Renal & Urology News - July/Aug 2018 issue

J U L Y /A U G U S T 2 0 1 8

■ ■ ■

V O L U M E 17, I S S U E N U M B E R 4

■ ■ ■

www.renalandurologynews.com

Robotics’ Rise in Urologic Cancer Surgery In 2015, 69% of prostate, bladder, and kidney cancer surgeries involved robotics, meta-analysis finds

© AGE FOTOSTOCK / ALAMY STOCK PHOTO

ROBOTIC SURGERY SOARS

Robotic urologic cancer surgery cases increased substantially from 2005 to 2015, a meta-analysis found.

Shown here are the proportions of major urologic cancer surgeries performed with robotic assistance in 2015.

85.4%

Radical prostatectomy

32.8%

Radical cystectomy

66.1%

Radical nephrectomy

Source: Gill I, Cacciamani G. The changing face of urologic oncologic surgery from 2000–2018 (63,141 patients) Impact of robotics.

Presented at the 2018 American Urological Association annual meeting in San Francisco, May 18–21. Abstract LBA3.

BPH, Peyronie’s Disease Linked SAN FRANCISCO—Men with Peyronie’s disease (PD) are at higher risk of benign prostatic hyperplasia (BPH), prostatitis, and various malignancies, including testis, prostate, and stomach cancer and melanoma, according to study findings presented at the American Urological Association’s 2018 Annual Meeting.

The findings are from separate studies by the same research team led by Alexander W. Pastuszak MD, PhD, of Baylor College of Medicine in Houston. For both studies, investigators relied on 2007–2013 data from the Truven Health MarketScan database, which includes information on continued on page 24

HOW TO DEAL WITH A ‘DIFFICULT’ PATIENT

Doctors must manage their own emotions, medical ethicist says.

PAGE 27

BY JODY A. CHARNOW SAN FRANCISCO—Most urologic cancer surgeries in the United States today are performed with robotic assistance, according to the first meta-analysis looking at overall trends in the use of robotics in urologic oncology.

Robotic surgeries are associated with less blood loss, fewer perioperative complications, and shorter hospital length of stay compared with open surgery, but it costs more and takes longer to perform than open surgery, the metaanalysis showed.

Of 105,300 prostate, bladder, and kidney cancer surgeries performed in 2005, robotics were used in 29.6% of cases. This proportion increased to 69.2% of 88,198 surgeries in 2015,

Advanced PCa Predicts More Complications

BY JODY A. CHARNOW MEN WITH ADVANCED prostate cancer (PCa), especially those with castration-resistant prostate cancer (CRPC), have an elevated risk of disease-related complications near the end of life, including spinal cord compression and renal failure, study findings presented at the American Society of Clinical Oncology’s 2018 Annual Meeting in Chicago suggest.

“Many patients with prostate cancer can expect excellent survival outcomes, even those with metastatic disease,” said lead investigator Divya Yerramilli, MD, of Massachusetts General Hospital in Boston. “However, there has been no comprehensive examination of how patients with prostate cancer experience major disease-related complications, such as cord compression and renal failure at the end of their lives. In other words, patients with prostate cancer live a long time, but a significant proportion of these patients suffer for a long time, too.” continued on page 24

Inderbir Gill, MD, and Giovanni Cacciamani, MD, of the University of Southern California Keck School of Medicine in Los Angeles, reported.

Of all patients undergoing radical prostatectomy (RP), radical cystectomy (RC), and partial nephrectomy (PN) in 2015, surgeons used robotic assistance in 85.4%, 32.8%, and 66.1% of cases, respectively. These data show that use of robotic surgery increased 4-, 11- and 110-fold for RP, RC, and PN, respectively, compared with 2005, according to Drs Gill and Cacciamani.

The meta-analysis, which included data from 181 papers comprising 63,141 unique surgical cases, also compared robotic and open surgery continued on page 24

IN THIS ISSUE 2

Postoperative AKI risk linked to preoperative proteinuria

4

Black race ups survival odds among men with mCRPC

12

Nocturnal polyuria possibly linked to non-dipping BP

17

Pre-radical cystectomy aspirin use may increase survival

22

PUL is effective for obstructive middle prostatic lobes

22

TRT is associated with an elevated risk of urinary stones

25

Study supports percutaneous ablation for selected RCC cases

Imaging advances may improve the treatment of oligometastatic PCa. PAGE 26

2 Renal & Urology News

JULY/AUGUST 2018 www.renalandurologynews.com

Pre-Surgery Proteinuria Associated With AKI Risk PATIENTS WHO HAVE proteinuria prior to surgery may be at elevated risk of postoperative acute kidney injury (AKI) and 30-day unplanned hospital readmission, regardless of preoperative estimated glomerular filtration rate (eGFR).

In a retrospective, population-based study of 153,767 surgeries performed

at 119 Veterans Affairs facilities from October 1, 2007 to September 30, 2014, a team led by Mary T. Hawn, MD, MPH, of Stanford University in Stanford, California, found that preoperative proteinuria was associated with postoperative AKI in a dose-­dependent ­relationship. Compared with the absence

of proteinuria, urine protein concentrations of 15–29 (trace proteinuria), 30–100, 101–300, and 301–1000 mg/ dL were associated with 1.2-, 1.3-, 1.7-, and 2-fold greater odds of postoperative AKI, respectively, after adjusting for eGFR and other covariates, the investigators reported in JAMA Surgery.

Cosmos Communications 38004a

K

07.13.18

1

133

ej 1

Q1

Q2

These proteinuria values were associated with 1.2-, 1.3-, 1.7-, and 1.7-fold increased odds of postoperative AKI, respectively, among patients with a normal eGFR (greater than 60 mL/ min/1.73 m 2) before surgery, and 1.3-, 1.3-, 1.7-, and 2.2-fold increased odds, respectively, among those with

www.renalandurologynews.com JULY/AUGUST 2018

abnormal eGFR before surgery. Urine protein concentrations of 30–100, 101– 300, and 301–1000 mg/dL were associated with 1.1-, 1.1-, and 1.3-fold greater odds of 30-day unplanned readmission.

“Preoperative proteinuria was independently associated with postoperative AKI and 30-day postdischarge, unplanned readmission among patients with and without preoperative renal dysfunction,” Dr Hawn and her team concluded.

“Pre­op­er­a­tive proteinuria is a marker for perioperative AKI risk and readmission in his population. Identification and early intervention with patients at risk for AKI … through preoperative urinalysis assessments may improve patient outcomes by alerting care teams of excess risk despite normal eGFR.” In their discussion of study limitations, they noted that the study’s observational, retrospective design limits their ability

Cosmos Communications 38004a

K

07.13.18

1

133

ej 1

Q1

Q2

to assign causation. “Furthermore, the results of this study may be attributable to additional unmeasured residual confounders, despite rigorous controlling for available clinically and statistically significant confounders.”

All patients in the study underwent elective non-emergent surgery. Eligibility criteria included evidence of at least 1 preoperative urinalysis result and both a preoperative and postoperative serum

Renal & Urology News 3

creatinine level result to assess AKI. The authors pointed out that their study included a surgery demographic unique to a VA population “and the results may not be generalizable to patient characteristics or specialties not represented.”

The study cohort, which was 93.2% male, had a mean age of 63.7 years. The racial composition was 80.6% white, 17.5% black, and 1.9% other races or ethnicities. n

4 Renal & Urology News

JULY/AUGUST 2018 www.renalandurologynews.com

Calcified Plaques Lower PD Therapy Success Rate PLAQUE calcification in Peyronie’s disease (PD) is associated with a significantly lower rate of successful treatment with collagenase clostridium histolyticum (CCH) injections, according to a new study.

In addition, the study found that greater baseline curvature is associated

with increased likelihood of successful curvature improvement.

Kevin Wymer, MD, and colleagues at Mayo Clinic in Rochester, Minnesota, collected data prospectively on 192 men who underwent 1–4 cycles of CCH for PD. Of these, 115 completed 2 or more CCH cycles and had data

available on curvature assessment. The primary outcome was the proportion of men with 20% or greater improvement in composite curvature (primary and secondary curvatures).

The investigators identified calcified plaques in 34 (30%) of the 115 patients. On multivariate analysis, men

with non-calcified plaques had significant 2.5-fold increased odds of a 20% or greater improvement in composite curvature compared with men who had calcified plaques, Dr Wymer’s team reported online ahead of print in Urology. Baseline penile curvature of 60 degrees or more was associated with significant 5-fold increased odds of a 20% or greater improvement in composite curvature.

Further, compared with men who had moderate or severe calcification, those with no calcification had significantly greater improvement in curvature (28.1 vs 10.3 degrees).

“Identifying plaque calcification is critical for appropriate patient counseling and may serve as a differentiating factor when selecting appropriate therapies for men with PD,” Dr Wymer’s team concluded. n

Black Race Ups Survival in mCRPC RESEARCHERS who studied men treated for metastatic castrationresistant prostate cancer (mCRPC) in 9 phase 3 trials found that blacks have better survival than whites, according to an oral presentation at the American Society of Clinical Oncology 2018 Annual Meeting in Chicago.

The study, by Susan Halabi, PhD, of Duke University School of Medicine in Durham, North Carolina, and colleagues, included 7528 whites and 500 blacks. All were treated with docetaxel/prednisone or a regimen including those medications. Patients had a median age of 69 years, and 94% had performance status 0–1.

The median overall survival for whites and blacks was 21.2 and 21.0 months, respectively. On multivariate analysis, blacks had a significant 19% decreased risk of death compared with whites.

Of the patients in the study, 72% had bone metastases with or without lymph node involvement, 9% had lung metastases, 9% had liver metastases, and 7% had lymph node metastases only, Dr Halabi’s group reported. n

Cosmos Communications 38004a

K

07.13.18

1

133

ej 1

Q1

Q2

Contents

www.renalandurologynews.com

JULY/AUGUST 2018

J U LY / A U G U S T 2 0 1 8 ■ V O L U M E 1 7 , I S S U E N U M B E R 4

Nephrology 2

ONLINE

8

this month at renalandurologynews.com 10

Clinical Quiz Test your knowledge by taking our latest quiz at renalandurologynews.com/ ClinicalQuiz

16

HIPAA Compliance Read timely articles on various issues related to keeping protected health information secure.

Drug Information Search a comprehensive drug database for prescribing and other information on more than 4000 drugs.

Be sure to check our latest listings for professional openings across the United States.

High FGF-23, Less Adiposity Linked in HD Patients Researchers speculate that the effect of fibroblast growth factor 23 on adipose tissue may have a role in the obesity paradox observed in patients with end-stage renal disease.

Preeclampsia Increases CKD Risk Post-Pregnancy The risk of chronic kidney disease among women who experience preeclampsia is especially pronounced within 5 years of delivery.

CKD Patients Often Excluded From Cancer Trials Of 310 randomized trials of drugs for the 5 most common solid cancers (prostate, breast, colorectal, lung, and bladder), 264 (85%) excluded patients with CKD, a study found.

Calcified Plaques Lower PD Therapy Success Rate Collagenase clostridium histolyticum does not work as well in men with calcified Peyronie’s disease plaques.

17

MIBC Patient Survival Better with Cystectomy Chemoradiation for muscle-invasive bladder cancer is associated with decreased overall survival compared with radical cystectomy, data show.

22

PUL Useful for Obstructive Middle Prostatic Lobes A new modification of the Urolift procedure is safe and effective for treating obstructive middle prostatic lobes in men with benign prostatic hyperplasia.

26

CALENDAR International Continence Society Annual Meeting Philadelphia August 28–31 American Society of Nephrology Kidney Week San Diego October 23–28 Large Urology Group Practice Association (LUGPA) 2018 Annual Meeting Chicago November 2–3 2019 Genitourinary Cancers Symposium San Francisco February 14–16 European Association of Urology 34th Congress Barcelona, Spain March 15–19 American Urological Association Annual Meeting Chicago May 3–6.

National Kidney Foundation Spring Clinical Meetings Boston May 7–11

4

News Coverage Visit our website for daily reports from Kidney Week 2018 in San Diego, October 23–28.

Pre-Surgery Proteinuria Associated With AKI Risk The likelihood of acute kidney injury and 30-day unplanned hospital readmission rose as urine protein levels increased, a study found.

Urology

Job Board

Renal & Urology News 5

Optimal Oligometastatic PCa Management Unclear Physicians have little guidance on the best approach due to a paucity of data from randomized clinical trials.

Although PSMA and fluciclovine PET are both capable of detecting metastases earlier than routine clinical imaging, it is not known if treatment of PET-only detected lesions will improve clinical outcomes.

See our story on page 26

28

Departments 11

From the Medical Director Rising China and modern medicine

12

News in Brief Hyponatremia may predict mortality in pediatric HUS

27

Ethical Issues in Medicine Dealing with abrasive and uncooperative patients

28

Practice Management Precautions needed to prevent hacking of medical devices

6 Renal & Urology News

JULY/AUGUST 2018 www.renalandurologynews.com

Hyperkalemia Rates, Risk Factors Characterized STUDY FINDINGS presented at the European Renal Association-European Dialysis and Transplant Association’s 55th Congress in Copenhagen, Denmark, provide new information about hyperkalemia rates, risk factors associated with the condition, and how pharmacotherapy-related hyperkalemia can impact clinical management.

In a longitudinal study of 752 patients with stage 2–5 chronic kidney disease (CKD) who had pre-planned rather than clinically-driven measurements of serum potassium, Vincenzo Panuccio, MD, of CNR-IFC, Reggio Calabria, Italy, and colleagues found a 27% point prevalence of hyperkalemia at baseline. Among patients with hyperkalemia at baseline, the risk of persistence or recurrence of hyperkalemia was 8 times higher than in those who had normal potassium levels at baseline.

The investigators defined hyperkalemia as a serum potassium level greater than 5.0 mEq/L.

Hyperkalemia risk related to metabolic acidosis and RAAS blockade quantified.

Among the patients without hyperkalemia at baseline, the condition developed in 51.7% during a median followup of 36 months (incidence rate of 19 per 100 person-years).

Overall, the point prevalence of hyperkalemia across study visits rose from 27% at baseline to 30% at the final visit, the investigators reported. In multivariate analysis, patients who took ACE inhibitors and angiotensin receptor blockers (ARBs) had a significant 1.73and 1.53-fold increased odds of hyperkalemia, respectively. Patients with diabetes had significant 1.48-fold increased odds.

Higher serum bicarbonate and estimated glomerular filtration rate were associated with decreased odds of hyperkalemia.

The substantially higher risk for persistence or recurrence of hyperkalemia among patients who have the condition at baseline indicates that mild hyperkalemia often is overlooked and/ or treated suboptimally, the investigators concluded in a poster presentation.

“Metabolic acidosis and the use of drugs interfering with the renin-angiotensin system rank as the strongest modifiable risk factors for this potentially life-threatening alteration,” they wrote.

The study population had a mean age of 61 years; 60% of participants were male, 35% had diabetes, and 32% had background cardiovascular comorbidities.

In a separate study of study of 434,027 patients receiving therapy with reninangiotensin-aldosterone system (RAAS)

inhibitors, David T. Gilbertson, PhD, of the Chronic Disease Research Group in Minneapolis, and colleagues found that the overall rate of moderate and severe hyperkalemia was 1.3 episodes per 100 patient-years (PY).

The rate increased from 0.8 episodes per 100 PY among patients aged 18 to

29 years to 2.4 per 100 PY for patients older than 80 years. The rates were 6.4 per 100 PY among patients with a history of hyperkalemia vs 0.6 per 100 PY among patients without such a history.

The rates were 3.1, 2.5, and 11.5 per 100 PY among patients with diabetes, stage 4 CKD, and stage 5 CKD, respectively.

www.renalandurologynews.com JULY/AUGUST 2018

The investigators defined moderate and severe hyperkalemia as potassium levels of 5.5–6.0 and greater than 6.0 mmol/L, respectively.

In a study of 13,726 new users of mineralocorticoid receptor antagonists (MRAs), Marco Trevisan, MS, of the Karolinska Institutet in Stockholm, Sweden, and colleagues demonstrated that within a year of starting treatment, 18.5% of them experienced at least

1 episode of hyperkalemia (potassium level greater than 5 mmol/L) detected, most within the first 3 months of therapy. CKD was associated with the greatest hyperkalemia risk, followed by older age, male sex, heart failure, peripheral vascular disease, diabetes, and concomitant use of ACE inhibitors, ARBs, and diuretics.

Among patients who had hyperkalemia, 47% discontinued MRA therapy

and only 10% had their prescribed dose decreased. Discontinuation rates were higher following development of moderate/severe hyperkalemia (potassium level greater than 5.5 mmol/L) and early in therapy (less than 3 months from initiation). MRA discontinuation was most likely among patients with CKD. When MRA was discontinued, 76% of patients were not reintroduced to MRA therapy in the following year.

Renal & Urology News 7

Lastly, Nada Sellami, MD, of La Rabta Hospital in Tunis, Tunisia, and colleagues reported on a study comparing hyperkalemia in 189 patients with acute kidney injury and 266 with CKD. Patients with AKI were more likely to be on RAAS inhibitors than patients with CKD (26.1% vs 12.4%), whereas diabetes was more common among patients with CKD (48.1% vs 30.7%). lower risk of mortality. n

8 Renal & Urology News

JULY/AUGUST 2018 www.renalandurologynews.com

High FGF-23, Less Adiposity Linked in HD Patients FIBROBLAST GROWTH factor 23 (FGF-23) is inversely associated with adiposity in patients on hemodialysis (HD), and this association may be mediated, at least in part, by leptin, new data suggest.

According to investigators, a decrease in adipose tissue may be a mechanism by which higher FGF-23 levels may

contribute to greater mortality among dialysis patients. They postulate that the effect of FGF-23 levels on adipose tissue may have a role in the obesity paradox observed in patients with endstage renal disease (ESRD).

In a study of 611 prevalent hemodialysis (HD) patients with a mean age of

56 years, Janet M. Chiang, MD, of the University of California, San Francisco, and colleagues found that FGF-23 was inversely associated with body mass index (BMI), waist circumference, and percent body fat. Each 50% increase in FGF-23 was associated with a 0.24 kg/m2 decrease in BMI,T:6.875” 0.44 cm decrease

in waist circumference, and 0.58% decrease in percent body fat, Dr Chiang’s team reported in the Journal of Renal Nutrition (2018;28:278-282).

Adding leptin to body composition models attenuated the associations between FGF-23 and measures of adiposity, but FGF-23 remained ­significantly

T:9.875”

SUAU18CDNY4737_Apr_2018_ADJ_Junior_Spread_BS_6_875_x_9_875_r6.indd 1

4/19/18 12:41 PM

SUAU18CDNY5082_Sutent_Adjuvant_Jrnl_Ad_Spread_UPDATE_BS_r3_FSU.indd 1

4/19/18 12:52 PM

www.renalandurologynews.com JULY/AUGUST 2018

associated with percent body fat, with each 50% increase in FGF-23 associated with a 0.17% decrease in percent body fat.

“In conclusion, we found that there is an inverse relationship between FGF23 and adiposity that is different from what is seen in individuals with normal renal function,” the authors wrote.

“This paradoxical association could be due to off-target signaling of FGF-23 in

the adipose tissue leading to increased lipolysis of fat. This observation could add to our understanding of factors that lead to the obesity paradox in ESRD.” They noted that multiple “endocrine factors, including FGF-23 and leptin, communicate between bone, kidney, and adipose tissue to balance mineral and energy homeostasis.”

Studies have repeatedly demonstrated that obesity in dialysis T:6.875” patients is associ-

ated with lower mortality, the authors stated. One theory is that adipose tissue may serve as a repository of energy that may be beneficial in the setting of inflammation or acute illness. “If high FGF-23 were to cause loss of protective adipose tissue, it might be detrimental in this vulnerable population and might provide a partial explanation for the association between high FGF-23 and higher mortality.”

Limitations of the study include its observational and cross-sectional design, which did not allow the investigators to establish a causal relationship between FGF-23 and adiposity.

“Although we have proposed plausible mechanisms linking FGF-23 to adiposity, our study does not provide the in vitro or in vivo evidence that will be needed to confirm these mechanisms,” they wrote. n

T:9.875”

SUAU18CDNY4737_Apr_2018_ADJ_Junior_Spread_BS_6_875_x_9_875_r6.indd 2

4/19/18 12:41 PM

SUAU18CDNY5082_Sutent_Adjuvant_Jrnl_Ad_Spread_UPDATE_BS_r3_FSU.indd 2

4/19/18 12:52 PM

Renal & Urology News 9

10 Renal & Urology News

JULY/AUGUST 2018 www.renalandurologynews.com

Preeclampsia Increases CKD Risk Post-Pregnancy PREECLAMPSIA increases the risk of post-pregnancy chronic kidney disease (CKD), especially in the first 5 years after pregnancy, according to study findings presented at the European Renal Association-European Dialysis and Transplant Association’s 55th Congress in Copenhagen, Denmark.

The findings, reported by Jonas H. Kristensen, MD, of Statens Seruminstitut in Copenhagen, and colleagues, is from a study of 1,072,330 women in Denmark with pregnancies lasting 20 weeks or more. During a mean follow-up of 18.6 years per woman, CKD developed in T:6.875” 3901 women. Compared with women

who did not have a history of preeclampsia who had delivered in the same gestational age, women with a history of early preterm (less than 34 weeks), late preterm (34–36 weeks), and term (37 weeks or more) preeclampsia had a significant 3.9-, 2.8- and 2.3-fold increased risk of post-pregnancy CKD, respectively.

The associations between preeclampsia and post-pregnancy glomerular diseases was particularly striking, the investigators noted. For example, early preterm preeclampsia was associated with a significant 5-fold increased risk of glomerular diseases years after delivery.

Associations with unspecific chronic kidney impairment and hypertensive kidney disease also were strong, according to the researchers. For example, preterm preeclampsia was associated with a significant 2.9- and 4.2-fold increased risk of these problems, respectively.

The associations between any preeclampsia and unspecific chronic kidney impairment and glomerular diseases were much more pronounced within 5 years of pregnancy. The risk of unspecific chronic kidney impairment and glomerular diseases among women with any preeclampsia was increased by 5.5- and 4.4 fold within 5 years of pregnancy and by 2.1- and 1.5-fold 5 or more years after pregnancy. n

Abiraterone May Benefit Blacks More BLACK MEN with metastatic castraT:9.875”

tion-resistant prostate cancer (mCRPC) experience a greater PSA response to treatment with abiraterone and prednisone than their white counterparts, investigators reported at the American Society of Clinical Oncology 2018 Annual Meeting in Chicago.

In the prospective multicenter Abi Race trial, in which 50 black and 50 white men with mCRPC were treated with abiraterone and prednisone, the median PSA progression-free survival (PFS) was significantly higher among black than white patients (16.6 vs 11.5 months), according to investigators Daniel J. George, MD, of Duke University Medical Center in Durham, North Carolina, and colleagues. Black patients also had numerically greater proportions of men who had at least a 30%, 50%, and 90% PSA decrease (86% vs 76%, 76% vs 66%, and 48% vs 38%, respectively). The races did not differ with respect to median radiographic PFS (both 16.8 months), the trial’s primary outcome of interest. n

SUAU18CDNY4737_Apr_2018_ADJ_Junior_Spread_BS_6_875_x_9_875_r6.indd 3

4/19/18 12:41 PM

SUAU18CDNY5082_Sutent_Adjuvant_Jrnl_Ad_Spread_UPDATE_BS_r3_FSU.indd 3

4/19/18 12:52 PM

www.renalandurologynews.com JULY/AUGUST 2018

Renal & Urology News 11

FROM THE MEDICAL DIRECTOR EDITORIAL ADVISORY BOARD 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 Professor & Chief Division of Nephrology & Hypertension University of California, Irvine School of Medicine Orange, Calif.

Urologists

Nephrologists

Christopher S. Cooper, MD Director, Pediatric Urology Children’s Hospital of Iowa Iowa City

Anthony J. Bleyer, MD, MS Professor of Internal Medicine/Nephrology Wake Forest University School of Medicine Winston-Salem, N.C.

R. John Honey, MD Head, Division of Urology, Endourology/Kidney Stone Diseases St. Michael’s Hospital University of Toronto

David S. Goldfarb, MD Professor, Department of Medicine Clinical Chief New York University Langone Medical Center Chief of Nephrology, NY Harbor VA Medical Center

Stanton Honig, MD Department of Urology Yale University School of Medicine New Haven, CT J. Stephen Jones, MD, FACS Chief Executive Officer Inova Health System Professor and Horvitz/Miller Distinguished Chair in Urologic Oncology CCLCM (ret.)

Jaime Landman, MD Professor of Urology and Radiology Chairman, Department of Urology University of California Irvine

Csaba P. Kovesdy, MD Chief of Nephrology Memphis VA Medical Center Fred Hatch Professor of Medicine University of Tennessee Health Science Center, Memphis Edgar V. Lerma, MD, FACP, FASN, FAHA Clinical Associate Professor of Medicine Section of Nephrology Department of Medicine University of Illinois at Chicago College of Medicine, Chicago Allen Nissenson, MD Emeritus Professor of Medicine The David Geffen School of Medicine at UCLA, Chief Medical Officer, DaVita Inc.

James M. McKiernan, MD John K. Lattimer Professor of Urology Chair, Department of Urology Director, Urologic Oncology Columbia University College of Physicians and Surgeons, New York City

Rulan Parekh, MD, MS Associate Professor of Pediatrics and Medicine University of Toronto

Kenneth Pace, MD, MSc, FRCSC Assistant Professor, Division of Urology St. Michael’s Hospital University of Toronto

Robert Provenzano, MD Chief, Section of Nephrology St. John Hospital and Medical Center Detroit

Ryan F. Paterson, MD, FRCSC Assistant Professor Division of Urologic Sciences University of British Columbia Vancouver, Canada

Robert S. Rigolosi, MD Director, Regional Hemodialysis Center Holy Name Hospital, Teaneck, N.J.

Renal & Urology News Staff Editor

Jody A. Charnow

Web editor

Natasha Persaud

Production editor

Kim Daigneau

Group art director, Haymarket Medical

Jennifer Dvoretz

Production manager

Krassi Varbanov

Director of production Circulation manager National accounts manager VP, content, medical communications

Louise Morrin Boyle Paul Silver William Canning Kathleen Walsh Tulley

General manager, medical communications

Jim Burke, RPh

CEO, Haymarket Media Inc.

Lee Maniscalco

Renal & Urology News (ISSN 1550-9478) Volume 17, Number 4. Published bimonthly by Haymarket Media, Inc., 275 7th Avenue, 10th Floor, New York, NY 10001. For Advertising Sales & Editorial, call (646) 638-6000 (M–F, 9am–5pm, ET). Postmaster: Send address changes to Renal & Urology News, c/o Direct Medical Data, 10255 W. Higgins Rd., Suite 280, Rosemont, IL 60018.

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 © 2018.

Rising China and Modern Medicine for Over 1 Billion

S

everal years ago, I was asked to perform a virtual consult on a 48-yearold Chinese business man with a complex hilar tumor in a solitary kidney.

He was advised by some of the best specialists in his country that the only option was nephrectomy and hemodialysis. Four years after successful nephron preservation and recuperation at our center, I visited him and his country. Together, facilitated by Robert G. Uzzo, MD, FACS the Champions of Medical Advancement, an American-based organization dedicated to improving Chinese health care delivery, we live streamed our experience to more than 50,000 viewers as I gained insight and appreciation for medicine in the world’s most populated nation.

Visitors to Shanghai and Beijing will quickly note a remarkably modern and orderly managed society. Its economy is incredibly industrialist and quickly catching up with the rest of Dan Zhang western world. Medicine in China is a unique amalgam of both Chinese and Western practices. Its hospitals are large, modern, and complex, typically with 4,000 to 10,000 inpatient beds, advanced imaging, robotic technology, and impressive research facilities. Operationally, no appointments are necessary and everyone receives care: just show up and wait.

For some specialties, queuing begins the night before as physicians see 80+ patients per day (3 to 5 minutes per encounter). Under their socialized medical system, everyone is covered and care is always delivered. A quick glance in the outpatient “VIP patient lounge,” however, suggests improved access to even more advanced equipment, medication, and specialists are available to those who demand higher quality.

Their socialized health care system, like so many others around the world, is undeniably tiered. Perhaps the most troubling aspect of these arrangements is that these systems risk the trust that sets the foundation for a healthy physician-patient relationship. When trust erodes, so too can quality.

It is obvious that Chinese physicians and researchers care deeply about their mission and the welfare of their patients. Despite limited resources to care for over a billion citizens, they are doing their best to search for solutions that deliver optimal care while recognizing the complex and myriad variables that may lead to unequal care despite their best intentions. Although the solutions are complex, the architects of our evolving health care delivery system should take note.

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 Dan Zhang President, Champions of Medical Advancement Associates Spring House, Pennsylvania

12 Renal & Urology News

JULY/AUGUST 2018 www.renalandurologynews.com

News in Brief

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

Short Takes FDA Approves Drug For Complicated UTIs

170 adult patients who were admit-

PLAZOMICIN HAS received FDA ap-

RRT. The preferred mode of RRT was

proval to treat complicated urinary

continuous venovenous hemofiltra-

tract infections (cUTI), including

tion. In-hospital mortality overall was

pyelonephritis, due to certain Entero-

50%. Among survivors, 21% required

bacteriaceae bacteria in adults.

RRT upon hospital discharge, and 9%

ted to 8 burn centers and received

continued to require RRT 6 months

The drug, which is being marketed

post-discharge.

as Zemdri by Achaogen, Inc., of South San Francisco, California), is nous infusion. According to a com-

Hyponatremia May Predict Mortality in Pediatric HUS

pany press release, it is indicated for

Hyponatremia may predict mortal-

patients aged 18 years or older for

ity among children with hemolytic

cUTI caused the following susceptible

uremic syndrome due to Shiga toxin-

bacteria: Escherichia coli, Klebsiella

producing Escherichia coli, investiga-

pneumoniae, Proteus mirabilis, and

tors reported online ahead of print in

Enterobacter cloacae.

Pediatric Nephrology.

administered once daily by intrave-

Laura F. Alconcher, MD, of ­Hospital

RRT for Severely Burned Patients Characterized

Dr. José Penna in Bahía Blanca,

Severely burned patients who undergo

younger than 18 years with Shiga

renal replacement therapy (RRT) for

toxin-producing E. coli HUS, of whom

acute kidney injury have a mortality

17 (3.65%) died. On multivariate anal-

rate similar to that of other critically

ysis, low sodium concentration, higher

ill populations who receive RRT,

hemoglobin level, and central nervous

researchers reported online in the

system involvement independently

Journal of Burn Care & Research.

predicted mortality. The best cut off

­Argentina, studied 466 patients

Kevin K. Chung, MD, of Brooke Army

value for sodium was 128 meq/L or

Medical Center, Fort Sam Houston,

less and, for hemoglobin, 10.8 g/dL

Texas, and collaborators studied

or higher.

ED Gout Visits Surge Emergency department (ED) visits for gout increased dramatically in the United States from 2006 to 2014, especially among individuals aged 45–64 years, according to a study. Shown below is the estimated changes in the prevalence of ED gout visits, per 100,000 population, according to age group.

150

137 133 116

120

n 2006 n 2014

91

90 60

128 132

44

56.5

48

67

30 0

18–44

45–64

65–84

85+

All ages

Source: Miathal A, Singh G. Emergency department visits for gout: a dramatic increase in the past decade. Data presented at the EULAR 2018 European Congress of Rheumatology in The Netherlands, June 13–16. Abstract OP0185.

Metformin Added to ADT Tied to Prolonged Survival M

etformin use may be associated with prolonged survival among men with advanced prostate cancer receiving androgen deprivation therapy (ADT).

In a study of US veterans receiving ADT for advanced PCa, Kyle A. Richards, MD, of the University of Wisconsin in Madison, and collaborators found that patients also receiving metformin for diabetes mellitus had a significant 18% decreased risk of death compared with men who did not have diabetes mellitus (reference group). In addition, metformin users had a significant 18% decreased risk of skeletal-related events (SREs) and 30% decreased risk of cancer-related death.

“The current study is unique in evaluating the impact of metformin on ADT as these drugs may have an additive effect,” Dr Richards’ team reported online ahead of print in The Journal of Urology.

The study included 87,344 men, of whom 17% had diabetes mellitus being treated with metformin, 22% had diabetes mellitus not treated with metformin, and 61% did not have diabetes mellitus.

Daily Coffee Drinking May Lower CKD Risk, Study Finds H

ealthy adults who habitually consume 1 or more cups of coffee daily may reduce their risk of chronic kidney disease (CKD), according to new study findings published online ahead of print in the American Journal of Medicine.

Of 8717 participants (mean age 52 years) with an estimated glomerular filtration rate above 60 mL/min/1.73 m2 from the Korean Genome and Epidemiology Study, 9.5% developed CKD over a mean of 11 years, Seung Hyeok Han, MD, PhD, of Yonsei University in Seoul, South Korea, and colleagues reported. In multivariable analysis, individuals who drank 1 cup or 2 or more cups of coffee daily had 24% and 20% lower risks of developing CKD, respectively.

Coffee may have positive hemodynamic effects on vascular health, according to Dr Han’s team. Coffee also may contain compounds with antioxidant and antiinflammatory effects.

Non-Dipping BP, Nocturnal Polyuria Possibly Linked N

on-dipping blood pressure (BP) may be associated with nocturnal polyuria (NP), according to a study.

NP was present in 130 (67%) of 194 men who had nocturia (2 or more voids nightly), Wataru Obara, MD, of Iwate Medical University, and colleagues reported. Reduced functional bladder capacity explained symptoms in only a minority overall (13.4%), suggesting that bladder storage problems were likely well treated, the investigators stated in a paper published online ahead of print in Lower Urinary Tract Symptoms.

A subset of 17 NP and 17 non-NP patients underwent ambulatory BP monitoring. Significantly more men with NP had non-dipping blood pressure than men with other causes of nocturia (77% vs 41%). NP patients also were more likely to use 2 or more antihypertensive medications. “We suggest that treatment for nondipping blood pressure may improve NP,” the researchers concluded.

14 Renal & Urology News

JULY/AUGUST 2018 www.renalandurologynews.com T:21”

Robotic, Open RC Offer Similar Oncologic Outcomes ROBOTIC radical cystectomy (RC) for invasive bladder cancer is associated with short-term oncologic outcomes comparable to that achieved with open RC, according to a new study.

In the randomized phase 3 RAZOR (Randomised Open versus Robotic Cystectomy) trial, patients who underwent robot-assisted RC (RARC) and open RC had similar 2-year progression-free survival rates (72.3% and 71.6%, respectively), a team led by Dipen J. Parekh, MD, of the Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine, reported in The Lancet (2018;391:2525-2536).

Robotic surgery was associated with significantly less median estimated blood loss than open surgery (300 vs 700 mL). A significantly smaller proportion of patients in the RARC group than open RC group required intraoperative blood transfusion (13% vs 34%) and post-­operative blood transfusion

bladder cancer (biopsy-proven clinical stage T1–T4, N0–N1, M0) or refractory carcinoma in situ. Of these, 150 patients underwent RARC and 152 had open RC. The robotic and open surgery groups had a median age of 70 and 67 years, respectively. In both groups, 84% of patients were men.

With regard to study limitations, the authors noted that participating centers were academic medical centers, and surgeons were either fellowship-trained or had a dedicated uro-oncology practice.

Not all institutions contributed equally to the trial, and the patients recruited represented only a percentage of all

S:14”

patients with bladder cancer treated at those institutions during the study period. Another limitation was that only surgeons with substantial experience were involved in the trial. Participating surgeons were required to have performed at least 10 robotic or open cystectomies in the year before the study.

Progression-free survival at 2 years found not to differ significantly.

(25% vs 40%). The robot-assisted RC group had a significantly shorter median hospital length of stay (6 vs 7 days) and a significantly larger proportion of patients who had a hospital stay of 5 or fewer days (29% vs 18%).

RARC required a significantly longer median operative time than open surgery (428 vs 361 minutes). The robotassisted and open surgery groups had similar rates of adverse events (67% vs 69%) and similar patient-reported quality-of-life (QoL) outcomes.

The trial provides the first multicenter randomized evidence of the oncologic efficacy of robotic cystectomy, according to Dr Parekh and his colleagues.

“In the setting of previous studies, robotic cystectomy did not compromise oncological outcomes compared with open cystectomy,” they wrote. “Our results showed that robotic cystectomy is associated with an improvement in perioperative parameters, such as blood loss and length of stay, without significant differences in complication rates and patient-reported QoL outcomes.”

The RAZOR trial involved patients recruited at 15 centers in the United States. The investigators included in their analysis 302 patients with invasive

A ir

•

•

•

•

E

P c

s

in

g

us

www.renalandurologynews.com JULY/AUGUST 2018

Renal & Urology News 15

T:21” S:14”

In an editorial accompanying the report by Dr Parekh’s team, Roland Seiler, MD, and George N. Thalmann, MD, of the University of Bern in Bern, Switzerland, said “the authors should be congratulated for their effort and for showing that although robotassisted radical cystectomy is probably more expensive than open cystectomy, when done by experienced surgeons and in selected cases, the approach is

c­ omparable to open radical cystectomy in terms of perioperative morbidity, quality of life, and short-term oncological outcomes.”

As for whether RARC should be recommended in daily clinical practice on the basis of the current findings, Drs Seiler and Thalmann pointed out that most cystectomies are performed in low-volume centers where the necessary expertise is not available.

A separate study published recently online ahead of print in European Urology found no significant difference in the risk of bladder cancer recurrence or death between RARC and open RC. Bernard H. Bochner, MD, of Memorial Sloan Kettering Cancer Center in New York, and colleagues enrolled 118 patients with bladder cancer scheduled to undergo RC with pelvic lymphadenectomy, randomly assigning 60 and 58 patients to undergo

RARC and open RC, respectively. The median follow-up was 4.9 years after surgery among surviving patients. Forty-five patients had recurrences and 36 patients died, 19 from bladder cancer. Recurrencefree and cancer-specific survival rates did not differ significantly, although the investigators acknowledged that the trial was not powered to detect differences in cancer recurrences, survival outcomes, or patterns of recurrence. n

16 Renal & Urology News

JULY/AUGUST 2018 www.renalandurologynews.com

CKD Patients Often Excluded From Cancer Trials PATIENTS WITH CHRONIC kidney disease (CKD) are frequently excluded from clinical trials of cancer drugs, according to a new study.

In a search of 6 selected high-profile general medicine and oncology journals, Abhijat Kitchlu, MD, of Toronto General Hospital in Canada, and c­olleagues

i­dentified 310 randomized trials of drugs for the 5 most common solid cancers (prostate, breast, colorectal, lung, and bladder). Of these trials, 264 (85%) excluded patientsT:7.875” with CKD. S:7” Trials frequently excluded patients with mild to moderate CKD without an apparent pharmacologic rationale,

such as nephrotoxicity or drug bioaccumulation, the researchers noted.

Trials of biologics or immunotherapies often excluded CKD patients, whereas trials of endocrine-based therapies were more inclusive.

“This finding is concerning because it was estimated that 32% of deaths

among patients with CKD in 2005– 2009 were attributable to malignancy,” Dr Kitchlu’s team reported online ahead of print in JAMA. “As a result of trial underrepresentation, patients with CKD may not be considered for cancer therapies that have potential to improve morbidity and mortality.”

Serum creatinine threshold values were the most common exclusion criteria (used in 62% of trials), followed by creatinine clearance (44%). Only 5% of trials used estimated glomerular filtration rate thresholds for exclusion.

“The exclusion of patients with CKD should be based on appropriate measures of kidney function and justifiable clinical or pharmacokinetic rationale,” the investigators concluded. “Judicious broadening of eligibility criteria in cancer trials to include the growing population of patients with CKD may enable more patients to benefit from novel cancer therapies while balancing the potential risk of adverse events.” n

Higher Fall Risk Found With OAB MEN AND WOMEN with overactive S:10

T:10.75”

bladder (OAB) symptoms such as nocturia are 59% more likely to fall than those without the condition, according to new study results published in Neurourology and Urodynamics.

Of the 33, 631 OAB patients on Medicare who were studied (mean age 78 years), only 14% received treatment. Treated patients had a 12% lower risk for falls vs untreated patients, Ravishankar Jayadevappa, PhD, and his colleagues reported.

With regard to study limitations, the authors did not account for OAB treatment duration or intensity, behavioral therapies, or direct measures of cognition and functional capacity.

Falls are an important health issue since they can lead to fracture and even death in seniors. “Preventive education, early diagnosis, and early treatment may help in lowering the risk of falls and thus improve the quality of life and morbidity among older adults with OAB,” Dr Jayadevappa’s team stated. n

www.renalandurologynews.com JULY/AUGUST 2018

■ AUA 2018, San Francisco

Renal & Urology News 17

American Urological Association 2018 Annual Meeting

Pre-RC Aspirin Use May Increase Survival Daily aspirin intake prior to radical cystectomy associated with lower mortality risk following surgery DAILY ASPIRIN USE prior to radical cystectomy (RC) for bladder cancer is associated with improved post-operative survival, investigators reported.

In a study of 1061 patients undergoing RC, including 461 (43%) who took daily aspirin preoperatively, Timothy D. Lyon, MD, and colleagues at Mayo Clinic in Rochester, Minnesota, found that, after multivariable adjustment, daily aspirin use was independently associated with significant 36% and 30% decreased risks of cancer-specific and all-cause mortality, respectively, compared with non-use of aspirin. Daily aspirin use was also associated with significantly greater 5-year cancer-specific survival (CSS, 68% vs 60%) and overall survival (59% vs 52%).

When the investigators categorized aspirin users according to low-dose (25, 81, or 162 mg) and high-dose (325 or 650 mg) use, they found that only

Ultrasound for Stones Underused ULTRASONOGRAPHY is being used increasingly in emergency departments as the first imaging modality for patients with acute renal colic, but initial use of computed tomography (CT) in this setting has remained stable despite concerns about unnecessarily exposing patients to excessive ionizing radiation, researchers reported.

In a study of 830,785 patients who sought care in an emergency department (ED) for acute renal colic, investigators led by Helena C. Chang, MD, of the University of Washington in Seattle, found that ultrasound (US) imaging alone increased from 2.7% in 2007 to 6.9% in 2015. During that same interval, initial use of CT scans declined only slightly—from 86.3% to 85.8%—despite previous studies establishing the safety of using US as the first imaging test for acute renal colic.

CT imaging within 6 months prior to the index ED presentation increases the likelihood of US for evaluating acute renal stones, the investigators

low-dose aspirin was associated with improved CSS. Daily users of low-dose aspirin had a significant 39% decreased risk of CSS compared with non-users.

The median follow-up after RC among patients who were alive at last follow-up was 4.2 years, during which

Only daily low-dose aspirin use is linked with improved CSS, new research shows.

442 patients died (331 from bladder cancer). Dr Lyon’s team classified patients as aspirin users if aspirin was listed as a daily medication at a visit within 90 days of RC or on discharge paperwork after RC. Patients taking

reported. Receiving US imaging in the ED decreases the average number of CT evaluations over 90 days by up to 0.4 CT evaluations.

The proportion of patients who went on to have a stone-related procedure within 90 days ranged from about 15% to 27%, depending on imaging type.

Compared with patients who underwent CT imaging in the ED, those who underwent only US imaging were more likely to get CT scans after the ED visit. Those with only US imaging in the ED were even more likely to receive a CT evaluation if a stone procedure was performed.

“The key buried in all the numbers is that many people do not go on to need a procedure for stone treatment, and thereby many may not ultimately need a CT scan for treatment planning if ultrasound is safe for initial imaging in the ED,” Dr Chang told Renal & Urology News. “In this context, national data show that ultrasound is still underutilized for reducing ionizing radiation, especially considering that stone forming patients are expected to have future ionizing radiation exposure over the course of the diagnosis and treatment of recurrent stone episodes.”

For the study, Dr Chang’s team analyzed 2007–2015 data from MarketScan, a private employer-based health insurance database. n

aspirin on an as-needed basis for pain were not classified as users. Aspirin users were significantly older than nonusers (median age 70 vs 66 years).

A potential association between aspirin use and survival after RC has not been well characterized previously, according to the researchers.

In an interview with Renal & Urology News, Dr Lyon said the study findings notably are limited by missing information on duration of preoperative aspirin use and an inability to identify patients who began using daily aspirin following cystectomy, as this information is not captured in their registry.

“As such, prospective validation of these findings is required before aspirin can be confidently recommended for routine postoperative use,” Dr Lyon said. “However, we believe that our data provide a background and

r­ ationale for future investigations into the role of aspirin in post-cystectomy care. If these data can be prospectively confirmed, aspirin could potentially serve as a cheap and relatively nontoxic treatment adjunct for patients undergoing radical cystectomy.”

Dr Lyon explained that aspirin has long been recognized for its potential antineoplastic properties through its downregulation of inflammatory cytokines, most notably prostaglandin E2, thereby leading to decreases in cellular proliferation and angiogenesis. Daily aspirin use, he said, has been associated with reduced cancer-specific mortality in patients with colorectal, breast, and prostate cancers, as well as with reduced recurrence rates among patients with non-muscle invasive bladder cancer treated with bacillus Calmette-Guérin. n

MIBC Patient Survival Better With Radical Cystectomy CHEMORADIATION for muscle-invasive

both unweighted and propensity score

bladder cancer (MIBC) is associated

weighted multivariate analyses. The

with decreased overall survival com-

5-year survival rates were significantly

pared with radical cystectomy, accord-

greater for RC than CMT patients

ing to a large study.

(40.4% vs 30%).

The study is the largest to date look-

Dr Kaushik and his colleagues identi-

ing at survival differences between

fied age, histology, and N -stage as

radical cystectomy (RC) and chemo-

variables with significant interaction

radiation therapy (CMT), noted lead

with treatment effects. Compared with

investigator Dharam Kaushik, MD, of

RC, CMT was associated with a signifi-

the University of Texas Health Science

cant 53% increased death risk among

Center in San Antonio.

patients younger than 70 years. CMT

Using the National Cancer Data

was associated with a significant 17%

Base, he and his colleagues examined

increased risk of death compared with

outcomes among 15,854 patients

RC among patients with non-neuroen-

with MIBC who underwent RC with or

docrine tumors and a significant 18%

without neoadjuvant chemotherapy

increased risk of death among those

and 2083 who underwent CMT, defined

with N0/N1 tumors.

as receiving a regional dose of at

Regardless of treatment, older age,

least 50 Gy plus chemotherapy within

T stage, and N stage were associ-

90 days of radiation therapy.

ated with an increased risk of death.

After a median follow-up of 25.8

Patients aged 80 years and older had

months, patients in the CMT group had

a 72% greater risk of death than those

a significant 15% higher risk of death

aged less than 60 years, in weighted

compared with RC-treated patients in

multivariate analysis. n

22 Renal & Urology News

American Urological Association 2018 Annual Meeting

PUL Useful for Obstructive Middle Prostatic Lobes

Study: TRT May Increase Stone Risk

Safety and efficacy established in the prospective MedLift trial

TESTOSTERONE replacement therapy (TRT) is associated with an elevated risk of urinary stones, investigators reported.

In a study of 26,585 men aged 40 to 64 years who received continuous TRT matched by birth year, race, marital status and other factors to 26,585 controls with clinical hypogonadism not on TRT, Tyler R. McClintock MD, MS, of Brigham and Women’s Hospital and Harvard Medical School in Boston, and colleagues found a significantly higher incidence of urinary stones among TRT recipients. The primary outcome was 2-year absolute risk of a stone-related event, which occurred in 659 men on TRT compared to 482 in the control group. The majority of stones were detected via clinical diagnosis, though interventions such as extracorporeal shockwave lithotripsy, percutaneous nephrolithotomy, and ureteroscopy with lithotripsy were also used to identify stone episodes. A subanalysis of

BY JODY A. CHARNOW PROSTATIC urethral lift (PUL) is a safe and effective treatment for obstructive middle prostatic lobes in men with benign prostatic hyperplasia (BPH), a researcher reported.

PUL (UroLift, NeoTract) is a minimally invasive device that pulls back obstructing prostatic lobes pressing on the urethra to improve urine flow.

Urolift was cleared by the FDA in September 2013 to treat blocked urine flow in men aged 50 years and older with BPH. Daniel Rukstalis, MD, Professor of Urology at Wake Forest Baptist Medical Center in Winston-Salem, North Carolina, presented the findings of the multicenter prospective MedLift trial, which enrolled 45 men with BPHrelated lower urinary tract symptoms at 9 sites. Inclusion criteria included age 50 years or older, AUA Symptom Index (AUASI) of 13 or higher, peak flow rate 12 mL/sec or less, and prostate volume no greater than 80 cc. The study was conducted as an FDA Investigational Device Exemption extension of the LIFT randomized trial, which examined the use of PUL for lateral lobes of the prostate.

Symptoms of patients with middle lobe obstruction responded at least as well to PUL at every time point as patients who had the procedure for lateral lobes only. For the middle lobe patients, the AUASI change at 1, 3, 6, and 12 months was at least a 13.5-point improvement and significantly better than baseline at every time point, Dr Rukstalis’s team found. Quality of life score and BPH Impact Index improved by more than 60% and 70%, respectively, at 3, 6, and 12 months. Peak flow rate improvement ranged from

Symptomatic relief is at least as good as that achieved with PUL for lateral lobes.

An obstructive prostatic middle lobe before a urethral lift procedure.

Displacement of the obstructive lobe with a Urolift device.

90% to 130% throughout follow-up.

At 1 month, 65% of patients reported a score of 80 or more on the Quality of Recovery scale, 80% reported being “much” or “very much better,” and 89% would recommend the procedure.

Improved ejaculatory function None of the patients reported new-onset sustained erectile or ejaculatory dysfunction. Erectile function, as measured by the International Index of Erectile Function-5 questionnaire, remained stable and ejaculatory function was significantly improved throughout followup, according to the investigators.

The middle lobe is part of the prostate that grows up beneath the bladder neck and either elevates the bladder neck or actually protrudes into the

bladder, Dr Rukstalis explained. “All of the treatments for middle lobe are made more difficult because of this protruding tissue into the bladder,” Dr Rukstalis told Renal & Urology News.

“Certainly, standard transurethral resection tools can resect a middle lobe, but there is real risk of bladder neck perforation and undermining the bladder neck.”

The original LIFT trial focused on the treatment of the lateral lobes. “It was decided at that time that men with middle lobe enlargement were a different group of men and would not be examined in that trial,” Dr Rukstalis related. “So ultimately after that trial was successfully completed, middle lobe became a contraindication for the use of the UroLift. The MedLift trial was then designed as an extension of the original LIFT trial to address the treatment of the middle lobe.”

Modified Urolift procedure For the MedLift trial, surgeons treated the lateral lobe in the standard manner and then treated the middle lobe with a new modification of the UroLift procedure that involved manipulating the middle lobe, displacing it to one side or the other of the prostate, and then implanting one of the lift devices to hold it displaced, further opening the bladder neck, he explained.

As with the established Urolift procedure, adverse events associated with middle lobe treatment were mild to moderate and resolved quickly. The improvements in LUTS mirrored, or even exceeded, those observed in the original LIFT trial.

In December of last year, the FDA approved extending the indications for UroLift to include treatment of the middle lobe. In addition, since the original approval of Urolift, FDA approved it for use in men aged 45 and older rather than 50 and older.

A prospective, randomized study published last year in the Canadian Journal of Urology (2017;24:8802-8813) found that improved outcomes from PUL are durable out to 5 years. n

Urinary stone risk linked to topical and injection forms of testosterone.

TRT types showed that there was a significant association between stone risk and both topical and injection forms of TRT, though not testosterone pellets.

“Given this is the first study to specifically examine the relationship of testosterone replacement therapy with stone events, we feel that our findings can be considered alongside other known risks and benefits of TRT as clinicians counsel their patients and determine appropriate candidates for therapy,” Dr McClintock told Renal & Urology News.

As for what may explain an association between TRT and urinary stone formation, Dr McClintock explained that prior animal studies have suggested that testosterone is associated with increased renal oxalate excretion and decreased citrate excretion, which may increase the risk of urinary stones.

Moreover, testosterone may play a role in the renal handling of calcium. n

IMAGES COURTESY OF NEOTRACT, INC.

■ AUA 2018, San Francisco

JULY/AUGUST 2018 www.renalandurologynews.com

www.renalandurologynews.com JULY/AUGUST 2018

Renal & Urology News 23

Tamsulosin Ineffective for Small Ureteral Stones MEDICAL expulsive therapy (MET) using the alpha blocker tamsulosin does not aid passage of ureteral stones less than 9 mm in diameter, according to a recent study.

In the double-blind STONE (Study of Tamsulosin for Urolithiasis in the Emergency Department) trial, ­investigators randomly assigned 512 patients who presented to an emergency department with a symptomatic stone to receive 0.4 mg daily tamsulosin or placebo for 28 days. Computed tomography was used to document stone size, location, and passage. The cohort had a mean stone diameter of 3.8 mm.

Stone passage rate did not differ significantly between groups (50% for tamsulosin vs 47% for placebo), Andrew C. Meltzer, MD, MS, of George Washington University in Washington DC, and colleagues reported online in JAMA Internal Medicine. In addition, the ­investigators observed no

Guidelines for medical explusive therapy may need to be revised, researchers concluded. s­ ignificant between-group differences with respect to time to stone passage, return to work time, analgesic use, hospitalization, need for surgery, or repeat visit to the emergency department.

The presumed mechanism of action of alpha blockers is inhibition of smooth muscle contraction in the ureter, facilitating passage of the stone into the bladder, the authors explained.

Current guidelines by the American Urological Association recommend alpha blockers for ureteral stones 10 mm or less in diameter.

“Our findings do not support the use of tamsulosin for symptomatic urinary stones smaller than 9 mm. Guidelines for medical expulsive therapy for urinary stones may need to be revised.,” Dr Meltzer and his team concluded.

Adverse events were similar between groups, but a greater proportion of men receiving tamsulosin experienced abnormal ejaculation.

In an accompanying editorial, Philip Dahm, MD, and John Hollingsworth, MD, MS, of the University of Michigan in Ann Arbor, agreed that guidelines need to change. They believe, however, that tamsulosin should still be considered for ureteral stones larger

than 5 mm in diameter based on other research and the small mean stone size in the current study.

At the 2018 European Association of Urology Congress in Copenhagen, Denmark, researchers reported on a study showing that tamsulosin did not improve the rate of spontaneous

stone passage (SSP) among patients with acute ureteric colic. As part of the MIMIC study, Taimur T. Shah, MBBS, of University College London, and colleagues collected data from 4181 patients admitted with acute ureteric colic. Of these, 3127 (75%) were discharged with conservative management,

and 2516 of them (80%) had confirmed SSP. In this group, 952 patients (44%) were prescribed tamsulosin and 1234 (56%) were not. The rate of SSP was 78% and 72%, respectively. On multivariable analysis, which included adjustment for stone size and position, the investigators found no significant difference in SSP. n

24 Renal & Urology News

JULY/AUGUST 2018 www.renalandurologynews.com

Robotics’ rise

continued from page 1

with respect to perioperative complications, functional, oncologic and survival outcomes, and cost. Overall, the meta-analysis showed that roboticassisted surgery was associated with less blood loss, fewer surgical complications, and shorter hospital length of stay compared with open surgery.

Robotic-assisted RP was associated with improved continence and potency rates compared with open RP. Contemporary outcomes of roboticassisted RP, RC, and PN surgery are now at a minimum equal, but mostly superior, to open surgery, except for operative time and costs, the investigators concluded.

“The findings are supportive of robotic vs open surgery, similar to the individual studies that serve as the underpinnings, but one must consider publication bias,” said Jim C. Hu, MD, MPH, Director of the LeFrak Center

PCa complications

continued from page 1

The study by Dr Yerramilli’s team included 2603 men diagnosed with PCa and who had died at the end of a 10-year follow-up period. The men had a mean age of 67.6 years at diagnosis and a mean age at death of 70.1 years. The cohort consisted of 490 patients with low/intermediate-risk PCa, 617 with high-risk PCa, and 1005 with metastatic disease at diagnosis. Of those with metastatic disease, 519 patients had CRPC and 481 had castration-sensitive PCa.

Bone metastases Radiologic evidence of bone metastases developed in 7.2% of patients with low/intermediate-risk PCa (stage T2c or less, Gleason score 7 or less, PSA 20 ng/mL or less) compared with 28.1% of men with high-risk PCa (stage T3,

BPH linked to PD continued from page 1

commercially insured patients. One study included 8738 men with PD, 204,147 men with erectile dysfunction (ED), and 87,280 controls without PD or ED matched by age and follow-up duration. Compared with men in the ED and control groups, men in the PD group had a 21% increased risk of BPH, 21% increased risk of prostatitis, and 10% increased risk of lower urinary tract symptoms (LUTS). In

for Robotic Surgery at Weill Cornell Medicine and New York-Presbyterian in New York. “These are meta-analyses of published studies. The question remains whether these findings are representative of community and academic centers that do not publish

Robotic-assisted surgery is associated with less blood loss vs open surgery. results. For instance, 30% of robotic utilization in 2005 is higher than population-based studies using insurance claims and industry estimates.”

The findings may be biased toward academic centers as early adopters of technology, particularly to be able to offer it to patients or because they have modern training platforms for surgeons to become skilled in using

Gleason score 8–9, PSA greater than 20 ng/mL) and 40.9% of those with metastatic (T4, N1, or M1) disease.

Pathologic fracture due to bone metastases occurred in 1.4%, 6.2%, and 16.3% of men with low/intermediaterisk, high-risk, and metastatic disease, respectively.

Spinal cord compression Spinal cord compression developed in 2.1%, 5.2%, and 18.8% of these groups, respectively. Ureteric obstruction developed in 2.5%, 10.6%, and 15.5%. Renal failure due to ureteric obstruction developed in 0.6%, 6.5%, and 10.3%.

Castration resistance developed at a median of 4.5, 2.9, and 1.2 years from diagnosis in patients with low/intermediate-risk, high-risk, and metastatic disease, respectively. Radiologic evidence of bone metastases in these groups developed at a median of 4.2, 2.9, and addition, compared with controls, PD patients had an elevated risk of developing keloids. The study found no association between PD and risk of any autoimmune disease.

“Men with PD have an increased risk of developing BPH, LUTS, prostatitis and keloids,” the authors concluded in their study abstract. “This may be related to myofibroblast activity, and these findings support a common etiology for these conditions that may manifest at different points during the male life cycle.”

the latest technology, he added.

“Regardless, it is a laborious and noteworthy study that demonstrates that the arrow is striking close to the bull’seye, for early robotic surgery adopters and those beyond the learning curve.”

The meta-analysis shows that robotic surgery “now should be considered the standard in many aspects of oncologic surgery,” said Douglas M. Dahl, MD, Chief of the Division of Urologic Surgery at Massachusetts General Hospital in Boston. “It’s become standard of care, I think, in radical prostatectomy, and becoming very much the standard of care in partial nephrectomy as well. In cystectomy, there’s still a lot of debate as to whether or not that’s ultimately going to prove most useful.”

He emphasized the benefit to patients. “The really neat experience with minimally invasive [robotic] surgery is that patients can go through these very complex operations and recover very quickly,” Dr Dahl told Renal & Urology News. “It avoids a lot

of the long-term disability of recovering from, say, an open kidney operation.”

Robotics enables surgeons to perform dissections more precisely, which gives them greater control in removing tissue and cuts down on bleeding, he said. Robotics also can make operations less physically demanding compared with open surgery. “Surgery can be a very athletic endeavor,” Dr Dahl said. “Often I feel less fatigued at the end of the day after doing robotic cases versus open surgery.”

Based on the meta-analysis, robotic surgery costs more and takes longer than open surgery, “which are important resource issues for the hospitals and medical system,” he said.

According to Dr Dahl, it is important that robotics win “comprehensive acceptance” in the health care system such that efforts are made to improve training and establish standards in robotic surgery and to increase the cost effectiveness and decrease the surgical time compared with open surgery. n

1.3 years from diagnosis. Spinal cord compression developed at a median of 4.5, 2.9, and 1.3 years, and ureteric obstruction developed at a median of 2.7, 3.6%, and 1.6 years from diagnosis, the study found.

Compared with patients who had castration-sensitive PCa, those with CRPC had 2-fold increased odds of bone metastases and ureteric obstruction, the researchers reported. They also had 64% and 56% greater odds of pathologic fracture due to bone metastases and spinal cord compression, respectively.

“Our team hopes that these data, presented by risk group at diagnosis, allows providers to explain the natural history of this disease to their patients and discuss upfront management strategies in the context of the development of these major diseaserelated events,” Dr Yerramilli told Renal & Urology News. “For example, for a patient with metastatic disease at diagnosis, we know that about a fifth of patients develop cord compression.

Therefore, should this patient develop back pain, it should raise concern for the risk of cord compression.”

Dr. Yerramilli said he and his colleagues hope the new findings provide opportunities to study early palliative interventions, such as screening and treatment of spinal metastasis, targeting improvements in bone health, or exploring strategies to manage urinary obstruction before it leads to renal failure. n

According to Dr Pastuszak and his colleagues, clinicians treating men with PD should have heightened awareness for these comorbidities.

The other study included 48,423 men with PD, 1,177,428 with ED, and 484,230 controls. The PD patients were matched by age and duration of follow-up with the ED patients and controls. The mean age of all 3 cohorts was 49 years, and the mean follow-up time was 4.4 years.

Compared with controls, the patients with PD had a significant 39% and

43% increased risk of testis and stomach cancer, respectively, and a 19% increased risk of melanoma, according to the researchers. Compared with men who had ED, those with PD had a 38% increased risk of prostate cancer.

Dr Pastuszak and his collaborators also performed whole exome sequencing on a father and son with both PD and Dupuytren’s disease, a related fibrotic disorder, and identified numerous shared mutations that may also be involved in gastrointestinal and genitourinary cancers. n

Advanced disease predicts a higher risk renal failure due to ureteric obstruction.

www.renalandurologynews.com JULY/AUGUST 2018

Renal & Urology News 25

Study Supports Ablation Use in Selected RCC Cases PERCUTANEOUS ablation for small renal cell carcinoma (RCC) tumors in well-selected older patients may result in oncologic outcomes similar to those of radical nephrectomy (RN), but with less long-term renal insufficiency and fewer perioperative complications, according to a new study.

In an observational study of 4310 patients aged 66 years or older who received treatment for renal tumors smaller than 4 cm (T1a RCC) from 2006 to 2011, the 5-year RCC-specific survival rate for patients who underwent percutaneous ablation (PA) and RN was 96% and 95%, respectively, a non-significant difference between treatment arms, Adam D. Talenfeld, MD, MS, of Weill Cornell Medicine/New YorkPresbyterian Hospital in New York, and

Cancer-specific survival similar to that of radical nephrectomy. colleagues reported online in Annals of Internal Medicine. The 5-year RCCspecific survival rate was slightly lower for PA compared with partial nephrectomy (PN): 95% vs 98%. The 5-year overall survival (OS) rates were similar for PA and RN (74% vs 75%) and lower for PA than PN (77% vs 86%).

In adjusted analyses, RCC-specific and all-cause mortality risk did not differ significantly between PA and RN. PA was associated with a non-significant 2-fold increased risk of RCCspecific mortality and a significant 2-fold increased risk of all-cause mortality compared with PN. The cumulative rates of renal insufficiency 31 to 365 days after PA, PN, and RN were 11%, 9%, and 18%, respectively. Rates of non-urologic complications within 30 days after PA, PN, and RN were 6%, 29%, and 30%, respectively.

The authors concluded that appropriately selected older patients with small renal tumors may expect oncologic outcomes from PA similar to those of RN, with fewer complications and less chronic renal insufficiency. “Although our conclusions about the comparability of oncologic outcomes for PA versus PN are less certain, our findings suggest that patients who receive ablation might have fewer complications.” they wrote. “This large, population-based, c­ omparative

analysis of PA outcomes strengthens the findings of recent institutional studies and raises the level of evidence in support of PA for well-selected older patients with small renal tumors.”

For the study, the investigators used the SEER (Surveillance, Epidemiology, and End Results) cancer registry linked

to Medicare claims data. The median follow-up for the entire cohort was 52 months for overall survival and 42 months for RCC-specific survival. The median follow-up for the PA, PN, and RN groups was 44, 51, and 55 months, respectively, for OS and 33, 40, and 46 months, respectively, for RCC-specific

survival, the researchers reported.

In a discussion of study limitations, the investigators noted that their use of SEER-Medicare linked files prevented analysis of patients who received treatment after 2011, “possibly reducing generalizability to the newest PA, PN, and RN techniques.” n

26 Renal & Urology News

JULY/AUGUST 2018 www.renalandurologynews.com

Optimal Oligometastatic PCa Management Unclear Lack of data from randomized clinical trials leaves clinicians with little guidance of cancer spread between localized disease and widespread metastases.

Prostate-specific membrane antigen (PSMA) PET can identify oligometastatic disease at initial diagnosis, he said. Conventional imaging versus PSMA PET has not been addressed in a clinical trial.

IMAGE COURTESY OF FOX CHASE CANCER CENTER, PHILADELPHIA

BY JOHN SCHIESZER DUE TO RECENT advances in molecular imaging, oligometastatic prostate cancer (PCa) is being diagnosed with increasing frequency. More data from randomized clinical trials, however, are needed to provide guidance on the most effective treatment approach, according

Positron emission tomography image showing oligometastatic prostate cancer.

to Felix Y. Feng, MD, of the University of California, San Francisco. In a presentation at the 2018 Genitourinary Cancers Symposium, Dr Feng said there is an urgent need for better predictors of less versus more aggressive oligometastatic disease.

“We are so early in the field of oligometastatic prostate cancer that we don’t have a lot of answers yet,” said Dr Feng, Associate Professor of Radiation Oncology, Urology, and Medicine.

Treatment intensification approaches involve local therapy to the primary tumor, metastases-directed therapy (MDT), and intensification of systemic therapy. Little clinical evidence is available regarding the effect on these modalities with respect to overall survival (OS).

Dr Feng’s presentation, “Management of Oligometastatic Prostate Cancer: From Imaging to Therapy,” emphasized that the use of advanced positron emission tomography (PET) imaging to detect extrapelvic disease in men with PSA recurrence has led to a new understanding of the disease. Oligometastatic PCa is defined as an intermediate state

“PSMA is a protein bound at the surface on prostate cells,” Dr Feng explained. “PSMA PET involves using an agent that binds to this PSA protein and this agent also has a radioisotope attached to it that allows for detection on a PET scan. We see a lot more disease when we use PSMA PET.”

Clinical trial data Clinicians are in a conundrum when it comes to combining prostate-directed therapy, systemic consolidative therapy, and MDT. The STOMP (Surveillance or metastasis-directed Therapy for OligoMetastatic Prostate cancer recurrence) trial showed that survival free of androgen-deprivation therapy was longer with MDT than with surveillance alone for oligorecurrent PCa, according to a report in the Journal of Clinical Oncology (2018;36:446-453). The multicenter, randomized, phase 2 study included 62 men with asymptomatic PCa who experienced biochemical recurrence after primary treatment.

At a median follow-up time of 3 years, the median ADT-free survival was 13 months for the surveillance group

compared with 21 months for the MDT group.

“It is a small study, but what it means is that if you look at 2 to 3 years after treatment about 20% of patients were free of disease,” Dr Feng said. “A proportion of oligometastatic disease may be treatable. Metastasis-directed therapy by itself may not be enough if 80% of the patents are recurring in the first 2 years, so there may be need for systemic therapy in addition.”

In the phase 2 randomized ORIOLE (Observation Versus Stereotactic Abla­ tive RadiatIOn for OLigometastatic Prostate CancEr) Trial, which included 54 men with hormone-sensitive oligometastatic PCa, 67% of men assigned to observation experienced disease progression at 6 months compared with only 29% of men treated with stereotactic ablative radiation, Dr Feng pointed out. Results of the ORIOLE trial were published in BMC Cancer (2017;17:453).

As the use of advanced PET imaging increases, “we are starting see a lot more patients with oligometastatic disease, and early trials suggest that treatment to these sites of metastasis with either surgery or radiation will improve outcomes, but only in a subset of patients,” Dr Feng said.

Benefits of early detection unclear Mark Garzotto, MD, Professor of Urology at Oregon Health & Science University in Portland and the Director of Urologic Oncology at the Portland VA Medical Center, Portland, Oregon, said early detection may lead to little clinical benefit if there are no available proven therapies. “Although PSMA and fluciclovine PET are both capable of detecting metastases earlier than routine clinical imaging, it is not known if treatment of PET-only detected lesions will improve clinical outcomes,” Dr Garzotto said.

The STOMP trial showed a trend towards delayed ADT, but failed to show a reduction in metastatic progression, he noted. An important limitation of both the STOMP and ORIOLE studies is that the investigators were unable to account for length-bias and may well have included metastatic patients with slower growing disease. n

Low Selenium Ups Mortality Risk in HD LOW LEVELS of selenium are independently associated with increased risks of death and hospitalization among patients on hemodialysis (HD), according to a study published in the Clinical Journal of the American Society of Nephrology (2018;13:907-915).

In a prospective longitudinal study examining blood concentrations of 25 trace elements and associated outcomes in 1278 HD patients, Marcello Tonelli, MD, of the University of Calgary in Calgary, Alberta, and colleagues found that patients in the lowest decile of selenium concentration had significant 3.4-fold increased odds of death and 3.6-fold increased odds of all-cause hospitalization in adjusted analyses compared with patients in deciles 2–9.

Each decile increment in selenium concentration was associated with a 14% decreased risk of death and 8% decreased risk of hospitalization.

Results also showed that the highest decile of cadmium levels was associated with significant 1.9-fold increased odds of death compared with the remaining deciles, and each decile increment in copper concentration was associated with significant 7% increased odds of death. Lower concentrations of zinc or

Blood levels in the lowest decile linked to 3.4-fold increased odds of death. manganese and higher concentrations of lead, arsenic, or mercury were not associated with a higher risk of clinical outcomes.

The investigators noted that selenium has multiple biologic functions, and lower selenium levels have been associated with various adverse clinical and biochemical outcomes, including cardiovascular disease, diabetes, and malnutrition.

Dr Tonelli’s team acknowledged some study limitations. For example, they had only considered plasma specimens as a measure of body burden, “which may not be optimal for all trace elements.” In addition, because referent concentrations for patients on HD have not been defined, they used reference concentrations derived from healthy populations without kidney failure. n

www.renalandurologynews.com JULY/AUGUST 2018

Renal & Urology News 27

Ethical Issues in Medicine G

lancing at the next day’s clinic schedule, you see that one of your most challenging patients is scheduled to arrive at 8:00 AM. This patient has chronic medical and psychiatric issues, is abrasive and argumentative, and frequently demands more of your time than your other patients. You are concerned that tomorrow’s 20-minute appointment will last an hour.

A patient like this one, whose prevalence may be as high as 20% in primary care populations, can generate conflict for physicians because of the ethical tension such patients create. Physicians may recognize their ethical obligation to serve all patients with unconditional regard and equanimity, but they may also find it challenging to work productively with such patients.

Although the literature historically described such patients as “difficult,” in the context of modern medical practice, this concept is increasingly problematic.

Such a label is pejorative and subjective, non-standardized, and not designed to advance a patient’s care. Labels like “difficult” also draw attention away from the health care professional’s primary responsibility to provide care by putting the onus on the patient to change, and by encouraging the clinician to relinquish their p ­ rofessional

broad principles are useful in empowering health care professionals to both promote the care of “difficult-to-help” patients as well as improve physician resilience in responding productively to clinically challenging encounters.

These strategies include fostering intellectual curiosity about our own strong emotions in these interactions, cultivating empathy for patients, and setting appropriate limits when necessary.

Clinicians are likely to have a range of strong feelings when working with these patients, some of which might interfere with their cognition or with developing empathy. This work required to identify, understand, and process the emotions that arise in clinical care is termed “emotional labor.” Before we can manage those emotions to ensure they do not unduly interfere with our ability to problem-solve, we have to recognize that we are having them. Even if physicians notice their heart racing or their neck stiffening when they become tense and angry, admitting to having anger can be difficult if they believe these emotions are considered unprofessional.

However, a range of positive or negative emotions is a normal human response to any relationship, whether one is a health care professional or not. What differentiates health care professionals

By depersonalizing a patient’s behavior, physicians may find it easier to cultivate curiousity and empathy for the patient. responsibility for managing the challenges that arise in the patient’s care.

It still takes “two to tango,” whenever there is conflict. For that reason, more accurate, objective, and patientcentered labels drawn from research on this population include, “difficult encounter,” “difficult patient-physician relationship,” and “difficult-to help.”1 How then should physicians manage these complicated relationships given their ethical obligations? Some

from others is not that they do not have emotions, but rather that their emotions should not unduly affect their professional behavior or judgment. Counting slowly to 5 or taking deep breaths can help maintain our cool and minimize the likelihood of becoming angry.

By managing these strong emotions, clinicians can more easily cultivate the intellectual curiosity necessary for good patient care and the development of empathy for the patient. As one author

© MANGOSTOCK / SHUTTERSTOCK

Clinicians can manage their emotions to work productively with sometimes abrasive and argumentative patients BY DAVID J. ALFANDRE, MD

Patients who exhibit difficult behavior often are struggling, in distress, and need help.

has written, many of these patients “come by their behavior honestly.”2 They are often struggling, in distress, and need help. Reframing the problem from that perspective can often help make for more productive work with these patients.

It is easy to take the patient’s behavior personally and conclude that the patient is deliberately behaving in a way to make the physician’s life more difficult. In fact, the patient’s behavior may be consistent across other providers, and even with others outside of the health care setting. Their behavior may also be part of their response to illness, and they may be functioning the only way they know how. By remembering what the patient brings to the encounter and by depersonalizing such behavior, it may be easier to cultivate curiosity and empathy for the patient.3 Finally, there may be a role for reasonable, fair, and consistent limit setting when patients display unsafe, disrespectful, or otherwise inappropriate behavior.4 Physicians are justified in expecting respectful interactions from patients, and they can set limits on patient’s behavior under appropriate clinical circumstances. Working with trusted colleagues can help clinicians

identify what kinds of limits are reasonable, how to maintain appropriate professional boundaries, and how best to ensure the patient continues to receive high quality care.

At a minimum, reconceptualizing the “difficult patient” as the “difficult encounter” for what may be a sizeable minority of encounters intends to draw clinicians closer to their professional commitments and professional identify as healers. These are the important first steps to take, and a lofty goal for sure. n David J. Alfandre MD, MSPH, is a health care ethicist for the National Center for Ethics in Health Care (NCEHC) at the Department of Veterans Affairs (VA) and an Associate Professor in the Department of Medicine and the Department of Population Health at the NYU School of Medicine in New York. The views expressed in this article are those of the author and do not necessarily reflect the position or policy of the NCEHC or the VA. REFERENCES 1. Alfandre D. Reconceiving the relationship and supporting physician responsibility. Am J Bioeth. 2012;12:9-11.

2. Kahn, MW. 2009. What would Osler do? Learning from “difficult” patients. New Engl J Med. 361: 442-443.

3. Dyche L, Epstein RM. Curiosity and medical education.

Med Educ. 2011;45:663-668.

4. Sharrock J, Rickard N. Limit setting: A useful strategy in rehabilitation.” Aust J Adv Nurs. 2002;19:21-26.

28 Renal & Urology News

JULY/AUGUST 2018 www.renalandurologynews.com

Practice Management Hackers who break into medical devices to steal patient information may cause those devices to malfunction and harm patients BY TAMMY WORTH

Where’s the exposure?

Any device that is connected to the internet is vulnerable. Such devices include implantable defibrillators, insulin pumps, and glucometers and wearable devices such as those that measure heart rate or manage pain by delivering transcutaneous electrical nerve stimulation. Dialysis machines,

change device parameters, potentially leading to patient harm, Young said.

For instance, functionality of an MRI or dialysis machine can be locked out, go offline, or only be available sporadically.

A diagnostic device might function, but return wrong data, which could cause a provider to alter treatment plans inappropriately. A breach could interfere with the dosage or mixture of medication directly provided to a patient by a device.

Prevention strategies The longevity of medical devices is good for providers’ pocketbooks, but not for their security. Many older devices on the market were created with Windows 95—easily hackable more than 2 decades after its release.

Despite the vulnerability of medical devices to hackers, security still does not appear to be much of a concern for many of the manufacturers or providers using the technology. The FDA issued guidance for keeping medical devices safe in 2016. Young cited a recent survey by Synopsys, Inc., conducted by the Ponemon Institute, an IT security research organization, showing that only 51% of device makers and 44% of health care delivery organizations follow FDA’s mitigation advice.

‘Lots of legacy medical devices still run on older systems, unlike modern operating systems which are harder to hack.’ magnetic resonance imaging (MRI) units, and infusion pumps also are susceptible.

Amy Young, a marketing manager specializing in health care at Cisco Systems, Inc., headquartered in San Jose, California, said an average hospital can have up to 15 devices at each bedside that are networked and susceptible to hacking. When attackers break into a device, they might be aiming for data, but this attempt can have a cascading effect that can turn off or

Although there is no foolproof way to prevent every cyberattack, providers can take measures to mitigate problems. One strategy is to patch systems. Bach said providers should ensure they are using the latest software patches available for their operating systems and devices, if available. The notorious WannaCry virus that attacked Windows operating systems, for instance, gained entry through a vulnerability in May 2017. This occurred even though a patch that could have prevented it was available earlier that spring.

© SCOTT CAMAZINE / SCIENCE SOURCE

M

edical devices, which are manufactured with functionality in mind, are an underappreciated but important source of vulnerability to hacking. “In the emerging practice of medical hijacking, hackers and cyber adversaries have figured out those devices present an easy way into a provider’s network,” said Ori Bach, Vice President of Products at TrapX Security, a cybersecurity firm based in San Jose, California. “Lots of legacy medical devices still run on older systems, unlike modern operating systems which are harder to hack.”

Older software makes medical devices particularly susceptible to breaches.

Although most hackers use them as an opening into a network to steal data, an attack can cause delays in medical care or even directly harm patients should the devices malfunction.

Implanted defibrillators and other medical devices may be vulnerable to cyber attacks.

Health care providers should actively monitor their systems for issues, said Ramakrishnan Pillai, Director of Healthcare Risk and Compliance for Coalfire, a cybersecurity advising firm with headquarters in Westminster, Colorado. Providers should also perform regular risk assessments on all their devices. The devices should be categorized into high, medium and low risk with respect to hacking potential, with attention paid to those with the greatest potential for patient harm. Understand what is in the office, what is at risk, what software and hardware is being used, and the security controls in place, he urged.

Managing a breach If a device appears to have been breached, what then? Should a provider just turn it off? Does it need to be replaced? Who should be contacted?

As part of the risk management process, a plan needs to be created for each kind of device so, should a breach occur, staff will know where to check and how to address it. Some manufacturers will be able to offer security patches on newer devices, but many legacy devices will not have plans, Pillai said.

He recommends looking to vendors for aid. Any new contracts with a vendor

should touch on device management and note who is responsible for cybersecurity incidents. Vendors should also be able to show they have tested devices for their security and have reports or other paperwork to document this. Providers can check to see if vendors have strong cybersecurity teams that can help respond to breaches and get a provider back on their feet quickly.

“This should all be part of the procurement process,” Pillai said.

“Providers are spending thousands of dollars on equipment; they need to check it from a security perspective as well as a clinical one.”

Bach pointed out that health care providers can also look into deception technology to secure their organizations and gain full visibility into their health care networks. This strategy creates an identical but fictitious network that’s full of traps and when an attacker tries to attack the organization, he will be interacting with a fake network and all of his actions will be recorded. The organization will know where their weak point is in their security and their real assets will never be touched by attackers. n Tammy Worth is a freelance medical journalist based in Blue Springs, MO.