Renal & Urology News May 2013 Issue by Haymarket Media

MAY 2013

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VOL UME 11, IS SUE NUMBER 5

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www.renalandurologynews.com

PCa Focal Therapy Moves Forward IMAGE COURTESY OF DAVID Y. T. CHEN, MD, FACS, FOX CHASE CANCER CENTER

Researchers report early but promising results for MRI-guided laser ablation and other approaches

MRI CAN PINPOINT a prostate tumor for targeted treatment.

BY JODY A. CHARNOW MILAN—Laser ablation, cryotherapy, and hemiablative brachytherapy are among the novel approaches that show promise for the focal treatment of localized prostate cancer (PCa), according to studies presented at the 28th annual congress of the European Association of Urology. Most of these treatments are performed under magnetic resonance imaging (MRI) guidance. Uri Lindner, MD, and collaborators at the University Health Network in Toronto reported on the first comprehensive safety study and initial biological response to MRI-guided and controlled laser focal ablation in men with localized PCa. The phase

Possible CIN Predictor Identified Pre-Transplant BY JILL STEIN the American College of Cardiology Cancers Might SAN FRANCISCO—The ratio of annual meeting. contrast volume to estimated glo“Our results suggest that contrast Be Overlooked merular filtration rate (CVeGFRr) can volume:eGFR ratio might be applied reliably predict the development of contrast-induced nephropathy (CIN) after a percutaneous coronary intervention (PCI), according to data from an observational study reported at

CME FEATURE

prospectively to calculate the maximum amount of contrast to give without increasing the risk of CIN after PCI,” said Venkate Dyanesh Vidi, MD, continued on page 12

Earn 1 CME credit in this issue

Medical and Surgical Management of Bladder Outlet Obstruction PAGE 37

BY ROSEMARY FREI, MSc LAKE LOUISE, Alberta—Many cancers found after kidney transplantation might have been present prior to surgery and possibly could have been detected during the pre-transplant workup, according to results from a new study. In a group of 3,524 kidney transplant recipients in Quebec, 36 neoplasias were detected within a year of surgery. Of these, 16 (44%) may have been present before transplantation and could have been detected during the routine pre-transplant workup. Another 12 (34%) were post-transplant lymphoproliferative disease caused by immunosuppression. The remaining eight (22%) may have been present before transplantation but would not have been detected because they were in areas that are not routinely covered by pre-transplant screening, for instance ear-nose and throat cancers. “The problem is that transplant can-

1 study included 38 men with low-tointermediate risk localized tumors. All patients underwent the procedure on an outpatient basis. Under MRI guidance, surgeons placed laser fibers within the prostate near the tumor via the perineum. The median follow-up was 538 days. No intra-procedure complications occurred. Of 34 patients who had post-procedure biopsy, 16 (47%) had negative fi ndings, and nine (26%) had a negative biopsy in the ablated quadrant of the prostate, but had cancer detected in the contralateral lobe. Of 10 patients with Gleason 3+4 disease, eight had negative findings. The average baseline PSA level was 5.6 ng/mL; continued on page 12

IN THIS ISSUE 11

Pregnancy outcomes worsen as CKD progresses

Large visceral fat area may benefit RCC patients

Emergency department stone visit rates on the rise

Intradialytic high-protein meals may be beneficial

Robotic-assisted RP suitable for large prostates

Long-term follow up required for small RCC tumors

Hypertension rates vary among Asian-Americans

Intradialytic parenteral supplementation PAGE 16

continued on page 13

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6 Renal & Urology News

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From the Editor Editorial Advisory Board

Hemoglobin Levels Fall, Transfusions On the Rise

wo studies presented at the recent National Kidney Foundation (NKF) 2013 Spring Clinical Meetings provide more evidence of a trend toward decreasing use of erythropoiesis-stimulating agents (ESAs) and decreasing hemoglobin levels following the introduction in January 2011 of the Medicare prospective payment system (“bundling”) for dialysis-related care and changes in ESA drug labeling that occurred in June 2011 (see article on page 18). Both studies also identified a trend toward higher blood transfusion rates, and the authors of one study cited data from the U.S. Renal Data System showing that the proportion of dialysis patients with a transfusion increased from 2.4% in September 2010 to 3.0% in September 2011, a 24% increase. Although the reasons for this increase require further study, the authors noted in a poster presentation that, because transfusions are excluded from bundling, there is a potential for increased use of transfusions to supplement ESA use. At this point, it is likely unclear how much this affects or will affect the federal government’s cost of dialysis-patient care, but it would not surprise me if the Centers for Medicare and Medicaid Services are monitoring the trend closely. Also at the NKF conference, physician thought-leaders took part in debates on various controversial clinical topics. We invited the same doctors to summarize their views for Renal & Urology News in video podcasts that we packaged as two Point-Counterpoint debates, which you can find at www.renalandurologynews.com. One debate centers on anticoagulant use for atrial fibrillation in chronic kidney disease/ end-stage renal disease and the other addresses population-based screening for kidney disease. This issue also has articles (on pages 14, 15, and 17) reporting on study findings from the European Association of Urology (EAU) 28th Annual Congress in Milan. Our coverage includes a report on an investigation showing that radical prostatectomy can be an appropriate treatment for patients with high-risk prostate cancer (PSA above 20 ng/mL and/or a Gleason score of 8 or higher, and/or T2c or greater disease). Men with one, two, or three of these risk factors had a five-year metastasis-free survival rate of 91.1%, 84.9%), and 71.7%, respectively. Our EAU coverage also includes a report on two U.S. studies of kidney stones, one showing an increase in emergency department visits for kidney stones, particularly among women, and the other demonstrating an increase in the use of percutaneous nephrolithotomy. From May 18-22, visit our website for our on-site coverage of the American Transplant Congress in Seattle. While visiting the website, check out our extensive coverage of the American Urological Association annual meeting in San Diego (May 4-8). As always, feel free to contact me with any comments or suggestions related to editorial content. Sincerely, Jody A. Charnow Editor

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Medical Director, Urology

Medical Director, Nephrology

Robert G. Uzzo, MD, FACS G. Willing “Wing” Pepper Chair in Cancer Research Professor and Chairman Department of Surgery Fox Chase Cancer Center Temple University School of Medicine Philadelphia

Kamyar Kalantar-Zadeh, MD, MPH, PhD Medical Director, Nephrology Professor & Chief Division of Nephrology & Hypertension University of California, Irvine School of Medicine Orange, Calif.

Nephrologists

Urologists Christopher S. Cooper, MD Director, Pediatric Urology Children’s Hospital of Iowa Iowa City R. John Honey, MD Head, Division of Urology, Endourology/Kidney Stone Diseases St. Michael’s Hospital University of Toronto Stanton Honig, MD Associate Clinical Professor of Surgery/Urology University of Connecticut School of Medicine, Urology Center New Haven J. Stephen Jones, MD, FACS, MBA Chief of Surgical Operations Fairview Hospital, a Cleveland Clinic hospital Professor of Surgery (Urology) Cleveland Clinic Lerner College of Medicine at Case Western Reserve University Leonard Horvitz and Samuel Miller Distinguished Chair in Urological Oncology Research Jaime Landman, MD Professor of Urology and Radiology Chairman, Department of Urology University of California, Irvine James M. McKiernan, MD Assistant Professor of Urology Columbia University College of Physicians and Surgeons New York City Kenneth Pace, MD, MSc, FRCSC Assistant Professor Division of Urology St. Michael’s Hospital University of Toronto Ryan F. Paterson, MD, FRCSC Assistant Professor Division of Urologic Sciences University of British Columbia Vancouver, Canada

Anthony J. Bleyer, MD, MS Professor of Internal Medicine/Nephrology Wake Forest University School of Medicine Winston-Salem, N.C. Suphamai Bunnapradist, MD Director of Research Department of Nephrology Kidney Transplant Research Center The David Geffen School of Medicine at UCLA R. Michael Hofmann, MD Associate Professor and Medical Director, Living Kidney Donor Program University of Wisconsin School of Medicine and Public Health, Madison Csaba P. Kovesdy, MD The Fred Hatch Professor of Medicine University of Tennessee Health Science Center Memphis Chief of Nephrology Memphis VAMC Allen Nissenson, MD Emeritus Professor of Medicine The David Geffen School of Medicine at UCLA, Chief Medical Officer, DaVita Inc. Rulan Parekh, MD, MS Associate Professor of Pediatrics and Medicine University of Toronto Robert Provenzano, MD Chief, Section of Nephrology St. John Hospital and Medical Center, Detroit Robert S. Rigolosi, MD Director, Regional Hemodialysis Center Holy Name Hospital, Teaneck, N.J. Lynda Anne Szczech, MD, MSCE Medical Director, Pharmacovigilence and Global Product Development, PPD, Inc. Morrisville, N.C.

Renal & Urology News Staff Editor Jody A. Charnow Executive editor Marina Galanakis Senior editor Delicia Honen Yard Web editor Stephan Cho Editorial coordinator Candy Iemma Art director Andrew Bass Group art director, Haymarket Medical Jennifer Dvoretz VP, audience development and operations John Crewe Production assistant Brian Wask Group production manager Kathleen Millea Product manager, digital products Chris Bubeck Circulation manager Paul Silver National accounts manager William Canning Editorial director Jeff Forster Publisher Dominic Barone VP medical magazines and digital products Jim Burke CEO, Haymarket Media Inc. Lee Maniscalco Renal & Urology News (ISSN 1550-9478) Volume 12, Number 5. Published monthly by Haymarket Media, Inc., 114 West 26th Street, 4th Floor, New York, NY 10001. Periodicals postage paid at New York, NY, and an additional mailing office. The subscription rates for one year are, in the U.S., $75.00; in Canada, $85.00; all other foreign countries, $110.00. Single issues, $20.00. www.renalandurologynews.com. Postmaster: Send address changes to Renal & Urology News, c/o DMD Data Inc., 2340 River Road, Des Plaines, IL 60018. For reprints, contact Wright’s Reprints at 1.877.652.5295. Copyright: All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means (electronic, mechanical, photocopying, recording, or otherwise) without the prior written permission of Haymarket Media, Inc. Copyright © 2013.

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Contents

M A Y

2 0 1 3

■

V O L U M E

1 2 ,

I S S U E

N U M B E R

Urology 9

ONLINE

this month at renalandurologynews.com

Data Support RP for High-Risk PCa Patients with high-risk prostate cancer who undergo radical prostatectomy do not necessarily have a poor prognosis.

Kidney Stone ED Visits On the Rise From 2006-2009, the estimated incidence of ED visits among women increased by a significant by 2.85% annually, compared with a non-significant 1.19% annual increase among men.

Outpatient Prostatic Embolization Safe for BPH Prostatic arterial embolization is associated with good clinical success rate among men with benign prostatic hyperplasia and moderate to severe lower urinary tract symptoms.

Expert Q&A

Samir N. Khleif, MD, talks about his research aimed at improving the survival benefit of the therapeutic cancer vaccine sipuleucil-T.

Clinical Quiz

Take our latest quiz at renalandurologynews.com /clinical-quiz/. Answer correctly and you will be entered to win a $50 American Express gift card. Congratulations to our February winner: Howard Adler, MD

News Coverage

Visit our website for coverage of the American Transplant Congress in Seattle (May 18-22).

CME Feature 37

Medical and Surgical Management of Bladder Outlet Obstruction Bilal Chughtai, MD, and Stephen A. Kaplan, MD, of Weill Cornell Medical College in New York, review the latest treatments for lower urinary tract symptoms secondary to benign prostatic hyperplasia.

Nephrology

The Medical Minute

Visit renalandurologynews.com /the-medical-minute/ to hear podcast reports on new studies. Our latest include: • Study Highlights Need to Bolster Efforts to Education ESRD Patients • Focal Laser Ablation a New Option for Low-Risk Prostate Cancer • New Immunoassay May Enable Early Kidney Cancer Detection

Metastases to the Kidney May Mislead Clinicians Non-renal cancers that have spread can be mistaken for primary tumors, according to researchers.

Pregnancy Outcomes Worsen As CKD Progresses As chronic kidney disease advances, pregnant women are at increased risk of adverse fetal and maternal outcomes, new findings suggest. Dialysis Patients’ Hb Levels Decline The trend follows the debut of bundling and labeling changes for erythropoiesisstimulating agents. CKD Mineral Metabolism Found to Differ by Race Researchers have confirmed the presence of racial differences in markers of mineral metabolism in patients with chronic kidney disease. Gout Often Found with Severe CKD Study of NHANES data reveals that the condition is present in 30% of patients with an eGFR below 30.

Doctors tend to be perfectionists and I think it is a frustrating experience when these things impact their ability to practice.

Departments 6

From the Editor Transfusions on the upswing

News in Brief Antibiotics misused in dialysis patients

Renal Nutrition Update Ghrelin may offer a good CKD outcome measure

Practice Management How doctors can combat burnout

Men’s Health Update Study links BPH with obesity

Legal Issues in Medicine Nephrologist vs. urologist in a malpractice case

See our story on page 29

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Renal & Urology News 9

Metastases to the Kidney May Mislead Clinicians BY ROSEMARY FREI, MSc BALTIMORE—It can be easy to mistake some metastases to the kidney for primary renal tumors, according to a presentation at the 2013 annual meeting of the U.S. and Canadian Academy of Pathology. Angela Wu, MD, Assistant professor in the Department of Pathology at the University of Michigan in Ann Arbor, and her team reviewed their institution’s experience with metastases to the kidney—particularly those with unusual or deceptive clinical or histologic features, and that would be encountered in a typical, busy pathology practice—from May 1987 to August 2012. They included only cases that involved a known primary tumor and a definitive final diagnosis of a metastatic tumor, and excluded autopsy cases. The set of cases in their analysis—15 nephrectomies, 26 core biopsies, and two fine-needle-aspiration cases— comprised less than 1% of all the renal masses they resected or biopsied in the 25-year period.

Non-renal cancers that have spread can be mistaken for primary tumors. The most common primary tumor sites were lung (20), followed by breast, head, and neck (four), prostate (two) and colon (two). There were also “a few cases from unusual sites” such as adrenal gland, skin, tibia, and testis, Dr. Wu said. In 88% of the cases (38/43) the primary cancer was diagnosed first, whereas in 2% (1/43) the kidney metastasis was diagnosed first. In the rest, the primary and the metastasis were diagnosed concurrently. The majority (93%) of the patients presented with a renal mass, but one patient presented with a renal cyst, and two with renal failure. In about 35% of patients, the clinical features favored a primary renal neoplasm over a kidney metastasis. Traditionally, metastases to the kidney are thought to be multiple and bilateral, Dr. Wu noted, but in this study most cases were solitary (70%) or unilateral (77%). Other unusual features included a greater than 10-year interval between the diagnosis of the primary and metastasis (19%

of cases); no other known distant organ metastasis at the time of the kidney metastasis diagnosis (37% of cases); and a medullary rather than a cortical location (11%). “While there are some unusual and deceptive clinical, radiologic, and histologic features seen in a subset

patient’s clinical history, a high index of suspicion, and diligent comparison between the primary tumor and the metastases. In the end, according to Dr. Wu. communication between the urologist and pathologist is key to arriving at the correct diagnosis. n

SPECIFIC

IMMUNOTHERAPY EMPOWERS THE IMMUNE SYSTEM TO FIGHT CANCER Immunotherapy primes T cells and B cells to recognize and target cancer cells expressing specific tumor antigens.1-3

It’s time to consider

IMMUNOTHERAPY

as an important treatment in your fight against cancer. For more information go to www.FightCancerWithImmunotherapy.com References: 1. Murphy K, et al, eds. Janeway’s Immunobiology. 7th ed. Garland Science, Taylor & Francis Group, LLC. New York, NY: 2008. 2. Namm JP, et al. J Surg Oncol. 2012;105:431-435. 3. Sharma P, et al. Nat Rev Cancer. 2011;11:805-812.

Dendreon and the Dendreon logo are registered trademarks of Dendreon Corporation.

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of metastases to the kidney, fortunately—at least in this cohort— a primary tumor had been diagnosed prior to the discovery of the metastasis,” Dr. Wu said. “This means that misdiagnosis can be avoided, but it would depend on a thorough investigation of the

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News in Brief

Please visit us at www.renalandurologynews.com for the latest news updates from the fields of urology and nephrology

Short Takes Antibiotics Misused in Dialysis Patients

Bradley Layton, PhD, of the University

In a 35-month retrospective evaluation

colleagues, post-CABG-AKI developed

of parenteral antibiotic use among pa-

in 3.4% of 17,077 CABG patients who

tients receiving chronic hemodialysis,

started statin therapy preoperatively

276 (29.8%) of 926 doses for which

compared with 6.2% who did not.

an indication for administration was

In adjusted analyses, statin use was

available were classified as inappropri-

associated with a 38% decreased risk

ate. Of these, 146 (52.9%) did not

of AKI among patients younger than

meet criteria for infection, 74 (26.8%)

65 and a 9% decreased risk among

represented failure to choose a more

those aged 65 and older.

of North Carolina at Chapel Hill, and

narrow-spectrum antimicrobial, and surgical prophylaxis. Vancomycin and

PCa Linked to Early Hair Loss in Blacks

third- or fourth-generation cephalospo-

Early-onset baldness was significantly

rins were the most common inap-

associated with prostate cancer (PCa)

propriately prescribed antimicrobials,

in a study of 318 black men with

according to findings published in

the disease and 219 controls. Any

Infection Control and Hospital

baldness was associated with a 69%

Epidemiology (2013;34:349-357).

increased PCa risk. Men with frontal

56 (20.3%) did not meet criteria for

baldness rather than vertex baldness

Statins May Prevent Post-CABG AKI

were more than twice as likely to be

Initiating a statin prior to coronary

relationship was stronger among men

artery bypass grafting (CABG) surgery

whose PCa was diagnosed before

may modestly reduce the risk of

age 60 years, with a sixfold increase

acute kidney injury (AKI) post-CABG,

in the risk of high-stage disease and

especially in patients younger than

a fourfold increase risk in high-grade

65 years old, researchers reported in

disease, according to data published

The American Journal of Cardiology

in Cancer Epidemiology, Biomarkers &

(2013;111:823-828). In a study by J.

Prevention (2013;22:589-596).

diagnosed with advanced PCa. The

HIPAA Privacy Rule In a recent online poll, Renal & Urology News asked urologists and nephrologists, â&#x20AC;&#x153;How has the HIPAA Privacy Rule affected the care you provide patients?â&#x20AC;? Here are the results of the poll based on 148 responses:

It is a major source of hassles: 45.95%

It occasionally impedes care: 40.54%

It has not affect care at all: 14%

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Healthy Lifestyle Lowers Mortality in CKD Patients I

n a study, patients with chronic kidney disease (CKD) who had the highest healthy lifestyle scores (did not smoke, followed a healthful diet, and maintained a body mass index above 22 kg/m2) were 53% less likely to die from any cause than those with the lowest healthy lifestyle scores, according to data published online ahead of print in the Clinical Journal of the American Society of Nephrology. After a median follow-up of 13 years and the deaths of 1,319 of the 2,288 original participants with CKD (estimated glomerular filtration rate lower than 60 mL/min/1.73m2 or microalbuminuria), Ana C. Ricardo, MD, of the University of Illinois Hospital and Health Sciences System, and colleagues found that mortality risk increased by 30% among patients with a BMI of at least 18.5 but less than 22 compared with a BMI of at least 22 but less than 25. The mortality risk was 46% lower for never-smokers than for current smokers, and 20% lower for subjects who were regularly physically active compared with those who engaged in no physical activity. Diet was not significantly associated with mortality.

Nocturia May Worsen Insomnia in Older Adults N

octuria is common in older individuals with insomnia and is significantly associated with increased nocturnal wakefulness and decreased subjective restedness after sleep, according to recent study findings published in the Journal of Clinical Sleep Medicine (2013;9:259-262). A total of 55 men (mean age 64.3 years) and 92 women (mean age 62.5 years) with insomnia were studied for two weeks using sleep logs and one week using actigraphy. More than half (54.2%) of all log-reported nocturnal awakenings were associated with nocturia. A greater number of trips to the toilet was linked with worse log-reported restedness and sleep efficiency. In addition, actigraph-determined wake bouts were 11.5% longer on nights on which there was a trip to the toilet, and wake after sleep onset was 20.8% longer during those nights.

Markers Shown to Predict Macroalbuminuria Risk H

igh levels of the inflammatory markers soluble E-selectin (sE-selectin) and soluble tumor necrosis factor receptor 1 (sTNFR-1) and sTNFR-2 are important predictors of macroalbuminuria in patients with type 1 diabetes, a recent study found. In a Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications cohort, a one-unit increase from baseline in the standardized levels of soluble E-selectin was associated with an 87% increase in the odds of developing macroalbuminuria, and one-unit increases in the levels of sTNFR-1 and -2 were associated with a 30%-50% increase. As Maria F. Lopes-Virella, MD, PhD, of the Medical University of South Carolina in Charleston, and colleagues reported online ahead of print in Diabetes Care, these associations remained significant following adjustment for DCCT baseline retinopathy status, age, sex, HbA1c, and duration of diabetes.

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Renal & Urology News 11

Reports from the National Kidney Foundation’s 2013 Spring Clinical Meetings, Orlando, Fla.

NKF 2013 ■

Pregnancy Outcomes Worsen As CKD Progresses As chronic kidney disease (CKD) advances, pregnant women are at increased risk of adverse fetal and maternal outcomes, new findings suggest. Compared with pregnant women with mild CKD, those with severe CKD have a significantly higher risk of pre-term delivery and giving birth to an infant that is small for gestational age (SGA), according to the investigators. Additionally, the study showed that the subjects with severe CKD experienced more rapid decline in renal function. Women with severe CKD—defined as an estimated glomerular filtration rate (eGFR) below 30 mL/min/ 1.73 m2—may benefit from earlier initiation of dialysis to reduce the incidence of adverse maternal and fetal outcomes, the researchers concluded.

Hip Fracture Rates Up in the Elderly Hip fracture rates among elderly patients starting dialysis are higher now than in 1996, researchers reported.

Zichun Feng, MD, and colleagues at Baylor College of Medicine in Houston, retrospectively studied 42 pregnant women: 10 with severe CKD and 32 with mild CKD (eGFR

of 30-100 mL/min/1.73 m2) and baseline proteinuria. Preterm delivery (less than 37 weeks’ gestation) occurred in nine women (90%) in the severe CKD group compared with 13 (40.6%) in

the mild CKD group. Six women (60%) in the severe CKD group versus four (12.5%) in the mild CKD group gave birth to SGA infants, the investigators reportedn

ADAPTABLE IMMUNOTHERAPY EMPOWERS THE IMMUNE SYSTEM TO FIGHT CANCER As tumor cells mutate, many cancers can become resistant to traditional cancer therapies.1-3 The activated immune system can adapt and recognize new tumor antigens to continue the attack over time.1,4--6

Sumi Sukumaran Nair, MD, of the Stanford University School of Medicine in Palo Alto, Calif., analyzed

It’s time to consider

14 years of data (1996-2009) from patients aged 67 years and older ini-

IMMUNOTHERAPY

tiating dialysis in the U.S. Compared with patients in 1996, adjusted hip

as an important treatment in your fight against cancer.

fracture rates increased until 2004, when the rates were 41% higher than in 1996. The rates declined thereafter so that by 2009, the rates were 25% higher than in 1996. The 30-day

For more information go to www.FightCancerWithImmunotherapy.com

mortality rate after hip fracture declined from 20% in 1996 to 16% in 2009.

References: 1. Murphy K, et al, eds. Janeway’s Immunobiology. 7th ed. Garland Science, Taylor & Francis Group, LLC. New York, NY: 2008. 2. DeVita VT, et al, eds. Cancer: Principles & Practice of Oncology. 8th ed. Lippincott, Williams & Wilkins; Philadelphia, PA: 2008. 3. Chabner BA, et al, eds. Cancer Chemotherapy & Biotherapy: Principles & Practices. 4th ed. Lippincott, Williams & Wilkins; Philadelphia, PA: 2006. 4. Ribas A, et al. J Clin Oncol. 2003;21:2415-2432. 5. Namm JP, et al. J Surg Oncol. 2012;105:431-435. 6. Kirkwood JM, et al. CA Cancer J Clin. 2012;62:309-335.

“While recent declines in incidence and steady declines in associated short-term mortality are encouraging, hip fractures remain among the most common and consequential non-cardiovascular complications of

Dendreon and the Dendreon logo are registered trademarks of Dendreon Corporation.

ESRD,” the authors concluded. n

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PCa focal therapy continued from page 1

at four months, the average PSA level was 3.6 ng/mL. No patient had a urinary tract infection or post-procedure fever. Of 32 patients with mild or no erectile dysfunction prior to the procedure, 31 (96%) maintained potency after the procedure without the use of phosphodiesterase-5 inhibitors. The researchers concluded that the initial biologic response to treatment suggests that tumors can be completely ablated in 75% of cases without incurring significant morbidity. They also noted that the procedure might be a viable option for patients with Gleason 3+4 disease. The pre- and post-procedure work-up imaging and biopsy schemes need to be evaluated further for better patient selection and significant tumor detection, they stated. In addition, the treatment technique needs to be refined to achieve higher rates of complete ablations.

Hemiablative brachytherapy In a separate study, Kazutaka Saito, MD, and colleagues at Tokyo Medical and Dental University Graduate used hemiablative brachytherapy using I-125 seeds to treat 16 men with unilateral prostate tumors as demonstrated with extended prostate biopsy. All had clinical stage T2a or less, Gleason score of 7 or less, a maximum cancer length less than 10 mm, and a PSA value less than

CIN predictor continued from page 1

a cardiology fellow at Long Island Jewish Medical Center in New Hyde Park, N.Y. Dr. Vidi and colleagues examined the usefulness of CVeGFRr for predicting CIN in 3,549 patients who had undergone PCI procedures during a recent 21-month period. CIN develops in about 10% of patients following a PCI procedure, Dr. Vidi said. The onset of CIN increases the in-hospital morbidity by roughly 10%-20%. The likelihood of CIN is driven by baseline risk factors such as patient age, diabetes, anemia, and heart failure, for example, he added. Conditions that increase the risk of CIN, however, are not typically modifiable at the time of PCI, and thus other strategies to reduce the risk of CIN are necessary. Currently, hydration with normal saline is recommended by various guidelines for the prevention of CIN, however about 10% of patients

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20 ng/mL. The target lobe was treated up to the midline as defined by the urethra. I-125 seed implantation was used to deliver a dose of 160 Gy under realtime ultrasonographic guidance. The men had a median age of 72 years, and 57% had low-risk and 43% had intermediate-risk PCa. The median follow-up was nine months. No post-treatment severe acute complications such as urinary retention or bleeding were observed. Among sexually active patients, ejaculatory function was preserved without dry ejaculation during follow-up. PSA values decreased significantly without biochemical failure based on the Phoenix definition (nadir plus 2 ng/ mL). MRI revealed no evidence of residual or new lesions at 12 months. All patients are alive except one who died from an unrelated cause 15 months after treatment, according to the investigators. “Based on the initial results, hemiablative brachytherapy can be a treatment option in focal therapy for unilateral prostate cancer in patients selected using extended biopsy and MRI,” the authors concluded in their study abstract.

Salvage cryoablation In a third presentation, researchers from The Netherlands reported findings of a study in which salvage cryotherapy was used to treat 10 men with histologically confirmed local will still develop CIN after PCI. In the present study, CIN occurred in 279 patients, or 7.65%, after PCI. Multivariate analysis showed that female gender, history of diabetes, left ventricular ejection fraction less than 45%, cardiogenic shock in the prior 24 hours, CVeGFRr greater than 3, and salvage PCI were independent predictors of CIN after PCI. CIN was 1.8 times as likely to develop in patients with a CVeGFRr of 3 or higher than in patients with a CVeGFR less than 3. “Essentially we have developed a simple tool which is independent of other baseline risk factors for identifying risk of CIN,” Dr. Vidi said. “And “3” is the important number to remember. So, for example, if the patient’s GFR is 50, I cannot give the patient more than 150 cc’s of contrast, or three times his/her GFR, or else I increase the risk of CIN significantly.” Dr. Vidi emphasized that a lack of information in the database on the type of contrast used during PCI (low-

recurrence of PCa following radiotherapy. Jurgen J. Fütterer, MD, PhD, of Radboud University Nijmegen Medical Centre in Nijmegen, and colleagues noted that cryosurgery for PCa under transrectal ultrasound guidance has been performed for several years for salvage treatment purposes after radical prostatectomy or radiotherapy. Due to poor visibility, however, high

MRI allows accurate lesion targeting and 3-D monitoring of ice ball growth. complication rates are not uncommon. MRI-guided cryosurgery may reduce these high complication rates because it has excellent soft tissue contrast. Additionally, they pointed out, MRI guidance enables both accurate lesion targeting as well as three-dimensional monitoring of iceball growth. For the procedure, surgeons inserted a urethral warmer into the urethra and placed a transperineal plate attached to a flexible arm against the perineum. They inserted cryoneedles with real-time MRI guidance and inserted a rectal warmer into the rectum. Both warmers were flushed with warm water to protect the tissue from freezing. Iceball formation and tissue coverage was monitored con-

tinuously under near real-time MRI guidance. Two freeze-and-thaw cycles were performed. Treatment time was defined as the interval between the first and last MRI scan. Follow-up consisted of PSA-level measurement every three months and a multi-parametric MRI after three, six, and 12 months. The procedure was technically feasible in all patients, the investigators reported. In one patient the urethralwarmer could not be inserted. This procedure was cancelled and successfully repeated two months later. The median age of the patients at the time of treatment was 67 years (range 52-76 years), their median PSA level was 3.7 ng/mL (range 0.98.7), and Gleason scores varied from 7-10. The median treatment time was 133 minutes (range 91-242 minutes). The median hospitalization time was two days. Two patients experienced mild urine retention and one had hematospermia. Three months of follow-up data were available for the first six patients, the researchers noted. Their PSA level decreased to a median of 1.3 and multi-parametric MRI showed no presence of recurrent tumor, according to the investigators. After six months, one of three assessed patients had a histopathologically proven local recurrence just above the area previously treated. He was retreated with MRI-guided cryoablation. n

12 Renal & Urology News

CIN develops in about 10% of patients after percutaneous coronary intervention.

osmolar versus iso-osmolar) may represent a limitation of his research. In addition, the study was retrospective, conducted at two high-volume centers, and included patients with the entire spectrum of coronary artery disease presentation, which might have decreased the effect size of CVeGFR in the multivariable model. Finally, while multivariate adjust-

ment was performed, the analysis does not categorically exclude the possibility of unmeasured confounding. The present study included “all comers with acute coronary syndrome,” he said, adding that future studies should focus on patients with ST-elevation myocardial infarction who have a markedly higher risk of CIN than other stable patients. n

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Pre-transplant continued from page 1

didates are screened once at the time of evaluation and put on the list to wait, and there are long and unpredictable wait times,” said Héloise Cardinal, MD, who presented the results at the 2013 annual meeting of the Canadian Society of Transplantation. “There should theoretically be an update in the cancer screening when patients have been waiting many years on the list, but implementing this is not always easy because the patients are usually followed in their dialysis centers far from the transplant center.” Dr. Cardinal, of the Centre Hospitalier de l’Université de Montréal, analyzed and presented the review of first-kidney-transplant recipients in five adult kidney-transplant centers in Quebec from January 1985 to January 2009. They excluded individuals who received another organ along with a kidney or who died or rejected the kidney within the first month of the surgery. The average age among the 3,524 patients was 47 years, 91% were Caucasian, and 64% were men. Their median time on dialysis before transplantation was 22 months. Forty percent had glomerular disease and 14% had polycystic kidney disease. Furthermore, 26% of patients had anti-lymphocyte induction therapy, 22% had anti-CD25 induction therapy, half had tacrolimus/

Patients waitlisted for long periods should have updated cancer screenings. mycophenolate mofetil/prednisone, and 25% had cyclosporine/prednisone immunosupression. Post-transplant cancers developed in 350 patients. Of these, 17% were renal cell carcinomas (with 8.3% occurring in the graft), 13% were in the prostate, 13% were in the lung, 10% were post-transplant lymphoproliferative disorders, 7% were in the breast, and 6% were colorectal. Thirtysix cancers were detected within a year of the transplant surgery. “An interesting question is whether these early lesions were present and missed before transplant, or if they truly did develop after transplantation because of increased immunosuppression,” Dr. Cardinal said.

Pre-transplant cancer screening includes mammography in women after age 50 or earlier if they have a positive family history; colonoscopy after age 50, or earlier if there is a strong positive family history; a Pap test and gynecologic exam; and a digital rectal examination plus PSA testing in men over 50. Most centers also perform an abdominal ultrasound to look for renal cell carcinoma because they develop more frequently

“Although reducing the burden of immunosuppression is clearly useful in some cancer types, for instance, post-transplant lymphoproliferative diseases, we don’t know if in cancer types that are not strongly linked to immunosuppression, this is effective or not, or if conversion to rapamycin in these cases would help, so it is food for thought and future studies,” Dr. Cardinal said. n

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as an important treatment in your fight against cancer. For more information go to www.FightCancerWithImmunotherapy.com References: 1. Murphy K, et al, eds. Janeway’s Immunobiology. 7th ed. Garland Science, Taylor & Francis Group, LLC. New York, NY: 2008. 2. Abbas AK, et al, eds. Basic Immunology. Functions and Disorders of the Immune System. 3rd ed. Saunders Elsevier; Philadelphia, PA: 2011. 3. Atanackovic D, et al. PNAS. 2008;105(5):1650-1655. 4. Perret R, et al. Tissue Antigens. 2008;72:187-194.

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in dialysis patients than in the general population, Dr. Cardinal said. Overall, patients who were diagnosed with cancer after transplantation often were given a reduced immunosuppression regimen, even those with neoplasms that are not usually associated with immunsuppression such as breast and prostate cancer. Fifty percent of those who developed cancer died within five years.

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■ EAU 2013

may 2013 www.renalandurologynews.com

Reports from the European Association of Urology 28th Annual Congress, Milan

Data Support RP for High-Risk PCa

Biochemical recurrence-free and metastasis-free survival can be achieved, researchers conclude

BY JODY A. CHARNOW Patients with high-risk prostate cancer (PCa) who undergo radical prostatectomy do not necessarily have a poor prognosis, researchers reported. Complete surgical resection and biochemical recurrence (BCR)and metastases-free survival can be achieved, particularly among patients with only one positive risk factor, according to investigators Andreas Becker, MD, and colleagues at the Martini-Clinic Prostate Cancer Center in Hamburg, Germany. As a result of study findings, the investigators concluded that RP should not be denied to otherwise appropriate surgical candidates because of a highrisk preoperative profile. Dr. Becker’s team identified 2,196 patients with high-risk PCa, defined as a PSA above 20 ng/mL and/or a Gleason score of 8 or higher and/or T2c or greater disease. The median followup was 28 months for the 1,659 patients

Tadalafil Response, CRP Linked Serum levels of C-reactive protein (CRP) may enable physicians to predict response to tadalafil treatment for erectile dysfunction (ED) in men with diabetes. Hyun Jun Park, MD, PhD, and colleagues at Pusan National University School of Medicine in Pusan, Korea, enrolled 102 ED sufferers with diabetes and

(76%) who had follow-up data available. BCR, which was defined as a PSA rise greater than 0.2, occurred in 592 patients (36%) and clinically evidence metastases developed in 118 (7%). The five-year BCR-free survival rates were 55.3%, 29.1%, and 13.6% for patients who had one, two, and three

Patients with one risk factor had a 55.3% five-year BCR survival rate. risk factors, respectively. The five-year metastasis-free survival rates were 91.1%, 84.9%, and 71.7%, respectively. In multivariable analyses, a PSA level above 20 was associated with a significant 2.4 times increased risk of BCR and 1.6 times increased risk of clinical metastases compared with a PSA level

of 20 or less. A Gleason score of 8 or higher was associated with a significant 2.2 times increased risk of BCR and a non-significant 1.5 times increased risk of clinical metastases compared with a Gleason score less than 8. Clinical stage T2c and higher was associated with a significant 50% increased risk of BCR and 2.1 times increased risk of clinical metastases compared with less advanced clinical stages. A total of 1,864 patients (85%) had one risk factor, 308 (14%) had two risk factors, and 24 (1%) had three risk factors. Gleason 8 or higher disease was present in 1,187 patients (54%), a PSA level above 20 was presented in 875 patients (39%), and T2c or greater disease was present in 578 patients (26%). The new findings are in line with those published last year in Advances in Urology. Dan Lewinshtein, MD, and collaborators at Virginia Mason Medical Center in Seattle studied 91 PCa patients with pathologic Gleason

8-10 disease. Sixty-two patients (68.9%) had stage T3 disease or higher and 48 (52.7%) had positive surgical margins. The median follow-up of these patients after RP was 8.2 years. The predicted 10-year rates of biochemical recurrence-free survival, metastasis-free survival, and prostate cancer-specific survival were 59%, 88%, and 94%, respectively. Only 12% of the patients who experienced BCR by 10 years progressed to metastases and 10% of patients died from their disease. “Taken together,” the authors concluded, “these long-term oncologic results support the use of RP for patients with high-risk localized prostate cancer.” Additionally, classical predictors of outcomes—such as pathologic stage and surgical margin status—were not significantly associated with outcomes in the current study, the investigators noted. n

MIBC Relapse Risk Factors Identified Bladder neck tumors and the presence of multiple tumors at the diagnosis of muscle-invasive bladder cancer (MIBC) are risk factors for the recurrence of intravesical tumors in patients treated with selective bladder-sparing approaches, a study found. The study, by Fumitaka Koga, MD, and collaborators at the Tokyo Medical and Dental University Graduate School, included 98 bladder-preserved patients who had achieved tumor-free status after induction chemoradiotherapy (CRT) for cT2-3N0M0 blad-

der cancer. Of these, 64 went on to undergo partial cystectomy. After a median follow-up of 50 months, 21 of these patients experienced recurrence of intravesical tumors, which translated into a five-year cumulative bladder tumor recurrence rate of 27%, the researchers reported. MIBC recurrence developed in four of the 21 patients, for a five-year cumulative recurrence rate of 4%. After accounting for multiple variables, bladder neck tumors and multiple tumors at MIBC diagnosis each

was independently and significantly associated with a fivefold and fourfold increased risk of intravesical bladder tumor recurrence, respectively. At five years from CRT, the cumulative incidence of tumor recurrence 18% for patients without either risk factor, 28% for those with one risk factor, and 78% for those with both risk factors, according to the investigators. The five-year overall and cancerspecific survival rate for the 98 patients in the study group was 84% and 92%, respectively. n

compared them to a control group of healthy men. After the start of tadalafil 5 mg once daily treatment, 71 patients (69.6%) achieved sufficient erection for sexual intercourse (responders) and 31 (30.4%) did not (non-responders). Responders had significantly lower serum CRP levels than non-responders (0.14 vs. 0.31 mg/dL). n

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More Biopsy Cores Do Not Up PCa Detection Increasing the number of prostate biopsy cores from 12 to 20 offers no significant advantage in detecting prostate cancer (PCa), data suggest. Jacque Irani, MD, CHU Hôpital de la Milétrie, Department of Urology, Poitiers, France, and colleagues randomized 339 men to undergo either

a 12-core or 20-core prostate biopsy. Subjects had PSA levels below 20 ng/ mL and negative findings on digital rectal examination. This was their first prostate biopsy. The two groups had similar preoperative variables. The biopsies revealed cancer in 71 patients (42%) of the 12-core group

and 81 (48.8%) of the 20-core group, a non-significant between-group difference. In addition, Gleason score and cancer length measured on biopsy cores were not significantly different between groups. PCa detection rate was linked to prostate volume, but the number of cores did not affect this. n

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■ EAU 2013

Renal & Urology News 15

Reports from the European Association of Urology 28th Annual Congress, Milan

Kidney Stone ED Visits On the Rise BY JODY A. CHARNOW Emergency department (ED) visits for kidney stones in the U.S. have increased, especially among women, but admission rates for kidney-stone patients have remained stable, according to new study findings. From 2006-2009, the estimated incidence of ED visits among women increased by a significant by 2.85% annually, compared with a non-significant 1.19% annual increase among men. The study also showed that the overall incidence of ED visits for kidney stones was highest in July and August (24.74 and 25.18 per 100,000 person-years, respectively) and lowest in February (17.40 per 100,000 person-years). Study investigator Khurshid R. Ghani, MD, a urology fellow at the Vattikuti Urology Institute, Henry Ford Health System, Detroit, said increased use of medical expulsive therapy for kidney stones—which only came into wide use in recent years—could explain why

Visceral Fat May Benefit RCC Patients A high body mass index (BMI) and visceral fat may offer advantages to patients being treated for renal cell carcinoma (RCC), according to separate studies. In one study, Gou Kaneko, MD, and collaborators at Keio University School of Medicine in Tokyo found that a high visceral fat area (VFA) as measured with preoperative computed tomography was associated with a decreased risk of cancer recurrence after surgery for localized clear-cell RCC. The study included 241 patients, of whom 151 underwent radical nephrectomy and 90 underwent partial nephrectomy. After a median follow-up of 35.6 months, 28 patients (11.6%) experienced recurrence. The five-year recurrence-free survival rate was 88.7% in patients with a high VFA (120 cm2 or above) versus 71% among patients with a low VFA (less than 120 cm2), a significant difference

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kidney-stone-related hospital admissions have not risen even though ED visits for kidney stones has increased. Dr. Ghani and his colleagues analyzed 2006-2009 data from the Nationwide Emergency Department Sample, the largest all-payer ED database in the U.S. The study looked at 3.6 million ED visits with upper urinary tract calculi as the primary diagnosis. The findings by Dr. Ghani’s team echoes those of a recently published study in Kidney International by Ziya Kirkali, MD, of the National Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Md., and colleagues. The study, which relied on data from the National Ambulatory Medical Care Survey and the National Health and Nutrition Examination Survey, found an increasing ED visit rate for kidney stones in the U.S., and showed that the ED visit rate increased to a greater extent among female patients than male patients. From 1992-2009, ED visit rates

between the groups. Compared with a high VFA, a low VFA was associated with a significant twofold increased risk of recurrence. High BMI did not predict independently predict recurrence. Visercal fat is thought to be the largest endocrine organ, the authors pointed out, and it produces several hormones and cytokines related to carcinogenesis and tumor progression. In the other study, German researchers reported that a high BMI at the start of systemic palliative treatment for advanced or metastatic RCC is associated with better overall survival compared with low or normal BMI. In a prospective study of 475 patients who received first-line systemic treatment for advanced or metastatic RCC, Peter-Jurgen Goebell, MD, of Friedrich Alexander University in Erlangen, Germany, and colleagues found that the median overall survival was 23.4 months among patients with a BMI above 28 kg/m2 compared with 10.0 and 16.7 months for those with a BMI less than 24 and 24-28, respectively. The researchers noted that the underlying mechanism by which high BMI is associated with longer survival is unclear. n

The trend is due mostly to an increasing incidence of visits by women, according to investigators

The incidence of kidney stones is increasing.

overall increased from 178 to 340 per 100,000 individuals, a 91% increase. Among female patients, the ED visit rate increased from 127 to 289 per 100,000, a 128% increase. By comparison, the rate among male patients increased from 231 to 393 per 100,000, a 70% jump.

In a separate presentation at the EAU congress, Dr. Ghani and colleagues reported that percutaneous nephrolithotomy (PCNL) use is increasing in the U.S.. The trend was more pronounced among women than men, with women now constituting the majority gender undergoing PCNL. Using the U.S. National Inpatient Sample database, Dr. Ghani and colleagues analyzed data from 80,097 patients who underwent PCNL from 1999-2009. The number of PCNLs per year increased 47%, according to the study, which is the largest to date to assess PCNL use in the U.S. The estimated annual percent change during the study period was significantly greater for women than men (2.54% vs. 0.03%). “We think this operation has become more popular in the U.S., and it’s been utilized in a greater range of patients, including older patients and sicker patients,” Dr. Ghani said. n

ONLINE ONLY

Visit renalandurologynews.com/gucs to watch videos of researchers discussing the findings of the following studies presented at the 2013 EAU Congress: Initial MRI May Help Predict Prostate Cancer Progression Interview with Ashley Ridout, BM BCh, University College London

PSADT Unreliable for Predicting Prostate Cancer Worsening Interview with Frederick B. Thomsen, MD, University of Copenhagen, Denmark

PCNL Rises Dramatically in the U.S. Interview with Khurshid R. Ghani, MD, Vattikuti Urology Institute, Henry Ford Health System, Detroit

Negative Second Biopsies Do Not Rule Out Prostate Cancer Progression Interview with Lih-Ming Wong, MD, Princess Margaret Cancer Centre, Toronto

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MAY 2013

www.renalandurologynews.com

Renal Nutrition Update G

hrelin is a hormone secreted by the stomach and small intestine. Three forms exist: acyl ghrelin, which exerts orexigenic effects, and desacyl ghrelin and obestatin, which exertsanorexigenic effects (Pediatr Nephrol 2013;28:611-616). Ghrelin is metabolized by the kidney; thus serum levels are elevated in chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients. More specifically, acyl-ghrelin levels are the same as controls, but the ratio of acyl ghrelin and total ghrelin is decreased. This hormonal profile promotes an anorexigenic response. Acyl/ total ghrelin levels positively correlate with albumin and negatively correlate with CKD stage and growth hormone. Rodent studies have found that ghrelin administration decreases muscle protein degradation and reduces inflammatory cytokines. Furthermore, rodent ghrelin infusions have improved oral food intake and lean body mass (Endocrinology 2008;149:827-835). The ghrelin infusion was also found to improve transcription factors associated with lipid metabolism, that, as a result, decreased muscle triglyceride concentrations (Kidney Int 2010;77: 23-28). Additionally, ghrelin has been found to have positive impacts on cardiovascular-related outcomes in rodent models. Conversely, inflammation has been shown to decrease ghrelin levels, and thus the reduction of ghrelin in response to inflammatory markers may make it a target for cardiovascular disease (CVD) risk assessment.

Effect of BMI In hemodialysis (HD) cohorts, studies have shown associations between low acyl ghrelin levels and protein-energy wasting (PEW) and between increased levels of des-acyl ghrelin and anorexia. In a study of 50 HD patients who were compared with healthy controls, the two groups had similar acyl ghrelin levels, whereas des-acyl ghrelin was elevated (Nutrition

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2010;26:1100-1104). Interestingly, as BMI increased in these patients, acyl ghrelin increased, but obestatin decreased. These results indicate that although the levels of the orexigenic ghrelin form remain similar between healthy patients and HD patients, the increased levels of anorexigenic ghrelin may be related to decreased appetite that caused or resulted from reduced BMI. Several studies have confirmed this trend of elevated total ghrelin levels but normal to low acyl ghrelin concentrations (Pediatr Nephrol 2010;25;2477-2482; J Ren Nutr 2010;20:151-157; Pediatr Nephrol 2010;25:2295-2301). Des-acyl ghrelin levels are shown to negatively correlate with protein intake while acyl-ghrelin levels negatively correlate with CRP. Primary predictors of total ghrelin levels are age and GFR. Acute administration of subcutaneous injections of acyl ghrelin increase serum ghrelin, decreased blood pressure for two hours, increase appetite, and increase energy intake (Kidney Int 2009;76:199-206).

Predictive ability In a prospective trial with 412 HD patients, CVD incidence was recorded over the course of three years (Intern Med 2010;49:2057-2064). Stratifying groups by low and high acyl ghrelin levels, acylated ghrelin and total ghrelin demonstrated significant hazard ratios for CVD after multivariate analysis. Low acylated ghrelin increased risk while high total ghrelin increased risk. The authors attributed these findings to the anti-inflammatory effects of acyl ghrelin and the potential protective effect this has on endothelial tissues. Of note, high levels of total ghrelin correlate with tumor necrosis factoralpha and interleukin-6, which is most likely due to increases in obestatin and des-acyl ghrelin. AIn another study, total

Ghrelin may offer a good outcome measure in CKD patients and a target for the management of protein-energy wasting and anorexia BY GRISSIM CLARK CONNERY, MS, RD, LD

Intradialytic parenteral nutritional supplementation may affect total ghrelin levels.

ghrelin was measured in 217 dialysis patients who were followed up for 20-38 months. Low ghrelin values were associated with increased risk for CVD-related mortality. When factoring ghrelin levels and PEW factors, the risk for all-cause and CVD related mortality more than doubled in the low ghrelin PEW patients. In a group of failed renal transplant patients, significantly elevated serum total ghrelin levels, elevated inflammatory factors, and low albumin were found in the failed transplant group (J Ren Nutr. 2012 Mar;22:258-67).

Nutritional interventions At this time, the application of ghrelin for nutritional assessment or interventions requires further research. On the other hand, ghrelin appears to be a more promising nutritional indicator than leptin. Of note, recent group studied the effect of intradialytic oral nutritional supplementation (IDON) and intradialytic parenteral nutritional supplementation (IDPN) on hormonal responses, including insulin, ghrelin, and glucagon-like peptide 1 in HD patients over four weeks (Am J Nephrol 2010;32:272-278). Although

dialysis sessions reduced total ghrelin levels in all study groups, the total ghrelin in the IDPN group was significantly lower than that of the control group, whereas the IDON group was not significantly different from either. These results indicate that the nutritional contribution of IDPN does have an effect beyond that of dialysis-related clearance alone, and the mechanism is most likely through hormonal cascades, possibly related to insulin. The blunted effect in IDON may be related to the increased time required for digestion or hormonal regulators of ghrelin secretion in the stomach and small intestine not triggered by parenteral administration. More research needs to be done on the predictive ability of ghrelin as a nutritional outcome in renal patients. At this time, it appears that ghrelin could offer not only a good outcome measure, but a pharmaceutical outlet for managing PEW and anorexia in renal disease patients. ■ Mr. Connery is Research Coordinator at Case Western Reserve University in Cleveland.

We’ve got more on our website highlighting effective diets for delaying CKD progression and helping patients manage sodium and phosphorus intake. See us at www.renalandurologynews.com/nutrition.

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Renal & Urology News 17

Reports from the European Association of Urology 28th Annual Congress, Milan

EAU 2013 ■

Outpatient Prostatic Embolization Safe for BPH Prostatic arterial embolization (PAE) is a safe outpatient procedure for patients with benign prostatic hyperplasia (BPH) and moderate to severe lower urinary tract symptoms (LUTS), data show. The procedure is associated with good short and mid-term results, particularly in patients with prostates larger than 100 cc and severe symptoms, according to Luis Campos Pinheiro, MD, of the Faculty of Medical Sciences of the New University of Lisbon in Portugal, and colleagues. The investigators studied 365 BPH patients with moderate to severe LUTs who underwent PAE. Patients ranged in age from 45-89 years and prostate volumes ranged from 40270 cc. Seventy-two patients had prostates larger than 100 cc and 42 were in acute urinary retention with a bladder

PSA Testing Lowers PCa Death Risk Systematic PSA-based screening for prostate cancer (PCa) reduces by nearly one third the risk of death from the malignancy among men aged 55-69 years at baseline. The findings, presented by Monique J. Roobol, PhD, an epidemiologist in the Department of Urology at Erasmus University Medical Center in Rotterdam, are the latest results from the European Randomized Study of Screening for Prostate Cancer. The study included men aged 54-74 years. A total of 21,210 men were randomized to a screening arm and 21,166 were randomized to a control arm. The total number of PCa

catheter. PAE was performed under local anesthesia. The researchers defined clinical success as a reduction of at least 25% in International Prostate Symptom Score (IPSS) and an IPSS

below 15 points and no need for additional treatment. The median follow-up period was 14 months. The patients experienced a mean reduction in IPSS of 10.9 points

and a mean prostate volume reduction of 16.2%. The cumulative clinical success rate was 84.9% at three months, 77.2% at 12 months, 74.3% at 24 months, and 74.3% at 36 months. n

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cases detected from 1993-2010 was 2,674 (12.6%) in the screening arm and 1,430 (6.8%) in the control arm. Screening decreased the risk of PCa mortality by 20% overall for men aged 55-74 and by 31.6% for men aged 55-69 years. Screening did not lower PCa mortality risk among men

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aged 70-74. n

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■ NKF 2013

may 2013 www.renalandurologynews.com

Reports from the National Kidney Foundation’s 2013 Spring Clinical Meetings, Orlando, Fla.

Dialysis Patients’ Hb Levels Decline The trend follows the debut of bundling and labeling changes for erythropoiesis-stimulating agents Hemoglobin (Hb) levels have decreased and transfusion rates have increased among dialysis patients since the introduction of the Medicare prospective payment system for endstage renal disease (ESRD) care and changes to drug labeling for erythropoiesis-stimulating agents (ESAs), new findings suggest. Under the prospective payment system (so-called “bundling”), which took effect in January 2011, dialysis centers are reimbursed a flat fee to cover dialysis and previously separately billable medications and services. In June 2011, the FDA changed ESA labeling to recommend more conservative ESA dosing in patients with chronic kidney disease. In an analysis of data from electronic medical records, Scott Sibbel, MPH, PhD, of DaVita Clinical Research in Minneapolis, Minn., and colleagues found that mean Hb levels declined from 11.4 g/dL in June 2010 to

Undiagnosed CKD in Type 2 Diabetics Undiagnosed chronic kidney disease (CKD) is common among patients with type 2 diabetes mellitus, researchers reported. In a study of 43,975 patients with type 2 diabetes mellitus, Shih-Yin Chen, MD, of the United BioSource Corporation in Lexington, Mass., and colleagues found that the prevalence

10.7 g/dL in April 2012. In addition, a larger proportion of patients had Hb levels below 10 g/dL. The proportion of patients with an Hb level below 10 g/dL was 9.64% in October 2010 (the low) and 24.25% in October 2011 (the high), according to the researchers. In addition, transfusion rates among the patients had increased. They observed no change in transfusion triggers after the label change for in-patient dialysis. “Among many risk factors, Hb was the most notable risk factor for patient transfusion during a hospitalization event prior to and after the label change and accounted for most of the transfusion risk in multivariate models,” the authors wrote in a poster presentation. In a separate study of 42,790 dialysis patients presented at the meeting, Zhun Cao, PhD, of Truven Health Analytics in Ann Arbor, Mich., and colleagues found an overall upward trend in transfusion rates from January 2007

Key Points ■■ Mean hemoglobin levels

(g/dL) in dialysis patients declined from 11.4 in June 2010 to 10.7 in April 2012. ■■ The proportion of patients

with a hemoglobin level below 10 rose from a low of 9.64% in October 2010 to a high of 24.25% in October 2011. ■■ Data from two studies

document an increase in transfusion rates.

through March 2012. Since January 2011, the percentage of patients who received a transfusion and the transfusion event rate increased more among Medicare patients than commercially insured patients.

The authors noted that decreases in ESA use and Hb levels may increase the potential need for transfusions in ESRD patients and, as these transfusions are excluded from bundling, there is a potential for increased use of transfusions to supplement ESA treatment. Analyses of data from the U.S. Renal Data System, which includes information on prevalent dialysis patients covered by Medicare, show that the proportion with a transfusion increased from 2.4% in September 2010 to 3.0% in September 2011 (a 24% increase), the researchers pointed out. Under the revised FDA approved labeling, dosing to a target Hb range of 10-12 g/dL is no longer suggested and labels now include a black box warning stating that patients experienced greater risks for death, serious adverse cardiovascular reactions, and stroke when given ESAs to a target Hb level greater than 11 g/dL. n

High Protein Meals During HD Tested Having hemodialysis (HD) patients eat high protein meals during dialysis sessions may offer a way to correct abnormally low albumin levels, according to researchers. This approach involves the concomitant use of a phosphate binder to control phosphorus levels. In a randomized study of 110 hypoalbuminemia HD patients (serum albumin levels below 4 mg/dL), significantly more patients treated with this novel approach experienced a rise in serum albumin greater than 0.2 g/dL while

maintaining target phosphorus levels compared with a control arm (25.5% vs. 9.8%). Phosphorus levels had to be at least 3.5 but less than 5.5 mg/dL. The researchers, led by Kamyar Kalantar-Zadeh, MD, MPH, PhD, of the University of California Irvine Medical Center, observed no serious adverse events. Patients reported satisfaction with high protein meals during HD. Dr. Kalantar-Zadeh’s group noted that the traditional approach of restricting protein to control phosphorus in dialysis patients may not be the most

appropriate method, especially in hypoalbuminemic dialysis patients. Patients in the treatment arm received eight weeks of high protein food in the form of cold meal boxes during each HD treatment, along with 0.5-1.5 g lanthanum carbonate. The meal boxes contained 51 g of protein, 850 calories, and a phosphorus-toprotein ratio less than 10 mg/g. Patients in the control arm received salad meal boxes containing less than 50 calories and less than 1 g of protein during each HD treatment. n

of CKD was 50.7% for stage 1-5 and 22.1% for stage 3-5. Among these patients, the rate of undiagnosed CKD was 87.8% for the stage 1-5 group and 76.1% for the stage 3-5 group. In addition, the researchers found a higher prevalence of stage 1-5 and stage 3-5 among patients aged 65 years or older (58.9 % and 32.7%, respectively) as well as AfricanAmericans (53.7% and 27.1%). n

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CKD Mineral Metabolism Found to Differ by Race Researchers have confirmed the presence of racial differences in markers of mineral metabolism in patients with chronic kidney disease. Patricia Wahl, MD, and colleagues at the University of Miami School of Medicine studied 1,287 participants in the Chronic Renal Insufficiency Cohort (CRIC) study, including 561

black and 728 non-black subjects. Significantly greater proportions of blacks than non-blacks were female, had a history of diabetes, and were smokers, according to researchers. Black race was associated with significantly higher parathyroid hormone levels compared with non-black race, after adjusting for age, gender, diabe-

tes and smoking status, dietary intake, 25-hydroxyvitamin D (25D) level, and numerous other potential confounders, the researchers reported. In similar adjusted models, black race also was associated with significantly higher serum calcium and lower 25D levels and significantly lower levels of fibroblast growth factor 23. n

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Renal & Urology News 19

Reports from the National Kidney Foundation’s 2013 Spring Clinical Meetings, Orlando, Fla.

NKF 2013 ■

Post-Tx BP Predicts Delayed Graft Function Risk Low diastolic and high systolic blood pressure (BP) immediately after kidney transplantation are associated with an increased likelihood of delayed graft function (DGF), researchers reported. In a retrospective study of 183 adult kidney transplant recipients, Dhiren Kumar, MD, and colleagues at Virginia Commonwealth University in Richmond found that systolic BP above 160 mm Hg and diastolic BP below 60 mm Hg during postoperative day 0-5 were associated with a 4.3 times and 3.5 times increased likelihood of DGF. Averaged over five days, patients with DGF had slightly lower diastolic BP compared with patients without DGF (70 vs. 74 mm Hg). Of the 183 patients, 87 (47%) had DGF, which the researchers defined as a need for dialysis within the first week

after transplantation, less than 50% reduction in serum creatinine in the first postoperative week, or both. Other risk factors for DGF included longer cold ischemia time, older donor

age, and receipt of a kidney from a donor after cardiac death, according to the researchers. Because allografts are unable to auto-regulate BP right away, both low

and high BP could be detrimental, with high pressure resulting in endothelial injury and low pressure potentiating ischemic injury, they explained. n

He had normal kidney function. He became critically ill.

Shared Visits Benefit Stone Patients

He was diagnosed with AKI.

Shared medical appointments (SMAs) for kidney stone patients may be an efficient approach to nephrolithasis prevention. Roy Jhagroo, MD, and colleagues at the University of Wisconsin in Madison looked at the effect of SMAs on new stone patients. A total of 112 patients were seen in 27 SMAs over 14 months. The SMAs involved 6-10 patients, a nephrologist or urologist, registered dietitian, and a medical assistant. The study found that appointment wait time decreased steadily from 180 days prior to SMAs to 84 with SMAs. The number of patients seen per month increased 43%. The number of new clinic patients who received nutrition education and intervention increased from

He was treated differently. AKI and ESRD patients are not the same. For the first time ever, KDIGO has published a Clinical Practice Guideline that focuses on acute kidney injury (AKI). The Guideline is based on systematic reviews of relevant clinical studies and aims to assist practitioners caring for patients at risk for or with AKI. If you want to optimize outcomes for AKI patients—treat them differently. Find out how by visiting crrtcounts.com/guideline or go to gambro.com/prismaflex to learn why the Prismaflex® System is the most widely used CRRT device in the world.

about 50% prior to SMAs to nearly 75%. In addition, 87% of patients who attended SMAs rated their satisfaction as “excellent” or “very good” and 90% said they would recommend this kind of visit to others. n

Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney International Supplements 2012; Volume 2, Issue 1: 1–126.

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New Prostate Center in Focus exciting this time around for Ashutosh K. Tewari, MB, BS, head of the new Center for Prostate Cancer at New York-Presbyterian/ Weill Cornell Medical Center in New York, as January marked the opening of the facility. Dr. Tewari tells Renal & Urology News how he plans to execute the comprehensive center’s dual mission of patient care and research with a multidisciplinary plan of attack. Why is the Center for Prostate Cancer at New York-Presbyterian/Weill Cornell Medical Center being established now?

clinical treatment, this will drive our research portfolio.

Dr. Tewari: Weill Cornell Medical College and New York-Presbyterian Hospital have always excelled in the treatment of prostate cancer. The impetus to create the center was driven by the opportunity to coalesce advances in treatment, diagnosis, and genomics. This fits in nicely with the institutional goals to transform care and focus on personalized translational medicine. The new Center for Prostate Cancer is an important part of the Cancer Center at Weill Cornell and NewYork-Presbyterian and its goals.

You are considered an expert in robotic prostatectomy, having performed more than 5,000 such surgeries. How will this influence services provided at the Center for Prostate Cancer?

Before the establishment of the center, you were the director of the Prostate Cancer Institute and the LeFrak Robotic Surgery Center at Weill Cornell Medical College. How will the new setup change the way you and your staff work?

Dr. Tewari: There is a strong move to build multidisciplinary centers around specific diseases. This center does just that. Within urology we are exploring several new diagnostic techniques and focal therapy options for prostate cancer. In addition, the scope of the center will span across multiple departments to better treat patients and their individual cancers. This includes formalized relationships with the departments of radiology, pathology, medical oncology, and radiation oncology. In addition, as these clinical departments start to work toward

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Dr. Tewari: Robotic prostatectomy is certainly a viable treatment choice for prostate cancer. Most prostatectomies in the United States are done robotically. I fully expect us to continue this work. In addition, we will offer a wide range of treatments, which before were beyond the scope of a urology department. We will have people with expertise in medical oncology, genomics, imaging and focal therapy, surgery, targeted therapies, and other areas. We’ll emphasize different approaches for different patients.

when intervention is possible, while leaving indolent cancers alone. What sort of real-time decision(s) could be made when using a given imaging technique? Would this be happening at the diagnostic stage or the treatment stage (or both)?

Dr. Tewari: The real-time imaging could be multiphoton imaging and also molecular probe-based imaging to identify residual cancer in the surgical field and also identify and avoid erectile nerves that are traveling close to the cancer cells. My personal interest is in the genetic nature of prostate cancer, especially looking at intratumor heterogeneity. Another area is inflammation in prostate cancer and molecular pathways that are making the cancer more aggressive. We are developing fusion and targeted biopsies, using the Artemis system. We also have a very large active surveillance program, in which I am working on strategies to minimize the use of biopsy and substitute it with novel imaging approaches.

What is your research focus?

Dr. Tewari: One of the areas I’m very excited about is real-time decision making using imaging techniques. I also focus on identifying genomic biomarkers for predicting aggressive prostate cancer and nerve-sparing strategies in robotic prostate cancer to protect against sexual dysfunction and urinary incontinence. Will the Center for Prostate Cancer have a particular research focus?

Dr. Tewari: Initially we will look to improve prostate cancer diagnosis— that is, diagnosing aggressive cancers

What new diagnostic methods/ techniques, or perhaps simply what new way of thinking, are available or are on the horizon to advance this mission?

Dr. Tewari: In order for us to make better decisions and identify aggressive cancers, the center has about 15 researchers working on developing better imaging modalities, such as molecular imaging and fusion of MRI molecular imaging and ultrasound. The scientists in this program are also working on single-cell genomics to identify the exact genetic switches that are getting abnormally turned on and off, resulting in aggressive cancer behavior. The lab here, in collaboration with Cold Spring Harbor and other institutions, is developing these noninvasive approaches to identifying the genomic signature of aggressive cancers. What aspect of the center is generating the most enthusiasm/interest for you, your staff, and/or your patients?

Dr. Tewari: Having the ability to come to one office to see a urologist, a medical oncologist, a nutritionist, and a radiologist to evaluate your prostate cancer is an exciting shift in the current treatment of patients. In the end we want to drive home the point that we are disease-specific and not modality-specific. What service, program, or equipment are you most eager to add to the center in the next two years or so?

Ringing in the new year was especially

There is a strong move to build multidisciplinary centers. —Ashutosh K. Tewari, MD

Dr. Tewari: In two years I fully expect us to offer a full range of genomic panels and imaging biomarkers to help doctors and patients understand prostate cancer. This will change how we monitor disease progression by obviating the need for repeat biopsies as well as diagnosing individuals when intervention is still possible and comorbidities are minimized. Approximately how many patients do you expect to serve in the new Center for Prostate Cancer on an annual basis?

Dr. Tewari: I’m seeing about 1,500 patients a year now. We hope to see between 3,000 and 4,000 a year in the center. ■

Continue the conversation online! We have many experts who weigh in on controversial topics important to you. Catch our discussions at www.renalandurologynews/expertqa.

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Scoring System Rates Transplant Program Quality A ‘quality index’ score indicates a higher rate of organ sharing BY ROSEMARY FREI, MSc MIAMI BEACH—Researchers have created a quality indicator that allows comparisons of different transplant centers. Regulatory agencies have made public transplant outcomes data such as patient and graft survival as well as length of hospital stay, and other factors such as transplant center level of organ sharing and use of organs from donors older than age 65. Centers are regulated and disciplined based mainly on survival data. At the American Society of Transplant Surgeons’ 13th Annual State of the Art Winter Symposium, a team from the Hartford Hospital in Hartford, Conn., showcased its quality index (QI), which is a simple formula that takes into account patient and graft survival as well as transplant rate. They found that centers with higher QI scores successfully balance a healthy amount of organ sharing with keeping the odds as high as possible for good transplant outcomes. Facilities with higher QI scores had higher rates of organ sharing than lower-QI centers and longer lengths of stay, but also lower rates of use of organs from donors above age 65, and

slightly lower rates of delayed graft function. “Having a good QI reflects a good balance of organ sharing—accepting riskier organs that other centers have turned down—and watching graft and patient survival rates, so not taking everything you are being offered,” lead investigator Caroline Rochon, MD, told Renal & Urology News. “But our QI also gives lower scores to centers that only use perfect ‘no-risk’ organs that result in great patient and graft survival but lower transplant rates and therefore long wait times for transplantation.” The formula for the new QI is: (observed patient survival/expected patient survival) × (0.7 if patient-survival ratio is less than 1, 1 if it is equal to 1, and 1.3 if the ratio is above 1) × (observed graft survival/expected graft survival) × (0.7, 1 or 1.3) × (observed transplant rate/ expected transplant rate). This formula goes beyond patient and graft survival, which are central in the Centers for Medicare & Medicaid Services (CMS) and the United Network for Organ Sharing (UNOS) determination of program performance. Dr. Rochon said her team chose the factors of 0.7, 1.0, and 1.3 arbitrarily. The most important point, however,

Top 10 Kidney Transplant Centers by Volume From January 1, 1988 to October 31, 2012, transplant centers in the United States performed 333,046 kidney transplants. The 10 centers performing the most kidney transplants during the period are: Transplant

No. Kidney Center Transplants

1. University of Alabama Hospital.................................................................... 6,725 2. University of California-San Francisco.......................................................6,580 3. University of Wisconsin Hospital and Clinics..........................................5,842 4. UCLA Medical Center....................................................................................... 5,599 5. University of Maryland Medical System...................................................4,838 6. University of Minnesota Medical Center................................................... 4,553 7. Ohio State University Medical Center........................................................ 4,342 8. University of Pittsburgh Medical Center...................................................4,293 9. University of Michigan Medical Center......................................................4,260 10. St. Vincent Medical Center............................................................................ 4,244 Source: Organ Procedure and Transplantation Network

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is that the formula reduces scores for programs that are below the expected performance in key parameters, including transplant rate, she said. The team analyzed Scientific Registry of Transplant Recipients data from 40 kidney transplant programs randomly selected from across the United States. The median QI value from these centers was 1.06 (range 0.33-3.68). The researchers observe that major academic centers—that is, those that produced at least three publications in 2012—did not have higher QI than non- academic ones. Nor was there a significant difference in the average QIs of centers that did at least 150 kidney transplants in 2012 and lower-volume facilities. The study also revealed a non-significant difference in the rate of delayed graft function between programs with a QI of greater than 0.8 and less than 0.8 (25% and 30%, respectively). Yet the average QI was 0.87 among centers with a median length of stay of less than five days and 1.33 among centers with an average length of stay longer than five days. “The longer hospital stays may be the consequence of a ‘non-cherry-picking’ practice on the part of higher-QI centers, where sicker patients get transplanted and their level of physical deconditioning, malnutrition and cardiac comorbidities impact their length of stay,” Dr. Rochon and her co-investigators noted in a poster presentation of the results. The average QI of programs that had greater than 25% organ sharing was 1.4, while it was 1.1 for programs that imported a smaller proportion of their kidneys, but this difference was not statistically significant. The difference in the rates of organ sharing between centers with a QI of more than or less than 0.8, was significant at 27% and 15%, respectively. Among higher-QI programs, however, the proportion of organs from donors over age 65 was 2%, compared with 5.6% for higherQI centers. Dr. Rochon said she next plans to compare the demographics and comorbidities of patients from lower- and higher-QI programs. She and her team have also designed a similar QI for liver-transplant programs. n

Hematuria Found Years After BT Gross hematuria can occur in men up to several years after undergoing prostate brachytherapy, according to a study. The condition is more likely to develop in men with larger prostates volumes (more than 40 cm3), those who also undergo external beam radiotherapy (EBRT), and those who are free from biochemical failure, researchers reported online ahead of print in BJU International. Michael S. Leapman, MD, and collaborators at the Mount Sinai School of Medicine in New York reviewed hematuria outcomes in 2,454 patients who had transperineal prostate brachytherapy over a 20-year period. The study population had a median follow-up of 5.9 years. Of the 2,454 patients, 218 (8.9%) reported gross hematuria at a median time of 772.2 days after seed implantation.

Men with larger prostates are at higher risk for blood in urine. Only 3.8% of men with PSA failure reported hematuria compared with 9.4% of those with biochemical control, the researchers noted. A possible explanation for this finding is that differences among patients may affect their response to radiation, with respect to both toxicity and disease control. Patients who are more sensitive to radiation may be more likely to have a favorable treatment response, but also experience increased mucosal injury or necrosis that leads to hematuria, Dr. Leapman’s group explained. The authors noted that the median time to the first hematuria episode was more than two years, with 25% of patients reported hematuria more than five years after seed implantation. The delay could be the result of several factors, such as the protracted contribution of radiation-altered prostatic and bladder tissue with accumulated physiologic causes of hematuria observed with aging and prostatic growth that may require years to develop, the investigators explained n

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Practice Management Pressures physicians face make them susceptible to burnout, but they can take steps to combat it BY TAMMY WORTH

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self-sacrifice for their job. This self sacrifice can lead to anger and resentment. “Just doing something for themselves goes a long way to extinguish that,” she said. She tells physicians to take some time, walk the dog, journal, meditate, work in the garden.They should do whatever they can to have some down time. This will give them room to breathe and clear their head.

Look on the bright side Ferrons talks with physicians about the importance of focusing on the positive part of work and engagement with patients. She also recommends thinking of three things every night before they go to bed that they enjoyed about work that day. A 2009 study published in the Journal of the American Medical Association found benefits in mindfulness. University of Rochester Medical Center researchers studied 70 primary care physicians who took part in a continuing education course dealing with self-awareness, mindfulness meditation and other positive reinforcement. Those taking part in the course showed reduced burnout rates, more empathy, and improved moods and emotional stability. “The nice thing about it is that is it doesn’t take a lot of time like exercising for an hour,” Ferrons said. “But people have to make a choice to do it.” Take a stand Richard Gunderman, MD, PhD, a professor at Indiana University in Indianapolis, said one of the major catalysts for burnout is the push for increased productivity in the office. “The rationale behind such pressures may be strong from a business perspective,” he said. “But doctors

he bad news is there is no simple solution to burnout. It is a complex issue and can stem from any one of the daily challenges being thrown at physicians from various directions. Doctor’s face pressure from insurers and employers to spend less time with patients; long hours with little work-life balance; growing accountability from ratings and surveys and reports; and an increasingly changing industry that offers less autonomy over a practice. Studies have shown that physicians are more likely to experience burnout than people in other occupations. A recent study in the Archives of Internal Medicine by Mayo Clinic researchers talked with more than 7,000 physicians. They found that nearly half had experienced burnout and more than one-third were unhappy with their work-life balance. “Doctors tend to be perfectionists and I think it is a frustrating experience when these things impact their ability to practice,” said Liz Ferrons, manager of clinical services for Physician Wellness Services, based in Minneapolis, Minn. “I am finding a lot of doctors who question if they want to continue in healthcare.” Burnout can induce minor issues like fatigue but it can also bring on problems like depression, alcoholism, and an increase in medical errors. The good news is that you can improve, or even stave off, burnout. Doing this depends upon figuring out why you, in particular, are crashing. “The first step is recognizing you are burned out,” Ferrons said. “It takes someone stepping back and saying, ‘I need to do something about this’. Ferrons said physicians are some of the worst offenders when it comes to

Carving out some down time is one way doctors can keep job pressures from getting to them.

may feel that threatens the quality of care and, even more fundamentally, prevents them from forming the relationships they aspire to with patients and families.”

Find support “I think physicians are encouraged to ‘grin and bear it’ from med school on,” Ferrons said. “But when the pain gets great enough, it does lead people to reach out.” For more than 30 years, William Zeckhausen has provided this kind of haven for physicians that gives them a place to restore themselves. Zeckhausen, a pastoral counselor in Gilford, NH, offers a weekly support group for physicians in his area. Pastoral counselors are required to go to counseling and it makes sense that physicians should as well to deal with professional pressures. The final tip to reduce burnout is to

understand and accept that healthcare is changing. “Physicians have to realize they can’t practice like they did in the past,” Ferrons said. “And working harder and sacrificing more only leads to burnout and less effectiveness.” You have to figure out how to work smarter, not harder. If you have only 15 minutes with a patient, find a way to make it the most effective 15 minutes possible. Be efficient and effective. Help your patients manage their expectations and understand what they should be getting from their time with you. “Current conditions don’t allow for perfection, so how do you do it good enough?” she said. “People need to learn to set limits and boundaries to increase effectiveness.” ■ Tammy Worth is a freelance medical journalist based out of Blue Springs, MO.

Want to improve your practice? Look for our tips on how to handle equipment issues, adjust to EHRs, comply with HIPAA, and more at www.renalandurologynews.com/practice.

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Men’s Health Update Short Takes Obesity Found to Increase BPH Risk Benign prostatic hyperplasia (BPH) has long been thought to be an inevitable function of genetic predisposition and age related changes in sex steroid hormones and detrusor function. A recent review of published data on obesity, BPH, lower urinary tract symptoms (LUTS), and physical activity suggests that systemic metabolic disturbances contribute to the pathogenesis of BPH. The findings, published in the Journal of Urology (2013; 189:S102-S106), included a positive association between body mass index (BMI), waste circumference, and prostate volume. The risk of prostate enlargement (40 g or more) was 41% greater in obese men (BMI greater than 35 kg/m2) than non-obese men (BMI less than 25).

Video Game Urinals Aim to Boost Prostate Knowledge New urinals installed at Coca Cola Park in Allentown by the Lehigh Valley health network were designed to bring attention to prostate health and prostate cancer. Urinal-mounted 12-inch LCD screens are a motion-activated, hands-free gaming system that allows the bathroom goer to compete against fellow voiders. All the while it quizzes and boosts the micturators’ knowledge about prostate health and prostate cancer. The first game to appear will be a snowmobiling game called “On the Piste,” but more games are in the pipeline. Practice up and get that prostate checked because scores are displayed in the restroom and on video displays throughout the ballpark.

NFL’s New Rule to Prevent Concussions The National Football League (NFL) has taken a new interest in the safety of its players. In September, several new rules will go into effect, among them a rule aimed at reducing concussions. The rule will impose a 15-yard penalty for delivery of a blow with the crown of the helmet. If the offensive and defensive player each lower their heads and uses the crown of the helmet to make contact, each will be penalized. New magnetic resonance imaging techniques have shown that the effects of concussions are more serious than previously thought, demonstrating global atrophy one year after just a single concussion, according to a paper published online ahead of print in Radiology by Yongxia Zhou, PhD, and colleagues.

BY JAIME LANDMAN, MD, and ADAM KAPLAN, MD, of the

University of California Irvine, Department of Urology

Vitamin D Deficiency, Daytime Fatigue Linked M

en who doze off during the day may benefit from salmon, eggs, or a bit more time in the sun, all of which increase vitamin D levels. New data reported by David E. McCarty, MD, and colleagues in the Journal of Clinical Sleep Medicine (2012; 8:693-697) indicate that suboptimal levels of vitamin D are associated with a greater likelihood of excessive daytime sleepiness. The reasons for these effects on sleepiness are many, including a relationship of vitamin D to obstructive sleep apnea, nonspecific musculoskeletal pain, and known sleep regulating substances such as tumor necrosis factor alfa and prostaglandin D2. Immune dysregulation is an important consequence of low vitamin D that could lead to excessive daytime sleepiness mediated by components of the inflammatory cascade. Beyond its effects on bony demineralization, studies have demonstrated the adverse consequences of vitamin D deficiency on the immune system, pulmonary disease, musculoskeletal pain, metabolic syndrome, hypertension, stress, and cognition.

High Fat Diet May Lower Sperm Count, Concentration A

lthough male factor infertility can be found in half of couples having difficulties trying to conceive, little is known regarding dietary habits and male reproduction. Jill A. Attaman, MD, of Dartmouth-Hitchcock Medical Center in Lebanon, N.H., and colleagues examined how specific nutritional factors can affect semen quality. Using a validated 131-item food frequency questionnaire and semen and semen fatty acid analyses, they discovered that higher intake of saturated fats negatively affected total sperm count and sperm concentrations, according to a report in Human Reproduction (2012;27:1466-1474). Men in the highest third of saturated fat intake had 41% lower sperm concentration than men in the lowest third. Intake of omega-3 fatty acids was positively correlated with favorable sperm morphology, including fewer head defects. Adopting these dietary and lifestyle changes of increased omega-3 fatty acid and decreased saturated fat can be beneficial not only for your patient’s general health, but their reproductive health as well.

PCa Mortality Higher Among Unmarried Men Unmarried men are significantly more likely than married men to die from (2013;20:6702-6706). In a study of 115,922 PCa cases reported to the Surveillance, Epidemiology, and End Results (SEER) database, Mark D. Tyson, MD, and colleagues at Mayo Clinic in Phoenix, Ariz., found that unmarried men (single, divorced, widowed, or separated) had a 40% and 51% increase in the risk of PCa-specific mortality and overall mortality, respectively, in adjusted analyses. The five-year disease-specific survival rate for married men was 89% compared with 80.5% for unmarried men.

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medistat

prostate cancer (PCa), researchers reported in the Canadian Journal of Urology

8.7

The age-adjusted estimated prevalence of diagnosed diabetes in the U.S. male population aged 18 and older.

percent

Source: January-September 2012 National Health Interview Survey, National Center for Health Statistics.

Please visit us at www.renalandurologynews.com for the latest news updates from the fields of urology and nephrology

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RARP Suitable for Large Prostates Robot-assisted prostatectomy is safe and can result in good oncologic and functional outcomes Robot-assisted radical prostatectomy (RARP) for prostate cancer is technically challenging for men with large prostates, but it can be performed safely and with good surgical, oncologic, and functional outcomes, researchers have reported. In a retrospective study, Apostolos P. Labanaris, MD, PhD, and colleagues at Prostate Center Northwest, St. Antonium Hospital, Gronau, Germany, compared 185 RARP patients with a pathologic prostate specimen weighing 100 grams or more with a matched control group of RARP patients with a pathologic prostate specimen weighing 50 grams or less and who had clinicopathologic characteristics similar to those of the large-prostate group. Compared with the control group, the large-prostate group had significantly greater median estimated blood loss (192 vs. 152 mL) and operative time (164 vs. 144 minutes), the investigators reported in Urologia Internationalis

Transfusions May Worsen BCa Outcomes Patients undergoing radical cystectomy for bladder cancer (BCa) may be at increased risk for worse outcomes if they receive a perioperative blood transfusion (PBT), according to a new study. The study, which led by Stephen A. Boorjian, MD, of Mayo Clinic in Rochester, Minn., included 2,060 patients who underwent radical cystectomy for BCa. Of these, 1,279 (62%) received PBT (median two units of blood). The median follow-up for the study population was 10.9 years. Compared with patients who did not receive PBT, those who did had significantly worse five-year recurrence-free survival (58% vs. 64%), cancer-specific survival (59% vs. 72%), and overall survival (45% vs. 63%), Dr. Boorjian and colleagues reported online ahead of print in European Urology. After adjusting for multiple variables, PBT was associated with a 20% increased risk of tumor recurrence, 31% increased risk of death from BCa, and a 27% increased risk of death from any cause.

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RARP in Large vs. Small Prostates In a study comparing RARP in men with large and small prostates, those with large prostates: • Had lower rates of aggressive tumors and positive surgical margins • Were less likely to have biochemical recurrence • Experienced more intraoperative blood loss • Had a higher rate of complications • Had similar continence rates • Had lower potency rates Source: Labanaris AP et al. Robot-assisted radical prostatectomy in patients with a pathologic prostate specimen weight ≥100 grams versus ≤50 grams: surgical, oncologic and short-term functional outcomes. Urol Int 2013;90:24-30.

(2013;90:24-30). Significantly more patients in the large-prostate group than the control group underwent bladder neck reconstruction (28% vs. 5.9%) and experienced intraoperative complications (4.8% vs. 1.6%). The patients with large prostates, however, had significantly lower rates of aggressive tumors and positive surgical margins (PSMs). Ninety patients (48.7%) in the large-prostate group had

Patients who received PBT were significantly older than those who did not (69 vs. 66 years) and were more likely to have muscle-invasive tumors (56% vs. 49%). They also had worse Eastern Cooperative Oncology Group performance status. “While these data require external validation,” the authors concluded, “continued efforts to limit the use of blood products in these patients are warranted; these efforts include implementing restrictive transfusion criteria or alternative strategies for blood replacement and surgical techniques to minimize blood loss.” Dr. Boorjian and his collaborators noted that the potential immuno suppressive effect of red blood cell transfusion was first described in a study published nearly four decades ago in the Lancet (1974;2:696-698). The study showed enhanced renal allograft survival among patients receiving a blood transfusion. Other studies have demonstrated an association between PBT and disease recurrence in patients with colon, esophageal, and hepatic carcinomas. Dr. Boorjian’s team pointed out that the mechanism by which PBT may affect cancer-related outcomes has not been definitively established and more research is needed. n

a Gleason score less than 7 compared with 76 patients (41.1%) in the control group. A Gleason score of 7 was found in 63 patients (34.1%) in the large-prostate group compared with 80 (43.3%) of the control group. The two groups had similar proportions of patients with a Gleason score above 7 (15.1% and 15.6%). Nine patients (4.8%) of the men with large prostates had PSMs compared with 20 (10.8%) control patients.

Furthermore, 8% of patients with large prostates experienced biochemical recurrence (BCR) after a median follow-up of 23.6 months, whereas 13.1% of control patients experienced BCR after a median follow-up of 21.6 months. The researchers defined BCR as a 0.2 ng/mL PSA rise above nadir or a PSA level that never reached nadir. The two treatment arms had similar continence rates, but the men with the large prostates had significantly lower potency rates. Dr. Labanaris’ group concluded that RARP in patients with a pathologic prostate specimen weight of 100 grams or more is a technically challenging procedure due to reduced mobility in the pelvis, impaired visualization, limited working space, and manipulation and rotation of the gland, but “in experienced hands it can be considered a safe procedure with excellent surgical, oncological and functional outcomes.” n

Beta-Blockers May Lower PCa Mortality in High-Risk Patients Beta-blocker use by men with

ing that beta-blockers can inhibit the

high-risk or metastatic prostate cancer

development of metastases from breast

(PCa) is associated with a decreased

cancer and PCa. In addition, epidemio-

risk of PCa-specific mortality.

logic evidence suggests a survival ben-

The study, led by Kristin Austlid Taskén, MD, of Oslo University Hospital and the

efit of beta-blocker use among breast cancer patients.

University of Oslo in Norway, examined

Dr. Taskén’s group noted that the

the association between beta-blocker

typical beta-blocker user is frequently

use and PCa-specific mortality in a

also treated with other drugs to prevent

cohort of 3,561 PCa patients with high-

cardiac events, such as low-dose aspirin

risk or metastatic disease at the time

and statins. Previous studies have found

of diagnosis.

that use of aspirin or statins is associ-

After a median follow-up of 39 months,

ated with improved outcomes in PCa

the researchers found that subjects who

patients. For example, a study found

used beta-blockers had a 21% decreased

that aspirin use was associated with a

risk of PCa-specific mortality compared

decreased risk of PCa-specific mortality

with non-users in adjusted analyses,

among PCa patients treated with radical

according to a report published online

prostatectomy or radiotherapy (J Clin

ahead of print in European Urology.

Oncol 2012;30:3540-3544). Another

The association was independent of

study showed that statin use by PCa

statin and aspirin use as well as clinical

patients treated with radiotherapy was

characteristics at diagnosis. In addition,

associated with a decreased risk of

the study found no association between

biochemical recurrence and improved

beta-blocker use and all-cause mortality.

relapse-free survival (J Clin Oncol

The authors cited animal studies show-

2010;28:2653-2659). n

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Renal & Urology News 33

Legal Issues in Medicine D

r. N, 62, was a pediatric nephrologist who was the head of the kidney transplant program in a major hospital. Over the past several years, he’d occasionally been asked to serve as an expert in medical malpractice cases. In one such case, Dr. N was contacted by the attorney for a young man, Mr. K, who wanted to file a lawsuit against the clinicians who treated him in his local emergency department (ED). The attorney called Dr. N and asked him to look at the medical records and assess whether the clinicians had been negligent in their care of Mr. K. Dr. N carefully reviewed the records which laid out the story. Mr. K was 15 years old when he first came to the ED with his mother. He complained of blood in his urine, and a urinalysis verified gross hematuria as well as protein in the urine. The attending urologist, Dr. U, diagnosed Mr. K as having a urinary tract infection, prescribed antibiotics, and sent the young man home. Six weeks later, Mr. K returned to the same ED complaining of continuing blood in his urine as well as new symptoms of a sore throat, fever and right flank pain. Mr. K was examined by Ms. A, a urology physician assistant. Ms. A called Dr. U to discuss the examination, evaluation and treatment plan, but neither Dr. U, nor any other physician, actually examined Mr. K. Again, Mr. K was given antibiotics, was told he had a urinary tract infection, and was sent home.

Undiagnosed kidney disease Almost two years later, Mr. K, now 17, returned to the same ED complaining that he was spitting up blood. Tests revealed that the teenager’s kidneys were no longer functioning. A renal biopsy indicated that he had late-stage IgA nephropathy, which would require him to be on hemodialysis three times

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a week for the rest of his life. It was determined that the kidney disease had progressed too long without treatment and the kidney failure was irreversible. After receiving this devastating news, Mr. K and his family hired the plaintiff’s attorney who had contacted Dr. N to review the records and give an opinion. In the state in which this took place, a certificate from a qualified expert needed to be filed to begin the lawsuit. After reviewing the records, Dr. N concluded that the clinicians had breached the standard of care by failing to include nephritis in the differential diagnosis when Mr. K presented to the ED on both occasions. A lawsuit was filed against Dr. U (the urologist) and Ms. A (the physician assistant) alleging negligent care in the treatment of Mr. K. Dr. U and Ms. A consulted with their malpractice attorney who told them “I think we may be able to get this whole case dismissed. The expert they used was a nephrologist, not a urologist, and therefore is not a ‘qualified expert’ under the statute. Without a certification from a qualified expert, they can’t proceed with their case.” The attorney filed a motion to dismiss the case. The court agreed that Dr. N was not a qualified expert in the case, and the case was dismissed. The plaintiff’s attorney immediately appealed. The attorney pointed out that the statute said that the expert “shall have had clinical experience, provided consultation relating to clinical practice, or taught medicine in the defendant’s specialty or a related field of health care.” The case went to the state appeals court, which had to decide whether nephrology was a related field of health care to urology, specifically in the context of developing a differential diagnosis for a patient who presents to the ED with blood and protein in the urine. The court ruled

Malpractice case tests whether a nephrologist may serve as an expert witness in a case against a urologist BY ANN W. LATNER, JD

A urologist should have included nephritis in a differential diagnosis, a nephrologist asserted.

that under the circumstances, urology and nephrology are related fields, and Dr. N’s certification of the case was valid.

Legal background Previous case law in the state had held that it was not necessary for a certifying or testifying expert witness in a medical malpractice case to be the same kind of health care provider as the defendant, but the expert must be in a related health field. First, the court looked at the definition of both fields of practice and concluded that both fields share a common focus on the kidneys. Next, the court looked at the circumstances of the case to determine whether nephrology and urology overlap in the context of “the treatment or procedure” at issue. Since the “treatment” in this case involved a differential diagnosis, the court questioned Dr. N about whether in his practice of nephrology he had participated in on-call services for emergency departments that required him to make

differential diagnoses. Dr. N testified that he had, and that he often had to refer patients to other specialists, particularly urologists. Dr. N also testified that he had treated patients in the ED with both hematuria and proteinuria.

Protecting yourself The case was returned to the lower court for trial, which is pending. As an expert, Dr. N had nothing to protect himself from; however, according to Dr. N’s testimony, both the urologist and the physician assistant should have considered nephritis as a potential diagnosis, especially after the patient returned the second time. ■ Ms. Latner, a former criminal defense attorney, is a freelance medical writer in Port Washington, N.Y. Cases presented are based on actual occurrences. Names of participants and details have been changed. Cases are informational only; no specific legal advice is intended.

What do you think? Did the jury make the right decision in this case? We want to know your thoughts. Leave us a comment at the end of this article—or any article—at www.renalandurologynews.com/legal.

4/25/13 4:52 PM

MAY 2013

www.renalandurologynews.com

Malpractice News Flaws in Patient Privacy, Data Security Must be Addressed Not enough is being done to protect patient privacy and data security, according to an article recently published in The New England Journal of Medicine. The authors write that medical identity theft and data security breaches are growing and that thousands of cases are reported per year. The authors cite statistics from the Centers for Medicare and Medicaid (CMS) services stating that they track almost 300,000 compromised Medicare-beneficiary numbers, and from the Office for Civil Rights, which has received over 77,000 complaints of breaches in health information privacy. These breaches can affect quality of care for patients. “Incorrect information can infiltrate the beneficiary’s medical record and corrupt later medical decision making,” write the authors. “Beneficiaries have been wrongly labeled as diabetic or HIV-positive when people with those conditions obtained services using a beneficiary’s medical identity.” Pharmacists sometimes reject legitimate prescriptions when records incorrectly show that the patient already received medication. When the Office of the Inspector General (OIG) started compliance

Medical data theft and security breaches are on the rise.

On The Web RUN0513_MalPractice.indd 34

audits of hospitals, it was discovered that auditors sitting in hospital parking lots with simple laptop computers could obtain patient information from unsecured hospital wireless networks. CMS and the OIG have collaborated to come up with best practices for promoting privacy and data security. Suggestions include the following: • Install and enable encryption systems • Use a password or other user identification • Install and activate programs that disable and/or erase data from lost or stolen devices • Disable and do not use file-sharing programs • Use firewalls to block unauthorized access • Install and use security software to protect against spyware, malware, viruses and malicious applications • Keep security software up to date • Maintain physical control of mobile devices, and research mobile applications before downloading • Delete all stored health information on mobile devices before discarding them • Use adequate security when sending or receiving health information over public WiFi networks.

NY Statute of Limitations Archaic, Deprives Patients In 2010, a Brooklyn resident went to the emergency department of the Kings County Hospital with complaints of chest pain. Doctors ordered an EKG and chest x-ray. The EKG was normal, but a radiologist identified a suspicious 2 cm mass in the patient’s left lung. No one, however, told the patient about this (it was early stage lung cancer), and instead she was sent home with advice to take Motrin. Two years later, she returned to the same ED with a chronic cough. A chest x-ray revealed that the cancer had metastasized to both lungs, her liver, brain and spine. Her condition

BY ANN W. LATNER, JD

information from other attorneys, that this happens several times a year.

Medical Malpractice Mediation Bill Passes in Oregon

New York’s statute of limitations for malpractice cases is unusual among states.

was terminal and she was given six months to live. A physician at the hospital noticed the earlier x-ray and confessed that the original diagnosis had been missed. Unfortunately, New York’s statute of limitations begins to run from the date of the malpractice, not the date of the discovery of the malpractice. A vast majority of other states begin the statute of limitations from the time the injury is discovered or should reasonably have been discovered. By the time the patient found out about the malpractice, the statute of limitations—2.5 years in an action against a private or nonprofit hospital, but just 15 months in an action against a municipally-owned hospital— had run its course and she could no longer sue. New York’s Health and Hospitals Corporation did offer a $625,000 settlement to the patient, but experts agree that it was likely just a fraction of what she could have been awarded by a jury. The 41-year old mother died from lung cancer last March. While there are no data on how many potential malpractice cases are affected by the New York statute, New York medical malpractice attorney Matthew Gaier, writing in The Daily News, estimates, based on his firm’s experience and anecdotal

Both the Oregon Senate and House have approved a new medical malpractice mediation bill. The bill was the product of a work group convened by Gov. John Kitzhaber to examine issues regarding how medical malpractice lawsuits were being handled in the state. The bill allows patients, providers or health care facilities to report medical errors to the Oregon Patient Safety Commission, and to begin confidential settlement negotiations and mediation. The out of court mediation is expected to reduce lengthy, expensive lawsuits, but the program is expected to cost the state an estimated $1.6 million in the current budget. Proponents of the bill believe it will give parties injured by medical malpractice a better way to resolve grievances than filing lawsuits, and will reduce frivolous malpractice claims. Opponents, however, feel that the bill doesn’t go far enough in addressing medical malpractice claims, and doesn’t live up to the governor’s promises. The work group originally proposed making the program mandatory, but this was met with opposition from doctors. The program will now be voluntary, making it slightly unclear as to how it might be used. The bill, however, has the support of both physicians and trial lawyers, who are usually at odds. Kitzhaber was expected to sign the bill into law. “I committed last year to bring a proposal to the Legislature to ensure that our medical liability system fits within our shared vision of health system transformation,” said Kitzhaber in a press release, “and I appreciate the Legislature supporting this effort.” ■ Ms. Latner, a former criminal defense attorney, is a freelance medical writer in Port Washington, N.Y.

34 Renal & Urology News

Looking for more malpractice news? Visit us at renalandurologynews.com/malpractice to see noteworthy jury verdicts, recent trends in legislation, and surprising settlements!

4/25/13 5:26 PM

36 Renal & Urology News

may 2013 www.renalandurologynews.com

Gout Often Found with Severe CKD NHANES data reveal that the condition is present in 30% of patients with an eGFR below 30 BY ROSEMARY FREI, MSc Gout is present in nearly one third of Americans with severe chronic kidney disease (CKD), according to a study. In addition, the prevalence of gout is higher among patients with lower average estimated glomerular filtration rates (eGFRs) or higher levels of albuminuria, even after adjusting for uric acid levels. “Two take-home points for nephrologists are that there is a high prevalence of gout among persons with kidney disease, and that albuminuria is associated with a higher prevalence of gout. While the latter association has been previously described, I think the magnitude we uncovered is noteworthy,” said first author Stephen Juraschek, an MD-PhD student in epidemiology at Johns Hopkins University in Baltimore. He and his colleagues published their findings online ahead of print in Seminars in Arthritis and Rheumatism. Juraschek, together with Allan

Small RCC Can Recur Long-Term Patients who undergo surgery for small renal cell carcinomas (RCCs) require long-term follow-up because of the risk of recurrence and RCC-related death even 10 years after treatment, according to researchers. Tetsuya Shindo, MD, and colleagues at Sapporo Medical University in Japan, included 172 patients (133 men, 39 women) who were treated for small, organ-confined RCC (pT1a). Of these, 18 (10.5%) experienced recurrence and eight of them (4.7%) died from their cancer during a median follow-up of 10.4.5 months (range 8-308 months), the investigators reported online ahead of print in BJU International. The median time to recurrence was 59 months. In a multivariate analysis, microvascular invasion (MVI) was associated with a significant eightfold increased risk of cancer-specific death compared with the absence of MVI. The 10-year cancer-specific survival rates were 85.1% and 96.5% in patients with and without MVI, respectively.

RUN0513_News2.indd 36

C. Gelber, MD, PhD, of the Johns Hopkins School of Public Health, and others based their findings on an analysis of data from 15,132 adult participants in the National Health and Nutrition Examination Surveys (NHANES) from 1988-1994 and 2007-2010. In both NHANES timeframes, approximately 1%-2% of subjects with eGFRs of 90 mL/min/1.73 m2 or higher had gout compared with 30% among participants with eGFRs below 30. The team observed a similar pattern for albuminuria, even after adjusting for factors such as age, sex, race/ ethnicity, hypertension, body mass index, and diabetes. They also found an overall 2.7% prevalence of gout among Americans in the 1988-1994 timeframe and of 3.7% in 2007-2010. In both periods, the researchers observed an inverse relationship between the proportion of individuals with a reduced eGFR and with gout or hyperuricemia,

“Early detection of recurrent disease may provide a chance for disease control with surgical treatment,” the authors wrote. “Therefore, careful follow-up is necessary for patients with RCC with MVI even though the disease is small and organ-confined.” The authors observed that there is no consensus on surveillance for small and organ-confined RCC later than five years postoperatively, but the data from their study suggest that “late recurrence of RCC after the initial treatment is not rare, which indicates that lifelong follow-up may be mandatory.” The researchers pointed out that the widespread use of routine abdominal imaging enables detection of small, organ-confined RCC, which generally has favorable pathologic characteristics and a good prognosis. Tumor size alone, however, is not sensitive enough to precisely predict long-term clinical behavior, they noted. Dr. Shindo’s group added that the development of molecular-targeted therapy has changed the therapeutic approaches for treatment of metastatic RCC. Their study included data from before the development of targeted therapy. “Therefore, we have no information on patients with small, organconfined RCC who received moleculartargeted therapy,” they stated. n

and a direct relationship between increased albuminuria and gout or hyperuricemia. In addition, in both NHANES timeframes, the mean eGFR for subjects with gout was 76-82, compared with 97-102 for subjects without gout.

New-onset joint pain or swelling in a CKD patient could signal undiagnosed gout. Furthermore, the median albuminto-creatinine ratio among those with gout was approximately 10 mg/g compared with 6 mg/g among those without gout. “We found that incremental changes in GFR, albuminuria, and CKD are associated with a higher prevalence of gout,” Juraschek said. “These findings

were not merely relegated to persons with severe CKD. And they also persist even after accounting for multiple risk factors associated with both CKD and gout, including levels of uric acid. Uric acid is arguably the most important mediator of gout, yet our findings show that there is a relationship between kidney disease and gout that is independent of uric acid.” He and his co-investigators believe health practitioners treating CKD patients with new-onset joint pain or swelling should be vigilant for undiagnosed gout, while physicians treating patients with gout should be wary of CKD as an underlying factor contributing to both hyperuricemia and gout risk, since many urate-lowering medications require renal dosing or have associated nephrotoxicity. The researchers noted that the NHANES studies are cross-sectional, so the causal direction of associations between kidney function and gout cannot be determined. n

Left Atrial Enlargement Linked to High Plasma Sodium in CKD Subclinical left atrial enlargement

The study also found that the preva-

(LAE) is highly prevalent in patients with

lence of LAE increased with the pres-

stage 3-5 chronic kidney disease (CKD)

ence of left ventricular (LV) hypertrophy

and it is strongly associated with plasma

and increased with increasing severity

sodium concentration, according to a

of CKD. The researchers observed mild/

newly published report.

moderate LAE and severe LAE in 22.9%

In a study of 261 stage 3-5 CKD

and 41.3% of patients with LV hypertro-

patients not on dialysis and free of

phy compared with 13.2% and 12.5% of

symptomatic cardiovascular disease,

those without LV hypertrophy.

109 (41.8%) had subclinical LAE

“To our knowledge, this study is

found on two-dimensional echocardiog-

the first ever to demonstrate a strong,

raphy, Angela Yee-Moon Wang, MD, of

positive relationship between plasma

Queen Mary Hospital, University of Hong

sodium concentration and subclinical

Kong, and colleagues reported online

LAE in CKD patients,” the authors wrote.

ahead of print in Nephrology Dialysis

The investigators pointed out that,

Transplantation. Compared with patients

contrary to a previous study by another

in the lowest tertile of plasma sodium

team, they did not observe any associa-

levels, those in the highest tertile had

tion between plasma sodium concentra-

a 23% increased odds having LAE in a

tion and estimated glomerular filtration

fully adjusted model, according to the

rate in their study population. “This

researchers. The importance of elevated

suggests that the association between

plasma sodium appears to outweigh

high plasma sodium concentration

other factors well known wto be associ-

and subclinical LAE is unlikely to be

ated with LAE, such as systolic hyperten-

explained by worsening kidney function,”

sion, anemia, and hypoalbuminemia.

the investigators stated. n

4/25/13 4:57 PM

www.renalandurologynews.com may 2013

Renal & Urology News 37

CME feature

Medical and Surgical Management of Bladder Outlet Obstruction Treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia has evolved from surgical therapy to medical monotherapy, and now combination therapy.

Release Date: May 2013 Expiration Date: May 2014 Estimated time to complete the educational activity: 1 hour This activity is jointly sponsored by Medical Education Resources and Haymarket Medical Education. Statement of Need: Treatment of BPH-related LUTS has evolved from surgical therapy to medical monotherapy, and now combination therapy. Urologists and support staff who treat patients with BPH need to be aware of current combination therapy protocols in the management of male LUTS. Target Audience: This activity has been designed to meet the needs of urologists, and allied healthcare clinicians who treat patients with bladder outlet obstruction. Educational Objectives: After completing the activity, the participant should be better able to: • Assess treatment options in males with benign prostatic hyperplasia, based on severity of voiding symptoms. • Identify varying oral agents used in the management of bladder outlet obstruction. Accreditation Statement: This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of Medical Education Resources (MER) and Haymarket Medical Education. MER is accredited by the ACCME to provide continuing medical education for physicians. Credit Designation: Medical Education Resources designates this enduring material for a maximum of 1.0 AMA PRA Category 1 Credit TM. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Disclosure of Conflicts of Interest: Medical Education Resources ensures balance, independence, objectivity, and scientific rigor in all our educational programs. In accordance with this policy, MER identifies conflicts of interest with its instructors, content managers, and other individuals who are in a position to control the content of an activity. Conflicts are resolved by MER to ensure all scientific research referred to, reported, or used in a CME activity conforms to the generally accepted standards of experimental design, data collection, and analysis. MER is committed to providing its learners with high-quality CME activities that promote improvements or quality in health care and not a commercial interest. The faculty reported the following financial relationships with commercial interests whose products or services may be mentioned in this CME activity: Name of Faculty Bilal Chughtai, MD Steven A. Kaplan, MD

Reported Financial Relationship No financial relationships to disclose Research Support: Pfizer

Bilal Chughtai, MD, and Steven A. Kaplan, MD

oiding symptoms in males are typically attributed to benign prostatic hyperplasia (BPH). A histologic diagnosis of BPH will develop in approximately half of men older than 40 years of age. Lower urinary tract symptoms (LUTS) secondary to bladder outlet obstruction (BOO) will develop in about half of these men.1,2 Treatments for BPH are aimed at improving subjective symptoms and quality of life (QoL). Using standardized survey instruments, such as the American Urological Association Symptom Score (AUA-SS), allows for a validated method to determine severity of disease. Those with minimal symptoms and low degree of bother can be observed or started on medications, whereas those with severe bother may require surgical intervention. The aim of this article is to provide a contemporary review of the current management protocols for male LUTS.

Observation Men with minimal clinical symptoms as per the AUA-SS (≤7) can be observed. In a study of men randomized to observation or lifestyle changes, those with lifestyle changes significantly reduced the frequency of treatment failure and severity of symptoms.3 These men can be advised about behavioral modifications that include fluid restriction, timed voiding, and double voiding. Observation can also be advised to those with moderate symptoms (8–19 points) with minimal bother. These patients do require periodic reevaluation to avoid recurrent infection, bladder stones, urinary retention, refractory hematuria, or renal dysfunction.

Phytotherapy Saw palmetto is a commonly used over-the-counter medication for symptoms of an enlarged prostate, but neither the American Urological Association (AUA) nor the European

The content managers, Jody A. Charnow and Marina Galanakis, of Haymarket Medical Education, and Julie Johnson, PharmD, of Medical Education Resources, have disclosed that they have no relevant financial relationships or conflicts of interest. Method of Participation: There are no fees for participating in and receiving CME credit for this activity. During the period May 2013 through May 2014, participants must: 1) read the learning objectives and faculty disclosures, 2) study the educational activity, 3) complete the posttest and submit it online. Physicians may register at www.myCME.com/ renalanurologynews, and 4) complete the evaluation form online. A statement of credit will be issued only upon receipt of a completed activity evaluation form and a completed post-test with a score of 70% or better.

RUN0513_CME.Kaplan.indd 37

Bilal Chughtai, MD (left), and Steven A. Kaplan, MD (right), are in the Department of Urology at Weill Cornell Medical College in New York. Dr. Chughtai is an Assistant Professor and Dr. Kaplan is the E. Daracott Vaughn Jr. Professor of Urology. Dr. Kaplan is also is Chief of the Institute for Bladder and Prostate Health and Director of the Iris Cantor Men’s Health Center.

4/25/13 5:01 PM

38 Renal & Urology News

may 2013 www.renalandurologynews.com

CME feature

Association of Urology support its use. The CAMUS (Complementary and Alternative Medicine for Urological Symptoms) trial, which included 357 men at 11 sites who were randomized to 320 mg, 640 mg, 960 mg of saw palmetto in an escalating fashion or placebo, found no difference in the escalating dose of saw palmetto compared with placebo.4

Alpha-adrenergic blockers Alpha-adrenergic antagonists (alpha blockers) are considered first-line treatment for male LUTS.5,6 It has been hypothesized that BPH causes BOO and symptoms partially through increased alpha-adrenergic stimulation leading to increased urethral smooth muscle tone and intraurethral pressure. Alpha-adrenerigic antagonists, therefore, are used to treat symptoms of increased urethral resistance. The alpha-adrenergic antagonists most commonly used for treating LUTS include alfuzosin, doxazosin, tamsulosin, and terazosin. All these agents are selective for the alpha-1 receptor subtype present in prostatic tissue. In the prostate and urethra, the alpha-1A receptor subtype is most prevalent. Numerous studies have confirmed the efficacy and tolerability of alpha-adrenergic antagonists.7-9 No single agent has been proven to be significantly more efficacious than another. Adverse effects are reported in approximately 5%-9% of patient populations taking alpha-adrenergic antagonists.10 These include dizziness, postural hypotension, asthenia, rhinitis, and sexual dysfunction, including abnormal ejaculation. The AUA Clinical Practice Guidelines Committee conducted a meta-analysis and concluded that alpha-adrenergic antagonists were beneficial in treating BOO and detrusor overactivity due to BPH.5 These agents generally improve the AUA symptom score by 4-6 points.

5-alpha-reductase inhibitors (5-ARIs) The enzyme 5-alpha-reductase converts testosterone to dihydrotestosterone (DHT). Castration and pharmacologic agents that suppress testosterone and/or DHT production have been shown to reduce prostate size in men with BPH.11 Reducing prostate volume

RUN0513_CME.Kaplan.indd 38

An enlarged prostate (shown above) can squeeze the bladder neck, impeding the flow of urine.

is hypothesized to decrease the static component of BOO caused by BPH. The 5-ARIs finasteride and dutasteride are safe and effective in the treatment of BPH. Dutasteride inhibits both type 1 and type 2 isoenzymes, whereas finasteride inhibits only the type 2 isoenzyme. Studies have found that 5-ARIs tend to be more efficacious in patients with larger rather than smaller prostates.12

Phosphodiesterase type 5 (PDE-5) inhibitors Several trials have shown subjective benefit to tadalafil for LUTS. Gacci et al reported on a meta-analysis that pooled 3,214 men. Seven of the trials compared PDE-5 inhibitors with placebo and five compared PDE-5 inhibitors plus alpha blockers with placebo.13 Median follow up was 12 weeks. There was a significant improvement in erectile function based on the International Index of Erectile Function (IIEF) and AUA-SS. Although there were statistically significant improvements in subjective parameters, there were no improvements in objective parameters. Although no direct relationship has been proven, PDE-5 inhibitors appear to improve BPH-related LUTS. Although subjective improvement has been reported via improvement in IPSS scores, no improvement in objective parameters such Qmax (maximal flow rate) or post-void residual (PVR) volume, however, was seen in these studies. As such, the use of PDE-5 inhibitors remains to be determined and should not be used as first-line therapy. In addition, long-term experience with PDE-5 inhibitors to treat

LUTS is still lacking. As a warning, all PDE-5 inhibitors should not be used in patients who are taking the alpha blockers doxazosin or terazosin due to the risk of hypotension.

Combination therapy Alpha blockers with 5-ARIs. The Medical Therapy of Prostatic Symptoms (MTOPS) trial was the first study to demonstrate the efficacy of combination therapy over alpha blocker or 5-alpha-reductase monotherapy.14 This study was followed by a 4,844-patient trial evaluating the efficacy of combination therapy using dutasteride and tamsulosin in men with moderate-tosevere LUTS secondary to BPH.15 This multicenter, randomized, double-blind trial demonstrated that combination treatment achieved significantly greater mean reductions in both voiding and storage symptoms than either monotherapy at 24 months. Dutasteride alone was as effective as tamsulosin for controlling storage symptoms, but provided significantly greater relief of voiding symptoms at 24 months. At this time point, combination therapy was more effective than monotherapy for voiding symptoms in men with prostate volumes of 30-42 cm3. Moreover, combination therapy led to significant increases in patientreported, disease-specific QoL.16 At four years, the study demonstrated that patients taking dutasteride significantly increased their time to first episode of acute urinary retention (AUR) or BPHrelated surgery compared with tamsulosin alone.17

Alpha blockers and PDE-5 inhibitors. Combination therapy using both alpha blockers and PDE-5 inhibitors for LUTS and erectile dysfunction (ED) is gaining interest because of the increasing frequency of co-prescription in the aging population. In a study by Kaplan et al, 62 men with previously untreated LUTS and ED were randomized to daily 25 mg sildenafil versus 10 mg alfuzosin versus combination therapy.18 Combination therapy was associated with greater improvement in IPSS and IIEF scores over either monotherapy. The most common adverse effects included dyspepsia, dizziness, and flushing.

Onabotulinumtoxin A Several single-arm trials have shown benefit of onabotulinumtoxinA (Botox) injection to the prostate either through a transrectal or transperineal route. In a multicenter, double blind, phase 2 dose-finding study, 380 men were randomized to receive either placebo or onabotulinumtoxin A either through a transperineal or transrectal route.19 All patients experienced an improvement in all parameters, including AUA-SS and Qmax. There was a large placebo effect noted from both transperineal and transrectal injections.

Minimally invasive therapy Transurethral microwave therapy (TUMT). In a Cochrane Review published in 2012, researchers reviewed 15 studies of TUMT involving 1,585 patients. These studies included six comparisons of TUMT with transurethral resection of the prostate (TURP), eight comparisons with sham thermotherapy procedures, and one comparison with an alpha blocker.20 Study durations ranged from 3-60 months. The pooled mean urinary symptom scores decreased by 65% with TUMT. The pooled mean peak urinary flow increased by 70% with TUMT. Compared with TURP, TUMT was associated with decreased risks for retrograde ejaculation, treatment for strictures, hematuria, blood transfusions, and the transurethral resection (TUR) syndrome, but increased risks for dysuria, urinary retention, and retreatment for BPH symptoms. No studies evaluated the effects of symptom

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Renal & Urology News 39

CME feature duration, patient characteristics, PSA levels, or prostate volume on treatment response.

Prostatic urethral lift (Urolift) The prostatic urethral lift system is a relatively new non-ablative technique that uses solely mechanical compression to open the prostatic urethra. A handheld delivery device is fired with transurethral sutures at the anterolateral lobes of the prostate. In a smaller prostate (e.g. 60 grams), two to four sutures are needed, whereas larger glands require more sutures. A relative contraindication for the prostatic urethral lift system is a large median lobe. The device has been tested in other countries, but has not been approved by the FDA. Initially the safety of the device was tested in 19 men with moderate-to-severe LUTS. 21 All patients tolerated the procedure with no serious or unexpected adverse events. The most common adverse event was hematuria (63%) or dysuria (58%) that resolved in three to five days. The device was then evaluated in a prospective multicenter trial in Australia that enrolled 64 men with moderate to severe LUTS.22 The study demonstrated a 42% improvement at two years in IPSS and 30% improvement in peak flow. About half of the patients did not have a post-operative catheter, and three quarters of the patients requiring post-operative catheters had the catheters removed the next day. In addition, there were no reports of anejaculation or retrograde ejaculation. Erectile function as measured using the Sexual Health Inventory for Men (SHIM) questionnaire, was slightly improved from baseline. The most common adverse effects included irritative symptoms and hematuria that resolved within the first few weeks. This initial data from this multicenter single-arm trial seems promising. The prostatic urethral lift system does require physician education, ease with insertion, and reproducibility. Furthermore, the device requires rigid cystoscopy in an awake male, which itself is a challenge.

RUN0513_CME.Kaplan.indd 39

GreenLight laser prostatectomy Lasers for the treatment of LUTS/BPH were introduced in part to decrease surgical morbidity. The 532 nm wavelength is selectively absorbed by hemoglobin, which acts as an intracellular chromophore and is fully transmitted through aqueous irrigants. The short optical penetration associated with this wavelength confines its high power laser energy to a superficial layer of prostatic tissue that is vaporized rapidly and hemostatically with only a 1-2 mm rim of coagulation.24 The GreenLight laser system has gone through several evolutions from the original 60-watt laser to the most recent 180-watt system with a larger water cooled fiber. A recent multicenter prospective study similarly demonstrated the performance of the 180-watt system. Bachman et al examined 201 patients with LUTS who had a mean follow-up of 5.8 ± 2.8 months.23 Improvements in Qmax, IPSS, PVR, QoL, and PSA from baseline measures were significant in all patients after surgery (p<0.001). The researchers reported that the 180-watt laser system applied three times the energy (324.4 ± 187.5 kJ) of the 80-watt laser in the same lasing time (38.2 ± 20.4 min) without additional complications, including in patients with urinary retention and on anticoagulants. The prevalence of perioperative complications was low, and included impaired visibility due to bleeding (10%), capsule perforation (3.5%), and urinary retention during the hospital stay (5%). They also reported mild to moderate dysuria (8.0%), urethral stricture (1.0%), temporary urinary incontinence (8.0%), urinary tract infection (UTI, 2.5%), and retention (2.5%).

Transurethral resection of the prostate Geavlete et al completed a prospective three-armed study with 510 randomized patients comparing monopolar TURP, bipolar TURP, and bipolar transurethral vaporization of the prostate (TUVP). Patients undergoing bipolar TUVP demonstrated significantly better improvements in IPSS and Qmax compared with both monopolar and bipolar TURP at 18 months (by 3.3 and 2.9, and 3.5 mL and 3.1 mL

respectively, p<0.05), although QoL, PVR, and PSA for each group were similar.24 Seckiner et al performed a prospective randomized study of 21 patients undergoing monopolar TURP and 23 with bipolar TUVP with one year follow-up. The investigators observed comparable improvements in IPSS, QoL, and Qmax, (by 14.9 and 15.4, 2.7 and 2.6, and 7.4 and 10.3 mL/ sec, respectively), but these differences were not reported to be statistically significant.25 In separate prospective randomized trials comparing monopolar TURP and bipolar TUVP, Hon et al reported similar improvements in IPSS, QoL, Qmax, and PVR (by 13.7 and 13.6, 2.8 and 2.5, 11.6 and 13.6 mL/ sec, and 113 and 83 mL, respectively), and Patankar et al reported similar improvements in IPSS and Qmax (by 16.01 and 17.19, and 14.27 and 13.26 mL/sec), although with shorter or uncertain durations of follow-up.26, 27 However, patients who had undergone bipolar TUVP were significantly less frequently affected by hyponatremia (p<0.005) and had significantly shorter catheter retention times (73.2±13.4h vs. 54.3±11.8h, p<0.005).28 In the longest reported study comparing monopolar TURP and bipolar TUVP, Xie et al reported that patients treated with bipolar TUVP demonstrated a 15.55 point decrease in IPSS, a 2.66 point decrease in QoL, a 1.09 ng/mL decrease in serum PSA, a 16.55 mL/sec increase in Qmax, and an 82.79 mL decrease in PVR after five years. Improvements in these parameters were similar to those seen for patients undergoing monopolar TURP.29 Complications for TURP can include retention, UTI, incontinence, capsule perforation, TUR syndrome, blood

transfusion, and urethral stricture.30 Other studies have reported mixed results with TUVP in regards to complications. Geavlete et al, for example, found that bipolar TUVP produced fewer complications than monopolar TURP (1.2% vs. 9.4% capsular perforation, p = 0.004; 23.5 vs. 72.8 hour catheterization period, p=0.0001; and 0.5 vs. 1.6 g/dL hemoglobin drop, p = 0.0001, respectively),24 whereas others observed statistically similar rates of complication between bipolar TUVP and monopolar TURP. For example, Xie et al reported similar rates of urinary retention, UTI, TUR syndrome, and blood transfusion between monopolar TURP and bipolar TUVP.29

Open Surgery Open surgery is typically reserved for those with prostate glands larger than 80 grams. The envelope for this has been pushed, especially in the hands of those very experienced with transurethral techniques. Open techniques lead to an improvement of AUA-SS by 11-20 points. Early complication rates are 17.3% and are associated with prolonged hospitalization and recovery.31

Conclusions Treatment of BPH-related LUTS has evolved from surgical therapy to medical monotherapy to combination therapy. The combination of 5-alpha-reductase inhibitors with alpha-adrenergic antagonists is effective in men with LUTS secondary to BPH. At present, only combination therapy with alpha-adrenergic antagonists and 5-ARIs is recommended in

Table 1. Choice of Oral Agents for BOO Alpha blockers • Alfuzosin

• Terazosin

• Doxazosin

•• Silodosin

• Tamsulosin

5-alpha-reductase inhibitors (5-ARIs) • Dutasteride

• Finasteride

Alpha blocker and 5-ARI • Dutasteride and tamsulosin

Phosphodiesterase-5 inhibitor • Tadalafil

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CME FEATURE clinical practice guidelines. Further studies are required to elucidate which specific population of patient benefits most from other combination therapies. ■ REFERENCES 1. Girman CJ. Natural history and epidemiology of benign prostatic hyperplasia: relationship among urologic measures. Urology 1998;51(4A Suppl):8-12. 2. Roehrborn CG. Etiology, pathophysiology, epidemiology and natural history of benign prostatic hyperplasia. Campbell-Walsh Urology. 3. Brown CT, Yap T, Cromwell DA, et al. Self management for men with lower urinary tract symptoms: randomised controlled trial. BMJ 2007;334(7583):25. 4. Avins AL, Lee JY, Meyers CM, Barry MJ. Safety and toxicity of saw palmetto in the Complementary and Alternative Medicine for Urological Symptoms (CAMUS) Trial. J Urol. 2012 (published online ahead of print Oct. 9) 5. Guideline on the Management of Benign Prostatic Hyperplasia (BPH). Clinical Guidelines [serial on the Internet]. 2003. 6. de La Rosette J, Alivizatos G, Madersbacher M, et al. Guidelines on Benign Prostatic Hyperplasia. Guidelines [serial on the Internet]. 2004. 7. Elhilali M, Ramsey E, Barkin J, et al. A multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of terazosin in the treatment of benign prostatic hyperplasia. Urology 1996;47:335-342. 8. Roehrborn C. Efficacy and safety of once-daily alfuzosin in the treatment of lower urinary tract symptoms and clinical benign prostatic hyperplasia: a randomized, placebo-controlled trial. Urology 2001;58:953-959. 9. Roehrborn C, Siegel R. Safety and efficacy of doxazosin in benign prostatic hyperplasia: a pooled analysis of three double-blind, placebo-controlled studies. Urology 1996;48:406-415. 10. Debruyne F. Alpha blockers: are all created equal? Urology 2000; 56(5 suppl 1):20-22. 11. McConnell J. Medical management of benign prostatic hyperplasia with androgen suppression. Prostate 1990;3(Suppl):49-59. 12. Kaplan S, McConnell J. Combination therapy with doxazosin and finasteride for benign prostatic hyperplasia in patients with lower urinary tract symptoms and a baseline total prostate volume of 25 mL or greater. J Urol 2006;175:217-220. 13. Marberger M, Chartier-Kastler E, Egerdie B, et al. A randomized double-blind placebo-controlled phase 2 dose-ranging study of onabotulinumtoxinA in men with benign prostatic hyperplasia. Eur Urol 2013;63:496-503. 14. McConnell JD, Roehrborn CG, Bautista OM, et al. The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med 2003;349:2387-2398. 15. Becher E, Roehrborn CG, Siami P, et al. The effects of dutasteride, tamsulosin, and the combination on storage and voiding in men with benign prostatic hyperplasia and prostatic enlargement: 2-year results from the Combination of Avodart and Tamsulosin study. Prostate Cancer Prostatic Dis. 2009;12:369-374.

16. Barkin J, Roehrborn CG, Siami P, et al. Effect of dutasteride, tamsulosin and the combination on patient-reported quality of life and treatment satisfaction in men with moderate-to-severe benign prostatic hyperplasia: 2-year data from the CombAT trial. BJU Int. 2009;103:919-926. 17. Roehrborn CG, Siami P, Barkin J, et al. The effects of combination therapy with dutasteride and tamsulosin on clinical outcomes in men with symptomatic benign prostatic hyperplasia: 4-year results from the CombAT study. Eur Urol. 2010;57:123-131. 18. Kaplan S, Gonzalez R, Te A. Combination of alfuzosin and sildenafil is superior to monotherapy in treating lower urinary tract symptoms and erectile dysfunction. Eur Urol 2007;51:1717-1723. 19. Marberger M, Chartier-Kastler E, Egerdie B, et al. A randomized double-blind placebo-controlled phase 2 dose-ranging study of onabotulinumtoxinA in men with benign prostatic hyperplasia. Eur Urol 2013;63:496-503. 20. Hoffman RM, Monga M, Elliott SP, et al. Microwave thermotherapy for benign prostatic hyperplasia. Cochrane Database Syst Rev. 2012;9). 21. Woo HH, Chin PT, McNicholas TA, et al. Safety and feasibility of the prostatic urethral lift: a novel, minimally invasive treatment for lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). BJU Int 2011;108:82-88. 22. Chin PT, Bolton DM, Jack G, et al. Prostatic urethral lift: two-year results after treatment for lower urinary tract symptoms secondary to benign prostatic hyperplasia. Urology 2012;79:5-11. 23. Bachmann A, Muir GH, Collins EJ et al. 180-W XPS GreenLight laser therapy for benign prostate hyperplasia: Early safety, efficacy, and perioperative outcome After 201 procedures. Eur Urol 2011;61:600-607. 24. Geavlete B, Georgescu D, Multescu R, Stanescu F, Jecu M, Geavlete P. Bipolar plasma vaporization vs monopolar and bipolar TURP–A prospective, randomized, long-term comparison. Urology 2011;78:930-935. 25. Seckiner I, Yesilli C, Akduman B, Altan K, Mungan NA. A prospective randomized study for comparing bipolar plasmakinetic resection of the prostate with standard TURP. Urol Int 2006;76:139-143. 26. Hon NH, Brathwaite D, Hussain Z, et al. A prospective, randomized trial comparing conventional transurethral prostate resection with PlasmaKinetic® vaporization of the prostate: physiological changes, early complications and long-term followup. J Urol 2006;176:205-209. 27. Patankar S, Jamkar A, Dobhada S, Gorde V. PlasmaKinetic Superpulse transurethral resection versus conventional transurethral resection of prostate. J Endourol 2006;20:215-219. 28. Nuho˘ glu B, Balci MBC, Aydin M, Hazar I, Onuk Ö, Tas¸ ’ T, et al. The role of bipolar transurethral vaporization in the management of benign prostatic hyperplasia. Urol Int 2011;87:400-404. 29. Xie C-Y, Zhu G-B, Wang X-H, Liu X-B. Five-Year follow-up results of a randomized controlled trial comparing bipolar plasmakinetic and monopolar transurethral resection of the prostate. Yonsei Med J 2012;53:734-741. 30. Rassweiler J, Teber D, Kuntz R, Hofmann R. Complications of transurethral resection of the prostate (TURP)—incidence, management, and prevention. Eur Urol 2006;50:969-979. 31. Gratzke C, Schlenker B, Seitz M, Karl A, Hermanek P, Lack N, et al. Complications and early postoperative outcome after open prostatectomy in patients with benign prostatic enlargement: results of a prospective multicenter study. J Urol 2007;177:1419-1422.

DISCLAIMER: The content and views presented in this educational activity are those of the authors and do not necessarily reflect those of Medical Education Resources or Haymarket Medical Education. The authors have disclosed if there is any discussion of published and/or investigational uses of agents that are not indicated by the FDA in their presentations. The opinions expressed in this educational activity are those of the faculty and do not necessarily represent the views of Medical Education Resources, or Haymarket Medical Education. Before prescribing any medicine, primary references and full prescribing information should be consulted. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patient’s conditions and possible contraindications on dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities. The information presented in this activity is not meant to serve as a guideline for patient management.

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CME Post-test Expiration Date: May 2014 Medical Education Resources designates this educational activity for a maximum of 1.0 AMA PRA Category 1 Credit™. Participants should claim only the credit commensurate with the extent of their participation in the activity. Physician post-tests must be completed and submitted online. Physicians may register at no charge at www.myCME.com /renalandurologynews. You must receive a score of 70% or better to receive credit. 1. Which of the following statements about alpha-adrenergic blockers is true with respect to efficacy in the treatment of male LUTS? a. Alfuzosin is significantly more effective than doxazosin b. Tamsulosin is significantly more effective than alfuzosin c. Doxazosin is significantly more effective than terazosin d. No single agent is significantly better than another 2. When is observation an appropriate management option for men with BPH-related LUTS? a. The patient has minimal clinical symptoms (American Urological Association Symptom Score [AUA-SS] ≤7) b. The patient has moderate symptoms (AUA-SS 8-19) and minimal bother c. Both a and b d. Neither a nor b 3. Saw palmetto is a recommended treatment for lower urinary tract symptoms (LUTS) from the American Urological Association (AUA). a. True b. False 4. Which of the following combination therapies do clinical guidelines recommend for the treatment of BPH-related LUTS? a. Alpha-adrenergic antagonists and 5-alpha-reductase inhibitors (5-ARIs) b. 5-ARIs and phosphodiesterase type 5 (PDE-5) inhibitors c. PDE-5 inhibitors and alpha-adrenergic antagonists 5. Which of the following statements is correct regarding benign prostatic hyperplasia (BPH)? a. Anticholinergics play no role in treating BPH since this class of medication decreases bladder contractility in the setting of bladder outlet obstruction b. Alpha 2 is the most prevalent alpha-receptor subtype in the prostate c. All men with BPH experience bladder outlet obstruction d. Treatment of BPH with finasteride leads to a reduction in serum levels of dihydroxytestosterone (DHT) by approximately 70% compared to approximately 95% with dutasteride 6. Onabotulinumtoxin injected into the prostate has shown clinical efficacy greater than placebo. a. True b. False 7. Rates of retrograde ejaculation in TUMT are compared to transurethral surgery. a. Less than b. Greater than c. Equal to

those as

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HTN Rates Found To Vary Among Asian-Americans A study of 242,790 patients found that Filipinos had the highest rates, followed by the Japanese BY JILL STEIN SAN FRANCISCO—Investigators have documented substantial heterogeneity in the rates of hypertension among Asian-American subgroups. The data, released at the American College of Cardiology annual meeting, also show that the Filipino subgroup has the highest rates of hypertension, followed by the Japanese subgroup. “Our results suggest that susceptible populations like the Filipino and Japanese subgroups may warrant early and aggressive intervention in blood pressure reduction to help decrease cardiovascular risk,” said Powell Jose, MD, Research Physician at the Palo Alto Medical Foundation Research Institute. “Physicians should attempt to better understand cultural differences and barriers that may influence diet and health behaviors in AsianAmerican subgroups. Nutrition and lifestyle counseling must be offered to these higher risk populations to help control hypertension in addition to medical therapy, when indicated.” Dr. Jose and his colleagues used electronic health records to compare the rates of hypertension for several AsianAmerican subgroups with other racial/ ethnic groups. Their analysis included 242,790 patients who were enrolled in a large, mixed-payer, outpatient health maintenance organization in the San Francisco Bay Area, who were identified through self-report or by their name to be Asian-American (AsianIndian, -Chinese , -Filipino, -Japanese, -Korean, or -Vietnamese), Hispanics, non-Hispanic blacks, or non-Hispanic whites. Higher rates of coronary heart disease have been reported for some Asian-American subgroups, especially Asian-Indians and Asian-Filipinos. Knowledge of cardiovascular risk factors among Asian-American subgroups is inadequate, he said. For example, hypertension is a major coronary risk factor, but hypertension rates among Asian-American subgroups are unknown, which is primarily because of underrepresentation or aggregation of Asian-American subgroups in epidemiologic studies. Individuals in the present analysis

were deemed hypertensive if their blood pressure was 140/90 mm Hg or higher during two separate nonemergent office visits or if they had an ICD-9 coding for hypertension, or reported using any anti-hypertensive medication. Results showed that hypertension rates controlled for age and sex were lower for aggregated Asian-Americans (34.9%) compared to non-Hispanic whites (38.9%). However, when disaggregated by Asian-American subgroups, Filipinos had markedly higher hypertension rates (51.9%) than nonHispanic whites. In addition, adjusted hypertension rates were lower among most Asian-American subgroups including Chinese (29.8%), Koreans (30.7%), Vietnamese (30.8%), and AsianIndians (36.9%) than non-Hispanic whites. The Japanese subgroup had

Early aggressive intervention may be warranted for susceptible groups. hypertension rates (38.2%) that were similar to non-Hispanic whites. Further analysis revealed that Filipinos and Japanese were the only high-risk Asian-American groups for hypertension compared to whites. The study found no significant gender differences in racial/ethnic patterns of hypertension rates. Dr. Jose cautioned that the study was confined to a single geographic area with small sample sizes in some Asian-American subgroups, thereby limiting the generalizability of the results. In addition, because of the study’s cross-sectional design, the researchers were not able to examine for potential causal relationships. Finally, the investigators were unable to control for some socioeconomic variables such as education and income, behavioral variables such as diet, and clinical variables such as medication adherence, all of which may influence prevalence rates. n

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PROVENGE® (sipuleucel-T) Suspension for Intravenous Infusion

Rx Only

BRIEF SUMMARY — See full Prescribing Information for complete product information

INDICATIONS AND USAGE: PROVENGE® (sipuleucel-T) is an autologous cellular immunotherapy indicated for the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer. DOSAGE AND ADMINISTRATION • For Autologous Use Only. • The recommended course of therapy for PROVENGE is 3 complete doses, given at approximately 2-week intervals. • Premedicate patients with oral acetaminophen and an antihistamine such as diphenhydramine. • Before infusion, confirm that the patient’s identity matches the patient identifiers on the infusion bag. • Do Not Initiate Infusion of Expired Product. • Infuse PROVENGE intravenously over a period of approximately 60 minutes. Do Not Use a Cell Filter. • Interrupt or slow infusion as necessary for acute infusion reactions, depending on the severity of the reaction. (See Dosage and Administration [2] of full Prescribing Information.) CONTRAINDICATIONS: None. WARNINGS AND PRECAUTIONS • PROVENGE is intended solely for autologous use. • Acute infusion reactions (reported within 1 day of infusion) included, but were not limited to, fever, chills, respiratory events (dyspnea, hypoxia, and bronchospasm), nausea, vomiting, fatigue, hypertension, and tachycardia. In controlled clinical trials, 71.2% of patients in the PROVENGE group developed an acute infusion reaction. I n controlled clinical trials, severe (Grade 3) acute infusion reactions were reported in 3.5% of patients in the PROVENGE group. Reactions included chills, fever, fatigue, asthenia, dyspnea, hypoxia, bronchospasm, dizziness, headache, hypertension, muscle ache, nausea, and vomiting. The incidence of severe events was greater following the second infusion (2.1% vs 0.8% following the first infusion), and decreased to 1.3% following the third infusion. Some (1.2%) patients in the PROVENGE group were hospitalized within 1 day of infusion for management of acute infusion reactions. No Grade 4 or 5 acute infusion reactions were reported in patients in the PROVENGE group. Closely monitor patients with cardiac or pulmonary conditions. In the event of an acute infusion reaction, the infusion rate may be decreased, or the infusion stopped, depending on the severity of the reaction. Appropriate medical therapy should be administered as needed. • Handling Precautions for Control of Infectious Disease. PROVENGE is not routinely tested for transmissible infectious diseases. Therefore, patient leukapheresis material and PROVENGE may carry the risk of transmitting infectious diseases to health care professionals handling the product. Universal precautions should be followed. • Concomitant Chemotherapy or Immunosuppressive Therapy. Use of either chemotherapy or immunosuppressive agents (such as systemic corticosteroids) given concurrently with the leukapheresis procedure or PROVENGE has not been studied. PROVENGE is designed to stimulate the immune system, and concurrent use of immunosuppressive agents may alter the efficacy and/or safety of PROVENGE. Therefore, patients should be carefully evaluated to determine whether it is medically appropriate to reduce or discontinue immunosuppressive agents prior to treatment with PROVENGE. • Product Safety Testing. PROVENGE is released for infusion based on the microbial and sterility results from several tests: microbial contamination determination by Gram stain, endotoxin content, and in-process sterility with a 2-day incubation to determine absence of microbial growth. The final (7-day incubation) sterility test results are not available at the time of infusion. If the sterility results become positive for microbial contamination after PROVENGE has been approved for infusion, Dendreon will notify the treating physician. Dendreon will attempt to identify the microorganism, perform antibiotic sensitivity testing on recovered microorganisms, and communicate the results to the treating physician. Dendreon may request additional information from the physician in order to determine the source of contamination. (See Warnings and Precautions [5] of full Prescribing Information.) ADVERSE REACTIONS Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the

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