University of Rochester Medical Center | URology News | Winter 2020

URology University of Rochester Medical Center | Urology News | Winter 2020

Male Infertility From Complex Care to Innovative Research. pg. 4

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Harnessing Research to Improve Care

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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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| Department of Urology | urology.urmc.edu

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The University of Rochester Medical Center has long been an innovator in the field of male infertility.

In the 1980’s the Medical Center created one of the nation’s first sperm banks. Under the leadership of Drs. Abraham Cockett and Robert Davis, complex surgical techniques were developed to address male factor related causes of infertility. Fast forward to today and we are now home to a robust clinical and research enterprise in the field – led by Drs. Jeanne O’Brien and Scott Gabrielsen – that not only specializes in advanced surgical procedures, but also in studying the genetic, hormonal, anatomical, and environmental factors that affect sperm production. You can read more about our important and innovative work on this topic in our cover story.

This issue of URology also features the ongoing groundbreaking work of our Simulation Innovation Lab. While the lab was initial created as a training platform for urological surgeons, its ability to create an immersive simulation environment is being tapped by other disciplines. The team recently created a simulation program that enabled Rochester surgeons to perform a robot-assisted live donor kidney transplant for both the donor and recipient, making URMC one of only five medical centers in

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the U.S. to perform this complex procedure.

Last month, we opened the doors on a new comprehensive Urology outpatient clinic. The new facility consolidates three locations into one while at the same time increasing overall space and the number of exam and procedure rooms. This new clinic will expand access to care and improve the patient experience, while allowing us to grow programs in kidney stones, cancer, male infertility, and urgent care.

Much of the work we do advancing our field, fulfilling our missions to pursue research and educate the next generation, would not be possible without the generosity of our grateful patients and members of our community. In this issue, we recognize the Weinberg family whose philanthropy supports our annual Men’s Health Day, an event now in its 15th year that provides participants with the tools and knowledge to take control of their own health.

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.”

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HA In December, UR Medicine opened the LL 223 0 doors on a new, state-of-the-art UrolA.1 E XA M1 2 ogy Clinic.

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The new space2134will house a comprehensive Kidney Stone Treatment Center and Men’s Health Center. It will expand the cancer and male infertility service lines, increase access for diagnostic procedures, and provide same day or next day patient access for acute clinical services. The new space will also house an expanding clinical trials team that will facilitate patient access and advance translational research.

“This new clinic will enable us to consolidate resources and realize the efficiencies of locating outpatient services in one location, all of which will improve the patient experience and meet the rising demand for urological care,” said Jean Joseph, M.D., M.B.A., F.A.C.S., chair of the Department of Urology.

The Department of Urology – which has added 13 new faculty and advanced practices providers since 2018 – experienced a 44 percent increase in patient volume over the last three years, a trend expected to continue as the population ages (more than 50 percent of urology patients are over the age of 65).

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Male Infertility One of the first academic medical centers in the nation to create a sperm bank continues to lead the way in male infertility research and in complex clinical care.

An andrology lab and sperm bank were created more than 30 years ago at the University of Rochester Medical Center (URMC). Grace M. Centola, Ph.D., H.C.L.D., former associate professor of Obstetrics and Gynecology at URMC, was instrumental in creating the bank, in collaboration with Robert Davis, M.D., and Abraham Cockett, M.D., from the Department of Urology.

Building on the groundbreaking sperm

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bank, today URMC’s Urology department now boasts two fellowship-trained male infertility specialists—Jeanne H. O’Brien, M.D. and J. Scott Gabrielsen, M.D., Ph.D.

A nationally recognized male-infertility expert, O’Brien has received numerous awards and recognitions for both her clinical and basic science research work.

Gabrielsen focuses on male reproductive health, including male infertility, erectile dysfunction, male sexual dysfunction and

| Department of Urology | urology.urmc.edu

low testosterone.

Both are fellowship-trained, male reproductive urologists prepared to deal with the most complex infertility cases and to perform complex microsurgeries, such as vasectomy reversals and testicular-sperm extraction.

Partnering with URMC’s female infertility experts, the male infertility clinic is part of a designated in-vitro fertilization center of excellence in New York state.

Complex Care URMC’s male infertility clinicians see a growing number of patients with malefactor infertility, such as decreased sperm counts, motility or morphology.

The first steps in the care process are a baseline semen analysis, coupled with an understanding of a patient’s health

history. Hormonal and other testing may be obtained based on these results to try to identify the cause of infertility and how it may be best treated.

Male fertility is complex and requires a number of genetic, hormonal, anatomical, environmental and other factors. As such, abnormalities in any of these areas can result in infertility. Additionally, many lifestyle factors, medications, drugs and environmental exposures can impair a man’s fertility. “Given all the factors that can impact fertility, it’s a wonder people ever get pregnant at all,” O’Brien said.

Infertility affects 10 to 15 percent of couples. It is estimated that a male factor contributes to 50 percent of cases.

Nonetheless, it is often viewed as a “female disease,” and with only a few sperm needed in order to do in-vitro fertilization, most men do not undergo evaluation.

Evaluation of the male partner is critical to improve the likelihood of successful pregnancy. “You can tell a lot from a physical exam and from patient history,” O’Brien added. “The information gleaned

from those help us to determine which type of testing to pursue. From there, we can recommend a solution, whether pharmacological or surgical.”

Medications can be used to help boost sperm production and quality. Microscopic surgical treatments range from sperm retrieval for patients with cystic fibrosis and vasectomy reversals on an outpatient basis, to microscopic testicular sperm extraction in an operating room. These treatments, combined with advances in assisted reproductive techniques, allow many men to become fathers.

The benefits of evaluating the male partner goes beyond just successful pregnancy. Both URMC male infertility specialists believe strongly that the time has come for a men’s reproductive health assessment to be part of a routine internal medical exam. There is evidence that men with infertility have higher rates of chronic disease, cancers and genetic abnormalities compared to fertile men. While evaluation can help identify the cause and guide treatment, it is also an opportunity to identify problems that could affect the health of the man or his future children.

Innovative Research Despite the advances in understanding male infertility, much remains that is not understood. To address this gap, URMC’s specialists are conducting a series of innovative research studies on male infertility.

About 1 percent of the adult male population is sterile because they don’t make sperm. For many of these men, no sperm are found in the testicle and so there are no options for them to have their own children. Gabrielsen, who also has a Ph.D. in Biochemistry, is looking to better understand why some men do not make sperm and how we might help them move from “no sperm to some sperm” — research that began during his andrology fellowship at Baylor College of Medicine.

Prior studies have had difficulty identifying new genetic abnormalities that contribute to infertility, in part because of the number of different potential causes.

For example, more than 3,000 genes are necessary to make sperm, abnormalities

in any of which could potentially disrupt the process. Meaning that in a group of men with infertility, each man could have a potentially different cause. Gabrielsen is using bioinformatics and machine learning to identify specific causes for infertility in hopes that future treatments can be personalized to the individual.

Discovering why some men do not make sperm may also provide more global insight into other causes of male infertility and how fertility and general health are linked. “Up to 87 percent of men who undergo sperm extraction won’t ever father a child,” says Gabrielsen. “Understanding the underlying etiology is critical to helping these men become fathers and understanding the health of the father and child.”

This is only part of the department’s innovative clinical and basic science research in male reproductive health.

Gabrielsen also is exploring why testosterone levels and fertility decrease with age in men, specifically looking at how body iron levels affect the male reproductive axis. O’Brien is looking at how vitamin D levels may affect testosterone levels. Both are collaborating to understand how blood sugar and body mass index affect testosterone and sperm levels, and how metformin may improve these parameters.

Preserving Testicular Tissue The institution that created one of the nation’s first sperm banks now is working to expand fertility preservation options beyond conventional sperm banking. Gabrielsen advocates for the development of a protocol to store testicular tissues.

“By preserving tissue ahead of a hormonal or surgical transition, it may be possible to preserve fertility or to treat infertility down the road,” Gabrielsen said.

“Such a bank could have enormous future benefits for children and for the transgender population who undergo fertility-threatening surgery, hormonal therapy or chemotherapy before they enter puberty and have the opportunity to bank sperm.”

URMC’s infertility experts will continue to provide innovative patient care and to achieve major advances in research.

Left Scott Gabrielsen, M.D., Ph.D. Right Jeanne H. O’Brien, M.D.

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Simulation Lays Groundwork for Complex Robot-Assisted Transplant Surgery Last September, URMC become one of only five medical centers in the U.S. to perform a robot-assisted live donor kidney harvest and transplant. This milestone was made possible due to an innovative, immersive simulation program developed by the Department of Urology that prepared transplant surgeons for this complex procedure.

The Simulation Innovation Laboratory (SIL), led by URMC urological surgeon Ahmed Ghazi, M.D., employs a technique that combines advancements in image segmentation, polymer molding, and 3D printing to produce lifelike replicas of organs, bones, tissue, and circulatory systems. These components – which are obtained via patient imaging – are assembled into a 3D printed torso that can then be used in robotic and minimally invasive surgical simulations.

While the practice of using robotic surgery to remove a donor kidney is common,

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typically the recipient receives the organ via an open incision. Employing robotic-assisted surgery for the recipient is complex, due to the speed with which the transplant must be completed in order to preserve kidney function and the complex suturing techniques required to re-vascularize the kidney. As a result, only a handful of medical centers in the U.S. have attempted the procedure.

Working with the URMC transplant surgeons, including Randeep S. Kashyap, M.D., M.P.H., the SIL first developed a series of simulation models that allowed the transplant team to transition from laparoscopic to robot-assisted removal of the donor kidney, allowing the surgeons to progress to surgical proficiency within a safe environment without exposing patient to harm. The team then moved to developing a simulation platform for the recipient portion of the surgery, constructing a bleeding simulation platform that included a kidney model fabricated from

| Department of Urology | urology.urmc.edu

the donor’s imaging and a pelvis model with pelvic vasculature and bladder, developed from the recipient’s imaging. These patient-specific surgical rehearsals were unique in that they allowed surgeons to realistically practice, plan, and address potential problems related to a specific patient’s case prior to the real intervention.

“This platform marks a distinctive shift in the use of simulation from the practice of a specific skill to a tool allowing complete rehearsal of a multi-step event like an operation, which realistically replicates a complete procedure with characteristics specific to each individual patient,” said Ghazi. “At the same time it allows us to quantify performance and measure improvements in clinical parameters such as blood loss and ischemia time which are essential in these cases to result in improved patient outcomes.”

Lab Profile

Education

WilliamTabayoyong, M.D., Ph.D. Michael Witthaus, M.D. William Tabayoyong, M.D., Ph.D., is investigating the therapeutic potential of immunotherapy for patients with bladder cancer.

The discovery of the PD-1/PD-L1 immune checkpoint pathway has led to significant breakthroughs in the understanding of how bladder cancer cells evade destruction by the immune system. The PD-1 receptor is expressed by cells of the immune system and binds to its ligand PD-L1, which is expressed by bladder cancer cells. The interaction between PD-1 with PD-L1 signals the immune cell to turn off its tumor killing function, allowing the cancer to survive and continue to grow. Recently, the FDA has approved five new immunotherapy drugs for patients with metastatic bladder cancer that disrupt the interaction between PD-1 and PD-L1. These drugs have shown significant responses for patients with limited options once the disease has progressed to chemotherapy. Despite these promising findings, the responses to these new immunotherapy drugs range between 17-24 percent, indicating there are many patients who still do not receive benefit. The Tabayoyong Lab is studying novel combinations of immunotherapy and chemotherapy with the goal of determining the optimal regimen that provides the greatest benefit to all patients with bladder cancer.

Michael Witthaus, M.D., is a 5th year Urology resident and his work in genitourinary reconstruction, plastic surgery, surgical simulation, and wound healing has already garnered significant recognition by his peers.

Witthaus’ presentation on surgical simulation for nerve-sparing robotic prostatectomy took 1st place at the 2019 AUA meeting and was published in the British Journal of Urology. His work on a simulation model for penile prosthesis surgery received the “Best Abstract” Award at the 2019 Sexual Medicine Society of North America meeting.

He also has an interest in the history of medicine, which he credits to URMC pediatric urologist Ronald Rabinowitz, M.D., historian for the AUA. Witthaus’ work on former URMC Urology chair Abraham Cockett, M.D., and his collaboration with NASA during the space race to reduce kidney stone risk in astronauts was recognized by the AUA and published in journal Urology.

Witthaus is continuing his research in the URMC Simulation Innovation Lab with a focus on prosthetic surgical education. He intends to complete a Genitourinary Reconstructive Surgery Fellowship and practice within academia, with a focus on the effects of radiation on wound healing and the role of the androgen receptor in urethral stricture development.

Profiles in Philanthropy

The Weinberg Family Irene and Alan Weinberg, who met and married in the 1950’s, have made a life characterized by service, love, and generosity. While the couple subsequently lived in Arizona and Hawaii, the deep ties to Rochester eventually called them home. They raised two children in Rochester while Alan grew the family business—a successful drug store chain called DAW’s founded in downtown Rochester during the Great Depression by Alan’s father, Frank G. Weinberg.

As a teenager, Alan was a patient of Winfield W. Scott, M.D., the founding chair of the URMC Department of Urology, when he underwent a nephrectomy. Later, because of frequent testing and treatments that that procedure necessitated, Alan would become a patient of Irwin Frank, M.D., past president of AUA and now Professor Emeritus. Most recently, Alan was cared for by Jean Joseph, M.D., M.B.A., the chair of the Department of Urology.

The Weinberg’s deep commitment to philanthropy meant that they always thought of ways of giving back and they supported a variety of charitable causes in the communities in which they resided. Before Alan passed away in 2016, the Weinberg family became the primary sponsor of URMC’s Men’s Health Day, a daylong event of presentations by URMC providers created to provide men the knowledge and tools to take control of their own health.

Thanks to Alan and Irene’s vision and generosity, this event – now in its 15th year – continues to be a valuable resource for the community.

To make a donation to the Department of Urology, visit: https://www.urmc.rochester.edu/urology/donations.aspx URology

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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 Divya Ajay, MD, MPH Assistant Professor of Urology Zaheer Alam, MD Assistant Professor of Clinical Urology Jonathan Bloom, MD Assistant Professor of Clinical Urology Jimena Cubillos, MD Associate Professor of Clinical Urology and Pediatrics 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

Ronald Rabinowitz, MD Professor of Urology and Pediatrics Hani Rashid, MD Professor of Urology and Oncology Director of Residency Program Annette E. Sessions, MD Assistant Professor of Clinical Urology

Diane Lu, MD Assistant Professor of Clinical Urology

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 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, PhD Professor of Urology, Oncology, Pathology and Laboratory Medicine

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