© 2022 Indian Journal of Urology | Published by Wolters Kluwer Medknow I happened to be chairing a session on an oft-repeated topic of bladder cancer. An accomplished medical oncologist and urologist were debating the need for neoadjuvant chemotherapy, where the discussion was to treat occult micrometastasis before even considering cystectomy. The second half of the session had one more debate on the template of lymph node dissection in bladder cancer. It was interesting to see speakers contesting convincingly to prove their points with supporting literature. In both the debates, I could observe an interesting contradiction in the philosophy of treatment.

Introduction: We aimed to present our experience in managing renal cell carcinoma (RCC) with inferior vena cava (IVC) thrombus. Methods: Records of all patients aged 18 years and older, with a diagnosis of primary renal masses with IVC thrombus, presenting to our institute from January 2012 to August 2020 were retrospectively reviewed. Patients with tumor thrombus limited only to renal vein were excluded from the analysis. Their hospital course and outcomes were recorded and evaluated for predictors of survival. Results: During the study period, we treated 61 patients with a renal mass and concurrent IVC thrombus and 56 of these underwent surgery. 7 of them had level III and 6 had level IV thrombus. A total of six patients received neoadjuvant tyrosine kinase inhibitor (TKI) therapy and all of them showed a decrease in size and level of tumor thrombus and cardiopulmonary bypass was safely avoided. Fourteen patients had distant metastasis and underwent cytoreductive surgery and of these 12 patients received TKI therapy after surgery with a mean survival of 26.8 months. The overall survival at 2 and 5 years of nonmetastatic group was 81.1% and 47.5% respectively and in metastatic group was 35.1% and 0%, respectively. Poor performance status, distant metastasis, higher T stage, higher thrombus levels, and positive surgical margins were all predictors of decreased survival. Conclusions: Complete surgical resection in both nonmetastatic and metastatic RCC with IVC thrombus has long-term survival benefits. Neoadjuvant TKI therapy, with adequate preoperative planning, helps in decreasing the size of the thrombus and in safely avoiding bypass in level III and IV IVC thrombi.

Introduction: We evaluated incidence ofprostate-specific antigen (PSA) positivity (>4ng/mL) and cancer detection rate on prostate biopsy in two populations of men, one undergoing opportunistic testing for lower urinary tract symptoms and another during routine health checks. Methods: Data regarding PSA screening, rectal examination (RE), transrectal ultrasound-guided biopsy, clinical stage, and risk assessment grouping according to NCCN guidelines were studied. Group A included patients with lower urinary tract symptoms (LUTS) (opportunistic screening) at SGPGIMS, Lucknow and Group B included healthy men who had executive health check-up with PSA testing at Medanta the Medicity, Gurugram. Results: PSA positivity rate in 9906 symptomatic men for LUTS (Group A) and 24919 healthy men (Group B) was 28.4% and 3% respectively. In group A, PSA positivity rate was 28.4% but only around half of all men with an indication underwent a biopsy. Among men with PSA of 4–10 ng/mL, cancer was detected in 93 of 241 who underwent a biopsy (38.5%). In Group B, only 69 men (9.3% of those with an elevated PSA) underwent a prostate biopsy, of which 38/57 (with PSA of 4–10 had cancer. In Group A, the cancers was metastatic in 61.5% men, while none in-Group B had metastatic disease. Conclusion: Opportunistic screening and executive health check with PSA identifies a significant number of men with PSA positivity and may help decrease the proportion of men diagnosed in metastatic prostate cancer.

Several metabolomics-derived biomarkers of prostate cancer (PC) have been reported with pre-radical prostatectomy (RP) (knock-in PC) conditions; however, uncontested PC biomarkers panel appraisal and investigation of correlative evidence of these measures is lacking through post-RP (knock-out PC). We sought to explore patients' filtered serum-based metabolomics derived signature measures in knock-in PC (n = 90) using nuclear magnetic resonance spectroscopy and multiple rigorous statistical analyses, and to develop the correlative evidence of these measures through knock-out PC (n = 90) follow-up on the 15th and 30th days. The glutamate, citrate and glycine were observed as hallmarks of PC. Observed trends revealed; augmented glutamate level in knock-in PC following a sudden drop and subsequently upside of glutamate at 15th and 30th days of knock-out PC, reduction of citrate in knock-in PC subsequently gradual increase of citrate in knock-out PC, and glycine lessening in knock-in PC following augmentation on 30th day of knock-out PC. This study-based evidence clears the doubts regarding the discovery of metabolomics-derived PC biomarkers.

With high morbidity and mortality, urinary bladder cancer (BC) ranks fifth among common cancers globally. The inherent limitations of urine cytology and cystoscopy, and marginal enhancements in the rate of survival promt us to develop surrogate serum based metabolic biomarkers of screening, identification, and follow-up protocols of management for BC patients. Earlier, we exhibited that abnormal expression levels of dimethylamine (DMA), malonate, lactate, glutamine, histidine, and valine in serum may be used as signature metabolites to differentiate BC from healthy controls (HC) (J. Proteome Res. 2013; 12(12):5839-50). Here we further gauge and validate these observations by comparing pre-operative to post-operative follow-up BC patients. This study was conducted on 160 sera samples involving HC (n = 52), pre -operative (n = 55) and post-operative (n = 53) BC cases. 1H nuclear magnetic resonance (NMR) spectroscopy was used to generate serum metabolic profiles and to gauge aberrantly expressed metabolites. The targeted metabolomic approach revealed that the expression levels of these signature metabolites were progressively and significantly decreased in post-operative follow-up at the interval of 30, 60, and 90 days compared to pre-operative BC sera samples and were maintained at HC levels. Serum metabolic biomarkers appear to be an inspiring and least-invasive tactic for detection and prognosticating BC patient follow-up. (C) 2020 Published by Elsevier B.V.

In the present study, quantitative expression of epithelial-to-mesenchymal transition (EMT)–associated markers was investigated immunohistochemically and their diagnostic and prognostic significance was evaluated in patients diagnosed with non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). Immunohistochemical (IHC) staining was performed in a cohort of 65 formalin-fixed and paraffin-embedded human urinary bladder tumor tissues. Tissues’ sections were obtained from archives of the Department of Pathology at SGPGIMS, India. Epithelial marker (E-cadherin), mesenchymal markers (N-cadherin and vimentin), and EMT-activating transcription factors (ATFs) (Snail and Slug) were examined for their cellular localization (membranous/cytoplasmic/nuclear) and quantitative expressions in terms of IHC score. Expression of the aforesaid markers was statistically correlated with various clinicohistopathological variables. These variables were obtained from histopathology reports and subsequent follow-up and OPD visits of patients. Impact of these markers was assessed on recurrence-free survival (RFS) in NMIBC cases and progression-free survival (PFS) in MIBC cases. The data was analyzed using SPSS 20.0 software. Focal loss of membranous E-cadherin showed statistical relevance with hematuria and tumor grade ( p < 0.001, p = 0.005: independent sample t test) in MIBC patients. Novel membranous expression of N-cadherin exhibited relevance with hematuria ( p = 0.011, one sample t test) in NMIBC, while membranous expression of vimentin showed correlation with tumor grade and age ( p < 0.001, p < 0.001, one sample t test) in MIBC cases. Nuclear immunopositivity of Snail showed statistical association with tumor grade in both NMIBC and MIBC cases ( p < 0.001, Moses non-parametric test; p < 0.001, one sample t test) and with hematuria in MIBC cases ( p = 0.007, independent sample t test). Additionally, nuclear immunopositivity of Slug showed statistical association with tumor type in NMIBC and tumor grade in MIBC cases ( p < 0.001, Moses non-parametric test; p < 0.001, one sample t test). Kaplan-Meier along with logrank statistics examined association between EMT profile and RFS in NMIBC cases ( p < 0.001). Significant association of EMT biomarkers with clinicohistopathological outcomes may aid urologists to correlate its dynamic functions in urothelial tumorigenesis.

Introduction: Renal cell carcinoma epitomizes a diversified group of tumors which contributes more than 15,000 deaths annually worldwide. In spite of tremendous efforts to identify prognostic factors apart from grade, histology and tumor size, they are not so obvious yet to fulfill the requirement. In this study, the prognostic role of serum matrix metalloproteinase, (MMP)-2, 9, and vascular endothelial growth factor (VEGF) levels in patients with pre and postoperative renal cell carcinoma are evaluated to use, as biomarker. Patients and methods: A total of 100 patients with;I diagnosis of renal cell carcinoma included in the study. Additionally, hundred healthy kidney donors enrolled as control, serum MMP-2, MMP-9, and VEGF levels were analyzed in the serum of post and preoperative patients and parallel in control serum samples by ELBA method. Result: Most of the patients with RCC were found to have high concentrations of serum MMP-2, MMP-9, and VEGF. The levels of MMP-2 in the serum of preoperative patients ranged from 627 to 1117 ng/ml (833.90 +/- 111.91), postoperative MMP-2 range 302-913 (553.02 +/- 150.08), control range 122-384 (228.33 +/- 72.52). In MMP-9 pre-operative range 61.9-1233 (862.32 +/- 119.77), post-operative range 124-909 (552.88 +/- 151.91) and control range 42-467 (245.44 +/- 116.52 and in VEGF preoperative range was 0.792-2.214 (1.3.5 +/- 0.36), postoperative range was 0.315-1.917 (0.81 +/- 0.46) and in control it was 0.01-0.39 (0.10 +/- 0.09). We observed that preoperative levels of all three markers, were significantly increased if compared with postoperative and control levels (P = 0.001) however, no any significant correlation found when the levels correlated with grade., stage, size, and type for MMP-2 and MMP-9, but VEGF shows some significance, in comparison. Conclusion: The present data shows relevance and strong significant decrease in the level of MMP-2, MMP-9, and VEGF after surgery, so they could use as biomarkers in early disease diagnosis and also in monitoring disease recurrence.

Tubulocystic renal cell carcinoma (TCRCC) is a recently described rare subtype of RCC. To best of our knowledge less than 70 cases have been reported till date. The concurrent papillary RCC (PRCC) and TCRCC has been documented in literature, but the co-occurrence of clear cell RCC (CCRCC) and TCRCC is very rare. We are describing a rare case of incidentally detected TCRCC occurring with CCRCC in a 45 years old male who presented with high grade fever with chills and rigors. Grossly, there were two distinct tumors in the total nephrectomy specimen. The larger tumor displayed the histopathological features of CCRCC and the smaller tumor revealed the features of TCRCC.treatment in the present case. SYNCHRONOUS CLEAR CELL RENAL CELL CARCINOMA AND TUBULOCYSTIC RENAL CELL CARCINOMA ERA’S JOURNAL OF MEDICAL RESEARCH VOL.3 NO.2 Manoj Jain, Shruti Agrawal, Sushila Jaiswal, Bharti Ramnani, Anil Mandhani* Department of Pathology and Department of Urology & Kidney Transplantation* Sanjay Gandhi Postgraduate Institute of Medical Sciences , Lucknow226014 Dr. Manoj Jain Department of Pathology Sanjay Gandhi Postgraduate Institute of Medical Sciences , Lucknow226014 Email: mnjjain@yahoo.com Phone: +91-9415024991 Address for correspondence

OBJECTIVE We present the outcomes of modification of cutaneous ureterostomy by extreme lateralization of the stoma and use of skin flap for formation of ureterostomy. MATERIAL AND METHODS Between June 2012 and June 2016, 36 patients had modified cutaneous ureterostomy for ureteral obstruction due to pelvic malignancy or genitourinary tuberculosis. Transureteroureterostomy was made with cutaneous stoma at anterior axillary line between iliac crest and lower rib cage, instead of spinoumbilical line. To prevent stenosis a 'V' shaped skin was fed into the stoma. Double J stents were used in all patients for 6 weeks. Perioperative morbidity and mortality were evaluated. All patients were followed up at 3 month intervals. RESULTS Of 36 patients, 22 had radical cystoprostatectomy (including nephroureterectomy in 2 patients) and 7 had palliative cystectomy. Others had locally advanced prostate cancer (n=1), locally advanced cervical cancer (n=3), ovarian cancer (n=1) and genitourinary tuberculosis with small capacity bladder along with a large vesicovaginal fistula (n=1). One patient developed ureteral necrosis requiring conversion to ileal conduit. Three patients developed stomal stenosis: two were managed by self-dilatation while one required revision of stoma. Thirteen patients died of the disease at a median follow up of 6 months with functioning stoma. Remaining 19 patients survived without any complications at a median follow-up of 20.5 months (5.5-43.5 months). None of the patients had any problem related to ureterostomy bag application. CONCLUSION Modified lateral cutaneous ureterostomy provides relatively straighter and shorter retroperitoneal course of ureter with acceptable morbidity and avoids use of bowel in selected patients.

Involvement of matrix metalloproteinases (MMPs) in the pathogenesis of urothelial carcinoma elects them to be sensitive marker for clinical and prognostic implications. MMPs regulate tumor growth and invasion by inducing epithelial-to-mesenchymal transition (EMT) which is characterized by the complex reprogramming of epithelial cells and ultimately bring about major changes in the structural organization of bladder urothelium. The present study has been undertaken to evaluate the clinical relevance of MMPs in two distinct types of bladder cancer disease. Expression analysis of MMPs namely MMP-2, MMP-7, MMP-9 and EMT markers including epithelial marker, E-cadherin; mesenchymal markers, N-cadherin and Vimentin; and EMT-activating transcriptional factors (EMT-ATFs), Snail, Slug, Twist and Zeb was done in 64 cases of bladder tumor tissues [{Non-muscle invasive bladder cancer (NMIBC): 35 cases} and {Muscle invasive bladder cancer (MIBC): 29 cases}] by real-time quantitative polymerase chain reaction (RT-qPCR). Immunohistochemistry (IHC) staining was done in matched bladder tumor tissues to evaluate the protein expression and localization of E-cadherin, N-cadherin, Vimentin, Snail, and Slug. Our data showed overexpression of MMP-2, MMP-7 and MMP-9 at transcriptome level in 32.8%, 25% and 37.5% bladder tumor cases respectively. These tumor tissues were examined for higher expression of mesenchymal markers (N-cadherin and Vimentin) at mRNA and protein level and exhibited statistical association with tumor stage and tumor grade (p = 0.02, p = 0.04, Mann-Whitney test). Significant statistical correlation in tumor tissues with overexpressed MMPs has also been observed between gain of transcriptional factors and weak expression of E-cadherin with tumor stage, grade, gender, presence of hematuria and smoking history of the patients. Gene expression patterns of EMT markers in bladder tumors with overexpressed MMPs and their significant association with clinical profile validate the important role of MMPs in the pathogenesis of urothelial carcinoma of bladder (UCB). Increased expression of specific MMPs may affect several downstream EMT programs and thus may improve its diagnostic and prognostic utility in clinical setting.