Bladder <p>The <em>Bladder</em> (ISSN 2327-2120) is an open-access journal committed to publishing peer-reviewed papers on cutting-edge and innovative research on bladder biology and disease.</p> <p>Bladder has been included by the following indexing and archiving services: PubMed Central (PMC), Google Scholar, CrossRef, OCLC, SHERPA/RoMEO and Portico.</p> <p><a href="">Read More</a></p> POL Scientific, LLC en-US Bladder 2327-2120 <p>Authors who publish with<em> the Bladder</em> agree to the following terms:</p> <ol> <li>Authors retain copyright and grant <em>the Bladder</em> right of first publication with the work simultaneously licensed under a <a href="" target="_blank" rel="noopener">Creative Commons Attribution License</a> that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.</li> <li>Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.</li> <li>Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See <a href="" target="_new">The Effect of Open Access</a>).</li> </ol> <p> </p> The Expression and Function of Piezo Channels in Bladder <p>The ability for bladder to perceive and analyze mechanical stimuli, such as stretch and filling, is crucial for its functions, such as urinary storage and voiding. The Piezo channel family, including Piezo1 and Piezo2, represents one of the most essential mechanosensitive ion channels in mammals and is involved in a wide array of physiological and pathological processes. It has been demonstrated in numerous investigations that Piezo channels play a key role in mechanical transduction in various types of cells in bladder by converting mechanical stimuli into biological signals. Notably, mounting evidence suggests that Piezo channels are functionally significant for bladder and are related to several bladder disorders. This review systematically summarizes the importance/role and features of Piezo channels in bladder, including their biophysical properties, location, and functions, with attention specifically paid to their association with the physiology and pathophysiology of bladder. This review aims to provide a novel perspective for the future clinical treatment of bladder dysfunction.</p> Zhipeng Li Dongxu Lin Changcheng Luo Pengyu Wei Bolang Deng Kang Li Langqing Cheng Zhong Chen Copyright (c) 2023 Zhipeng Li, Dongxu Lin, Changcheng Luo, Pengyu Wei, Bolang Deng, Kang Li, Langqing Cheng, Zhong Chen 2023-10-30 2023-10-30 10 e21200008 e21200008 10.14440/bladder.2023.870 How brain diseases affect the lower urinary tract function? <p>This article reviewed brain mechanism of the lower urinary tract (LUT). Among autonomic nervous systems, LUT is unique in terms of afferent pathophysiology; bladder sensation is perceived soon after the storage phase and throughout the voiding phase. Within the brain, this is measured in experimental animals by the firing of single neurons and in humans by evoked potentials/functional neuroimaging. The evidence indicates that sphincter information goes up to the precentral motor cortex and other brain areas, and bladder information goes up to the insular cortex (IC)/anterior cingulate (ACG) and further to the prefrontal cortex (PFC). Another LUT-specific phenomenon is efferent pathophysiology: detrusor overactivity (exaggerated micturition reflex) occurs in brain diseases such as stroke (focal disease) and dementia with Lewy bodies (diffuse diseases, may overlap with each other). With the turning off and on of the brain-switch of micturition (at the periaqueductal gray [PAG]), there is a bladder-inhibitory PFC-IC/ACG-hypothalamus-PAG pathway, with interconnections via the PFC with a PFC-nigrostriatal D1 dopaminergic pathway and a PFC-cerebellar pathway. Brain diseases that affect these areas may cause a loss of the brain's inhibition of the micturition reflex, leading to detrusor overactivity. This has a significant clinical impact on patients and requires appropriate management.</p> Ryuji Sakakibara Tatsuya Yamamoto Noritoshi Sekido Setsu Sawai Copyright (c) 2023 Ryuji Sakakibara, Tatsuya Yamamoto, Noritoshi Sekido, Setsu Sawai 2023-01-30 2023-01-30 10 e21200001 e21200001 10.14440/bladder.2023.854 Laparoscopic and Robotic-Assisted Extended Pelvic Lymph Node Dissection for Invasive Bladder Cancer: A Review <p>Minimally invasive surgical techniques, including laparoscopic and robotic-assisted radical cystectomy (RC), are emerging as the preferred treatment options for invasive bladder cancer. Mounting evidence has demonstrated that laparoscopic and robotic-assisted RC with extended pelvic lymph node dissection (PLND) is a viable alternative for managing invasive bladder cancer. In this review, we summarized recent advances and critically assessed the minimally invasive approaches and risk factors associated with extended PLND in patients undergoing laparoscopic or robotic-assisted RC. The findings indicated that laparoscopic and robotic-assisted PLND, employing either a standard or extended approach, is technically feasible and offers benefits such as minimal invasiveness, superior visualization, reduced blood loss, and expedited recovery. The risk factors involved in the laparoscopic extended PLND are minimal. Clinically, laparoscopic and robotic-assisted extended PLND is significantly advantageous in that it sticks to the principles of open surgery and respects anatomical boundaries. Nevertheless, laparoscopic and robotic-assisted extended PLND is technically challenging and necessitate extended operation time. Furthermore, large-scale, prospective, multicenter trials are warranted to validate the long-term efficacy of laparoscopic and robotic-assisted extended PLND in terms of disease-specific survival.</p> Weijun Fu Xu Zhang Copyright (c) 2023 Weijun Fu, Xu Zhang 2023-05-31 2023-05-31 10 e21200004 e21200004 10.14440/bladder.2023.849 Advances in HER2-Targeted Treatment for Advanced/Metastatic Urothelial Carcinoma <p>Urothelial carcinoma (UC) represents a common malignancy of the urinary system that can involve the kidneys, ureter, bladder, and urethra. Advanced/metastatic UC (mUC) tends to have a poor prognosis. UC ranks third in terms of human epidermal growth factor receptor 2 (HER2) overexpression among all tumors. However, multiple studies found that, unlike breast cancer, variable degrees of HER2 positivity and poor consistency between HER2 protein overexpression and gene amplification have been found. Trials involving trastuzumab, pertuzumab, lapatinib, afatinib, and neratinib have failed to prove their beneficial effect in patients with HER2-positive mUC, and a clinical trial on T-DM1 (trastuzumab emtansine) was terminated prematurely because of the adverse reactions. However, a phase II trial showed that RC48-ADC was effective. In this review, we provided an in-depth overview of the advances in the research regarding HER2-targeted therapy and the role of HER2 in mUC. Furthermore, we also discussed the prospects of potential strategies aimed at overcoming anti-HER2 resistance, and summarize the novel anti-HER2 approaches for the management of mUC used in recent clinical trials.</p> Mengnan Qu Li Zhou Xieqiao Yan Siming Li Xiaowen Wu Huayan Xu Juan Li Jun Guo Xu Zhang Hongzhao Li Xinan Sheng Copyright (c) 2023 Mengnan Qu, Li Zhou, Xieqiao Yan, Siming Li, Xiaowen Wu, Huayan Xu, Juan Li, Jun Guo, Xu Zhang, Hongzhao Li, Xinan Sheng 2023-12-11 2023-12-11 10 e21200012 e21200012 10.14440/bladder.2023.871 Advances in the bladder cancer research using 3D culture models <p>Bladder cancer represents the most common malignancy of the urinary system, posing a significant threat to patients' life. Animal models and two-dimensional (2D) cell cultures, among other traditional models, have been used for years to study various aspects of bladder cancer. However, these methods are subject to various limitations when mimicking the tumor microenvironment <em>in vivo</em>, thus hindering the further improvement of bladder cancer treatments. Recently, three-dimensional (3D) culture models have attracted extensive attention since they overcome the shortcomings of their traditional counterparts. Most importantly, 3D culture models more accurately reproduce the tumor microenvironment in the human body because they can recapitulate the cell-cell and cell-extracellular matrix interactions. 3D culture models can thereby help us gain deeper insight into the bladder cancer. The 3D culture models of tumor cells can extend the culture duration and allow for co-culturing with different cell types. Study of patient-specific bladder cancer mutations and subtypes is made possible by the ability to preserve cells isolated from particular patients in 3D culture models. It will be feasible to develop customized treatments that target relevant signaling pathways or biomarkers. This article reviews the development, application, advantages, and limitations of traditional modeling systems and 3D culture models used in the study of bladder cancer and discusses the potential application of 3D culture models.</p> Yexin Gu Ye Lu Yunqiang Xiong Xiangpeng Zhan Taobin Liu Min Tang An Xie Xiaoqiang Liu Bin Fu Copyright (c) 2023 Yexin Gu, Ye Lu, Yunqiang Xiong; Xiangpeng Zhan, Taobin Liu, Min Tang, An Xie; Xiaoqiang Liu, Bin Fu 2023-05-30 2023-05-30 10 e21200005 e21200005 10.14440/bladder.2023.856 Bladder Replacement Therapy <p>The bladder, as a vital organ of the urinary system, facilitates urine storage and micturition. The bladder can store urine under low pressure, sense volume changes, and coordinate with the urethral sphincter to ensure autonomous and efficient urination and bladder emptying. However, irreversible bladder damage may result from various conditions, such as nerve injuries, aging, or metabolic syndrome, compromising its normal physiological functions and necessitating various interventions for anatomical and functional bladder replacements. This review aimed to summarize advances on anatomical and functional bladder replacements.</p> Xinqi Liu Jiaxin Wang Lida Ren Qing Ling Copyright (c) 2023 Xinqi Liu, Jiaxin Wang, Lida Ren, Qing Ling 2023-11-13 2023-11-13 10 e21200010 e21200010 10.14440/bladder.2023.869 Transurethral Resection of Bladder Tumor: Novel Techniques in a New Era <p>Transurethral resection of bladder tumor (TURBT) serves both diagnostic and therapeutic purposes in the management of bladder cancer. Attaining a high-quality TURBT is not always guaranteed due to various factors. <em>En-bloc</em> resection of bladder tumors (ERBT) holds promise to be a primary technique for removing bladder tumors in most non-muscle invasive bladder cancers. However, so far, no conclusive evidence indicates the superiority of any specific energy source used for ERBT. While laser energy can prevent the activation of obturator nerve reflex during ERBT, it poses challenges such as thermal injury and imprecise controllability. Needle-shaped electrodes offer high-level precision and controllability, without causing tissue deterioration or vaporization. The primary limitation of ERBT at present is the extraction/harvesting of large <em>en-bloc</em> specimens. Effective tools have been developed to overcome this limitation. Enhanced cystoscopy improves the detection of flat and small bladder tumors, allowing for better removal of cancerous tissues and significantly reducing recurrence rates. Advances in medical technology have brought forth a multitude of strategies to address the shortcomings of traditional TURBT. Appliances with large operating channel provide a platform for conducting laparoscopic procedures within the context of pneumocystoscopy, facilitating the execution of super TURBT and conferring comparable advantages to <em>en-bloc</em> resection. Moreover, the utilization of pneumocystoscopy enables the safe and effective performance of transurethral partial cystectomy for localized muscle-invasive bladder cancer. Novel techniques significantly improve the precision of the transurethral surgery and lower the risk of complications.</p> Shengkun Sun Hengen Wang Xu Zhang Guangfu Chen Copyright (c) 2023 Shengkun Sun, Hengen Wang, Xu Zhang, Guangfu Chen 2023-11-09 2023-11-09 10 e21200009 e21200009 10.14440/bladder.2023.865 Should continuous bladder irrigation be recommended when single instillation of intravesical chemotherapy cannot be used after transurethral resection in low-risk non-muscle invasive bladder cancer? <p>Reducing the recurrence rate in patients with low-risk non-muscle invasive bladder cancer patients is a critical concern in the urologic community. The gold standard treatment is single instillation (SI) of intravesical chemotherapy after transurethral resection of bladder tumor (TURBT), but unfortunately, it is underused. Continuous bladder irrigation (CBI) after TURBT is an alternative strategy to SI for the prevention of bladder tumor implantation and recurrence. The aim of this review was to present the evidence that supports CBI after TURBT when SI is not possible.</p> Joaquin Chemi Gustavo Martin Villoldo Copyright (c) 2023 Joaquin Chemi, Gustavo Martin Villoldo 2023-03-17 2023-03-17 10 e21200002 e21200002 10.14440/bladder.2023.848 Efficacy of Pentosan Polysulfate Treatment in Patients with Interstitial Cystitis/Bladder Pain Syndrome <p><strong>Objectives</strong>: Pentosan Polysulfate (PPS) is the only oral treatment for interstitial cystitis (IC)-bladder pain syndrome (BPS) approved by the World Health Organization. Self-evaluation scales can provide more objective results on pre- and post-treatment satisfaction. The aim of this study was to investigate the effect of pentosan polysulfate treatment on symptoms in IC-BPS patients.<br /><strong>Methods</strong>: This study included 37 adult male and female patients with IC-BPS who reported pain, urinary urgency, polyurea, and nocturia without urinary tract infection for a minimum of six months prior to the study and were taking 300 mg/day oral pentosan polysulfate. Pre- and post-treatment symptoms, Interstitial Cystitis Symptom Index (ICSI) Scores, quality of life (QoL) scores (1‒4), and satisfaction conditions were examined.<br /><strong>Results</strong>: Following the application of inclusion and exclusion criteria, mean age of 37 suitable patients was 46.0±11.9 years and 27% (10 individuals) of the patients were male. Pre-treatment, ICSI scores, and measures of satisfaction degree and QoL increased significantly after the treatment (p&lt;0.001). Adverse reaction was detected in two patients (5.4%) among the patients treated with pentosan polysulfate.<br /><strong>Conclusions</strong>: Oral pentosan polysulfate for the treatment of interstitial cystitis/bladder pain syndrome treatment could achieve recovery in symptoms, increase Interstitial Cystitis Symptom Index score and improve quality of life and patient satisfaction.</p> Mehmet Gürkan Arıkan Basri Cakiroglu Copyright (c) 2023 Mehmet Gürkan Arıkan, Basri Cakiroglu 2023-09-15 2023-09-15 10 e21200007 e21200007 10.14440/bladder.2023.866 Global status quo and trends of research on urinary incontinence: a bibliometric and visualized study <p><strong>Background</strong></p> <p>Urinary incontinence (UI) is highly prevalent and poses a considerable social and economic burden on both victims and the society at large. This study reviewed the UI-related literature to present the current status and predict future trends of UI researh.</p> <p><strong>Methods</strong></p> <p>Studies related to UI published between 2012 and 2022 were retrieved from the Web of Science Core Collection. The bibliometric analysis and visualized study were performed by using VOSviewer.</p> <p><strong>Results</strong></p> <p>A total of 3092 publications were retrieved for further analysis. The United States ranked the first in terms of the total number of publications, citations, the H-index of publications. The institutions with the most cited publications was the N8 Research Partnership. <em>Neurourology and Urodynamics</em> published most papers, was cited most frequently, and scored the highest H-index. The author with the most citations, and the greatest average citations per article was Nitti VW. The author with the highest H-index was Herschorn S. Articles were divided into five main clusters based on keyword analysis: epidemiological studies, diagnosis studies, therapy studies, female urinary incontinence studies, and male urinary incontinence studies. UI-related epidemiology, therapies and male UI will continue to be the hot topics.</p> <p><strong>Conclusions</strong></p> <p>This study indicated that the UI research is more intensive in Europe and North America, <em>Neurourology and Urodynamics</em> was the most influencial journal in the field. Moreover, epidemiology, therapy and male urinary incontinence will continue to be hot topics. Our study contributes to a more comprehensive understanding of the status quo and provides clues to future research directions of UI.</p> Teng Li Yuqing Li Song Wu Copyright (c) 2023 Song Wu, Teng Li, Yuqing Li 2023-12-11 2023-12-11 10 e21200014 e21200014 10.14440/bladder.2023.873 The diagnostic value of fluorescence in situ hybridization in secondary electroresection of bladder cancer <p><strong>OBJECTIVE</strong>: To investigate the utility of fluorescence <em>in situ</em> hybridization (FISH) in secondary electroresection of bladder cancer. <br /><strong>METHODS</strong>: From January 2016 to April 2022, bladder cancer patients who had undergone secondary electroresection in Tongji Hospital and had preoperative urine FISH were recruited, and the positive rate, accuracy, sensitivity, specificity, genetic material changes and predictive power on malignancy degree of FISH in the secondary electroresection of bladder cancer were examined. <br /><strong>RESULTS</strong>: Twenty-six patients with bladder cancer were included in this study, and 8 were confirmed by secondary electroresection, including 6 cases positive for FISH positive and 2 negative for FISH. Besides, among the subjects, 18 were without tumor recurrence, including 1 case with positive FISH results and 17 with negative FISH results. Tumor recurrence was diagnosed in 85.71% (6/7) of FISH-positive patients in secondary electroresection while only 10.53% (2/19) of FISH-negative patients were found to develop tumor recurrence in the secondary electroresection. The sensitivity of FISH for the detection of bladder cancer before secondary electroresection was 75%, with a specificity of 94.44%, and an accuracy of 88.46%. A 6-month follow-up revealed that 2 of the 8 recurrent patients underwent radical resection of bladder cancer, and the remaining 6 patients had no recurrence, as confirmed by regular bladder perfusion and microscopy. In the 18 non-recurrent patients during secondary electroresection, no recurrence developed.<br /><strong>CONCLUSIONS</strong>: Urine FISH can achieve a high detection rate and specificity for secondary electroresection of bladder cancer. If a bladder cancer patient who are indicated for secondary electroresection is negative for urine FISH, the recurrence rate after secondary electroresection will be low, and the cystoscopy can be performed before deciding whether to perform secondary electroresection.</p> Bowen Chen Bo Shu Zhenghao Liu Junyu Zhu Chunjin Ke Xing Zeng Zhiquan Hu Chunguang Yang Copyright (c) 2023 Bowen Chen, Bo Shu, Zhenghao Liu, Junyu Zhu, Chunjin Ke, Xing Zeng, Zhiquan Hu; Chunguang Yang 2023-07-25 2023-07-25 10 e21200006 e21200006 10.14440/bladder.2023.861 Single-cell analyses EMP1 as a marker of the ratio of M1/M2 macrophages is associated with EMT, immune infiltration, and prognosis in bladder cancer <p><strong>Background:</strong> Bladder cancer is among the most lethal urinary system cancers across the globe. Macrophage 1 and Macrophage 2 play an essential role in the pathogenesis of tumors. Nevertheless, prior studies failed to investigate the implication of the two cells, working in combination, in the development, growth, progression and metastasis of bladder cancer.</p> <p><strong>Methods:</strong> We computed the M1/M2 ratio of the samples retrieved from The Cancer Genome Atlas (TCGA) by using the Cibersortx algorithm and calculated the ratio in 32 patients in our series by employing flow cytometry. SurvivalRandomForest was utilized to reduce the dimension of the list of the M1/M2-related genes, with an aim to obtain the most survival-predictive gene (<em>EMP1</em>) encoding epithelial membrane protein 1 (EMP1). The EMP1 was biologically characterized by using Gene Set Enrichment Analysis (GSEA), Gene Set Variation Analysis (GSVA), and Gene Ontology (GO). The single-cell transcriptome (sc-RNA) analysis was then applied to further look into the function of <em>EMP1</em>. Finally, Cellchat was employed to examine the interaction between macrophages and epithelium cells.</p> <p><strong>Results:</strong> The results showed that higher M1/M2 ratio was found to be associated with a more favorable prognosis of bladder cancer. <em>EMP1</em> was identified to be the key gene indicative of M1/M2 ratio and higher <em>EMP1</em> expression was associated with poor prognosis. Further analyses showed that <em>EMP1</em> might promote tumor invasion and metastasis via epithelial-mesenchymal transition (EMT) and focal adhesion (FA). Moreover, the expression level of <em>EMP1</em> could serve as an indicator of immunotherapy efficacy. The scRNA-seq data indicated that <em>EMP1</em> in cancer cells was strongly associated with tumor proliferation. Finally, the Cellchat results exhibited that <em>EMP1</em> might promote the interaction between macrophages and cancer cells through the fibronectin 1-syndecan 1 (FN1-SDC1) pathway.</p> <p><strong>Conclusion:</strong> Our study identified <em>EMP1</em>, an M1/M2-related gene, the expression of which may act as a prognostic indicator for the proliferation, metastasis, and response to immunotherapy. <em>EMP1</em> might be involved in the regulation on M1/M2 ratio.<strong> </strong></p> Jinqiao Li Jianyu Liu Honglei Wang Jinpeng Ma Yueze Wang Wanhai Xu Copyright (c) 2023 Jinqiao Li, Jianyu Liu, Honglei Wang, Jinpeng Ma, Yueze Wang, Wanhai Xu 2023-12-18 2023-12-18 10 e21200011 e21200011 10.14440/bladder.2023.852 Patterns of chemotherapy use in muscle-invasive bladder cancer in a tertiary centre <p>Objectives: Although neoadjuvant chemotherapy (NAC) has been demonstrated to have significant benefits to survival in patients with muscle-invasive bladder cancer (MIBC), the current utilization of NAC in Australia is unknown. The aim of this study was to evaluate the patterns of neoadjuvant and adjuvant chemotherapy (AC) use in patients undergoing cystectomy for MIBC at a large tertiary institution in Australia.</p> <p>Methods: A retrospective study was conducted using data of patients who underwent a radical cystectomy (RC) at a high-volume centre for MIBC between 2011 and 2021.</p> <p>Results: Of 69 patients who had a cystectomy for ≥ pT2 bladder cancer, 73.9% were eligible for NAC. However, of those eligible, only five patients received NAC (9.8%). Of the total patients who were eligible for AC, only 44.4% received postoperative chemotherapy. Common reasons for the lack of uptake were due to patients being unfit or declining treatment. There was no difference in progression-free survival or overall survival in those who received NAC and AC.</p> <p>Conclusions: The majority of patients undergoing RC for MIBC received AC compared to NAC, reflecting the real-world challenge of NAC uptake. This highlights the need for ongoing improvements in selection and usage of NAC and less reliance of AC utilization post RC.</p> Kylie Yen-Yi Lim Kevin Chu Nieroshan Rajarubendra James Huang David Pook Paul Manohar Matthew Harper Scott Donnellan Weranja Ranasinghe Copyright (c) 2023 Kylie Yen-Yi Lim, Kevin Chu, Nieroshan Rajarubendra, James Huang, David Pook, Paul Manohar, Matthew Harper, Scott Donnellan, Weranja Ranasinghe 2023-12-11 2023-12-11 10 e21200013 e21200013 10.14440/bladder.2023.872 Bladder leiomyoma and the utility of 18F-Fluorodeoxyglucose-Positron Emission Tomography – a Case Report <p>Bladder leiomyomas are rare neoplasms and various diagnostic methods are available to assist in confirming diagnosis preoperatively. Presented here is a case of bladder leiomyoma in a 41-year-old female who presented with urinary symptoms and right thigh pain. Imaging revealed a soft tissue density mass in the bladder wall. However concerns of a leiomyosarcoma remained. An <sup>18</sup>F-fluorodeoxyglucose (FDG) positron emission tomography/computerized tomography (PET/CT) demonstrated low FDG uptake and absence of metastatic lesions. In combination with operative findings, the tumor allowed for localized resection instead of more invasive partial cystectomy. Therefore, FDG-PET might be used to support the diagnosis of leiomyoma and potentially facilitate a less aggressive surgical management.</p> Kylie Yen-Yi Lim Kerelus Morkos Sidney M Levy Paul Davis Copyright (c) 2023 Kylie Yen-Yi Lim, Kerelus Morkos, Sidney M Levy, Paul Davis 2023-05-04 2023-05-04 10 e21200003 e21200003 10.14440/bladder.2023.859