Treatment Of Bladder Cancer Research Articles

Development and validation of a recurrence risk assessment model for high-grade bladder cancer based on TCGA and GEO.

Bladder cancer is one of the most commonly diagnosed urinary cancers worldwide. Although muscle-invasive bladder cancer (MIBC) accounts for only 25% of bladder cancer cases, it has a high recurrence rate and poor prognosis, especially among high-grade cases. Despite the existence of some molecular markers, there is a clear clinical need for a robust recurrence prediction model that can assist in patient management and therapeutic decision-making. Therefore, we aimed to use public databases to develop such an effective assessment model. We developed a recurrence risk assessment model for high-grade bladder cancer based on the clinical information of 217 cases from The Cancer Genome Atlas (TCGA) and profiles of 87 samples from GSE31684 in the Gene Expression Omnibus (GEO) database. Edge R was used to analyze differences between RNAs of bladder cancer in the TCGA database, with thresholds of P<0.05 and |log2(fold change)| >1; least absolute shrinkage and selection operator (LASSO) Cox regression models were used to screen the RNAs significantly related to recurrence with minimum λ. Survival receiver operating characteristic (ROC) and area under the curve (AUC) was used to assess the predictive accuracy of the model in the training and validation sets of GSE31684. There were 2,876 differential RNAs obtained from TCGA data. Among a total of 284 RNAs identified as significantly related to recurrence of bladder cancer, 49 were obtained by LASSO regression, and 30 were finally obtained by multifactor risk regression to construct a risk assessment model. The model was found to predict the prognosis of bladder cancer recurrence well, with an AUC of 0.911 in the TCGA training set and an adjusted AUC value of 0.839 in the GEO validation set. The recurrence assessment model is a relatively accurate recurrence prediction tool for high-grade bladder cancer and could provide a guidance for the treatment of bladder cancer.

Nanomedicine in Bladder Cancer Therapy.

Bladder cancer (BC) is one of the most common malignant neoplasms of the genitourinary system. Traditional BC therapies include chemotherapy, targeted therapy, and immunotherapy. However, limitations such as lack of specificity, cytotoxicity, and multidrug resistance pose serious challenges to the benefits of BC therapies. Consequently, current studies focus on the search for new therapeutic solutions. In recent years, there has been a growing interest in using nanotechnology in the treatment of both non-invasive (NMIBC) and invasive bladder cancer (MIBC). Nanotechnology is based on the use of both organic molecules (chitosan, liposomes) and inorganic molecules (superparamagnetic iron oxide nanoparticles) as carriers of active substances. The main aim of such molecules is the targeted transport and prolonged retention of the drug in the target tissue, which increases the therapeutic efficacy of the active substance. This review discusses the numerous types of nanoparticles (including chitosan, polymeric nanoparticles, liposomes, and protein nanoparticles), targeting mechanisms, and approved nanotherapeutics with oncological implications in cancer treatment. We also present nanoformulation applications in phototherapy, gene therapy, and immunotherapy. Moreover, we summarise the current perspectives, advantages, and challenges in clinical translation.

Lymphatic embolization for early post-operative lymphatic leakage after radical cystectomy for bladder cancer.

Although radical cystectomy (RC) with pelvic lymph node dissection (PLND) is the standard treatment of muscle invasive bladder cancer, it may cause lymphatic leakage. Recent studies describe lymphatic embolization (LE) as an option to manage post-operative lymphatic leakage. Hence, this study evaluated the outcome of LE in patients receiving RC and analyzed factors associated with outcomes. This was a retrospective analysis of patients who underwent LE after RC for bladder cancer between August 2017 and June 2023. The data was assessed for analysis at January 2024. The patients were divided into a clinical success group and a clinical failure group. Clinical failure was defined as the following: 1) those who required drainage catheter placement >7 days after LE, 2) those who needed re-intervention before catheter removal, and 3) those who experienced adverse events associated with LE. Logistic regression analysis was performed to identify the factors associated with outcomes of LE. We analyzed 45 patients who underwent LE after RC. Twenty-eight (62.2%) patients were identified as clinically successful. Four patients required re-embolization, but none required more than two sessions of intervention. Three patients experienced lymphatic complications after LE. In multivariable analysis, maximal daily drainage volume of >1,000 mL/day (odds ratio [OR] = 4.729, 95% confidence interval [CI]: 1.018-21.974, p = 0.047) and diabetes mellitus (DM) (OR = 4.571, 95% CI: 1.128-18.510, p = 0.033) were factors associated with LE outcome. Our results suggest LE as a potentially effective procedure for controlling post-operative lymphatic leaks after RC, with few minor side effects. Patients exceeding a daily drainage of 1,000mL/day or with a medical history of DM have a higher risk for re-intervention and clinical failure after LE.

Targeting CD47 and Angiogenesis Demonstrates Effective Anti-Tumor Effect in Bladder Cancer.

Background: Although immunotherapy has shown potential in cancer treatment, current immunotherapeutics for bladder cancer are limited by a low response rate. Therefore, it is necessary to investigate other suitable immunotherapeutic targets and strategies for bladder cancer. Methods: To evaluate whether CD47 could be a suitable target for bladder cancer immunotherapy, CD47 protein expression levels in 116 bladder cancer tissue samples were assessed by IHC staining. In vitro anti-tumor effect of blocking CD47 was examined by phagocytosis assays. In vivo anti-tumor effects of targeting CD47 and angiogenesis were experimented in the HSPCs-CDX model. Results: We find that CD47 is highly expressed in bladder cancer samples and is associated with poor prognosis. Blocking CD47 could enhance the human PBMC-derived macrophages' phagocytosis of T24 (from 10.40% to 29.70%) and 5637 (from 5.31% to 33.52%) human bladder cancer cells, as well as demonstrate anti-tumor effects in the HSPCs-CDX model (tumor growth inhibition rate, TGI: 33.05%). During CD47 treatment, we observed that the level of angiogenesis increased after CD47 blockade, and it might undermine the effect of CD47 immunotherapy. We then combined CD47 blockade with anti-angiogenic drugs to treat bladder cancer and discovered that inhibiting angiogenesis could further improve the anti-tumor effect of CD47 blockade (TGI: 76.39%). Finally, we tested the anti-tumor effect of co-targeting CD47 and angiogenesis using a bispecific fusion protein, SIRPα-VEGFR1, which successfully inhibited tumor growth to a similar extent as a combination therapy. Conclusions: Our study suggests that targeting CD47 could inhibit the growth of bladder cancer by promoting macrophage-mediated anti-tumor immunity. Moreover, blocking CD47 and angiogenesis could achieve a potent anti-tumor effect and could be an effective immunotherapy strategy for bladder cancer.

Follow-up strategies after trimodal treatment for muscle-invasive bladder cancer: a systematic review

PurposeOptimal follow-up strategies following trimodal treatment for muscle invasive bladder cancer play a crucial role in detecting and managing relapse and side-effects. This article provides a comprehensive summary of the patterns and risk factors of relapse, functional outcomes, and follow-up protocols.MethodsA systematic literature search on PubMed and review of current guidelines and institutional follow-up protocols after trimodal therapy were conducted.ResultsOut of 200 identified publications, 43 studies (28 retrospective, 15 prospective) were selected, encompassing 7447 patients (study sizes from 24 to 728 patients). Recurrence rates in the urinary bladder varied between 14–52%; 3–16% were muscle-invasive while 11–36% were non-muscle invasive. Nodal recurrence occurred at 13–16% and distant metastases at 15–35%. After 5 and 10 years of follow-up, around 60–85% and 45–75% of patients could preserve their bladder, respectively. Various prognostic risk factors associated with relapse and inferior survival were proposed, including higher disease stage (> c/pT2), presence of extensive/multifocal carcinoma in situ (CIS), hydronephrosis, multifocality, histological subtypes, incomplete transurethral resection of bladder tumor (TURBT) and incomplete response to radio-chemotherapy. The analyzed follow-up guidelines varied slightly in terms of the number, timing, and types of investigations, but overall, the recommendations were similar.ConclusionRandomized prospective studies should focus on evaluating the impact of specific follow-up protocols on oncological and functional outcomes following trimodal treatment for muscle-invasive bladder cancer. It is crucial to evaluate personalized adaption of follow-up protocols based on established risk factors, as there is potential for improved patient outcomes and resource allocation.

Integrating oxidative-stress biomarkers into a precision oncology risk-stratification model for bladder cancer prognosis and therapy.

Bladder cancer is a common malignant tumor with significant heterogeneity, making personalized risk stratification crucial for optimizing treatment and prognosis. This study aimed to develop a prognostic model based on oxidative stress-related genes to guide risk assessment in bladder cancer. Differentially expressed oxidative stress-related genes were identified using the GEO database. Functional enrichment and survival analyses were performed on these genes. A risk-scoring model was built and tested for prognostic value and therapeutic response prediction. Expression of key genes was validated by qRT-PCR in samples from two muscle-invasive and two non-muscle-invasive bladder cancer patients. Several oxidative stress-related genes were identified as significantly associated with survival. The risk-scoring model stratified patients into high- and low-risk groups, accurately predicting prognosis and therapeutic responses. qRT-PCR confirmed the differential expression of key genes in patient samples. The study provides a concise risk stratification model based on oxidative stress-related genes, offering a practical tool for improving personalized treatment in bladder cancer. Further validation is required for broader clinical application.

Pharmacological Inhibition of Endogenous Hydrogen Sulfide Production Slows Bladder Cancer Progression in an Intravesical Murine Model.

Present bladder cancer therapies have relatively limited therapeutic impact and account for one of the highest lifetime treatment costs per patient. Therefore, there is an urgent need to explore novel and optimized treatment strategies. The present study investigated the effects of inhibiting endogenous hydrogen sulfide (H2S) production on bladder cell viability and in vivo tumor progression. We targeted the H2S-producing enzyme, cystathionine γ-lyase, in 5637 cells using propargylglycine (H2S inhibitor) and performed cytofluorimetric analysis to evaluate cell viability. We then tested the efficacy of propargylglycine alone or in combination with gemcitabine (conventional chemotherapy) in an intravesical murine model of bladder cancer. Magnetic resonance imaging and immunohistochemical staining for cell proliferation, apoptosis, immune-cell infiltration, and neovascularization were performed to evaluate tumor response. Compared to control conditions or cohorts, propargylglycine administration significantly attenuated bladder cancer cell viability in vitro (p < 0.0001) and tumor growth (p < 0.002) and invasion in vivo. Furthermore, propargylglycine enhanced the anti-cancer effects of gemcitabine, resulting in tumor regression (p < 0.0001). Moreover, propargylglycine induced cleaved PARP-1-activated apoptosis (p < 0.05), as well as intratumoral CD8+ T cell (p < 0.05) and F4/80+ macrophage (p < 0.002) infiltration. Propargylglycine also reduced intratumoral neovascularization (p < 0.0001) and cell proliferation (p < 0.0002). Importantly, the pro-apoptotic and anti-neovascularization effects of gemcitabine were enhanced by propargylglycine co-administration. Our findings suggest that inhibition of endogenous H2S production can be protective against bladder cancer by enhancing the chemotherapeutic action of gemcitabine and may be a novel pharmacological target and approach for improved bladder cancer diagnosis and treatments in the future.

2‐Ethenyl Imidazolium Salts: Synthesis, Characterization, and Evaluation as Potential Chemotherapeutics

AbstractAs candidates for intravesical exfoliants to treat bladder cancer, we have prepared fourteen new imidazolium compounds substituted at the 2 position. These compounds were produced by use of the Knoevenagel reaction between a series of aryl aldehydes and 2‐methyl imidazolium salts. Two azolium systems were examined (benzimidazole and 4,5‐dichloroimidazole) and each of these heterocycles are substituted off the nitrogen atom positions with naphthalen‐2‐ylmethyl groups. NMR spectroscopy confirms formation of the carbon‐carbon double bond, and X‐ray crystallography confirmed that the alkenes adopt the E conformation. These new imidazolium salts were evaluated for their chemotherapeutic activity using the NCI‐60 Human Tumor Cell Line Screen, and we observed that the benzimidazolium systems were more toxic than the dichloroimidazolium systems, and that the methyl phenol ether or dimethyl aniline modified compounds showed the highest activities.

Hsa_circ_0000520 suppresses vasculogenic mimicry formation and metastasis in bladder cancer through Lin28a/PTEN/PI3K signaling

BackgroundVasculogenic mimicry (VM) is a potential cause of resistance to antiangiogenic therapy and is closely related to the malignant progression of tumors. It has been shown that noncoding RNAs play an important role in the formation of VM in malignant tumors. However, the role of circRNAs in VM of bladder cancer and the regulatory mechanisms are unclear.MethodsFirstly, hsa_circ_0000520 was identified to have circular character by Sanger sequencing and Rnase R assays. Secondly, the potential clinical value of hsa_circ_0000520 was explored by quantitative real-time polymerase chain reaction (qRT-PCR) and fluorescence in situ hybridization (FISH) of clinical specimens. Thirdly, the role of hsa_circ_0000520 in bladder cancer invasion, migration, and VM formation was examined by in vivo and in vitro experiments. Finally, the regulatory mechanisms of hsa_circ_0000520 in the malignant progression of bladder cancer were elucidated by RNA binding protein immunoprecipitation (RIP), RNA pulldown, co-immunoprecipitation (co-IP), qRT-PCR, Western blot (WB), and fluorescence co-localization.ResultsHsa_circ_0000520 was characterized as a circular RNA and was lowly expressed in bladder cancer compared with the paracancer. Bladder cancer patients with high expression of hsa_circ_0000520 had better survival prognosis. Functionally, hsa_circ_0000520 inhibited bladder cancer invasion, migration, and VM formation. Mechanistically, hsa_circ_0000520 acted as a scaffold to promote binding of UBE2V1/UBC13 to Lin28a, further promoting the ubiquitous degradation of Lin28a, improving PTEN mRNA stability, and inhibiting the phosphorylation of the PI3K/AKT pathway. The formation of hsa_circ_0000520 in bladder cancer was regulated by RNA binding protein QKI.ConclusionsHsa_circ_0000520 inhibits metastasis and VM formation in bladder cancer and is a potential target for bladder cancer diagnosis and treatment.

Bladder-Preserving Trimodality Treatment for High-Grade T1 Bladder Cancer: Results From Phase II Protocol NRG Oncology/RTOG 0926.

To investigate the use of radiation with radiosensitizing chemotherapy following repeated transurethral resection (trimodality therapy) as an alternative to radical cystectomy in T1 bladder cancer which has failed Bacillus Calmette-Guerin (BCG). Patients with recurrent T1 bladders who had failed BCG and were recommended to undergo cystectomy were treated with trimodality therapy. The primary end point was 3-year freedom from cystectomy. Secondary end points were distant metastasis at 3 and 5 years, local recurrence, disease-specific and overall survival (OS), and safety. This single-arm phase II study enrolled 37 patients. Efficacy and safety were evaluated in 34 patients after three exclusions. The median follow-up was 5.1 years. The 3-year freedom from cystectomy rate was 88% (lower one-sided 97.5% confidence limit [CI], 72%), meeting the primary study goal. OS at 3 and 5 years was 69% (95% CI, 54 to 85) and 56% (95% CI, 39 to 74), respectively. The distant metastasis rates at 3 and 5 years were 12% (95% CI, 4 to 26) and 19% (95% CI, 7 to 34), respectively. Eight patients died due to urothelial cancer, 12 exhibited local recurrence at 3 years (cumulative incidence: 32%; 95% CI, 17 to 48), 18 experienced grade 3 adverse events, mostly hematological, and one developed grade 4 neutropenia. Trimodality therapy is an effective potential alternative to radical cystectomy for recurrent high-grade T1 urothelial cancer of the bladder. At 3 years, 88% of the patients remained free of cystectomy.

Integrated Machine Learning Algorithms for Stratification of Patients with Bladder Cancer

Background: Bladder cancer is a prevalent malignancy globally, characterized by rising incidence and mortality rates. Stratifying bladder cancer patients into different subtypes is crucial for the effective treatment of this form of cancer. Therefore, there is a need to develop a stratification model specific to bladder cancer. Purpose: This study aims to establish a prognostic prediction model for bladder cancer, with the primary goal of accurately predicting prognosis and treatment outcomes. Methods: We collected datasets from 10 bladder cancer samples sourced from the Gene Expression Omnibus (GEO), the Cancer Genome Atlas (TCGA) databases, and IMvigor210 dataset. The machine learning based algorithms were used to generate 96 models for establishing the risk score for each patient. Based on the risk score, all the patients was classified into two different risk score groups. Results: The two groups of bladder cancer patients exhibited significant differences in prognosis, biological functions, and drug sensitivity. Nomogram model demonstrated that the risk score had a robust predictive effect with good clinical utility. Conclusion: The risk score constructed in this study can be utilized to predict the prognosis, response to drug treatment, and immunotherapy of bladder cancer patients, providing assistance for personalized clinical treatment of bladder cancer.

PGK1 can affect the prognosis and development of bladder cancer.

Previous studies have demonstrated that the glycolytic enzyme phosphoglycerate kinase 1 (PGK1) can promote tumor development. This study sought to investigate the specific role of PGK1 in bladder cancer (BLCA). Public databases and immunohistochemistry assays were utilized to analyze the expression of PGK1 in BLCA and its prognostic significance. Cell proliferation was assessed through CCK-8 and colony formation assays, while the level of metastasis was evaluated using transwell migration experiments. Additionally, IC50 experiments were conducted to assess the impact of PGK1 on cisplatin sensitivity. The mRNA and protein expression levels of PGK1 were significantly upregulated in BLCA. Cox proportional hazards model analysis revealed that PGK1 and T stage were independent prognostic factors for BLCA patients. Both CCK-8 and colony assays demonstrated that PGK1 promotes proliferation. Furthermore, a positive correlation was observed between PGK1 and Ki67, a proliferation index. Transwell migration assays confirmed the ability of PGK1 to enhance metastasis. Finally, PGK1 increased the IC50 associated with cisplatin treatment in BLCA. Collectively, these findings suggest that PGK1 may hold clinical value in predicting BLCA prognosis and improving the outcomes of this patient population.

24 Hypofractionated Intensity Modulated Radiation Therapy and Weekly Gemcitabine is an Effective and Safe Curative Treatment in Muscle Invasive Bladder Cancer: Long-Term Results

24 Hypofractionated Intensity Modulated Radiation Therapy and Weekly Gemcitabine is an Effective and Safe Curative Treatment in Muscle Invasive Bladder Cancer: Long-Term Results

Introduction of an Advanced Nurse Practitioner (ANP) Led Non-Muscle Invasive Bladder Cancer (NMIBC) Treatment and Surveillance Clinic in Tallaght University Hospital (TUH)

Introduction of an Advanced Nurse Practitioner (ANP) Led Non-Muscle Invasive Bladder Cancer (NMIBC) Treatment and Surveillance Clinic in Tallaght University Hospital (TUH)

KLF1 Activates RAC3 to Mediate Fatty Acid Synthesis and Enhance Cisplatin Resistance in Bladder Cancer Cells.

While cisplatin remains a frontline treatment for bladder cancer (BCa), the onset of resistance greatly hampers its effectiveness. RAC3 is closely linked to chemoresistance in cancer cells, but its specific role in cisplatin resistance within BCa is still elusive. RAC3 expression in BCa was analyzed using bioinformatics and quantitative polymerase chain reaction (qPCR). The gene set enrichment analysis (GSEA) identified RAC3-enriched pathways and the correlation between RAC3 and fatty acid synthase (FASN), a gene involved in fatty acid synthesis. Potential upstream transcription factors of RAC3 were predicted and their interaction with RAC3 was confirmed via dual-luciferase and chromatin immunoprecipitation (ChIP) assays. T24/DDP, a cisplatin-resistant BCa cell line, was established to probe into the regulatory role of RAC3 in cisplatin resistance. Cell proliferation was evaluated by colony formation and the IC50 values after cisplatin treatment were determined using cell counting kit-8 (CCK-8). The levels of free fatty acids and triglycerides (TGs), as well as the expression of DGAT2 and FASN proteins, were measured to gauge the extent of fatty acid synthesis in cells. Elevated expression of RAC3 was observed in BCa and the cisplatin-resistant BCa cells (T24/DDP). The knockdown of RAC3 within T24/DDP cells was demonstrated to counteract cisplatin resistance. Subsequent analyses identified RAC3 as being notably enriched in the fatty acid synthesis pathway, with Kruppel-like factor 1 (KLF1) emerging as a key upstream regulator. The overexpression of RAC3 was correlated with increased cisplatin resistance in T24/DDP cells, an effect that was mitigated by the addition of the FASN inhibitor, Orlistat. Furthermore, the downregulation of KLF1 suppressed RAC3 expression, disrupted fatty acid synthesis, and attenuated cisplatin resistance in T24/DDP cells. Conversely, the co-overexpression of RAC3 counteracted the effects conferred by KLF1 knockdown. Our study has validated that KLF1 activates RAC3 to mediate fatty acid synthesis and promote cisplatin resistance in BCa, suggesting the KLF1/RAC3 axis as a potential target for combating cisplatin-resistant BCa.

First Case of Robot-assisted Radical Cysto-prostatectomy and Intracorporeal Orthotopic Neobladder Reconstruction for the Treatment of Bladder Cancer in Ireland: Step-by-step Description of Operative Technique

First Case of Robot-assisted Radical Cysto-prostatectomy and Intracorporeal Orthotopic Neobladder Reconstruction for the Treatment of Bladder Cancer in Ireland: Step-by-step Description of Operative Technique

A comparative study of survival outcomes between partial and radical cystectomy in octogenarians with muscle-invasive bladder cancer.

Neoadjuvant chemotherapy with radical cystectomy (RC) is the preferred first-line treatment for localized muscle-invasive bladder cancer (MIBC). Due to the concern about morbidity associated with RC, the elderly population considers bladder preservation alternatives. Guidelines suggest partial cystectomy (PC) can be considered a viable option in carefully selected individuals. We used the National Cancer Database (NCDB) to compare the overall survival (OS) among octogenarians treated with PC and RC. Using NCDB, we retrospectively evaluated individuals aged 80 years and above diagnosed with localized MIBC (cT2-4aN0M0) with tumor size less than 5 cm and urothelial histology between 2004 and 2018. Our primary cohort was divided into the RC cohort, which included patients who underwent RC with or without chemotherapy/radiotherapy, and the PC cohort, which included those who underwent PC. After propensity-matching, we compared the OS. Of 94,104 patients with MIBC, 2,528 octogenarians met our selection criteria. Among them, 313 were treated with PC, and 2,215 were treated with RC. A total of 151 (48.2%) PC patients had pelvic lymph node dissection, while 1,967 (88.8%) RC patients had lymph node dissection (P<0.001). The OS for matched PC and RC was 33.4 and 29.9 months, respectively (P=0.68). In T2 tumors, the OS for PC and RC was 37 and 33.5 months, respectively (P=0.52); for T3 tumors, the OS was 22.3 and 24.4 months, respectively (P=0.98). Our study compared PC and RC in octogenarians with localized MIBC and observed that PC is safe and not inferior to RC in carefully selected octogenarians. The role of PC needs further exploration by comparing or integrating with strategies like concurrent chemoradiation to improve the oncological and survival outcomes.

Impact of Age, Period, Cohort, Region, Race, and Health Services on Bladder Cancer Mortality in Brazil: A 23-Year Ecological Study.

Bladder cancer is one of the most economically costly types of cancer, but few studies have evaluated its mortality considering the factors that impact this outcome. This study aimed to investigate the impact of sociodemographic factors, period, cohort, and health services on bladder cancer mortality. This ecological study analyzed bladder cancer mortality data in Brazil from 2000 to 2022 and evaluated sociodemographic variables (race, region of residence), socioeconomic variables (gross domestic product per capita, Gini index of household income per capita, number of health professionals per inhabitant, expenditure on public health services, and consultations per inhabitant), and bladder cancer diagnosis and treatment procedures. These data were subjected to statistical analysis, which revealed that after the age of 50, there was a progressive increase in the risk of bladder cancer. Indigenous people had the lowest mortality rate, while white people had a significantly greater mortality rate than black and brown people. The North Region and Northeast Region presented the lowest mortality rates, whereas the South Region presented the highest mortality rates. In the South and Southeast Regions, a higher GDP was related to lower mortality. In the South, higher mortality was associated with a lower number of consultations per inhabitant per region. Fewer bladder punctures/aspirations and bladder biopsies were associated with higher mortality rates. In oncology, more procedures, such as total cystectomy, cystoenteroplasty, and total cystectomy with a single shunt, do not reduce the mortality rate. These results can serve as guidelines for adjusting public health policies.

Advanced nanomaterials in prognostic implication of oncogenic role of CDCA7 and GALNT6 for bladder cancer treatment

Cell division cycle associated 7 (CDCA7) functions in Myc-mediated tumorigenesis. Glycosylation, which is frequently altered in malignancies, is regulated by polypeptide N-acetylgalactosaminyltransferase 6 (GALNT6) and is crucial for cancer growth. However, their prognostic value and biological roles in bladder cancer (BLCA) remain unknown. The primary objective of this research is to investigate the potential applications of cutting-edge nanomaterials in the therapeutic management of bladder cancer. A key focus of the study is to thoroughly examine the influence and involvement of the CDCA7 and GALNT6 genes in the treatment process. We assessed clinicopathological traits and prognostic value of CDCA7 and GALNT6 in BLCA.CDCA7 and GALNT6 were overexpressed in BLCA tissues from TCGA-BLCA datasets. Changes in BLCA were associated with DNA-binding transcription activator activity, mitotic cell cycle phase changes, transcription regulator complex, p53 signaling pathway, cell cycle, and pathways associated with transcriptional dysregulation in cancer. Survival analysis showed that they were crucial to the incidence and prognosis of BLCA. The expression levels of CDCA7 and GALNT6 were significantly correlated with the therapeutic effect of nanomaterials, and their down-regulation could enhance the anti-tumor effect of nanomaterials. Patients with BLCA who expressed high CDCA7 and GALNT6 levels had poorer disease outcome compared with patients with low levels.These findings have new implications for precision therapy and individualized risk stratification that will benefit patients with BLCA.

Perioperative complications of orthotopic neobladder after radical cystectomy for carcinoma of urinary bladder: A Retrospective Study

Background: The gold standard treatment for muscle-invasive bladder cancer is radical cystectomy (RC) with urinary diversion. Urinary diversion is performed in either as continent or incontinent forms. Orthotopic neobladder has the benefits of continent reservoir with voiding from the urethra. The mortality and morbidity rates ranged from 0 to 9.0% and 30 to 70%, respectively in various reports. For surgical outcome assessment, Clavien-Dindo classification is widely accepted for classification of complications of most of the surgical procedures. This study will be helpful to identify the potential complications and possibly minimize the morbidity and mortality of this surgery in the future. Materials and Methods: Data of 20 consecutively enrolled patients who underwent radical cystectomy and orthotopic neobladder form January 2023 to July 2024 at Urology unit of B.P. Koirala Memorial Cancer Hospital were taken for study from hospital medical records. The various demographic data and perioperative parameters were recorded. The early complications were defined as the complications during the period of hospitalization and up to 30 days of surgery, they were enlisted and then classified according to Clavein-Dindo Classification and the continence was reviewed at 1 month of surgery after catheter removal and after 3 months of surgery. Data was entered in SPSS 27 software and analyzed. Results: Complications were seen in 18 (90%) patients out of which 1 (5%) patients had Grade I complication, 12 (60%) patients had Grade II, 3 (15%) patients had grade IVA and 2(10%) had died. 5 (25%) patients developed high grade(≥ Grade III) complications. Mortality rate was 5%. Conclusion: Radical cystectomy with any forms of diversion is associated with high rate of morbidity and mortality. In order to identify and minimize the complications of this surgery in future, Clavein-Dindo classification is the standardized way of reporting the complications.