Efficacy and safety of intravesical dimethyl sulfoxide treatment for patients with refractory Hunner-type interstitial cystitis: Real-world data postofficial approval in Japan.

OBJECTIVES: To examine real-world data regarding intravesical dimethyl sulfoxide (DMSO) therapy after official approval as a treatment for Hunner-type interstitial cystitis (HIC) in Japan. METHODS: This single institution, retrospective observational study was conducted between 2021 and 2022 to evaluate the outcomes of 30 patients with refractory HIC who received intravesical DMSO therapy according to the approved standardized regimen: administration of DMSO every 2 weeks for a total of 12 weeks. Treatment outcomes were evaluated using a 7-graded global response assessment scale, O'Leary and Sant's symptom and problem indices (OSSI/OSPI), the overactive bladder symptom score (OABSS), an 11-point pain intensity numerical rating scale, quality of life (QOL) score, and frequency volume chart variables. Related complications were also documented. RESULTS: The response rates at 2, 4, 6, 8, 10, and 12 weeks were 36.7%, 43.3%, 53.3%, 60.0%, 70.0%, and 70.0%, respectively. Compared with baseline, OSSI/OSPI, pain intensity, urinary frequency, and the QOL score improved significantly from 4 weeks of treatment. The OABSS score and functional bladder capacity also showed a tendency toward moderate improvement, but the difference was not significant. The mean duration of symptom relapse after termination of treatment was 6.4 ± 3.9 months. No patients discontinued treatment due to adverse events, although acute bladder irritation during infusion was noted in 21 patients (70%), which disappeared within 3 days. CONCLUSIONS: This study verifies the safety, moderately durable efficacy, and tolerability of the standard intravesical treatment with DMSO for HIC in Japan.

Th1/17 polarization and potential treatment by an anti-interferon-γ DNA aptamer in Hunner-type interstitial cystitis.

Hunner-type interstitial cystitis (HIC) is a rare, enigmatic inflammatory disease of the urinary bladder with no curative treatments. In this study, we aimed to characterize the unique cellular and immunological factors specifically involved in HIC by comparing with cystitis induced by Mycobacterium bovis bacillus Calmette-Guérin, which presents similar clinicopathological features to HIC. Here, we show that T helper 1/17 +polarized immune responses accompanied by prominent overexpression of interferon (IFN)-γ, enhanced cGAS-STING cytosolic DNA sensing pathway, and increased plasma cell infiltration are the characteristic inflammatory features in HIC bladder. Further, we developed a mouse anti-IFN-γ DNA aptamer and observed that the intravesical instillation of the aptamer significantly ameliorated bladder inflammation, pelvic pain and voiding dysfunction in a recently developed murine HIC model with little migration into the blood. Our study provides the plausible basis for the clinical translation of the anti-IFN-γ DNA aptamer in the treatment of human HIC.

Efficacy and Safety of Low-dose Oral Prednisolone for Patients with Refractory Hunner-type Interstitial Cystitis.

Background: Hunner-type interstitial cystitis (HIC) is an immunological, chronic inflammatory disease. The efficacy of corticosteroid as a treatment for HIC is unclear. Objective: To assess the efficacy and safety of low-dose oral prednisolone (PSL) treatment for patients with refractory HIC. Design setting and participants: This retrospective observational study reviewed the clinical outcomes of 31 patients with refractory HIC who received oral PSL daily (initial dose, 5.0 or 7.5 mg) for at least 12 mo between 2016 and 2023. The dose was tapered to the minimum that maintained symptom relief during follow-up. Outcome measurements and statistical analysis: Treatment outcomes were evaluated using a seven-graded global response assessment (scores ≥+2, moderately or markedly improved, were defined as treatment response), O'Leary and Sant symptom and problem indices (OSSI/OSPI), overactive bladder symptom score (OABSS), an 11-point pain intensity numerical rating scale, a quality of life (QOL) score, and frequency-volume chart variables. Related complications were also documented. Results and limitations: The mean follow-up period was 20.1 ± 14.6 mo. The overall response rates at 1, 3, 6, 9, and 12 mo at doses of 6.7, 6.7, 5.2, 4.0, and 3.0 mg were 38.7%, 48.4%, 54.8%, 61.3%, and 64.5%, respectively. Compared with baseline, OSSI/OSPI and pain intensity improved significantly from 1 mo after PSL induction. The OABSS, QOL score, urinary frequency, and voided volume improved significantly from 9 mo after PSL induction. No patients discontinued treatment due to adverse events, although hypertension and glucose intolerance occurred in two patients, but these were resolved by temporal medications. Conclusions: This study showed that low-dose oral PSL significantly improves bladder pain, urinary symptoms, and QOL in patients with HIC, without serious adverse events. Further prospective evaluation is warranted to verify the potential efficacy and safety of low-dose PSL for HIC. Patient summary: This retrospective observational study reviewed the clinical outcomes of 31 patients suffering from refractory Hunner-type interstitial cystitis treated with low-dose oral prednisolone. Low-dose prednisolone improved bladder pain, urinary symptoms, and quality of life significantly, without serious adverse events. The response rate of 64.5% at 12 mo was comparable with the rates reported in previous studies that used higher doses of prednisolone. This study provides a rationale for further prospective evaluation of low-dose prednisolone for this intractable disease.

Genome-wide association study identifies risk loci within the major histocompatibility complex region for Hunner-type interstitial cystitis.

Hunner-type interstitial cystitis (HIC) is a rare, chronic inflammatory disease of the urinary bladder with unknown etiology and genetic background. Here, we conduct a genome-wide association study of 144 patients with HIC and 41,516 controls of Japanese ancestry. The genetic variant, rs1794275, in the major histocompatibility complex (MHC) region (chromosome 6p21.3) is associated with HIC risk (odds ratio [OR] = 2.32; p = 3.4 × 10-9). The association is confirmed in a replication set of 26 cases and 1,026 controls (p = 0.014). Fine mapping demonstrates the contribution to the disease risk of a completely linked haplotype of three human leukocyte antigen HLA-DQß1 amino acid positions, 71, 74, and 75 (OR = 1.94; p = 5 × 10-8) and of HLA-DPß1 amino acid position 178, which tags HLA-DPB1∗04:02 (OR = 2.35; p = 7.5 × 10-8). The three HLA-DQß1 amino acid positions are located together at the peptide binding groove, suggesting their functional importance in antigen presentation. Our study reveals genetic contributions to HIC risk that may be associated with class II MHC molecule antigen presentation.

Deep Learning Models for Cystoscopic Recognition of Hunner Lesion in Interstitial Cystitis.

Background: Accurate cystoscopic recognition of Hunner lesions (HLs) is indispensable for better treatment prognosis in managing patients with Hunner-type interstitial cystitis (HIC), but frequently challenging due to its varying appearance. Objective: To develop a deep learning (DL) system for cystoscopic recognition of a HL using artificial intelligence (AI). Design setting and participants: A total of 626 cystoscopic images collected from January 8, 2019 to December 24, 2020, consisting of 360 images of HLs from 41 patients with HIC and 266 images of flat reddish mucosal lesions resembling HLs from 41 control patients including those with bladder cancer and other chronic cystitis, were used to create a dataset with an 8:2 ratio of training images and test images for transfer learning and external validation, respectively. AI-based five DL models were constructed, using a pretrained convolutional neural network model that was retrained to output 1 for a HL and 0 for control. A five-fold cross-validation method was applied for internal validation. Outcome measurements and statistical analysis: True- and false-positive rates were plotted as a receiver operating curve when the threshold changed from 0 to 1. Accuracy, sensitivity, and specificity were evaluated at a threshold of 0.5. Diagnostic performance of the models was compared with that of urologists as a reader study. Results and limitations: The mean area under the curve of the models reached 0.919, with mean sensitivity of 81.9% and specificity of 85.2% in the test dataset. In the reader study, the mean accuracy, sensitivity, and specificity were, respectively, 83.0%, 80.4%, and 85.6% for the models, and 62.4%, 79.6%, and 45.2% for expert urologists. Limitations include the diagnostic nature of a HL as warranted assertibility. Conclusions: We constructed the first DL system that recognizes HLs with accuracy exceeding that of humans. This AI-driven system assists physicians with proper cystoscopic recognition of a HL. Patient summary: In this diagnostic study, we developed a deep learning system for cystoscopic recognition of Hunner lesions in patients with interstitial cystitis. The mean area under the curve of the constructed system reached 0.919 with mean sensitivity of 81.9% and specificity of 85.2%, demonstrating diagnostic accuracy exceeding that of human expert urologists in detecting Hunner lesions. This deep learning system assists physicians with proper diagnosis of a Hunner lesion.

Bladder Preservation After Bilateral Kidney Loss and Bladder Cancer After Renal Transplantation: A Case Report.

Kidney transplantation is now a well-established renal replacement therapy. However, renal transplant recipients are reported to have an increased incidence of cancer. Although the recommended waiting period after each cancerous event in a recipient is indicated in the literature, there is no absolute certainty that cancer will develop even after the recommended waiting period. In this study, we experienced a case of bladder cancer after the recommended waiting period in a patient who had bladder preservation after a right nephrectomy and left nephroureterectomy. A 61-year-old man lost his right kidney due to renal cancer in 2007 and his left kidney to urothelial carcinoma in November 2017. The patient wanted a kidney transplant and bladder preservation at the time of the left nephroureterectomy. The patient's wife offered to donate a kidney. After 2 years of hemodialysis, there was no recurrence or metastasis, and with the approval of the Ethics Committee, the patient received a kidney transplant in January 2020. Although the patient's renal function was good after the transplant, a bladder tumor was found 20 months later and was resected transurethrally. The pathology was nonmuscle invasive bladder cancer. This patient, who had lost both kidneys, was treated with bladder preservation therapy. After subsequent kidney transplantation, he developed bladder cancer. Explaining to the patient the possibility of recurrence after a certain period and the increased risk of cancer, in-depth consultation with the patient is necessary regarding bladder preservation. Regular checkups should be continued after transplantation.

Impact of early ureteral drainage on mortality in obstructive pyelonephritis with urolithiasis: an analysis of the Japanese National Database.

BACKGROUND: The impact of early drainage on mortality in patients with obstructive pyelonephritis with urolithiasis was evaluated. METHODS: We identified 34,924 patients in the Japanese Diagnosis Procedure Combination database with obstructive pyelonephritis with urolithiasis receiving ureteral drainage. The effects of early drainage (1-2 days) compared to those of delayed drainage (on 3-4 and ≥ 5 hospital days) on mortality were evaluated among 31,696 patients hospitalized for ≥ 5 days. Multivariate analysis was performed to identify independent factors for mortality. RESULTS: The mortality rates for overall cases and those hospitalized for ≥ 5 days were 2.0% and 1.6%, respectively. Those receiving drainage on 1-2, 3-4, and ≥ 5 days had mortality rates of 1.5%, 2.0%, and 2.5%, respectively (p < 0.001). Multivariate analysis revealed that delayed drainage was an independent factor for higher mortality (odds ratio [OR] on days 3-4 and ≥ 5; 1.44, p = 0.018; and 1.69, p < 0.001). Increasing age (OR for 60 s, 70 s, and ≥ 80 years; 2.02, 3.85, and 7.77), Charlson comorbidity index score (OR, 1.41 by 1-point increase), disseminated intravascular coagulation (OR, 2.40), ambulance use (OR, 1.22), impaired consciousness at admission (disoriented, arousable with stimulation, and unarousable; OR 1.58, 2.84, and 5.50), and nephrostomy (OR, 1.65) were associated with higher mortality. In contrast, female sex (OR, 0.76) and high hospital volume (OR on 9-16, and ≥ 17 cases/year; 0.80, and 0.75) were associated with lower mortality. CONCLUSION: Ureteral drainage within 2 hospital days was an independent factor for low mortality in obstructive pyelonephritis with urolithiasis. Delayed drainage could increase mortality in a time-dependent manner.

A case of cystic mucinous adenocarcinoma of the prostate treated by robot-assisted radical prostatectomy.

A 66-year-old male visited with constipation. Intra-pelvic cystic mass (332 cm3) was found, and PSA was 32.4 ng/ml. Biopsy of the prostate was performed. It wasn't adequate specimen for diagnosis, but the PSA of the fluid was 4791.0 ng/ml. RARP was performed. To make surgical field more visible, fine needle was stuck from the patient's perineum into the cyst intraoperatively. The patient was discharged with nothing complications. It was mucinous adenocarcinoma of the prostate, pT3b, RM1. The patient is now receiving ADT but no recurrence and metastasis are seen to date.

Cystectomy for patients with Hunner-type interstitial cystitis at a tertiary referral center in Japan.

OBJECTIVES: To evaluate the outcomes of partial and total cystectomy in patients with refractory Hunner-type interstitial cystitis (HIC). METHODS: Patients with end-stage HIC who underwent supratrigonal partial cystectomy with augmentation ileocystoplasty (PC-CP) or total cystectomy with ileal conduit (TC-IC) were identified retrospectively. Changes in the 11-point numerical rating scale of bladder pain and in 7-grade quality of life (QOL) scores were evaluated. Changes in the O'Leary and Sant's Symptom Index (OSSI) and O'Leary and Sant's Problem Index (OSPI) were analyzed in patients with PC-CP. Peri- and postoperative complications and patient satisfaction with overall outcomes were examined. RESULTS: Four patients (one female) underwent PC-CP and 13 (nine females) underwent TC-IC. Bladder pain persisted in three PC-CP patients, but resolved completely in all TC-IC patients. Pain scale and QOL scores improved significantly in patients with TC-IC (P < .01), but not in those with PC-CP. OSSI/OSPI scores did not improve significantly in patients with PC-CP. Three PC-CP patients required clean intermittent catheterization due to voiding dysfunction or persistent pain. Two TC-IC patients developed stricture of the ureteroileal anastomosis, resulting in permanent placement of a ureteral stent in one case and nephrostomy in the other. Satisfaction rate was higher in the TC-IC than in the PC-CP group (76.9% vs 25.0%, P < .05). CONCLUSIONS: TC-IC provided reliable pain relief and improved QOL in patients with end-stage HIC, but the small case number and limited methodology restrict interpretation of the results. Further studies are needed to identify appropriate candidates and optimal surgical procedures.

Overexpression of HIF1α in Hunner Lesions of Interstitial Cystitis: Pathophysiological Implications.

PURPOSE: The aim of our study was to elucidate biological changes in Hunner lesions, which underlie the pathophysiology of Hunner-type interstitial cystitis, by characterizing their whole transcriptome and immunopathological profiles. MATERIALS AND METHODS: Paired bladder mucosal biopsies, 1 sample each from the Hunner lesion and nonlesion area, were obtained from 25 patients with Hunner-type interstitial cystitis. The samples were subjected to whole-transcriptome profiling; immunohistochemical quantification of CD3, CD4, CD8, CD20, CD138, mast cell tryptase, cytokeratin and HIF1α; and quantitative polymerase chain reaction for IFN-α, IFN-ß, IFN-γ, TNF, TGF-ß1, HIF1α, IL-2, IL-4, IL-6, IL-10 and IL-12A. The results were compared between the lesion and nonlesion areas. RESULTS: RNA sequencing identified 109 differentially expressed genes and 30 significantly enriched biological pathways in Hunner lesions. Up-regulated pathways (24) included HIF1α signaling pathway, PI3K-Akt signaling pathway, RAS signaling pathway and MAPK signaling pathway. By contrast, down-regulated pathways (6) included basal cell carcinoma and protein digestion and absorption. The mRNA levels of HIF1α, IFN-γ and IL-2, and the HIF1α protein level were significantly higher in lesion areas. Otherwise, there were no significant differences between the lesion and nonlesion samples in terms of mRNA levels of inflammatory cytokines or histological features such as lymphoplasmacytic and mast cell infiltration, epithelial denudation and CD4/CD8 T-lymphocyte ratio. CONCLUSIONS: Our findings demonstrate significant overexpression of HIF1α and up-regulation of its related biological pathways in Hunner lesions. The results indicate that ischemia, in conjunction with inflammation, plays a pathophysiological role in this subtype of interstitial cystitis/bladder pain syndrome, particularly in Hunner lesions.

Prevalence and factors associated with overactive bladder and stress urinary incontinence in the Japan Nurses' Health Study.

OBJECTIVE: In this study, we aimed to investigate the prevalence and factors associated with urinary symptoms using cross-sectional data from the Japan Nurses' Health Study, a prospective cohort study among female nurses. METHODS: A total of 12,198 women were included. We calculated the prevalence of urinary symptoms. Odds ratios with 95% confidence intervals were estimated to determine the odds for overactive bladder (OAB), stress urinary incontinence, and mixed urinary incontinence. RESULTS: The mean age and body mass index (standard deviation, range) were 46.5 (±8.1, 27-82) years and 22.1 (±3.1, 12.9-44.6) kg/m2, respectively. The prevalence of OAB was 9.5% (OAB with urinary incontinence [-wet]: 5.4%, OAB without urinary incontinence: 4.1%), that of stress urinary incontinence (without OAB-wet) was 13.9%, and that of mixed urinary incontinence was 2.1%. Multivariable-adjusted logistic regression analysis showed a significant association between OAB and age 45 to 54 years, and postmenopausal status was moderately associated with OAB in that analysis. In the multivariable-adjusted model, age groups 45 to 49 and 50 to 54 years, body mass index 23-27.4 and ≥ 27.5 kg/m2, and parous status were significantly associated with stress urinary incontinence (without OAB-wet). CONCLUSIONS: This study showed a significant association of OAB with ages 45 to 54 years and postmenopausal status. Further studies should consider the association between time since menopause and OAB symptoms in the perimenopausal period. A high body mass index and parous status are strongly associated with stress urinary incontinence, and stress urinary incontinence symptoms may become less frequent after menopause.

Video Summary:http://links.lww.com/MENO/A853 .

Molecular classification and diagnostics of upper urinary tract urothelial carcinoma.

Upper urinary tract urothelial carcinoma (UTUC) is one of the common urothelial cancers. Its molecular pathogenesis, however, is poorly understood, with no useful biomarkers available for accurate diagnosis and molecular classification. Through an integrated genetic study involving 199 UTUC samples, we delineate the landscape of genetic alterations in UTUC enabling genetic/molecular classification. According to the mutational status of TP53, MDM2, RAS, and FGFR3, UTUC is classified into five subtypes having discrete profiles of gene expression, tumor location/histology, and clinical outcome, which is largely recapitulated in an independent UTUC cohort. Sequencing of urine sediment-derived DNA has a high diagnostic value for UTUC with 82.2% sensitivity and 100% specificity. These results provide a solid basis for better diagnosis and management of UTUC.

Efficacy and safety of intravesical instillation of KRP-116D (50% dimethyl sulfoxide solution) for interstitial cystitis/bladder pain syndrome in Japanese patients: A multicenter, randomized, double-blind, placebo-controlled, clinical study.

OBJECTIVE: To evaluate the efficacy and safety of intravesical KRP-116D, 50% dimethyl sulfoxide solution compared with placebo, in interstitial cystitis/bladder pain syndrome patients. METHODS: Japanese interstitial cystitis/bladder pain syndrome patients with an O'Leary-Sant Interstitial Cystitis Symptom Index score of ≥9, who exhibited the bladder-centric phenotype of interstitial cystitis/bladder pain syndrome diagnosed by cystoscopy and bladder-derived pain, were enrolled. Patients were allocated to receive either KRP-116D (n = 49) or placebo (n = 47). The study drug was intravesically administered every 2 weeks for 12 weeks. RESULTS: For the primary endpoint, the change in the mean O'Leary-Sant Interstitial Cystitis Symptom Index score from baseline to week 12 was -5.2 in the KRP-116D group and -3.4 in the placebo group. The estimated difference between the KRP-116D and placebo groups was -1.8 (95% confidence interval -3.3, -0.3; P = 0.0188). Statistically significant improvements for KRP-116D were also observed in the secondary endpoints including O'Leary-Sant Interstitial Cystitis Problem Index score, micturition episodes/24 h, voided volume/micturition, maximum voided volume/micturition, numerical rating scale score for bladder pain, and global response assessment score. The adverse drug reactions were mild to moderate, and manageable. CONCLUSIONS: This first randomized, double-blind, placebo-controlled trial shows that KRP-116D improves symptoms, voiding parameters, and global response assessment, compared with placebo, and has a well-tolerated safety profile in interstitial cystitis/bladder pain syndrome patients with the bladder-centric phenotype.

Validation of the Overactive Bladder-Bladder Assessment Tool (OAB-BAT): A Potential Alternative to the Standard Bladder Diary for Monitoring OAB Outcomes.

BACKGROUND: An advisory board concluded that a new, comprehensive overactive bladder (OAB) patient-reported outcome (PRO) measure should be developed in accordance with regulatory guidelines. The OAB-Bladder Assessment Tool (OAB-BAT) was developed with qualitative input from OAB patients and experts to measure symptoms, bother, impacts, and satisfaction with treatment. OBJECTIVE: Psychometric evaluation of the OAB-BAT assessing PRO OAB symptoms, bother, and impacts during a 7-d recall period. DESIGN, SETTING, AND PARTICIPANTS: Psychometric testing was conducted for a 28-d observational study of 170 OAB patients. Eligibility criteria included clinician-confirmed OAB diagnosis with at least eight micturitions per day. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Assessments included the OAB-BAT, a 7-d bladder diary, and co-validating OAB PROs. Analysis included classical and modern test theories. A scoring algorithm was developed and psychometric properties were assessed. RESULTS AND LIMITATIONS: The majority of participants were women (72.4%) with moderate OAB symptom severity (53.5%). More than one-third of participants (34.1%) were incontinent. Responses were well balanced across bother and impact items, while symptom frequency items showed sparse responses. Analysis supported an eight-item unidimensional model based on bother and impacts. No items performed differently by gender or continence status. The OAB-BAT showed internal consistency (ω=0.918), retest reliability (two-way random intraclass correlation coefficient=0.81), and convergent validity with the OAB-q (r>0.4). Known groups showed the expected trend. Comparisons between OAB-BAT scores and components of the bladder diary showed a moderate effect size (r>0.4). CONCLUSIONS: The eight-item OAB-BAT with 7-d recall is valid and reliable as an OAB PRO measure. Structural modeling, balanced with content validity considerations, produced robust scores. The OAB-BAT is a useful addition to the clinical assessment of patients, designed to complement the use of bladder diaries for monitoring OAB outcomes, in clinical trial and clinical practice environments. Future studies will need to assess the treatment satisfaction items in a larger sample of patients receiving OAB treatment. PATIENT SUMMARY: We tested a questionnaire designed to assess overactive bladder (OAB) symptoms, bother, satisfaction, and impacts by asking patients to complete it on a weekly basis. We found that the questionnaire accurately captures the symptoms and impacts that are most important to patients with OAB. We conclude that the questionnaire could be a useful instrument and, after further assessment in clinical practice and research, a possible alternative to a bladder diary in measuring OAB outcomes.

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.

[A CASE OF IgG4-RELATED DISEASE OF THE URETER DIAGNOSED BY TRANSVAGINAL ULTRASOUND-GUIDED BIOPSY].

IgG4-related disease (IgG4-RD) is a chronic inflammatory disorder that systemically causes tissue fibrosis due to infiltration of IgG4-positive plasma cells. Here, we reported a rare case of ureteral IgG4-RD that formed a nodular lesion and diagnosed by trans-vaginal ultrasound-guided needle biopsy.A 72-year-old woman presented with loss of appetite. The patient underwent Computed Tomography (CT), and she was pointed out the thickening of the left side bladder wall. So we performed a transurethral bladder biopsy under lumber anesthesia, but histopathological findings were almost normal. After that, she developed pyelonephritis repeatedly. We performed CT again. A CT revealed a nodular lesion at the end of her left ureter and hydronephrosis. The tumor was gradually getting larger. So we performed placement the ureteral stent for urinary tract obstruction. Left ureteral urine cytology was classIIIa. We performed transvaginal ultrasound needle biopsy for the nodular lesion of the left ureter. Histopathological findings showed infiltration of lymphocytes and fibrosis and infiltration of IgG4 positive plasma cells: the ratio of IgG4/IgG positive cells>0.6, 30>IgG4 positive plasma cells/high power field. The serum IgG and IgG4 levels were also elevated 1,943 and 210 mg/dl. We finally diagnosed IgG4-RD of the ureter and started using steroid for her treatment. One month later, the tumor had reduced after steroid treatment. The ureteral stent was removed. Since then, recurrent ureteral obstruction of the left ureter has not occurred.IgG4-RD of the ureter with nodular type is rare, and the imaging findings are similar to malignant tumors. Accurate diagnosis is very important to rule out malignancy. In our case, transvaginal needle biopsy was helpful to reach final diagnosis.

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

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Lacking transient receptor potential melastatin 2 attenuates lipopolysaccharide-induced bladder inflammation and its associated hypersensitivity in mice.

OBJECTIVE: To study the role of transient receptor potential melastatin 2 in bladder function and inflammation-associated hypersensitivity. METHODS: We evaluated physiological function of the bladder and intravesical lipopolysaccharide-induced inflammatory nociceptive responses in female wild-type and transient receptor potential melastatin 2-knockout mice. In vivo frequency/volume and decerebrated unanesthetized cystometry measurements, as well as in vitro detrusor strip functional studies, were carried out to evaluate bladder function. Mice received intravesical lipopolysaccharide (2.0 mg/mL) or saline instillation to evaluate responses to bladder inflammation. Voiding and bladder pain-like behaviors, cystometry measurements and histological evaluation were carried out before and after intravesical lipopolysaccharide instillation. RESULTS: Few phenotypic differences in in vivo and in vitro physiological function were found between the two genotypes. Comparison of measurements taken before and 24-48 h after intravesical lipopolysaccharide instillation showed that voiding parameters did not change in transient receptor potential melastatin 2-knockout mice, whereas an increased voiding frequency was observed in wild-type mice. At 24 h after intravesical lipopolysaccharide instillation, the numbers of bladder pain-like behaviors and of infiltrated inflammatory cells in the bladder submucosal layer were significantly increased, and the voided volume and the intercontraction interval were significantly decreased on cystometry measurements in wild-type mice compared with those in both transient receptor potential melastatin 2-knockout mice and in wild-type mice treated with saline instillation. CONCLUSIONS: Although the physiological roles of transient receptor potential melastatin 2 channels in the bladder might be limited, inflammation and associated hypersensitivity of the bladder caused by intravesical lipopolysaccharide instillation are attenuated in transient receptor potential melastatin 2-knockout mice, suggesting pathophysiological roles of transient receptor potential melastatin 2 channels in these processes.

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.