Painful Bladder Syndrome/interstitial Cystitis Research Articles

No viable bacterial communities reside in the urinary bladder of cats with feline idiopathic cystitis

Urinary microbial diversities have been reported in humans according to sex, age and clinical status, including painful bladder syndrome/interstitial cystitis (PBS/IC). To date, the role of the urinary microbiome in the pathogenesis of PBS/IC is debated. Feline idiopathic cystitis (FIC) is a chronic lower urinary tract disorder affecting cats with similarities to PBS/IC in women and represents an important problem in veterinary medicine as its aetiology is currently unknown. In this study, the presence of a bacterial community residing in the urinary bladder of cats with a diagnosis of FIC was investigated. Nineteen cats with clinical signs and history of FIC and without growing bacteria in standard urine culture were included and urine collected with ultrasound-guided cystocentesis. Bacterial community was investigated using a culture-dependent approach consisted of expanded quantitative urine culture techniques and a culture-independent approach consisted of 16S rRNA NGS. Several methodological practices were adopted to both avoid and detect any contamination or bias introduced by means of urine collection and processing which could be relevant due to the low microbial biomass environment of the bladder and urinary tract, including negative controls analysis. All the cats included showed no growing bacteria in the urine analysed. Although few reads were originated using 16S rRNA NGS, a comparable pattern was observed between urine samples and negative controls, and no taxa were confidently classified as non-contaminant. The results obtained suggest the absence of viable bacteria and of bacterial DNA of urinary origin in the urinary bladder of cats with FIC.

Monoclonal Antibody Therapy for the Treatment of Interstitial Cystitis.

An emerging theory regarding the potentially autoimmune nature of painful bladder syndrome/interstitial cystitis (PBS/IC) had led to several studies being conducted to assess the possible therapeutic effect of immunotherapeutic options for PBS/IC. This review presents the available evidence regarding the potential autoimmunity-based pathogenesis of PBS/IC and focuses on a main representative of the immunotherapeutic modalities for PBS/IC, aiming to summarize, evaluate, and present available data regarding the potential therapeutic role of monoclonal antibodies for PBS/IC patients. A non-systematic narrative and interpretative literature review was performed. The monoclonal antibodies included in the review were the anti-tumor necrosis factor-α (anti-TNF-α) agents adalimumab, which showed no difference compared to placebo, and certolizumab pegol, which showed statistically important differences in all outcome measures compared to placebo at the 18-week follow-up visit. Anti-nerve growth factor (anti-NGF) agents were also reviewed, including tanezumab, which showed both positive and negative efficacy results compared to placebo, and fulranumab, the study of which was discontinued owing to adverse events. In summary, monoclonal antibody therapy remains to be further researched in order for it to be proposed as a promising future treatment option for PBS/IC.

Investigations of urethral sphincter activity in mice with bladder hyperalgesia before and after drug administration of gabapentin.

This study investigated the effect of gabapentin on lower urinary tract dysfunction focusing on urethral activities and cystitis-induced hyperalgesia in a mouse model of painful bladder syndrome/interstitial cystitis (PBS/IC). The electromyography(EMG) of external urethral sphincter(EUS) was difficult to obtain, but contained useful information to examine the drug effect in mice. Female C57BL/6J mice were intraperitoneally (ip) administration with either saline or 200mg/kg of cyclophosphamide (CYP) 48h before experimental evaluation. Cystitis mice were treated with administration of gabapentin (25 or 50mg/kg, ip). Cystometry and EUS EMG were obtained and analyzed during continuous bladder infusion. The visceral pain-related visceromotor reflex (VMR) was recorded in response to isotonic bladder distension. Cystitis mice showed shorter inter-contraction intervals and increased occurrence of non-voiding contractions during bladder infusion, with increased VMR during isotonic bladder distension, indicating cystitis-induced bladder hyperalgesia. Gabapentin (50mg/kg) suppressed effects of CYP on cystometry, but not on EUS EMG activity, during bladder infusion. The effect on urodynamic recordings lasted 4h. VMR was significantly reduced by gabapentin. The present study showed that CYP-induced cystitis in mice is a model of visceral hyperalgesia affecting detrusor contractions, not urethral activations. The technique of using EUSEMG to evaluate the drug effects on urethral activities is novel and useful for future investigations. Gabapentin can be as a potential treatment for detrusor overactivity and PBS/IC.

Assessment of treatment with Intravesical alkalinized lidocaine and heparin in Painful bladder syndrome /Interstitial cystitis (PBS/IC)

Assessment of treatment with Intravesical alkalinized lidocaine and heparin in Painful bladder syndrome /Interstitial cystitis (PBS/IC)

A prospective randomized controlled multicentre trial comparing intravesical DMSO and chondroïtin sulphate 2% for painful bladder syndrome/interstitial cystitis.

ABSTRACTObjective To compare effectiveness of intravesical chondroïtin sulphate (CS) 2% and dimethyl sulphoxide (DMSO) 50% in patients with painful bladder syndrome/interstitial cystitis (PBS/IC).Materials and methods Patients were randomized to receive either 6 weekly instillations of CS 2% or 50% DMSO. Primary endpoint was difference in proportion of patients achieving score 6 (moderately improved) or 7 (markedly improved) in both groups using the Global Response Assessment (GRA) scale. Secondary parameters were mean 24-hours frequency and nocturia on a 3-day micturition dairy, changes from baseline in O’Leary-Sant questionnaire score and visual analog scale (VAS) for suprapubic pain.Results Thirty-six patients were the intention to treat population (22 in CS and 14 in DMSO group). In DMSO group, 57% withdrew consent and only 6 concluded the trial. Major reasons were pain during and after instillation, intolerable garlic odor and lack of efficacy. In CS group, 27% withdrew consent. Compared with DMSO group, more patients in CS group (72.7% vs. 14%) reported moderate or marked improvement (P=0.002, 95% CI 0.05-0.72) and achieved a reduction in VAS scores (20% vs. 8.3%). CS group performed significantly better in pain reduction (-1.2 vs. -0.6) and nocturia (-2.4 vs. -0.7) and better in total O’Leary reduction (-9.8 vs. -7.2). CS was better tolerated. The trial was stopped due to high number of drop-outs with DMSO.Conclusions Intravesical CS 2% is viable treatment for PBS/IC with minimal side effects. DMSO should be used with caution and with active monitoring of side effects. More randomized controlled studies on intravesical treatments are needed.

Treatment effect of cyclosporine A in patients with painful bladder syndrome/interstitial cystitis: A systematic review.

Cyclosporine A (CyA) is emerging as a potential therapeutic strategy for painful bladder syndrome/interstitial cystitis (PBS/IC), which is currently an incurable disease. The purpose of this systematic review was to evaluate the treatment effects of CyA in PBS/IC. Electronic and manual retrieval procedures were carried out to identify eligible references for the systematic review. The entire contents of the included articles were assessed, from study design to reported results. Eight studies, comprising three randomized controlled trials (RCTs), four prospective studies and one retrospective cohort study, were included, involving a total of 298 subjects. Meta-analysis was not implemented due to heterogeneity of the manner of reporting the outcome parameters. All studies reported an improvement in symptoms following treatment with CyA. The results of the three RCTs implied that the treatment effects of CyA were better than those of pentosan polysulfate sodium. Some adverse events, for example, elevation of serum creatinine levels and an increase in blood pressure, were noted in five studies. In conclusion, the evidence from the studies implied that treatment of CyA can result in a long-term benefit in patients of PBS/IC; however, further evidence is required to verify this.

Sexually dimorphic effects of early life stress in rat pups on urinary bladder detrusor muscle contractility in adulthood.

BackgroundPainful bladder syndrome/interstitial cystitis (PBS/IC) is a chronic disorder that is commonly seen in women who report a history of adversity in early life. Here, we test the hypothesis that early life stress (ELS) induces sexually dimorphic abnormalities in urinary bladder smooth muscle function in adulthood.MethodsMale and female rat pups were conditioned on postnatal (PN) days 8–12 with either a “predictable or “unpredictable” odor-shock, or odor only control treatment. In adulthood, urinary bladder function was assessed in vivo via urine spot analysis and in vitro via contractile responses to electrical field stimulation (EFS) and membrane depolarization with potassium chloride (KCl).ResultsIn adulthood, we found that female rats exposed to unpredictable ELS showed a significant (p < 0.05) increase in urine voiding volume compared to predictable ELS or controls. We also found that detrusor muscle contractile responses to EFS were significantly (p < 0.001) decreased following unpredictable ELS in adult female rats compared to the predictable ELS or controls. In male rats exposed to ELS, there was no difference in voiding volume or EFS-induced contractility between groups. In adulthood, the myogenic smooth muscle response to KCl was not significantly different between groups. Histological analysis from adult female and male rats revealed no differences in the appearance of the urinary bladder in rats exposed to ELS.ConclusionsIn summary, our findings provide evidence to support abnormalities in the nerve-mediated contractile responses of the detrusor smooth muscle in adult female rats following ELS. We speculate that these sexually dimorphic alterations in urinary bladder function may account, at least in part, for the female predominance of PBS/IC.

Treatment of painful bladder syndrome/interstitial cystitis with botulinum toxin A: why isn't it effective in all patients?

Botulinum toxin A (BTA) is currently used to treat a variety of painful disorders, including painful bladder syndrome/interstitial cystitis (PBS/IC). However, BTA is not consistently effective in all patients. This may be due to the disparity of causes of pain, but this may also relate to the processes by which BTA exerts anti-nociceptive effects. This review discusses mechanisms by which BTA may inhibit pain and studies of the use of BTA in PSB/IC patients. It is doubtful that any single treatment will effectively control pain in PBS/IC patients, and it is highly probable that multiple strategies will be required, both within individual patients and across the population of PBS/IC patients. The purpose of this review is to discuss those mechanisms by which BTA acts, with the intent that alternative strategies exploiting these mechanism, or work through alternative pathways, can be identified to more effectively treat pain in PBS/IC patients in the future.

The effects of intravesical therapy with hyaluronic acid for painful bladder syndrome: Preliminary Chinese experience and systematic review

ObjectiveTo present the preliminary results of treating a series of Chinese patients with painful bladder syndrome/interstitial cystitis (PBS/IC) using intravesical hyaluronic acid (HA). Materials and methodsA series of 13 patients with PBS/IC received first-line therapy followed by HA once-a-week for 4 weeks and then once monthly for 4 months. Outcomes measured included O'Leary-Sant Interstitial Cystitis Symptom Index (ICSI) and Interstitial Cystitis Problem Index (ISPI) scores, voiding frequency, and bladder capacity. ResultsISPI and ICSI scores were significantly (p < 0.001) decreased after treatment [median change (interquartile range): ISPI = 2 (2–3); ICSI = 3 (2–3)]. Voiding frequency and functional bladder capacity were significantly (p < 0.001) decreased [median change: 7 (6–8) times/d] and increased [median change: 190 (116–233) mL], respectively after treatment. ConclusionOur case series supports the efficacy of intravesical HA in the treatment of PBS/IC.

PD20-03 PILOT STUDY EVALUATING SAFETY AND FEASIBILITY OF INTRAVESICAL INSTILLATION OF BOTULINUM TOXIN IN HYDROGEL-BASED SLOW RELEASE DELIVERY SYSTEM IN PBS/IC PATIENTS

You have accessJournal of UrologyInfections/Inflammation of the Genitourinary Tract: Interstitial Cystitis1 Apr 2015PD20-03 PILOT STUDY EVALUATING SAFETY AND FEASIBILITY OF INTRAVESICAL INSTILLATION OF BOTULINUM TOXIN IN HYDROGEL-BASED SLOW RELEASE DELIVERY SYSTEM IN PBS/IC PATIENTS Kobi Stav, Yuri Vinshtok, Michal Jeshurun, Neely Ivgy-May, Tami Gerassi, and Amnon Zisman Kobi StavKobi Stav More articles by this author , Yuri VinshtokYuri Vinshtok More articles by this author , Michal JeshurunMichal Jeshurun More articles by this author , Neely Ivgy-MayNeely Ivgy-May More articles by this author , Tami GerassiTami Gerassi More articles by this author , and Amnon ZismanAmnon Zisman More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.674AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Intravesical instillation of botulinum toxin-A (BTX) is an appealing alternative to intradetrusor injection for treating painful bladder syndrome/interstitial cystitis (PBS/IC) but lacks a sustained effect due to a short exposure of urothelium to BTX. TCGel (TheraCoat Ltd) is a novel reverse-thermal gelation hydrogel allowing for instillations of liquid TCGel+BTX mixture into the bladder where it solidifies and BTX gradually releases for 6-8 hours. We investigated the feasibility and safety of intravesical instillation of BTX dissolved in TCGel preparation in patients with PBS/IC. METHODS A single intravesical instillation of 200U onabotulinumtoxin-A premixed with 40ml TCGel through 12Fr urethral catheter was delivered. Adverse events (AEs) and preliminary efficacy outcome measures were: bladder diary, Visual Analogue Scale (VAS), IC symptom and problem index (ICSI, ICPI). They were assessed at 2, 6 and 12 weeks following instillation. RESULTS 15 (M/F=4/11, age 24-76) severely symptomatic PBS/IC patients (ICSI range 12-19, ICPI range 12-16, median VAS=7) were enrolled. Safety: No increase in VAS score was noted at instillation. One severe AE was reported - an excisional biopsy of pre-existing sub-mandibular lymphadenopathy (benign histology). Three cases of mild constipation 24h to 3 weeks following instillation were noted as possibly drug-related AE's. Non-related AEs include post-instillation mild urogenital infection, flu and a case of worsening of bladder pain and depression symptoms at Week 12. Possible efficacy: Reduction in ICSI, ICPI and VAS was maintained throughout the follow-up period. Voiding frequency, nocturia and urge decreased up to Week 6 but returned to baseline level at Week12 (figure). CONCLUSIONS The results suggest that intravesical instillation of the novel TCGel+BTX is safe and tolerable. Preliminary results suggest sustained efficacy for weeks. A randomized controlled trial is warranted. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byTyagi P, Kashyap M, Yoshimura N, Chancellor M and Chermansky C (2016) Past, Present and Future of Chemodenervation with Botulinum Toxin in the Treatment of Overactive BladderJournal of Urology, VOL. 197, NO. 4, (982-990), Online publication date: 1-Apr-2017. Volume 193Issue 4SApril 2015Page: e398 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kobi Stav More articles by this author Yuri Vinshtok More articles by this author Michal Jeshurun More articles by this author Neely Ivgy-May More articles by this author Tami Gerassi More articles by this author Amnon Zisman More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Onabotulinum-Toxin-A in Urology: An Update A Review of Recent Publications about Lower Urinary Tract Dysfunction Managed With Botulinum Toxin

Onabotulinum toxin A (BTX-A) injection is a safe and effective treatment for adults with several conditions determining lower urinary tract dysfunctions (LUTD), such as neurogenic detrusor overactivity (NDO) and idiopathic overactive bladder (OAB) with or without urge urinary incontinence (UUI), not responder to conservative treatment options, including anticholinergic drugs. This review article analyzes recent studies who were using BTX-A to treat NDO and OAB; in addition, some other conditions causing LUTDs, such as benign prostatic hyperplasia (BPH) and painful bladder syndrome/interstitial cystitis (PBS/IC) were considered, even though in these conditions larger scale trials are still mandatory to confirm its usefulness.

Polyomavirus BK – A potential new therapeutic target for painful bladder syndrome/interstitial cystitis?

AimsTo investigate the role of urinary BK polyoma virus (BKPyV) in the pathophysiology and prognosis of patients with painful bladder syndrome/interstitial cystitis (PBS/IC). MethodsUrine samples were collected from 15 patients with PBS/IC and 8 control patients (with urolithiasis, overactive bladder and benign prostatic hyperplasia). BKPyV titres were quantitatively determined using real time PCR. Fisher’s exact test was used to compare virus titre levels between the two groups. The PBS/IC patients subsequently underwent cystoscopy, hydrodistension and bladder biopsy. Finally, a chart review was performed in order to correlate PBS/IC subtype and treatment outcomes with BKPyV status. ResultsPositive BKPyV titres were found in 11 out of 15 PBS/IC patients but none of the controls. Cystoscopy was performed in 13 of the 15 PBS/IC patients (in 2 BKPyV positive patients, cystoscopy was not performed). Bladder ulceration and glomerulations were observed in all 9 BKPyV positive PBS/IC patients but only 1 out of 4 BKPyV negative patients. None of the non-ulcerative PBS/IC patients had BKPyV positive urine. Viral titres were not predictive of the clinical course however, 3 patients with the highest viral titres eventually underwent cystectomy. ConclusionsWe identified BKPyV in the urine of virtually all our patients with ulcerative PBS/IC. This finding suggests there may be a pathophysiological association between the virus and the haemorrhagic manifestations of PBS/IC. Classifying PBS/IC patients into BKPyV positive or negative groups may prove useful in future research on markers of disease prognosis and the subtypes of PBS/IC. We believe that BKPyV may therefore have a role as a potential therapeutic target in PBS/IC.

The mouse cyclophosphamide model of bladder pain syndrome: tissue characterization, immune profiling, and relationship to metabotropic glutamate receptors.

Painful bladder syndrome/Interstitial cystitis (PBS/IC) is a chronic disorder characterized clinically by recurring episodes of pelvic pain and increased urination frequency, significantly impairing patients' quality of life. Despite this, there is an unmet medical need in terms of effective diagnostics and treatment. Animal models are crucial in this endeavor. Systemic chronic administration of cyclophosphamide (CYP) in mice has been proposed as a relevant preclinical model of chronic bladder pain. However, molecular mechanisms underlying the pathogenesis of this model are lacking. Here, we show that mice, subjected to repetitive systemic injections of CYP, developed mild inflammatory response in bladder tissue characterized by submucosal edema, moderate increase in proinflammatory cytokine gene expression, and mastocytosis. No signs of massive inflammatory infiltrate, tissue hemorrhages, mucosal ulcerations and urothelium loss were observed. Instead, CYP treatment induced urothelium hyperplasia, accompanied by activation of proliferative signaling cascades, and a decrease in the expression of urothelium‐specific markers. Metabotropic glutamate (mGlu) receptors have been implicated in chronic pain disorders. CYP administration induced differential changes in mGlu receptors mRNA levels in bladder tissue, without affecting gene expression at spinal cord level, pointing to the potential link between peripheral mGlu receptors and inflammation‐induced bladder malfunction and hyperalgesia. Taken together, these data indicate that chronic CYP treatment in mice is a model of PBS mostly relevant to the major, nonulcerative subtype of the syndrome, characterized by a relatively unaltered mucosa and a sparse inflammatory response. This model can help to elucidate the pathogenetic mechanisms of the disease.

Evaluation of the metabolism of glycosaminoglycans in patients with interstitial cystis

Painful bladder syndrome/interstitial cystitis (PBS/IC) pathogenesis is not fully known, but evidence shows that glycosaminoglycans (GAG) of bladder urothelium can participate in its genesis. The loss of these compounds facilitates the contact of urine compounds with deeper portions of bladder wall triggering an inflammatory process. We investigated GAG in urine and tissue of PBS/IC and pure stress urinary incontinence (SUI) patients to better understand its metabolism. Tissue and urine of 11 patients with PBS/IC according to NIDDK criteria were compared to 11 SUI patients. Tissue samples were analyzed by histological, immunohistochemistry and immunofluorescence methods. Statistical analysis were performed using t Student test and Anova, considering significant when p < 0.05. PBS/IC patients had lower concentration of GAG in urine when compared to SUI (respectively 0.45 ± 0.11 x 0.62 ± 0.13 mg/mg creatinine, p < 0.05). However, there was no reduction of the content of GAG in the urothelium of both groups. Immunofluorescence showed that PBS/IC patients had a stronger staining of TGF-beta, decorin (a proteoglycan of chondroitin/dermatan sulfate), fibronectin and hyaluronic acid. the results suggest that GAG may be related to the ongoing process of inflammation and remodeling of the dysfunctional urothelium that is present in the PBS/IC.

Effects of temperature, anesthesia, and infection on urinary bladder pain‐like responses in mice

Painful bladder syndrome/interstitial cystitis (PBS/IC) is a condition characterized by chronic bladder pain. Patients suffering from PBS/IC are commonly unresponsive to regular pain treatment and current models of bladder pain in animals do not recapitulate many of the important features. We sought to improve this situation through the use of urinary tract infections (UTI) in mice to model the bladder sensitization seen in human patients. In our new system, following UTI, urinary bladder distension (UBD) was combined with visceromotor response (VMR) measurements to evaluate the pain‐like response to bladder distension. In designing this model we discovered several potentially confounding variables such as body temperature and length of isoflurane anesthesia. We found that UBD‐induced VMRs decrease as body temperature decreases. These data suggest that body temperature must be closely controlled during UBD testing. In addition, we found a significant effect related to the length of time under anesthesia. When mice were tested with anesthesia times under two hours, VMR was reduced with increasing length of anesthesia time. Interestingly, after two hours no significant decrease in VMR was seen with increasing length of anesthesia. After controlling for these variables, preliminary data was gathered on the effect of UTI on VMR. The data suggests a modulation of VMR following UTI. Support provided by APS UGSRF.

Elimination of Hunner's Ulcers by Fulguration in Patients With Interstitial Cystitis: Is It Effective and Long Lasting?

PurposeTo evaluate the outcome of fulguration of Hunner's ulcers (HUs) in painful bladder syndrome/interstitial cystitis (PBS/IC) that is refractory to conservative treatment.Materials and MethodsPatients diagnosed with refractory PBS/IC and treated with fulguration between 2011 and 2013 were identified through screening of medical records. To evaluate treatment outcomes, voiding diaries, the visual analogue scale (VAS) for pain, and two IC symptom questionnaires (pelvic pain and urgency/frequency scale [PUF] and O'Leary-Sant IC symptom index and IC problem index [OS]) were used. Fulguration was deemed to be successful if the VAS score was <2 or less than half of the preoperative VAS score.ResultsIn total, 27 patients with PBS/IC in whom conservative treatments had failed were enrolled. Two months after fulguration, decreases were observed in the mean 24-hour urinary frequency (from 16.0 to 10.2), 24-hour urgency episodes (8.0 to 1.8), and the VAS (5.8 to 1.2), PUF symptom (15.1 to 7.0), PUF bother (8.4 to 2.7), OS symptom (15.1 to 7.2), and OS problem (13.8 to 6.0) scores. At 5 and 10 months, all variables had worsened. At 2, 5, and 10 months, the success rates were 94.1%, 70.0%, and 33.3%, respectively. Four patients underwent one repeat fulguration on average 11.3 months after the first fulguration. Repeat fulguration was not significantly associated with any clinical characteristics.ConclusionsIn PBS/IC that was refractory to medication or other conservative treatments, HU elimination by fulguration effectively improved symptoms. However, this effect decreased gradually over time.

The combination therapy of prednisolone and tacrolimus for severe painful bladder syndrome/interstitial cystitis

A 47-year-old woman visited our hospital with complaints of frequent urination and intensive pelvic pain. Painful bladder syndrome/ interstitial cystitis (PBS/IC) was suspected based on her symptoms. Hydrodistention was performed, and crack and petechial hemorrhage were found, and she was treated with tricyclic antidepressants and antihistamine. However, these treatments were ineffective. An allergy or autoimmune reaction was suspected as the pathogenesis due to eosinophilia and elevation of serum IgE levels. The patient was then treated with immunosuppressive agents. Although her symptoms were not sufficiently improved by single-agent therapy with prednisolone or tacrolimus, they were completely improved by their combined administration. This is the first case to report the effectiveness of combination therapy consisting of prednisolone and tacrolimus to treat PBS/IC.

Increased expression of TNF ligand-related molecule 1A and death receptor 3 in bladder tissues of patients with painful bladder syndrome/interstitial cystitis

Members of the tumor necrosis factor (TNF) superfamily have been revealed to be associated with painful bladder syndrome/interstitial cystitis (PBS/IC). TNF ligand-related molecule 1A (TL1A) and its receptor, death receptor 3 (DR3), belong to the TNF superfamily and have been implicated in chronic inflammatory diseases. Bladder biopsies from 8 female patients clinically diagnosed with PBS/IC according to the National Institute for Diabetes and Digestive and Kidney Diseases criteria and 8 female bladder carcinoma control patients were investigated to test the protein and mRNA expression levels of TL1A and DR3 using western blotting and real-time RT-PCR. The protein level ratio of TL1A to β-actin (IC, 0.65±0.03 vs. controls, 0.25±0.02, P<0.001) and of its receptor DR3 to β-actin (IC, 0.66±0.06 vs. controls, 0.27±0.02, P<0.001) were observed to be significantly higher in the patients with IC. The real-time RT-PCR ΔCts of TL1A minus GAPDH (IC, 7.60±0.52 vs. controls, 10.08±0.32, P<0.001) and the DR3 minus GAPDH (IC, 6.68±0.60 vs. controls, 8.99±0.61, P=0.017) were observed to be significantly lower in the patients with IC, suggesting that the mRNA levels of TL1A and DR3 were higher in the PBS/IC patients. The protein and mRNA expression of TL1A and DR3 are upregulated in the bladder tissues of PBS/IC patients and may be involved in inflammation and apoptosis in PBS/IC.

The Clinical Effectiveness of Intravesical Sodium Hyaluronate (Cystistat®) in Patients with Interstitial Cystitis/Painful Bladder Syndrome and Recurrent Urinary Tract Infections

Objective: Painful bladder syndrome/interstitial cystitis (PBS/IC) and recurrent urinary tract infections (UTI) are clinically challenging conditions to manage in patients. We evaluate the clinical use of intravesical sodium hyaluronate (Cystistat®) in both these patient groups who have completed treatment. Patients and Methods: Thirteen patients with recurrent UTIs (Group I) and 8 patients with PBS/IC (Group II) received intravesical sodium hyaluronate (Cystistat®). Preinstallation demographic parameters were statically comparable in both groups. The mean age of presentation was 54.6 years in Group I and 57.5 years in Group II (p = 0.9). All 13 patients in Group I were on low dose antibiotics. The mean number of installations completed in both groups was 9 (range 4–21). Results: Data was collected prospectively using a standard pre- and post-treatment questioner with the pelvic pain and urinary/frequency patient symptom scale. At a mean follow-up of 21 months a significant improvement in bladder pain (p = 0.05), daytime frequency (p = 0.03) and quality of life (p = 0.02) was noted in patients in Group I. Two patients had breakthrough UTIs during treatment. Within Group I, 7 (53%) patients responded well to treatment. Patients in Group II had a significant improvement in bladder pain (p = 0.02), urgency (p = 0.01), nocturia (p = 0.01) and quality of life (p = 0.04). Within Group II, 6 patients (75%) responded to treatment. Conclusion: Intravesical sodium hyaluronate (Cystistat®) can be used with minimal side effects and good compliance in both groups of patients with PBS and recurrent UTIs. Longer follow-up and larger patient numbers in both groups will be required to confirm the long-term efficacy of these two clinically challenging groups of patients.

Intravesical hyaluronic acid and alkalinized lidocaine for the treatment of severe painful bladder syndrome/interstitial cystitis

Intravesical instillation of hyaluronic acid (HA) may restore the integrity of glycosaminoglycan layer in patients with painful bladder syndrome/interstitial cystitis (PBS/IC), and the benefit may be improved with addition of alkalinized lidocaine (AL). 48 women with severe PBS/IC who failed oral medications were enrolled and divided into one trial and two control groups. The trial group received intravesical 40 mg HA, 10 ml of 2 % lidocaine and 5 ml of 8.4 % sodium bicarbonate on a weekly basis for 8 weeks and then monthly for 4 months with a subsequent follow-up of 24 weeks, while the two control groups received 40 mg HA and mixture of 10 ml of 2 % lidocaine and 5 ml of 8.4%sodium bicarbonate respectively following the same procedure. Response to therapy was evaluated by Global Response Assessment, voids per day, Visual Analogue Scale for pain, frequency and urgency, O'leary-Sant Interstitial Cystitis Symptom Index and Problem Index, cystoscopy and bladder capacity. Overall 45 patients finished this study protocol. The HA + AL group and the AL group showed significant improvement at week 2 (P < 0.01), while the HA group began to show effect at week 4 (P < 0.01). There was no improvement in the AL group at week 24 and these patients quitted the study without follow up. Contrarily, the HA + AL and HA group kept on improving till the end of the study without significant difference between the two groups. Intravesical instillation of HA and AL may provide both immediate and sustained relief of symptoms in severe PBS/IC in this preliminary study.