APRIL/BAFF upregulation is associated with clonal B-cell expansion in Hunner-type interstitial cystitis.

Hunner-type interstitial cystitis (HIC) is a chronic inflammatory disease of the urinary bladder with an unknown etiology. We conducted comprehensive immunogenomic profiling of bladder specimens obtained by biopsy and cystectomy from 37 patients with HIC. Next-generation RNA sequencing demonstrated abundant plasma cell infiltration with frequent light chain restriction in HIC-affected bladder tissue. Subsequent analysis of the B-cell receptor repertoire revealed spatial and temporal expansion of B-cell clones. The extent of B-cell clonal expansion was significantly correlated with the gene expression levels of TNFSF13 and TNFSF13B, which encode APRIL and BAFF, respectively. These findings indicate that APRIL and BAFF are the key regulators of clonal B-cell expansion in HIC and might serve as therapeutic targets in this debilitating disease. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Efficacy of a pharmacist care protocol to manage uncomplicated female cystitis in community pharmacies: an open-label, multicenter, randomized, controlled, cluster study: the PharmaCyst' protocol.

BACKGROUND: Urinary tract infections are common affections, especially for women. Difficult access to a general practitioner to obtain a prescription has led France to offer dispensing under protocol by community pharmacists. The primary objective of this study is to evaluate the effectiveness of a pharmacist care protocol provided to manage women with urinary tract infection symptoms. This objective will be assessed using the Acute Cystitis Symptom Score. METHODS: PharmaCyst' is an open-label, multicenter, controlled, cluster-randomized study conducted in the Loire region, France. Women aged between 18 and 65 years presenting to a pharmacy complaining of at least one symptom of an uncomplicated urinary tract infection present over the last 3 days (including burning pain during micturition, dysuria, pollakiuria, urgent urination) will be considered for inclusion. All patients will be contacted on day 3, 10, and month 3. A total of 480 patients need to be recruited for the 24 clusters participating in the research. The quantitative data will be described using means and standard deviations and compared using Student's t-test. The qualitative data will be described using numbers and percentages and compared using chi2 test (or Fisher's exact test if necessary). The primary and secondary outcomes analyses will consider the intention-to-treat population. DISCUSSION: PharmaCyst' is the first clinical trial conducted in France only by community pharmacists. Its results could lead to an extension of the protocol. TRIAL REGISTRATION: The protocol has been approved by the French ethics committee on 2022/12/02 and is registered under the number 49RC22_0240 on ClinicalTrials.gov.

Management of ketamine cystitis: National Guidelines from the French Association of Urology (CUROPF/CTMH).

OBJECTIVE: The objective of the CUROPF and CTMH was to establish recommendations about ketamine induced uropathy management. METHODS: A systematic review of the literature was conducted on Pubmed/Medline by the members of the French committees of female urology and male lower urinary tract symptoms focusing on the epidemiology, pathophysiology, diagnosis and treatment of ketamine induced uropathy, evaluating references and level of evidence. RESULTS: Recommendations include epidemiology, pathophysiology, diagnosis and treatment of ketamine induced uropathy. It represents a rising healthcare issue, with major augmentation of ketamine consumers and new patients across the world. Several pathophysiology pathways are suspected and need clinical validation. The diagnosis is clinical, with hyperactive bladder symptoms mostly including pollakiuria, but also lower urinary tract symptoms, and histological, requiring bladder biopsies to rule out carcinoma and show specific features and inflammation. Therapeutics are currently limited and non-specific, combining abstinence, hydrodistension, pentosane polysulfate and Botox injections. Complex reconstructive surgeries should be avoided and be considered as a last resort. CONCLUSION: These guidelines should provide tools to help every physician confronted to ketamine induced uropathy patients, which represents a growing issue. Hopefully, this work will allow the improvement of the screening, management and care of ketamine induced uropathy in the future.

Necrotizing Fasciitis Mimicking Interstitial Cystitis: An Atypical Clinical Presentation.

Necrotizing fasciitis is a severe, life-threatening disease with a nonspecific clinical presentation, making it a challenging diagnosis. Early treatment with broad-spectrum antibiotics and surgical debridement is crucial to prevent rapid disease progression and poor outcomes. Given its high mortality rate and ambiguous presentation, maintaining a high index of suspicion for necrotizing fasciitis is essential. In this case, a 60-year-old woman presented to her gynecologist with urinary tract infection symptoms of frequency, hematuria, and suprapubic pain, with a year-long history of night sweats, hematuria, dysuria, and incomplete voiding. Although initially treated with outpatient antibiotics, she returned to the emergency department one day later with severe lower abdominal pain, overlying erythema, and a high fever. Abdominal imaging revealed extensive cellulitis. Upon the development of rapidly expanding erythema and crepitus, there was concern for necrotizing fasciitis. The patient received immediate treatment with broad-spectrum antibiotics and underwent urgent surgical debridement. While she showed clinical improvement in the following days, laboratory studies revealed profound hypercalcemia, anemia, and persistent leukocytosis. Additional testing ultimately led to the diagnosis of advanced bladder cancer. This case underscores the importance of prompt recognition and treatment of necrotizing fasciitis. It also highlights the influence of confirmation and availability biases, which can lead to overlooking symptoms that may indicate more serious underlying conditions. As medical professionals, it is crucial to remain vigilant and not disregard seemingly insignificant symptoms, as they could be indicative of life-threatening diagnoses.

Ketamine-induced cystitis: A case report and literature review.

Ketamine, a dissociative anesthetic drug, has gained popularity as a recreational substance, particularly among young adults. However, chronic ketamine abuse can lead to various complications including ketamine-induced cystitis. We present the case of a 46-year-old Caucasian male with a history of HIV infection and daily recreational ketamine use for 7 months, who was admitted to the emergency room with hypogastric pain and hematuria. Laboratory examinations and contrast-enhanced abdominal CT tomography revealed significant irregular circumferential thickening of both ureters, substantial bilateral pyeloureteral ectasia, and a bladder with markedly thickened walls. Bilateral flexible ureteropyeloscopy, bladder transurethral resection, and bladder fulguration were performed, and pathology confirmed the diagnosis of ketamine-induced cystitis. Treatment consisted of ketamine withdrawal, pain relief, and support from psychiatrists and urologists. The patient's symptoms improved and he was discharged without complications. This case highlights the importance of recognizing the potential adverse effects of recreational ketamine use and the need for a multidisciplinary approach to managing ketamine-induced cystitis. Further research is necessary to elucidate the precise mechanisms underlying this condition and develop effective prevention and treatment strategies.

Evaluation of outcomes of clinical phenotyping-based treatment for bladder pain syndrome/interstitial cystitis.

Introduction: Bladder pain syndrome/Interstitial cystitis (BPS/IC) is clinically of diverse types because different causes contribute to the development of their symptoms. It is important to classify patients into various groups based on the possible etiopathogenesis of their condition. Treatment may be tailored to each specific group according to the possible cause. Methodology: Twenty-five patients diagnosed with BPS/IC were categorized into four different clinical phenotypes (CP) based on their history of symptoms, allergy, dysfunctional voiding, neuropathic pain, and the presence of Hunner's ulcer. Some patients could be classified into multiple groups. The patients were given oral pentosan polysulfate, and treatment specific to their CP. Patients in CP1, CP2, and CP3 groups received, respectively hydroxyzine, clonazepam, and amitriptyline. Patients with Hunner's lesions (HL) (CP4) underwent hydro distension and ablation of the lesion, followed by intravesical instillation of heparin and hydrocortisone. The patients were evaluated using the Apollo clinical scoring (ACS) system and their clinical scores were recorded at 1, 3, and 6 month(s). Results: Among the 25 patients, 5, 7, 4, and 9 patients were classified into CP 1 - CP4 groups respectively, and were all subjected to ACS assessment. In CP1 group (allergy group), 80% (4/5) of patients responded well to the treatment and 20% (1/5) had unsatisfactory responses. In CP2 group (dysfunctional voiding group), 71.42% (5/7) patients had good, and 28.57% (2/7) had excellent responses. In CP3 group (neuropathic pain group), 28.57% (3/4) patients had excellent, and 75% (1/4) patients had good responses. In CP4 group (HL group), 33.33% (3/9) patients had unsatisfactory, 44.44% (4/9) achieved good, and 22.22% (2/9) had excellent responses. Overall, 16% (4/25) patients had unsatisfactory, 56% (14/25) attained good, and 28% (7/25) had an excellent response at the completion of the study. Conclusion: Using clinical phenotyping-based features indicative of etiology could potentially improve treatment outcomes by targeting the specific pathological processes contributing to the patients' symptoms.

A cynomolgus monkey E. coli urinary tract infection model confirms efficacy of new FimH vaccine candidates.

The increase in urinary tract infections (UTI) caused by antibiotic-resistant Escherichia coli requires the development of new therapeutic agents and prophylactic vaccines. To evaluate the efficacy of new lead candidates, we implemented a cynomolgus macaque UTI challenge model that mimics human uncomplicated cystitis in response to transurethral challenge with a multidrug-resistant (MDR) E. coli serotype O25b ST131 isolate. E. coli fimbrial adhesin FimH and O-antigens are separately under clinical evaluation by others as vaccine candidates to prevent UTI and invasive urosepsis disease, respectively. Accordingly, we assessed the protective efficacy of three 50-µg intramuscular doses of a novel recombinant FimH antigen adjuvanted with liposomal QS21/MPLA compared with saline placebo in groups of nine animals. A third group was vaccinated with this FimH formulation in combination with 1 µg each of a four-valent mixture of serotype O1a, O2, O6, and O25b O-antigen CRM197 lattice glycoconjugates. Both vaccines elicited high levels of serum FimH IgG and adhesin blocking antibodies at the time of bacterial challenge and, for the combination group, O-antigen-specific antibodies. Following bacterial challenge, both vaccinated groups showed >200- and >700-fold reduction in bacteriuria at day 2 and day 7 post-infection compared with placebo, respectively. In parallel, both vaccines significantly reduced levels of inflammatory biomarkers IL-8 and myeloperoxidase in the urine at day 2 post-infection relative to placebo. Results provide preclinical proof-of-concept for the prevention of an MDR UTI infection by these new vaccine formulations.

Establishment of an Antimicrobial Stewardship Program to Spare the Use of Oral Fluoroquinolones for Acute Uncomplicated Cystitis in Outpatients.

The increase in fluoroquinolone (FQ)-resistant Escherichia coli (EC) is a serious global problem. In addition, much of acute uncomplicated cystitis (AUC) cases are caused by EC. FQs have been selected for the treatment of cystitis in outpatients, and there is concern about treatment failure. It is therefore necessary to select appropriate antimicrobials to spare FQs. However, there are few reported effective antimicrobial stewardship programs (ASPs) for outpatients. We aimed to establish the effective ASP for outpatients diagnosed with AUC caused by EC, to spare the use of FQs, and to explore optimal oral antimicrobials for AUC. The study subjects were outpatients treated for AUC caused by extended-spectrum ß-lactamase-non-producing EC (non-ESBL-EC). Based on the antibiogram results, we recommended cefaclor (CCL) as the initial treatment for AUC, and educated clinical pharmacists who also worked together to advocate for CCL or cephalexin (CEX) prescriptions. FQ usages decreased, and cephalosporin (Ceph) prescriptions increased in all medical departments. The Ceph group (n = 114; CCL = 60, CEX = 54) in the non-FQ group had fewer treatment failures than the FQ group (n = 86) (12.3% vs. 31.4%). Cephs, including CCL and CEX, were effective treatments for AUC caused by non-ESBL-EC. Antimicrobial selection based on antibiogram results and the practice of an ASP in collaboration with clinical pharmacists were useful for optimizing antimicrobial therapy in outpatients.

Recurrent Cystitis in Women-A Real-World Analysis of Bacteria Spectrum and Resistance Situation for Calculated Therapy.

Recurrent cystitis in women represents an everyday challenge; however, little to no data regarding this population are available. This study aimed to evaluate this collective with respect to a rational calculated antibiotic therapy. Urine cultures and antibiograms from a urological office were retrospectively evaluated from patient data collected between January 2017 and June 2019. The evaluation was conducted using SPSS ©. In total, 84 female patients, who were aged between 18 and 87 years old (median 60 years), suffered from recurrent cystitis. Escherichia coli was found in 53.9% of cases, Staphylococcus aureus and enterococci were each found in 6.7%, and Proteus spp. and Streptococcus agalactiae were each found in 5.6%. The resistance levels to ciprofloxacin (CIP), trimethoprim-sulfamethoxazole (TRS), nitrofurantoin (NIT), and nitroxoline (NOX) were 18.2%, 30.7%, 16.1%, and 12.5% in the tested cases, respectively. Regarding E. coli, resistance to CIP, TRS, and NIT was found in 17.8%, 25%, and 4.2% of the tested cases, and no resistance to NOX was found. The resistance level to CIP was in a tolerable range of <20% in the overall cohort and the E. coli subgroup. More than a quarter of the bacteria were resistant to TRS. The low resistance rates for NIT and NOX are remarkable, promoting the use of these substances if they are not yet used.

Treatment of a urethral stricture by image-guided placement of a custom-made absorbable stent in a standing, sedated horse.

A 10-year-old Irish Sport Horse gelding developed complications from a general anesthesia resulting in sling support and recurrent urinary catheterization. The horse subsequently presented signs of dysuria and pollakiuria, was diagnosed with sabulous cystitis, and developed a urethral stricture from the repeated catheterizations, which was confirmed on urethroscopy. Clinical signs persisted despite conservative management with topical corticosteroids and urethral bougienage with balloon dilators. An image-guided approach was used to treat the stricture with a custom-made polydioxanone stent placed in the urethra after which the horse was able to void normally and fully empty his bladder. Repeat urethroscopy and ultrasonography 6 months after the procedure showed the stent to have completely reabsorbed with urethra remaining patent. Nineten months after the procedure, the owner reports the horse remaining at his intended level of athletic performance with no dysuria.

Evaluation of the efficacy of a live Escherichia coli biotherapeutic product (asymptomatic bacteriuria E. coli 212).

BACKGROUND: Recurrent bacterial cystitis, often referred to as recurrent urinary tract infection (UTI), can be difficult to manage and alternative treatments are needed. HYPOTHESIS/OBJECTIVE: Intravesicular administration of asymptomatic bacteriuria (ASB) E. coli 212 will not be inferior to antimicrobial treatment for the management of recurrent UTI in dogs. ANIMALS: Thirty-four dogs with >1 UTI in the 12 months before presentation. METHODS: All dogs were deemed normal otherwise based on absence of abnormalities on physical examination, CBC, serum biochemical panel, and abdominal ultrasonography. Dogs were randomized to 1 of 2 treatment groups: Group 1 antimicrobials for 7 days or group 2 intravesicular administration of ASB E. coli 212. Owners were provided a voiding questionnaire regarding their dogs' clinical signs, which was completed daily for 14 days to assess clinical cure. Dogs were examined on days 7 and 14 to assess clinical cure, and urine specimens were submitted for urinalysis and bacterial culture. RESULTS: Clinical cure rates for ASB E. coli 212-treated dogs were not inferior to 7 days of antimicrobial treatment with a 12% margin of difference to determine non-inferiority. No significant difference was found between the treatment groups on days 7 and 14 in the proportion of dogs achieving ≥50% or ≥75% reduction in their clinical score compared with baseline. CONCLUSIONS AND CLINICAL IMPORTANCE: These data suggest that intravesicular administration of ASB E. coli 212 is not inferior to antimicrobials for the treatment of recurrent UTI in dogs. This biotherapeutic agent could help alleviate the need for antimicrobials for some dogs with recurrent UTI, improving antimicrobial stewardship.

A Pain Desensitization Algorithm for Phenotyping and Treating Chronic Pelvic Pain.

Background: Chronic pelvic pain remains challenging for physicians to manage due to central and peripheral sensitization and multiple pain generators including the bladder, pelvic floor, and pudendal nerve. Pain management providers have used nerve blocks for years for diagnosis and treatment. We developed a desensitization algorithm that provides a stepwise approach to improve patients pain scores. Methods: This is a prospective observational cohort study of 182 women aged 15-90 years old with chronic pelvic pain using an algorithm from 2016 to 2018. Treatment started with an Anesthetic Challenge Test of the bladder to guide us through a protocol of intravesical therapy and/or pudendal nerve blocks as a second step. Results: ACT POSITIVE patients, who received intravesical therapy: 84% had a Visual Analog Score pain improvement of at least 50%, 64% improved at least 80% (41% pain-free). Those desiring additional relief that received further Pudendal Blocks: 83% had final improvement of at least 50% (67% pain-free). ACT NEGATIVE patients received Pudendal Blocks with 80% of subjects achieving at least 50% relief, 65% improved at least 80% (35% pain-free). All final groups showed a statistically significance of P < .05% when compared to their initial pain scores. Conclusion: Management of women with chronic pelvic pain would ideally start with treating a specific diagnosis which, in most cases, is difficult to establish since the majority have more than one pain generator. Our algorithm simplified the approach and reduced the severity of pain scores prior to any further necessary surgical interventions.

Mathematical Approach to Synergistic Management of Bladder Pain Syndrome/Interstitial Cystitis and Vulvodynia: A Case Series Utilizing Principal Component Analysis, Cluster Analysis, and Combination Laser Therapy.

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.

Antibiotic prescribing for acute uncomplicated cystitis among community pharmacists in Thailand.

OBJECTIVES: This study aimed to evaluate the knowledge of community pharmacists toward acute uncomplicated cystitis regarding diagnosis, referral, and conformity to guidelines of the chosen antibiotic and to identify the associated factors with the pharmacist's knowledge. METHODS: This was a descriptive cross-sectional survey using a questionnaire. Data was collected from 349 community pharmacies in upper southern Thailand between December 2021 and February 2022. Univariate logistic regression analysis was used to assess factors associated with an inappropriate diagnosis of acute uncomplicated cystitis. The variables with P-value < 0.2 were included in the multivariate model. The statistically significant level was set as P-value < 0.05. KEY FINDINGS: Three hundred and forty-nine pharmacists from 349 community pharmacies were included. Approximately 65% and 69% of the participants had the knowledge to identify which patients should be considered for cystitis and which patients should be considered for acute uncomplicated cystitis. Ninety eight percentage of pharmacists could select the appropriate antibiotic for uncomplicated cystitis patients. The most prescribed antibiotics were ciprofloxacin (44.7%), norfloxacin (40.7%), and ofloxacin (10.3%). Inappropriate diagnosis was significantly related to age (P = 0.016) and role in the community pharmacy (P = 0.033). CONCLUSION: The majority of participants had misconceptions about the differential diagnosis between complicated and uncomplicated cystitis. These were related to the community pharmacists' advanced age. Continuous pharmacy education should be established to advocate rational antibiotic use, especially in a country where community pharmacists are legally allowed to dispense antimicrobials without a prescription.

Adult zymosan re-exposure exacerbates the molecular alterations in the brainstem rostral ventromedial medulla of rats with early life zymosan-induced cystitis.

Recent evidence suggests that the descending modulatory pathways from the brainstem rostral ventromedial medulla (RVM) are important for bladder inflammatory pain. This study aimed to identify the long-term molecular changes in RVM neurons due to early life cystitis during neuronal development and the effect of reexposure later in adulthood. RVM tissues from two treatment protocols were used: (1) neonatal zymosan exposures with acute adult rechallenge (RC) and (2) only neonatal zymosan exposures (NRC). RNAseq analysis showed upregulation of several genes associated with synaptic plasticity (Grin1, Grip2, Notch1, Arc, and Scn2b) in the cystitis groups compared to controls in both protocols. The RC protocol exhibited a stronger treatment effect with significantly higher fold differences between the groups compared to the NRC protocol (p < 0.001, fold differences RC vs NRC). In microarrays, miR-34a-5p showed cystitis-induced downregulation in both protocols. Bioinformatics analysis identified multiple 3'UTRs complementary binding sites for miR-34a-5p on Grin2b, Notch1, Grip2, Scn2b, and Arc genes. The enhanced response in the RC protocol indicates a possible priming effect of early life cystitis on rechallenge in adulthood. These long-term molecular alterations may play a critical role in the development of chronic bladder pain conditions as seen in patients with Interstitial Cystitis/Bladder pain syndrome.

Case reports of immune-related cystitis and the antibody combination hypothesis.

Immune-related cystitis is a rare condition, and its diagnostic criteria and pathogenesis are not yet fully understood. Here, we report two cases of immune-related cystitis. Both patients were previously diagnosed with lung squamous cell carcinoma and received combined treatment with immune checkpoint inhibitors and chemotherapy, leading to hemorrhagic cystitis. We reviewed the cystoscopic images and pathological features of previous cases and found that autoantibodies against hemidesmosomes may be the cause of immune-related cystitis, proposing the "antibody combination" hypothesis to explain the tissue specificity of the condition.

Lung squamous cell carcinoma can produce certain proteins called autoantigens. Some patients treated with immune checkpoint inhibitors might develop antibodies against these autoantigens. A specific combination of these antibodies may cause the bladder lining to slough, leading to immune-related cystitis. Symptoms of this condition include frequent urination, urgent need to urinate, painful urination and blood in the urine. These patients typically require treatment with steroids.

Successful treatment of Candida albicans-induced fungal cystitis in a dog using caspofungin: a case report.

A 7-year-old castrated male poodle was brought to the referral Animal Medical Center and diagnosed with diabetes and pancreatitis. One month later, the patient presented with cloudy urine, and ultrasonography revealed a large number of spherical substances. The patient was subsequently diagnosed with fungal cystitis with Candida albicans. Initially, 10.00 mg kg-1 itraconazole was prescribed twice daily for six weeks, and the symptoms of prolonged urination improved; however, the fungal balls persisted in the bladder. The six months later, the patient showed recurrent symptoms, such as dysuria and stranguria; therefore, 5.00 mg kg-1 fluconazole was prescribed twice daily; however, it was not effective. Subsequently, 1.00 mg kg-1 caspofungin once daily was administered for three consecutive days. Finally, the fungal balls in the bladder disappeared. The patient was regularly monitored after completion of treatment and, 17 months later, doing well without recurrence. Few reports exist on the use of caspofungin in veterinary medicine. The recommended dose of caspofungin in dogs remains unknown. In the case of azole-resistant Candida, treatment using caspofungin should be considered; although, additional studies on the established dosing and side effects are needed.

Unusual coexistence: A case of mixed small and large cell neuroendocrine tumor in a bladder previously affected by bilharzial cystitis.

Neuroendocrine tumors of the bladder are rare, accounting for less than 1% of all bladder tumors. Among these, large cell neuroendocrine carcinoma is an extremely uncommon subtype. We report on a histologically confirmed case of mixed both large and small cells neuroendocrine tumor of the bladder in a 64-year-old male with a history of bilharzial cystitis. The diagnosis was made after radical cystectomy with Immunohistochemical staining revealing positivity for synaptophysin, CD56, and AE1/3. While bilharzia is commonly linked to squamous cell carcinoma in the bladder, the potential relationship with neuroendocrine tumors is still relatively unexplored in this context. This case marks the first reported instance of the atypical coexistence of bilharzial cystitis and mixed large and small cell neuroendocrine carcinoma of the bladder. This unique case of coexisting highlights a rare phenomenon warranting further study. Similar associations have been documented in other organs, emphasizing the importance of exploring underlying mechanisms and clinical implications for improved patient care and outcomes.

Association between non-neoplastic bladder diseases and bladder cancer risk: insights from Mendelian randomization studies.

PURPOSE: Our aim is to explore the relation between non-neoplastic bladder diseases and bladder cancer (BC) from a genetic level utilizing Mendelian randomization (MR). METHODS: Single nucleotide polymorphisms (SNPs) related to cystitis, bladder stones, and neuropathic bladder were gathered from the IEU genome-wide association studies database. Quality control on SNPs was performed via stringent screening criteria. The relation between non-neoplastic bladder diseases and BC risk was evaluated using inverse-variance weighted, MR-Egger, weighted median, simple mode, and weighted mode methods. Cochran's Q test was conducted to assess the heterogeneity of SNPs; in addition, the MR-Egger intercept test was employed to examine the horizontal pleiotropy of SNPs. Exposure and outcomes were validated using a validation database. Finally, BC was used as the exposure and non-neoplastic bladder diseases as the outcome to evaluate reverse causality. RESULTS: The outcomes showcased that genetically predicted cystitis is significantly correlated to a raised risk of BC (inverse-variance weighted: odds ratio [95%] = 1.1737 [1.0317, 1.3352], P = .0149), consistent with the BC validation cohort in the MR analysis. Nevertheless, no causal relation was found between bladder stone and neuropathic bladder with BC risk (P > .05). In this study, sensitivity analysis indicated no heterogeneity or horizontal pleiotropy. CONCLUSION: The study presents proof of a genetic-level causal relation between cystitis and increased BC risk, while bladder stones and neuropathic bladder do not show similar associations.

Definition Change and Update of Clinical Guidelines for Interstitial Cystitis and Bladder Pain Syndrome.

The clinical guidelines for interstitial cystitis (IC) and bladder pain syndrome (BPS) have been revised by updating our previous guidelines. The symptoms of IC and BPS, collectively called as hypersensitive bladder (HSB) symptoms, are virtually indistinguishable between IC and BPS; however, IC and BPS should be considered as a separate entity of disorders. We define IC as a bladder disease with Hunner lesions, usually associated with HSB symptoms and bladder inflammation, and BPS as a condition with HSB symptoms in the absence of Hunner lesions and any confusable diseases. Pathophysiology totally differs between IC and BPS. IC involves immunological inflammation probably resulting from autoimmunity, while BPS is associated with the interaction of multiple factors such as neurogenic inflammation, exogenous substances, urothelial defects, psychological stress, and neural hyperactivity. Histopathology also differs between IC and BPS. IC is associated with severe inflammation of the whole bladder accompanied by plasma cell infiltration and urothelial denudation, while BPS shows little pathological changes. Management should begin with a differential diagnosis of IC or BPS, which would require cystoscopy to determine the presence or absence of Hunner lesions. The patients should be treated differently based on the diagnosis following the algorithm, although pain management would be common to IC and BPS. Clinical studies are also to be designed and analyzed separately for IC and BPS.