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Non-muscle invasive bladder cancer (NMIBC) is currently mainly treated with the approach of transurethral resection of bladder tumor (TURBT) followed by pathology investigation of the obtained specimens. However, this approach—TURBT—has a few drawbacks, owing to the inherent technical defect—"piecemeal" resection. With development of medical science and surgical techniques, a new kind of surgical operation—"en bloc" resection of bladder tumor (ERBT)—emerged, hoping to completely remove bladder tumor with surrounding normal tissue. The detrusor muscle layer beneath the tumor is removed, and the surgical quality of bladder tumor is enhanced, with a better pathological outcome, reduced intraoperative complications and lower recurrence rate eventually. This paper reviews current literature concerning a brief history of ERBT developing, surgical steps, its indications, advantages on surgical margin, recurrence during follow-up, pathological performance—presence of detrusor muscle, residual tumor and upstage, as well as such issue as "is reTURBT necessary after ERBT?" and the guiding significance of ERBT in substaging of T1 bladder cancer. [ABSTRACT FROM AUTHOR]

Bladder cancer is one of the most frequent malignant tumors of the urinary system. The prevalence of bladder cancer among men and women is roughly 5:2, and both its incidence and death have been rising steadily over the past few years. At the moment, metastasis and recurrence of advanced bladder cancer—which are believed to be connected to the malfunction of multigene and multilevel cell signaling network—remain the leading causes of bladder cancer-related death. The therapeutic treatment of bladder cancer will be greatly aided by the elucidation of these mechanisms. New concepts for the treatment of bladder cancer have been made possible by the advancement of research technologies and a number of new treatment options, including immunotherapy and targeted therapy. In this paper, we will extensively review the development of the tumor microenvironment and the possible molecular mechanisms of bladder cancer. [ABSTRACT FROM AUTHOR]

Panel count data are frequently encountered in follow-up studies such as clinical trials, reliability researches, and insurance studies. Models about this type data usually assume the linearity form of the covariate variables on the log conditional mean function. However, the linearity assumption cannot be always guaranteed in practical applications, especially when high-dimensional covariates exist under investigation. In this paper, we propose a more flexible conditional mean regression model of panel count data with an unknown link function to describe the possible nonlinearity of the covariate effects. The partial likelihood procedure is developed to estimate the unknown link function and the regression parameters simultaneously by first approximating the unknown link function by polynomial splines, and then a two-step iterative algorithm is developed for computing implementation. Finally, the Breslow-type estimator is constructed for the baseline mean function. Asymptotic results of the proposed estimators are discussed under some regularity conditions. In addition, penalized spline estimation procedure is also introduced as an extension. Extensive numerical studies are carried out and indicate that the proposed procedure works well. Finally, two applications of bladder cancer study and skin cancer study are also presented for illustration. [ABSTRACT FROM AUTHOR]

Purpose: Electronic patient-reported outcomes (ePROs) are increasingly being used for symptom monitoring during routine cancer care, but have rarely been evaluated in diverse patient populations. We assessed ePRO user experiences and perceived value among Black and White cancer patients.Methods: We recruited 30 Black and 49 White bladder and prostate cancer patients from a single institution. Participants reported symptoms using either a web-based or automated telephone interface over 3 months and completed satisfaction surveys and qualitative interviews focused on user experiences and value. Using a narrative mixed methods approach, we evaluated overall and race-specific differences in ePRO user experiences and perceived value.Results: Most participants selected the web-based system, but Blacks were more likely to use the automated telephone-based system than Whites. In satisfaction surveys, Whites more commonly reported ease in understanding and reporting symptoms compared with Blacks. Blacks more often reported that the ePRO system was helpful in facilitating symptom-related discussions with clinicians. During interviews, Blacks described how the ePRO helped them recognize symptoms, while Whites found value in better understanding and tracking symptoms longitudinally. Blacks also expressed preferences for paper-based ePRO options due to perceived ease in better understanding of symptom items.Conclusion: Electronic patient-reported outcomes are perceived as valuable for variable reasons by Black and White cancer populations, with greater perceived value for communicating with clinicians reported among Blacks. To optimize equitable uptake of ePROs, oncology practices should offer several ePRO options (e.g., web-based, phone-based), as well as paper-based options, and consider the e-health literacy needs of patients during implementation. [ABSTRACT FROM AUTHOR]

Purpose: Electronic cigarette (e-cig) use is prevalent. The health implications of e-cig use on the genitourinary (GU) system are uncertain. This systematic review aims to evaluate how e-cig use impacts the GU system. Methods: A systematic search was conducted in PubMed, Embase and Ovid alongside citation searching. Review articles, non-English papers, animal model/cell line studies or articles only on combustible cigarettes were excluded. Quality assessment was undertaken using the Joanna Briggs Institute checklists. The primary endpoint was the impact of e-cig use on bladder cancer incidence. Secondary outcomes included urinary carcinogens, chronic kidney disease (CKD), reproductive disorders, and other GU diseases. Results: The search yielded 244 articles, 28 were ultimately included. One study assessed risk of bladder cancer and found the use of e-cig was associated with an increased odds ratio of 1.577 for its diagnosis. Twenty-one articles measured potential urinary carcinogens—including crotonaldehyde and benzene—associated with bladder cancer. Two articles evaluated the association of e-cig use with CKD and reported mixed outcomes. Three articles reported on reproductive disorders, specifically, stuttering priapism and changes to sperm quantity and quality. One study reported on other GU diseases, specifically burns to the GU system. After quality assessment, all articles were deemed to be of acceptable quality for inclusion. Conclusions: E-cig use was associated with an increased risk of bladder cancer, increased exposure to carcinogenic compounds, mixed evidence on CKD, increased risk of reproductive disorders and burns to the GU system. Further studies are needed to understand long-term GU effects. [ABSTRACT FROM AUTHOR]

Purpose of Review: As patients with spina bifida are living longer, more long-term outcomes are being reported. Today, the conversation surrounding neurogenic bladder care has evolved from reducing mortality to enhancing quality of life, namely, reducing urinary incontinence while still preserving upper tract function. In this paper, we seek to review risks of bladder malignancy in neurogenic bladder patients with history of augmentation or chronic catheters. Recent Findings: Recent data has demonstrated that cancers in bladders with prior augmentation or chronic catheters tend to be advanced, aggressive, and occur at a younger age. However, bladder cancer in this population is difficult to predict and difficult to diagnose before it is too late. Summary: Screening protocols and early diagnostic tools remain elusive as these cancers may present with symptoms that can be easily overlooked or attributed to other disease processes. Current work with biomarkers may yield better diagnostic tools than cystoscopy or cytology. [ABSTRACT FROM AUTHOR]

Background: In Japan, comprehensive cancer statistics are collected through cancer registries. However, data on urological cancers are rarely summarized or published in research papers. Methods: This retrospective study was performed using publicly available statistical data on urological cancers (prostate cancer [PCa], bladder cancer [BCa], and cancers of kidney and urinary tract [except urinary bladder]) in Japan, including a summary of the Ministry's mortality statistics, cancer incidence statistics from the Regional Cancer Registries through 2015, and the National Cancer Registry statistics from 2016. We examined the incidence and mortality rates of urological cancers stratified by age groups. Results: The number of new cases of PCa, BCa, and cancers of kidney and urinary tract (except urinary bladder) in 2019 was 94,748, 23,383, and 30,458, respectively, and the number of deaths in 2022 was 13,439, 9,598, and 9,795, respectively. The incidence and mortality rates of urological cancers have consistently increased. Since 2000, there has been a noteworthy increase in the mortality rate of urological cancers among individuals aged > 85 years. The incidence and mortality rates of BCa and cancers of kidney and urinary tract (except urinary bladder) were significantly higher in males than in females. Conclusions: Urological cancers in very elderly patients (> 85 years) will become increasingly important in the future. [ABSTRACT FROM AUTHOR]

Panel count data refer to interval-censored recurrent event data. Each study subject can only be observed at discrete time points, leading to knowledge about the total number of events occurring between observations. The observation times can be also different among subjects and carry important information about the underlying recurrent process. In this paper, an empirical likelihood (EL) method for panel count data with informative observation times is proposed. Based on the influence function, we formulate an empirical likelihood ratio for the vector of regression coefficients, and the Wilks' theorem is established. Simulation studies are carried out to compare the performance of empirical likelihood with normal approximation methods. Finally, the EL method is compared with existing approaches, utilizing an illustrative example drawn from a bladder cancer study. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this paper is to present evidence regarding the associations between smoking and the following urologic cancers: prostate, bladder, renal, and upper tract urothelial cancer (UTUC). Methods: This is a narrative review. PubMed was queried for evidence-based analyses and trials regarding the associations between smoking and prostate, bladder, renal, and UTUC tumors from inception to September 1, 2022. Emphasis was placed on articles referenced in national guidelines and protocols. Results: Prostate—multiple studies associate smoking with higher Gleason score, higher tumor stage, and extracapsular invasion. Though smoking has not yet been linked to tumorigenesis, there is evidence that it plays a role in biochemical recurrence and cancer-specific mortality. Bladder—smoking is strongly associated with bladder cancer, likely due to DNA damage from the release of carcinogenic compounds. Additionally, smoking has been linked to increased cancer-specific mortality and higher risk of tumor recurrence. Renal—smoking tobacco has been associated with tumorigenesis, higher tumor grade and stage, poorer mortality rates, and a greater risk of tumor recurrence. UTUC—tumorigenesis has been associated with smoking tobacco. Additionally, more advanced disease, higher stage, lymph node metastases, poorer survival outcomes, and tumor recurrence have been linked to smoking. Conclusion: Smoking has been shown to significantly affect most urologic cancers and has been associated with more aggressive disease, poorer outcomes, and tumor recurrence. The role of smoking cessation is still unclear, but appears to provide some protective effect. Urologists have an opportunity to engage in primary prevention by encouraging cessation practices. [ABSTRACT FROM AUTHOR]

In many longitudinal studies, information is collected on the times of different kinds of events. Some of these studies involve repeated events, where a subject or sample unit may experience a well-defined event several times throughout their history. Such events are called recurrent events. In this paper, we introduce nonparametric methods for estimating the marginal and joint distribution functions for recurrent event data. New estimators are introduced and their extensions to several gap times are also given. Nonparametric inference conditional on current or past covariate measures is also considered. We study by simulation the behavior of the proposed estimators in finite samples, considering two or three gap times. Our proposed methods are applied to the study of (multiple) recurrence times in patients with bladder tumors. Software in the form of an R package, called survivalREC, has been developed, implementing all methods. [ABSTRACT FROM AUTHOR]

Deep learning integration in cancer diagnosis enhances accuracy and diagnosis speed which helps clinical decision-making and improves health outcomes. Despite all these benefits in cancer diagnosis, the present AI models in urology cancer diagnosis have not been sufficiently reviewed systematically. This paper reviews the artificial intelligence approaches used in cancer diagnosis, prediction, and treatment of urology cancer. AI models and their applications in urology subspecialties are evaluated and discussed. The Scopus, Microsoft Academic and PubMed/MEDLINE databases were searched in November 2022 using the terms "artificial intelligence", "neural network", "machine learning," or "deep learning" combined with the phrase "urology cancers". The search was limited to publications published within the previous 20 years to identify cutting-edge deep-learning applications published in English. Irrelevant review articles and publications were eliminated. The included research involves two kinds of research analysis: quantitative and qualitative. 48 articles were included in this survey. 25 studies proposed several approaches for prostate cancers, while 15 were for bladder cancers. 8 studies discussed renal cell carcinoma and kidney cancer. The models presented to detect urology cancers have achieved high detection accuracy (77–95%). Deep learning approaches that use convolutional neural networks have achieved the highest accuracy among other techniques. Although it is still progressing, the development of AI models for urology cancer detection, prediction, and therapy has shown significant promise. Additional research is required to employ more extensive, higher-quality, and more recent datasets to the clinical performance of the proposed AI models in urology cancer applications. [ABSTRACT FROM AUTHOR]

Recurrent event data are commonly encountered in many scientific fields, including biomedical studies, clinical trials and epidemiological surveys, and many statistical methods have been proposed for their analysis. In this paper, we consider to use a weighted composite endpoint of recurrent and terminal events, which is weighted by the severity of each event, to assess the overall effects of covariates on the two types of events. A flexible additive-multiplicative model incorporating both multiplicative and additive effects on the rate function is proposed to analyze such weighted composite event process, and more importantly, the dependence structure among the recurrent and terminal events is left unspecified. For the estimation, we construct the unbiased estimating equations by virtue of the inverse probability weighting technique, and the resulting estimators are shown to be consistent and asymptotically normal under some mild regularity conditions. We evaluate the finite-sample performance of the proposed method via simulation studies and apply the proposed method to a set of real data arising from a bladder cancer study. [ABSTRACT FROM AUTHOR]

Since the identification of microRNAs (miRNAs), empirical research has demonstrated their crucial involvement in the functioning of organisms. Investigating miRNAs significantly bolsters efforts related to averting, diagnosing, and treating intricate human maladies. Yet, exploring every conceivable miRNA–disease association consumes significant resources and time within conventional wet experiments. On the computational front, forecasting potential miRNA–disease connections serves as a valuable source of preliminary insights for medical investigators. As a result, we have developed a novel matrix factorization model known as Hessian-regularized L 2 , 1 nonnegative matrix factorization in combination with deep learning for predicting associations between miRNAs and diseases, denoted as H R L 2 , 1 -NMF-DF. In particular, we introduce a novel iterative fusion approach to integrate all similarities. This method effectively diminishes the sparsity of the initial miRNA–disease associations matrix. Additionally, we devise a mixed model framework that utilizes deep learning, matrix decomposition, and singular value decomposition to capture and depict the intricate nonlinear features of miRNA and disease. The prediction performance of the six matrix factorization methods is improved by comparison and analysis, similarity matrix fusion, data preprocessing, and parameter adjustment. The AUC and AUPR obtained by the new matrix factorization model under fivefold cross validation are comparative or better with other matrix factorization models. Finally, we select three diseases including lung tumor, bladder tumor and breast tumor for case analysis, and further extend the matrix factorization model based on deep learning. The results show that the hybrid algorithm combining matrix factorization with deep learning proposed in this paper can predict miRNAs related to different diseases with high accuracy. [ABSTRACT FROM AUTHOR]

As a means of applying cold atmospheric plasma (CAP), plasma-activated solutions have received extensive attention for their excellent anticancer effects. However, previous studies have focused mainly on the local injection of plasma-activated solutions for cancer treatment while ignoring the anticancer effects of intraluminal plasma-activated solution perfusion. In this paper, the anticancer effects of flowing plasma-activated saline (PAS) on human bladder cancer cell lines (J82) were studied in vitro in a microfluidic system. It is noteworthy that flowing PAS can kill cancer cells more efficiently than PAS immersion. Further experimental results show that the anticancer effects of PAS on J82 cells in the microcavity are affected by plasma irradiation time, perfusion time and liquid flow rate. Our research suggests that PAS perfusion therapy can become a controllable alternative therapy pathway in the future clinical treatment of intracavitary tumors. [ABSTRACT FROM AUTHOR]

Purpose: Bladder cancer (BC) is a common malignancy with well-established differences in incidence, clinical manifestation and outcomes between men and women. It is unknown to what extent disparities in outcomes are influenced by differences in treatment approaches. This paper describes treatment patterns among men and women with muscle-invasive BC focusing on curative treatment (radical cystectomy or trimodal therapy). Methods: A retrospective population-based cohort study was performed with data from the Netherlands Cancer Registry. All patients newly diagnosed with muscle-invasive, non-advanced BC (MIBC, cT2-4a, N0/X, M0/X) in the years 2018, 2019 and 2020 were identified. Patient and tumor characteristics and initial treatment were compared between men and women with descriptive statistics and multivariable logistic regression analyses. Results: A total of 3484 patients were diagnosed with non-advanced MIBC in 2018–2020 in the Netherlands, of whom 28% were women. Women had higher T-stage and more often non-urothelial histology. Among all strata of clinical T-stage, women less often received treatment with curative intent (radical cystectomy [RC] or trimodality treatment). Among RC-treated patients, women more often received neoadjuvant treatment (except for cT4a disease). After adjustment for pre-treatment factors, odds ratios were indicative of women having lower probability of receiving curative treatment and RC specifically, and higher probability to receive NAC when treated with RC then men, although not statistically significant. Conclusions: Considerable differences in treatment patterns between men and women with MIBC exist. A more considerate role of the patient's sex in treatment decisions could help decrease these differences and might mitigate disparities in outcomes. [ABSTRACT FROM AUTHOR]

Bladder cancer (BC) has the highest lifetime treatment costs per patient of all cancers. The high recurrence rate and ongoing invasive monitoring requirement are the key contributors to the economic and human toll of this disease. The purpose of this paper was to utilize the recent literature to identify opportunities for improving the benefits and costs of BC care. A PubMed search was performed of recent publications concerning (BC) cost-effectiveness. We reviewed studies, reviews, opinion papers and cost-effectiveness analyses, focusing primarily on non-muscle-invasive bladder cancer (Ta/T1; NMIBC). New diagnostic tools such as urine markers may assist in more cost-effectively detecting BC at an earlier stage, however, these markers cannot replace the cystoscopy, which is the current standard of care. A photodynamic diagnostic tool (PDD) using hexylaminolevulinate (Hexvix®) enhances tumor visibility and improves transurethral resection of bladder cancer (TURB) results, potentially reducing recurrence rates and lowering treatment costs. While the importance of BC research has been acknowledged, research investment has been continuously reduced during the last 5 years. The economic burden of BC is well-characterized in the literature. This study suggests that new technologies (i.e., urine-based tests, PDD) and therapeutic regimes (intravesical chemotherapy, adjuvant immunotherapy) have significant potential to improve the diagnosis, treatment and on-going monitoring of BC patients, with potential improvements in clinical outcomes and concurrent cost-savings. A renewed interest and investment in BC research are required to ensure future advancements. [ABSTRACT FROM AUTHOR]

Purpose of Review: Intravesical BCG therapy (ivBCG) is a treatment for bladder cancer that complements surgery and prevents tumor progression. Reactive arthritis (ReA) is a rare osteoarticular manifestation that can complicate this treatment. An updated systematic literature review has been investigated to identify clinical, biological, and therapeutic data of this pathology. Recent Findings: A systematic literature was performed on October 2020 to identify papers published from 2000 to 2020. Study eligibility criteria included case reports, case series, cohort studies, systematic reviews, meta-analysis, and letters to the editor, in English and French. Independent extraction of articles was performed by two investigators. Thirteen studies met the search criteria for the systematic review with a good quality assessment. The total number of patients was 107, with an average age of 61.5 [24–80]. The symptoms of ReA appeared after a mean number of 5.71 instillations and 13.9 days. Arthritis was the most common symptom (98.13%) followed by fever (80.76%) and conjunctivitis (64.42%). Human leukocyte antigen (HLAB27) was positive in 28.97% of patients. Therapeutic modalities included non-steroidal anti-inflammatory drugs (NSAIDs) (51.4%), corticosteroids (27.1%), conventional synthetic disease-modifying antirheumatic drugs (3.84%), antitubercular drugs (14.42%), and tocilizumab (0.93%). BCG therapy was discontinued in 29.9% of patients. Remission was achieved in 92.3% of patients and one patient progressed to spondyloarthritis. Summary: ReA is a rare complication of BCG therapy. Clinical signs are similar to those of typical ReA and treatment is primarily based on NSAIDs and corticosteroids. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

Purpose: Patients harboring high-grade non-muscle-invasive bladder cancer (NMIBC) experience high rates of both recurrence and progression. Currently, few treatment options besides cystectomy exist for this at-risk population, especially those with BCG-unresponsive disease. The purpose of this review is to present the current status and describe future directions of immunotherapy in NMIBC. Methods: The PubMed and Google Scholar databases were searched for articles pertaining to immunotherapy in NMIBC. Relevant planned and ongoing clinical trials were identified using www.ClinicalTrials.gov. Published randomized control trials, reviews, other retrospective and prospective studies deemed relevant were used in this review paper. Results: Novel immunotherapies used in the treatment of high-grade NMIBC and BCG-unresponsive disease allow patients more options and have the potential to reduce the need for radical cystectomy. Currently, several options target the programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) axis as this mechanism of immunotherapy has been shown to be effective in several cancers, including bladder, melanoma, and lung cancers. In addition, other immunotherapy options for the treatment of NMIBC include viral gene therapies, interleukin-15 superagonists, small molecule inhibitors of indoleamine (2,3)-dioxygenase 1, and vaccines. Conclusions: The current landscape of immunotherapy in bladder cancer is rapidly evolving, with much literature pertaining to muscle-invasive and metastatic disease. However, the implementation of these treatment options in high-grade NMIBC may allow patients to avoid life-altering surgery. Reliable biomarkers for response are needed to further select patients who may benefit from such therapies. [ABSTRACT FROM AUTHOR]

Long noncoding RNAs (lncRNAs) have gained much attention in the past few years. Long intergenic non-protein coding RNA 520 (LINC00520) was one of the newly discovered lncRNA which has been demonstrated to be dysregulated in several cancers. So far, the function and mechanism of LINC00520 in non-small cell lung cancer (NSCLC) are unclear. In this paper, our group first showed that LINC00520 level was elevated in non-small cell lung cancer (NSCLC) tissue and cells. In addition, SP1 could bind directly to the promoter region of LINC00520 and thus promote its transcription. Increased LINC00520 was distinctly correlated with advanced tumor stage and shorter survival time in NSCLC patients. Further functional investigations provided evidences that forced down regulation of LINC00520 inhibited NSCLC cell proliferation, invasion, metastasis and EMT, while contributing to cells apoptosis. Mechanistically, we found that LINC00520 serving as a competing endogenous RNA to be involved in the modulation of miR-577 expressions, and thus affected the expression of CCNE2 which was a target gene of miR-577. Moreover, in NSCLC cells with si-LINC00520, up regulation of CCNE2 led to an increase of cell growth and invasion. Taken together, LINC00520 displayed its tumor-promotive roles through modulating the miR-577/CCNE2 axis, highlighting a potential therapeutic strategy for NSCLC patients. [ABSTRACT FROM AUTHOR]

Objective: Non-muscle invasive bladder cancer (NMIBC) is a chronic condition requiring repeated treatment and endoscopic examinations that can occur life-long. In this context, patient-reported outcomes (PROs) are important considerations to patients and managing clinicians. We undertook a systematic review to synthesise PRO results relevant to NMIBC treatment to explore trajectories overtime and differences between treatment options. Methods: We searched databases AMED, MEDLINE, EMbase, PsycINFO, Web of Knowledge and Scopus (inception to 5th December 2019), reference lists and contacted key authors to identify studies that reported PROs after NMIBC treatment. Two reviewers independently applied inclusion and quality criteria and extracted findings. Results for PROs were synthesised for treatment groups across three time periods: acute/during induction therapy; during maintenance therapy; and long-term follow-up (> 1 year). Results: Of 3193 papers screened, 29 were eligible. These provided evidence about induction treatment effects, but few reported maintenance or long-term evidence, and evidence about differences between NMIBC treatment options was lacking. A range of symptoms (pain in bladder area, urinary frequency and urgency, pain or burning during urination) were commonly experienced during and soon after treatment for NMIBC. Less common symptoms included fatigue, disrupted sleep and gastrointestinal problems. Conclusions: Treatments for NMIBC can cause symptoms and functional impairment during the acute treatment phase and reduce quality of life. Clinicians should be aware of these impairments to prepare patients for short-term sequelae and enable those with treatment options to exercise preferences in choosing among them. However, gaps in current evidence limit our understanding of PRO trajectories from diagnosis through to long-term survivorship and treatment effects. [ABSTRACT FROM AUTHOR]

Introduction: Numerous case series of robot-assisted radical cystectomy have emerged which describe complication rates comparable to open series. However, various reports have outlined preoperative factors as predictors of postoperative complications. Understanding these factors and the methods to optimize the perioperative care of the robotic cystectomy patient is essential for successful outcomes. Methods: In this topic paper, we briefly review the literature surrounding complication rates following robot-assisted radical cystectomy as well as describe our experience after >250 cases, outlining our suggestions for avoidance of surgical complications when building a practice that incorporates this technique. Results: Due to numerous variables, there are a number of intra-operative considerations, including patient selection, perioperative care pathway, intra-operative technique, and equipment choice that we have found to decrease post-operative complications and improve patient outcomes. Conclusion: Through careful patient selection, use of appropriate equipment and perioperative surgical management, robotic cystectomy is a feasible procedure with excellent perioperative results. [ABSTRACT FROM AUTHOR]

Bladder cancer is a major public health problem. Currently available therapeutic options seem to be unable to prevent bladder cancer recurrence and progression. To enable preclinical testing of new intravesical therapeutic agents, a suitable bladder tumor model that resembles human disease is highly desirable. The aim of this topic paper was to discuss the problems associated with current in vivo animal bladder tumor models, focusing on the orthotopic syngeneic rat bladder tumor model. In the second part of the paper the development of a potential new orthotopic rat bladder tumor model is described. [ABSTRACT FROM AUTHOR]

The cause of failure in cohort studies that involve competing risks is frequently incompletely observed. To address this, several methods have been proposed for the semiparametric proportional cause-specific hazards model under a missing at random assumption. However, these proposals provide inference for the regression coefficients only, and do not consider the infinite dimensional parameters, such as the covariate-specific cumulative incidence function. Nevertheless, the latter quantity is essential for risk prediction in modern medicine. In this paper we propose a unified framework for inference about both the regression coefficients of the proportional cause-specific hazards model and the covariate-specific cumulative incidence functions under missing at random cause of failure. Our approach is based on a novel computationally efficient maximum pseudo-partial-likelihood estimation method for the semiparametric proportional cause-specific hazards model. Using modern empirical process theory we derive the asymptotic properties of the proposed estimators for the regression coefficients and the covariate-specific cumulative incidence functions, and provide methodology for constructing simultaneous confidence bands for the latter. Simulation studies show that our estimators perform well even in the presence of a large fraction of missing cause of failures, and that the regression coefficient estimator can be substantially more efficient compared to the previously proposed augmented inverse probability weighting estimator. The method is applied using data from an HIV cohort study and a bladder cancer clinical trial. [ABSTRACT FROM AUTHOR]

Most patients with bladder carcinoma are diagnosed with non-muscle-invasive disease, stage Ta, and pT1. Stage remains as the single most important prognostic indicator in urothelial carcinoma. Among the pT1 bladder cancer patients, recurrence and progression of disease occur in 50% and 10%, respectively. The identification of high-risk patients within the pT1 subgroup remains an important clinical goal and an active field of research. Substaging of pT1 disease has been claimed as important histologic discriminator by the 2016 World Health Organization (WHO) classification of the genitourinary tract tumors and by the 8th edition of the American Joint Committee on Cancer (AJCC) staging manual supporting its implementation in clinical practice. Interobserver variation in pT1 diagnosis and the associated pitfalls in pT1 assessment are the critical pathological issues. The aim of this review paper is to provide the practicing pathologist with the state of the art of morphological and immunohistochemical features useful for the diagnosis of early invasive bladder carcinomas, including practical clues on how to avoid relevant interpretative pitfalls, and to summarize the current status of pT1 substaging. [ABSTRACT FROM AUTHOR]

Purpose: The Bladder Cancer Quality of Life Study collected detailed and sensitive patient-reported outcomes from bladder cancer survivors in the period after bladder removal surgery, when participation in survey research may present a burden. This paper describes the study recruitment methods and examines the response rates and patterns of missing data.Methods: Detailed surveys focusing on quality of life, healthcare decision-making, and healthcare expenses were mailed to patients 5-7 months after cystectomy. We conducted up to 10 follow-up recruitment calls. We analyzed survey completion rates following each contact in relation to demographic and clinical characteristics, and patterns of missing data across survey content areas.Results: The overall response rate was 71% (n = 269/379). This was consistent across patient clinical characteristics; response rates were significantly higher among patients over age 70 and significantly lower among racial and ethnic minority patients compared to non-Hispanic white patients. Each follow-up contact resulted in marginal survey completion rates of at least 10%. Rates of missing data were low across most content areas, even for potentially sensitive questions. Rates of missing data differed significantly by sex, age, and race/ethnicity.Conclusions: Despite the effort required to participate in research, this population of cancer survivors showed willingness to share detailed information about quality of life, health care decision-making, and expenses, soon after major cancer surgery. Additional contacts were effective at increasing participation. Response patterns differed by race/ethnicity and other demographic factors. Our data collection methods show that it is feasible to gather detailed patient-reported outcomes during this challenging period. [ABSTRACT FROM AUTHOR]

Precise survival risk stratification is crucial for personalized therapy in bladder cancer (BCa). This study developed and validated an end-to-end deep learning system using histological slides to predict overall survival (OS) risk in BCa patients. We employed the BlaPaSeg tile classifier to generate tissue probability heatmaps and segmentation maps, trained two prognostic networks, MacroVisionNet and UniVisionNet, and explored six potential BCa prognostic biomarkers. Across all cohorts, the AUC for BlaPaSeg ranged from 0.9906 to 0.9945, while the C-index varied from 0.655 to 0.834 for MacroVisionNet and 0.661 to 0.853 for UniVisionNet. After covariate adjustment, the hazard ratio (HR) values for high-risk groups were 1.97 to 5.06 in MacroVisionNet and 2.13 to 4.01 in UniVisionNet. The high-risk Coloc (Tumor Co-localization score) and IMTS (Integrated Muscle Tumor Score) groups illustrated a higher death risk with HR values from 1.41 to 10.16. The system improves BCa survival prediction and supports refined patient management. [ABSTRACT FROM AUTHOR]

Gremlin 1 (GREM1) can regulate the development of many cancers. However, a few studies have revealed the role of GREM1 in bladder cancer (BC). To evaluate the expression and potential function of GREM1 in bladder cancer, we used R version 3.6.3 and related packages to analyze the data from common databases. Samples from our institution were assessed by immunohistochemical staining (IHC), which was approved by the Institutional Ethics Committee (K20220830). GREM1 was highly expressed in BC tissues according to the TCGA and IHC data. Data from TCGA, GSE31684, GSE32894, and IHC showed that GREM1 has significant prognostic value for BC patients. GREM1 is involved in immune and metabolism-related pathways. According to the TIDE algorithm, 61.0% of patients with low GREM1 expression responded well to immunotherapy, compared to only 13.3% in the high GREM1 expression group. High GREM1 expression was associated with sensitivity to cisplatin, docetaxel, gemcitabine, and vinblastine. Thus, GREM1 can predict prognosis and responses to immunotherapy and chemotherapy in BC patients, making it a potential biomarker and therapeutic target. [ABSTRACT FROM AUTHOR]

The poor 5-year survival rate for bladder cancers is associated with the lack of efficient diagnostic and treatment techniques. Despite cystoscopy-assisted photomedicine and external radiation being promising modalities to supplement or replace surgery, they remain invasive or fail to provide real-time navigation. Here, we report non-invasive fractionated photodynamic therapy of bladder cancer with full-course real-time near-infrared-II imaging based on engineered X-ray-activated nanotransducers that contain lanthanide-doped nanoscintillators with concurrent emissions in visible and the second near-infrared regions and conjugated photosensitizers. Following intravesical instillation in mice with carcinogen-induced autochthonous bladder tumours, tumour-homing peptide-labelled nanotransducers realize enhanced tumour regression, robust recurrence inhibition, improved survival rates, and restored immune homeostasis under X-ray irradiation with accompanied near-infrared-II imaging. On-demand fractionated photodynamic therapy with customized doses is further achieved based on quantifiable near-infrared-II imaging signal-to-background ratios. Our study presents a promising non-invasive strategy to confront the current bladder cancer dilemma from diagnosis to treatment and prognosis. The poor survival rate for bladder cancers is associated with the lack of effective non-invasive theranostic techniques. Here this group reports a lanthanide-doped nanotransducer activated for real-time NIR-II imaging thereby navigates the photodynamic treatment of bladder cancer. [ABSTRACT FROM AUTHOR]

Background: The textile industry is the second risk factor for bladder cancer, after smoking. Previous studies focused on the impact of exposure to high concentrations of bladder carcinogenic chemicals in the textile dyeing industry on the elevation of bladder cancer biomarkers. This study aimed to evaluate bladder carcinogenic air pollutants in a textile dyeing factory and investigate its role and the role of serum 25-hydroxyvitamin D (25-OH vit. D) on cancer bladder biomarkers in exposed workers. Methods: A cross-sectional study was conducted. Particulate and vapor forms of polycyclic aromatic hydrocarbons (PAHs) and volatile organic compounds (VOCs) were monitored in the printing, dyeing, and preparing sections of a textile factory. Bladder tumor antigen (BTA), nuclear matrix protein 22 (NMP-22), and 25-OH vit. D were estimated in all the exposed workers (147 exposed workers) and in workers not occupationally exposed to chemicals (130 unexposed workers). Results: Aromatic bladder carcinogenic compounds were either in low concentrations or not detected in the air samples of working areas. BTA and NMP-22 of exposed workers were not significantly different from the unexposed. However, 25-OH vit. D was significantly lower in the exposed than unexposed workers. There was a significant inverse correlation between 25-OH vit. D and duration of exposure in exposed workers. Conclusion: The mean levels of PAHs and VOCs were within the safe standard levels in the working areas. The non-significant difference in BTA and NMP-22 between the exposed and unexposed groups suggests the presence of occupational exposures to safe levels of bladder carcinogenic aromatics, while the significantly lower 25-OH vit. D levels among the exposed than the unexposed groups could suggest the potential association of 25-OH vit. D with occupational exposures to low levels of PAHs and VOCs, and this association was found to be inversely correlated with the duration of exposures. Accordingly, more specific predictor tests must be applied for early diagnosis of bladder cancer among the exposed workers. [ABSTRACT FROM AUTHOR]

Bladder cancer was one of the most common carcinomas around the world. However, the mechanism of the disease still remained to be investigated. We expected to establish a prognostic survival model with 9 prognostic genes to predict overall survival (OS) in patients of bladder cancer. The gene expression data of bladder cancer were obtained from TCGA and GEO datasets. TCGA and GEO datasets were used for screening prognostic genes along with developing and validating a 9-gene prognostic survival model by method of weighted gene co-expression network analysis (WGCNA) and LASSO with Cox regression. The relative analysis of evaluate tumor burden mutation (TBM), GO, KEGG, chemotherapy drug and functional pathway were also performed based on CAF-related mRNAs. 151 Overlapping CAF-related genes were distinguished after intersecting differentially expressed genes from 945 genes in TCGA and 491 genes in GEO dataset. 9 Prognostic genes (MSRB2, AGMAT, KLF6, DDAH2, GADD45B, SERPINE2, STMN3, TEAD2, and COMP) were used for construction of prognostic model after LASSO with Cox regression. Receiver operating characteristic (ROC) curves showed a good survival prediction by this model. Functional analysis indicated chemokine, cytokine, ECM interaction, oxidative stress and apoptosis were highly appeared. Potential drugs targeted different CAF-related genes like vemurafenib, irofulven, ghiotepa, and idarubicin were found as well. We constructed a novel 9 CAF-related mRNAs prognostic model and explored the gene expression and potential functional information of related genes, which might be worthy of clinical application. In addition, potential chemotherapy drugs could provide useful insights into the potential clinical treatment of bladder cancer. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

Purpose: Diagnosis and follow-up in patients with non-muscle invasive bladder cancer (NMIBC) rely on cystoscopy and urine cytology. The aim of this review paper is to give an update on urinary biomarkers and their diagnosis and surveillance potential. Besides FDA-approved markers, recent approaches like DNA methylation assays, mRNA gene expression assays and cell-free DNA (cfDNA) are evaluated to assess whether replacing cystoscopy with urine markers is a potential scenario for the future. Methods: We performed a non-systematic review of current literature without time period restriction using the National Library of Medicine database (http://ww.pubmed.gov). The search included the following key words in different combinations: "urothelial carcinoma", "urinary marker", "hematuria", "cytology" and "bladder cancer". Further, references were extracted from identified articles. The results were evaluated regarding their clinical relevance and study quality. Results: Currently, replacing cystoscopy with available urine markers is not recommended by international guidelines. For FDA-approved markers, prospective randomized trials are lacking. Newer approaches focusing on molecular, genomic and transcriptomic aberrations are promising with good accuracies. Furthermore, these assays may provide additional molecular information to guide individualized surveillance strategies and therapy. Currently ongoing prospective trials will determine if cystoscopy reduction is feasible. Conclusion: Urinary markers represent a non-invasive approach for molecular characterization of the disease. Although fully replacing cystoscopy seems unrealistic in the near future, enhancing the current gold standard by additional molecular information is feasible. A reliable classification and differentiation between aggressive and nonaggressive tumors by applying DNA, mRNA, and cfDNA assays may change surveillance to help reduce cystoscopies. [ABSTRACT FROM AUTHOR]

Purpose: To provide a comprehensive overview and update of the joint consultation of the International Consultation on Urological Diseases (ICUD) and Société Internationale d'Urologie on Bladder Cancer Urinary Diversion (UD).Methods: A detailed analysis of the literature was conducted reporting on the different modalities of UD. For this updated publication, an exhaustive search was conducted in PubMed for recent relevant papers published between October 2013 and August 2018. Via this search, a total of 438 references were identified and 52 of them were finally eligible for analysis. An international, multidisciplinary expert committee evaluated and graded the data according to the Oxford System of Evidence-based Medicine.Results: The incidence of early complications has been reported retrospectively in the range of 20-57%. Unfortunately, only a few randomized controlled studies exist within the field of UD. Consequently, almost all studies used in this report are of level 3-4 evidence including expert opinion based on "first principles" research.Conclusions: Complications rates overall following RC and UD are significant, and when strict reporting criteria are incorporated, they are much higher than previously published. Complications can occur up to 20 years after surgery, emphasizing the need for lifelong follow-up. Progress has been made to prevent complications implementing robotic surgery and fast track protocols. Preoperative patient information, patient selection, surgical techniques, and careful postoperative follow-up are the cornerstones to achieve good results. [ABSTRACT FROM AUTHOR]

As research focus in oncology has recently shifted from oral targeted therapy to immunomodulation, the era of successful drug development in bladder cancer has just begun. This has led to unprecedented approval of five immunotherapeutic agents by regulatory agencies for metastatic bladder cancer within a span of 12 months. With an initial triumph of anti-programmed cell death-1 (anti-PD-1) and anti-programmed cell death ligand-1 (anti-PDL-1) drugs, ongoing efforts are aimed at identification and validation of new druggable immune targets to consolidate the initial gains. In this paper, we review the role of immunotherapy in the treatment of bladder cancer as well as the various emerging immunotherapeutic agents and their possible use in bladder cancer. [ABSTRACT FROM AUTHOR]

Cardamomin has been widely studied in cancer, but its role in cancer bladder cancer has not been mentioned. In this study, we validated the anti-cancer effect of cardamom and whether its potential mechanism is related to the PI3K/AKT pathway. After treating with different doses of cardamomin, the cytotoxicity was studied by CCK8. Secondly, we analyzed the effect of cardamomin on the proliferation, apoptosis and cell movement. Next, we analyzed the regulation of ESR1 by western blot and its impact on the PI3K/AKT pathway. We also transfected ESR1 overexpression and silencing vectors, and verified the transfection efficiency through RT-qPCR. Further, the specific mechanism of the drug's inhibitory effect on bladder cancer was also determined. We constructed the subcutaneous tumor model in vivo. After cardamomin administration, we mainly analyzed the positive expression of KI67 in tumor tissues by immunohistochemistry, and the apoptotic cells in tumor tissues by TUNEL, and related proteins in PI3K/AKT pathway by western blot. In this paper, cardamomin inhibited cell proliferation and invasion ability, blocked the transition of G0/G1 phase to S phase, and increased apoptotic rate of 5637 and HT1376 cells, as well as raised ESR1 expression. Cardamomin exerted anti-tumor effect through PI3K/AKT pathway. In vivo animal experiments indicated the inhibitory effect of cardamomin on subcutaneous implanted tumor. Cardamomin inhibited the positive expression of KI67 and promoted the TUNEL-positive cells in tumor tissues. Consistent with in vitro assay, cardamomin increased the expression of ESR1 and downregulated the PI3K/AKT pathway. Cardamomin has a significant inhibitory effect on bladder cancer, and upregulate the expression of ESR1 in bladder cancer through PI3K/AKT. [ABSTRACT FROM AUTHOR]

The causal relationship between lipid levels and bladder cancer is still inconclusive currently. We aimed to reveal the causal relationship between triglycerides, HDL, and LDL and the risk of bladder cancer by univariable and multivariable Mendelian randomization (MR) analysis. The single nucleotide polymorphisms (SNPs) of exposure (triglycerides: 441,016 samples; HDL: 403,943 samples; LDL: 440,546 samples) were obtained from UK Biobank. The Genetic variation related to bladder cancer included 1554 cases and 359,640 controls. Univariable and multivariable MR methods were conducted with subsequent analysis, and smoking was regarded as a confounder. The inverse-variance weighted (IVW), MR-Egger, weighted-median method, Cochran's Q test, and MR-PRESSO were considered the main MR analysis and sensitivity analysis methods. Univariable MR analysis results suggested the triglycerides level (P = 0.011, OR = 1.001, 95% CI = 1.000–1.002) was causally associated with increased risk of bladder cancer. Multivariable MR results indicated that higher triglyceride levels could still increase the risk of bladder cancer after adjusting the effects of HDL, LDL, and smoking (P = 0.042, OR = 1.001, 95% CI = 1.000–1.002). Our findings supported that triglyceride level is causally associated with an increased risk of bladder cancer independent of LDL and HDL at the genetic level. Timely attention to changes in blood lipid levels might reduce the risk of bladder cancer. [ABSTRACT FROM AUTHOR]

Muscle invasive bladder cancers (BCs) can be divided into 2 major subgroups-basal/squamous (BASQ) tumors and luminal tumors. Since Pparg has low or undetectable expression in BASQ tumors, we tested the effects of rosiglitazone, Pparg agonist, in a mouse model of BASQ BC. We find that rosiglitazone reduces proliferation while treatment with rosiglitazone plus trametinib, a MEK inhibitor, induces apoptosis and reduces tumor volume by 91% after 1 month. Rosiglitazone and trametinib also induce a shift from BASQ to luminal differentiation in tumors, which our analysis suggests is mediated by retinoid signaling, a pathway known to drive the luminal differentiation program. Our data suggest that rosiglitazone, trametinib, and retinoids, which are all FDA approved, may be clinically active in BASQ tumors in patients. New treatments are needed for muscle invasive bladder cancers. Here, the authors show that combined Pparg activation and MEK inhibition using FDA approved drugs shrinks tumor volume and induces a Basal/Squamous-to-Luminal shift in the urothelium as well as in invading tumors. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) are effective agents for tumor immunotherapy. However, their clinical effectiveness is unsatisfactory due to off-target effects and a suppressive immune microenvironment. This study developed a nanodrug delivery system for bladder cancer (BCa) using PCL-MPEG and PCL-PEG-CHO to synthesize internal hydrophobic and external hydrophilic micelles (PP) that encapsulated water-insoluble astragaloside IV (PPA). The aldehyde group on the surface of PPA reacted with the amino group of aPD-L1, allowing the decoration of this antibody on the surface of the micelles. The resultingPPA@aPD-L1effectively piggybacked astragaloside IV and aPD-L1 antibody. These findings suggest that PPA@aPD-L1 is relatively stable in circulation and efficiently binds to BCa cells with the aid of aPD-L1. Additionally, this strategy prolongs the drug's retention time in tumors. Compared to PBS, PP, and PPA with PPA + aPD-L1 groups, PPA@aPD-L1significantly prolonged the survival of mice with BCa and reduced tumor volume. Mechanistic studies showed that PPA inhibited the NF-κB and STAT3 signaling pathways in tumor cells. Additionally, PPA@aPD-L1increased IFN-γ and decreased IL-10 expression in bladder tumors, affecting the number and type of intratumorally infiltrating T cells. Our study presents a simple and effective drug delivery system that combines herbal monomers with ICIs. It has demonstrated a potent ability to suppress tumor growth and holds potential for future applications. [ABSTRACT FROM AUTHOR]

Arsenic is a bladder carcinogen though less is known regarding the specific temporal relationship between exposure and bladder cancer diagnosis. In this study, we modeled time-varying mixtures of arsenic exposures at many historic temporal windows to evaluate their association with bladder cancer risk in the New England Bladder Cancer Study. We used arsenic exposure estimates up to 60 years prior to study entry and compared the goodness of fit of models using these mixtures to those using summary measures of arsenic exposures. We used the Bayesian index low rank kriging multiple membership model (LRK-MMM) to estimate the associations of these mixtures with bladder cancer and estimate cumulative spatial risk for bladder cancer using participants' residential histories. We found consistent evidence that modeling arsenic exposures as a time-varying mixture provided better fit to the data than using a single arsenic exposure summary measure. We estimated several positive though not significant associations of the time-varying arsenic mixtures with bladder cancer having odds ratios (ORs) of 1.03–1.14 and identified many significant and positive associations for an interaction among those who consumed water from a private dug well (ORs 1.28–1.60). Arsenic exposures 40–50 years before study entry received elevated importance weights in these mixtures. Additionally, we found two small areas of elevated cumulative spatial risk for bladder cancer in southern New Hampshire and in south central Maine. These results emphasize the importance of considering time-varying mixtures of exposures for diseases with long latencies such as bladder cancer. [ABSTRACT FROM AUTHOR]

Bladder cancer is one of the leading causes of cancer-related mortality in the urinary system. Understanding genomic information is important in the treatment and prognosis of bladder cancer, but the current method used to identify mutations is time-consuming and labor-intensive. There are now many novel and convenient ways to predict cancerous genomics from pathological slides. However, the publicly available datasets are limited, especially for Asian populations. In this study, we developed a dataset consisting of 75 Asian cases of bladder cancers and 112 Whole-Slide Images with one to two images obtained for each patient. This dataset provides information on the most frequently and clinically significant mutated genes derived by whole-exome sequencing in these patients. This dataset will facilitate exploration and development of novel diagnostic and therapeutic technologies for bladder cancer. [ABSTRACT FROM AUTHOR]

Objective: To develop a prognostic risk model for Bladder Cancer (BLCA) based on mitochondrial-related long non-coding RNAs (lncRNAs). Methods: Transcriptome and clinical data of BLCA patients were retrieved from the TCGA database. Mitochondrial-related lncRNAs with independent prognostic significance were screened to develop a prognostic risk model. Patients were categorized into high- and low-risk groups using the model. Various methods including Kaplan–Meier (KM) analysis, ROC curve analysis, Gene Set Enrichment Analysis (GSEA), immune analysis, and chemotherapy drug analysis were used to verify and evaluate the model. Results: A mitochondrial-associated lncRNA prognostic risk model with independent prognostic significance was developed. High-risk group (HRG) patients exhibited significantly shorter survival periods compared to low-risk group (LRG) patients (P < 0.01). The risk score from the model was an independent predictor of BLCA prognosis, correlating with tumor grade, pathological stage, and lymph node metastasis (P < 0.05). The HRG showed significant positive correlations with high expressions of immune checkpoints (CTLA4, LAG3, PD-1, TIGIT, PD-L1, PD-L2, and TIM-3) and lower IC50 for chemotherapy drugs (cisplatin, docetaxel, paclitaxel, methotrexate, and vinblastine) (P < 0.001). Conclusions: The mitochondrial-related lncRNA-based prognostic risk model effectively predicts BLCA prognosis and can guide individualized treatment for BLCA patients. [ABSTRACT FROM AUTHOR]

Muscle invasive bladder cancer (MIBC) is a molecularly diverse disease with varied clinical outcomes. Molecular studies typically employ bulk sequencing analysis, giving a transcriptomic snapshot of a section of the tumour. However, tumour tissues are not homogeneous, but are composed of distinct compartments such as the tumour and stroma. To investigate the molecular profiles of bladder cancer, whilst also maintaining the spatial complexity of the tumours, we employed whole transcriptome Digital Spatial Profiling (DSP). With this method we generated a dataset of transcriptomic profiles of tumour epithelium, stroma, and immune infiltrate. With these data we investigate the spatial relationship of molecular subtype signatures and ligand signalling events. We find that Basal/Squamous and Classical subtypes are mostly restricted to tumour regions, while the stroma-rich subtype signatures are abundant within the stroma itself. Additionally, we identify ligand signalling events occurring between tumour, stroma, and immune infiltrate regions, such as immune infiltrate derived GPNMB, which was highly correlated with VEGFA expression within the tumour. These findings give us new insights into the diversity of MIBC at a molecular level and provide a dataset with detailed spatial information that was not available before in bladder cancer research. A spatial transcriptomics study in bladder cancer investigates the spatial localization of molecular subtype signatures and ligand signaling events. [ABSTRACT FROM AUTHOR]

Urinary exfoliated tumor cells have emerged as promising biomarkers for predicting, diagnosing, and guiding therapy in bladder cancer. Several methodologies based on biological and physical differences between normal cells and malignant tumor cells have been developed over the past few years. However, these methods still did not have sufficient sensitivity or specificity. In this study, a remote analysis protocol was devised utilizing motion microscopy. This technique amplifies vibrations within a recorded video by re-rendering motions, thereby generating highly magnified visuals. This approach aims to detect dynamic motions that may not be perceptible to the human eye under normal observation. Remarkably, motion microscopy unveiled discernible fluctuations surrounding bladder malignant tumor cells, which we referred to herein as cellular trail. The cellular trails were predominantly evident at around 1 Hz in amplified video images, with a velocity of 22 μm/s. Moreover, cellular trails were observed regardless of whether they were in a non-Newtonian or Newtonian fluid environment. Significantly, this phenomenon was distinguishable even in urine samples. In conclusion, we suggest motion microscopy as an innovative approach for detecting urinary malignant tumors with potential clinical utility as a complementary tool to cytology. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the performance of histogram features of non-Gaussian diffusion metrics for diagnosing muscle invasion and histological grade in bladder cancer (BCa). Methods: Patients were prospectively allocated to MR scanner1 (training cohort) or MR2 (testing cohort) for conventional diffusion-weighted imaging (DWIconv) and multi-b-value DWI. Metrics of continuous time random walk (CTRW), diffusion kurtosis imaging (DKI), fractional-order calculus (FROC), intravoxel incoherent motion (IVIM), and stretched exponential model (SEM) were simultaneously calculated using multi-b-value DWI. Whole-tumor histogram features were extracted from DWIconv and non-Gaussian diffusion metrics for logistic regression analysis to develop diffusion models diagnosing muscle invasion and histological grade. The models' performances were quantified by area under the receiver operating characteristic curve (AUC). Results: MR1 included 267 pathologically-confirmed BCa patients (median age, 67 years [IQR, 46–82], 222 men) and MR2 included 83 (median age, 65 years [IQR, 31–82], 73 men). For discriminating muscle invasion, CTRW achieved the highest testing AUC of 0.915, higher than DWIconv's 0.805 (p = 0.014), and similar to the combined diffusion model's AUC of 0.885 (p = 0.076). For differentiating histological grade of non-muscle-invasion bladder cancer, IVIM outperformed a testing AUC of 0.897, higher than DWIconv's 0.694 (p = 0.020), and similar to the combined diffusion model's AUC of 0.917 (p = 0.650). In both tasks, DKI, FROC, and SEM failed to show diagnostic superiority over DWIconv (p > 0.05). Conclusion: CTRW and IVIM are two potential non-Gaussian diffusion models to improve the MRI application in assessing muscle invasion and histological grade of BCa, respectively. Critical relevance statement: Our study validates non-Gaussian diffusion imaging as a reliable, non-invasive technique for early assessment of muscle invasion and histological grade in BCa, enhancing accuracy in diagnosis and improving MRI application in BCa diagnostic procedures. Key Points: Muscular invasion largely determines bladder salvageability in bladder cancer patients. Evaluated non-Gaussian diffusion metrics surpassed DWIconv in BCa muscle invasion and histological grade diagnosis. Non-Gaussian diffusion imaging improved MRI application in preoperative diagnosis of BCa. [ABSTRACT FROM AUTHOR]

Objectives: To investigate whether reduced field-of-view (rFOV) diffusion-weighted imaging (DWI) with deep learning reconstruction (DLR) can improve the accuracy of evaluating muscle invasion using VI-RADS. Methods: Eighty-six bladder cancer participants who were evaluated by conventional full field-of-view (fFOV) DWI, standard rFOV (rFOVSTA) DWI, and fast rFOV with DLR (rFOVDLR) DWI were included in this prospective study. Tumors were categorized according to the vesical imaging reporting and data system (VI-RADS). Qualitative image quality scoring, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and ADC value were evaluated. Friedman test with post hoc test revealed the difference across the three DWIs. Receiver operating characteristic analysis was performed to calculate the areas under the curve (AUCs). Results: The AUC of the rFOVSTA DWI and rFOVDLR DWI were higher than that of fFOV DWI. rFOVDLR DWI reduced the acquisition time from 5:02 min to 3:25 min, and showed higher scores in overall image quality with higher CNR and SNR, compared to rFOVSTA DWI (p < 0.05). The mean ADC of all cases of rFOVSTA DWI and rFOVDLR DWI was significantly lower than that of fFOV DWI (all p < 0.05). There was no difference in mean ADC value and the AUC for evaluating muscle invasion between rFOVSTA DWI and rFOVDLR DWI (p > 0.05). Conclusions: rFOV DWI with DLR can improve the diagnostic accuracy of fFOV DWI for evaluating muscle invasion. Applying DLR to rFOV DWI reduced the acquisition time and improved overall image quality while maintaining ADC value and diagnostic accuracy. Critical relevance statement: The diagnostic performance and image quality of full field-of-view DWI, reduced field-of-view (rFOV) DWI with and without DLR were compared. DLR would benefit the wide clinical application of rFOV DWI by reducing the acquisition time and improving the image quality. Key Points: Deep learning reconstruction (DLR) can reduce scan time and improve image quality. Reduced field-of-view (rFOV) diffusion-weighted imaging (DWI) with DLR showed better diagnostic performances than full field-of-view DWI. There was no difference of diagnostic accuracy between rFOV DWI with DLR and standard rFOV DWI. [ABSTRACT FROM AUTHOR]

Intravesical BacillusCalmette-Guérin (BCG) is a treatment for superficial bladder cancer. A mathematical model of pulsed BCG immunotherapy for superficial bladder cancer is considered. The mathematical model using impulsive differential equations is turned into a discrete-time dynamical system for bifurcation analysis. A numerical method is then proposed for identifying the fixed points and the bifurcations of the fixed points. One-parameter bifurcation diagrams are computed for showing fixed-point curves. Bistability exists in the model. Both tumor-free and high-tumor states are stable in a parameter range. The minimum dosage for successful treatment which depends on the initial tumor size and individual patient is determined. Two-parameter bifurcation diagrams are computed. The parameter domain is divided into regions for failure treatment, successful treatment of a tumor with a restricted initial size, and treatment with side-effect occurrence. It is believed that the numerical method proposed in this paper can be applied to a class of mathematical models of periodically pulsed drug therapies. [ABSTRACT FROM AUTHOR]

Background: Making healthcare treatment decisions is a complex process involving a broad stakeholder base including patients, their families, health professionals, clinical practice guideline developers and funders of healthcare. Methods: This paper presents a review of a methodology for the development of urological cancer care pathways (UCAN care pathways), which reflects an appreciation of this broad stakeholder base. The methods section includes an overview of the steps in the development of the UCAN care pathways and engagement with clinical content experts and patient groups. Results: The development process is outlined, the uses of the urological cancer care pathways discussed and the implications for clinical practice highlighted. The full set of UCAN care pathways is published in this paper. These include care pathways on localised prostate cancer, locally advanced prostate cancer, metastatic prostate cancer, hormone-resistant prostate cancer, localised renal cell cancer, advanced renal cell cancer, testicular cancer, penile cancer, muscle invasive and metastatic bladder cancer and non-muscle invasive bladder cancer. Conclusion: The process provides a useful framework for improving urological cancer care through evidence synthesis, research prioritisation, stakeholder involvement and international collaboration. Although the focus of this work is urological cancers, the methodology can be applied to all aspects of urology and is transferable to other clinical specialties. [ABSTRACT FROM AUTHOR]