The relationship between illness perception and worsening of interstitial cystitis/painful bladder syndrome symptoms: A cross-sectional study.

OBJECTIVE: To evaluate disease perception in a cohort of patients with interstitial cystitis/painful bladder syndrome (IC/PBS) using the Brief Illness Perception-Questionnaire (BIP-Q) and to evaluate how this might relate to disease severity. MATERIALS AND METHODS: The study is a cross-sectional survey amongst members of Bladder Health UK who had previously received a clinical diagnosis of IC/PBS. A hyperlink containing the questionnaire was sent to the patient group's website and interested members accessed and completed the survey. Participants' inclusion was based on a prior clinical diagnosis of IC/PBS, current O'Leary Sant scores supportive of the diagnosis, and age between 18 and 80. A sample size of 171 was used in the study. The Brief Illness Perception Questionnaire (BIP-Q) and the O'Leary/Sant symptoms and problem indices questionnaire were used to collect data. A multivariable logistic regression analysis was used to test the relationship between items of BIP-Q and severity of IC/PBS. Content analysis was used for the causal domain and subsequently analysed as percentages. RESULTS: Six hundred and one members accessed the questionnaire of whom 159 returned completed questionnaires. One hundred and twenty-two of 159 (≥75%) respondents believe that their illness will continue indefinitely. The majority of the respondents indicated that IC/PBS had a negative impact on their daily lives, caused them worry and made them emotionally unstable. Of the 8 BIP-Q items, those most predictive of disease severity were (adjusted odd ratio and confidence intervals): consequence 0.094 (0.023-0.386); treatment control 2.702 (1.256-5.812); identity 0.141 (0.033-0.600); concern 9.363 (1.521-57.632). CONCLUSIONS: Our findings show that IC/PBS negatively impacts participant's quality of life and emotional wellbeing. Higher expectation for treatment benefit and increasing levels of patient concern are predictive for severity of IC/PBS.

Effects of non-ablative vaginal erbium:YAG laser treatment for interstitial cystitis/bladder pain syndrome: a case series (UNICORN-2 study).

Purpose: There are no established treatments for treating interstitial cystitis/bladder pain syndrome (IC/BPS). We conducted a study to verify the effectiveness of non-ablative vaginal erbium:YAG laser (VEL) treatment for patients with IC/BPS who were resistant to conventional treatments.Methods: A total of 12 patients without improvement after several treatments before 2016 underwent VEL treatment once a month for 12 months as per their convenience. The numeric rating scale-11 (NRS-11), O'Leary-Sant interstitial cystitis symptom and problem indexes (ICSI and ICPI), functional bladder capacity, and daily urinary frequency were obtained.Results: In total, nine patients responded to the treatment and three did not. The NRS-11 scores and ICSI and ICPI improved in all responders. The bladder capacity and urinary frequency also normalized. The residual effect lasted for 18 months from the first treatment without long-term side-effects.Conclusions: VEL treatment is a safe and effective treatment in patients with IC/BPS.

[Electron microscopic characterization of the mucous membrane of the bladder with interstitial cystitis/painful bladder syndrome in the experiment].

OBJECTIVES: the study of the nature and severity of the reorganization of the structural elements of the bladder wall on experimental models of IC / BPS at the optical and ultrastructural levels. MATERIALS AND METHODS: The experimental model of IC / SBMP was created on 22 white New Zealand female rabbits weighing 1500-2000 g. The animals were divided into 2 groups: group 1 - 15 rabbits, which were introduced into the bladder wall urine taken from the animals bladder; Group 2 (control) - 7 animals that were injected into the bladder wall with a 0.9% NaCl solution. The biomaterial was examined by electron microscopy. The structural elements of the lamina propria of the bladder mucosa were evaluated. RESULTS: In the bladder mucosa of the experimental model, perivascular infiltration by inflammatory cells, pronounced edema of the lamina propria of the bladder mucosa, and the presence of numerous plasma cells having close contacts with macrophages, fibroblasts, and lymphocytes were revealed. In the nucleus of lymphocytes of a peripherally located supercondensed heterochromatin showed their apoptotic state. Edematous fluid was determined, penetrating mainly through the fenestra, located in the peripheral parts of the endothelial cells of capillaries and postcapillary venules. CONCLUSION: The study of the structural elements of the lamina propria of the bladder mucosa in the experiment by the method of electron microscopy made it possible to identify changes caused by the inflammatory process, both of an acute and productive nature. The results obtained showed that toxic damage to the lamina propria of the bladder mucosa causes apoptosis of fibroblasts of the lamina propria, leads to loosening of collagen fibers and, ultimately, to a decrease in the protective factors of the mucous membrane.

Molecular determinants of afferent sensitization in a rat model of cystitis with urothelial barrier dysfunction.

The internal surface of the urinary bladder is covered by the urothelium, a stratified epithelium that forms an impermeable barrier to urinary solutes. Increased urothelial permeability is thought to contribute to symptom generation in several forms of cystitis by sensitizing bladder afferents. In this report we investigate the physiological mechanisms that mediate bladder afferent hyperexcitability in a rat model of cystitis induced by overexpression in the urothelium of claudin-2 (Cldn2), a tight junction-associated protein upregulated in bladder biopsies from patients with interstitial cystitis/bladder pain syndrome. Patch-clamp studies showed that overexpression of Cldn2 in the urothelium sensitizes a population of isolectin GS-IB4-negative [IB4(-)] bladder sensory neurons with tetrodotoxin-sensitive (TTX-S) action potentials. Gene expression analysis revealed a significant increase in mRNA levels of the delayed-rectifier voltage-gated K+ channel (Kv)2.2 and the accessory subunit Kv9.1 in this population of bladder sensory neurons. Consistent with this finding, Kv2/Kv9.1 channel activity was greater in IB4(-) bladder sensory neurons from rats overexpressing Cldn2 in the urothelium than in control counterparts. Likewise, current density of TTX-S voltage-gated Na+ (Nav) channels was greater in sensitized neurons than in control counterparts. Significantly, guangxitoxin-1E (GxTX-1E), a selective blocker of Kv2 channels, blunted the repetitive firing of sensitized IB4(-) sensory neurons. In summary, our studies indicate that an increase in the activity of TTX-S Nav and Kv2/Kv9.1 channels mediates repetitive firing of sensitized bladder sensory neurons in rats with increased urothelial permeability.NEW & NOTEWORTHY Hyperexcitability of sensitized bladder sensory neurons in a rat model of interstitial cystitis/bladder pain syndrome (IC/BPS) results from increased activity of tetrodotoxin-sensitive voltage-gated Na+ and delayed-rectifier voltage-gated K+ (Kv)2/Kv9.1 channels. Of major significance, our studies indicate that Kv2/Kv9.1 channels play a major role in symptom generation in this model of IC/BPS by maintaining the sustained firing of the sensitized bladder sensory neurons.

Differentiation of Urothelium from Mouse Embryonic Stem Cells in Chemically Defined Conditions.

The urothelium of the bladder and urethra are derived from the definitive endoderm during development. Cellular signaling molecules important to the developmental specification of the urothelium are also implicated in the dysregulation of the tissue repair mechanism characteristic of bladder disease. Hence, a complete understanding of the regulation of urothelium development is central to understanding the processes of bladder disease, and in development of simple chemically defined methods for use in regenerative medicine. Key to this is a suitable in vitro model that readily allows for the prosecution of biologically pertinent questions. Here a method for differentiating urothelium from mouse embryonic stem cells in chemically defined conditions is described. The method includes a description of flow cytometry and RT-PCR analysis of definitive endoderm markers Cxcr4, c-Kit, and FoxA2, and of terminally differentiated urothelial cell markers Upk1b and Upk2.

[Efficacy of electroacupuncture nerve stimulation therapy for interstitial cystitis/bladder pain syndrome].

OBJECTIVE: To explore the clinical efficacy of electroacupuncture nerve stimulation therapy (ENST) for interstitial cystitis/painful bladder syndrome (IC/PBS). METHODS: A total of 68 patients with IC/PBS were randomly divided into an observation group and a control group, 34 cases in each one. The patients in the observation group were treated with ENST; abdominal four acupoints and sacral four acupoints were connected with a pair of electrodes and treated alternately every other day. The ENST was given 50 min per times, three times a week for 3 months. The patients in the control group were treated with perfusion therapy of four-medication combination (heparin sodinm, lidocaine, sodium bicarbonate, gentamicin sulfate), twice a week for the first 6-8 weeks, followed by twice per month for 3 months. The infusion fluid remained for 1 h before discharging. The O' Leary-Sant score, including interstitial cystitis symptom index (ICSI) and interstitial cystitis problem index (ICPI), 24 h urination frequency, visual analogue scale (VAS) and maximum bladder volume were observed before treatment and treatment of 1 month, 3 months and 6 months after treatment respectively; the adverse events during the treatment were also recorded. RESULTS: Compared before treatment, the O'Leary-Sant score (ICSI, ICPI), 24 h urination frequency, VAS and maximum bladder volume in the two groups were improved after 1, 3 months treatment and 6 months after treatment (all P<0.05). The scores of ICSI, ICPI, VAS and 24 h urination frequency in the observation group were significantly lower than those in the control group (P<0.05). The maximum bladder volume in the observation group was significantly higher than that in the control group (P<0.05). Six months after treatment, the total effective rate in the observation group was 87.5% (28/32), which was higher than 69.7% (23/33) in the control group (P<0.01). No significant adverse events occurred during the treatment. CONCLUSION: ENST could effectively relieve the clinical symptoms of IC/PBS, but its long-term efficacy needs further observation.

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

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

Efficacy of electroacupuncture nerve stimulation therapy for interstitial cystitis/bladder pain syndrome / 中国针灸

OBJECTIVE@#To explore the clinical efficacy of electroacupuncture nerve stimulation therapy (ENST) for interstitial cystitis/painful bladder syndrome (IC/PBS).@*METHODS@#A total of 68 patients with IC/PBS were randomly divided into an observation group and a control group, 34 cases in each one. The patients in the observation group were treated with ENST; abdominal four acupoints and sacral four acupoints were connected with a pair of electrodes and treated alternately every other day. The ENST was given 50 min per times, three times a week for 3 months. The patients in the control group were treated with perfusion therapy of four-medication combination (heparin sodinm, lidocaine, sodium bicarbonate, gentamicin sulfate), twice a week for the first 6-8 weeks, followed by twice per month for 3 months. The infusion fluid remained for 1 h before discharging. The O' Leary-Sant score, including interstitial cystitis symptom index (ICSI) and interstitial cystitis problem index (ICPI), 24 h urination frequency, visual analogue scale (VAS) and maximum bladder volume were observed before treatment and treatment of 1 month, 3 months and 6 months after treatment respectively; the adverse events during the treatment were also recorded.@*RESULTS@#Compared before treatment, the O'Leary-Sant score (ICSI, ICPI), 24 h urination frequency, VAS and maximum bladder volume in the two groups were improved after 1, 3 months treatment and 6 months after treatment (all <0.05). The scores of ICSI, ICPI, VAS and 24 h urination frequency in the observation group were significantly lower than those in the control group (<0.05). The maximum bladder volume in the observation group was significantly higher than that in the control group (<0.05). Six months after treatment, the total effective rate in the observation group was 87.5% (28/32), which was higher than 69.7% (23/33) in the control group (<0.01). No significant adverse events occurred during the treatment.@*CONCLUSION@#ENST could effectively relieve the clinical symptoms of IC/PBS, but its long-term efficacy needs further observation.

Morbidity rate and medical utilization in interstitial cystitis/painful bladder syndrome.

INTRODUCTION AND HYPOTHESIS: The objective was to calculate the morbidity rate and medical utilization of interstitial cystitis/painful bladder syndrome (IC/PBS) over 12 years using a nationwide database of Taiwan. METHODS: This was a cohort study of the Longitudinal Health Insurance Database 2010 with new diagnoses of IC/PBS from 2002 through 2013. The morbidity rate was adjusted for age, sex, and calendar date using density methods. Moreover, medical utilization during the study period was measured. RESULTS: It was observed that the incidence of IC/PBS was 21.8/100,000 in 2002 and 21.1/100,000 in 2013. The prevalence of IC/PBS was 21.8/100,000 in 2002 and 40.2/100,000 in 2013. In 2003, the incidence and prevalence of women was 28.6/100,000 and 63.5/100,000 respectively. The incidence and prevalence of men was 12.3/100,000 and 19.4/100,000 respectively. In 2002, the incidence was 45.5/100,000, 32.4/100,000, and 9/100,000 in the age groups above 65, 40-65, and under 40 years respectively. The prevalence in 2003 was 86.3/100,000, 63.1/100,000, and 16.4/100,000 in age groups above 65, 40-65, and under 40 years respectively. This pattern was similar until 2013. The mean outpatient and inpatient visit time was 4.8 and 1.8 times per year respectively. The mean surgical fee (US$ 246.6 ± 304.5) was 23.6% of the total fee. CONCLUSIONS: The morbidity rate of IC/PBS showed a higher incidence and prevalence in women and older patients. A new drug for the treatment of IC/PBS may be a factor of the peak in the morbidity rate. The increase in medical utilization could be explained by the awareness of physicians and patients seeking medical help.

Endogenous H2S sensitizes PAR4-induced bladder pain.

Bladder pain is a prominent symptom of interstitial cystitis/painful bladder syndrome. Hydrogen sulfide (H2S) generated by cystathionine ß-synthase (CBS) or cystathionine γ-lyase (CSE) facilitates bladder hypersensitivity. We assessed involvement of the H2S pathway in protease-activated receptor 4 (PAR4)-induced bladder pain. A bladder pain model was induced by intravesical instillation of PAR4-activating peptide in mice. The role of H2S in this model was evaluated by intraperitoneal preadministration of d,l-propargylglycine (PAG), aminooxyacetic acid (AOAA), or S-adenosylmethionine or the preintravesical administration of NaHS. SV-HUC-1 cells were treated in similar manners. Assessments of CBS, CSE, and macrophage migration inhibitory factor (MIF) expression, bladder voiding function, bladder inflammation, H2S production, and referred bladder pain were performed. The CSE and CBS pathways existed in both mouse bladders and SV-HUC-1 cells. H2S signaling was upregulated in PAR4-induced bladder pain models, and H2S-generating enzyme activity was upregulated in human bladders, mouse bladders, and SV-HUC-1 cells. Pretreatment with AOAA or NaHS inhibited or promoted PAR4-induced mechanical hyperalgesia, respectively; however, PAG only partially inhibited PAR4-induced bladder pain. Treatment with PAG or AOAA decreased H2S production in both mouse bladders and SV-HUC-1 cells. Pretreatment with AOAA increased MIF protein levels in bladder tissues and cells, whereas pretreatment with NaHS lowered MIF protein levels. Bladder pain triggered by the H2S pathway was not accompanied by inflammation or altered micturition behavior. Thus endogenous H2S generated by CBS or CSE caused referred hyperalgesia mediated through MIF in mice with PAR4-induced bladder pain, without causing bladder injury or altering micturition behavior.

Treatment of ulcerative compared to non-ulcerative interstitial cystitis with hyperbaric oxygen: a pilot study.

BACKGROUND: The etiology of interstitial cystitis (IC) is often idiopathic but can be due to Hunner's ulcers. Hyperbaric oxygen (HBO) is used to treat ulcerative disease of the superficial skin. We hypothesized that HBO can treat ulcerative IC (UIC) but would be less efficacious for non-ulcerative IC (NIC). METHODS: Patients with NIC and UIC enrolled in this study. Following informed consent, demographic information was collected. A visual analog pain scale and validated questionnaires were collected; each patient underwent cystoscopy prior to treatment. Each subject met with a hyperbaric specialist and after clearance underwent 30 treatments over 6 weeks. Adverse events were monitored. Patients repeated questionnaires, visual analog pain scale and global response assessment (GRA) immediately, 2 weeks, 3, 6 and 12 months after treatment. Patients also underwent cystoscopy 6 months after treatment. Differences before and after treatment were compared. RESULTS: Nine patients were recruited to this study. One was unable to participate, leaving two subjects with NIC and six with UIC. All patients completed HBO without adverse events. Three patients completed HBO but pursued other therapies 7, 8.5 and 11 months after treatment. On GRA, 83% of patients with UIC were improved. This treatment effect persisted, as 66% of UIC patients remained better at 6 months. In contrast, only one patient in the NIC group improved. Questionnaire scores improved in both groups. Pain scores improved by 2 points in the UIC group but worsened by 1.5 points in the NIC group. Two patients with ulcers resolved at 6-month cystoscopy. CONCLUSION: HBO appeared beneficial for both UIC and NIC. Data shows slightly better benefit in patients with UIC compared to NIC; both groups showed improvement. Given the small sample size, it is difficult to draw definitive conclusions from these data. Larger studies with randomization would be beneficial to show treatment effect.

A retrospective analysis of sacral neuromodulation for female overactive bladder and interstitial cystitis/painful blader syndrome / 中华泌尿外科杂志

Objective To evaluate the effects of sacral neuromodulation (SNM) on female overactive bladder (OAB) and interstitial cystitis/ painful bladder syndrome (IC/PBS).Methods From May 2016 to April 2017,13 patients with OAB or IC/PBS who had been treated with SNM were assessed retrospectively.Among them,6 cases were OAB patients,and 7 cases were IC/PBS patients.The average age was 52.3 (42-67)years old,and the preoperative and postoperative 24 h urine frequency,night urination frequency and average voided volume were compared.Results Totally 13 patients underwent stage Ⅰprocedure.The operation time for stage Ⅰ was 52-125min(average 92 min).After an average follow-up of 3.6 weeks,stage 11 procedures were performed on responders.Four OAB patients accepted stage Ⅱ1 surgery (conversion rate:66.7％),and the 24h frequency and night urination frequency reduced from preoperative 22.5 and 5.2 times to postoperative 14.3 and 2.3 times (P ＜ 0.05) respectively,and average voided volume increased from 120.3ml to 166.4ml (P ＜ 0.05).Among 4 patients presenting IC/PBS who had underwent stage Ⅱ surgery (conversion rate:57.1％),VAS score and 24 h voiding frequency reduced from 7.3 and 21.6 to 3.8 and 16.8 (P ＜ 0.05),respectively.No adverse event,such as wound infection or electrode translocation was detected during an average follow-up of 8.3 months.Conclusions Stage Ⅰ procedure is crucial for the long term efficacy of SNM.Postsurgical wound management and parameter adjustment are equal essential in order to achieve a maximum benefits.SNM has advantages in minimal invasiveness and less bleeding,which provides a minimal invasive approach for the managemem of OAB and IC/PBS.

A retrospective analysis of sacral neuromodulation for female overactive bladder and interstitial cystitis/painful blader syndrome / 中华泌尿外科杂志

Objective To evaluate the effects of sacral neuromodulation (SNM) on female overactive bladder (OAB) and interstitial cystitis/ painful bladder syndrome (IC/PBS).Methods From May 2016 to April 2017,13 patients with OAB or IC/PBS who had been treated with SNM were assessed retrospectively.Among them,6 cases were OAB patients,and 7 cases were IC/PBS patients.The average age was 52.3 (42-67)years old,and the preoperative and postoperative 24 h urine frequency,night urination frequency and average voided volume were compared.Results Totally 13 patients underwent stage Ⅰprocedure.The operation time for stage Ⅰ was 52-125min(average 92 min).After an average follow-up of 3.6 weeks,stage 11 procedures were performed on responders.Four OAB patients accepted stage Ⅱ1 surgery (conversion rate:66.7％),and the 24h frequency and night urination frequency reduced from preoperative 22.5 and 5.2 times to postoperative 14.3 and 2.3 times (P ＜ 0.05) respectively,and average voided volume increased from 120.3ml to 166.4ml (P ＜ 0.05).Among 4 patients presenting IC/PBS who had underwent stage Ⅱ surgery (conversion rate:57.1％),VAS score and 24 h voiding frequency reduced from 7.3 and 21.6 to 3.8 and 16.8 (P ＜ 0.05),respectively.No adverse event,such as wound infection or electrode translocation was detected during an average follow-up of 8.3 months.Conclusions Stage Ⅰ procedure is crucial for the long term efficacy of SNM.Postsurgical wound management and parameter adjustment are equal essential in order to achieve a maximum benefits.SNM has advantages in minimal invasiveness and less bleeding,which provides a minimal invasive approach for the managemem of OAB and IC/PBS.

Increased urothelial paracellular transport promotes cystitis.

Changes in the urothelial barrier are observed in patients with cystitis, but whether this leads to inflammation or occurs in response to it is currently unknown. To determine whether urothelial barrier dysfunction is sufficient to promote cystitis, we employed in situ adenoviral transduction to selectively overexpress the pore-forming tight junction-associated protein claudin-2 (CLDN-2). As expected, the expression of CLDN-2 in the umbrella cells increased the permeability of the paracellular route toward ions, but not to large organic molecules. In vivo studies of bladder function revealed higher intravesical basal pressures, reduced compliance, and increased voiding frequency in rats transduced with CLDN-2 vs. controls transduced with green fluorescent protein. While the integrity of the urothelial barrier was preserved in the rats transduced with CLDN-2, we found that the expression of this protein in the umbrella cells initiated an inflammatory process in the urinary bladder characterized by edema and the presence of a lymphocytic infiltrate. Taken together, these results are consistent with the notion that urothelial barrier dysfunction may be sufficient to trigger bladder inflammation and to alter bladder function.

Chronic psychological stress in high-anxiety rats induces sustained bladder hyperalgesia.

OBJECTIVE: To evaluate whether anxiety-prone rats exposed to chronic water avoidance stress (WAS) develop visceral bladder hyperalgesia in addition to increased voiding frequency and anxiety-related behaviors. MATERIALS AND METHODS: Female Wistar-Kyoto (WKY) rats were exposed to chronic (10-day) WAS or sham paradigms. Referred hyperalgesia and tactile allodynia were tested using von Frey filaments applied to the suprapubic region and plantar region of the hindpaw, respectively. To confirm that suprapubic nociception represented referred visceral bladder hyperalgesia, we recorded abdominal visceromotor responses (VMR) to slow (100 µl/min) and fast (1 cc/sec) bladder filling with room temperature or ice-cold saline. We assessed the development of hyperalgesia over the 10-day WAS protocol and the durability of increased pain sensations over time. RESULTS: Animals exposed to chronic WAS had significantly lower hindpaw withdrawal thresholds post-stress and significant differences in referred hyperalgesia. Rats exposed to chronic WAS demonstrated an increased pain response to suprapubic stimulation and decreased response threshold to mechanical hindpaw stimulation by day 8 of the stress protocol, which persisted for more than one month. Animals exposed to chronic WAS showed increased VMR to fast filling and ice water testing in comparison to sham animals. Cystometry under anesthesia did not show increases in the frequency of non-voiding contractions. CONCLUSION: Chronic WAS induces sustained bladder hyperalgesia, lasting over a month after exposure to stress. The urinary frequency demonstrated previously in anxiety-prone rats exposed to chronic WAS seems to be associated with bladder hyperalgesia, suggesting that this is a potential model for future studies of bladder hypersensitivity syndromes such as interstitial cystitis/painful bladder syndrome (IC/PBS).

Interstitial cystitis/painful bladder syndrome: the influence of modern diagnostic criteria on epidemiology and on Internet search activity by the public.

Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic debilitating condition that is characterised by suprapubic pain and urinary symptoms such as urgency, nocturia and urinary frequency. The prevalence of the condition is increasing due to more inclusive diagnostic criteria. Herein, we review the evolving epidemiology of IC/PBS and investigate health seeking behaviour for the condition through Internet search activity. Study selection was performed in accordance with PRISMA. In addition, global search trends for the terms 'Interstitial Cystitis' and 'Painful Bladder Syndrome' from 2005 to 2015 were also evaluated using the 'Google Trends' search application. The mean search activity per month was recorded and mean activity at annual intervals calculated. Regional search activity by country and city was also measured. Prevalence rates for IC/PBS vary according to diagnostic criteria and range from 2% to 17.3% among the general population. Increased prevalence is associated with female gender and females with one first-degree relative affected. There has been an increase in global mean search activity for IC/PBS on an annual basis since 2005. The greatest increase in search activity was in USA, Canada, United Kingdom, Australia, Ireland and India respectively. The top five cities for search activity for IC/PBS were in the USA. As diagnostic criteria for IC/PBS continues to become more inclusive it is likely that the prevalence will continue to increase. This is particularly true for the USA and Canada as these regions have demonstrated the greatest increase in Internet search activity for IC/ PBS.

Efficacy comparison of interstitial cystitis/painful bladder syndrome patients treated with four-drug combination and sodium hyaluronate intravesical instillation / 中华泌尿外科杂志

Objective To compare the outcomes between interstitial cystitis/painful bladder syndrome (IC/PBS) patients treated with four-drug combination (heparin,lidocaine,sodium bicarbonate,gentamicin) and sodium hyaluronate intravesical instillation.Methods There were 23 IC/PBS patients from Jan.1,2011 to Mar.1,2013.Ten patients (group A) received four-drug combination (heparin 40 000 U,'gentamicin 160 000 U,sodium bicarbonate 1％,lidocaine 0.4％) instillation treatment.Thirteen patients received instillation of sodium hyaluronate (40 mg/50 ml) therapy (group B).In group B,intravesical instillations were performed weekly in the first 6-8 weeks,and monthly until one year.Patients in group A received intravesical instillation twice a week in the first 6-8 weeks and twice a month for 10 months.All the patients were instructed to retain the instillation volume for at least one hour.Clinical symptoms (24 h frequency of urination,maximal micturition volume),O'Leary-Sant symptom and problem index were assessed at baseline and 1,6 and 12 months after treatment.The 2 therapies were compared within curative effects and side effects.Results Twenty-two of the 23 patients were followed up to 12 months.Patients in group A had no adverse events reported.One case of group B dropped out from treatment for recurrent urinary tract infection,and the other two cases felt painful in bladder area during instillation.There was no significant difference in initial scores between the 2 groups (P＞0.05).At 1,6,12 months after intravesical instillation,interstitial cystitis symptom index,interstitial cystitis problem index,24 h frequency of urination,the maximum bladder capacity were improved in both groups.All indicators in group A and B were improved significantly after treatment compared with pretreatment (P ＜ 0.05).≥ 25％ decrease of interstitial cystitis symptom index or ≥25％ decrease of 24 h frequency of urination were defined as remission.Remission rates of the 2 groups at each time point were:1 month after treatment (100％ versus 100％,P=1.000),6 months after treatment (80％ versus 83％,P=1.000),1 year after treatment (70％ versus 75％,P=1.000).There were no significant differences between the 2 groups in all time points for the outcomes (P ＞ 0.05).Conclusion The four-drug combination intravesical instillation could achieve a similar effect with hyaluronic acid therapy in patients with IC/PBS.

Interstitial cystitis/painful bladder syndrome: epidemiology, pathophysiology and evidence-based treatment options.

Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic debilitating condition that can have a severely negative impact on a patient's quality of life. Its prevalence ranges from 52 to 500/100,000 in females compared to 8-41/100,000 in males, and its incidence is increasing globally. Treatment algorithms are sub-classified into behavioural, pharmacological, intravesical, interventional and surgical therapies. Short-term (i.e. <1 year) cure rates range from 50% to 75% for non-/minimally-invasive therapies, but repeat administration of a therapeutic agent is required. Although definitive surgical intervention is associated with greater long-term cure rates (≥80%); significant short- and long-term adverse effects occur more frequently. Clinicians are likely to experience increasing numbers of patients with IC/PBS as more is understood about its pathophysiology and evolving epidemiology. Therefore urogynaecologists should familiarise themselves with appropriate diagnostic criteria and evidence based therapies to optimise clinical outcomes in this patient cohort.

Physiological relevance of LL-37 induced bladder inflammation and mast cells.

PURPOSE: We established the physiological relevance of LL-37 induced bladder inflammation. We hypothesized that 1) human urinary LL-37 is increased in pediatric patients with spina bifida, 2) LL-37 induced inflammation occurs in our mouse model via urothelial binding and is dose dependent and 3) LL-37 induced inflammation involves mast cells. MATERIALS AND METHODS: To test our first hypothesis, we obtained urine samples from 56 pediatric patients with spina bifida and 22 normal patients. LL-37 was measured by enzyme-linked immunosorbent assay. Our second hypothesis was tested in C57Bl/6 mice challenged with 7 LL-37 concentrations intravesically for 1 hour. At 24 hours tissues were examined histologically and myeloperoxidase assay was done to quantitate inflammation. In separate experiments fluorescent LL-37 was instilled and tissues were obtained immediately (time = 0) and at 24 hours (time = 24). To test our final hypothesis, we performed immunohistochemistry for mast cell tryptase and evaluated 5 high power fields per bladder to determine the mean number of mast cells per mm(2). RESULTS: Urinary LL-37 was 89-fold higher in patients with spina bifida. Mouse LL-37 dose escalation experiments revealed increased inflammation at higher LL-37 concentrations. Fluorescent LL-37 demonstrated global urothelial binding at time = 0 but was not visible at time = 24. Immunohistochemistry for tryptase revealed mast cell infiltration in all tissue layers. At higher concentrations the LL-37 challenge led to significantly greater mast cell infiltration. CONCLUSIONS: Urinary LL-37 was significantly increased in pediatric patients with spina bifida. To our knowledge we report for the first time that LL-37 can elicit profound, dose dependent bladder inflammation involving the urothelium. Finally, inflammation propagation involves mast cells.

Application of psychological evaluation in patients with interstitial cystitis/bladder pain syndrome / 中华泌尿外科杂志

Objective To explore the correlation between anxiety,depression and the symptoms of interstitial cystitis/bladder pain syndrome (IC/PBS) patients,improving the psychological knowledge of IC/PBS patients,providing theoretical basis for psychological intervention.Methods During November 2009 to October 2011,54 IC/PBS patients including 42 women and 12 men patients were treated,with mean age of (41.0±12.4) years and mean course of the disease of (63.0±59.2) months.O'Leary-Sant questionnaire was used for IC/PBS symptoms assessment,and Visual Analogue Scale (VAS) was used to evaluate pain associated with bladder,Self-rating Anxiety Scale (SAS) was used for anxiety assessment,and Beck Depression Inventory Ⅱ (BDI-Ⅱ) was used for depression assessment.The relationship between depression,anxiety and the symptoms of IC/PBS patients was evaluated.Results Of the 54 IC/PBS patients,mean ICSI score was (15.0±1.84) points,mean ICPI score was (8.0±2.6) points,mean O'Leary-Sant questionnaire score was (24.0±3.9) points,mean VAS score was (7.0± 1.0) points,mean anxiety score was (52.0± 7.2) points,with 35 cases (64.8％) suffering from anxiety symptoms.Mean depression symptoms score was (16.0±4.5) points,with 41 cases (75.9％) suffering from depressive symptoms.The degree of anxiety and depression were associated with education level,the sleep quality and monthly income of IC/PBS patients.Anxiety and depression had no definite correlation with marital status and working conditions.Anxiety and depression were closely related (proportion) with the symptoms (frequency,urgency,pain or discomfortrelated to bladder) of IC/PBS patients.Conclusions Anxiety and depression are common in patients with IC/PBS,and they are related to symptom severity.In order to improve the quality of life,much attention must be paid to psychological condition assessment and treatment of IC/PBS patients.