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Find video protocols related to scientific articles indexed in Pubmed.
Efficacy and Safety of MCNA in Patients with Non-Muscle Invasive Bladder Cancer at High-Risk of Recurrence and Progression who Have Failed Treatment with Bacillus Calmette-Guérin.
J. Urol.
PUBLISHED: 09-30-2014
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Patients with high-risk recurrences after BCG failure have limited options. We performed an open-label study to evaluate the efficacy and safety of intravesical MCNA in this setting.
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Hexaminolevulinate blue-light cystoscopy in non-muscle-invasive bladder cancer: review of the clinical evidence and consensus statement on appropriate use in the USA.
Nat Rev Urol
PUBLISHED: 09-23-2014
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Hexaminolevulinate (HAL) is a tumour photosensitizer that is used in combination with blue-light cystoscopy (BLC) as an adjunct to white-light cystoscopy (WLC) in the diagnosis and management of non-muscle-invasive bladder cancer (NMIBC). Since being licensed in Europe in 2005, HAL has been used in >200,000 procedures, with consistent evidence that it improves detection compared with WLC alone. Current data support an additional role in the reduction of recurrence of NMIBC. Since the approval of HAL by the FDA in 2010, experience of HAL-BLC in the USA continues to expand. To define areas of need and to identify the benefits of HAL-BLC in clinical practice, a focus group of expert urologists specializing in the management of patients with bladder cancer convened to review the clinical evidence, share their experiences and reach a consensus regarding the optimal use of HAL-BLC in the USA. The focus group concluded that HAL-BLC should be considered for initial assessment of NMIBC, surveillance for recurrent tumours, diagnosis in patients with positive urine cytology but negative WLC findings, and for tumour staging.
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Intravesical Tumor Involvement of the Trigone Is Associated With Nodal Metastasis in Patients Undergoing Radical Cystectomy.
Urology
PUBLISHED: 08-28-2014
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To evaluate the influence of intravesical tumor location on nodal metastasis and mortality after cystectomy. The microvascular anatomy of the urinary bladder is variable in distinct regions of the bladder and thus tumor location may influence the tumors' ability to access lymphatic and vascular structures.
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Assessing the quality of studies on the diagnostic accuracy of tumor markers.
Urol. Oncol.
PUBLISHED: 08-19-2014
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With rapidly increasing numbers of publications, assessments of study quality, reporting quality, and classification of studies according to their level of evidence or developmental stage have become key issues in weighing the relevance of new information reported. Diagnostic marker studies are often criticized for yielding highly discrepant and even controversial results. Much of this discrepancy has been attributed to differences in study quality. So far, numerous tools for measuring study quality have been developed, but few of them have been used for systematic reviews and meta-analysis. This is owing to the fact that most tools are complicated and time consuming, suffer from poor reproducibility, and do not permit quantitative scoring.
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Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33.
Zhaoming Wang, Bin Zhu, Mingfeng Zhang, Hemang Parikh, Jinping Jia, Charles C Chung, Joshua N Sampson, Jason W Hoskins, Amy Hutchinson, Laurie Burdette, Abdisamad Ibrahim, Christopher Hautman, Preethi S Raj, Christian C Abnet, Andrew A Adjei, Anders Ahlbom, Demetrius Albanes, Naomi E Allen, Christine B Ambrosone, Melinda Aldrich, Pilar Amiano, Christopher Amos, Ulrika Andersson, Gerald Andriole, Irene L Andrulis, Cecilia Arici, Alan A Arslan, Melissa A Austin, Dalsu Baris, Donald A Barkauskas, Bryan A Bassig, Laura E Beane Freeman, Christine D Berg, Sonja I Berndt, Pier Alberto Bertazzi, Richard B Biritwum, Amanda Black, William Blot, Heiner Boeing, Paolo Boffetta, Kelly Bolton, Marie-Christine Boutron-Ruault, Paige M Bracci, Paul Brennan, Louise A Brinton, Michelle Brotzman, H Bas Bueno-de-Mesquita, Julie E Buring, Mary Ann Butler, Qiuyin Cai, Géraldine Cancel-Tassin, Federico Canzian, Guangwen Cao, Neil E Caporaso, Alfredo Carrato, Tania Carreon, Angela Carta, Gee-Chen Chang, I-Shou Chang, Jenny Chang-Claude, Xu Che, Chien-Jen Chen, Chih-Yi Chen, Chung-Hsing Chen, Constance Chen, Kuan-Yu Chen, Yuh-Min Chen, Anand P Chokkalingam, Lisa W Chu, Francoise Clavel-Chapelon, Graham A Colditz, Joanne S Colt, David Conti, Michael B Cook, Victoria K Cortessis, E David Crawford, Olivier Cussenot, Faith G Davis, Immaculata De Vivo, Xiang Deng, Ti Ding, Colin P Dinney, Anna Luisa Di Stefano, W Ryan Diver, Eric J Duell, Joanne W Elena, Jin-Hu Fan, Heather Spencer Feigelson, Maria Feychting, Jonine D Figueroa, Adrienne M Flanagan, Joseph F Fraumeni, Neal D Freedman, Brooke L Fridley, Charles S Fuchs, Manuela Gago-Dominguez, Steven Gallinger, Yu-Tang Gao, Susan M Gapstur, Montserrat Garcia-Closas, Reina Garcia-Closas, Julie M Gastier-Foster, J Michael Gaziano, Daniela S Gerhard, Carol A Giffen, Graham G Giles, Elizabeth M Gillanders, Edward L Giovannucci, Michael Goggins, Nalan Gokgoz, Alisa M Goldstein, Carlos González, Richard Gorlick, Mark H Greene, Myron Gross, H Barton Grossman, Robert Grubb, Jian Gu, Peng Guan, Christopher A Haiman, Göran Hallmans, Susan E Hankinson, Curtis C Harris, Patricia Hartge, Claudia Hattinger, Richard B Hayes, Qincheng He, Lee Helman, Brian E Henderson, Roger Henriksson, Judith Hoffman-Bolton, Chancellor Hohensee, Elizabeth A Holly, Yun-Chul Hong, Robert N Hoover, H Dean Hosgood, Chin-Fu Hsiao, Ann W Hsing, Chao Agnes Hsiung, Nan Hu, Wei Hu, Zhibin Hu, Ming-Shyan Huang, David J Hunter, Peter D Inskip, Hidemi Ito, Eric J Jacobs, Kevin B Jacobs, Mazda Jenab, Bu-Tian Ji, Christoffer Johansen, Mattias Johansson, Alison Johnson, Rudolf Kaaks, Ashish M Kamat, Aruna Kamineni, Margaret Karagas, Chand Khanna, Kay-Tee Khaw, Christopher Kim, In-Sam Kim, Jin Hee Kim, Yeul Hong Kim, Young-Chul Kim, Young Tae Kim, Chang Hyun Kang, Yoo Jin Jung, Cari M Kitahara, Alison P Klein, Robert Klein, Manolis Kogevinas, Woon-Puay Koh, Takashi Kohno, Laurence N Kolonel, Charles Kooperberg, Christian P Kratz, Vittorio Krogh, Hideo Kunitoh, Robert C Kurtz, Nilgun Kurucu, Qing Lan, Mark Lathrop, Ching C Lau, Fernando Lecanda, Kyoung-Mu Lee, Maxwell P Lee, Loic Le Marchand, Seth P Lerner, Donghui Li, Linda M Liao, Wei-Yen Lim, Dongxin Lin, Jie Lin, Sara Lindstrom, Martha S Linet, Jolanta Lissowska, Jianjun Liu, Börje Ljungberg, Josep Lloreta, Daru Lu, Jing Ma, Nuria Malats, Satu Mannisto, Neyssa Marina, Giuseppe Mastrangelo, Keitaro Matsuo, Katherine A McGlynn, Roberta Mckean-Cowdin, Lorna H McNeill, Robert R McWilliams, Beatrice S Melin, Paul S Meltzer, James E Mensah, Xiaoping Miao, Dominique S Michaud, Alison M Mondul, Lee E Moore, Kenneth Muir, Shelley Niwa, Sara H Olson, Nick Orr, Salvatore Panico, Jae Yong Park, Alpa V Patel, Ana Patiño-García, Sofia Pavanello, Petra H M Peeters, Beata Peplonska, Ulrike Peters, Gloria M Petersen, Piero Picci, Malcolm C Pike, Stefano Porru, Jennifer Prescott, Xia Pu, Mark P Purdue, You-Lin Qiao, Preetha Rajaraman, Elio Riboli, Harvey A Risch, Rebecca J Rodabough, Nathaniel Rothman, Avima M Ruder, Jeong-Seon Ryu, Marc Sanson, Alan Schned, Fredrick R Schumacher, Ann G Schwartz, Kendra L Schwartz, Molly Schwenn, Katia Scotlandi, Adeline Seow, Consol Serra, Massimo Serra, Howard D Sesso, Gianluca Severi, Hongbing Shen, Min Shen, Sanjay Shete, Kouya Shiraishi, Xiao-Ou Shu, Afshan Siddiq, Luis Sierrasesúmaga, Sabina Sierri, Alan Dart Loon Sihoe, Debra T Silverman, Matthias Simon, Melissa C Southey, Logan Spector, Margaret Spitz, Meir Stampfer, Pär Stattin, Mariana C Stern, Victoria L Stevens, Rachael Z Stolzenberg-Solomon, Daniel O Stram, Sara S Strom, Wu-Chou Su, Malin Sund, Sook Whan Sung, Anthony Swerdlow, Wen Tan, Hideo Tanaka, Wei Tang, Ze-Zhang Tang, Adonina Tardón, Evelyn Tay, Philip R Taylor, Yao Tettey, David M Thomas, Roberto Tirabosco, Anne Tjonneland, Geoffrey S Tobias, Jorge R Toro, Ruth C Travis, Dimitrios Trichopoulos, Rebecca Troisi, Ann Truelove, Ying-Huang Tsai, Margaret A Tucker, Rosario Tumino, David Van Den Berg, Stephen K Van Den Eeden, Roel Vermeulen, Paolo Vineis, Kala Visvanathan, Ulla Vogel, Chaoyu Wang, Chengfeng Wang, Junwen Wang, Sophia S Wang, Elisabete Weiderpass, Stephanie J Weinstein, Nicolas Wentzensen, William Wheeler, Emily White, John K Wiencke, Alicja Wolk, Brian M Wolpin, Maria Pik Wong, Margaret Wrensch, Chen Wu, Tangchun Wu, Xifeng Wu, Yi-Long Wu, Jay S Wunder, Yong-Bing Xiang, Jun Xu, Hannah P Yang, Pan-Chyr Yang, Yasushi Yatabe, Yuanqing Ye, Edward D Yeboah, Zhihua Yin, Chen Ying, Chong-Jen Yu, Kai Yu, Jian-Min Yuan, Krista A Zanetti, Anne Zeleniuch-Jacquotte, Wei Zheng, Baosen Zhou, Lisa Mirabello, Sharon A Savage, Peter Kraft, Stephen J Chanock, Meredith Yeager, Maria Terese Landi, Jianxin Shi, Nilanjan Chatterjee, Laufey T Amundadottir.
Hum. Mol. Genet.
PUBLISHED: 07-15-2014
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Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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Variant histology: role in management and prognosis of nonmuscle invasive bladder cancer.
Curr Opin Urol
PUBLISHED: 06-13-2014
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The true clinical significance of variant histology is controversial and diagnosis is challenging, especially in the setting of nonmuscle invasive (NMI) disease. If the presence of variant architecture in NMI identifies a high-risk population with a worse prognosis and better suited for early aggressive intervention (i.e., radical cystectomy), then treatment recommendations should reflect this notion. This review outlines the current evidence and determines whether histologic variants should change management of patients with nonmuscle invasive bladder cancer.
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Summary of the 8th Annual Bladder Cancer Think Tank: Collaborating to move research forward.
Urol. Oncol.
PUBLISHED: 03-29-2014
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The 8th Annual Bladder Cancer Think Tank (BCAN-TT ) brought together a multidisciplinary group of clinicians, researchers, and patient advocates in an effort to advance bladder cancer research.
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Differential expression of GATA-3 in urothelial carcinoma variants.
Hum. Pathol.
PUBLISHED: 02-24-2014
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GATA binding protein 3 (GATA-3) is a novel immunohistochemical marker for urothelial carcinoma (UC); however, few studies have investigated GATA-3's role as a marker for UC variants. We used immunohistochemistry to assess GATA-3 expression in different UC variants, including micropapillary (n = 46), sarcomatoid (n = 43), small cell carcinoma (n = 22), and plasmacytoid (n = 16) variants, and we also compared GATA-3 expression in conventional bladder UC (n = 103) to that in squamous cell carcinoma (n = 14). GATA-3 expression was present in 70% (72/103) of conventional bladder UCs and highly concordant between matched primary and metastatic UCs. The GATA-3 expression levels of the micropapillary variants (57%; 26/46) and plasmacytoid variants (44%; 7/16) were not significantly different from that of conventional UC. However, the GATA-3 expression levels of the sarcomatoid variants (16%; 7/43) and small cell carcinoma variants (5%; 1/22), which only weakly expressed the protein, were significantly lower than that of conventional UC (P < .001). Only 7% of squamous cell carcinomas (1/14) expressed GATA-3, and it was also significantly lower than that of conventional UC (P < .001). GATA-3 expression was not significantly associated with tumor stage or patients' clinical outcomes. In conclusion, GATA-3 expression differed among UC variants. GATA-3 is a useful marker for confirming the urothelial origin of micropapillary and plasmacytoid UC variants but not that of sarcomatoid or small cell carcinoma variants. GATA-3 can also be used in differentiating UC from squamous cell carcinoma.
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Defining and treating the spectrum of intermediate risk nonmuscle invasive bladder cancer.
J. Urol.
PUBLISHED: 02-17-2014
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Low, intermediate and high risk categories have been defined to help guide the treatment of patients with nonmuscle invasive bladder cancer (Ta, T1, CIS). However, while low and high risk disease has been well classified, the intermediate risk category has traditionally comprised a heterogeneous group that does not fit into either of these categories. As a result, many urologists remain uncertain about the categorization of patients as intermediate risk as well as the selection of the most appropriate therapeutic option for this patient population. We review the current literature and clinical practice guidelines on intermediate risk nonmuscle invasive bladder cancer and, based on our findings, provide urologists with a better understanding of this heterogeneous risk group as well as practical recommendations for the treatment of intermediate risk patients.
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Alvimopan accelerates gastrointestinal recovery after radical cystectomy: a multicenter randomized placebo-controlled trial.
Eur. Urol.
PUBLISHED: 02-13-2014
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Radical cystectomy (RC) for bladder cancer is frequently associated with delayed gastrointestinal (GI) recovery that prolongs hospital length of stay (LOS).
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Neoadjuvant chemotherapy improves survival of patients with upper tract urothelial carcinoma.
Cancer
PUBLISHED: 02-05-2014
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High-grade upper tract urothelial carcinoma (UTUC) is frequently upstaged after surgery and is associated with uniformly poor survival. Neoadjuvant chemotherapy may offer a way to improve clinical outcomes. The authors compared the survival rates of patients with UTUC who received neoadjuvant chemotherapy before surgery with the rates among patients who did not.
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Considerations on the use of urine markers in the management of patients with high-grade non-muscle-invasive bladder cancer.
Urol. Oncol.
PUBLISHED: 02-01-2014
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Diagnosis and surveillance of high risk non muscle-invasive bladder cancer (NMIBC) represent specific challenges to urologists. In contrast to low/intermediate risk tumors, these tumors recur more frequently. A significant number will eventually progress to muscle-invasive bladder cancer, a life threatening disease requiring extensive therapeutic efforts. Although clinical risk factors have been identified that may predict tumor recurrence and progression, additional biomarkers are desperately needed to improve tumor diagnosis and guide clinical management of these patients. In this article, the role of molecular urine markers in the management of high risk NMIBC is analyzed.
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Micropapillary bladder cancer: current treatment patterns and review of the literature.
Urol. Oncol.
PUBLISHED: 01-23-2014
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No guidelines exist for the management of micropapillary bladder cancer (MPBC) and most reports of this variant of urothelial carcinoma are case series comprising small numbers of patients. We sought to determine current practice patterns for MPBC using a survey sent to the Society of Urologic Oncology (SUO) and to present those results in the setting of a comprehensive review of the existing literature.
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Considerations on the use of urine markers in the management of patients with low-/intermediate-risk non-muscle invasive bladder cancer.
Urol. Oncol.
PUBLISHED: 01-14-2014
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Many molecular assays for bladder cancer diagnosis and surveillance have been developed over the past several decades. However, none of these markers have been routinely implemented into clinical decision making. Beyond their potential for screening high-risk populations, urine markers likely have the greatest potential in the follow-up of patients with non-muscle invasive bladder cancer (NMIBC).
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Anterior fascial fixation does not reduce the parastomal hernia rate after radical cystectomy and ileal conduit.
Urology
PUBLISHED: 01-07-2014
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To compare the rate of parastomal hernia in patients undergoing anterior fascial fixation of the ileal conduit with that in patients without fascial fixation. Limited data exist on whether anterior fascial fixation of the ileal conduit impacts the rate of parastomal hernia.
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Clinical-pathologic stage discrepancy in bladder cancer patients treated with radical cystectomy: results from the national cancer data base.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 01-04-2014
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To examine the accuracy of clinical staging and its effects on outcome in bladder cancer (BC) patients treated with radical cystectomy (RC), using a large national database.
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Alvimopan, a Peripherally Acting Mu-Opioid Receptor Antagonist, Is Associated With Reduced Costs After Radical Cystectomy-Economic Analysis of a Phase 4 Randomized, Controlled Trial.
J. Urol.
PUBLISHED: 12-09-2013
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To evaluate the effect of alvimopan treatment versus placebo on healthcare utilization and costs related to gastrointestinal recovery in patients undergoing radical cystectomy in a randomized phase 4 clinical trial.
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Genome-wide association study identifies multiple loci associated with bladder cancer risk.
Jonine D Figueroa, Yuanqing Ye, Afshan Siddiq, Montserrat Garcia-Closas, Nilanjan Chatterjee, Ludmila Prokunina-Olsson, Victoria K Cortessis, Charles Kooperberg, Olivier Cussenot, Simone Benhamou, Jennifer Prescott, Stefano Porru, Colin P Dinney, Nuria Malats, Dalsu Baris, Mark Purdue, Eric J Jacobs, Demetrius Albanes, Zhaoming Wang, Xiang Deng, Charles C Chung, Wei Tang, H Bas Bueno-de-Mesquita, Dimitrios Trichopoulos, Börje Ljungberg, Francoise Clavel-Chapelon, Elisabete Weiderpass, Vittorio Krogh, Miren Dorronsoro, Ruth Travis, Anne Tjønneland, Paul Brenan, Jenny Chang-Claude, Elio Riboli, David Conti, Manuela Gago-Dominguez, Mariana C Stern, Malcolm C Pike, David Van Den Berg, Jian-Min Yuan, Chancellor Hohensee, Rebecca Rodabough, Géraldine Cancel-Tassin, Morgan Rouprêt, Eva Compérat, Constance Chen, Immaculata De Vivo, Edward Giovannucci, David J Hunter, Peter Kraft, Sara Lindstrom, Angela Carta, Sofia Pavanello, Cecilia Arici, Giuseppe Mastrangelo, Ashish M Kamat, Seth P Lerner, H Barton Grossman, Jie Lin, Jian Gu, Xia Pu, Amy Hutchinson, Laurie Burdette, William Wheeler, Manolis Kogevinas, Adonina Tardón, Consol Serra, Alfredo Carrato, Reina Garcia-Closas, Josep Lloreta, Molly Schwenn, Margaret R Karagas, Alison Johnson, Alan Schned, Karla R Armenti, G M Hosain, Gerald Andriole, Robert Grubb, Amanda Black, W Ryan Diver, Susan M Gapstur, Stephanie J Weinstein, Jarmo Virtamo, Chris A Haiman, Maria T Landi, Neil Caporaso, Joseph F Fraumeni, Paolo Vineis, Xifeng Wu, Debra T Silverman, Stephen Chanock, Nathaniel Rothman.
Hum. Mol. Genet.
PUBLISHED: 10-24-2013
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Candidate gene and genome-wide association studies (GWAS) have identified 11 independent susceptibility loci associated with bladder cancer risk. To discover additional risk variants, we conducted a new GWAS of 2422 bladder cancer cases and 5751 controls, followed by a meta-analysis with two independently published bladder cancer GWAS, resulting in a combined analysis of 6911 cases and 11 814 controls of European descent. TaqMan genotyping of 13 promising single nucleotide polymorphisms with P < 1 × 10(-5) was pursued in a follow-up set of 801 cases and 1307 controls. Two new loci achieved genome-wide statistical significance: rs10936599 on 3q26.2 (P = 4.53 × 10(-9)) and rs907611 on 11p15.5 (P = 4.11 × 10(-8)). Two notable loci were also identified that approached genome-wide statistical significance: rs6104690 on 20p12.2 (P = 7.13 × 10(-7)) and rs4510656 on 6p22.3 (P = 6.98 × 10(-7)); these require further studies for confirmation. In conclusion, our study has identified new susceptibility alleles for bladder cancer risk that require fine-mapping and laboratory investigation, which could further understanding into the biological underpinnings of bladder carcinogenesis.
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Myths and Mysteries Surrounding Bacillus Calmette-Guérin Therapy for Bladder Cancer.
Eur. Urol.
PUBLISHED: 09-11-2013
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Intravesical therapy with bacillus Calmette-Guérin has proven effects for reducing recurrence, progression, and death from non-muscle-invasive bladder cancer. These advantages are seen mainly when appropriate maintenance therapy is used for 1-3 years, in the context of appropriate patient selection, tumor management, and symptom support for potential side effects.
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?-H2AX level in peripheral blood lymphocytes as a risk predictor for bladder cancer.
Carcinogenesis
PUBLISHED: 08-14-2013
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Identification of susceptibility to double-strand breaks (DSBs) may provide valuable information about individual bladder cancer (BC) risk. The formation of ?-H2AX foci is a highly sensitive marker for DNA DSBs induction. We assessed whether levels of ?-H2AX in peripheral blood lymphocytes (PBL) obtained after stimulation by ionizing radiation (IR) are able to predict BC risk. Patients were enrolled from an ongoing BC case-control study. Baseline- and IR-induced H2AX phosphorylation was assessed in PBL from 174 newly diagnosed and untreated BC patients and from 174 matched control subjects by a novel, image-based, high-throughput phenotypic assay. The ratio of ?-H2AX level of IR-treated cells to that of non-treated cells (baseline) was used as the parameter to assess the sensitivity to the mutagen. The mean ?-H2AX ratios were significantly higher for cases than for controls (1.43±0.14 versus 1.35±0.12; P = 8.45×10(-8)). This trend was irrespective of age, sex and smoking status. The risk estimates of BC for induced DSBs by tertile distributions in controls showed also a significant trend for increased risk at the highest tertile for the whole cohort (odds ratio = 5.16; 95% confidence interval = 2.69, 9.89; P = 7.78 × 10(-7)) as well as for each category. Our findings suggest that a higher susceptibility to induction of DSBs as measured by the ?-H2AX assay is significantly associated with an increased risk for BC. This might help to identify individuals at high risk for this cancer, adding new perspectives to established epidemiological and genetic risk factors. Further research of the role of ?-H2AX in biological processes of BC is warranted.
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Should histologic variants alter definitive treatment of bladder cancer?
Curr Opin Urol
PUBLISHED: 07-25-2013
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The clinical significance of variant histology is controversial and diagnosis is challenging. If variant architecture truly identifies high-risk patients, or those with a differential response to therapy, than treatment algorithms should be altered. This review outlines the current evidence and determines whether histologic variants should indeed alter definitive treatment.
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Defining Progression in Nonmuscle Invasive Bladder Cancer: It is Time for a New, Standard Definition.
J. Urol.
PUBLISHED: 07-22-2013
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Despite being one of the most important clinical outcomes in nonmuscle invasive bladder cancer, there is currently no standard definition of disease progression. Major clinical trials and meta-analyses have used varying definitions or have failed to define this end point altogether. A standard definition of nonmuscle invasive bladder cancer progression as determined by reproducible and reliable procedures is needed. We examine current definitions of nonmuscle invasive bladder cancer progression, and propose a new definition that will be more clinically useful in determining patient prognosis and comparing treatment options.
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Refining Patient Selection for Neoadjuvant Chemotherapy before Radical Cystectomy.
J. Urol.
PUBLISHED: 07-22-2013
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We evaluated the survival of patients with muscle invasive bladder cancer undergoing radical cystectomy without neoadjuvant chemotherapy to confirm the utility of existing clinical tools to identify low risk patients who could be treated with radical cystectomy alone and a high risk group most likely to benefit from neoadjuvant chemotherapy.
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Commentary on "The clinical epidemiology of urachal carcinoma: results of a large, population based study." Bruins HM, Visser O, Ploeg M, Hulsbergen-van de Kaa CA, Kiemeney LA, Witjes JA, Department of Urology, Radboud University Medical Centre, Utrecht,
Urol. Oncol.
PUBLISHED: 06-26-2013
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Survival data on urachal carcinoma are sparse due to the low prevalence of this cancer. We report urachal carcinoma clinical outcomes and prognostic factors in a large, population based cohort of patients with long-term followup.
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Commentary on "Phase II trial of cetuximab with or without paclitaxel in patients with advanced urothelial tract carcinoma." Wong YN, Litwin S, Vaughn D, Cohen S, Plimack ER, Lee J, Song W, Dabrow M, Brody M, Tuttle H, Hudes G, University of Pennsylvania,
Urol. Oncol.
PUBLISHED: 06-26-2013
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The benefit of salvage chemotherapy is modest in metastatic urothelial cancer. We conducted a randomized, noncomparative phase II study to measure the efficacy of cetuximab with or without paclitaxel in patients with previously treated urothelial cancer.
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Commentary on "Predictive capacity of four comorbidity indices estimating perioperative mortality after radical cystectomy for urothelial carcinoma of the bladder." Mayr R, May M, Martini T, Lodde M, Pycha A, Comploj E, Wieland WF, Denzinger S, Otto W, Bu
Urol. Oncol.
PUBLISHED: 06-26-2013
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Whats known on the subject? and What does the study add? The degree of comorbidity significantly affects the course of patients with bladder cancer undergoing radical cystectomy (RC). To our knowledge this is the first study comparing four different comorbidity indices in patients undergoing RC for urothelial carcinoma to assess the best clinical predictors for 90-day perioperative mortality. We concluded that the ASA score should be the method of choice, as it showed a predictive ability superior to that of ECOG and CCI, and is much easier to generate than the ACE-27.
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Commentary on "Surveillance guidelines based on recurrence patterns after radical cystectomy for bladder cancer: the Canadian Bladder Cancer Network experience." Yafi FA, Aprikian AG, Fradet Y, Chin JL, Izawa J, Rendon R, Estey E, Fairey A, Cagiannos I, L
Urol. Oncol.
PUBLISHED: 06-26-2013
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Study Type-Prognosis (cohort) Level of Evidence 2a. Whats known on the subject? and What does the study add? Radical cystectomy with pelvic lymph node dissection is recognized as the standard of care for carcinoma invading bladder muscle and for refractory non-muscle-invasive bladder cancer. Owing to high recurrence and progression rates, a two-pronged strict surveillance regimen, consisting of both functional and oncological follow-up, has been advocated. It is also well recognized that more aggressive tumours with extravesical disease and node-positive disease recur more frequently and have worse outcomes. This study adds to the scant body of literature available regarding surveillance strategies after radical cystectomy for bladder cancer. In the absence of any solid evidence supporting the role of strict surveillance regimens, this extensive examination of recurrence patterns in a large multi-institutional project lends further support to the continued use of risk-stratified follow-up and emphasizes the need for earlier strict surveillance in patients with extravesical and node-positive disease.
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A Smac mimetic augments the response of urothelial cancer cells to gemcitabine and cisplatin.
Cancer Biol. Ther.
PUBLISHED: 06-19-2013
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Cisplatin-based chemotherapy is considered the gold standard for patients with advanced bladder cancer. However, despite initial response, many patients will relapse; therefore, novel salvage treatment strategies are desperately needed. Herein, we studied a mechanism based treatment combination using a Smac mimetic with standard chemotherapy. Using a panel of 10 urothelial cancer cell lines, we exposed them to a combination of gemcitabine, cisplatin and a Smac mimetic. Sensitivity was determined using a DNA fragmentation assay. We determined that three cell lines (UMUC-3, UMUC-13 and RT4v6) were considered sensitive to the combination of gemcitabine and cisplatin and an additional three cell lines were sensitized to gemcitabine and cisplatin with the addition of the Smac mimetic (UMUC-6, UMUC-12 and UMUC-18). We next explored the constitutive expression of selected members of the IAP family (XIAP, cIAP-1, cIAP-2, Survivin), the BCL family (BCL-2, BCLXL and BAX) and Smac using gene expression profiling and western blotting. We determined that RNA and protein expression of SMAC, selected members of the IAP family and members of the BCL family did not correlate to drug sensitivity. Lastly, using an in vivo mouse model, we determined that treatment with the Smac mimetic in combination with gemcitabine and cisplatin resulted in increased apoptosis, decreased microvessel density and decreased cellular proliferation. This novel treatment strategy may be effective in patients with advanced urothelial carcinoma and warrants further investigation.
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Lymphadenectomy with robotic cystectomy.
Curr Urol Rep
PUBLISHED: 06-15-2013
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It is now established that an experienced, dedicated robotic surgeon can perform a high quality extended template pelvic lymph node dissection at the time of robot-assisted radical cystectomy. The evidence for this conclusion can be seen in comparing absolute lymph node counts, percent positive lymph nodes, and oncologic outcomes from N1 patients. In this report, we outline the endpoints of study for this question, and report recent data on efforts to advance robot-assisted urinary diversion, cost-focused studies, and standardized complication reporting. These studies demonstrate maintenance of adequate lymph node dissections while advancing the goal of reducing morbidity for patients needing radical cystectomy for invasive disease.
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Genetic variations in regulator of G-protein signaling (RGS) confer risk of bladder cancer.
Cancer
PUBLISHED: 03-25-2013
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Alterations in the regulator of G-protein signaling (RGS) pathway have been implicated in several cancers; therefore, the authors investigated the role of such alterations in overall bladder cancer risk, recurrence, progression, and survival.
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Phase I trial of intravesical recombinant adenovirus mediated interferon-?2b formulated in Syn3 for Bacillus Calmette-Guérin failures in nonmuscle invasive bladder cancer.
J. Urol.
PUBLISHED: 03-07-2013
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A phase I trial of intravesical recombinant adenovirus mediated interferon-?2b gene therapy (rAd-IFN?) formulated with the excipient SCH Syn3 was conducted in patients with nonmuscle invasive bladder cancer who had disease recurrence after treatment with bacillus Calmette-Guérin. The primary objective was to determine the safety of rAd-IFN?/Syn3. Secondary end points were demonstrated effective rAd-IFN? gene expression and preliminary evidence of clinical activity at 3 months.
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Current clinical practice gaps in the treatment of intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC) with emphasis on the use of bacillus Calmette-Guérin (BCG): results of an international individual patient data survey (IPDS).
BJU Int.
PUBLISHED: 03-01-2013
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To examine the management of intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC), particularly with regard to the use of bacillus Calmette-Guérin (BCG) therapy, in North America and Europe. To compare NMIBC management practices to European Association of Urology (EAU) and American Urological Association (AUA) guideline recommendations for the management of intermediate- and high-risk NMIBC.
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Strategies for optimizing bacillus Calmette-Guérin.
Urol. Clin. North Am.
PUBLISHED: 02-27-2013
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For treating patients with superficial bladder cancer and a moderate-to-high risk of tumor recurrence or progression, intravesical BCG has been the key development of the last generation. However, BCG has also brought with it a novel set of challenges. An understanding of when, to whom, and how BCG should be given is critical if optimal outcomes are to be achieved. This article the authors reviews the role that BCG has played in the management of bladder cancer over the last several decades and discusses specific approaches to optimize BCG. It focuses on selection and technical strategies.
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ZKSCAN3 is a master transcriptional repressor of autophagy.
Mol. Cell
PUBLISHED: 01-18-2013
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Autophagy constitutes a major cell-protective mechanism that eliminates damaged components and maintains energy homeostasis via recycling nutrients under normal/stressed conditions. Although the core components of autophagy have been well studied, regulation of autophagy at the transcriptional level is poorly understood. Herein, we establish ZKSCAN3, a zinc finger family DNA-binding protein, as a transcriptional repressor of autophagy. Silencing of ZKSCAN3 induced autophagy and increased lysosome biogenesis. Importantly, we show that ZKSCAN3 represses transcription of a large gene set (>60) integral to, or regulatory for, autophagy and lysosome biogenesis/function and that a subset of these genes, including Map1lC3b and Wipi2, represent direct targets. Interestingly, ZKSCAN3 and TFEB are oppositely regulated by starvation and in turn oppositely regulate lysosomal biogenesis and autophagy, suggesting that they act in conjunction. Altogether, our study uncovers an autophagy master switch regulating the expression of a transcriptional network of genes integral to autophagy and lysosome biogenesis/function.
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Contemporary management of locally invasive bladder cancer.
Oncology (Williston Park, N.Y.)
PUBLISHED: 12-18-2011
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Bladder cancer is a heterogeneous disease that carries a significant risk of progression and lethality. Radical cystectomy with pelvic lymph node dissection remains the predominant treatment for patients with muscle-invasive disease and offers the best chance of long-term disease control. However, radical surgery is insufficient in patients with advanced-stage disease. Current staging techniques are limited in their ability to detect extravesical disease and lymph node metastases. Thus, integration of systemic therapy with surgery to potentially eradicate micrometastases provides survival superior to that with surgery alone. Yet, because bladder cancer is typically a disease that affects an elderly population of patients with multiple comorbidities, there is a need for less invasive and bladder-conserving therapies. Some physicians have attempted to minimize morbidity by pursuing minimally invasive surgical techniques; however, the long-term effectiveness of this approach remains unproven. Trimodality therapy could be considered in patients with favorable disease status, and may be offered as a reasonable alternative, but does not replace standard treatments for patients with more aggressive disease. Consequently, further improvements in outcomes will rely on improved patient selection based on clinical and molecular assessments.
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Bladder cancer: imperatives for personalized medicine.
Oncology (Williston Park, N.Y.)
PUBLISHED: 10-21-2011
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Although the age-adjusted incidence of urothelial carcinoma has stabilized or declined in developed nations as a result of tobacco and environmental regulations, the rising numbers of the elderly and the shift in the tobacco epidemic to underdeveloped and rapidly industrializing nations with less stringent environmental controls augur a major growth in the worldwide burden of this disease. Current understanding of the molecular pedigree of urothelial carcinoma indicates that the disease follows a two-pathway model. The first of these, the common non-muscle-invasive papillary disease (Ta) defined by fibroblast growth factor receptor 3 (FGFR3) mutations and Ras pathway signaling, is characterized by a very low (< 5%) incidence of progression to invasive disease and very low disease-specific mortality.The second, or more lethal form is characterized by carcinoma in situ and invasive (lamina propria or deeper) tumors featuring p53 and Rb defects with a high risk of disease-specific mortality. For high-risk non-muscle-invasive disease, optimized intravesical therapeutics, including adequate transurethral resection, peri-operative intravesical chemotherapy, adjuvant intravesical bacille Calmette-Guérin and/or timely cystectomy, are needed to minimize disease-specific mortality and maximize quality of life. In muscle-invasive organ-confined disease, surgery remains the standard of care, with neoadjuvant chemotherapy providing a survival benefit in a subset of patients. Research strategies that identify disease subsets of muscle-invasive bladder cancer that benefit or do not benefit from adjunctive chemotherapy are required to reduce the relatively high number-needed-to-treat associated with this approach. To facilitate major therapeutic progress in the disease, accelerated study of experimental therapeutics connected to a fuller portrait of the heterogeneous molecular pathophysiology of bladder cancer is needed. Effective multidisciplinary collaboration is imperative in order to implement existing knowledge, enable priority research, reduce costs, and improve on the clinically relevant endpoints of survival and quality of life.
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Comprehensive handbook for developing a bladder cancer cystectomy database.
Urol. Oncol.
PUBLISHED: 08-09-2011
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In an effort to standardize data collection for research regarding bladder cancer, the Bladder Cancer Working Group sought to provide a handbook that can be used as a guide for prospective or retrospective data collection.
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A genome-wide association study of bladder cancer identifies a new susceptibility locus within SLC14A1, a urea transporter gene on chromosome 18q12.3.
Hum. Mol. Genet.
PUBLISHED: 08-08-2011
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Genome-wide and candidate-gene association studies of bladder cancer have identified 10 susceptibility loci thus far. We conducted a meta-analysis of two previously published genome-wide scans (4501 cases and 6076 controls of European background) and followed up the most significant association signals [17 single nucleotide polymorphisms (SNPs) in 10 genomic regions] in 1382 cases and 2201 controls from four studies. A combined analysis adjusted for study center, age, sex, and smoking status identified a novel susceptibility locus that mapped to a region of 18q12.3, marked by rs7238033 (P = 8.7 × 10(-9); allelic odds ratio 1.20 with 95% CI: 1.13-1.28) and two highly correlated SNPs, rs10775480/rs10853535 (r(2)= 1.00; P = 8.9 × 10(-9); allelic odds ratio 1.16 with 95% CI: 1.10-1.22). The signal localizes to the solute carrier family 14 member 1 gene, SLC14A1, a urea transporter that regulates cellular osmotic pressure. In the kidney, SLC14A1 regulates urine volume and concentration whereas in erythrocytes it determines the Kidd blood groups. Our findings suggest that genetic variation in SLC14A1 could provide new etiological insights into bladder carcinogenesis.
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A genome-wide association study identifies a locus on chromosome 14q21 as a predictor of leukocyte telomere length and as a marker of susceptibility for bladder cancer.
Cancer Prev Res (Phila)
PUBLISHED: 04-02-2011
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Telomeres play a critical role in maintaining genome integrity. Telomere shortening is associated with the risk of many aging-related diseases. Classic twin studies have shown that genetic components may contribute up to 80% of the heritability of telomere length. In the study we report here that we used a multistage genome-wide association study to identify genetic determinants of telomere length. The mean telomere length in peripheral blood leukocytes was measured by quantitative real-time PCR. We first analyzed 300,000 single-nucleotide polymorphisms (SNPs) in 459 healthy controls, finding 15,120 SNPs associated with telomere length at P < 0.05. We then validated these SNPs in two independent populations comprising 890 and 270 healthy controls, respectively. Four SNPs, including rs398652 on 14q21, were associated with telomere length across all three populations (pooled P values of <10(-5)). The variant alleles of these SNPs were associated with longer telomere length. We then analyzed the association of these SNPs with the risk of bladder cancer in a large case-control study. The variant allele of rs398652 was associated with a significantly reduced risk of bladder cancer (odds ratio = 0.81; 95% confidence interval, 0.67-0.97; P = 0.025), consistent with the correlation of this variant allele with longer telomeres. We then conducted a mediation analysis to examine whether the association between rs398652 and reduced bladder cancer risk is mediated by telomere length, finding that telomere length was a significant mediator of the relationship between rs398652 and bladder cancer (P = 0.013), explaining 14% of the effect. In conclusion, we found that the SNP rs398652 on 14q21 was associated with longer telomere length and a reduced risk of bladder cancer and that a portion of the effect of this SNP on bladder cancer risk was mediated by telomere length.
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Prospective trial to identify optimal bladder cancer surveillance protocol: reducing costs while maximizing sensitivity.
BJU Int.
PUBLISHED: 03-22-2011
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• To assess the cost-effectiveness of using cytological evaluation, NMP22 BladderChek®, and fluorescence in situ hybridization (FISH) UroVysion® in addition to cystoscopy in patients with a history of bladder cancer undergoing surveillance for recurrence.
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The role of FISH and cytology in upper urinary tract surveillance after radical cystectomy for bladder cancer.
Urol. Oncol.
PUBLISHED: 03-10-2011
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Cytology and fluorescence in situ hybridization (FISH) (Urovysion) assay are often used during upper urinary tract surveillance in patients following radical cystectomy with urinary diversion, without much available data regarding efficacy in this population. Here, we evaluate the value of FISH and cytology in detecting upper tract recurrence in the face of a urinary diversion.
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Critical analysis and validation of lymph node density as prognostic variable in urothelial carcinoma of bladder.
Urol. Oncol.
PUBLISHED: 01-31-2011
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To validate the prognostic relevance of lymph node density (LND) and identify its optimal cut-points in a large international multicenter series of patients treated with radical cystectomy (RC) for invasive bladder cancer.
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Discrepancy between clinical and pathological stage: external validation of the impact on prognosis in an international radical cystectomy cohort.
BJU Int.
PUBLISHED: 01-18-2011
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• To compare the clinical and pathologic stage among a large, multi-institutional series of patients undergoing radical and to determine the effect of stage discrepancy on outcomes.
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Perioperative outcomes of laparoscopic radical nephroureterectomy and regional lymphadenectomy in patients with upper urinary tract urothelial carcinoma after neoadjuvant chemotherapy.
Urology
PUBLISHED: 01-01-2011
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To determine the effect of neoadjuvant chemotherapy on the surgical outcomes in patients undergoing laparoscopic radical nephroureterectomy (LNUX) for upper urinary tract urothelial carcinoma (UTUC).
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Smac mimetic reverses resistance to TRAIL and chemotherapy in human urothelial cancer cells.
Cancer Biol. Ther.
PUBLISHED: 11-01-2010
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inhibitors of apoptosis proteins (IAPs) have been shown to contribute to resistance of neoplastic cells to chemotherapy and to biologic antineoplastic agents. Consequently, new agents are being developed targeting this family of proteins. In a panel of bladder cancer cell lines, we evaluated a Smac mimetic that antagonizes several IAPs for its suitability for bladder cancer therapy. Experimental design: A panel of seven bladder cancer cell lines were evaluated for sensitivity to the Smac mimetic compound-A alone, TRAIL alone, chemotherapy alone, compound-A plus TRAIL, and compound-A plus chemotherapy by DNA fragmentation analysis. IAP levels and caspase activation were examined by western blotting. Release of caspase-3 from X-linked inhibitor of apoptosis protein (XIAP), the most effective IAP, was assessed by immunoprecipitation and western blotting. Finally, siRNA knockdown of XIAP was correlated with the sensitivity of cells to apoptosis induced by compound-A plus TRAIL by DNA fragmentation and western blotting.
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Significance of upper urinary tract urothelial thickening and filling defect seen on MDCT urography in patients with a history of urothelial neoplasms.
AJR Am J Roentgenol
PUBLISHED: 09-23-2010
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The purpose of this article is to assess the ability of CT urography to depict urothelial tumors in the upper renal collecting systems, compared with ureteroscopy and pathologic analysis, and to describe the relative implication of the radiologic signs of urothelial thickening and endoluminal filling defects.
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Genetic variations in the sonic hedgehog pathway affect clinical outcomes in non-muscle-invasive bladder cancer.
Cancer Prev Res (Phila)
PUBLISHED: 09-21-2010
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Sonic hedgehog (Shh) pathway genetic variations may affect bladder cancer risk and clinical outcomes. Therefore, we genotyped 177 single-nucleotide polymorphisms (SNP) in 11 Shh pathway genes in a study including 803 bladder cancer cases and 803 controls. We assessed SNP associations with cancer risk and clinical outcomes in 419 cases of non-muscle-invasive bladder cancer (NMIBC) and 318 cases of muscle-invasive and metastatic bladder cancer (MiMBC). Only three SNPs (GLI3 rs3823720, rs3735361, and rs10951671) reached nominal significance in association with risk (P ? 0.05), which became nonsignificant after adjusting for multiple comparisons. Nine SNPs reached a nominally significant individual association with recurrence of NMIBC in patients who received transurethral resection (TUR) only (P ? 0.05), of which two (SHH rs1233560 and GLI2 rs11685068) were replicated independently in 356 TUR-only NMIBC patients, with P values of 1.0 × 10(-3) (SHH rs1233560) and 1.3 × 10(-3) (GLI2 rs11685068). Nine SNPs also reached a nominally significant individual association with clinical outcome of NMIBC patients who received Bacillus Calmette-Guérin (BCG; P ? 0.05), of which two, the independent GLI3 variants rs6463089 and rs3801192, remained significant after adjusting for multiple comparisons (P = 2 × 10(-4) and 9 × 10(-4), respectively). The wild-type genotype of either of these SNPs was associated with a lower recurrence rate and longer recurrence-free survival (versus the variants). Although three SNPs (GLI2 rs735557, GLI2 rs4848632, and SHH rs208684) showed nominal significance in association with overall survival in MiMBC patients (P ? 0.05), none remained significant after multiple-comparison adjustments. Germ-line genetic variations in the Shh pathway predicted clinical outcomes of TUR and BCG for NMIBC patients.
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High-frequency endoluminal ultrasonography as an aid to the staging of upper tract urothelial carcinoma: imaging findings and pathologic correlation.
J Ultrasound Med
PUBLISHED: 08-25-2010
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We analyzed endoluminal ultrasonography (ELUS) for evaluating renal pelvic and ureteral, or upper tract, urothelial carcinoma (UTUC).
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Fluorescence in situ hybridization for detecting urothelial carcinoma: a clinicopathologic study.
Cancer Cytopathol
PUBLISHED: 07-29-2010
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Because urothelial carcinoma (UC) is associated with a significantly high risk of disease recurrence and progression, patients with UC require long-term surveillance. Fluorescence in situ hybridization (FISH) has been shown to be more sensitive than cytology in the detection of UC. The current study evaluated the use of FISH for detecting UC.
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Optimal timing of chemotherapy and cystectomy.
F1000 Med Rep
PUBLISHED: 06-23-2010
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Radical cystectomy with pelvic lymphadenectomy is the standard treatment for muscle-invasive bladder cancer. However, the high recurrence rates and high death rate from metastases after radical cystectomy for locally advanced bladder cancer emphasize the high risk of occult distant disease. To improve patient survival, multimodal therapy whereby chemotherapy and surgery are used in concert with each other is necessary. The preponderance of data suggests that neoadjuvant chemotherapy offers patients a clear - albeit small - survival advantage, whereas the data for adjuvant chemotherapy are less convincing. Currently, trials to improve the results of such neoadjuvant therapy using biologic targets in conjunction with cytotoxic regimens are under way.
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Incidence of downstaging and complete remission after neoadjuvant chemotherapy for high-risk upper tract transitional cell carcinoma.
Cancer
PUBLISHED: 06-22-2010
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The authors evaluated the incidence of pathologic downstaging and complete remission (CR) in patients with high-grade ureteral and renal pelvic transitional cell carcinoma (TCC) (upper tract TCC) who received neoadjuvant chemotherapy followed by surgery.
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Bladder cancer stem cells.
Curr Stem Cell Res Ther
PUBLISHED: 06-18-2010
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Stem cells are undifferentiated cells that renew themselves while simultaneously producing differentiated tissue- or organspecific cells through asymmetric cell division. The appreciation of the importance of stem cells in normal tissue biology has prompted the idea that cancers may also develop from a progenitor pool (the "cancer stem cell (CSC) hypothesis"), and this idea is gaining increasing acceptance among scientists. CSCs are sub-populations of cancer cells responsible for tumor initiation, differentiation, recurrence, metastasis, and drug resistance. First identified in the hematopoietic system, CSCs have also been discovered in solid tumors of the breast, colon, pancreas, and brain. Recently, the tissue-specific stem cells of the normal urothelium have been proposed to reside in the basal layer, and investigators have isolated phenotypically similar populations of cells from urothelial cancer cell lines and primary tumors. Herein, we review the CSC hypothesis and apply it to explain the development of the two different types of bladder cancer: noninvasive ("superficial") carcinoma and invasive carcinoma. We also examine potential approaches to identify CSCs in bladder cancer as well as therapeutic applications of these findings. While exciting, the verification of the existence of CSCs in bladder cancer raises several new questions. Herein, we identify and answer some of these questions to help readers better understand bladder cancer development and identify reasonable therapeutic strategy for targeting stem cells.
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Robot assisted extended pelvic lymphadenectomy at radical cystectomy: lymph node yield compared with second look open dissection.
J. Urol.
PUBLISHED: 05-17-2010
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Robot assisted radical cystectomy outcomes show feasibility and potential benefits for patient recovery. However, it is difficult to judge the completeness of extended robot assisted vs open pelvic lymph node dissection using only the lymph node count and template description. We performed a prospective protocol in which radical cystectomy and pelvic lymph node dissection done in robot assisted fashion were followed by second look open pelvic lymph node dissection. Our primary objective was to determine the fraction of lymph nodes yielded by robot assisted pelvic lymph node dissection.
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Preoperative CTLA-4 blockade: tolerability and immune monitoring in the setting of a presurgical clinical trial.
Clin. Cancer Res.
PUBLISHED: 05-11-2010
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Cytotoxic T lymphocyte associated antigen (CTLA-4) blockade is being explored in numerous clinical trials as an immune-based therapy for different malignancies. Our group conducted the first preoperative clinical trial with the anti-CTLA-4 antibody ipilimumab in 12 patients with localized urothelial carcinoma of the bladder.
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BCAN Think Tank session 3: Prevention of bladder cancer.
Urol. Oncol.
PUBLISHED: 05-05-2010
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The Bladder Cancer Think Tank III brought together a multidisciplinary group of clinician scientists, patient advocates, representatives from the National Cancer Institute, and Industry leaders to discuss the current state of the field in urothelial cancer and to develop strategies to move forward. This paper summarizes the session devoted to prevention. Experts sought to define primary, secondary, and tertiary prevention and discussed clinical trials performed to date testing retinoids, difluoromethylornithine, celecoxib, and other oral agents in a tertiary prevention setting following transurethral resection with or without intravesical therapy. Urologists practice tertiary prevention in the form of intravesical therapy, and strategies were discussed to identify biomarkers, including urinary cytokines and pathway single nucleotide polymorphism analysis associated with response to treatment. Optimizing delivery of intravesical chemotherapy to the target tissue with simple pharmacologic manipulations or packaging drugs in nanoparticles may improve treatment outcome. Defining a premalignant lesion should be a focus of future research as a strategy for early detection and secondary prevention. Cigarette smoking is the most prevalent risk factor for urothelial cancer, and emphasis was placed on smoking cessation as a powerful tool to reduce the burden of urothelial cancer, and the central role physicians must play in educating patients and providing resources. There is a strong need for research to develop markers of disease initiation and progression. These markers, combined with histories of environmental exposure to bladder carcinogens, may provide a tool to identify patients who will benefit from primary prevention.
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BCAN Think Tank session 2: Molecular detection of bladder cancer: the path to progress.
Urol. Oncol.
PUBLISHED: 05-05-2010
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Initial detection of bladder cancer and surveillance for cancer recurrence and progression are central topics in the field of urologic oncology. A session at the 3rd Annual Bladder Cancer Think Tank Meeting focused on urine-based markers for bladder cancer screening and surveillance. Here, we review the key points from the presentations, as well as the recommendations from a working group tasked with critically evaluating the information discussed in the session. Although the practicality of markers has been challenged, the resounding consensus was that continued research efforts directed at developing and evaluating markers for screening and early detection are warranted.
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The role of radical cystectomy in patients with clinical T4b bladder cancer.
Urol. Oncol.
PUBLISHED: 04-24-2010
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Patients with clinical T4b bladder cancer (extension to pelvic wall and/or adjacent organs other than prostate, vagina, or uterus) are commonly considered unresectable. We hypothesized that select patients might achieve durable benefit from multiagent chemotherapy and extirpative surgery.
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Upper tract urothelial carcinoma: impact of time to surgery.
Urol. Oncol.
PUBLISHED: 04-01-2010
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Patients diagnosed with upper tract urothelial carcinoma (UTUC) sometimes experience a delay from diagnosis to extirpative surgery (nephroureterectomy or ureterectomy) as a result of attempted endoscopic management and/or neoadjuvant chemotherapy. The purpose of this analysis is to examine the impact of such delay on survival outcomes.
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Age and body mass index are independent risk factors for the development of postoperative paralytic ileus after radical cystectomy.
Urology
PUBLISHED: 02-15-2010
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To identify the risk factors that would aid in the identification of patients at the greatest risk of developing postoperative paralytic ileus (POI). POI is a common complication after radical cystectomy and can result in a prolonged hospital stay and delayed recovery.
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Reconstruction of the pelvic floor with human acellular dermal matrix and omental flap following anterior pelvic exenteration.
J Plast Reconstr Aesthet Surg
PUBLISHED: 01-27-2010
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Pelvic floor reconstruction after pelvic exenteration is challenging, particularly with bacterial contamination and/or pelvic irradiation. Traditional regional myocutaneous flap options are not always avaliable, especially in the multiply operated patient. Human acellular dermal matrix (HADM) confers several advantages and is associated with less morbidity when compared to synthetic mesh used in these compromised wound beds. We report a clinical case of an elderly patient with an anterior pelvic floor defect, who underwent successful reconstruction with a combination of human acellular dermal matrix and an omental flap.
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Risk factor analysis in a contemporary cystectomy cohort using standardized reporting methodology and adverse event criteria.
J. Urol.
PUBLISHED: 01-18-2010
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Adverse event reporting is poorly classified and nonstandardized in the urological literature. We report adverse event data and associated risk factors using standardized reporting methods and Common Terminology Criteria for Adverse Events, version 3.0 to minimize interpretation bias and allow reliable comparisons with other populations.
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Activation of nerve growth factor-induced B alpha by methylene-substituted diindolylmethanes in bladder cancer cells induces apoptosis and inhibits tumor growth.
Mol. Pharmacol.
PUBLISHED: 12-18-2009
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Nerve growth factor-induced B (NGFI-B) genes are orphan nuclear receptors, and NGFI-B alpha (Nur77, TR3) is overexpressed in bladder tumors and bladder cancer cells compared with nontumorous bladder tissue. 1,1-Bis(3-indolyl)-1-(p-methoxyphenyl)-methane (DIM-C-pPhOCH(3)) and 1,1-bis(3-indolyl)-1-(p-phenyl)methane have previously been identified as activators of Nur77, and both compounds inhibited growth and induced apoptosis of UC-5 and KU7 bladder cancer cells. The proapoptotic effects of methylene-substituted diindolylmethanes (C-DIMs) were unaffected by cotreatment with leptomycin B and were dependent on nuclear Nur77, and RNA interference with a small inhibitory RNA for Nur77 (iNur77) demonstrated that C-DIM-induced activation of apoptosis was Nur77-dependent. Microarray analysis of DIM-C-pPhOCH(3)-induced genes in UC-5 bladder cancer cells showed that this compound induced multiple Nur77-dependent proapoptotic or growth inhibitory genes including tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), cystathionase, p21, p8, and sestrin-2. DIM-C-pPhOCH(3) (25 mg/kg/d) also induced apoptosis and inhibited tumor growth in athymic nude mice bearing KU7 cells as xenografts, demonstrating that Nur77-active C-DIMs exhibit potential for bladder cancer chemotherapy by targeting Nur77, which is overexpressed in this tumor type.
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Role of epithelial-to-mesenchymal transition (EMT) in drug sensitivity and metastasis in bladder cancer.
Cancer Metastasis Rev.
PUBLISHED: 12-17-2009
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Epithelial-to-mesenchymal transition (EMT) is a process that plays essential roles in development and wound healing that is characterized by loss of homotypic adhesion and cell polarity and increased invasion and migration. At the molecular level, EMT is characterized by loss of E-cadherin and increased expression of several transcriptional repressors of E-cadherin expression (Zeb-1, Zeb-2, Twist, Snail, and Slug). Early work established that loss of E-cadherin and increased expression of MMP-9 was associated with a poor clinical outcome in patients with urothelial tumors, suggesting that EMT might also be associated with bladder cancer progression and metastasis. More recently, we have used global gene expression profiling to characterize the molecular heterogeneity in human urothelial cancer cell lines (n = 20) and primary patient tumors, and unsupervised clustering analyses revealed that the cells naturally segregate into two discrete "epithelial" and "mesenchymal" subsets, the latter consisting entirely of muscle-invasive tumors. Importantly, sensitivity to inhibitors of the epidermal growth factor receptor (EGFR) or type-3 fibroblast growth factor receptor (FGFR3) was confined to the "epithelial" subset, and sensitivity to EGFR inhibitors could be reestablished by micro-RNA-mediated molecular reversal of EMT. The results suggest that EMT coordinately regulates drug resistance and muscle invasion/metastasis in urothelial cancer and is a dominant feature of overall cancer biology.
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Management of urethral recurrence after orthotopic urinary diversion.
BJU Int.
PUBLISHED: 12-11-2009
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Therapy (case series) Level of Evidence 4 OBJECTIVE To evaluate our experience with urethral recurrences in patients treated by radical cystectomy(RC) and orthotopic neobladder urinary diversion for carcinoma of the bladder.
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Curcumin potentiates the antitumor effects of Bacillus Calmette-Guerin against bladder cancer through the downregulation of NF-kappaB and upregulation of TRAIL receptors.
Cancer Res.
PUBLISHED: 11-10-2009
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Although Bacillus Calmette-Guerin (BCG) intravesical therapy is a standard treatment for bladder cancer, eventual failure of response is a major problem. Treatments that can augment BCG therapy are urgently needed. We investigated whether curcumin, a component of Curcuma longa (also called turmeric), has potential to improve the current therapy using in vitro and in vivo MBT-2 murine tumor models. We found that curcumin potentiated BCG-induced apoptosis of human bladder cancer cells. BCG stimulated the release of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) from peripheral mononuclear neutrophils in a dose- and time-dependent manner, whereas curcumin enhanced the upregulation of TRAIL receptors. Electrophoretic mobility shift assay revealed that curcumin also suppressed the BCG-induced activation of the cell survival transcription factor NF-kappaB. In a syngeneic bladder cancer model, curcumin alone reduced the bladder tumor volume, but a significantly greater reduction was observed when BCG and curcumin were used in combination (P < 0.0001 versus control; P < 0.003 versus BCG alone). This was accompanied by a significant decrease in the proliferation marker Ki-67 (P < 0.01 versus control; P < 0.01 versus BCG alone) and microvessel density (CD31; P < 0.01 versus control; P < 0.01 versus BCG alone), decreased NF-kappaB in tumor tissue compared with the control, induced apoptosis, and decreased cyclin D1, vascular endothelial growth factor, cyclooxygenase-2, c-myc, and Bcl-2 expression in the tumor tissue. Upregulation of TRAIL receptor by the combination was also observed in tumor tissues. Overall, our results suggest that curcumin potentiates the antitumor effect of BCG through the inhibition of NF-kappaB and induction of TRAIL receptors in bladder cancer cells.
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Initial experience of teaching robot-assisted radical prostatectomy to surgeons-in-training: can training be evaluated and standardized?
BJU Int.
PUBLISHED: 10-28-2009
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To measure the time and subjective quality of individual steps of robot-assisted radical prostatectomy (RARP), as RARP performed by trainees has recently become the most common technique of RP in the USA, and although outcomes from expert surgeons are reported, limited data are available to document training experiences.
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An updated critical analysis of the treatment strategy for newly diagnosed high-grade T1 (previously T1G3) bladder cancer.
Eur. Urol.
PUBLISHED: 06-26-2009
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High-grade T1 (formerly T1G3) bladder cancer (BCa) has a high propensity to recur and progress. As a result, decisions pertaining to its treatment are difficult. Treatment with bacillus Calmette-Guérin (BCG) risks progression and metastases but may preserve the bladder. Cystectomy may offer the best opportunity for cure but is associated with morbidity and a risk of mortality, and it may constitute potential overtreatment for many cases of T1G3 tumours. For purposes of this review, we continue to refer to high-grade T1 lesions as "T1G3."
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.