapy prolongs the recurrence-free time in patients with Hunner type interstitial cystitis (IC).MethodsThe study enrolled patients with Hunner type IC who required repeat HD/FUL due to recurrence of IC symptoms after the first HD/FUL at our institution. All patients received a second HD/FUL plus maintenance DMSO therapy. The maintenance DMSO therapy was performed every 2 weeks for a total of 8 instillations, and then once every 4 weeks thereafter. The recurrencefree time from HD/FUL to therapeutic failure was estimated using the Kaplan-Meier method. The recurrence-free time between the first HD/FUL and second HD/FUL plus maintenance DMSO therapy was statistically compared using the log-rank test.ResultsA total of 21 patients (mean age, 66.3±10.8 years) with Hunner type IC were evaluated. The recurrence-free time for the second HD/FUL plus maintenance DMSO therapy was significantly longer than that for the first HD/FUL (P<0.0001). The median recurrence-free time for the first HD/FUL was 10.1 months, while that for the second HD/FUL plus maintenance DMSO therapy has yet to be reached. The recurrence-free rate for the first HD/FUL was 81.0% at 6 months, 38.1% at 1 year, 9.5% at 2 years, and 4.8% at 3 years. In contrast, the rate for the second HD/FUL plus maintenance DMSO therapy was 100% at 6 months, 94.7% at 1 year, 82.6% at 2 years, and 82.6% at 3 years. There were no significant differences in efficacy between the first and second HD/FUL.ConclusionsHD/FUL plus maintenance DMSO therapy clearly prolongs the recurrence-free time compared with HD/FUL alone in Hunner type IC.

Classification, Characterization, and Sub-Grouping of Interstitial Cystitis

Interstitial cystitis (IC) and IC-related conditions such as painful bladder syndrome (PBS), bladder pain syndrome (BPS), and hypersensitive bladder (HSB) have a similar symptomatic profile but probably different etiologies. A reasonable classification of these diseases/conditions is mandatory for clinical and investigational progress. We reviewed definition of current terminology and recent research evidence regarding IC and related conditions to propose a sensible classification system. The condition with Hunner lesions (Hunner type IC: HIC) is obviously distinct from other categories in terms of histopathology, gene expression, and clinical management; HIC is a bladder-centric disease with heavy inflammation, epithelial denudation, and oligoclonal B cell expansion. Presence of glomerulations or mucosal bleeding after distension appears of least clinical significance. Classification should thus clearly differentiate the condition with Hunner lesions from those without Hunner lesions. The term covering patients as a whole should contain IC, since IC is historically a well-known name and used for insurance reimbursement. The proposed classification/taxonomy features an umbrella term (IC/BPS) and two sub-groups, HIC (IC/BPS with Hunner lesions) and BPS (IC/BPS without Hunner lesions). IC/BPS is convenient for the initial management of symptomatic patients, and sub-groups can categorize the patients for the specific management. The characteristic symptom profile of bladder pain, urinary urgency, and increased urinary frequency is to be collectively termed as hypersensitive bladder symptoms.

Long noncoding RNA (MEG3) in urinal exosomes functions as a biomarker for the diagnosis of Hunner-type interstitial cystitis (HIC).

Toll-like receptor-7 (TLR7) is functionally involved in the pathogenesis of Hunner-type interstitial cystitis (HIC). In addition, maternally expressed gene 3 (MEG3) is implicated in many urethral diseases. In this study, we aimed to verify the hypothesis that exosomal MEG3 in urine can be used as a novel diagnostic biomarker for HIC. Electron microscopy was utilized to observe the distribution of urinary exosomes between the case group and the control group. Receiver operating characteristic analysis was utilized to compare the diagnostic values of MEG3 and miR-19a-3p. Computational analysis and luciferase assay were conducted to identify the correlation between MEG3 and miR-19a-3p as well as between TLR7 and miR-19a-3p. In addition, real-time polymerase chain reaction and Western blot were performed to establish the signaling pathways implicated in the pathogenesis of HIC. When age and gender distributions are excluded, urinary exosomes were equally distributed between case and control groups. The area under the curve of MEG3 was larger than that of miR-19a-3p, indicating that MEG3 has a better value in the diagnosis of HIC. In addition, patients with HIC showed elevated MEG3 expression and inhibited miR-19a-3p expression, thus establishing a negative correlation between MEG3 and miR-19a-3p. MEG3 and TLR7 were both identified as targets of miR-19a-3p, establishing a MEG3/miR-19a-3p/TLR7 signaling pathway, in which MEG3 enhances the expression of TLR7 via inhibiting the expression of miR-19a-3p. MEG3 level was upregulated in patients with HIC. In addition, MEG3 downregulated miR-19a-3p expression while upregulating TLR7 expression. Furthermore, MEG3 contributes to the pathogenesis of HIC. Therefore, exosomal MEG3 in urine can be used as a biomarker for HIC diagnosis.

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 ...

Angiogenesis in bladder tissues is strongly correlated with urinary frequency and bladder pain in patients with interstitial cystitis/bladder pain syndrome.

To examine the correlation among bladder inflammation, angiogenesis, fibrosis and urothelial denudation in biopsied bladder specimens, and O'Leary-Sant symptom indexes, O'Leary-Sant problem indexes and visual analog scale pain scores in interstitial cystitis/bladder pain syndrome patients with or without Hunner lesions (Hunner type interstitial cystitis or non-Hunner type interstitial cystitis). Bladder biopsied tissues were collected from 12 Hunner type interstitial cystitis female patients, 12 non-Hunner type interstitial cystitis female patients and 12 age-matched non-interstitial cystitis female patients (controls). Immunohistochemical stainings of tissue necrotic factor-α, mast cell tryptase, vascular endothelial growth factor, CD31, transforming growth factor-β, SLUG associated with epithelial mesenchymal transition and E-cadherin as well as Masson trichrome staining were evaluated. The significant correlation between the expression of tissue necrotic factor-α, mast cell tryptase, vascular endothelial growth factor, CD31, transforming growth factor-β, collagen, SLUG or E-cadherin, and O'Leary-Sant symptom indexes, O'Leary-Sant problem indexes or visual analog scale pain scores was then examined. The expression of tissue necrotic factor-α, vascular endothelial growth factor, CD31, transforming growth factor-β and SLUG was significantly increased in non-Hunner type interstitial cystitis and Hunner type interstitial cystitis patients compared with controls whereas the significant increases in the expression of mast cell tryptase and collagen were observed in Hunner type interstitial cystitis patients compared with controls and non-Hunner type interstitial cystitis patients. On the other hand, the expression of E-cadherin was significantly decreased in Hunner type interstitial cystitis patients compared with controls and non-Hunner type interstitial cystitis patients. In addition, the increased expression of CD31 in bladder tissues was strongly correlated with O'Leary-Sant symptom indexes, O'Leary-Sant problem indexes and visual analog scale pain scores. These results suggest that bladder angiogenesis evident as the increased expression of CD31 is strongly correlated with urinary frequency and bladder pain in patients with non-Hunner type interstitial cystitis and Hunner type interstitial cystitis.

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.

Greetings.

I should like to congratulate Dr Ueda and all the members gathering in Kyoto in the beautiful Spring of 2018 once again for this wonderful ICICJ meeting. The ICICJ meeting is held jointly with the annual meeting of the Society of Interstitial Cystitis of Japan (SICJ). As the representative of SICJ, I cordially welcome those from abroad, who are fascinated by the mysterious disease, interstitial cystitis (IC). SICJ (http://sicj.umin.jp/) was established in 2001, and this was the very first medical society specializing in IC globally. The society started as a group of only four urologists and now comprises more than 170 members. SICJ has had a significant impact on medical society with regard to recognizing IC through scientific activities; IC has been a common and hot topic in recent Japanese Urological Congresses. We have had a tremendous impact on public awareness of IC; IC is now approved as an intractable disease by the Japanese government. A patient registry system has been set up to collect patient data and update the current condition of IC. At a scientific level, we published Clinical Guidelines for Interstitial Cystitis (in Japanese) in 2007. These were also the first clinical guidelines for IC based on medical evidence. The guidelines were updated by cooperating with Korean and Taiwanese urologists in 2016. Recently we have been emphasizing the distinct histopathology and pathophysiology of IC with Hunner lesions (Hunner type IC: HIC), as compared to that without Hunner lesions. In this special issue, we propose a new classification; IC/BPS as the umbrella term for the patients and HIC as a subgroup term for a distinct clinical entity. I hope that these social and scientific activities of SICJ have contributed to the success of the ICICJ meeting and importantly to the patients’ wellbeing. None declared.

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

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

Does repeated hydrodistension with transurethral fulguration for interstitial cystitis with Hunner’s lesion cause bladder contraction?

ABSTRACTObjective: To evaluate the effect of repeated bladder hydrodistension with transurethral resection or fulguration (TUF) of Hunner’s lesions on bladder capacity and interstitial cystitis (IC) symptoms. TUF for Hunner’s lesion is recommended in several IC/BPS guidelines, although recurrence is highly probable.Patients and methods: The study cohort comprised 44 IC patients with Hunner’s lesions who underwent multiple bladder hydrodistensions with TUF and electrocautery (EC) at our institution between July 2005 and June 2018. We analysed their frequency–volume chart, O’Leary Sant Interstitial Cystitis Symptom Index (ICSI), Interstitial Cystitis Problem Index (ICPI), and visual analogue scale (VAS) for pain, before and at 2, 6, and 12 months after surgery.Results: The 44 Hunner-type IC patients underwent a total of 117 surgeries. Patients were divided into three groups based upon the number of hydrodistensions with TUF they underwent. Group 1 (n = 44), Group 2 (n = 44) and Group 3 (n = 21) underwent one, two, and three surgeries, respectively. At 6 months after surgery, the mean average voided volume (AVV) and maximum voided volume (MVV) were 157 mL and 228 mL in Group 1; 203 mL, 283 mL in Group 2; and 193 mL, 264 mL in Group 3. The AVV in Group 2 (P < 0.01) and Group 3 (P < 0.03), and the MVV in Group 2 (P < 0.02) increased significantly compared to Group 1. ICSI, ICPI and VAS pain score in groups 2 (P < 0.003, P < 0.01, P < 0.05) and 3 (P < 0.001, P < 0.001, P < 0.001) decreased significantly compared to Group 1.Conclusion: Repeated hydrodistension and TUF with EC of Hunner’s lesions for recurrent Hunner-type IC patients improved their symptoms. There was a tendency toward an increase in bladder capacity and repeated hydrodistension with TUF did not appear to be a direct cause of bladder contraction.Abbreviations: AVV: average voided volume; BPS: bladder pain syndrome; EC: electrical cautery; IC: interstitial cystitis; ICPI: Interstitial Cystitis Problem Index; ICSI: Interstitial Cystitis Symptom Index; MVV: maximum voided volume; TUF: transurethral fulguration; TUR: transurethral resection; VAS: visual analogue scale

MP39-10 NOVEL CONTRAST MIXTURE ACHIEVES CONTRAST RESOLUTION OF HUMAN BLADDER WALL SUITABLE FOR T1 MAPPING: APPLICATIONS IN INTERSTITIAL CYSTITIS (IC) AND BEYOND

You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis1 Apr 2018MP39-10 NOVEL CONTRAST MIXTURE ACHIEVES CONTRAST RESOLUTION OF HUMAN BLADDER WALL SUITABLE FOR T1 MAPPING: APPLICATIONS IN INTERSTITIAL CYSTITIS (IC) AND BEYOND Pradeep Tyagi, Joe Janicki, Chan-Hong Moon, Jonathan Kaufman, and Christopher Chermansky Pradeep TyagiPradeep Tyagi More articles by this author , Joe JanickiJoe Janicki More articles by this author , Chan-Hong MoonChan-Hong Moon More articles by this author , Jonathan KaufmanJonathan Kaufman More articles by this author , and Christopher ChermanskyChristopher Chermansky More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.1257AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Instillation of novel contrast mixture (NCM) was recently shown to improve the contrast resolution of rat bladder wall with high contrast-to-noise ratio (CNR). Here, the clinical safety and the feasibility of NCM enhanced MRI to achieve artifact-free visualization of human bladder wall suitable for quantitative measurement of the magnetic resonance (MR) longitudinal relaxation time (T1) was accessed. METHODS Six female subjects [2 controls and 4 IC] consented for MRI at 3T before and after instillation of NCM [4mM Gadobutrol and 5mM Ferumoxytol in 50mL of sterile water for injection]. Respiratory monitoring belt was placed under the receiver coil for monitoring the breath-hold. Single breath hold fast MR acquisition from 5mm thick single slice in large readout bandwidth at variable flip angles was applied to minimize the motion and chemical shift artifacts in the measurements of bladder wall thickness (BWT), CNR and T1 from 20 pixels. RESULTS Subjects did not complain of any pain or discomfort from 50mL NCM instillation, beyond that caused by the catheterization process. Four-fold increase in bladder wall CNR (*p<0.02) and spatial resolution of 0.35mm with minimal influence of artifacts made it feasible to determine the significant bladder wall thinning of ~0.46mm (*p<0.05) from 50mL NCM. Pre-contrast bladder wall T1 of 1544± 34.2ms was shortened by Gadobutrol diffusion into the bladder wall to 860.09 ±13.95 ms in Hunner type IC (*p<0.0001, two way ANOVA) relative to only 1257.42± 20.59 ms and 1258.16 ± 6.16ms in non-Hunner type IC and controls, respectively. Post-contrast pixel-wise T1 mapping differentiated the bladder wall into layers with greater Gadobutrol mediated T1 shortening in pixels representing the urothelium and lamina propria (blue and green) compared to the detrusor region (yellow in attached picture). CONCLUSIONS Recapitulation of the published pre-clinical findings in the clinical setting demonstrates the safety and feasibility of NCM enhanced MRI to achieve artifact-free differential contrast and spatial resolution of human bladder wall, which is suitable for first pixel-wise measurement of T1 in both pre-and post-contrast settings. Quantitative T1 measurement holds promise in the non-invasive characterization of diffuse pathophysiological changes in bladder wall of IC patients. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e513-e514 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Pradeep Tyagi More articles by this author Joe Janicki More articles by this author Chan-Hong Moon More articles by this author Jonathan Kaufman More articles by this author Christopher Chermansky More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Novel contrast mixture achieves contrast resolution of human bladder wall suitable for T1 mapping: applications in interstitial cystitis and beyond.

Instillation of novel contrast mixture (NCM) was recently shown to improve the contrast resolution of rat bladder wall with high contrast-to-noise ratio (CNR). Here, the clinical safety and the feasibility of NCM-enhanced MRI to achieve artifact-free visualization of human bladder wall suitable for quantitative measurement of the magnetic resonance (MR) longitudinal relaxation time (T1) was assessed. Six female subjects [two controls and two with Hunner-type interstitial cystitis ICand two with non-Hunner-type IC] consented for MRI at 3T before and after instillation of NCM [4mM gadobutrol and 5mM ferumoxytol in 50mL of sterile water for injection]. Single breath-hold fast MR acquisition in large readout bandwidth for 5-mm-thick single slice with variable flip angle was applied to minimize the motion and chemical shift artifacts in measurements of bladder wall thickness (BWT), CNR and T1 from 20 pixels. NCM instillation in subjects did not evoke pain or discomfort. Fourfold increase in bladder wall CNR (*p<0.02) and pixel size of 0.35mm with minimal influence of artifacts allowed accurate determination of bladder wall thinning~0.46mm from 50mL NCM (*p<0.05). Pre-contrast bladder wall T1 of 1544±34.2ms was shortened to 860.09±13.95ms in Hunner-type IC (*p<0.0001) relative to only 1257.42±20.59 and 1258.16±6.16ms in non-Hunner-type IC and controls, respectively. Findings demonstrate the safety and feasibility of NCM-enhanced MRI to achieve artifact-free differential contrast and spatial resolution of human bladder wall, which is suitable for measuring BWT and pixel-wise measurement of T1 in post-contrast setting.

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

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

Therapeutic effects of endoscopic ablation in patients with Hunner type interstitial cystitis

To investigate the efficacy of endoscopic ablation of Hunner lesions (HLs) in patients with interstitial cystitis (IC) and to find predictors of early recurrence of HLs. A prospective study was performed of patients with Hunner type IC who underwent transurethral ablation. We repeated endoscopic ablation when symptoms and HLs recurred during the follow-up period. The primary endpoint was recurrence-free time. Secondary endpoints were a change in frequency, nocturia, and urgency episodes, and changes in visual analogue scale (VAS) pain scores and other symptom indices at follow-up visits. A total of 72 patients were analysed. The median (range) follow-up period was 29.5 (12.0-50.0) months. After primary ablation treatment, HLs recurred in 75.0% (54/72) of patients, and the median (sd) recurrence-free time was 12.0 (1.6) months. Amongst the 54 patients with recurrence, 50 underwent a second ablation treatment. HLs occurred in 44.0% (22/50) of individuals after the second operation, and the median (sd) recurrence-free time was 18.0 (5.1) months. Lower maximal cystometric capacity (odds ratio 1.01, 95% confidence interval 1.001-1.013) was the predictive factor for early recurrence. There were significant improvements in the VAS pain scores, O'Leary-Sant Interstitial Cystitis Symptom Index and Problem Index, Pelvic Pain and Urgency/Frequency Patient Symptom Scale after treatment (all, P < 0.05). Endoscopic ablation is an effective treatment option for HLs and significantly reduces pain and improves voiding symptoms. Repeat ablation upon recurrence could help symptom control and bladder preservation only if the bladder capacity is maintained.

Digital quantitative analysis of mast cell infiltration in interstitial cystitis.

To evaluate the significance of mast cell infiltration in interstitial cystitis (IC) by comparison with equally inflamed controls using a digital quantification technique. Bladder biopsy specimens from 31 patients with Hunner type IC and 38 patients with non-Hunner type IC were analyzed. Bladder biopsy specimens from 37 patients without IC, including 19 non-specific chronic cystitis ("non-IC cystitis") specimens and 18 non-inflamed bladder ("normal bladder") specimens, were used as controls. Mast cell tryptase-, CD3-, CD20-, and CD138-immunoreactive cells were quantified using digital image analysis software to evaluate both mast cell and lymphoplasmacytic cell densities. Mast cell and lymphoplasmacytic cell densities were counted independently in the entire lamina propria and detrusor areas and compared among the four groups. In the lamina propria, there were no significant differences in mast cell and lymphoplasmacytic cell densities between Hunner type IC and non-IC cystitis or between non-Hunner type IC and normal bladder specimens. In the detrusor, the mast cell densities were not significantly different among the four groups. Mast cell density was correlated with lymphoplasmacytic cell density, but not with clinical parameters. Mast cell density is not significantly different between IC specimens and non-IC control specimens with a similar degree of background inflammation. The intensity of mast cell infiltration generally correlated with that of lymphoplasmacytic cells. We conclude that mast cell count is of no value in the differential diagnosis between IC and other etiologies.

Diagnostic value of urinary CXCL10 as a biomarker for predicting Hunner type interstitial cystitis

To investigate the feasibility of chemokines and cytokines potentially elevated in the bladder tissue of Hunner type interstitial cystitis (HIC) as urinary markers for distinguishing HIC from non-Hunner type interstitial cystitis (NHIC) METHODS: Urine specimens were collected from 41 HIC patients, 25 NHIC patients, and 31 healthy volunteers (control). The supernatants of urine specimens were subjected to ELISA kits for measurements of 10 cytokines and chemokines, whose gene expression was known to be elevated in HIC bladder tissue. Urinary levels normalized by urinary creatinine (Cr) concentration were compared among three groups. Efficiency in differentiating IC and IC subtypes was explored by ROC analysis. The correlation of marker levels with symptom severity, assessed by O'Leary-Sant's symptom index (OSSI) and problem index (OSPI), was examined. The urinary levels of CXCL10 and NGF were significantly higher in HIC than NHIC. CXCL10 and NGF differentiated HIC against NHIC with AUC of 0.78 and 0.68, respectively. Combination of CXCL10 and NGF levels yielded an AUS of 0.81. The CXCL10 cut-off of 53.2 pg/mg Cr had sensitivity of 46.1%, specificity of 93.7%, positive predictive value of 97.7%, and negative predictive value of 60.0%. The urinary level of other cytokines showed no significant difference between HIC and NHIC. Significant correlation with symptoms was detected for CXCL10 alone. The results suggested that increased urinary level of CXCL10 combined with or without high NGF level could be a promising supplementary biomarker for differentiating HIC from NHIC with modest sensitivity and high specificity.