Programmed Cell Death Ligand 1 (PD-L1) Immunohistochemical Expression in Advanced Urothelial Bladder Carcinoma: An Updated Review with Clinical and Pathological Implications.

The management of advanced bladder carcinoma involves a multidisciplinary approach, but the prognosis remains poor for many patients. The immune system plays a crucial role in this disease, influencing both tumor development and response to treatment, and exploiting the immune system against the tumor can be a valuable strategy to destroy neoplastic cells. This is the biological principle underlying Bacillus Calmette-Guérin (BCG) use and, more recently, immune checkpoint inhibitors (ICIs), like PD-1 (programmed death-1)/PD-L1 (programmed death-ligand 1) inhibitors. In fact, one of the best studied immune checkpoints is represented by the PD-1/PD-L1 axis, which is a well-known immune escape system adopted by neoplastic bladder cells. PD-L1 expression has been associated with a higher pathologic stage and has shown prognostic value in bladder carcinoma. Interestingly, high-grade bladder cancers tend to express higher levels of PD-1 and PD-L1, suggesting a potential role of such an axis in mediating disease progression. Immunotherapy with PD-1 and PD-L1 inhibitors has therefore emerged as a valuable treatment option and has shown efficacy in advanced bladder cancer patients, with high PD-L1 expression levels associated with better treatment responses. Our review aims to provide a comprehensive overview of the role of PD-L1 in advanced bladder cancer, focusing on its implications for treatment decisions and the prediction of treatment response. Overall, our work aims to contribute to the understanding of PD-L1 as a predictive biomarker and highlight its role in shaping therapeutic approaches for advanced bladder cancer.

Delineating the mechanistic relevance of the TP53 gene and its mutational impact on gene expression and patients' survival in bladder cancer.

Bladder carcinoma (BLCA) is a widespread urological malignancy causing significant global mortality, often hindered by delayed diagnosis and limited treatments. BLCA frequently exhibits TP53 mutations, playing a pivotal role in its pathogenesis and underscoring the potential of targeting TP53 as a therapeutic approach for this prevalent urological malignancy. Tumor tissues from 50 bladder cancer patients were used for mutational analysis in TP53's mutation-rich exons (5, 7, & 8). The gene expression of the TP53 gene, along with a TP53-target gene B-cell translocation gene 2 (BTG2) was also assessed in the cDNA samples from the same BLCA tissues and 15 urine controls of healthy people. The analysis revealed 22 % of patients with somatic hotspot mutations, 18 % with pathogenic missense mutations, and 12 % with intronic variants. Patients with somatic mutations exhibited the worst prognosis, supported by survival analysis from The Cancer Genome Atlas (TCGA) BLCA data. Interestingly, H296Y missense mutation correlated with higher TP53 expression and improved survival, while intronic SNPs were linked to worse outcomes. Additionally, upregulated BTG2 expression in mutated patients was observed which was correlated with poor prognosis, emphasizing the role of TP53 mutations in bladder cancer progression. The multivariate analysis highlighted the predictive power of TP53 mutations, with a high frequency of high-grade tumors (78.57 %) in mutated patients, underscoring their role in cancer progression. In conclusion, this study emphasizes the crucial role of TP53 mutations in bladder cancer patients from Bangladesh.

Discovery of new 13(17)-epoxymyrsinane diterpenes from aerial flowering parts of euphorbia spinidens Bornm. ex Prokh. with proapoptotic activities against human bladder cancer EJ138 cells.

Phytochemical analysis of aerial flowering parts of Euphorbia spinidens Bornm. ex Prokh. from Euphorbiaceae family (local name: Farfion-e-dandaneh-khari) led to the isolation of five diterpenes based on myrsinane backbone. Using HRESI-MS, 1D, and 2D NMR, they were identified as two previously unreported: 33,7,14,15(ß)-tetraacetyl-5(α)-butanoyl-13α(17)epoxy-8,10(18)-myrsinadiene (1), 7,14,15(ß)-triacetyl-3(ß),5(α)-dibutanoyl-13α(17)epoxy-8,10(18)-myrsinadiene (2), and three known diterpenes: 3,7,14,15(ß)-tetraacetyl-5(α)-propanoyl-13(17)-epoxy-8,10(18)-myrsinadiene (3), and 3,7,10,14,15(ß)-Pentaacetyl-5(α)-butanoyl-13,17-epoxy-8-myrsinene (4), 3,7,10,14,15(ß)-pentaacetyl-5(α)-propanoyl-13,17-epoxy-8-myrsinene (5). Compound 5 was previously reported in the roots of the same plant but without NMR data. Therefore, its mass pattern,1H-, and 13C-NMR data are reported. The cytotoxicity and proapoptotic properties of 1-3 were evaluated against EJ-138 bladder carcinoma cells through standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay for cytotoxicity screening and annexin V-FITC/PI apoptosis detection kit. In the cytotoxicity assay, the IC50 values found against EJ-138 were: (1) 41.6 ± 3.54 µM; (2) 38.4 ± 2.54 µM; (3) 57.3 ± 5.4 µM, whilst the IC50 value of doxorubicin was 1.7 ± 0.3 µM, respectively. In apoptosis assay, total apoptosis of compounds 1-3 at higher concentrations (100 µM) were 57.6 ± 3.54, 46.3 ± 2.82, and 57.2 ± 4.35%, respectively.

Giant intravesical prostatic protrusion mimicking bladder carcinoma: Navigating diagnostic and management challenges.

INTRODUCTION AND IMPORTANCE: Benign prostate hyperplasia is common condition among elderly men, but giant intravesical prostatic protrusion is rare and may be confused with bladder carcinoma. CASE PRESENTATION: We report an unusual case of giant intravesical prostatic protrusion mimicking bladder carcinoma. A diagnosis of giant intravesical prostatic protrusion was confirmed with the assistance of cystoscopy and patient was managed by transvesical simple open prostatectomy where he had uneventfully recovery. CLINICAL DISCUSSION: Both bladder carcinoma and benign prostate hyperplasia are more prevalent in elderly men and they all present with lower urinary tract symptoms. Ultrasound and computer tomography may all suggest bladder carcinoma. The two conditions are treated differently, and therefore having correct diagnosis is mandatory. Cystoscopy is an important investigation that can act as a tiebreaker in differentiating giant intravesical prostatic protrusion from bladder carcinoma. Transvesical simple open prostatectomy is the preferred surgical approach with good postoperative outcome. CONCLUSION: This case report reminds urology surgeons on the possibility of having giant intravesical prostate mimicking bladder carcinoma and the importance of cystoscopy in differentiating the two. Transvesical simple open prostatectomy has promising result.

Antibody-Drug Conjugates in the Treatment of Genitourinary Cancers: An Updated Review of Data.

The treatment landscape of genitourinary cancers has significantly evolved over the past few years. Renal cell carcinoma, bladder cancer, and prostate cancer are the most common genitourinary malignancies. Recent advancements have produced new targeted therapies, particularly antibody-drug conjugates (ADCs), due to a better understanding of the underlying oncogenic factors and molecular mechanisms involved. ADCs function as a 'drug delivery into the tumor' system. They are composed of an antigen-directed antibody linked to a cytotoxic drug that releases cytotoxic components after binding to the tumor cell's surface antigen. ADCs have been proven to be extremely promising in the treatment of several cancer types. For GU cancers, this novel treatment has only benefited patients with metastatic urothelial cancer (mUC). The rest of the GU cancer paradigm does not have any FDA-approved ADC treatment options available yet. In this study, we have thoroughly completed a narrative review of the current literature and summarized preclinical studies and clinical trials that evaluated the utility, activity, and toxicity of ADCs in GU cancers, the prospects of ADC development, and the ongoing clinical trials. Prospective clinical trials, retrospective studies, case reports, and scoping reviews were included.

A study on the significance of serine hydroxymethyl transferase expression and its role in bladder cancer.

Bladder cancer (BLCA) is a common malignant tumor in urinary system all over the world. However, due to its high recurrence rate and complex causes, clinicians often have limited options for surgical and drug treatments. Recent researchs on the molecular mechanism of BLCA have reveals its biological progress and potential for early diagnosis. Serine hydroxymethyltransferase 1/2 (SHMT1/2) is a crucial enzyme in the one-carbon metabolism of tumor cells, and the expression levels of these isozymes have been found to be associated with the biological progression of various malignant tumors. However, the impact of SHMT1/2 on the biological progression of bladder cancer and its molecular regulation mechanism remain unclear. In this research utilizes BLCA clinical sample data, the TCGA database, and in vitro cell experiments to predict the expression levels of SHMT1/2 in BLCA. The findings indicate that SHMT1 remained unchanged, while SHMT2 expression is increased in BLCA, which was related to poor prognosis. Additionally, SHMT2 affects the growth, migration, and apoptosis of bladder cancer cells in vitro. It also influences the expression levels of E-cadherin and N-cadherin, ultimately impacting the malignant biological progression of bladder tumors. These results establish a correlation between SHMT2 and the malignant biological progression of BLCA, providing a theoretical basis for the early diagnosis and treatment of bladder cancer.

Tumor Predisposing Post-Zygotic Chromosomal Alterations in Bladder Cancer-Insights from Histologically Normal Urothelium.

Bladder urothelial carcinoma (BLCA) is the 10th most common cancer with a low survival rate and strong male bias. We studied the field cancerization in BLCA using multi-sample- and multi-tissue-per-patient protocol for sensitive detection of autosomal post-zygotic chromosomal alterations and loss of chromosome Y (LOY). We analysed 277 samples of histologically normal urothelium, 145 tumors and 63 blood samples from 52 males and 15 females, using the in-house adapted Mosaic Chromosomal Alterations (MoChA) pipeline. This approach allows identification of the early aberrations in urothelium from BLCA patients. Overall, 45% of patients exhibited at least one alteration in at least one normal urothelium sample. Recurrence analysis resulted in 16 hotspots composed of either gains and copy number neutral loss of heterozygosity (CN-LOH) or deletions and CN-LOH, encompassing well-known and new BLCA cancer driver genes. Conservative assessment of LOY showed 29%, 27% and 18% of LOY-cells in tumors, blood and normal urothelium, respectively. We provide a proof of principle that our approach can characterize the earliest alterations preconditioning normal urothelium to BLCA development. Frequent LOY in blood and urothelium-derived tissues suggest its involvement in BLCA.

Dysregulation and antimetastatic function of circLRIG1 modulated by miR-214-3p/LRIG1 axis in bladder carcinoma.

CircLRIG1, a newly discovered circRNA, has yet to have its potential function and biological processes reported. This study explored the role of circLRIG1 in the development and progression of bladder carcinoma and its potential molecular mechanisms. Techniques such as qRT-PCR, Western blot, various cellular assays, and in vivo models were used to investigate mRNA and protein levels, cell behavior, molecular interactions, and tumor growth. The results showed that both circLRIG1 and LRIG1 were significantly reduced in bladder carcinoma tissues and cell lines. Low circLRIG1 expression was associated with poor patient prognosis. Overexpressing circLRIG1 inhibited bladder carcinoma cell growth, migration, and invasion, promoted apoptosis, and decreased tumor growth and metastasis in vivo. Importantly, circLRIG1 was found to sponge miR-214-3p, enhancing LRIG1 expression, and its overexpression also modulated protein levels of E-cadherin, N-cadherin, Vimentin, and LRIG1. Similar effects were observed with LRIG1 overexpression. Notably, a positive correlation was found between circLRIG1 and LRIG1 expression in bladder carcinoma tissues. Additionally, the tumor-suppressing effect of circLRIG1 was reversed by overexpressing miR-214-3p or silencing LRIG1. The study concludes that circLRIG1 suppresses bladder carcinoma progression by enhancing LRIG1 expression via sponging miR-214-3p, providing a potential strategy for early diagnosis and treatment of bladder carcinoma.

Long-Term Survival After Definitive Concurrent Chemoradiation Therapy for Synchronous Small Cell Neuroendocrine Carcinoma of the Urinary Bladder and Adenocarcinoma of the Prostate: A Case Report.

Available reports of synchronous prostate and bladder cancer have exclusively described radical cystoprostatectomy with or without perioperative chemotherapy as the treatment of choice. There are no reports of curative intent or definitive chemoradiation therapy for synchronous primary bladder and primary prostate cancers. Small cell carcinoma of the bladder is a rare and aggressive tumor. We present the first case of synchronous mixed small cell carcinoma and urothelial carcinoma of the urinary bladder and adenocarcinoma of the prostate in a 70-year-old male who attained long-term survival after curative intent and definitive concurrent chemoradiotherapy with minimal acute and late toxicities. The patient remained alive and disease-free at 41 months post-treatment and achieved excellent functional outcomes with organ preservation. Definitive chemoradiation therapy offers a safe and effective, curative-intent organ preservation treatment for localized synchronous prostate and bladder cancers.

Three cancers in the renal pelvis, bladder, and colon: A case report.

BACKGROUND: Multiple primary cancers are rare occurrences that can involve either metachronous or synchronous development. It is particularly rare for an individual to have more than two primary cancers. In this report, we present a case study of an elderly man who was diagnosed with three heterochronous cancers in the renal pelvis, bladder, and colon. CASE SUMMARY: On December 30, 2014, a 51-year-old Chinese man was admitted to our hospital with complaints of intermittent painless gross hematuria for the preceding week. A computed tomography (CT) scan revealed wall thickening in the left ureter's upper segment, while a CT urography revealed a left renal pelvis tumor. A successful laparoscopic radical resection of the left renal pelvis tumor was subsequently performed at Shanghai Zhongshan Hospital in January 2015. The pathological findings after the surgery revealed a low-grade papillary urothelial carcinoma of the renal pelvis. The final pathological tumor stage was pT1N0M0. After surgery, this patient received 6 cycles of intravenous chemotherapy with gemcitabine and carboplatin, as well as bladder infusion therapy with gemcitabine. On December 18, 2017, the patient was admitted once again to our hospital with a one-day history of painless gross hematuria. A CT scan showed the presence of a space-occupying lesion on the posterior wall of bladder. Cystoscopic examination revealed multiple tumors in the bladder and right cutaneous ureterostomy was performed under general anesthesia on December 29, 2017. The postoperative pathological findings disclosed multifocal papillary urothelial carcinoma of the bladder (maximum size 3.7 cm × 2.6 cm). The bladder cancer was considered a metastasis of the renal pelvis cancer after surgery. The pathological tumor stage was pT1N0M1. The patient refused chemotherapy after surgery. After another six years, the patient returned on February 28, 2023, complaining of periumbilical pain that had lasted six days. This time, a CT scan of the abdomen showed a tumor in the ascending colon, but a subsequent colonoscopy examination indicated a tumor in the descending colon. On March 12, 2023, a subtotal colectomy and an ileosigmoidal anastomosis were carried out under general anesthesia. Postoperative pathological findings revealed that all three tumors were adenocarcinomas. The final pathological tumor stage was pT3N0M0. The patient had an uneventful postoperative recovery and was discharged without complications. CONCLUSION: The case of this elderly man presents a rare occurrence of metachronous primary cancers in the renal pelvis and colon. Bladder cancer is considered a metastasis of renal pelvis cancer after surgery. Optimal treatment can be implemented by evaluating the patient's histological features, clinical history, and tumor distribution correctly.

Clinical efficacy analysis of partial cystectomy and radical cystectomy in the treatment of muscle-invasive sarcomatoid carcinoma of the urinary bladder.

Objective: This study compares the clinical efficacy of partial cystectomy (PC) versus radical cystectomy (RC) in the treatment of muscle-invasive bladder urothelial carcinoma (SCUB) through a retrospective analysis. Methods: We retrospectively analyzed the clinical data of 20 patients diagnosed with muscle-invasive SCUB from July 2015 to August 2023 at Ganzhou People's Hospital. All patients underwent surgical treatment followed by chemotherapy, with 9 receiving PC and 11 undergoing RC. We compared the average survival time of deceased patients for both treatments and conducted survival and multivariate analyses using the Kaplan-Meier method and Cox proportional hazards model, respectively. Results: All 20 patients were postoperatively diagnosed with muscle-invasive SCUB and were followed up for 4 to 60 months. The average survival time for patients undergoing PC was 11.5 months, with survival rates at 1 year, 2 years, and 5 years of 55.56%, 22.22%, and 11.11%, respectively. In contrast, patients receiving RC had an extended average survival time of 22.5 months, and their 1-year, 2-year, and 5-year survival rates increased to 63.64%, 36.36%, and 18.18%, respectively. Survival analysis revealed statistically significant differences in prognosis between PC and RC for the treatment of muscle-invasive SCUB (P<0.05). Conclusion: SCUB is a rare malignant tumor with unique biological characteristics often associated with poor prognosis. Upon diagnosis, RC should be considered as an early treatment approach when the patient's overall condition permits.

Targeting cancer-derived extracellular vesicles by combining CD147 inhibition with tissue factor pathway inhibitor for the management of urothelial cancer cells.

BACKGROUND: Extracellular vesicles (EVs), including microvesicles, hold promise for the management of bladder urothelial carcinoma (BLCA), particularly because of their utility in identifying therapeutic targets and their diagnostic potential using easily accessible urine samples. Among the transmembrane glycoproteins highly enriched in cancer-derived EVs, tissue factor (TF) and CD147 have been implicated in promoting tumor progression. In this in vitro study, we explored a novel approach to impede cancer cell migration and metastasis by simultaneously targeting these molecules on urothelial cancer-derived EVs. METHODS: Cell culture supernatants from invasive and non-invasive bladder cancer cell lines and urine samples from patients with BLCA were collected. Large, microvesicle-like EVs were isolated using sequential centrifugation and characterized by electron microscopy, nanoparticle tracking analysis, and flow cytometry. The impact of urinary or cell supernatant-derived EVs on cellular phenotypes was evaluated using cell-based assays following combined treatment with a specific CD147 inhibitor alone or in combination with a tissue factor pathway inhibitor (TFPI), an endogenous anticoagulant protein that can be released by low-molecular-weight heparins. RESULTS: We observed that EVs obtained from the urine samples of patients with muscle-invasive BLCA and from the aggressive bladder cancer cell line J82 exhibited higher TF activity and CD147 expression levels than did their non-invasive counterparts. The shedding of GFP-tagged CD147 into isolated vesicles demonstrated that the vesicles originated from plasma cell membranes. EVs originating from invasive cancer cells were found to trigger migration, secretion of matrix metalloproteinases (MMPs), and invasion. The same induction of MMP activity was replicated using EVs obtained from urine samples of patients with invasive BLCA. EVs derived from cancer cell clones overexpressing TF and CD147 were produced in higher quantities and exhibited a higher invasive potential than those from control cancer cells. TFPI interfered with the effect when used in conjunction with the CD147 inhibitor, further suppressing homotypic EV-induced migration, MMP production, and invasion. CONCLUSIONS: Our findings suggest that combining a CD147 inhibitor with low molecular weight heparins to induce TFPI release may be a promising therapeutic approach for urothelial cancer management. This combination can potentially suppress the tumor-promoting actions of cancer-derived microvesicle-like EVs, including collective matrix invasion.

Small particles or vesicles released by cancer cells into their surroundings have the potential to stimulate the spread and growth of cancer cells. In this study, we focused on two specific molecules presented by these cancer cell-derived vesicles that could play a role in promoting the dissemination of cancer cells: a protein related to blood clotting and a protein on the cell surface.We found that large vesicles from bladder cancer cells that have the ability to spread had higher levels of these proteins than vesicles from nonspreading cancer cells. We also found that the former could make cancer cells move about more, produce more of a substance that helps cancer cells spread, and invade other tissues.To counteract the cancer-promoting actions of these vesicles, we examined the impact of combining a naturally occurring anticlotting protein that can be released by medications derived from heparin with an inhibitor targeting the cancer cell surface protein. We found that this combination stopped the vesicles from helping cancer cells move about more, produce more of the spreading substance, and invade other tissues.This approach of simultaneously targeting the two protein molecules present on cancer cell-derived vesicles might be a new way to treat bladder cancer.

Unlocking the Potential of Adequate Bacillus Calmette-Guérin Immunotherapy in Very-high-risk Non-muscle-invasive Bladder Carcinoma: A Multicenter Analysis of Oncological Outcomes and Risk Dynamics.

BACKGROUND: The European Association of Urology (EAU) recommends discussing upfront radical cystectomy for all patients with very high risk (VHR) non-muscle-invasive bladder carcinoma (NMIBC), but the role of bacillus Calmette-Guérin (BCG) treatment remains controversial. OBJECTIVE: To analyze oncological outcomes in VHR NMIBC patients (EAU risk groups) treated with adequate BCG. DESIGN, SETTING, AND PARTICIPANTS: A multi-institutional retrospective study involving patients with VHR NMIBC who received adequate BCG therapy from 2007 to 2020 was conducted. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A survival analysis estimated recurrence-free survival (RFS), progression-free survival (PFS), and the cumulative incidence of cancer-specific mortality (CSM) after accounting for other causes of mortality as competing risk events and of the overall mortality (OM). Conditional survival probabilities for 0-4 yr without events were computed. Cox regression assessed the predictors of oncological outcomes. RESULTS AND LIMITATION: A total of 640 patients, with a median 47 (32-67) mo follow-up for event-free individuals, were analyzed. High-grade RFS and PFS at 5 yr were 53% (49-57%) and 78% (74-82%), respectively. The cumulative incidence of CSM and OM at 5 yr was 13% (10-16%) and 16% (13-19%), respectively. Conditional RFS, PFS, overall survival, and cancer-specific survival at 4 yr were 91%, 96%, 87%, and 94%, respectively. Cox regression identified tumor grade (hazard ratio [HR]: 1.54; 1.1-2) and size (HR: 1.3; 1.1-1.7) as RFS predictors. Tumor multiplicity predicted RFS (HR: 1.6; 1.3-2), PFS (HR: 2; 1.2-3.3), and CSM (HR: 2; 1.2-3.2), while age predicted OM (HR: 1.48; 1.1-2). CONCLUSIONS: Patients with VHR NMIBC who receive adequate BCG therapy have a more favorable prognosis than predicted by EAU risk groups, especially among those with a sustained response, in whom continuing maintenance therapy emerges as a viable alternative to radical cystectomy. PATIENT SUMMARY: Our research shows that a sustained response to bacillus Calmette-Guérin in patients can lead to favorable outcomes, serving as a viable alternative to cystectomy for select cases.

GEMIN4 Variants: Risk Profiling, Bioinformatics, and Dynamic Simulations Uncover Susceptibility to Bladder Carcinoma.

BACKGROUND: The relationship between GEMIN4 genetic variants and cancer, especially bladder carcinoma (BLCA), has been explored without conclusive results. This study aims to elucidate the link between GEMIN4 polymorphisms and BLCA susceptibility through genetic analyses, bioinformatics, and molecular dynamics (MD) simulations. METHODS: A cohort of 249 participants (121 BLCA patients and 128 unrelated controls) was enrolled. PCR was employed for allelic discrimination of GEMIN4 variants, followed by subgroup stratification, haplotype analyses, structural prediction using the AlphaFold2 prediction tool, subsequent MD simulations, structural analysis, and residue interaction mapping using Desmond, UCSF ChimeraX, and Cytoscape softwares. RESULTS: The rs.2740348*G variant demonstrated a protective role against BLCA in allelic (OR = 0.55, p = 0.002) and recessive (OR = 0.54, p = 0.017) models, whereas the rs.7813*T variant increased BLCA risk under the recessive model (OR = 1.90, p = 0.019). Haplotype analysis revealed a significant association between GEMIN4 haplotype (rs.2740348*C/rs.7813*T) with increased BLCA risk (OR = 2.01, p = 0.004). Univariate analysis revealed associations of the variants with albumin levels and absolute neutrophil count in BLCA patients. Pathogenicity evaluation categorized p.Gln450Glu as neutral and p.Arg1033Cys as deleterious. MD simulations revealed structural alterations and conformational shifts in the GEMIN4 protein induced by the Glu450 and Cys1033 mutations. CONCLUSIONS: The study highlights the dual role of GEMIN4 variants in BLCA susceptibility, with rs.2740348 conferring protection and rs.7813 increasing risk. The Glu450 residue positively impacted protein stability, while Cys1033 had a detrimental effect on protein function. These findings underscore the significance of GEMIN4 variants in BLCA susceptibility and pave the way for future diagnostic and therapeutic initiatives.

A study on immunohistochemical expression of HER2/Neu and p63 and its association with grade and invasiveness in case of bladder carcinoma.

INTRODUCTION: Bladder cancer is a global disease, ranks as the fourth most prevalent cancer. The incidence and prevalence increase with age. Grade and aggressiveness have been found to be related with different genetic expression and mutation. AIMS: To evaluate any relation of grade and invasiveness of urothelial cancer with varied expression of immune histochemical marker p63 and her2/neu. MATERIALS AND METHODS: The present study was a hospital based prospective cross-sectional study. This Study was conducted from July 2021 to April 2023 in the Urology department of a tertiary care hospital. Total 90 patients undergoing trans urethral resection of bladder tumour (TURBT) were included in this study. RESULT: It was found that, patients who had decreased p63 expression had high grade in tumours (93.1%) compared to patients who were expressing normal p63 (32.8%) and this was statistically significant (p < 0.0001). Tumours with decreased p63 also appeared to be more invasive, 62.1% were found to be muscle invasive. Tumours with her2 neu expression found to be more aggressive in nature, 85.7% had high grade features and 53.6% were muscle invasive. CONCLUSION: Our findings suggest that immunohistochemical expression of HER2/neu positive and decreased p63 expression were associated with high grade and invasiveness in case of bladder carcinoma.

Feasibility and safety of laparoscopic radical cystectomy for male octogenarians with muscle-invasive bladder cancer.

This study was designed to evaluate the safety and feasibility of laparoscopic radical cystectomy (LRC) for male octogenarian patients with muscle-invasive bladder cancer (MIBC). Briefly, a total of 57 male octogenarian patients (A group) with bladder carcinoma were enrolled and underwent LRC and intracorporeal pelvic lymph node dissection with bilateral cutaneous ureterostomy from May 2016 to December 2022. Besides, 63 male patients (age < 80 years old) with bladder carcinoma undergoing LRC and 17 octogenarian male patients with bladder carcinoma undergoing open radical cystectomy (ORC) were enrolled in B and C groups as control. All perioperative clinical materials and outcomes of long-term follow-up, and complication were collected. The specific results were shown as follows. Compared with C group, the operation time and resected lymph node in A group was increased, and the estimated blood loss, the number of transfusion needed, duration of pelvic drainage and hospital stay after surgery was decreased. The death rate and ileus complication rate were higher in A group (12 cases) than in C group (15 cases). The cases of ureteral stricture in A group (13 cases) was decreased compared with that in C group. Overall, LRC and bilateral cutaneous ureterostomy are safe, feasible and better choices for the treatment of male octogenarian patients with MIBC. The octogenarian receiving cutaneous ureterostomy heals slowly and exists certain incomplete intestinal obstruction after surgery.

Quarter-Century PET/Computed Tomography Transformation of Oncology: Hepatobiliary and Pancreatic Cancer.

[18F] Fluorodeoxyglucose (18F-FDG) PET/CT can improve the staging accuracy and clinical management of patients with hepatobiliary and pancreatic cancers, by detection of unsuspected metastases. 18F-FDG PET/CT metabolic parameters are valuable in predicting treatment response and survival. Metabolic response on 18F-FDG PET/CT can predict preoperative pathologic response to neoadjuvant therapy in patients with pancreatic cancer and determine prognosis. Several novel non-FDG tracers, such as 68Ga prostate-specific membrane antigen (PSMA) and 68Ga-fibroblast activation protein inhibitor (FAPI) PET/CT, show promise for imaging hepatobiliary and pancreatic cancers with potential for radioligand therapy.

MRI-based automated machine learning model for preoperative identification of variant histology in muscle-invasive bladder carcinoma.

OBJECTIVES: It is essential yet highly challenging to preoperatively diagnose variant histologies such as urothelial carcinoma with squamous differentiation (UC w/SD) from pure UC in patients with muscle-invasive bladder carcinoma (MIBC), as their treatment strategy varies significantly. We developed a non-invasive automated machine learning (AutoML) model to preoperatively differentiate UC w/SD from pure UC in patients with MIBC. METHODS: A total of 119 MIBC patients who underwent baseline bladder MRI were enrolled in this study, including 38 patients with UC w/SD and 81 patients with pure UC. These patients were randomly assigned to a training set or a test set (3:1). An AutoML model was built from the training set, using 13 selected radiomic features from T2-weighted imaging, semantic features (ADC values), and clinical features (tumor length, tumor stage, lymph node metastasis status), and subsequent ten-fold cross-validation was performed. A test set was used to validate the proposed model. The AUC of the ROC curve was then calculated for the model. RESULTS: This AutoML model enabled robust differentiation of UC w/SD and pure UC in patients with MIBC in both training set (ten-fold cross-validation AUC = 0.955, 95% confidence interval [CI]: 0.944-0.965) and test set (AUC = 0.932, 95% CI: 0.812-1.000). CONCLUSION: The presented AutoML model, that incorporates the radiomic, semantic, and clinical features from baseline MRI, could be useful for preoperative differentiation of UC w/SD and pure UC. CLINICAL RELEVANCE STATEMENT: This MRI-based automated machine learning (AutoML) study provides a non-invasive and low-cost preoperative prediction tool to identify the muscle-invasive bladder cancer patients with variant histology, which may serve as a useful tool for clinical decision-making. KEY POINTS: • It is important to preoperatively diagnose variant histology from urothelial carcinoma in patients with muscle-invasive bladder carcinoma (MIBC), as their treatment strategy varies significantly. • An automated machine learning (AutoML) model based on baseline bladder MRI can identify the variant histology (squamous differentiation) from urothelial carcinoma preoperatively in patients with MIBC. • The developed AutoML model is a non-invasive and low-cost preoperative prediction tool, which may be useful for clinical decision-making.

Endoplasmic Reticulum-Targeting AIE Photosensitizers to Boost Immunogenic Cell Death for Immunotherapy of Bladder Carcinoma.

Bladder cancer is characterized by high rates of recurrence and multifocality. Immunogenic cell death (ICD) of cancer cells has emerged as a promising strategy to improve the immunogenicity of tumor cells for enhanced cancer immunotherapy. Although photosensitizer-based photodynamic therapy (PDT) has been validated as capable of inducing ICD in cancer cells, the photosensitizers with a sufficient ICD induction ability are still rare, and there have been few reports on the development of advanced photosensitizers to strongly evoke the ICD of bladder cancer cells for eliciting potent antitumor immune responses and eradicating bladder carcinoma in situ. In this work, we have synthesized a new kind of endoplasmic reticulum (ER)-targeting aggregation-induced emission (AIE) photosensitizer (named DPASCP-Tos), which could effectively anchor to the cellular ER and trigger focused reactive oxygen species (ROS) production within the ER, thereby boosting ICD in bladder cancer cells. Furthermore, we have demonstrated that bladder cancer cells killed by ER-targeted PDT could serve as a therapeutic cancer vaccine to elicit a strong antitumor immunity. Prophylactic vaccination of the bladder cancer cells killed by DPASCP-Tos under light irradiation promoted the maturation of dendritic cells (DCs) and the expansion of tumor antigen-specific CD8+ T cells in vivo and protected mice from subsequent in situ bladder tumor rechallenge and extended animal survival. In summary, the ER-targeted AIEgens developed here significantly amplified the ICD of bladder cells through focused ROS-based ER oxidative stress and transformed bladder cancer cells into the therapeutic vaccine to enhance immunogenicity against orthotopic bladder cancer, providing valuable insights for bladder carcinoma treatment.

The expression of SP263 in muscle invasive bladder carcinoma and its relationship with clinicopathological features.

Context: The expression of programmed cell death ligand1 (PDL1) is a research hotspot of immunotherapy. The treatment targeted for its expression has shown effectiveness in many tumors. Objective: The aim of the study was to determine PD-L1 expression in urothelial carcinoma (UC) and to compare the PD-L1 expression in muscle invasive bladder carcinoma (MIBC) and upper urinary tract urothelial carcinoma (UTUC). The predictive value of CD8+ tumor-infiltrating lymphocyte (TIL) density for the diagnosis of PD-L1 positivity and the association between CD8+ TIL density and prognosis in MIBC were also explored. Materials and Methods: Immunohistochemistry (IHC) staining for PD-L1 (SP263), CK5/6, CK20, CD44, and p53 was carried out using a 3D Histech digital scanner to scan and determine CD8+ TIL density. Results: 122 patients received radical cystectomy, and the overall PD-L1 positivity was 34.43% (42/122). PD-L1 positivity in whole sections was higher than in tissue micro-array (TMA) (all P < 0.05). If multiple lesions were detected simultaneously, the number of patients with positive results increased from 42 to 49. The areas under the curve (AUCs) of CD8+ TIL density for the diagnosis of PD-L1 positivity were 0.739, 0.713, and 0.826. Univariate cox regression analysis demonstrated that high CD8+ TIL density and CD8highPDL1+ were protective factors of overall survival (OS), and multivariate cox analyses showed that only CD8+ TIL density was an independent prognostic factor for OS. For UTUC, the overall PD-L1 expression was 40.0% (16/40). Conclusions: Our study results emphasize the importance of detecting PD-L1 expression in multiple tumor lesions from the same patient. In MIBC, CD8+ TIL density could be used as a prognostic marker for predicting the status of PD-L1 expression.