Experience with management of renal cell carcinoma with inferior vena cava/right atrial tumor thrombus.

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.

Metabolomics of prostate cancer: Knock-in versus knock-out prostate.

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.

Prostate-specific antigen screening of men with lower urinary tract symptoms (opportunistic screening) and of asymptomatic men undergoing executive health check: an audit from two institutions.

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.

Dynamically crosslinked polydimethylsiloxane-based polyurethanes with contact-killing antimicrobial properties as implantable alloplasts for urological reconstruction.

A large population of patients is reported to suffer from urinary bladder-associated irreversible physiological disorders, rationalizing a continuous surge for structural and functional substitutes of urinary tissues, including ureters, bladder-wall, and urethra. The current gold standard for bladder reconstruction, an autologous gastrointestinal graft, is proven not to be an ideal substitute in the clinic. While addressing this unmet clinical need, a unique platform of antimicrobial polydimethyl siloxane-modified polyurethanes (TPU/PDMS) is designed and developed for its potential application as a urological implant. To the best of our knowledge, this study reports for the first time the successful integration of varying contents of PDMS within the molten polyurethane matrix using in situ crosslinking methodology. Thus, compatibilized binary blends possess clinically relevant viscoelastic properties to sustain high pressure, large distensions, and surgical manipulation. Furthermore, different chemical strategies are explored to covalently incorporate quaternized moieties, including 4-vinyl pyridine (4-VP), branched-polyethyleneimine (bPEI) as well as bPEI-grafted-(acrylic acid-co-vinylbenzyltriphenyl phosphonium chloride) (PAP), and counter urinary tract infections. The modified compositions, endowed with contact killing surfaces, reveal nearly three log reduction in bacterial growth in pathogenically infected artificial urine. Importantly, the antimicrobial TPU/PDMS blends support the uninhibited growth of mitochondrially viable murine fibroblasts, in a manner comparable to the medical-grade polyurethane. Collectively, the obtained results affirmed the newly developed polymers as promising biomaterials in reconstructive urology. STATEMENT OF SIGNIFICANCE: The clinical procedure for end-stage bladder disease remains replacement or augmentation of the bladder wall with a section of the patient's gastrointestinal tract. However, the absorptive and mucus-producing epithelium of intestinal segment is liable to short- and long-term complications. The dynamically crosslinked polydimethyl siloxane-based polyurethanes proposed herein, and the associated synthesis strategies to induce polycation grafted non-exhaustive contact-killing surfaces against uropathogents, have a significant clinical prospect in reconstructive urology. As an 'off-the-shelf' available alloplastic substitute, these blends offer the potential to circumvent the challenges associated with non-urinary autografts or scaffold based regenerative engineering and, thereby, shorten as well as simplify the surgical treatment. The targeted application has been conceived for a bladder patch to assist in various urinary diseases including, bladder carcinoma, refractory overactive bladder, interstitial cystitis, etc. However, given the ease of fabrication, moldability and the wide spectrum of mechanical properties that could be encompassed, these blends also present the possibility to be manifested into artificial ureteral or urethral conduits.

NMR-derived targeted serum metabolic biomarkers appraisal of bladder cancer: A pre- and post-operative evaluation.

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.

A modified cutaneous ureterostomy provides satisfactory short and midterm outcomes in select cases.

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.

Relevance of MIC-1 in the Era of PSA as a Serum Based Predictor of Prostate Cancer: A Critical Evaluation.

To reduce the ambiguity of contradictory observations in different studies regarding the expression level of Macrophage Inhibitory Cytokine-1 (MIC-1) in serum in prostate cancer (PC), benign prostatic hyperplasia (BPH) and healthy controls (HC), we designed this double-blind study. The study comprises 240 sera from PC, BPH and HC subjects. The expression level of MIC-1 in PC, BPH and HC were appraised using Western blot (WB) and ELISA based approach. WB and ELISA appraisal reveals that the expression level of MIC-1 is significantly higher in PC than in HC or BPH subjects. Regression analysis revealed a significant correlation between MIC-1 vs. PSA (r = 0.09; p < 0.001) and MIC-1 vs. GS (r = 0.7; p < 0.001). ROC analysis using discriminant predicted probability revealed that the MIC-1 was better than PSA. Moreover, the combination of MIC-1 and PSA was allowing 99.1% AUC for the differentiation of BPH + PC from HC, 97.9% AUC for differentiation of BPH from HC, 98.6% AUC for differentiation of PC from HC, and 96.7% AUC for the differentiation of PC from BPH. The augmented expression of MIC-1 in PC compared to BPH and HC subjects is in concurrent of the over-expression of MIC-1 in PC reports and confiscates the contradictory findings of other studies.

MicroRNA-21 could be a molecular marker to predict the recurrence of nonmuscle invasive bladder cancer.

INTRODUCTION: High relapse rate of nonmuscle invasive bladder cancer (NMIBC) is a major challenge. Overexpression of microRNA-21 (miR-21) which targets phosphatase and tensin homolog (PTEN), a gene associated with malignancy, has been reported in the bladder tumor tissue compared to normal mucosa by us and others. We have tested whether miR-21 levels in bladder mucosa could predict tumor recurrence. METHODS: In a prospective cohort setting, tumor tissues and normal bladder mucosa (NBM) were taken from BC patients during transurethral resection of bladder tumor. Age- and ethnicity-matched NBM from benign prostate hyperplasia patients was taken as controls. The expression of miR-21 was analyzed using quantitative reverse transcription polymerase chain reaction. Patients were followed for 4 years for tumor reoccurrence. Postoperative recurrence were recorded and calculated by Kaplan-Meier curve. RESULTS: In 31 patients, miR-21 was up-regulated (>4-fold, P = 0.003), and PTEN levels were significantly lower (<7-folds, P = 0.001) in tumor tissue relative to NBM. Moreover, the fold change in miR-21 levels was significantly higher (>3-folds, P = 0.03) in patients showing recurrence compared to those in which tumor did not recur. Further, Kaplan-Meier analysis shows overexpression of miR-21 corresponds to less time to recurrence with higher cumulative hazard. CONCLUSION: We found overexpression of miR-21 in tumor tissue and its association with recurrence, time to recurrence and invasiveness in BC. Quantification of miR-21 along with other pathological parameters could be more objective molecular approach to predict recurrence in NMIBC.

Utility of anteroposterior diameter ratio of tumor and abdomen for laparoscopic approach for radical nephrectomy in large renal masses.

INTRODUCTION: Laparoscopic radical nephrectomy (LRN) is now increasingly done for tumors larger than 10 cm. Despite selection of favorable cases, LRN may not be successful due to lack of adequate working space with large tumors. We describe a new feature on Contrast Enhanced Computed Tomography (CECT) abdomen to predict feasibility of LRN for large renal masses between 10 and 15 cm. METHODS: From January 2005 to December 2015, renal tumors between 10 and 15 cm were selected retrospectively for LRN. Patients with retroperitoneal lymphadenopathy, Inferior vena cava (IVC) thrombus and involvement of adjacent organs were excluded. Anteroposterior (AP) diameter ratio of renal tumor and abdomen (APROTA) was calculated by dividing the maximum AP diameter of tumor along with normal renal parenchyma, by the AP diameter of abdomen on CECT. The patients were stratified into two groups: Group A (successful LRN) and Group B (conversion to open surgery) and outcomes were compared. The reasons for conversion were also noted. RESULTS: Of 29 patients, 16 (55.2%) had successful LRN (Group A), while 13 (44.8%) had conversion to open surgery (group B). The median tumor size in Group A was 11.3 ± 1.8 cm and in Group B was 13.6 ± 1.26 cm. Eleven of 13 patients had conversion due to large tumor size causing failure to progress. Two conversions were due to bleeding and injury to the colon each. There was a significant difference in the APROTA in group A and B [0.43 ± 0.09 in group A and 0.64 ± 0.14 in group B (p = 0.0001)]. CONCLUSIONS: Patients with APROTA of more than 0.65 are unlikely to have successful outcome with LRN.

Bladder cancer: Micro RNAs as biomolecules for prognostication and surveillance.

INTRODUCTION: Bladder cancer (BC) has varied clinical behavior in terms of recurrence and progression. Current pathological characteristics are insufficient to prognosticate the outcome of a given treatment. Cellular metabolic regulatory molecules, such as micro RNA (miRNA), could be a potential biomarker to prognosticate the treatment outcomes. MATERIALS AND METHODS: PubMed and Google Scholar databases were searched for publications from 1990 to 2016, related to miRNA biogenesis, its function, and role in the pathogenesis of bladder as well as other cancers. Articles were searched using MeSH terms micrornas, micrornas AND neoplasm, and micrornas AND urinary bladder neoplasm. Out of the 108 publications reviewed 75 references were selected based on the clinical relevance. Articles were reviewed to assess the role of miRNA in various cancers and those in BC as a diagnostic or therapeutic tool. RESULTS: More than 35 miRNAs were found to be associated with different pathways of cellular dedifferentiation, proliferation, and progression of BC as well as other cancers. A normal looking mucosa may show molecular changes preceding phenotypic changes in the form of varied expression of miR-129, miR-200a, and miR-205. miR-214, miR-99a, and miR-125b have been shown to be potential urinary biomarkers of BC. miRNAs could act as a repressor for protein molecule functioning or activator of different pathways to be used as a therapeutic target too. CONCLUSIONS: Despite certain limitations, such as instability, rapid plasma clearance, and targeting antagonist proteins of cellular metabolic pathways, miRNAs have potential to be studied as a biomarker or a therapeutic target for BC.

Reduced Insulin Receptor Expression Enhances Proximal Tubule Gluconeogenesis.

Reduced insulin receptor protein levels have been reported in the kidney cortex from diabetic humans and animals. We recently reported that, targeted deletion of insulin receptor (IR) from proximal tubules (PT) resulted in hyperglycemia in non-obese mice. To elucidate the mechanism, we examined human proximal tubule cells (hPTC) and C57BL/6 mice fed with high-fat diet (HFD, 60% fat for 20 weeks). Immunoblotting revealed a significantly lower protein level of IR in HFD compare to normal chow diet (NCD). Furthermore, a blunted rise in p-AKT308 levels in the kidney cortex of HFD mice was observed in response to acute insulin (0.75 IU/kg body weight, i.p) relative to NCD n = 8/group, P < 0.05). Moreover, we found significantly higher transcript levels of phosphoenolpyruvate carboxykinase (PEPCK, a key gluconeogenic enzyme) in the kidney cortex from HFD, relative to mice on NCD. The higher level of PEPCK in HFD was confirmed by immunoblotting. However, no significant differences were observed in cortical glucose-6-phosphatase (G6Pase) or fructose-1,6, bisphosphosphatase (FBPase) enzyme transcript levels. Furthermore, we demonstrated insulin inhibited glucose production in hPTC treated with cyclic AMP and dexamethasone (cAMP/DEXA) to stimulate gluconeogenesis. Transcript levels of the gluconeogenic enzyme PEPCK were significantly increased in cAMP/DEXA-stimulated hPTC cells (n = 3, P < 0.05), and insulin attenuated this upregulation Furthermore, the effect of insulin on cAMP/DEXA-induced gluconeogenesis and PEPCK induction was significantly attenuated in IR (siRNA) silenced hPTC (n = 3, P < 0.05). Overall the above data indicate a direct role for IR expression as a determinant of PT-gluconeogenesis. Thus reduced insulin signaling of the proximal tubule may contribute to hyperglycemia in the metabolic syndrome via elevated gluconeogenesis. J. Cell. Biochem. 118: 276-285, 2017. © 2016 Wiley Periodicals, Inc.

Epithelial-To-Mesenchymal Transition and Its Correlation With Clinicopathologic Features in Patients With Urothelial Carcinoma of the Bladder.

INTRODUCTION: Epithelial-to-mesenchymal transition (EMT) is a dynamic process in the pathogenesis of urinary bladder cancer. Despite significant advancements in its diagnosis and treatment, the outcomes have more or less remained the same. In the present study, the expression of EMT markers was investigated to evaluate its prognostic significance in patients with non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: The present study was undertaken to examine the expression of EMT markers, including E-cadherin, N-cadherin, vimentin, Snail, Twist, Zeb, and Slug, on 28 bladder tumor tissues (15 cases of NMIBC and 13 of MIBC) using reverse transcription-polymerase chain reaction. Immunohistochemical (IHC) staining was performed to check the protein expression and localization of E-cadherin, N-cadherin, vimentin, Snail, and Slug. RESULTS: At the message level, reduced expression of E-cadherin correlated with gender (P = .004), enhanced expression of N-cadherin correlated with stage and age (P = .02, for both), and increased expression of EMT transcription factors correlated significantly with stage, grade, or age. Inverse correlation of reduced levels of E-cadherin were observed with new expression of N-cadherin (P = .001; Mann-Whitney U test) and vimentin (P = .001; Mann-Whitney U test). On IHC, novel expression of vimentin and N-cadherin was associated with enhanced expression of Snail and Slug (P = .005; Wilcoxon signed rank test). CONCLUSION: Molecular validation of the EMT marker profile proved to be a sensitive and an effective prognostic tool for objective and systematic investigation of EMT function in the pathogenesis of urinary bladder cancer. Nevertheless, further studies are required with a greater number of clinical samples.

Current Concepts in the Management of Non-Muscle Invasive Bladder Cancer.

Non-muscle invasive bladder cancer, despite advances in the field of medicine, remains an enigmatic problem with no tangible solution of one-time treatment as it needs an invasive surveillance in the form of cystoscopy. There are issues related to diagnosis, ideal resection technique, BCG treatment, and follow-up. In this article, we review the recent developments in the diagnosis of the disease and describe optimal management strategies.

An audit of early complications of radical cystectomy using Clavien-Dindo classification.

INTRODUCTION: Despite the major improvements in surgical technique and perioperative care, radical cystectomy (RC) remains a major operative procedure with a significant morbidity and mortality. The present study analyzes the early complications of RC and urinary diversion using a standardized reporting system. MATERIALS AND METHODS: Modified Clavien-Dindo classification was used to retrospectively assess the peri-operative course of 212 patients who had RC with urinary diversion between October 2003 and October 2014 at a single institution. The indications for surgery were muscle invasive urothelial carcinoma, high-grade nonmuscle invasive bladder cancer (BC), and Bacillus Calmette-Guerin-resistant nonmuscle invasive BCs. Data on age, sex, comorbidities, smoking history, American Society of Anaesthesiologists score, and peri-operative complications (up to 90 days) were captured. Statistical analysis was performed using SPSS 20.0 software (Chicago, USA). RESULTS: The mean age was 56.15 ± 10.82. Orthotopic neobladder was created in 113 patients, ileal conduit in 88 patients, and cutaneous ureterostomy in 11 patients. A total of 292 complications were recorded in 136/212 patients. 242 complications (81.16%) occurred in the first 30 days, with the remaining 50 complications (18.83%) occurring thereafter. The rates for overall complication were 64.1%. The most common complications were hematologic (21.6%). Most of the complications were of Grade I and II (22.9% and 48.9%, respectively). Grade IIIa, IIIb, IVa, IVb, and V complications were observed in 10.2%, 8.9%, 3.4%, 2.7%, and 2.7% of the patients, respectively. CONCLUSIONS: RC and urinary diversion are associated with significant morbidity. This audit would help in setting a benchmark for further improvement in the outcome.

Predictors for progression of metastatic prostate cancer to castration-resistant prostate cancer in Indians.

BACKGROUND & OBJECTIVES: There is lack of data on natural history and progression of prostate cancer (PC) which have implications in the management of the disease. We undertook this retrospective study to analyze factors predicting progression of metastatic PC to castration-resistant prostate cancer (CRPC) in Indian men. METHODS: Complete records of 223 of the 489 patients with metastatic PC were obtained from computerized data based system in a tertiary care hospital in north India between January 2000 to June 2012. Patients with follow up of < 6 months were excluded. Age (≤ and > 65 yr), baseline PSA (< and ≥ 50 ng/ml), bone scan and Gleason score (≤7 and >7) were recorded. Extent of bone disease (EOD) was stratified according to the number of bone lesions i.e., < 5, 5-10, > 10. CRPC was defined as two consecutive PSA rise of > 50 per cent from nadir or an absolute value of > 5 ng/ml. RESULTS: Mean age of patients was 61.5 ± 12.45 yr and their PSA level was 325.6 ± 631.35 ng/dl. Of the 223 patients, 193 (86%) progressed to CRPC at median time of 10.7 (4-124) months. Median follow up was 24 (6-137) months. On univariate and multivariate analyses EOD on bone scan was found to be a significant predictor ( P=0.006) for time to CRPC. Median time to CRPC was 10 months (CI 95%, 7.5-12.48) with >10 lesions or super scan versus 16 months (CI 95%, 10.3-21.6) with <10 bone lesion (P=0.01). Ninety (46.6 %) patients of CRPC died with median time to death from time of CRPC 21 (10-120) months. INTERPRETATION & CONCLUSIONS: Median time for progression of metastatic PC to CRPC ranged from 10-16 months depending on the extent of the bone involvement. In Indians, the aggressive course of advanced prostate cancer warrants further clinical trials to explore the need for additional treatment along with initial castration.

Impact of changing trends in technique and learning curve on outcome of hypospadias repair: An experience from tertiary care center.

INTRODUCTION: Apart from numerous clinical factors, surgical experience and technique are important determinants of hypospadias repair outcome. This study was aimed to evaluate the learning curve of hypospadias repair and the impact of changing trends in surgical techniques on the success of primary hypospadias repair. MATERIALS AND METHODS: We retrospectively analyzed of data of 324 patients who underwent primary repair of hypospadias between January 1997 and December 2013 at our center. During the initial 8 years, repairs were performed by multiple 5 different urologists. From 2005 onwards, all procedures were performed by a single urologist. The study cohorts was categorized into three groups; Group I, surgeries performed between 1997-2004 by multiple surgeons, Group II, between 2005-2006 during the initial learning curve of a single surgeon, and Group III, from 2007 onwards after completion of the learning curve of the single surgeon. The groups were compared in respect to surgical techniques, overall success and complications. RESULTS: Overall 296 patients fulfilled the inclusion criterion, 93 (31.4%), 50 (16.9%), and 153 (51.7%) in Group I, II, and III, respectively. Overall success was achieved in 60 (64.5%), 32 (64%), and 128 (83.7%) patients among the three groups respectively (P < 0.01). Nineteen (20.4%), 20 (40%), and 96 (62.7%) patients underwent tubularized incised plate repair in Group I, II, and III, with successful outcome in 12 (63.2%), 15 (75%), and 91 (94.8%) patients, respectively (P < 0.01). The most common complication among all groups was urethrocutaneous fistula, 20 (21.5%) in Group I, 11 (22%) in Group II, and 17 (11.1%) in Group III. CONCLUSION: There is a learning curve for attaining surgical skills in hypospadias surgery. Surgeons dedicated for this surgery provide better results. Tubularized incised plate urethroplasty appear promising in both distal and proximal type hypospadias.

NMR spectroscopy of filtered serum of prostate cancer: A new frontier in metabolomics.

BACKGROUND: To address the shortcomings of digital rectal examinations (DRE), serum prostate-specific antigen (PSA), and trans-rectal ultrasound (TRUS) for precise determination of prostate cancer (PC) and differentiation from benign prostatic hyperplasia (BPH), we applied (1) H-nuclear magnetic resonance (NMR) spectroscopy as a surrogate tactic for probing and prediction of PC and BPH. METHODS: The study comprises 210 filtered sera from suspected PC, BPH, and a healthy subjects' cohort (HC). The filtered serum approach delineates to identify and quantify 52 metabolites using (1) H NMR spectroscopy. All subjects had undergone clinical evaluations (DRE, PSA, and TRUS) followed by biopsy for Gleason score, if needed. NMR-measured metabolites and clinical evaluation data were examined separately using linear multivariate discriminant function analysis (DFA) to probe the signature descriptors for each cohort. RESULTS: DFA indicated that glycine, sarcosine, alanine, creatine, xanthine, and hypoxanthine were able to determine abnormal prostate (BPH + PC). DFA-based classification presented high precision (86.2% by NMR and 68.1% by clinical laboratory method) in discriminating HC from BPH + PC. DFA reveals that alanine, sarcosine, creatinine, glycine, and citrate were able to discriminate PC from BPH. DFA-based categorization exhibited high accuracy (88.3% by NMR and 75.2% by clinical laboratory method) to differentiate PC from BPH. CONCLUSIONS: (1) H NMR-based metabolic profiling of filtered-serum sample appears to be assuring, swift, and least-invasive for probing and prediction of PC and BPH with its signature metabolic profile. This novel technique is not only on a par with histopathological evaluation of PC determination but is also comparable to liquid chromatography-based mass spectrometry to identify the metabolites. Prostate 76:1106-1119, 2016. © 2016 Wiley Periodicals, Inc.

Molecular cystoscopy: Micro-RNAs could be a marker for identifying genotypic changes for transitional cell carcinoma of the urinary bladder.

INTRODUCTION: Normal-looking mucosa may harbor genetic changes preceding a visible tumor. This study was aimed at exploring the role of the quantitative expression of micro-RNAs (miRNAs) in bladder cancer tissue in comparison with normal mucosa and healthy controls (HCs) as a molecular marker. MATERIALS AND METHODS: Between October 2011 to December 2012, tissue from the bladder tumor of 21 patients (cases tumor, CT), normal mucosa (case control, CC) of the same patients (n-21) and normal bladder mucosa from 10 HCs were obtained. miRNAs of angiogenesis, endothelial mesenchymal transition and apoptosis were quantified using stem-loop RT Taq Man polymerase chain reaction. Statistical analysis was performed using the Chi square and independent sample T tests by using SPSS version 16. RESULTS: The mean age of the patients and controls were 55.41 ± 11.03 and 52.14 ± 13.04 years. miR-21, miR-205, miR-126, miR-10b and miR-200a were highly expressed in CT (P < 0.027, <0.048, <0.025, <0.029 and < 0.005) as compared with HC. Expression of miR-21 and miR-129 were both correlated with grade and stage (P = 0.001 and < 0.009, respectively) and the level of expression was different in the same grade of non-muscle invasive tumors. The fold change of miR129, miR205 and miR200a was significantly higher in the normal-looking mucosa of bladder tumor patients than the HC (P < 0.005). CONCLUSION: Expression of miR129, miR205 and miR200a in the normal-looking mucosa of bladder cancer patients was significantly higher than the normal mucosa of a HC. This may help in predicting recurrence and formulating the follow-up strategy.

A new classification of inferior vena cava thrombus in renal cell carcinoma could define the need for cardiopulmonary or venovenous bypass.

INTRODUCTION: Although the level of inferior vena cava (IVC) thrombus governs the type of surgical approach, there is no consistency in reporting the levels of IVC thrombus in the literature. This prospective study illustrates a simple three-level classification based on the need for clamping hepatoduodenal ligament and venovenous or cardiopulmonary bypass. MATERIALS AND METHODS: Between January 2010 and June 2014, 30 patients of renal mass with renal vein and/or IVC thrombus were treated after classifying the IVC thrombus into three levels on the basis of need for clamping the hepatoduodenal ligament. After excluding renal vein thrombi, level I was described as thrombus located caudal to the hepatic vein. Level II included all retrohepatic, suprahepatic infradiaphragmatic or supradiaphragmatic thrombi reaching till the right atrium. Atrial thrombi were categorized as level III. Level I and II thrombi were managed without venovenous or cardiopulmonary bypass. Level III thrombus required cardiopulmonary bypass. RESULTS: Of 26 patients with thrombus, 13 had level I thrombus. Of eight cases with level II thrombus, three were retrohepatic, three were suprahepatic infradiaphragmatic and two were supradiaphragmatic. All were removed successfully. Of five patients with level III thrombus, three were operated with cardiopulmonary bypass while the remaining two patients were too sick to be taken up for surgery. The median hepatoduodenal ligament clamp time was 10 min. One patient with level II thrombus had transient liver enzyme elevation. CONCLUSION: Renal vein thrombus should not be categorized as level I thrombus. Level II thrombus, irrespective of its relation to the diaphragm, could be managed without venovenous or cardiopulmonary bypass.