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When is a Negative Prostate Biopsy Really Negative? Repeat Biopsies in Detection and Active Surveillance

Repeat biopsies are commonly performed in the diagnostic setting and increasingly for men on active surveillance. A prior study using SEER (Surveillance, Epidemiology, and End Results)-Medicare data reported that 11.8% of men with a negative prostate biopsy underwent repeat biopsy within 1 year and 38% did so within 5 years.1 A major problem is the significant sampling error with the traditional random systematic biopsy and the resulting lack of confidence that a negative biopsy is really negative.
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The Current Status of Clinical Drug Trials in Pediatric Urology

The development of a compound to a specific therapy is a long process, often taking years and in some cases even decades. This process, although time consuming and costly, is necessary for safety and efficacy reasons. For children these concerns may become magnified due to the shifting and evolving physiology that fragment pediatric subjects into as many as 5 different test groups, ie premature babies, infants, young children, peripubertal adolescents and postpubertal adolescents who are not yet legally adults.
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Adenocarcinoma in Continent Anal Urinary Diversion: Is a Sigma-Rectum Pouch a Surgical Option after Failed Ureterosigmoidostomy?

Urology (Gold Journal) In Press - Wed, 01/18/2017 - 00:00
To report our experience of radical resection of secondary cancers after ureterosigmoidostomy. Ureterosigmoidostomy was the most common continent urinary diversion before the era of continent cutaneous diversion and neobladders, specifically in children. When performed for bladder exstrophy, patients have been living with this kind of diversion for quite a long time. As a result urologists are now confronted with patients presenting with an adenocarcinoma in their ureterosigmoidostomy. In most cases reported in the literature, an ileal conduit was used for urinary conversion.
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Re: Detection of Micrometastases by Flow Cytometry in Sentinel Lymph Nodes from Patients with Renal Tumours

Footnotes

Department of Urology, Division of Surgical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands

Corresponding author. Department of Urology, Division of Surgical Oncology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066CX Amsterdam, The Netherlands.

Article information

PII: S0302-2838(17)30009-X
DOI: 10.1016/j.eururo.2017.01.002
© 2017 European Association of Urology, Published by Elsevier B.V.

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Reply to Christian Daniel Fankhauser, Lorelei A. Mucci, and Travis A. Gerke's Letter to the Editor re: Won Sik Ham, Heather J. Chalfin, Zhaoyong Feng, et al. New Prostate Cancer Grading System Predicts Long-term Survival Following Surgery for Gleason...

Refers to article:

Re: Won Sik Ham, Heather J. Chalfin, Zhaoyong Feng, et al. New Prostate Cancer Grading System Predicts Long-term Survival Following Surgery for Gleason Score 8–10 Prostate Cancer. Eur Urol. In press. http://dx.doi.org/10.1016/j.eururo.2016.11.006

Christian Daniel Fankhauser, Lorelei A. Mucci and Travis A. Gerke

Accepted 6 January 2017

Refers to article:

New Prostate Cancer Grading System Predicts Long-term Survival Following Surgery for Gleason Score 8–10 Prostate Cancer

Won Sik Ham, Heather J. Chalfin, Zhaoyong Feng, Bruce J. Trock, Jonathan I. Epstein, Carling Cheung, Elizabeth Humphreys, Alan W. Partin and Misop Han

Accepted 4 November 2016

Footnotes

a Department of Urology, James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, MD, USA

b Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA

Corresponding author. Department of Urology, James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, MD, USA.

Article information

PII: S0302-2838(17)30011-8
DOI: 10.1016/j.eururo.2017.01.004
© 2017 European Association of Urology, Published by Elsevier B.V.

Categories: Urology News Feeds

Re: Won Sik Ham, Heather J. Chalfin, Zhaoyong Feng, et al. New Prostate Cancer Grading System Predicts Long-term Survival Following Surgery for Gleason Score 8–10 Prostate Cancer. Eur Urol. In press. http://dx.doi.org/10.1016/j.eururo.2016.11.006

Refers to article:

New Prostate Cancer Grading System Predicts Long-term Survival Following Surgery for Gleason Score 8–10 Prostate Cancer

Won Sik Ham, Heather J. Chalfin, Zhaoyong Feng, Bruce J. Trock, Jonathan I. Epstein, Carling Cheung, Elizabeth Humphreys, Alan W. Partin and Misop Han

Accepted 4 November 2016

Footnotes

a Department of Urology, University Hospital Zurich, University of Zurich, Zurich, Switzerland

b Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA

c Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, USA

Corresponding author. Moffitt Cancer Center, Cancer Epidemiology, 12902 Magnolia Drive, MRC-CANCONT, Tampa, FL 33612, USA. Tel. +1 813 745 6448; Fax: +1 813 745 6525.

Article information

PII: S0302-2838(17)30032-5
DOI: 10.1016/j.eururo.2017.01.016
© 2017 European Association of Urology, Published by Elsevier B.V.

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A Functional Genetic Screen Identifies the Phosphoinositide 3-kinase Pathway as a Determinant of Resistance to Fibroblast Growth Factor Receptor Inhibitors in FGFR Mutant Urothelial Cell Carcinoma

Abstract

Activating mutations and translocations of the FGFR3 gene are commonly seen in urothelial cell carcinoma (UCC) of the bladder and urinary tract. Several fibroblast growth factor receptor (FGFR) inhibitors are currently in clinical development and response rates appear promising for advanced UCC. A common problem with targeted therapeutics is intrinsic or acquired resistance of the cancer cells. To find potential drug targets that can act synergistically with FGFR inhibition, we performed a synthetic lethality screen for the FGFR inhibitor AZD4547 using a short hairpin RNA library targeting the human kinome in the UCC cell line RT112 (FGFR3-TACC3 translocation). We identified multiple members of the phosphoinositide 3-kinase (PI3K) pathway and found that inhibition of PIK3CA acts synergistically with FGFR inhibitors. The PI3K inhibitor BKM120 acted synergistically with inhibition of FGFR in multiple UCC and lung cancer cell lines having FGFR mutations. Consistently, we observed an elevated PI3K-protein kinase B pathway activity resulting from epidermal growth factor receptor or Erb-B2 receptor tyrosine kinase 3 reactivation caused by FGFR inhibition as the underlying molecular mechanism of the synergy. Our data show that feedback pathways activated by FGFR inhibition converge on the PI3K pathway. These findings provide a strong rationale to test FGFR inhibitors in combination with PI3K inhibitors in cancers harboring genetic activation of FGFR genes.

Take Home Message

Fibroblast growth factor receptor (FGFR) inhibitors are tested in bladder cancer patients. A genetic screen identified the phosphoinositide 3-kinase pathway to determine drug resistance. Combined treatment with FGFR and phosphoinositide 3-kinase inhibitors may improve response rates in patients with cancers harboring activating FGFR mutations

Keywords: FGFR, Bladder cancer, PI3K, Synergy.

Footnotes

a Division of Molecular Carcinogenesis, Cancer Genomics Netherlands, The Netherlands Cancer Institute, Amsterdam, The Netherlands

b Mouse Clinic Intervention Unit, The Netherlands Cancer Institute, Amsterdam, The Netherlands

c Division of Medical Oncology, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands

Corresponding authors. Department of Medical Oncology, Division of Molecular Carcinogenesis, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. Tel. +31 20 512 6245; Fax: +31 20 512 2572 (M.S. van der Heijden); Department of Medical Oncology, Division of Molecular Carcinogenesis, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. Tel. +31 20 512 1952 (R. Bernards).

These authors contributed equally.

Article information

PII: S0302-2838(17)30037-4
DOI: 10.1016/j.eururo.2017.01.021
© 2017 European Association of Urology, Published by Elsevier B.V.

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Re: James J. Hsieh, David Chen, Patricia I. Wang, et al. Genomic Biomarkers of a Randomized Trial Comparing First-line Everolimus and Sunitinib in Patients with Metastatic Renal Cell Carcinoma. Eur Urol. In press. http://dx.doi.org/10.1016/j.eururo...

Refers to article:

Genomic Biomarkers of a Randomized Trial Comparing First-line Everolimus and Sunitinib in Patients with Metastatic Renal Cell Carcinoma

James J. Hsieh, David Chen, Patricia I. Wang, Mahtab Marker, Almedina Redzematovic, Ying-Bei Chen, S. Duygu Selcuklu, Nils Weinhold, Nancy Bouvier, Kety H. Huberman, Umesh Bhanot, Michael S. Chevinsky, Parul Patel, Patrizia Pinciroli, Helen H. Won, Daoqi You, Agnes Viale, William Lee, A. Ari Hakimi, Michael F. Berger, Nicholas D. Socci, Emily H. Cheng, Jennifer Knox, Martin H. Voss, Maurizio Voi and Robert J. Motzer

Accepted 5 October 2016

Footnotes

a Department of Urology, Xiangya Hospital, Central South University, Changsha, P.R. China

b Department of Urology, Diakonie Klinikum Stuttgart, Stuttgart, Germany

Corresponding author. Department of Urology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, P.R. China. Tel. +86 13517319380.

Article information

PII: S0302-2838(17)30019-2
DOI: 10.1016/j.eururo.2017.01.012
© 2017 European Association of Urology, Published by Elsevier B.V.

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Re: Amar U. Kishan, Talha Shaikh, Pin-Chieh Wang, et al. Clinical Outcomes for Patients with Gleason Score 9–10 Prostate Adenocarcinoma Treated With Radiotherapy or Radical Prostatectomy: A Multi-institutional Comparative Analysis. Eur Urol 2016. In...

Refers to article:

Clinical Outcomes for Patients with Gleason Score 9–10 Prostate Adenocarcinoma Treated With Radiotherapy or Radical Prostatectomy: A Multi-institutional Comparative Analysis

Amar U. Kishan, Talha Shaikh, Pin-Chieh Wang, Robert E. Reiter, Jonathan Said, Govind Raghavan, Nicholas G. Nickols, William J. Aronson, Ahmad Sadeghi, Mitchell Kamrava, David Jeffrey Demanes, Michael L. Steinberg, Eric M. Horwitz, Patrick A. Kupelian and Christopher R. King

Accepted 30 June 2016

Footnotes

a Laboratory of Molecular Endocrinology, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium

b Department of Urology, University Hospitals Leuven, Leuven, Belgium

c Department of Urology, Mayo Clinic, Rochester, MN, USA

Corresponding author. Department of Urology, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium. Tel. +32 16 346930; Fax: +32 16 330735.

Article information

PII: S0302-2838(17)30034-9
DOI: 10.1016/j.eururo.2017.01.018
© 2017 European Association of Urology, Published by Elsevier B.V.

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The Circle Nephrostomy Tube: an Attractive Nephrostomy Drainage System Following Complex Percutaneous Nephrolithotomy

Urology (Gold Journal) In Press - Tue, 01/17/2017 - 00:00
To describe our experience with the circle NT (Cook® Medical), a drainage system uniquely designed for use after multiple access PNL.
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Reply

Urology (Gold Journal) In Press - Tue, 01/17/2017 - 00:00
The immunomodulatory effect of blood transfusion (BT) has recently garnered significant attention in regard to oncological and perioperative outcomes for bladder cancer patients. Our results were unique in failing to show BT as a significant, prognosticator of worse recurrence, cancer, and overall survival.
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Editorial Comment

Urology (Gold Journal) In Press - Tue, 01/17/2017 - 00:00
The impact of perioperative blood transfusion (BT) and specifically intraoperative BT on survival outcomes in radical cystectomy (RC) patients has been established in retrospective series.1,2 Whether several theories have been proposed to explain this association, one of the most intriguing is represented by the direct immunosuppressive effect exerted by BT. Specifically, it has been postulated that BT might modulate the immune system due to the presentation of large amounts of antigen.3 Therefore, it is certainly of interest to evaluate if leukocyte-depleted BT impact on survival outcomes in RC patients.
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Comprehensive Profiling of the Androgen Receptor in Liquid Biopsies from Castration-resistant Prostate Cancer Reveals Novel Intra-AR Structural Variation and Splice Variant Expression Patterns

Abstract Background

Expression of the androgen receptor splice variant 7 (AR-V7) is associated with poor response to second-line endocrine therapy in castration-resistant prostate cancer (CRPC). However, a large fraction of nonresponding patients are AR-V7–negative.

Objective

To investigate if a comprehensive liquid biopsy–based AR profile may improve patient stratification in the context of second-line endocrine therapy.

Design, setting, and participants

Peripheral blood was collected from patients with CRPC (n = 30) before initiation of a new line of systemic therapy. We performed profiling of circulating tumour DNA via low-pass whole-genome sequencing and targeted sequencing of the entire AR gene, including introns. Targeted RNA sequencing was performed on enriched circulating tumour cell fractions to assess the expression levels of seven AR splice variants (ARVs).

Outcome measurements and statistical analysis

Somatic AR variations, including copy-number alterations, structural variations, and point mutations, were combined with ARV expression patterns and correlated to clinicopathologic parameters.

Results and limitations

Collectively, any AR perturbation, including ARV, was detected in 25/30 patients. Surprisingly, intra-AR structural variation was present in 15/30 patients, of whom 14 expressed ARVs. The majority of ARV-positive patients expressed multiple ARVs, with AR-V3 the most abundantly expressed. The presence of any ARV was associated with progression-free survival after second-line endocrine treatment (hazard ratio 4.53, 95% confidence interval 1.424–14.41; p = 0.0105). Six out of 17 poor responders were AR-V7–negative, but four carried other AR perturbations.

Conclusions

Comprehensive AR profiling, which is feasible using liquid biopsies, is necessary to increase our understanding of the mechanisms underpinning resistance to endocrine treatment.

Patient summary

Alterations in the androgen receptor are associated with endocrine treatment outcomes. This study demonstrates that it is possible to identify different types of alterations via simple blood draws. Follow-up studies are needed to determine the effect of such alterations on hormonal therapy.

Take Home Message

Structural variation is prevalent in the androgen receptor (AR), suggesting a connection to the expression of splice variants. Comprehensive AR profiling, which is possible to perform on liquid biopsies, is necessary to reveal the complexity of the AR signalling processes underpinning resistance to endocrine treatment.

Keywords: Castration-resistant prostate cancer, AR splice variants, AR-V7, Circulating tumour DNA, Structural variation, Endocrine treatment, Androgen receptor.

Footnotes

a Centre for Oncological Research, University of Antwerp, Antwerp, Belgium

b Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

c Department of Medical Epidemiology and Biostatistics, Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden

d Department of Pathology, GZA Hospitals Sint-Augustinus, Antwerp, Belgium

e Department of Oncology, GZA Hospitals Sint-Augustinus, Antwerp, Belgium

f Multiplicom N.V., Niel, Belgium

Corresponding author. Department of Medical Epidemiology and Biostatistics, Science for Life Laboratory, Karolinska Institutet, Stockholm SE-171 77, Sweden. Tel. +46 76 0509767.

1 These authors jointly supervised this work.

Article information

PII: S0302-2838(17)30018-0
DOI: 10.1016/j.eururo.2017.01.011
© 2017 European Association of Urology, Published by Elsevier B.V.

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Re: Pascal Rischmann, Albert Gelet, Benjamin Riche, et al. Focal High Intensity Focused Ultrasound of Unilateral Localized Prostate Cancer: A Prospective Multicentric Hemiablation Study of 111 Patients. Eur Urol. In press. http://dx.doi.org/10.1016/j...

Refers to article:

Focal High Intensity Focused Ultrasound of Unilateral Localized Prostate Cancer: A Prospective Multicentric Hemiablation Study of 111 Patients

Pascal Rischmann, Albert Gelet, Benjamin Riche, Arnauld Villers, Gilles Pasticier, Pierre Bondil, Jean-Luc Jung, Hubert Bugel, Jacques Petit, Harry Toledano, Stéphane Mallick, Olivier Rouvière, Muriel Rabilloud, Hélène Tonoli-Catez and Sebastien Crouzet

Accepted 25 September 2016

February 2017 (Vol. 71, Issue 2, pages 267 - 273)

Footnotes

a Department of Radiation Oncology, Geneva University Hospital, Geneva, Switzerland

b Department of Radiation Oncology, Centre Georges Francois Leclerc, 1, Dijon, France

c Department of Radiation Oncology, Centre Hospitalier Lyon Sud, Lyon, France

Corresponding author. Department of Radiation Oncology, Geneva University Hospital, CH-1211 Geneva 14, Switzerland. Tel. +41 22 3727090; Fax: +41 22 3727117.

Article information

PII: S0302-2838(17)30016-7
DOI: 10.1016/j.eururo.2017.01.009
© 2017 European Association of Urology, Published by Elsevier B.V.

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Re: Long-term Results of Active Surveillance in the Göteborg Randomized, Population-based Prostate Cancer Screening Trial

Footnotes

Department of Urology, University of Patras, Patras, Greece

Corresponding author. Department of Urology, University of Patras, Patras 26504, Greece.

Article information

PII: S0302-2838(17)30014-3
DOI: 10.1016/j.eururo.2017.01.007
© 2017 European Association of Urology, Published by Elsevier B.V.

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Atrial fibrillation more prevalent in dialysis patients than expected

MedicalNewsToday - Mon, 01/16/2017 - 08:00
Atrial fibrillation, which is the most common cardiac arrhythmia, is an important risk factor for strokes.
Categories: Urology News Feeds

Pelvic Hardware Eroding into the Bladder: A Rare Case Presentation of Gross Hematuria, Bladder Pain, and Refractory LUTS

Urology (Gold Journal) In Press - Mon, 01/16/2017 - 00:00
We present a 60 year-old male who presented with gross hematuria, refractory lower urinary tract symptoms, and increasing bladder pain for 3 months. The patient had a prior history of a motorcycle accident and pelvic fracture requiring an extensive pelvic open reduction and internal fixation. During evaluation, the patient was found to have an orthopedic screw from his hardware eroding through the left lateral wall of his bladder and irritating his trigone. The patient underwent pelvic exploration with open cystotomy and hardware removal with the orthopedic service.
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Tipless Nitinol Stone Baskets: Comparison of Penetration Force, Radial Dilation Force, Opening Dynamics, and Deflection

Urology (Gold Journal) In Press - Mon, 01/16/2017 - 00:00
To evaluate 5 commercially available tipless nitinol baskets (2.2F) in 4performance factors: penetration force, radial dilation force, opening dynamics and deflection limitation.
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Use of a Novel Flexible Mini-Nephroscope in Minimally-Invasive Percutaneous Nephrolithotomy

Urology (Gold Journal) In Press - Mon, 01/16/2017 - 00:00
To assess the feasibility and safety of a novel flexible mini-nephroscope in minimally-invasive PCNL. Presumably, limiting the size and number of tracts during percutaneous-nephrolithotomy(PCNL) has the potential of decreasing the morbidity of the procedure. We present our experience with, this new technique.
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Assessing Cancer Progression and Stable Disease after Neoadjuvant Chemotherapy for Organ-Confined Muscle-Invasive Bladder Cancer

Urology (Gold Journal) In Press - Mon, 01/16/2017 - 00:00
To propose and validate a new approach to stratify clinically staged organ-confined muscle-invasive bladder cancer patients (cT2N0M0) that are pathologic non-responders to neoadjuvant chemotherapy (NAC) to better characterize NAC non-response.
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