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Mini-review: perspective of the microbiome in the pathogenesis of urothelial carcinoma

Xu, Weisheng; Yang, Liying; Lee, Peng; Huang, William C; Nossa, Carlos; Ma, Yingfei; Deng, Fang-Ming; Zhou, Ming; Melamed, Jonathan; Pei, Zhiheng
The microbiome is a new center of attention for studies on the pathogenesis of human disease by focusing on the alterations of all microorganisms living in a particular site or system of human body, referred as microbiota. Evidence suggests that microbiota could contribute to the pathogenesis of a number of chronic diseases, including cancers, both locally and remotely. Multiple mechanisms have been proposed and/or proven for the microbiota's role in tumorigenesis, such as via induction of chronic inflammation, genotoxicity, bacterium-mediated cell proliferation, and activation of procarcinogens. Emerging data suggest that indigenous microbiota in the urinary tract may play an important role in the tumorigenesis of urothelial carcinoma, similar to other tumors. Future studies are needed to adequately define the microbiota composition and correlate its change with urothelial carcinoma.
PMCID:4127805
PMID: 25126590
ISSN: 2330-1910
CID: 1126972

Acrolein- and 4-Aminobiphenyl-DNA adducts in human bladder mucosa and tumor tissue and their mutagenicity in human urothelial cells

Lee, Hyun-Wook; Wang, Hsiang-Tsui; Weng, Mao-Wen; Hu, Yu; Chen, Wei-Sheng; Chou, David; Liu, Yan; Donin, Nicholas; Huang, William C; Lepor, Herbert; Wu, Xue-Ru; Wang, Hailin; Beland, Frederick A; Tang, Moon-Shong
Tobacco smoke (TS) is a major cause of human bladder cancer (BC). Two components in TS, 4-aminobiphenyl (4-ABP) and acrolein, which also are environmental contaminants, can cause bladder tumor in rat models. Their role in TS related BC has not been forthcoming. To establish the relationship between acrolein and 4-ABP exposure and BC, we analyzed acrolein-deoxyguanosine (dG) and 4-ABP-DNA adducts in normal human urothelial mucosa (NHUM) and bladder tumor tissues (BTT), and measured their mutagenicity in human urothelial cells. We found that the acrolein-dG levels in NHUM and BTT are 10-30 fold higher than 4-ABP-DNA adduct levels and that the acrolein-dG levels in BTT are 2 fold higher than in NHUM. Both acrolein-dG and 4-ABP-DNA adducts are mutagenic; however, the former are 5 fold more mutagenic than the latter. These two types of DNA adducts induce different mutational signatures and spectra. We found that acrolein inhibits nucleotide excision and base excision repair and induces repair protein degradation in urothelial cells. Since acrolein is abundant in TS, inhaled acrolein is excreted into urine and accumulates in the bladder and because acrolein inhibits DNA repair and acrolein-dG DNA adducts are mutagenic, we propose that acrolein is a major bladder carcinogen in TS.
PMCID:4116500
PMID: 24939871
ISSN: 1949-2553
CID: 1036762

Solid renal masses: what the numbers tell us

Kang, Stella K; Huang, William C; Pandharipande, Pari V; Chandarana, Hersh
OBJECTIVE. Solid renal masses are most often incidentally detected at imaging as small (
PMCID:4174582
PMID: 24848816
ISSN: 0361-803x
CID: 1005042

A Prospective, Blinded Comparison of Magnetic Resonance (MR) Imaging-Ultrasound Fusion and Visual Estimation in the Performance of MR-targeted Prostate Biopsy: The PROFUS Trial

Wysock, James S; Rosenkrantz, Andrew B; Huang, William C; Stifelman, Michael D; Lepor, Herbert; Deng, Fang-Ming; Melamed, Jonathan; Taneja, Samir S
BACKGROUND: Increasing evidence supports the use of magnetic resonance (MR)-targeted prostate biopsy. The optimal method for such biopsy remains undefined, however. OBJECTIVE: To prospectively compare targeted biopsy outcomes between MR imaging (MRI)-ultrasound fusion and visual targeting. DESIGN, SETTING, AND PARTICIPANTS: From June 2012 to March 2013, prospective targeted biopsy was performed in 125 consecutive men with suspicious regions identified on prebiopsy 3-T MRI consisting of T2-weighted, diffusion-weighted, and dynamic-contrast enhanced sequences. INTERVENTION: Two MRI-ultrasound fusion targeted cores per target were performed by one operator using the ei-Nav|Artemis system. Targets were then blinded, and a second operator took two visually targeted cores and a 12-core biopsy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Biopsy information yield was compared between targeting techniques and to 12-core biopsy. Results were analyzed using the McNemar test. Multivariate analysis was performed using binomial logistic regression. RESULTS AND LIMITATIONS: Among 172 targets, fusion biopsy detected 55 (32.0%) cancers and 35 (20.3%) Gleason sum >/=7 cancers compared with 46 (26.7%) and 26 (15.1%), respectively, using visual targeting (p=0.1374, p=0.0523). Fusion biopsy provided informative nonbenign histology in 77 targets compared with 60 by visual (p=0.0104). Targeted biopsy detected 75.0% of all clinically significant cancers and 86.4% of Gleason sum >/=7 cancers detected on standard biopsy. On multivariate analysis, fusion performed best among smaller targets. The study is limited by lack of comparison with whole-gland specimens and sample size. Furthermore, cancer detection on visual targeting is likely higher than in community settings, where experience with this technique may be limited. CONCLUSIONS: Fusion biopsy was more often histologically informative than visual targeting but did not increase cancer detection. A trend toward increased detection with fusion biopsy was observed across all study subsets, suggesting a need for a larger study size. Fusion targeting improved accuracy for smaller lesions. Its use may reduce the learning curve necessary for visual targeting and improve community adoption of MR-targeted biopsy.
PMID: 24262102
ISSN: 0302-2838
CID: 666702

Rationale for partial nephrectomy

Chapter by: Donin, N; Huang, W
in: Renal Cancer: Contemporary Management by
pp. 179-200
ISBN: 9781461472360
CID: 2169192

A PROSPECTIVE COMPARATIVE STUDY OF TARGETED PROSTATE BIOPSY DIRECTED TO MRI-SUSPICIOUS REGIONS VERSUS ARTEMIS (TM) COMPUTERIZED 12 CORE TEMPLATE BIOPSY [Meeting Abstract]

Wysock, James S; Rosenkrantz, Andrew B; Huang, William C; Stifelman, Michael; Lepor, Herbert; Taneja, Samir S
ISI:000320281603061
ISSN: 0022-5347
CID: 1871422

Gender disparity in kidney cancer treatment: women are more likely to undergo radical excision of a localized renal mass

O'Malley, Rebecca L; Underwood, Willie 3rd; Brewer, Katherine A; Hayn, Matthew H; Kim, Hyung L; Mehedint, Diana C; Safwat, Mohab W; Huang, William C; Schwaab, Thomas
OBJECTIVE: To investigate gender effects on the type of nephrectomy performed for a stage I renal mass and differences that might account for disparity in treatment patterns according to gender. METHODS: Using a single-institution database, patients who underwent nephrectomy at a tertiary referral center for a localized, solitary tumor, 1 in 38% vs 50%; P = .027) and lower mean preoperative creatinine (0.09 +/- 0.3 vs 1.1 +/- 0.3; P <.001). Despite lower creatinine, women had inferior preoperative renal function with a mean estimated glomerular filtration rate of 71.4 +/- 21 vs 78.9 +/- 21 mL/min/1.73 m2 in men (P <.001). Multivariable analysis indicated that female patients were 2.5 times more likely to undergo radical nephrectomy compared with their male counterparts (P = .022). Women were less likely to have malignancy (odds ratio male gender 2.50; P = .013). CONCLUSION: Women are more likely than men to undergo radical vs partial excision of a localized renal mass, despite less comorbid burden, inferior renal function, and increased likelihood of benign disease.
PMID: 24358483
ISSN: 0090-4295
CID: 844622

National Trends in the Utilization of Partial Nephrectomy Before and After the Establishment of AUA Guidelines for the Management of Renal Masses

Bjurlin, Marc A; Walter, Dawn; Taksler, Glen B; Huang, William C; Wysock, James S; Sivarajan, Ganesh; Loeb, Stacy; Taneja, Samir S; Makarov, Danil V
OBJECTIVE: To assess the impact of the American Urological Association (AUA) guidelines advocating partial nephrectomy for T1 tumors guidelines on the likelihood of undergoing partial nephrectomy. MATERIALS AND METHODS: We analyzed the Nationwide Inpatient Sample (NIS), a dataset encompassing 20% of all United States inpatient hospitalizations, from 2007 through 2010. Our dependent variable was receipt of radical vs partial nephrectomy (55.50, 55.51, 55.52, and 55.54 vs 55.4) for a renal mass (International Classification of Disease, 9th Revision [ICD-9] code 189.0). The independent variable of interest was time of surgery (before or after the establishment of AUA guidelines); covariates included a diagnosis of chronic kidney disease (CKD), overall comorbidity, age, race, gender, geographic region, income, and hospital characteristics. Bivariate and multivariable adjusted logistic regression was used to determine the association between receipt of partial nephrectomy and time of guideline establishment. RESULTS: We identified 26,165 patients with renal tumors who underwent surgery. Before the guidelines, 4031 patients (27%) underwent partial nephrectomy compared to 3559 (32%) after. On multivariable analysis, undergoing surgery after the establishment of guidelines (odds ratio [OR] 1.20, 95% confidence interval [CI] 1.08-1.32, P <.01) was an independent predictor of partial nephrectomy. Other factors associated with partial nephrectomy were urban location, surgery at a teaching hospital, large hospital bed size, Northeast location, and Black race. Female gender and CKD were not associated with partial nephrectomy. CONCLUSION: Although adoption of partial nephrectomy increased after establishment of new guidelines on renal masses, partial nephrectomy remains an underutilized procedure. Future research must focus on barriers to adoption of partial nephrectomy and how to overcome them.
PMCID:3852430
PMID: 24295245
ISSN: 0090-4295
CID: 666322

Utility of quantitative MRI metrics for assessment of stage and grade of urothelial carcinoma of the bladder: preliminary results

Rosenkrantz, Andrew B; Haghighi, Mohammad; Horn, Jeremy; Naik, Mohit; Hardie, Andrew D; Somberg, Molly B; Melamed, Jonathan; Xiao, Guang-Qian; Huang, William C; Taouli, Bachir
OBJECTIVE. The purpose of this study was to assess associations between quantitative MRI metrics and pathologic indicators of aggressiveness of urothelial carcinoma of the bladder. MATERIALS AND METHODS. In this retrospective biinstitutional study, 37 patients (28 men and nine women; mean age, 73 +/- 12 years) who underwent pelvic MRI including diffusion-weighted imaging (b values 0, 400, and 800 s/mm(2)) and T2-weighted imaging before transurethral resection or cystectomy for urothelial carcinoma of the bladder were identified. Tumor diameter (measured on T2-weighted imaging), normalized T2 signal intensity (to muscle; hereafter labeled normalized T2) and apparent diffusion coefficient (ADC) were measured for all tumors. Mann-Whitney test and receiver operating characteristic analyses were used to identify associations between these metrics and histopathologic tumor stage and grade. RESULTS. Thirty-seven tumors were assessed (mean size, 35 +/- 23 mm; range 8-88 mm). At histopathologic analysis, 16 of 37 (43%) tumors were stage T2 or greater and 21 of 37 (57%) were stage T1 or lower, whereas 34 of 37 (92%) were high grade and three of 37 (8%) were low grade. High-stage (>/= T2) tumors showed greater tumor diameter, lower normalized T2, and lower ADC (p = 0.005-0.032) than low-stage (
PMID: 24261364
ISSN: 0361-803x
CID: 652362

Surgery versus surveillance of small renal masses: a call for comparative effectiveness research in the management of kidney tumors

Bjurlin, Marc A; Huang, William C
PMID: 24236733
ISSN: 2042-6305
CID: 641602