Monopolar versus bipolar transurethral resection of bladder Tumour: post-hoc analysis of a prospective trial.

INTRODUCTION: Previously, in a randomised trial we demonstrated bipolar transurethral resection of bladder tumor (TURBT) could achieve a higher detrusor sampling rate than monopolar TURBT. We hereby report the long-term oncological outcomes following study intervention. METHODS: This is a post-hoc analysis of a randomized phase III trial comparing monopolar and bipolar TURBT. Only patients with pathology of non-muscle invasive bladder cancer (NMIBC) were included in the analysis. Per-patient analysis was performed. Primary outcome was recurrence-free survival (RFS). Secondary outcomes included progression-free survival (PFS), cancer-specific survival (CSS) and overall survival (OS). RESULTS: From the initial trial, 160 cases were randomised to receive monopolar or bipolar TURBT. 24 cases of non-urothelial carcinoma, 22 cases of muscle-invasive bladder cancer, and 9 cases of recurrences were excluded. A total of 97 patients were included in the analysis, with 46 in the monopolar and 51 in the bipolar group. The median follow-up was 97.1 months. Loss-to-follow-up rate was 7.2%. Regarding the primary outcome of RFS, there was no significant difference (HR = 0.731; 95%CI = 0.433-1.236; P = 0.242) between the two groups. PFS (HR = 1.014; 95%CI = 0.511-2.012; P = 0.969), CSS (HR = 0.718; 95%CI = 0.219-2.352; P = 0.584) and OS (HR = 1.135; 95%CI = 0.564-2.283; P = 0.722) were also similar between the two groups. Multifocal tumours were the only factor that was associated with worse RFS. CONCLUSION: Despite the superiority in detrusor sampling rate, bipolar TURBT was unable to confer long-term oncological benefits over monopolar TURBT.

Comparative study on the impact of remimazolam and sevoflurane on quality of recovery after transurethral resection of bladder tumor: A randomized controlled noninferiority study.

BACKGROUND: Remimazolam is manifested by rapid action, hemodynamic stability, and fast recovery. Our study aimed to investigate whether the quality of recovery (QoR) after remimazolam anesthesia in patients undergoing transurethral resection of bladder tumor, which is predominantly performed in the elderly population, is not inferior to that after conventional anesthesia using sevoflurane. METHODS: Thirty-four patients were randomly allocated into either of group S (n = 17, receiving sevoflurane anesthesia), or group R (n = 17, receiving remimazolam anesthesia). The QoR was assessed by Korean version of QoR-15 questionnaire, on the day before and after the surgery. Scores acquired for each individual item, QoR-15 scores categorized into 5 dimensions (physical comfort, physical independence, psychological support, emotional state, and pain), and overall global score were subjected to comparative analysis. The primary outcome was postoperative global QoR-15, and a noninferiority delta value of 8.0 was employed. RESULTS: The postoperative global QoR-15 in the group S was 141 (134-146), and in the groups R was 133 (128-142) (P = .152). The mean difference of global QoR-15 (group S-group R) was 1.471 (95% confidence interval of -10.204 to 13.146), and the lower 95% confidence interval margin was lower than the noninferiority margin of -8.0. When comparing the QoR-15 sorted by 5 dimensions, pain scored higher in the group S (20 [18-20]) compared to the group R (15 [15-20], P = .032). CONCLUSION: The postoperative QoR following transurethral resection of bladder tumor was found to be lower in patients anesthetized with remimazolam in comparison to those anesthetized with sevoflurane.

Rosiglitazone and trametinib exhibit potent anti-tumor activity in a mouse model of muscle invasive bladder cancer.

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.

CT and MRI features of sarcomatoid urothelial carcinoma of the bladder and its differential diagnosis with conventional urothelial carcinoma.

BACKGROUND: Sarcomatoid urothelial carcinoma (SUC) is a rare and highly malignant form of bladder cancer with a poor prognosis. Currently, there is limited information on the imaging features of bladder SUC and reliable indicators for distinguishing it from conventional urothelial carcinoma (CUC). The objective of our study was to identify the unique imaging characteristics of bladder SUC and determine factors that aid in its differential diagnosis. MATERIALS AND METHODS: This retrospective study enrolled 22 participants with bladder SUC and 61 participants with CUC. The clinical, pathologic, and CT/MRI data from both groups were recorded, and a comparison was conducted using univariate analysis and multinomial logistic regression for distinguishing SUC from CUC. RESULTS: The majority of SUCs were located in the trigone of the bladder and exhibited large tumor size, irregular shape, low ADC values, Vesical Imaging-Reporting and Data System (VI-RADS) score ≥ 4, the presence of necrosis, and an invasive nature. Univariate analysis revealed significant differences in terms of tumor location, shape, the maximum long-axis diameter (LAD), the short-axis diameter (SAD), ADC-value, VI-RADS scores, necrosis, extravesical extension (EVE), pelvic peritoneal spread (PPS), and hydronephrosis/ureteral effusion (p < .001 ~ p = .037) between SUCs and CUCs. Multinomial logistic regression found that only SAD (p = .014) and necrosis (p = .003) emerged as independent predictors for differentiating between SUC and CUC. The model based on these two factors achieved an area under curve (AUC) of 0.849 in ROC curve analysis. CONCLUSION: Bladder SUC demonstrates several distinct imaging features, including a high incidence of trigone involvement, large tumor size, and obvious invasiveness accompanied by necrosis. A bladder tumor with a large SAD and evidence of necrosis is more likely to be SUC rather than CUC.

[Several key and difficult issues related to the grading of urothelial carcinoma of urinary bladder].

Grading and staging are the most important prognostic factors for both non-invasive and invasive urothelial carcinomas, and are also one of the most common difficulties encountered by pathologists in the daily diagnostic practice of urothelial carcinoma. Recently, the International Society of Urological Pathology organized a survey and questionnaire conference on various issues related to the diagnosis, grading, and staging of urothelial carcinoma, and ultimately formed a series of consensus opinions. This article briefly summarizes the consensus opinions of this series, and combines them with the current pathological diagnosis status of urothelial carcinoma in China. It briefly comments on how to apply this series of consensus opinions in the daily diagnostic practice of pathologists, deeply understand relevant diagnostic problems, and carry out relevant clinical pathological research to further solve problems.

Cabazitaxel as a promising therapy for cisplatin-resistant bladder cancer: a preliminary study.

Bladder cancer is a common malignancy worldwide, posing a substantial healthcare challenge. Current standard treatment regimens are primarily based on cisplatin, but their success is often limited by cisplatin resistance and associated toxicities. Therefore, there is an urgent need to develop effective and less toxic therapies as alternatives to cisplatin. We screened the activity of FDA-approved anti-cancer drugs on a panel of cisplatin-resistant bladder cancer cell lines. Based on initial responses, cabazitaxel was selected for further evaluation of its inhibitory effects on the phenotypic properties of these cells. Cabazitaxel, primarily used for metastatic castration-resistant prostate cancer, demonstrated remarkable efficacy in inhibiting colony formation, proliferation, and migration of cisplatin-resistant bladder cancer cells. This study highlights the potential of drug repurposing as a cost-effective and efficient strategy to overcome drug resistance in bladder cancer.

Molecular findings and virological assessment of bladder papillomavirus infection in cattle.

Bovine and ovine papillomaviruses (BPVs - OaPVs) are infectious agents that have an important role in bladder carcinogenesis of cattle. In an attempt to better understand territorial prevalence of papillomavirus genotypes and gain insights into their molecular pathway(s), a virological assessment of papillomavirus infection was performed on 52 bladder tumors in cattle using droplet digital polymerase chain reaction (ddPCR), an improved version of conventional PCR. ddPCR detected and quantified BPV DNA and mRNAs in all tumor samples, showing that these viruses play a determinant role in bovine bladder carcinogenesis. OaPV DNA and mRNA were detected and quantified in 45 bladder tumors. BPV14, BPV13, BPV2, OaPV2, OaPV1, and OaPV3 were the genotypes most closely related to bladder tumors. ddPCR quantified BPV1 and OaPV4 DNA and their transcripts less frequently. Western blot analysis revealed a significant overexpression of the phosphorylated platelet derived growth factor ß receptor (PDGFßR) as well as the transcription factor E2F3, which modulate cell cycle progression in urothelial neoplasia. Furthermore, significant overexpression of calpain1, a Cys protease, was observed in bladder tumors related to BPVs alone and in BPV and OaPV coinfection. Calpain1 has been shown to play a role in producing free transcription factors of the E2F family, and molecular findings suggest that calpain family members work cooperatively to mutually regulate their protease activities in cattle bladder tumors. Altogether, these results showed territorial prevalence of BPV and OaPV genotypes and suggested that PDGFßR and the calpain system appeared to be molecular partners of both BPVs and OaPVs.

Advancing bladder cancer management: development of a prognostic model and personalized therapy.

Background: Bladder cancer (BLCA) was recognized as a significant public health challenge due to its high incidence and mortality rates. The influence of molecular subtypes on treatment outcomes was well-acknowledged, necessitating further exploration of their characterization and application. This study was aimed at enhancing the understanding of BLCA by mapping its molecular heterogeneity and developing a robust prognostic model using single-cell and bulk RNA sequencing data. Additionally, immunological characteristics and personalized treatment strategies were investigated through the risk score. Methods: Single-cell RNA sequencing (scRNA-seq) data from GSE135337 and bulk RNA-seq data from several sources, including GSE13507, GSE31684, GSE32894, GSE69795, and TCGA-BLCA, were utilized. Molecular subtypes, particularly the basal-squamous (Ba/Sq) subtype associated with poor prognosis, were identified. A prognostic model was constructed using LASSO and Cox regression analyses focused on genes linked with the Ba/Sq subtype. this model was validated across internal and external datasets to ensure predictive accuracy. High- and low-risk groups based on the risk score derived from TCGA-BLCA data were analyzed to examine their immune-related molecular profiles and treatment responses. Results: Six molecular subtypes were identified, with the Ba/Sq subtype being consistently associated with poor prognosis. The prognostic model, based on basal-squamous subtype-related genes (BSSRGs), was shown to have strong predictive performance across diverse clinical settings with AUC values at 1, 3, and 5 years indicating robust predictability in training, testing, and entire datasets. Analysis of the different risk groups revealed distinct immune infiltration and microenvironments. Generally higher tumor mutation burden (TMB) scores and lower tumor immune dysfunction and exclusion (TIDE) scores were exhibited by the low-risk group, suggesting varied potentials for systemic drug response between the groups. Finally, significant differences in potential systemic drug response rates were also observed between risk groups. Conclusions: The study introduced and validated a new prognostic model for BLCA based on BSSRGs, which was proven effective in prognosis prediction. The potential for personalized therapy, optimized by patient stratification and immune profiling, was highlighted by our risk score, aiming to improve treatment efficacy. This approach was promised to offer significant advancements in managing BLCA, tailoring treatments based on detailed molecular and immunological insights.

Single-Port Robot assisted partial cystectomy for urachal adenocarcinoma.

OBJECTIVE: We present a novel technique to perform single-port (SP) robot-assisted partial cystectomy with excision of the urachal remnant and bilateral pelvic lymph node dissection for urachal adenocarcinoma (1-7). MATERIALS AND METHODS: A 41-year-old male presented to the clinic for multiple episodes of hematuria and mucousuria. Office cystoscopy revealed a small solitary tumor at the dome of the bladder, with a diagnostic bladder biopsy revealing a tubule-villous bladder adenoma. Cross-sectional imaging of the chest/abdomen/pelvis revealed a 4.5 cm cystic mass arising from the urachus without evidence of local invasion and metastatic spread. He underwent SP robotic-assisted partial cystectomy with excision of the urachal remnant and bilateral pelvic lymph node dissection. Surgical steps include: 1) peritoneal incision to release the urachus and drop bladder 2) identification of urachal tumor 3) intraoperative live cystoscopic identification of bladder mass and scoring of tumor margins using Toggle Pro feature 4) tumor excision with partial cystectomy 5) cystorrhaphy 6) bilateral pelvic lymph node dissection 7) peritoneal interposition flap to mitigate lymphocele formation. RESULTS: Surgery was successful, with no intraoperative complications, an operative time of 100 minutes, and estimated blood loss of 20 mL. The patient was discharged on post-op day one, and the Foley catheter removed one week after surgery. Final pathology revealed a 7.5 cm infiltrating urachal muscle-invasive adenocarcinoma of the bladder (pT2b). Negative surgical margins were achieved. CONCLUSIONS: Single-port robot-assisted partial cystectomy for urachal adenocarcinoma is safe and can achieve equivalent oncologic outcomes to the standard of care with minimally invasive and open techniques.

Patient-derived bladder cancer organoids show stable transcript expression along cultivation.

INTRODUCTION: Bladder cancer (BC) is a prevalent malignancy with high recurrence rates. Patient-derived bladder cancer organoids (BCO) pose as a promising approach in both, disease modeling and individualized treatment screening. The aim of this study was to investigate the transcriptomic plasticity in BCOs as a function of cultivation times to define ideal time periods for the applications envisioned. METHODS: Tumor samples of three patients with pathologically confirmed non-muscle invasive and muscle-invasive bladder cancer were included in this study and expanded as BCOs. RNA expression was investigated at different time periods of cells in culture using differential gene expression for overall transcript expression and quantitative real-time PCR (qRT-PCR) for pathological relevant markers. RESULTS: Differential gene expression of the BCO lines was investigated across passages 1-4, in passages 5-9 and above 9, respectively. Analysis of the entire transcriptome of the respective BCO lines revealed consistent profiles without significant alterations throughout the cultivation and expansion procedure. Notably, key transcripts like TP53, PIK3CA, BRCA1, among others, exhibited stable expression levels in the quantitative RNA analysis during the cultivation period. CONCLUSION: The robust transcriptome during BCO cultivation advocates for the use of earlier passages of BCOs in personalized medicine providing a time-efficient drug screening option to accelerate the counseling of patients' treatment options. Higher passages of BCOs still hold the potential in topics demanding for expanded cell masses such as medical device development and others.

miR-182, miR-221 and miR-222 are potential urinary extracellular vesicle biomarkers for canine urothelial carcinoma.

Current diagnostic methods for canine urothelial carcinoma (UC) are technically challenging or can lack specificity, hence there is a need for novel biomarkers of UC. To this end, we analysed the microRNA (miRNA) cargo of extracellular vesicles (EVs) from urine samples of dogs with UC to identify candidate miRNA biomarkers. Urine was fractionated using ultrafiltration combined with size-exclusion chromatography and small RNA sequencing analysis was performed on both the EV enriched and (EV free) protein fractions. A greater number of candidate miRNA biomarkers were detected in the EV fraction than the protein fraction, and further validation using droplet digital PCR (ddPCR) was performed on the EV enriched fraction of a second cohort of dogs with UC which indicated that miR-182, miR-221 and miR-222 were significantly overrepresented in dogs with UC when compared with healthy dogs and dogs with urinary tract infections. Pathway analysis confirmed that these three miRNAs are involved in cancer. In addition, their potential downstream gene targets were predicted and PIK3R1, a well-known oncogene is likely to be a shared target between miRNA-182 and miRNA-221/222. In summary, this study highlights the potential of urinary EV-associated miRNAs as a source of biomarkers for the diagnosis of canine UC.

Psychological Impact of Bladder Cancer: Insights from 219 Patients and Caregivers in Indonesia Using DASS-21 (2019-2023).

BACKGROUND Bladder cancer (BC) is a common disease worldwide. Low survival rates and high recurrence lead to the risk of mental disorders. This study analyzed 219 patients with bladder cancer using the Indonesian Version of the 21-item Depression, Anxiety, and Stress Scale (DASS-21) and related factors. MATERIAL AND METHODS This cross-sectional study included 219 patients diagnosed with bladder cancer during 2019-2023 in a referral hospital in Indonesia. Data were collected using a questionnaire that assessed the characteristics of the patients and a DASS-21 questionnaire. RESULTS Some patients and caregivers experienced depression, stress, and anxiety. The percentage of caregivers who experienced anxiety was higher than for patients (47.9% vs 45.7%). Statistical analysis showed that age, income, and marital status were associated with the incidence of depression (p=0.000, p=0.001, and p=0.000, respectively), anxiety (p=0.000, p=0.012, and p=0.001, respectively), and stress (p=0.000, p=0.007, and p=0.000, respectively). Routes of patient admission (p=0.043, respectively) and employment status (p=0.005, respectively) were associated with the incidence of depression in patients (p=0.043, respectively). Employment status was also associated with stress in patients (p=0.038, respectively). Statistical analysis of caregivers found that routes of patient admission and marital status were related to the incidence of depression among caregivers (p=0.036 and p=0.007, respectively). CONCLUSIONS Monitoring and providing support for patients and caregivers are needed to prevent poor prognosis due to psychological problems, including paying attention to sociodemographic factors.

Mathematical Modeling of Tumor Immune Interactions: The Role of Anti-FGFR and Anti-PD-1 in the Combination Therapy.

Bladder cancer poses a significant global health burden with high incidence and recurrence rates. This study addresses the therapeutic challenges in advanced bladder cancer, focusing on the competitive mechanisms of ligand or drug binding to receptors. We developed a refined mathematical model that integrates the dynamics of tumor cells and immune responses, particularly targeting fibroblast growth factor receptor 3 (FGFR3) and immune checkpoint inhibitors (ICIs). This study contributes to understanding combination therapies by elucidating the competitive binding dynamics and quantifying the synergistic effects. The findings highlight the importance of personalized immunotherapeutic strategies, considering factors such as drug dosage, dosing schedules, and patient-specific parameters. Our model further reveals that ligand-independent activated-state receptors are the most essential drivers of tumor proliferation. Moreover, we found that PD-L1 expression rate was more important than PD-1 in driving the dynamic evolution of tumor and immune cells. The proposed mathematical model provides a comprehensive framework for unraveling the complexities of combination therapies in advanced bladder cancer. As research progresses, this multidisciplinary approach contributes valuable insights toward optimizing therapeutic strategies and advancing cancer treatment paradigms.

Results from a real-world study: a novel glycosyltransferase risk score for prognosis, tumor microenvironment phenotypes and immunotherapy in bladder cancer.

BACKGROUND: Although immunotherapy shows tremendous potential in the treatment of bladder cancer (BLCA), the overall prognosis and response rates to immunotherapy in BLCA remain suboptimal. METHODS: We performed an extensive evaluation of glycosyltransferase expression patterns in BLCA patients by analyzing 210 glycosyltransferase-related genes. Subsequently, we established correlations between these glycosyltransferase patterns, prognosis, and tumor microenvironment (TME) phenotypes. To offer personalized patient assessments, we developed a glycosyltransferase risk score that accurately predicts prognosis, TME phenotypes, and molecular subtypes. Importantly, we developed a RNA-seq cohort, named Xiangya cohort, to validate our results. RESULTS: Two distinct patterns of glycosyltransferase expression were identified, corresponding to inflamed and noninflamed TME phenotypes, and demonstrated the potential to predict prognosis. We developed and validated a comprehensive risk score that accurately predicted individual patient prognosis in the TCGA-BLCA cohort. Additionally, we constructed a nomogram that integrated the risk score with several key clinical factors. Importantly, this risk score was successfully validated in external cohorts, including the Xiangya cohort and GSE48075. Furthermore, we discovered a positive correlation between this risk score and tumor-infiltrating lymphocytes in both the TCGA-BLCA and Xiangya cohorts, suggesting that patients with a higher risk score exhibited an inflamed TME phenotype and were more responsive to immunotherapy. Finally, we observed that the high and low risk score groups were consistent with the luminal and basal subtypes of BLCA, respectively, providing further validation of the risk score's role in the TME in terms of molecular subtypes. CONCLUSIONS: Glycosyltransferase patterns exhibit distinct TME phenotypes in BLCA. Our comprehensive risk score provides a promising approach for prognostic prediction and assessment of immunotherapy efficacy, offering valuable guidance for precision medicine.

Tranexamic acid reduces perioperative blood transfusions following open radical cystectomy - a propensity-score matched analysis.

PURPOSE: Radical cystectomy is associated with bleeding and high transfusion rates, presenting challenges in patient management. This study investigated the prophylactic use of tranexamic acid during radical cystectomy. METHODS: All consecutive patients treated with radical cystectomy at a tertiary care university center were included from a prospectively maintained database. After an institutional change in the cystectomy protocol patients received 1 g of intravenous bolus of tranexamic acid as prophylaxis. To prevent bias, propensity score matching was applied, accounting for differences in preoperative hemoglobin, neoadjuvant chemotherapy, tumor stage, and surgeon experience. Key outcomes included transfusion rates, complications, and occurrence of venous thromboembolism. RESULTS: In total, 420 patients were included in the analysis, of whom 35 received tranexamic acid. After propensity score matching, 32 patients and 32 controls were matched with regard to clinicopathologic characteristics. Tranexamic acid significantly reduced the number of patients who received transfusions compared to controls (19% [95%-Confidence interval = 8.3; 37.1] vs. 47% [29.8; 64.8]; p = 0.033). Intraoperative and postoperative transfusion rates were lower with tranexamic acid, though not statistically significant (6% [1.5; 23.2] vs. 19% [8.3; 37.1], and 16% [6.3; 33.7] vs. 38% [21.9; 56.1]; p = 0.257 and p = 0.089, respectively). The occurrence of venous thromboembolism did not differ significantly between the groups (9% [2.9; 26.7] vs. 3% [0.4; 20.9]; p = 0.606). CONCLUSION: Prophylactic tranexamic administration, using a simplified preoperative dosing regimen of 1 g as a bolus, significantly lowered the rate of blood transfusion after cystectomy. This exploratory study indicates the potential of tranexamic acid in enhancing outcomes of open radical cystectomy.

Do we need a re-TUR after en bloc resection of T1 stage bladder cancer?

BACKGROUND: A second look trans-urethral resection of the bladder (re-TUR) is recommended after the diagnosis of T1 high grade (T1HG) bladder cancer. Few studies have evaluated the results of re-TUR after a first en bloc resection (EBR) and none of them have specifically reported the pathological results on the field of previous T1 disease. OBJECTIVE: To report the rate of upstaging and the rate of residual disease (RD) on the field of T1HG lesions resected with EBR. MATERIALS AND METHODS: Between 01/2014 and 06/2022, patients from 2 centers who had a re-TUR after an EBR for T1HG urothelial carcinoma were retrospectively included. Primary endpoint was the rate of RD including the rate of upstaging to T2 disease on the scar of the primary resection. Secondary endpoints were the rate of any residual disease outside the field. RESULTS: Seventy-five patients were included. No muscle invasive bladder cancer lesions were found after re-TUR. Among the 16 patients who had a RD, 4 were on the resection scar. All of these lesions were papillary and high grade. RD outside the field of the first EBR was observed in 12 patients. CONCLUSION: After EBR of T1HG disease, none of our patients had an upstaging to MIBC. However, the rate of RD either on and outside the field of the EBR remains quite significant. We suggested that predictive factors of residual papillary disease (number of tumors at the initial TUR and concomitant CIS) might be suitable to select patient who will benefit of the re-TUR.