University of Rochester Medical Center | URology News

URology University of Rochester Medical Center | Urology News | Fall / Winter 2019–20

The Robotic Revolution UR Medicine’s dedicated robotic simulation program focuses on team-based training. pg. 4

URology

| Fall / Winter 2019–20

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Technology Transforming Care Urology, as a discipline, has always been at the fore in the quest to lessen the invasiveness associated with surgical interventions.

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

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The wide adoption of robotic technologies is one such example, with a number of procedures where the application of robotics has become routine. The use of the robot has changed the operative experience for both patients and surgeons alike. It has transformed the surgical craft, both in terms of skill sets required to perform these procedures, and also how we train the next generation of surgeons.

This issue of URology examines how the University of Rochester Medical Center (URMC), an early adopter of robotic surgery, has embraced this technology and has been a leader and innovator in robotic surgical training and its applications. Our collaborative environment has facilitated the growth of minimally invasive approaches in a variety of other surgical disciplines. URMC recently became one of the first institutions worldwide to perform a robot-assisted transplant for kidney recipients. With the continued goal of developing new, innovative and less invasive approaches, our team has been pursuing single-port robotic surgeries.

Whether through multiport or single-port approaches, we will continue to innovate how to best care for our patients.

The faculty in Rochester continues to grow as our health network expands not only in the number of hospitals, affiliates and referring physicians, but also in its geographic reach. We have recruited outstanding physicians and surgeon scientists, adding to our talented team and providing expertise in every urological subspecialty. We are delighted to welcome Jonathan Bloom, M.D., who joined us | Department of Urology | urology.urmc.edu

after completing an oncology fellowship at the National Cancer Institute. William Tabayoyong M.D., Ph.D., and Divya Ajay, M.D., M.P.H., completed their fellowships in urologic oncology and reconstructive urology respectively at MD Anderson Cancer Center. Scott Gabrielsen M.D., Ph.D., joined our team after completing his fellowship at Baylor University, adding to our expertise in infertility and men’s health.

Our gratitude and best wishes also go to Erdal Erturk, M.D., and William Hulbert, M.D., upon their retirement for their tremendous contributions and devotion to our team for many decades. Their tireless work has led to the growth of the Department and the ongoing transformation our team is experiencing.

The health system’s expansion, which accelerated in the wake of the passage of the Accountable Care Act, presents the opportunity to provide more specialized urological care to patients closer to home.

To accomplish this, we continue to build the infrastructure and systems that, whenever possible, bring care to the patients. Technology plays a role in this effort as well; electronic medical records and telemedicine are enabling our physicians to provide coordinated care and extend access.

This issue also details the innovative research that is being conducted in Rochester in kidney, prostate and bladder cancer.

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.”

Research

New tool meets urgent need in bladder cancer A URMC scientist has developed a new way to study how bladder cancer spreads and to investigate potential new treatments.

The tool, described in the journal Scientific Reports, is essential for the field of bladder cancer research, said lead author Yi-Fen Lee, Ph.D., a professor in the URMC Department of Urology.

Lee’s study focused on the key biological events that cause certain highly tumorigenic cancer cells to escape the lesion and seed in other areas. Her laboratory studied these cells in a new mouse model designed by her lab, and discovered a subpopulation of cancer stem cells more likely to metastasize and colonize elsewhere. In addition, the lab’s researchers found two genes active in promoting bladder cancer metastasis to the lungs.

“Animal models are invaluable for inves-

“Our approach offers a unique opportunity to pursue research that could translate into better treatments for patients.” — Yi-Fen Lee, Ph.D. tigating the complex, multi-step process that enables cancer cells to detach from primary tumors and invade other areas, but the availability of these models is limited,” said Lee. “Our approach offers a unique opportunity to pursue research that could translate into better treatments for patients.”

The majority of bladder cancer cases involve non-muscle invasive tumors, but they tend to recur after initial treatment, and can progress to more serious muscle-invading bladder cancer. When the cancer spreads

to the lymph nodes, bones, lungs, or peritoneum, there are fewer treatment options.

Lee also investigates the “tiny vesicles,” or exosomes, released by cells that nurture metastasis and have a role in the patient’s response to treatment.

Lee’s study, which was funded by the NCI, comes on the heels of other recent improvements in understanding and treating bladder cancer by URMC scientists. Last summer, for example, Edward Messing, M.D., published the results of a nationwide clinical trial showing that a simple, post-surgery step to inject a type of chemotherapy directly into the bladder area significantly reduces the chances of the cancer returning. The results were shared with clinicians via the Journal of the American Medical Association.

A molecular “switch” prolongs survival URMC scientists believe they have figured out why a commonly used drug to treat latestage prostate cancer often stops working after four or five months and appears to have a dual function that later turns the cancer into a relentless aggressor.

By describing how the drug, enzalutamide, inadvertently causes the harmful transformation, Chawnshang Chang, Ph.D., a professor in the URMC Department of Pathology and Laboratory Medicine, and colleagues believe they have also discovered a way to block it from occurring, at least in mice. The study was published in the journal Nature Communications.

“As more patients look to enzalutamide to extend their lives, even for just a few months, our goal is to find ways to make the drug work for longer periods and to block the dangerous pathways that lead to adverse side effects,” Chang said.

For men with the aggressive form of metastatic prostate cancer known as castration-resistant prostate cancer who are no longer responding to chemotherapy,

enzalutamide can extend survival by an average of five months. In 2018, the Food and Drug Administration also approved the drug to treat men who have castrate-resistant prostate cancer that had not yet spread.

But enzalutamide can cause side effects.

One of the worst effects is neuroendocrine differentiation (NED), an increase of neuro­ endocrine cells in the prostate tumors.

An abundance of NED cells makes tumors resistant to treatment.

Chang and his colleagues identified non-coding RNAp-21 as the main culprit for inducing neuroendocrine differentiation, by the fact that IncRNAp-21 can switch the function of a key gene, EZH2. They also showed that IncRNAp-21 is highly expressed in NED prostate tumors.

Earlier, scientists believed that only a tiny percentage of advanced prostate cancer tumors underwent neuroendocrine differentiation. But recent studies estimate that 30 to 40 percent of patients have tumors containing aggressive neuroendocrine prostate cancer cells for which the average URology

survival rate after detection is less than one year — making more patients vulnerable to the worst-case disease progression.

Edward Messing, M.D., a national and international authority on urologic cancers, said the latest discovery has the potential to impact men with challenging cases.

“Dr. Chang’s team has identified an important molecular mechanism that affects many of the thousands of men with advanced prostate cancer who will eventually succumb to their disease,” Messing said.

“Understanding and reversing the ‘switch’ that causes neuroendocrine differentiation should prolong the lives of these men and significantly reduce their suffering.”

Although no treatments are available yet in clinical trials to block molecular switch, Chang’s lab identified a small molecule drug that appears to work in mice; researchers elsewhere have revealed similar drugs and further study is needed.

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The Robotic Revolution Jean Joseph, M.D., M.B.A., the Winfield W. Scott Professor and chair of the Department of Urology at the University of Rochester Medical Center (URMC), remembers the day when everything changed.

In 2001, Joseph was one of a handful of surgeons in the U.S. to perform a laparoscopic radical prostatectomy using a robotic surgical system.

Originally conceived in the 1980s by the U.S. military as a system to remotely perform surgeries in war zones, the Intuitive da Vinci ÂŽ Surgical System was approved by the FDA in 2000. Since then, it has become a ubiquitous presence in

many hospital’s surgical suites and its use has expanded beyond prostatectomies to partial nephrectomies, cholecystectomies, gynecological, ENT and colorectal procedures, as well as kidney and liver transplants.

Joseph has lost track, but estimates that UR Medicine urologic surgeons have performed over 10,000 robotic procedures over the past two decades. The URMC

A dedicated robotic simulation suite at Strong Memorial Hospital provides the entire team with an immersive, hands-on surgical environment.

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| Department of Urology | urology.urmc.edu

Urology team was an early adopter of the technology, due to the number of surgeons skilled in laparoscopic urologic surgery, and is now one of the top centers in the U.S. in the volume of robotic procedures with a team of nine experienced urologic surgeons currently using the robots for a range of procedures for both adult and pediatric patients. UR Medicine offers robotic surgery at three of its hospitals: Strong Memorial, Highland and F.F. Thompson.

URMC has been recognized as a leader and innovator in this field by leveraging its research and education missions.

UR Medicine surgeons led the study assessing the use of indocyanine green, which is now commonplace in robotic surgery. In 2010, URMC surgeons performed the first live robotic prostatectomy, which

was broadcast to an American Urological Association meeting in San Francisco.

More recently, Joseph, Ghazi, Rashid, Wu and Frye performed a robotic prostatectomy and nephrectomy in Rochester that was shared live with attendees of the North American Robotic Surgery Symposium in Las Vegas in 2018. The Rochester team has also been pioneering the use of the da Vinci Single-Port Surgical System, which was recently approved by the FDA. In 2008, URMC created the Center for Robotic Surgery & Innovation, which was initially led by Joseph, to advance care, research, and training using the technology.

A focus of the center is team training, which supports the creation of integrated surgical teams that will deliver consistent and coordinated care of the highest quality.

As the technology has evolved and has been adopted for more procedures, robotic surgery has driven improved outcomes for patients. Studies have demonstrated low risk of serious complications and benefits of laparoscopic surgery, including reduced

hospital stays and quicker recovery, less anastomotic stricture, fewer respiratory complications, reduced risk of surgical site infection, and less need for blood transfusion. Research has also shown that hospitals with high volumes of robotic cases have the best patient outcomes.

While robotic surgery has been a boon in terms of improving outcomes, the technology presents challenges in terms of training.

Like many other surgical methods, there is a direct correlation between the success of individual surgeons and experience using the robotic system. There is also a steep learning curve in becoming proficient with the system’s complex controls. It is estimated that a surgeon requires about 60 cases to become comfortable with the procedure and about 250 cases to become an expert. However, because only one surgeon operates the robot during a procedure, training opportunities during live surgeries are limited.

There are many virtual robotic training and simulation systems, but the team

at URMC has taken the concept one step further and developed its own platform to provide both trainees and experienced surgeons with an immersive hands-on training environment. URMC has created a dedicated robotic surgical suite, which allows not only the surgeon but the entire surgical team to train with the system.

The Department’s Simulation Innovation Lab, which is led by Ghazi, builds lifelike models of human anatomy consisting of entire sections of the abdomen with all of the accompanying skin, fat, muscle and organs that even bleed when cut.

The models are then used to replicate the entire procedure from the incisions and insertion of trocars to the completion of the surgery in a team-based simulation environment.

The work of the UR Medicine urological team has paved the way for many other disciplines to safely embark on robotic procedures with associated benefits to patients.

UR Medicine Department of Urology Robotic Surgery Team

Jean V. Joseph, M.D., M.B.A. Johnathan Bloom, M.D. Jimena Cubillos, M.D.

Thomas Frye, D.O. Ahmed Ghazi, M.D. Diane Lu, M.D.

Hani H. Rashid, M.D. William Tabayoyong, M.D., Ph.D. Guan Wu, M.D., Ph.D.

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| Fall / Winter 2019–20

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Lab Profile

Profiles in Phlanthropy

Shu-Yuan Yeh, Ph.D.

Honoring W. W. Scott

Tumors require a blood supply for growth and vasculogenic mimicry (vascular mimicry, VM), which has increasingly been recognized as a similar form of blood vessel creation without the involvement of endothelial cells. Studies suggest that targeted therapy drugs (angiogenesis inhibitors and anti-VEGF/VEGFR therapy) for treating kidney cancer may not effectively suppress VM, because the tumor cells lack the appropriate level of VEGF receptor for the inhibitors to act effectively. Supplements from VM development that provide nutrients for cancer cells could significantly reduce the stress imposed by anti-angiogenesis agents. Although targeted therapy (angiogenesis inhibitors) remains the mainstay treatment for latestage metastatic kidney cancer patients, it is necessary to discover new strategies to block the VM-mediated nutrition supply.

Yeh’s lab analyzed clinical databases and new findings showed that higher expression levels and functions of the estrogen receptor beta (ERß) in kidney tumor tissues are associated with worse overall survival. Further studies show estrogen/ERß signals can stimulate VM molecules and angiogenetic factors to facilitate kidney cancer progression. ERß may function via controlling VM-related signals to promote the kidney cancer progression, and functional studies/ mechanism dissection of such signals could help to develop better therapies to suppress metastatic kidney cancer. This work could lead to new biomarkers to predict clinical outcomes and her findings have been reported in the journals Cancer Research and Oncogene.

The Winfield W. Scott Chair in Urology was established in 1983 with a bequest gift from Winfield W. Scott, M.D., founding chair of the Department. The former chief urologist at Strong Memorial Hospital, Scott was an internationally known specialist who trained at Johns Hopkins University under the “father of urology,” Hugh H. Young, M.D. One of Scott’s major contributions was as a teacher of medical students and residents, training outstanding clinical urologists and academicians for more than 30 years.

Perhaps his greatest contribution was the recognition that research was of paramount importance in furthering the long-term goals in the field. By his example, raising dollars to support research funding continues to be a cornerstone for urologic research at URMC.

For more information about supporting the Department of Urology, please contact Diane Quinlisk: diane.quinlisk@rochester.edu or

(585) 273-4854.

A Man and His Prostate

Dr. Pearle Visiting Professor

Press Conference on BCG Shortage

The UR Medicine Department of Urology was the lead sponsor of the drama/comedy A Man and His Prostate. Based on a true-life experience, the one-man comedy was portrayed by 8-Time Emmy Award-Winner Ed Asner and held at the Jewish Community Center in Rochester.

The Department of Urology works closely with patient support groups and various organizations to raise prostate cancer awareness.

The Department of Urology hosted Margaret Pearle, M.D., Ph.D., vice chair of Urology at UT Southwestern, as a visiting professor.

Pearle is an internationally renowned stone disease expert and educator.

UR Medicine urologists Jean Joseph, M.D. and Ed Messing, M.D., and URMC CEO Mark Taubman, M.D., held a press conference at the Wilmot Cancer Institute with U.S. Senator Charles Schumer (NY) calling on the CDC and drug manufacturers to take steps to end the nationwide shortage of the bladder cancer drug TICE BCG.

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| Department of Urology | urology.urmc.edu

Upstate New York’s leader in advanced urological care the state of Connecticut), our faculty see approximately 3 million visits annually. Together, URMC and UR Medicine affiliates employ more than 24,000 full- and part-time staff members.

This UR Medicine health care network provides a platform to both deliver advanced urological clinical services and provide this care closer to home. The Department’s 32 adult and pediatric physicians and APPs conduct urological clinics in 13 locations across the region.

The Department is also leveraging technologies such as EMRs and telemedicine to extend access and consultation services to providers across the UR Medicine network.

UR Medicine health care delivery network consists of seven hospitals and is anchored by Strong Memorial Hospital, a university-owned teaching hospital with 886 licensed beds and offering a full spectrum of tertiary and quaternary services.

The UR Medicine clinical enterprise is comprised of more than 1,500 physicians, includes 1,452 licensed beds, and records 70,000 inpatient discharges and 53,000 ambulatory surgeries per year, in addition to 56,000 observation cases. Its outpatient providers log 1.2 million annual outpatient encounters. With more than 325 practices located throughout the Greater Rochester, Finger Lakes, and Southern Tier regions (a catchment area larger than

UR Medicine Urology Clinical Locations

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Sawgrass Urology Clinic Brighton 490 Pathways to Health

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

NONPROFIT ORG U.S. POSTAGE

PAID

UNIVERSITY OF ROCHESTER PERMIT 780

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 Divya Ajay, MD, PhD Assistant Professor of Urology Zaheer Alam, MBBS Assistant Professor of Clinical Urology Jonathan Bloom, MD Assistant Professor of Clinical Urology Jimena Cubillos, MD Associate Professor of Clinical Urology and Pediatrics Associate Chief of Pediatric Urology Director of Quality Improvement Manizheh Eghbali, PhD Associate Professor Urology Director of Residency Education

Thomas Frye, DO Assistant Professor of Urology and Oncology Associate Director, Clinical Trials

Edward M. Messing, MD, FACS Professor of Urology and Oncology Director, Clinical Trials

Joseph Gabrielsen, MD, PhD Assistant Professor of Urology

Joy Michaelides, MD Assistant Professor of Urology

David Gentile, MD, FACS Professor of Clinical Urology Chief of Urology, Highland Hospital

Jeanne H. O’Brien, MD Professor of Urology Associate Chair of Faculty Development and Resident Education

Ahmed Ghazi, MD, MSc Assistant Professor of Urology Co-Director, Endourology, Robotic/MIS Fellowship Director, Simulation Innovation Lab Rajat Jain, MD Assistant Professor of Urology Yi-Fen Lee, PhD Professor of Urology, Oncology, Pathology and Laboratory Medicine

Jamie Connor, NP Jason Donovan, PA Karrah Gantz, NP Diane Giordano, PA Kim Hoadley, PA Shawna Hyland, NP Maureen Kiernan, NP

William Tabayoyong, MD, PhD Assistant Professor of Urology Jared Wachterman, MD Assistant Professor of Urology

Ronald Rabinowitz, MD Professor of Urology and Pediatrics

Gareth Warren, MD Assistant Professor of Urology and Obstetrics and Gynecology

Hani Rashid, MD Professor of Urology and Oncology Director, Robotic Surgery, Highland Hospital Director of Residency Program

Guan Wu, MD, PhD Professor of Urology and Oncology Director of Urologic Oncology Co-Director, Fellowship in Robotic Surgery

Annette E. Sessions, MD Assistant Professor of Clinical Urology

Shu-Yuan Yeh, PhD Professor of Urology, Oncology, Pathology and Laboratory Medicine

Diane Lu, MD Assistant Professor of Clinical Urology

DEPARTMENT OF UROLOGY RESIDENTS/FELLOWS

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

Paul Shapiro, MD Associate Professor of Clinical Urology Chief of Urology, FF Thompson and Clifton Springs Hospitals

Victoria Mesko, FNP-C Robyn Reis, NP Parker Remelt, PA Claire Smith, PA Kristin Smith, RPA-C

Pratik Gurung, MD, Fellow Prabhakar Mithal, MD, Chief Resident Phillip Rappold, MD, Chief Resident Jacob Gantz, MD, PGY5 Michael Witthaus, MD, PGY5 Thomas Osinski, MD, PGY4 Alexander Cranwell, MD, PGY3

Alexis Steinmetz, MD, PGY3 Kit Yuen, MD, PGY3 Karen Doersch, MD, PGY2 Elizabeth Ellis, MD, PGY2 Austin Lee, MD, PGY1 Aaron Saxton, MD, PGY1 Christopher Wanderling, MD, PGY1