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

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

Depression and Coping Behaviors Are Key Factors in Understanding Pain in Interstitial Cystitis/Bladder Pain Syndrome.

BACKGROUND: Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) is a urologic chronic pelvic pain syndrome with suboptimal treatment outcomes. Catastrophizing is an empirically supported risk factor for greater IC/BPS pain. AIMS: In this study, a moderated multiple mediation model is tested in which several additional psychosocial risk factors (depression, illness and wellness-focused behavioral coping strategies) are proposed as mediators or moderators in the existing relationship between catastrophizing and IC/BPS pain. DESIGN: The present questionnaire study employed a cross-sectional design. SETTINGS AND PARTICIPANTS: Female patients with an IC/BPS diagnosis (n = 341) were recruited at tertiary care sites. METHODS: Participants completed questionnaires assessing pain, catastrophizing, behavioral coping strategies, and depressive symptoms. Aggregate factor scores were calculated following exploratory factor analyses. RESULTS: It was found that patients with a greater tendency to catastrophize were more likely to engage in illness-focused coping strategies, which contributed to the reporting of greater sensory and affective pain. Furthermore, this mediating effect of illness-focused coping on affective pain was more likely to occur in those patients reporting greater depressive symptoms. CONCLUSIONS: Illness-focused behavioral coping is an important mechanism between maladaptive pain cognition and aspects of patient pain, with patients reporting greater depressive symptoms at increased risk for elevated pain. Patient management techniques, including screening for catastrophizing, coping, and depression, are recommended to enrich IC/BPS management.

A standard for terminology in chronic pelvic pain syndromes: A report from the chronic pelvic pain working group of the international continence society.

AIMS: Terms used in the field of chronic pelvic pain (CPP) are poorly defined and often confusing. An International Continence Society (ICS) Standard for Terminology in chronic pelvic pain syndromes (CPPS) has been developed with the aim of improving diagnosis and treatment of patients affected by chronic pelvic pain syndromes. The standard aims to facilitate research, enhance therapy development and support healthcare delivery, for healthcare providers, and patients. This document looks at the whole person and all the domains (organ systems) in a systematic way. METHODS: A dedicated working group (WG) was instituted by the ICS Standardisation Steering Committee according to published procedures. The WG extracted information from existing relevant guidelines, consensus documents, and scientific publications. Medline and other databases were searched in relation to each chronic pelvic pain domain from 1980 to 2014. Existing ICS Standards for terminology were utilized where appropriate to ensure transparency, accessibility, flexibility, and evolution. Consensus was based on majority agreement. RESULTS: The multidisciplinary CPPS Standard reports updated consensus terminology in nine domains; lower urinary tract, female genital, male genital, gastrointestinal, musculoskeletal, neurological aspects, psychological aspects, sexual aspects, and comorbidities. Each is described in terms of symptoms, signs and further evaluation. CONCLUSION: The document presents preferred terms and definitions for symptoms, signs, and evaluation (diagnostic work-up) of female and male patients with chronic pelvic pain syndromes, serving as a platform for ongoing development in this field. Neurourol. Urodynam. 36:984-1008, 2017. © 2016 Wiley Periodicals, Inc.

The Role of Glomerulations in Bladder Pain Syndrome: A Review.

PURPOSE: As a diagnostic marker for bladder pain syndrome/interstitial cystitis, glomerulations were first popularized by Messing and Stamey in 1978. Later this was included in the National Institute of Diabetes and Digestive and Kidney Diseases criteria for research and consequently used by many urologists as a default diagnostic criterion. Today the connection between glomerulations and bladder pain syndrome/interstitial cystitis is much debated as research has found glomerulations in asymptomatic populations. In this review we systematically examine the available research to see if there are valid data to support the use of glomerulations as a marker for bladder pain syndrome/interstitial cystitis. MATERIALS AND METHODS: A systematic literature search of the PubMed® database in March 2014 using the search term "Cystitis, Interstitial/diagnosis" [MAJR] OR (glomerulations OR glomerulation OR bladder petechiae) was performed, yielding 463 hits. An Embase® search using the search term "glomerulations" yielded 110 references, of which 68 were duplicates. Relevant articles were reviewed and included in the study. Bibliographies of reviews, articles and status reports were examined to find studies not included in the search. A total of 29 publications were included in this review. RESULTS: There is no consistent relationship between glomerulations and the diagnosis of bladder pain syndrome/interstitial cystitis. In the reviewed studies we found evidence of the grade of glomerulations changing with time. Furthermore, many studies showed no link between the severity of symptoms and the number of glomerulations. There were studies that found glomerulations in healthy asymptomatic populations as well as in symptomatic populations with another primary diagnosis. One study showed no glomerulations in an asymptomatic population. CONCLUSIONS: We found no convincing evidence in the reviewed literature that glomerulations should be included in the diagnosis or phenotyping of bladder pain syndrome/interstitial cystitis. Glomerulations do not correlate with symptoms and are found in patients without bladder pain syndrome/interstitial cystitis.

Upper urinary tract tumors: how does the contrast enhancement measured in a split-bolus CTU correlate to histological staging?

BACKGROUND: Computed tomography urography (CTU) is used widely in the work-up of patients with symptoms of urinary tract lesions. Preoperative knowledge of whether a tumor is invasive or non-invasive is important for the choice of surgery. So far there are no studies about the distinction of invasive and non-invasive tumors in ureter and renal pelvis based on the enhancement measured with Hounsfield Units. PURPOSE: To examine the value of CTU using split-bolus technique to distinguish non-invasive from invasive urothelial carcinomas in the upper urinary tract. MATERIAL AND METHODS: Patients who underwent nephroureterectomy between 2006 and 2011 and who had split-bolus CTU prior to surgery were included. The images were available electronically. The attenuation values before and after administration of iodine-based contrast media were measured. The radiology, patient, and pathology records were reviewed. RESULTS: Of the 158 patients who underwent unilateral nephroureterectomy 69 fulfilled the inclusion criteria. Histopathological examination revealed 31 patients with non-invasive and 38 with invasive urothelial carcinoma. Neither absolute attenuation nor change in attenuation values obtained at CTU could distinguish between invasive and non-invasive lesions. No patients had a CTU within the last year before the examination that resulted in surgery. CONCLUSION: A split-bolus CTU cannot distinguish between invasive and non-invasive urothelial tumors in the upper urinary tract, but the examination is useful to diagnose a tumor in the renal pelvis and the ureter.

Global concepts of bladder pain syndrome (interstitial cystitis).

BACKGROUND: Bladder pain syndrome (BPS), commonly referred to as "interstitial cystitis", is no longer considered a rare disorder. It may affect up to 2.7% of the adult female population (Ueda et al. in Int J Urol 10:1-70, 2003) with up to 20% of cases occurring in men. METHODS: The last two decades have seen a worldwide effort to try to standardize its nomenclature, definition, diagnosis, and treatment algorithm. The literature has been reviewed. RESULTS: In this article, we will detail current terminology, diagnostic approaches and treatment. Standard therapies will be discussed, and a section that concentrates on the management of the subset of patients with a Hunner's lesion will be highlighted. CONCLUSIONS: BPS is today viewed through a new paradigm. It is no longer considered primarily a bladder disease, but rather one of a number of chronic pain syndromes that is distinguished by being manifest through bladder-related symptoms. A distinct subgroup of patients with Hunner's lesion has specific characteristics, and successful treatment of this subgroup is available.

Adjustable continence balloons: clinical results of a new minimally invasive treatment for male urinary incontinence.

OBJECTIVE: This study aimed to evaluate the results of the Danish experience with the ProACT urinary continence device inserted in men with stress urinary incontinence. MATERIAL AND METHODS: The ProACT was inserted in 114 patients. Data were registered prospectively. The main endpoints were complications, pad use per day and 24 h urinary leakage. A questionnaire evaluating symptoms and satisfaction was sent to the patients. RESULTS: Data including preoperative and postoperative pad use and urinary leakage were available for 92 and 90 patients, respectively. A decrease in the median 24 h urinary leakage (352.5 vs 11 ml, p < 0.001) and in the median number of pads used per day (4.75 vs 2.25, p = 0.001) was demonstrated. Forty-six patients had a pad use of 0-1 pads per day and/or a daily urinary leakage less than 8 g, corresponding to an overall dry rate of 50%. A decrease in urinary leakage > 50% was seen in 72 patients (80%). Complications were seen in 23 patients. All of these were treated successfully by removal of the device in the outpatient setting followed by replacement of the device. Another eight patients had a third balloon inserted to improve continence further. Fourteen patients (12%) ended up with an artificial sphincter or a urethral sling. Sixty patients (63%) experienced no discomfort and 58 (61%) reported being dry or markedly improved. Overall, 50 patients (53%) reported being very or predominantly satisfied. CONCLUSIONS: Adjustable continence balloons seem to be a good alternative in the treatment of male urinary incontinence. Complications are mild and easily treated.

Effect of the SK/IK channel modulator 4,5-dichloro-1,3-diethyl-1,3-dihydro-benzoimidazol-2-one (NS4591) on contractile force in rat, pig and human detrusor smooth muscle.

OBJECTIVE: • To investigate the importance of small (SK)- and intermediate (IK)-conductance Ca2(+) -activated K(+) channels on bladder function, by studying the effects of 4,5-dichloro-1,3-diethyl-1,3-dihydro-benzoimidazol-2-one (NS4591), a new modulator of SK/IK channels, on contractions induced by electrical field stimulation (EFS) and carbachol in rat, pig and human detrusor. PATIENTS AND METHODS: • Detrusor biopsies were obtained from rats, pigs and male patients undergoing cystectomy because of bladder cancer. • Force was recorded using myographs. • Intracellular free Ca(2+) was measured in myocytes using microfluorimetry. RESULTS: • In rat bladder rings subjected to EFS, cumulative addition of NS4591 (0.1-30 µM) decreased force by 82 ± 2.9% (n = 6).This effect was reduced by 64 ± 5.2% in the presence of 0.3 µM apamin, a specific inhibitor of SK channels. Apamin increased the force evoked by EFS significantly: force was increased by 14.2 ± 3.4% (n = 5) and 10.1 ± 2.6% (n = 7) in pig and human detrusor strips, respectively (P = 0.04 and P = 0.02). • The cumulative addition of NS4591 (0.3-30 µM) significantly reduced the amplitude of carbachol-induced rhythmic oscillations by 62.0 ± 12.0% (n = 12) and the minimum force between oscillations by 30 ± 5% (n = 9) in pig detrusor strips (P < 0.005). In the presence of 10 µM NS4591, carbachol (1 µM) induced rhythmic contractions with an amplitude and normalized mean power frequency (nmeanPF) of 8.4 ± 5.1% and 0.11 ± 0.06 mN root mean square (rms) Hz (n = 12), respectively, vs. 21 ± 3.4% and 0.17 ± 0.04 mN rms Hz in control strips (n = 13). Apamin induced 6- and 11-fold increases in amplitude and nmeanPF vs. 1.3- and 2-fold increases in control strips. • In human detrusor strips (n = 15), the cumulative addition of NS4591 (1-30 µM) significantly reduced the amplitude by 69 ± 11%, the nmeanPF by 78 ± 6% and the minimum force between carbachol-induced oscillations by 59 ± 5% (P < 0.008). The addition of apamin (0.3 µM) before application of 1 µM carbachol abolished the effects of NS4591 on amplitude and partially abolished its effect on nmeanPF by 41 ± 7%, vs. a 78 ± 6% reduction in the absence of apamin (n = 8). • In spontaneously active detrusor preparations, NS4591 reduced or abolished contractions. • Furthermore, NS4591 (10 µM) decreased the carbachol-induced increase in the fura-2 ratio by 43 ± 3% compared with control (n = 12) (P < 0.03). CONCLUSIONS: • The SK/IK channel modulator NS4591 inhibits EFS- and carbachol-induced contractions in rat, pig and human detrusor muscle. • NS4591 may have therapeutic potential for treatment of detrusor overactivity.

Sarcosine induces increase in HER2/neu expression in androgen-dependent prostate cancer cells.

Increasing evidence suggests that Human epidermal growth factor receptor 2 (HER2/neu) is involved in progression of prostate cancer. Recently, sarcosine was reported to be highly increased during prostate cancer progression, and exogenous sarcosine induces an invasive phenotype in benign prostate epithelial cells. The aim of this work was to investigate the effect of sarcosine on HER2/neu expression in prostate cancer cell lines LNCaP (androgen dependent), PC-3 and DU145 (both androgen independent). Relative amounts of HER2/neu and androgen receptor (AR) transcripts were determined using RT-qPCR. Total expression of HER2/neu was confirmed by Western blot (WB). HER2/neu protein on the surface of living LNCaP cells was visualized by confocal microscopy using a HER2/neu-specific fluorescent probe. Exposure of LNCaP cells to 50 µM sarcosine for 24 h resulted in a 58% increase of the HER2/neu mRNA level (P < 0.001) indicating that sarcosine effects HER2/neu expression on the level of transcription. Control experiments with alanine, an isomer of sarcosine, showed no significant effect on HER2/neu transcription. The upregulation of HER2/neu mRNA preceded the corresponding increment of the protein level after the 48-h exposure to sarcosine as shown by WB and confocal microscopy. Interestingly, sarcosine had no effect on the activated (phosphorylated) form of HER2/neu. No significant change in AR expression was observed after exposure to sarcosine. This is the first report indicating that sarcosine is involved in the regulation of the oncoprotein HER2/neu. Thus, sarcosine may induce prostate cancer progression by increased HER2/neu expression. However, detailed information on cellular mechanisms remains to be elucidated.

Psychosocial phenotyping in women with interstitial cystitis/painful bladder syndrome: a case control study.

PURPOSE: We characterized and compared psychosocial phenotypes in a female interstitial cystitis/painful bladder syndrome cohort and an age matched cohort without that diagnosis. MATERIALS AND METHODS: Female patients with interstitial cystitis/painful bladder syndrome and controls without the condition completed a psychosocial phenotyping questionnaire battery, including a demographics/history form and validated questionnaires focused on a range of presenting symptoms, psychosocial parameters and quality of life. Specific measures included interstitial cystitis symptom and problem index, McGill Pain Questionnaire, Medical Outcomes Study Sleep Scale, Center for Epidemiological Studies Depression Scale, State-Trait Anxiety Inventory, Pain Catastrophizing Scale, Female Sexual Functioning Index and Multidimensional Scale of Perceived Social Support and Medical Outcomes Study Short Form-12 quality of life. Direct comparisons and correlations were made to establish group differences and the strength of associations for psychosocial parameters in patients with interstitial cystitis/painful bladder syndrome. RESULTS: Questionnaires completed by 207 patients with interstitial cystitis/painful bladder syndrome were compared to those of 117 controls matched for age, partner status and education. Compared to controls patients reported significantly more pain (total, sensory and affective), worse physical quality of life, increased sleep dysfunction, depression, catastrophizing, anxiety, stress and moderately more sexual/social function problems. These suffering, coping and social parameters correlated with the degree of general pain but stress, anxiety, depression and catastrophizing further correlated with IC specific symptoms and strongly with decreased quality of life. Pain was strongly associated with physical quality of life, while depression, catastrophizing and stress, and to a lesser extent social support were associated with poor mental quality of life. CONCLUSIONS: Patients with interstitial cystitis/painful bladder syndrome have significant cognitive and psychosocial alterations compared to controls.

Interstitial cystitis/painful bladder syndrome and associated medical conditions with an emphasis on irritable bowel syndrome, fibromyalgia and chronic fatigue syndrome.

PURPOSE: We characterized and compared the impact of clinical phenotypic associations between interstitial cystitis/painful bladder syndrome and controls in relation to potentially related conditions, particularly irritable bowel syndrome, fibromyalgia and chronic fatigue syndrome. MATERIALS AND METHODS: Female patients with interstitial cystitis/painful bladder syndrome and controls with no interstitial cystitis/painful bladder syndrome completed a biopsychosocial phenotyping questionnaire battery which included demographics/history form, self-reported history of associated conditions, and 10 validated questionnaires focused on symptoms, suffering/coping and behavioral/social factors. RESULTS: Questionnaires were completed by 205 patients with interstitial cystitis/painful bladder syndrome and 117 controls matched for age. Prevalence of self-reported associated condition diagnosis in interstitial cystitis/painful bladder syndrome vs controls was irritable bowel syndrome 38.6% vs 5.2%, fibromyalgia 17.7% vs 2.6% and chronic fatigue syndrome 9.5% vs 1.7% (all p <0.001). In the interstitial cystitis/painful bladder syndrome cohort 50.3% reported no other associated condition, 24.4% had interstitial cystitis/painful bladder syndrome + irritable bowel syndrome only, 2.5% had interstitial cystitis/painful bladder syndrome + fibromyalgia only, 1.5% had interstitial cystitis/painful bladder syndrome + chronic fatigue syndrome only, while 20.2% had multiple associated conditions. As the number of associated conditions increased (ie localized, regional, systemic), pain, stress, depression and sleep disturbance increased while social support, sexual functioning and quality of life deteriorated. Anxiety and catastrophizing remained increased in all groups. Symptom duration was associated with this apparent phenotypic progression. CONCLUSIONS: Irritable bowel syndrome, fibromyalgia and chronic fatigue syndrome are more prevalent in patients with interstitial cystitis/painful bladder syndrome than in asymptomatic control subjects, and result in significant impact. There are at least 3 distinct clinical phenotypes based on identification of overlapping syndrome patterns. A suggestion that remains to be proven with longitudinal studies is that there may be progression over time from an organ centric to a regional and finally to a systemic pain syndrome with progression of symptom severity, and deterioration of cognitive and psychosocial parameters.

YKL-40 and mast cells are associated with detrusor fibrosis in patients diagnosed with bladder pain syndrome/interstitial cystitis according to the 2008 criteria of the European Society for the Study of Interstitial Cystitis.

AIMS: Bladder pain syndrome/interstitial cystitis (BPS/IC), diagnosed according to the new 2008 criteria of the European Society for the Study of Interstitial Cystitis (ESSIC), may lead to detrusor fibrosis. In some inflammatory diseases, fibrosis is related to YKL-40. The aims were to examine YKL-40 antigenic expression in bladder tissue and levels in serum and urine in BPS/IC and to evaluate whether YKL-40 could be a non-invasive, prognostic biomarker for bladder fibrogenesis and treatment intensity. METHODS AND RESULTS: Immunohistochemistry, immunoelectron microscopy and enzyme-linked immunosorbent assay (ELISA) analyses in 45 patients showed YKL-40 expression in detrusor mast cell granules and submucosal macrophages, and elevated YKL-40 levels in serum and urine compared to healthy individuals (median 72 versus 7 µg/l, P < 0.001). Clinicopathological parameters showed associations of detrusor fibrosis with YKL-40-positive cells (P = 0.001), mast cells (P = 0.014) and urine YKL-40 (P = 0.009). Bladder capacity correlated inversely with YKL-40-positive cells (P < 0.001) and mast cells (P = 0.029). Treatment intensity was not associated with YKL-40. CONCLUSION: Serum and urine levels of YKL-40 may be used as non-invasive biomarkers in BPS/IC for the evaluation of bladder fibrogenesis.

Bladder pain syndrome/interstitial cystitis in a Danish population: a study using the 2008 criteria of the European Society for the Study of Interstitial Cystitis.

OBJECTIVE: To characterize and evaluate a Danish patient population with bladder pain syndrome/interstitial cystitis (BPS/IC), using a working definition for BPS/IC incorporating six variables, and a set of criteria defined by the European Society for the Study of Interstitial Cystitis (ESSIC); to describe the clinical course and treatment intensity in relation to these variables. PATIENTS AND METHODS: Clinical data were obtained retrospectively from medical records for 349 consecutive patients with IC referred to the Department of Urology, Copenhagen University Hospital Herlev, Denmark between 1966 and 2008. The median (range) age at diagnosis was 53 (16-88) years; 64% were followed for at least 2 years. The outcome was expressed in terms of treatment intensity and was correlated with clinical data (pain, nocturnal frequency, bladder capacity, mucosal glomerulations, detrusor mastocytosis, detrusor intrafascicular fibrosis, IFF). RESULTS: All patients had pain and 75% had nocturia at least twice. The bladder capacity estimated under general anaesthesia was <500 mL in 42%; 53% presented with detrusor mastocytosis (> or =28 mast cells/mm(2)) and 50% with IFF. The detrusor mast cell count (P < 0.001), IFF (P = 0.004) and nocturnal frequency (P = 0.043) had statistically significant prognostic value for treatment intensity, whereas bladder capacity and glomerulations were not significant. CONCLUSION: Nocturia, detrusor mastocytosis and IFF are associated with multiple treatments and presumed failure of standard urological therapy in patients with BPS/IC, while bladder capacity and glomerulations are not. Valid conclusions cannot be drawn because of numerous limitations to the study.

Bladder Pain Syndrome Committee of the International Consultation on Incontinence.

AIMS OF STUDY: The Bladder Pain Syndrome Committee of the International Consultation on Incontinence was assigned the task by the consultation of reviewing the syndrome, formerly known as interstitial cystitis, in a comprehensive fashion. This included the topics of definition, nomenclature, taxonomy, epidemiology, etiology, pathology, diagnosis, symptom scales, outcome assessment, principles of management, specific therapies, and future directions in research. STUDY DESIGN, MATERIALS, METHODS: The emphasis was on new information developed since the last consultation 4 years previously. Where possible, existing evidence was assessed and a level of recommendation was developed according to the Oxford system of classification. RESULTS: The consultation decided to refer to the condition as "bladder pain syndrome" (BPS) because the designation is more descriptive of the clinical condition and better fits standard classification taxonomy. Reasonable definitions of BPS include the definition of the ESSIC European group and a slight modification made at a SUFU sponsored Miami meeting in early 2008. Males or females with pain, pressure, or discomfort that they perceive to be related to the bladder with at least one urinary symptom, such as frequency not obviously related to high fluid intake, or a persistent urge to void should be evaluated for possible BPS. The initial assessment consists of a frequency/volume chart, focused physical examination, urinalysis, and urine culture. Urine cytology and cystoscopy are recommended if clinically indicated. Treatment progresses from conservative management through various oral and intravesical therapies, with most surgical therapies reserved for unresponsive cases. Pain management is critical throughout the treatment process. The consultation believes that the disorder is best viewed as one of a group of chronic pain syndromes, rather than as primarily an inflammatory bladder disorder. Recommendations for future research pathways are suggested.

Hunner lesion disease differs in diagnosis, treatment and outcome from bladder pain syndrome: an ESSIC working group report.

Objectives: There is confusion about the terms of bladder pain syndrome (BPS) and Interstitial Cystitis (IC). The European Society for the Study of IC (ESSIC) classified these according to objective findings [9]. One phenotype, Hunner lesion disease (HLD or ESSIC 3C) differs markedly from other presentations. Therefore, the question was raised as to whether this is a separate condition or BPS subtype.Methods: An evaluation was made to explore if HLD differs from other BPS presentations regarding symptomatology, physical examination findings, laboratory tests, endoscopy, histopathology, natural history, epidemiology, prognosis and treatment outcomes.Results: Cystoscopy is the method of choice to identify Hunner lesions, histopathology the method to confirm it. You cannot distinguish between main forms of BPS by means of symptoms, physical examination or laboratory tests. Epidemiologic data are incomplete. HLD seems relatively uncommon, although more frequent in older patients than non-HLD. No indication has been presented of BPS and HLD as a continuum of conditions, one developing into the other.Conclusions: A paradigm shift in the understanding of BPS/IC is urgent. A highly topical issue is to separate HLD and BPS: treatment results and prognoses differ substantially. Since historically, IC was tantamount to Hunner lesions and interstitial inflammation in the bladder wall, still, a valid definition, the term IC should preferably be reserved for HLD patients. BPS is a symptom syndrome without specific objective findings and should be used for other patients fulfilling the ESSIC definitions.

Quantifying mast cells in bladder pain syndrome by immunohistochemical analysis.

OBJECTIVES: To evaluate a simple method for counting mast cells, thought to have a role in the pathophysiology of bladder pain syndrome (BPS, formerly interstitial cystitis, a syndrome of pelvic pain perceived to be related to the urinary bladder and accompanied by other urinary symptoms, e.g. frequency and nocturia), as >28 mast cells/mm(2) is defined as mastocytosis and correlated with clinical outcome. PATIENTS AND METHODS: The current enzymatic staining method (naphtolesterase) on 10 microm sections for quantifying mast cells is complicated. In the present study, 61 patients had detrusor biopsies taken between 2002 and 2005; the patients were given a clinical score, and sections of the biopsy stained with (i) naphtolesterase on 10 microm sections, staining every third section, or (ii) immunohistochemically with antitryptase on both 10 microm and 3 microm sections, with two and six unstained sections between, respectively. Mast cells were counted according to a well-defined procedure. RESULTS: The old and the new methods, on 10 and 3 microm sections, showed a good correlation between mast cell counts. When using tryptase staining and 3 microm sections, the mast cell number correlated well with the clinical score (Spearman's rho 0.576; 95% confidence interval 0.155-0.820) and 27 mast cells/mm(2) was the threshold suggesting mastocytosis. CONCLUSIONS: We recommend taking biopsies from the detrusor of patients with suspected BPS and examining them with tryptase-stained 3 microm thick sections, with every seventh section used for quantification; 27 mast cells/mm(2) is considered indicative of mastocytosis.

What is new in bladder pain syndrome/interstitial cystitis?

PURPOSE OF REVIEW: Bladder pain syndrome/interstitial cystitis is an important and poorly understood disorder. This review highlights current research findings that may be of benefit to the clinician who is responsible for the diagnosis and treatment of patients who suffer from this condition. RECENT FINDINGS: The perspective from which we view bladder pain syndrome/interstitial cystitis is evolving, as is apparent in the literature this year. It is best perceived as one of many chronic pain syndromes, some of which may be related. International efforts aimed at consistent definition and nomenclature are ongoing. Some new treatments have been reported that may be of benefit. SUMMARY: In the age of the internet, it is incumbent upon the clinician to keep up with current ideas, epidemiology, and treatment findings to be able to discuss these with well informed patients who come to clinics around the world. In this review we hope to bring practicing healthcare providers up to date with the literature on bladder pain syndrome/interstitial cystitis, and the implications for their patients.