This case series presents three patients with bladder pain syndrome/interstitial cystitis (BPS/IC) and vulvodynia, demonstrating the efficacy of an individualized treatment approach using cluster analysis and combination laser therapy. Principal component analysis (PCA) was used to visualize the dynamic nature of symptom clusters and guide treatment decisions. Case 1 was a 41-year-old woman initially classified as Cluster 1 (PCA coordinates: 1.65, 0.03) transitioned to Cluster 2 (-16.93, -21.75) after bladder hydrodistension. Subsequent Fotona laser (Ljubljana, Slovenia) treatment resulted in the complete resolution of symptoms. Case 2 was a 55-year-old woman, contraindicated for hormone therapy due to breast cancer history, presented as Cluster 2 (PCA coordinates: -24.16, 8.74). Fotona laser treatment shifted her to Cluster 1 (11.22, -20.22), followed by bladder hydrodistension for complete cure. Case 3 was a 49-year-old woman, initially in Cluster 0 (PCA coordinates: 1.892, 30.11), who underwent fulguration for Hunner\'s lesions. Posttreatment, she moved to Cluster 2 (-24.31, 1.767) and achieved full recovery after Fotona laser therapy. The dynamic nature of symptom clusters, visualized through PCA, guided treatment decisions. The PCA transformation, represented as y =WTz, where z is the standardized symptom vector and W is the principal component matrix, allows for the objective tracking of symptom changes. Combination Fotona laser therapy, including vaginal erbium YAG and neodymium YAG, has proven effective in managing vulvar pain, particularly when hormone therapy is contraindicated. This approach, addressing both urological and gynecological aspects, resulted in sustained symptom improvement for over 12 months in all cases. This case series highlights the synergistic relationship between BPS/IC and vulvodynia, demonstrating the efficacy of comprehensive, adaptive treatment strategies guided by mathematical analysis for complex pelvic pain syndromes.

A húgyhólyagfájdalom-szindróma (latin nevén cystitis interstitialis) kivizsgálásának és kezelésének számos elismert és tudományosan alátámasztott, ugyanakkor sok alternatív, kevesebb evidenciával rendelkező megoldása és módozata ismert. Munkánkban összegyűjtöttük a kórállapotra vonatkozó hazai és nemzetközi irányvonalakat és útmutatásokat, hogy tisztázzuk, melyek azok a nagy evidenciájú módszerek, amelyek a legnagyobb biztonsággal és bizonyossággal segítenek a helyes diagnózis megállapításában, és vezetnek a krónikus hólyagfájdalomtól szenvedő személyek panaszainak enyhítéséhez. Orv Hetil. 2024; 165(31): 1191–1196.

OBJECTIVE: To analyze the results of excluding confusable diseases in patients with a presumptive diagnosis of interstitial cystitis (IC).
METHODS: We retrospectively reviewed the electronic medical records of consecutive patients with IC between October 2005 and December 2019.
RESULTS: Patients with pelvic pain underwent an initial workup. Of these, 646 patients (164 men, 25.4%; 482 women, 74.6%) underwent observational cystoscopy under the suspicion of IC. Fourteen patients had genitourinary tract malignancies (2.2%) (bladder cancer, n = 13; prostate cancer, n = 1). Of the 13 patients with bladder cancer, three were diagnosed during initial observation cystoscopy. The remaining 10 patients were diagnosed during subsequent follow-up cystoscopic surgery. Urinary tuberculosis was identified in seven (1.1%) of 646 patients during the examination. Five (0.8%) of the six patients with suspected urinary tuberculosis at baseline imaging were positive for tuberculosis in the acid-fast bacillus test. One patient developed tuberculous granulomas in the bladder tissue after a cystectomy for intractable pelvic pain.
CONCLUSIONS: Our results show that continuous efforts to rule out bladder tumors or tuberculosis are still essential in the follow up of patients with suspected IC, even if these diseases are not excluded at the initial examination. Imaging studies are necessary to rule out tuberculosis.

Interstitial cystitis/bladder pain Syndrome (IC/BPS) remains a mysterious and intricate urological disorder, presenting significant challenges to healthcare providers. Traditional guidelines for IC/BPS follow a hierarchical model based on symptom severity, advocating for conservative interventions as the initial step, followed by oral pharmacotherapy, intravesical treatments, and, in refractory cases, invasive surgical procedures. This approach embraces a multi-tiered strategy. However, the evolving understanding that IC/BPS represents a paroxysmal chronic pain syndrome, often involving extravesical manifestations and different subtypes, calls for a departure from this uniform approach. This review provides insights into recent advancements in experimental strategies in animal models and human studies. The identified therapeutic approaches fall into four categories: (i) anti-inflammation and anti-angiogenesis using monoclonal antibodies or immune modulation, (ii) regenerative medicine, including stem cell therapy, platelet-rich plasma, and low-intensity extracorporeal shock wave therapy, (iii) drug delivery systems leveraging nanotechnology, and (iv) drug delivery systems assisted by energy devices. Future investigations will require a broader range of animal models, studies on human bladder tissues, and well-designed clinical trials to establish the efficacy and safety of these therapeutic interventions.

Evidence from previous studies have demonstrated that gut microbiota are closely associated with occurrence of interstitial cystitis/bladder pain syndrome (IC/BPS), yet the causal link between the two is not well known. In this study, we performed a two-sample Mendelian randomization (MR) analysis to determine the possible causal association between gut microbiota with IC/BPS. Gut microbiota summary level data were derived from the genome-wide association study (GWAS) conducted by MiBioGen and the IC/BPS GWAS summary level data were obtained from the GWAS Catalog. Next, we performed an MR study to investigate the causal link between gut microbiota and IC/BPS. The primary method for causal analysis was the inverse variance weighted (IVW), and the MR results were validated through multiple sensitivity analyses. A positive association was found between IC/BPS and eight gut microbial taxa, including genus Bacteroides, genus Haemophilus, genus Veillonella, genus Coprococcus1, genus Butyricimonas, family Bacteroidaceae, family Christensenellaceae, and order Lactobacillales. Sensitivity analysis revealed lack of significant pleiotropy or heterogeneity in the obtained results. This MR analysis reveals that a causal association exists between some gut microbiota with IC/BPS. This finding may is expected to guide future research and development of IC/BPS preventions and treatments based on the bladder-gut axis. However, given the clinical complexity and diagnostic challenges of IC/BPS, along with the limitations of using large-scale GWAS summary data for analysis, our MR results require further validation through additional research.

OBJECTIVE: To systematically review the classification systems for male chronic pelvic pain (CPP).
METHODS: The Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica dataBASE (EMBASE), and Web of Science were searched. Any publication, with no restriction to publication date, was eligible. Publications had to propose a classification system for CPP in males or provide additional information of a system that had been identified. Systems were assessed with an adapted Critical Appraisal of Classification Systems tool.
RESULTS: A total of 33 relevant publications were identified, with 22 proposing an original classification system. Systems aimed to: (i) diagnose CPP and/or differentially diagnose CPP from other conditions, (ii) differentially diagnose subtypes within CPP, or (iii) identify features that could inform underlying mechanisms and/or treatment selection. Conditions referred to as chronic prostatitis/chronic pelvic pain syndrome and interstitial cystitis/bladder pain syndrome were most represented. Clinical signs/symptoms, pathoanatomical investigations, and presumed pain mechanisms were used for classification. Quality of systems was low to moderate, implying limitations to consider for their interpretation.
CONCLUSIONS: Many classification systems for CPP in males exist. Careful consideration of their intended purpose is required. Future work should examine whether outcomes for patients are improved when decisions are guided by their use.

UNASSIGNED: The correlation between gut microbiota and interstitial cystitis has garnered significant attention in previous studies. Nevertheless, the causal relationship between them remains to be clarified.
UNASSIGNED: Genetic variation serves as a tool in Mendelian randomization analyses, facilitating the inference of causal relationships between exposure factors and disease outcomes. In this study, summary statistics derived from a comprehensive genome-wide association study conducted by the MiBioGen consortium were utilized as exposure factors, while interstitial cystitis data sourced from the GWAS Catalog served as the disease outcome. Then, a two-sample Mendelian randomization analysis was performed by applying inverse variance-weighted, MR-Egger, Weighted Median, Simple Mode, and Weighted Mode. In addition, heterogeneity and horizontal pleiotropy were excluded by sensitivity analysis.
UNASSIGNED: IVW results confirmed that genus Haemophilus (OR = 2.20, 95% CI: 1.16-4.15, p = 0.015), genus Butyricimonas (OR = 2.26, 95% CI: 1.15-4.45, p = 0.018), genus Bacteroides (OR = 4.27, 95% CI: 1.36-13.4, p = 0.013) and Coprococcus1 (OR = 3.39, 95% CI: 1.28-8.99, p = 0.014) had a risk effect on interstitial cystitis. Sensitivity analysis did not find outlier SNPs.
UNASSIGNED: Our analysis has identified a causal relationship between specific genera and interstitial cystitis. However, further validation through randomized controlled trials is essential to substantiate these findings.

Oxidative stress resulting from reactive oxygen species (ROS) is often considered to be the leading cause of interstitial cystitis (IC), which is a chronic inflammatory disease. Antioxidants have been proven to have promising therapeutic effects on IC. In this study, we present an antioxidant intervention for IC by introducing curcumin-loaded cerium oxide nanoparticles (Cur-CONPs). Recognizing oxidative stress as the primary contributor to IC, our research builds on previous work utilizing cerium oxide nanoparticles (CONPs) for their outstanding antioxidant and anti-inflammatory properties. However, given the need to effectively relieve acute inflammation, we engineered Cur-CONPs to harness the short-term radical-scavenging antioxidant prowess of curcumin. Through in vitro studies, we demonstrate that the Cur-CONPs exhibit not only robust antioxidant capabilities but also superior anti-inflammatory properties over CONPs alone. Furthermore, in vivo studies validate the therapeutic effects of Cur-CONPs on IC. Mice with IC subjected to the Cur-CONP treatment exhibited improved micturition behaviors, relief from pelvic pain sensitivity, and reduced expression of inflammatory proteins (IL-6, IL-1β, TNF-α, Cox2). These findings suggest that the synergistic antioxidant properties of the Cur-CONPs that combine the sustained antioxidant properties of CONPs and acute anti-inflammatory capabilities of curcumin hold promise as a novel treatment strategy for IC.

Background Bladder pain syndrome/interstitial cystitis (BPS/IC) is a chronic condition characterized by pelvic pain and urinary symptoms. Despite its significant impact on patients\' quality of life, the heterogeneity of BPS/IC symptoms and the presence of comorbidities such as vulvodynia may not be adequately captured by validated questionnaires. Identifying vulvodynia in BPS/IC patients is crucial for providing appropriate treatment options. This study aimed to identify subtypes of BPS/IC patients using unsupervised machine learning and to investigate the prevalence of vulvodynia in each subtype. Methods We conducted a prospective cross-sectional study of 123 BPS/IC patients and 64 age-matched controls. Hierarchical clustering was performed using data from validated questionnaires, including the Numerical Rating Scale-11, Interstitial Cystitis Symptom Index (ICSI), Interstitial Cystitis Problem Index (ICPI), Pelvic Pain and Urgency/Frequency scores, Overactive Bladder Questionnaire Short Form (OABq SF), Overactive Bladder Symptom Score (OABSS), and Pelvic Floor Distress Inventory-20. The optimal number of clusters was determined using the elbow method, and the characteristics of each cluster were analyzed. All participants underwent a vulvodynia swab test to assess vulvodynia symptoms. Results Unsupervised machine learning revealed three distinct clusters of BPS/IC patients. Clusters 0 and 2 differed significantly, with Cluster 2 characterized by significantly higher vulvodynia scores compared to other clusters (P < 0.001). In contrast, Cluster 2 had lower bladder pain scores (ICSI and ICPI) and overactive bladder symptom scores (OABq SF and OABSS) compared to other clusters. Clusters 0 and 1 were characterized by a predominance of bladder pain and urinary frequency symptoms, with Cluster 0 exhibiting more severe symptoms. Conclusions Our study identified distinct subtypes of BPS/IC patients using unsupervised machine learning, with Cluster 2 representing a vulvodynia-predominant subtype. This finding, along with the potential of targeted therapies such as non-ablative erbium YAG laser for vulvodynia, underscores the importance of assessing extravesical symptoms, particularly vulvodynia, for the diagnosis and treatment of BPS/IC. A tailored approach, including laser therapy for vulvodynia-predominant patients, may be necessary for optimal management of BPS/IC. The vulvodynia swab test plays a crucial role in assessing vulvodynia symptoms, underlining the limitations of validated questionnaires in capturing the full spectrum of BPS/IC symptoms. A comprehensive evaluation of patients, including the vulvodynia swab test, is essential for accurate subtyping and management of BPS/IC. Further research with larger sample sizes and investigation of the relationship between identified subtypes and other clinical data is warranted to advance our understanding and management of BPS/IC.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a complex chronic pain disorder with an elusive etiology and nonspecific symptoms. Although numerous animal models with phenotypes similar to human disease have been established, no available regimen can consistently alleviate clinical symptoms. This dilemma led us to question whether current animal models adequately represent IC/BPS. We compared four commonly used IC/BPS rat models to determine their diverse histopathological and molecular patterns. Female rats were given single treatments with hydrochloric acid (HCL), acetic acid (AA), protamine sulfate plus lipopolysaccharide (PS + LPS), or cyclophosphamide (CYP) to induce IC/BPS. Bladder sections were stained for histopathologic evaluation, and mRNA expression profiles were examined using next-generation sequencing and gene set analyses. Mast cell counts were significantly higher in the HCL and AA groups than in the PS + LPS, CYP, and control groups, but only the AA group showed significant collagen accumulation. The models differed substantially in terms of their gene ontology and Kyoto encyclopedia of genes and genomes pathways. Our observations suggest that none of these rat models fully reflects the complexity of IC/BPS. We recommend that future studies apply and compare multiple models simultaneously to fully replicate the complicated features of IC/BPS.