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Background: Epithelial-mesenchymal transition (EMT) plays an important role in bladder carcinoma (BC) invasiveness and metastasis. Studies have shown that muscle-invasive BC (MIBC) and non-MIBC (NMIBC) are different at the molecular level owing to different EMT-related programming. Recent studies suggest that dysregulation of specific miRNAs is linked to EMT in BC. With this background, we aimed to study the immunoexpression of EMT-markers and its correlation with miRNA-200c expression in a series of MIBCs and NMIBCs. Materials and Methods: Quantitative real-time-polymerase chain reaction for the quantification of miR-200c expression was performed on 50 cases of urinary BC obtained from transurethral resection of bladder tumor (TURBT), cystectomy specimens, and ten peritumoral bladder tissue. Immunohistochemistry for ZEB1, ZEB2, TWIST, E-cadherin, and β-catenin was performed on tumor and peritumoral bladder tissue. Results: Thirty-five TURBT and 15 cystectomy specimens were assessed. Among MIBC, loss of expression of E-cadherin (72.3%), β-catenin (66.7%), and ZEB1, ZEB2, and TWIST2 immunoreactivity was noted in 53.3%, 86.7%, and 73.3% of cases, respectively. Among NMIBC, loss of expression of E-cadherin (22.5%), β-catenin (17.1%) and ZEB1, ZEB2, and TWIST immunoreactivity was noted in 11.5%, 51.4%, and 91.4% of cases, respectively. Upregulation of miRNA-200c was noted in cases with retained E-cadherin and negative TWIST expression. Downregulation of miRNA-200c expression was noted in all the cases showing loss of E-cadherin, β-catenin, and in cases immunoreactive for ZEB1, ZEB2, and TWIST in MIBC. Downregulation of miRNA-200c expression was also noted in cases of MIBC with retained β-catenin and those immunonegative for ZEB1 and ZEB2. A similar trend was noted in NMIBC. Median miRNA-200c expression was low in both high-grade and low-grade NMIBC compared to peritumoral bladder tissue and was not statistically significant. Conclusion: This study for the first time explores the relation of miR200C with E-cadherin, b-catenin, and its direct transcriptional regulators, namely Zeb1, Zeb2, and Twist in the same cohort of BC. We observed that miRNA-200c is downregulated in both MIBC and NMIBC. We identified novel expression of TWIST in cases of BC showing downregulation of miR200Cs suggesting that it is one of the protein targets of altered miRNA-200c expression contributing to EMT and can serve as a promising diagnostic marker and therapeutic target. Loss of E-cadherin and ZEB1 immunoexpression in high-grade NMIBC suggests an aggressive clinical behavior. However, ZEB2 heterogeneous expression in BC limits its diagnostic and prognostic utility. [ABSTRACT FROM AUTHOR]

The diagnosis of bladder cancer and necessity of urostomy is profoundly life changing. This qualitative study was conducted in order to assess lived experiences of patients who had received urostomy due to bladder cancer or any other urinary pathology. The sample included 30 patients with urostomy admitted in the Urology ward, AIIMS, New Delhi. Purposive sampling was used and data was collected using semi structured interviews. Narrative data was analysed using Colaizzi’s steps of analysis for qualitative data. Ten themes emerged from the analyses which were further categorized into sub themes. The theoretical framework of the themes and subthemes defined the phenomenon of living with urostomy in entirety. [ABSTRACT FROM AUTHOR]

The Corona Virus Disease-2019 (COVID-19), one of the most devastating pandemics ever, has left thousands of cancer patients to their fate. The future course of this pandemic is still an enigma, but health care services are expected to resume soon in a phased manner. This might be a long drawn process and we need to have policies in place, to be able to fight both, the SARS-CoV-2 virus and cancer, simultaneously, and emerge triumphant. An extensive literature search for impact of delay in management of various urological malignancies was carried out. Expert opinions were sought wherever there was paucity of evidence, in order to reach a consensus and come up with recommendations for directing uro-oncology services in the times of COVID-19. The panel recommends deferring treatment of patients with renal cell carcinoma by 3 to 6 months, except for those with ongoing hematuria and/or inferior vena cava thrombus, which warrant immediate surgery. Metastatic renal cell cancers should be started on targeted therapy. Low grade non-muscle invasive bladder cancers can be kept on active surveillance while high risk non-muscle invasive bladder cancers and muscle invasive bladder cancers should be treated within 3 months. Neoadjuvant chemotherapy should be avoided. Management of low and intermediate risk prostate cancer can be deferred for 3 to 6months while high risk prostate cancer patients can be initiated on neoadjuvant androgen deprivation therapy. Patients with testicular tumors should undergo high inguinal orchiectomy and be treated according to stage without delay, with stage I patients being offered surveillance. Penile cancers should undergo penectomy, while clinically negative groins can be kept on surveillance. Neoadjuvant chemotherapy should be avoided and adjuvant therapy should be deferred. We need to tailor our treatment strategies to the prevailing present conditions, so as to fight and defeat both, the SARS-CoV-2 virus and cancer. Protection of health care workers, judicious use of available resources, and a rational and balanced outlook towards different malignancies is the need of the hour. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the diagnostic performance of stalk morphology on diffusion-weighted imaging (DWI) in comparison with conventional MRI in predicting muscle invasion in urinary bladder cancer.Methods: The study was prospective and approved by the institutional ethics committee. A written informed consent was obtained from all the patients. The study included 56 patients who presented with bladder mass between January 2014 and November 2015. After excluding 16 patients, 40 patients with 92 tumors were assessed. All the 40 patients underwent MRI at 3.0 Tesla (Achieva, Philips) inclusive of DWI (b0, 500, 1000 and 1500). Two radiologists evaluated the images independently, and disparities were resolved through consensus. For predicting muscle invasion on T2-weighted images, tumor morphology (papillary versus non-papillary), distensibility of the underlying bladder wall, and perivesical fat infiltration were evaluated. On DWI, the criterion used in a previous study (Takeuchi et al.) was used along with tumor stalk morphology. Findings were compared with histopathology using Pearson’s χ2 test, and diagnostic performance indices were calculated.Results: All the evaluated features were present with significantly higher frequency in muscle-invasive tumors (p < 0.001). The finding of absent or distorted stalk on DWI had the highest sensitivity (87.5%) and specificity (97.6%). Conventional imaging features of non-papillary stalk morphology, restricted distension of underlying bladder wall, perivesical fat infiltration, as well as the previous DWI criterion were less sensitive (56.3%, 68.8%, 56.3% and 56.3%, respectively) in predicting muscle invasion.Conclusions: Assessment of the morphology of the reactive tumor stalk on DWI has better diagnostic performance in predicting muscle invasion than conventional MRI. [ABSTRACT FROM AUTHOR]

Background: Majority of bladder cancer deaths are caused due to transitional cell carcinoma (TCC) which is the most prevalent and chemoresistant malignancy of urinary bladder. Therefore, we analyzed the role of Sperm associated antigen 9 (SPAG9) in bladder TCC. Methodology and Findings: We examined SPAG9 expression and humoral response in 125 bladder TCC patients. Four bladder cancer cell lines were assessed for SPAG9 expression. In addition, we investigated the effect of SPAG9 ablation on cellular proliferation, cell cycle, migration and invasion in UM-UC-3 bladder cancer cells by employing gene silencing approach. Our SPAG9 gene and protein expression analysis revealed SPAG9 expression in 81% of bladder TCC tissue specimens. High SPAG9 expression (>60% SPAG9 positive cells) was found to be significantly associated with superficial non-muscle invasive stage (P = 0.042) and low grade tumors (P = 0.002) suggesting SPAG9 putative role in early spread and tumorigenesis. Humoral response against SPAG9 was observed in 95% of patients found positive for SPAG9 expression. All four bladder cancer cell lines revealed SPAG9 expression. In addition, SPAG9 gene silencing in UM-UC-3 cells resulted in induction of G0–G1 arrest characterized by up-regulation of p16 and p21 and consequent down-regulation of cyclin E, cyclin D and cyclin B, CDK4 and CDK1. Further, SPAG9 gene silencing also resulted in reduction in cellular growth, and migration and invasion ability of cancer cells in vitro. Conclusions: Collectively, our data in clinical specimens indicated that SPAG9 is potential biomarker and therapeutic target for bladder TCC. [ABSTRACT FROM AUTHOR]

We present the outcomes of a large series of patients treated with radical cystectomy and pelvic lymphadenectomy for transitional cell carcinoma of bladder. Materials and Methods: A total of 502 patients underwent radical cystectomy (RC) for bladder cancer from 1992 till December 2006. Of these, 432 patients with primary transitional cell carcinoma of bladder underwent RC with bilateral pelvic lymphadenectomy with a curative intent. The clinical course, pathologic characteristics and long-term clinical outcomes were evaluated in this group of patients. Results: The median follow-up was 62 months. There were 30 (6.9%) perioperative deaths and 111(25.7%) early complications. The recurrence-free survival (RFS) and overall survival (OAS) were 66% and 62% at five years and 62% and 40% respectively at 10 years. The RFS and OAS were significantly related to the pathological stage and lymph node status with increasing pathological stage and lymph node positivity associated with higher rate of recurrence and worse OAS (P < 0.001). A total of 145 patients (33.5%) developed bladder cancer recurrence. Of these, 40 (27.6%) developed local pelvic recurrence and 105 patients (72.4%) developed distant recurrence. The median time to local and distant recurrence was 12 and 16 months respectively. Conclusion: The clinical results reported from this large group of patients demonstrate that radical cystectomy provides good survival results for invasive bladder cancer patients with low incidence of pelvic recurrence. [ABSTRACT FROM AUTHOR]

Radical cystectomy is the standard of care for patients with muscle invasive bladder cancer. While open radical cystectomy is now a standard procedure, laparoscopic radical cystectomy is still in its infancy. We performed this surgery laparoscopically in 11 patients and review the procedure specific complications. Beginning in February 1999, 11 patients underwent laparoscopic radical cystectomy at the Department of Urology, All India Institute of Medical Sciences, New Dehli. Urinary diversion was performed by an open-hand sewn ileal conduit. There were three intraoperative complications specifically related to the laparoscopic radical cystectomy. These included injury to the external iliac vein in one patient and a small rectal tear in two. All were repaired with laparoscopic free hand suturing with normal postoperative recovery. Other laparoscopy-related complications were subcutaneous emphysema in one patient and hypercarbia necessitating conversion to open surgery in a patient who, four weeks after surgery, died of multiple organ failure. One patient had margins positive and received cisplatinum-based chemotherapy. All patients had normal renal function and preserved upper tracts with no evidence of metastasis at a mean of 18.4 months follow up (range 1–48 months). Though there were three complications specific to the laparoscopic radical cystectomy, none necessitated a conversion to open surgery or hampered the overall outcome. Absence of local recurrence or metastatic disease at four years of follow up suggests that the procedure is oncologically valid. Laparoscopic radical cystectomy is a new procedure and it is important to critically analyze the complications in order to reduce their occurrence and allow the development of a better technique. [ABSTRACT FROM AUTHOR]

Introduction: The objective of the study was to determine the pattern of p53 expression in patients with muscle invasive bladder cancer treated with cystectomy and to assess the prognostic value of p53 expression in this group of patients. Materials and Methods: We retrospectively analyzed data of 100 patients who underwent cystectomy for invasive transitional cell carcinoma of the urinary bladder. These patients were seen at 3-monthly intervals during the first 2 years, 6-monthly in the third year, and yearly thereafter. Immunohistochemical analysis for p53 was done on paraffin-fixed tissues with DO-7 antibodies. The tumours with >30% cells staining for p53 proteins were considered p53 positive. Results: There were 95 males and 5 females with a mean age of 54 years. Two patients died in the perioperative period and were excluded from analysis. Over a median follow-up period of 2 years (range 3 months to 10 years) 62 patients are alive without disease while 36 had relapse and of these, 31 have died. The p53 expression was significantly related to stage and grade of the tumour. p53-negative tumours were more likely to be organ confined and of lower grade as compared to p53-positive tumours. The stage of tumour was significantly related to outcome but grade and p53 immunohistochemistry did not provide any prognostic information. Conclusions: p53 immunostaining was positive in 57% of muscle invasive urinary bladder tumours. The p53 positivity correlated well with the stage and grade of the disease, whereas it has no additional prognostic value.Copyright © 2003 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

To explore the utility of first-order MRI-texture analysis (TA) parameters in predicting histologic grade and muscle invasion in urinary bladder cancer (UBC). After ethical clearance, 40 patients with UBC, who were imaged on a 3.0-Tesla scanner, were retrospectively included. Using the TexRADTM platform, two readers placed freehand ROI on the sections demonstrating the largest dimension of the tumor, evaluating only one tumor per patient. Interobserver reproducibility was assessed using the intraclass correlation coefficient (ICC). Mann–Whitney U test and ROC curve analysis were used to identify statistical significance and select parameters with high class separation capacity (AUC >0.8), respectively. Pearson's test was used to identify redundancy in the results. All texture parameters showed excellent ICC. The best parameters in differentiating high and low-grade tumors were mean/ mean of positive pixels (MPP) at SSF 0 (AUC: 0.897) and kurtosis at SSF 5 (AUC: 0.828) on the ADC images. In differentiating muscle invasive from non-muscle invasive tumors, mean/ MPP at SSF 0 on the ADC images showed AUC >0.8; however, this finding resulted from the confounding effect of high-grade histology on the ADC values of muscle invasive tumors. MRI-TA generated few parameters which were reproducible and useful in predicting histologic grade. No independent parameters predicted muscle invasion. There is lacuna in the literature concerning the role of MRI-TA in the prediction of histologic grade and muscle invasion in UBC. Our study generated a few first-order parameters which were useful in predicting high-grade histology. [ABSTRACT FROM AUTHOR]

Abstract: Background: Urothelial carcinoma of the bladder is characterised by very high recurrence rate, followed up by cystoscopy which being invasive technique makes the need for non-invasive markers important for Transitional Cell Carcinoma (TCC) detection. CD147 is a transmembrane protein highly expressed in tumour cells which aids in tumour invasion and growth. BIGH3, an Extracellular matrix protein (ECM) which interacts with various ECM component in different tissue system and Stathmin(STMN1) is cytosolic microtubule destabilising protein also called as Oncoprotein18 due to its role in tumour promotion. So far the expression of BIGH3 and STMN1 remains undetermined in cancer subjects including TCC. We therefore studied the levels and molecular expression of these molecules in TCC patients, to evaluate their usefulness as diagnostic markers. Methods: Thirty consecutive TCC patients and two sets of control- 15 Benign prostatic hyperplasia (BPH) patient and 15 healthy were taken. Serum and urine levels of these molecules were estimated by ELISA and relative mRNA expression by Q-PCR from tumour and normal urothelium. Post-Hoc analysis and ROC curve were determined to evaluate the significance and sensitivity and specificity. Results: The mean concentrations of these molecules were found to be significantly increased (p<0.001) in the serum and urine of TCC patients, with varying significance in each grade for different molecules. The urinary levels of CD147 (67pg/ml) and serum STMN1 concentration (1.38ng/ml) showed a specific increase as compared to the controls, while BIGH3 was elevated in both serum and urine samples. Molecular (mRNA) expression was elevated in the high grade (Muscle Invasive) stage of the disease for all the molecules, with a significant 3-fold increase that correlated with disease severity being observed for STMN1. ROC analysis gave optimal combination of sensitivity and specificity for diagnosis of the disease in urine and serum sample for STMN1. Conclusion: Of CD147, BIGH3 and STMN1, significant results were obtained for STMN1 and it could serve as the best possible diagnostic marker for TCC detection in future. [Copyright &y& Elsevier]

Abstract: Objectives: Bladder cancer is a common tumor of the urinary tract, accounting for 6% to 8% of all male malignancies and 2% to 3% of all female malignancies. Urothelial carcinoma (UC) of bladder is the second most common urologic malignancy after prostate cancer. Earlier report has elucidated immunologic unreactivity in cancer patients. Cytokines play a pivotal role in the induction of cell mediated and humoral immunity. Quantification of cytokine response in cancer patients can give significant insights about the cellular immunologic potency against the neoplastic cells. In the present study, we aimed to assess alterations of Th1 and Th2 derived cytokines in progression of UC of bladder by determining their circulatory concentration in bladder cancer patients and healthy controls and to correlate the observations with grade and severity of the disease. Materials and methods: The study cohort consisted of 122 subjects; 72 patients with bladder UC (28, low grade; 17, high grade; 27, muscle invasive) and 50 healthy controls. The circulatory levels of various cytokines were measured using commercially available sandwich enzyme linked immunosorbent assay (ELISA) kit from BD Biosciences, San Diego, CA, and were statistically correlated according to the grade and the severity of disease. Results: The serum levels of typical Th1 cytokines: IL-2 and IFN-γ were found to be significantly lower (P < 0.001) while levels of Th2 cytokines i.e., IL-4, IL-5, and IL-10 were significantly higher (P < 0.001) in patients than in controls. The levels of all the cytokines were correlated with the grade and severity of the disease. There were significant differences between the patients with low grade tumors and muscle invasive tumors for all cytokines (P < 0.001); except IL-10 (P < 0.626). Conclusions: The results of our study delineate that in bladder tumor patients a marked polarization exists towards the expression of Th2 type cytokines while Th1 remain suppressed. Furthermore, the levels of all the cytokines alter according to the grades of the tumor. This can give significant insights about the use of Th1 type cytokines for the administration of immunotherapy to bladder cancer patients. Development of new strategies attempting to manipulate the equilibrium between Th1 and Th2 cells would be beneficial in the management of UC of bladder in future. [Copyright &y& Elsevier]

Abstract: Objectives: Urothelial carcinoma of bladder is the second most common urological malignancy after prostate cancer. Recently, there has been increased interest in research of the role of free radicals and antioxidant materials in the prevention, treatment, and alleviation of therapy-related side effects of cancer. In the present study, we aimed to assess the alterations in the levels of antioxidant vitamins, activities of defense enzymes, circulating lipid peroxide, and total antioxidant activity (AOA) in patients with urothelial carcinoma of bladder and correlate these changes with the grade and severity of the disease. Materials and methods: The study cohort consisted of 90 subjects; 50 patients with bladder UC (25, low grade; 10, high grade; 15, muscle invasive) and 40 healthy controls. Vitamins C and E, malondialdehyde (MDA), and AOA were estimated using standard protocols. Superoxide dismutase (SOD) and glutathione peroxidase (GPx) were assayed using commercially available kits. Results: The serum levels of vitamins C and E, whole blood levels of SOD and GPx, and serum AOA was significantly lower (P < 0.001) while serum MDA levels were significantly higher (P < 0.001) in patients than in controls, indicating presence of oxidative stress in bladder UC patients. The levels of all the biochemical parameters were correlated with the grade and severity of the disease. There were significant differences between the patients with low grade tumors and muscle invasive tumors for all parameters (P < 0.001); except AOA (P < 0.279). Conclusions: The observed redox imbalance in UC of bladder in correlation with the grade and stage, as a consequence of decreased levels of antioxidant vitamins, enzymes, and AOA, along with increased MDA levels in circulation, may be important factors in tumor development and growth. Our results suggest that with advancing stage of bladder UC, the levels of oxidative stress increase, while levels of antioxidant molecules decrease. These findings suggest possible use of antioxidant supplementation as prophylactic agents for prevention and treatment of bladder cancer. [Copyright &y& Elsevier]