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Medicine on the Midway - Spring 2010
University of Chicago Biological Sciences Division - Medicine on the Midway
Medicine Midway U NI V ERSIT Y OF CHICAGO on the Biological Sciences Division Attacking cancer from every angle page 7 S P R I N G / S U M M E R 2 010 Contents Diagnosing Cancer's Chaos By Rob Mitchum When a pathologist peers into a microscope searching for telltale signs of a dangerous cancer in a tissue sample, the first clue is often an aesthetic one. "In the normal tissue, there is a beautiful order," said Thomas Krausz, MD, FRCPath, director of anatomic and surgical pathology at the University of Chicago Medical Center. "In cancer, depending on how aggressive it is, there is chaos." A cell can become a tumor through many routes, growing uncontrollably and invading surrounding areas with, as Krausz puts it, "no respect for its neighborhood." And as the electron micrograph images on these pages show, cells that have become cancerous can take on shapes that are both fascinating and horrific: sprouting tendrils and vesicles that disrupt normal symmetry and reflect inner turmoil. For surgical pathologists charged with determining the diagnosis from a biopsy, the story is rarely so simple as the isolated, cultured cells pictured here. In some cases when a piece of potentially cancerous tissue is taken intraoperatively from a patient, pathologists have a mere 20 minutes to prepare the sample with freezing and stains, examine it with the naked eye and microscopes, and answer several critical questions: Is the tumor benign or malignant? How far has it spread? Has it invaded surrounding blood vessels? Those answers are crucial to a patient's care, determining the course of treatment both immediately through the size of the area removed in surgery and long-term through the use of radiation or chemotherapeutic drugs. "At the end of the day, cancer is diagnosed by pathologists," Krausz said. "Without a pathology diagnosis, there is no appropriate cancer treatment." Newer techniques, like immunohistochemistry and molecular pathology that help categorize tumors by identifying aberrant genes and proteins, have changed pathology and have proven essential in the developing era of personalized medicine. But most decisions are still made with the microscope, a centuries-old technology that -- combined with the experience of a pathologist who has viewed hundreds of thousands of slides -- remains the most powerful tool in classifying cancer. For the trickiest cases, where a firm conclusion eludes the initial pathologist, the department's extensive knowledge across different organ types and diseases is pooled. Daily meetings, in a room equipped with a special microscope through which 16 pathologists can simultaneously view a sample, help pathologists to collaborate, resolve these difficult cases and reach the proper diagnoses. "There's no room for error; we have to be 100 percent accurate," said Husain Sattar, MD, assistant professor of pathology. "We think multiple times before we sign and release our final diagnosis." "There is only one diagnosis," Krausz added. "The correct diagnosis." Special Cancer Issue: Attacking Cancer from Every Angle by Rob Mitchum features Mapping the Genes that Help Cancer Drugs by Rob Mitchum and Susan Chandler Finding Answers through Clinical Trials by Rob Mitchum Advanced Approaches to Treating Breast Cancer by Cheryl L. Reed Getting a Clearer Picture of Breast Cancer by Cheryl L. Reed Life After Cancer is a New Focus for Research by Greg Borzo Saving a Cancer Patient's Baby by Emily Stone Special Urban Health Initiative Pull-Out Section: Transforming Health on the South Side by Stephen Phillips On the Trail Less Traveled by Cheryl L. Reed Finding a Compatible Match for a Gift of Life Before an organ transplant is performed, both donor and recipient undergo months of meticulous tests to determine any incompatibilities. by Rob Mitchum A New Pediatric Comfort Team Makes Life Better for Kids Comer Children's Hospital at the University of Chicago has formed a medical team that alleviates pain for kids. by Emily Stone The Man of Many Coats: Daniel Sulmasy, MD, PhD As a doctor, ethicist and Franciscan friar, he brings fresh perspectives to the Medical Center. by Susan Chandler International Adoption Clinic Assists in Promoting Health of Children Medical Center team works with prospective parents, particularly those who are adopting from other countries. by Katie Scarlett Brandt Nitric Oxide Therapy Proving Beneficial to Preemies' Development For more than 10 years, Comer Children's Hospital physicians have been studying the effects of a new therapy for treating premature babies. They have hundreds of living testaments to its success. by Kevin Davis Medical School Rocks This Future Doc John Paro thought he'd given up music when he entered the Pritzker School of Medicine, but medical school inspired a new album. by Cheryl L. Reed 7 12 13 15 19 29 31 21 25 34 35 36 38 40 44 Top right: A colored scanning electron micrograph of a breast cancer cell. Middle right: Close-up view of lung cancer. Bottom: A colored transmission electron micrograph of a carcinoma cell. Far right: A colored scanning electron micrograph of breast cancer cells. departments Letters/Midway News Read follow-up letters and catch up on the latest research and news in medicine and biological sciences. Medicine off the Midway: Cancer Research Goes to Hollywood Harry Connick Jr., plays him in a Hollywood film, but Dennis Slamon, PhD '74, MD '75, doesn't let his fame distract him. For Slamon, the real stars are the breast cancer patients who participated in clinical trials that led to the FDA approval of his drug Herceptin. by Don Reneau Pritzker News/Alumni Updates/Class Notes Read about students and alumni of the Pritzker School of Medicine and the Biological Sciences Division. 2 32 42 48 Front cover: Radiation oncologists at the Medical Center use a linear accelerator to precisely target tumors within the body. Because of the precision of the machine, radiation oncologists can increasingly treat multiple metastatic tumors. Photo by Dan Dry Perspectives: Four Medical Opinions on Continuing Health Care Reform Four different physicians associated with the University of Chicago Medical Center weigh in on what they hope and fear about the continuing health care reform. Letters Letter from the Editor: It's not often that scientists call to say that a story in Medicine on the Midway made them cry. But that's what Deberah Simon told me when she called to ask if I could forward a letter she'd written to Alyssa Smith and her mother Teri. Alyssa, as readers may recall, was featured on the cover of our fall issue on the 20th anniversary of the first living-donor liver transplant performed in the United States. The transplant occurred at the Medical Center when Christoph Broelsch, MD, then chief of the Medical Center's liver surgery service, and a team of doctors and nurses removed 2-year-old Alyssa's diseased liver and replaced it with one-third of her mother's. Now, 20 years later, Alyssa Smith graduated college on May 9 with a degree in social work and is exploring careers that involve children with transplants. I was so touched by Deberah's letter and her connection to Alyssa -- Deberah was a scientist who worked to prove that a living-donor liver transplant was possible -- that I asked if I could share her letter with readers. I think you'll agree it's a perfect example of how "translational research" at the Medical Center connects scientists to doctors and then doctors to patients. Midway News Coworker Donates Liver to Child Raquel Allen was 3 months old when she was diagnosed with biliary atresia, a congenital condition that affects the liver's ability to secrete bile. Occurring roughly once in every 15,000 births, the disease causes serious and, eventually, fatal liver damage if left untreated. Raquel's parents were told in May 2009 that their daughter would soon need a liver transplant. A living-donor transplant was an option, but neither Coral Grinage nor Melvin Allen, Raquel's parents, matched Raquel's Type O blood, a prerequisite for successful transplantation. "After we found out we weren't a match, we started telling people...just kind of putting the word out there," Grinage said. One person she told was Catherine Ortiz, a 27-year-old Alsip woman who worked with Grinage. Ortiz asked questions, discussed the matter with her husband and decided to volunteer to be Raquel's liver donor. On August 25, 2009, Ortiz donated part of her liver to little Raquel during an eight-hour, living-donor liver transplant performed at Comer Children's Hospital at the University of Chicago. The transplant occurred nearly 20 years after the procedure was performed for the first time in the United States by doctors at the Medical Center. Now, the procedure is performed 12 to 15 times a year at the hospital. Raquel Allen celebrating her one-year birthday at Comer Children's Hospital. Photo by David Christopher It's this kind of advanced care we are highlighting in this issue: scientists and doctors engaged in breakthrough cancer research, translating discoveries in the lab to treating advanced cancer. Here at the University of Chicago Medical Center, we're finding answers where others have found roadblocks. I hope these stories inspire you, and I look forward to hearing from you. Sincerely, Cheryl L. Reed Editor email@example.com Ortiz recovered quickly from her surgery, returning home after two days in the hospital. Meanwhile, 11 days after surgery, Raquel celebrated her first birthday in her Comer Children's Hospital room. Raquel's father said those extra years will be the best birthday present his daughter could ever receive: "What better gift to have than the gift of life?" When Comfort Food Becomes Dangerous October 30, 2009 Dear Alyssa and family, I came home from work today, opened the mail and there was the current issue of Medicine on the Midway with your picture on the cover, and the headline "A Medical First, 20 Years Later." I didn't have to read the article to know what they meant, for, you see, I was part of the team that did the research that led to your surgery. My work was a decade before the actual surgery, so I missed the news when it occurred, and I never knew who it was, only that it was a little girl, and that it was successful. When I saw your face, I sat in my kitchen and cried and cried; I was so overwhelmed -- and I know this sounds silly -- that you were real and alive and such a beautiful person. In the late 1970s, I worked in Dr. James Boyer's hepatology research lab. I was a "lab rat" -- a chemist who worked in medical research. At the Deberah Simon time, the idea was around that you could probably take out a portion of a healthy liver and that the liver would re-grow, or at least that the donor would be able to tolerate the removal and lead a normal life. My job was to try this with an animal model and carefully document the results. There were three of us who learned to operate on rats and then document the chemical and morphological changes. It was incredibly meticulous work, challenging on so many levels. Everything was so tiny, and the changes were so small. We worked for a long time just to be able to complete the surgery successfully. After the difficult work of extracting the sample, it had to be analyzed, and that job was mine. The sample had to be kept cold, and an ice bucket on a bench top didn't work (believe me, I tried). I set up shop in a cold room, which was a small, closet-like room like an old-fashioned meat locker, dim and damp, with a huge thick door and latch, and I did all the chemical work in there. I'd work for an hour or so, then come out and sit on a big radiator under a window until I thawed out, then head back in to work some more. The sample was first run in a blender, then all the cellular components had to be separated. We did this by making a layered column of sucrose solutions of differing densities, then putting the extract on top and spinning it in an ultracentrifuge. I did this day after day, for months, as we slowly built up evidence that it worked. I tell you about this in some detail because I think you'll be interested in how I've used this experience over the years. I teach chemistry at Whitman College, in Walla Walla, Wash. The very first lab I designed, and the one that kicks off the start of fall semester every year for my freshman class, is "Sucrose Density Gradient Columns" -- the lab I wrote using the technique I learned doing the hepatology research 30 years ago. And every single year I tell the story of working in the cold room, and what a tiny little piece I played in a much bigger story, and of how you never know where life will lead you. But in all these years, I've never had a name or a face to put with this story, until now. And that's why I sat in my kitchen and cried to see your smiling face. I wish you, and your incredibly brave family, the very best life has to offer. I feel very privileged to have played even so tiny a part in all of this. Best, Deberah Simon Whitman College Department of Chemistry firstname.lastname@example.com Anyone who's ever eaten a bag of chips in one sitting knows the truth of the slogan, "Betcha Can't Eat Just One!" But chips may not be the only food capable of putting you in an overeating zone, as new research finds that chocolate or water can actually blunt pain. When rats are eating or drinking, they are slower to move their feet away from a hot light bulb, according to research conducted by Hayley Foo, PhD, research associate professor of neurobiology, and Peggy Mason, PhD, professor of neurobiology, at the University of Chicago. The results suggest rats are so focused on completing their meals that their brains make them less susceptible to distractions. "It's a strong, strong effect, but it's not about hunger or appetite," Mason said. "If you have all this food in front of you that's easily available to reach out and get, you're not going to stop eating, for basically almost any reason." In the wild, where food is scarce, ignoring distractions while eating is a good skill to have. But for modern humans, where the next meal is only as far as the nearest supermarket, an unshakable focus on finishing the food in front of you and drowning out distractions can be unhealthy. But the study may also suggest positive uses for pain-blunting effects of eating or drinking. Previous studies have shown that giving sugar water to infants can reduce the pain of an injection, a trick frequently replicated in pediatric offices. A piece of good news from Foo and Mason's study is that the substance used for this pain relief doesn't have to be alcoholic, or even caloric -- water was just as effective as chocolate chips at blunting pain in rats. Only substances that the rats did not naturally enjoy, such as a bitter quinine solution or very salty water, failed to trigger the reduced sensitivity to pain. The results excited Don Katz, PhD, an associate professor of psychology and neuroscience at Brandeis University in Massachusetts, who said it suggests an important biological purpose for taste. "They're saying that the purpose of the taste system is to give an animal a cue that helps it decide what stimuli it should or shouldn't pay attention to," Katz said. "It's really important for them to know when they should stop eating if they don't have to stop eating." Foo and Mason traced the pain relief effects of eating or drinking to the raphe magnus, an area of the brain stem responsible for reflexive actions, suggesting that this effect is as automatic as sweating during exercise. "You're essentially at the mercy of your brain stem, and the raphe magnus is part of that," Mason said. "It tells you, `you're going to finish eating this, whether you like it or not,' just like you sweat while running, whether you like it or not." Hayley Foo, PhD, research associate professor, observes a rat eating chocolate from her neurobiology lab. Photo by David Christopher 2 University of Chicago Medicine on the Midway Spring/Summer 2010 3 Rodney L. Goldstein named Chair of University of Chicago Medical Center Board of Trustees Rodney L. Goldstein, an accomplished Chicago business executive and longtime leader in the university community, has been appointed as chair of the University of Chicago Medical Center Board of Trustees. Goldstein succeeds James S. Crown, who served as interim chair of the Medical Center Board. "Rod's background in planning for the success of varied enterprises will be invaluable as the Medical Center enters a critical period of growth and new opportunities," said Everett E. Vokes, MD, interim dean of the Biological Sciences Division and the Pritzker School of Medicine, and interim CEO of the Medical Center. Goldstein joined the Medical Center Board in 1992. He has been a Trustee of the University since 2006. NOTEWORTHY Don't do it on your own. Gilda's Club, a nationwide support group for cancer patients and their families, meets every Wednesday from 11 a.m. to 1 p.m. in the fourth floor atrium in Duchossois Center for Advanced Medicine, and 2 p.m. to 4 p.m. in room TC-614. For more information, call Kathleen Boss at 312-464-9900 or visit www. GildasClubChicago.org. The University of Chicago's neurosurgery service risk-adjusted mortality rate was ranked second among 105 academic medical centers in the University HealthSystem Consortium's (UHC) Clinical Outcomes Report for July 2008 through June 2009. The Medical Center inaugurated a new pharmacy residency program in 2009, attracting pharmacists from around the nation seeking to enhance their clinical and academic knowledge. The program houses six post-doctorate pharmacists and will double that amount next year as well as expand its duration to two years to provide specialty training for pediatrics and clinical care. Medical Center physicians offering services at the new Vascular Institute of Chicago are, left to right: Tina Desai, MD; Giancarlo Piano, MD; Christopher Skelly, MD; Hisham Bassiouny, MD; and Daniel Katz, MD, chief of Vascular Surgery at Weiss Memorial. A New Vein of Care for Vascular Disease University of Chicago Medical Center physicians now offer their services at the new Vascular Institute of Chicago at Weiss Memorial Hospital, bringing experienced vein and artery care to the city's North Side. The new institute provides a home for all vascular services, using Medical Center physicians to help diagnose patients and create tailored treatment plans based on the patient's condition, medical history and lifestyle. For patients familiar with the University of Chicago Medical Center, Weiss offers the same technology and expertise as those on the main campus, said Hisham Bassiouny, MD, medical director of the new Vascular Institute and chief of the Section of Vascular Surgery and Endovascular Therapy at the Medical Center. The new institute offers state-of-theart diagnostics and minimally invasive, innovative treatments. Bassiouny is the only Chicago-area surgeon who is FDAapproved to use the da Vinci� Surgical System for lower extremity vascular reconstruction. "This unique capability exemplifies our commitment for continually evaluating emerging technologies which can best improve outcomes for our patients," Bassiouny said. "Our enterprise thrives on successfully managing the most complex of cases, and we are thrilled to offer the Chicago North Side our leading edge services for vascular disease management." The Medical Center has an established relationship with Weiss in regard to vascular care. In 2008, the two hospitals collaborated on establishing the Vein Clinic at Weiss, which has successfully treated varicose and spider veins, deep vein thrombosis and other conditions for many years. As a part of the Vein Clinic, the Non-Invasive Vascular Laboratory excels in using ultrasound and doctors' expertise to safely and accurately diagnose vascular conditions. This laboratory is nationally accredited and unparalleled among Chicago's community hospitals. University Research Stimulated by Federal Recovery Act Funds When Barack Obama promised in his inaugural address that his administration would "restore science to its rightful place," researchers across the United States hoped it was more than mere rhetoric. After years of flat budgets from scientific funding agencies such as the National Science Foundation (NSF) and the National Institutes of Health (NIH), many laboratories were in dire need of funding to continue projects and launch new experiments. Eight months into his first term, President Obama delivered on his promise to the scientific community with the American Recovery and Reinvestment Act, which included more than $5 billion directed toward science and medical research. At the University of Chicago, more than 150 researchers received Recovery Act money from the NIH, NSF, National Endowment for the Arts and the Department of Education, totaling nearly $72 million campus-wide over two years. An estimated 79 jobs will be created or preserved due to the funding, according to a university calculation. The majority of that money was awarded to researchers at the Medical Center and in the Biological Sciences Division, with more than $43 million from NIH grants for fiscal year 2009 and an additional $1.3 million from the NSF. An additional $17 million will be awarded by the NIH in the second year of the grants. Some grants as small as $10,000 will help laboratories with day-to-day supply and personnel costs, while several multimillion dollar grants will launch new nationwide clinical trials administered from the University of Chicago. The largest grant, at $5.6 million, was designated to fund the EVE project -- the "mother of all asthma studies," according to Carole Ober, PhD, professor of human genetics and obstetrics and gynecology. Ober and Dan Nicolae, PhD, associate professor of genetic medicine, statistics and human genetics, are primary investigators on the project, which will coordinate researchers at 10 institutions to perform genome-wide association studies on more than 30,000 subjects. The researchers hope to find novel gene variants associated with asthma that will lead to new treatments. "We're excited to receive the funds to launch a project that may open promising new avenues for asthma research," Ober said. Another multicenter clinical research effort will be directed from the Medical Center by Jerry Krishnan, MD, PhD, associate professor of pulmonary medicine. CONCERT, a collaboration among six health care institutions, was given nearly $4 million to begin studies comparing treatments for chronic obstructive pulmonary disorder, which is expected to be the third most common cause of U.S. deaths by 2020. Basic science research also received several large grants from the Recovery Act funds. Kevin White, PhD, professor of human genetics and ecology and evolution, received two $900,000 grants to help the NIH ENCODE project create an encyclopedia of DNA elements. A new technique created in White's laboratory will be applied to the genomes of humans and Drosophila, the fruit fly that has historically been an important scientific model for genetic function. Summaries of all university projects that received Recovery grants can be found at http://arrafunding.uchicago.edu Esra Tasali, MD, received $1 million to research the relationship between sleep apnea and the onset of Type 2 diabetes. Photo by Lloyd DeGrane BRIEFLY Tiny dinosaur, big discovery The smallest dinosaur ever discovered in North America was recently identified from bones that have been housed at the Natural History Museum of Los Angeles County. Originally discovered in Colorado in the 1970s, the bones have been in storage ever since. In Praise of Genetic Diversity It was an intriguing find for evolutionary biology: two genes involved in the size of the developing human brain were subject to selection in recent human history, and may still be evolving today. But when Bruce Lahn, PhD, a University of Chicago professor of human genetics, published this discovery in 2005, he knew that it might create controversy alongside excitement. A variant of one of the genes, microcephalin, occurred less often in sub-Saharan Africa than other regions of the world, while the other gene, ASPM, had a variant seen commonly in Europe, North Africa, the Middle East and South Asia but less often in East Asia, Native Americans and Sub-Saharan Africa. Lahn suspected extremists would distort his evidence of these genetic differences to inappropriately justify racist beliefs. What he didn't expect was that credible scientists would also distort his findings, and that some would actually question whether his research should have even been performed in the first place. After that experience, Lahn decided that both the scientific community and society in general needed a new moral framework to deal with rapidly growing information about how genes differ between individuals and groups. In an "Instead of trying to suppress the science, we should try to build a moral consensus that is constructive to the overall well-being of the species," Lahn said. Lahn argues that the idea that there are no significant differences between ethnic groups is in fact more dangerous than the potential misuse of human genetics research. Scientists may be pushed away from important research questions instead of adding to growing evidence that the grouping of individuals can be medically useful in the growing fields of personalized medicine. (See the mapping genes article on page 12.) The solution, Lahn and Ebenstein argue, is to convince people to accept genetic diversity as much as they have grown to appreciate cultural diversity in recent decades. "Genetic diversity is a strength, not a weakness, of humanity," Lahn and Ebenstein wrote. "On the whole, humanity has been and will be stronger, not despite our differences, but because of them." Fruitadens haagarorum stood only four inches tall, weighed two pounds and was 28 inches long. The agile, fast-running omnivore lived 150 million years ago during the Late Jurassic Period, which makes it one of the earliest dinosaurs. The new species was identified from parts of skulls, vertebrae and limbs of four specimens. Fruitadens belonged to the heterodontosaurids, an important group of dinosaurs previously unknown in North America. The species was identified by Richard Butler, PhD, of the Bavarian State Collection for Paleontology in Munich, and his team. The team, along with Laura Porro, PhD, postdoctoral research associate in Organismal Biology and Anatomy at the University of Chicago, discovered the species. An illustration of a marked chromosome. opinion piece published in the journal Nature last October, Lahn and co-author Lanny Ebenstein, PhD, of the Department of Economics at the University of California, Santa Barbara, argued that researchers must embrace and even celebrate the idea of genetic diversity. Bones of fruitadens haagarorum 4 For more information, call 1-888-UCH-0200 or visit uchospitals.edu Spring/Summer 2010 5 Special Cancer Feature Donna Van Ryn in her front yard. Photo by Bart Harris Scorpion Venom Keeps Brain Tumor in Check A drug derived from scorpion venom appears to be helping a 49-year-old Tinley Park, Ill., woman beat the odds. Diagnosed in December 2005 with a deadly glioblastoma multiforme, Donna Van Ryn has lived almost three times the median survival of 15 months -- and feels fine. She has been through two brain surgeries to remove her cancer, which oncologists suspect is the same type as the late Sen. Edward Kennedy's. She went through aggressive radiation and chemotherapy, and two clinical trials of investigational drugs. But the treatment to which she is currently responding involves a medication fashioned from a scorpion's sting. Van Ryn says she now feels better than she ever has since noticing her first symptoms, and her scans show no evidence of recurrent disease. She walks three miles a day and just started a new job as a secondgrade teacher. "I'm pretty much back to my normal self," she said. The drug, known as I131-TM601, is produced by TransMolecular, Inc., a small biotechnology company based in Cambridge, Mass., that focuses on targeted therapies for cancer. It combines radioactive iodine (I131) with a piece of a toxin (TM601) derived from the venom of the Israeli desert scorpion, ominously referred to as "deathstalker." The toxin fragment recognizes and binds to receptors found on the surface of glioma cells while bypassing normal, healthy cells. It is given intravenously, enabling it to travel throughout the body and target tumor cells. Within the brain, it "shockingly homes right in on glioma cells," said trial director Steven Chmura, MD, PhD, radiation oncologist at the Medical Center. "We often talk about targeted therapy, but this is far more targeted than most of what we see." Attacking cancer from every angle By Rob Mitchum With contributions from Don Reneau and Susan Chandler Cancer has been a deadly riddle without a solution for centuries. The desperation to find a cure led to unusual theories from visionary scientists, such as Leon Jacobson, MD, at the University of Chicago in 1943. Observing that soldiers exposed to the chemical weapon mustard gas exhibited low white blood cell counts, Jacobson proposed that the toxin could be used to treat leukemias -- cancers that produce an excess of those very cells. The experiments worked, and what we now know as chemotherapy was born. Many patients showed remission of their cancer when exposed to nitrogen mustard, the active ingredient of mustard gas, but at a price -- the side effects were severe and unpleasant. A tool for treating cancer had been found, but it took the coarse strategy of using poison to cure. In today's cancer treatment, the strategy is the same, but the tools are far more advanced. A cancer patient lies immobilized on a platform in a dark room of the Duchossois Center for Advanced Medicine. Silently, a meshwork of lasers crisscrosses his body, almost completely covered by a protective lead gown. Above his head, a mechanical arm glides in a semicircle, imaging the patient's tumor immediately before firing beams of radiation from multiple finely calibrated angles calculated by a powerful computer. The procedure, Image-Guided Radiation Therapy, or IGRT, shares a purpose with the chemotherapy of nearly 70 years prior: to kill cancer cells with a destructive force. But rather than applying radiation broadly and damaging healthy cells along with cancerous ones, IGRT uses the latest technology to focus radiation directly at the tumor, minimizing collateral damage and side effects. The University of Chicago Medical Center and Joseph Salama, MD, assistant professor of radiation and cellular oncology, were the first to bring IGRT to patients in the Chicago area. But IGRT is only one of a multitude of breakthrough cancer treatments currently applied, researched, or developed at the Medical Center, where more than 200 physicians and scientists constantly seek new ways to outsmart this deadly disease. "It's not hopeless, and we are making progress," said Ralph Weichselbaum, MD, co-director of the Ludwig Center for Metastasis Research at the Medical Center and chairman of the Department of Radiation and Cellular Oncology. Like the machinery behind IGRT, the Medical Center is attacking cancer from all angles, using every possible tool: radiation, genetics, drugs, surgery and medical engineering. With each new innovation, more cancers become treatable, side effects become less severe and optimism is restored for those stricken with the disease. "The University of Chicago Comprehensive Cancer Center really takes a multi-faceted approach that involves hundreds of individuals," said Michelle Le Beau, PhD, professor of medicine and director of the Comprehensive Cancer Center. "One of the things that makes us so unique is that we have expertise in the whole scheme, from cancer detection to diagnosis to treatment." The ultimate answer to the riddle of cancer has yet to be discovered. But the momentum is shifting -- cancer death rates in the United States have fallen 1.6 percent each year since 2001, and 5-year survival rates for cancer patients have increased from 10 percent to more than 65 percent in the last 30 years. With recent genetic and technological discoveries bringing even more promise to the fight against cancer, researchers are optimistic that great strides will continue to be made. "These technologies simply were not available 15 years ago," said Blase Polite, MD, assistant professor of medicine and an expert in gastrointestinal cancers. "Add to that the recent mapping of the human genome, one of the greatest scientific feats of the millennium, and we now can explore the very heart of the cancer machine and find ways to turn it off." Team Pairs Cardiac and Vascular Specialists For decades, physicians at the University of Chicago Medical Center have provided patients with state-of-theart diagnostic and treatment services for all types of aortic diseases. The University of Chicago Aortic Specialty Team (UCAST), formed in 2009, ensures that patients who require elective or emergent intervention for complex aortic conditions benefit from expedient and coordinated care from a multidisciplinary team of cardiac and vascular specialists. UCAST provides patients the most advanced care with both straightforward and complex aortic disease using minimally invasive approaches whenever possible. 1 The team recently cared for a 68-yearold man who came to the Medical Center with a large dumbbell-shaped aortic aneurysm involving the blood supply to the gut and kidneys (Figure 1), a dangerous bulge in the life-supporting blood vessel that can lead to fatal rupture. Using minimally invasive endovascular techniques best performed by highly skilled surgeons at an academic medical center, the team repaired the aneurysm in two stages. During the first stage, blood supply was redirected to the gut and kidneys utilizing a multibranched bypass around the diseased portion of the aorta, allowing continued blood flow and greatly 2 thoracoabdominal stent graft T debranching graft reducing the risk for liver, intestinal and kidney damage during the rest of the procedure. In the second stage, the surgeons deployed a specialized covered stent from the distal thoracic aorta to the iliac arteries. By diverting blood flow through the covered stent, the blood pressure and tension on the aneurismal aortic wall was virtually eliminated (Figure 2). The patient had an uncomplicated recovery and quickly returned to his usual daily activities. "This case epitomizes the strategy of the University of Chicago Medical Center," said Jai Raman, MD, PhD, codirector of UCAST, "which is to develop and deliver techniques that treat high-risk patients with lower mortality, less trauma and shorter recovery time." Hisham Bassiouny, MD, co-director of UCAST and chief of the Section of Vascular Surgery and Endovascular Therapy at the Medical Center, agreed: "Without access to the highest level of care provided by highly skilled specialists, this patient may have experienced significant organ damage, or, in the worst case scenario, death. We are pleased to be able to bring life-saving techniques to patients like him who require a collaborative approach to care." Figure 1: A large dumbbell-shaped aortic aneurysm Figure 2: Blood supply is redirected by using a debranching graft. 6 University of Chicago Medicine on the Midway Spring/Summer 2010 7 Ralph Weichselbaum, MD, (pointing) and Joseph Salama, MD, examine tumors during a patient's radiation session. Photo by Dan Dry Disrupting the March of Metastatic Cancer and Weichselbaum proposed in 2009, a secondary mechanism Metastatic cancer is cancer at its deadliest, responsible for as by which radiation attacks cancer, through activation of the much as 90 percent of cancer deaths, and by far the hardest to body's own immune defenses. A better understanding of these treat. Greek for "removal from one place to another," metastasis immune effects could point the way toward new treatment occurs when cancer spreads from the primary tumor to other combinations that employ interventions from both radiation locations in the body. Once this has occurred, the conventional oncology and immunology. treatments of drugs and surgery become far less effective. But before reaching the unfortunate terminus of metastasis, How Tumors are Like Snowflakes cancer may go through phases that are vulnerable to aggressive, targeted treatment. In the 1990s, Weichselbaum and colWhen Janet Rowley, MD, was looking for the cause of certain leagues at the Medical Center established the existence of an leukemia types at the University of Chicago in the early 1970s, intermediate stage of cancer called "oligometastases." Cancer the relationship between genetics and cancer remained hazy. may change, they theorized, from when it is established in The discovery of chromosomal abnormalities leading to inapthe primary tumor site to when it is spreading throughout the propriate activation of tumor-promoting genes by Rowley, today body, becoming more difficult to treat. A team the Blum-Riese Distinguished Service Professor led by Salama and Weichselbaum hypothesized of Medicine, Molecular Genetics & Cell Biology that such oligometastases, though resistant to and Human Genetics, firmly established cancer chemotherapy and inoperable, could be treated as a genetic disease. with precisely targeted doses of radiation. Today, with the human genome fully decoded The team tested stereotactic body radiation and gene-sequencing technology growing expotherapy, a technique that applies higher doses nentially faster and cheaper, cancer is among of radiation to a narrow region of cancer cells, the highest priorities for the application of our on patients with Stage IV metastatic cancer -- new genetic knowledge. Researchers are tracking the most severe cases. In 2008, they published down the specific genetic errors that lead to canincredible results: Cancer was completely concer. That information leads to the development trolled in 1 out of 5 patients with fewer than of new drug treatments that attempt to correct five metastatic sites, with no detectable level of or offset those errors. New strides also are being Everett Vokes, MD, interim dean of made in the way different cancers are categorized, disease 15 months after treatment. Biological Sciences Division and "For a certain group of people, their tumors the Pritzker School of Medicine, and the understanding of how some cancers grow the were controlled, showing you can use radiation interim CEO at the Medical Center, resistant to treatment and why some cancers are for some patients where you might not have talks with a patient. prone to become metastatic. used it before," Salama said. Increasingly, this research supports the theory Medical Center researchers also are looking more closely at that tumors are like snowflakes: No two are exactly alike. how radiation works to kill cancer cells. The prevailing theory Understanding this diversity will allow for earlier, more specific since the first use of X-rays to treat cancer by Chicagoan Emil diagnosis and individualized treatment plans that increase Grubbe, in 1896, is that radiation kills tumor cells by disrupting effectiveness and reduce side effects. (See the mapping genes their DNA. But Yang-Xin Fu, MD, PhD, professor of pathology, article on page 12.) It's not hopeless, and we are making progress. --Ralph Weichselbaum, MD 8 For more information, call 1-888-UCH-0200 or visit uchospitals.edu `` `` "Tumors start out quite different from each other," explained Geoffrey Greene, PhD, vice chairman for the Ben May Department for Cancer Research and co-director of the Ludwig Center for Metastasis Research. "But in later stages they become more alike and less treatable." Greene's research focuses on the activity of the estrogen receptors in specific types of breast cancer. In breast tumors, the absence or presence of these receptors dictates the type of treatment a patient is given -- a model that researchers of other cancers hope to emulate. Greene's characterization of how different drugs target the estrogen receptor has suggested new strategies for the treatment and prevention of breast and uterine cancer. (See the breast cancer article on page 15.) The laboratory of Marsha Rosner, PhD, professor and chair of the Ben May Department for Cancer Research -- along with work by Andy Minn, MD, PhD, former assistant professor of radiation and cellular oncology now at the University of Pennsylvania -- seeks to understand the genetic signatures of metastasis. The team looked for genes that could predict metastasis in the early stages of triple-negative breast cancer, the most aggressive form of the disease. Genes from over 1,000 tumors were analyzed, and new signaling changes were found that can serve as early warning signs about the metastatic potential of a tumor. Tumors with a high metastatic risk can then be attacked with more aggressive methods earlier in the patient's treatment, to try to overwhelm the cancer while it is still vulnerable. New ways of thinking about cancer also may come from the Chicago Cancer Genome Project, an effort led by Kevin White, PhD, the James and Karen Frank Family Professor of Human Genetics and the director of the Institute for Genomics and Systems Biology. In partnership with Medical Center physicians treating and researching all types of cancer, White hopes to sequence at least 1,000 tumors to find new genetic patterns that can be used as markers for better treatment and diagnosis of individual tumors. "It's a long road from having a piece of genome sequence to actually implementing that into patient care, but the path is at least clear enough that we can shine a light down it and see the end," White said. "If we know enough about the genetic basis of the tumors, we should be able to at least connect the dots and draw a path toward clinical trials, and if those work out, toward actually getting things into the clinic." Paving New Paths from Bench to Bedside Poised at the transition point between the laboratory and the clinic, drug trials determine whether the gradual process of basic research will bear fruit as a new strategy for cancer treatment. The process is one riddled with both successes and failures. A substance that kills cancer cells in a laboratory dish might have little effect in patients, or be effective in only a subset of cancers. For every successful new drug that has reached the clinic, dozens of failed compounds have fallen by the wayside. "You can never predict when something works in the lab, whether it will work for the patient," said Everett Vokes, MD, interim dean of the Pritzker School of Medicine and Biological Sciences Division, and interim CEO of the Medical Center and an internationally known specialist in head and neck cancer. "It's impossible because the two are never completely correlated." Meeting those challenges requires both scope and ingenuity. More clinical drug trials are in progress at the Medical Center than at any other site in the Chicago area, with more than 300 trials open in 2009. Many of these trials are first-in-human studies, drawing upon findings developed through University of Chicago laboratory research. Experimentation goes down to the very structure of the trials themselves, with researchers who have overseen thousands of clinical trials seeking better tests to reveal the full therapeutic potential of a new compound. (See the clinical trials article on page 13.) Richard L. Schilsky, MD, chief of hematology/oncology at the Medical Center, also served as chair of the Cancer and Leukemia Group B, the largest and oldest cancer clinical trials group in the United States. Schilsky's research has spanned from simple preventive measures to complex combinations of chemotherapy drugs. One trial tested the potential of taking an aspirin a day to prevent the development of precancerous polyps in patients at risk for colorectal cancer. Another developed a promising new drug combination for treatment of pancreatic cancer. Geoffrey Greene, PhD, is co-director of the Ludwig Center for Metastasis Research. Photo by Hoyee Leong Michelle Le Beau, PhD, professor of medicine and director of the University of Chicago Comprehensive Cancer Center. University of Chicago Comprehensive Cancer Center Founded in 1973, the University of Chicago Comprehensive Cancer Center (UCCCC) is one of two National Cancer Institute-designated Comprehensive Cancer Centers in Illinois. The UCCCC received its NCI designation because of its research in three major areas: laboratory, clinical and population-based research. The UCCCC has 220 members with peer-reviewed cancer research grants of about $98 million, and $25 million in non-peer reviewed grants and contracts. The University of Chicago has been a leader in cancer research for many decades. Its scientists have made groundbreaking discoveries that have led to advances in chemotherapy, hormonal therapy, gene therapy and bone marrow transplantation. Nobel Prize recipient Charles Huggins, MD, discovered in 1939 that cells were not autonomous and self perpetuating, as previously believed, but were dependent on chemical signals, such as hormones, to grow and survive. His discoveries offered researchers new perspectives on the behavior of hormone responsive cancers, and redefined treatment of metastatic cancers. In 1943, Leon Jacobson, MD, performed the first successful cancer treatment using chemotherapy, and demonstrated the potential of bone marrow transplantation. In the 2009 fiscal year, the pediatric and adult bone marrow transplant programs performed 180 bone marrow transplants. Janet Rowley, MD, who discovered recurring chromosomal abnormalities in leukemias and lymphomas, revolutionized the understanding and treatment of cancer. Spring/Summer 2010 9 Nicole LaMont, a 27-year-old Minooka woman who is receiving treatment at the Medical Center. Photo by Dan Dry With metastatic disease, it doesn't mean that the surgeon is ruled out. --Mitchell Posner, MD Maximum Effectiveness with Minimal Invasion Surgery may be the oldest known treatment for cancer, based on the early theory that a tumor represented a deadly interloper in the body and that the life of the patient depended on somehow getting it out. Surgeons these days bear no real comparison with their early predecessors, yet surgery remains a first, critical line of defense for many cancers and in most instances the only proven curative modality. Using state-of-the-art techniques, 10 University of Chicago Medicine on the Midway Mitchell Posner, MD, discusses the viability of surgery for cancer patients in conference with other physicians and nurses. Photo by Bart Harris `` Striking that balance also has been a research priority of Mark Ratain, MD, the Leon O. Jacobson Professor of Medicine and director of the new Center for Personalized Therapeutics and the associate director for Clinical Sciences in the Comprehensive Care Center. Research conducted by Ratain and colleagues discovered a genetic variant that predicts a patient's toxic response to a drug called irinotecan, used as a common chemotherapy in treatment of colorectal cancers. A screening test for the UGT1A1 gene, which can predict the severity of a patient's side effects to irinotecan, was made available to physicians worldwide in 2005. (See the mapping genes article on page 12.) Such a genetic test seeks a "biomarker" for improving cancer treatment, an objective measure that can guide physicians in fine-tuning the medication each individual patient receives. Michael Maitland, MD, PhD, is testing even simpler biomarkers that can convey information quickly to physicians about the effectiveness of a drug class called angiogenesis inhibitors. These drugs are designed to prevent the formation of new blood vessels that facilitate tumor growth, but may cause high blood pressure in some patients. Maitland, medical oncologist and assistant professor of medicine, proposed using that side effect as an informative signal for the proper dosing of drugs such as sorafenib or sunitinib. By measuring blood pressure on the very first day of treatment with an angiogenesis inhibitor, physicians might quickly find the most effective and safe dose of the drug. That method is now being tested in clinical trials with various drugs to see if the protocol can improve patient outcomes. "These are the newest investigational drugs and often we are the only place in the city that can provide them," Le Beau said. "We have the ability to treat patients with unique forms of therapy that they may not have access to otherwise." `` `` We should think in terms of making metastatic cancer a chronic disease. Then it becomes something you can live with. --Geoffrey Greene, PhD such as minimally-invasive and robotic surgery, surgeons are increasingly attempting to achieve the same cancer outcomes but with approaches that may result in less pain and shorter hospital stays. "Surgery is an integral part of the treatment of cancer," said Jeffrey Matthews, MD, the Dallas B. Phemister Professor of Surgery, chair of the Department of Surgery and dean for clinical affairs. "For many types of cancer, surgery remains the only cure." Many cancer treatment plans today involve combinations of radiation, drugs and surgery, with surgical resection of the tumor occurring either before or after other types of therapies. Research has refined the delicate timing of these plans to optimize the interactions between different methods. Pre-surgery chemotherapy and/or radiation may make the tumor more effectively operable, or surgery may remove the most inaccessible parts of a tumor so that radiation and chemotherapy can destroy the rest. Recent advances in minimally invasive surgical techniques performed on the prostate, colon, esophagus and other organs have enabled a smoother transition between treatment methods, Matthews said. "Where technically possible, minimally invasive approaches are very successful in helping the patient recover faster from surgery," Matthews said. "If the patient needs post-operative chemotherapy or radiation therapy, they'll be able to start that process much more quickly." Surgery also is useful in select cases of advanced cancer, where the tumor may have spread to sites beyond where it started. In colorectal cancer, for example, about half of patients develop liver metastases, 10 to 20 percent of whom are candidates for surgery. Of those patients who have their liver metastases resected, 25 to 30 percent will be long-term survivors. "With metastatic disease, it doesn't mean that the surgeon is not involved," said Mitchell Posner, MD, the Thomas D. Jones Professor and chief of the Section of General Surgery and Surgical Oncology. "We've always performed surgery on patients with advanced cancer. But new drugs are working better and reducing the size of tumors before surgery so that surgery is an option for an even greater number of patients." Having experts specialized in surgical removal of tumors from particular organs and systems is of growing importance as cancer treatment becomes more individualized. In cases of liver cancer, whether surgery is an option frequently depends on how much of the organ must be removed. Michael Millis, MD, chief of the Section of Transplantation, and Giuliano Testa, MD, director of liver transplantation and hepatobiliary surgery, are well-known for their willingness to take on patients who have been turned down for surgery elsewhere. Mark Ferguson, MD, professor of surgery and a specialist in treating lung and thoracic cancers, and Marco Patti, MD, professor of surgery and the director of the Center for Esophageal Diseases, also show the value of having surgeons with experience in treating particular organs. "The really crucial element is having a team of experts who know the latest about radiation therapy, the latest about surgery and the latest about emerging protocols and how they fit together," Matthews said. "You need an experienced team to know the right timing of when these treatments should be done." New Frontiers from Unexpected Places As the "big three" of traditional cancer treatment -- radiation, drugs and surgery -- are continuously revamped and improved, inventive new strategies also are being tested to thwart cancer. These methods draw upon the latest discoveries in fields such as engineering, the science of new materials, stem cell biology and computer science, bringing those advances into the medical arsenal against cancer. In collaboration with scientists at Argonne National Laboratory, Maciej Lesniak, MD, director of neurosurgical oncology and the Brain Tumor Center, has been looking for ways to use incredibly small nanoparticles as weapons against glioblastomas, an especially hard-to-treat cancer of the brain. The research is exploring multiple ways of using nanoparticles, small enough to fit 10 million inside a single centimeter, to attack tumor cells. In one experiment, the particles are attached to a photocatalyst and targeted to tumor cells. When exposed to light, the particles will release free radicals, molecules that are deadly to cells. Another strategy employs flat "microdiscs" that bind selectively to tumor cells and rotate when exposed to a magnetic field, literally stretching the cells to death. (See the breast imaging article on page 19.) "In some cancers, the brain or pancreatic cells are multiplying at such a rapid rate," Lesniak said. "When you have a cancer that grows that rapidly, the prognosis can usually be measured in months or years at most. It's always a battle between how quickly the cancer is growing and the available therapies. In this case, we are trying to actually damage the cancer cell in a mechanical fashion." The laboratory of Ezra Cohen, MD, associate professor of medicine and an expert on squamous cell carcinoma of the head and neck (SCCHN), is testing nanoparticles as a therapeutic delivery mechanism. Cohen, in partnership with Argonne, has created nanoparticles that contain the chemotherapy drug cisplatin. When injected into a mouse model of SCCHN, the particles found their way to their tumors and released the drug, causing significant tumor regression. Bakhtiar Yamini, MD, assistant professor of surgery, is developing a similar drug-filled nanoparticle that can be used to treat brain tumors. Yamini's laboratory also is developing new ways to transport those particles across the blood-brain barrier, allowing for easier administration. Researchers in the relatively young field of molecular engineering also are offering new perspectives on fighting cancer away from the campus of the Medical Center. Milan Mrksich, PhD, Richard Schilsky, MD, chief of professor of chemistry, is studying how hematology/oncology at the the shape of cells affects their develop- Medical Center. Photo by Dan Dry ment and behavior. He proposes that migrating cells that lead to metastases take on a particular shape that can perhaps be prevented. Margaret Gardel, PhD, assistant professor of physics, is looking at cells as machines, with component parts that allow them to take shape and move -- work at the border of cell biology and condensed matter physics. Such adventurous theories are likely to be at least several years from clinical trials and treatment therapies. But the recruitment of ideas and expertise from all corners of science is testament to the all-out search for treatments that will cure, or at least control, cancers in our lifetime. "One of the things that we do best is develop teams of investigators," Le Beau said. "By bringing investigators together from multiple disciplines, we actually create a new discipline and create new science that addresses questions that would not otherwise be able to be studied." Science is a gradual process. Every victory and advancement is accompanied by 10 times the amount of failure and frustration. But significant progress has been made from the first revolutionary but crude experiments with radiation and chemotherapy in Chicago to today's broad spectrum of treatments that make more cancers vulnerable. "Instead of thinking too grandly -- that we're going to cure all advanced cancers -- we should first think in terms of making metastatic cancer a chronic disease," Geoffrey Greene said. "Then it becomes something you can live with." Personalized genomics, computer-calibrated radiation therapy, advanced surgical options and biotechnology -- all these innovations are both the present and the future in making cancer treatment dramatically safer and more effective. Surrounded from every side, cancer is being tamed, stripped of its deadliness and rendered manageable, if not cured. `` Spring/Summer 2010 11 Finding Answers through Clinical Trials By Rob Mitchum E Eileen Dolan, PhD, in her lab. In the early 2000s, Dolan's lab discovered that cytotoxicity to certain chemotherapy drugs is heritable. Photo by Dan Dry Mapping the Genes that Help Cancer Drugs label changes to the drug warning doctors to use lower doses with ancer treatment is a tightrope. The goal of chemopatients carrying the UGT1A1 variant. therapy, radiation or surgery is to kill malignant cells, Medical Center researchers are now building on those imporwhile leaving healthy cells intact. But the modern tant early steps to broaden the reach of pharmacogenomics in the tools of oncology are not perfect and cancer patients often must clinic. Dolan's laboratory continues to compare drug effects in cells suffer through severe side effects as physicians work to calibrate taken from different populations, and those results are analyzed the perfect balance between therapy and toxicity. using software developed by the research group of Nancy Cox, These challenges make cancer treatment a great candidate PhD, chief of the Section of Genetic Medicine for the Medical for what many scientists and clinicians hope will be the medical Center. Drawing upon public directories of gene variants colrevolution of the coming decade: pharmacogenomics. lected from hundreds of sequenced human volunteers, Dolan "Pharmacogenomics is a great and exciting field, but to me it's and Cox hope to identify "genetic signatures" that predict drug really important in the field of cancer," said Eileen Dolan, PhD, response and toxicity. professor of medicine, and chair of the Committee on Clinical "Pharmacogenomics is likely to be the first complex genetic Pharmacology and Pharmacogenomics. "Doctors are making trait translated to medical care on a larger scale basis," Cox said. decisions right now with a sort of one-size-fits-all philosophy, "The very nature of the pharmacogenomics research almost but the reality is you have this huge variation in patients who ensures it will be more clinically meaningful." respond and don't respond." Ratain said he is devoting his energy With this tool, doctors could use to systemic changes in medicine that genetic information to make decisions will be necessary for pharmacogenomabout what drugs and dosages would ics to become standard practice, useful most effectively treat a patient's disnot just in the treatment of cancer but ease while minimizing dangerous side virtually every human disease. effects. At the University of Chicago "I think pharmacogenomics is Medical Center, the Pharmacogenomics going to have the biggest long-term of Anticancer Agents Research group, ramifications in the primary care mode known as PAAR, has unified basic as a new way of managing patients in science, computational and clinical general," Ratain said. "We'll do history, researchers to bring this promising new physicals and genetic exams; it'll just be field to reality. integral to medical care." In the early 2000s, Dolan's lab dis- Nancy Cox, PhD, chief of genetic medicine, is drawing upon public directories of gene variants. Photo by Dan Dry Those translations may ease some covered in cell culture experiments that of the frustration that, six years after the the cytotoxicity of certain chemotherapy drugs is heritable; about Human Genome Project was completed, our newly expanded a quarter to a third of drug toxicity can be explained by genes, knowledge of the blueprint of human life has had only shallow she said. Meanwhile, Mark J. Ratain, MD, the Leon O. Jacobson effects on the field of medicine. Professor of Medicine and director of the new Center for "In general, personalized genomic sites will provide a risk of Personalized Therapeutics and the associate director for Clinical different diseases, but other than living a healthy lifestyle there's Sciences in the Comprehensive Care Center, found that people not a lot you can do about it," Dolan said. "People are very intercarrying a variant in a gene called UGT1A1 were more sensitive ested in how genetics will change medical decisions and that's to the toxic effects of an anti-cancer drug called irinotecan. That much more concrete in the field of pharmacogenomics." discovery prompted the Food & Drug Administration to make 12 For more information, call 1-888-UCH-0200 or visit uchospitals.edu C By Rob Mitchum and Susan Chandler normous strides have been made in treating cancer over the last several decades. But that success is conditional, with remission and cures seen in too small a percentage of cancer patients. As a result, the search for better cancer drug therapies remains intense. Researchers around the world are looking at nearly 1,000 different compounds, seeking drugs for cancers with no effective treatment or for patients who don't respond to established therapies. More of those drugs are being tested clinically at the University of Chicago Medical Center than at any other center in the region. The Medical Center is one of the few programs in the country funded by the National Cancer Institute (NCI) to conduct hundreds of Phase-I, Phase-II and Phase-III trials. Many of these trials involve drugs currently under investigation at the Medical Center. "There are a zillion theories; that's why we have so many investigational drugs," said Mark J. Ratain, MD, the Leon O. Jacobson Professor of Medicine and director of the new Center for Personalized Therapeutics and the associate director for Clinical Sciences in the Comprehensive Care Center. Ratain directs the Phase-I program at the Medical Center. "One of these theories will be right one day. What we have to offer now is hope. Some patients actually get benefits, but everybody gets hope." With treatments under investigation for virtually every type of cancer, the Medical Center frequently receives patients from other hospitals in the area, including other academic medical centers, Ratain said. For many of these patients, established treatments have failed to slow the progression of their disease, leading them to decide to take a chance on new drugs with unknown benefits and consequences. "The patients are motivated to participate because of the potential for benefit in a setting where presumably there are no other alternatives that even offer that potential," said Chris Daugherty, MD, professor of medicine and chair of the Medical Center's Institutional Review Board. "Rather than take a standard therapy that you know will not work, it is justifiable to consider taking something where you don't know if it will work and where there is good scientific judgment that says we know that this agent kills cancer cells in the laboratory, so there is a scientific rationale to justify testing in real patients with real tumors." Daugherty's research on the motivations and attitudes of participants in clinical trials is just one feature that makes the Medical Center a unique investigational entity. An NCIdesignated Cancer Center for nearly 40 years, the Medical Center can boast an experienced infrastructure for clinical trials, either originating from in-house research or from pharmaceutical companies needing to test out new drugs. Frequent communication between different medical disciplines and researchers at clinical and basic research levels also fosters innovative new ideas about treatments and how to test them. "In many ways, we're big enough so that there is broad expertise in a wide variety of different areas," said Walter Stadler, MD, Fred C. Buffett Professor of Medicine and director of the Medical Center's Phase-II program, "but small enough that it's easy to have these conversations between disciplines. The fact that the epidemiologists, basic scientists and clinicians are all relatively close is a good thing." Mark J. Ratain, MD, director of the Center for Personalized Therapeutics. Photo by Anne Ryan Spring/Summer 2010 13 One such multi-disciplinary interaction led to the Food and Drug Administration's approval of one of the first drugs to treat advanced kidney cancer, sorafenib. This drug was originally developed to inhibit Raf, a protein involved in a variety of common cancers, including colorectal cancer. But Medical Center researchers convinced the sponsor to allow broader testing and observed a positive effect of the drug upon kidney tumors, leading to successful Phase-II and Phase-III trials overseen by Ratain and Stadler. Those clinical trials also employed new strategies created by Ratain to solve a recurring issue -- how do you study the effectiveness of a drug that may only Ravi Salgia, MD, PhD, professor of medicine and director of the Chest Oncology and Thoracic Oncology be effective in a fraction of patients? New Research Program, in his lab. Photo by Bart Harris approaches that allow for treatments to be tested in more selective populations will be increasingly Those principles are being applied to studies conducted by important as pharmacogenomic research identifies genes that researchers such as Olatoyosi Odenike, MD, assistant professor make patients more susceptible to the benefits or risks of a parof medicine. Odenike's research on novel treatments for leuketicular drug, Ratain said. (See the mapping genes article on page mias and other diseases has led her to the study of agents that 12.) The Medical Center also is launching new trials to exploit affect epigenetic processes that switch genes off and on. Clinical the genetics of cancer for more individualized treatments. trials using a drug called romidepsin to treat acute myeloid leu"For the last 50 years, we have treated cancers based on their kemia found that only certain patients responded. In collaboraorgan of origin, where they happened to start. And that's a usetion with basic scientists from the Biological Sciences Division, ful division," Stadler said. "However there are other additional Odenike now is analyzing patient samples for clues as to why divisions that are important, including the genetic makeup of this approach was beneficial in certain patients and looking the tumor and the individual that we can use to try to better beyond the clinical trial. personalize the therapy for patients. That's where cancer therapy "I don't think that the clinical trial should be the end of the is going. Our infrastructure allows us to test these various ideas process; it may only be the middle of it," Odenike said. "This in patients." research needs to be bi-directional for us to fully understand the mechanisms." That philosophy is shared by Ravi Salgia, MD, PhD, professor of medicine and director of the Chest Oncology and Thoracic Oncology Research Program. "Many times people think of translational research as only bench to bedside, but we do the opposite too -- we're also bedside to bench," Salgia said. Salgia's research, which spans from testing the effects of cigarette smoke and gene mutations in microscopic worms to clinical studies of drugs that affect an over-active signaling pathway in lung cancer patients, reflects the smooth connection between laboratory and clinic that underlies Medical Center studies. Some of those same drugs are being tested in other trials on other types of cancers -- head and neck cancer, mesotheliomas, neuroblastoma. Other innovative trials include Ezra Cohen's research on the amplifying effect of grapefruit juice upon rapamycin, and Steven Chmura's study of a drug derived from scorpion toxin used to treat brain tumors. "Right now, we tell many patients that we hope they can live a couple years longer," Ratain said. "But we hope we can find drug therapy that's going to keep patients alive indefinitely, Walter Stadler, MD, Fred C. Buffett Professor of Medicine and director of the Medical Center's Phase-II program, with a patient. Photo by Dan Dry like HIV therapy. You never know when it's going to happen, but that's the patient's hope and our hope, too." Physicians on the breast cancer team discuss the treatment for a patient during a weekly meeting. Pictured left to right: Nora Jaskowiak, MD, surgical director of the Medical Center's Breast Center; Rita Nanda, MD, assistant professor of medicine; Steven Chmura, MD, PhD, assistant professor of radiation and cellular oncology; and David Song, MD, chief of plastic and reconstructive surgery. Photos by David Christopher Advanced Approaches to Treating Breast Cancer By Cheryl L. Reed hen a woman first feels a lump in her breast or "We have almost a perfect storm here," said David Song, learns that there are irregularities in her mammoMD, chief of plastic and reconstructive surgery. "We have the gram, she fears the worst. It's a worry realized by all-stars of the field here in one place; the foremost leaders in one in eight women who develops breast cancer in the United breast oncology, in oncologic surgery, in breast imaging and States. With advances in treatment, though, women have more reconstructive surgery. A patient is in the worst part of her life options than they might have thought. being diagnosed with breast cancer, and we're able to offer her Among the innovative approaches offered at the University of palpable hope." Chicago Medical Center are customToday, there is nothing static ized treatments that not only target about treating breast cancer. Some a woman's specific type of tumor patients receive chemotherapy before but also take into account her body surgery, others after, and for some, type and genetic markers to deterboth prior to and post surgery. mine how best to treat her disease Some patients receive radiation with the least adverse side effects. before surgery, others afterwards. Since the 1970s, when researchEven the methods of radiation are ers at the Medical Center developed customized to a patient's shape, the first tests to detect and treat her breathing pattern and comfort. hormone-sensitive breast cancers, If a woman has large breasts, she the university has been a leader in receives radiation in a prone posiadvancing new breast cancer treattion to stabilize her and to reduce ments and surgical procedures. The For the past five years, Shirley Mertz's radiology scans have shown short-term skin toxicity, while a Medical Center was among the first no evidence of metastatic cancer. After a doctor in 2003 told Mertz, woman with smaller breasts is treated to use "staging MRIs" that allow left, she would live for a year, she sought a second opinion from in a supine position. surgeons to precisely locate cancer the Medical Center and Olufunmilayo Olopade, MD, FACP, right. "It's very clear that one size and avoid extracting healthy tissue. Radiation oncologists tailor doesn't fit all," explained Olufunmilayo Olopade, MD, FACP, treatments for women with larger breasts and are developing director of the Medical Center's Cancer Risk Clinic. "We look at ways to treat women who previously have been radiated and the tumor, the individual and the quality of life." those whose tumors have metastasized. Oncologists are testing The thrust of Olopade's research and clinical application treatments that target cancer without using standard chemocenters around what makes different tumors grow and then therapy. Reconstructive plastic surgeons continue to perfect customizes each patient's treatment for the best chance of techniques in microsurgery that preserve a woman's muscle putting the disease into remission or at least slowing down tissue and are leading the field using liposuction and fat grafting the cancer's growth. to shape breasts, even after lumpectomies. Spring/Summer 2010 15 W 14 University of Chicago Medicine on the Midway We have the all-stars here... That's the reason we are getting these results -- the way our team collaborates is really unparalleled. --David Song, MD Director of the breast cancer Specialized Program of Research Among the many ongoing clinical trials are studies that assess Excellence (SPORE) and associate dean for global health and using alternative drugs to standard chemotherapy. Another thrust professor of medicine and human genetics, Olopade is an interof research tests various approaches to using chemotherapy nationally recognized expert in designing individual treatments before surgery. Many oncologists, like Rita Nanda, MD, assistant for breast cancer patients. She charts a course of treatment professor of medicine, prefer to give their patients chemotherdepending on the type of tumor, the patient's other medical conapy prior to surgery to shrink a patient's tumor, which allows ditions and the likelihood that a patient will respond to a certain for a better cosmetic outcome. Physicians also like to assess a course of chemotherapy. She also addresses the side effects of patient's response to the drugs and whether they need to adjust treatments, which run the gamut from hair loss to infertility. treatment to spare her the side effects or switch to another drug Physicians also need to be aware of whether a patient is taking that might have a better chance of working. antidepressants that might interact with certain chemotherapy Nanda is the principal investigator for 10 current studies. Her drugs. Those with heart problems should avoid drugs that will personal interest is in studying triple-negative breast cancer, a aggravate their conditions just as diabetics should steer clear of cancer that is more prone to occur in younger women, women therapies known to involve nerve damage. with BRCA1 mutations and in African-American women. Nanda Approaching each patient as an individual allows physicians is currently running a Phase II study that looks at the combinato try new treatments in cases where other doctors have given tion of two drugs, carboplatin and bevacizumab, to treat women up. That was certainly the case with Olopade's patient Shirley who have triple-negative cancer -- meaning their cancers are Mertz, 63, who was diagnosed with Stage IV metastatic disease negative for the estrogen receptor, progesterone receptor and in September 2003. HER2. Triple-negative tumors have been shown to have impaired "A doctor told me I would probably live only one more year," DNA repair capabilities, and this trial hopes to exploit this defect said Mertz, former principal of William Fremd High School in by damaging the tumor's DNA with carboplatin. Another focus Palatine, Ill. of her research involves studying how the tumor microenvironThat's when Mertz, who was originally diagnosed with breast ment may contribute to the aggressiveness of breast cancer. cancer in 1991 and decided to undergo a double mastectomy, "Our clinical trials are trying to study the biology of tumors sought out Olopade and the Medical and not just the drugs that tumors Center. Olopade used the results from respond to," explained Nanda. "We a biopsy to revise Mertz's treatment study tumor tissue so that we underto match her tumor type. Mertz was stand why some patients may respond HER2-positive, indicating a more better to therapy than others." aggressive form of breast cancer. Her Nanda points to two other criticancer was treated with Herceptin and cal studies at the Medical Center that a chemotherapy drug. (See the profile look at the effect of drugs that stop the of Dennis Slamon, MD, PhD, a Pritzker growth of cancer and shrink tumors alumnus who developed Herceptin, without using standard chemotherapy on page 32.) to kill the cancer. Mertz recently celebrated six years "I actively enroll patients into of survival. For almost five years of clinical trials," Nanda said. "It offers that time, her radiological scans have Breast cancer patient Carol Sibley and her physician, them access to newer drugs that could Rita Nanda, MD, assistant professor of medicine. shown no evidence of disease. improve their outcomes. For many Photo by David Christopher patients, it is empowering to know Breakthroughs in Clinical Trials that by enrolling in clinical trials, they are advancing the greater As an academic medical center, the University of Chicago good by helping us to better understand the disease." offers more clinical trials than any hospital in the Midwest. One of her patients, Carol Sibley, 62, is currently on her fifth Medical Center physicians encourage their patients to take clinical trial. In 2004, the Fox Lake woman was diagnosed with advantage of these studies that feature the latest arsenal of cancer breast cancer after she felt a lump in her breast. Sibley picked her drugs, radiation treatments and surgical techniques. These studies oncologist from the phone book. But after four biopsies, a niece allow physicians to continue to define individual regimens. who is married to a physician in another state insisted Sibley Besides the SPORE, the Medical Center is the only hospital seek a second opinion from the University of Chicago Medical in Chicago and Illinois that is part of the Translational Breast Center and even made an appointment for her. Cancer Research Consortium (TBCRC), a group of 14 research After her first meeting with her surgeon, Sibley decided to centers in the United States dedicated to conducting innovative stop seeing her other physician. clinical trials for breast cancer. The Consortium not only tests "My Medical Center physician said, `You and I are going to novel, laboratory-based strategies, but also attempts to understand manage your cancer,'" Sibley remembered. "It gave me hope the underlying causes and biology of breast cancer. 16 For more information, call 1-888-UCH-0200 or visit uchospitals.edu when I came here and that was huge. I had a chance. My other doctor was so negative. I wanted a doctor who involved me in the decisions." Sibley's course of treatment was a mastectomy, chemotherapy, radiation, then breast reconstruction with implants in both breasts. Because Sibley's mother died after she was diagnosed with breast cancer at age 57, she wanted to make sure that doctors could learn as much as they could from her own situation and signed up to be a part of a succession of clinical trials. Sibley has a daughter and nieces and was concerned for their health as well. While some patients see clinical trials as a means to get access to better drugs or advanced treatment, Sibley says those factors were never her motivation: "If there's any way to find out more about cancer, and I can help, I'll do it. I did the clinical trials to give doctors more answers, not to help me." Sibley's first clinical trial was a randomized trial in which she was given extra cycles of standard chemotherapy to see if it would improve outcomes. Her second trial was a randomized Phase III trial that tested anti-estrogen therapies for early stage breast cancer. Her third trial added an estrogen therapy shot once a month to her ongoing treatment to see if adding an agent that targeted growth factors of hormone-sensitive cancers could slow down the spread of the disease by blocking estrogen pathways. The fourth study tracked markers in patients' DNA to see if physicians could predict a better outcome based on genetics. Sibley's current clinical trial is one run by Eileen Dolan, PhD, professor of medicine, in which researchers are studying whether they can predict toxicity or the effects of capecitabine, a standard chemotherapy drug, based on genetic markers. (See the mapping genes article on page 12.) "I'm so grateful that my niece got me here," Sibley said. "I've told my daughter and nieces to all get tested." An Individualized Platform of Care Though physicians at the Medical Center are striving for the day when drugs, radiation and even ultrasound will be used to obliterate tumors, surgical removal of breast cancer is still the standard treatment for all patients. Surgeons strive to make surgery as minimal as possible to lessen recovery time and make reconstruction easier. "Particularly for breast cancer and breast issues, there is no cookie-cutter plan," said Nora Jaskowiak, MD, surgical director of the university's Breast Center. "The vast majority of breast cancer patients are long-term survivors." Women with certain kinds of tumors can benefit from pre-surgical chemotherapy because it can shrink their tumors significantly. This can mean avoiding a full mastectomy in favor of a lumpectomy, or a more localized lumpectomy that removes a smaller portion of the breast. For some women whose tumors appear inoperable, chemotherapy can shrink the tumor to the point where surgery is possible. About a quarter of Jaskowiak's patients receive chemotherapy before surgery. In lumpectomies, the surgeons have found that it's difficult to reconstruct the breast after a woman has had radiation. So the plastic surgeon is called in for consultation before the original surgery and then performs the reconstruction before radiation begins, which delivers much better results, Jaskowiak said. About a decade ago, David Song, MD, chief of plastic and reconstructive surgery, helped define the Medical Center's perforator flap treatment, which uses fat on a woman's abdomen while preserving muscle to reconstruct resected breasts. "These techniques help women regain confidence," Song said. "The patient can even look better and more youthful than before her diagnosis." Medical Center surgeons perform 200 perforator flap operations a year, more than any other hospital in the Midwest. The surgery takes upwards of six to eight hours per breast and can be done immediately following surgery to remove the cancer, if the patient doesn't require radiation. As the dominant center in the Midwest for breast reconstruction, Medical Center plastic surgeons are leading the development of a new surgical field called oncoplastic surgery. This technique utilizes a woman's own body fat to restore breast tissue after a lumpectomy. Breast cancer patients often elect to Spring/Summer 2010 17 `` `` `` `` Yasmin Hasan, MD, instructor of radiation and cellular oncology, checks a breast cancer patient before her radiation treatment in the prone position. Photo by Jason Smith Some types of metastatic disease can be compared to diabetes and heart disease -- chronic conditions --Yasmin Hasan, MD that can be managed. have lumpectomies instead of mastectomies to preserve breast The Department of Radiation and Cellular Oncology has tissue, but if the resected cancer is in the bottom portion of the several ongoing clinical trials testing developing protocols for breast, the remaining breast tissue often collapses, resulting in a women whose breasts have previously been radiated. Other deformed-looking breast, as illustrated (below). trials are testing outcomes of partial breast radiation for early "People don't even know that this kind of surgery is possible," stage, low-risk breast cancer and higher-dose radiation in cases Song said. "They thought it was only possible in a mastectomy. where patients can't always get to the hospital daily for treatThe surgery is rather new in the Midwest. It's been very popular ment, or where health problems prevent the patient from receivin Europe, especially France, but not in the United States." ing the standard 33 doses of radiation every day for six and a The logistics of oncoplastic surgery require coordination half weeks. between the radiation oncologists, plastic surgeons and the A joint study between radiation oncology and plastic surgery oncologic surgeon, an attribute of the Medical Center's breast is examining whether skin should be a primary target of radiacancer multidisciplinary team where tion for mastectomy patients. This each woman's treatment is decided in a study, conducted by Steven Chmura, collaborative approach. All disciplines MD, PhD, assistant professor of consult with each other to decide the radiation and cellular oncology, and best individualized treatment plan. Julie Park, MD, assistant profes"The problem other institutions sor of surgery, attempts to improve face is that the surgical oncologists, cosmetic outcomes of breast cancer the plastic surgeons and the radipatients by removing portions of the ologists tend to work independently breast skin while preserving the skin from one another," Song said. "Ours envelope to reduce scar deformities is a unique place and that's the reaand maintain natural breast contour son why we are getting these results and color. -- because the way our team colPerhaps the most exciting trial is laborates is really unparalleled." called BEAM ON (Biologic Endpoints Surgeons also are defining new in the Annihilation of Metastases for surgical techniques in which the Oligometastasis). Researchers hope nipple and areola are spared during that this pilot study will become a mastectomy and used in immediavailable nationally in the next ate reconstruction. year. A National Cancer InstituteSong and his team just finished sponsored cooperative study led by a Phase III trial in which they tested Chmura and in collaboration with skin from humans against pig skin With lumpectomies, the remaining breast tissue can collapse. the MD Anderson Cancer Center that has been decellularized for breast A new surgical field called oncoplastic surgery allows surgeons in Houston, BEAM ON is testing a implants. They are still analyzing the to reconstruct lumpectomies. Illustration by Richard Laurent national protocol for treating localdata, but the results appear "very ized breast cancer among a select promising," Song said. group of patients with oligometastases -- limited metastatic The Department of Surgery has started to use fat-grafting disease progression. The treatment targets patients with Stage IV surgery in which fat from a patient's stomach is liposuctioned cancer with five tumors or less with high doses of radiation. In and used as material for breast reconstruction. Medical Center addition, patients in BEAM ON are routinely tested to see if the surgeons have taken a conservative approach since the breast is a radiation can diminish the number of tumor cells circulating in much larger area of the body than the facial wrinkles and creases their blood stream. where fat grafting is normally used. The procedure is not yet an "The ultimate goal of the research is to personalize the option for complete breast reconstruction but is being used for treatment to the patient and her disease by understanding the partial areas, like lumpectomies and contour irregularities. biology," Chmura said. "The question, which we hope to answer, "It's probably the biggest thing to come out of plastic surgery is which patients would benefit from aggressive local treatment?" in the last half a decade," Song said. "It's kind of like human The research makes the approach to treating cancer even spackle. It's your own body and then the patient gets the added more personalized. Previously, there were just a few defined benefit of having liposuction plus adding your own stem cells." paths to fight specific types of cancer. Now, with a plethora of approaches available, physicians can incorporate diverse eleTailoring to a Woman's Breath ments from many treatment options to create a specific plan Before a patient receives radiation therapy, the radiation targeted to each cancer. oncologist times her treatment to her respiratory gate -- the "The whole purpose of this is to change the contemporary rhythm in which a woman inhales and exhales. The radiation thinking that Stage IV patients are to be put aside and told there beam is turned on and off with each breath, using a 3D optiis nothing we can do for them," explained Yasmin Hasan, MD, cal guidance system so as to avoid injuring tissue surrounding instructor of radiation and cellular oncology. "Patients with a targeted tumor while the patient is exhaling and inhaling. some types of metastatic disease can be compared to patients That way a patient receives radiation only when her chest wall who have diabetes and heart disease. It's like a chronic condiis stable. A plaster mold is also constructed from each patient's tion that can be managed. The goal is to provide a definitive body to hold her steady as she receives treatment. treatment so that these patients who are living with metastatic disease may have the hope of a cure." 18 University of Chicago Medicine on the Midway Mammography technologist Theresa Howard directs a patient during a screening. Photo by David Christopher Getting a Clearer Picture of Breast Cancer By Cheryl L. Reed nce a week, oncologists, surgeons, radiation oncologists, pathologists and radiologists all crowd into a conference room to view breast images on an 8-foot screen. It is the cornerstone of the University of Chicago Medical Center's breast cancer program, where specialists outline what they believe is the best course of treatment for each patient. Their conclusions are based on repeated and careful examinations of MRIs, mammograms, CT scans and ultrasounds along with a pathologist's report about the biology of a tumor. What few patients realize is that the precision of their doctors' diagnoses is directly dependent on the quality of the diagnostic images. "Because we have more accurate images, it changes how we treat patients," said Gillian Newstead, MD, clinical director for the Section of Breast Imaging at the Medical Center. "We have perfected MRI techniques here. We are able to show the extent of the cancer. Our whole tool box has become much larger. With our datasets, we are able to make diagnoses as well as prognoses." By working with scientists, physicists and the companies that produce imaging technology, the Medical Center's Section of Breast Imaging is able to combine the latest technology with sophisticated treatment and surgery to ensure that the full extent of a patient's cancer is detected and removed. The Medical Center's push to advance imaging is being funded by an $11.5 million National O Cancer Institute's Specialized Programs of Research Excellence (SPORE) grant. Two of the grant's four major projects focus on improving mammography and MRIs. One project concentrates on developing image-based markers to determine the risk of breast cancer. The other is looking for ways to use MRIs to find very small early cancers or precancerous lesions by correlating genetic and biologic markers found in tissue biopsies with findings from MRI scans. "What's unique is that half of the SPORE grants are for taking standard images and analyzing the data further and coming up with new ways of imaging," Newstead explained. "Our surgeons work very closely with us. Every time they have a cancer that can't be felt, they come down, and we go over the images immediately before and during surgery, to be sure that the cancer is excised completely. That's not the standard of care elsewhere." MRIs, which give a more precise picture of tumors than mammograms or ultrasounds, have become an important tool to help doctors more accurately locate tumors in a woman's breast. As part of another research study, high-risk women, such as those with a genetic predisposition for breast cancer or those who received radiation to their thorax as young adults, are screened with an MRI every six months for tumors as opposed to national recommendations to screen once a year. This helps catch tumors earlier, Newstead explained. Additionally, every woman diagnosed with breast cancer at the Medical Center is given what's called a "staging MRI" to create a clearer picture of the known tumors and locate any smaller ones False-color mammogram of a female breast showing a cancerous tumor, which appears as the red-orange mass with an uneven border. Spring/Summer 2010 19 that remain stubbornly hidden in other tests. The Medical Center was one of the first hospitals in the Midwest to offer staging MRIs to all diagnosed women, Newstead said. Physicians also can perform biopsies using MRI guidance, allowing them to accurately pinpoint the tumor for the test. Newstead said the next step will be to start treating women inside an MRI machine by aiming a High Intensity Focused Ultrasound (HIFU) beam at tumors to remove them. "We have been using it in animals, not humans yet," Newstead said. "It's the same kind of technique that they are using on brain tumors with mouse models. The holdup is with the FDA. It's going to be another year or two, but we'll be pioneering that effort here." Last fall, the Section of Breast Imaging expanded its hours for screenings, even adding Saturday appointments. The additional scheduling increased mammogram patients initially by 20 percent. Breast Imaging also added digital imaging mammography machines to its screening department. The diagnostic department has used digital mammograms since 2002. Digital images are better at detecting cancer in younger women and women with dense breast tissue, Newstead said. Having digital images also makes it easier for patients to take their results to another physician if they want a second opinion. Despite a government panel last fall that suggested women with no family history of breast cancer not undergo annual mammography screenings until they are at least 50, physicians at the Section of Breast Imaging remain adamant that all women over the age of 40 should schedule mammograms once a year. If any imaging reveals a tumor, the patient is referred to a surgeon. "There's overwhelming evidence that regular mammograms save lives," Newstead said. "We don't have anything else. We know we find small cancers through mammography. What are we going to do? Wait until they grow and they become palpable and the patient's prognosis is worse?" Newstead and a team of other Medical Center physicians -- Robert Schmidt, MD, professor of radiology; Hiroyuki Abe, MD, PhD, assistant professor of radiology; Charlene Sennett, MD, assistant professor of radiology; and Kirti Kulkarni, MD, assistant professor of radiology -- are working with Philips, the company that makes MRI machines and the work stations to view them. The goal is to design a multi-media database and work station where physicians can view MRIs, ultrasounds and mammograms. That database also would catalogue all imaging, clinical and medical records. A colored scanning electron micrograph of breast cancer cells. `` `` Our whole tool box has become much larger. With our datasets, we are able to make diagnoses as well as prognoses. --Gillian Newstead, MD Transforming Health on the South Side By Stephen Phillips Gillian Newstead, MD, clinical director for the Section of Breast Imaging. Photo by David Christopher "We are working not just with the equipment we have, but we're working to develop new equipment and advanced integration techniques with the company," Newstead explained. One thrust of research at the Medical Center is finding better ways to distinguish between aggressive and "innocent" cancers in patients who have Ductal Carcinoma In Situ (DCIS), an early cancer that has not spread beyond the milk duct. "We can't differentiate between the good guys and the bad guys," said Newstead. "We are over-treating a lot of women who have this kind of cancer." The other focus of research is detecting cancer in lymph nodes. Newstead is collaborating with researchers in the university's physics department to analyze the mathematics of cancerous tumors and their linkage to metastases in lymph nodes. The goal, she said, would be to allow less invasive treatment, perhaps ultimately avoiding surgery of lymph nodes in some cases. "There's no such thing as a breast cancer," Newstead said. "It's very heterogeneous. There are multiple different types. Some of them are fairly good cancers. Some are horrible cancers. There is a huge range." Susan Chandler and Emily Stone contributed to this report. For Eric Whitaker, it's personal. "I wrote on my application to Pritzker in 1986 that I wanted to become a doctor to improve health on the South Side," he recalled. "This brings me back to where I started," said Whitaker, MD, executive vice president for strategic affiliations and associate dean for communitybased research at the University of Chicago Medical Center. "It's exciting to have the resources of this campus to work with the community to improve the health of the place where I grew up and am raising my family." Under the Urban Health Initiative (UHI), Whitaker -- who led the Illinois Department of Public Health from 2003 until joining the Medical Center in 2007 -- is leading a multi-pronged effort to transform health in the community he calls home. The South Side is one of the nation's largest medically underserved urban areas. Forty percent of residents are Medicaid recipients and 42 percent are uninsured, according to the city's health department. It's also the Medical Center's primary service area and a place where the ills of a dysfunctional health care system are a daily reality. The 1.1 million population suffers disproportionately from diabetes, hypertension, asthma and other chronic, but preventable or treatable conditions -- disparities compounded by widespread lack of insurance and a health care system that has been substantially less than the sum of its parts. Photo by Dan Dry Spring/Summer 2010 21 Spring/Summer 2010 "| ecanproduceallthedoctorswewant,butiftheyallgo W toworkonMichiganAvenue,we'renothavinganimpact." --EricWhitaker,MD Through UHI, the Medical Center is pursuing an ambitious program, pulling together experts from across the university, such as the Office of Civic Engagement and even across the Midway, such as the School of Social Service Administration. Local civic and church leaders also are helping to attack these glaring inequities from all sides. This starts with building a coordinated system of care. Under the South Side Healthcare Collaborative, the Medical Center has joined forces with 25 community health centers and five community hospitals to create a cohesive health care network. The effort cuts to the heart of the national health care debate and the all-important issue of access, said Whitaker. "We're creating a system that ensures people not only have insurance, but access to care, too." Central to this effort is connecting people to a primary care provider they can count on for prompt attention, checkups and screenings, management of chronic conditions, referrals to specialists and health education. residents, 64 percent didn't know community health centers existed, Whitaker said. "These facilities have typically not had resources for marketing," he explained. "We're letting people know about these gems." Based in the Bernard Mitchell Hospital ER, Rebecca McNicholas and Vanessa Muhammad are key players in this effort. They are part of a cadre of eight "patient advocates" stationed in the ERs of Comer and Mitchell, under UHI, tasked with connecting people to a community medical provider. Typical emergency conditions seen at Mitchell include chest pain, abdominal pain and respiratory distress. And although the adult ER is not a trauma center, occasionally it treats gunshot wounds and other critical injuries. The facility also sees its share of patients with non-life threatening conditions -- lacerations, abscesses, rashes, headaches and confusion over medication, for example -- who are better served by a primary care provider with whom the patient can forge a long-term relationship. These are the people in whom McNicholas and Muhammad are interested. "| eoplehavebeensocializedto P cometotheER;we'retrying tochangesocialnorms." --EricWhitaker,MD Patient Advocates Serve as the Mortar It's late on a weekday afternoon, and the ER is filling up. The mood is calm but tense. McNicholas and Muhammad put the average wait-time for non-life-threatening cases at six to nine hours. "Is there anyone here without a primary care doctor who'd like to be set up with one?" Muhammad asks over the general hubbub. Five hands go up, and she speaks to each person to determine his or her needs. Denise Austin, 57, is in a wheelchair with chronic leg pain from falling recently at a South Side bus station where she's a cleaner and attendant. Austin says she has no doctor because her job doesn't provide health insurance. "The way it is, you have to have health insurance," she says. Muhammad discusses several South Side Healthcare Collaborative sites where Austin can receive follow-up care after she's been treated. Austin chooses ACCESS AuburnGresham Family Health Center, where she will be seen the following week. UHI has an arrangement with some South Side Healthcare Collaborative partners in which appointments are reserved as needed for patients referred from the Medical Center. The co-pay is approximately $45, but ACCESS operates on a need-based sliding scale if Austin can bring a pay stub. The records from Austin's treatment in the ER will be faxed to ACCESS before her appointment. Muhammad also does the rounds of patients in the examination rooms. She treads carefully amid the whirl of activity, parting the curtains that screen patients to snatch time with them. Trying to catch those who might fall through the cracks, Muhammad will later call patients who left the ER without being seen to discuss if they can be connected with a medical home. McNicholas, who also works the phones, says she reminds patients of upcoming appointments at South Side Healthcare Collaborative sites and checks in afterward to find out how appointments went. She's not afraid to cajole when someone misses an appointment and has to reschedule. "I say, `promise me you'll go.'" Visiting federally qualified health centers can be revelatory, noted Whitaker, whose own family receives care at a community health center. "When people see them, they're like, `wow, this is nice.'" Eric Whitaker, MD, leads the Urban Health Initiative. Photo by Anne Ryan The primary care provider model is gaining traction nationally. Studies have shown that improving access to primary care reduces hospitalization, particularly for chronic diseases, in urban areas. Within UHI, connecting people to a primary care provider is a key lever for shifting the focus from sporadic, reactive care to wellness and prevention. Lacking a stable health provider, many South Side residents currently turn to the Medical Center's Emergency Department for care. Their immediate symptoms can be treated, but because the hospital is geared toward acute and complex care, underlying conditions may go unresolved and preventive services cannot be offered. The habit of visiting the ER for routine medical needs runs deep, ingrained by established folkways, observed Whitaker. "People have been socialized to come to the ER; we're trying to change social norms." This begins with raising awareness of alternatives such as federally qualified health centers. They are the "backbone of the safety net," said Laura Derks, director of the South Side Healthcare Collaborative. Many of these centers provide services on a sliding-fee scale and offer the kinds of specialties, such as dentistry and nutrition counseling, that are simply unavailable in the ER. But the very people these centers are designed to serve are frequently unaware they exist. A survey in the fall of 2007 revealed that, out of 500 University of Chicago Medicine on the Midway Photo by Dan Dry Spring/Summer 2010 Emergency Room Patient Advocate Vanessa Muhammad in the patient advocate consultation area. Photo by Dan Dry Photos in the patient advocate consultation area were all taken in South Side neighborhoods by photographer Dan Dry. This could describe someone's reaction on visiting Chicago Family Health Center in South Chicago. The facility includes 30 examination rooms, a dispensing pharmacy, a 75-person waiting room with six patient registration bays and a dental clinic. In 2008, UHI funded a new women's health wing. Like other health centers, it offers a comprehensive menu of services that "wrap around" medical care, including a nutritionist for dietary advice, financial counselors to assess eligibility for public assistance, case workers to help navigate the system, a social worker and a clinically-licensed psychologist. For "working poor" patients, for whom time out of work represents forfeited income, this collection of services provides an invaluable one-stop shop, said CEO Warren Brodine. Treating non-critical patients in such settings also meshes with the economics governing health care -- a key consideration amid a wave of hospital closures, locally and nationally. The overheads of education, research and equipmentintensive advanced care means it costs the Medical Center's ER $1,200 to deliver the same primary care a health center can provide for $120. Meanwhile, the government provides incentives to federally qualified health centers to offer primary care services to low-income patients, allotting a typical reimbursement of $120 for primary care services rendered to Medicaid patients versus the $35 the Medical Center receives on average for delivering equivalent services. The federal government underwrites community health centers because they focus on serving low-income and uninsured populations. Building a robust health care system also means addressing a growing shortfall of primary care physicians -- projected by the National Association of Community Health Centers to balloon to 40,000 by 2035. "It's a big problem," observed Whitaker. "We can produce all the doctors we want, but if they all go to work on Michigan Avenue, we're not having an impact." Another key UHI goal is to inspire Pritzker students to pursue careers in primary care and community medicine. Luring New Doctors to the South Side Sarah-Anne Schumann is a family medicine doctor at Chicago Family. Under UHI, she's also Pritzker's new For more information, call 1-888-UCH-0200 or visit uchospitals.edu director of Community Health and Service-Learning. "I want students to see how satisfying a career in the community can be," she said. Schumann, MD, presides over several programs that train students in community medicine. Students can enroll in a community health track within the new Pritzker curriculum. Graduates committing to practice on the South Side can apply, through the REACH Program, for financial breaks of $40,000 a year (up to a maximum of $160,000 over four years) to defray their student debt -- a boon for Pritzker alumni who graduate on average with more than $200,000 in debt. Schumann works closely with the forthcoming Center for Community Health and Vitality, a key organization within UHI charged with tackling the socioeconomic and environmental determinants of health. "Improving health is not just about what doctor you see," explained Center Director Doriane Miller, MD. "There are multiple factors, including proper nutrition, community safety and healthy behaviors." Besides administering the South Side Health and Vitality Studies (see accompanying article), the Center will be the seat of a range of programs designed to connect people to essential services, jump-start grassroots initiatives, provide health education and train local youth for health care careers. Another critical function is ensuring the community is heard loud and clear within UHI. "This is a departure for the Medical Center," Whitaker noted. "Historically, we've been focused on this campus." UHI doesn't just require a shift in the way the Medical Center relates to its community, he added; it demands that the Medical Center recast how it views itself. "If Medical Center physicians have a practice at Mercy Hospital, is that still seen as part of the University of Chicago? Previously, the answer would have been, `No, the University of Chicago is just the campus,' " he observed. "The new view is that we have a satellite branch where our faculty can see patients and teach." The effort is being closely watched by other academic medical centers, some 70 percent of which are situated in communities with similar health indices, Whitaker said. He and others hope UHI also can become a model for urban health nationwide. On the Trail Less Traveled By Cheryl L. Reed Learning how to keep in contact with the most elusive population will inform researchers about how to conduct the larger South Side Health and Vitality Studies, a longitudinal analysis of 5,000 randomly selected South Side residents. These studies are slated to begin in three years. he sign on the door reads: Private Property. No Trespassing. "These are the broad brush strokes of what will be a comInside, a plastic strip secured with masking tape leads a path through the dark, twisting hallway. plicated study of the South Side," said John Schneider, MD, The trail ends at a bulletproof window. There, a hotel clerk raises her eyebrows at the red clipboard in instructor of medicine and epidemiology and director of Ramya Iyer's arms and the Nextel phone box in Billy Jackson's hands. global health programs "We're from the University of Chicago's at the Medical Center. South Side Health and Vitality Studies, and we Schneider, who designed have a couple of people from our survey in this the pilot study and is part building," announced Iyer, a 26-year-old Social of the team devising the Services Administration graduate student. "We larger study, spends up don't have names, just numbers of their rooms." to three months a year in The clerk buzzes the two field researchers India tracking down men through a side door. They climb a set of stairs susceptible to contracting and knock on the doors that correspond to the HIV. He understands the numbers derived from a database back at the complications of tracking University of Chicago Survey Lab. But no one elusive populations. responds. The researchers hang tags on the The South Side Studies doors, offering $15 for a 15-minute interview. will monitor the health Had someone answered, he or she would have of the sample for 20-plus had the option of taking a cell phone, with free years and will be patterned texting, so researchers could follow up in six after Boston University's weeks and then in three months. Framingham Heart Study, The incentives are part of the Recruitment which started in 1948 and and Retention Survey, a pilot study tracking now has tracked three residents from six South Side neighborhoods: generations of residents Kenwood, Grand Boulevard, Washington Park, from that Boston suburb. Woodlawn, Roseland and Pullman. A separate Just as the Framingham sampling includes people from those neighstudy focused on heart borhoods who are especially difficult to track disease and stroke, the South -- those who live in single room occupancies Side Studies will likely focus (SROs), who move frequently, don't have landon rates of obesity and lines or are known to the post office as difficult diabetes, the health effects to track down for mail delivery. University of Chicago survey researchers Billy Jackson, left, and Ramya Iyer. Photo by Anne Ryan of violence and mental Researchers track down the most elusive South Side residents in a pilot study about health care T health issues of South Side residents -- issues that were ranked as the most pressing among community leaders. "People talk about food deserts on the South Side, but there are health care provider deserts too," explained Schneider. "Part of the secondary objectives of this pilot study is to ask the greater questions about residents' access to health care. A lot of people are telling us that they don't know where to go to see a dentist or to get HIV care." The hope is that the long-term study will be able to establish a baseline picture of health for South Side residents which, in turn, will inform specific programs to target those health problems down to the neighborhood or even block. The studies would track the efficiency of health programs and how well they are addressing problems. Information collected would be used to attract federal and state funds by documenting the needs of the community. Funding for the South Side Studies, though, remains an obstacle. Because of its breadth and depth, the longitudinal study is estimated to cost anywhere from $8 million to $15 million, turning researchers into salesmen as they try to convince major donors, government entities and foundations to support the project. "We need to find philanthropists who are passionate about this issue," explained Stacy Tessler Lindau, MD, assistant professor of obstetrics and gynecology and principal investigator for the South Side Studies. "Those sources of support are going to be very important in securing funding from the federal government." Currently, the Resource and Retention pilot study and another pilot study last summer that mapped every nonresidential building in six South Side neighborhoods have cost the university about $200,000, not including faculty and staff time and overhead expenses. The Medical Center has committed an initial $1.5 million for development of the pilot studies, which includes building community partnerships and fundraising to extend the mapping project to all 34 South Side neighborhoods. The funding came from the studies' parent program known as the Urban Health Initiative, the Medical Center's major, long-term commitment to help improve the health status of the surrounding communities. (See adjoining article.) money has made it easier. One of the survey questions asks how likely they would be to do the study if we paid them $100 each time we talked to them. They just look at you and laugh and say: `Uh, very likely.'" The pilot study is not only testing the best way to get someone to parFinding incentives ticipate -- is $2 or $5 a better incenBy mid-October, the Recruitment tive or will it require a $15 gift card and Retention pilot study had reached or a walkie-talkie phone -- but what 168 people out of an initial computermethods are best to keep in contact: ized sample of 640, and researchers phone, e-mail or an in-person visit were beginning to apply a full-court (no one has turned down $100 yet). press to reach the stragglers before The study also taps into respondents' re-contacting respondents for sixaccess to health care and technology. week and three-month follow ups. Currently, only 20 percent of houseStanding in an unseasonably chilly holds on the South Side have Internet downpour, Iyer and Jackson, a 23-year- John Schneider, MD, designed the pilot study access through a home computer. old South Side freelance artist who that tracks elusive populations. Photo by Dan Dry Researchers hope to use information lives near the survey lab, waited for from the mapping study to apply for stimulus money that someone to answer an apartment call button. The wind whipped would provide free Internet access through community cenacross their jackets as they huddled together outside the brick ters and churches on the South Side. That way residents could building protected by an ominous steel gate. Though no one get health information and stay in contact with doctors even if stirred in the building, the Grand Boulevard neighborhood they don't have a phone or a stable address. was alive with activity. Church bells sounded across the street Though the young researchers aren't strangers to urban and an elderly woman passed by, pushing a cart of groceries. populations, they say they've been surprised by the divergent The young researchers had lucked out in their first contact lifestyles and disparate housing they've encountered on the that morning: A couple living in an SRO were eager to visit South Side. They've interviewed residents with high-ceiling and opted for the phone over a Target gift card. Instead of apartments and grand pianos, but they've also encountered being shooed away and having doors slammed in their faces, people who share boarded-up buildings. the researchers say their biggest problem is that residents like "It's informed my work as a therapist and given me a better the company and keep talking outside the scope of the study. understanding of the range of their environments," Iyer said. "Some people are very lonely," explained one of the field They've also been pleased by the number of people who researchers, Jeff Bean, 23, who recently graduated from the have agreed to do the survey. "People are just surprised that University of Chicago. "Offering money has made a differthe university is taking an interest in them," Bean said. ence. I think a lot of people would still do it, but offering Spring/Summer 2010 Spring/Summer 2010 University of Chicago Medicine on the Midway Denise Wysocki, left, with her daughter Elizabeth Noreen, who was first diagnosed with a tumor at 6 years old. Photo by Dan Dry Photo by Dan Dry Life After Cancer is a New Focus for Research By Greg Borzo s if beating cancer wasn't enough, cancer survivors face an even greater risk for health problems, such as heart disease, infertility, sexual dysfunction, depression, substance abuse, suicide, lack of insurability, pulmonary disease, anxiety and poor continuity of care. Add to that the risk of developing a second cancer, and you have a recipe for serious problems and stress, all of which are magnified if you are financially disadvantaged. Secondary stresses, apart from surviving cancer, are becoming more apparent as more cancer patients live longer. There are about 14 million people living in the United States who have been previously diagnosed with cancer, according to the National Cancer Institute. A 2009 study in the Journal of Clinical Oncology showed that about 80 percent of children will survive at least five years after diagnosis. "In pediatric cancer, we've had tremendous success in the cure rate. But as the population of survivors grows, they have significant long-term health issues, which can be attributed to their cancer therapies," said Tara Henderson, MD, director of the Medical Center's Childhood Cancer Survivors Center. "As patients are transitioned to survivorship, we have to consider their health throughout the remainder of their lives. Now, our focus in pediatric oncology is on minimizing the long-term morbidities from the very beginning while still maintaining or improving our cure rates." Each age group of cancer survivors faces different issues. Elders often struggle with hypertension and lack of social support, while adults often struggle with infertility, employment-related problems and marital and family issues. Children are especially vulnerable because some treatments harm their developing bodies. In 1997, 6-year-old Elizabeth Noreen of Palos Hills, Ill., was diagnosed with a primitive neural ectodermal tumor, a rare cancer with a survival rate of less than 40 percent. Worse yet, the cancer was Stage IV and had metastasized to the lungs. " neofthesurveyquestionsaskshowlikelytheywouldbeto O dothestudyifwepaidthem$100eachtimewetalkedtothem. Theyjustlookatyouandlaughandsay:`Uh,verylikely.'" --JeffBean,FieldResearcher Mapping neighborhoods This past summer, Bean and Johnson were both field researchers in the mapping project that plotted everything but homes in six neighborhoods: Hyde Park, Kenwood, Woodlawn, Washington Park, Grand Boulevard and Eastside. That pilot study, called the Resource Mapping Project, was completed by summer's end and the results were made available online in mid-October at www.southsidehealth.org. Visitors to the site can conduct precise searches of everything from car repair shops to health care clinics on the neighborhood level. Although researchers are still fine-tuning the website and aspire to extend the project to include all 34 South Side neighborhoods, the data was made available to the public before it was picture-perfect -- part of the Medical Center's promise to community leaders to share findings quickly and to solicit feedback on how to tailor data for community use. "We have definitely heard people say: `We're tired of researchers parachuting in and doing studies and never getting information back,'" explained Lindau. "We're doing things differently now. We're working with the community and putting our joint product out in an early phase. This gives community and university folks a chance to work with the data, tell us how they want to use it, and then we work together to ensure it translates." The information gathered in Woodlawn has already been handed over to community leaders like Arthur M. Brazier, For more information, call 1-888-UCH-0200 or visit uchospitals.edu A bishop emeritus of the neighborhood's mega church, Apostolic Church of God. Brazier has been working to revamp Woodlawn's elementary school curricula to stress parent-teacher engagement and push the importance of college, starting from pre-school. Brazier is hoping the information from the mapping project will help make the case for a $25 million grant from the U.S. Department of Education that would enable them to change the curricula. Part of the Medical Center's motivation behind the mapping project was to prove to community members that the university could be an equal partner and would live up to its stated commitments. At the mapping website's unveiling, dozens of community members packed into the DuSable Museum of African American History, near the Medical Center's campus, to give their unbridled input. Some openly admitted they'd been skeptical in the beginning, but the project had helped them warm to partnering with the university. "I was born and raised on the South Side and have a healthy skepticism about the university," said Shirley Fleming, a member of the health ministry at Trinity United Church of Christ, also on the South Side. "We want to contribute to the process and to promote health in our community. This data allows us to apply for grants and be on the ground level. Let's just say it's made me hopeful." Spending most of the next eight months at Comer Children's Hospital at the University of Chicago, Elizabeth received radiation therapy, chemotherapy and a stem cell transplant. Now, at age 18 and long-since cancer free, Elizabeth has to deal with a host of issues related to her cancer treatment. Because of all the radiation, she has a lung capacity of 50 percent, which has led to multiple lung infections. She has thyroid problems and will not be able to conceive. And she has missed so much school that her test scores and academics are below par. Meanwhile, transitioning from pediatric to adult caregivers is proving to be difficult. "This has been tough, but with good family and friends and the top-notch care, we pulled through," said Denise Wysocki, Elizabeth's mother. "Still, the issues never seem to end." Nevertheless, Elizabeth has demonstrated strong resolve. "First, you have to stick with your treatments even if they say you have a good chance of dying," she said. "Then, you have to keep trying to cope with everything else that comes along and stay positive." Elizabeth is so positive that she wants to become a clinical care specialist and take care of kids at Comer Children's Hospital. She and her mother appreciate the well-rounded care they received at the Medical Center, where providers are very attuned to the special needs of patients who survive childhood cancers. "Cancer therapies can impact just about any organ you can think of," Henderson said. "We administer toxic drugs and radiation to growing organs. Survivors are not aware of their risks, and need screening and follow-up care. It's no surprise that mortality and morbidity are high for childhood cancer survivors." A striking example of this is the fact that approximately 20 percent of females who survive childhood cancer and have received chest radiation as girls develop breast cancer by the age of 45, compared to about 1 percent in the general population, Henderson said. Spring/Summer 2010 27 Spring 29 Psychosocial Effects of Cancer To address such problems, the Medical Center conducts research and offers cancer survivors counseling and support groups. The Psycho-oncology Service offers evaluation, consultation and therapy for adult cancer patients, collaborating with oncologists, social workers, chaplains and nurse practitioners. Last year, the Medical Center joined the Childhood Cancer Survivorship Study, the largest, most comprehensive cohort study of childhood cancer survivors in North America. This After Niki, a 33-year-old Chicago woman living in Las Vegas, found out she carried the BRCA1 genetic mutation, which increases her risk of breast and ovarian cancer, she took extraordinary precautions to prevent getting cancer. She has had blood tests and a transvaginal and pelvic ultrasound twice a year for the past seven years. She even had a double mastectomy. "I work out a lot and was getting screened twice a year through ultrasounds and blood work for ovarian cancer, so I thought I was doing a good job staying on top of everything," said Niki. One day in May 2009, Niki's blood work showed the possibility that there was a presence of cancer in her body, so the next day she had a CT scan. It revealed a large mass in her abdomen. Niki immediately moved from Las Vegas back to her native hometown, Chicago, where Diane Yamada, MD, chief of the Section of Gynecologic Oncology, agreed to do emergency surgery. Yamada found that Niki had primary peritoneal cancer, which is quite rare. The cancer was advanced -- Stage IV -- with tumors on several of her organs. The median survival for patients in her condition is five years. After surgery, Niki had six cycles of aggressive chemotherapy. "I'd like to tell other women, especially those with BRCA1 genetic mutation, that today's screening tools are not adequate," Niki said. "I hope doctors and researchers are developing better screening tools." To help cope, Niki remembers a lesson she learned from her father, who died of pancreatic cancer last summer: Live every day to the fullest. Niki credits Siston, her counselor, for helping her to keep such a positive attitude. "I see her weekly, and she has been amazing," she said. "Amy has helped me realize that there are things worse than dying -- like dying without having lived." Saving a Cancer Patient's Baby By Emily Stone Jennifer Sowacke with her daughter Olivia, now 6 years old. Photo by Dan Dry J Amy Siston, PhD, with Niki after one of their sessions. Photo by Anne Ryan Every time I started crying or felt bad, I would feel that baby kick...she was telling me to knock it off. --Jennifer Sowacke Spring/Summer 2010 31 30 University of Chicago Medicine on the Midway `` study was initiated in 1993 with a grant from the National Cancer Institute and is coordinated through the St. Jude Children's Research Hospital. It allows investigation of treatment and follow-up data for 14,000 patients diagnosed with cancer from 1970 to 1986 at 30 medical institutions in the United States and Canada. Medical Center research builds on this and other studies. For example, in an effort to reduce the incidence of breast cancer in survivors, Henderson is trying to identify which children with Hodgkin's Disease should forgo radiation therapy. Also, she is studying how awareness of late effects of cancer therapy and second cancers impact outcomes. "We're discovering that many cancer survivors don't know they're under increased risk," Henderson said. "New research that we'll publish soon reveals even pediatric oncologists are unaware of these risks." This lack of physician awareness may be alleviated because internists and pediatricians are developing subspecialties in cancer survivorship, noted Michelle Le Beau, PhD, director of the University of Chicago Comprehensive Cancer Center. "Our overall goal at the Medical Center is to provide comprehensive care: diagnosis and treatment, support and survivorship," she said. Cancer survivors and their caregivers -- in addition to being vigilant about medical issues -- must deal with psychosocial effects, such as emotional, spiritual and economic challenges. "We need to help cancer survivors achieve and maintain a good quality of life," said Amy Siston, PhD, clinical associate in psychiatry and behavioral neuroscience. "Patients may complete their cancer treatment, but there are physical and psychosocial issues, such as depression, anxiety and fear of reoccurrence, that patients deal with many years later." ennifer Sowacke had been trying for two years after the birth of her second child to get pregnant. The day she discovered she was five weeks pregnant, she also felt a lump in her breast. It was too early in the pregnancy to safely have a mammogram, and her doctor told her not to worry about the lump. She pressed him for a biopsy. It showed that she had a malignant tumor. She immediately saw a surgeon, but he refused to treat her. "He wouldn't touch me until I terminated the pregnancy," she said. Devastated, Sowacke made an appointment for a second opinion at the University of Chicago Medical Center at the suggestion of a neighbor. She met Nora Jaskowiak, MD, the surgical director of the Breast Center. Jaskowiak told her that it would be harder to treat her while pregnant, but it wasn't impossible. Sowacke and her husband, Paul, decided to keep the baby. "She was going to have to treat it as a patient within a patient," said Sowacke, of Homewood, Ill., who was 32 at the time with no history of breast cancer in her family. "I knew they were going to treat me with the baby in mind, and that was very important to us." The next eight months were an emotional mix of fear of the cancer and what the treatment might be doing to her fetus, and excitement about having a new baby. "It was something so good going on while something so evil was going on," Sowacke said of the ordeal she went through seven years ago. Tara Henderson, MD, director of the Medical Center's Childhood Cancer Survivors Center, says chilhood cancer survivors are often not aware of the risks of toxic drugs that show up later in life. Sowacke, now 39, remembers Jaskowiak walking her and her husband through the treatment options and explaining the added complications the pregnancy presented. For example, she had to wait until she was 11 weeks pregnant to have a mastectomy because it's dangerous for a fetus to undergo anesthesia earlier than that. Sowacke could only be safely anesthetized for five hours, so Jaskowiak had to remove one breast and all the attached lymph nodes within that deadline. Sowacke needed to have a mastectomy because she could not receive radiation while pregnant. In addition, her tumor was estrogen sensitive so anti-estrogen medication played a big role in her treatment. Jaskowiak said that Medical Center physicians treat about two pregnant women a year for breast cancer. Jaskowiak, who was also pregnant at the time, said Sowacke was the first such patient she had ever had. "My pregnancy gave me a deep connection to Jen and her family and their very strong desire to save the pregnancy," Jaskowiak said. "There is no doubt that there is a special bond between us." Jaskowiak listened to the Sowackes explain their desire to keep their baby and began planning Sowacke's treatment. "We said, `OK, if this is one of your goals to preserve the pregnancy, it can happen,'" Jaskowiak said. The mastectomy went well, and there didn't seem to be any harm done to the fetus. Sowacke's test results came back clean, meaning Jaskowiak had removed all the cancerous cells. Sowacke waited to have chemotherapy until after the baby was born. So the rest of the pregnancy was a waiting game of trying to keep her spirits up and put on a brave face for her other two daughters, Abbey, then 4, and Grace, then 2. "There were times I cried," Sowacke said. "But, every time I started crying or felt bad, I would feel that baby kick. It was almost like she was telling me to knock it off. I never felt alone." In March 2003, Sowacke delivered a healthy little girl, Olivia. She started chemotherapy three weeks later and has been cancer free ever since. Olivia likes to hear the story about how Jaskowiak saved her and her mom's life, and she always asks to go with her mom for checkups. "It's been a thrill to watch her grow up," Jaskowiak said. Sowacke is eternally grateful to Jaskowiak and the other doctors at the Medical Center who refused to give up on her baby. "If I hadn't gone to the University of Chicago," she said, "if I had stayed at my local hospital, my story would be totally different." `` Jennifer, cancer survivor, with her husband, Paul, and daughters Olivia, Abbey and Grace. Photo by Dan Dry Medicine off the Midway Dennis Slamon, MD, PhD in his lab at UCLA. Photos provided by Dennis Slamon A cancer research pioneer, Slamon is shown here in the lab in his younger years. Just when it seemed the project might be sidelined, Slamon's phone rang. It was Lilly Tartikoff, a prominent LA figure and anti-cancer activist with an eye for promising developments. The question for Slamon and coworkers was, "why?" Translational medicine -- recognizing the two-way street between knowledge gained directly from working with patients and scientific findings emerging from the labs -- has become well established since the 1970s, when the approach was being pioneered by Rowley, professor of molecular genetics and cell biology. Bringing together clinical experience with laboratory knowledge encouraged researchers to see that something had to be going on at the molecular level to explain the divergence in clinical outcomes. "There must be biology there," Slamon said, recalling the fundamental insight. "It was understanding that there must be molecular diversity that caused the field to take a quantum leap forward." The insight can be traced to one of Rowley's early findings. Using ordinary scissors to snip apart photographs of abnormal cells from leukemia patients, she was able to demonstrate in 1972 that bits of separate chromosomes had broken off and regulates division and growth, appears in abnormal cells in too many copies, resulting in overly rapid growth and a cancerous tumor. Herceptin works by inactivating a protein produced by the HER2 gene, which triggers the excessive growth. Used in combination with chemotherapy, the drug has transformed a very aggressive form of breast cancer, for which little effective treatment had been available, into a highly treatable disease. Some patients seem to overcome the malignancy altogether, living cancer-free years later, while in others the progress of the cancer is significantly slowed. Taking advantage of the conceptual breakthrough afforded by a translational approach was one thing; generating the level of funding necessary to turn the idea into a treatment is quite another. This is where the Hollywood connection comes in. By 1989, Slamon and his team found themselves at a crossroads, armed with promising new data but encountering resistance from funding sources in government and industry. "We tried to explain to them that we were targeting not just the marker of tumor cells but something that was playing a role in causing the tumor cell behavior," he said. "But even with all the data, there were lots of naysayers." Just when it seemed the project might be sidelined, Slamon's phone rang. It was Lilly Tartikoff, a prominent LA figure and anti-cancer activist with an eye for promising developments. Of course, it didn't hurt that since 1982 Slamon had been successfully treating Tartikoff 's husband, the television producer Brandon Tartikoff, for a recurrence of Hodgkin's disease. (Tartikoff died in 1997.) Lilly Tartikoff turned to Ronald Perelman of Revlon, persuading him to set up an unusual donor arrangement in 1990 that helped put Slamon's research over the top and continues funding cancer research to this day. It was not just having celebrity backers that led eventually to "Living Proof," the 2008 film about Slamon and his groundbreaking work. The story itself -- determined scientist perseveres in the face of powerful resistance, succeeding against long odds in the nick of time to save an innocent life -- is the stuff of a screenwriter's dreams. With Harry Connick Jr., in the lead as the indefatigable Slamon and Bernadette Peters as Barbara Bradfield, the first woman whose life was saved by Herceptin, the film was guaranteed to attract some favorable attention. But, it also benefitted from an all-star cast behind the scenes, including Ren�e Zellweger as executive producer. The early funding difficulties, in Slamon's judgment, delayed medical progress by as much as five to seven years. But, there is no doubt in his mind about Herceptin representing a paradigm shift in cancer treatment. With similar promising drugs already in use, and new ones in the pipeline targeting lung, prostate and other cancers, Slamon is confident that the future of this kind of research is secure. He foresees fundamental changes in the way a number of cancers will be treated just within the next four or five years. If he is right, and the success of Herceptin is matched for other malignancies, it will come, for a great many people the world over, as very good news indeed. Spring/Summer 2010 33 RESEARCH By Don Reneau CANCER GOES TO HOLLYWOOD Dennis Slamon makes a quiet impression. Especially for a famous Los Angeles physician whose work was featured recently in a film backed by major Hollywood star power. Slamon owes his fame to the lead role he played developing the drug Herceptin, a revolutionary treatment approved in 1998 for a common type of breast cancer. Sharing the credit seems to come naturally to the doctor. Among those he lists as contributors to the breakthrough development are research collaborators over the years and his advisors at the University of Chicago, where he earned PhD and MD degrees in 1974 and 1975. But Slamon reserves special mention for breast cancer patients themselves, women who agreed to take part in the early clinical trials leading to the Food and Drug Administration's approval for the effective new drug. A professor of medicine and director, since 1988, of Clinical/ Translational Research at UCLA's Jonsson Comprehensive Cancer Center, Slamon appreciates Southern California as a fine place to pursue his work. But Los Angeles has never replaced Chicago in his affections. The product of small-town life in western Pennsylvania, Slamon remembers Chicago as his eye-opening introduction to life in the big city. "It was a great time in my life," he recalled. "Chicago was just a great city, with all the things a big city has to offer. But it had a blue-collar feel, with friendly people, and it worked very well for me." Clearly a good match for the modest, determined, hard-working personal style for which Slamon has been noted throughout his career. Whatever the benefits of living in a major urban center, the real payoff for all concerned was the postgraduate training Slamon received at the University of Chicago. Exposure to the excellent faculty -- Slamon recalled Janet Rowley, MD, Winston Anderson, MD, and Werner Kirsten, MD, in particular -- was "more than educational. It was formative." Working in Kirsten's 32 For more information, call 1-888-UCH-0200 or visit uchospitals.edu Slamon with Jonsson Comprehensive Cancer Center Director Judy Gasson, PhD, left, and Lilly Tartikoff, right. lab, Slamon helped identify an early example of the so-called oncogenes, or cancer-causing genes, which can be shown in experiments to be associated with malignancies. It was an "incredibly rich and robust environment for training people like myself, who would be armed to come at the problem from both sides of the fence." The problem, in a nutshell, was the discrepancy between the apparent promise of chemotherapies based on new experimental findings in the laboratory, and the radically divergent patient outcomes being seen in the clinical setting of a hospital. "The one thing that kicked the whole process off," said Slamon, "was that we had been using one-size-fits-all approaches." The chemotherapy cocktails designed on the basis of lab experiments were being administered to patients based largely on where the cancer arose, in the lung, say, or in the breast. "What should have told us something was off was that the clinical outcomes were different," he said. "Some people did incredibly well. Some people did incredibly poorly." exchanged places. It was because of this translocation of partial chromosomes that normal genes turned into oncogenes. In their original location they had regulated cell division and growth. Now they were causing normal cells to become cancerous. This was the initial discovery of the link between cancer and genetic abnormalities, for which Rowley was awarded the Presidential Medal of Freedom in August 2009. Given the relatively primitive technology available to Rowley at the time, Slamon marvels at her accomplishment. Productive findings can be hard to come by even today, using sophisticated computer software to compare huge panels of cancer cell lines in an attempt to link observed abnormalities to the underlying genetic constitution of the cell. But the results are unambiguous. Just because cancers originate in the same organ does not mean they are alike. Biologically speaking, some breast cancers are more like ovarian cancers, some lung cancers more like sarcomas. How a malignancy develops in the clinical setting -- and thus what kind of intervention might be developed to stop it and save a patient's life -- depends not on the affected organ but on the molecular makeup of the disease. Herceptin, the drug developed based on Slamon's preclinical and clinical research, targets a genetic abnormality that appears in about 20 to 25 percent of breast cancers, affecting more than 200,000 women each year worldwide. In these cases the HER2 gene, once again a gene that in normal cells Finding a Compatible Match for a Gift of Life By Rob Mitchum An organ transplant is a priceless gift that can save a person's life. But the body is notoriously ungracious and has picky tastes that need to be satisfied with close compatibility or tricked by suppressing the immune system. As such, the actual transplant is the culmination of months of meticulous laboratory testing to create the right match between donor and recipient. At the University of Chicago Medical Center, that matchadult leukemias and lymphomas, require more selective donormaking process happens in one lab where the most advanced recipient matching and demonstrate the advantages of having the tests of today -- and potentially tomorrow -- are applied to each most powerful testing technology on site. Since the laboratory transplant case. Established in 2007 by Director Susana R. opened in 2007, the wait for the advanced test results required for Marino, MD, PhD, the Transplant Immunology & Immunostem cell transplants has dropped from weeks to days. genetics Laboratory allows physicians to find the most compat"In this institution, we have protocols that go a little bit ible donors for transplant recipients and track them afterwards beyond many other institutions, and we also receive sicker to monitor their successes. patients," Marino said. "Otherwise, these patients would never "The fact that the laboratory is here allows us to really react be transplanted; it would be too difficult to identify compatible very rapidly to changes in the field, to constantly introduce new donors for them." procedures to re-evaluate our own program, and Having a leading transplant immunology also to do research in the area," said Koen van laboratory on site also allows testing experts to Besien, MD, director of the stem cell transplant be closely involved with the transplant team, and lymphoma programs at the Medical Center. meeting with clinicians and surgeons to create During testing, human leukocyte antigens safe and effective plans for patients. (HLA) -- unique signals that the body uses to Such close collaborations are an advantage recognize its own cells from foreign cells -- and when faced with unanticipated complications. antibodies that the recipient may carry against During Theresa Gonsiorowski's transplant in potential donors are identified in separate tests. which she received a portion of her husband Finding a compatible donor-recipient pair can Ron's liver, surgeons noticed signs of a possible minimize the chances of rejection, when the hyperacute rejection -- a rapid antibody response immune system strikes back against the new that occurs very rarely in the procedure. organ in the days after the transplant. Immediate testing by Marino's laboratory With the latest technology, compatibility confirmed the immune response, prompting can be tested several ways -- the HLA genes rapid treatment to prevent Gonsiorowski's of the donor and recipient can be sequenced, immune system from rejecting the liver. antibodies of the recipient can be characterized, Susana R. Marino, MD, PhD, runs the Because of the rapid response, Marino said, or the recipient's antibodies can be directly Transplant Immunology & "the liver had time to recover and do the job Immunogenetics Laboratory. tested against a potential donor's cells in a Photo by Dan Dry when the level of antibodies was down. I think, cross-match test. In the transplant of a solid probably, if we hadn't done that, the patient organ such as kidney, heart or lung, basic HLA typing is sufficient wouldn't have survived." in most cases. However, testing for the presence of preformed With more than 1,200 tests performed each month by HLA antibodies against the donor is critical. Expertise in newer, Marino's team, it's clear that the laboratory has become an more advanced testing can make transplants possible for even integral part of the Medical Center. difficult-to-match patients. "We are able to transplant patients who wouldn't have been Stem cell transplants, performed by van Besien to treat cases of transplanted before," Marino said. By Emily Stone Melanie Brown, MD, often gets the same reaction when she Parker said she loves being able to walk into patients' rooms says she's part of Comer Children's Hospital at the University and focus solely on making them feel better. She knows parents of Chicago's new palliative care team. People assume it's a very like it, too. sad job. "That's very important to them, that someone is thinking But Brown loves her role with the Pediatric Comfort Team, specifically about their child's comfort," she said. which helps patients with painful or terminal illnesses enjoy This shift in focus made a huge difference for Rhonda Atkins their lives to the fullest. That may mean switching medications so and her 12-year-old son, Tai Penn, who has Stage IV neuroblasthey sleep better, using alternative medicine to reduce stress and toma cancer. improve appetite, or figuring out a way Tai had a stem cell transplant last for them to leave the hospital and live year and Atkins was worried that the at home. The team helps children with type of morphine the doctor preferred life-threatening diseases as well as those would cause unbearable side effects. with non-life threatening diseases that She requested a consultation with the are particularly painful or disruptive to Comfort Team, and Brown explained their lives. the different pain-killing options to her "Usually, I can make the kids feel betand Tai. ter. I can be a part of them being happy Then Brown said they should figure and enjoying their lives," said Brown, the out what all three of them thought was team's medical director. "I just don't see the best choice. "She said `we.' That how that can be sad." was key," Atkins said. Both she and Tai The team includes Brown -- who is felt empowered by being part of the a pediatric critical care physician -- a decision-making process, and he reacted nurse, pharmacist, nutritionist, social well to the painkiller they chose. worker, chaplain and child life specialist. After the operation, Brown and Parker All, except nurse Katie Parker, RN, work used two types of alternative therapies to full-time in their regular hospital posihelp reduce Tai's pain. Brown has been tions and volunteer with the Comfort Melanie Brown, MD, left, looks over patient trained in sound therapy, which uses Team during work hours and after work. records with Katie Parker, RN. Photo by Dan Dry tuning forks as a form of energy healing They've worked with about 100 patients so far. Most have along the lines of acupuncture or reiki. Atkins said it put Tai to cancer, though the team has seen children with AIDS, inflamsleep, a considerable feat given his pain at the time. matory bowel disease and rheumatoid disorders like lupus They also used aromatherapy by mixing lavender oil with and fibromyalgia. sterile water to make a room spray, which Atkins said created a Their job is to talk with parents and patients to find out what peaceful, calming atmosphere. their goals are -- be it reduced pain or the ability to go back Brown has long been interested in alternative therapies and to school -- and then work as advocates to achieve those goals. was eager to integrate them into the Comfort Team. She's hopThey don't take over patients' medical care. ing to get funding for training in hypnosis and guided imagery, "This is the first time that there's a comprehensive team that is which involves having children picture a calming place. focusing not on the disease process but on the child," Brown said. Brown knows some doctors are skeptical about alternative For example, one boy with a terminal diagnosis wanted to therapies, but all she's concerned about is that the patients enjoy spend his last few months in the country where his parents were the sessions. "I think we should give the kids all the tools at our from and where his extended family still lives. The team was able disposal," she said. to work with his doctors and different government agencies The team works with inpatients and outpatients, and checks to make that happen. Another time, the team helped arrange in with families often to see if their concerns are being addressed. for a photographer to take portraits of a child who was When asked if the ultimate goal is for children to be healthy hooked up to several medical devices and couldn't easily go to a enough that they no longer need to see her, Brown laughed. photography studio. "I want to dance at their weddings and go to their college Often the goals are simpler. If parents want their child to graduations," she said. "I want a Christmas card that says, `Doing start eating and sleeping better, the team may recommend a fine. Loving school.'" change in medication along with advice on creating a regular bedtime routine. 34 University of Chicago Medicine on the Midway Spring/Summer 2010 35 F F X or Daniel Sulmasy, it was a life-changing moment. While Sulmasy, then a fourth-year medical student, was standing nearby in a patient's hospital room, a brusque neurologist delivered the devastating news to the patient: "Lady, you have a big, fat tumor on your spinal cord. We're going to have to give you radiation so you don't end up paralyzed." The physician and his white-coated entourage swept out of the room, leaving Sulmasy to comfort the weeping patient. That's when he decided that medical ethics would be his calling. Today, Sulmasy, MD, PhD, is a 53-year-old internist and nationally recognized expert on spirituality and clinical care. He joined the Medical Center faculty in July 2009 after being recruited to fill a newly endowed chair in the MacLean Center for Clinical Medical Ethics by its founder and current director, Mark Siegler, MD. In April, Sulmasy was named to the Presidential Commission for the Study of Bioethical Issues. The Commission advises the President on policies and practices regarding advances in biomedicine and related areas of science and technology. Most physicians wear more than one hat, but few don as many as Sulmasy. He is supervising interns who are treating outpatients at the Duchossois Center for Advanced Medicine (DCAM). He is teaching ethics classes and researching the overlap between medicine and religion. He is available at any hour for emergency consults about delicate end-of-life issues. And when he goes home at night, Sulmasy heads to a friary where he is a Franciscan brother. "A friar is who I am. What I do is medicine and ethics," he explained during an interview in a book-filled office in the Medical Center's Bernard Mitchell Hospital. If Sulmasy's schedule weren't full enough already, he plans to start practicing internal medicine with the Faculty Practice Group at DCAM in the coming months. In his previous life in New York, Sulmasy handled a patient load of about 250 at St. Vincent's Hospital and New York Medical College in addition to his other duties. These days he is looking forward to being part of the Medical Center's Urban Health Initiative, which he considers a moral imperative. "People of reason and goodwill can agree that it makes good sense for a world-class medical center to share its knowledge and talent with the community around it," Sulmasy said. There is no shortage of ethical issues in medicine to keep Sulmasy busy. "The technology keeps creating them," he pointed out. One recurring question concerns whether it is morally permissible to give a dying patient a powerful pain medication like morphine even if the drug might hasten death. He comes down on the side of "yes," and his philosophical argument is based on something called the "rule of double effect," which states that if a person only intends a good outcome and certain other conditions are met, the action is permissible. "Dose does matter," Sulmasy said. "But from a moral point of view, the dose should be given with the right intention." Many of the questions Sulmasy tackles aren't theoretical. He has conducted research with patients and family members about how accurately loved ones are able to use "substituted judgment" about end-of-life issues for relatives who can no longer speak for themselves. Right: Daniel Sulmasy, MD, PhD, in clinic at the Medical Center. Left: At his friary before prayers. Photos by David Christopher The law says that when a patient is beyond being able to communicate his or her wishes, family members should do their best to proceed with what the patient would want. Sulmasy looked at patients with either cancer or Lou Gehrig's disease and asked them how they would want to be treated at the end of life. Then he asked family members the same question. The family members got it right only 67 percent of the time. "That's statistically significant, but it isn't great," he said. Even if there were a way to get that number higher, that might not be the best answer. Only 25 percent of patients surveyed wanted family members to make decisions solely based on the patient's own personal preferences. Another 20 percent wanted family members to make the decision for them while 55 percent wanted a mix. Sulmasy takes seriously the burden that society and the medical profession place on family members when they are asked to make end-of-life decisions. "Bioethics pays most attention to the patient. Loved ones, however, are usually the ones being asked to make decisions about life-sustaining treatments, and they are under as much stress as someone whose house has burned down," he said. "We're urging people to discuss not just what they want now but who they want to make decisions. It's as much about process as content." The Man of Many Coats: Daniel ulmasy By Susan Chandler "A friar is who I am. What I do is medicine and ethics." The process that brought Sulmasy to this point involved nearly two decades of education and religious training. He decided to join the Franciscans after his internship and spent two years contemplating his vocation during a "formation process." Then he returned to finish his residency at Johns Hopkins in Baltimore, where he ended up as chief resident. He later added a PhD in philosophy from Georgetown University, finishing his education at the age of 39. Initially, Sulmasy thought he wanted to become a priest but later decided that being a non-ordained brother who engaged in works of service was the best path for him. As a member of a Franciscan community, Sulmasy is bound by the order's vows of poverty, chastity and obedience. His salary goes to the order, and he receives a stipend to cover everyday expenses. Having a member of a religious community teaching and consulting on ethical issues at a secular medical school may seem an odd juxtaposition. Sulmasy acknowledges that he agrees with the Catholic Church's position on many questions. But church doctrine is not the only guide to his thinking, and he sees no conflict between his position as a Franciscan and an ethicist. "We always ask `What is the right and good healing act for this patient in this particular circumstance?' We answer that, and then we consider any legal constraints. Most of the time, the law allows us to do the right thing," he said. "My position on most issues will be consistent with the church, but most of my positions are largely based on secular arguments. My degree is in philosophical ethics, not theological." X 36 For more information, call 1-888-UCH-0200 or visit uchospitals.edu Spring/Summer 2010 37 ne afternoon, pediatrician Larry Gray, MD, picked up his phone and dialed the number of a man in Michigan whom he had never met to discuss a little boy in China whom neither of them had ever seen. The man in Michigan and his wife wanted to adopt the Chinese boy and had sent Gray, who heads the International Adoption Clinic at Comer Children's Hospital at the University of Chicago, the boy's medical information from the Chinese orphanage. Gray started the Clinic in 2002, after approaching then-Chairman of Pediatrics Herb Abelson, MD, and explaining his vision. He wanted to assist parents before and after they adopted. And he wanted to help families by connecting them to specialists within the Medical Center, similar to how the Medical Center's Comprehensive Cancer Above: Linda Walsh, RN, and Larry Gray, MD, talk with parents Donna and Center operates. "We're trying to Steve Tucker about the latest additions to the Tucker family: Katherine, 2, help these kids get off to a good and Emily, 3. It's the girls' first visit to the International Adoption Clinic start or get back on the right track," since their arrival in the United States from Russia. Right: Walsh examines Emily Tucker. Photos by Jason Smith Gray said. Gray specializes in behavioral A lack of information forces and developmental pediatrics. Of the more than 20 adoption Gray to "read into the tea leaves health clinics across the country, the Medical Center's Clinic was a bit," and may make the parents' the first in Chicago to offer evaluations from developmental and decision on whether or not to adopt behavioral pediatric specialists. more difficult. "Well-intentioned In the early phases of the adoption process, Gray consults parents are trying to chart a course with the potential parents about whatever health information with no landmarks," Gray said. the orphanage sends on the child. Sometimes all the information Potential parents, he added, might an orphanage sends consists of two sentences in an e-mail; not be aware of the total realm of problems they could face. Of other times, in the case of the Chinese boy, the orphanage sends the 4-year-old boy in China, Gray said that he may have trouble detailed information on height, weight, head circumference and bonding or attachment issues. "He has to be aware that he's been psychological state. abandoned. At 4 years old, a child knows what's going on. He Gray also warns potential parents of problems such as knows that his mom is missing." malnourishment or fetal alcohol syndrome, both of which can After the pre-evaluation, if the potential parents decide to hinder physical and mental development. "Oftentimes, I worry go ahead with the adoption, Walsh prepares for their return we over focus on the negative. Parents also want to hear about appointment. The child will undergo an infectious disease what they can do to help this child." With sufficient information, and developmental work up, which includes screenings for Gray can plot the child's health data on charts provided by the behavioral and developmental problems, as well as mental and World Health Organization that show where a child should fall physical delays. for his or her age. Walsh is the key member of the team and sees all patients, Once the child arrives in the United States, Gray and nurse referring them to specialists as needed. "This has been a great way practitioner Linda Walsh, FNP, conduct an evaluation at the to use my skills of being a provider," she said. Before she joined Medical Center, looking specifically for issues common among the Clinic two years ago, Walsh worked only with HIV patients at children placed in foreign orphanages at a young age -- behavioral the Medical Center, which took an emotional toll. and developmental problems, as well as infectious diseases. International Adoption Clinic Assists in Promoting Health of Children By Katie Scarlett Brandt By Katie Scarlett Brandt O But the Clinic offers some relief from that complex work, and her compassion for the families is obvious. "These families have just been through the big ordeal of bringing a crying kid home on a trans-Atlantic flight. They're vulnerable," she said. Three and a half years ago, Sandra Spadoni and her husband Dan Krebs, as featured in our fall issue of Medicine on the Midway, became one of those families. They were in Zambia conducting HIV research and volunteering in an orphanage when they decided to adopt their first child. For the remainder of their trip, they split their time between research and raising the newest member of their family, infant Josephine. Now in Chicago, Spadoni serves as assistant director for programming in the International Student Adviser Office at the university, and Krebs is a Pritzker School of Medicine student. Last year, they brought home a second adopted child. "We wanted to make sure that Josie had another member of our family who looked like her, who was from the same continent," Spadoni said. As part of their home evaluation before the second adoption, Spadoni and Krebs had to supply a list of resources. In composing the list, they learned about the International Adoption Clinic. "Everything was very streamlined," Spadoni said of their first experiences with the Clinic. "Not only did they take tons of time with us, but they really hooked us up with other services. They were so familiar with the issues of international adoption, with all the bugs that these kids can bring home." According to Walsh, everything comes down to faith -- faith in the children, faith that the parents can make a difference and faith that with a strong medical team in place, everything will work out. "This is the forefront of medicine," Gray added. "We bring this high level medical care and technology to where the parents are. And these parents are pushing the envelope because they're going to the far ends of the earth to adopt a child with HIV, and (overnight) they end up in a Chicago suburb because modern technology allows it -- the airplanes, the Internet, the medicine. It's just wonderful." Providing Hope and Love Through Adoption The Twietmeyers gather in their Joliet, Ill., living room. From left to right: Rachel, 14; Kylie, 17; Hank, 7; parents Carolyn and Kiel; Danny, 5; Brendan, 15; Gracie, 9; Seth, 3; Selah, 11; Ethan, 12; Sam, 8; (not pictured) Matthew, 19, and newly adopted children Andarge, 16, and Eyerusalem, 15. Photo by Jason Smith Parents of 13, Carolyn and Kiel Twietmeyer first used the Medical Center's International Adoption Clinic two years ago when they adopted three siblings from Ethiopia. Since then, Carolyn and Kiel founded a not-for-profit organization called Project Hopeful that partners with Medical Center physicians to educate families who want to adopt children with HIV or AIDS. "HIV is a lot more manageable now," Carolyn said, attributing the evolution to new medications and technological advancements. "People assume it's still the tragedy it was in the '80s and '90s, but it's not." Carolyn has made advocating for these children her life's work. In the past two years, she also has partnered with lawyers in Washington, D.C., and successfully lessened the restrictions on bringing children with autoimmune diseases into the country. She rattled off government statistics that support her efforts: eight HIV adoptions in 2007 and 150 in 2009. "These are kids who absolutely had no chance for a long life," Carolyn said. She traces her passion back to her childhood. At age 6, she watched an Ethiopian drought unfold on the local news. Why, she wondered, were people there starving and living in the streets when the people closest to her lived in homes with spare bedrooms and pantries full of food? "It was a very simple thought process, but it's still how I think," she said. Currently, Carolyn, who home schools her children, and Kiel, a construction worker, have seven biological children, ranging in age from 3 to 19. Two years ago, they decided to adopt a sibling group of three from Ethiopia. The middle child of the three, Sam, had HIV. The orphanage where the children lived had been trying to split the siblings in order to give the other two children, Rachel and baby Seth, a better chance of being adopted. The Twietmeyers refused to tear the children apart, and included their biological children in the decision making process as well. "The kids felt that if there were needs to be met and we could meet them, why wouldn't we?" Carolyn said. Bringing the siblings back from Ethiopia proved complicated. United States restrictions on HIV adoptions resulted in endless paperwork and three- to ninemonth waiting periods. Those experiences led to the founding of Project Hopeful. Carolyn and Kiel also adopted a fourth child, Selah, who had Stage IV AIDS when they met her on a trip to Ethiopia to bring Sam, Rachel and Seth to the United States. This spring, the Twietmeyers were awaiting approval to travel to Ethiopia to pick up their latest adoptions, Selah's brother Andarge, 16, and her sister, Eyerusalem, 15. Carolyn is finally answering the question that has been a part of her life since she was 6. She and Kiel are making a future possible for kids around the world. "We just set our priorities a lot different than most people," she said. For more information, visit Project Hopeful on the web at www.ProjectHopeful.org. Spring/Summer 2010 39 38 University of Chicago Medicine on the Midway Nitric Oxide Therapy By Kevin Davis Families, Caregivers Celebrate Life at Preemie Reunion By Kevin Davis At 13 years old, Berachah Dubose is a bright, curious, talented girl who enjoys classical music, plays cello and piano and likes watching old black and white movies. There was a time when her life and her future were in limbo. She and her parents drove some 12 hours from Washington, D.C., to Chicago to offer their gratitude to the doctors and nurses who helped their once critically ill, premature daughter become a healthy, thriving young girl. They were among hundreds of parents and children who came to Comer Children's Hospital at the University of Chicago on October 11 for a reunion of parents, preemies and their caregivers from the Neonatal Intensive Care Unit (NICU). Preemies' Development Linda Ramos was 27 weeks pregnant and seriously ill because of complications from diabetes when she and her husband Jorge had to make a critical decision before doctors induced labor. At this premature stage, the baby faced the possibility of serious respiratory problems, brain hemorrhaging and a host of other physical and neurological complications that could last a lifetime. If the Ramos family were willing, the baby could be part of a clinical trial testing a new respiratory therapy for premature infants. Michael Schreiber, MD, professor of pediatrics at the University In the first follow-up, the researchers found nitric oxide also of Chicago Medical Center, offered them the option of enrolling might help reduce developmental problems and disabilities. in the trial, which was testing nitric oxide on premature babies. By age 2, only 24 percent of the children who got nitric oxide He explained that the gas already was being used for full-term had delayed mental development, compared with 46 percent of infants to help relax the blood vessels in the lungs, allowing more those who received the standard treatment. oxygen absorption. But it also carried the risk of brain bleeding, Bree Andrews, MD, medical director of the Neonatal Intensive which could lead to serious developmental problems. Care Unit (NICU) Follow-Up Clinic at Comer Children's "I was incredibly sick and my husband made the decision," Hospital at the University of Chicago, has seen many of those said Linda Ramos. "You just have to turn it over and just pray and babies in her clinic. "A lot of us ask ourselves after they're released hope for the best and that she's going to be put in good hands." how they're doing," she said. "I have a lot of kids here who are Jorge gave the go-ahead, and Sara Ramos was born at 1 pound, doing quite well." 15 ounces. She was placed on a breathing machine, which delivJaideep Singh, MD, director of the NICU, says about 50 ered nitric oxide along with oxygen. Her lungs soon became percent of extremely small preemies face some type of developstrong, and the brain bleeding doctors mental problems. Anxious parents had feared did not occur. always want to know how their child Surviving those first few weeks was will fare. one hurdle to overcome, but Sara's "The answer we give them is there parents still were concerned about her is no way we can tell," Singh said. "All long-term prospects. "The first thing of us have been humbled by babies we're concerned about is will she who we didn't expect to do well based survive? And then, how severe will the on what we were finding -- but who complications be?" Linda Ramos said. did do very well. By the same token, It's now 10 years later, and Sara is babies that did beautifully come back thriving. Not only is she an A-student in and we see significant problems." the fifth grade, she's a medal-winning, Despite the research team's posilong distance runner in cross-country tive results, nitric oxide therapy is events. "She's done just phenomenally," still controversial. A separate study Jaideep Singh, MD, and Michael Schreiber, MD, check on her mother said proudly. published in 2005 found that nitric infants in the NICU. Photo by Dan Dry Sara has been part of two followoxide did not reduce lung problems up studies that examined the use of nitric oxide and its effect in infants with severe breathing problems. That study, however, on cognitive development and readiness for school. Schreiber focused on extremely ill babies, half of whom died. It further and a team of researchers at the University of Chicago are leading found that the smaller preemies who got nitric oxide were more research on the use of nitric oxide for premature infants and its likely to suffer bleeding in the brain. Subsequent studies have had long-term effects so far. mixed results. The team, directed by Schreiber, includes Jeremy D. Marks, One theory is the difference in the populations studied. MD, PhD; Michael E. Msall, MD; Melissa White, NNP; and The majority of babies in the University of Chicago study were Dezheng Huo, MD, PhD. Their initial study 10 years ago showed African-American, a reflection of the hospital's community. The infants who received nitric oxide were more likely to survive newborns also were heavier and had less severe lung problems. without chronic lung disease and with reduced incidence of Schreiber agrees further multicenter studies are needed. severe brain bleeding than those in a placebo group. 40 For more information, call 1-888-UCH-0200 or visit uchospitals.edu Bree Andrews, MD, checks the heartbeat of a preemie in the NICU. Photo by Dan Dry Proving Beneficial to Still, Schreiber's team continues to follow the original group and recently examined their readiness for school and the long-term safety of the therapy. They found that nitric oxide is as safe as a placebo, and may actually improve health. But they also found school readiness levels were similar between the children who received nitric oxide and those who didn't. Schreiber believed this was likely because of the effects of the child's social environment on development. Studies have shown socioeconomic factors influence development, and poor children are more likely to experience fragmented medical, developmental and educational support. The majority of the children in the study came from socially disadvantaged families. "Any benefit medicine can give to a baby, in a sense, can be undone by one's socioeconomic status and lack of mental stimulation," Schreiber said. "Poor children may not have access to quality, early intervention programs. We believe that's so important to recognize." Researchers are moving to the next step and will study nitric oxide's effect during the critical period of brain development. They will compare infants receiving nitric oxide for seven days with another group receiving it through full term, covering that critical time of brain development. The success of patients inspires physicians to keep looking for new methods. "Babies, like Sara, are why I wake up in the morning, anxious to pursue new studies," Schreiber said. "This is why we do what we do." Linda and Jorge Ramos with Sara, now 10 years old, at the reunion. Photos by Chris Lake "It's exciting to see my old nurses and doctors," said Berachah, who was born at 26 weeks and weighed 1 pound, 8 ounces. "I know how these young kids feel." "It means a lot to her to keep that connection" said her father, Michael DuBose, a music teacher. The family, who moved to the Washington area four years ago, has been coming to the reunion for every one of Berachah's 13 years. In all, more than 500 people attended the reunion and health fair at the Duchossois Center for Advanced Medicine where children -- who were once tiny preemies -- jumped in a bounce house, had their faces painted, played games and giggled with clowns. "It's amazing to all of us," said Nicholas O'Hearn, RN, director of pediatric and NICU nursing. "We had these children when they were at their most vulnerable. We rarely, if ever, get to see the fruits of our labor." Many nurses were clearly moved after being reunited with these children who came to them as the tiniest of infants, some weighing just barely more than a pound, fragile and struggling to breathe. "The nurses have a lot of compassion to take care of the babies like this. It takes very special people," said Kim Mlynski, a staff nurse in the NICU and coordinator of the reunion. "We send them on their way, and we don't know what they're going to end up like. It's amazing to see them when they are walking and talking. It touches your heart." Renee Hubbs of Chicago brought her Renee Hubbs and Alyssa at the reunion. daughter, Alyssa, now 2 years old and weighing 30 pounds. Born at 24 weeks, Alyssa was 1 pound, 11 ounces and remained on a ventilator for a month. Her mother said she was the size of a small water bottle. "The nurses were really phenomenal. They helped us through," Hubbs said. Andy and Andrea Kmieciak, of LaGrange Park, Ill., brought their twins, Nicholas and Tyler, 16 months. Both were born weighing less than two pounds at 24 weeks and spent more than four months in the hospital. They reunited with nurses Kristie Minton and Brittany Hayes. "We had fantastic nurses," Andy Kmieciak said, "and were blessed to have great care." Spring/Summer 2010 41 Pritzker News SPREADING Pritzker ABROAD By Greg Borzo Getting to Know the South Side: Pritzker Day of Service By Allison Horton First-year medical students got a chance to learn more about the South Side neighborhoods served by the Medical Center through participating in the second annual "Pritzker Day of Service." "The idea is to introduce first-year medical students to this community and also to give some manpower to ongoing community service projects in South Chicago," said Laura Blinkhorn, a secondyear medical student involved in the Pritzker Community Service Fellowship, a student organization that sponsored the event last fall and is devoted to developing physician leaders. She helped direct other medical students last year as they prepared a community garden for the winter. Blinkhorn was one of more than 20 Pritzker School of Medicine students who harvested crops, such as peppers and tomatoes, and turned over the garden for the South Chicago Art Center, 3217 E. 91st St., which provides free in-school and after-school art programs to eight schools in the Washington Park and Englewood neighborhoods. Community residents take care of the garden and receive the crops, which help an area where the average annual household income of $12,000 is well below the poverty line. Any excess produce is donated to local food pantries. Sarah Ward, executive director of the art center, said the garden was once a parking lot for area steel mills and a gas station. "I wanted the kids to feel better about themselves," she said. "To be able to see a butterfly land on a flower and draw it and enjoy the outdoors that's not concrete and broken glass," she said. Other Pritzker students volunteered at the Gary Comer Youth Center, 7200 S. Ingleside Ave., which provides after-school programs such as health and wellness classes, academic tutoring and college mentoring to youth in the Grand Crossing neighborhood. The center also is home to the South Shore Drill Team, a nearly 30-year-old organization that trains young people to perform flag, rifle and dance routines and takes them around the world to show their stuff. More than 50 medical students cleaned fitness equipment, worked in a rooftop garden and helped kids make Halloween crafts. Gabrielle Zeigler, a 16-year-old Hyde Park Academy student who has been attending the center for three years, said she enjoyed doing Halloween crafts with the medical students. "It was fun," she said. "We got a chance to meet new people and work with them. If we needed extra help with what we were doing, we had the extra help." When Olufunmilayo Olopade, MD, FACP, and associate dean of the University of Chicago Medical Center's new Global Health Initiative, surveyed the faculty to gauge the university's presence around the world, she was surprised to learn that faculty members were already active in more than 100 different countries. Laura Blinkhorn, a second-year Pritzker student, and Andrew Schram, a first-year student, show off their harvested vegetables. Photo by David Christopher "That's why I can say with stem the brain drain that has practically devastated confidence that we'll rely on some developing countries," said Olopade, who is our existing strengths to build from Nigeria. our Global Health Initiative," In terms of education, the Initiative will expose Olopade said at the launch students to global health issues, provide training and this past fall. service learning opportunities for students and faculty Another survey showed and develop local capacity for sustained educational that more than 60 percent development in countries with limited resources. of the incoming housestaff Olufunmilayo Olopade, MD, a native of Nigeria, "Global health is already institutionalized in the and medical students say stands with her mother, Dorcas Falusi. medical curriculum," Olopade said, "because the they want a global health experience, she said. "Increasingly, reforms being rolled out added global health to the list of tracks students are deciding where to enroll and work based on their students can pursue in medical school." anticipated exposure to global health training and issues." The Initiative has formed or is forming partnerships in Olopade, also professor of medicine and human genetics Bangladesh, Brazil, Chile, China, India, Liberia, Malawi, Nigeria and director of the Cancer Risk Clinic, believes that alumni, too, and South Africa. will get involved. "We are extremely interested in exploring "Our biggest success so far has been raising awareness and ways alumni could contribute and participate," she said. "Small excitement about global health within the university community donations from alumni would have tremendous impact on and building a strong foundation," Olopade said. improving opportunities for trainees and faculty, expanding Peter Singer, MD, director of the McLaughlin-Rotman Centre programs and supporting international field experiences. for Global Health at the University of Toronto and keynote Additionally, they would provide important training opportuspeaker at the launch, described what motivated him to work in nities for students and researchers from partner institutions in global health: "It was the day I learned that the life expectancy limited resource settings." of people in Canada and the United States is 80 years and rising, The Initiative's goal is to build sustainable solutions to comwhile the life expectancy of people in many developing countries plex health challenges through research, education and clinical is 40 years and falling." programs in partnerships with communities around the world. Infectious diseases are rampant in developing countries, From a clinical approach, the program will deliver care to the he said. Malaria, tuberculosis and HIV kill 4.3 million a year; most vulnerable populations abroad as well as in the United States pneumonia and diarrhea kill 2 million and 1.7 million children through links with the Medical Center's Urban Health Initiative. a year, respectively. It also will provide clinical training and support through exchange Despite these high numbers, even more deaths are caused by programs and international collaborations. "This is not missionary chronic non-communicable diseases in developing countries, work," Olopade said. "We want to contribute to building up the Singer said. Nevertheless, a fraction of 1 percent of the world's clinical capacity of health care workers in other countries." development funding is aimed at these diseases, he added. For research, the Global Health Initiative will partner "Our Global Health Initiative is an extension of the uniwith institutions worldwide to find sustainable solutions to versity's commitment to work on the biggest problems of our development and health challenges and to research the ethical, time," said Donald Levy, PhD, vice president of the university's social and legal implications of international research. "We'll help Research and National Laboratories. 42 University of Chicago Medicine on the Midway Rebecca Levine, a second-year medical student and a fellowship board member, said volunteering helps the Medical Center grow roots in the community. "There is a significant degree of passion at our school for service and for giving back, and we are really focusing on these long-term partnerships in the South Side neighborhoods," she said. Peer-to-Peer Mentoring at Pritzker By Susan Chandler The Pritzker School of Medicine has always provided counseling to students during their third year, a stressful watershed when they move out of the classroom and into hospitals. Some students may be seeing seriously ill and dying people for the first time. On top of that, third-years must decide what area of medicine to specialize in. That adds up to a lot of pressure. Much of the career guidance students receive comes from Pritzker faculty members through formal advising societies. Two Pritzker students in their fourth year decided some grass-roots input was needed. In August, Josephine Kim and Gautam Malhotra approached Shalini Reddy, MD, associate dean for student programs and professional development, with an idea. Why not ask fourth-year students to act as mentors to third-years and post their profiles so the third-years could see which students shared their same career or personal interests? Reddy gave the go-ahead and so far, more than half of the fourth-year class has signed up to be mentors. "It is a fantastic addition," said Reddy. "Peer mentoring provides perspective. If you're talking to someone who has been through what you're going through, you take it to heart. I think there's a need for connectedness because medical students tend to feel they're experiencing everything by themselves. I want them to know they have each other." The issues that concern third-years may run the gamut from "When can I find time to exercise?" and "What should I eat?" to "Someone just died. How do I handle it?" Reddy said. Kim says the idea for peer mentoring came to her at the end of her third year when she was looking for someone to talk to about choosing obstetrics/gynecology as a specialty. A friend suggested she talk to another student who turned out to be "unbelievably helpful," Kim said. Prospective mentors were asked to fill out a survey listing their choice of field, organization memberships, research work and hobbies. That information is being posted on a website where third-years can make their own choice about whom to contact. There's a risk, of course, that fourthyear mentors may find themselves busier than they expect and not be as diligent as hoped about responding to inquiries. There's also the chance that the program will fade away after Kim and Malhotra move on. But Kim says they won't let that happen. "We haven't laid out the nitty gritty yet, but we'll make sure it gets passed on." Spring/Summer 2010 43 Medical School This Future Doc The dedication has paid off, though. The album sells on iTunes and also is available at Amazon.com. Paro also has a website, www.medschoolrock.com where people can listen to the songs and read the complicated lyrics. Paro gets a percentage of sales, which so far has netted him a few hundred dollars. Paro insists that if the CD takes off, he'd like to establish a mini-scholarship fund in which he would hand out $500 to medical students each year to support their outside interests and hobbies. The application would be a paragraph in an e-mail that would explain how the student would use the money to further a hobby, like buying a new camera for a photo buff. The concept may seem a bit lofty, but Paro is a strong believer in living a balanced life. "People often ask me how I have time to write songs and play music," he said. "Some people can study from 10 a.m. to midnight. I can't. I reach a critical point, and then I have to do something else." Though he'd decided to become a doctor while in high school in Hinsdale in Chicago's west suburbs, Paro was determined to have John Paro in his home recording studio. Photo by Dan Dry some fun before he started medical school. He took a year off after college, during which time he tended While laying down the vocal track bar at Howl at the Moon in downtown Chicago, formed his own tutoring service for kids, played music in Nashville and spent for "Taco Bell's Canon," Paro had two months backpacking through Europe. "I had a finite amount of time, and I wanted to get out of my to keep chanting "diarrhea, diarsystem all the things I'd always wanted to do but didn't have the time to do," he said. "I work hard; I play hard. I live by that rhea" as loud as he could into philosophy." At Howl at the Moon, the managers let Paro step out from the microphone. "I just knew my the bar at least once a night to play piano. "I learned that if you smile, the girls really like you," he said. "It was so much fun, a different experience every night." His favorite song to perform neighbors thought I was nuts." was "Jump" by Van Halen. In Paro's version, he would jump around playing "keytar" while mimicking the rock star. In March, Paro and his fianc� were both matched in a couples It wasn't such a stretch for Paro, a self-admitted "ham" who residency at Stanford University, which was their top choice. performed magic in high school, acted in school plays -- he was Paro will be doing a general surgery residency while Rodriguez the wizard in the "Wizard of Oz" -- and in college played in will be in a pediatrics residency. the band "Husky Dave," named after a guy who filmed himself In his last few months at Pritzker, Paro tackled songs that eating food in grocery stores. were more than cerebral farce. He wrote and recorded songs for Despite his love of theatrics, Paro says he feels most invigoDana Suskind, MD, director of the Pediatric Cochlear Implant rated when he's in the OR. The operating room has long been Program at Comer Children's Hospital at the University of referred to as the great medical stage and a place where physiChicago. The songs are designed to help drive home key facts cians are known to play music loudly -- Paro once won brownie about speech therapy for parents of kids with cochlear implants. points from a surgeon for being able to name a Led Zeppelin "This is something that is more legitimate and helpful," song and album that was playing on OR speakers -- but Paro Paro said. insists his attraction has more to do with the physicality of Paro also is starting to mull over material for his next being a surgeon. "MedSchoolRock" album. For this one, he wants to be a bit more "The OR is a great combination of teams coming together serious. His ideas range from songs about H1N1 flu to the Krebs in an organized choreography to make the patient better," Paro Cycle, a mess of complicated medical terms. "It's the medical said. "It's treatment in real time. Instead of a doctor who gives field," he said. "I have vast, endless material." medicine and has to wait to see if it works, a surgeon works with his hands to bring about treatment. There's a physical prowess, and yet, you still have a relationship with the patient." Spring/Summer 2010 45 By Cheryl L. Reed John Paro has spent much of his young life entertaining others. Whether mimicking the sounds of stringed instruments with his mouth in an a cappella choir, banging drums in a punk rock band at frat parties, or channeling Eddie Van Halen for drunken bachelorettes, Paro has enjoyed amusing his varied audiences. But when Paro entered the Pritzker School of Medicine in 2006, he thought his minstrel ways were behind him. Not so, apparently. During his first year, Paro struggled to remember medical terms for an upcoming anatomy exam and started strumming his guitar during study breaks. The result was a techno dance tune called "Shake That Lower Limb" that used complicated medical terms to describe the lower anatomy parts a man uses while dancing. Paro e-mailed the song to his classmates as a joke. "I thought they would just delete it," said Paro, now 26 and finishing his fourth year. "But they liked it, and they sent it out to their friends." So Paro wrote another song called the "Pelvis Ho-Down" set to country music, the chorus of which goes like this: "Shake your labia, Shake your testicles according to which gender you belong give it up for labia, yee-haw for testicles come on everybody sing this song." There are lots of medical terms, like Ileum, Ischium, Sacrum and Coccyx, thrown in there, too, along with detailed accounts of cadaver dissections, but we'll skip over those parts. Suffice it to say, Paro was writing and singing for a specific audience. "People started telling me that they remembered terms for tests by singing my lyrics," said Paro, a tall, thin, tawny-haired man whose wide grin and eagerness evoke Doogie Howser more than Dr. House. That was all the encouragement Paro needed to keep playing. "I started incorporating more class material into the songs," he said. He modeled his lyrics after the School House Rock cartoons in which lessons in English, history and politics are delivered in mnemonic rhyming lyrics that almost anyone who came of age after the 1970s can recite, like: "Conjunction Junction, what's your function?" or "I'm just a bill. Yes, I'm only a bill. And I'm sitting here on Capitol Hill." Paro remembered the silly lyrics from his own middle school days, and he thought the technique could help him in medical school. "For me it was a hobby. It allowed me to entertain my classmates," he said. "Half of it was entertaining, and half was using effectual memory tools." But then his audience grew. Classmates were sending the songs to other medical students at other schools. "Then I started thinking that maybe this is marketable," he said. This past summer, just as he was about to enter his final year of medical school, Paro decided to make a CD. By then, he had more than a dozen songs written. So he took out references to Pritzker -- the inside jokes that only his cohorts could understand -- and recorded the album that he named "MedSchoolRock." Paro layered the instruments on the tracks by using a software program called Garage Band. He recorded each track separately in his music studio -- the extra bedroom that converts into a guest bedroom when company arrives at the apartment he shares with his fianc�, Renee Rodriguez, also a Pritzker medical student. While laying down the vocal track for "Taco Bell's Canon," a song that deals with the various causes of a common medical condition, Paro had to keep chanting "diarrhea, diarrhea" as loud as he could into the microphone. "I just knew my neighbors thought I was nuts," he recalled, laughing. 44 For more information, call 1-888-UCH-0200 or visit uchospitals.edu Class Notes 1970s Arnold Barry Calica, SM '61, MD '75, retired from active practice of neurological surgery last year. He is still involved with international neurosurgery (in Nepal and Vietnam). He is working with the Bioengineering Department at Arizona State University. His family is well and happy. He reports that he "continues to play geriatric squash." Mark G. Coan, MD '70, retired in June 2008 after 30-plus years as a vascular surgeon in Atlanta. He travels, reads, visits family and does some volunteer work, "including the to-do's provided by my wife of 40 years, Ruth." Eugene C. Corbett, Jr., MD '70, writes that he and his wife, Sue, still live on the same farm in Virginia (since 1975), and are enjoying their kids and grandkids, and rural life in general. He said: "We talk about retirement lots, but both of us remain full time in the nursing and medical professions. My new deanship will put off my retirement some. Looking forward to our 40th reunion!" Lawrence D. Devoe, MD '70, is in the process of completing a 40year career in obstetrics and gynecology. In 2010, he will retire from full-time work and become a part-time emeritus faculty member. "It's been a great run since my U of C days," he said. "Looking forward to Reunion 40 in June 2010." Lisa Glauser Kaplowitz, MD '75, has been at her present position as director of the city health department in Alexandria, Va., since July 2008. She is responsible for all aspects of public health in the city of Alexandria. She is also very involved with public health and emergency response issues in the National Capital Region, consisting of Washington, D.C., and the Virginia and Maryland suburbs. H1N1 response in the city and the NCR is the major issue occupying public health at the present time. Robert L. Karp, MD '70, writes: "Mariela and I are looking forward to visiting the campus to celebrate our 40th wedding anniversary and my graduation from the university and to visit our classmates and friends." Arthur G. Robins, AB '66, MD '70, is about to retire after 32 years at the Veterans Affairs. medical education and her impact on internal medicine nationally, including as chair of the board in 2006-2007. Humphrey also received the Outstanding Alumni Award from her undergraduate alma mater, North Central College in Naperville, Ill. The Outstanding Alumni Award is presented each year to alumni who graduated more than 15 years ago, have excelled in their careers and demonstrated service to the community and to their alma mater. Humphrey has been a trustee of North Central College since 2004. In December, Humphrey served as a visiting professor at the University of Pennsylvania where she presented the Risa LavizzoMourey Lecture. Anthony Michael Lin, MD '85, writes: "Hard to believe it's been 24 years since my graduation from Pritzker. I am an anesthesiologist in a private practice group in the San Francisco Bay Area. I've lived in Palo Alto with my wife and two children since 1991. My daughter, Alexandra, is 18 and will be a freshman at Yale this fall, while Nicholas is 13 and a rising eighth grader. I hope I will be able to attend our class's 25th Reunion!" Roger Morton Lyon, LAB '77, AB '81, MD '85, practices pediatric orthopaedic surgery at the Medical College of Wisconsin at the Children's Hospital in Milwaukee, Wis. His daughter is a first-year college student at the University of Chicago. Jack D. Rush, MD '80, is in family medicine in the same upstate New York small town where he started after his residency. It's in a beautiful location on the St. Lawrence River region called the Thousand Islands. In Memoriam 1940s David S. Fox, MD '44, passed away in April 2009 at the age of 87. A veteran of World War II, Fox started a general surgery practice at Woodlawn Hospital in 1949, where he was named medical director and director of medical education in 1979. A former president of the Illinois Medical Society and the Chicago Medical Society, he worked at Bethany Hospital and Hyde Park Community Hospital before retiring in 1995. Fox played a pivotal role in early medical peer-review efforts, chairing the state medical practice examining committee and directing the Illinois Foundation for Medical Review. He was the beloved husband of the late Mary K. and the loving father of Andrew (Patricia), David S. Jr. (Janet), Brian (Jan), John, MD, (Monica) and Paul (Nancy) Fox and the late Stephanie (Thomas, DDS) Ward, grandfather of 10, great-grandfather of one. 1950s Attie Yvonne Russell, MD, '58, passed away in Laurinburg, N.C. on December 8, 2009, at the age of 86. She was born in Washington, D.C., and held a bachelor's degree from American University, a master's and doctorate degrees from Iowa State University, and an MD from the University of Chicago Medical School. She completed postdoctoral research in physiology at the Royal College of Physicians in London, and clinical training in pediatric cardiology at the Albert Einstein College of Medicine in New York. She was a World War II Navy veteran and later a captain in the U. S. Public Health Service. She was particularly known as a skilled diagnostician. Her greatest interests in practice and research were maternal and child health, particularly for those without easy access to health care. She was an advocate for the medical and scientific education of women and other historically underrepresented groups. She held professorships in pediatrics at the Medical College of Pennsylvania, University of Cincinnati Medical School, Stanford Medical School, Harvard Medical School, Johns Hopkins Medical School, and the University of Texas Medical Branch at Galveston. She is survived by her husband of 25 years, Harry Camper, seven children, nine grandchildren, and a sister, Helen Odette Lineweaver. Betty L. Tricou, MD '55, PhD '61, passed away in late fall 2009. 1960s Jeffrey P. Froehlich, MD '69, died of surgical complications in August 2009 at age 66. In 1972, he joined the Gerontology Research Center at the National Institutes of Health National Institute on Aging where he served until his retirement in 1999 as chief of the Membrane Biology Section, Laboratory of Cardiovascular Science. His passion for scientific inquiry led him to subsequent positions as professor, Department of Biochemistry and Molecular Biology at the University of Maryland School of Medicine and visiting professor, Division of Cardiology, Johns Hopkins University School of Medicine. An eminent researcher in mechanisms of cellular transport, particularly ATPase, his later work focused on the development of drug eluting stents for the treatment of coronary restenosis and clinical applications of Nitroxyl. In addition to his scientific contributions, he will be remembered for his generosity, breadth and depth of interests (for example, classical music, philosophy, classic films, hiking, antique cars and firearms) and his playful sense of humor. He is survived by his wife, Sandra Leichtman, PhD; his son, Paul; a sister, Susan Raynovic; and two granddaughters. 1990s Rebecca Ann Beach, MD '90, writes: "Divorced again -- back to the name you all know! My oldest daughter just won the Janesville spelling bee, and my younger daughter and I are purple belts in karate. Hope to make it back for reunion." 2000s Birgitt Lucille Dau, MD '02, reports: "I finally landed my first job in July after 11 years of medical training! I did my fellowship in Infectious Diseases at Stanford and am now working for San Mateo County specializing in HIV, infectious disease and public health, and I am incredibly happy to be there." Erica Collins Delgado, MD '05, writes: "Mike and I have a new baby girl, Emilia Corinne, born May 22, 2009 (our fourth wedding anniversary). I finished my IM residency in 2008, and Mike will be done with the ortho marathon next year. From there, we will head to Taos, N.M. for Mike's sports fellowship." Eric Hao-Ming Leung, SM '03, MD '05, is currently pursuing a glaucoma fellowship at University of California San Diego Shiley Eye Center to be completed in summer 2010. 1980s Jeffrey A. Cohen, MD '80, has been at Cleveland Clinic since 1994, where he is director of experimental therapeutics at the Mellen MC Center. He is married to Sally Farwell (they married during medical school) and has two children, Joshua, who is at Ohio State, and Jennifer, who graduated from the University of Chicago Law School. Holly Humphrey, MD '83, dean for medical education at the University of Chicago Pritzker School of Medicine, received a number of accolades during the past year. Humphrey was named a 2009 "Woman to Watch" by Crain's Chicago Business in May. In November, she was named a trustee of the American Board of Internal Medicine Foundation in recognition for her leadership in Medicine on the Midway A publication of the University of Chicago Medical Center Spring/Summer 2010, Volume 63, No. 2 Executive and Managing Editor Cheryl L. Reed Contributing Editors Denise Alamad, director of publications, and John Easton, director of communications Editorial Contributors Don Reneau; Stephen Phillips; Rob Mitchum; Katie Scarlett Brandt; Susan Chandler; Kelly Smith; Casey Reid; Greg Borzo; Emily Stone; Allison Horton; Martin C. Burke, MD; Leah Mooshil Durst, MD; John R. Benfield, MD, FACS; Robert Sargis, MD, PhD; Tom Hallman; Kadesha Thomas and Ankur Thakkar Photo Contributors Dan Dry, David Christopher, Anne Ryan, Jason Smith, Chris Lake, Hoyee Leong and Lloyd DeGrane Design Firm Words&Pictures, Inc. Editorial Committee Chairwoman Chris Albanis, AB '96, MD '00; Lampis Anagnostopoulos, SB '57, MD '61; John Benfield, MD '55; Arnold Calica, SM '61, MD '75; James Hopson, PhD '65; Patricia Martin, AB '74, MD '78; Jerrold Seckler, MD '68; and Coleman Seskind, AB '55, SB '56, SM/MD '59 Medicine on the Midway is published for friends, alumni and faculty of the University of Chicago Medical Center, the University of Chicago Biological Sciences Division and the Pritzker School of Medicine. Articles may be reprinted in full or part with permission of the editor. We welcome your comments and letters to the editor. Address correspondence to: Editor, Medicine on the Midway University of Chicago Medical Center 950 E. 61st Street Third Floor, Suite 323 Chicago, IL 60637-1470 Telephone (773) 834-8089 Facsimile (773) 702-3171 E-mail editor firstname.lastname@example.com E-mail class news email@example.com Find us on the Web uchospitals.edu/midway 46 University of Chicago Medicine on the Midway � May 2010. University of Chicago Medical Center, Division of Communications and Marketing Spring/Summer 2010 47 Perspectives: Four Medical Opinions on Continuing Health Care Reform Martin C. Burke, DO Associate Professor of Medicine Director, 150 East Huron Clinic Director, Heart Rhythm Center Photo by Anne Ryan Leah Mooshil Durst, MD Former Medical Director, Friend Family Health Center, Inc. Chief Medical Officer, Medical Home Network Clinical Associate, Dept. of Pediatrics, University of Chicago Photo by Dan Dry John R. Benfield, MD, FACS Professor of Surgery Emeritus David Geffen School of Medicine at UCLA Photo provided by John Benfield Robert M. Sargis, MD, PhD Endocrinology Fellow University of Chicago Medical Center Photo by Dan Dry From a Medical Center Physician American medicine is a behemoth of special interests that contributes to, as well as consumes, our economy. The American adage, "You have nothing without your health," is the philosophy behind our ever-expanding, entropic health industry. A systematic and well-planned approach is needed to navigate a useful and lasting change to the current health delivery system. This will require completely dismantling and rebuilding our medical delivery system in a way that focuses on the doctor-patient relationship as its core mission. The doctor-patient relationship is alive within American medicine, though it is under attack by government policy, agencies, third-party insurers, pharmaceutical and device manufacturers and hospital conglomerates that secure huge profits without personal risk. The economics of health care costs have no seat at the doctor-patient table. The recent health care bill alienates this relationship further. The commerce of health maintenance or treatment will continue to be carried out without participation from these two key players and an understanding of the true cost of care. Charges are so extremely high that it defies any logical ability to qualify them to me, a doctor, or to the patient who is billed. Having health care rates negotiated between a doctor and patient rather than an insurance company and hospital or declared by the federal government would instantly contain costs. The special interests in the American health system do not want this action. The current system does not reward quality or complexity of care, which can only be judged by a patient and a doctor, not the "Wizard of Oz" behind a curtain. My fear that health care reform will not be done systematically and, consequently, will perpetuate the current third-party payer system in lieu of a strong nonprofit, fiscally sound public insurance option focusing on quality doctor-patient interaction is realized. It is egregious that health insurance executives are paid tens of millions of dollars annually because they raise premiums and pay providers less. How do we negotiate this corruption in our care of sick Americans? Wall Street encourages it, while our government believes this greed can be regulated. It is hard to rationalize sanely that expanding the current third-party payer system, without a sound, competitive, nonprofit public option, can be done without huge cost to patients, their care and the clinical caregivers delivering it. From a Community Health Center Physician Recently, a middle-aged gentleman came into my office for the first time after a three-day hospital stay for newly diagnosed congestive heart failure. The heart failure was caused by longstanding hypertension, which he never knew because he had not seen a doctor in almost 20 years. In his reasoning, why would he? He always felt fine. Besides, he didn't have health coverage and could not afford to see a doctor. He worked but did not qualify for Medicaid insurance. He was referred to my federally qualified health center because of proximity to his home and our sliding-scale fee for the uninsured. Within this scope, he could establish a medical home for office visits and blood work and be connected with low-cost, generic medicines. But without insurance, he could not get diagnostic tests or a subspecialist's consult, if needed. Especially with these barriers, I silently hoped we could stave off these needs. At his appointment, we discussed the new medications he'll need to stay out of the hospital and improve his outcome. He'll have regular office visits to monitor his symptoms, blood pressure and lab work. Nevertheless, statistics show heart failure will limit his life expectancy. I wish he were not in this predicament and that he received regular health care before his condition progressed to hypertension and heart failure. Diet and exercise could have been significant prescriptions in controlling this disease in early stages, but he didn't receive that medical advice 20 years ago. At this point, even if there were affordable insurance options for him, he would have been denied coverage with these diagnoses. Our current health care system failed this patient and thousands like him. Medical benefits are primarily tied to employment, but not all employers can provide these benefits. For those with insurance, more often the care of disease is paid, but preventive measures are not, so paradoxically, we finance a sicker society. Once a patient has a disease considered to be a pre-existing condition, the next time the patient tries to get health insurance, obtaining coverage may be impossible. And those with chronic conditions also face loss of medical coverage and limited health care options if they lose their jobs. Thankfully, health care reform legislation addresses these issues; however, it does not comprehensively cover all individuals who live in this country. And there will be temporary gaps for many based on the timetable of rolling out various components of reform. However, these first steps are big gains that move us in the right direction. From a Pritzker Alumnus Three headlines from The New York Times on November 9, 2009, illustrated the problems posed by the health care revolution. "Sweeping Health Care Overhaul Passes the House: Slim Margin for Plan to Cover 36 Million" It is good that our health care system is striving to pay for the care of more than 36 million uninsured Americans but regrettable that we will still fall short of universal coverage. "Abortion Was at the Heart of Last Minute Wrangling Over a Contentious Bill" Abortion is a relatively small part of the health care issue. It should not be a central focus. It is shameful that political wrangling and obstructionist methods impede progress. "Curing Health Care" American health care is the most expensive without providing better results. The infant mortality rate in the United States is the highest among 16 nations; life expectancy of American newborns is 1.7 years less than the non-U.S. average. Americans neither live longer nor do we have better results from cancer therapy than other nations. My suggestions: 1. Initiate change where government control already exists. Allow Medicare patients to access government-controlled health care systems, such as the Veterans Affairs, the Public Health Service facilities and perhaps even military facilities, by adding the required resources and making the needed changes. 2. Decrease costs by changing practice patterns. Existing practices are inefficient. For example, nearly all patients with acute appendicitis do not need CT scans for diagnosis and cure. The army of employees for billing is excessive. A system that provides rewards for resisting overuse of testing and therapies should be developed. Only qualified medical practitioners can decide how to trim fat, maintain quality and allow doctors the freedom needed for individual care. 3. Give leadership roles and authority to people who have personal experience in the practice of medicine. A common denominator among Mayo Clinic, Cleveland Clinic and Kaiser-Permanente, frequently cited as models, is their leadership by doctors who have actively practiced. The health care bill has passed -- a giant step forward. Too bad that it will be four years before mandated changes occur and that cost containment efforts continue to be largely the turf of administrators instead of the responsibility of doctors. It is time to stop being politically correct and timid. Let us step forward with courage and determination to reform health care. From a Medical Center Fellow My greatest hope for health care reform is that it will transform health care economics to be more focused on patients and their health. The current system is entirely unsustainable. While we pay vastly more per capita than any other industrialized country, objective measures of health outcomes consistently show that our system fails to provide us with appreciably better results than countries spending a fraction of what we do. This results from several fundamental flaws that must be addressed. First, the current for-profit health care model creates a fundamental conflict between patients' needs and insurance companies' goals. Patients suffering with illness should not have to fight with their insurance companies to cover needed care. The health care system should be structured to protect patients and not to deny them care and drive them into bankruptcy in order to support company profits. While provisions in the bill to prevent denial of care based on pre-existing conditions are a tremendous leap forward, we must also ensure that patients have unencumbered access to requisite care. Second, by heavily relying on an employer-based insurance system, patients are placed at enormous risk if they lose their jobs or if they're self-employed and cannot afford high insurance premiums. This sets up a vicious cycle with unemployment leading to the loss of insurance resulting in deterioration of health, making it difficult to re-enter the workforce. While the recently passed health bill works to alleviate this problem, rapidly rising insurance premiums may outstrip government subsidies and re-establish a situation in which health care remains unaffordable to many. Finally, the present fee-for-service model of physician reimbursement should be replaced with a system that rewards doctors for improving the health of their patients. This will undoubtedly be a challenge since doctors may be wary of setting up practice in communities with pre-existing poor health. But if we want a health care system that works, we need to appropriately align the interests of all involved to the ultimate goal of patients' health. The cumulative effect of this would be to ensure that more patients are getting highly-involved, quality care while simultaneously reducing costs through the abandonment of diagnostic and therapeutic approaches that don't work. My greatest disappointment with health care reform is that it stopped short of universal coverage, and I fear that we will lose the political will to change the fundamental flaws in the system. This moment in history offers a unique opportunity to address the disparities in health care that are tremendous barriers to social equality in our country. If we neglect to meet this challenge now, we risk perpetuating a system that fails all of us. Spring/Summer 2010 49 48 For more information, call 1-888-UCH-0200 or visit uchospitals.edu Nonprofit Organization U.S. Postage Chicago, IL Permit No. 5179 PAID Alumni Association 1170 East 58th Street Chicago, IL 60637