URology | 2019 | Winter

University of Rochester Medical Center Urology News | Volume 1 | Winter 2019

Fake Organs Advancing Care for Real Patients pg. 4

Messing Celebrated for Career of Leadership, Innovation in Urological Care pg. 2

Celebrating Our Past – Planning for a Bright Future Welcome to the inaugural edition of URology News.

The goal of this newsletter is to share the exciting developments taking place in the Department of Urology at the University of Rochester Medical Center.

We will showcase how the members of the department and their collaborators are performing groundbreaking research and innovating in how we educate and provide patient-family centered care.

Since its foundation by Dr. Winfield Wallace Scott and the leaders who followed, the Department’s contributions have been significant.

Our faculty members have always been active in basic and translational research that has furthered our understanding of urologic diseases. Our faculty has trained countless urologic surgeons who are now providing state-of-theart care at medical centers around the world.

Under Dr. Ed Messing’s leadership, the Department expanded its clinical and research activities, and has become a regional center for advanced urological care. I will continue to work with our dynamic faculty to build upon this strong foundation, our tradition of excellence, and will strengthen the Department as one of the nation’s leading centers for advanced patientcentered urological care, scientific innovation, and a destination that attracts and trains the next generation of physicians and surgeons.

Our faculty continues to grow, with three members added in the last four months. We are delighted to welcome Dr. Rajat Jain, who joined us after fellowship training at the Cleveland Clinic, expanding our clinical and research expertise in stone disease.Dr. Diane Lu also joined the faculty after fellowship training in robotic surgery at URMC and will be expanding the robotic services at UR Medicine’s F.F. Thompson Hospital. Dr. Zaheer Alam will strengthen our specialty care at UR Medicine’s Noyes and Jones Memorial

Hospitals, while pursuing subspecialty interest in transitional medicine at Strong Memorial Hospital.

In this newsletter we recognize Dr. Messing, someone who is truly a giant in our field and who, over the 35 years of his career, has transformed the way we diagnose and treat a wide range of urological malignancies. This past October, our department hosted a Festschrift to celebrate Ed’s career.

A number of national and international leaders, clinicians, and scientists from across the globe came to Rochester to share their expertise in various areas of urology, while recognizing Dr. Messing for his mentorship and collaborations.

This newsletter also details an advanced simulation program developed here in Rochester that is rapidly changing how we train surgeons and improve patient outcomes. Our Department’s Simulation Innovation Lab, led by Dr. Ahmed Ghazi, harnesses a suite of technologies to produce lifelike replicas of organs and other detailed patient anatomy that can be used in full robotic surgical simulations.

Our simulation program is gaining national and international recognition in the fields of urology and robotic surgery.

These are but a few examples of the work being done here at URMC that is having a national impact on our field and, in the words of the University of Rochester’s motto Meliora, making the world “ever better.”

Jean Joseph, M.D., M.B.A., F.A.C.S. Winfield W. Scott Professor and Chair Department of Urology Professor of Oncology Wilmot Cancer Institute University of Rochester Medical Center

FEATURE

Left to Right: Dr. Jean Joseph, University of Rochester President Richard Feldman, Dr. Ed Messing, UR Medical Center CEO Dr. Mark Taubman

Messing Honored for Career of Innovation and Leadership in Urological Care Leading researchers and clinicians from across the globe gathered in Rochester on October 18-19 to recognize the career of Edward Messing, M.D., F.A.C.S., and his 35 years of accomplishments in improving care for individuals with bladder, kidney, prostate, and testicular cancer. The Festschrift honoring Messing, a professor in the University of Rochester Medical Center (URMC) Department of Urology and the Wilmot Cancer Institute, was the subject of a special edition of the journal Bladder Cancer.

“Dr. Messing is a legend in the field and over the last three plus decades has transformed how we diagnose and treat patients with genitourinary cancers,” said Jean Joseph, M.D., M.B.A., F.A.C.S., chair of the URMC Department of Urology. “His dedication to his craft, the personal connections he developed with his patients, and his commitment to improve care

through the rigorous application of science have been an inspiration to me personally and to countless others who have been impacted by his work.”

As a busy clinician and renowned surgeon, one of the principles that has guided Messing’s career is a strong belief that science is an integral part of the practice of medicine and necessary to provide patients with the best possible care. His research has been focused on early detection, prevention, and treatment of urologic malignancies.

Messing’s scientific contributions have ranged from enhancing our knowledge of the basic molecular and genetic components that contribute to the development and progression of cancers of the bladder, prostate, and kidney, and translating this research into new ways to diagnose and treat these diseases.

He has designed and conducted landmark phase III clinical trials for

several genitourinary cancers, led a bladder cancer study that resulted in a simple in-office urine test to screen for the disease, has helped shape the national recommendations for the screening of prostate cancer, and demonstrated the value of radiation therapy after prostatectomy for stage pT3 prostate cancer.

“Ed’s kindness and concern for others are evident in all of his personal interactions but are also manifest in his medical accomplishments,” said Joseph A Smith, M.D., a professor in the Department of Urologic Surgery at Vanderbilt University Medical Center and editor of the Journal of Urology.

“One always has the sense that his primary interest is in advancing patient care rather than advancing his own self interests. I am fortunate to be able to have him as a colleague but, mostly, as a friend.”

Messing, who grew up in Brooklyn and often proudly claims that he is a URology | WINTER 2019

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product of the New York City public school system, received his medical degree from New York University (NYU) in 1972 and conducted his training at NYU, Stanford University, and the University of California, Los Angeles. He served on the faculty at the University of Wisconsin for 13 years before arriving URMC in 1995 to become chair of the Department of Urology, a position he held until January 1, 2018.

Upon arriving in Rochester, Messing oversaw the growth of the URMC Department of Urology from a faculty of 6 adult and pediatric urologists to 17 by the end of his tenure as chair. The department has become upstate New York’s leading provider of advanced urological care. During that period, the number of basic science faculty in the department increased from zero to 3 researchers who are making important contributions in the fields of renal, bladder, and prostate cancer.

In addition to maintaining an active clinical schedule, Messing continues to teach residents, medical students, and graduate students.

Over the years, Messing has received numerous awards and accolades. In 2013, he was awarded the prestigious Presidential Citation from the American Urological Association (AUA) for his work in bladder cancer research and urologic education. Earlier this year he received the Ramon Guiteras Award, the highest honor given to an academic urologist by the AUA. “It is, or should be, the goal of every academic physician to achieve two things during their career,” said Ian M. Thompson Jr., M.D., president of CHRISTUS Santa Rosa Hospital – Medical Center in Texas and a member of the Board of Scientific Advisors for the National Cancer Institute. “The first of these is to train individuals who will carry the torch of innovation and exceptional clinical care. The second goal we all have is to change or improve the standard-ofcare for patients. If we are successful, conversations between physicians and patients about what their best treatment is will be different based on our research. This is a far more difficult

Special edition of Bladder Cancer dedicated to Messing Festschrift by editors Seth Lerner and Dan Theodorescu.

challenge, one that few of us will achieve. Ed has done this on so many occasions. His legacy is thus assured both through generations of urologists who will care for millions of patients as well as through his intellectual and innovative contributions of better care for our patients.”

LAB PROFILE

Investigating the Role of Extracellular Vesicles in Bladder Cancer Yi-Fen Lee, Ph.D., is investigating the role of extracellular vesicles (EVs), often called exosomes, in cancer recurrence, metastasis, and response to treatment, with a focus on urological cancers such as bladder and prostate cancers.

Small vesicles, ranging in size from 30-250 nm, are secreted by almost all types of cells and contain various cargo molecules such as DNA, RNA and proteins resembling the cells of origin. Lee’s lab isolates EVs from cell 3

lines and cancer patient specimens for use in pre-clinical and clinical models to study their functional roles in modifying the tumor microenvironment to facilitate cancer recurrence and metastasis. Through gene array and proteomics analysis, the lab is seeking to identify the signature EV protein and RNA profiles that can be used for disease prognosis.

Lee’s lab is also studying the involvement of EV machinery in response to two commonly applied bladder cancer treatments: BCG immunotherapy and cisplatin chemotherapy. The lab is a part of the SWOG clinical trial which is investigating a bacteria-based therapy for bladder cancer and is collecting and

UR Medicine | Department of Urology | urology.urmc.edu

analyzing patients’ urine- and bloodborne EV profiles before, during, and after therapy.

The lab’s goal is to establish rapid body fluid biopsy assays that can be used as indicators of patients’ disease status and responsiveness to therapy.

The molecular/genetic contents within EVs from each individual patient could also provide an opportunity to develop precision personalized medicine in the future.

FEATURE

Fake Organs Advancing Care for Real Patients

Like many experienced surgeons, URMC urologist Ahmed Ghazi, M.D., is passionate about honing his skills and perfecting his craft. While there are many different systems that allow surgeons to simulate robotic surgery, Ghazi found that none of them were capable of fully recreating the complete surgical experience, including the environment of the operating room, the pressure of racing against the clock, and the feel and responsiveness of real organs.

Ghazi’s drive to “build a better mousetrap” and years of trial and error led to the creation of the Simulation Innovation Lab, which harnesses medical imaging, computer modeling, and 3D printing systems to fabricate lifelike organs that look and feel like the real thing and even bleed when cut. This system is being used to train medical students and trainees

and even help experienced surgeons sharpen their skills. Increasingly, it is being employed by surgeons at URMC to rehearse procedures prior to complex cases.

“Very few surgical simulations are successful at recreating the live event from the beginning to the end,” said Ghazi. “What we have created is a model that looks, feels, and reacts like a live organ and allows trainees and surgeons to replicate the same experience they would face in the operating room with a real patient.”

The Simulation Innovation Lab is gaining international recognition.

Presentations of the simulation program took honors at the annual meeting of the American Urological Association (2015, 2016, and 2017), the World Congress of Endourology meeting in Paris in 2018, and the 2018 Falling Walls Lab competition

in Berlin. In February 2018, UR Medicine surgeons Thomas Frye, Jean Joseph, Hani Rashid, and Guan Wu performed a robotic prostatectomy and nephrectomy that were broadcasted live to the North American Robotic Surgery Symposium in Las Vegas.

Wu, who performed the live partial nephrectomy, had practiced the procedure on a patient specific model created by the Simulation Innovation Lab. The process of fabricating the artificial organs, which was developed

by Ghazi in collaboration URMC neurosurgeon Jonathan Stone, M.D., begins by converting images obtained from MRI, CT, or ultrasound scans into computer-assisted designs (CAD).

Instead of using these designs to create rigid plastic replicas of human anatomy, which is being done in many other places, the team instead URology | WINTER 2019

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“What we have created is a model that looks, feels, and reacts like a live organ and allows trainees and surgeons to replicate the same experience they would face in the operating room with a real patient.”

Ahmed Ghazi, M.D.

converts the CADs of organs into molds, or negatives, which are built using a 3D printer. In a process akin to casting a bronze statue, the molds are injected with a hydrogel which, after freezing, assumes a solid state.

In collaboration with the University of Rochester Department of Biomedical Engineering, the team subjected the models to a battery of scientific tests to ensure that the end product had the same mechanical properties as real tissue.

By altering the concentration of the hydrogel, the team can add denser tumor mass and other components, such as blood vessels and the ureter.

The team assembles entire segments of the body, complete with artificial muscle tissue, skin and fat, and, depending upon the area of interest, the liver, intestines, spleen, kidney, and other adjacent organs and structures.

Artificial blood vessels are connected to bags of red dye that will “bleed” if cut.

The assembled section of the abdomen is then brought to an OR in URMC’s Strong Memorial Hospital that houses a Da Vinci surgical system that is dedicated to the simulation program.

In some instances, the entire surgical team will participate in the rehearsals, allowing the participants to replicate the entire process from the incision

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and placement of trocars to the resection and removal of tumors.

The program is being used by the University of Rochester School of Medicine and Dentistry to expose third year medical students to a full laparoscopic surgical simulation.

Surgical fellows regularly train on the system. In October, surgeons from across upstate New York visited Rochester for a hands-on course in advanced robotic techniques using the simulation platform.

The simulations are increasingly being employed to directly improve patient outcomes. Earlier this year,

Ghazi successfully removed five tumors from the kidney of a patient with von Hippel-Lindau disease. Ghazi rehearsed the surgery using the simulation program half a dozen times and was able to perform the actual robotic tumor resection in less than 24 minutes, with minimal blood loss, and preserve 90 percent of the kidney.

“These rehearsals allow you to save operating time, decrease blood loss, potentially avoid complications, and prevent time you have to trouble shoot,” said Ghazi. “All of this directly impact patient outcomes.”

Left: live surgery of partial nephrectomy of patient with 5 tumors in right kidney.

Right: surgical simulation on replica of patient’s kidney 48 hours prior to actual procedure.

UR Medicine | Department of Urology | urology.urmc.edu

STUDY

Simple Post-Surgery Step Reduces Bladder Cancer Recurrence

Ed Messing, M.D.

Flushing the bladder with a common chemotherapy drug immediately after surgery significantly reduces the chances of bladder cancer returning, according to a major study led by Ed Messing, M.D., and an international clinical trials network funded by the National Cancer Institute.

Published in the Journal of the American Medical Association (JAMA), the study notes this may be the first phase III trial in the U.S. in two

decades to show a benefit from this treatment strategy. European and Canadian urologists have been using it for years, with their own clinical trial data to support the procedure.

The randomized, double-blind trial – which was conducted in collaboration with the SWOG Cancer Research Network and supported by the National Cancer Institute and Eli Lilly and Company – involved 406 bladder cancer patients at 23 cancer centers.

JAMA also published an editorial about the trial, noting that the investigators focused on a problem that’s meaningful to patients, and concluding that their findings have “practicechanging implications.”

Surgeons performed a transurethral resection of bladder tumor (TURBT) on all study participants. Then roughly half of the patients received the chemotherapy drug, gemcitabine, mixed with saline, administered via catheter to the bladder area within

three hours after surgery. Gemcitabine interferes with DNA replication and kills dividing cells. The drug is used to treat several other cancers, including advanced bladder cancer, but had not been studied among low-grade cancer patients. The second group of 205 patients received saline alone.

Researchers followed all patients for four years.

The researchers observed a 34 percent reduction in the risk of recurrence for patients receiving the gemcitabine infusion. Sixty-seven patients in the gemcitabine group, or 35 percent, experienced a recurrence, compared with 91 patients in the saline group, or 47 percent. Additional research is needed to compare various chemotherapy agents for their effectiveness. About 80,000 Americans a year are diagnosed with bladder cancer, and the low-grade non-muscle invasive form makes up more than half of the new cases annually.

EDUCATION

Residency Research Evaluates Cost Savings in Bladder Cancer

Jacob Gantz, M.D.

Jacob Gantz, M.D., a fourth year Urology resident at the University of Rochester, has been selected for the prestigious Urology Care Foundation Residency Research Award, which provides $40,000 of funding for motivated and exceptional urology residents to prepare them for careers that include urologic research.

Gantz is currently pursuing multiple research projects related to urologic oncology with a particular focus on bladder cancer.

Specifically, he is investigating the potential cost savings associated with immediate post-operative intravesical instillation of gemcitabine for low-grade, non-muscle invasive bladder cancer. Bladder cancer is

the most expensive disease to treat over a patient’s lifetime and his research could help reduce the economic burden associated with bladder cancer and improve care.

Gantz has presented his work at multiple meetings, including a podium presentation at the American Urologic Association Annual Meeting in San Francisco.

Prior to residency, Gantz received his B.A. in Biology from Franklin and Marshall College and his M.D. from the University of Rochester School of Medicine and Dentistry. He plans to pursue a career in ether urologic oncology or minimally invasive surgery after completing his residency.

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University of Rochester Medical Center Department of Urology 601 Elmwood Avenue, Box 656 Rochester, NY 14642

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DEPARTMENT OF UROLOGY FACULTY Jean V. Joseph, MD, MBA, F.A.C.S Professor of Urology and Oncology Winfield W. Scott Professor and Chair of the Urology Department

Ahmed Ghazi, MD, M.Sc. Assistant Professor of Urology Co-Director, Endourology, Robotic/MIS Fellowship Director, Simulation Innovation Lab

Zaheer Alam, MBBS Assistant Professor of Clinical Urology

William Hulbert, MD Professor of Urology and Pediatrics Chief, Pediatric Urology Director, Residency Program

Jimena Cubillos, MD Associate Professor of Clinical Urology and Pediatrics Associate Chief of Pediatric Urology Director of Quality Improvement

Rajat Jain, MD Assistant Professor of Urology

Manizheh Eghbali, PhD Associate Professor Urology Director of Residency Education

Yi-Fen Lee, Ph.D. Professor of Urology, Oncology, Pathology and Laboratory Medicine

Erdal Erturk, MD Professor of Urology Director, Kidney Stone Center Director, Fellowship in Endourology

Diane Lu, MD Assistant Professor of Clinical Urology

Thomas Frye, DO Assistant Professor of Urology and Oncology Associate Director, Clinical Trials David Gentile, MD, F.A.C.S Professor of Clinical Urology Chief of Urology, Highland Hospital

Edward M. Messing, MD, F.A.C.S Professor of Urology and Oncology Director, Clinical Trials Joy Michaelides, MD Assistant Professor of Urology Jeanne H. O’Brien, MD Professor of Urology Associate Chair of Faculty Development and Resident Education

Ronald Rabinowitz, MD Professor of Urology and Pediatrics Hani Rashid, MD Professor of Urology and Oncology Director, Robotic Surgery, Highland Hospital Annette E. Sessions, MD Assistant Professor of Clinical Urology Paul Shapiro, MD Associate Professor of Clinical Urology Chief of Urology, FF Thompson and Clifton Springs Hospitals Jared Wachterman, MD Assistant Professor of Urology Gareth Warren, MD Assistant Professor of Urology and Obstetrics and Gynecology Guan Wu, MD, PhD Professor of Urology and Oncology Director of Urologic Oncology Co-Director, Fellowship in Robotic Surgery Shu-Yuan Yeh, Ph.D. Professor of Urology, Oncology, Pathology and Laboratory Medicine

ADVANCED PRACTICE PROFESSIONALS Meredith Abbasi, CPNP Jamie Allen, FNP-C Katie Bates, PA Dan Barney, PA Amy Beyrle, RPA-C Steve Blount, PA-C

Mariya Canham, NP Jamie Connor, NP Jason Donovan, PA Karrah Gantz, NP Diane Giordano, PA Kim Hoadley, PA

Shawna Hyland, NP Maureen Kiernan, NP Victoria Mesko, FNP-C Robyn Reis, NP Claire Smith, PA Kristin Smith, RPA-C

DEPARTMENT OF UROLOGY RESIDENTS/FELLOWS Pratik Gurung, MD, Fellow Scott Quarrier, MD, Chief Resident Matthew Truong, MD, Chief Resident Prabhakar Mithal, MD, PGY5 Phillip Rappold, MD, PGY5

Jacob Gantz, MD, PGY4 Michael Witthaus, MD, PGY4 Thomas Osinski, MD, PGY3 Alexander Cranwell, MD, PGY2 Alexis Steinmetz, MD, PGY2

Kit Yuen, MD, PGY2 Karen Doersch, MD, PGY1 Elizabeth Ellis, MD, PGY1