Comparative effectiveness and safety of intravesical instillation treatment of interstitial cystitis/bladder pain syndrome: a systematic review and network meta-analysis of randomized controlled trials.
International urogynecology journal
INTRODUCTION AND HYPOTHESIS:A large variety of agents are available for intravesical instillation treatment of interstitial cystitis/bladder pain syndrome (IC/BPS). The purpose of the study was to compare the efficacy and safety of those agents. METHODS:PubMed, the Cochrane Library, and Embase were searched from database inception to February 2020 for randomized controlled trials. The language of publication was limited in English. Population, intervention, comparison, outcome, and study design was used to assess the eligible studies for inclusion and the Cochrane Collaboration's risk of bias tool was used to assess the methodological quality of the studies included. The primary outcome was O'Leary-Sant Interstitial Cystitis Problem Index (ICPI) and O'Leary-Sant Interstitial Cystitis Symptom Index (ICSI) improvement. RESULTS:Eleven randomized controlled trials covering 8 agents with 902 patients were enrolled. According to the results of the ICPI and ICSI, 0.1 μM resiniferatoxin was more effective than other therapies. Combination therapy of hyaluronic acid and chondroitin sulphate ranked second in ICSI, third in ICPI, and first in the visual analog scale (VAS). Among regimens included for complication comparison, chondroitin sulphate was safer than other agents, with a probability of 78.5%. CONCLUSIONS:Resiniferatoxin (0.1 μM) is more effective at ICPI and ICSI improvement than other agents. More well-designed randomized controlled trials with a large sample size directly comparing the efficacy and safety of those agents are in need in the future to confirm our findings.
10.1007/s00192-020-04490-3
Biomaterial-assisted drug delivery for interstitial cystitis/bladder pain syndrome treatment.
Lin Zhijun,Hu Hanze,Liu Bolong,Chen Yanyan,Tao Yu,Zhou Xiangfu,Li Mingqiang
Journal of materials chemistry. B
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic and painful bladder condition afflicting patients with increased urinary urgency and frequency as well as incontinence. Owing to the elusive pathogenesis of IC/BPS, obtaining effective therapeutic outcomes remains challenging. Current administrational routes such as intravesical-bladder injection improve the treatment efficacy and reduce systemic side effects. However, the bladder permeability barrier hinders drug penetration into the bladder wall to meet the desired therapeutic expectation. These issues can be addressed by encapsulating drugs into biomaterials. When appropriately exploited, they would increase the drug dwelling time in the bladder, enhance the penetration of mucosa and improve the therapeutic response of IC/BPS. In this review, we first elucidate the pathogenesis and animal models of IC/BPS. Then, we highlight recent representative biomaterial-assisted drug delivery systems for IC/BPS treatment. Finally, we discuss the challenges and outlook for further developing biomaterial-based delivery systems for IC/BPS management.
10.1039/d0tb02094j
Interstitial Cystitis/Bladder Pain Syndrome Treatment: A Systematic Review of Sexual Health Outcomes.
Chen Andrew,Shahiyan Robert H,Anger Jennifer T
Sexual medicine reviews
INTRODUCTION:Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic condition with highly prevalent negative consequences on sexual health and quality of life. However, there is a lack of consensus regarding treatment options that improve sexual function in this population. This study aims to review the current literature on sexual health outcomes in patients treated for IC/BPS. METHODS:We conducted a systematic review of the literature on sexual health outcomes after treatment of IC/BPS. PubMed, MEDLINE, EMBASE, CINHAL, and Google Scholar were queried, and results were screened using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Inclusion criteria for this review were: IC/BPS was clearly defined in the cohort, sexual health outcomes were measured as the primary or a secondary outcome, manuscript was written in English from January 2000 to April 2020. Studies on cystectomy were excluded as radical surgery is a confounding factor for sexual dysfunction. RESULTS:We identified 1611 items with our search algorithm and determined that 10 studies ultimately met inclusion criteria. 4 of 10 studies reported improved sexual function after treatment. 4 of 10 studies were randomized control trials and reported no improvement in sexual function in each of the therapies that were investigated. Data were conflicting regarding the effect of intravesical hyaluronic acid. CONCLUSION:This systematic review demonstrates the lack of focus on sexual health outcomes in studies of the IC/BPS. There was no strong evidence that any modality used to treat IC/BPS also improves sexual function despite the higher prevalence in this population. Chen A, Shahiyan RH, Anger J. Interstitial Cystitis/Bladder Pain Syndrome Treatment: A Systematic Review of Sexual Health Outcomes. Sex Med Rev 2022;10:71-76.
10.1016/j.sxmr.2020.12.005
Urine nerve growth factor (NGF) level, bladder nerve staining and symptom/problem scores in patients with interstitial cystitis.
Tonyali Senol,Ates Deniz,Akbiyik Filiz,Kankaya Duygu,Baydar Dilek,Ergen Ali
Advances in clinical and experimental medicine : official organ Wroclaw Medical University
BACKGROUND:Interstitial cystitis (IC)/bladder pain syndrome (BPS) is a challenging disease, affecting thousands of people all around the world, especially women. Although there have been numerous theories regarding IC/BPS etiology, the physiopathology of the disease still remains unclear and there is a lack of certain treatment. OBJECTIVES:The aim of the study was to assess the role of nerve fibers and nerve growth factor (NGF) in the etiopathogenesis of IC/BPS symptoms by demonstrating if there is a correlation between urine NGF levels, amount of peripheral nerves in bladder mucosa and symptom severity. MATERIAL AND METHODS:A prospective clinical study was conducted with 15 IC/BPS patients and 18 controls. Urine NGF levels were measured by enzyme-linked immunosorbent assay (ELISA). Bladder punch biopsies were obtained from 15 IC/BPS patients and 9 controls. Immunohistochemistry was performed for S-100 to highlight peripheral nerve twigs in bladder mucosa. The O'Leary-Sant Interstitial Cystitis Symptom and Problem Index (OSICSPI) was used to assess symptom severity and effects of the disease on the patients' life. RESULTS:NGF normalized to urine creatinine (NGF/Cr) levels in IC/BPS patients were significantly higher than in controls, 0.34 ±0.22 and 0.09 ±0.08 pg/mL: mg/dL, respectively (p < 0.001). The mean symptom score in IC patients was 12.27 ±2.4 (median: 12) and the mean problem score was 10.9 ±2.3 (median: 12). The mean mucosal nerve (S-100 stained) area in the IC/BPS group was significantly higher than in the controls, 2.53 ±1.90 vs 1.0 ±0.70, respectively (p = 0.018). In correlation analyses, the NGF/Cr level in IC/BPS patients was found significantly correlated with the O'Leary-Sant IC Symptom and Problem Index scores independently (p = 0.001 and p = 0.028, respectively). CONCLUSIONS:NGF seems to be a promising biomarker in IC/BPS. It may help clinicians in diagnoses and patient follow-up. Thus, unnecessary, expensive and invasive tests, interventions and treatments might be avoided.
10.17219/acem/69231
Nerve growth factor-dependent hyperexcitability of capsaicin-sensitive bladder afferent neurones in mice with spinal cord injury.
Shimizu Takahiro,Majima Tsuyoshi,Suzuki Takahisa,Shimizu Nobutaka,Wada Naoki,Kadekawa Katsumi,Takai Shun,Takaoka Eiichiro,Kwon Joonbeom,Kanai Anthony J,de Groat William C,Tyagi Pradeep,Saito Motoaki,Yoshimura Naoki
Experimental physiology
NEW FINDINGS:What is the central question of this study? Nerve growth factor (NGF) is reportedly a mediator inducing urinary bladder dysfunction. Is NGF directly involved in hyperexcitability of capsaicin-sensitive C-fibre bladder afferent pathways after spinal cord injury (SCI)? What is the main finding and its importance? Neutralization of NGF by anti-NGF antibody treatment reversed the SCI-induced increase in the number of action potentials and the reduction in spike thresholds and A-type K current density in mouse capsaicin-sensitive bladder afferent neurones. Thus, NGF plays an important and direct role in hyperexcitability of capsaicin-sensitive C-fibre bladder afferent neurones attributable to the reduction in A-type K channel activity in SCI. ABSTRACT:Nerve growth factor (NGF) has been implicated as an important mediator in the induction of C-fibre bladder afferent hyperexcitability, which contributes to the emergence of neurogenic lower urinary tract dysfunction after spinal cord injury (SCI). In this study, we determined whether NGF immunoneutralization using an anti-NGF antibody (NGF-Ab) normalizes the SCI-induced changes in electrophysiological properties of capsaicin-sensitive C-fibre bladder afferent neurones in female C57BL/6 mice. The spinal cord was transected at the Th8/Th9 level. Two weeks later, continuous administration of NGF-Ab (10 μg kg h , s.c. for 2 weeks) was started. Bladder afferent neurones were labelled with Fast-Blue (FB), a fluorescent retrograde tracer, injected into the bladder wall 3 weeks after SCI. Four weeks after SCI, freshly dissociated L6-S1 dorsal root ganglion neurones were prepared. Whole-cell patch-clamp recordings were then performed in FB-labelled neurones. After recording action potentials or voltage-gated K currents, the sensitivity of each neurone to capsaicin was evaluated. In capsaicin-sensitive FB-labelled neurones, SCI significantly reduced the spike threshold and increased the number of action potentials during membrane depolarization for 800 ms. These SCI-induced changes were reversed by NGF-Ab. Densities of slow-decaying A-type K (K ) and sustained delayed rectifier-type K currents were significantly reduced by SCI. The NGF-Ab treatment reversed the SCI-induced reduction in the K current density. These results indicate that NGF plays an important role in hyperexcitability of mouse capsaicin-sensitive C-fibre bladder afferent neurones attributable to a reduction in K channel activity. Thus, NGF-targeting therapies could be effective for treatment of afferent hyperexcitability and neurogenic lower urinary tract dysfunction after SCI.
10.1113/EP086951
[Experimental evaluation of interaction of the nerve growth factor and mast cells in patients with interstitial cystitis/bladder pain syndrome].
Sholan R F
Urologiia (Moscow, Russia : 1999)
AIM:to evaluate the level of nerve growth factor (NGF) in the blood and urine and mast cell infiltration of the bladder wall in a model of interstitial cystitis/bladder pain syndrome (IC/BPS) and to analyze their relationships. MATERIALS AND METHODS:IC/BPS modeling was performed on 38 female rabbits, which were divided into 4 groups. In the group 1, IC/BPS was simulated by an instillation of 70% alcohol into the bladder, while in group 2 and 3 animals own urine and normal saline were injected into the bladder wall. The group 4 consisted of intact animals. The NGF level was determined by ELISA. To determine the concentration of mast cell in tissues, each cross-section was divided into 10 sections. The severity of mast cell infiltration was evaluated in each area using the following scale: 0 - no mast cells; 1 - less than 20 cells; 2 - 20-45 cells; 3 - more than 45 cells. The points of all 10 areas were added up, divided by 30 (the maximum possible score) and multiplied by 100. RESULTS:An increase in the NGF level in the blood and urine was seen in different models of IC/BPS, but it was significantly more pronounced in the group 2 (toxic model). Mast cells were determined only in the group 1 (0.25+/-0.707) and 2 (14,200+/-5,796). In animals with the urinary toxicity model, mast cell activity was significantly higher in comparison with those in the model with an instillation of 70% alcohol (p<0.001). The level of NGF in blood and urine correlated in different directions. Mast cell proliferation and activation was determined in case of impairment of the bladder wall integrity by the injection of urine. CONCLUSION:Our animal model of IC/BPS, which was created by instillation of 70% alcohol into the bladder and the injection of urine into the bladder wall, showed an increase in the level of NGF in urine and blood and the concentration of mast cells. These findings, as well as relationship between these values indicate the development of neuroimmune inflammation in this pathological condition. Considering the involvement of many factors in the pathogenesis of this syndrome, further researches are required.
Comparative safety review of current pharmacological treatments for interstitial cystitis/ bladder pain syndrome.
Chen Po-Yen,Lee Wei-Chia,Chuang Yao-Chi
Expert opinion on drug safety
: Interstitial cystitis (IC)/bladder pain syndrome (BPS) is a frustrating disease of chronic bladder pain associated with lower urinary tract symptoms. Although there are many proposed treatment algorithms, the uncertainty as to their etiology has a negative impact on the therapeutic outcome. Oftentimes combination therapy of drugs with different mechanisms of action will be utilized to relieve the symptoms. With the various treatment options available to patients and providers, there is an ever-growing need to implement drug efficacy as well as safety to promote best practice in use of the approved drug.: This review will focus on guideline-based pharmacotherapies as described by the AUA and EAU, specifically oral, and intravesical therapies with the most up-to-date published literature. Pharmacotherapies targeting bladder, and/or systemic factors in the overall treatment of IC/BPS are discussed with a particular focus on efficacy and drug safety evaluation.: IC/BPS is a syndrome that requires bladder targeting agents to restore the urothelium barrier function and inhibit bladder hypersensitivity as well as various drugs with anti-inflammatory effects, and immune modulation effects. Current pharmacotherapies for IC/BPS have various therapeutic effects and adverse effects depending on the dose and individual response.
10.1080/14740338.2021.1921733
[Diagnosis and treatment of interstitial cystitis (IC/PBS) : S2k guideline of the German Society of Urology].
Bschleipfer T,Doggweiler R,Schultz-Lampel D,de Jong J,Gonsior A,Hensen J,Heßdörfer E,Kaftan B T,Kuhn A,Kunzendorf U,Lampel A,Landmesser A,Loch A,Moormann O,Müller B,Neuhaus J,Reich A,Roth R,Schumacher S,Stratmeyer R,Vahlensieck W,Wördehoff A,Münder-Hensen B
Der Urologe. Ausg. A
In this review article, the authors describe all relevant aspects of the new S2k guideline from the German Society of Urology (Deutschen Gesellschaft für Urologie, DGU) for the diagnosis and treatment of IC/PBS (interstitial cystitis/painful bladder syndrome). A list of necessary and optional examinations and the necessity of diagnosis of exclusion are summarized and evaluated. The treatment options listed (ranging from conservative, oral drug, and complementary medicine to interventional surgical procedures) also give the reader a good overview of the contents of the guideline and possible therapeutic approaches. Finally, the recommendations including consensus of the guideline group are also summarized in various information boxes.
10.1007/s00120-019-01054-2
An evaluation of the pharmacotherapy for interstitial cystitis.
Giusto Laura L,Zahner Patricia M,Shoskes Daniel A
Expert opinion on pharmacotherapy
INTRODUCTION:Interstitial cystitis (IC) and bladder pain syndrome (BPS) are chronic conditions that can be debilitating for patients. There is no consensus as to their etiology, and there are many proposed treatment algorithms. Oftentimes multimodal therapy, such as combining behavioral modification and physical therapy alongside pharmacotherapies, will be utilized. With the various treatment options available to patients and providers, there is an ever-growing need to implement evidence-based therapies. AREAS COVERED:The authors explore the different pharmacotherapies as commonly recommended in the American Urological Association (AUA) and European Association of Urology (EAU) multitiered guidelines for IC/BPS treatment as well as other investigational therapies. Pharmacotherapies targeting bladder, pelvic, and/or systemic factors in the overall treatment of IC/BPS are discussed with a particular focus on evidence-based guideline therapies. This article also looks at emerging therapies of interest. EXPERT OPINION:IC/BPS is a syndrome that requires a multimodal approach, including clinical phenotyping and directed therapy based on the patient's symptoms. The AUA and EAU provide guidelines for practitioners to follow, but adequate treatment requires the therapy to be targeted toward the patient's phenotypic domain.
10.1080/14656566.2018.1491968
Guideline of guidelines: bladder pain syndrome.
Malde Sachin,Palmisani Stefano,Al-Kaisy Adnan,Sahai Arun
BJU international
OBJECTIVES:Bladder pain syndrome (BPS) is a debilitating condition which can be difficult to diagnose and treat due to the lack of consensus on aetiology, definition, and management. The aim of this review is to summarise the findings from major national and international guidelines on the management of BPS, highlighting areas of disagreement and uncertainty. METHODS:We performed a Medline/PubMed search from 1st January 2000 to 31st December 2017 in order to identify relevant guidelines addressing BPS/interstitial cystitis. We also manually searched the websites of major national and international societies. The following guidelines were included in this review: European Association of Urology, American Urological Association, International Society for the Study of BPS, International Consultation on Incontinence, International Continence Society, East Asian guideline, Royal College of Obstetricians and Gynaecologists/British Society of Urogynaecology, and the Canadian Urological Association. RESULTS:There is disagreement between guidelines on the exact definition of BPS and the nomenclature to use to describe this condition. However, all agree that the diagnosis is dependent on the presence of pain, pressure, or discomfort, in addition to at least one urinary symptom, in the absence of other diseases that could cause pain. Exclusion of other pathology that could cause similar symptoms requires thorough evaluation, and is recommended in all guidelines. There is also disparity in the recommended diagnostic investigation of BPS, with hydrodistension and bladder biopsy either recommended, considered optional, or not recommended, by different guidelines. It is accepted that BPS can be diagnosed clinically, without invasive investigation, but cystoscopy and diagnostic hydrodistension aids sub-typing of patients and may help direct treatment strategies. Patients should be phenotyped in order to direct multimodal treatment (including behavioural, physical, emotional, and psychological therapy), and treatments should follow a stepwise approach starting with the most conservative. Although widely performed, hydrodistension as a therapeutic strategy has a limited evidence base and is unlikely to provide long-term resolution of symptoms CONCLUSION: There are multiple national and international guidelines for the diagnosis and management of BPS, and this review has highlighted the differences in nomenclature, definitions, and recommended diagnostic tests between guidelines. The overall evidence base for the majority of treatments for BPS/IC is of low-quality, and larger randomised trials are required to more accurately inform guideline recommendations and clinical management of this complex group of patients.
10.1111/bju.14399
Diagnosis and treatment of interstitial cystitis/bladder pain syndrome: AUA guideline amendment.
Hanno Philip M,Erickson Deborah,Moldwin Robert,Faraday Martha M,
The Journal of urology
PURPOSE:The purpose of this amendment is to provide an updated clinical framework for the diagnosis and treatment of interstitial cystitis/bladder pain syndrome based upon data received since the publication of original guideline in 2011. MATERIALS AND METHODS:A systematic literature review using the MEDLINE(®) database (search dates 1/1/83-7/22/09) was conducted to identify peer-reviewed publications relevant to the diagnosis and treatment of IC/BPS. This initial review yielded an evidence base of 86 treatment articles after application of inclusion/exclusion criteria. The AUA update literature review process, in which an additional systematic review is conducted periodically to maintain guideline currency with newly published relevant literature, was conducted in July 2013. This review identified an additional 31 articles, which were added to the evidence base of this Guideline. RESULTS:Newly incorporated literature describing the treatment of IC/BPS was integrated into the Guideline with additional treatment information provided as Clinical Principles and Expert Opinions when insufficient evidence existed. The diagnostic portion of the Guideline remains unchanged from the original publication and is still based on Expert Opinions and Clinical Principles. CONCLUSIONS:The management of IC/BPS continues to evolve as can be seen by an expanding literature on the topic. This document constitutes a clinical strategy and is not intended to be interpreted rigidly. The most effective approach for a particular patient is best determined by the individual clinician and patient. As the science relevant to IC/BPS evolves and improves, the strategies presented will require amendment to remain consistent with the highest standards of care.
10.1016/j.juro.2015.01.086
Clinical guidelines for interstitial cystitis and hypersensitive bladder updated in 2015.
Homma Yukio,Ueda Tomohiro,Tomoe Hikaru,Lin Alex Tl,Kuo Hann-Chorng,Lee Ming-Huei,Oh Seung-June,Kim Joon Chul,Lee Kyu-Sung
International journal of urology : official journal of the Japanese Urological Association
Clinical guidelines for interstitial cystitis and hypersensitive bladder have been updated as of 2015. The guidelines define interstitial cystitis by the presence of hypersensitive bladder symptoms (discomfort, pressure or pain in the bladder usually associated with urinary frequency and nocturia) and bladder pathology, after excluding other diseases explaining symptoms. Interstitial cystitis is further classified by bladder pathology; either Hunner type interstitial cystitis with Hunner lesions or non-Hunner type interstitial cystitis with mucosal bleeding after distension in the absence of Hunner lesions. Hypersensitive bladder refers to a condition, where hypersensitive bladder symptoms are present, but bladder pathology or other explainable diseases are unproven. Interstitial cystitis and hypersensitive bladder severely affect patients' quality of life as a result of disabling symptoms and/or comorbidities. Reported prevalence suggestive of these disorders varies greatly from 0.01% to >6%. Pathophysiology would be an interaction of multiple factors including urothelial dysfunction, inflammation, neural hyperactivity, exogenous substances and extrabladder disorders. Definite diagnosis of interstitial cystitis and hypersensitive bladder requires cystoscopy with or without hydrodistension. Most of the therapeutic options lack a high level of evidence, leaving a few as recommended therapeutic options.
10.1111/iju.13118