Urology & Kidney Disease News

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Glickman Urological & Kidney Institute A Physician Journal of Developments in Urology and Nephrology Vol. 21 | Winter 2012 G lickman Urological & Kidney & Kidney Urological lickman I n stitute stitute | Urology & Kidney Disease News News Disease & Kidney Urology | l. 21 V o

012 In This Issue: 17 45 58 Robotic Surgery with the Post-Transrectal Ultrasound The ABCDs of Antibiotic Dosing Adjunctive Use of Fluorescent (TRUS)- Guided Prostate Biopsy in Continuous Dialysis Imaging for Prostate Cancer Infection – Importance of Quality and Outcomes Surveillance 60 36 The Potential Role of Stem Cells Determinants of Renal Function 51 in Relief of Urinary Incontinence After Partial Nephrectomy: Molecular Insights into Implications for Surgical Technique Salt-Sensitive Hypertension 72 NextGenSM Home Sperm Banking Kit clevelandclinic.org/glickman 44 56 for Men from Geographically Remote Gene Expression Profiling of Critical Care Nephrology – Testing Sites Seeking Fertility Preservation Prostate Cancer: First Step to the Old and Finding the New Services: An Exciting Development Identifying Best Candidates for Active Surveillance

78224_CCFBCH_Cover_ACG.indd 1 12/12/11 7:37 PM Urology & Kidney Resources for Physicians Resources for Patients Physician Directory Disease News View all Cleveland Clinic staff online at Medical Concierge clevelandclinic.org/staff. For complimentary assistance for out-of-state patients and families, call 800.223.2273, ext. Referring Physician Center Chairman’s Report...... 4 55580, or email [email protected]. For help with service-related issues, information about our News from the Glickman Urological & Kidney Institute clinical specialists and services, details about CME oppor- Global Patient Services tunities, and more, contact the Referring Physician Center Chair Established in Urological Oncology Research...... 5 For complimentary assistance for national at [email protected], or 216.448.0900 or 888.637.0568. NIH Grant Addresses Navigating the and international patients and families, call Challenges of Kidney Disease...... 5 001.216.444.8184 or visit clevelandclinic.org/gps. Track Your Patient’s Care Online Partners Receive $1 Million Ohio Third Frontier Grant ® for Organ Imaging Project...... 5 DrConnect is a secure online service providing our MyChart Summer Internship at the Department of Urology - Leading physician colleagues with real-time information about the Cleveland Clinic MyChart® is a secure, online the Way in Medical Research and Education...... 6 treatment their patients receive at Cleveland Clinic. To personal healthcare management tool that connects New Staff...... 7 receive your next patient report electronically, establish patients to portions of their medical record at any Staff Awards and Appointments...... 7 a DrConnect account at clevelandclinic.org/drconnect. time of day or night. Patients may view test results, Case-Based Urology Learning Program Provides renew prescriptions, review past appointments and Request for Medical Records Real-World Experience...... 8 request new ones. A new feature, Schedule My 216.445.2547 or 800.223.2273, ext. 52547 Cleveland Clinic’s Indiana Partner Surpasses Appointment, allows patients to view their primary 100 Kidney Transplants...... 8 physician’s open schedule and make appoint- Cleveland Clinic Marks Milestone In Prostate Cancer Treatment. ....9 Critical Care Transport Worldwide Cleveland Clinic’s critical care transport teams and fleet ments online in real time. Patients may register for Six Fresenius Medical Care Facilities in MyChart through their physician’s office or by going Cleveland Honored for Superior Patient Care...... 9 of mobile ICU vehicles, helicopters and fixed-wing aircraft serve critically ill and highly complex patients across the online to clevelandclinic.org/mychart. Fluorescence cystoscopy demonstrates selective update of Center for Robotics & Image-Guided Surgery globe. Transport is available for children and adults. hexaminolevulinate HCl in bladder cancer with Cysview.™ Malignant Largest Reported Single-Institution Experience of 300 To arrange a transfer for STEMI (ST elevated myocardial tissue fluoresces bright pink, whereas normal urothelium is seen Robotic Partial Nephrectomies: Evolving Technique infarction), acute stroke, ICH (intracerebral hemorrhage), in blue. and Surgical Outcomes ...... 10 Image-Guided Percutaneous Thermal Ablation for Renal Tumors SAH (subarachnoid hemorrhage) or aortic syndromes, in 65 Solitary Kidneys: A Historical Review of Functional and call 877.379.CODE (2633). For all other critical care Oncological Outcomes...... 12 transfers, call 216.448.7000 or 866.547.1467 or visit Laparoendoscopic Single-Site Surgery in Urology: clevelandclinic.org/criticalcaretransport. Cleveland Clinic Claims Worldwide Multi-Institutional Analysis of 1,076 Cases...... 14 Robotic Surgery with the Adjunctive Outcomes Data Two No. 2 Spots in Latest Use of Fluorescent Imaging for Prostate Cancer...... 17 View clinical Outcomes books from Glickman Urological & U.S.News Rankings Thermal Ablation as Salvage Therapy for Renal Tumors in Kidney Institute and other Cleveland Clinic institutes von Hippel-Lindau Patients: Cleveland Clinic Experience...... 18 at clevelandclinic.org/quality/outcomes. Urology and Kidney Disorders Immediate Impact of a Robotic Kidney Surgery Course on Attendees’ Practice Patterns...... 20 both ranked No. 2 in the nation. CME Opportunities: Live and Online Robotic Laparoendoscopic Single-Site Radical Nephrectomy: Cleveland Clinic’s Center for Continuing Education’s website Surgical Technique and Comparative Outcomes...... 22 offers convenient, complimentary learning opportunities, Glickman Urological & Kidney Institute now has Novel Robotic System for Percutaneous Renal Probe Placement....24 from patient simulations, webcasts and podcasts to a host the distinction of holding two No. 2 positions in the SPIDER™ Surgical System for Urologic LESS: From Initial of medical publications and a schedule of live CME courses. U.S.News & World Report hospital rankings, with Laboratory Experience to First Clinical Application...... 25 Physicians can manage CME credits using the myCME.com No. 2 slots in both urology and kidney disorders. Robotic-Assisted Laparoscopic Partial Nephrectomy for a 7 cm Mass in a Renal Allograft...... 26 web portal available 24/7. Visit ccfcme.org. The 2011 “America’s Best Hospitals” survey Robotic vs. Laparoscopic Partial Nephrectomy for recognized Cleveland Clinic as one of the nation’s Bilateral Synchronous Kidney Tumors: Comparative best overall, ranking the hospital as No. 4 in the Analysis at a Single Institution...... 28 country. Cleveland Clinic ranked in all 16 of the Novel Robotic Renorrhaphy Technique for Hilar Tumors: specialties surveyed by the magazine. “V” Hilar Suture (VHS)...... 30 Feasibility, Advantages and Challenges of Thirteen of its specialties were listed among Retroperitoneoscopic LESS Nephrectomy...... 32 the top 10 in the United States. For details, visit ViKY Robotic Scope Holder: Preliminary Results clevelandclinic.org. Using Instrument Tracking...... 33 Center for Urologic Oncology: Bladder Cancer Outcome of Delayed Radical Cystectomy for Recurrent, Non-Muscle-Invasive, High-Grade Bladder Cancer Refractory to Bacille Calmette-Guérin (BCG)...... 34 clevelandclinic.org/glickman Fluorescence Cystoscopy Proves Its Worth in Management of Bladder Cancer...... 35

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Center for Urologic Oncology: Kidney Cancer Center for Genitourinary Reconstruction Male Transobturator Urethral Sling: Determinants of Renal Function after Partial Nephrectomy: Intermediate-Term Outcomes ...... 64 Implications for Surgical Technique ...... 36 Transitional Urology: Caring for the Urological Needs of Adults Center for Urologic Oncology: Prostate Cancer and Adolescents Born with Complex Congenital Anomalies ...... 65 Comparative Effectiveness of Radical Prostatectomy, External-Beam Radiotherapy, and Brachytherapy for Localized Center for Kidney/Pancreas Transplantation ProstateCancer in the Prostate-Specific Antigen Era ...... 38 The ORION Study: Optimizing Renal Transplant Immunosuppression to Overcome Nephrotoxicity ...... 66 Study of Active Surveillance of Localized Prostate Cancer May Show Promise of Method ...... 39 Toward Identifying Risk and Individualization of Care for Kidney Transplant Recipients ...... 67 Decision-Making for Localized Prostate Cancer: the Prostate Cancer ‘Metagram’ ...... 40 Participation in Research by Kidney Transplant Recipients ...... 68 PCA3 in Daily Practice ...... 41 Short- and Long-Term Outcomes of Acute Kidney Injury after Lung Transplantation ...... 70 Focal Therapy Classification System: Creating a Common Language for Organ Sparing Treatment of Prostate Cancer ...... 42 Kidney and Pancreas Outcomes and Innovations...... 71 Do Margins Matter? The Influence of Positive Surgical Center for Male Infertility Margins on Prostate Cancer-Specific Mortality ...... 43 NextGenSM Home Sperm Banking Kit for Men From Gene Expression Profiling of Prostate Cancer: First Step Geographically Remote Sites Seeking Fertility Preservation to Identifying Best Candidates for Active Surveillance ...... 44 Services: An Exciting Development ...... 72 Post-Transrectal Ultrasound Guided (TRUS) Prostate Biopsy Infection – Importance of Quality and Outcomes Surveillance ...... 45 Center for Pediatric Urology Post-Cryoablation Voiding Symptom Five-Year Experience With Sacral Neuromodulation in Control Study Shows Promise ...... 46 20 Children at a High-Volume Community Referral Center ...... 73 Comparison of Office-Based Transrectal Saturation Biopsy to Standard Biopsy: Superior Cancer Detection for Repeat Biopsy ...47 Center for Renal Diseases Intracellular Synthesis of Hyaluronan Induces ER Center for Urologic Oncology: Testis Cancer Stress/Autophagy in Diabetic Nephropathy ...... 74 Testis Cancer: Practice Guidelines for the Polycystic Kidney Disease and MicroRNAs: Management of Clinical Stage I Nonseminoma from Cyst Formation Mechanism Examined ...... 75 the Société Internationale d’Urologie ...... 48 Author Index ...... 76 Center for Blood Pressure Disorders ...... 77 Resistant Hypertension Clinic Provides Complete, Physician Resource Guide Specialized Care to Patients ...... 50 The articles in the publication are written for educational Molecular Insights into Salt-Sensitive Hypertension ...... 51 purposes only and are presented as a convenience. Cleveland Aldosterone: Newly Discovered Biosynthetic Pathways and Clinic has no financial interest nor is it endorsing any product Their Increasing Role in Various Cardiovascular Disorders ...... 52 or device mentioned herein. Center for Chronic Kidney Disease 25-Hydroxy Vitamin D Deficiency in Nondialysis-Dependent Chronic Kidney Disease ...... 53 Measurement of Biomarkers by Liquid Chromatography-Tandem Upcoming Events – Save These Dates Mass Spectrometry in Biological Matrices ...... 54 Metabolic Syndrome and Chronic Kidney Disease ...... 55 April 13-14, 2012 Critical Care Nephrology – Testing the Old and Finding the New .. 56 The CKD Clinic as Managed by a Nurse Practitioner ...... 57 Ambulatory Urology Course Led by Dr. J. Stephen Jones and Dr. Edmund Sabanegh Center for Dialysis The ABCDs of Antibiotic Dosing in Continuous Dialysis ...... 58 Oct. 25, 2012 Center for Endourology and Stone Disease Kidney Stones: Medical, Surgical Stone Clinic Study Shows Promise in Dietary Interventions and Dietary Approaches in Kidney Stone Treatment and Prevention ...... 59 Course Director: Dr. Manoj Monga

Center for Female Pelvic Medicine & Reconstructive Surgery Oct. 26-27, 2012 The Potential Role of Stem Cells in Relief of Urinary Incontinence ...... 60 Fourth Annual Purely Transvaginal/Transperineal Management Robotic Kidney Course of Complex Mesh Complications ...... 61 Course Director: Dr. Jihad Kaouk Pudendal Nerve Stretch Reduces External Urethral Sphincter Activity in Rats ...... 62 Please visit ccfcme.org for more details on these Creating the first Telomerase-immortalized, Non-transformed events as they become available. Urothelial Cell Lines for Urological Basic Science Research ...... 63

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Chairman’s Report

scientists and surgeons continue to work together on the Eric A. Klein, MD development of an implantable bioartificial kidney that Chairman, Cleveland Clinic Glickman will bridge the need for dialysis until the time of transplant. Urological & Kidney Institute Our CKD team was recently recognized by winning Cleveland Clinic’s Human Subjects Research Annual Excellence Award for its work in developing a CKD registry that serves as a national resource for understanding trends in the management of CKD, and by a three-year, more than $700,000 grant from the National Institute of Diabetes and Greetings! We are pleased to bring you another edition of Digestive and Kidney Diseases to study patient navigation Urology & Kidney Disease News, containing a broad overview issues for patients with this condition. of the scientific, clinical and educational activities of the Glickman Urological & Kidney Institute in the last year. Synergy among specialists is not limited to our own institute For the 11th straight year, in 2011, our urologists were – in September, and in collaboration with physicians and recognized by U.S.News & World Report as one of the two others in the Taussig Cancer Institute, our brachytherapy best urologic programs in the country, a ranking we are now team celebrated the 15th anniversary of the brachytherapy pleased to share with our nephrologists, who jumped from program for treatment of prostate cancer. Together, the team fourth to second place. has performed more than 4,000 procedures in men with localized, locally advanced and locally recurrent disease, These twin rankings are reflective not only of strengths with patients benefiting from the ultrasound expertise in our individual departments, but of the synergy that of the urologists and the radiation and physics expertise the Institute model brings to bear on patient care. As of radiation oncologists. government and private reimbursement moves toward a value-based purchasing environment that emphasizes Articles in this issue detail aspects of these programs, but quality of care (best outcome for least cost) and patient also highlight the work of individual clinical centers, ranging News from the Glickman Urological & Kidney Institute satisfaction with the processes of care, we are uniquely from the molecular biology of bladder and prostate cancer, situated to meet both challenges by the establishment to new diagnostic approaches, to the latest in GU reconstruc- of joint clinical and research programs. tion and minimally invasive surgery for a variety of urologic conditions. Patients seen in our institute benefit from both urologic and nephrologic expertise in a single visit to one of our shared We hope you will enjoying learning about our efforts. programs – kidney stone disease, refractory hypertension, chronic kidney disease (CKD), and renal and pancreas transplantation. A newly established Acute Kidney Injury program has all patients scheduled for renal surgery undergo nephrologic evaluation preoperatively to ensure that treatment is medically optimized to minimize the impact of renal ischemia and nephron loss on overall renal function. An- Eric Klein, MD other new program in Transitional Urology combines forces to ease the transition of care for those born with complex congenital anomalies and urinary reconstruction from childhood to adolescence and adulthood. For the CKD cohort, our

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Chair Established in Urological Oncology Research

J. Stephen Jones, MD, Chairman of Cleveland Clinic’s Partners Receive $1 Million Institute Kidney & Urological Glickman the from News Department of Regional Urology, is the holder of the new Leonard Horvitz and Samuel Miller Distinguished Chair in Ohio Third Frontier Grant Urological Oncology Research for the Glickman Urological & for Organ Imaging Project Kidney Institute. The chair, supported by the Horvitz and Miller families, will advance the work of Dr. Jones, whose research On Aug. 29, 2011, the Ohio Third Frontier Commission focuses on bladder and prostate cancer. The author of more unanimously approved Quality Electrodynamics’ (QED) than 160 publications in major urological journals and nearly grant proposal for the company’s novel organ viability 30 book chapters, Dr. Jones also has edited four urological imaging project. QED’s proposal was successfully judged textbooks and has written books for the lay public, including among other grant requests (No. 2 out of 18 proposals) The Complete Prostate Book and Overcoming Impotence. in the areas of technical innovation, commercialization potential and economic development opportunities for Ohio. The Third Frontier will fund this project for the entire requested amount of $1 million.

NIH Grant Addresses Quality Electrodynamics LLC, located in Mayfield Navigating the Challenges of Village, in collaboration with the Glickman Urological & Kidney Institute, Case Western Reserve University, Toshi- Kidney Disease ba Medical Systems and Canon Inc., received the funding for the project titled Development and Commercializa- Cleveland Clinic’s Joseph Nally, Jr. MD, was recently tion of a Novel Imaging System to Determine Organ awarded a three-year, $720,000 grant to study and Viability. The project will develop specialty MRI coils for develop support approaches for disease management for imaging donor kidneys to determine their viability before patients with chronic kidney disease. Dr. Nally received transplantation. The unique system will allow transplant the first installment of $274,750 in September from centers to directly test kidneys and potentially other the National Institute of Diabetes and Digestive and organs, to determine if they are viable for transplantation, Kidney Diseases. which may serve to expand the available transplant pool.

Chronic kidney disease is a large and costly public health Glickman Urological & Kidney Institute’s David problem in the United States that will continue to grow Goldfarb, MD, participated in the project. with the aging of the population and increasing incidenc- Total funding awards for this round total $30 million in es of obesity, hypertension and diabetes. Although evi- six distinct areas. The Medical Imaging Program grantees dence-based treatments and self-management regimens will receive a total of $3,579,649 in awards this year. are available that are effective in slowing the progression of CKD to end-stage renal disease, inadequate aware- The goal of the Ohio Third Frontier Medical Imaging ness and coordination among patients and primary care Program is to accelerate the development and growth providers has prevented widespread implementation of of the medical imaging industry and its supply chain in those approaches. Ohio by direct financial support to organizations seeking to investigate near-term specific commercial objectives The grant will fund a clinical trial to test two interac- with respect to products or processes. The program tive informational approaches to improving chronic care seeks to commercialize new products; adapt or modify and ultimately outcomes of CKD patients. The trials will existing devices or components in order to address issues involve adapting a successful patient navigator model for including cost, resolution quality or image acquisition this population, enhancing an electronic health record time; address technical and commercialization barriers; for specific use for CKD patients and using a randomized or demonstrate market readiness. clinical trial to test both approaches. Ohio Third Frontier is a bipartisan commitment to create The results of the study will lay the foundation for a new technology-based products, companies, industries larger multicenter national clinical trial that will build and jobs. The commission has attracted more than $5.9 upon the feasibility and knowledge gained from this billion in other investments to Ohio and has a nearly planning grant to work toward translating effective in- 9-to-1 return on investment since its inception. Ohio Third terventions into routine clinical practice and ultimately Frontier has also assisted in the creation and retention of improving the care of those with CKD. more than 68,000 direct and indirect jobs for Ohioans. For more information, contact Dr. Nally at For more information, visit ohiothirdfrontier.com. [email protected].

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Summer Internship at the Department of Urology - Leading the Way in Medical Research and Education

Ashok Agarwal, PhD, and Edmund Sabanegh, MD Program Goals:

The summer internship program offered by the Center for • Encourage students to consider a career in medicine Reproductive Medicine is a unique, well-structured and • Provide a wide range of high-quality research experiences highly integrated research internship for premed and medical students. The program is now in its fourth year. The • Allow participation in research programs in a real eight-week-long, highly sought-after program introduces laboratory setting the fundamentals of clinical research to college and medi- • Facilitate close interaction with reproductive cal students from around the world. endocrinologists, gynecologists, urologists and The interns receive rigorous training and ample opportu- male infertility specialists. nities for scientific education, research and writing. They

receive personal coaching by a team of mentors to write and publish high-quality scientific articles in high-impact jour- Rewards of Summer Internship: nals, an experience that distinguishes this program from • Interns have the opportunity to obtain six research any other internship. In the past four years, 100 interns credits through the University of South Alabama, from across the U.S. and around the world have completed transferable to any major college or university upon the program. These features make this program among the completion of the course. most unique of its kind in the world. • Students from previous classes have joined highly The course faculty is drawn from many medical specialties. competitive medical schools. The faculty delivers lectures on important topics related to scientific writing, reproductive medicine, bioethics, labora- • The majority of interns have authored research tory medicine, endocrinology, public speaking and more. articles that were published in peer-reviewed journals Summer interns work alongside reproductive scientists or in a medical textbook. and staff clinicians on interesting research projects in real The summer internship offers a unique opportunity for laboratory environments. The interns have opportunities students interested in acquiring research experience in to interact with infertility specialists - reproductive endo- human fertility and reproductive biology. Students gain crinologists (gynecologists) or male infertility specialists the opportunity to work with world-renowned physicians, (urologists) - and observe those specialists in clinics scientists and researchers.

News from the Glickman Urological & Kidney Institute or in surgery. For more information about the internship program, Interns participate in writing please email the editor. research articles, reviews and invited book chapters in reproductive biology and human infertility. Each year since 2008, there has been a steady increase in publications. Eighteen articles and reviews were published in 2008; 25 were published in 2009; and in 2010, interns published more than 30 articles, with some still in the works. The students attend weekly research meetings, lectures and group discussions. The internship faculty guides the interns in conducting cutting- edge bench research projects. In 2010, five bench projects were conducted; four projects were conducted thus far this year.

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Edgard Wehbe, MD, received his medical New Staff The Glickman Urological & Kidney degree from Lebanese University Medical Institute welcomes the following new staff members: School and completed a residency in internal medicine at the University of Kansas Medical Center. He also completed a Jennifer Lisette Bennett, MD,

fellowship in nephrology and hypertension Institute Kidney & Urological Glickman the from News received her medical degree from at Cleveland Clinic. His specialty interests the Boston University School of Medicine. are in acute kidney injury hypertension - She completed an internship in general high blood pressure, kidney disease, renal surgery as well as a residency in urology failure and dialysis. at the University of California San Diego Medical Center. Dr. Bennett serves in the Department of Regional Urology at Hillcrest Hospital and the Twinsburg Resident Awards Family Health and Surgery Center.

Christopher J. Weight was awarded the George and Michael Ganz, MD, received his Grace Crile Traveling Fellowship, 2010. medical degree from the Medical College of Pennsylvania and Hahnemann Amit R. Patel, MD was awarded the 2010 Outstanding University. He completed an internship Laparoendoscopic Resident Award. at the University of Illinois at Chicago and Michael C. Lee, MD was awarded The Society of a residency at Veterans Affairs Chicago Laparoendoscopic Surgeons Award for Best Poster at Health Care System. He also completed the 9th SLS Annual Meeting and Endo Expo 2010 for a fellowship in nephrology at Yale New “Tumor in Solitary Kidney Laparoscopic Partial Nephrec- Haven Hospital, as well as a research fellowship, also in tomy vs. Laparoscopic Cryoablation, September 2010. nephrology, at West Haven Veterans Administration Hospital. Christina B. Ching, MD was awarded the 2010 Dr. Ganz has offices at both the main campus and the Stephanie John B. Silbar Award from the North Central Section Tubbs Jones Health Center. of the American Urological Association (AUA),

September 2010. Islam Ghoneim, MD, received his medical degree from the University of Cairo Christina B. Ching, MD was awarded the National and completed a residency in urology at Institutes of Health (NIH) supported Trainee Travel the Cairo University Hospital. He also Award to support her presentation at the 36th completed a research fellowship in urologic Annual American Society of Andrology conference oncology at Cleveland Clinic as well as in Montreal, Quebec, Canada, April 2011. a fellowship in urology and pancreas Kiranpreet Khurana, MD was awarded Best Poster at transplantation. He joins the Department AUA, Washington, D.C., Moderated Poster Session, of Regional Urology/Renal and Pancreas Transplantation program “Localized Prostate Cancer,” May 2011. at St. Vincent’s Hospital in Indianapolis. Christina B. Ching, MD was awarded the Bruce Hubbard Thomas Picklow, MD, received his Stewart Award for Humanistic Medicine, May 2011. medical degree from The Ohio State Christina B. Ching, MD was awarded best AUA video University College of Medicine and Public for video on “Ex vivo RAA repair and autotransplanta- Health. He received his postgraduate tion” at AUA, Washington, D.C., May 2011. training at the University of Cincinnati Christopher M. Brede, MD won Best Poster for Medical Center/University Hospital, where “Medical Expulsive Therapy (MET) for Ureteral Calculi he completed residencies in both general in the Real World” at AUA, Washington, D.C., May 2011. surgery and urology. Dr. Picklow serves in the Department of Regional Urology at Byron H. Lee, MD, PhD, was awarded the 2011 the Wooster Specialty Center. His specialties include bladder Outstanding Laparoendoscopic Resident Award. He was cancer, bladder retention, kidney stones, prostate disease, nominated for demonstrating great promise in laparo- urinary obstruction and urinary tract infection. scopic, endoscopic and minimally invasive surgery.

Oliver Wessely, Ph.D, received his doctorate in cell biology from the University of Vienna. Dr. Wessely has a joint appointment in cell biology at the Lerner Research Institute.

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Case-Based Urology Learning Program Provides Real-World Experience

Steven C. Campbell, MD, Devon Snow, MD, and the selected reading is also available for more detailed David A. Goldfarb, MD perspective if so desired. Today’s residents prefer an electronic format for learning, ideally provided in a flexible We have recently rolled out a new Case-Based Urology manner, and CBULP is designed specifically with these Learning Program (CBULP) for our residents and fellows that considerations in mind. should prove to be a valuable resource for building a strong knowledge base. We do so with the belief that a solid knowl- This program is being developed in collaboration with our edge base will facilitate optimal enjoyment of the partici- colleagues at University Hospitals Urologic Institute and pants’ clinical practices as the years go by. The program Rainbow Babies and Children’s Hospital. Jonathan Ross, will also help our trainees and faculty prepare for Board of MD, is serving as associate editor and is overseeing the Pedi- Urology and recertification examinations. atric Urology components of the program. David Goldfarb, MD, from our faculty is also serving as an associate editor. The program is based on cases that cover the most common and important clinical scenarios that a urologist will en- This program uses our unique strengths within each sub- counter during routine practice. The goal of each case is to specialty of the field to their best advantage. It also has as its illustrate the main principles of the disease process and the foundation the dedication of our faculty to resident and fel- fundamentals of clinical evaluation and management. lowship training and the education mission in general. Thus far, we have released more than 50 items, with an ultimate The rationale for developing a novel learning program is goal of approximately 20-30 within each subspecialty of the now strong. In this era of duty hours, all programs have had field, covering all of the important topics in urology. to restrict the amount of conference time (e.g., no Saturday conferences) and to be as efficient as possible with their For a selection of representative cases used in the program, daily operations. The number of in-house calls is also more visit clevelandclinic.org/CBULP. restricted than it was in the past, and the amount of time For more information, please email the editor. that the residents spend in clinic has also been substantially

reduced in most programs, including our own. Hence, the number of seminal learning cases that the typical resident encounters in the clinics, emergency ward or other clinical Cleveland Clinic’s Indiana settings has been substantially reduced, and teaching related to these encounters is not always optimal, despite our best Partner Surpasses 100

News from the Glickman Urological & Kidney Institute efforts. In addition, the field is now suffering from informational overload, and a concise, clinically oriented learning Kidney Transplants program is now more relevant than ever. Alvin Wee, MD

Furthermore, trainees are now learning three types of Since first offering kidney transplants in January surgery rather than two, and they are naturally focused on 2009, our St. Vincent Indianapolis Hospital surgical skills acquisition. At the same time, other core program has surpassed the 100-transplant mark. competencies such as professionalism and communication This 100-transplant milestone was reached in skills have been upgraded by the ACGME, and rightfully so. August 2011. Many residents are also focused on academic productivity in According to the Scientific Registry of Transplant an effort to optimize their chances for a top-level fellowship. Recipients (srtr.org), our program showed a one-year, Along the way, knowledge base has become “the neglected 100 percent graft and patient survival rate. Our me- core competency.” dian waiting time is eight months, which is one of the CBULP will help to fill in these gaps in a proactive, shortest nationwide. As of mid-2011, all of our living constructive manner and will complement our conventional donor procedures were performed laparoscopically. Monday and Wednesday morning teaching conferences. Mona Zaweidah, MD, pediatric nephrologist, is the Emails are distributed on Tuesday and Thursday of each Medical Director of the newly developed pediatric week, each containing a case as a PDF along with a selected renal transplant program, which recently began reading. Each item utilizes the Socratic method, with a brief evaluating pediatric patients. clinical scenario followed by a series of questions with the answer provided on the next slide. The trainees are strongly We are also pleased to announce that we have encouraged to challenge themselves prior to accessing the received approval for commencement of a pancreas answer in an effort to optimize the learning experience. Each transplant program, which is expected to begin case can be reviewed in 10 -15 minutes in this manner, and in late 2011.

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Cleveland Clinic Marks Milestone Brachytherapy is most often offered as a method for treating low- and medium-risk cancers that are confined to the pros- in Prostate Cancer Treatment tate. A team of more than 20 specialists, including urologists, radiation oncologists, physicists and radiation therapists, offer the therapy at five locations throughout the Cleveland Prostate cancer specialists at Cleveland Clinic marked two

Clinic health system. Institute Kidney & Urological Glickman the from News milestones this past September: the 15th anniversary of introducing brachytherapy treatment and the completion of “Patients have come to us from 32 states and 15 countries more than 4,000 brachytherapy cases. because of our brachytherapy expertise and experience, which incorporates advanced imaging technology and still Prostate brachytherapy is a minimally invasive procedure allows for same-day planning and implantation,” said during which radioactive seeds are permanently implanted radiation oncologist Jay Ciezki, MD. into the prostate. Cleveland Clinic began offering prostate brachytherapy in September 1996. The team surpassed 1,000 Cleveland Clinic also maintains one of the largest interna- cases in 2004, and the program has since grown to become tional databases that tracks prostate cancer patients and one of the largest in the country. their outcomes, sorted by treatment method. The information is shared with new patients so that they can evaluate “Patients at Cleveland Clinic benefit from being able to what options work best for many other men. consult with a multidisciplinary team that has shown strong results in identifying cancer types and offering treatment op- Outcomes tracked by Cleveland Clinic starting in 1996 show tions that consider the risk of recurrence and optimal quality that among patients with low-risk prostate cancer, at least of life,” said Eric Klein, MD, chairman of the Glickman Uro- 93 percent of patients tested were cancer-free after five years. logical & Kidney Institute. Outcomes after 10 years showed that at least 83 percent of patients had not relapsed, across all treatment approaches. The number and placement of these seeds are determined by a computer-generated treatment plan. Prostate cancer pa- In addition to brachytherapy, Cleveland Clinic offers a variety tients can receive up to 300 or more pellets at once, depend- of treatment options that include surgical and nonsurgical ing on the size and shape of the prostate. The targeted place- approaches. Options include radical prostatectomy, and ment of the pellets avoids radiation exposure to surrounding variations include robotic or minimally invasive techniques healthy tissue. The seeds remain in place permanently but designed to preserve urinary and sexual function. become biologically inert after about 10 months. Nonsurgical treatment options include active surveillance. For more aggressive cancers, options include radiation through brachytherapy or external beam radiation, cryotherapy and hormone therapy.

Six Fresenius Medical Care Facilities in Cleveland Honored for Superior Patient Care

Fresenius Medical Care North America recently named • Fresenius Medical Care Cleveland Clinic Westside Cleveland Clinic’s dialysis facilities Centers of Excellence (Brook Park) for achieving the highest standards in patient care in 2010. • Fresenius Medical Care Farnsworth (Cleveland) These annual awards recognize the facilities that perform the best, based on multiple objective measures of dialysis • Fresenius Medic al Care North Randall clinical quality. • Fresenius Medical Care Solon All Fresenius Medical Care dialysis clinics share the • Fresenius Medical Care Willoughby company’s mission of delivering excellent, patient-centered care through innovative programs, the latest technology, Fresenius Medical Care has established high standards continuous quality improvement and a focus on superior of clinical quality in keeping with those published by customer service. the Kidney Disease Outcomes Quality Initiative of the National Kidney Foundation. Fresenius Medical Care This year’s Center of Excellence award winners in the selects Centers of Excellence facilities by reviewing the Cleveland area are: patients’ outcome measures such as dialysis adequacy, • Fresenius Medical Care Cleveland Clinic Eastside control of anemia, nutritional status, vascular access, patient satisfaction and transplant education.

78224_CCFBCH_Text_ACG.indd 9 12/7/11 12:14 PM 78224_CCFBCH_Text_ACG.indd 10 Center for Robotics & Image – Guided Surgery News Disease Kidney & Urology 10 Nephrectomies: Evolving Technique and Surgical OutcomesLargest Reported Single-Institution Experience of 300 Robotic Partial than 300 patients, the largest single-institution experience. for robotic partial nephrectomy and describe results in more Herein, we describe the evolution of our present technique more challenging tumors. mally invasive approach for partial nephrectomy and for benefit may be the ability for more surgeons to offer a mini- burdensome and operator fatigue decreased. The largest advantages. As a result, learning curves are likely to be less higher complication rates largely due to hemorrhagic events. for more difficult tumors, and have been associated with scopic approaches have not been widely adopted, especially benefits of minimally invasive surgery. Nevertheless, laparo- cellent oncologic outcomes while providing the recovery Laparoscopic partial nephrectomy has demonstrated ex- ablative procedures with respect to disease-free survival. phrectomy rivals radical nephrectomy and surpasses probe terms of treatment options for sporadic tumors, partial ne- tages and decreased pain compared to open techniques. In have become increasingly popular due to recovery advan- Minimally invasive techniques for treatment of renal tumors Haber, MD,andRobertJ.Stein,MD Jihad Kaouk, MD,ShahabHillyer, MD,Georges-Pascal 3-D visualization, precision movement and ergonomic underscores certain technological benefits including The rapid adoption of robotic techniques for prostatectomy trainees and considerable ergonomic disadvantages. skills, considerable learning curve, difficulty in teaching tomy likely include requirement for advanced laparoscopic Reasons for lack of adoption of laparoscopic partial nephrec- (mean ±S.D.,median[Range]) Age, years Table 1.Baselinepatientcharacteristicsforbothtechniquegroups (mean ±S.D.,median [Range]) (mean ±S.D.,median[Range]) BMI (mean ±S.D.,median[Range]) ASA score (mean ±S.D.,median[Range]) Charlson score (mean ±S.D.,median[Range]) Radiographic tumorsize,cm Male gendernumber(%) Multiple tumorsnumber(%) Caucasian racenumber(%) Bilateral tumorsnumber(%) (mean ±S.D.,median[Range]) Preop serumcreatininemg/dL kidney number(%) orfunctionallysolitary Solitary ml/min/1.73 m eop MDRD eGFR Pr 2

80.47 [31.98,131.19] Prior to Contemporary Prior toContemporary Technique (N=61) 27.4 [20.05,47] 0.9 [0.51,1.69] 61.36 ±12.41, 82.99 ±20.75, 29.24 ±5.87, 2.39 ±0.53, 0.67 ±1.01, 2.90 ±1.43, 0.94 ±0.24, 2.6 [1.1,11] 62 [30,88] 6 (9.83%) 7 (11.5%) 36 (58%) 57 (93%) 2 [2,4] 0 [0,4] 0 (0%)

Contemporary TechniqueContemporary 85.95 [19.88,494.89] 29.31 [17.40,60.33] 0.89 [0.16,2.58] comes and extended indications complex tumors. for more the robotic approach continue to evolve with improving out- invasive nephron-sparing surgery. Modified techniques for is technically safe and effective as an option for minimally Initial experience suggests that robotic partial nephrectomy 1 and 2 for complete results and patient characteristics.) focally positive margins (0.8 percent) were noted. (See Tables four patients developed urine leaks (1.5 percent) and two complications (0.8 percent ) requiring angioembolization, In this series, only two patients experienced hemorrhagic of postoperative complications (p=0.005). time (p<0.0001) and hospital stay (p<0.02) and greater risk porary technique in terms of transfusion rate (9.1 percent vs. Significantly better outcomes were noted using the contem- ischemia time and nephrometry scores. depending upon renorrhaphy technique, length of warm closure (Fig 1A-F). Perioperative results were evaluated continuous horizontal mattress stitch for the capsular renorrhaphy, while our contemporary technique uses a experience, included a standard interrupted bolstered adopted from our laparoscopic partial nephrectomy predicted longer operative time (p<0.001), warm ischemia Increasing tumor complexity based on RENAL score complication rate (15.2 percent vs. 31.2 percent, p<0.01). p<0.001), hospital stay (3.7 vs. 4.3 days, p=0.02) and overall 26.2 percent, p<0.001), operative time (182 vs. 219 minutes, from June 2007 to March 2011. Our original technique, base yielded 302 robotic partial nephrectomy procedures maintained minimally invasive partial nephrectomy data- A retrospective review of our IRB-approved, prospectively 57.61 ±11.93, 85.95 ±35.60, 31.01 ±7.25, 2.52 ±0.59, 3.18 ±1.66, 0.85 ±1.00, 0.97 ±0.34, 58 [18,86] 2.7 [1,8.6] 11 (4.56%) 22 (9.13%) 138 (57%) 209 (87%) (N=241) 2 (0.8%) 3 [1,4] 0 [0,3] 85.50 [19.88,494.89] 29.10 [17.40,60.33] 0.89 [0.16,2.58] 58.46 ±12.00, 85.38 ±33.18, 30.62 ±7.02, 3.11 ±1.61, 2.50 ±0.58, 0.80 ±1.01, 0.96 ±0.32, 59 [18,88] 2.7 [1,11] 174 (58%) 266 (88%) 17 (5.6%) 29 (9.6%) (N=302) 2 (0.7%) 2 [1,4] 0 [0,4] Overall

p-value 0.03 0.82 0.24 0 0.12 0.33 0 0.15 0.22 0.78 0.57 1.0 .08 .78

12/21/11 9:36 AM 11 Center for Robotics & Image – Guided Surgery 12/16/11 1:39 AM 0.001 0.02 0.27 0.58 0.10 0.14 0.87 0.09 0.09 0.81 0.71 0.018 p-value 0.0003 0.0018 0.0046 0.0015 < clevelandclinic.org/glickman NA NA NA NA NA NA Overall 3 [1, 20] 8 [6, 13] 7 [4, 11] (N=302) 19 [0, 90] 3.80 ± 1.97, 8.75 ± 1.72, 6.87 ± 1.76, 180 [90, 540] 9.87 ± 15.06, -9.59 ± 16.50, -9.12 ± 18.46, 200 [10, 2500] 19.13 ± 10.98, 12.21 ± 19.64, 191.00 ± 56.73, 8.25 [-30, 42.86] 279.79 ± 310.06, -8.93 [-100, 50.92] 9.33 [-25.58, 87.50] -9.78 [-51.59, 40.63] Figure 1C: Tumor resection using cold scissors resection using cold Tumor 1C: Figure Figure 1F: Renal capsular closure with original technique, capsular closure with original technique, Renal 1F: Figure Note that interrupted sutures placed over cellulose bolster. completely the capsule can be gradually approximated, as eliminating the need for traditional bolster placement described frequently in the laparoscopic approach. 3 (1.2%) 6 (2.5%) 1 (0.4%) 3 [1, 20] 8 [6, 13] 7 [4, 11] (N=241) 22 (9.1%) 20 (8.3%) 37 (15.4%) 18.5 [0, 90] 3.66 ± 2.02, 8.83 ± 1.77, 6.88 ± 1.77, 180 [90, 390] 18.93 ± 9.85, 9.46 ± 14.33, 5.63 ± 13.54, -9.44 ± 18.90, -4.09 ± 16.18, 200 [10, 2500] 182.78 ± 48.88, .21 [-25.58, 26.25] 264.61 ± 318.14, -8.64 [-100, 42.41] 8.05 [-26.39, 42.11] 4 -4.65 [-23.58, 40.63] Contemporary Technique (8.2%) 2 (3.3%) 6 (9.8%) 5 4 [2, 10] 8 [7, 11] 7 [4, 10] 16 (26.2%) 14 (23.0%) 19 (31.2%) 21.5 [0, 83] 4.33 ± 1.70, 8.35 ± 1.43, 6.82 ± 1.75, -8.42 ± 17.79, 200 [118, 540] 300 [50, 1400] 19.83 ± 14.39, 10.74 ± 16.73, 17.15 ± 22.26, -13.71 ± 15.89, 219.51 ± 71.65, 8.87 [-30, 42.86] Technique (N=61) Technique 337.05 ± 272.30, lok clips Prior to ContemporaryPrior -9.34 [-33.74, 50.92] 14.09 [-11.11, 87.50] -14.09 [-51.59, 14.56] Figure 1E: Renal capsule is reapproximat- 1E: Renal Figure mattress horizontal continuous, a using ed suture with intermittent placement of sliding hem-o- Figure 1B: Renal vessels are occluded Renal 1B: Figure with bulldog clamps DUA Score Total blood transfusions number (%) Total Intraop blood transfusions number (%) blood transfusions number (%) Postop Intraop complications number (%) Postop complications number (%) Postop Conversions number (%) Hospital Stay (days) Operative Time (min) Operative Time Warm Ischemia Time (min) Ischemia Time Warm Estimated Blood Loss (cc) PA RENAL Score % change serum creatinine – 1 month Table 2: Robotic partial 2: Robotic nephrectomy data based on differences in technique Table mean ± S.D., median [Range] % change eGFR – 1 month % change eGFR – 6 month % change serum creatinine – 6 month Figure 1D: Running suture of the suture 1D: Running Figure vessels bed to oversew larger excision as well as entries into the collecting system Figure 1A: Patient and port 1A: Figure Patient positioning for RPN 78224_CCFBCH_Text_ACG.indd 11 82_CBHTx_C.nd12 78224_CCFBCH_Text_ACG.indd Center for Robotics & Image – Guided Surgery News Disease Kidney & Urology 12 eGFR (ml/min/1.73m Median (IQR) Mean ±SD Serum creatinine(mg/dl): remnant No. solitary disease Heart Cancer otherthanrenal Diabetes H No. comorbidities Median (IQR) Mean ±SD Mean ±SD Body massindex (kg/m Median (IQR) Mean ±SD ASA score: Other White No. Race: M F No. gender: Median (IQR) Mean ±SD 29/36 Age (yrs): No. tumors No. pts/No.procedures Table 1(a)Patient characteristics Median (IQR) ypertension Solitary Kidneys: Image-Guided Percutaneous Thermal Ablation for Renal Tumors in 65 p Even iftheultimategoalremainscancercontrol,maximal ical outcomescomparabletothoseofpartialnephrectomy. represents anattractiveoptionwithreportedearlyoncolog- mors andhereditarytumorsyndromes,ablativetherapy In casesofrenalmassesinasolitarykidney,bilateraltu- and preservedrenalfunction. ity, shorterhospitalization,earlierreturntonormalactivity these cases. n patients whoarepoorsurgicalcandidates.Thesetech- ablative procedureshavebeenincreasinglyappliedtotreat the besttreatmentoptionforsmallrenalmasses,probe Although surgicalnephron-sparingproceduresrepresent and ErickM.Remer, MD Autorino,Riccardo MD,CharlesM.O’Malley, MD, Jihad H. Kaouk, MD,Fatih MD, Altunrende, reservation ofrenalfunctionisanothermajorgoalin iques providethepotentialbenefitsofdecreasedmorbid- 2 ): 2 ): 71(886.)52.4(44.8-64.3) 57.1 (48.8-66.8) 28 49 09 26 0.4 60.90±12.69 62.80 ±14.98 29.90 (17.14- . 1215 1.4(1.1-1.6) 1.3 (1.2-1.5) .5±03 .4±05 0.3 1.44±0.51 1.35 ±0.34 73±1. 4±1. 0.4 54± 16.6 57.3 ±16.6 .7±03 .0±06 0.6 3.00±0.66 2.97 ±0.37 5(57)63(52-72) 65 (45-74) 9±56 04 .20.1 30.40 ± 6.32 29 ±5.67 3 (3-3) 42.98) Cryo 14 12 18 26 19 10 40 8 6 3 A Historical Review of Functional and Oncological Outcomes 29 (17.97-53.16) 3 (2-3) 36/48 F pValue RFA 17 31 32 21 15 54 9 6 9 4 0.3 0.9 0.3 0.8 0.2 0.9 0.5 performed betweentheablationcyclesandactivethawis For Radio FrequencyAblation(RFA and sedation. guidance onanoutpatientbasisusinglocalanesthesia were performedpercutaneouslyunderCTfluoroscopic coagulation profileandbiochemicalstudy. Allprocedures Preoperative assessmentincludedcompletebloodcount, a solitarykidneywereincludedinthisanalysis. and thesecondcyclelastingeightminutes.Pa performed, withthefirstcycleusuallylasting10minutes by CTbeforeablation.Twocyclesofcryoablationarethen ball coversthetumor. Finalprobepositionisconfirmed mass underCTguidanceandpositionedsuchthattheice CT fluoroscopicguidance.Thecryoprobe(s)isplacedinthe s 200 W, generatingacoretemperatureof105degreesCel- and itspositionconfirmedbyCT. Ablationisperformedat A 25cm7.3Frablationelectrodeisplacedintherenalmass ance andthespecimenissentforcytologicalassessment. ration biopsyistakenfromtherenalmassunderCTguid- localized. After draping in sterile fashion, a fine needle aspi- prone orobliqueinaCTscannerandtherenallesionis A or obliqueinaCTscannerandtherenallesionislocalized. For percutaneouscryotherapy,thepatientisplacedprone discharged homethesameday. recover inthepost-anesthesiacareunitandaregenerally is repeatedtoevaluateperinephrichematoma.Patients The numberofcyclesisdeterminedbytumorsize.CT t radiofrequency) ablationforarenalmassfromApril2002 patients treatedwithpercutaneousthermal(eithercryoor We retrospectivelyreviewedthemedicalrecordsof249 hrough March2010atourinstitution.Onlypatientswith Medial Lat Posterior Anterior No. position Lower Mid 2.7(1.9-3.4) Upper 2.72±1.05 No. site: 2.1(1.8-3.0) 2.43±0.9 Median (IQR) Mean ±SD Size (cm): Rt Lt No. Side: Table 1(b)Tumor characteristics ius. Thistargettemperatureismaintainedfor10minutes. fineneedleaspirationrenaltumorbiopsyistakenunder Cryo 18 14 10 11 25 4 7 6 4 ), thepatientisplaced RFA 11 25 12 21 15 17 30 7 5 ssive thawis 21/115 AM 1:56 12/16/11 13 Center for Robotics & Image – Guided Surgery 12/7/11 12:14 PM clevelandclinic.org/glickman es indicate In the RFA group, 14 In the RFA o partial nephrectomy, providing low Figure 1. Kaplan-Meier product limit product 1. Kaplan-Meier Figure estimates of overall, cancer-specific, recurrence-free and metastasis-free survival (log rank test p=0.6098, 0.4795, 0.3593 and 0.4407, respectively) with number of patients at risk. Blue curv cryo. Pink curves indicate RFA. Tick marks Tick cryo. Pink curves indicate RFA. indicate censored. Bars indicate CI. 2. Comparative assessment of renal Figure function based on eGFR In patients at high risk who have a solitary kidney, CT-guided percutaneous probe ablation is a safe alternative t morbidity, acceptable cancer control and minimal clinical impact on postoperative renal function. email the editor. references, please For

8 8 0 0 2 6 CRYO CRYO RFA 3 6 T. In the RFA group, imaging was consistent with residual group, imaging RFA In the T. compare obtainedto curveswere Kaplan-Meier Measurements were made before surgery and postopera- before surgery made were Measurements 12 months; and annually one; at three, six and tively on day thereafter. outcomes in the cryo and RFA groups. Differences in over- groups. Differences the cryo and RFA outcomes in and metastasis-free recurrence-free all, cancer-specific, analyzed. the groups were survival between included in the analysis. All proce- Overall, 65 patients were successfully, and no major complica- dures were completed with cryo. The patients were re-treated tions occurred. Four other patient was stable on serial recurrent lesion in the C disease. Figure patients died, including two of metastatic estimates of overall, cancer-specific, 1 shows Kaplan-Meier The log rank recurrence-free and metastasis-free survival. the groups. test revealed no significant differences between tumor in two patients on postoperative day one. They un- tumor in two patients and showed no evidence of residual derwent re-treatment showed recur- Another 12 patients tumor after repeat RFA. on follow-up imaging or biopsy. rent or residual disease three patients treated with cryo died During the follow-up, of causes other than renal malignancy.

4 0 7 4 0 4 10 3 12 3 19 Follow up (years) Follow Follow up (years) Follow 2 10 16 2 10 25 14 20 15 27 0 0 29 36 29 36 1 2 1 2

1.0 0.8 0.6 0.4 0.2 0.0 0.8 0.6 0.4 0.2 0.0 0.0

Survival Probability Survival Survival Probability Survival Metastasis free survival Cancer-specific survivalCancer-specific

8 8 Follow-up time (months) Follow-up 0 3 6 0 6

4 1 4 0 3 4 0 19 0 4 8 12 16 20 24 p=0.8 3 8 3 19 Follow up (years) Follow up (years) Follow 2 2 7 12 10 25 0 90 80 70 60 50 40 30 20 10

100 12 15 15 27

eGFR (mL/min/1.73m eGFR 2 0 0 29 36 29 36 1 2 1 2

1.0 0.8 0.6 0.4 0.2 0.0 1.0 0.8 0.6 0.4 0.2 0.0

Survival Probability Survival Survival Probability Survival ively on day one; at three, six and 12 months; and annually ively on day one; at three, nitial negative imaging or positive post-treatment biopsy nitial negative imaging Recurrence free survival Overall survival was considered recurrent tumor. Renal functional out- functional Renal was considered recurrent tumor. and estimated comes were evaluated by serum creatinine of diet in glomerular filtration rate using the modification renal disease equation. done after the second cycle. The probes are removed after after are removed The probes cycle. after the second done is temperature. CT to an appropriate they have warmed cycle to document late in the first ablation typically done the is 5 to 10 mm beyond and coverage, which ice ball size after the probes are Final CT is performed tumor edge. evaluate potential hematoma. removed to and cryo. CT was used for RFA A similar follow-up protocol imaging was performed postopera- or magnetic resonance t thereafter. Biopsy at the ablation site was tentatively done Biopsy at the ablation thereafter. The presence or absence of six months after treatment. pattern and a change in enhancement, the enhancement on initial enhancement Persistent defect size were noted. considered incomplete treatment. follow-up imaging was on subsequent imaging after Enhancement or enlargement i 78224_CCFBCH_Text_ACG.indd 13 0.8 0.1 0.13 5 7 3017 0.5 1521 12 0.5 0.9 25 11 RFA p Value 4 6 7 4 25 11 10 14 18 Cryo Rt Size (cm): Mean ± SDMedian (IQR) 2.43 ± 0.9 2.1 (1.8-3.0)No. site: 2.72 ± 1.05Upper 2.7 (1.9-3.4)Mid 0.2 0.3 Lower No. position Anterior Posterior Lat Medial Table 1 (b) Tumor characteristics 1 (b) Tumor Table No. Side: Lt A Historical Review of Functional and Oncological Outcomes Oncological and Functional of Review Historical A Image-Guided Percutaneous Thermal Ablation for Renal Tumors in 65 65 in Tumors Renal for Ablation Thermal Percutaneous Image-Guided Kidneys: Solitary 82_CBHTx_C.nd14 78224_CCFBCH_Text_ACG.indd Center for Robotics & Image – Guided Surgery News Disease Kidney & Urology 14 Worldwide Multi-Institutional Analysis of 1,076 Cases Laparoendoscopic Single-Site Surgery in Urology: p age, gender,race,BMI,pasthistoryofpreviousabdominal/ Demographic datacollectedfortheanalysisincluded that wasspecificallybuiltforthisstudy. tively collectedandgatheredintoastandardizeddatasheet techniques. Raw datawithoutanyidentifierwereretrospec- cedures accordingtoitsownprotocols,entrycriteriaand participate inthestudy. Eachgroupperformedthepro- i institutions pioneeringthedevelopmentofthistechnique purpose ofreportingthecontemporarypracticeLESSat This studywasinitiatedasacollaborativeeffortwiththe performed byusingLESS. laparoscopic operationsinurologyhavebeensuccessfully and cosmesis.Overthepastfewyears,manyofstandard t The followingoutcomeparameterswereanalyzed:opera- of five,meaninganextremelydifficultcase. representing aslightlydifficultcase,ascendingtoscore The scoreswerebasedonaLikertscalewithscoreofone “reconstructive” andas“upperurinarytract”or“pelvic.” Procedures werecategorizedas“extirpative/ablative”or for LESS. b with reportedexperienceinurologicLESSwereidentified ipating institutions.Groupsatmedicalcentersworldwide LESS betweenAugust2007andDecember2010at18partic- Our cohortconsistedofconsecutivepatientstreatedwith in avariablehospitalsettingworldwide. of indications,techniquesandoutcomesurologicLESS i access totheabdominal/pelviccavitymaybenefitpatients by thehypothesisthatminimizationofskinincisiontogain worldwide sinceitsintroduction.Conceptually,itisdriven roscopy andhasbeenincreasinglyadoptedbyurologists proposed asanevolutionarystepbeyondstandardlapa- Laparoendoscopic single-site(LESS)surgeryhasbeen Jihad H. Kaouk, MD* i retroperitoneal), useofarticulating/prebentlaparoscopic (umbilical orextra-umbilical),approach(transperitoneal nique (single-portorsingle-incision/single-site),accesssite surgical procedurewererecorded,includingaccesstech- pain (VAS) score.Relevant operativedatarelatedtothe events, transfusions,lengthofstayandvisualanalogue ports. device, anduseofancillaryneedlescopic/mini-laparoscopic n termsofport-relatedcomplications,recoverytime,pain nstruments, useofthedaVinci n urology. Theaimwastoprovideananalyticaloverview ive time,estimatedbloodloss,intraoperativeadverse elvic surgery,ASAscore,comorbiditiesandindication y searchingavailableliteratureandweretheninvitedto ® robot,typeofsingle-port a A single-porttechniquewaschosenin77percentofcases, the timeframe(Table 1andFigure1). significant increaseinuseofthedaVincirobotover varicocelectomy andureterolithotomy).Therewasa nephrectomy, renalcystdecortication,adrenalectomy, frequently performed(i.e.,radicalnephrectomy,partial were lower,whereassomeotherproceduresmore s types ofprocedures(i.e.,pyeloplasty,donornephrectomy, month duringtheperiod2009-10,whererateofsome There wasasignificantincreaseinthenumberofcasesper of thedaVincirobot. or 13percent,ofthesurgerieswereperformedwithuse adopted (92percentofthecases).Onehundredforty-three, mm additionalportwasrequired. u port withtrocars.Articulating/prebentinstrumentswere combination ofmultipletrocarswasusedormultichannel When asingle-incisiontechniquewaschosen,variable and acommerciallyavailabledevicein54percentofcases. used, thiswasahomemadedevicein46percentofcases (71 percentofcases).Whenasingle-portplatformwas ( upper urinarytract,beingmostlyextirpative/ablativeones time frame.Mostprocedures(86percent)weredoneinthe performed attheparticipatinginstitutionsduringsame 59 percent)oftheoveralllaparoscopic/roboticprocedures study period,comprisingonaverage15percent(range4to Overall, 1,076patientsunderwenturologicLESSduringthe t 2007-08 andtheotherincludingyears2009-10.Acompara- Two periodswerearbitrarilydefined:oneincludingyears Clavien-Dindo system. complications werescoredaccordingtothestandardized abdominal incisiontoperformtheoperation.Postoperative dure. Conversiontoopensurgerywasdefinedofunplanned i LESS tolaparoscopicsurgerywasdefinedasanunplanned to reduced-portlaparoscopy,whereasconversionfrom Addition ofoneextratrocarwasconsideredasconversion w percent ofthesurgeries,a2-3mm extraportwasused, An additionalportwasusedin23percentofcases.In34 performed proceduresarepresentedinTable 2. discharge of1.5/10.Perioperative outcomesforthemost- 3.5 cm.Meanhospitalstaywas3.6dayswithapainVAS at blood losswas148mL.Skinincisionlengthatclosure Overall, operativetimewas160minutesandestimated nstallation ofmorethanonetrocartocompletetheproce- 84 percent).Atransperitonealaccesswaspreferentially ive analysisbetweentheseperiodswasconducted. imple prostatectomy,cryoablationandsacrocolpopexy) nd theumbilicuswasmostlyusedassiteofaccess sed in73percentofcases. hereas intheremaining66percent ofcasesanextra5-12 Continued onpage16 21/174 PM 7:44 12/12/11 15 Center for Robotics & Image – Guided Surgery 12/12/11 9:06 PM clevelandclinic.org/glickman .6 ± 1.2 1.2 ± 1 3.8 ± 4 1.9 ± 1.5 3.6 ± 1.5 1.9 ± 1.5 3.2 ± 1.6 1.8 ± 1.5 2 3.7 ± 2.6 2 ± 1.4 4.1 ± 2.6 1.5 ± 1.1 0.894 0.151 0.074 0.270 0.533 0.004 0.092 0.849 0.830 0.193 0.002 0.048 p value − − − − − − <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 ◊ 9 3 0 34 30 72 50 32 53 42 31 20 47 24 21 20 50 96† 152 108 108 15.4 <0.001 21.5 <0.001 186‡ Period Period (n=842) 2009-2010 2009-2010 9 4 2 1 2 2 7 3 8 5 29 32 18 11 42 27 24 21 19 17 13 5.5 33.3 34** Period Period (n=234) ORT, minORT, EBL, ml min WIT, d LOS, VAS 138 ± 62 63.8 ± 60.3 2007-2008 2007-2008 175.2 ± 53 118.3 ± 96 5.1 ± 1.8 2.5 ± 1.1 1.4 ± 1.6 158 ± 47.5 168.3 ±217.6 90.9 ± 35.5 29.5 ± 41.5 223.7 ± 72.4153.5 ± 65.1 69.7 ± 70 123.3 ±118.6 160.7 ± 71.5 165.9 ±313.9 208.3 ± 165.3 276.9 ±294.3 18.4 ±15.5‡ 1.6 ± 1.7 1 ± 0.2 2 6 51 89 55 8 43 34 43 11 51 55 44 51 42 37 39 25 89 13 13 24 51† 115 127 210 101 170 115 130 172 127 130** Overall (n=1076) Cases, no. 27.3 ± 14.5 13.9 ± 5.1 37.1 ± 11.4 <0.001 adical nephrectomy Including one case done in conjunction with a simple nephrectomy and one case done with a varicocelectomy. Including one case done in conjunction with a simple nephrectomy and one case done with a varicocelectomy. ‡ Including cases with off-clamp technique. Ureterolithotomy Donor nephrectomy analog score at discharge. of stay; VAS=visual ORT=operative room time; EBL=estimated blood loss; WIT=warm ischemia time; LOS=length * >50 cases. ** Including four bilateral cases. † Pyeloplasty Adrenalectomy Renal cyst decorticationRenal Partial nephrectomy Partial Simple nephrectomy Radical nephrectomy Table 2. Outcomes for most commonly performed urologic laparoendoscopic single-site surgery procedures* Table Procedure Table 1. Temporal trends in urologic laparoendoscopic single-site (LESS) surgery (LESS) single-site laparoendoscopic in urologic trends Temporal 1. Table Use of additional 2-3 mm instruments only Others Postoperative from Autorino et al [5] and Guilloneau et al [10]. * Score: 4-5, according to the classification adopted ** Including one bilateral case. † Including three bilateral cases. ‡ Including one bilateral case and seven cases with a renal vein thrombus. ◊ Complications Intraoperative To conventional laparoscopy To open surgery To Conversions reduced-port laparoscopy To Ureterolithotomy Adrenalectomy Varicocelectomy Renal cyst decorticationRenal Radical cystectomy Donor nephrectomy Simple prostatectomy Cryoablation Nephroureterectomy Radical prostatectomy Type of procedures Type Pyeloplasty Simple nephrectomy R nephrectomy Partial Sacrocolpopexy Robotic LESS procedures, % LESS Robotic Mean cases per month, no. Mean cases procedures, % High-score* 78224_CCFBCH_Text_ACG.indd 15 Continued on page 16 82_CBHTx_C.nd16 78224_CCFBCH_Text_ACG.indd Center for Robotics & Image – Guided Surgery News Disease Kidney & Urology 16

Cases, n Laparoendoscopic Single-Site Surgery in Urology p with urologicLESStodate.Itprovidesareal-lifepractice studyreportsthelargestmulti-institutionalexperience This rate was6.1percent. of cases,withmostbeinglow-grade.Overalltransfusion erative complicationswereencounteredin9.5percent to openinthreecasesandlaparoscopyfivecases. Postop- complication ratewas3.3percentwithneedforconversion that abroadrangeofprocedurescanbeeffectivelyand technique inarelativelyshorttime.Outcomesdemonstrate it hassignificantlyevolved,becomingawidelyapplicable emerging trendinminimallyinvasiveurologicsurgeryand Despite unsolvedchallenges,LESScanberegardedasan Figure 1.Trends numberofLESSandroboticcases overthestudyperiod. inroboticlaparoendoscopic single-site(LESS)surgery: ( cent), difficultsuturing(11percent),retraction cases), failuretoprogress(21percent),bleeding(25per- as follows:difficultdissection(37percentofconverted open surgery,respectively. Reasons forconversionwere port” laparoscopy,conventionallaparoscopy/roboticand percent, 4percentand1performedas“reduced The overallconversionratewas20.8percent,with15.8 10 20 30 40 50 60 70 3 percent)anddifficultaccess(3percent).Intraoperative icture ofwhathasbeendonesofarinthisfieldworldwide. 0

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4.09 v affiliations. For afulllistoftheauthorsandtheirinstitutions, * Thisarticlewasauthoredbynumerousauthorswithvarious technology mayfurtherfacilitateLESS. are criticalforasuccessfulLESS. Applicationofrobotic surgical backgroundandstringentpatientselectioncriteria riety ofhospitalsettings.Undeniably,asolidlaparoscopic safely donebyapplyingdifferentLESStechniquesinava- 6.09 isit clevelandclinic.org/ukdnews.

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6.10

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10.10 21/115 AM 1:59 12/16/11 17 Center for Robotics & Image – Guided Surgery 12/7/11 12:14 PM clevelandclinic.org/glickman Non-fluorescing Tumor Prostate Fluorescing Fluorescing Tumor Prostate PSMA+tumor on the subjects right side which binds PSMA+tumor on the subjects right side which binds the fluorescing compound. PSMA-tumor on the subjects left side which does not bind the fluorescing compound. Fluorescent staining of prostate tissue on the top (A), non-staining tissue for comparison on the bottom (B).

hus far there are few adjunctive techniques that allow the hus far there are few adjunctive otic fluorescent scope in a prostate cancer mouse model. otic fluorescent scope in a prostate cancer ye as easily. Therefore, we have successfully developed a ye as easily. ptimize the intensity of tissue fluorescence. Potential ptimize the intensity of tissue fluorescence. xpressed the PSMA protein was indeed noted to fluoresce isually identify structures that he or she normally could isually identify structures that he or she normally molecule that binds the fluorescent dye and specifically molecule that binds the fluorescent dye and benefits of targets the PSMA protein of the prostate. The by clearly this include potentially optimizing nerve-sparing nerves. differentiating the prostate from the cavernosal da Vinci ro- In order to test the molecule, we used the novel b Wahib Isaac, MD, Rakesh Khanna, MD, Shahab Hillyer, MD, MD, Hillyer, Shahab MD, Khanna, Rakesh MD, Isaac, Wahib MD, Julien Guillotreau, MD, Yakoubi, Rachid MD, Haber, MD, Georges-Pascal Rao, K. Pravin Heston, PhD MD, and Warren Kaouk, Jihad H. T not as precisely distinguish. already been In the field of urology, this technology has blood vessels used for kidney tumors as the kidney and its tumor usually fluoresce brightly with the dye because the of the does not fluoresce. Therefore, precise dissection kidney may tumor with decreased injury to the normal be possible. the fluorescent Unfortunately, the prostate does not take up d Robert J. Stein, MD, Humberto Laydner, MD, Robert MD, Humberto J. Stein, Laydner, MD, MD, PhD, RiccardoSteve Huang, Autorino, Magi-Galluzzi, PhD, Cristina MD, Xinning Wang, surgeon to use tissue-specific properties to enhance the surgeon to use tissue-specific Intuitive Recently, precise surgery. ability to perform more that manufactures the da Vinci robot, Sugical, the company for a robotic scope that can has received FDA approval imaging, the organ detect fluorescent dye. With fluorescent to or area of interest “lights up” to allow the surgeon v benefits of this technology include improving nerve preservation, decreasing positive surgical margins and guiding intraoperative directed biopsies. In the study, we implanted a human prostate tumor that In the study, we implanted a human prostate of the mouse expressed the PSMA protein on the right side and a tumor that did not express the PSMA protein on the left side. The tumors in the mouse were then removed robotically, during which the robotic fluorescent scope was used to identify the prostate tissue. The prostate tumor that e in two of three mice while the tumor from the contralateral side without PSMA protein did not fluoresce in any mice. Presently, the molecule that we have developed is not FDA- approved for clinical use and therefore further testing is required. Additionally, modifications to the scope as well as changes in the dosing of the molecule are needed to o Robotic Surgery with the Adjunctive Adjunctive the with Surgery Robotic Cancer Prostate for Imaging Fluorescent of Use 78224_CCFBCH_Text_ACG.indd 17 82_CBHTx_C.nd18 78224_CCFBCH_Text_ACG.indd Center for Robotics & Image – Guided Surgery News Disease Kidney & Urology 18 in von Hippel-Lindau Patients: Cleveland Clinic ExperienceThermal Ablation as Salvage Therapy for Renal Tumors and laterally by percutaneous approach. percutaneous by laterally and more posteriorly oriented are that tumors and approach, alaparoscopic by managed are cally typi- or adjacent bowel organs the to proximity or anteriorly located tumors location: on tumor based mainly proach was ap- or percutaneous choice of alaparoscopic The size. and position tumor on the based determined was target ablation the lesions, of multifocal characteristic the to Due nephrectomy. of partial history previous with patients VHL 2010 in January and 2003 March between tion institu- at our therapy ablative thermal salvage In this study, we analyzed the outcomes the study, analyzed we this In patients. for VHL option treatment attractive anew represent might they outcomes, oncologic encouraging and trauma less offer techniques these because comorbidities medical or serious age advanced with those such as RCC patients, of selected management the in applied (RFA) increasingly been have ablation radiofrequency and cryotherapy such as cedures surgical invasive minimally new decade, last the In hands. experienced in even rate, complication tive major periopera- increased an carries and challenging be can procedure PN, the of repeated setting the in rence, and recur- of tumor risk ahigher carries multifocality tumor (RCC). carcinoma However, cell renal with patients VHL Partial kidney. a solitary with in cases especially failure, renal stage avoidance of the end- and progression prevention of tumor the between abalance keep to aneed is there as task, ing achalleng- represents of VHL Therefore, management patients. of these of death major causes two are function of renal deterioration and metastasis and age, at ayounger patients 40 of uppercent VHL to in occur will tumors renal the VHL tumor-suppressor gene. Multicentric and bilateral and gene. Multicentric tumor-suppressor VHL the in mutations germline by caused syndrome inherited nant, domi- autosomal an is Von (VHL) Hippel-Lindau disease Charles M. O’Malley, MD, and Erick M. Remer, MD Jihad H. Kaouk, MD, Riccardo Autorino, MD, BoYang, MD, nephrectomy represents an attractive option for option attractive an represents nephrectomy medially in close close in medially of pro-

Lesion size,cm Procedures, no. Table 1.Outcomes *Fine needleaspirationorbiopsyduringablationsession. = laparoscopiccryotherapy.L-Cryo P-Cryo =percutaneouscry RCC Inconclusive Pathology resultonablatedmass* Length ofstay, hours Ablation time,min. siae lo os l<50 Estimated bloodloss,ml Type ofanesthesia,no. Mean ±SD Median (range) Mean ±SD General Local Sedation temperature-based For a RFA, hematoma. for potential evaluate to probes the of removal after performed was scan CT A final edge. tumor the 10 5to is beyond which mm ice ball, of the andcoverage the size cycleto document ablation first the in late performed typically was scan CT second. the after thaw active and cycles ablation the between performed for second the and for minutes 10 lasting cycleusually first the with performed, then were of cryoablation cycles Two 1). (Figure mass of the margin the just beyond going tip the with mass centerof the the into percutaneously anesthesia, local and sedation IV under 1.7inserted, was or mm 2.4 measuring cryoprobe the P-Cryo, For pathology. for aspiration needle afine obtain under CT fluoroscopic guidance into guidance fluoroscopic CT under passed was needle biopsy aChiba ablation, Just the before other complications. other and hematomas were there if reveal done to was scan CT aspiral of ablation, cycles four to two After size. tumor by per treatment cycle. The number cycle. treatment per for 10 minutes maintained was temperature target This Celcius. of 105 degrees temperature acore ating W, of 200 gener- setting at apower performed was Ablation generator. radiofrequency the to attached then and eter diam- in 3cm up to advanced were needle of the tines the tumor; centerof the the into directed was needle Starburst between eight and 10 minutes. Passive thaw was was thaw 10 Passive eight and minutes. between energy delivery system was used. A used. was system delivery energy otherapy; RFA =radiofrequencyablation; .4±11 .1±07 2.73±0.33 2.61±0.70 2.74 ±1.15 83±213. 717.3±4 36.7±17 18.3 ±2.1 8(32)2 1-7 18(13-21) 27(17-67) 18 (13-20) P-Cryo <24 13 12 − 7 8 1 of cycles was determined determined was of cycles the mass in order to order to in mass the <24 <50 F L-Cryo RFA 14 12 12 − − 3 <24 <50 − − 3 2 1 3 21/120 AM 2:02 12/16/11 19 Center for Robotics & Image – Guided Surgery 12/12/11 9:08 PM clevelandclinic.org/glickman ollow-up: P=0.038. Figure 2. Change in mean eGFR level Figure after base- ablation. P values as follows: line vs. day one: P=0.052; baseline vs. one month: P=0.182; baseline vs. three months: P=0.107; baseline vs. latest f technically successful. Overall mean history partial of nephrectomy because offers it The presence or absence presence enhancement, or of The enhancement pattern, and change in defect size were noted. Persistent enhancementinitial on follow-up imaging was considered to be an incomplete treatment. Renal functional outcomes were evaluated with serum creatinine and estimated glomerular filtration using(eGFR) the rateMDRD equation. All procedures were follow-up was 37.6 months. patient No entered end-stagefollow-up was 37.6 renal disease and required none renal substitution ther- metastasis No apy. was detected. Actuarial overall and cancer-specific survivals10092 were percent percent, and respectively. These findings suggest thatprobe ablative therapy represents a suitable treatment option VHL for patients with a previous a repeatable operation with a high technical successrate, with only minor changes in renal function. references,For please email the editor or [email protected].

® three, six and months 12 probes more One or were then inserted into the needle biopsy was then performed under the ultrasound guidance. center of thecenter of tumor and freezing was started. After two freeze cycles, the probe was removed, and the ablation site was thencauterized with an argon beam. Percutaneous ablative procedures were performed on an outpatient basis, whereas L-Cryo patients were hospital- ized overnight CT an or only. MRI was performed postoperatively day on and one then at and annually thereafter. Figure 1. MRI scan: (A) target lesions before percutaneous cryoablation 1. MRI scan: (A) target lesions Figure (arrows shown); (B) postoperative control at day one after the ablation (arrows shown). For theFor laparoscopic cryotherapy, under general anesthesia, the patient was placed in the flank position. The wasabdomen insufflated, and the laparoscope was inserted. Adhesions were dissected carefully, and the was colon reflectedmedially to expose the The tumorlocationkidney. was confirmed by the intraoperative ultrasound. Tru-Cut 78224_CCFBCH_Text_ACG.indd 19 82_CBHTx_C.nd20 78224_CCFBCH_Text_ACG.indd Center for Robotics & Image – Guided Surgery News Disease Kidney & Urology 20

Score (range 1-5) Figure 1.End-o Course on Attendees’ Practice Patterns Immediate Impact of a Robotic Kidney Surgery requested. r interval fromresidency,practicetypeandpattern,prior designed tocollectbaselinedata,includingdemographics, questionnaire wasadministeredduringthecourseand held atClevelandCliniconOctober29-30,2009.Thefirst tional SymposiumonRobotic KidneyandAdrenalSurgery were administeredtoalltheparticipantsofInterna- m erally thoughttobemoreeffectivethanothercontinuing clinical practice.Hands-oneducationalactivitiesaregen- significant needtorapidlyacquireskillsforapplicationin programs tolearnthesenewtechnologiesbecauseofa robot-assisted surgery,surgeonsseekeffectiveeducation With therapiddevelopmentofnewtechnologies,suchas To laboratory experience. live surgerysessions,andsimulator-animal-based learning experienceincludeslectures,videoanalysis, kidney surgeryisannuallyheldatourinstitution.This A dedicatededucationalprogramfocusingonrobotic and performanceand,ultimately,improvingpatientcare. d of urologiclaparoscopy,therebyeasingthetranslational nology facilitatesboththetechnicalandergonomicaspects urological surgery. Thisisprimarilybecauserobotic tech- assumed alargerroleinthefieldofminimallyinvasive In thepastfewyears,robotic-assistedlaparoscopyhas Laydner,Humberto MD,andRobertJ.Stein,MD Jihad H. Kaouk,Autorino, MD,Riccardo MD, 0.5 1.5 2.5 3.5 4.5 obotic surgicalexperience.Acourseevaluationwasalso ifficulty ofopentominimallyinvasivesurgery. edical educationactivitiesinchangingphysicianattitude 0 1 2 3 4 5 evaluatetheeffectivenessofprogram,twosurveys f-course ratingforeachcomponentofthecourse(valuesexpressed asmean;scale 1–5) etrsVdoaayi iesreyRobotic Livesurgery Videoanalysis Lectures simulator most frequentlycitedplannedprocedure. the course,withroboticpartialnephrectomybeing the course)procedureintheirpracticeimmediatelyafter to performa“new”(besidesthosealreadyperformedbefore 1). Interestingly,92percentoftheparticipantsplanned All coursecomponentsreceivedameanscore>4.5(Figure s Some oftheattendeeshadonlylaparoscopicorrobotic robotics, but70percenthadattendedacourseinrobotics. fellowship ormini-residencytraininginlaparoscopy Only 22percentoftherespondentshadcompleteda (85 percent)ofrespondentswereinprivatepractice. residency was13.7years(range1–30years).Themajority ( agreed toparticipate.Meanparticipantagewas44years foreign countriesparticipatedintheroboticcourseand Twenty-seven urologistsfromatotalof13statesandtwo practice byasubjectiveassessment. pants andtheperceivedimpactofcourseontheir the typeandnumberofcasesperformedbypartici- ed the robotic surgical practice after the course by recording an additionalsurvey. contacted viaemailinFebruary 2010andaskedtocomplete All attendeeswhocompletedtheinitialsurveywere perform roboticallyassistedproceduresafterthecourse. Participants werealsoqueriedabouttheirintentto p performed procedure,with77percentofthe1,312 prostatectomy representedbyfarthemostcommonly of betweenzeroand235procedurescompleted.Robotic per physicianbeforethecoursewas54.6,witharange and robotics.Themeannumberofroboticcasesperformed majority (78percent)hadfamiliaritywithbothlaparoscopy range 33–65years).Meantimefromcompletionof urgical experience(11percentineachcategory),whilethe rocedures performedfallingintothiscategory. animal lab Hands-on Hands-on Thissecondquestionnaireinvestigat- 21/121 AM 2:11 12/16/11 21 Center for Robotics & Image – Guided Surgery 12/16/11 2:20 AM clevelandclinic.org/glickman nable participants to successfully incorporate and/or incorporate and/or to successfully nable participants or the translation of acquired robotic skills into the or the translation of acquired Our findings suggest that a two-day intensive kidney kidney a two-day intensive that suggest Our findings invited lectures, video course, including surgery robotic sessions, seems to surgery and hands-on analysis, live e practice of postgraduate urologists. practice of postgraduate references, please email the editor or [email protected]. For improve their robotic surgical practice. Thus, it can be Thus, it can be robotic surgical practice. improve their that is immediately an educational model regarded as and ultimately spreading robotic skills effective in and performance in clinical changing physician attitude will ultimately determine practice. Continued follow-up of this educational program the long-term effectiveness f ormed by participants after as percentage of increase) the course (values expressed rocedures after the course and for one participant, these one participant, these after the course and for rocedures Figure 3. Types of robotic procedures performed of robotic procedures by the participants before 3. Types Figure and afternumber of reported as the course (values expressed cases) Figure 2. Volume of robotic cases perf 2. Volume Figure Twelve people returned the three-month questionnaire. questionnaire. three-month the people returned Twelve similar baseline char- of participants had This subgroup of residency, prac- (age, time from completion acteristics of with the entire group etc.) in comparison tice setting, individuals had attended participants. Only two registered performed robotic surgical course. All had another robotic p represented his initial robotic cases. Overall, there was represented his initial in robotic cases in the surgical an increase of 56 percent (Figure 2). practice of the participants positively estimated the actual Overall, the participants course on starting or implementing impact of attending the practice. their robotic surgery 78224_CCFBCH_Text_ACG.indd 21 82_CBHTx_C.nd22 78224_CCFBCH_Text_ACG.indd Center for Robotics & Image – Guided Surgery News Disease Kidney & Urology 22 closure, 6cminlength. (d) postoperativeincision radical nephrectomyspecimen; (c)extraction of inserted; (b) 15mmentrapmentsacis with trocarconfiguration; Figure 1.(a)GelPOINT Surgical Technique and Comparative Outcomes Robotic Laparoendoscopic Single-Site Radical Nephrectomy: limitations, thedaVinci ics fortheoperatingsurgeon.Inordertoovercomethese technically challengingsecondarytounfavorableergonom- patient-reported convalescence.Atthistime,LESSremains outcomes, postoperativepain,lengthofhospitalizationand v This techniquemayhavepromisecomparedwithitscon- of thelateststepsinfieldminimallyinvasivesurgery. Laparoendoscopic single-site(LESS)surgeryrepresentsone Georges-Pascal Haber, MD,andRobertJ.Stein,MD White, MD,ShahabP. Hillyer, Laydner, MD,Humberto MD, Jihad H. Kaouk,Autorino, MD,Riccardo MD,MichaelA. radical nephrectomy. In thisstudywedescribeourexperiencewithR-LESS nephrectomy andradical(RN). LESS, includingradicalprostatectomy,pyeloplasty,partial of urologicproceduressuccessfullyperformedbyusingR- clinical seriesin2009.Sincethen,wereportedonavariety Our grouppioneeredR-LESSbyreportingthefirst A case-controlstudycomparingasinglesurgeon’sexperi- radical nephrectomy. gold-standard techniqueofconventionallaparoscopic early outcomesareanalyzedandcomparedtothe demonstrated, thesurgicaltechniqueisillustrated,and d cal) hasbeenappliedtoLESSandtermedrobotic-laparoen- entional laparoscopiccounterpartintermsofoperative oscopic single-site(R-LESS)surgery. Thefeasibilityoftheprocedureis ® platform

TM SurgicalSystem(IntuitiveSurgi- o After comprehensivediscussion,informedconsentwas workup whenindicated. staging whenrequired,andfurthercardiac/pulmonary physical exam,basiclaboratorybloodwork,metastatic preoperative evaluationconsistedofstandardhistoryand BMI, ASAscore,surgicalindicationandtumorsize.The control groupwasmatchedwithrespecttopatientage, r ence with10R-LESSandconventionallaparoscopic w inhibitor treatment,andlargeupper-poletumorsthat masses requiringcytoreduction,previoustyrosinekinase metastatic renalcellcarcinoma,bulkylymphadenopathy, gery tothediseasedkidney,advancedTNMclinicalstaging, procedure. Exclusioncriteriaincludedpreviousrenalsur- sions mightbenecessaryaswarrantedduringthesurgical malignant ascites,wereexcluded. peritonitis orretroperitonealabscess,andsuspected hemoperitoneum orhemoretroperitoneum,generalized intestinal obstruction,abdominalwallinfection,massive scopic procedures,suchasuncorrectablecoagulopathy, patients withconventionalcontraindicationstolaparo- adical nephrectomyprocedureswasconducted.The btained, andpatientswerecounseledthatadditionalinci- ould requirehepaticorsplenicretraction.Additionally, 21/121 AM 2:14 12/16/11 23 Center for Robotics & Image – Guided Surgery 12/12/11 9:38 PM clevelandclinic.org/glickman − 1.0 0.50 0.44 0.76 0.34 0.29 0.67 0.34 0.28 0.39 0.54 0.03 0.049 p value 6 4 6 4 2 10 3 (2-3) 0 (0-2) 3.0 (3-4) 1 (grade I) Conventional 64.5 (61-74) 7.6 (5.0-8.4) 100 (81-150) 150 (150-173) 29.9 (26.0-35.5) 37.5 (33.4-51.3) ovember 2010 are provided in Table 2 in comparison in Table ovember 2010 are provided dvantage of reduced analgesic use and a decreased dvantage of reduced analgesic use and a decreased The standard steps of the radical nephrectomy procedure nephrectomy procedure steps of the radical The standard ureteral identification, colon mobilization, were followed: kidney mobilization, kidney hilar dissection and control, extraction, and closure. RNs performed from May 2008 to Outcomes of 10 R-LESS N with those of the control group. No cases were converted with those of the control In addition, or open surgery. to conventional laparoscopy instruments were required beyond no trocars or additional the single incision. R-LESS RN is technically Our findings show that to the feasible, with perioperative outcomes comparable the potential conventional laparoscopic procedure and a hospital stay. Further prospective comparisons are needed Further prospective comparisons are needed hospital stay. invasive to definitively establish its position in minimally urologic surgery. email the editor or [email protected]. references, please For

TM 4 6 5 5 1 10 3 (3-3) 2 (0-5) R-LESS (grade II) 2.5 (2-3) .8 (4.5-7.1) 1 64 (57-77) 4 100 (50-100) 28.7 (26.3-33.3) 167.5 (150-210) 25.3 (11.0-38.3) or da Vinci Si TM , (range) 2 Male Female Right Left wo single-port devices were used. The patient was wo single-port devices were used. The patient Patients,no. Age, years, median (range) Gender BMI, kg/m ASA score size, cm, median (range) Tumor R-LESS = robotic laparoendoscopic single-site surgery; BMI = body mass index; EBL = estimated blood loss; LOS = length of = robotic laparoendoscopic single-site surgery; EBL = estimated blood loss; LOS BMI = body mass index; R-LESS Range represents the interquartile range (IQR). stay. Side, no. Upper-pole tumor location Upper-pole Operative time, min, median (range) EBL, ml, median (range) VAS, median (range) VAS, Morphine equivalents, mg, median (range) days, median (range) LOS, Complications (Clavien grade) Table 1. Comparison of patient demographics and outcomes for patients undergoing radical nephrectomy by either robotic 1. Comparison of patient demographics and outcomes for patients undergoing radical Table laparoendoscopic single-site (LESS) surgery or conventional laparoscopy. ification system. he patient’s shoulder, with the camera oriented in line he patient’s shoulder, with the camera oriented Perioperative data, intraoperative complications, length complications, length data, intraoperative Perioperative and post- narcotic requirements scores, VAS of stay (LOS), were recorded. All surgical com- operative complications as according to the Clavien clas- plications were classified s for an inci- were followed at one week after surgery Patients weeks for kidney function analysis sional check and at four They were then seen every and blood pressure monitoring. and annually thereafter for a physi- six months for one year analysis, including complete cal exam and basic laboratory tests and imaging, if indicated. blood counts, liver function T positioned in the modified flank position with the table positioned in the modified flank position An incision flexed and in slight Trendelenberg position. 1 cm below the was made, intraumbilically, 2 cm above and midline using umbilicus and the abdomen entered in the an open technique. Either the da Vinci S system (in a three-arm approach) was then positioned over system (in a three-arm approach) was then t with the kidney, and docked in the same fashion as tradi- with the kidney, and docked in the same fashion tional robotic renal procedures. 78224_CCFBCH_Text_ACG.indd 23 78224_CCFBCH_Text_ACG.indd 24 Center for Robotics & Image – Guided Surgery News Disease Kidney & Urology 24 Novel Robotic System for Percutaneous Renal Probe Placement p was steeredintopositionallowingmanualinsertionofthe entry point,trajectoryandtargetpoint.Theroboticarm synchronization, preplanificationconsistedofdefiningthe DICOM dataweretransferredtotheROSA system.After scan acquisition. cial markersweresubsequentlyplacedattimeofthe3-DCT water. Thesetargets wereplacedinsideabodymodel.Fidu- fi by usingamixturepreparedcombiningagarose,natural vanced roboticfunctions.Incrementaltargetswerecreated handle. Itintegratesasoftwarenavigationinterfaceandad- active roboticarmanda2.1mmneedleguidetargeting ROSA™ (Medtech)isamulti-applicationplatformwithone percutaneous renalfocaltherapy. t precision ininstrumentguidance.Theaimofthisstudywas developed forneurosurgicaltreatments,whichhasshown cal outcomes.ROSA™ isanewroboticsystem,initially morbidity withencouragingrenalfunctionandoncologi- ous image-guidedtumorablationhasdemonstratedlow role inthemanagementofsmallrenalmasses.Percutane- Ablative treatmentsareplayinganincreasinglyimportant MD,andGeorges-PascalJulien Guillotreau, Haber, MD o evaluatethefeasibilityandaccuracyofthisplatformfor robe intothetarget.Accuracywasthenevaluated. ber, glycerol,contrastmedium,methyleneblueand Figure 2.Target planification time ofthe3-DCTscanacquisition. Figure 1.Fiducial markerswereplacedat r was 142mm(range115-201mm).Allprobessuccessfully a registrationerrorof2.23mm.Mediantrajectorylength ± 4.3mm,respectively. Synchronizationwasobtained with Average targetvolumeandsizewere1.15±0.7ml11.3 of motionwithnounexpectedmovements. was 3.71mm.Therobotmovedsuccessfullyinitsfullrange were used.Cumulatedmeantargetingregistrationerror Preplanification wassuccessfulinallcases. Ten targets i convenience. ClevelandClinichasnofinancialinterestinnor This articleiswrittenforeducationalpurposesonlyandasa guidance forprobepositioninginpreclinicalstudies. tion ofrenaltumorsisfeasibleandoffersprecise ROSA platform.Robotic assistanceforpercutaneousabla- We believethistobethefirsturologicalapplicationof s itendorsinganyproductordevicedescribedinthisarticle. eached theplannedtarget(Figure4). Figure 4. Manual insertion oftheprobe Figure 4.Manualinsertion tioning in renal focal therapy. form has the potential to improve guidance of probe posi- urology. Preclinical data are encouraging. The ROSA plat We reported the first application of the ROSA platform in signed for high-precision percutaneous renal focal therapy. Herein we describe an image-guided robotic system de- Key Point: Figure 3.Robotic armsteeredintoposition - 12/7/11 12:14 PM 25 Center for Robotics & Image – Guided Surgery 12/16/11 2:16 AM − − − − − − WIT, min WIT, clevelandclinic.org/glickman − − − 60 28 35 20 25 29 19 29 control, min Time to hilar Time No No No No No No No No Addition of an extra supportan extra No No No No No No No side; R = right side; PN = partial nephrectomy; Key Point: Key in concept new a represents system surgical SPIDER The maneuverability intuitive offering armamentarium, LESS the triangulation restored cavity, abdominal the in instruments of applica- clinical First clashing. instrument external without reported. is device this of tion f the system. The SPIDER Surgical System This article is written for educational purposes only and as a This article is written for educational purposes interest in nor convenience. Cleveland Clinic has no financial is it endorsing any product or device described in this article. significant gas leakage. Drawbacks of the first-generation significant gas leakage. Drawbacks of the and system include its challenging clinical application, the role further refinements are awaited to define o 0 0 100 Bleeding (1 x 5 mm) Yes 60 EBL, ml Complications

− − − 30 0 20 0 2128 80 Bleeding 0 22 0 24 0 Suturing time, min 85 (Single-Port Instrument (Single-Port ® − Side OR time, min Low L 90 Low L 60 High R 45 High L 45 High R 67 Medium R 75 Medium Medium R 90 Medium R 65 surgical system represents a new concept in surgical system represents a new concept ® of expertise* Surgeon’s level level Surgeon’s ith the tips of the instruments fully deployed. erformed with one hand, as the other is necessary for ap- erformed with one hand, nd they were able to gain proficiency in performing tasks nd they were able to gain proficiency in performing the LESS armamentarium, offering intuitive maneuver- the LESS armamentarium, offering intuitive restored ability of instruments in the abdominal cavity, and no clashing instrument external without triangulation Delivery Extended Reach, TransEnterix) surgical system Delivery Extended Reach, this issue and to facilitate safe and was designed to address surgery. efficient single-port setting and The SPIDER system was tested in a laboratory Three used for a clinical case of renal cyst decortication. differ- and session, lab dry the during performed were tasks model. porcine a in conducted were procedures urologic ent The SPIDER regardless of their level of expertise. The highest scores regardless of their level of expertise. The highest instrument recorded were for ease of device insertion, During the clini- insertion, and exchange and triangulation. without cal case, the platform provided good triangulation was challenging instrument clashing. However, retraction maneuverability because of the lack of strength and precise w The time to complete the tasks and penalties were regis- The time to complete the tasks and penalties outcomes tered during the dry lab session. Perioperative were registered. and subjective assessment by the surgeons the SPIDER The surgeons had a positive experience with a scale of 1–5), system, with a mean overall score of 3.6 (on a propriate retraction. The SPIDER propriate retraction. Georges-Pascal Haber, MD, Riccardo Autorino, MD, Shahab MD, MD, Riccardo Autorino, Haber, Georges-Pascal MD, Isaac, MD, Wahib MD, Humberto Laydner, Hillyer, MD, Robert J. Yakoubi, Julien Guillotreau, MD, Raschid MD Kaouk, H. Stein, MD, and Jihad The major drawback is the lack of of single-site surgery use of frigid instruments. Further- triangulation with the ports, most procedures are more, with lack of additional p SPIDER Surgical System for Urologic LESS: From Initial Initial From LESS: Urologic for System Surgical SPIDER Application Clinical First to Experience Laboratory Procedure Nephrectomy Pyeloplasty PC OR = operating room; EBL = estimated blood loss; WIT = warm ischemia time; L = left PN PC = partial laparoendoscopic single-site surgery. cystectomy; LESS= high; advanced LESS experience. LESS experience; and limited medium: advanced laparoscopic experience *Low: early laparoscopic experience; 78224_CCFBCH_Text_ACG.indd 25 82_CBHTx_C.nd26 78224_CCFBCH_Text_ACG.indd Center for Robotics & Image – Guided Surgery News Disease Kidney & Urology 26 for a 7 cm Mass in a Renal Allograft Robotic-Assisted Laparoscopic Partial Nephrectomy laparoscopic bulldogclamps. 3). Therenalarteryandveinwereseparatelyclampedwith the-shoulder positiontoanover-the-hip(Figure The robotpositioningwasmodifiedfromthestandardover- port, 12mmassistantportandthree8roboticports. placement isillustratedinFigure2usinga12mmcamera s right lateraldecubituspositionata45-degreeangle.Po sa intheextraperitonealspace,andshewasplaced form. Thepatient’sallograftwaslocatedintheleftiliacfos- using thedaVinciSurgicalSystem(IntuitiveSurgical)plat- We chose atransperitoneal,four-robotic-armtechniques mass ofthetransplantedkidney(Figure1). phrectomy. In 1978,attheageof3,sheunderwentanativerightne- of refluxnephropathy,obesity(BMI35)andhypertension. The patientisa35-year-oldwomanwithmedicalhistory nephrectomy. first (RPN)renalallograft RCC treatedbyroboticpartial a significantlyreducedlifeexpectancy. Herewereportthe p munosuppressed patient.Althougheffective,graftremoval due toconcernoverarapidlyprogressiveRCC inanim- radical nephrectomywasconsideredfirst-linetreatment tumors, thereisnotreatmentconsensus.Historically, true tumorincidence.Giventhesmallnumberofallograft which isavoluntaryregistrythatanapproximationofthe the IsraelPenn InternationalTransplantTumorRegistry, mg/dL withaneGFRof25mL/min/1.73m cyst ofthelowerpole(Figure4).Serumcreatininewas2.2 ing theupperpoleoftransplantedkidneyandasimple ultrasound showeda7cmcomplexcysticrenalmassinvolv- his leftkidney. InSeptember2010,ascreeningabdominal related donorrenaltransplantwithherfatherdonating e occurring intheallograft.Thelargestsingle-centerexperi- RCC primarilyoccursinthenativekidneys,with10percent kidney transplantrecipients.Inthepopulation, of thegeneralpopulationandoccursin4.6percent Renal cellcancer(RCC) occursinapproximately3percent David Goldfarb,MD Jihad H. Kaouk,Spana,MD,and MD,Greg Forty-five casesofallograft RC a 0.2–0.4percentrateofrenalallograftRCC. by severalotherlargekidneytransplantseriesthatreported diagnosis ofRCC was13.8years.Thisdataissupported In thisseries,theaveragetimefromtransplantationto patients outofatotal2,050transplantedrecipients. can withIVcontrastconfirmeda7cmBosniakIIIcystic nce withRCC inatransplantedkidneyidentifiedseven laces thepatientbackondialysis,whichisassociatedwith In1986,attheageof11,sheunderwentaliving C havebeenreportedto 2 . Afollow-upCT rt demonstrating a7cmcomplex massoftherenalallograft. Figure 1.CTscanofabdomenandpelviswithIVcontrast t is anattractiveoption.Thiscaseillustratesthemodifica- size, theuseofRPNinrarecasearenalallograftmass Given theimprovedconvalescenceandsmallerincision for RPNintheallograftkidney. fashion. Table 1demonstratesthe perioperativeoutcomes the freeend.Thissuturewasruninahorizontalmattress i convenience. ClevelandClinichasnofinancialinterestinnoris This articleiswrittenforeducationalpurposesonlyandasa For references,[email protected]. allograft mass. RPN isasafeandfeasibleoptionfortreatmentofrenal margin and good short-term functional results indicate that ating onapelvickidney. Inaddition,thenegativesurgical w reapproximated usinga0vicrylCT-1suturecutto6inches, vessels andcollectingsystemdefects.Theparenchymawas from thefreeend.Thissuturewasusedtooversewopen inches, withoneWeck clipandseveralknotsplaced1cm in arunningfashionusing2-0vicrylSHsuturecutto6 Weck cliptechnique.Thebaseofthetumorbedwasclosed Renorrhaphy wasperformedusingourstandardsliding t endorsinganyproductordevicedescribedinthisarticle. ions tothestandardRPNtechniquesthatfacilitatedoper- Histopathology 1.8mg/dL Postop follow-up Serum creatinineat12monthspostop Estimated bloodloss Warm ischemiatime Operative time Table 1.Outcomes ith oneWeck clipandseveralknotsplaced1cmfrom 7.3 cm Papillary RCCtypeI 12 months 100 ml 26.5 min 210 min 21/174 PM 7:49 12/12/11 27 Center for Robotics & Image – Guided Surgery 12/7/11 12:14 PM clevelandclinic.org/glickman Figure 3. Illustration of surgical robot positioning 3. Illustration of surgical robot Figure Figure 2. Illustration of port 2. Figure placement and patient positioning Figure 4. Renal ultrasound at six months postoperative 4. Renal Figure demonstrating renal blood flow and no renal mass 78224_CCFBCH_Text_ACG.indd 27 78224_CCFBCH_Text_ACG.indd 28 Center for Robotics & Image – Guided Surgery News Disease Kidney & Urology 28 Synchronous Kidney Tumors: Comparative Analysis at a RoboticSingle Institution vs. Laparoscopic Partial Nephrectomy for Bilateral Overall, 26 patients were included in the analysis, 17 patients patients whounderwentbilateralLPN. undergoing bilateralRPNwerecomparedwiththoseof laparoscopically orrobotically. Theoutcomesofpatients and sequentialbilateralpartialnephrectomy,either masses, asconfirmedbyradiologicalimaging(Figure1), inclusion criteriawerediagnosisofbilateralenhancing tion fromJanuary2001toMarch2010werequeried.Study a without compromisingoncologicalcontrolhasbeen The treatmentparadigmfavoringrenalpreservation partial nephrectomy(LPN). of ashorterlearningcurvewhencomparedtolaparoscopic compared withopensurgery,theadditionaladvantage decreased convalescenceandimprovedcosmesisas sparing approachforrenaltumors.Itofferslesspain, is emergingasanattractive,minimallyinvasive,nephron- vs. RPN, respectively (p<0.43). tomy was 4.9 months ( ±0.94) and 4.78 months ( ±1.9) for LPN went bilateral RPN. The interval between partial nephrec- who underwent bilateral LPN and nine patients who under- m population. Medicalrecordsofpatientswhounderwent kidney cancerdatabasewasusedtoidentifythestudy Our ongoingIRB-approved,prospectivelymaintained synchronous renaltumors. LPN inacontemporarycohortofpatientswithbilateral we presentacomparativeoutcomeanalysisofRPNvs. function outcomes.Ro approaches showingequaloncologicalaswellrenal debated overthelastyears,withopenandlaparoscopic The bestapproachtoextirpativekidneysurgeryhasbeen while maintainingexcellentcancercontrol. to beexaminedinordermaximizerenalpreservation oncological control.Idealsurgicalmanagementcontinues d Bilateral tumorspresentauniquetreatmentchallenge which beingearlyage(lessthan40years)atdiagnosis. risk factorshavebeenproposed,themostsignificantof been reportedtovaryfrom1.811percent.Anumberof The incidenceofbilateralrenalcellcarcinoma(RCC) has Jihad H. Kaouk, MD,andRobertJ.Stein,MD pplied alsoinpatientswithbilateraldisease.Herein, ue toissuesrelatedlong-termrenalfunctionaswell inimally invasivenephron-sparingsurgeryatourinstitu- botic partialnephrectomy(RPN)

primary neoplasm primary system, suspiciousfor renal massabuttingcollecting i cm heterogeneouslyenhanc- side(bluearrow)5.2 Left Figure 1.Bilateralenhancingrenaltumors For references,[email protected]. RPN group. months fortheLPNpatientsand13.4in with notumorrecurrencesatameanfollow-upof22.1 p=0.056). Surgicalmarginswerenegativeinbothgroups, w tendency towardashorterwarmischemiatimecompared and 32proceduresintheLPNgroup.RPNpatientshada A totalof18procedureswereperformedintheRPNgroup at 61percentvs.22intheLPNpatients(p=0.006). the RPNgroupweremorelikelytoinvaderenalsinus LPN groups,respectively(p=0.003).Tumorsofpatientsin Mean tumorsizewas3.7cmand2.7intheRPN ng partial exophyticng partial central ith theLPNgroup(23vs.29.5minutesrespectively, collecting system renal massabutting central, somewhatinfiltrating heterogeneously enhancing Right side(redarrow) 12/7/11 12:14 PM 29 Center for Robotics & Image – Guided Surgery 12/7/11 12:14 PM clevelandclinic.org/glickman 0.08 0.7 0.2 p value p value* 0 32 32 LPN 6 (2) 88 16 (5) LPN 17.6 47 (15) 31 (10) (n=17) 3.7 ± 0.4 0.16 4 (12.5%) 0.73 51.2 ± 6.6 0.004 225 ± 54.7 0.14 -32.2 ± 9.6 0.03 29.5 ± 37.522.1 ± 14.5 0.056 0.24 0.08 0.02 0 0.008 RPN 77.8 p value* (n=9) 0 0 18 18 59 ± 4.3 57.9 ± 4.5 0.72 RPN (11%) 11 (2) 17 (3) 30.6 ± 3.485.6 ± 9.8 29.3 ± 2.2 78.8 ± 8 0.48 0.27 2.67 ± 0.33 2.5 ± 0.2 0.26 72 (13) 2 23 ± 5.2 4.7 ± 1.5 13.4 ± 4.5 68.7 ± 9.8 -18.6 ± 8.6 333 ± 138.6 5 4 8 4 3 10 12 10 22 10 LPN (n=32) 7 (22%) 0.006 4 9 3 6 5 7 6 7 3 4 RPN (n=18) 11 (61%) 3.7 ± 0.8 2.7 ± 0.4 0.03 Exo Size Endo Meso Medial Lateral Pattern Anterior Position Posterior Location Inter-polar Lower pole Upper pole 2 Sinus fat invasion Group comparison p-value performedGroup comparison p-value using two-tailed t-test and Fisher’s test exact Male, % African-American, % African-American, Age, years BMI, kg/m Values expressed as mean + standard deviation unless otherwise expressed specified. Values ASA=American Society of Anesthesiologists eGFR=estimated glomerular filtration rate; BMI=Body Mass Index; * Average warm ischemia time (min) Average length of time to discharge (days) Number of follow-up months Latest postop GFR (mean, std) Average % decrease in GFR Number of patients with postoperative complications (%) % with positive margins (# of patients) Pathology: % Clear cell (n) (n) % Papillary % Unclassified (n) % Oncocytoma (n) *Group comparison p-value performed two-tailed using t-test. Preoperative eGFR, ml/min eGFR, Preoperative ASA score Table 3. Outcomes Table Number of procedures Mean estimated blood loss (mL) Table 2. Tumor characteristics 2. Tumor Table Table 1. Demographic data Table Average size; Location: upper, middle, lower pole; exophytic more than 50 percent, more than 50 percent, middle, lower pole; exophytic Average size; Location: upper, entirely mesophytic less than 50 percent and endophytic 78224_CCFBCH_Text_ACG.indd 29 78224_CCFBCH_Text_ACG.indd 30 Center for Robotics & Image – Guided Surgery News Disease Kidney & Urology 30 “V” “V” Hilar Suture (VHS) Novel Robotic Renorrhaphy Technique for Hilar Tumors: c applied. TheVHSinvolvesaninteriorlayersuture using coldscissors(Figures1-2a),theVHStechniqueis After tumorresectionalongthepreviouslyscoredmargin reconstruction duringRPNforhilartumors. the “V”hilarstitch(VHS),anoveltechniqueforrenal as appliedinthissubsetoftumorcases,hereinwedescribe Hem-o-Lok clips. with afinalthrowandsecuredtwosliding technique. Thesutureisbroughtthroughtherenalcapsule an opposingapexofrenalparenchymausingasliding-clip Hem-o-Lok clip(Weck) fixedtothefreeendfromavertex W closure oftheparenchymaldefectaftertumorresection. challenge isthedifficultyinperformingrenorrhaphyfor in thehilum.DuringRPNforhilartumors,amajor to includeRPNforcomplexrenaltumors,includingthose proaches. IndicationsforRPNhavesignificantlyexpanded evolved towardnephron-sparing,minimallyinvasiveap- Over thepasttwodecades,renalsurgeryhasgradually Jihad H. Kaouk, MD,andShahabHillyer, MD onsisting ofan8-inch2-0vicrylsuture,withaknotand Figure 1.Hilartumorlocationwithresection ith theaimofspecificallyaddressingthissurgicalstep Fi The hilarvesselsareindicatedbytheblueandredblocks gure 2a.Tumor resectionwithlimitedtissue. bedafter 12/7/11 12:14 PM 31 Center for Robotics & Image – Guided Surgery 12/7/11 12:14 PM org. clevelandclinic.org/glickman aparoscopic entrapment sac and removed from an extend- aparoscopic entrapment This article is written for educational purposes only and as a This article is written for educational purposes interest in nor is convenience. Cleveland Clinic has no financial in this article. it endorsing any product or device described ing provides adequate renal tissue for reapproximation of ing provides adequate outer parenchymal layer is closed the renal capsule. The mattress 0 vicryl suture with by a continuous, horizontal placed after each suture pass a sliding Hem-o-Lok clip for the reapproximation of renal through the capsule, capsule (Figure 2c). after completing the renorrhaphy The hilum is unclamped The specimen is placed in a and hemostasis is secured. l ed lower quadrant port site. A Jackson-Pratt drain is placed ed lower quadrant port through a lower lateral port. reconstruction VHS can be applied effectively during renal secure hemo- after excision of hilar tumors. VHS allows for without stasis by approximating renal capsular edges compromising renal hilum. email the editor or kaoukj@ccf. references, please For Figure 2c. Horizontal mattress renorrhaphy to reapproximate reapproximate to renorrhaphy mattress Horizontal 2c. Figure the edges of the renal defect Figure 2b. V stitch involves 2 interior sutures from a 2b. Figure using of renal parenchyma vertex to an opposing apex a sliding-clip technique. These inner-layer sutures provide closure of the larger These inner-layer sutures the collecting system. Additionally, vessels and entries into in reshaping of the renal parenchy- the inner sutures result of the central-lateral border of the ma with medialization 2b). In this way, the “V”-shaped sutur- resection bed (Figure 78224_CCFBCH_Text_ACG.indd 31 Figure 2a. Tumor bed after resection with limited tissue. Tumor 2a. Figure by the blue and red blocks The hilar vessels are indicated 82_CBHTx_C.nd32 78224_CCFBCH_Text_ACG.indd Center for Robotics & Image – Guided Surgery News Disease Kidney & Urology 32 Retroperitoneoscopic LESS Nephrectomy Feasibility, Advantages and Challenges of i a 2.5-5cmsingleincisionovertheflank(Figure1).The and safelyremoved15kidneysfrom13patientsthrough o median visualanalogpainscoreatdischargewas2.1out was 30mgparentalmorphinesulfateequivalent.The of betweenoneandthreedays.Themediannarcoticused Median lengthofhospitalstaywastwodays,witharange minutes andmedianestimatedbloodlosswas43mL. too muchdiscomfort.Medianoperativetimewas132 All patientsrecoveredquicklyandsmoothlywithout f and finallythewholekidneywasmobilizedremoved renal pediclesweredissectedandcontrolled(Figure3), a 30-degreeor45-degreescopewasused,theureterand 2). Aftertheretroperitonealworkingspacewasdeveloped, between thelowercostalmarginandiliaccrest(Figure By using a GelPOINT the peritonealenvelope. approach) sincethekidneysarelocatedonelayerbehind without disturbingthebowels(aretroperitonealLESS experience andtechniquesofperformingsuchoperation c the incisionatoraroundumbilicus(thusoftenalso done inmostcasesthroughatransabdominalroutewith nephrectomy) isacutting-edgeprocedureandhasbeen under thelaparoscope(laparoendoscopicsinglesite[LESS] Removing adiseasedkidneythroughonlysmallincision J. StephenJones,MD Jeff Chueh,MD,PhD,BashirR. Sankari,MD,and nephrectomy located over the left flankmeasuring3.5cminlength. nephrectomy locatedovertheleft retroperitoneoscopicLESS Figure 1.Ahealedwoundofaleft ncision waslocatedovertheflankatmid-axillaryline rom theLESSincision. alled “bellybutton”surgery.) Inthisarticle,weshare our f 10,witharangeofonetothree. ® LESS access platform, we successfully For references,pleaseemailtheeditor. urologists as well. and this technique poses a steeper learning curve for limited by a small number of patients and no control cohort, a history of transabdominal surgery. This observation is peritoneal space, such as in cases where the patient has function, or those with potentially abnormal or obliterated peritoneal dialysis in patients with deteriorating kidney t tomy series.Itisespeciallyvaluableforpatientswhoneed series orwiththoseofconventionallaparoscopicnephrec- those ofpublishedtransabdominalLESSnephrectomy and satisfactoryoperativeoutcomes,ascomparedwith This approachprovidedacceptablesurgicalparameters three instrumentsandascopetogothrough. inside thegel-cap.Thesizeofincisionallowsforonlytwoor LESS incisionwhilethescopestayedoutsideincision,butstill Figure 2.Intraoperativeviewofaninstrumentgoingthroughthe artery inthisimage. artery sidetothe The anteriorlylocatedrenalveinwas ontheleft Figure 3. The renal artery wasligatedwith Hem-o- Figure 3.Therenalartery o havean intact peritoneal envelope for example, for future lok ® clips.

21/195 PM 9:54 12/12/11 33 Center for Robotics & Image – Guided Surgery 12/7/11 12:14 PM clevelandclinic.org/glickman Key Point: Key field surgical the in instruments the of detection Automatic in instrument the center to holder scope robotic the allows is procedure the Once endoscope. the of view of field the robotic take to potential the has technology this fine-tuned, assist intelligently robot the letting by level new a to surgery surgeon. the rror was inferior to 5 pixels, and in 87 percent of the cases, rror was inferior to 5 pixels, and in 87 percent n five laparoscopic kidney and adrenal surgeries. However, Instrument detection time was on average 40 ms for a Instrument detection time was on average a 480x360 pixels 200x100 pixels subsampled and 300 ms for the image subsampled image. In 70 percent of the cases, e inferior to 11 pixels. This image error allows the surgeon inferior to 11 pixels. This image error allows camera stayed to perform fine tool displacement while the that the motionless. It is only for larger tool displacements robotic scope holder will follow the tool’s displacement. A pilot study in an animal model evaluated the tool tracking system in surgical conditions. This concept was found valid i we observed two main reasons for a tracking failure: specu- lar reflections on the organs and presence of organs with long and straight edges. Robotic endoscopic surgeryRobotic robotic scope holder ® ointed by a surgical instrument, or an automatic adjust- ointed by a surgical instrument, or an automatic urgeon and the system remain limited (e.g., left, right, urgeon and the system enal procedures. This step allowed us to pre-validate the o the symmetry axis of the instrument in the image. Once o the symmetry axis of the instrument in the mage are computed using its 3-D coordinates in a fixed mage are computed using its 3-D coordinates the symmetry axis of the instrument is found, the tip of the the symmetry axis of the instrument is found, information. instrument along the axis is found using color is inte- The 2-D position of the instrument in the image grated into a visual servoing loop in order to automatically move the endoscope toward the tip of the instrument. The method was tested on several surgical videos of r (EndoControl). Once the robot and the imaging system are (EndoControl). Once the robot and the imaging the endoscopic calibrated, the 2-D coordinates of a point in i “world frame” linked to the robot. to The 3-D position of the insertion point corresponding on the image the instrument we wish to track is projected in the im- plane to constrain the search for the instrument correspond- age. This constraint is used to detect the lines and then ing to the edges of the instrument in the image, t tool segmentation approach with several instruments in the image and different types of laparoscopic surgical instruments. ment of the zoom to maintain a given number of instrument of the zoom to maintain a given number ments in the field of view of the endoscope. of automatic detection and present here the method We instrument tracking using the ViKY Georges-Pascal Haber, MD, and Jean-Alexandre Long, MD Haber, Georges-Pascal holders provide a “third hand” to the endoscope Robotic stability and quality of the images, surgeon, enhance the of the endoscope. The robotic and reduce the staining be controlled by a vocal command endoscope holders can but the interactions between the or head movements, s zoom out). up, down, zoom in and aimed at developing more sophisti- One elegant solution the surgeon and the system is cated interactions between of the surgical instruments. based on the visual servoing of “high Such an approach would allow for the development the automatic level” command of the endoscope such as area of interest displacement of the endoscope toward an p ViKY Robotic Scope Holder: Preliminary Results Using Instrument Tracking Instrument Using Results Preliminary Holder: Scope Robotic ViKY 78224_CCFBCH_Text_ACG.indd 33 78224_CCFBCH_Text_ACG.indd 34 Center for Urologic Oncology: Bladder Cancer News Disease Kidney & Urology 34 High-Grade Bladder Cancer Refractory to Bacille Calmette-GuérinOutcome (BCG) of Delayed Radical Cystectomy for Recurrent, Non-Muscle-Invasive, n Despite presentingwithpresumedcurablediseaseatdiag- the timeofcystectomy. underwent earlycystectomyandhadclinicalNMIBCat (defined aswithintwoyearsofdiagnosis);83(39percent) tomy and126(59percent)underwent“early”cystectomy patients hadnoclinicalevidenceofMIBCpriortocystec- group. Inthedelayedcystectomygroup,135(63percent) B (e.g., re-TURpriortoBCG),treatmentfull-strength preservation strategyrequiresappropriatepatientselection approach comparedtoimmediatecystectomy. Abladder lected patientsandsimilarlong-termsurvivalwiththis risks ofrecurrenceandprogressioninappropriatelyse- Advocates ofbladderpreservationwithBCGcitethelow urinary diversion. b for recurrentand/orprogressiveNMIBC-HGafteraninitial survival of215patientswhounderwentdelayedcystectomy We recentlycomparedthepathologicaloutcomesand by cystectomy. progression whilethecancerisstillatacurablestage cystoscopy) toidentifypatientswithrecurrenceand/or re-biopsy followinginductionBCG,vigilantsurveillance o risks ofperioperativemorbidityandmortalitydeleteri- tively. However,cystectomyisassociatedwithsubstantial ed inupto50percentand34ofpatients,respec- mortality frombladdercancerwithBCG,whicharereport- high probabilityofcureandtherisksprogression The rationaleforimmediatecystectomyisbasedonthe cystectomy. d diagnosis toradicalcystectomywastwomonthsinthe immediate cystectomygroup.Themediantimefrom group hadNMIBCandonly24percentinthe 2004 and2010.Atdiagnosis,allpatientsinthedelayed high-risk cT1disease,managedatourinstitutionbetween went immediatecystectomyformuscle-invasive(cT2)or cystectomy grouphadpathological non-organ-confined at cystectomy,74(34percent)patients inthedelayed t preservation strategyinvolvingrepeattransurethralresec- guidelines, thesepatientsmaybetreatedwithabladder TaHG, CISorT1)iscontroversial. According topublished invasive, high-gradebladdercancer(NMIBC-HG;definedas The optimalmanagementofpatientswithnon-muscle- Ranko J.Stephenson,MD Miocinovic,MD,andAndrew ion (TUR)+/-intravesicalBCGorimmediateradical us impactsonqualityoflifearisingfromintestinal elayed groupvs.20monthsintheimmediatecystectomy ladder preservationstrategyvs.277patientswhounder- osis and a substantial proportion (64 percent) with NMIBC CG +/-maintenancetherapy)andmonitoring(e.g., w pacts onthemortalityfrombladdercancermaybegained the timeofcystectomy. Ourresultsindicatesubstantialim- “early” cystectomyorwithoutclinicalevidenceofMIBCat at thetimeofcystectomy,evenamongthoseundergoing these patientshadpNOCBCand/orlymphnodemetastasis consisting ofintravesicalBCG.Asubstantialproportion i 0.07). Evenamongafavorablesubsetofpatientsundergo- at thetimeofcystectomy(30percentvs.42percent;p= or amongthosewhohadclinicalNMIBCvs.MIBC “late” delayedcystectomy(37percentvs.30percent;p=0.3) pNOCBC wasobservedamongthoseundergoing“early”vs. subgroup analyses,nosignificantdifferenceintherateof g percent; p=0.5)wasobservedintheearlyvs.latecystectomy percent; p=0.1)orcancer-specificsurvival(68percentvs.76 significant differenceinoverallsurvival(45percentvs.53 the subgroupanalysisofpatientsindelayedgroup,no served amongpatientsinthedelayedcystectomygroup.In rate and38percentofcancer-specificdeathwereob- Overamedianfollow-upof19months,45percentdeath v vs.24percent)andatthetimeofcystectomy(63percent delayed grouphadclinicalNMIBCatdiagnosis(100percent pN1-3 (p=0.5)despitethefactthatmorepatientsin cystectomy wasnotassociatedwithpNOCBC(p=0.3)or In multivariableanalysis,immediateversusdelayed progression toMIBC,therateofpNOCBCwas33percent. N in ourcystectomyseriesoccurredpatientswithinitial In summary,approximatelyhalfofthedeathsobserved disease atdiagnosis. sis, despitethefactthatformerhadpresumedcurable and delayedcystectomygroupsinthemultivariableanaly- overall orcancer-specificsurvivalbetweentheimmediate i bladder cancer(pNOCBC,definedaspT3-4and/orpN1-2), For references,pleaseemailtheeditor. tients withNMIBC-HGwhohavealonglifeexpectancy. for immediatecystectomyshouldbegiventohealthypa- disease whiletheyarestillatacurablestage.Consideration vigilant monitoringtoidentifypatientswithBCG-refractory ncluding 60(28percent)withlymphnodemetastasis.In ng “early”delayedcystectomywithoutclinicalevidenceof s. 24percent). roups, respectively. Therewasnosignificantdifferencein ith appropriatepatientselectionofpatientsforBCGand MIBC managedfirstwithabladderpreservationstrategy 12/21/11 9:38 AM 35 Center for Urologic Oncology: Bladder Cancer 12/12/11 9:14 PM clevelandclinic.org/glickman ence cystoscopy in the office setting. umors that were not evident using conventional cystoscopy. using conventional cystoscopy. umors that were not evident Fluorescence cystoscopy demonstrates selective update of hexaminolevulinate HCl in bladder cancer through the Cysview™ device. Malignant tissue fluoresces bright pink, whereas normal urothelium is seen in blue. have it if no muscle is included in the TUR specimen. If this in the TUR specimen. muscle is included have it if no po- there is substantial remains unrecognized, understaging risk and for disease progression. tential for underestimating we have been able to identify Using fluorescence cystoscopy, or areas of unrecognized high-grade muscle-invasive tumors t Although the multicenter trials demonstrated ability to Although the multicenter were not evident otherwise, the identify areas of CIS that for patients with CIS alone, so technology is not approved for that specific purpose. Further- studies are soon to begin using flexible cystoscopy instru- more, we anticipate trials allow fluores- mentation in the coming months, which may c ne of the most interesting areas of investigation for this hotoactive porphyrins accumulate preferentially in hotoactive porphyrins accumulate preferentially atients with suspected papillary bladder tumors in the atients with suspected papillary bladder tumors umor. This can be identified in approximately one-fourth umor. he high rate of cancer recurrence within the months fol- he high rate of cancer n a multicenter trial reduced the likelihood of tumor n a multicenter trial reduced the likelihood neoplastic tissue. Under certain spectra of blue light they neoplastic tissue. Under certain spectra of the diagnosis emit red fluorescence, which can assist in approved by of indiscernible malignant lesions. Recently acid the FDA, intravesical application of 5-aminolevulinic of photoactive Cysview™ (Photocure/GE, USA), a precursor tumors, and porphyrin, improves the detection of bladder i technology at Cleveland Clinic has been in patients undergoing restaging TUR for high-grade non-muscle-invasive group has shown that urothelial tumors. The Vanderbilt approximately one-third of these patients actually have unrecognized muscle invasion if the detrusor muscle was included in the resection specimen, and almost two-thirds of patients, primarily outside the normal-appearing areas of bladder tumor, but we have also identified cancer in the resected bed of the tumor deep in the detrusor muscle. In that circumstance, muscle invasion may be established in patients who would have otherwise been believed to harbor only non-muscle-invasive disease. O J. Stephen Jones, MD J. Stephen traditionally suspect malignancy Endoscopically, urologists of visible changes such as tumors based on the presence Nevertheless, evidence continues or “red velvety patches.” that many areas of bladder to accumulate demonstrating using traditional cystoscopy. malignancy are not visible of cystoscopy potentially explains This imperfect sensitivity t spring of 2011. Our experience has confirmed the study spring of 2011. Our experience has confirmed in the manage- findings and has led to significant changes ment of certain patients with apparent non-muscle- invasive bladder cancer. It is now a frequent observation in patients undergoing TURBT that additional areas of fluorescing tissue are identified following complete resection of the entire visible t lowing complete removal of all visible tumors. It is likely lowing complete removal present in many of these patients that cancer was already time of resection and simply became but not visible at the it became morphologically visible in follow-up when from adjacent abnormal or large enough to differentiate normal urothelium. P recurrence by approximately 16 percent. video optics When using this technology combined with Storz, both small papillary tumors and developed by Karl by cystos- almost one-third more cases of CIS overlooked participated copy are identified. Cleveland Clinic urologists and they in the multicenter trial leading to FDA approval, care of began using fluorescence cystoscopy for routine p Fluorescence Cystoscopy Proves Its Worth in Management of Bladder Cancer Bladder of Management in Worth Its Proves Cystoscopy Fluorescence 78224_CCFBCH_Text_ACG.indd 35 78224_CCFBCH_Text_ACG.indd 36 Center for Urologic Oncology: Kidney Cancer News Disease Kidney & Urology 36 Partial Nephrectomy: Implications for Surgical TechniqueDeterminants of Renal Function After h to developtechniquesperformPNwithoutclampingthe emia canbehighlyproblematic.Somecentershavebegun outcomes, andthereisnodoubtthatprolongedwarmisch- and havereportedastrongcorrelationwithfunctional Previous studieshavefocusedprimarilyonischemiatime fromischemicinjury(currentlyunderstudied). • • w primarily withlimitedwarmischemia(<25minutes)or thought. Ouranalysisof660solitarykidneysmanaged conventional PNisnotnearlyasdeleteriouspreviously found thatischemiatimeduringthetightparametersof However, whenwelookedatthisissueingreaterdetail, factor duringPN. sumption thatischemiaisthemostimportantmodifiable f emia timewasnotasignificantpredictorofultimaterenal after recoveryfromsurgerywasonly10percent,andisch- .00001). Inthisanalysis,themedianlossofrenalfunction ity andquantityofpreservedparenchyma(bothpvalues< factors determiningultimaterenalfunctionwerethequal- • canbepreservedwiththesurgery • essentiallyanonmodifiablefactor • function afterPNareintuitiveandinclude: functional outcomes.Thefactorsthatcaninfluencerenal this purpose–acontralateralkidneyisnotpresenttomask w determine renalfunctionafterPN,focusingonpatients performed acomprehensiveanalysisofthefactorsthat ing asmuchrenalfunctionpossible.We haverecently cancer controlbyobtainingnegativemarginswhilepreserv- The objectivesofpartialnephrectomy(PN)aretooptimize Steven C.Campbell,MD,andMatthewN.Simmons,MD for evaluationofthetrueimpactwarmischemia. were ratherlimited.Hence,itwasnotthebestpopulation MIS cases,sotheischemicintervalsforwarmcases unction. Thispopulationwasheterogeneousandexcluded

ilum inanefforttominimizeischemia,undertheas- ith hypothermiademonstratedthatthemostimportant ith asolitarykidney. Thesolitarykidneymodelisbest for Ischemia time Comorbidities thatmightmitigateagainstrecovery Type ofischemia:warmvs.cold Quantity ofvascularizedrenalparenchymathat Quality oftherenalparenchymapriortosurgery, m quantity factorhasbeendeterminedsubjectively,asesti- One validcriticismofourperspectivehasbeenthatthe determinant. the misleadingconclusionthatischemiatimeisaprimary time tosubsumeitspredictivepower,therebyleading quantity factorintotheanalysis,thusallowingischemia substantial. Mostpriorstudiesdidnotincorporatethe P the primarydeterminantofultimaterenalfunctionafter of thepreviousstudiesthatimplicatedischemicintervalas One otherfindingisfascinatingandhelpstoexplainmany renal functionafterPN. 1, whichillustratestheparametersdeterminingultimate tivariate analysis.TheseresultsaresummarizedinFigure the qualityandquantityfactorswereincludedinmul- of renalfunction. facilitate aprecisePNandthus allow foroptimalrecovery short ischemicinterval,byprovidingabloodlessfield,may r at volumetricCTscanspre-andpost-surgerytofurther strongly supportsthesefindings. We arenowalsolooking cal modelingofparenchymalvolumepreservationalso the primacyofthisfactor. Inaddition,recentmathemati- this parameter,despitepotentialvariance,supports dure. However,theverystrongstatisticalsignificanceof i 50 percentofthekidneyispreserved,willhavealonger a shortischemicinterval,whilechallengingPN,inwhich PN, inwhich95percentofthekidneyispreserved,willhave ity, thisshouldnotbesurprising--itisintuitivethataneasy tween warmischemiatimeandthequantityfactor. Inreal- c managed onlywithwarmischemiaandincludedmore A subsequentanalysisthusfocusedon362solitarykidneys m PN. Aslongastheischemicintervalisshortorahypother- important factordeterminingultimaterenalfunctionafter the quantityofpreservedparenchyma,maybemost while stillobtainingnegativemargins,whichwilloptimize preserving asmuchvascularizedparenchymapossible In theend,ourstudiessuggestthatprecisionofsurgery, ( subgroup, theriskofdevelopingnew-onsetStageIVCKD looked atcaseswithwarmischemia>25minutes.Inthis continuous parameter. Apreplannedsecondaryanalysis interval loststatisticalsignificancewhenevaluatedasa and quantityofpreservedparenchyma,whiletheischemic determinants ofultimaterenalfunctionwerethequality schemic interval,becausethereconstructionwillbemore eGFR <30)wasincreasedmorethantwofold,evenwhen efine theseobservations. ases withprolongedwarmischemia.Again,theprimary N; thisistheverytightcorrelationthatweobservedbe- ic approachisadopted,mostnephronswillrecover. A ated bytheprimarysurgeonatcompletionofproce- 12/7/11 12:15 PM 37 Center for Urologic Oncology: Kidney Cancer 12/12/11 7:54 PM clevelandclinic.org/glickman Renal p<0.001 Ultimate Function to Surgery (non-modiﬁable) to Surgery Quality of Parenchyma Prior Quality of Parenchyma p<0.001 >25min Signiﬁcant if p<0.0001 Quality and Quantity Predominate Quality and Quantity Quality and Quantity Predominate Quality and Quantity Warm Ischemia Time Warm Quantity of Preserved Parenchyma Quantity of Preserved Figure Legend: The main factors that determine ultimate renal function after Legend: The main factors Figure and quantity of preserved PN are the quality parenchyma. of the surgery ischemia time reflects the complexity the quantity of preserved because it is tightly correlated with parenchyma. Warm unless prolonged beyond 25 minutes. ischemia time loses statistical significance on multivariate analysis However, 78224_CCFBCH_Text_ACG.indd 37 82_CBHTx_C.nd38 78224_CCFBCH_Text_ACG.indd Center for Urologic Oncology: Prostate Cancer News Disease Kidney & Urology 38 not PCSM (HR 1.3; 95 percent CI: 0.7-2.4; p = 0.5) compared overall survival (HR 1.7; 95 percent CI: 1.4-2.1; p< 0.001) but tatectomy. Brachytherapy was associated with diminished 95 percent CI: 1.0-2.3; p = 0.041) compared to radical pros- percent CI: 1.4-1.9; p < 0.001) and increased PCSM (HR 1.5; was associated with diminished overall survival (HR 1.6; 95 In multivariable analysis using propensity score, EBRT (Figure 1b). and is an imprecise proxy for all-cause mortality (ACM) and reasons, BCR is not a valid comparator between treatments not uniformly lead to clinical metastases or death. For these significantly influence the time to BCR. Lastly, BCR does androgen deprivation therapy with radiation therapy can ferent definitions of BCR. In addition, the frequent use of due to differences in post-treatment PSA kinetics and dif- vast majority of EBRT patients were treated with conformal porary treatment standards, between 1995 and 2005. The Barnes-Jewish Hospital (St. Louis, Mo.) according to contem- treated by RP, EBRT and brachytherapy at Cleveland Clinic or between treatments, we analyzed a cohort of 10,259 patients To investigate if differences in overall survival or PCSM exist prostate cancer-specific mortality (PCSM). 2.6-3.3) and 2.3 percent (95 percent CI: 2.0-2.6), respectively percent (95 percent CI: 1.6-2.1), 2.9 percent (95 percent CI: respectively (Figure 1a). The adjusted 10-year PCSM was 1.8 84.4) for radical prostatectomy, EBRT and brachytherapy, percent CI: 79.8-85), and 81.7 percent (95 percent CI: 78.7- was 88.9 percent (95 percent CI: 87.5-90.1), 82.6 percent (95 limited by methodological flaws, premature closure due to quantity or quality of life. Prior randomized trials have been clusive evidence that any treatment is superior in terms of for localized prostate cancer. Unfortunately, there is no con- (EBRT) and brachytherapy are accepted treatment options Radical prostatectomy (RP), external-beam radiotherapy J.Stephenson,MD Andrew Localized Prostate Cancer in the Prostate-Specific AntigenExternal-Beam Era Radiotherapy and Brachytherapy for Comparative Effectiveness of Radical Prostatectomy, to radical prostatectomy. 10 years or longer. The adjusted 10-year overall survival rate 1,550 (11 percent) of the patients studied had follow-up of The median follow-up among survivors was 67 months and classified as low-, intermediate- and high-risk, respectively. istered to 12 percent, 45 percent and 82 percent of patients and/or adjuvant androgen deprivation therapy was admin- radiotherapy (3DCRT or IMRT), and neoadjuvant, concurren, score. However, comparisons using BCR are problematic specific antigen (PSA), clinical stage and biopsy Gleason cal recurrence (BCR) rates when stratified by serum prostate- Retrospective studies have demonstrated similar biochemi- preference and/or physician bias. As such, treatment decisions are based largely on patient poor accrual and inferior radiation therapy techniques.

For references, please email the editor. and we did not consider effects on quality of life. we only considered survival differences between treatments, men appear to be at risk for PCSM for up to 20 years. Lastly, overall survival and PCSM within 10 years of treatment, but despite our efforts to control for them. Our study evaluated our models may not adjust completely for these imbalances bidity scores and had more adverse cancer profiles. Thus, On average, EBRT patients were older, had higher comor- performed as initial therapy. or improved cancer control when radical prostatectomy is confounders, differences in treatment-related mortality and/ These survival differences may arise from an imbalance of improvement in overall survival compared to brachytherapy. and cancer-specific survival compared to EBRT and a small small but statistically significant improvement in overall confounders, radical prostatectomy was associated with a ing to current treatment standards. After adjusting for major temporary patients treated at high-volume hospitals accord- This study represents the largest comparative analysis of con-

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ACM (aHR 0.5; 95 percent CI: 0.4-0.6) and no significant significant no and 0.4-0.6) CI: percent 95 0.5; (aHR ACM com- 0.5-2.8) CI: percent 95 1.2; (aHR PCSM in difference associ- ACM increased The therapy. local definitive to pared receiving patients among observed was treatment with ated 1.03-5.3) CI: percent 95 2.3; (aHR radiotherapy external-beam not but 1.5-2.6) CI: percent 95 2.1; (aHR: brachytherapy and may optimize quality of life without compromising compromising without life of quality optimize may life. of quantity editor. the email please references, For beam radiotherapy (n=2,467), or brachytherapy (n=2,319) (n=2,319) brachytherapy or (n=2,467), radiotherapy beam and percent (16 surveillance activ by managed were 452 and features, high-risk and intermediate- had whom of percent 5 respectively.) PSA, age, for adjusting analyses regression multivariable In ac- diagnosis, of year and score Gleason biopsy stage, clinical reduced significantly a with associated was surveillance tive and efficacy of watchful waiting compared to radical pros- radical to compared waiting watchful of efficacy and active that evidence further provides study Our tatectomy. screen- with patients selected appropriately in surveillance diminished with associated not is cancer prostate detected a over therapy local definitive to compared PCSM or ACM those or patients low-risk among even years, 10 of follow-up dura- the assess to required is study Further confounders. beyond. and follow-up of years 15 at findings these of bility and study our from evidence accumulating the However, acceptable an is surveillance active that indicates others not need and patients low-risk for strategy management high a or expectancy life limited with those to restricted be approach an Such cancer. prostate indolent of probability radical prostatectomy (aHR: 1.2; 95 percent CI: 0.9-1.6). Simi- 0.9-1.6). CI: percent 95 1.2; (aHR: prostatectomy radical restricted were analyses the when observed were results lar low-risk and/or comorbidity no or minimal with men to diagnosis. at features is more or years 20 to 15 of follow-up with trial randomized A screen- for treatment whether assess definitively to needed and quantity improves significantly cancer prostate detected exist- the However, observation. to compared life of quality safety the demonstrate trials PIVOT and Scandinavian ing with minimal or no comorbidity. comorbidity. no or minimal with in ACM increased an was study our of finding surprising A brachy- and radiotherapy external-beam by treated men from death of risk increased significantly a to due therapy, obvious an be to appear not does There causes. competing may we though findings, these explain to bias cohort healthy other and comorbidity patient for adjusted fully have not

Kiranpreet and Andrew Khurana, MD, MD J. Stephenson, per- 50 about cancers, prostate screen-detected of era the In low-risk a have cancer prostate with diagnosed men of cent longevity man’s a to pose tumors these that risk The disease. years 10-15 within low very be to appears life of quality and rea- a be to appear would surveillance Active diagnosis. of cancer, prostate low-risk for strategy management sonable reduction in PCSM at 15 years (14.6 percent vs. 20.7 percent) percent) 20.7 vs. percent (14.6 years 15 at PCSM in reduction 52.7 vs. percent (46.1 ACM in improvement percent 6.6 a and this analysis, secondary unplanned an in However, percent). Considering age. of years <65 men to restricted was benefit associ- diagnosis in time lead year 10 and five between the with men to translate would result this screening, with ated age. of years 55-60 are who cancer screen-detected 731 involved (which trial PIVOT reported recently The similar a in cancers screen-detected with men American or ACM in difference significant no reported design) trial watch- and prostatectomy radical between years 12 at PCSM the of any in observed was ACM in difference No waiting. ful Sunnybrook and Mo.) Louis, (St. Hospital Barnes-Jewish local definitive of impact the Canada), (Toronto, Hospital screen- for PCSM and ACM on surveillance active vs. therapy multi- contemporary, a in analyzed was cancers detected were whom of 12,458 patients, 12,910 of cohort institutional external- (n=7,672), prostatectomy radical either by treated radiotherapy, brachytherapy and radical prostatectomy. Ac- prostatectomy. radical and brachytherapy radiotherapy, waiting; watchful from substantially differs surveillance tive to biopsy repeat with monitoring close involves former the curable a at still are they while cancers important identify administering involves typically waiting watchful while stage, symptomatic of time the at therapy androgen-deprivation progression. distant or local prostatecto- radical of trial randomized Scandinavian the In can- detected clinically with men in waiting watchful vs. my percent 6 a with associated was prostatectomy radical cers, though acceptance rates among healthy men with long life life long with men healthy among rates acceptance though safety the to attesting evidence despite low are expectancies approach. this of efficacy and mortality all-cause comparing studies large no are There among (PCSM) mortality cancer-specific prostate and (ACM) external-beam surveillance, active with managed patients subgroups analyzed, and only high-risk patients treated by by treated patients high-risk only and analyzed, subgroups PCSM. of risk lower significantly had prostatectomy radical under men among outcomes favorable more envisions One active by managed were they if trials these in observation with administered is given) (when treatment as surveillance intent. curative Clinic, Cleveland from investigators involving study a In Cancer May Show Promise of Method of Promise Show May Cancer Study of Active Surveillance of Localized Prostate Localized of Surveillance Active of Study 78224_CCFBCH_Text_ACG.indd 39 78224_CCFBCH_Text_ACG.indd 40 Center for Urologic Oncology: Prostate Cancer News Disease Kidney & Urology 40 Decision-Making for Localized Prostate Cancer: The Prostate Cancer “Metagram” decision because treatment involves significant tradeoffs prostate cancer treatment is inevitably faced with a complex be considered. Thus, a man who receives counseling about the probability of recurrence; HRQOL outcomes must also more complex than simply choosing the one that minimizes than based on their preferences. Choosing a treatment is on the content of the information patients receive, rather helping patients understand and balance the complex issues men will regret their treatment choice. Progress is needed in garding multiple important outcomes. Subsequently, many Patients have difficulty weighing complex information re- option and do not consider their values and preferences. anecdotes and opinions of others when choosing a treatment prostate cancer. Patients typically rely on physician opinion, edge and unrealistic expectations regarding treatment of Prior studies have indicated that patients have poor knowl- benefits of treatment relative to its harms. United States suggests that men’s focus is on the potential of treatment (particularly among low-risk patients) in the sensitive to his values and preferences. The high prevalence between potential benefits and harms that are likely to be cancer. regarding treatment decision-making for localized prostate my, external-beam radiation therapy and brachytherapy are health-related quality of life (HRQOL). Radical prostatecto- a cancer that may pose little threat to his longevity and/or choose between radical therapy and active surveillance for lenging process of selecting the optimal treatment. He must A man with localized prostate cancer is faced with a chal- Michael W. Kattan, MD J.Stephenson,MD,TracyAndrew and Krebs, Recent surveys suggest treatment choices are based largely values and priorities. When balancing this information, he must also consider his impact urinary, sexual and bowel function to varying degrees. been proven to be superior. All treatments may negatively accepted treatment alternatives, and none has definitively Bowel dysfunction Voiding dysfunction Incontinence Erectile dysfunction Cancer mortality Metastatic disease PSA recurrence 10 35 23 57 0.2 - 5 (percentage) Radical Prostatectomy

18 53 1 10 1.8 - 21 (percentage) Radiotherapy External-Beam

patients evidenced-based and individualized predictions abilities (termed the prostate cancer metagram) that offers We have incorporated these nomograms into a table of prob- therapy. associated with moderate to severe bother) at two years after bother) and bowel dysfunction (defined as bowel symptoms urinary tract symptoms associated with moderate to severe use of protective pads), voiding dysfunction (defined as lower (defined as leakage at least once a day and/or requiring the on at least 50 percent of attempts), urinary incontinence dysfunction (defined as erections inadequate for intercourse high-volume hospitals to predict the probability of erectile large, prospective, longitudinal quality-of-life studies from we have compiled patient-reported outcomes from four tality for men managed by watchful waiting. Most recently, developing distant metastasis and of prostate cancer mor- We have also developed models to predict the probability of oncology. and they are among the most widely used prediction tools in regarding treatment options for localized prostate cancer, The nomogorams are helpful when counseling patients individual rather than a heterogeneous group of patients. groups at predicting outcomes because they predict for the prostate cancer mortality. Nomograms are better than risk brachytherapy in terms of biochemical recurrence and/or by radical prostatectomy, external-beam radiotherapy and ment outcome for localized prostate cancer for men treated We have previously constructed nomograms to predict treat- treatment options. experience to enable one to make valid comparisons among predictions for all the relevant outcomes that a man may is intended to provide patients with accurate and unbiased for localized prostate cancer. The prostate cancer metagram for multiple endpoints after all standard treatment options

20 69 2 17 1.3 - 11 (percentage) Brachytherapy 6 9 (percentage) Watchful Waiting

12/7/11 12:15 PM 41 Center for Urologic Oncology: Prostate Cancer 12/12/11 7:59 PM clevelandclinic.org/glickman and therapy ve deci- the in assist can it ve, currently may score 3 sion for men in whom deferral of repeat biopsy is desired. desired. is biopsy repeat of deferral whom in men for sion PCA3 biopsies, negative withtwo prior men in Furthermore, clinicallysignificant reassurance that significant add can present. not is cancer editor. the contact please references, For cancer. prostate a as PCA3 of role the determine should Futurestudies We treatment. of initiation to prior outcomes of predictor patient a primarilyof setting the test in the use currently consid- is biopsy repeat whom in biopsy negative withprior findings. DRE or PSA percentage-free PSA, on based ered definiti not is test the Although otherwise indolent surveillance for active cancer prostate biopsy prostate prior no and ng/ml 3. 2.5–10 PSA concomitant a 4. and total PSA Elevated urinarycondition acti between make to 5. decision A biopsy prostate 2. family history a of and total Normal PSA metagram on decision quality, decisional conflict, decisional decisional conflict, decisional quality, decision on metagram com- trial randomized a in outcome treatment and regret a involves that model analytical decision formal a to pared prefer- (or utilities patient of assessment quantitative formal the demonstrate we If outcomes. these of each for ences) decision-mak- impacts favorably metagram cancer prostate available application web-based the make to intend we ing, in the public domain for patients and physicians. and patients for domain public the in editor. the email please references, For accuracy by as much as 5.5 percent. 5.5 as much as by accuracy colleagues and Schilling data, other and these on Based PCA the in scenarios five identified screen- cancer prostate of practice clinical the to contribute with: men are These management. and ing negative prior 1 > 1. and total PSA Elevated

mRNAin PSA to mRNArelative 3 at the value of a PCA3 score in predicting outcomes at initial at outcomes predicting in score PCA3 a of value the at initial undergoing men 516 study, that In biopsy. prostate PCA3 a had ng/ml 2.5–10 of value PSA witha biopsy prostate found was score PCA3 The biopsy. to prior performed score density PSA and free, total,percentage to superior be to operat- receiver a curve the on under area calculating when point set a curve.using Furthermore, characteristics ing score of 35, PCA3 was found to be predictive of Gleason score score Gleason of predictive be to found was PCA3 35, of score clini- and percent, >33 positive cores of percentage and >7 in included When criteria. Epstein using callysignificant predictive increased score PCA3 the models, multivariable the initial urine collected after prostatic massage ([PCA3 ([PCA3 massage afterprostatic initialcollected urine the witha patients of setting the In mRNA]*1000). mRNA]/[PSA sev- biopsy, prostate negative prior one least at and >3 PSA in score PCA3 the of superiority the shown have studies eral percentage- total and over biopsy repeat at cancer predicting levels. PSA free trial European looked multicenter prospective a Recently, developed in alternative tumor markers, and one marker marker one and markers, tumor alternative in developed cancer prostate the is value clinical some generated has that (PCA3). 3 gene nontranslated a is it and 1999, in discovered was PCA3 the in concentrations greater in produced is mRNA that PROGENSA The cancer. withprostate patients of urine on based score PCA3 a generates (Gen-Probe) assay PCA3 PCA of concentration the PCA3 in Daily Practice Daily in PCA3 K. Berglund, MD Ryan wide- most remains the (PSA) antigen prostate-specific Total Prostate the as but cancer, prostate for screen to tool used ly point set specific no Trial demonstrated, Prevention Cancer hasexists that biopsy for recommendation making a for elevated Often, specificity. and sensitivity acceptable both as such conditions urologic other represent levels PSA has Interest inflammation. or hyperplasia prostatic benign A prostate cancer metagram for a hypothetical patient who who patient hypothetical a for metagram cancer prostate A one in cancer prostate 6 Gleason T1c, with age of years 61 is illus- is ng/mL 7.11 of PSA preoperative a with cores eight of erections, good reports he diagnosis, At table. the in trated no and symptoms tract urinary lower mild incontinence, no substantial are there illustrates, table the As problems. bowel out- HRQOL-related and cancer-related between trade-offs incidence and nature the treatments; the of each with comes considerably. varies options the of each with effects side of enables that application web-based a developed have We prostate the for results generate to patients and physicians clinic. busy a of setting the in time real in metagram cancer cancer prostate the of impact the evaluating currently are We 78224_CCFBCH_Text_ACG.indd 41 78224_CCFBCH_Text_ACG.indd 42 Center for Urologic Oncology: Prostate Cancer News Disease Kidney & Urology 42 Focal Therapy Classification System: Creating a Common Language for Organ-Sparing Treatment of Prostate Cancer therapy or any other source of localized cancer therapy. ed States, this classification system applies to HIFU, brachy- approved ablation technology in widespread use in the Unit- portion of the gland. Although cryotherapy is the only FDA- describe management of prostate cancer that treats only a son Cancer Center, we developed a classification system to Thus, in conjunction with John F. Ward, MD, of MD Ander- broad, potentially misleading, term “focal therapy.” as hemi-ablation. destruction zone crosses the midline in many cases intended location of cancer intended for treatment. In reality, the tissue to the left or right of the urethra, determined by the 2. Hemi-Ablation: Unilateral destruction of all prostate ing the neurovascular bundle(s). to posterior, excepting the posterior lateral region(s) harbor- Destruction of all prostate tissue from base to apex, anterior 1. Nerve-Sparing Prostate Ablation (unilateral or bilateral): Defining Ablative Templates or preserved is highly variable among physicians using the that the volume and location of tissue that is either destroyed tors report the actual performance of focal therapy. It is clear ing of nomenclature, especially as it relates to how investiga- therapy is the need for a common language and understand- One of the glaring issues to be dealt with regarding focal exponential growth. cians alike have developed significant interest, driving its potential role in highly selected patients. Patients and physi- popularity in recent years, with emerging data supporting its Focal therapy for prostate cancer has gained significant J. StephenJones,MD

anterior region harbors little risk to sexual function. region of the prostate, based on the belief that treating the of the hemi-ablation to include the contralateral anterior 3. Anterior 3/4 Ablation (anterior hockey-stick): Extension 5. Zonal Ablation (anterior or posterior): Treatment confined identified to contain a carcinoma. tissue destruction only to the area of prostate that has been 5. Targeted Focal Therapy: Intended to limit the area of more of the peripheral zone, known to harbor most cancer. include the contralateral posterior region, in order to treat 4. Posterior 3/4 Ablation: Extension of the hemi-ablation to area believed to harbor a small tumor. tumor location, so this gives a margin of cell kill around the rently possible to reliably identify an exact demarcation of base to apex. This is based on recognition that it is not cur- cancer, most likely involving a quadrant at any point from to a region allowing broad margins beyond known areas of

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In an extended model that also adjusted for “early” postoper- “early” for adjusted also that model extended an In ng/ 0.5 < PSA pre-radiotherapy as (defined radiotherapy ative > PSA as (defined radiotherapy postoperative “late” and mL) signifi- no covariates, time-dependent as modeled ng/mL) 0.5 (HR observed was PCSM and PSM between association cant 0.9). p= 0.7-1.4; CI: percent 95 1.01; has PCSM and PSM between association an of lack The of BCR and need for secondary therapy, and may be a source source a be may and therapy, secondary for need and BCR of that perception lay the given anxiety patient considerable of urologists Thus, resection. cancer incomplete an implies it rates. PSM reduce to strive to continue should email the editor. references, please For important implications. First, it calls into question the the question into calls it First, implications. important the in PSM for radiotherapy postoperative for rationale vesicle seminal as such features adverse other of absence 10, and 8 between of score Gleason pathological invasion, question into calls it Second, time. doubling PSA short a or quality. surgical of measure a as rates PSM of relevance the risk man’s a increases it as matter does PSM Nevertheless,

of prostate cancer-specific mortality (PCSM). In an analysis analysis an In (PCSM). mortality cancer-specific prostate of aca- four at prostatectomy radical by treated men 11,521 of presence the identified previously we centers, medical demic vesicle seminal and cancer -10 8 Gleason pathological of sig- not was PSM PCSM. determinants prime the as invasion analy- multivariable the in PCSM with associated nificantly be may PCSM and PSM between association of lack The sis. AndrewMD J. Stephenson, prostatectomy radical in (PSM) margins surgical Positive are cancer prostate localized of treatment the for specimens risk recognized a are and men of percent 48 to 11 in reported biochemi- defined (PSA) antigen prostate-specific for factor with men for outcome the improve To (BCR). recurrence cal trials randomized three prostatectomy, radical after PSM analysis, men with PSM had a significantly increased PCSM PCSM increased significantly a had PSM with men analysis, (15-year margins surgical negative with those to compared multivariable In 0.001). p< percent; 6 vs. percent 10 PCSM PCSM with associated significantly not was PSM analysis, for adjusting after 0.9) p= 0.7-1.4; CI: percent 95 1.04; (HR covariates. fixed major have investigated the role of adjuvant radiotherapy vs. obser- vs. radiotherapy adjuvant of role the investigated have adju- with BCR of risk the in reduction significant A vation. these Given trials. three all in observed was radiotherapy vant the as radiotherapy adjuvant advocated have some results, PSM. with men for care of standard with men all for radiotherapy adjuvant of policy a However, es- an as majority, the for overtreatment represents PSM after recurrence cancer of free be will percent 60 timated years 15 within BCR; of history natural variable the to due cancer, prostate from die will men of one-third only BCR, of causes competing from death of risk the to similar is which of lack this that hypothesized we Alternatively, mortality. of postopera- of effect protective the to due be may association radiotherapy. salvage) or (adjuvant tive of risk long-term the analyzed we possibility, this explore To PCSM based on the pathological features of prostate cancer, cancer, prostate of features pathological the on based PCSM Overall, radiotherapy. postoperative of use the for adjusting them of 788 and PSM had patients these of percent) (23 2,607 that of percent) (96 756 radiotherapy; postoperative received (median level PSA pre-radiotherapy detectable a had group univariable In 0.24-1.10). range: interquartile ng/mL; 0.50 radical prostatectomy alone. Close observation and salvage salvage and observation Close alone. prostatectomy radical PSA the when (i.e., BCR of sign earliest the at radiotherapy and alternative reasonable a is levels) detectable reaches first results. similar give may PSM for radiotherapy adjuvant against argument strong A risk the increases significantly it that evidence of lack the is on Prostate Cancer-Specific Mortality Do Margins Matter? The Influence of Positive Surgical Margins 78224_CCFBCH_Text_ACG.indd 43 78224_CCFBCH_Text_ACG.indd 44 Center for Urologic Oncology: Prostate Cancer News Disease Kidney & Urology 44 First Step to Identifying Best Candidates for Active SurveillanceGene Expression Profiling of Prostate Cancer: delayed to the time of tumor progression, a strategy that has who may safely consider initial surveillance with intervention who are likely to benefit from immediate therapy vs. those biopsy-based tool could help identify newly diagnosed men lent from potentially lethal cancers. The development of a is the lack of prognostic tools that reliably distinguish indo- An important cause of the overtreatment of prostate cancer screening. some public health agencies to question the value of routine with substantial cost and unnecessary morbidity, leading tive intent. Overtreatment of prostate cancer is associated low-risk disease are treated by radiation or surgery with cura- more than 90 percent of men who are newly diagnosed with data suggesting no survival advantage to their treatment, Despite the indolent nature of most prostate cancers and 12 to 100 patients. number needed to treat to prevent one death ranging from and 2) estimates from large-scale screening trials of the percent) and tumor-related death (3 percent lifetime risk); clinical incidence (United States lifetime risk of diagnosis 17 these nonlethal cancers: 1) a significant discrepancy between era, two lines of evidence suggest a marked overdiagnosis of functions. with relatedbiological cluster intogenefamilies with clinicaloutcome Genes associated number of prostate cancers from radical prostatectomy Working with Genomic Health, we have studied a large tality in appropriately selected patients. been associated with a minimal risk of cancer-specific mor- symptoms or death. In the prostate-specific antigen (PSA) indolent and even if untreated will not progress to cause visceral malignancies in that the majority of tumors are The natural history of prostate cancer is unusual among Eric A.Klein,MD

the need for immediate therapy vs. active surveillance. to develop this test to help clinicians and patients decide on men, and 3) gene expression signatures were similar across dependent of the Gleason grade in the prostatectomy speci- and PSA), 2) a subset of these genes predicted outcomes in- of the usual preoperative parameters (biopsy grade, stage specific expression profiles predicted outcome independent chance of clinical recurrence. The results indicated that 1) PSA-related and stress genes are associated with decreased while increased expression of cytoskeletal/migration and guish indolent from aggressive disease. Our ultimate goal is velopment of a biopsy-based assay that may be able to distin- beyond Gleason grading, and serve as a first step in the de- profiling can reveal an underlying biology that provides value The results of this study demonstrate that gene expression different tumor foci in the same patient. are associated with increased risk of clinical recurrence, proliferation, basal epithelial and extracellular matrix genes genes can predict these outcomes - increased expression of The results demonstrated that the expression profiles of 295 recurrence or metastasis) and death due to prostate cancer. comes including PSA recurrence, clinical recurrence (local expression signatures were then correlated with clinical out- candidate genes by quantitative real-time RT-PCR. Gene and the isolated RNA was assayed for the expression of 726 between 1987 and 2004. The tumors were microdissected, The study included 501 men who underwent prostatectomy patient can safely adopt a strategy of active surveillance. test that can help determine whether a newly diagnosed an initial step toward developing a biopsy-based molecular predict clinical recurrence or death from prostate cancer, as specimens to determine if a gene expression signature could

12/7/11 12:15 PM 45 Center for Urologic Oncology: Prostate Cancer 12/7/11 12:15 PM clevelandclinic.org/glickman ed our prostate biopsy prophylaxis regimen. In order to ed our prostate biopsy nstitute’s Center for Quality and Patient Safety. Safety. nstitute’s Center for Quality and Patient ng post-prostate biopsy infections as well as an AUA alert alert infections as well as an AUA ng post-prostate biopsy Based on these findings, our quality team, the section team, the section findings, our quality Based on these consultants modi- and infectious disease of uro-oncology fi have come out to make practitioners aware of this problem. have come out to make quality and A careful team approach to monitoring the involved both outcomes experienced by our patients, which this issue early nurses and physicians, allowed us to note it. and institute protocol changes to help prevent & Kidney Goldman is the Director of the Glickman Urologic Dr. I utilize effective agents while bearing costs in mind, a dose utilize effective agents was added to the quinolone of intramuscular gentamicin patients are In addition, biopsy. given before prostate about recent exposure to quinolones now routinely queried been exposed they are given an and if indeed they have alternate regimen. above-mentioned abstracts regard- Subsequent to this, the i

istances to come to our department, not all of the routine istances to come to our department, not all uality reviews in 2010. Based on these QPSI findings, uality reviews in 2010. han 24 hours of a quinolone, which is in line with national han 24 hours of a quinolone, which is in line Howard B. Goldman, MD publicity of late about a recent in- There has been much of post-TRUS prostate biopsy infec- crease in the number in the lay press and a number of tions, including articles meeting. The Quality the 2011 AUA abstracts presented at Glickman Safety (QPSI) Institute within the and Patient noted this phenomenon during Urologic & Kidney Institute q increase in the proportion of patients who had experienced a experienced had who patients of proportion the in increase Among complication. infectious biopsy prostate post-TRUS investigation Further sepsis. of cases of number a were these had prophylaxis appropriate the cases all in that revealed an revealed cases of majority the However, performed. been many addition, In quinolone-resistant. was that organism of these patients had been exposed to a quinolone in the six six the in quinolone a to exposed been had patients these of pre- for treatment a as sometimes – biopsy to prior months infection. other some or “prostatitis” sumed follow-up is done in Cleveland; some follow-up takes place follow-up is done in Cleveland; some follow-up contacting all at the patient’s local site. Our review entails of weeks patients who had a procedure during a number interview as chosen at random and, through a telephone any post-proce- well as a chart review, evaluating them for dure morbidity. sharp a find to surprised were we review, 2010 our During antibiotic prophylaxis recommendations. This approach antibiotic prophylaxis recommendations. department. was standardized in 2009 across our entire group conducts In the fourth quarter of every year, the QPSI who have a careful telephone callback review of all patients during spe- a procedure completed at one of our offices travel long cific time periods. Since many of our patients d our prophylaxis for these patients was changed. our prophylaxis for these Clinic by Zaytoun, et al over the Studies done at Cleveland a post-biopsy infection rate past few years demonstrated of those of approximately 2.8 percent. During the course from multiple studies, the antibiotic prophylaxis evolved biopsy to less doses of oral antibiotics both before and after t Post-Transrectal Ultrasound (TRUS)-Guided Prostate Biopsy Biopsy Prostate (TRUS)-Guided Ultrasound Post-Transrectal Surveillance Outcomes and Quality of Importance – Infection 78224_CCFBCH_Text_ACG.indd 45 78224_CCFBCH_Text_ACG.indd 46 Center for Urologic Oncology: Prostate Cancer News Disease Kidney & Urology 46 Post-Cryoablation Voiding Symptom Control Study Shows Promise with external sphincter temperature (OR = 0.31, 95 percent Voiding symptoms in passive thaw patients correlated a 10 percent chance of having voiding symptoms (p=0.008). = 0.01, 95 percent CI: 0.02 - 0.55). Active thaw patients had cycle thaw patients had postoperative voiding symptoms (OR Ten percent of active and 35.9 percent of passive second- patients was assessed. and retention in 53 passive and 60 active second-cycle thaw ume and IPSS scores on the incidence of urgency/frequency number of cores positive, percent core positive, prostate vol- PSA, Gleason score, prostate gland volume, clinical stage, land Clinic was conducted. Impact of patient age, initial randomized prostate cryoablation patients treated at Cleve- A retrospective IRB-approved study of 113 consecutive non- studied. and contribute to quality of life, this method was formally incidence of urinary frequency, retention and urgency, on post-cryoablation voiding symptoms. To improve patient the impact of complete second-cycle active prostate thawing Recently, a team of urologists at Cleveland Clinic studied David A.Levy, MD Table 1.Descriptivestatisticsandunivariatecomparisons Variables IPSS.post-pre IPSS.post IPSS.pre Denon. tmp. Sphc. tmp. Apex. tmp. Ant. tmp. Initial PSA Max% Pos. cores Total cores Volume Gleason score Age (%) (n=94) Mean (SD)/Count Overall 3.4 (6.0) 6.2 (6.6) 2.5 (2.2) 5.8 (19.2) 19.8 (14) -54.6 (36) -59.1 (34.3) 10.3 (10.7) 32.8 (26.9) 3.4 (2.7) 13.1 (2.6) 31.2 (14.4) 6.6 (0.8) 66.1 (6.9)

8.4 (7.5) 8.4 (7.5) 3.4 (2.5) -6.4 (15.0) 24.4 (7.7) -46.1 (36.6) -47.7 (28.4) 7.2 (4.6) 37.8 (26.5) 3.7 (3.0) 12.9 (2.6) 32.7 (11.5) 6.6 (0.9) 66.1 (7.5) (n=58) Mean (SD)/Count(%) Passive thawing

of the impact of an alteration of an intraoperative aspect of data analysis on this surgical technique and the first report (p=0.008). This is the most comprehensive and detailed significantly decreases post-cryoablation voiding symptoms Conclusion: Complete second-cycle active prostate thawing groups (p<0.166) Changes in pre-and post-IPSS scores did not differ between marginally (OR = 2.24, 95 percent CI: 0.91-5.48, p=0.078). morbidity. the procedure that significantly impacts procedure-related (OR=3.07, 95 percent CI: 0.86-10.97, p=0.083) and older age, CI: 0.11 - 0.89, p=0.029), lower Denonvilliers’ temperature or activethawingoftheprostate withpassive cryoablation voiding symptomsafter Table 2.Multivariablelogisticregressionof Age Denon. tmp. Sphc. tmp. Active thawing Covariates 1.5 (2.7) 3.08 (3.2) 1.3 (1.2) 16.7 (15.72) 15.9 (16) -61.5 (34.2) -69.1 (35.9) 12.9 (13.6) 28.4 (26.8) 3.11 (2.4) 13.4 (2.6) 29.9 (16.5) 6.7 (0.8) 66.1 (6.3) (n=36) Mean (SD)/Count(%) Active thawing .4(.1–54)0.078 0.084 0.029 2.24 (0.91–5.48) 0.008 3.07 (0.86-10.97) 0.31 (0.11–0.89) p-value 0.01 (0.02–0.55) Adjusted OR(95%CI) . <.003 <.00001 <.0000 .019 .018 .0007 .573 .053 . .837 .527 .662 .995 p-value 165 339

12/7/11 12:15 PM 47 Center for Urologic Oncology: Prostate Cancer 12/7/11 12:15 PM

clevelandclinic.org/glickman

p-value operating room under general anesthesia. Until CPT CPT Until anesthesia. general under room operating “satura- term the of misuse confusing this corrects be should biopsy transrectal any biopsy,” tion 55700. coded Update: Infection Biopsy levels increasing see to continue worldwide Centers bac- resistant to due sepsis biopsy post-prostate of fluoroquino- especially antibiotics, of Overuse teria. bacterial altered has population, urology the in lones Special Concerns in This Practice: This in Concerns Special Confusion: Terminology occasional causes biopsy” “saturation term The term This community. urological the in confusion 20 involving biopsy transrectal a to refers accurately urological the in been has and cores, more or decade. a than more for literature created CPT later, years eight Unfortunately, for code to term established this using by confusion the in performed biopsy mapping guided template resistance patterns. resistance drug dual include this reduce to Approaches antibiotic for test to culture wall rectal and/or therapy Clinic, Cleveland At prophylaxis. guide to resistance a and ciprofloxacin of dose single a both give we prior hour one within aminoglycoside of dose single should management sepsis Post-biopsy biopsy. to logically and antibiotics, broad-spectrum include should not depend on antibiotics that failed to to failed that antibiotics on depend not should prophylaxis. adequate provide Saturation PBx (percent)

Extended PBx (percent) Total detection Total (percent) 50/196 (25.5) 16/74 ( 21.6) 34/122 (28) 0.33 86/305 (28.2) 27/116 (23.3) 59/189 (31.2) 0.13 tal Indication Benign biopsy findings Pathological 229/751 (30.5) HGPIN 71/277 (25.6)ASAP (±HGPIN) To 158/474 (33.3) 11/42 (26.2) 36/109 (33) 0.027 25/67 (37.3) 0.23 whether and how to perform repeat biopsy. Nevertheless, for for Nevertheless, biopsy. repeat perform to how and whether cancer prostate unrecognized of risk at be to considered men biopsy saturation office-based biopsy, negative following detection cancer increases and well tolerated be to appears higher no are complications and Pain one-third. almost by biopsy. standard for than J. Stephen Jones, MD J. Stephen has cores 12-14 obtaining (PBx) biopsy prostate Extended However, diagnosis. cancer prostate for standard the become (PCa) cancer prostate of cases many that well-recognized is it routinely are urologists so approach, systematic this elude challenged with determining indications and preferred preferred and indications determining with challenged persistent with patients in biopsy repeat for techniques cancer. of suspicion increased about concern block, periprostatic of use the With appears biopsy saturation office-based of morbidity or pain have biopsy saturation of efficacy and Safety unfounded. own. our including series, many in established well been dem- been not have rates complication intuitively, Counter- major The PBx. extended with than higher be to onstrated has it although that, was recently until persisted that issue detection PCa improves PBx saturation that assumed been cancer comparing actually data biopsy, repeat during have biopsy repeat extended with rates to rates detection lacking. been undergone have patients 2,000 than more decade, past the In saturation biopsy at Cleveland Clinic. We recently reported reported recently We Clinic. Cleveland at biopsy saturation un- who patients comparable defined clearly 1,056 in results biopsy. negative initial an following biopsy prostate derwent and saturation the between detection cancer compared We patients. biopsy extended detection higher percent 31.3 a had group saturation The percent, 24.9 vs. percent (32.7 PBx extended the than rate p=0.008). Of 315 positive biopsies, 119 (37.8 percent) revealed revealed percent) (37.8 119 biopsies, positive 315 Of p=0.008). percent). 32.6 vs. percent (40.1 cancer insignificant clinically (p=0.2), significance statistical reach not did this Although an have biopsy repeat undergoing patients all that note we This cancer. insignificant clinically of likelihood increased so biopsy, saturation with moderately increase to appears regarding decision the into weighed be must factor this Table: Detection rates in patients with benign findings, HGPIN and ASAP on initial biopsy. Table: Comparison of Office-Based Transrectal Saturation Biopsy With Standard Biopsy: Superior Cancer Detection for Repeat Biopsy Repeat for Detection Cancer Superior Biopsy: Standard With 78224_CCFBCH_Text_ACG.indd 47 78224_CCFBCH_Text_ACG.indd 48 Center for Urologic Oncology: Testis Cancer 48 Urology &KidneyDiseaseNews Stage INonseminomafromtheSociétéInternationaled’Urologie Testis Cancer: Practice GuidelinesfortheManagementofClinical cancer. For stagingpurposes,abdominal-pelvicimaging prognostic factorsbypathologistswithexpertiseintestis ment ofprimarytumorspecimensforhistopathological as prognosticfactors.Thepanelrecommendstheassess- onal carcinoma(EC)andMIB-1stainingmayalsobeused ence ofoccultmetastaticdisease.Predominanceembry- phovascular invasiontoriskstratifypatientsforthepres- Risk Stratification:Thepanelrecommendstheuseoflym- Clinical StageINSGCT pathological assessmentandtreatmentoftestiscancer. at institutionswithexpertiseinthediagnosis,staging, should beassessedandhavemanagementplansdeveloped compromising survival.Patients withlow-stageNSGCT mize seriouslong-termtreatment-relatedsequelaewithout ate therapy,thepanel’srecommendationsattempttomini- cancer-specific survivaloflow-stageNSGCTwithappropri- for medicalpractitioners.Giventheexcellentlong-term ate practicevariation,andprovidedecisionsupporttools outcomes andmedicalpractice,minimizeinappropri- The clinicalpracticeguidelinesareintendedtoimprove guidelines forthemanagementoflow-stageNSGCT. The panelwaschargedwithdevelopingclinicalpractice five countriesfromNorthAmerica,EuropeandAustralia. NSGCT fromurologyandmedicaloncology,representing consisting ofexpertsinthemanagementCSI,IIAandIIB Société Internationaled’Urologieconvenedanexpertpanel The InternationalConsultationonUrologicDiseasesand J.Stephenson,MD Andrew Figure 1. tients beinformedoftheirriskoccultmetastasisbased additional treatments.Thepanelrecommendsthatpa- treatment-related toxicity,andtheriskfornatureofany chemotherapy, andRPLND)potentialshort-long-term be madeawareofalltreatments(surveillance,primary Treatment: Thepanelrecommendsthatpatientsshould zone. cious” iftheyarelocatedintheappropriateprimarylanding lymph nodeslessthan10mmshouldbeconsidered“suspi- to ruleoutthepresenceofretroperitonealmetastasis,and dications toCTexist.Asizecutoffof10mmisinsufficient (MRI) isalesswell-establishedalternativetoCTifcontrain- contrast isrecommended.Magneticresonanceimaging with computedtomography(CT)intravenousandoral tion chemotherapyorRPLNDastheinitialintervention. forapproachesthatemployeitherinduc- have beenreported ratesof95 percentorgreater CS IIA-B,long-termsurvival ratesof97percent orgreater.with long-termsurvival For tablished treatmentoptionsforCSI,andallareassociated chemotherapyarees- node dissection(RPLND)andprimary retroperitoneal lymph GCT iscontroversial.Surveillance, chemotherapy, theoptimalmanagementoflow-stageNS- cm) andCSIII(distantmetastasis)shouldreceiveprimary (classified asCSIS),IIC(retroperitonealadenopathy>5 there isconsensusthatCSIpatientswithelevatedSTM ease atdiagnosis(clinicalstage[CS]I,IIAandIIB).While tous germcelltesticularcancer(NSGCT)havelow-stagedis- Approximately 50percentofpatientswithnonseminoma- Key Point:

12/7/11 12:15 PM 49 Center for Urologic Oncology: Testis Cancer 12/7/11 12:15 PM clevelandclinic.org/glickman Clinical Stage IIA and IIB NSGCT IIA and IIB Stage Clinical AFP or HCG should elevated post-orchiectomy with Patients The panel considers chemotherapy. receive induction RPLND to be accept- and primary induction chemotherapy with CS IIA with normal options for patients able treatment CS patients with levels. For AFP and HCG post-orchiectomy AFP and HCG levels, in- IIB and normal post-orchiectomy is the preferred approach, although duction chemotherapy for select CS IIB patients with RPLND may be considered informed should be Patients limited nodal involvement. the potential short- and long- of both treatments including toxicity, and the risk for and nature term treatment-related of any additional treatments. with induction chemotherapy or The decision to proceed on patient preference and the RPLND should be based the treating physician and institution. specific expertise of with equivocal Surveillance may be considered for patients low risk CT retroperitoneal findings who are at otherwise treated with induc- for occult metastatic disease. Patients appropriate to tion chemotherapy should receive regimens should the IGCCCG risk, and those with residual masses CS I NSGCT, undergo post-chemotherapy RPLND. As for of RPLND, the panel’s recommendations for the technique requirement the use of adjuvant chemotherapy and the CS IIA and IIB of surgeon experience apply to RPLND for for clinical Stage IIA and IIB A treatment algorithm NSGCT. NSGCT is outlined in Figure 2. to improve These clinical practice guidelines are designed and expert clinical practice based on the available evidence recommenda- opinion of the panel. Deviation from these consid- tions should be based on sound clinical judgment, the expertise ering the unique situation of the patient and of the treating physician and institution. email the editor. references, please For Figure 2. Figure Clinical Stage IS NSGCT with no clinical evidence of metastatic NSGCT Patients or rising after orchiectomy other than persistently elevated as for advanced AFP or HCG should receive chemotherapy The panel disease, usually with either BEPx3 or EPx4. elevated and recommends caution in interpreting slightly as these may stable AFP and HCG levels after orchiectomy, not necessarily stem from disseminated NSGCT. on the presence of known risk factors (as listed above), and above), and (as listed risk factors of known presence on the be employed. The panel approach should a risk-adapted of for patients at low risk active surveillance recommends For is not feasible. unless this approach occult metastasis active surveil- high risk for occult metastasis, patients at of with two cycles and primary chemotherapy lance, RPLND all acceptable treatment chemotherapy are cisplatin-based the use of patients desiring active treatment, options. For or RPLND should be based on the primary chemotherapy the treating physician and institution. specific expertise of of CS I NSGCT is illus- An algorithm for the management trated in Figure 1. the panel recommends a full, When RPLND is performed, with nerve-sparing in patients bilateral template dissection at nerve-sparing Attempts who desire future paternity. the completeness of resection. should not compromise evidence to support laparoscop- The panel cites insufficient chemo- ic RPLND as a therapeutic procedure. Adjuvant options therapy and observation are acceptable treatment and patients for patients with pathological stage II disease, RPLND and should be informed of the risk of relapse after The the potential benefits and risks of these approaches. by panel emphasizes that RPLND should be performed experienced surgeons. 78224_CCFBCH_Text_ACG.indd 49 78224_CCFBCH_Text_ACG.indd 50 Center for Blood Pressure Disorders News Disease Kidney & Urology 50 Specialized Care to Patients Resistant Hypertension Clinic Provides Complete, who undergo24-hourambulatoryBPmeasurementstohelp t known, epidemiologicanalysesandclinicaltrialssuggest While theactualprevalenceofresistanthypertensionisun- mediated andrenovascularcauses. curable) causesofhypertension,whichincludeendocrine- use, excessalcoholintakeoridentifiable(andpotentially inadequate diuretictherapy,inappropriatemedication include improperBPmeasurement,excesssodiumintake, N The resistanthypertensionclinicintheDepartmentof guidelines andprocessimprovement. and difficultcasescanalsoassistwithadviceregarding cians areidentifiedasconsultantsforthemorecomplex clinical hypertensionandrelateddisorders.Thesephysi- with expertskillsandknowledgeinthemanagementof ciety ofHypertension(ASH),whichrecognizesphysicians r who areadheringtofulldosesofanappropriatethree-drug as thefailuretoreachgoalbloodpressure(BP)inpatients Evaluation, andTreatmentofHighBloodPressure(JNC7) the JointNationalCommitteeonPrevention,Detection, Resistant hypertensionisdefinedintheSeventh Report of J.Schreiber, Thomas,MD,andMartin MD George o Besides thestandardizeduseofautomatedBPdevicesin and testing. space andequipmentdedicatedtohypertensionevaluation sion specialists,andhasadedicatedhypertensionlabwith search inhypertension,isstaffedbyASH-certifiedhyperten- Kidney Institutehasarichhistoryofinnovationandre- A not beachieved. consultation withahypertensionspecialistifgoalBPcan- cardiovascular morbidityandmortality. JNC7recommends tension associatedwithotherriskfactorsportendshigher hypertension isunclear,butlong-standingseverehyper- of studyparticipants.Likewise,theprognosisresistant hat itisnotuncommon,involvingatleast20to30percent egimen thatincludesadiuretic.Potential reasonsforthis ur outpatientclinics,wehavealargecohortofpatients hypertensionspecialistiscertifiedbytheAmericanSo- ephrology andHypertensionattheGlickmanUrological& s ed tothediagnosisandmanagementofprimaryhyperaldo- of secondaryhypertensionmanagement,specificallyrelat- Nephrology andHypertensionalsohasexpertiseinthefield for assessmentofcardiovascularrisk.TheDepartment which couldhelpearlydetectionofendothelialdysfunction capability tostudyendothelialfunctionnoninvasively, In addition,theresistanthypertensionclinicalsohas For references,pleaseemailtheeditor. v applanation tonometry,includingmeasuresofpulsewave BP measurements,andweassesscentralindicesusing more stronglywithvasculardiseasethanroutineperipheral lab. Centralbloodpressureshavebeenshowntocorrelate assessing hemodynamicparametersinourhypertension to helpguidetreatmentdecisionsandtailortherapyby The clinicalsousesnoninvasiveimpedancecardiography the assessmentofefficacytherapy. This around-the-clockmethodofmeasurementalsoaidsin pertension, labilehypertensionand/ornocturnaldipping. with thediagnosisofwhite-coathypertension,maskedhy- elocity andaugmentationindex. teronism, pheochromocytomaandrenalarterystenosis.

12/7/11 12:15 PM 51 Center for Blood Pressure Disorders 12/12/11 8:00 PM clevelandclinic.org/glickman ypertension and heart disease. Together, our findings in- ypertension and heart disease. Together, rimitive vertebrates for their adaptation to changing rimitive vertebrates for dequately adapting to changes in dietary salts, indicating dequately adapting to dicate that corin defects may represent an important mech- dicate that corin defects may represent an in patients. anism underlying salt-sensitive hypertension email the editor. references, please For Evolutionarily, natriuretic peptides were developed in were developed in natriuretic peptides Evolutionarily, p species, many migratory marine fish environments. For peptides are critical for maintain- for example, natriuretic when these animals travel ing electrolyte homeostasis during their life cycles. Corin is from fresh to salty water natriuretic peptide processing. an essential enzyme for deficiency prevents the mice from Now we show that corin a mechanism is well-preserved in that this ancient molecular purposes. mammals for similar of the corin- Our studies provide new insights into the role Previ- mediated pathway in salt-sensitive hypertension. ously, corin gene variants were found in African-Americans, of salt-sensitive a population known for its high prevalance h found that, compared to that in wild-type (wt) mice, found that, compared to that in wild-type atients are in the genes involved in sodium homeostasis, atients are in the genes enesis of hypertension are yet to be identified. miloride, an ENaC blocker that inhibits renal sodium miloride, an ENaC blocker that inhibits renal reabsorption, increased urinary sodium excretion and reabsorption, increased urinary sodium excretion lowered high blood pressure in corin ko mice. Our data show that corin is critical in regulating sodium homeostasis upon dietary salt challenges and that corin deficiency causes salt-sensitive hypertension in mice. which include epithelial sodium channels (ENaC), sodium/ which include epithelial and proteins in the renin-angioten- potassium transporters sin-aldosterone system. date, however, the number of hypertensive patients with To fraction known gene mutations represents only a small genes and of the overall patient population. Thus, more to the patho- molecular mechanisms that may contribute g peptide, Corin is a protease that activates atrial natriuretic salt-water bal- a cardiac hormone important in maintaining we used corin knockout ance and blood pressure. Recently, of corin in (ko) mice as a model to study the importance to dietary salt. regulating the sensitivity of blood pressure We Qingyu Wu, MD, PhD Qingyu Wu, a pathological condition in which Hypertension represents is inadequately controlled. Exces- the salt-water balance to be an important risk factor in sive dietary salt is known patients with essential hypertension, hypertension. Among are salt-sensitive. Genetic stud- approximately 50 percent identified in hypertensive ies show that most mutations p blood pressure in corin ko mice was more sensitive to blood pressure in corin ko mice was more for example, dietary salt loading. On a 4 percent NaCl diet, increased, blood pressure in corin ko mice was markedly in similarly whereas no significant changes were observed treated wt mice. excretion Corin ko mice also had impaired urinary sodium with when they were fed with high-salt diets. Treatment a Molecular Insights into Salt-Sensitive Hypertension Salt-Sensitive into Insights Molecular 78224_CCFBCH_Text_ACG.indd 51 78224_CCFBCH_Text_ACG.indd 52 Center for Blood Pressure Disorders News Disease Kidney & Urology 52 Their Increasing Role in Various Cardiovascular and Pathways Biosynthetic Discovered Disorders Newly Aldosterone: m production andglomerulosacellproliferation,bothhall- molecular andcellularlevelsthatleadtoexcessaldosterone Another importantstudyhasevaluatedmechanismsat normal levels. an aldosteroneantagonist,resultedinloweringofBPto sion. Subsequenttreatmentofthesemicewitheplerenone, that lackcircadianrhythmandhavesalt-sensitivehyperten- c excess aldosteronesynthesisanddevelopmentincrypto- regulation ofthisenzyme(Hsd3b6)thatisassociatedwith tion ofaldosteroneandhypertension.Itdemonstratesup- a linkbetweendisruptedcircadianrhythm,excessproduc- role inexcessaldosteroneproduction.Thisstudyunravels steroid dehydrogenase(Hsd3b6)thatmayalsoplayamajor p ters withseverehypertensionand bilateraladrenalhyper- patients. Inanotherthreepatients (fatherandtwodaugh- ing thepotassiumselectivityfilter, KCNJ5, ineightofthese adenomas. Theyidentifiedtwo mutations ingenesencod- mia, elevatedaldosterone-renin ratioandunilateraladrenal of 22patientswhopresentedwithhypertension,hypokale- n from theadrenalcortexandareductioninreninlevelsby altered: thereisunregulatedreleaseofexcessaldosterone in theprimaryhyperaldosteronestate,thisrelationshipis preceded byanelevationinplasmareninlevels.Incontrast, In thenormalsetting,ariseinaldosteronelevelisalways are thesubjectofdebateamongexpertsinhypertension. t reported ahigherprevalenceofhyperaldosteronisminpa- cardiovascular outcomes.Morerecently,somestudieshave sterone effectsusinganaldosteroneantagonistimproves pecially theheartandvasculature,thatblockingaldo- aldosterone levelscancausedamagetotargetorgans,es- Further, therearecleardatademonstratingthatelevated s pathways thatleadtoproductionofaldosterone.Inarecent most importantandcrucialenzymeinfinalbiosynthetic Until now,aldosteronesynthasehasbeenrecognizedasthe vascular disorders. aldosterone biosynthesisanditsrelationshipwithcardio- provide interestingnewinsightsintothemechanismof Here, wesummarizefourrecentlypublishedstudiesthat s rone inleadingtoacommonformofsecondaryhyperten- addition, theroleofunregulatedreleaseplasmaaldoste- within thenormalrangehasbeenknownforalongtime.In taining volumehomeostasisandbloodpressure(BP)levels The vitalroleoftheadrenalhormonealdosteroneinmain- Mohammed A.Rafey, MD,MS,andEmmanuelL.Bravo,MD ients diagnosedwithresistanthypertension,findingsthat tudy, DoietalidentifyanenzymetypeVI3beta-hydroxy- ion (primaryaldosteronestate)isalsowell-recognized. hrome-1 (Cry1)andcryptochrome-2(Cry2)(Cry-null)mice lasia), theydemonstratedadifferent mutationencoding egative feedbackmechanism. arks ofprimaryaldosteronism.Choietalevaluatedaset c Alvarez-Madrazo etalonceagainhighlightthefactthatARR the tumorsdirectly. Importantly,resultsfromthestudyby may lateronleadtothedevelopmentofdrugsthattarget development ofaldosterone-producingtumors,which biosynthetic pathwaysincreaseourunderstandingofthe the areaofhyperaldosteronism.Thenewlydiscovered These fourremarkablestudiesaddvastknowledgein t true bloodpressureexperiencedbytargetorgansincluding BP, aparameterthatisbeingincreasinglyacceptedasthe study thataddressestherelationshipofARRwithcentral genesis ofuncontrolledhypertension.Itisalsothefirst clearly identifiestheroleofincreasingARRinpatho- respective ofrenalandcardiacfunction.Thus,thisstudy F elevation inARR. pared withhypertensiveindividuals)mighthavesimilar individuals (althoughinamuchlowerproportioncom- with primaryhyperaldosteronism,becausenormotensive trary cutoffpointsforelevatedARRdonotidentifypatients and isstronglyheritable.Thisstudyalsoclarifiedthatarbi- a ously distributed;isaffectedbyseveralfactors,including Results fromthisstudydemonstratethatARRiscontinu- (ARR) in1,172normotensiveandhypertensivesubjects. tribution andheritabilityofthealdosterone-to-reninratio A thirdstudy,byAlvarez-Madrazoetalevaluatedthedis- aldosterone expressionandgranulosacellproliferation. l granulosa cells,abnormalandexcesssodiumconductance tance ofsodiumandmembranedepolarization.Inadrenal channel ledtoalteredionselectivity,increasedconduc- KCNJ5. ThislossoffunctionmutationatthelevelKCNJ5 a also centralBP, withthe implicationthatadditionofan have asignificantrelationshipwithnotonlyperipheralbut salt loadingtest.Tomaschiz etalconfirmthatARRlevels patients whoneedfurtherevaluationwithaconfirmatory ism; atbest,itisascreeningtestthathelpsstratifythose B steady riseinperipheralandcentralsystolicdiastolic BP. IncreasinglyhigherARRdecileswereassociatedwitha between theARRandincreasingperipheralcentral study demonstratedasteadyandsignificantrelationship cess, ARR,andperipheralcentralBP. Results fromthis ship betweenplasmaaldosteroneconcentration(PAC) ex- For references,pleaseemailthe editor. outcomes inthesepatients. eads toactivationofcalcium-gatedchannels,constitutive he heart,brainandkidneys. annot bereliedonforthediagnosisofprimaryaldosteron- ge, gender,plasmapotassiumlevelsandbodymassindex; ldosterone antagonistwilllikely improvecardiovascular inally, astudybyTomaschiz etalevaluatedtherelation- P andsystolicaorticBP. Thisrelationshippersistedir- 12/7/11 12:15 PM 53 Center for Chronic Kidney Disease 12/7/11 12:15 PM clevelandclinic.org/glickman CKD should be explored in clinical trials. ase and mortality in patients withCKD. ase and mortality in patients ure on the effects of 25[OH]D supplementation in patients ure on the effects of 25[OH]D population. Controlled studies examining whether 25[OH] Controlled studies population. outcomes are limited. We D supplementation improves review of the available litera- earlier reported a systematic t For references, please email the editor. references, please For In summary, 25[OH]D is associated with cardiovascular In summary, 25[OH]D is associated with cardiovascular Future studies risk factors and death among CKD patients. might explain should explore the mechanistic links that and mortality. the observed association between 25[OH]D could re- Importantly, whether 25[OH]D supplementation 3 and Stage duce mortality rates among patients with Stage 4 with 25[OH]D deficiency and varying degrees of CKD. This with 25[OH]D deficiency in biochemical endpoints with a revealed an improvement serum 25[OH]D and an associated significant increase in published of the none PTH levels. But, significant decline in of 25[OH]D supplementation studies explored the impact fracture risk, cardiovascular dis- on bone mineral density, e ortality among nondialysis-dependent CKD patients. ortality among nondialysis-dependent CKD as not significantly associated with increased mortality. mortality. as not significantly associated with increased 5[OH]D deficient and who have parathyroid hormone nd lower eGFR were significantly associated with 25[OH] nd lower eGFR were significantly associated o 80 percent prevalence in some parts of the world. In the o 80 percent prevalence National Kidney Foundation Kidney Disease Outcomes National Kidney Foundation vitamin Quality Initiative guidelines currently recommend with 25[OH]D D supplementation in Stage 3-4 CKD patients Disease Improv- released Kidney level <30 ng/ml. Recently ing Global Outcomes guidelines recommend using vitamin D in patients with Stage 3-5 CKD (not on dialysis) who are 2 levels above the normal range. However, these studies were based on extrapolation from studies conducted in general D <30 ng/ml. A graded increase in the risk for 25[OH]D <30 D <30 ng/ml. A graded increase in the risk 25[OH]D ng/ml was evident across increasing BMI levels. was associated with deficiency defined as a level <15 ng/mL for mul- a 34 percent increased risk of death after adjusting and tiple variables. The effect was similar for Caucasians (level <30 ng/ml) African-Americans. 25[OH]D insufficiency w We included 12,763 Stage 3 and 4 CKD patients (estimated included 12,763 Stage We glomerular filtration rate [eGFR] 15-59 ml/min/1.73m2) Of registry. from our electronic health record-based CKD and 5,749 these, 1,970 (15 percent) were 25[OH]D deficient Male gender, (45 percent) had 25[OH]D insufficiency. artery disease African-American race, diabetes, coronary a Sankar D. Navaneethan, MD, MPH Sankar D. worldwide are either 25-hydroxy More than a billion people deficient or insufficient. Prevalence of vitamin D (25[OH]D) with extremes of age, post- 25[OH]D deficiency increases race, and presence of menopausal state, African-American (CKD). Studies have reported vary- chronic kidney disease 25[OH]D deficiency in CKD, with 70 ing prevalence rates of t general population, low 25[OH]D levels are associated with general population, low cardiovascular disease and all- cardiovascular risk factors, 25[OH]D levels and Evidence linking low cause mortality. CKD cardiovascular risk factors in nondialysis-dependent recently We has been accumulating in the recent years. associated with examined whether 25(OH)D deficiency is m 25-Hydroxy Vitamin DDisease Deficiency in Kidney Chronic Nondialysis-Dependent 78224_CCFBCH_Text_ACG.indd 53 78224_CCFBCH_Text_ACG.indd 54 Center for Chronic Kidney Disease News Disease Kidney & Urology 54 Mass Spectrometry in Biological Matrices Measurement of Biomarkers by Liquid Chromatography-Tandem o Another advantageworthmentioningistherelativeease nine asanexample),therapeuticdrugsandmanyothers. ganic acids,acylcarnitines,endogenousmetabolites(creati- analytes includinghormones,steroids,aminoacids,or- clinical laboratorycommunityforquantifyingavarietyof ries. Thistechnologyisconsideredthegoldstandardby clinical use. development andvalidationofHPLC-MSMSmethodsfor l patient specimensiscriticaltoensureaccurateresults.Our cal properties.Therefore,rigorousvalidationinappropriate with thesamemolecularweightandsimilarphysicochemi- to the matrix effect and interference from other compounds However, LC-MSMSisnotproblem-free.Itmaybesubject ity resultinginaccurateresults. e Recently, liquid-chromatographytandemmassspectrom- ence maycauseinaccurateresults. for manyclinicaltests,especiallyimmunoassays,interfer- results fordiagnosisandpatientmanagement.However, laboratory areaccurate,andphysiciansdependonthose There isabeliefthattheresultsrenderedbyclinical Sihe Wang, PhD,DABCC, FACB o through theirmass/chargeratios.Theuniquecombination by measuringionizedmoleculesand/orthefragments mobile phase.Massspectrometrydistinguishesmolecules cal affinityofthecompoundswithstationaryphaseand separates compoundsbasedondifferentialphysicochemi- tography andmassspectrometry. Liquidchromatography LC-MSMS gainsspecificityfromboththeliquidchroma- aboratory hasestablishedastandardprotocolforboth try (LC-MSMS)hasbeenintroducedtoclinicallaborato- f thetwotechnologiesoffershighsensitivityandspecific- f developinganewmethodtoquicklyestablishtest. For references,pleaseemailtheeditor. Proteomics for biomarker discovery. • Organic acids for inborn errors of metabolism • Acylcarnitines for inborn errors of metabolism • Measurement of iothalamate for nonradiation GFR • 12-iyrxvtmnDi eu o igoi n 1,25-dihydroxyvitamin D in serum for diagnosis and • 25-hydroxyvitamin D in serum for evaluating vitamin D • nephrology include: and applicationspertinenttothefieldsofurology clinical researchandpatientcare.Recent developments technology andhaveappliedthesemethodsinboth We havelaunchedmanynewclinicaltestsusingthis t Tests ourteamplanstodevelopinthefutureinclude Arginine derivatives as biomarkers for cardiovascular • Metanephrine and normetanephrine in plasma for • Metanephrine and normetanephrine in urine for • diagnosisandmanagementofpheochromacytoma he following: p management ofmanydiseasesincludingmanaging nutritional status disease andkidneyfunction. diagnosis andmanagementofpheochromacytoma of this expertise. cal studies has been greatly enhanced due to the availability capacity for biomarker measurement and discovery for clini- in-house that used to be sent to other laboratories. The ing immunoassays while other tests have been brought significantly improved accuracy compared with correspond many tests using this technology. Some of these tests have We have established service anand LC-MSMS launched Key Point: atients withchronickidneydisease

- 12/7/11 12:15 PM 55 Center for Chronic Kidney Disease 12/7/11 12:15 PM clevelandclinic.org/glickman etabolic risk factors earlier. Our findings also highlight etabolic risk factors earlier. ercent higher for abdominal obesity and 14 percent higher ercent higher for abdominal ted with the development of CKD (odds ratio 1.55, 95 per- ted with the development for impaired fasting glucose. The risk for development of for impaired fasting glucose. differ based on the definition of MetS CKD did not seem to study population. used, duration of follow-up or ethnicity of and its components are associated conclude that MetS We and that there is with a higher risk for development of CKD of these a need to identify individuals with the constellation m Eleven studies with a total sample size of 30,146 subjects size of 30,146 subjects with a total sample Eleven studies associ- was significantly in our analysis. MetS were included a the need to consider multidisciplinary interventions to tar- the need to consider multidisciplinary interventions of CKD. get multiple risk factors related to the development email the editor. references, please For cent CI 1.34-1.79) (Figure). The strength of this association cent CI 1.34-1.79) (Figure). number of components of increased with an increasing elevated Among the individual components of MetS, MetS. with 61 percent higher odds blood pressure was associated the odds were 27 percent higher of developing CKD, while 23 percent higher for low HDL, 19 for elevated triglycerides, p

DL cholesterol), elevated blood pressure and impaired DL cholesterol), elevated ohort studies that reported the development of microal- ohort studies that reported the development his condition. Metabolic syndrome and development of chronic kidney disease Metabolic syndrome and development of chronic Sankar D. Navaneethan, MD, MPH Sankar D. (MetS) includes the constellation of Metabolic syndrome that have been associated various metabolic abnormalities stroke and all-cause mortality with cardiovascular disease, The components of MetS include in the general population. (high triglycerides and low central obesity, dyslipidemia H George MD, and Srinivas, Thomas, MD, Titte between association an reported have studies Observational and chronic MetS and microalbuminuria or proteinuria con- We kidney disease (CKD) with varying risk estimates. to synthesize ducted a systematic review and meta-analysis on the rela- the results of existing epidemiologic evidence reviewed MEDLINE, tionship between MetS and CKD. We Science databases for prospective of Scopus and the Web c buminuria or proteinuria and/or CKD in participants with buminuria or proteinuria and/or CKD in participants Risk estimates for eGFR <60 ml/min/1.7m2 were MetS. using a extracted from individual studies and pooled random effects model. glucose metabolism. Although the definition of MetS pro- glucose metabolism. such as the National Cholesterol posed by various agencies the Inter- Adult Treatment Panel-III, Education Program’s Health Organi- and the World national Diabetes Federation obesity zation differ, insulin resistance and abdominal of are the common denominators for the development t Metabolic Syndrome and Chronic Kidney Disease Kidney Chronic and Syndrome Metabolic 78224_CCFBCH_Text_ACG.indd 55 82_CBHTx_C.nd56 78224_CCFBCH_Text_ACG.indd Center for Chronic Kidney Disease News Disease Kidney & Urology 56 Critical Care Nephrology – Testing the Old and Finding the New Hemodialysis-associated hypotension base ofremoval(HD:Kt/Vurea1.2;CRRT: delivered, increasingurearemovalbeyondanaccepted ATN study,whileureaisstillusefulfordosingthetherapy in patientswithAKI.Asnotedourinvolvementthe criteria, whichhavebeenshowntohelppredictoutcome in serumcreatininegaverisetotheRIFLEandlaterAKIN for patientoutcome. generic volumeconsiderationsareimportantadjudicators collateral treatment initiatives, comorbid disease states and corporeal support.Membranechoice,timingofsupport, alone doesnotrevealtheentirepotentialbenefitsofextra- increase intheriskofmortality. Thus,focusedurearemoval but asanentityinandofitself,carriesonlya4percent mortality inpatientswithsignificantcomorbiddiseases, bered thatthepresenceofAKIwillincreasemorbidityand not associatedwithimprovedoutcomes.Itmustberemem- a closer attentiontoacuterenaldysfunction.Classifying acute kidneyinjury(AKI)hasonpatientsfostered More recently,agreaterawarenessofthenegativeinfluence ing inroadsinthecareofESRDpatient. and closerattentiontovascularaccesshavemadecontinu- advances, medicationdiscoveriessuchaserythropoietin t population astheyprogresstowardendstage,well that time,classificationofthechronickidneydisease Dialysis Studyfromthelate1970sandearly1980s.Since Kinetic ModelingisbasedontheNationalCooperative Modeling toestablishadosingregimenforadequacy. Urea renal disease(ESRD)populationhasreliedonUreaKinetic Judging theeffectofdialytictherapyinendstage Emil P. Paganini, MD,FACP, FRCP he developmentofbiocompatiblemembranes,equipment nd stagingpatientsbaseduponurineoutputandchanges 20ml/kg/hr)was

i level ofanyindicatorhasalsoshowntohavesignificant Correction forvolumestatuswhenjudgingtheactual ICU andtotalhospitalstay. real volumeremovalhasbeeneffectiveisshortening focusing onseverecongestiveheartfailurethatextracorpo- of recovery,wehavefoundinourrecentlypublishedstudy continues toholdpromiseinearlydiagnosisandprediction v renal supportofferedhavealsobeenunderscrutiny. Since Finally, boththetimingofinitiationandtype all activelybeinginvestigated. judged bychangesinhematocritoralbuminvaluesare or dynamicchangesinrelativeintravascularvolumesas tion oflargeveins,radioisotopedistributionevaluations i herald renaldysfunction.Thebestwaytomeasurevolume normal renalfunction)ratherthananincreasethatmay expanded statesmayreflectalowervalue(thusindicating is overlooked,thenpostoperativecreatinineinvolume- is tightlyboundtomostAKIpredictors.Ifvolumestatus using aparticularindicator. For example,serumcreatinine t as theinfluenceofsepsisinetiologyAKI.While importance ofvolumemanagementandcontrolaswell What seemstobeevolvinginthecriticalcarearenais while continuousstillseemstohavesuperiorhemodynam- tages seenwithconvectionoverdiffusiveformsofsupport, practice trend.Also,therehavebeennoclear-cutadvan- than whatwastraditionallytaughtseemstobethecurrent as causaleffectinrenaldysfunction,earlierdialyticsupport s stillunknown.Centralpressurereadings,echoevalua- nfluence ontheaccuracyofpredictivemodelwhen he searchforbiomarkersasindicatorsoftissueinjury olume hasbeenshowntoplaybothanassociativeaswell 21/191 PM 9:16 12/12/11 57 Center for Chronic Kidney Disease 12/7/11 12:15 PM clevelandclinic.org/glickman edication and also had more frequent office visits. edication and also had more frequent office ffectiveness of the CNP-driven CKD Clinic. ear follow-up. We measured the proportion of these pa- measured ear follow-up. We he blood pressure control and referral rates for transplant ndicator for extracorporeal therapy initiation. ndicator for extracorporeal In the course of our study, we looked at 2,091 patients seen In the course of our study, we looked at 2,091 at least a one- between 2006 and 2009. These patients had y had more ad- The population seen by the CNP was older, to be African- vanced kidney disease and was more likely American. As the CKD Clinic continues to grow, we hope to compare What is the loss of outcomes more specific to mortality. GFR over time in patients managed by the CNP vs. those would like to compare followed by a physician only? We t between the two groups of patients. Another outcome that greatly affects mortality that we would like to look at is AVF placement prior to initiating hemodialysis. Does the CNP place- management make a difference in the timing of AVF ment prior to hemodialysis vs. doctor-only management? The answers to these questions will continue to prove the e tients who had reached target parameters in relation to the tients who had reached target parameters up. Of the KDOQI guidelines during that one-year follow by the CNP. 2,091 patients, 425 of them were followed followed by the CNP had a found that the patients We pertinent to higher percentage of lab parameters measured with a statin their CKD. They were more likely to be treated m For references, please email the editor. For Emil P. Paganini, MD, FACP, FRCP, is a senior consultant in FRCP, MD, FACP, Emil P. Paganini, Critical Care Nephrology. references, please email the editor. For value in both urine (slight advantage) and serum determi- urine (slight advantage) value in both NGAL as a potential some actually favoring nations, with i ent options for end stage renal disease, including hemo- he information gathered thus far indicates favorable isease may progress. It is important that these patients isease may progress. It is important that these n earlier recognition of renal dysfunction might lead to n earlier recognition are educated on medications and what needs to be done are educated on medications and what needs pressure and to halt the progression of CKD, such as blood also need to be educated on what glucose control. Patients to expect if their condition does progress. There is a dedi- cated education visit that patients attend to address treat- m Jennifer Lyons, RN, MSN, CNP RN, Jennifer Lyons, began seeing The Chronic Kidney Disease (CKD) Clinic to serve more patients in May 2006 and has since grown are seen by the than 500 patients. These 500-plus patients majority of their Certified Nurse Practitioner (CNP) at the nephrologist at office visits and are seen by their referring least once per year. patients about The purpose of the CKD Clinic is to educate their kidney their medical condition, their eGFR and how d outcomes in the CNP-run clinic. Most recently, we have submitted these outcomes in abstract form at the National Nevada. in Las Vegas, meeting Kidney Foundation dialysis, peritoneal dialysis and renal transplant. areas that are ad- During the office visit with the CNP, dressed include blood pressure management, glucose control (in diabetics), anemia management, mineral and bone disorders, and lipid management. have begun to query the population within the CNP-run We CKD Clinic vs. the patients followed only by a physician. T earlier intervention, which should have either a curative or earlier intervention, which effect on AKI development. The at the very least a softening include NGAL, IL-18, KIM-1 and most promising of these at their predictive studies have looked cystatin-C. Various ic-hemodynamic stability vs. intermittent techniques in techniques stability vs. intermittent ic-hemodynamic ATN a quick review of the ICU patient. Indeed, the unstable of intradialytic hypotension with study shows the presence more hemodynamically unstable IHD not seen with the trial). - adapted from ATN CRRT population (Figure biomarker development, It is hoped that with accurate a The CKD Clinic as Managed by a Nurse Practitioner Nurse a by Managed as Clinic CKD The 78224_CCFBCH_Text_ACG.indd 57 78224_CCFBCH_Text_ACG.indd 58 Center for Dialysis 58 Urology &KidneyDiseaseNews The ABCDsofAntibioticDosinginContinuousDialysis Maria E.Taylor, PharmD dently associatedwithKe. whereas CRRTdose(p<0.003)wastheonlyfactorindepen- were theonlyfactorsindependentlyassociatedwithVd, Age (p<0.01)andweightgainsinceadmission(p<0.002) and Ke (r2=0.30)topatientanddialysisprescription data. A multivariatelinearregressionmodelfitted Vd (r2=0.49) had acuterenalfailureandcompletedataforanalysis. Fifty-three subjectswereenrolledinthestudy,and39 clinical dataandPK/PDparameters. regression wasusedtotesttheassociationbetween standard PK/PDparametersfromplasmalevels.Logistic were measuredbyHPLC.Thestudyteamthencalculated consisted oftotal,freeandeffluentpiperacillinlevelsthat blood andeffluentsamplesweredrawn.Druganalysis ing uninterruptedCRRT, trough,peak,andsecondtrough eters wererecorded.Afterthefourthdoseofantibioticdur- pregnant women.Patient demographicandCRRTparam- group didnotincludeESLD,patientsundertheageof18or chronic renalfailurereceivingCRRTintheICU. Thestudy Patients includedinthestudywerethosewithacuteor Philadelphia inNovember2011. at theAmericanSocietyofNephrology’sKidneyWeek in antibiotic dosinginthecriticallyillpatientwerepresented injury. Results fromthismulticenter clinicalstudyof impact ofachievingPDtargetsonsurvivalinacutekidney performed alogisticregressionanalysistodeterminethe factors associatedwithfailuretoreachPDgoals.We then pared withpharmacodynamic(PD)goals,andweidentified phic dataandCRRTprescription.Druglevelswerecom- the ICU. PKparameterswerecomparedwithanthropomor- measured piperacillinlevelsinpatientsreceivingCRRT In anIRB-approvedmulticenterstudy,weprospectively the volumeofdistributionandclearance. edge ofpharmacokinetic(PK)parameters,particularly survival insepsis,butdosecalculationsdependonknowl- (AKI). Earlyappropriateantimicrobialtherapyimproves Sepsis istheleadingcauseofdeathinacutekidneyinjury 3 Seth R. Bauer, PharmD Ashita J.Tolwani, MD 1 Michael J.ConnorJr., MD University ofAlabama,Birmingham,Ala. Cleveland Clinic, 2 Emory University,Emory 3 , andWilliam H. Fissell, MD 1 3 , CharbelSalem,MD , Peilin Wei, MD 1,2 , Joseph Groszek, BS, JosephGroszek, 3 , 1 , 1 , 1 piperacillin dosesforpatientswithAKIreceivingCRRT. information isneededtoprospectivelycalculateoptimal tailed analysisoftheeffectPDonsurvivalinCRRT. More PD goals.Alargermulticenterstudymaypermitmorede- Higher CRRTclearanceincreasestheriskoffailingtomeet available data.CRRTsignificantlyaffectspiperacillinPD. tients receivingCRRTareimperfectlypredictedbyclinically parameters neededtocalculatepiperacillindoseinpa- tailored antibioticdosing,butmorestudyisneeded.PK dependent acuterenalfailuremightbeimprovedby In conclusion,thisstudysuggeststhatsurvivalindialysis- cant minorityofsubjectswerefailingtoattainPDgoals. attained anfT>MIC>50percent,suggestingthatasignifi- mL/min ofCRRTclearance).Only53percentsubjects T>MIC of64mcg/mL(OR0.80[95percentCI0.60-0.94]per negatively predictiveofachievingaPDgoal>50percent endogenous clearance,CRRTclearancewasstronglyand dose. WhentotalclearancewasdividedintoCRRTand goals ofpercentT>MIC=64,asdidtotaldailypiperacillin Pharmacokinetic parameterspredictedattainmentofPD 12/7/11 12:15 PM 59 Center for Endourology and Stone Disease 12/12/11 8:02 PM clevelandclinic.org/glickman High Sodium Foods High Oxalate Foods to Avoid Foods High Oxalate Twenty-four hour ietary and supplement changes. The daily dietary recom- ietary and supplement changes. The daily tilization of a registered dietitian who develops individual- ay to 620 mg/day) and 56 percent demonstrated decreases ompliant? We recently evaluated the outcomes of patient- recently ompliant? We reatment and prevention for affected patients. reatment and prevention mendations included limiting protein consumption to 6-8 mendations included limiting protein consumption in conjunc- ounces, suggesting 1000-1200 mg of calcium increase of juice tion with meals for oxalate binding and an ½ cup. Any with citrates, such as lemon juice, equal to preventive patient requiring additional pharmacological measures was eliminated from the study. Insights into preventing or minimizing urolithiasis through Insights into preventing are a focus of the new multi-disci- dietary modifications Cleveland Clinic. Coordinated care plinary Stone Clinic at and registered dietitian is between urologist, nephrologist the cornerstone of this new initiative. Are patients But does dietary intervention make an impact? c Manoj Monga, MD, and Carolyn Snyder, MPH, RD, LD MPH, MD, and CarolynManoj Monga, Snyder, This is the question paramount in Why did my stone form? as he or she faces the rigors of renal the patient’s mind even the next logical closely behind that query is colic. Following a new of another stone. Fortunately, concern of prevention Clinic seeks to successfully blend initiative at Cleveland t urine collections were repeated to evaluate the impact of urine collections were repeated to evaluate dietary modification. of patients At an average follow-up of 15 months, 71 percent demonstrated improvements in urinary volume (from 58 percent demonstrated decreases in urinary 1.7L to 2.6L), sodium (from 230 mmol/day to 145 mmol/day), 50 percent demonstrated decreases in urinary uric acid (from 820 mg/ d focused dietary interventions on 24-hour urinary stone risk focused dietary interventions on 24-hour urinary performed parameters. The initial urine collection was Based on without any dietary counseling or restrictions. dietary the 24-hour urine content results, individualized instruction was provided to each patient. water The primary dietary counseling included increasing output and intake, resulting in >2 liters per day of urine d ly tailored diet plans - based upon the 24-hour urinary stone risk profile - to prevent or minimize further recurrences of painful stones. references, please email the editor. For in urinary oxalate (from 46 mg/day to 33 mg/day). Urinary citrate increased in 51 percent of patients (from 580 mg/ significant modifications, dietary day to 800 mg/day). With noted. were oxalate calcium for supersaturation in decreases Dietary interventions can impact outcomes in kidney stone disease. Unique to Cleveland Clinic’s Stone Clinic is the u Stone Clinic Study Shows Promise in Dietary Interventions Interventions Dietary in Promise Shows Study Clinic Stone Prevention and Treatment Stone Kidney in 78224_CCFBCH_Text_ACG.indd 59 78224_CCFBCH_Text_ACG.indd 60 Center for Female Pelvic Medicine & Reconstructive Surgery 60 Urology &KidneyDiseaseNews The Potential Incontinence Role ofStemCellsinRelief ofUrinary development ofSUI. up-regulation ofstemcellfactorscorrelateswithfuture the effectofobesityonstemcellupregulation,orwhether of stemcellhomingfactorsinwomenaftervaginaldelivery, date therearenostudieslookingattheserumexpression repair ofpelvicfloortissuesfollowingvaginaldelivery,to of specificstemcellhomingfactorsmaybeinvolvedinthe While animalmodelshavesuggestedthattheexpression ated recoveryofSUI. VD resultsinhomingofMSCstotheurethraandacceler- preliminary datademonstratingthatinfusionofMSCsafter in pelvicfloortissuesoffemalerats.Inaddition,wehave mesenchymal stemcells(MSCs),areupregulatedafterVD homing cytokines,particularlythosethatattractadult man maternalinjuriesofchildbirth,andthatstemcell that vaginaldistension(VD)inrodentssimulatesthehu- The sectionofFemale Reconstructive Surgeryhasshown serve asbiomarkersforlaterdevelopmentofSUI. increase inproportiontothedegreeofinjuryandthereby involved inhoming.Levelsofthosecytokinesserummay sometimes viathesamereceptor-mediatedmechanisms to sitesofinjury,wheretheyfacilitatetherepairprocess, by theinjuredtissuesattractorhomecirculatingstemcells of childbirth-relatedinjuries.Cytokinegradientsproduced fore havethepotentialtobeharnessedfacilitaterepair Stem cellsparticipateinnormalrepairprocessesandthere- ed tocontinueincreasesubstantiallyinthefuture. obesity ontherise,incidenceofSUIinwomenisexpect- are othermajorriskfactorsfordevelopmentofSUI.With continence. Obesity,diabetesmellitusandadvancedage muscles andsupportivetissuesresponsiblefor maintaining women isvaginalchildbirth,whichcaninjurethenerves, the strongestlifetimeriskfactorfordevelopmentofSUIin one’s qualityoflife.Thereisincreasingagreementthat Although notlife-threatening,SUIcanbedevastatingto about 35percentofwomenovertheage40. the mostcommonformofurinaryincontinence,affecting effort orexertion(e.g.,sneezing,coughingexercise),is continence (SUI),definedasinvoluntaryleakageofurineon billion in1995andhasrisensincethen.Stressurinaryin- direct medicalcostofUIintheU.S. wasestimatedat$26.3 women worldwideacrossdifferentculturesandraces.The Urinary incontinence(UI)isaproblemthataffectsadult Damaser, MD,andMargot Moore, PhD Courtenay therapies designedtoacceleratehealingandpreventSUI. patients mostlikelytobenefitfromstemcell-related maternal injuriesofchildbirthcouldenableselection or moreofthosecytokinesasreliableserummarkersfor women tolaterdevelopmentofSUI.Identificationone of maternalinjurieschildbirththatmaypredispose the increasesmaybedirectlyproportionaltoseverity increase intheserumresponsetovaginaldelivery,and The levelsofoneormorestemcellhomingcytokinesmay year ofdelivery. non-obese womenwiththeseverityofSUIwithinone the maternalcytokineresponsetodeliveryinobeseand obesity onthatresponse.Inaddition,wearecorrelating response tovaginaldeliveryandassesstheeffectsof in theserumconcentrationsofstemcellhoming We arecurrentlyconductingastudytomeasurechanges of allisshownintherightcolumn,displayedasyellow. alpha actin-stainedcellsindicatingsmoothmuscle.Thecomposite cells indicatingthelocationofnuclei.Red showssmoothmuscle Green indicates GFP-labeled stemcells.BlueindicatesDAPI-stained vaginaldistension. (middle row)andarat10daysafter vaginaldistension of stemcells(toprow),aratfourdaysafter infusion Fluorescent micrographsofacontrolratfourdaysafter ofurethraltissue. distension tofacilitateacceleratedrecovery vaginal in femaleratsselectivelyhometotheurethraafter Figure 1.Intravenouslyinjectedmesenchymalstemcells(MSCs) 12/12/11 8:03 PM 61 Center for Female Pelvic Medicine & Reconstructive Surgery 12/7/11 12:15 PM 6 6 6 6 48 48 39 39 28 11 clevelandclinic.org/glickman Percentage

Vaginal pain Vaginal Dyspareunia mesh extrusion/exposure Vaginal Urinary incontinence prolapse Recurrent Bladder mesh perforation mesh perforationRectal Ureteral perforation injury foreign body Retained fistula Vesicovaginal *A majority of patients cited more than one presenting complaint for removal of mesh. Table 1. Indications for removal of mesh 1. Indications Table of Mesh* Indication for Removal All of the patients in our series had their mesh complica- in our series had All of the patients the without transvaginally/transperineally, tions managed abdominal approach as has been requirement of an open to dem- were able series. We the norm in most reported invasive approach is safe and onstrate that this minimally of presenting symptoms. It is evident resolves the majority for placement of these mesh kits that the same route used of mesh perforations involving the can be used for excision outcomes and minimal periop- bladder, with good clinical erative morbidity. Farzeen Firoozi, MD, and Howard MD, B. Goldman, MD Firoozi, Farzeen have shown that 11 percent of wom- Epidemiologic studies undergo surgery for either urinary en in the United States organ prolapse (POP), with a reop- incontinence or pelvic Given the high recurrence and eration rate of 29 percent. repairs augmented with synthet- reoperation rate, prolapse to improve both the anatomic and ic mesh were designed after pelvic floor reconstruction. functional outcomes previously used transvaginally placed While some surgeons use of mesh for pelvic floor recon- mesh patch grafts, the been limited to abdominal sacrocol- struction had largely midurethral popexy for vaginal vault prolapse and synthetic the relative slings for stress urinary incontinence. Despite use of trans- dearth of long-term randomized studies, the of POP has vaginal prolapse mesh kits for the management become commonplace. with mesh Multiple centers have reported their experience available mesh complications after the use of commercially primarily prolapse kits. A majority of these reports include of mesh descriptions of vaginal mesh extrusion (exposure the mi- through the vaginal wall). Although they represent perforations nority of cases reported, more complex mesh the bladder, involving other pelvic structures including these case series. ureter and rectum have been described in pelvic The management of mesh perforation involving required a com- structures such as the bladder has typically had significant bined vaginal and abdominal approach that associated morbidity. complications At our institution, we have managed mesh a purely trans- stemming from the use of prolapse kits with patients vaginal/transperineal approach. Twenty-three our institution. underwent transvaginal removal of mesh at The mean age was 61 years. Median period of latency to mesh-related complication was 10 months (range one to 27 months). Indications for removal of mesh are listed 1. in Table A majority of the mesh complications were managed purely patient with rectal mesh perforation One transvaginally. One patient with was able to be managed transperineally. vaginal mesh extrusion/exposure and concomitant ureteral perforation injury was managed with a combined transvaginal and percutaneous/endoscopic approach. Two patients had persistence of symptoms postoperatively - one had urge incontinence treated successfully with anticholinergics, and a second patient with stress incontinence was treated successfully with collagen injection. Purely Transvaginal/Transperineal Management of Management Transvaginal/Transperineal Purely Complex Mesh Complications Complex 78224_CCFBCH_Text_ACG.indd 61 78224_CCFBCH_Text_ACG.indd 62 Center for Female Pelvic Medicine & Reconstructive Surgery 62 Urology &KidneyDiseaseNews Urethral SphincterActivityinRats StretchReducesPudendal External Nerve For references,pleaseemailtheeditor. also provideaprototypewithwhichtotestnewtreatments. would SUI, but pathophysiology of of the our understanding vaginal childbirth.Suchamodelwouldnotonlyimprove models toproduceamorephysiologiccorrelatehuman a measurableeffectthatcouldbecombinedwithother Although EUSEMGactivityrecoversquickly,PNSproduces able histologicormolecularchanges. activity, butwithoutacuteimpairmentinLPPormeasur- rapid, demonstrableandreversiblereductioninEUSEMG Compared withashaminjury,ourmodelofPNSproduced per beneaththenerveandpassivelystretchingit(Figure1). formed byinsinuatingaforcepsorCastroviejosurgicalcali- measured byelectromyography(EMG).Stretchwasper- rat thatproducesreversiblereductioninEUSactivity,as In arecentpilotstudy,wedevelopedmodelofPNSinthe more accuratelyreplicatehumanvaginalchildbirthinjury. including multiple physiologicmechanismsofinjurymay the recoveryofotherpelvicinjuries.Anintegratedmodel eled inanimalsandmaybethemissingelementthatslows Pudendal nervestretch(PNS),however,hasneverbeenmod- that stretchingthenerveresultsinsignificantdysfunction. studies ofotherperipheralnerveshaveshown animal and stretches significantlyduringvaginalchildbirth.Human We knowfrom3-Dmodelsthatthepudendalnerve do notrecover. SUI, theyarerecoverable,whereasmanywomenwithSUI pudendal nerve.Althoughtheinjuriesmodeledsimulate ischemic anddirectpelvicfloordamage,orcrushingofthe animal modelsofvaginalchildbirthinjuryhavefocusedon thral sphincter(EUS)andthepudendalnerve.Previous to thepelvicfloorandinnervationofexternalure- stress urinaryincontinence(SUI)andresultsininjury Vaginal childbirthinjuryisasignificant riskfactorfor Damaser,and Margot PhD Kamran B.Goldman,MD, Sajadi,MD,Howard

pre-stretch (a),andduringstretchwiththeforcepsinplace(b). bladder. Asurgicalmarkerisusedtomeasurethenerves Anterior transpubicexposure oftheurethra,pelvicfloor, and

12/7/11 12:15 PM 63 Center for Female Pelvic Medicine & Reconstructive Surgery 12/7/11 12:15 PM clevelandclinic.org/glickman

Researchers in the Glickman Urothelial Biology lab were, Urothelial Biology in the Glickman Researchers hTERT immortalized the first to develop in 2004, among along with their collaborators, urothelial cell lines and, this year related to isolation and published unique findings nontransformed urothelial cell line characterization of a normal tissue and immortalized originally explanted from the catalytic subunit of telomerase. with hTERT, has proven valuable for studies This particular cell line urothelial cell biology and of both benign and malignant material to use in testing will give researchers ample normal and disease conditions. More molecular studies of Urological & Kidney Institute re- recently, the Glickman tech- searchers have again applied these novel molecular cystitis patients niques to explanted cells from interstitial more and established two cell lines that have undergone than 100 passages in cell isolation and characterization rise to even studies. Further characterization should give from hav- more exciting and accelerated findings generated lines from both ing continuous, immortalized urothelial cell normal and interstitial cystitis conditions. email the editor. references, please For Immortalized (FNU) Immortalized (AA-Urothelial) Normal (FNU) Normal (AA-Urothelial) Light microscopy evaluation of two bladder urothelial cells lines before and afterLight microscopy evaluation of two bladder urothelial telomerase prior to molecular comparisons. transfection, revealing similar morphological features Raymond R. Rackley, MD Rackley, R. Raymond of the urothelium, the specialized Basic science studies urinary bladder, are critical for epithelial lining of the affecting the lower urinary tract, understanding conditions infections, cancer and interstitial including urinary tract understanding these conditions fully cystitis. Our ability to a lack of appropriate normal cells in has been hampered by use in basic science research labs to cell culture testing to normal and disease conditions. comparatively test between from tissue have a limited ability Normal cells explanted which limits the scalability to replicate in cell culture, without of performing multiple molecular experiments more tissue running out of cells and having to re-explant from patients or animal models. of the human telomerase reverse transcrip- Re-expression strategy for tase (hTERT) has been used as an effective various different immortalization of primary cell cultures of hTERT cell types from urological tissues. By introducing replica- into cells established in cell culture, the normal prevented with tive senescence inherent in normal cells is minimal genetic alterations and stable, nontransformed traditional phenotypes that are unavoidable with other approaches that may use viral oncogenes. Urothelial Cell Lines for Urological Basic Science Research Basic Science for Urological Cell Lines Urothelial Creating the First Telomerase-Immortalized, Nontransformed Telomerase-Immortalized, the First Creating 78224_CCFBCH_Text_ACG.indd 63 78224_CCFBCH_Text_ACG.indd 64 Center for Genitourinary Reconstruction News Disease Kidney & Urology 64 Male Transobturator Urethral Sling: Intermediate-Term Outcomes choice, many patients favor a sling over the AUS b sphincter urinary and(AUS). the artificial Whengiven a incontinenceprostatectomy urinary sling are a urethral the most commonly used procedures surgical to treat post- In those who fail to respond to conservative measures, remain of utmost importance. quality-of-life issuessurvival, incontinencesuch as urinary have adequate continence following an AUS. Bec moderatewith to severe incontinence are more likely to good outcomes following a sling procedure, whereas those mildwith to moderate incontinence tend to have relatively pump. However, experience has indicated that patients normal voiding without the need to manipulate a scrotal of its relative simplicity and the ability to experience more patients undergoing and highsurgery rates of overall Given the age of tinence following surgery. of persistentincon- urinary experiencewill some degree ing radical prostatectomy 18 percent of men undergo- advances, approximately 7 to Despite ongoing technical W. Angermeier, MD Vasavada, MD, and Kenneth Hadley M. Wood, MD, Sandip MD, Drogo Montague, MD, Hanhan Li, MD, Bradley Gill, group of patients w A telephone-based was conducted survey on our initial implantation.after of the transobturator sling immediately and years two patient-perceived and objective outcomes placementafter is beinggradually accumulated. Therefore, we investigated sling,urethral longer-term information on outcome the recent introduction of the AdVance ™ transobturator included AUS (four), p Median preoperative paddaily use was two. Prior therapies sling at a median 23 months following prostatectomy. patients Sixty-six (mean age 67) were treated the with day) and improvement (decrease to one or padstwo per day). better. Quantitative success included cure (zero pads per was definedas aPGI-I response of very much better or much ficacywas p friend, complications following surgery, and whether ef- use, whether the patient would recommend to the a surgery I), as well as questions concerning current and prior pad Global Impression of (PGI-S)Severity and Improvement (PGI- includedSurveys instruments, the Patient standardized two ratorsling urethral between May 2007 and December 2009. anchored sling (one), and four patients had undergone pelvic erceived to change over time. Subjective success ho underwent placement of a transobtu- eri-urethral collageneri-urethral (seven) and bone- Quantitative cure Mean pads/day(sd) Quantitative improvement iesnesigi ots(i-a)72(.-67 89(404.)<0.0001* 28.9(24.0-42.6) 7.2(2.2-16.7) Time sinceslinginmonths(min-max) Table 1to2(n=25) 1.Changesinefficacyovertimefromsurvey Quantitative success Subjective success *Wilcoxon signed-rank,statisticallysignificant**McNemar’ ause of ecause

post-prostatectomy incontinence, morewith ofhalf than our and valid treatment option for men mildwith to moderate The sling transobturator urethral continues to be a safe cent reduction in pad usage. fined above, butthreedid experiencegreater than 50 per- Of these, only one patient was considered a success as de- sling placement despite recommendationinitial of an AUS. For references, please email the editor. tion experience.and surgical nation of predictors of outcome, refinement of patient selec- anticipate that resultsimprove will continuedwith determi- incontinence and previous treatment history, and one would was somewhat mixed in terms of preoperative ofseverity (PGI-I). It should be noted treatmentthat initial this group to remain relatively stable based on subjective success rates in overall quantitative success, patient satisfaction appeared ing pad use in some patients. However, despite the decline in quantitative measures over time as evidenced by increas- at an average follow-up. two-year We demonstrated a decline cohort reporting both quantitative and subjective successes of our patients using more five than pad mildwith or moderate post-prostatectomy incontinence, six Although sling procedures are indicatedfor primarily men represented in Table 1. at both the mean seven-month and 29-month is intervals factor.a primary A subgroup ofanalysis 25 men interviewed and 21.4 percent would not, patients two with citing cost as vealed 39.3 percent cured and 23.2 p Telephone administered 24surveys months re- surgery after improved. 50.7 percent of patients were cured and 36.5 percent were radiotherapy. At the first follow-up six weeksafter surgery, 67.9 percent of patients would, 10.7 p time. When asked if they would refer the sling to a friend, that sling efficacyhad improved or remained stable over percent, and approximately of patientstwo-thirds reported 24 months, subjective success based on the PGI-I was 53.4 up and considering nonresponders failures or successes). At success rate 53-68 percent when adjusting for loss to follow- 11 (44.0) 19 (76.0) 13 (52.0) 1.4 (2.2) Survey 1 Survey 8 (32.0) s test,statisticallysignificant s per day requested 14 (56.0) 12 (48.0) 2.3 (3.2) Survey 2 Survey 8 (32.0) 6 (24.0) ercent improved (overall ercent replied maybe p Value 0.03** 0.01* 0.18 0.32 0.56

12/7/11 12:15 PM 65 Center for Genitourinary Reconstruction 12/12/11 8:04 PM clevelandclinic.org/glickman ent pouch reduction, continent 15% 85% Figure 1. An IVP demonstrating hydronephrosis in an exstrophy patient hydronephrosis in an exstrophy 1. An IVP demonstrating Figure who had undergone ileal conduit urinary A renal diversion in childhood. to the majority scan demonstrated that the obstructed kidney contributed of his renal function (85%) Figure 3. Retrograde urethrogram of a reconstructed urethras in a patients with 3. Retrograde Figure showing recurrent stricture (a) and a large diverticulumbladder exstrophy (b) Figure 2. An exstrophy patient with a continent urinary 2. An exstrophy pouch filled with Figure stones who presented with multiple, multi-drug resistent urinary infections and renal deterioration. He subsequently underw stoma revision,and removal of a right non-functioning kidney.

s. For For s. een the main foci mainfoci the een al health and age- and health al struction (Figure 3), con- 3), (Figure struction cerns about genital appearance and sexual function, and sexual function, and genitalappearance about cerns fertility. impaired chal- many the of glimpse small a just provide images These population. patient thisunique for opportunities and lenges at Wood Dr. email program, the about information more For [email protected]. related cancer screening status is obtained. Sometimes ad- Sometimes obtained. is status screening cancer related diagnostic imaging, specialized with highly testing ditional the assess to performed is work lab additional or procedures status. urological current patient’s plan a out map we evaluated, is Afterallthis information or he genitourinary the repair problems to patient witheach futureneed discuss and experiencing currently is she Hadley M. Wood, MD, Kenneth W. Angermeier, MD, MD, Angermeier, W. Kenneth MD, Wood, M. Hadley MD Simon, James and frequently most system genitourinary the is The tract solitary be can defects Such defects. congenital by affected (e.g., organsystems multiple involve or hypospadias) (e.g., survival adulthood, to recently, Until myelodysplasia). b have continence and preservation renal competing urological and personal needs. We combine our our combine We needs. personal and urological competing objectives health personal own patient’s the with plan medical needs. patient’s the address to plans treatment develop to reviewof detailed a typically visit involves initialpatient The surgical assessment and history and medical patient’s the about Information status. urological current her or his of sexustatus, continence function, renal patients with congenital anomalies affecting multiple organ affectingmultiple anomalies withcongenital patients withspecialty-specific closely work we systems, departments. other in specialists Medicine Transitional with born patients is group patient such one of Anexample withbladder patients adulthood, In exstrophy. bladder (Figure function renal impaired experience often exstrophy urinary a having to res- related either urinary problems 1), urethral recon or 2) (Figure ervoir of other medical comorbidities, patients with congenital congenital with patients comorbidities, medical other of problems age-related urological typical experience anomalies com- further often are that cancer) prostate and BPH as (such operations. prior and anomalies co-existing their by plicated on often is center specialty a of typical the focus While program works Urology Transitional our problems, single sometimes and complex multiple balance to withpatients of care provided by the pediatric urologic community for for community urologic pediatric the by provided care of patients. such ex- with adulthood to surviving are now patients these As ap- genital post-pubertal sexuality, of issues health, cellent and incontinence, fecal and urinary function, and pearance and health important becoming are pregnancy and fertility development and aging with Moreover, issues. life of- quality- Transitional Urology: Caring for the Urological Needs of Adults and Adults of Needs Urological the for Caring Urology: Transitional Adolescents Born with Complex Congenital Anomalies Congenital Complex with Born Adolescents 78224_CCFBCH_Text_ACG.indd 65 82_CBHTx_C.nd66 78224_CCFBCH_Text_ACG.indd Center for Kidney/Pancreas Transplantation News Disease Kidney & Urology 66 Immunosuppression to Overcome Nephrotoxicity The ORION Study: Optimizing Renal Transplant G cent) andpatient(Group1:97.3percent94.4percent; cent and89.9percent;Group3:96.2percent95.4per- (Group 1:92.8percentand88.5;Group2:90.6per- line demographics.Atoneandtwoyears,respectively,graft SRL+MMF; n=139inTAC+MMF groups;withsimilarbase- tion totreat):n=152inSRL+TAC-Elimination; n=152in 443 patientswereincludedinthestudyanalysis(inten- son, GroupTwowassponsor-terminated at322meandays. respectively (Group2vs.3,p<0.001), Figure1.For thisrea- 32.8 percent;andGroup3:8.2percent and12.3percent, 15.2 percentand17.4percent;Group 2:31.3percentand One- andtwo-yearacuterejectionincidencewasGroup1: and 97percent)survivalratesweresimilar,p=NS. e porate atwo-yearstudywindowwiththeprimaryefficacy daclizumab. Thestudyprotocolwasdesignedtoincor- 3). Allpatientsreceivedcorticosteroidsandinductionwith tion (Group1),SRL+MMF2)andTAC+MMF (Group (1:1:1) tooneofthreetreatmentgroups:SRL+TAC-Elimina- renal allograftrecipients(n=469)wererandomlyassigned not receiveatleastonedoseoftheassignedtherapy. patients enrolledbutnottransplanted),sevendid Of the450patientswhounderwenttransplantation(19 munosuppressive sideeffects. and severityofbiopsy-confirmedacuterejection,im- ary endpointsincludedpatientandgraftsurvival,incidence Re was thePrincipalInvestigatorofstudy,andGUKI Journal ofTransplantation.StuartFlechner,MD,FACS, results ofwhichwererecentlypublishedintheAmerican ters inCanada,UnitedStates,EuropeandAustralia,the This studyinvolved469patientsfrom65transplantcen- and livedonortransplantation. a years andscheduledtoreceiveaprimaryorsecondaryrenal May 2006.Patients eligibleforenrollmentwereage>18 Subjects wereenrolledinthestudyfromMarch2005to nolate mofetil(MMF). (SRL) basedregimenswithtacrolimus(TAC) andmycophe- comparative, multinationaltrialcomparingtwosirolimus- patients inthetrial.Thiswasanopen-label,randomized, a sought toexaminetheroleofcalcineurininhibitorsparing tion. Thetrial,sponsoredbyWyethInc.,nowPfizerInc, several immunosuppressiveregimensinrenaltransplanta- a largeinternational,multicenterPhaseIVtrialevaluating & KidneyInstitute(GUKI)hasbeenamajorcontributorto The KidneyTransplantProgramintheGlickmanUrological Flechner,Stuart MD,FACS ndpoint ofGFR(Nankivell)at12and24months.Second- llograft fromalivingdonorordeceaseddonor. Denovo nd avoidanceonrenalfunctionafterbothdeceaseddonor roup 2:95.2percentand94.5percent;Group3:97 nal TransplantProgramenrolledthelargestnumberof Thus, C intention-to-treat population;however,thosethatremained were notassociatedwithimprovedrenalfunctioninan due toproblemswithdosing,thesirolimus-basedregimens and 3vs.2,17percent6percent;p=0.004).Primarily plantation wasgreaterintacrolimusrecipients(Groups1 One-year posthocanalysisofnew-onsetdiabetestrans- w mus inmanyGroup2patients.InGroups1and2,delayed were similar,likelyreflectingthereintroductionoftacroli- The meanone-andtwo-yearmodifiedintent-to-treatGFRs peutic dosingofsirolimus(Figure2). group mayhavebeenduetoalargenumberwithsubthera- The higherratesofacuterejectionintheCNIavoidance For references,pleaseemailtheeditor. two years. <10ng/ml or1level <10ngmlwithinaweekofBCAR months 1,3,6Sub-therapeuticdefined as2ormoreSRLC0levels Therapeutic definedasSRLC0levels 10-15ng/mlatweek1and Biopsy-Confirmed Acute Rejection Biopsy-Confirmed Frequency ofLowSRLBloodLevelsinGroupIIPatients: Acute Rejection bySeverity(on-therapy): NI freehad8-10cc/minbetterestimatedGFRatoneand ound healingandhyperlipidemiaweremorefrequent. R+A-lm7%(52)2%(/0 0 25%(5/20) 75%(15/20) SRL+TAC-Elim R+M 67 3/3 33 1/3 0 23.3%(10/43) 76.7%(33/43) SRL+MMF A+M 38 71)4.%(/3 0 46.2%(6/13) 53.8%(7/13) TAC+MMF Group Grade I rd IGradeIII Grade II 21/180 PM 8:06 12/12/11 67 Center for Kidney/Pancreas Transplantation 12/12/11 8:07 PM

clevelandclinic.org/glickman r references, please email the editor. e delivered could be tailored to those at high risk in order e delivered could be tailored nti-thymocyte globulin indeed eliminated donor-reactive nti-thymocyte globulin indeed eliminated ear post-transplantation. The induction immunosuppres- ear post-transplantation. circulating T-cells in those in whom these cells were pres- circulating T-cells in those in whom these have done just ent, a significant number of patients might and less potent as well if they had received the less expensive patients per- medication. On the other hand, some of the ceived to be at low risk could have benefited from receiving donor-reactive detected we as globulin anti-thymocyte rabbit sive therapy was delivered at the discretion of the treating sive therapy was delivered at the discretion on the “perceived physician. The therapy was selected based of T-cell immunological risk” rather than a direct measure commercially donor antigen reactivity (as this test is not available). anti- Those believed to be at high risk received rabbit antibody. thymocyte globulin, a potent T-cell depleting Therefore, it is evident that early identification of patients identification of patients it is evident that early Therefore, to (lymphocytes reactive allo reactive T-cells with circulating could be helpful for individualization transplant antigens) the immunosuppressive therapy to of care. In this regard, b The advantage of this drug is that it is a strong immunosup- The advantage of this drug is that it is a strong the disadvan- pressive drug and rejection is less likely, but eventually tage is that more infections or cancers could Those perceived to be at low risk receive an anti-IL-2 occur. receptor blocker, a less potent immunosuppressive drug and less costly. for the The results of the study were very interesting with rabbit following reason: While induction therapy a T-cells prior to transplantation. to prior T-cells If these results are confirmed by ongoing NIH-sponsored studies, this information is important because future care of patients should be individualized according to measured rather than estimated immunological risk in order to maxi- mize desired effects of the treatment, minimize adverse events and practice cost-effective medicine. Fo to avoid rejection, or be avoided in those who do not need to avoid rejection, or it so as to avoid side effects. has recently published an observa- In this respect, our group Journal of Transplantation in tional study in the American transplant recipients at the time which we studied 31 kidney for at least a followed each patient of transplantation. We y ith previous transplants or blood transfusions or through ith previous transplants or blood transfusions he higher the number of preformed allo antibodies, the emographic and clinical information. nd thus personalization of care is hard to provide. There nd thus personalization of care is hard to provide. nd CD8+ T-cells, the key players in organ rejection. How- ndividualization of care is important. ndividualization of care mmunological risk by novel laboratory techniques might mmunological risk by novel laboratory techniques Even when organs become available for a particular patient, patient, particular a for available become organs when Even immunological risk stratification recurrent approaches to on the physician’s perception of risk main limited, relying to be used. to determine the immunosuppression protocols physician In this respect, patients perceived by the treating are truly at high to be at low risk for organ rejection but who i pregnancy. Similarly, the immune system could build up pregnancy. infections or immunity to transplant antigens through to pa- other medical events (by cross-reactivity) common tients on dialysis treatment. As a result, all patients on the waiting list for a kidney transplant are routinely tested for such alloantibodies (humeral arm of the immune system). T more difficult it is to find a matching organ. Analogously, T-cells reactive to transplant antigens (cellular arm of the immune system) can also develop while awaiting transplantation and could have a negative impact in the post-transplant period. Importantly, the induction therapy to be delivered to the patient is directed to CD4+ a receive therapies that are suboptimal. On the other hand, receive therapies that are suboptimal. On be at high risk truly low-risk patients who are perceived to and im- might unnecessarily be exposed to the undesired portant side effects related to these drugs. cannot This “immune” risk against transplant antigens testing, currently be fully predicted by routine laboratory a Emilio Poggio, MD Emilio Poggio, is the best treatment for subjects Kidney transplantation renal disease, providing patients suffering from end-stage quality of life than other forms of with better quantity and organ shortage con- However, renal replacement therapy. and, therefore, prolonging tinues to be a major limitation available transplanted kidneys by the half-life of currently i is some evidence that the strength of the immunity against is some evidence that the strength of the immunity begins even human organ transplant antigens in general especially when before the actual time of transplantation, during the patients are awaiting kidney transplantation example, antibodies against com- dialysis treatment. For in patients mon transplant antigens can be generated w ever, the challenge that transplant physicians face is that no laboratory techniques are currently available to determine if a particular patient does or does not have T-cells that are reactive to the transplant antigens present in the donor, and thus determination of future immunosuppressive therapy is chosen based on “perceived risk” using simply d Toward Identifying Risk and Individualization Individualization and Risk Identifying Toward Recipients Transplant Kidney for Care of 78224_CCFBCH_Text_ACG.indd 67 Frequency of Low SRL Blood Levels in Group II Patients: Frequency 82_CBHTx_C.nd68 78224_CCFBCH_Text_ACG.indd Center for Kidney/Pancreas Transplantation News Disease Kidney & Urology 68 Participation in Research by Kidney Transplant Recipients of kidneytransplantation. among patientswhodoparticipateinresearchthefield little research addressing participation rates and differences difference inpatientoutcomes.To date,therehasbeen reflect accesstocareandpotentiallyexplainasourceof differences may affect the external validity of study findings, which theyareconsentedtoparticipateinresearch.These nomic status,educationalattainmentandthemodalitiesby ticipants basedondemographiccharacteristics,socioeco- who participateinresearchprotocolsdifferfromnonpar- In manyhealthcarecontexts,evidenceexiststhatpatients Jesse D.Schold,PhD (20-29 kg/m Recipient BMI Transplant number(primary) Primary diagnosis(GN) Primary PRA %(0) insurance(Medicare) Recipient primary Recipient race(Caucasian) Recipient education(graduate school) Parameter (referencegroup) Table inresearch 1.Multivariablelogisticmodelforlikelihoodtoparticipate Recipient age(18-49) Recipient gender(male) 2 )

t tional attainment,insurance,genderandage,donor Factors associatedwithPRPincludedrecipients’educa- 8.2 percentforkidneyand2.8SPKrecipients. The nationalproportionofparticipationatoneyearwas among centersandmedications. pants, andassessvariabilityofparticipationinresearch compare outcomesbetweenparticipantsandnonpartici- p munosuppressive medicationsisreportedatfollow-up.Our United Statesforwhomparticipationinresearchim- taneous pancreas/kidney(SPK)transplantrecipientsinthe Recipients (SRTR)from2000to2008forkidneyandsimul- We evaluatedthenationalScientific Registry forTransplant ransplant number,income,andcentervolume(Table 1). rimary aimsweretoevaluateparticipantcharacteristics, Other (<25yearsold) Less thanhighschool African American H High school 30+ kg/m <20 kg/m ypertension Medicaid Diabetes Hispanic 11-29% Missing Missing missing College Female Repeat 1-10% Private 30+% 50-64 Other Other O Asian Level 65+ <18 PKD ther 2 2 .70.42-0.51 0.47 .40.89-1.01 0.94 .61.08-1.26 1.16 .10.93-1.10 1.01 .20.87-0.99 0.71-1.04 0.92 0.86 .20.91-1.14 1.02 .50.70-1.04 0.73-0.85 0.85 0.93-1.08 0.79 1.00 .70.90-1.06 0.97 .70.82-0.92 0.87 .50.89-1.01 0.95 .70.84-1.12 0.89-1.10 0.97 0.99-1.21 0.99 0.95-1.16 1.10 0.73-0.98 1.05 0.84 1.30 1.04 1.21 .80.82-0.95 0.94-1.06 0.88 1.00 .10.93-1.10 1.01-1.12 1.01 0.86-1.02 1.06 0.94 .10.87-0.96 0.91 .60.39-0.55 0.46 O 95%CI AOR 1.15-1.51 0.94-1.16 1.15-1.28 21/191 PM 9:19 12/12/11 69 Center for Kidney/Pancreas Transplantation 12/7/11 12:15 PM clevelandclinic.org/glickman 1.170.97 1.10-1.23 0.92-1.03 0.90 0.82-0.99 0.82 0.78-0.86 0.770.96 0.70-0.86 0.88-1.03 0.99 0.95-1.04 0.95 0.87-1.02 1.16 1.01-1.34 0.89 0.71-1.11 1.17 1.08-1.27 1.27 1.17-1.38 1.261.23 1.17-1.39 1.03-1.48 1.04 0.96-1.13 0.971.01 0.89-1.07 0.95 0.92-1.11 0.79-1.14 1.03 0.99-1.08 1.02 1.01-1.03 <18 60+ Asian Other 40-59 Female Missing Missing per year 60,000+ Hispanic $ Preemptive >120 miles 30-60 miles ≥ 24 months 61-120 miles Deceased donor African-American $35,000-44,999 $45,000-59,999 Table 1. Continued Table months) dialysis time (<24 Pre-transplant Donor type (living donor) Donor age (18-39) Donor race Median income (<$35,000) Distance to center (<30 miles) Donor gender (Male) Year of transplant Year Abbreviations: GN = glomerulonephritis; PKD = polycystic kidney disease; PRA = panel reactive antibody; Abbreviations: GN = glomerulonephritis; PKD = polycystic kidney disease; PRA = panel reactive DGF = delayed graft of model = 0.62. function. Concordance index articipants and nonparticipants in research in the kidney articipants and nonparticipants mong participants is needed. Graft and patient survival were significantly higher among higher among survival were significantly Graft and patient a 14 percent adjusted in research including participants nonparticipants as compared with hazard for death among (95 percent CI, 1.05-1.22)) for soli- participants (AHR=1.14 markedly rates varied Participation tary kidney recipients. 0-58 percent) and by immunosup- among centers (range pressant medications. systematic differences between In conclusion, there are p transplant population that may affect the external validity transplant population Superior outcomes among partici- of research findings. participation in research itself pants may suggest that evaluating the affords certain benefits. Future research rates, impact mechanisms for differential participation survival of informed consent processes and improved a 78224_CCFBCH_Text_ACG.indd 69 78224_CCFBCH_Text_ACG.indd 70 Center for Kidney/Pancreas Transplantation News Disease Kidney & Urology 70 After Lung Transplantation Short- and Long-Term Outcomes of Acute Kidney Injury t most severeformsofAKI,i.e.,dialysis-requiring,post-lung numbers oflungtransplantrecipientsindicatedonlythe Preliminary reportsfromcenterswithrelativelysmall acute kidneyinjury(AKI)inthisparticularpopulation. of lungtransplantation,relativelylittleisknownabout Despite extensivedataonsuchlong-termrenalsequelae enough tolivemanyyearswiththeirallograft. of CKDwas5.8percent,12.8percent and24.5percent after transplantation.Atoneyear,thecumulativeincidence and 115[17percent]AKINII-III)eventinthefirsttwoweeks who hadatleastoneAKI(309patients,or47percentAKINI We identified 424patients(65percentofthestudygroup) W long-term outcomes. baseline ofaslittle0.3mg/dL,predictsworseshort-and contemporary definitions,e.g.,ariseincreatininefrom even mildandself-limitedAKIeventsdefinedbymore of largeregistriesnontransplantpatientsdemonstrate consequences. However,emergingdatafromanalyses 1 657 patientswhounderwentlungtransplantationbetween and CKD.To dothis,weretrospectivelyevaluateddataon ma todeterminetheeffectofalldegreesAKIonmortality pattern ofAKIusingsuchupdatedclassificationsche- are inauniqueandadvantageouspositiontostudythe annually thananyothercenterintheUnitedStates,we p with improvedoverallsurvival.However,aslungtransplant poor results,thecurrentexperienceismorepromising to rise.Althoughtheearlyexperienceyieldedextremely number oflungtransplantsperformedannuallycontinues lung diseasewasperformedin1963.Sincethattime,the The firstsuccessfullungtransplantationforend-stage Brian Stephany, Wehbe, MD,andEdgard MD t weeks withnorecoveryonfollow-uportheneedforkidney the onsetofESRDasdefinedbyneedforRRTeight CKD asdefinedbyaneGFR≤29ml/min/1.73m2,and/or (AKIN) classification(Table 1);cumulativeincidenceof to creatininecriteriafromtheAcuteKidneyInjuryNetwork AKI asdefinedandcategorizedintothreestagesaccording d persists inmostandoftenprogressestoend-stagerenal in thefirstsixmonthsaftertransplantation,afindingthat that mostlungtransplantrecipientslosekidneyfunction sive chronickidneydisease(CKD).Priordatahaveshown complications, oneofthemostsignificantbeingprogres- ransplant andlong-termmortality. ransplant predictedadverselong-termmorbidandmortal 997 and2009.Outcomesanalyzedweretheincidenceof atients survivelonger,theyaremorepronetomedical isease (ESRD)inmanylong-termsurvivorsfortunate ith ClevelandClinicperformingmorelungtransplants short- andlong-termoutcomes. in decreasingthechanceofAKIandtranslateintobetter maneuvers inthoseathighestriskwouldproveeffective as “atrisk”patients.Itisunknownwhetherperioperative p can bedrawnregardingcausalityfromthisstudy,clearly morbidity andlong-termmortality. Thoughnoconclusions creatinine by0.3mg/dl)predictssignificantpostoperative plantation. EventhemildestformofAKI(i.e.,increase In conclusion,AKIoccurscommonlyafterlungtrans- p <0.001)forAKINIandAKINII-III,respectively. p tes, andhypertension,thehazardratiofordeathwas1.7(95 age, gender,race,typeandcauseoflungtransplant,diabe- and AKINII-IIIgroups,respectively(Figure2).Adjustingfor percent ,82and66intheno-AKI,AKINI 277 (42percent)haddied.One-yearpatientsurvivalwas91 (Figure 1).Afteramedianfollow-upof2.2years,total in theno-AKI,AKINIandAKINII-IIIgroups,respectively atients whosufferAKIearlyaftertransplantcanbeviewed ercent CI:1.2-2.2p=0.0002)and2.9(95percent1.7-3.7 3 2 Serumcreatininecriteria 1 Stages Networkschema according totheAcuteKidneyInjury Table 1.Classification/stagingsystemofacutekidneyinjury at least0.5mg/dL)orneedforRRT. o from baseline(orserumcreatinineofmorethan Increase inserumcreatininetomorethan3-fold 3-fold frombaseline Increase inserumcreatininetomorethan2- equal to1.5-2-foldfrombaseline equal to0.3mg/dLorincreasemorethan Increase inserumcreatinineofmorethanor r equalto4.0mg/dLwithanacuteincreaseof 12/7/11 12:15 PM 71 Center for Kidney/Pancreas Transplantation 12/12/11 8:28 PM clevelandclinic.org/glickman r additional information on the procedure, contact ccess to the allograft pancreas to perform such procedures he most common source of bowel complications following he most common source of bowel complications Figure 2. SurvivalFigure curves following lung transplants per different stages of acute kidney injury (AKINI vs. no AKI, p=0.001; p=0.04) AKINII-III vs. no AKI, p<0.001; AKINII-III vs. AKINI, Dr. Rabets at [email protected]. Rabets Dr. atic allograft is via a graft duodenum to recipient jejunum atic allograft is via a graft duodenum to recipient This is anastamosis (duodenojejunostomy) or connection. t pancreas transplantation. In an effort to minimize such complications, we now routinely perform a graft duodenum to native recipient duodenum anastamosis (duodenoduodenostomy). This procedure has the advantage of minimizing the potential for bowel complications such as bowel obstruction. In addition, the procedure also gives the surgeon endoscopic a as an endoscopic biopsy. Our experience with this novel technique has been very favorable without any additional incidence of complica- feel that this technique has many advantages over tions. We the standard technique and may promote more durable long-term survival of the pancreatic allograft. Fo he endocrine function is insulin production which is lants since 2008. The program has also had a 100 percent secreted into the venous circulation for blood-sugar control. The pancreas also secretes digestive enzymes (exocrine function) through a duct that traverses the duodenum. The standard method of exocrine drainage of the pancre- John Rabets, MD Rabets, John The program in kidney and pancreas transplantation and within the Glickman Urological & Kidney Institute Division of Transplantation continues to be among the 10 largest and busiest programs in the nation. According to Recipients (SRTR), Registry for Transplant the Scientific the program has boasted a more than 95 percent one-year patient survival for combined kidney and pancreas trans- p one-year patient survival for pancreas transplants alone and pancreas after kidney transplants during this period. been a key to our continued suc- innovation has Technical have recently reported our experience with a novel cess. We technique for enteric drainage of the pancreatic allograft. The pancreas has both endocrine and exocrine functions. T Figure 1. Cumulative incidence of chronic kidney disease stratified 1. Cumulative incidence of Figure per acute kidney injury stages (AKINII-III vs. no AKI, p<0.001; .AKINI, p=0.07) AKINI vs. no AKI, p<0.001; AKINII-III vs Kidney and Pancreas Outcomes and Innovations and Outcomes Pancreas and Kidney 78224_CCFBCH_Text_ACG.indd 71 82_CBHTx_C.nd72 78224_CCFBCH_Text_ACG.indd Center for Male Infertility News Disease Kidney & Urology 72 Sites Seeking Fertility Preservation Services: An Exciting Development NextGen a overnight transportationthatcouldtakeupto24hours well asthepropercoolingcomponentsnecessaryduring We standardizedthetransportmediausedinkitas to theWorld HealthOrganization(WHO)guidelines. viability onthebasisofnormalsemenanalysisaccording to overnightshipmentandanalyzedformotility,count 4 was 26.97million±22.73.ThepercentrecoveryofTMS (TMS) was59.46million±42.76,andpost-shipmentTMS shipping (24h).Averagepre-shipmenttotalmotilesperm establish abaselineonwhichtocomparetheovernight samples wereanalyzedbeforetreatment(0hour)to and establishanoptimizedcoolingenvironment.Semen were comparedtodeterminethesustainabilityofmedia w kit constructions.Oncetheappropriatecomponents to optimizetransportmedia,temperaturesandmostideal Twenty-two samplesweresubjectedtopreliminarytesting personnel goingonlong-termdeployment. a desiretoensurepotentialfuturefertilityand4)military to cryopreserveinadvanceoftheirvasectomy,3)menwith n sometimes travelgreatdistances(fromothercitiesor ation byassistedreproductivetechniques.Thesepatients adequate numbersofspermthatcanbeusedforprocre- before thestartofcancertreatment,inordertohave to bankmultiplespecimensinashortperiodoftime, in azoospermia.Thesepatientsaregenerallyinstructed l Cancer therapiescanbesignificantlygonadotoxic,causing and diagnosedwithcancerbutdesiretostartafamily. traumatic formenwhoarestillintheirreproductiveyears a semensampleinclinicalsetting.Thisisevenmore situation madeparticularlydifficultbytheneedtoproduce Infertility isastressfulexperienceformanycouples, PhDandEdmundSabanegh,MD Ashok Agarwal, s particular valuefor1)menwithcancerorunderlying cryopreservation atourspermbank.Thissystemisof transport cycleandtoretainadequateviabilityprior semen specimenstoremainviablethroughashort We setouttoidentifyanddevelopasystemthatallows from workandincursignificanttravelexpenses. showed adecreaseofapproximately50percentduringin ong-term deteriorationinsemenqualitythatoftenresults ubfertility, 2)pre-vasectomypatientswhomaywant nd mimicatemperatureof37degreesCelcius.Results 1.28 percent±19.46percent.Spermmotilityandviability eighboring states)tofindaspermbank,taketimeoff ere formalized,nineadditionalsamplesweresubjected SM Home Sperm Banking Kit for Men From Geographically Remote program byvisitingclevelandclinic.org/nextgen. i consistent withthepercentagechangeinmotilityseen vitro incubationviaovernightshipment.Thisdecreasewas in transportmediatheNextGen the NextGen ship semensamplesforsubsequentbanking.Furthermore, Cancer andinfertilepatientswholiveintheU.S. caneasily future fertility. preserves spermmotilityandviabilityforsecuring e of theirhometocollectthesemensampleandmakethis More informationcanbeobtainedabouttheNextGen n samplescollectedonsite.Overnightshipmentofsperm xperience convenientandlessstressful. from any part of the United States. method for men to ship their samples to Cleveland Clinic Results from our pilot study indicate that the NextGen Key Point: NextGen prevailing temperature conditions. Results show that the samples shipped from different parts of the country under is successful in maintaining sperm motility and viability in TM TM kit provides a safe, reliable and convenient bankingkitallowsthepatientsprivacy SM HomeBankingKit TM kit SM

21/183 PM 8:36 12/12/11 73 Center for Pediatric Urology 12/12/11 8:36 PM clevelandclinic.org/glickman

Four patients (20 percent) turned off the device and have the device and have (20 percent) turned off patients Four childbirth, psychologic a variety of reasons: kept it off for One patient (5 percent) continued reasons and MRI testing. required the use of anti-choliner- to use the device but also (30 percent) were lost to follow-up, gic drugs. Six patients their home state and were seeing as half had returned to purpose of the follow-up care. For their local urologist for were counted as failures. Five this analysis, these patients underwent lead revisions for fractured patients (25 percent) three revisions. Two patients leads; one patient underwent device removal for infection and (10 percent) underwent for lack of efficacy. two patients (10 percent) a viable option for In conclusion, sacral neuromodulation is results show children who have failed other therapies. Our therapy have that our group of children treated with this follow-up, only a 30 percent success rate at medium-term The center. despite referral to a high-volume community children as com- rates of revision and removal are higher in to be carefully pared with our adults, and this therapy needs parent. considered with education of the patient and

2 is approved in ®

Center for Continence Care,Center for Continence 2 2 , Jodi S. Michaels MD, , Jodi S. Michaels 1 ) therapy. ) therapy. ® Cleveland Clinic Florida;

and Steven W. Siegel MD Siegel W. and Steven the United States for use in adults and has been used in the United States for In this review, we report our children in limited studies. who have failed intensive medical experience in children behavioral therapies for a treatments with combined voiding syndromes and variety of severe dysfunctional InterStim placement. subsequently underwent old presented A total of 20 patients between 8 and 20 years and were to us with symptoms of dysfunctional voiding, patients had treated with sacral neuromodulation. Ten incon- idiopathic refractory urinary urgency-frequency/urge two with tinence, four presented with Hinman’s Syndrome, syndrome, three with encephalopathies and one Fowler’s for a mean with sacral agenesis. The patients were followed of 22 months after device placement. follow-up, six Of the 20 patients at average of 22 months with urinary (30 percent) patients report improvement improve- incontinence (four have greater than 75 percent improvement). ment and two have greater than 50 percent have their device Two patients (10 percent) have gone on to tibial removed and are currently undergoing percutaneous fracture and the nerve stimulation; one after the third lead pulse genera- other for infection at the site of the internal patient (5 percent) failed the InterStim after im- One tor. plantation and went onto onabotulinumtoxinA (Botox Sneha S. Vaish MD Sneha S. Vaish 1 Metropolitan Minn. Urologic Specialists, St. Paul, with InterStim Sacral neuromodulation Five-Year Experience With Sacral Neuromodulation in Neuromodulation Sacral With Experience Five-Year 20 Children at a High-Volume Community Referral Center Referral Community at a High-Volume 20 Children 78224_CCFBCH_Text_ACG.indd 73 82_CBHTx_C.nd74 78224_CCFBCH_Text_ACG.indd Center for Renal Diseases News Disease Kidney & Urology 74 i these cellularandmoleculareventswillprovidesignificant monocyte-adhesive HAmatrix(24-48h).Understanding clin D3-mediatedformationoftheabnormalextracellular that initiatesanERstress/autophagicresponseand3)cy- 2) intracellularsynthesisandaccumulationofHA(8-24h) ways activatedinRMCsdividinghyperglycemicglucose, through synthesisofHA,averylarge,linear may betolowerglucoselevelsbyaneffectivemechanism A primaryresponseofcellsortissuestohyperglycemia to hyperglycemiathatinitiatetheprogressionofDN. d within oneweekaftertheonsetofdiabetesinSTZ-treated of DN),andhyaluronan(HA)matrixformationtakeplace proliferation andactivation,TGF-ß synthesis(ahallmark Previous studieshaveshownthatglomerularmesangialcell progression stage. may helptodevelopstrategiespreventDNduringthe extracellular HA(red). vesicles(right)and transport demonstrate ER/golgilocalization(left), transfected withGFP-Has3 (green)andstained for HA(red).They and extrude HA.Theconfocal micrographsshowlivecellsthatwere the ERtoplasmamembranewhere itisactivatedtosynthesize ofhyaluronansynthasefrom Figure 1.Modelfornormaltransport c leading toirreversiblerenalfailure.Understandingthe sion stagewithadvancedstructuralandfunctionalchanges structural andfunctionalchangessecond,theprogres- intotwostages:first,thegenesisstagewithearlycellular, In general,diabeticnephropathy(DN)canbedivided Aimin Wang, PhD Stress/Autophagy in Diabetic Nephropathy Intracellular Synthesis of Hyaluronan Induces ER a adhesive HAmatrixbyratmesangialcells(RMCs)invivo process thatleadstotherapidformationofamonocyte- Our studieshaveprovidednovelevidenceforamultiphase matrix synthesis. more TGF-ß thatacceleratesmesangialcellhypertrophyand for subsequentmesangialexpansionandtobeasourceof monocytes/macrophages thatarethoughttoberesponsible nsights intothemechanismscontrollingcellularresponses ellular andmolecularmechanismsinthegenesisstage nd invitro.Thisprocessrequires1)PKC signalingpath- iabetic rats.Theseeventscoincidewithinfiltrationof t re-oxidized toNADPyieldATP. Itisalsonowapparent oxidation ofUDP-glucosetoUDP-glcUA, whichcanbe sors isrecoveredbytheproductionofNADPHfrom the metaboliccostofsynthesizingUDP-sugarprecur- minimal. Itrequiresasingleenzyme(Fig.1),andsomeof The energycostforsynthesisofadisaccharideHAis ( units ofN-acetylglucosamine(glcNAc)andglucuronicacid glycosaminoglycan composedofrepeatingdisaccharide For references,pleaseemailtheeditor. mechanisms. h will haveamajorimpactonunderstandingtheroleof in thegenesisstageofDN.Understandingthesepathways and determiningitsrelevanceinvivoasthedefiningevents studies arehighlyfocusedontestingthismodelinvitro unknown. Therefore,theoverallobjectivesofourcurrent s perglycemia isoneofthemajorinducersforanautophagic transport toaggresomesthatcontainproteasomes.Hy- an attemptbythecelltodisposeofunfoldedproteins Autophagy isacellresponsethatinvolvesERstress,and mechanism (Fig.1). (Fig. 2),whichisindependentofthenormalcellsurface inside thecellinearlyproliferatingphase,(8-16h) middle. and nuclei(blue).AnenlargedEMofanaggresomeisshowninthe permeabilized cell(right)stainedforHA(green),cyclinD3(red) andanon- images ontherightshowpermeabilizedcells(left) vesicles.The intracellular HAinER/golgiregionandtransport t Figure 2.ModelforintracellularactivationofHAsynthasesincells hat divide in hyperglycemic glucose. The images on the left show hat divideinhyperglycemicglucose.Theimagesontheleft glcUA) withalternatingb-1,4andb-1,3glycosidicbonds. hat RMCsdividinginhyperglycemiainitiateHAsynthesis tress response,andthemechanism(s)underlyingthiswas yperglycemia indiabeticpathologiesandautophagic 21/184 PM 8:42 12/12/11 75 Center for Renal Diseases 12/12/11 8:47 PM clevelandclinic.org/glickman o the primary cilia. Instead it is present in cytoplasmic o the primary cilia. Instead BicC1) and PKD. As in other mouse models of PKD, BicC1 BicC1) and PKD. As in Bicaudal-C. Interestingly, mouse mutants of BicC1 develop mutants of BicC1 develop Interestingly, mouse Bicaudal-C. of PKD. This prompted reminiscent kidney abnormalities connection between Bicaudal-C us to characterize the ( mutant mice form cysts along the entire length of mutant mice form cysts These epithelial malformations the nephron (Figure 1). proliferation. Instead, BicC1 are not caused by increased of polycystin-2, one of the genes regulates the expression Interestingly, in contrast to the mutated in human ADPKD. BicC1 protein was not localized majority of cyst protein, t foci that regulate mRNA stability and translation. Indeed, foci that regulate mRNA acted as a post- molecular analyses demonstrate that BicC1 antagonized the transcriptional regulator of polycystin-2. It family on the repressive activity of the miR-17 microRNA 3UTR of polycystin-2 mRNA. phenotype kidney the that postulate we data, these on Based in BicC1 mutant mice is caused by dysregulation of a mi- in BicC1 mutant mice is caused by dysregulation It demon- croRNA-based translational control mechanism. regula- strates - for the first time - that post-transcriptional structures and tion is important in maintaining epithelial formation. that the disruption thereof can result in disease email the editor. references, please For stnatal day1kidneysfromBicc1 NA-binding molecule first identified in Drosophila as a NA-binding molecule first identified in olycystic kidney disease (ADPKD). olycystic kidney disease ics has been solely on targeting the massive cyst expansion ics has been solely on targeting the massive ng PKD. With its fast development (a functional proneph- ng PKD. With its fast development (a functional Oliver Wessely, PhD Oliver Wessely, cause of Kidney Disease (PKD) is the leading Polycystic in the United States. It is character- end-stage renal failure epithelial-lined, fluid-filled cysts ized by the presence of in enlarged bilateral kidneys. PKD in the nephron resulting two forms: autosomal recessive poly- is mainly inherited in (ARPKD) and autosomal dominant cystic kidney disease p ric kidney is formed by two days) and ease of molecular ric kidney is formed by two days) and ease to the study manipulations, it is an ideal companion system advantages of PKD in humans or mice. Using the distinct and of both organisms greatly facilitates the formulation experimental testing of new hypotheses. (BicC1), a Our PKD research is centered on Bicaudal-C R protein regulating anterior-posterior development. We We protein regulating anterior-posterior development. Xenopus and mouse homologues of have identified the seen in PKD patients, but not disease initiation. uses a two-model organism ap- laboratory The Wessely of mouse and proach imploring the metanephric kidney laevis. While mice have the pronephric kidney of Xenopus the been successfully used to study PKD, we established as a valuable alternative amphibian pronephros of Xenopus underly- to explore the molecular and cellular mechanisms i The genes mutated in humans, Polycystin-1, Polycystin-2 Polycystin-2 humans, Polycystin-1, The genes mutated in but the have been identified, and Polyductin/Fibrocystin, cyst formation is only starting to actual mechanism of and kidney emerge. This is reflected by the fact that dialysis options for transplantation are still the primary treatment therapeu- PKD. Moreover, the primary focus in developing t Figure 1. Polycystic Kidney Phenotype in Bicaudal-C Mutant Mice. Po 1. Polycystic Figure heterozygous (A) and homozygous mutant (B) mice were stained with Lotus Tetragonolobus Lectin (green) heterozygous (A) and homozygous mutant (B) mice were stained with Lotus Tetragonolobus tubules. (blue) to visualize the renal cysts present in the proximal counterstained with DAPI Polycystic Kidney Disease and MicroRNAs: MicroRNAs: and Disease Kidney Polycystic Examined Mechanism Formation Cyst 78224_CCFBCH_Text_ACG.indd 75 76 Urology & Kidney Disease News

Author Index

Agarwal, Ashok ...... 6,72 Angermeier, Kenneth ...... 64,65 Urology & Kidney Disease News Bauer, Seth ...... 58 Vol. 21 / Winter 2012 Berglund, Ryan ...... 41 Bravo, Emmanuel ...... 52 Urology & Kidney Disease News is a publication of the Cleveland Clinic Glickman Urological & Kidney Institute. Campbell, Steven ...... 8,36 Chueh, Shih-Jeff ...... 32 Urology & Kidney Disease News is written for physicians Damaser, Margot ...... 62 and should be relied upon for medical education pur- Fissell, William ...... 58 poses only. It does not provide a complete overview of the topics covered and should not replace the independent Flechner, Stuart ...... 66 judgment of a physician about the appropriateness or Goldfarb, David ...... 8,26 risks of a procedure for a given patient. Goldman, Howard ...... 45,61,62 Haber, Georges-Pascal ...... 10,17,22,24,25,33 Eric A. Klein, MD Chairman Jones, J. Stephen ...... 32,35,42,47 Glickman Urological & Kidney Institute Kaouk, Jihad ...... 10,12,14,17,18,20,22,25,26,28,30 Kattan, Michael ...... 40 J. Stephen Jones, MD, FACS Klein, Eric ...... 44 Chairman, Department of Regional Urology Glickman Urological & Kidney Institute Krebs, Tracy ...... 40 Medical Editor Levy, David ...... 46 Lyons, Jennifer ...... 57 Sankar Navaneethan, MD Monga, Manoj ...... 59 Glickman Urological & Kidney Institute Nephrology Section Editor Montague, Drogo ...... 64 Moore, Courtenay ...... 60 Kimberley Sirk Navaneethan, Sankar ...... 53,55 Managing Editor Paganini, Emil ...... 56 [email protected] Poggio, Emilio ...... 67 Irwin Krieger Rabets, John ...... 71 Graphic Designer Rackley, Raymond ...... 63 Sabanegh, Edmund ...... 6,72 Jade Needham Schold, Jesse ...... 68 Marketing Manager [email protected] Schreiber, Martin ...... 50 Simmons, Matthew ...... 36 Simon, James ...... 65 Snyder, Carolyn ...... 59 Stein, Robert ...... 10,17,20,22,25,28 Stephany, Brian ...... 70 Stephenson, Andrew ...... 34,38,39,40,43,48 Thomas, George ...... 50,55 Vaish, Sneha ...... 73 Vasavada, Sandip ...... 64 Wang, Aimin ...... 74 Wang, Sihe ...... 54 Wee, Alvin ...... 8 Wehbe, Edgard ...... 70 Wessely, Oliver ...... 75 Wood, Hadley ...... 64,65 Wu, Qingyu ...... 51

78224_CCFBCH_Text_ACG.indd 76 12/12/11 8:55 PM Urology & Kidney Resources for Physicians Resources for Patients Physician Directory Disease News View all Cleveland Clinic staff online at Medical Concierge clevelandclinic.org/staff. For complimentary assistance for out-of-state patients and families, call 800.223.2273, ext. Referring Physician Center Chairman’s Report...... 4 55580, or email [email protected]. For help with service-related issues, information about our News from the Glickman Urological & Kidney Institute clinical specialists and services, details about CME oppor- Global Patient Services tunities, and more, contact the Referring Physician Center Chair Established in Urological Oncology Research...... 5 For complimentary assistance for national at [email protected], or 216.448.0900 or 888.637.0568. NIH Grant Addresses Navigating the and international patients and families, call Challenges of Kidney Disease...... 5 001.216.444.8184 or visit clevelandclinic.org/gps. Track Your Patient’s Care Online Partners Receive $1 Million Ohio Third Frontier Grant ® for Organ Imaging Project...... 5 DrConnect is a secure online service providing our MyChart Summer Internship at the Department of Urology - Leading physician colleagues with real-time information about the Cleveland Clinic MyChart® is a secure, online the Way in Medical Research and Education...... 6 treatment their patients receive at Cleveland Clinic. To personal healthcare management tool that connects New Staff...... 7 receive your next patient report electronically, establish patients to portions of their medical record at any Staff Awards and Appointments...... 7 a DrConnect account at clevelandclinic.org/drconnect. time of day or night. Patients may view test results, Case-Based Urology Learning Program Provides renew prescriptions, review past appointments and Request for Medical Records Real-World Experience...... 8 request new ones. A new feature, Schedule My 216.445.2547 or 800.223.2273, ext. 52547 Cleveland Clinic’s Indiana Partner Surpasses Appointment, allows patients to view their primary 100 Kidney Transplants...... 8 physician’s open schedule and make appoint- Cleveland Clinic Marks Milestone In Prostate Cancer Treatment. ....9 Critical Care Transport Worldwide Cleveland Clinic’s critical care transport teams and fleet ments online in real time. Patients may register for Six Fresenius Medical Care Facilities in MyChart through their physician’s office or by going Cleveland Honored for Superior Patient Care...... 9 of mobile ICU vehicles, helicopters and fixed-wing aircraft serve critically ill and highly complex patients across the online to clevelandclinic.org/mychart. Fluorescence cystoscopy demonstrates selective update of Center for Robotics & Image-Guided Surgery globe. Transport is available for children and adults. hexaminolevulinate HCl in bladder cancer with Cysview.™ Malignant Largest Reported Single-Institution Experience of 300 To arrange a transfer for STEMI (ST elevated myocardial tissue fluoresces bright pink, whereas normal urothelium is seen Robotic Partial Nephrectomies: Evolving Technique infarction), acute stroke, ICH (intracerebral hemorrhage), in blue. and Surgical Outcomes ...... 10 Image-Guided Percutaneous Thermal Ablation for Renal Tumors SAH (subarachnoid hemorrhage) or aortic syndromes, in 65 Solitary Kidneys: A Historical Review of Functional and call 877.379.CODE (2633). For all other critical care Oncological Outcomes...... 12 transfers, call 216.448.7000 or 866.547.1467 or visit Laparoendoscopic Single-Site Surgery in Urology: clevelandclinic.org/criticalcaretransport. Cleveland Clinic Claims Worldwide Multi-Institutional Analysis of 1,076 Cases...... 14 Robotic Surgery with the Adjunctive Outcomes Data Two No. 2 Spots in Latest Use of Fluorescent Imaging for Prostate Cancer...... 17 View clinical Outcomes books from Glickman Urological & U.S.News Rankings Thermal Ablation as Salvage Therapy for Renal Tumors in Kidney Institute and other Cleveland Clinic institutes von Hippel-Lindau Patients: Cleveland Clinic Experience...... 18 at clevelandclinic.org/quality/outcomes. Urology and Kidney Disorders Immediate Impact of a Robotic Kidney Surgery Course on Attendees’ Practice Patterns...... 20 both ranked No. 2 in the nation. CME Opportunities: Live and Online Robotic Laparoendoscopic Single-Site Radical Nephrectomy: Cleveland Clinic’s Center for Continuing Education’s website Surgical Technique and Comparative Outcomes...... 22 offers convenient, complimentary learning opportunities, Glickman Urological & Kidney Institute now has Novel Robotic System for Percutaneous Renal Probe Placement....24 from patient simulations, webcasts and podcasts to a host the distinction of holding two No. 2 positions in the SPIDER™ Surgical System for Urologic LESS: From Initial of medical publications and a schedule of live CME courses. U.S.News & World Report hospital rankings, with Laboratory Experience to First Clinical Application...... 25 Physicians can manage CME credits using the myCME.com No. 2 slots in both urology and kidney disorders. Robotic-Assisted Laparoscopic Partial Nephrectomy for a 7 cm Mass in a Renal Allograft...... 26 web portal available 24/7. Visit ccfcme.org. The 2011 “America’s Best Hospitals” survey Robotic vs. Laparoscopic Partial Nephrectomy for recognized Cleveland Clinic as one of the nation’s Bilateral Synchronous Kidney Tumors: Comparative best overall, ranking the hospital as No. 4 in the Analysis at a Single Institution...... 28 country. Cleveland Clinic ranked in all 16 of the Novel Robotic Renorrhaphy Technique for Hilar Tumors: specialties surveyed by the magazine. “V” Hilar Suture (VHS)...... 30 Feasibility, Advantages and Challenges of Thirteen of its specialties were listed among Retroperitoneoscopic LESS Nephrectomy...... 32 the top 10 in the United States. For details, visit ViKY Robotic Scope Holder: Preliminary Results clevelandclinic.org. Using Instrument Tracking...... 33 Center for Urologic Oncology: Bladder Cancer Outcome of Delayed Radical Cystectomy for Recurrent, Non-Muscle-Invasive, High-Grade Bladder Cancer Refractory to Bacille Calmette-Guérin (BCG)...... 34 clevelandclinic.org/glickman Fluorescence Cystoscopy Proves Its Worth in Management of Bladder Cancer...... 35

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