MRI evaluation of vesical imaging reporting and data system for bladder cancer after neoadjuvant chemotherapy.

BACKGROUND: The Vesical Imaging-Reporting and Data System (VI-RADS) has demonstrated effectiveness in predicting muscle invasion in bladder cancer before treatment. The urgent need currently is to evaluate the muscle invasion status after neoadjuvant chemotherapy (NAC) for bladder cancer. This study aims to ascertain the accuracy of VI-RADS in detecting muscle invasion post-NAC treatment and assess its diagnostic performance across readers with varying experience levels. METHODS: In this retrospective study, patients with muscle-invasive bladder cancer who underwent magnetic resonance imaging (MRI) after NAC from September 2015 to September 2018 were included. VI-RADS scores were independently assessed by five radiologists, consisting of three experienced in bladder MRI and two inexperienced radiologists. Comparison of VI-RADS scores was made with postoperative histopathological diagnosis. Receiver operating characteristic curve analysis (ROC) was used for evaluating diagnostic performance, calculating sensitivity, specificity, and area under ROC (AUC)). Interobserver agreement was assessed using the weighted kappa statistic. RESULTS: The final analysis included 46 patients (mean age: 61 years ± 9 [standard deviation]; age range: 39-70 years; 42 men). The pooled AUC for predicting muscle invasion was 0.945 (95% confidence interval (CI): 0.893-0.977) for experienced readers, and 0.910 (95% CI: 0.831-0.959) for inexperienced readers, and 0.932 (95% CI: 0.892-0.961) for all readers. At an optimal cut-off value ≥ 4, pooled sensitivity and specificity were 74.1% (range: 66.0-80.9%) and 94.1% (range: 88.6-97.7%) for experienced readers, and 63.9% (range: 59.6-68.1%) and 86.4% (range: 84.1-88.6%) for inexperienced readers. Interobserver agreement ranged from substantial to excellent between all readers (k = 0.79-0.92). CONCLUSIONS: VI-RADS accurately assesses muscle invasion in bladder cancer patients after NAC and exhibits good diagnostic performance across readers with different experience levels.

Stromal osseous metaplasia in urothelial carcinoma of the bladder: An unusual and challenging feature. A case report.

A 62-year-old male presented with pain and haematuria starting 3 months before. The computed tomography showed focal and mural bladder thickening with ureteropelvic dilatation. The following transurethral bladder resection revealed a high-grade muscle-invasive urothelial carcinoma. In the subsequent cystoprostatectomy we found the same tumour, but adding focal tumour-associated stromal osseous metaplasia. Ossifying metaplasia is an extremely rare feature in urothelial carcinoma, with a few reported cases and represents a diagnostic challenge, mimicking radiotherapy-induced sarcoma or sarcomatoid carcinoma.

Expression of Cyclin D1 in Urothelial Carcinoma of Urinary Bladder and its Association with Tumour Grade.

Urothelial carcinoma (UC) is the most common malignancy of urinary bladder. It is the 9th leading cause of death worldwide and second most common genitourinary malignancy among male. Incidence is increasing in developing countries like Bangladesh. About 80% of patients are found between 50 to 80 years of age. It is 3-4 times more common in male than in female. Determination of therapeutic strategy and prediction of progression of urothelial carcinoma is a major clinical challenge. Treatment of urothelial carcinoma still now mostly depends on pathological stages. Amplification or genomic alteration of Cyclin D1 (a proto-oncogene) may cause protein overexpression which is frequently realized as a clonal pathology in various human neoplasms including bladder cancer. Evaluation of Cyclin D1 expression is promising for guiding therapeutic strategies, risk stratification and prediction of tumor progression. The aim of the study was to determine the expression of Cyclin D1 in urothelial carcinoma of urinary bladder and its association with tumour grade. This cross-sectional observational study was conducted in Department of Pathology, Dhaka Medical College, Dhaka, Bangladesh from July 2019 to June 2021. Histomorphologically diagnosed 51 urothelial carcinomas were included. Sections were stained with hematoxylin and eosin. Immunostaining with Cyclin D1 antibody was also done. Relevant information was collected and recorded in a predesigned data sheet. Statistical analysis was carried out as required. Mean age ±SD was 57.8±10.55 years. Male female ratio was 4.6:1. In this study 39(76.5%) patients were smoker. Regarding clinical presentations 36(70.6%) patients presented with painless hematuria alone. Lateral wall (64.7%) was the most frequent tumor location. Among 51 cases, 38(74.5%) cases were high grade urothelial carcinoma (HGUC) and 13(25.5%) cases were low grade urothelial carcinoma (LGUC). Considering Cyclin D1 expression, most of the LGUC cases showed high level of expression by both percentage (84.6%) and intensity (84.6%). Most of the HGUC cases showed low level of expression by both percentage (63.2%) and intensity (60.5%). Cyclin D1 showed significant inverse association with HGUC (p<0.05). In urothelial carcinoma of urinary bladder, Cyclin D1 expression was decreased with increasing grade of the tumor. Cyclin D1 expression was inversely associated with tumour grade.

Clinical performance and utility of a noninvasive urine-based methylation biomarker: TWIST1/Vimentin to detect urothelial carcinoma of the bladder.

Traditional clinical modalities for diagnosing bladder urothelial carcinoma (BUC) remain limited due to their invasive nature, significant costs, discomfort associated with cystoscopy, and low sensitivity to urine cytology. Therefore, there is an urgent need to identify highly sensitive, specific, and noninvasive biomarkers for the early detection of this neoplasm. Hypermethylated TWIST1/Vimentin promoter may be a noninvasive biomarker using urine sample. We assessed the TWIST1/Vimentin promoter methylation status in urine samples using the Methylated Human TWIST1 and Vimentin Gene Detection Kit (Jiangsu MicroDiag Biomedicine Co., Ltd., China). The samples were collected from five groups: group 1 consisted of patients with BUC, group 2 contained other patients with urologic tumors, group 3 consisted of patients with benign diseases (e.g., urinary tract infections, lithiasis, and benign prostatic hyperplasia), Group 4 included UTUC (upper tract urothelial carcinoma) patients and group5 comprised healthy individuals. The study encompassed 77 BUC patients, and we evaluated the degree of methylation of the TWIST1/Vimentin gene in their urine samples. Notably, TWIST1/Vimentin positivity was significantly elevated in comparison to groups 2, 3 and 5 (all p < 0.001) at a rate of 77.9%, but no significant difference was observed when compared to group 4. In the relationship between TWIST1/Vimentin methylation and clinicopathological features of BC patients from our center, we found there was no significant association between TWIST1/Vimentin status and proteinuria and/or hematuria, and hypermethylation of TWIST1 / VIM genes was found in both high and low tumor grade and in both non-muscle invasive bladder cancer (stages Tis, Ta, or T1) and muscle-invasive bladder cancer (stage T2 or above). In the multivariable analysis for cancer detection, a positive TWIST1/Vimentin methylation were significantly linked to a heightened risk of BC. Moreover, TWIST1/Vimentin promoter methylation demonstrated an ability to detect BUC in urine samples with a sensitivity of 78% and a specificity of 83%. Our findings reveal that hypermethylation of the TWIST1/Vimentin promoter occurs in bladder urothelial carcinoma, and its high sensitivity and specificity suggest its potential as a screening and therapeutic biomarker for urothelial carcinoma of the bladder.

A paclitaxel-hyaluronan conjugate (ONCOFID-P-B™) in patients with BCG-unresponsive carcinoma in situ of the bladder: a dynamic assessment of the tumor microenvironment.

BACKGROUND: The intravesical instillation of the paclitaxel-hyaluronan conjugate ONCOFID-P-B™ in patients with bacillus Calmette-Guérin (BCG)-unresponsive bladder carcinoma in situ (CIS; NCT04798703 phase I study), induced 75 and 40% of complete response (CR) after 12 weeks of intensive phase and 12 months of maintenance phase, respectively. The aim of this study was to provide a detailed description of the tumor microenvironment (TME) of ONCOFID-P-B™-treated BCG-unresponsive bladder CIS patients enrolled in the NCT04798703 phase I study, in order to identify predictive biomarkers of response. METHODS: The composition and spatial interactions of tumor-infiltrating immune cells and the expression of the most relevant hyaluronic acid (HA) receptors on cancer cells, were analyzed in biopsies from the 20 patients enrolled in the NCT04798703 phase I study collected before starting ONCOFID-P-B™ therapy (baseline), and after the intensive and the maintenance phases. Clinical data were correlated with cell densities, cell distribution and cell interactions. Associations between immune populations or HA receptors expression and outcome were analyzed using univariate Cox regression and log-rank analysis. RESULTS: In baseline biopsies, patients achieving CR after the intensive phase had a lower density of intra-tumoral CD8+ cytotoxic T lymphocytes (CTL), but also fewer interactions between CTL and macrophages or T-regulatory cells, as compared to non-responders (NR). NR expressed higher levels of the HA receptors CD44v6, ICAM-1 and RHAMM. The intra-tumoral macrophage density was positively correlated with the expression of the pro-metastatic and aggressive variant CD44v6, and the combined score of intra-tumoral macrophage density and CD44v6 expression had an AUC of 0.85 (95% CI 0.68-1.00) for patient response prediction. CONCLUSIONS: The clinical response to ONCOFID-P-B™ in bladder CIS likely relies on several components of the TME, and the combined evaluation of intra-tumoral macrophages density and CD44v6 expression is a potentially new predictive biomarker for patient response. Overall, our data allow to advance a potential rationale for combinatorial treatments targeting the immune infiltrate such as immune checkpoint inhibitors, to make bladder CIS more responsive to ONCOFID-P-B™ treatment.

Diagnostic value of urine cyclic RNA-0071196 for bladder urothelial carcinoma.

OBJECTIVE: To investigate the diagnostic value of urine cyclic RNA-0071196 (circRNA-0071196) in the patients with bladder urothelial carcinoma (BUC). METHOD: The expression of circRNA-0071196 was detected in the urine samples using qRT-PCR from 40 BUC patients and 30 non-UBC patients at our department from December 2018 to September 2021. The expression difference of circRNA-0071196 was compared between the two groups, and the relationship between the expression of circRNA-0071196 in the urine of UBC patients and the clinical pathological characteristics was analyzed. RESULTS: (1) The expression of circRNA-0071196 in the urine of BUC group was significantly higher than that in the non-BUC group (P < 0.05). (2) The expression of circRNA-0071196 in the urine of BUC group was not related to age, sex, or lymph node metastasis (P > 0.05). (3) The expression of circRNA-0071196 in the urine of BUC group was related to tumor T stage, tumor grade and muscle invasion. (4) The urine circRNA-0071196 expression effectively distinguished BUC patients from non-BUC patients. CONCLUSION: The elevated expression of urine circRNA-0071196 in BUC patients indicates that circRNA-0071196 has promising potential as a non-invasive urinary biomarker for detecting BUC.

Expression of BCL2, TP53, FOXA1, and GATA3 in pTa bladder cancer recurrence.

OBJECTIVES: In this study, we analyzed pTa bladder cancer (BC) for molecular markers BCL2, TP53, FOXA1, and GATA3 in relation to cancer recurrence. METHODS: We analyzed samples of 79 patients with the pTa stage of BC using a real-time polymerase chain reaction (real-time PCR) between September 2018 and September 2020. The expression levels of BCL2, TP53, FOXA1, and GATA3 were compared with homologous non-tumor bladder tissue. RESULTS: Expression of FOXA1, GATA3, and TP53 was significantly higher (p<0.01) in NMIBC samples compared to homologous non-tumor tissue. The expression of TP53 and FOXA1 in pTa was significantly lower (p<0.01) in the high-grade (HG) tumor when compared to the low-grade (LG) tumor. In contrast, the relative quantification (RQ) of GATA3 was significantly higher (p<0.01) in HG pTa. Patients with recurrence (pTa=33) had significantly higher expression of TP53, and GATA3 (p<0.01), and the gene of FOXA1 (p<0.01) had a significantly lower expression when compared to pTa tumors without recurrence. The expression of Bcl-2 was not statistically significant. CONCLUSION: Our results, indicate, that comparing expression levels of these genes in cancer and cancer-free tissue could provide valuable data, as patients with pTa BC recurrence within up to 54 months of follow-up had a significantly higher RQ of TP53, GATA3, and FOXA1 when compared to pTa BC patients without recurrence (Tab. 2, Fig. 8, Ref. 54). Text in PDF www.elis.sk Keywords: bladder cancer, gene expression, recurrence, GATA3, FOXA1, TP53, BCL2.

Challenges and technical aspects in the management of muscle invasive bladder cancer as retrograde radical cystectomy with ileal conduit.

Objective: To evaluate long-term outcomes in patients homogenously treated with radical cystectomy and ileal conduit for muscle invasive bladder cancer. METHODS: The retrospective study was conducted at the Urology Department of Pakistan Kidney and Liver Institute and Research Centre, Lahore, Pakistan, and comprised data from December 25, 2017, to January 16, 2023, related to patients who underwent radical cystectomy with ileal conduit with or without neo-adjuvant and adjuvant radiation, chemotherapy, or immunotherapy for papillary urothelial carcinom of the bladder. Clinical trajectory, histopathological characteristics and long-term clinical outcomes were noted. Data was analysed using SPSS 20. RESULTS: In our study of 40 patients with muscle invasive bladder cancer, males predominated (32, 80%), with a median age of 57.4 years (IQR: 29-80). Diagnosis was early in 5 (12.5%) patients with varying haematuria durations, while 34 (85%) patients had a smoking history. Comorbidities included hypertension in 17 (42.5%) patients, diabetes in 1 (2.5%) patient, both hypertension and diabetes in 9 (22.5%) patients and a combination of hypertension, diabetes, and ischaemic heart disease in 3 (7.5%) patients. Transurethral resection was performed once in 13 (32.5%) patients and multiple times in 27 (67.5%) patients. Additionally, 5 (12.5%) patients received immunotherapy, 11 (27.5%) patients underwent non-adjuvant radiation, and 14 (35%) patients received non-adjuvant chemotherapy. Papillary urothelial carcinoma was the predominant histological subtype among 37 (92.5%) patients. Patients receiving chemotherapy had significantly better overall survival (p=0.02). No significant differences were noted in recurrence or survival by therapy modality (p>0.05). These findings highlight the significance of early diagnosis, tailored treatments, and comorbidity management in muscle invasive bladder cancer patients. Age stratification revealed significant survival differences across groups (χ²=10.923, df=3, p= 0.012). Analysis by complications did not show age-related survival variations (χ² =3.978, df = 3, p=0.264). Conclusion: Achieving excellent long-term survival in MIBC patients requires a multidisciplinary approach, emphasizing early diagnosis, tailored treatment, and adherence to guidelines and protocols.

Paraganglioma of the urinary bladder: A case report.

It is very un comm on to discover Paraga ngliomas in the uri nar y bladder. Thes e tu mo ur s origina te from the sympathetic nerves which supp ly chromaffin cells in the bladde r wall. They can be classified as functional or nonfunctional. If functional, the most common presentations are with hypertensive crisis or post-micturition syncope. A si lent pa raganglioma of th e bl adder ca n be easily m isdiagnosed w hich can resu lt in severe pe ri- oper ative morbidity. We pre sent a ca se of a male pati ent who was being m a naged fo r hype rt ension for 2-3 ye ars. He presented at The Indus Hospital, Karachi o n 7th August 2022 with gross painless haematuria. An ultrasound scan revealed an echogenic lesion aris ing from base of the urinar y bladder, wh ic h was trea ted via Transurethral Resection o f Bladde r Tumour (TURBT). Histopathological report revealed Paraganglioma of the Bladder. He was later scheduled for Partial Cystectomy (PC) and has been doing well ever since.

Determining the clinicopathological significance of the VI-RADS ≧4 group: a retrospective study.

BACKGROUND: The Vesical Imaging Reporting and Data System (VI-RADS) is widely used for predicting muscle-invasive bladder cancer (MIBC). This study aimed to determine the clinicopathological significance of the VI-RADS ≧4 (VI≧4) group. METHODS: Patients who underwent transurethral resections of bladder tumors during the study period and preoperative magnetic resonance imaging were considered. The patients were pathologically diagnosed with urothelial carcinoma (UC). We first compared the results of patients with VI-RADS scores of 3 and 4 to determine the cut-off score for MIBC; thereafter, the patients were divided into the VI≧4 and VI-RADS ≦3 (VI≦3) groups using VI-RADS. The clinicopathological significance of the VI≧4 group was examined retrospectively by comparing the characteristics of each group. RESULTS: In total, 121 cases were examined, of which 28 were pathologically diagnosed with MIBC. Of the 28 MIBC cases, three (10.7%) had a VI-RADS score of ≦3, and 25 (89.3%) had a VI-RADS score of ≧4. Of the 93 NMIBC cases, 86 (92.5%) had a VI-RADS score of ≦3, and seven (7.5%) had a VI-RADS score of ≧4. The diagnostic performance of the VI-RADS with a cut-off score of 4 was 89.3% for sensitivity, 92.5% for specificity, and an area under the curve (AUC) of 0.91. Contrastingly, for a cut-off score of 3, the sensitivity was 89.3%, specificity was 62.0%, and AUC was 0.72. A VI-RADS score of ≥ 4 could predict MIBC. In the VI≧4 group, 30 of 32 (93.8%) patients had high-grade tumors. The VI≧4 group had significantly more high-grade bladder cancers than the VI≦3 group (p < 0.001 OR = 31.77 95%CI:8.47-1119.07). In addition, the VI≧4 group had more tumor necrosis (VI≧4 vs VI≦3, p < 0.001 OR = 7.46 95%CI:2.61-21.34) and more UC variant cases (VI≧4 vs VI≦3, p = 0.034 OR = 3.28 95%CI:1.05-10.25) than the VI≦3 group. CONCLUSIONS: This study suggests that VI-RADS has a high diagnostic performance in predicting MIBC and that VI-RADS could diagnose high-grade tumors, necrosis, and UC variants.

[Exploration of the method and efficacy of treatments for intractable pelvic pain caused by rectal or bladder fistula].

Objective: To explore the causes and therapeutic effects of pelvic pain caused by rectal fistula or bladder fistula after comprehensive treatment of cervical cancer and rectal cancer (radiotherapy, surgery, chemotherapy, and other treatments). Methods: A retrospective analysis was conducted on the clinical and pathological data of patients with pelvic tumors admitted to the First People's Hospital of Yinchuan City, Ningxia and the Affiliated Cancer Hospital of Zhengzhou University from June 2016 to June 2022. The causes of persistent pelvic pain in patients after comprehensive treatment was investigated, and the corresponding therapeutic effects after clinical treatment was observed. Results: Thirty-two tumor patients experienced persistent pain after comprehensive treatment, including 22 cases of cervical cancer and 10 cases of rectal cancer. The preoperative pain of the entire group of patients was evaluated using the digital grading method, with a pain score of (7.88±1.31) points. Among the 32 patients, there were 16 cases of rectovaginal fistula or ileovaginal fistula, 9 cases of vesicovaginal fistula, 5 cases of rectoperineal fistula, and 2 cases of vesicovaginorectal fistula. Thirty-two patients were initially treated with medication to relieve pain, and according to the ruptured organs, a fistula was made to the corresponding proximal intestinal canal and renal pelvis to intercept the intestinal contents and urine. However, the pain did not significantly be improved. The pain score of treatment with the above methods for one week was (8.13±1.13) points, and there was no statistically significant difference compared to preoperative treatment (P=0.417). In the later stage, based on a comprehensive evaluation of whether the tumor had recurred, the value of organ preservation, the benefits of surgery, the balance between survival time and improving quality of life, pathological organ resection or repair was performed. The surgical methods included repair of leaks, local debridement combined with irrigation of proximal intestinal fluid, distal closure of the sigmoid colon combined with proximal ostomy, posterior pelvic organ resection, anterior pelvic organ resection, and total pelvic organ resection. One week after surgery, the patients' pain completely relieved or disappeared, with the pain score of (1.72±1.37) points, which was significantly divergent from the preoperative and initial surgical treatments (P＜0.001). Conclusions: Palliative pyelostomy and proximal enterostomy cannot effectively alleviate persistent pelvic floor pain. The fundamental way to alleviate pain is complete blocking of the inflammatory erosion of the intestinal fluid and urine.

Quantitative differentiation of non-invasive bladder urothelial carcinoma and inverted papilloma based on CT urography.

PURPOSE: To investigate the value of CT urography (CTU) indicators in the quantitative differential diagnosis of bladder urothelial carcinoma (BUC) and inverted papilloma of the bladder (IPB). MATERIAL AND METHODS: The clinical and preoperative CTU imaging data of continuous 103 patients with histologically confirmed BUC or IPB were retrospectively analyzed. The imaging data included 6 qualitative indicators and 7 quantitative measures. The recorded clinical information and imaging features were subjected to univariate and multivariate logistic regression analysis to find independent risk factors for BUC, and a combined multi-indicator prediction model was constructed, and the prediction model was visualized using nomogram. ROC curve analysis was used to calculate and compare the predictive efficacy of independent risk factors and nomogram. RESULTS: Junction smoothness, maximum longitudinal diameter, tumor-wall interface and arterial reinforcement rate were independent risk factors for distinguishing BUC from IPB. The AUC of the combined model was 0.934 (sensitivity = 0.808, specificity = 0.920, accuracy = 0.835), and its diagnostic efficiency was higher than that of junction smoothness (AUC=0.667, sensitivity = 0.654, specificity = 0.680, accuracy = 0.660), maximum longitudinal diameter (AUC=0.757, sensitivity = 0.833, specificity = 0.604, accuracy = 0.786), tumor-wall interface (AUC=0.888, sensitivity = 0.755, specificity = 0.808, accuracy = 0.816) and Arterial reinforcement rate (AUC=0.786, sensitivity = 0.936, specificity = 0.640, accuracy = 0.864). CONCLUSION: Above qualitative and quantitative indicators based on CTU and the combination of them may be helpful to the differential diagnosis of BUC and IPB, thus better assisting in clinical decision-making. KEY POINTS: 1. Bladder urothelial carcinoma (BUC) and inverted papilloma of the bladder (IPB) exhibit similar clinical symptoms and imaging presentations. 2. The diagnostic value of CT urography (CTU) in distinguishing between BUC and IPB has not been documented. 3. BUC and IPB differ in lesion size, growth pattern and blood supply. 4. The diagnostic efficiency is optimized by integrating multiple independent risk factors into the prediction model.

Identification of Molecular Mechanisms in Radiation Cystitis: Insights from RNA Sequencing.

Pelvic cancer survivors who were treated with radiation therapy are at risk for developing (hemorrhagic) radiation cystitis (RC) many years after completion of radiation therapy. Patients with RC suffer from lower urinary tract symptoms, including frequency, nocturia, pelvic pain, and incontinence. In advanced stages, hematuria can occur, potentially escalating to life-threatening levels. Current therapeutic options for RC are limited, partly due to ethical concerns regarding bladder biopsy in patients with fragile bladder tissue. This study aimed to leverage our established preclinical model to elucidate the molecular pathways implicated in radiation-induced tissue changes in the bladder. Female C57Bl/6 mice received a single dose of 40 Gy using CT-guided imaging and a two-beam irradiation approach using the SARRP irradiator. Bladders from irradiated and age-matched littermate controls were harvested at 1 week [n = 5/group] or 6 months [n = 5/group] after irradiation, RNA was harvested, and mRNA sequencing was performed at paired-end 150bp on the Illumina NovaSeq6000 with a target of 30 million reads per sample. Following RNA sequencing, thorough bioinformatics analysis was performed using iPathwayGuide v2012 (ADVAITA Bioinformatics). Findings of the RNA sequencing were validated using qPCR analysis. At 1 week post-irradiation, altered gene expression was detected in genes involved in DNA damage response, apoptosis, and transcriptional regulation. By 6 months post-irradiation, significant changes in gene expression were observed in inflammation, collagen catabolism, and vascular health. Affected pathways included the p53, JAK-STAT, and PI3K-Akt pathways. These findings were validated in vivo in bladder tissues from our preclinical model. This is the first study to determine the molecular changes in the bladder in response to radiation treatment. We have successfully pinpointed several pathways and specific genes that undergo modification, thereby contributing to the progression of radiation cystitis. These insights enhance our understanding of the pathophysiology of radiation cystitis and may ultimately pave the way to the identification of potential new therapeutic targets.

TROP-2, NECTIN-4 and predictive biomarkers in sarcomatoid and rhabdoid bladder urothelial carcinoma.

Introduction: The surface protein TROP-2/TACSTD2 and the cell adhesion protein NECTIN-4/NECTIN4 are responsible for the efficacy of anticancer therapies based on antibody-drug conjugates (ADC) targeting intracellular microtubules. In contrast with common histologic subtypes of bladder urothelial carcinoma (BUC), little is known of TROP-2 and NECTIN-4 expression in sarcomatoid and rhabdoid BUC. Aims: In this study, we aimed to analyze TROP-2 and NECTIN-4 expression and additional predictive biomarkers by immunohistochemistry and fluorescence in situ hybridization (FISH) on 35 undifferentiated BUC (28 sarcomatoid and 7 rhabdoid). Wide genomic investigation was also performed on 411 BUC cases of the PanCancer Atlas, focusing on genes related to the microtubule pathways. Results: Seven of 35 (20%) undifferentiated BUC showed expression of TROP-2. NECTIN-4 was expressed in 10 cases (29%). Seven cases (20%) co-expressed TROP-2 and NECTIN-4. HER-2 FISH was amplified in 5 cases (14%) while HER-2 immunoexpression was observed in 14 cases (40%). PD-L1 scored positive for combined proportion score (CPS) in 66% of cases and for tumor proportion score (TPS) in 51% of cases. Pan-NTRK1-2/3 was elevated in 9 cases (26%) and FGFR-2/3 was broken in 7 of 35 cases (20%). Of 28 sarcomatoid BUC, 9 (32%) were negative for all (TROP-2, NECTIN-4, PD-L1, HER-2, FGFR and pan-NTRK) biomarkers and 3 (11%) expressed all five biomarkers. Among cases with rhabdoid dedifferentiation, 1 of 7 (14%) showed activation of all biomarkers, whereas 2 of 7 (28%) showed none. The mRNA analysis identified microtubule-related genes and pathways suitable for combined ADC treatments in BUC. Conclusion: Sarcomatoid and rhabdoid BUC do harbor positive expression of the ADC targets TROP-2 or NECTIN-4 in a relatively modest subset of cases, whereas the majority do not. Different combinations of other positive biomarkers may help the choice of medical therapies. Overall, these findings have important clinical implications for targeted therapy for BUC.

Unmasking the Metabolite Signature of Bladder Cancer: A Systematic Review.

Bladder cancer (BCa) research relying on Omics approaches has increased over the last few decades, improving the understanding of BCa pathology and contributing to a better molecular classification of BCa subtypes. To gain further insight into the molecular profile underlying the development of BCa, a systematic literature search was performed in PubMed until November 2023, following the PRISMA guidelines. This search enabled the identification of 25 experimental studies using mass spectrometry or nuclear magnetic resonance-based approaches to characterize the metabolite signature associated with BCa. A total of 1562 metabolites were identified to be altered by BCa in different types of samples. Urine samples displayed a higher likelihood of containing metabolites that are also present in bladder tumor tissue and cell line cultures. The data from these comparisons suggest that increased concentrations of L-isoleucine, L-carnitine, oleamide, palmitamide, arachidonic acid and glycoursodeoxycholic acid and decreased content of deoxycytidine, 5-aminolevulinic acid and pantothenic acid should be considered components of a BCa metabolome signature. Overall, molecular profiling of biological samples by metabolomics is a promising approach to identifying potential biomarkers for early diagnosis of different BCa subtypes. However, future studies are needed to understand its biological significance in the context of BCa and to validate its clinical application.

Aberrantly Glycosylated GLUT1 as a Poor Prognosis Marker in Aggressive Bladder Cancer.

Muscle-invasive bladder cancer (MIBC) remains a pressing health concern due to conventional treatment failure and significant molecular heterogeneity, hampering the development of novel targeted therapeutics. In our quest for novel targetable markers, recent glycoproteomics and bioinformatics data have pinpointed (glucose transporter 1) GLUT1 as a potential biomarker due to its increased expression in tumours compared to healthy tissues. This study explores this hypothesis in more detail, with emphasis on GLUT1 glycosylation patterns and cancer specificity. Immunohistochemistry analysis across a diverse set of human bladder tumours representing all disease stages revealed increasing GLUT1 expression with lesion severity, extending to metastasis, while remaining undetectable in healthy urothelium. In line with this, GLUT1 emerged as a marker of reduced overall survival. Revisiting nanoLC-EThcD-MS/MS data targeting immature O-glycosylation on muscle-invasive tumours identified GLUT1 as a carrier of short glycosylation associated with invasive disease. Precise glycosite mapping uncovered significant heterogeneity between patient samples, but also common glycopatterns that could provide the molecular basis for targeted solutions. Immature O-glycosylation conferred cancer specificity to GLUT1, laying the molecular groundwork for enhanced targeted therapeutics in bladder cancer. Future studies should focus on a comprehensive mapping of GLUT1 glycosites for highly specific cancer-targeted therapy development for bladder cancer.

Mild magnetic hyperthermia-activated immuno-responses for primary bladder cancer therapy.

Surgical intervention followed by chemotherapy is the principal treatment strategy for bladder cancer, which is hindered by significant surgical risks, toxicity from chemotherapy, and high rates of recurrence after surgery. In this context, a novel approach using mild magnetic hyperthermia therapy (MHT) for bladder cancer treatment through the intra-bladder delivery of magnetic nanoparticles is presented for the first time. This method overcomes the limitations of low magnetic thermal efficiency, inadequate tumor targeting, and reduced therapeutic effectiveness associated with the traditional intravenous administration of magnetic nanoparticles. Core-shell Zn-CoFe2O4@Zn-MnFe2O4 (MNP) nanoparticles were developed and further modified with hyaluronic acid (HA) to enhance their targeting ability toward tumor cells. The application of controlled mild MHT using MNP-HA at temperatures of 43-44 °C successfully suppressed the proliferation of bladder tumor cells and tumor growth, while also decreasing the expression levels of heat shock protein 70 (HSP70). Crucially, this therapeutic approach also activated the body's innate immune response involving macrophages, as well as the adaptive immune responses of dendritic cells (DCs) and T cells, thereby reversing the immunosuppressive environment of the bladder tumor and effectively reducing tumor recurrence. This study uncovers the potential immune-activating mechanism of mild MHT in the treatment of bladder cancer and confirms the effectiveness and safety of this strategy, indicating its promising potential for the clinical management of bladder cancer with a high tendency for relapse.

A novel trauma induced urethral stricture in rat model.

Urethral stricture (US) is a longstanding disease, while there has not existed a suitable animal model to mimic the condition. We aimed to establish a trauma-induced US animal model to simulate this clinical scenario. A total of 30 rats were equally distributed into two groups, sham and US group. All rats were anesthetized with isoflurane and undergone cystostomy. In the US group, a 2 mm incision was made in the urethra and sutured to induce US. The sham group only make a skin incision on the ventral side of the anterior urethra. 4 weeks later, ultrasound and cystourethrography were performed to evaluate the degree of urethral stricture, pathological examinations were carried out to evaluate the degree of fibrosis. Urodynamic evaluation and mechanical tissue testing were performed to evaluate the bladder function and urethral tissue stiffness. The results showed that the urethral mucosa was disrupted and urethral lumen was stenosed in the US group. Additionally, the US group showed elevated bladder pressure, prolonged micturition intervals and increased tissue stiffness. In conclusion, the rat urethral stricture model induced by trauma provides a closer representation of the real clinical scenario. This model will significantly contribute to advancing research on the mechanisms underlying traumatic urethral stricture.

Recurrent bladder leiomyoma: a case report.

BACKGROUND: Bladder leiomyomas are rare benign growths in the bladder, comprising less than 0.5% of bladder tumors with only 250 cases reported globally. They are more common in women. This case involves a 70-year-old woman with recurrent leiomyoma, presenting with lower urinary tract symptoms and painless hematuria. A recurrent bladder leiomyoma is rarely reported, making its presence exceptionally rare. CASE PRESENTATION: A 70-year-old Pakistani woman with hypertension and diabetes presented with lower urinary tract symptoms (LUTS) and painless hematuria. She had a history of similar symptoms in 2010, leading to a diagnosis of bladder leiomyoma via cystoscopy and biopsy. Imaging studies revealed a substantial 3.7 × 4 × 4.0 cm isodense mass with calcifications at the bladder base, along with bladder wall thickening and diverticula. Pathological examination during Transurethral Resection of Bladder Tumor (TURBT) confirmed the presence of bladder tissue with smooth muscle, ruling out malignancy. Immunohistochemical studies supported the diagnosis. A successful TURBT was performed, and the patient recovered well. DISCUSSION: Recurrent bladder leiomyoma is a rarely-discussed topic in medical literature. This article primarily aims to review existing studies and present a detailed case study, shedding light on this rare phenomenon.