Stromal osseous metaplasia in urothelial carcinoma of the bladder: An unusual and challenging feature. A case report / Carcinoma urotelial de vejiga con metaplasia ósea estromal: una característica inusual y desafiante. Presentación de un caso

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. (AU)

Varón de 62 años que consulta por dolor y hematuria desde hace 3 meses. En la tomografía computarizada se observó un engrosamiento focal y mural de la vejiga con dilatación ureteropélvica. La resección vesical transuretral reveló un carcinoma urotelial infiltrante de alto grado músculo-invasivo. En la cistoprostatectomía posterior encontramos el mismo tumor, pero añadiendo focos de metaplasia ósea estromal asociada al tumor. La metaplasia osificante es una característica extremadamente rara en el carcinoma urotelial, con algunos casos informados, y representa un desafío diagnóstico, ya que simula un sarcoma inducido por radioterapia o un carcinoma sarcomatoide. (AU)

Palinopsia in the Setting of Normal Pressure Hydrocephalus.

Normal pressure hydrocephalus (NPH) is characterized by pathologic ventriculomegaly with normal opening pressures on lumbar puncture. It commonly presents with a triad of gait disturbance, cognitive impairment, and urinary bladder detrusor dysfunction. Its pathogenesis is complex but is thought to arise in the setting of imbalanced cerebrospinal fluid (CSF) secretion and absorption. Given that intracranial pressure often remains normal in the setting of NPH, visual symptoms are quite uncommon. Here we present a case of a 70-year-old female with a subacute history of visual aberration described as a seconds-long persistent recurrence of visual images after the stimulus was removed from the visual field in the setting of slowed and unstable gait, urinary urgency, and cognitive impairment. This patient was evaluated and ultimately diagnosed with NPH before undergoing definitive treatment with ventriculoperitoneal shunt implantation. She has shown persistent responsiveness to shunting of the CSF as manifested by sustained improvement in gait speed and stability, urinary bladder urgency, and palinopsia resolution at the six-month follow-up assessment.

A Rare Case of Complete Inguinoscrotal Bladder Herniation With Ureteric Involvement: Assessing Diagnostic Challenges and Complex Surgical Management.

Inguinoscrotal hernias involving the urinary bladder are exceedingly rare, constituting a small subset of inguinal hernias. We present a case of a 47-year-old male with long-standing scrotal enlargement and obstructive uropathy due to complete herniation of the bladder with ureteric involvement. Diagnostic imaging confirmed the condition. Following an open laparotomy, the bladder was reduced, and a modified Bassini technique with orchiopexy was used for repair. Recurrence of the inguinoscrotal hernia with evidence of the bladder in the scrotal sac required additional surgery. This case underscores the rarity, diagnostic complexity, and potential complications of inguinoscrotal bladder hernias. Specialized surgical techniques and a multidisciplinary approach are crucial for successful management, especially in cases of complete bladder herniation. Future considerations should include innovative approaches to enhance primary repair outcomes for extensive hernias involving the bladder.

Investigation of Ki67 and Phospho-Histone H3 Expressions in Urothelial Carcinoma of the Bladder by Immunohistochemical Method.

BACKGROUND: In our study, it is aimed to investigate the relationship between Ki67 and phospho-histone H3 (pHH3) expressions in bladder urothelial carcinomas, with clinicopathological parameters and survival, which have prognostic value. METHODS: The study included 44 cases of high-grade urothelial carcinoma (HGUC), 37 cases of low-grade urothelial carcinoma (LGUC), and 11 nontumoral bladder cases. Ki67 and pHH3 were applied to the paraffin blocks of the tissues of 81 urothelial carcinoma and 11 nontumoral bladder cases by immunohistochemical method. Percentages of Ki67 and pHH3 expressions were evaluated by digital imaging analysis method. Expression percentages were compared with various clinicopathological parameters, and the relationship between them was evaluated. RESULTS: Ki67 was expressed in 28% of urothelial carcinoma cases and 1% of nontumoral cases. pHH3 was expressed in 10.32% of urothelial carcinoma cases and 0.16% of nontumoral cases. In our study, we found significantly higher Ki67 and pHH3 expressions in urothelial carcinoma compared to nontumoral cases. There was a statistically significant relationship (p < 0.05) and a positive correlation between Ki67 expression and lymphovascular invasion, pT stage, and histological grade. A statistically significant relationship (p < 0.05) and a positive correlation were found between pHH3 expression and lymphovascular invasion, pT stage, recurrence, and histological grade. In addition, a statistically significant relationship was found between Ki67 and pHH3 expressions. In our study, survival was found to be low in high-grade urothelial carcinoma cases with lymphovascular invasion, advanced age (65 years and older), and high Ki67 and pHH3 expression rates. CONCLUSIONS: According to our findings, high Ki67 and pHH3 expressions were found to be associated with poor prognostic parameters such as advanced pathologic stage, high histologic grade, and low survival. Our findings suggest that Ki67 and pHH3 may play a role in the differentiation, progression, and aggressive behavior of urothelial carcinoma. However, further studies are needed to confirm our findings and determine the role of these markers in urothelial carcinoma.

Urothelial Carcinoma With Bone Metastasis Mimicking Sciatica: A Common Neoplasm With an Uncommon Presentation.

Bone metastasis in urothelial cancer is underreported and not well-researched. A case of urothelial carcinoma (UC) with bone metastasis presenting as musculoskeletal pain is reported. The patient presented with persistent lower back pain associated with right lower extremity pain, numbness, and tingling. Initially, a diagnosis of sciatica was suspected, but the patient did not respond to treatment. An MRI spine was done, which revealed a bright signal mass in the vertebral body suspicious for a metastatic lesion, left hydroureteronephrosis, and a nonspecific cystic focus in the right iliacus muscle. Subsequent imaging revealed an irregular soft tissue mass at the left posterolateral bladder base, resulting in apparent obstruction of the left ureter, highly suggestive of neoplasm, along with numerous lytic bone lesions in the pelvic girdle with associated soft tissue masses, consistent with metastatic disease. The patient underwent an interventional radiology biopsy of the right iliac soft tissue mass to evaluate the lytic bony lesions, which revealed metastatic carcinoma, consistent with UC. A prompt referral was made for urology and oncology consultations. The patient underwent left percutaneous nephrostomy placement for obstruction, but he was not a candidate for any systemic therapy because of his poor performance status, and hospice was recommended as his metastatic disease was not curable and the goal of any kind of treatment was palliative. The optimal treatment for UC with bone metastasis remains divergent, and the management options should be determined as part of a shared decision-making process. This case highlights the importance of having a high suspicion of neoplastic pathology in patients presenting with musculoskeletal pain, like back pain, and not responding to treatment. This should alert the physicians to the potential for serious disease processes.

Clinical Trial Protocol for "Replace Cysto": Replacing Invasive Cystoscopy with Urine Testing for Non-muscle-invasive Bladder Cancer Surveillance-A Multicenter, Randomized, Phase 2 Healthcare Delivery Trial Comparing Quality of Life During Cancer Surveillance with Xpert Bladder Cancer Monitor or Bladder EpiCheck Urine Testing Versus Frequent Cystoscopy.

"Replace Cysto" is a multisite randomized phase 2 trial including 240 participants with low-grade intermediate-risk non-muscle-invasive bladder cancer, in which participants will be randomized 1:1:1 to one of two urine marker-based approaches alternating a urine marker test (Xpert Bladder Cancer Monitor or Bladder EpiCheck) with cystoscopy or to frequent scheduled cystoscopy. The primary objective is to determine whether urinary quality of life after surveillance is significantly improved in the urine marker arms. The primary outcome will be the patient-reported urinary quality of life domain score of the validated QLQ-NMIBC24 instrument, measured 1-3 d after surveillance. Exploratory outcomes include discomfort after surveillance, the number of invasive procedures that participants undergo per 1000 person years, complications from these procedures per 1000 person years, nonurinary quality of life, acceptability of surveillance, and bladder cancer recurrence and progression. Comparators include surveillance using (1) the Xpert Bladder Cancer Monitor test, (2) the Bladder EpiCheck urinary marker, or (3) frequent cystoscopy alone. After a negative cystoscopy ≤4 mo following bladder tumor resection, all the participants will undergo surveillance at 6, 12, 18, and 24 mo (with time zero defined as the date of the most recent bladder tumor resection). In the urine marker arms, surveillance at 6 and 18 mo will be performed with the marker. Regardless of the arm, participants will undergo cystoscopy at 12 and 24 mo. End of study for each participant will be their 24-mo cystoscopy. Overall trial duration is estimated at 5 yr from when the study opens to enrollment until completion of data analyses. The trial is registered at clinicaltrials.gov (NCT05796375).

Mechanism of action of nadofaragene firadenovec-vncg.

Effective bladder-preserving therapeutic options are needed for patients with bacillus Calmette-Guérin unresponsive non-muscle-invasive bladder cancer. Nadofaragene firadenovec-vncg (Adstiladrin®) was approved by the US Food and Drug Administration as the first gene therapy in urology and the first intravesical gene therapy indicated for the treatment of adult patients with high-risk bacillus Calmette-Guérin-unresponsive non-muscle-invasive bladder cancer with carcinoma in situ with or without papillary tumors. The proposed mechanism of action underlying nadofaragene firadenovec efficacy is likely due to the pleiotropic nature of interferon-α and its direct and indirect antitumor activities. Direct activities include cell death and the mediation of an antiangiogenic effect, and indirect activities are those initiated through immunomodulation of the innate and adaptive immune responses. The sustained expression of interferon-α that results from this treatment modality contributes to a durable response. This review provides insight into potential mechanisms of action underlying nadofaragene firadenovec efficacy.

Enhancing m6A modification of lncRNA through METTL3 and RBM15 to promote malignant progression in bladder cancer.

Objective: Bladder cancer is one of the most prominent malignancies affecting the urinary tract, characterized by a poor prognosis. Our previous research has underscored the pivotal role of m6A methylation in the progression of bladder cancer. Nevertheless, the precise relationship between N6-methyladenosine (m6A) regulation of long non-coding RNA (lncRNA) and bladder cancer remains elusive. Methods: This study harnessed sequencing data and clinical records from 408 bladder cancer patients in the TCGA database. Employing R software, we conducted bioinformatics analysis to establish an m6A-lncRNA co-expression network. Analyzing the differences between high and low-risk groups, particularly at the immunological level, and subsequently investigating the primary regulatory factors of these lncRNA, validating the findings through experiments, and exploring their specific cellular functions. Results: We identified 50 m6A-related lncRNA with prognostic significance through univariate Cox regression analysis. In parallel, we employed a LASSO-Cox regression model to pinpoint 11 lncRNA and calculate risk scores for bladder cancer patients. Based on the median risk score, patients were categorized into low-risk and high-risk groups. The high-risk cohort exhibited notably lower survival rates than their low-risk counterparts. Further analysis pointed to RBM15 and METTL3 as potential master regulators of these m6A-lncRNA. Experimental findings also shed light on the upregulated expression of METTlL3 and RBM15 in bladder cancer, where they contributed to the malignant progression of tumors. The experimental findings demonstrated a significant upregulation of METTL3 and RBM15 in bladder cancer specimens, implicating their contributory role in the oncogenic progression. Knockdown of METTL3 and RBM15 resulted in a marked attenuation of tumor cell proliferation, invasion, and migration, which was concomitant with a downregulation in the cellular m6A methylation status. Moreover, these results revealed that RBM15 and METTL3 function in a synergistic capacity, positing their involvement in cancer promotion via the upregulation of m6A modifications in long non-coding RNAs. Additionally, this study successfully developed an N-methyl-N-nitrosourea (MNU)-induced rat model of in situ bladder carcinoma, confirming the elevated expression of RBM15 and METTL3, which paralleled the overexpression of m6A-related- lncRNAs observed in bladder cancer cell lines. This congruence underscores the potential utility of these molecular markers in in vivo models that mirror human malignancies. Conclusion: This study not only offers novel molecular targets,but also enriches the research on m6A modification in bladder cancer, thereby facilitating its clinical translation.

Pre- and postnatal findings with rare congenital anomalies of urinary bladder.

Bladder duplication and congenital bladder diverticulum are rare anomalies. We described two boys with rare bladder anomalies found on prenatal ultrasounds. Postnatal investigations and surgical findings confirmed these bladder anomalies. The malformation was associated with other system anomalies. This report of pre- and postnatal imaging with surgical correlation contributes to our understanding about these rare bladder anomalies.

Clinical implications of single cell sequencing for bladder cancer.

Bladder cancer (BC) is the 10th most common cancer worldwide, with about 0.5 million reported new cases and about 0.2 million deaths per year. In this scoping review, we summarize the current evidence regarding the clinical implications of single-cell sequencing for bladder cancer based on PRISMA guidelines. We searched PubMed, CENTRAL, Embase, and supplemented with manual searches through the Scopus, and Web of Science for published studies until February 2023. We included original studies that used at least one single-cell technology to study bladder cancer. Forty-one publications were included in the review. Twenty-nine studies showed that this technology can identify cell subtypes in the tumor microenvironment that may predict prognosis or response to immune checkpoint inhibition therapy. Two studies were able to diagnose BC by identifying neoplastic cells through single-cell sequencing urine samples. The remaining studies were mainly a preclinical exploration of tumor microenvironment at single cell level. Single-cell sequencing technology can discriminate heterogeneity in bladder tumor cells and determine the key molecular properties that can lead to the discovery of novel perspectives on cancer management. This nascent tool can advance the early diagnosis, prognosis judgment, and targeted therapy of bladder cancer.

Examining the safety of mirabegron: an analysis of real-world pharmacovigilance data from the US FDA adverse event reporting system (FAERS) database.

Background: Mirabegron, the first ß-3 adrenergic receptor agonist, received approval from the Food and Drug Administration (FDA) in 2012 for the treatment of overactive bladder (OAB). This pharmacovigilance study investigated the safety profile of mirabegron treatment using the US FDA Adverse Event Reporting System (FAERS) database. Methods: This study employed disproportionality analyses, including the reporting odds ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN) algorithm, to quantify signals of adverse events associated with mirabegron. Results: From the first quarter of 2012 to the third quarter of 2023, a comprehensive total of 14,356,234 adverse event (AE) reports were submitted to the FDA Adverse Event Reporting System database. Within this dataset, encompassing 18,763 reports specifically associated with mirabegron, healthcare professionals notably contributed 2,902 of these reports. A total of 80 preferred terms (PTs) of interest were identified using both the ROR and information component algorithms. The most common AEs included blood pressure increased, urinary retention, atrial fibrillation, dry mouth, and tachycardia, which were consistent with the product instructions. Unexpected significant AEs, such as arrhythmia, palpitations, dementia, transient ischemic attack, Parkinson's disease, anti-neutrophil cytoplasmic antibody positive vasculitis, lip swelling, and swollen tongue, were also identified. The study findings indicated that the majority of onset time occurred within 30 days (n = 358, 55.68%). However, AEs were still possible after 1 year of mirabegron treatment. Conclusion: This study provided valuable evidence for the real-world safety of mirabegron, helping clinical professionals enhance their understanding of mirabegron's safety in clinical practice. It also contributed valuable evidence for further safety studies on mirabegron.

Impact of antioxidant potential of rohu (Labeo rohita) swim bladder gelatin hydrolysate on oxidative stability, textural and sensory properties of fish sausage enriched with polyunsaturated fatty acids.

The impact of rohu swim bladder gelatin hydrolysate (SBGH) at different levels on textural, sensory, oxidative, and microbial properties of polyunsaturated fatty acids enriched rohu fish cooked sausages (PUFA-RFS) were investigated in the current study. SBGH addition enhanced the lightness values of PUFA-RFS compared to both control sausages (without SBGH and with butylated hydroxyanisole (BHA) (P > 0.05). PUFA-RFS added with 3% SBGH exhibited higher hardness, cohesiveness, and gumminess throughout the storage duration at both 4 °C and -20 °C temperatures when compared to other sausages counterparts. PUFA-RFS added with SBGH displayed lower PV, TBARS, and total microbial counts than the control sausages. Furthermore, PV, TBARS, and total microbial count values of sausage decreased with an increase in SBGH level, indicating retardation in lipid oxidation and microbial growth by SBGH in a dose-depended manner. Nevertheless, sausage added with 3% SBGH had higher overall acceptability than other sausage counterparts. Therefore, SBGH could retard lipid oxidation and improves textural properties of PUFA-enriched fish sausage.

Therapeutic approaches for UCPPS management: research advances, experimental targets, and future directions.

Urologic Chronic Pelvic Pain Syndrome (UCPPS) is a painful chronic condition with persistent pain originating from the pelvis that often leads to detrimental lifestyle changes in the affected patients. The syndrome develops in both sexes, with an estimated prevalence of 5.7% to 26.6% worldwide. This narrative review summarizes currently recommended therapies for UCPPS, followed by the latest animal and clinical research advances in the field. The diagnosis of UCPPS by clinicians has room for improvement despite the changes in the past decade aiming to decrease the time to treatment. Therapeutic approaches targeting growth factors (i.e., NGF, VEGF), amniotic bladder therapy and stem cell treatments gain more attention as experimental treatment options for UCPPS. The development of novel diagnostic tests based on the latest advances in urinary biomarkers would be beneficial to assist with the clinical diagnosis of UCPPS. Future research directions should address the role of chronic psychological stress and the mechanisms of pain refractory to conventional management strategies in UCPPS etiology. Testing the applicability of cognitive behavioral therapy in this cohort of UCPPS patients might be promising to increase their QoL. The search for novel lead compounds and innovative drug delivery systems requires clinically relevant translational animal models. The role of autoimmune responses triggered by environmental factors is another promising research direction to clarify the impact of the immune system in UCPPS pathophysiology. Significance Statement This minireview provides an up-to-date summary of the therapeutic approaches for UCPPS with focus on recent advancements in the clinical diagnosis and treatments of the disease, pathophysiological mechanisms of UCPPS, signaling pathways and molecular targets involved in pelvic nociception.

Predictors of persistent opioid use in bladder cancer patients undergoing radical cystectomy: A SEER-Medicare analysis.

PURPOSE: To evaluate patient and provider characteristics that predict persistent opioid use following radical cystectomy for bladder cancer including non-opioid naïve patients. METHODS: Patients undergoing cystectomy between July 2007 and December 2015 were identified using the SEER-Medicare database. Opioid exposure was identified before and after cystectomy using Medicare Part D data. Multivariable analyses were used to identify predictors of the primary outcomes: persistent opioid use (prescription 3-6 months after surgery) and postoperative opioid prescriptions (within 30 days of surgery). Secondary outcomes included physician prescribing practices and rates of persistent opioid use in their patient cohorts. RESULTS: A total of 1,774 patients were included; 29% had prior opioid exposure. Compared to opioid-naïve patients, non-opioid naïve patients were more frequently younger, Black, and living in less educated communities. The percentage of persistent postoperative use was 10% overall and 24% in non-opioid naïve patients. Adjusting for patient factors, opioid naïve individuals were less likely to develop persistent use (OR 0.23) while a 50-unit increase in oral morphine equivalent per day prescribed following surgery nearly doubled the likelihood of persistent use (OR 1.98). Practice factors such as hospital size, teaching affiliation, and hospital ownership failed to predict persistent use. 29% of patients filled an opioid prescription postoperatively. Opioid naïve patients (OR 0.13) and those cared for at government hospitals (OR 0.59) were less likely to fill an opioid script along with those residing in the Northeast. Variability between physicians was seen in prescribing practices and rates of persistent use. CONCLUSIONS: Non-opioid naïve patients have higher rates of post-operative opioid prescription than opioid-naïve patients. Physician prescribing practices play a role in persistent use, as initial prescription amount predicts persistent use even in non-opioid naïve patients. Significant physician variation in both prescribing practices and rates of persistent use suggest a role for standardizing practices.

Carcinoma arising in ileal conduit or orthotopic ileal neobladder reconstruction: A 20-year single institute experience.

CONTEXT: Carcinomas found in urinary diversion specimens are uncommon, particularly new primary tumours. New primary tumours primarily occur when the large intestine is utilised, whereas the occurrence is infrequent with the use of the ileum. These tumours include both the recurrence of primary malignancy or the development of a new primary malignancy originating from the small intestine. DESIGN: A search was performed within the pathology laboratory system to identify cases of malignancies involving ileal conduit/reconstruction from 2002 to 2022. Data on demographics, clinical details, pathology and management was recorded. RESULTS: A total of 13 male patients, with a mean age of 67 years (range = 49-81 years) were included in the study. The initial procedure performed included cystoprostatectomy (n = 10, including one case with right nephroureterectomy) and cystectomy (n = 3, including one case for bladder exstrophy) for initial diagnoses including urothelial carcinoma (n = 11; conventional, 6; sarcomatoid, 1; glandular 1; plasmacytoid, 1; micropapillary, 2) and adenocarcinoma (n = 1). The initial management included radical surgery with neoadjuvant chemotherapy/immunotherapy (n = 1), adjuvant chemotherapy (n = 3), intravesical adjuvant BCG (n = 2) and intravesical adjuvant chemotherapy (n = 1). Malignancies in ileal conduit or orthotopic ileal neobladder included recurrent urothelial carcinoma (n = 10) and new secondary adenocarcinomas (n = 3), which developed as early as 3 months (usually recurrence) and up to 13, 33 and 45 years (new primary malignancy) following primary resection. CONCLUSIONS: Utilising the ileum as conduit/neobladder presents a viable alternative for urinary diversion with a reduced malignancy risk compared to using a segment of the large intestine. However, there remains a potential for malignancy, either tumour recurrence or a new primary malignancy. In our study, tumour recurrence occurred up to 4 years following the initial diagnosis and the development of a new primary malignancy occurred up to 45 years after the initial diagnosis. Consequently, it is crucial to prioritise long-term follow-up for these patients undergoing this procedure.

Conception and implementation of an MRI-compatible device to elicit the bulbocavernosus reflex for an open spinal cord study.

OBJECTIVE: Functional MRI (fMRI) can be employed to assess neuronal activity in the central nervous system. However, investigating the spinal cord using fMRI poses several technical difficulties. Enhancing the fMRI signal intensity in the spinal cord can improve the visualization and analysis of different neural pathways, particularly those involved in bladder function. The bulbocavernosus reflex (BCR) is an excellent method for evaluating the integrity of the sacral spinal cord. Instead of stimulating the glans penis or clitoris, the BCR can be simulated comfortably by tapping the suprapubic region. In this study, we explain the necessity and development of a device to elicit the simulated BCR (sBCR) via suprapubic tapping while conducting an fMRI scan. METHODS: The device was successfully tested on a group of 20 healthy individuals. Two stimulation task block protocols were administered (empty vs. full bladder). Each block consisted of 40 s of suprapubic tapping followed by 40 s of rest, and the entire sequence was repeated four times. RESULTS: Our device can reliably and consistently elicit sBCR noninvasively as demonstrated by electromyographic recording of pelvic muscles and anal winking. Participants did note mild to moderate discomfort and urge to void during the full bladder task. CONCLUSION: Our device demonstrates an efficacious approach to elicit sBCR within an MRI bore to assess sacral spinal cord functional activity without generating any significant motion artifacts. SIGNIFICANCE: This device can explore the mechanisms and processes controlling urinary, digestive, or sexual function within this region in humans.

Management of Extraperitoneal Bladder Injuries in Patients With Pelvic Fractures.

BACKGROUND: The management of extraperitoneal bladder injuries (EBIs) when present with concomitant pelvic fractures is controversial. Current evidence is divided between supporting non-operative management with catheter drainage compared to operative management of bladder injury. The purpose of this study was to evaluate current management of EBI in the setting of pelvic fractures at our institution. We hypothesize there is no difference between operative and non-operative groups. METHODS: Retrospective review of patients with concomitant bladder injuries and pelvic fractures at a level 1 trauma center from 2017 to 2022 was performed. Demographics, injury characteristics, management strategies, and complications were collected. Patients were stratified by management (cystorrhaphy vs non-operative) and compared. RESULTS: Of 90 patients with bladder injuries and pelvic fractures, 50 patients (56%) presented with EBI, 26 patients (29%) presented with only intraperitoneal injuries, and 14 patients (16%) presented with a combined injury. Of patients with EBI, 18 (36%) underwent cystorrhaphy and 32 (64%) underwent non-operative management. There was no difference in demographics, orthopedic pelvic operative intervention, length of stay, or mortality between groups. Patients in the operative cohort had more bladder leaks [7 (39%) vs 4 (13%), P = .0406], compared to those in the non-operative cohort. Composite complications [7 (39%) vs 7 (22%), P = .1984] were similar between groups. CONCLUSIONS: Patients with EBI and pelvic fractures who underwent cystorrhaphy had more bladder leaks on follow-up imaging, although there was no difference in composite complications, when compared to those who underwent non-operative management.

The role of circular RNA during the urological cancer metastasis: exploring regulatory mechanisms and potential therapeutic targets.

Metastasis is a major contributor to treatment failure and death in urological cancers, representing an important biomedical challenge at present. Metastases form as a result of cancer cells leaving the primary site, entering the vasculature and lymphatic vessels, and colonizing clones elsewhere in the body. However, the specific regulatory mechanisms of action underlying the metastatic process of urological cancers remain incompletely elucidated. With the deepening of research, circular RNAs (circRNAs) have been found to not only play a significant role in tumor progression and prognosis but also show aberrant expression in various tumor metastases, consequently impacting tumor metastasis through multiple pathways. Therefore, circRNAs are emerging as potential tumor markers and treatment targets. This review summarizes the research progress on elucidating how circRNAs regulate the urological cancer invasion-metastasis cascade response and related processes, as well as their role in immune microenvironment remodeling and circRNA vaccines. This body of work highlights circRNA regulation as an emerging therapeutic target for urological cancers, which should motivate further specific research in this regard.

Prognostic significance of E-Cadherin and B-Catenin in non-muscle invasive bladder cancer.

Non muscle invasive bladder cancer (NMIBC) has unpredictable outcomes with a variable risk of recurrence and progression. Many clinic-pathological prognostic factors have been identified but remain insufficient, raising the need to investigate new biomarkers. The aim of our study was to assess the prognostic value of the immunohistochemical (IHC) markers E-Cadherin and B-Catenin in NMIBC. All cases of NMIBC were collected between 2008 and 2013. IHC analysis was performed using E-Cadherin and B-Catenin. Reduced or loss of E-Cadherin expression was assessed as abnormal. Only cases with B-Catenin intense membranous staining were considered normal. A correlation was found between abnormal E-Cadherin expression and stage (p = 0.001), grade (p = 0.0000000), recurrence (p = 0.0000000), progression (p = 0.01), recurrence-free survival (p = 0.00000001), and progression-free survival (p = 0.01). A statistically significant association was found between B-Catenin and stage (p = 0. 05), grade (p = 0.02), and recurrence (p = 0.02). The abnormal expression of these markers could help to identify a high-risk subgroup of NMIBC that might benefit from either more accurate follow-up or more aggressive treatment.

Sialylation on vesicular integrin ß1 determined endocytic entry of small extracellular vesicles into recipient cells.

BACKGROUND: Small extracellular vesicles (sEV) are closely associated with the development and metastasis of many types of mammalian cancer. Glycoconjugates are highly expressed on sEV and play important roles in sEV biogenesis and their interaction with other cells. However, the study on vesicular glycoconjugates are far behind proteins and nucleic acids. Especially, the functions of sialic acids which are the terminal components of glycoconjugates, are poorly understood in sEV. METHODS: Sialic acid levels on sEV from plasma and bladder cancer cells were determined by ELISA and lectin blotting. Effects of sialylation on sEV uptake were determined by flow cytometry. Vesicular glycoproteins bearing sialic acids responsible for sEV uptake was identified by proteomics and density gradient centrifugation, and their site-specific sialylation functions were assayed by N-glycosylation site mutation. Effects of integrin ß1 bearing sialic acids on the pro-metastatic function of sEV in vivo were explored using Balb/c nu/nu mice. RESULTS: (1) Increased sialic acid levels were observed in sEV from malignant bladder cancer cells. (2) Elimination of sialic acids on sEV impaired sEV uptake by recipient cells. (3) Vesicular integrin ß1 bearing sialic acids was identified to play a key role in sEV uptake. (4) Desialylation of the hybrid domain of vesicular integrin ß1 inhibited its binding to matrix fibronectin, and reduced sEV entry into recipient cells. (5) Sialylation on integrin ß1 affected pro-metastatic function of sEV in Balb/c nu/nu mice. CONCLUSIONS: Taken together, our findings indicate important functional roles of sialic acids in sEV uptake and reprogramming plasticity of surrounding normal epithelial cells.