urology at yale | 2018

Collaboration & Innovation at Work “As we look ahead to 2018, we will continue to bring the best minds in urology together to deliver patient- centric, innovative care to our patients, their families, and our field.” – Peter G. Schulam, MD, PhD

I am pleased to introduce to you our new annual publication, Urology at Yale. Born from a desire to share the impact of our work with our colleagues, counterparts, patients and friends, we hope Urology at Yale provides you with a snapshot into the meaningful and innovative work happening here in New Haven. 2 In this inaugural issue, you will learn about the goals Dr. Leslie Rickey has in year three of her five-year NIH contents grant to promote and destigmatize conversation around Chairman 2 Collaboration and Innovation at Work women’s bladder health. Dr. Preston Sprenkle is pushing the Peter G. Schulam, MD, PhD The collaborative efforts of Yale’s Stone Disease and Stone Research teams, boundaries to improve imaging of the prostate for precise including the development of the nationally-recognized S.T.O.N.E. Score and the diagnosis for men with prostate cancer. Dr. Dinesh Singh Deputy Director, multidisciplinary approach to preventing kidney stones, has moved them to the Administration & Clinical Affairs forefront of stone disease diagnosis and treatment. As a result, our patients are the and the stone team take a multidisciplinary approach to Kevin Vest, MBA, FACHE benefactors. treatment and prevention of kidney stones. Genomic profiling of renal tumors has given patients of Dr. Brian Shuch new Director, Public Affairs & Marketing hope, and we explain why. The rapidly-growing Gender Renee Gaudette 4 Yale Joins National Effort to Improve Women’s Bladder Health Affirming Program led by Dr. Stan Honig is opening doors Dr. Leslie Rickey wants to redefine how we think about bladder conditions in girls and Associate Communications Officer for transgender patients in Connecticut and across New women and promote bladder health. As one of seven clinical sites in the Prevention Eliza Folsom of Lower Urinary Tract Symptoms (PLUS) consortium, her multidisciplinary team is England. helping to create a definition for bladder health, developing a robust community Growth has been a recurring theme since I joined Yale Designer network to open the lines of communication to the public, and utilizing focus groups University as the Chair of Urology in 2012. It was our priority Frankie Winter to determine a knowledge baseline. to grow and expand the department to meet the needs of our Photographer patients, and we certainly have met that challenge. Our team Peter Baker 6 The Brain-Bladder Connection of physicians, scientists, and advanced practice providers has After two and a half years of consulting with specialists, the Anderson family was grown to 44 since I arrived, which is an increase of more than Writers at their wit’s end in trying to help their young son resolve his bladder pain and 150 percent, and our faculty recruitment has allowed us to Eliza Folsom 4 Steve Kemper incontinence. But after meeting with Dr. Israel Franco, Director of Yale’s Pediatric continue to add many talented individuals. In parallel, patient Bladder & Continence Program, he devised a non-invasive treatment approach that Kristin Rattini visits have increased more than 1,200 percent since 2013. As transformed their lives. Colleen Shaddox part of our commitment to train future leaders, our residency Urology at Yale program has grown from two to three residents per year, with Is published annually by the Department of Urology at Yale School the hope to increase again in the near future. 8 Surgery – and an Environment – that Breaks New Ground of Medicine and Yale New Haven Hospital. As the Director of the only Gender Affirming Surgery Program in Connecticut and a As we look ahead to 2018, we will continue to bring the best reconstructive urologist, Dr. Stanton Honig has established a state-of-the-art program minds in urology together to deliver patient-centric, innovative Yale Urology for his transgender patients. By creating a patient-friendly environment and providing care to our patients, their families, and our field. medicine.yale.edu/urology reproductive planning and social worker assessments in line with WPATH guidelines, Dr. Honig has developed a program that is meeting and exceeding expectations. Most sincerely, © Copyright 2018, Yale Urology. All rights reserved. No part of this periodical may be reproduced by any means, prints, electronic, or any other, 10 Advances in the Detection of Prostate Cancer without prior written permission of the publisher. Current imaging tools for prostate cancer lag behind technologies used in other Peter G. Schulam, MD, PhD Editorial Office cancers, but Dr. Preston Sprenkle is working to change this and push the field Chairman Yale Urology forward. Merging experience with collaboration, he aims to improve imaging 2 Church Street South, Suite 312 interpretation software to create a precise image of the prostate. Department of Urology New Haven, CT 06519 urology.yale.edu 12 Codebreaker: Profiling Kidney Cancers [email protected] Genetic profiling of renal tumors is a complex process, but it provides acrucial 10 window into the composition – and potential treatment – of a tumor. Dr. Brian Shuch believes such profiling can guide the decision to monitor a lesion or perform surgery to remove the lesion or entire kidney. His patient, Dr. Jerome Serling, can attest. STONE DISEASE

Collaboration & Innovation at Work Kidney stones are formed to develop in nearly of patient stones and provides options for “Not only was the STONE score an exceptional one in every ten Americans. Often, this results patients to managing their care with medicine development by our team, but receiving external in severe pain and a trip to the emergency in combination with diet. Nearly 25% of the validation from our counterparts at Mass General room, leading to missed work and high genetic component to stones is familial, and was especially exciting,” said Dr. Singh. healthcare expenditures. The rate of kidney when a patient has a first degree relative (parent, The Yale Stone Research Team next took this stone occurrences has risen in recent years, and sibling, or child) with stones, their own risk study one step further and explored the concept as a result, the economic impact of kidney stones increases significantly. Dr. Dahl uses a battery of using the STONE score to filter patients away – direct treatment and indirect costs from lost of tests from both urine and serum to identify from unnecessary high-dose CT scans and worker productivity – has exceeded $5 billion the patient’s individual risk factors for stones instead to ultra low-dose CT scans. Dinesh Singh, MD annually. But the Yale Stone Team believes and thus, can modify that patient’s risk for future In a randomized study of more than 250 kidney stones can be a preventable disease. stones. Amy Bragagnini, RD, Clinical Dietician, patients, they determined that those who received “We believe failure of patients to prevent provides dietary recommendations based on the the low dose scans received nearly the same stones is not only due to a lack of implentation of context of all medical issues present, including diagnosis as patients given the standard scan. standard hydration and diet recommendations, obesity and diabetes, two common issues found 2-5% of stones were missed with the low dose but rather a lack of education and identification of in kidney stone patients. procedure, but were found to be 5MM or less in individualized risk factors for stones,” suggested Expanding beyond the clinical setting, the size and thus, non-clinically important. Dr. Dinesh Singh, Assistant Professor, Urology Yale Stone Research Team, a collaboration The number of high-dose CT scans performed and Director, Endourology and Laproscopy. representing urology, emergency medicine, on kidney stone patients has skyrocketed in part Dr. Singh and the other members of Yale’s biostatistics, and radiology, is leading efforts due to an overall increase in patients developing stone team deploy a collaborative and proactive to better manage patients who present with stones, and simply, because of the indiscriminate approach to treatment. Urology, nephrology, and flank pain, to better identify patients who need use of CT scans. In 2007, the rate of CT scans nutrition experts work together to help patients imaging, and to reduce the harms of radiation in performed in the U.S. was nearly 228 per 1,000 with treatment, teaching them how to manage their stone patients who are often subjected to multiple people, more than double the rate in Canada and existing stones and providing strategies to reduce and sometimes high dose CT scans. four times the rate in the United Kingdom. This the risk of future kidney stone development. Once The team discovered five factors most has led to an estimated 1 in every 500 to 1 in every one stone has formed, odds increase to 50-50 that predictive of a kidney stone: Sex of the patient, 1,500 patients being put at risk of developing another will develop within the next ten years. Timing or duration of their pain, Origin or race additional malignancies from radiation exposure. Dr. Singh and his team are working to make that of the patient, Nausea or vomiting symptoms, Yale is an ardent advocate in its efforts to probability more favorable to the patient. and Erythrocytes or blood in the patient’s increase the utilization of low dose CT scans by When patients arrive for their appointment, urine, which is known as a “STONE score.” publishing research articles with randomized At their first appointment, it is a “one-stop shop” according to Dr. Singh. These factors were determined to accurately studies as well as giving lectures across the US. They meet with physicians representing each and reliably predict which patients do and do Its efforts have not gone unrecognized. When aspect of the clinic team, receiving a unified, but not have a stone present in their ureter, based the study results were published, only 2% of patients meet with unique message from each physician based on on their STONE score. This groundbreaking academic healthcare institutions were utilizing their specialty. The urologists, Drs. Dinesh Singh discovery led the team to publish their findings low dose scans, and the most recent estimate physicians representing and Piruz Motamedenia, Assistant Professor in The BMJ in 2014. shows an increase of up to 8%. of Urology, use innovative, low radiation Two years later in 2016, a group of physicians The collaborative efforts led by the Yale Stone each aspect of the clinic imaging to identify stones and best decide what and researchers from Massachusetts General Disease Team and the Stone Research Team options are available for treatment. If surgery Hospital, who, after applying their own patient have moved Yale to the forefront of stone disease team, receiving a unified, is needed, priority is placed on performing data to the STONE algorithm and found the diagnosis and treatment. And as a result, patients state-of-the-art procedures that are minimally same results, published an external validation of are the benefactors. “They truly become our but unique message. invasive for the patient and offer the optimal the STONE score. The STONE score is used in patients,” said Dr. Singh. “We are shepherds of outcome. Dr. Neera Dahl, Associate Professor, emergency rooms at Yale New Haven Hospital their stones and it is our duty to provide the latest Medicine (Nephrology), studies the genetics and its application is increasing nationwide. in technology and be surgically state-of-the-art.”

2 urology at yale | 2018 urology.yale.edu 3 FEMALE PELVIC MEDICINE

Yale Joins National Effort to Improve Women’s

Leslie Rickey, MPH, MD Bladder Health Dr. Leslie Rickey treats women for a Rickey. “I utilize both non-surgical treatments affects so many women throughout their lives constellation of lower urinary tract symptoms, and minimally invasive procedures for women and it can really limit the activities that women including incontinence. Ideally, she would that can really improve their quality of life.” can be involved in later in their lives,” said like to have ways to better identify girls However, she believes that there are women for Jessica Lewis, Deputy Director of Pregnancy and women at risk and intervene earlier, whom earlier detection and intervention might Research at the Yale School of Public Health. but research has focused almost exclusively prevent the need for a surgery down the line. “Our hope is that once women become more on developing better treatments rather than Dr. Rickey would like bladder problems to aware of their bladder health and realize there maintaining good bladder health. Dr. Rickey be destigmatized to the point where patients are things they can do, they will concentrate is committed to changing that. seek care earlier, when simpler remedies may on those pieces of behaviors or environmental The Associate Professor of Urology solve the problem. Even more so, she wants stressors that are modifiable.” recruited a multidisciplinary team and to be able to offer advice on prevention. Each of the PLUS sites is conducting focus successfully competed to make Yale one At present, however, little is known about groups to learn more about women’s current of seven clinical sites in the nation for the the factors that protect women from bladder knowledge and experience with bladder health. Prevention of Lower Urinary Tract Symptoms problems. In fact, one of the first goals of the At Yale, the focus groups will concentrate (PLUS) consortium. The National Institute of project is to define what a healthy bladder is. on young women from the New Haven area. Diabetes and Digestive and Kidney Diseases No such standard exists now. “It takes some skill to get young people to at the National Institutes of Health is funding PLUS researchers hope to make discoveries speak about a topic that they’ve never thought the first large-scale study of bladder health that will substantially change the way clinicians about,” said Dr. Deepa Camenga. Though Dr. in women. The PLUS consortium brings support women, but those findings should not Camenga, whose expertise is in adolescent together a diverse group of investigators from be confined to professional journals. “One health, has an office close to Dr. Rickey’s, they the medical and social sciences that includes of the things I really like about what I do is had never met before they began discussing the epidemiologists, clinicians, and prevention education,” said Dr. Rickey. “The level of possibility of making Yale a PLUS site. One specialists. The group is taking the unique lower urinary tract information housed in day, Dr. Camenga looked up from her desk to approach of using a public health lens to shift the scientific community that doesn’t get well see a woman in scrubs, Dr. Rickey, a bit flushed research and practice towards promotion of disseminated to the public is just stunning.” because she’d just run from the operating room bladder health. For this reason, the PLUS consortium has to get in a conversation between surgeries. “Although lower urinary tract issues affect prioritized developing a robust community “Are you Doctor Camenga? I’ve been trying up to 1 in 3 women, bladder health isn’t engagement network in order for community to meet you. Do you have a few minutes to This is a large, public health something that people talk about,” said Dr. members to have input on everything from talk to me?” she asked. Dr. Camenga laughs at Rickey. She regularly sees patients who have research constructs to language used in survey the memory. “I thought, ‘Wow, that woman issue that affects almost coped long-term with incontinence by using items and eventually, help with getting the is excited.’” She continued: “I think this pads, limiting fluid intake, avoiding exercise message across to the public. There could highlights the great diversity of experience every girl or woman – it and travel, or by mapping out the bathrooms even be implications for policy change, said at Yale. We were awarded this because Dr. wherever they need to be. “Sooner or later, the Dr. Rickey, such as workplace rules about Rickey was able to bring together people with affects their physical and bladder dysfunction overwhelms their ability bathroom breaks or equitable toilet availability very diverse experiences.” to compensate for it,” she said. in work places, schools, and public spaces. Three years into the project, Dr. Rickey emotional health. “I don’t want to downplay the extremely Dr. Rickey formed a team of people who remains excited. “This is a large, public health effective treatments we have for people with had never worked together before but quickly issue that affects almost every girl or woman – incontinence or overactive bladder,” said Dr. bonded around the task. “I think it’s huge. It it affects their physical and emotional health.”

4 urology at yale | 2018 urology.yale.edu 5 PEDIATRIC UROLOGY

The Brain-Bladder Connection

Erik and Salina Andersen were at wits’ end. hardship and recovery time for his young He had already failed novel medical treatments Since the age of 3 ½, their son, Alek, suffered patients. He was among the earliest practitioners that his urologist had tried at the suggestion of from torturous spasms. Sudden, intense pain of biofeedback therapy, which attunes patients Dr Franco. Instead of a continuing down a path in his bladder area would drop their son to to the sensation of the proper muscle relaxation of standard medications, Dr. Franco suggested his knees 20 to 30 times a day and trigger necessary for controlled urination. they first try TENS. This non-invasive treatment incontinence. “Alek called them ‘twisties,’” Dr. Franco’s practice took another giant leap is most often used for back pain, but Dr. said Erik Andersen. “You could see the pain forward with the advent of functional MRI. Franco has incorporated its use in his treatment in his face.” “It opened up the field by showing us what armamentarium with great success. Israel Franco, MD Their search for answers for Alek’s ‘twisties’ was going on in the brain,” he said. “It became In TENS, a small battery-operated device led the Chicago couple to multiple specialists, clear that the sites of the brain associated transmits a low-voltage electric current whose conflicting diagnoses offered no relief with the voiding function were the same sites through two electrodes adhered to the skin. from the debilitating episodes. After 2 ½ years associated with what we call ‘syndrome mix,’ For Alek and other pediatric urology patients, of endless frustration, the Andersens finally or executive-function disorders such as ADD, the electrodes are placed over the “dimples” found the help they needed from Israel Franco, OCD, anxiety, depression, etc. We started on both sides of the lower spine, where the MD, Director of the Yale New Haven Children’s exploring whether there was a link between sacral nerve lies close to the surface. The Bladder and Continence Program. the two.” treatment lasts 30 to 45 minutes each day. “It Throughout his three decades of leadership Dr. Franco’s research into the mind-bladder seems that those sites in the brain associated in pediatric incontinence, Dr. Franco connection marked a paradigm shift in the with the control of the urge to void are being has repeatedly revolutionized the field by field of pediatric incontinence. “Prior to then, activated,” Dr. Franco explained. “Somehow, championing the link between the brain and everything was the bladder, bladder, bladder,” through neuroplasticity changes in the brain, bladder in urinary incontinence and had sought he said. “But the bladder doesn’t stretch we’re able to reset the sensation in their brain non-invasive methods as a means—to reset the itself out if the brain doesn’t let it. In the that allows the child to begin to stay dry or fix brain-bladder connection and restore his young end it’s an interplay of bladder physiology, the way they urinate.” patients’ continence and confidence. neurophysiology, the gastrointestinal tract, and Typically, after eight weeks of TENS, parents It now seems a bit ironic that Dr. Franco was psychiatry. They are four points in a square that will see a sudden, dramatic improvement in their first drawn to pediatric urology because of its all come together. You need knowledge of all child’s bladder control. But, Alek’s case was not opportunities to perform complex surgeries. of them.” typical. “In one week, our son was cured,” Mr. Dr. Franco’s research marked As he learned more about his patients, he The Yale New Haven Children’s Bladder Andersen said. “Dr. Franco transformed our concluded that the standard diagnostic and and Continence Program helps children age lives. Alek was cured just in time for first grade. a paradigm shift in the field. treatment protocols were failing them. “A lot 5 to 21, like Alek, gain bladder control. When He’s such an outgoing and friendly kid/boy, and of the things we were doing were not evidence- families like the Andersens first arrive, Dr. he is finally able to engage in social activities in In the end it’s an interplay based,” he explained. “There was a clear-cut Franco reviews an extensive questionnaire with a way he was afraid to before.” lack of anyone who had any true insights. I them that enables him to quickly distinguish As Alek continues his daily at-home TENS of bladder physiology, became that person, simply because I was the if the core issue is one of emptying, urgency, treatment, Dr. Franco continues to explore one seeing these patients. I started thinking or sensation. “We were very grateful that Dr. the mind-bladder connection. “I was drawn to neurophysiology, the outside the box to try to change the way we Franco spent quite a bit of time with us,” Mr. work at Yale because of the research potential approach the problem.” Andersen said. “He was interested in really here,” he said. “Yale has 13 MRI machines just gastrointestinal tract, and His interest dovetailed perfectly with understanding Alek’s total history.” for research. And we’ll be able to do genetic advancements in medical technology. Dr. Franco Dr. Franco concluded that Alek’s bladder testing as well. I knew Yale was the ideal place psychiatry. was an early adopter of laparoscopic and robotic spasms were caused by an inability to modulate for me to be able to study these children. We bladder surgery, which minimized the physical signals from the bladder appropiate in his brain. are dedicated to taking care of these children.”

6 urology at yale | 2018 urology.yale.edu 7 TRANSGENDER CARE & GENDER AFFIRMING SURGERY

Surgery – and an Environment – that Breaks New Ground

Yale was the first medical center in New reconstructive urology,” he explained. The patients to transportation, housing and other England to provide gender affirming surgery inverted skin of the former penis becomes necessities. She also tries to “think outside the for male-to-female transgender patients and a vagina. Making a new clitoris with good box” to help patients build a support network Stanton Honig, MD remains the only site in Connecticut to offer sensation is similar to other operations we do of extended families and friends. Soon the the procedure. The Director of the Gender on the penis. Dr. Honig has been performing program will provide a patient support group. Affirming Surgery Program, Dr. Stanton the operations together with a plastic surgeon, The Gender Affirming Program surgery Honig, is most proud of the environment that and together, they are dedicated to providing team is also working to arrange affordable his team has created. state of the art surgical care. patient lodging near the medical center. Many “We have worked very hard to make our The Program follows the guidelines of World patients travel from out of state to have the center a place where transgender patients Professional Association of Transgender surgery at Yale and all must return for follow feel comfortable, because that’s what they Health (WPATH). Patients must be 18, have up visits within a week after the procedure. deserve,” said Dr. Honig. “One of the things care letters from mental health professionals “We’re continuing to learn and improve that you have to realize is this population attesting that they understand the procedure our technique, and we’re dedicated to being historically has not been treated well by the is irreversible, and understand the risks and a state of art center for gender affirming medical profession.” nature of the surgical transition. Patients surgery,” Dr. Honig said. He travels to share The Program provides training for everyone must also be on continuous hormonal therapy experiences with other urologists performing – from the clinical receptionists who answer and dress in the gender that they feel most gender affirming surgery and expands the the phones to the attending physicians – comfortable for at least one year. Most, said field through his leadership on the American to create a welcoming environment for Dr. Honig, have been living as transgender Urological Association’s transgender transgender patients. women for much longer. education working group. “A lot of our patients haven’t received Dr. Honig is also Director of Yale’s Male An estimated 1.4 million adults in the proper healthcare for most of their lives,” said Reproductive Health Program and can assist United States identify as transgender. Though Meghan Curran, RN, assistant patient services his patients to freeze their sperm to preserve they will choose from a variety of surgeries, manager for the Department of Urology. their ability to have biol ogical children, if they or choose no surgery at all, the need for more She described an all-too-common scenario so desire. Care is long-term, in keeping with urologists trained in gender affirming surgery in a doctor’s office of a transgender woman the patients’ unique needs. For example, the is clear, particularly as changes in insurance wearing a dress and getting the “third degree” women will need the same prostate screenings reimbursement have made the surgery when her driver’s license showed a different as male patients following their surgery. a possibility for more people, especially in first name and gender – and never making it Care is also holistic and includes an Connecticut, explained Dr. Honig. past the waiting room for her appointment. assessment by the team’s social worker, But he also emphasized that training clinicians We’re dedicated to being Listening to his patients was what led Dr. Fentyshia Daniels, LMSW. The discrimination in the interpersonal side of the practice is every Honig to begin offering gender affirming that transgender patients frequently experience bit as important as passing on technical and a state-of-the-art center for “bottom” surgery. A reconstructive urologist, causes many to be separated from family, suffer surgical knowledge. “It used to be called gender Dr. Honig began performing the surgeries economically, or experience mental health confirming surgery. Nobody needs to confirm gender affirming surgery. when patients themselves requested them. challenges like depression and substance their gender! Patients affirm their own gender “The best way to explain it is: each part of the abuse. When counseling her patients, Ms. and call it gender affirming surgery because operation is something that we already do in Daniels starts with basics, such as connecting that’s what it is. Affirming,” he said. 8 urology at yale | 2018 urology.yale.edu 9 UROLOGIC ONCOLOGY: PROSTATE CANCER

Advances in the Detection of Prostate Cancer

Aside from skin cancer, the most common site technology. Using software algorithms, MR-US the rectum, so it’s pushing against the prostate, Preston Sprenkle, MD for cancer in American men is the prostate, fuses the two different images to capitalize which causes some compression-deformation. with an estimated 160,000 new cases last year on information from both. The resulting 3-D The Artemis system stretches and shrinks and [ed.—2017]. Prostate cancer is also the third images enable physicians to identify suspicious grows one surface to make it fit into the other, most deadly for American men, with more lesions in specific locations within the prostate. and then you cut in the rest of the image.” than 26,000 deaths in 2017. Yet the standard “By doing that,” explained Dr. Sprenkle, “we The partial deformation of the prostate diagnostic method of searching for prostate know where to place our needle to sample the during ultrasound introduces a degree of tumors lags behind technologies used in other tissue. These targeted biopsies have increased imprecision that can lead to missed lesions. cancers. Researchers in the Yale School of our detection of higher-risk prostate cancers.” Drs. Papademetris and Sprenkle are trying to Medicine’s Department of Urology are working MR-US fusion isn’t yet the standard for reduce that imprecision by translating clinical to change that. They are developing imaging several reasons. First, adding MR to the biopsy experience—Dr. Sprenkle has done about 800 tools to give surgeons and radiologists a clearer adds cost, which some hospitals and insurance biopsies using MR-US—and data from previous picture of prostate cancers. Clearer images companies resist. Second, fusion technology is patients into better software that calculates and translate into more accurate diagnoses and still new, and data about its benefits and cost corrects for probable deformations, and thus more precise targeting of the tumors. effectiveness aren’t yet conclusive. And third, creates a more accurate image. “We’re working to push the field forward,” though MR-US is an immense improvement The new software is now being validated. said Preston C. Sprenkle, MD, Assistant over ultrasound alone, the two images fuse Drs. Sprenkle and Papademetris expect to test Professor of Urology and Chief of the Division imperfectly, leaving room for errors in it in a clinical trial early this year [ed.—2018], of Urology at the VA Connecticut Healthcare diagnosis. Not all practices have the expertise along with partners at Stanford University. System. The field needs a push. If a urologist and experience to create the fused images and The ultimate goal is to make fusion imaging wants to determine whether a patient has interpret them correctly. so precise that it automates interpretation and prostate cancer, the standard procedure is to Making interpretation easier is where Dr. eliminates errors. use ultrasound to locate the organ and then to Sprenkle saw an opportunity. He is part of a Dr. Sprenkle is also a pioneer in several kinds insert biopsy needles that take random samples multidisciplinary group at Yale Cancer Center of “focal therapy,” a targeted approach made from the prostate. that collaborates on research related to prostate possible by MR images, which reveal small “It’s as if you can see an apple, and you know cancer. He proposed a project to improve the lesions that can be treated using a variety of Until recently, the prostate there’s a worm in there somewhere, so you put computer system, called Artemis, that does energy sources, saving patients from the severe darts in to get it,” said Dr. Sprenkle. “But since the fusion imagery. He began working with side effects caused by intensive radiation or was the only solid organ you don’t know where the worm is, you have to Xenophon Papademetris, PhD, Professor of removal of the entire prostate. guess—you evenly space the darts and hope you Imaging Processing and Analysis, who involved All of this reflects the commitment of Dr. where physicians didn’t hit it.” This haphazard method has predictably the makers of Artemis. The project is funded by Sprenkle, Dr. Papademetris, and their colleagues mediocre results, missing about a third of all the NIH through its Small Business Technology to deploy better ways of finding and defeating have access to imaging prostate cancers. Transfer Program (STTR). prostate cancer. “It takes a multidisciplinary Until recently, the prostate was the only “Part of the challenge is that images from MR effort,” said Dr. Sprenkle. “We have outstanding technology to see inside it. solid organ where physicians didn’t have and ultrasound look very different,” said Dr. nationally-recognized radiologists and access to imaging technology to see inside Papademetris. “The second problem is that the outstanding nationally-recognized pathologists. Yale was an early adopter of it. That has started to change thanks to new prostate doesn’t have the same shape in an MRI We are very experienced, and experience systems that blend ultrasound with magnetic as in ultrasound, because the MRI is done with matters. In biopsies, being a millimeter or two new technology. resonance (MR), a combination known as the patient lying on his back in a scanner, and the from where the cancer is located can make a MR-US fusion. Yale was an early adopter of the ultrasound is done by inserting a probe through significant difference.”

10 urology at yale | 2018 urology.yale.edu 11 UROLOGIC ONCOLOGY: KIDNEY CANCER

Brian Shuch, MD Codebreaker: Profiling Kidney Cancers Brian Shuch, MD, uses genetic profiling that would suggest renal cell carcinoma and this history of the disease spanning back several to guide the management of renal tumors. tumor had all the characteristics of a common generations. Among the many roles that physicians assume benign tumor. Dr. Shuch and Dr. Serling agreed Dr. Shuch and his colleagues at Smilow’s is that of interpreter. Doctors must be adept that close monitoring of the lesion was the best Cancer Genetics and Prevention Program are on at interpreting a patient’s symptoms and test course of action. “Because of the genetic test, I high alert for these red flags when they evaluate results to reach the right diagnosis. Then they was able to avoid surgery,” Dr. Serling said. “I patients with urologic cancers including kidney must translate that diagnosis into terms that a was very grateful for Dr. Shuch’s use of the test cancer. “Unfortunately, most patients who patient can understand. and his keen clinical judgement.” have a genetic or hereditary component are In his cutting-edge work treating patients With support from an $800,000 NIH grant, never diagnosed,” said Dr. Shuch, who leads with kidney cancers, Brian Shuch, MD, Dr. Shuch is continuing his research on genetic the Program’s Genitourinary Cancers Division. Assistant Professor of Urology and of Radiology profiling, focusing on the heterogeneity of small “In the cases when it is recognized, it’s usually and Biomedical Imaging, has proven himself a renal tumors. “Sometimes tumors can be a after the patient has had treatment and gone gifted interpreter. By evaluating tumors not by mixture of different types of cells,” he explained. for genetic counseling. Most have had surgical shape and size—as has been standard protocol “It can be like a bag of M&Ms with different management of the kidney cancer. If they had for decades—but by genetic profile, Dr. Shuch colors. We know that for small tumors, when known their condition prior, surgery might has launched an entirely new dialogue about the you stick your hand in a bag and find a green have been avoided or different management identification and treatment of these cancers. M&M, then most of the bag is going to be green. strategies could have been employed.” But as his patients can attest, Dr. Shuch also But for large tumors, if you pull one sample, it As part of his evaluation, Dr. Shuch conducts has a talent for conveying the results of this might be a red M&M, but in the bag, there will a genetic screening panel of a patient’s tumor. incredibly complex genetic testing with simple likely be a lot more different colors.” A Yale panel, developed by Dr. Shuch and analogies that help them clearly understand “The importance of this to kidney cancer colleagues, enables screening for the 15 known their diagnosis and treatment options. research is that, if you profile one part of the syndromes of hereditary kidney cancer with just A tumor’s genetic profile reveals crucial tumor and get an answer that this tumor is bad one test. Yale is one of the first centers to promote information: the type of kidney tumor, or good, you want to be sure that you are giving such a panel for kidney cancer, which now is whether it’s benign or cancerous, what kind the patient the best idea of what is in the whole offered by a variety of genetic testing companies. of kidney cancer, and how aggressive it is. bag of M&Ms,” he said. “You don’t want to base Testing multiple genes at once significantly “Some renal tumors may not need to have your diagnosis on an incomplete sample.” streamlines and expedites the diagnostic process. surgery immediately,” he said. “Some can be Another aspect of integrating genetics “Each of the known kidney cancer syndromes are faithfully observed up to a certain size.” He to clinical care is how Dr. Shuch evaluates linked to a specific gene of interest that may not considers these tumors to be “guppies”—not individuals with suspected hereditary forms of be able to be identified clinically,” he explained. harmful—as compared to “sharks,” which cancer. An estimated five to eight percent of “By casting a wider net and testing all the genes at Some renal tumors may require immediate, aggressive treatment. kidney cancer patients have a strong hereditary once, we have a better chance of finding the cause Before his consult with Dr. Shuch, or genetic component. Because of the rarity of of someone’s predisposition.” not need to have surgery patient Jerome Serling, DMD had already these cancers, many caregivers are not familiar Dr. Shuch’s groundbreaking work on genetic been diagnosed with presumptive renal cell with the distinct symptoms associated with profiling holds promise not only for his current immediately. Some can carcinoma. The traditional protocol would them. The median age of onset for hereditary patients but for their families as well. “We’ll be to remove the lesion or kidney. But Dr. kidney cancer is around 36—about 30 years be able to screen their family members and be faithfully observed Shuch first suggested Dr. Serling undergo a younger than other kidney cancer patients. children to detect a tumor before it causes a renal mass biopsy with genomic profiling to Instead of a single tumor, patients may have problem,” he explained. “Because where do big up to a certain size. determine if the lesion was, in fact, dangerous. bilateral or multifocal tumors. A handful of problems come from? Little problems. If we can To Dr. Serling’s great relief, his lesion was a the conditions have related dermatological find it early and fix it, we can prevent them from “guppy.” There were no chromosomal changes symptoms. And in some families, there’s a having significant harm to their livelihood.”

12 urology at yale | 2018 urology.yale.edu 13 333 Cedar Street, PO Box 208058 New Haven, CT 06520-8058

Yale Urology Faculty and Advanced Practice Providers

Angela M. Arlen, MD David G. Hesse, MD Rafaela M. Penarreta, PA-C Ryan Artigliere, PA-C Adam B. Hittelman, MD, PhD Brian Picciano, PA-C Leonid Bilenkin, PA-C Tania Hossin, NP-C Gerald Portman, MD Thomas M. Buckley, MD Stanton C. Honig, MD Victor Quintanilla, PA-C Toby C. Chai, MD Marissa Jacko, PA-C Leslie M. Rickey, MD, MPH John W. Colberg, MD Daniel S. Kellner, MD James S. Rosoff, MD Therese F. Collett-Gardere, APRN, CPNP Patrick A. Kenney, MD Peter G. Schulam, MD, PhD Cynthia L. Curto, MSN, FNP, APRN Sarah M. Lambert, MD Brian M. Shuch, MD Ralph J. DeVito, MD Michael S. Leapman, MD Dinesh Singh, MD Harris E. Foster, Jr., MD Darryl Martin, PhD Preston C. Sprenkle, MD Israel Franco, MD Thomas V. Martin, MD Ralph F. Stroup, MD Kamyar Ghabili Amirkhiz, MD Kaitlyn Murphy, MSN, APRN, CPNP Alfredo Suarez-Sarmiento, MD Mary Grey Maher, MD Piruz Motamedinia, MD Lee Venancio, PA-C George Hayner, PA-C Rebecca Orsulak, PA-C Robert M. Weiss, MD Gillian Hepburn, PA-C Marianne G. Passarelli, MD