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Advances in recombinant Bacillus Calmette-Guérin therapy for bladder cancer from 2015 to 2024: Innovations and challenges. 2015 - 2024年重组卡介苗-谷氨酰胺治疗膀胱癌进展:创新与挑战。
Pub Date : 2025-05-20 eCollection Date: 2025-01-01 DOI: 10.14440/bladder.2024.0072
Hanzhao Zhu, Jiani Li, Xintong Zhou, Kaixia Mi

Background: Non-muscle invasive bladder cancer is commonly treated by Bacillus Calmette-Guérin (BCG) therapy, but its efficacy is limited. Research into recombinant BCG (rBCG) aims to enhance its effectiveness and minimize side effects through genetic modifications.

Objective: This review explored advancements in rBCG therapy (2015 - 2024), focusing on genetic modifications designed to enhance cytokine production, introduce bacterial effectors, and boost immune responses. It also discusses future research on alternatives such as Mycobacterium smegmatis for safety concerns and integrating rBCG with other therapies to improve patient outcomes.

Conclusion: While rBCG therapies offer promising potential, overcoming translational challenges entails interdisciplinary endeavor to address the issues of safety, cost, and accessibility, and ultimately maximize their benefits for bladder cancer patients.

背景:非肌肉浸润性膀胱癌常用卡介苗治疗,但其疗效有限。重组卡介苗(rBCG)的研究目的是通过基因修饰来提高其有效性并减少其副作用。目的:本文综述了rBCG治疗的进展(2015 - 2024),重点介绍了旨在增强细胞因子产生、引入细菌效应物和增强免疫反应的基因修饰。它还讨论了未来的替代研究,如出于安全性考虑的耻垢分枝杆菌,以及将rBCG与其他疗法结合以改善患者预后。结论:虽然rBCG治疗具有良好的潜力,但克服转化挑战需要跨学科的努力,解决安全性,成本和可及性问题,并最终最大化其对膀胱癌患者的益处。
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引用次数: 0
Potential synergistic effect of radiotherapy and immune checkpoint inhibitors on advanced bladder cancer: A case report. 放疗和免疫检查点抑制剂对晚期膀胱癌的潜在协同作用:1例报告。
Pub Date : 2025-05-20 eCollection Date: 2025-01-01 DOI: 10.14440/bladder.2024.0075
Adeel Jafri, Rachel Hubbard, Syed A Hussain

Background: The combination of immune checkpoint inhibitors and radiotherapy (RT) is emerging as a promising therapeutic approach for advanced bladder cancer. However, clinical evidence of the abscopal effect in this context is still limited.

Case presentation: Presented here is a 61-year-old female with high-grade urothelial carcinoma who had initially undergone chemotherapy, followed by treatment with atezolizumab (an anti-programmed death-ligand 1 antibody). Due to disease progression and symptoms, she received palliative RT alongside continued immunotherapy. Post-RT staging scans showed a significant reduction in the size of the bladder mass and a marked improvement in the patient's quality of life. Although this case did not demonstrate a definite abscopal effect, it underscores the potential benefits of combining immunotherapy and RT.

Conclusion: The observed outcomes suggest that this combination can effectively manage advanced bladder cancer, highlighting the need for further research to refine and optimize these treatment strategies.

背景:免疫检查点抑制剂联合放射治疗(RT)正在成为晚期膀胱癌的一种有前景的治疗方法。然而,在这种情况下,体外作用的临床证据仍然有限。病例介绍:这里报告的是一位61岁的高级别尿路上皮癌女性患者,她最初接受了化疗,随后接受了atezolizumab(一种抗程序性死亡配体1抗体)治疗。由于疾病进展和症状,她在继续免疫治疗的同时接受了姑息性放疗。rt后分期扫描显示膀胱肿块的大小明显减小,患者的生活质量明显改善。虽然该病例未显示出明确的体外效应,但它强调了免疫治疗与rt联合治疗的潜在益处。结论:观察到的结果表明,这种联合治疗可以有效地治疗晚期膀胱癌,需要进一步研究来完善和优化这些治疗策略。
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引用次数: 0
Omental wrap for salvaging bladder repair: A novel approach. 网膜包裹术抢救膀胱修复:一种新方法。
Pub Date : 2025-05-06 eCollection Date: 2025-01-01 DOI: 10.14440/bladder.2024.0058
Tariq F Al-Shaiji, Said M Yaiesh

Background: The bladder represents one of the genitourinary organs most vulnerable to iatrogenic injuries. Ideal repair can be challenging and may require augmentation to fully preserve bladder structure and function. The omentum has been employed as a flap or graft to close bladder defects.

Objective: This study presented a novel approach involving a complete omental wrap for repairing a small-capacity, irreparably damaged bladder following cystotomy in a complex transvesical vesicouterine fistula repair.

Methods: Salvage repair was performed on a severely damaged bladder that had resulted from a chronic vesicouterine fistula, using an omental wrap for augmentation. The omental wrap fully enclosed the bladder to enhance its recovery. The patient had an uneventful post-operative recovery, and follow-up cystography showed a small-capacity bladder with no leakage. Extended follow-up demonstrated resolution of the patient's symptoms and an improvement in bladder capacity.

Results: This was the first documented application of the omentum as a complete wrap to support an irreparable bladder. The omentum's mechanical and anti-inflammatory properties provided significant support, leading to a rapid and complete healing of a bladder that initially appeared to have an unfavorable outcome due to extensive inflammation.

Conclusion: The use of omental wrap for bladder repair leverages the omentum's unique properties to support and augment challenging repairs, resulting in outstanding outcomes and expedited restoration in what would be considered a poor outcome procedure.

背景:膀胱是泌尿生殖器官中最容易受到医源性损伤的器官之一。理想的修复是具有挑战性的,可能需要增加以充分保留膀胱的结构和功能。网膜已被用作皮瓣或移植物来关闭膀胱缺损。目的:本研究提出了一种新的方法,在复杂的经膀胱膀胱外瘘修补术中,采用全网膜包裹修复膀胱切除术后的小容量、不可修复的损伤膀胱。方法:对慢性膀胱外瘘致严重膀胱损伤患者,采用大网膜包裹术进行修复。网膜包裹完全包裹膀胱以促进其恢复。患者术后恢复顺利,随访膀胱造影显示膀胱容量小,无渗漏。长期随访显示患者症状缓解,膀胱容量改善。结果:这是第一次有文献记载的应用大网膜作为一个完整的包裹来支持一个不可修复的膀胱。大网膜的机械和抗炎特性提供了重要的支持,导致膀胱的快速和完全愈合,最初由于广泛的炎症而出现不利的结果。结论:大网膜包裹用于膀胱修复利用了大网膜的独特特性来支持和增加具有挑战性的修复,在被认为结果较差的手术中获得了出色的结果和快速的恢复。
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引用次数: 0
Buccal versus lingual mucosal grafts for anterior urethral stricture management: A prospective surgical outcome and morbidity comparison. 颊与舌粘膜移植治疗前尿道狭窄:前瞻性手术结果和发病率比较。
Pub Date : 2025-05-05 eCollection Date: 2025-01-01 DOI: 10.14440/bladder.2024.0063
Ahmed Moustafa Nafie, Mahmoud Moustafa Nafie, Ahmed Aosmali, Basma Mohamed Soliman

Background: Urethral stricture is characterized by long-term scarring and narrowing of the urethral canal caused by acute trauma, inflammation, or medical procedures, such as urethral instrumentation or surgery. Despite the widespread use of both buccal and lingual mucosal grafts (LMG) in urethroplasty, few prospective studies have directly compared their surgical outcomes and donor site morbidity. This study aims to fill that gap.

Objective: This study compares the use of buccal and LMG in managing anterior urethral stricture with surgical outcomes and donor site morbidity evaluations.

Methods: This case-control comparative study was conducted at Ain Shams University Hospital. Patients who attended the urology outpatient clinic, presenting with lower urinary tract symptoms secondary to stricture anterior urethra and underwent surgical management by urethroplasty with a dorsal onlay technique, were selected as cases.

Results: No statistically significant differences were observed between the studied groups regarding age, smoking status, comorbidities, related urinary conditions, or the presence of a urinary catheter. In addition, the groups had no significant differences concerning stricture characteristics, graft details, or operation specifics. Similarly, general and urethral outcomes showed no statistically significant variation between the groups. Problems with drinking, soft food consumption, solid food consumption, dysgeusia, and speaking were significantly less frequent in the buccal mucosal graft (BMG) group than in the LMG group. In contrast, oral tightness was significantly more frequent in the BMG group than in the LMG group.

Conclusion: The study concluded that buccal and LMG effectively repair anterior urethral stricture, showing similar success rates. However, LMG patients experience earlier oral complications, while BMG patients face more long-term oral tightness, making graft choice dependent on patient-specific tolerances.

背景:尿道狭窄以急性创伤、炎症或医疗程序(如尿道内固定或手术)引起的尿道管长期瘢痕和狭窄为特征。尽管在尿道成形术中广泛使用颊和舌粘膜移植物(LMG),但很少有前瞻性研究直接比较它们的手术效果和供区发病率。这项研究旨在填补这一空白。目的:本研究比较使用颊部和LMG治疗前尿道狭窄的手术结果和供区发病率评估。方法:在艾因沙姆斯大学医院进行病例对照研究。患者就诊于泌尿外科门诊,表现为前尿道狭窄继发的下尿路症状,并接受手术治疗,采用背侧尿道成形术。结果:在年龄、吸烟状况、合并症、相关泌尿系统疾病或是否有导尿管方面,实验组之间没有统计学上的显著差异。此外,两组在狭窄特征、移植物细节或手术细节方面没有显著差异。同样,一般和尿道结果在两组之间没有统计学上的显著差异。与LMG组相比,BMG组在饮酒、软食、固体食物、语言障碍和说话方面的问题明显较少。相比之下,BMG组口腔紧绷明显多于LMG组。结论:颊部吻合术和LMG吻合术均能有效修复前尿道狭窄,成功率相近。然而,LMG患者经历较早的口腔并发症,而BMG患者面临更长期的口腔紧绷,使得移植物的选择取决于患者的特异性耐受性。
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引用次数: 0
SPEF1 and SPEF2 as potential biomarkers in bladder cancer: Insights from a comprehensive bioinformatic analysis. SPEF1和SPEF2作为膀胱癌的潜在生物标志物:来自综合生物信息学分析的见解。
Pub Date : 2025-04-11 eCollection Date: 2025-01-01 DOI: 10.14440/bladder.2024.0071
Mohamed A A A Hegazi, Fabio Pasqualini, Maurizio Chiriva-Internati, Gianluigi Taverna, Fabio Grizzi

Background: Bladder cancer (BLCA) remains a prevalent and complex malignancy characterized by significant heterogeneity. Treatment strategies are diverse, based on patient characteristics and cancer stage. Early identification of biomarkers is crucial for improving diagnosis, staging, and treatment planning. These biomarkers offer valuable insights into lesion features, tumor differentiation, and disease progression, thereby playing a pivotal role in the personalized management of BLCA.

Objective: This study investigated the expression of cancer-testis antigens SPEF1 and SPEF2 in BLCA using comprehensive bioinformatic analyses to assess their potential as biomarkers.

Methods: The UALCAN database, based on The Cancer Genome Atlas datasets, was employed to compare SPEF1 and SPEF2 expression levels in normal bladder tissues and BLCA samples. In addition, the Kaplan-Meier Plotter, OncoDB, and TIMER 2.0 platforms were utilized to evaluate the prognostic and immunotherapeutic relevance of these antigens.

Results: The findings suggest that SPEF1 and SPEF2 are integral to various biological processes driving BLCA onset and progression. Both genes appear to facilitate BLCA cell progression and migration, contributing to poor prognosis through specific pathways and by altering tumor microenvironment. Notably, SPEF1 expression was significantly upregulated in BLCA tissues compared to normal tissues. Conversely, higher SPEF2 expression was associated with longer overall survival and positively correlated with immunotherapeutic targets.

Conclusion: Although these results were derived from in silico analyses, they offer insights into the potential roles of SPEF1 and SPEF2 as biomarkers. Further studies are warranted to validate these biomarkers in retrospective patient cohorts to establish their clinical utility.

背景:膀胱癌(BLCA)是一种普遍而复杂的恶性肿瘤,具有显著的异质性。根据患者特点和癌症分期,治疗策略多种多样。早期识别生物标志物对于改善诊断、分期和治疗计划至关重要。这些生物标志物对病变特征、肿瘤分化和疾病进展提供了有价值的见解,因此在BLCA的个性化治疗中发挥了关键作用。目的:利用综合生物信息学分析方法研究前列腺癌抗原SPEF1和SPEF2在BLCA中的表达,以评估其作为生物标志物的潜力。方法:采用基于The Cancer Genome Atlas数据集的UALCAN数据库,比较正常膀胱组织和BLCA样本中SPEF1和SPEF2的表达水平。此外,利用Kaplan-Meier Plotter、OncoDB和TIMER 2.0平台评估这些抗原的预后和免疫治疗相关性。结果:研究结果表明,SPEF1和SPEF2在驱动BLCA发病和进展的各种生物学过程中是不可或缺的。这两个基因似乎都促进了BLCA细胞的进展和迁移,通过特定途径和改变肿瘤微环境导致预后不良。值得注意的是,与正常组织相比,SPEF1在BLCA组织中的表达明显上调。相反,较高的SPEF2表达与较长的总生存期相关,并与免疫治疗靶点呈正相关。结论:尽管这些结果来源于计算机分析,但它们为SPEF1和SPEF2作为生物标志物的潜在作用提供了见解。进一步的研究需要在回顾性患者队列中验证这些生物标志物,以确定其临床应用。
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引用次数: 0
Tolerability and efficacy of induction Bacillus Calmette-Guérin for non-muscle invasive bladder cancer. 卡介苗-谷氨酰胺诱导治疗非肌性浸润性膀胱癌的耐受性和疗效。
Pub Date : 2025-04-11 eCollection Date: 2025-01-01 DOI: 10.14440/bladder.2024.0051
Mann Patel, Aravind Rajagopalan, Ellen M Cahill, Kevin J Chua, Rachel Passarelli, John Pfail, Sai Krishnaraya Doppalapudi, David Golombos, Thomas Jang, Vignesh T Packiam, Saum Ghodoussipour

Background: Intravesical Bacillus Calmette-Guérin (BCG) is the standard treatment for intermediate-risk, high-grade, and high-risk non-muscle invasive bladder cancer (NMIBC). However, it is associated with adverse effects, potentially causing treatment interruptions or discontinuation.

Objectives: This study analyzed the tolerability and efficacy of induction BCG, with associated patient- and disease-related factors.

Methods: A retrospective analysis was conducted on BCG-naive patients diagnosed with high-grade NMIBC, who received induction BCG at our institution between 2011 and 2021. Tolerability was defined as the completion of a 6-week induction course of BCG without treatment interruption or discontinuation. Multivariable logistic regression was performed to determine risk factors associated with the inability to tolerate treatment.

Results: Induction BCG was given to 203 NMIBC patients, where 147 (72%) patients tolerated the treatment. Treatment interruptions occurred in 44 (22%) patients, while 12 (5.9%) patients discontinued the treatment. The median length of interruption was 1 week, primarily due to concerns about urinary tract infection (UTI) (n = 18, 41%) or gross hematuria (n = 5, 11%). No significant difference in 1-year recurrence rates was observed between those who tolerated BCG and those who did not (50% vs. 48%). Risk factors associated with the inability to tolerate induction BCG included male sex (odds ratio [OR] = 5.76, p < 0.01), hypertension (OR = 3.47, p = 0.02), and low pre-treatment hemoglobin levels (OR = 0.73, p = 0.03).

Conclusion: Inability to tolerate BCG occurred in 28% of patients, with 5.9% experiencing discontinuation. Interruptions were short, mostly concerning UTI, and rarely leading to discontinuation. Poor tolerability was associated with male sex, hypertension, and low pre-treatment hemoglobin levels, highlighting critical targets for reducing the risk of BCG interruption or discontinuation.

背景:膀胱内卡介苗(BCG)是治疗中危、高级别、高风险非肌肉浸润性膀胱癌(NMIBC)的标准治疗方法。然而,它与不良反应有关,可能导致治疗中断或停止。目的:本研究分析诱导卡介苗的耐受性和疗效,以及相关的患者和疾病相关因素。方法:回顾性分析2011年至2021年在我院接受诱导BCG治疗的高级别NMIBC患者。耐受性定义为完成了6周的卡介苗诱导疗程,没有中断或停止治疗。采用多变量logistic回归来确定与不能耐受治疗相关的危险因素。结果:203例NMIBC患者接受诱导BCG治疗,其中147例(72%)耐受。44例(22%)患者出现治疗中断,12例(5.9%)患者停止治疗。中断的中位长度为1周,主要是由于担心尿路感染(n = 18, 41%)或总血尿(n = 5, 11%)。耐受卡介苗组和不耐受卡介苗组的1年复发率无显著差异(50% vs 48%)。与诱导卡介苗不能耐受相关的危险因素包括男性(优势比[OR] = 5.76, p < 0.01)、高血压(OR = 3.47, p = 0.02)和治疗前低血红蛋白水平(OR = 0.73, p = 0.03)。结论:28%的患者无法耐受卡介苗,5.9%的患者停药。中断时间很短,主要与尿路感染有关,很少导致中断。耐受性差与男性、高血压和治疗前血红蛋白水平低有关,这突出了降低卡介苗中断或停药风险的关键目标。
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引用次数: 0
Artificial intelligence for diagnosing bladder pathophysiology: An updated review and future prospects. 人工智能诊断膀胱病理生理:最新综述及未来展望。
Pub Date : 2025-04-10 eCollection Date: 2025-01-01 DOI: 10.14440/bladder.2024.0054
Chitaranjan Mahapatra

Background: Bladder pathophysiology encompasses a wide array of disorders, including bladder cancer, interstitial cystitis, overactive and underactive bladder, and bladder outlet obstruction. It also involves conditions such as neurogenic bladder, bladder infections, trauma, and congenital anomalies. Each of these conditions presents unique challenges for diagnosis and treatment. Recent advancements in artificial intelligence (AI) have shown significant potential in revolutionizing diagnostic methodologies within this domain.

Objective: This review provides an updated and comprehensive examination of the integration of AI into the diagnosis of bladder pathophysiology. It highlights key AI techniques, including machine learning and deep learning, and their applications in identifying and classifying bladder conditions. The review also assesses current AI-driven diagnostic tools, their accuracy, and clinical utility. Furthermore, it explores the challenges and limitations confronted in the implementation of AI technologies, such as data quality, interpretability, and integration into clinical workflows, among others. Finally, the paper discusses future directions and advancements, proposing pathways for enhancing AI applications in bladder pathophysiology diagnosis. This review aims to provide a valuable resource for clinicians, researchers, and technologists, fostering an in-depth understanding of AI's roles and potential in transforming bladder disease diagnosis.

Conclusion: While AI demonstrates considerable promise in enhancing the diagnosis of bladder pathophysiology, ongoing progresses in data quality, algorithm interpretability, and clinical integration are essential for maximizing its potential. The future of AI in bladder disease diagnosis holds great promise, with continued innovation and collaboration opening the possibility of more accurate, efficient, and personalized care for patients.

背景:膀胱病理生理学包括一系列广泛的疾病,包括膀胱癌、间质性膀胱炎、膀胱过度活跃和不活跃以及膀胱出口梗阻。它还涉及神经源性膀胱、膀胱感染、创伤和先天性异常等疾病。每一种情况都对诊断和治疗提出了独特的挑战。人工智能(AI)的最新进展显示出在该领域内革命性诊断方法的巨大潜力。目的:本文综述了人工智能在膀胱病理生理诊断中的最新和全面的研究。它强调了关键的人工智能技术,包括机器学习和深度学习,以及它们在识别和分类膀胱状况方面的应用。该综述还评估了当前人工智能驱动的诊断工具,其准确性和临床实用性。此外,它还探讨了人工智能技术实施中面临的挑战和限制,例如数据质量、可解释性和与临床工作流程的集成等。最后,对人工智能在膀胱病理生理诊断中的应用前景进行了展望。本综述旨在为临床医生、研究人员和技术人员提供宝贵的资源,促进对人工智能在改变膀胱疾病诊断中的作用和潜力的深入了解。结论:虽然人工智能在增强膀胱病理生理诊断方面表现出相当大的前景,但数据质量、算法可解释性和临床整合方面的持续进步对于最大限度地发挥其潜力至关重要。人工智能在膀胱疾病诊断中的未来前景广阔,随着不断的创新和合作,为患者提供更准确、更高效、更个性化的护理成为可能。
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引用次数: 0
Quality review of typical value ranges in urodynamic measurements using statistical process control: A single-center retrospective study. 采用统计过程控制的尿动力学测量典型值范围的质量评价:一项单中心回顾性研究。
Pub Date : 2025-03-27 eCollection Date: 2025-01-01 DOI: 10.14440/bladder.2024.0073
Xiao Zeng, Hong Shen, Tao Jin, Deyi Luo

Background: Urodynamic study (UDS) is essential for assessing lower urinary tract function, but quality control methods remain limited. Statistical process control (SPC), a tool originally developed in manufacturing, has shown promise in healthcare for improving quality and reducing variability.

Objective: This study explored the application of SPC to analyze the typical value ranges (TVR) of urodynamic measurements.

Methods: A total of 84 urodynamic traces that met all inclusion criteria were included for analysis. We recorded the TVR for initial intravesical pressure (Pves), initial abdominal pressure (Pabd), and initial detrusor pressure (Pdet) from each enrolled UDS trace. These data were then compared with the standard TVR. In addition, we used the X-bar and S control charts of SPC for process performance analysis.

Results: The study included 20 females and 64 males, with an average age of 58.02 ± 16.09 years. Of the participants, 32 were diagnosed with neurogenic bladder dysfunction, and 52 were diagnosed with non-neurogenic bladder dysfunction. The average TVR for initial Pves was 34.81 ± 10.78 cmH2O, Pabd 30.92 ± 11.14 cmH2O, and Pdet 4.20 ± 3.73 cmH2O. We further analyzed the data using scatter plots. In the X-bar control chart, the control limit (CL) was 22.48, the upper CL (UCL) was 32.04, and the lower CL (LCL) was 12.92. In the S control chart, the CL was 15.78, the UCL was 22.57, and the LCL was 8.9. Two cases exceeded the UCL in the X-bar control chart, and one case exceeded the UCL in the S control chart.

Conclusion: The clinical value of SPC in the quality review of UDS has been confirmed in previous studies. In this study, we preliminarily verified the use of SPC for continuous variable data, such as the TVR of UDS parameters. The results of this study need to be further validated in a larger sample size, multi-center, and prospective study.

背景:尿动力学研究(UDS)对评估下尿路功能至关重要,但质量控制方法仍然有限。统计过程控制(SPC)是一种最初在制造业中开发的工具,在医疗保健领域显示出提高质量和减少可变性的前景。目的:探讨SPC在尿动力学测量典型值范围(TVR)分析中的应用。方法:共84例符合所有纳入标准的尿动力学痕迹进行分析。我们记录了TVR的初始膀胱压力(Pves),初始腹部压力(Pabd)和初始逼尿肌压力(Pdet)从每个登记的UDS追踪。然后将这些数据与标准TVR进行比较。此外,我们还使用了SPC的X-bar和S控制图进行过程性能分析。结果:女性20例,男性64例,平均年龄58.02±16.09岁。在参与者中,32人被诊断为神经源性膀胱功能障碍,52人被诊断为非神经源性膀胱功能障碍。初始Pves的平均TVR为34.81±10.78 cmH2O, Pabd为30.92±11.14 cmH2O, Pdet为4.20±3.73 cmH2O。我们使用散点图进一步分析数据。在x柱状控制图中,控制极限(CL)为22.48,上限(UCL)为32.04,下限(LCL)为12.92。在S控制图中,CL为15.78,UCL为22.57,LCL为8.9。2例在x柱控制图中超过UCL, 1例在S柱控制图中超过UCL。结论:SPC在UDS质量评价中的临床价值已得到前期研究的证实。在本研究中,我们初步验证了SPC对连续变量数据的使用,例如UDS参数的TVR。本研究结果需要在更大样本量、多中心、前瞻性研究中进一步验证。
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引用次数: 0
Pentosan polysulfate alleviates interstitial cystitis/bladder pain syndrome by modulating bile acid metabolism and activating the TGR5 receptor through gut microbiota regulation. 聚硫酸戊聚糖通过调节肠道菌群调节胆酸代谢,激活TGR5受体,减轻间质性膀胱炎/膀胱痛综合征。
Pub Date : 2025-03-24 eCollection Date: 2025-01-01 DOI: 10.14440/bladder.2024.0060
Zhangrui Zhu, Yuexuan Zhu, Qi Sun, Jingwen Xue, Ming Xie, Yao Yu, Benlin Wang, Wentai Shangguan, Zhengyuan Feng, Peng Wu

Background: The disrupted gut microbiome has been found to be implicated in the development of interstitial cystitis/bladder pain syndrome (IC/BPS). Pentosan polysulfate (PPS) is an oral medication used for treating IC/BPS, acting as both an anti-inflammatory agent and a bladder barrier protector. However, the precise mechanisms by which the PPS-mediated modulation of the gut microbiome alleviates IC/BPS are not fully understood.

Objective: This study aimed to identify the key gut microbiota species and metabolites involved in PPS's protective effects against IC/BPS.

Methods: We employed a multifaceted approach, including 16S rDNA gene sequencing, antibiotic treatment, and fecal microbiota transplantation, to validate the dependency of PPS's protective effects on the gut microbiome. Furthermore, we performed a comprehensive metabolomic profiling using non-targeted metabolomics and liquid chromatography-tandem mass spectrometry.

Results: PPS significantly elevated the abundance of the xylan-degrading bacteria, Eubacterium xylanophilum group, which, through its interaction with the gut microbiome, markedly reduced inflammation and barrier damage induced by cyclophosphamide in IC/BPS. In addition, PPS significantly increased the level of ursodeoxycholic acid (UDCA), a secondary bile acid, demonstrating a strong correlation with the abundance of the E. xylanophilum group. Ex vivo supplementation with UDCA mitigated lipopolysaccharide-induced inflammation and barrier disruption in SV-HUC-1 cells by activating the TGR5 receptor.

Conclusion: PPS exerts its protective effects against IC/BPS by modulating the gut microbiome and its metabolites.

背景:已发现肠道微生物群紊乱与间质性膀胱炎/膀胱疼痛综合征(IC/BPS)的发展有关。聚硫酸戊聚糖(PPS)是一种用于治疗IC/BPS的口服药物,可作为抗炎剂和膀胱屏障保护剂。然而,pps介导的肠道微生物组调节减轻IC/BPS的确切机制尚不完全清楚。目的:本研究旨在确定PPS对IC/BPS保护作用的关键肠道菌群和代谢物。方法:我们采用多方面的方法,包括16S rDNA基因测序、抗生素治疗和粪便微生物群移植,来验证PPS对肠道微生物群的保护作用的依赖性。此外,我们使用非靶向代谢组学和液相色谱-串联质谱法进行了全面的代谢组学分析。结果:PPS显著提高了木聚糖降解菌群(Eubacterium xylanophilum group)的丰度,该菌群通过与肠道微生物群的相互作用,显著减轻了IC/BPS中环磷酰胺引起的炎症和屏障损伤。此外,PPS显著提高了熊去氧胆酸(UDCA)的水平,UDCA是一种次级胆汁酸,与嗜木杆菌群的丰度有很强的相关性。体外补充UDCA通过激活TGR5受体,减轻了脂多糖诱导的SV-HUC-1细胞的炎症和屏障破坏。结论:PPS通过调节肠道菌群及其代谢产物对IC/BPS有保护作用。
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引用次数: 0
Hyaluronic acid as a treatment for refractory Bacillus Calmette-Guérin-induced cystitis: A narrative review. 透明质酸治疗难治性卡介苗-谷氨酰胺诱导的膀胱炎:综述。
Pub Date : 2025-03-24 eCollection Date: 2025-01-01 DOI: 10.14440/bladder.2024.0066
Ayoub Gomati, Mai Teggaz, Mazen Allam, Wasim Mahmalji

Background: Hyaluronic acid (HA) instillation has emerged as a potential alternative treatment for Bacillus Calmette-Guérin (BCG)-induced cystitis, a common complication of BCG intravesical therapy for non-muscle-invasive bladder cancer (NMIBC). BCG-induced cystitis presents with symptoms similar to bacterial infections, such as urinary urgency, frequency, and pain. Conventional treatments, such as BCG discontinuation, antibiotic therapy, and corticosteroid use, are often insufficient. HA therapy works by restoring the bladder's glycosaminoglycan layer, reducing inflammation, and promoting tissue repair.

Objectives: This narrative review assessed the efficacy and safety of HA in managing BCG-induced cystitis based on a literature search of PubMed, Google Scholar, and Cochrane databases, identifying seven relevant studies.

Conclusion: HA treatment has been associated with improvements in bladder symptoms, including reductions in pain, urgency, and frequency, as well as an increase in bladder capacity. Combination treatments with chondroitin sulfate or pirarubicin demonstrated superior outcomes compared to HA alone. While the studies reported minimal adverse effects, variability in study design, sample sizes, and follow-up durations limited the strength of the evidence. These findings suggest that HA can be safely administered to NMIBC patients alongside BCG therapy with minimal side effects and no adverse impact on treatment outcomes.

背景:透明质酸(HA)灌注已成为卡介苗诱导的膀胱炎的潜在替代治疗方法,这是卡介苗膀胱内治疗非肌肉浸润性膀胱癌(NMIBC)的常见并发症。bcg引起的膀胱炎表现出与细菌感染相似的症状,如尿急、尿频和疼痛。常规治疗,如停用卡介苗、抗生素治疗和使用皮质类固醇,往往是不够的。透明质酸疗法的作用是恢复膀胱的糖胺聚糖层,减少炎症,促进组织修复。目的:本文通过对PubMed、谷歌Scholar和Cochrane数据库的文献检索,确定了7项相关研究,评估了HA治疗bcg性膀胱炎的疗效和安全性。结论:透明质酸治疗与膀胱症状的改善有关,包括疼痛、尿急和尿频的减轻,以及膀胱容量的增加。与单独使用HA相比,联合使用硫酸软骨素或吡柔比星显示出更好的结果。虽然这些研究报告了最小的不良反应,但研究设计、样本量和随访时间的可变性限制了证据的强度。这些研究结果表明,HA可安全用于NMIBC患者与卡介苗治疗,副作用最小,对治疗结果无不良影响。
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Bladder (San Francisco, Calif.)
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