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Survival and Functional Stability in Chronic Kidney Disease Due to Surgical Removal of Nephrons: Importance of the New Baseline Glomerular Filtration Rate

Abstract Background

Chronic kidney disease (CKD) can be associated with a higher risk of progression to end-stage renal disease and mortality, but the etiology of nephron loss may modify this. Previous studies suggested that CKD primarily due to surgical removal of nephrons (CKD-S) may be more stable and associated with better survival than CKD due to medical causes (CKD-M).

Objective

We addressed limitations of our previous work with comprehensive control for confounding factors, differentiation of non–renal cancer-related mortality, and longer follow-up for more discriminatory assessment of the impact of CKD-S.

Design, setting, and participants

From 1999 to 2008, 4299 patients underwent surgery for renal cancer at a single institution. The median follow-up was 9.4 yr (7.3–11.0). The new baseline glomerular filtration rate (GFR) was defined as the highest GFR between the nadir and 42 d after surgery. Three cohorts were retrospectively evaluated: no CKD (new baseline GFR >60 ml/min/1.73 m2); CKD-S (new baseline GFR<60 but preoperative >60 ml/min/1.73 m2); and CKD-M/S (new baseline and preoperative GFR both <60 ml/min/1.73 m2). Cohort status was permanently set at 42 d after surgery.

Intervention

Renal surgery.

Outcome measurements and statistical analysis

Decline in renal function (50% reduction in GFR or dialysis), all-cause mortality, and non–renal cancer mortality were examined using a multivariable Cox proportional hazards model.

Results and limitations

CKD-M/S had a higher incidence of relevant comorbidities and the new baseline GFR was lower. On multivariable analysis (controlling for age, gender, race, diabetes, hypertension, and cardiac disease), CKD-M/S had higher rates of progressive decline in renal function, all-cause mortality, and non–renal cancer mortality when compared to CKD-S and no CKD (hazard ratio [HR] 1.69–2.33, allp < 0.05). All-cause mortality was modestly higher for CKD-S than for no CKD (HR 1.19,p = 0.030), but renal stability and non–renal cancer mortality were similar for these groups. New baseline GFR of <45 ml/min/1.73 m2significantly predicted adverse outcomes. The main limitation is the retrospective design.

Conclusions

CKD-S is more stable than CKD-M/S and has better survival, approximating that for no CKD. However, if the new baseline GFR is <45 ml/min/1.73 m2, the risks of functional decline and mortality increase. These findings may influence counseling for patients with localized renal cell carcinoma and higher oncologic potential when a normal contralateral kidney is present.

Patient summary

Survival is better for surgically induced chronic kidney disease (CKD) than for medically induced CKD, particularly if the postoperative glomerular filtration rate is ≥45 ml/min/1.73 m2. Patients with preexisting CKD are at risk of a significant decline in kidney function after surgery, and kidney-preserving treatment should be strongly considered in such cases.

Take Home Message

Chronic kidney disease primarily due to surgical removal of nephrons has better survival than chronic kidney disease due to medical causes, particularly if the postoperative glomerular filtration rate is ≥45 ml/min/1.73 m2.

Keywords: Chronic kidney disease, Renal function, Nephrectomy, Renal cell carcinoma, Overall survival.

Footnotes

a Division of Urology, Spectrum Health, Michigan State University, Grand Rapids, MI, USA

b Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA

c University of California San Diego, San Diego, CA, USA

d Department of Urology, Sun Yat-Sen University Cancer Center, Guangzhou, China

Corresponding author. Section of Urologic Oncology, Department of Urology, Glickman Urological and Kidney Institute, 9500 Euclid Avenue, Desk Q10-120, Cleveland Clinic, Cleveland, OH 44195, USA. Tel. +1 216 4445595; Fax: +1 216 6360770.

Article information

PII: S0302-2838(15)00402-9
DOI: 10.1016/j.eururo.2015.04.043
© 2015 European Association of Urology, Published by Elsevier B.V.

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Is Hypospadias Associated with Prenatal Exposure to Endocrine Disruptors? A French Collaborative Controlled Study of a Cohort of 300 Consecutive Children Without Genetic Defect

Abstract Background

Numerous studies have focused on the association between endocrine-disrupting chemicals (EDCs) and hypospadias. Phenotype variability, the absence of representative comparison groups and concomitant genetic testing prevent any definitive conclusions.

Objective

To identify the role of occupational and environmental exposures to EDCs in nongenetic isolated hypospadias.

Design, setting, and participants

A total of 408 consecutive children with isolated hypospadias and 302 normal boys were prospectively included (2009–2014) in a multi-institutional study in the south of France, the area of the country with the highest prevalence of hypospadias surgery.

Outcome measurements and statistical analysis

In patients withoutAR,SRD5A2, andMAMLD1mutations, parental occupational and professional exposures to EDCs were evaluated based on European questionnaire QLK4-1999-01422 and a validated job-exposure matrix for EDCs. Environmental exposure was estimated using the zip code, the type of surrounding hazards, and distance from these hazards. Multivariate analysis was performed.

Results

Fetal exposure to EDCs around the window of genital differentiation was more frequent in the case of hypospadias (40.00% vs 17.55%, odds ratio 3.13, 95% confidence interval 2.11–4.65). The substances were paints/solvents/adhesives (16.0%), detergents (11.0%), pesticides (9.0%), cosmetics (5.6%), and industrial chemicals (4.0%). Jobs with exposure were more frequent in mothers of hypospadiac boys (19.73% vs 10.26%,p = 0.0019), especially cleaners, hairdressers, beauticians, and laboratory workers. Paternal job exposure was more frequent in the cases of hypospadias (40.13% vs 27.48%,p = 0.02). Industrial areas, incinerators, and waste areas were more frequent within a 3-km radius for mothers of hypospadiac boys (13.29% vs. 6.64%,p < 0.00005). Association of occupational and environmental exposures increases this risk.

Conclusions

This multicenter prospective controlled study with a homogeneous cohort of hypospadiac boys without genetic defects strongly suggests that EDCs are a risk factor for hypospadias through occupational and environmental exposure during fetal life. The association of various types of exposures may increase this risk.

Patient summary

Our multi-institutional study showed that parental professional, occupational, and environmental exposures to chemical products increase the risk of hypospadias in children.

Take Home Message

This multicenter prospective controlled study of a cohort of hypospadiac boys without genetic defects shows that endocrine-disrupting chemicals are a risk factor for hypospadias through occupational, professional, and environmental exposure during fetal life. The association of various exposures increases this risk.

Keywords: Hypospadias, Disorder of sex determination, Environment, Endocrine-disrupting chemicals, Pesticides, Occupation, Birth defect.

Footnotes

a Service de Chirurgie et Urologie Pédiatrique, Hôpital Lapeyronie, CHU de Montpellier et Université Montpellier 1, Montpellier, France

b Service d’Hormonologie, Hôpital Lapeyronie, CHU de Montpellier et Université Montpellier 1, Montpellier, France

c Unité d’Endocrinologie et Gynécologie Pédiatriques, Service de Pédiatrie, Hôpital Arnaud de Villeneuve et Université Montpellier 1, CHU de Montpellier, Montpellier, France

d Institut Universitaire de Recherche Clinique, Laboratoire de Biostatistiques et d’Epidémiologie, Université Montpellier 1, Montpellier, France

e Service de Chirurgie et Urologie Pédiatrique, Hôpital la Timone, Marseille, France

f Unité d’Endocrinologie et Diabétologie Pédiatriques, Hôpital la Timone, Marseille, France

g Service de Chirurgie et Urologie Pédiatrique, Hôpital Nord, Marseille, France

h Service de Pédiatrie, Hôpital Lenval, CHU de Nice, France

i Service de Chirurgie et Urologie Pédiatrique, Hôpital Lenval, Nice, France

j Service de Chirurgie et Urologie Pédiatrique, Hôpital Saint-Joseph, Marseille, France

k Service de Chirurgie Pédiatrique, Hôpital Pellegrin Enfants, Bordeaux, France

Corresponding author: Service de Chirurgie et Urologie Pédiatrique, Hôpital Lapeyronie, 171 Avenue Giraud, Montpellier 34295, France. Tel. +33 4 67338784; fax: +33 4 67339512.

Article information

PII: S0302-2838(15)00409-1
DOI: 10.1016/j.eururo.2015.05.008
© 2015 European Association of Urology, Published by Elsevier B.V.

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Re: Craig Rogers, Ravi Barod, Scott Schwartz, Mani Menon. Endovascular Extraction of Caval Tumor Thrombus to Facilitate Minimally Invasive Cytoreductive Nephrectomy for Metastatic Kidney Cancer. Eur Urol. In press. http://dx.doi.org/10.1016/j.eururo...

Refers to article:

Endovascular Extraction of Caval Tumor Thrombus to Facilitate Minimally Invasive Cytoreductive Nephrectomy for Metastatic Kidney Cancer

Craig Rogers, Ravi Barod, Scott Schwartz and Mani Menon

Accepted 23 March 2015

Footnotes

a Department of Genitourinary Oncology, Moffitt Cancer Center, Tampa, FL, USA

b Department of Interventional Cardiology, Florida Hospital, Tampa, FL, USA

Corresponding author. Department of Genitourinary Oncology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612, USA. Tel. +1 813 7452484; Fax: +1 813 7458494.

Article information

PII: S0302-2838(15)00415-7
DOI: 10.1016/j.eururo.2015.05.013
© 2015 European Association of Urology, Published by Elsevier B.V.

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Long-term acetaminophen use during pregnancy may affect boys' fertility

MedicalNewsToday - Fri, 05/22/2015 - 03:00
Three daily acetaminophen pills for a week lowers testosterone levels in male fetuses, according to a new mouse study, but occasional pills during pregnancy do not cause harm.
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Improving What Matters

Refers to article:

Survivorship and Improving Quality of Life in Men with Prostate Cancer

Liam Bourke, Stephen A. Boorjian, Alberto Briganti, Laurence Klotz, Lorelei Mucci, Matthew J. Resnick, Derek J. Rosario, Ted A. Skolarus and David F. Penson

Accepted 16 April 2015

Footnotes

Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, MA, USA

Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, 75 Francis Street, ASB-I, L2, Boston MA 02115, USA. Tel. +1 617 732 7948; Fax: +1 617 975 0912.

Article information

PII: S0302-2838(15)00405-4
DOI: 10.1016/j.eururo.2015.05.004
© 2015 European Association of Urology, Published by Elsevier B.V.

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Duration of Androgen Deprivation Therapy Influences Outcomes for Patients Receiving Radiation Therapy Following Radical Prostatectomy

Abstract Background

Limited data exist to guide the use of androgen deprivation therapy (ADT) for men treated with radiation therapy (RT) after radical prostatectomy (RP). The optimal duration of ADT in this setting is unknown.

Objective

To determine if the duration of ADT influences clinical outcomes for men receiving post-RP RT.

Design, setting, and participants

A total of 680 men who received adjuvant radiation therapy (n = 105) or salvage radiation therapy (n = 575) between 1986 and 2010 at a single tertiary care institution were reviewed retrospectively. Median follow-up post-RT was 57.8 mo.

Intervention

RT was delivered using three-dimensional conformal or intensity-modulated RT in 1.8-Gy fractions. For patients treated with ADT, >80% were treated with a gonadotropin-releasing hormone agonist with or without a nonsteroidal antiandrogen.

Outcome measurements and statistical analysis

Biochemical failure (BF), distant metastasis (DM), prostate cancer–specific mortality (PCSM), and overall mortality were assessed using Kaplan-Meier analysis and propensity score analysis.

Results and limitations

Overall, 144 patients (21%) received ADT with post-RP RT, most of whom had high-risk disease features such as Gleason score 8–10, seminal vesicle invasion, or pre-RT prostate-specific antigen >1 ng/ml. Median ADT duration was 12 mo (interquartile range: 6.0–23.7). Patients who received <12 mo of ADT had an association with increased BF (hazard ratio [HR]: 2.27;p = 0.003) and DM (HR: 2.48;p = 0.03) compared with patients receiving ≥12 mo of ADT. The 5-yr rates of DM were 6.0% and 23% for ≥12 and <12 mo of ADT, respectively. On propensity score analysis controlling for pretreatment and treatment-related factors, each month of ADT was associated with a decreased risk for BF (HR: 0.95;p = 0.0004), DM (HR: 0.88;p = 0.0004), and PCSM (HR: 0.90;p = 0.037). These findings are limited by the retrospective nature of our analysis.

Conclusions

For men with high-risk disease features receiving ADT with post-RP RT, the duration of ADT is associated with clinical outcomes. Our findings suggest that for these men an extended course of ADT ≥12 mo may be preferable. Validation of our findings is needed.

Patient summary

We evaluated outcomes for men with high-risk disease features treated with androgen deprivation therapy (ADT) and radiotherapy after radical prostatectomy. Longer durations of ADT resulted in improved patient outcomes.

Take Home Message

We evaluated outcomes for men treated with the combination therapy of androgen deprivation therapy (ADT) and radiation therapy following radical prostatectomy. We concluded that the best outcomes were observed in men treated with longer durations of ADT.

Keywords: Prostate cancer, Androgen deprivation therapy, Postprostatectomy radiotherapy.

Footnotes

a Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, MI, USA

b Department of Radiation Oncology, Cedars-Sinai, Los Angeles, CA, USA

c Department of Urology, University of Michigan Medical Center, Ann Arbor, MI, USA

Corresponding author. Department of Radiation Oncology, University of Michigan Medical Center, 1500 E. Medical Center Drive, Ann Arbor, MI 48109, USA. Tel. +1 734 936 4302.

Article information

PII: S0302-2838(15)00410-8
DOI: 10.1016/j.eururo.2015.05.009
© 2015 European Association of Urology, Published by Elsevier B.V.

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Reply to Pranav Sharma, Asad Sawar and Philippe Spiess’ Letter to the Editor re: Re: Craig Rogers, Ravi Barod, Scott Schwartz, Mani Menon. Endovascular Extraction of Caval Tumor Thrombus to Facilitate Minimally Invasive Cytoreductive Nephrectomy for...

Refers to article:

Endovascular Extraction of Caval Tumor Thrombus to Facilitate Minimally Invasive Cytoreductive Nephrectomy for Metastatic Kidney Cancer

Craig Rogers, Ravi Barod, Scott Schwartz and Mani Menon

Accepted 23 March 2015

Footnotes

Vattikuti Urology Institute, Henry Ford Hospital, Detroit, MI, USA

Corresponding author. Vattikuti Urology Institute, Henry Ford Hospital, 2799 West Grand Blvd., Detroit, MI 48202-2689, USA.

Article information

PII: S0302-2838(15)00416-9
DOI: 10.1016/j.eururo.2015.05.014
© 2015 Published by Elsevier B.V.

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Renal Tumor Biopsy: More Dogma Belied

Refers to article:

Renal Tumor Biopsy for Small Renal Masses: A Single-center 13-year Experience

Patrick O. Richard, Michael A.S. Jewett, Jaimin R. Bhatt, John R. Kachura, Andrew J. Evans, Alexandre R. Zlotta, Thomas Hermanns, Tristan Juvet and Antonio Finelli

Accepted 1 April 2015

Footnotes

a Department of Urology, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, Italy

b Division of Experimental Oncology, URI, Urological Research Institute, Renal Cancer Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy

c Division of Urology, Department of Translational Medicine, University of Eastern Piedmont, Maggiore della Carità Hospital, Novara, Italy

Corresponding author. Department of Urology, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, via Olgettina 60, 20132, Milan, Italy.

Article information

PII: S0302-2838(15)00408-X
DOI: 10.1016/j.eururo.2015.05.007
© 2015 European Association of Urology, Published by Elsevier B.V.

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Management of Small Renal Mass: An Opportunity to Address a Growing Problem in Early Stage Kidney Cancer

Refers to article:

Five-year Analysis of a Multi-institutional Prospective Clinical Trial of Delayed Intervention and Surveillance for Small Renal Masses: The DISSRM Registry

Phillip M. Pierorazio, Michael H. Johnson, Mark W. Ball, Michael A. Gorin, Bruce J. Trock, Peter Chang, Andrew A. Wagner, James M. McKiernan and Mohamad E. Allaf

Accepted 2 February 2015

Footnotes

Division of Urology, Departments of Surgery and Surgical Oncology, Princess Margaret Cancer Centre, University Health Network and the University of Toronto, Toronto, Ontario, Canada

Corresponding author. Division of Urology, University of Toronto, 610 University Avenue, 3-130, Toronto, Ontario M5G 2C4, Canada. Tel. +1 416 946 2909; Fax: +1 416 598 9997.

Article information

PII: S0302-2838(15)00413-3
DOI: 10.1016/j.eururo.2015.05.011
© 2015 Published by Elsevier B.V.

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Study: Using isosmolar contrast agent during angioplasty reduces risk of renal and cardiac events

MedicalNewsToday - Thu, 05/21/2015 - 09:00
Significantly fewer renal and cardiac events are associated with angioplasty procedures using isosmolar contrast medium (IOCM) agent Visipaque™ (iodixanol) than those using low-osmolar...
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Kidney failure impacts survival of sepsis patients

MedicalNewsToday - Thu, 05/21/2015 - 06:00
Researchers at Duke Medicine have determined that kidney function plays a critical role in the fate of patients being treated for sepsis, a potentially life-threatening complication of an infection.
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PRPS2 expression correlates with Sertoli cell-only syndrome and inhibits the apoptosis of TM4 Sertoli cells

Sertoli cell-only syndrome (SCOS) is one of reasons for male infertility, however, its pathogenesis remains unclear. PRPS2 (phosphoribosylpyrophosphate synthetases 2), a subset of PRS (phosphoribosylpyrophosphate synthetases), is reported to be a potential protein associated with SCOS. In this study, we aim to further investigate the correlation between PRPS2 and SCOS, and evaluate the effect of PRPS2 expression on the apoptosis of TM4 Sertoli cells.
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Microsurgical Spermatic Cord Denervation as a Treatment for Chronic Scrotal Content Pain: A Multicenter Open Label Trial

To prospectively evaluate the results of microsurgical spermatic cord denervation in a series of patients with chronic scrotal content pain in a multicenter study, including one center in Germany and three centers in Chile.
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Activation of P2Y receptors facilitates non-neuronal ATP and acetylcholine release from urothelium with the of men with bladder outlet obstruction

Deregulation of purinergic bladder signaling may contribute to persistent detrusor overactivity in patients with bladder outlet obstruction. Activation of UDP-sensitive P2Y6 receptors increases the voiding frequency in rats indirectly by releasing ATP from the urothelium, but this mechanism was never tested in the human bladder.
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Pathologic Lymph Node–positive Prostate Cancer: Some Answers … with Many More Questions

Refers to article:

Patterns of Clinical Recurrence of Node-positive Prostate Cancer and Impact on Long-term Survival

Alessandro Nini, Giorgio Gandaglia, Nicola Fossati, Nazareno Suardi, Vito Cucchiara, Paolo Dell’Oglio, Walter Cazzaniga, Stefano Luzzago, Francesco Montorsi and Alberto Briganti

Accepted 22 April 2015

Footnotes

Brady Urological Institute, Johns Hopkins University, Baltimore, MD, USA

Corresponding author. Brady Urological Institute, Johns Hopkins University, 600 N Wolfe Street, Marburg 146, Baltimore, MD 21231, USA. Tel. +1 410 5022733; Fax: +1 410 9550833.

Article information

PII: S0302-2838(15)00403-0
DOI: 10.1016/j.eururo.2015.05.002
© 2015 European Association of Urology, Published by Elsevier B.V.

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Treatment of the Primary Tumor in Metastatic Prostate Cancer: Current Concepts and Future Perspectives

Abstract Context

Multimodal treatment for men with locally advanced prostate cancer (PCa) using neoadjuvant/adjuvant systemic therapy, surgery, and radiation therapy is being increasingly explored. There is also interest in the oncologic benefit of treating the primary tumor in the setting of metastatic PCa (mPCa).

Objective

To perform a review of the literature regarding the treatment of the primary tumor in the setting of mPCa.

Evidence acquisition

Medline, PubMed, and Scopus electronic databases were queried for English language articles from January 1990 to September 2014. Prospective and retrospective studies were included.

Evidence synthesis

There is no published randomized controlled trial (RCT) comparing local therapy and systemic therapy to systemic therapy alone in the treatment of mPCa. Prospective studies of men with locally advanced PCa and retrospective studies of occult node-positive PCa have consistently shown the addition of local therapy to a multimodal treatment regimen improves outcomes. Molecular and genomic evidence further suggests the primary tumor may have an active role in mPCa.

Conclusions

Treatment of the primary tumor in mPCa is being increasingly explored. While preclinical, translational, and retrospective evidence supports local therapy in advanced disease, further prospective studies are under way to evaluate this multimodal approach and identify the patients most likely to benefit from the inclusion of local therapy in the setting of metastatic disease.

Patient summary

In this review we explored preclinical and clinical evidence for treatment of the primary tumor in metastatic prostate cancer (mPCa). We found evidence to support clinical trials investigating mPCa therapy that includes local treatment of the primary tumor. Currently, treating the primary tumor in mPCa is controversial and lacks high-level evidence sufficient for routine recommendation.

Take Home Message

Emerging preclinical and translational evidence, as well as an established body of retrospective clinical evidence, provides an impetus for clinical trials investigating local treatment of the primary tumor as part of a multimodal approach to the treatment of metastatic prostate cancer.

Keywords: Prostatic neoplasms, Neoplasm metastasis, Prostatectomy, Chemotherapy, Survival.

Footnotes

a Department of Urology, The George Washington University, Washington, DC, USA

b Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

c Departments of Urology and Epidemiology and Biostatistics, University of California, San Francisco, CA, USA

d The Vancouver Prostate Centre, University of British Columbia, Vancouver, BC, Canada

e Martini-Clinic Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany

f Division of Oncology, IRCCS Ospedale San Raffaele, Milan, Italy

g Department of Surgery, Oncology, and Gastroenterology–Urology Clinic, University of Padua, Italy

h Division of Urologic Oncology, Fox Chase Cancer Center-Temple University Health System, Philadelphia, PA, USA

i Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

j Surgical Intervention Trials Unit, Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK

Corresponding author. Department of Urology, The University of Texas MD Anderson Cancer Center, Unit 1373, 1515 Holcombe Blvd, Houston, TX 77030, USA. Tel. +1 713 7923250; Fax: +1 713 7944824.

Article information

PII: S0302-2838(15)00378-4
DOI: 10.1016/j.eururo.2015.04.036
© 2015 Published by Elsevier B.V.

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European consensus group calls for standards to move renal denervation field forward

MedicalNewsToday - Wed, 05/20/2015 - 05:00
Experts participating in a European Clinical Consensus Conference (CCC) have concluded that research into the use of renal denervation for high blood pressure in patients unable to control the...
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Repeat excision and primary anastomotic urethroplasty for salvage of recurrent bulbar urethral stricture

We compared the results of initial excision and primary anastomosis (EPA) urethroplasty to EPA outcomes from other challenging re-operative clinical settings (secondary [prior urethroplasty of any technique other than EPA] and repeat [prior EPA] cases).
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Natural History of Pathologically Benign Multi-parametric MRI Cancer Suspicious Regions Following MRI-Ultrasound Fusion-targeted Biopsy

The objective of this study is to determine the natural history of pathologically benign multi-parametric MRI (mpMRI) cancer suspicious regions (CSR) following targeted biopsy.
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Redefining the Autonomic Nerve Distribution of the Urinary Bladder Using Three-Dimensional Image Reconstruction

To create a three-dimensional (3D) reconstruction of the autonomic nervous tissue innervating the urinary bladder using male and female cadaver histopathology.
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