Innovate Fall 2014

B A R N E S - J E W I S H H O S P I TA L A N D WA S H I N G T O N U N I V E R S I T Y P H Y S I C I A N S

Innovate

Fall 2014

THE UNIVERSE WITHIN: HARNESSING GUT BACTERIA TO SHAPE HEALTH AND TREAT DISEASE

Mammography in 3-D

The fasting diet

Personalized medicine defined

Pregnancy and aging

Misdiagnosed for two years. That was Erica Griffin’s story before she arrived at Siteman Cancer Center.

At Siteman, Erica had a team of Washington University specialists who gave her an aggressive treatment plan based on her specific type of cancer and her own genetic make-up. It’s a level of care that offers more reasons for hope.

Today, Erica has celebrated her fifth year of survivorship and is back to her active, fulfilling life. To learn more about Erica’s story go to NationalLeaders.siteman.wustl.edu. To make an appointment, call 314-747-7222 or call toll-free at 800-600-3606.

National Leaders in:

ST. LOUIS • WEST COUN T Y • SOU T H COUN T Y • ST. CH A R LES COUN T Y

In this issue

24

11

UP FRONT 3 By the numbers Breakthroughs

18

5 Making cancer glow 6 Restoring rhythm 6 Aiming for precision 7 Aiding stroke recovery Health beat 8 Age has advantages—even in pregnancy 9 Genetic risks for autism 10 Your mammogram—in 3-D 11 Exercise, for your heart’s sake 12 Does fasting yield health benefits?

13 A closer look at hip-replacement surgery 14 Face to face

UP FRONT

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Meet Lisa de las Fuentes, MD, and Murali Chakinala, MD—married to each other and experts in their fields

MEDICAL MYSTERY 16 Migratory joint pain + abnormal blood protein + rash and night sweats = X

IN DEPTH 18 Cover story: The universe within: harnessing gut bacteria to shape health and treat disease 24 Feature story: From personal to personalized: how genetics is transforming cancer care

LAST WORD 29 Fighting the flu

ON THE COVER

Microbes that live in and on our bodies outnumber our cells 10 to one. Read more about this universe in miniature on Page 18.

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This new-and-improved edition of Innovate is both bigger and better— and we hope it piques your curiosity about medicine and satisfies your need to know more about health care and your health.We’d love to hear your thoughts about the new design; you can send them via email to innovate@bjc.org.

As you can see when you drive along Kingshighway Boulevard or walk the eastern edge of Forest Park in St. Louis, the Washington University Medical Center Campus Renewal Project, which will create new patient care space for Barnes-Jewish Hospital and St. Louis Children’s Hospital, has broken ground and soon will begin rising above street level. Our new buildings, shown in the artist’s rendering (above) of the future Kingshighway streetscape, will enhance the patient and family experience and transform not only our campus, but our ability to provide exceptional care for future generations.

The smaller changes you’ll find in this magazine and the larger ones taking place on our campus are indicative of our excitement about the future.What breakthroughs lie ahead? What new insights about disease and ways to maintain health are just around the corner? The feature on Page 24 of this magazine explores personalized medicine— what it is, how it’s possible, who is changing cancer treatment—and the one on Page 18 considers what we know about the microbes that live in us, and what we’ve yet to discover about their ability to influence health.

I hope you enjoy this edition of Innovate.

With sincere regards,

BARNES-JEWISH HOSPITAL, a nonprofit academic institution, is the largest hospital in Missouri and is consistently ranked among the Honor Roll of America’s best hospitals by U.S. News & World Report, ranked No. 1 in St. Louis and No. 1 in Missouri. The adult teaching hospital of Washington University School of Medicine, Barnes-Jewish Hospital was the first adult hospital in Missouri to be certified as a Magnet hospital for its nursing excellence.

Barnes-Jewish Hospital is a member of BJC HealthCare, one of the largest nonprofit health care organizations in the United States.

The Alvin J. Siteman Cancer Center at BarnesJewish Hospital and Washington University School of Medicine is the only cancer center in Missouri to hold the Comprehensive Cancer Center designation from the National Cancer Institute and membership in the National Comprehensive Cancer Network.

WASHINGTON UNIVERSITY SCHOOL OF MEDICINE’s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish Hospital and St. Louis Children’s Hospital. The School of Medicine is among the country’s leading medical research, teaching and patient care institutions, currently ranked sixth in the nation by U.S. News & World Report.

Innovate is published biannually by Barnes-Jewish Hospital.

Editor Anne Makeever Contributing editors Kay Franks, Donna Heroux, Juli Leistner Contributing writers Anne Bassett, Jim Dryden, Jim Goodwin, Jan Niehaus, Gaia Remerowski, Hannah Toel, Diane Duke Williams Address changes Innovate Circulation Mailstop 90-75-585 4901 Forest Park Ave., Suite 1221 St. Louis, MO 63108

Richard Liekwig President, Barnes-Jewish Hospital

The rendering above illustrates the new facilities planned for the east side of Kingshighway Boulevard, St. Louis, Mo., across from Forest Park.

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Innovate | fall 2014, vol. xix | Barnes-Jewish Hospital and Washington University Physicians

Visit barnesjewish.org/e-news to manage your Innovate subscription and to request e-newsletters and additional information.

To make an appointment with a physician, call 314-TOP-DOCS (314-867-3627) or 866-867-3627 (toll free).

A LOOK AT HOW THIS ISSUE OF INNOVATE ADDS UP

UP FRONT

THE AVERAGE HUMAN IS HOME TO TRILLIONS OF MICROBES, LIVING ON THE SKIN AND IN THE GUT.

COMBINED, THEY CAN WEIGH A TOTAL OF 4 POUNDS PAGE 20

IN A HEALTHY ADULT: THE HEART PUMPS

5 LITERS

OF BLOOD PER MINUTE

THE HEART BEATS

300 MILLION

18,000+

ABOUT 50%

WILL DEVELOP

SWALLOWING DIFFICULTIES

U.S. CITIZENS SUFFER A

STROKE EACH YEAR

PAGE 7

TIMES PER YEAR

PARTICIPANTS IN A CALORIE-RESTRICTION STUDY THE LUNGS INHALE AND EXHALE

7-8 LITERS

OF AIR PER MINUTE

WILL EAT LESS THAN

600 CALORIES A DAY, 2 DAYS A WEEK, FOR 1 YEAR PAGE 12

15 MINUTES

OF EXERCISE PER DAY REDUCES HEART-DISEASE RISK BY

30 PERCENT PAGE 11

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UP FRONT

AUTISM AFFECTS

1 IN 68 CHILDREN IN THE U.S.

BOYS ARE

More than

5 MILLION PEOPLE NATIONWIDE

have cardiac arrhythmia;

MORE THAN 1.2 MILLION are hospitalized for it annually PAGE 6

IN THE U.S., THERE ARE ABOUT

PEOPLE LIVING WITH ARTIFICIAL HIPS AND

4 TIMES MORE LIKELY TO HAVE AUTISM THAN GIRLS PAGE 9

2.8 MILLION BREAST-CANCER SURVIVORS LIVE IN THE U.S. SINCE 1990 BREAST-CANCER MORTALITY HAS DECREASED BY

34%

4

WITH ARTIFICIAL KNEES

LIKELY DUE TO IMPROVED TREATMENT AND EARLY DETECTION

PAGE 13

PAGE 10

Innovate | fall 2014, vol. xix | Barnes-Jewish Hospital and Washington University Physicians

RESEARCH AND PATIENT CARE THAT BREAK BOUNDARIES AND MOVE MEDICINE FORWARD

Photos by Robert Boston

UP FRONT

Making cancer glow A new technology developed at Washington University School of Medicine and used by surgeons at the Alvin J. Siteman Cancer Center makes cancer easier to see. These glasses, designed to make cancer cells glow blue when viewed through their lenses, can help physicians distinguish cancer cells from healthy ones during surgery.

Cancer cells have a reputation for being difficult to see, even under high-powered magnification. Currently, when a surgeon operates to remove a cancerous tumor, he or she collects tumor cells and cells from neighboring tissue,

which are sent to a lab for review. If cancer cells are found in the sample taken from tissue near the tumor, a second surgery is often recommended.

For example, about 20 to 25 percent of patients with breast cancer who have a lumpectomy to remove a tumor require a second surgery because current technology doesn’t allow the surgeon to see the extent of the disease during the first operation. Though still being tested, researchers and surgeons hope the glasses will reduce the need for additional surgeries, alleviate patient stress and save time and money.

– J. Goodwin

Washington University surgeon Julie Margenthaler, MD, FACS, was the first to use the new glasses in surgery.

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UP FRONT

Restoring rhythm

Mevion Medical Systems

Arrhythmias are caused by changes in the heart’s electrical impulses. Some are so short-lived that the heart’s rate or rhythm isn’t greatly affected. But when an arrhythmia is longer in length, it can cause a dangerously slow or dangerously fast rhythm.

Heart specialists at the Washington University and Barnes-Jewish Heart & Vascular Center were the first in Missouri to implant a new defibrillator A new device for treating arrhythmia device designed to treat this condition.

Called a subcutaneous implantable minimizes risk by delivering a needed cardioverter defibrillator (S-ICD), this shock from outside technology differs from traditional the heart. devices because it doesn’t rely on placement of wires inside the heart or blood vessels. Instead, the S-ICD uses a single wire that is placed under the skin (subcutaneously) on the front of the chest. The wire is then connected to a cardioverter defibrillator device (ICD) that is placed under the skin on the side of the chest.

Aiming for precision The S. Lee Kling Proton Therapy Center at Siteman Cancer Center is the only proton therapy center in Missouri and the surrounding region. It houses the world’s first compact proton beam accelerator. The compact

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During arrhythmia, a traditional ICD delivers a shock from inside the heart, which can cause damage. The S-ICD delivers its shock from outside the heart, minimizing the risk of damage. — A. Bassett

nature of the technology makes it more versatile and more cost-effective.

Proton therapy’s main advantage is that radiation specialists can control its beams by depth, shape and dose.

In other external radiation therapies, beams pass through a patient to a defined location and then exit the body, leaving deposits of radiation all along their path. Because proton therapy allows for depth control, little to no radiation is delivered beyond the tumor, meaning less healthy tissue is affected by the radiation beam.

Siteman Cancer Center’s proton device is ideal for patients with solid tumors located near sensitive areas, such as the eyes, brain or spinal cord. Proton therapy is particularly beneficial for children, because its precise targeting can help protect growing bones and tissue. — J. Goodwin

Innovate | fall 2014, vol. xix | Barnes-Jewish Hospital and Washington University Physicians

Aiding stroke recovery Half of all patients who suffer a stroke will develop dysphagia, or swallowing difficulties. Dysphagia is associated with higher mortality, aspiration pneumonia and even malnutrition.

To avoid these complications, a patient who has experienced a stroke is screened for dysphagia before he or she can eat and drink again. In fact, in 2008 the Joint Commission, which oversees U.S. hospitals, stipulated that patients with stroke could not take anything by mouth, including food, drink and medications, until they had been screened for dysphagia. In the past, that meant some patients could have up to a 14-hour wait to receive test results— and 14 hours of fasting and other treatment delays.

Thanks to a new dysphagia screening tool developed at Barnes-Jewish Hospital, that wait has been reduced to minutes. The new screening process is a five-part questionnaire easily administered by a nurse at the patient’s bedside. The results are immediate: Patients with stroke who don’t have dysphagia can begin eating the least restrictive diet as soon as possible; those who do have dysphagia are quickly identified and consequently have a reduced risk of developing aspiration pneumonia. As a result, recovery comes that much faster. — A. Bassett

Washington University physicians at Barnes-Jewish Hospital developed a screening test for patients with stroke that can speed recovery and protect against certain risks.

FOR THE CURIOUS: Aiming for precision > To view a video about proton therapy, visit: goo.gl/WnO5LE.

Restoring rhythm > Learn more about arrhythmias and treatment: barnesjewish.org/ heart-vascular/arrhythmias-heartrhythm-disorders.

Making cancer glow > To read more about the glasses that make cancer cells glow blue, visit: wumcnews. org/cancer-glasses.

Aiding stroke recovery > For the latest information about stroke—its signs, prevention and recovery—visit: barnesjewish.org/ stroke-center.

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NEWS FROM THE LEADING EDGE OF RESEARCH AND MEDICINE

UP FRONT

Age has advantages–even in pregnancy Women 35 and older face increased risks for many pregnancy complications, but they appear to have at least one advantage: a lower risk of having a baby with a major congenital problem, which can include a physical defect of the heart, brain, kidney and bones.

Advanced maternal age, normally defined as 35 and older, is a well-established risk factor for having a child with a chromosomal abnormality such as Down syndrome. But until recently, few studies looked at whether an older woman has an increased risk for a major fetal congenital problem when chromosomal abnormalities are absent.

Katherine Goetzinger, MD, a Washington University fetal medicine specialist at Barnes-Jewish Hospital, and colleagues recently studied that very issue. “Everyone,

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including my co-authors, was a little surprised by the findings,” says Goetzinger.

“As more women delay having children, they are faced with many increased pregnancy risks,” Goetzinger says.

“Findings from this study may provide some reassurance for these women.”

Researchers involved in the study looked at information collected from more than 76,000 women during their routine second-trimester ultrasound. They compared the incidence of one or more major congenital problems diagnosed at the time of ultrasound in women younger than 35 to that of women 35 and older. They also examined the incidence of major brain, kidney, heart and central nervous system defects in the fetus. >

Innovate | fall 2014, vol. xix | Barnes-Jewish Hospital and Washington University Physicians

WOMEN 35 AND OLDER ARE

40%

Advanced maternal age was associated with a 40 percent decreased risk of one or more major congenital problems, after controlling for other risk factors such as gestational diabetes and alcohol use. The incidence of kidney, brain and abdominal wall defects was lower in babies born to women 35 and older.The frequency of heart defects was the same in UP FRONT both age groups.

LESS LIKELY TO HAVE A BABY WITH CONGENITAL DEFECTS COMPARED TO WOMEN YOUNGER THAN AGE 35

Goetzinger speculates that women 35 and older may be more likely than younger women to maintain healthy behaviors during their pregnancy, which means they could be more likely to eat a healthy diet, exercise and take prenatal vitamins.

“I hope this study opens the door to more research that will help us advise and care for women 35 and older who are considering pregnancy,” Goetzinger says. — D. Duke Williams

Genetic risks for autism Researchers have found that when a child has autism, his or her parents are more likely to have autistic traits than parents who don’t have a child with an autism spectrum disorder.

Past studies have found that the siblings of children with autism tended to have more autistic traits than the siblings of kids without autism. But this new study is the first to connect significant numbers of autistic traits in parents to diagnoses of autism in their children. Researchers at Washington University School of Medicine, the Harvard School of Public Health and the University of California, Davis, conducted the study.

“When there was a child with autism in the family, both parents more often scored in the top 20 percent of the adult population on the survey we use to measure the presence of autistic traits,” says John Constantino, MD, one of the lead researchers of the study and a Washington University psychiatrist at St. Louis Children’s Hospital.

“It could be that the mother or father is just a little bit repetitive or slightly overfocused on details,” Constantino explains. “Higher scores don’t mean a parent has problems.

In fact, there may be advantages to having some of those traits.

The problem comes when those traits are so intense that they begin to impair a person’s ability to function.”

It might seem unlikely that couples with high levels of autistic traits would get together and have children, but when one parent scores high for autistic traits, it’s likely the other parent will, too.

“It turns out that people tend to select one another on the basis of many of the same traits that the survey measures,” Constantino says. “Likes attract. If one person has a high score, he or she is more likely to partner with another person who also scores high.” And that likelihood can raise the chances that their offspring will have elevated scores.

“When both parents have scores at or above the top 20 percent, the child’s score is 20 to 30 points higher than when neither parent has an elevated score,” says Constantino.

To better understand how the genetic risks for autism are transmitted from parents to children—and what might protect some individuals in a family from experiencing an autism spectrum disorder even when they inherit the same risk factors—Constantino and his colleagues are conducting studies to trace autism susceptibility across generations in families. — J. Dryden

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UP FRONT

Except for nonmelanoma skin cancer, breast cancer remains the most frequently diagnosed cancer in women. But there is good reason, says the American Cancer Society, to be encouraged by breakthroughs in detection and treatment of breast cancer. These advances, along with greater public awareness of the importance of breast exams, have caused a steady decline in breast cancer deaths in women since 1990.

Now, physicians and their patients have a sophisticated new tool that aids in early detection. Called tomosynthesis, the technology produces a three-dimensional image of the breast.

“Initial findings show that this technology is effective in two important ways,” says radiologist Catherine Appleton, MD, chief of the Breast Imaging Section at Siteman Cancer Center. Studies comparing traditional mammography to tomosynthesis show that the 3-D exam results in a higher rate of cancer detection, and it produces fewer false-positive results.

Conventional mammography has a false-positive rate of about 10 percent, Appleton says. That number represents a lot of unnecessary stress—and expense—for women who receive an initial positive test result and must undergo additional diagnostic testing to determine whether cancer is present or not. Studies of the 3-D imaging system suggest UP FRONT that its accuracy can reduce the number of false-positive results by 40 percent. — H. Toel

Schedule Your Exam > J oanne Knight Breast Health Center Center for Advanced Medicine 4921 Parkview Place, 5th floor l 314-454-7500 > H ighlands Medical Building 1110 Highlands Plaza Drive East

l

314-454-7500

> B arnes-Jewish West County Hospital 969 North Mason Road l 314-454-7500 > S iteman Mammography Van Visit siteman.wustl.edu for a schedule of locations 314-747-7222

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Scans courtesy of Hologic Corporation Inc.

Your mammogram–in 3-D

The breast image at left was produced by traditional mammography.

The yellow arrow points to a just-visible detected mass. The image at right is of the same breast but was produced by tomosynthesis.

The yellow arrow points to the same mass, which is more clearly outlined and visible.

Your 3-D mammography will not be noticeably different from a conventional exam. During the procedure, breast tissue is compressed between two plates. An X-ray arm moves above the breast in an arc-like sweep, taking a series of 15 low-dose images. When these images are assembled, they give radiologists a view of the breast in three dimensions.

The exam lasts just a few seconds longer than conventional mammography.

The Joanne Knight Breast Health Center, Highlands Medical Building mammography center and Barnes-Jewish West County Hospital offer 3-D mammography.

Innovate | fall 2014, vol. xix | Barnes-Jewish Hospital and Washington University Physicians

Exercise, for your heart’s sake You’re sweating, your heart is thumping, you’re breathing just hard enough to make chatting with your pal on the neighboring treadmill somewhat difficult. That’s good.

You’re engaged in exercise that will change your body and, if you keep it up, your life.

The benefits of regular exercise are well documented in both scientific and consumer literature: lower blood pressure, greater resistance to disease including cancer, greater ability to maintain healthy weight, increased bone density, lower risk of diabetes, reduced anxiety, depression and anger, greater mental acuity, reduced risk of dementia and Alzheimer’s disease, and prevention of cardiovascular disease.

Linda Peterson, MD, a Washington University cardiologist at Barnes-Jewish Hospital, is one of the region’s top experts on cardiovascular disease and exercise. Her research focuses on the causes of obesity-related cardiac dysfunction. She says, “Obesity contributes to 11 to 14 percent of all cases of heart failure.”

Naturally, Peterson advocates exercise. “The best kind of exercise is the one that you’ll actually do.” A lighthearted statement, perhaps, but she’s completely serious.

During hard physical activity, your lungs take in oxygen, filter and diffuse it into the bloodstream and send it straight to your heart, which pumps it out to power the muscles you’re using to walk, run, swim, dance or kickbox.

Exercise training strengthens your heart, enabling it to pump more blood with each beat—and supply your working muscles with more of the oxygen-rich blood they need during exercise. Meanwhile, your muscles are gaining in capacity, consuming greater volumes of oxygen more quickly. Your muscles are like engines, needing fuel to operate. And the fuels they burn are fat and carbohydrates.

Just one week’s worth of exercise— 30 minutes a day—produces noticeable changes in most adults.

The American Heart Association recommends 30 minutes of moderate exercise—a brisk walk qualifies—every day, which is enough to bring about noticeable changes after only a week for most adults. And there are studies that suggest as little as 10 minutes of exercise three times a day can make a difference.

Here’s Peterson’s advice: “Listen to your body. If you are exhausted, take a break. If you thought a workout was too easy, increase the intensity the next time out.” — J. Niehaus

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UP FRONT

Does fasting yield health benefits?

Since the British physician and journalist Michael Mosley wrote a best-selling book and produced a television documentary touting the benefits of the 5:2 diet—fasting two days a week and eating normally the other five— thousands of people worldwide have tried it. But Luigi Fontana, MD, PhD, a Washington University nutrition researcher and specialist in aging, says physicians and scientists don’t yet know enough about the effects this pattern of eating has on the human body. To learn more, he is recruiting volunteers for two studies.

“We know that counting calories every day is effective, but most people don’t want to do it. It’s too tough,” says Fontana, the studies’ principal investigator. The 5:2 diet is an alternative to severely restricting calories every day—an approach shown in Washington University studies to extend Participants in a Washington University study of the popular 5:2 diet will fast two days a week, eating only salad and raw or cooked green vegetables.

lifespan and yield health benefits in animals. “The good news is that data from studies involving animals show that intermittent fasting may be just as effective as daily caloriecounting in extending lifespan and improving health.”

Possible health benefits include preventing diabetes, heart disease and certain cancers.

“These are the first studies of the 5:2 diet that look comprehensively at its effects,” Fontana says.The studies will measure markers of gut inflammation, changes in metabolic and cardiovascular function and overall health.

Instead of cutting calorie intake by 25 to 30 percent at every meal, which is what those who practice calorie restriction do, participants in these studies will be asked to fast for two or three days each week. “But they won’t have to completely abstain from food on days they fast,” Fontana says. “At dinnertime, they can eat a large salad or raw or cooked green vegetables with a small amount of olive oil.”

On non-fasting days, participants in one of the studies will eat like they normally would. In the second study,

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participants will be placed in one of two groups; one group will eat their normal diet on non-fast days and on the others will eat a Mediterranean Diet that includes vegetables, beans and grains, whole-wheat breads and pasta, and fish or poultry.

Fontana’s team will monitor participants’ weight loss, but they are less concerned with intermittent fasting’s effects on weight than its relationship to aging and longevity.

“We want to find out whether intermittent fasting provides health benefits that are like those seen in people who practice calorie restriction, but we also want to know whether cutting fat and eating more legumes and whole grains will produce even better results,” Fontana explains.

UP FRONT “We believe these studies will help answer those questions, both for weight loss and for health and longevity.” — J. Dryden

FOR THE CURIOUS: > To be considered for the study, call 314-362-2300 or send an email to sjamalab@dom.wustl.edu.

> Read a story about one St. Louisan’s calorie-restricted diet and lifestyle: wumcnews.org/calcut.

> Learn more about calorie-restriction research: wusmnews.org/young-heart.

Innovate | fall 2014, vol. xix | Barnes-Jewish Hospital and Washington University Physicians

A closer look: hip-replacement surgery If “have hip replaced” is at the top of your to-do list, you’re not alone. There are millions of Americans living with artificial joints: 2.5 million with new hips and 4.7 million with new knees, according to the American Academy of Orthopaedic Surgeons. And though Medicare is the primary payer for the majority of these replaced joints—which means most of the patients are 65 years old and older—the trend is skewing younger.

Hip mechanics: The hip joint is essentially a ball-and-socket

structure. In a healthy hip, smooth cartilage covers the ends of the thigh bone and pelvis, allowing the ball to swivel easily within the socket. In a damaged hip, the cartilage is worn away and no longer serves as a cushion between the ball and socket. When these worn areas rub together, movement is painful.

Total-hip-replacement surgery removes the worn, rough parts and replaces them with smooth parts. The femoral head, or ball, of the hip is replaced with a prosthetic ball and stem, and the acetabulum, or socket, is lined with an artificial cup.

The result is a new ball designed to move easily within a newly lined socket.

Choosing your team: If you need hip-replacement surgery,

one of the most important decisions you’ll make is selecting

Tendon Ball at head of thighbone covered with cartilage

The path to success: Rosemary Schriefer had her hip

replaced in 2011. She went from walking with a cane to working out on an elliptical machine and taking Zumba classes. It took Schriefer seven months to get from point A to point B, but, she says, “I didn’t give up on myself.”

Clohisy says, “Rosemary’s commitment to fitness indicated that she would be a good candidate for a successful hip replacement.” — H. Toel To read Rosemary Schriefer’s story and learn more about joint-replacement surgery, visit barnesjewish.org/orthopedics/patient-success-stories.

Cup Cartilage damage

Ball

Stem

Pelvic bone Thigh bone (femur)

HEALTHY HIP

DAMAGED HIP

Images courtesy of Krames StayWell

Socket (acetabulum) lined with cartilage

Muscle

an experienced orthopedic surgeon. Look for someone who does 30 or more hip-replacement surgeries a year and has at least 100 under his or her belt.

“Choosing a qualified orthopedic surgeon is fundamental to minimizing the risk of complications and poor outcomes,” says John Clohisy, MD, a Washington University orthopedic surgeon and co-director of the adult reconstructive surgery service at Barnes-Jewish Hospital. “In general, surgeons who dedicate a significant portion of their practice to jointreplacement surgery, specifically hip replacement, are most suitable to provide high-quality care.”

And you should choose a good hospital, Clohisy says.

Medicare recently released a list of the best and worst hospitals for hip- and knee-replacement surgery, identifying 97 hospitals where patients were most likely to have smooth recoveries. In the St. Louis area, Barnes-Jewish Hospital was the only hospital where patients fared better than the national average.

You can also decide to be as healthy as possible before surgery—loose weight if needed, keep muscles flexible and toned. And you can determine ahead of time that you will adhere to the physical-therapy regimen your doctor prescribes for you once you’re discharged from the hospital.

HIP REPLACEMENT

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UP FRONT UP FRONT

UP FRONT

Marriage and medicine Recently, the editor of Innovate magazine sat down with Murali Chakinala, MD, a pulmonologist, and Lisa de las Fuentes, MD, a cardiologist, to talk about their lives as husband and wife and as Washington University physicians and researchers who care for patients at Barnes-Jewish Hospital.

Editor: Was

it difficult for both of you to find fellowships in the same city?

Lisa: Match week was the week after our wedding. (Editor’s

note: Match week is when residents find out where they will go to complete their specialty training in a fellowship program.) We knew we wanted to end up at an academic medical center like Washington University and Barnes-Jewish Hospital. I wanted to specialize in cardiology, and Murali was interested in pulmonology.

Murali: We had two requirements:We wanted to be Husband-and-wife physicians Murali Chakinala, MD, and Lisa de las Fuentes, MD

Editor: How

did you meet?

Lisa: I was a medical student in Dallas and he was a resident,

though he never supervised me.We were part of a group of friends who went to a Dallas Mavericks basketball game together.We made a connection that day, but— Murali: It took me six months to ask her out.When I finally

did, she said, “Call me back in a month.”

Lisa: I was getting ready to leave the country for a two-

week train trip in Europe. But he did call when I got back.We started dating in September of 1995, and we got married in May of 1998.

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together, and we didn’t want to go too far north; as Southerners we were worried about cold winters. So we drew a line on a map and said, “Nothing north of St. Louis.”

We moved here in 1999.

Editor: What

is it like to be married to a doctor?

Lisa: Well, our lives are a delicate balancing act.We keep a

detailed calendar that includes work and home life. It’s what gets us all to the right places at the right time.We’ve learned that any addition to one of our schedules has immediate ramifications for the others’. Our two young sons (ages 12 and 9) have learned how to read the calendar, so they know what to expect from day to day. Life gets complicated—but we make it work.

Murali: It helps that Lisa and I work at the same place.

We park our cars next to each other, and we work two floors apart. >

Innovate | fall 2014, vol. xix | Barnes-Jewish Hospital and Washington University Physicians

Murali: My father was a pulmonologist, and Lisa’s mother

was a CRNA (certified registered nurse anesthetist).

Editor: What

do you love about your work?

Lisa: I’m involved in research looking at metabolic traits

such as high cholesterol and diabetes. I’m curious about the genetic characteristics of these conditions. And I’m interested in intervention; what can we do to prevent these illnesses and the conditions they cause? Right now, I’m involved in a study with Sam Klein looking at the changes significant weight loss can have on the heart.

(Samuel Klein, MD, is a Washington University physician at Barnes-Jewish Hospital.)

Editor: So, do

you have lunch together often?

[lots of laughter] Lisa: Maybe once a year!

Murali: In all seriousness, though, we each benefit from

being married to another physician.We can empathize with each other and are more understanding when one of us is stressed about work or has a big deadline upcoming.

Editor: What

are your two boys interested in?

How have your careers influenced them?

Lisa: Well, it’s not surprising that they are both analytical,

concrete thinkers. They like math and the sciences.

Murali: Our boys know that we work pretty hard at our

jobs.They understand that we take care of people who are sick and that what we do is important.

Lisa: And they can be pretty

popular when we can help them with a medical show-and-tell.

Medicine is part of our family.

I was visiting operating rooms when I was a 10-year-old.

I love that my work introduces me to new things, new ideas. It’s never boring. My career has allowed me to learn, grow and reinvent myself.

Murali: I thought I’d be like my

father, a lung specialist in private practice who treated patients with all kinds of lung disorders. But thanks to the medical center and its opportunities, some hard work and some serendipity, I’ve found an unexpected niche. I focus on pulmonary vascular disorders, primarily pulmonary hypertension, which is a rare but serious condition. I’ve become an expert on this rare disease and conduct clinical research that will determine future treatments.

I’m also heavily involved in national initiatives that will shape the future delivery of health care for pulmonary hypertension patients. The medical center is a wonderful place, filled with diverse and brilliant minds. St. Louis has turned out to be a great home for us. — A. Makeever Photography by Jay Fram. Shot on location at Central Table in the Central West End.

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MEDICAL MYSTERY

Migratory joint pain + abnormal blood protein + rash and night sweats = X Solving a diagnostic equation is both a science and an art. And the path to the solution can take unexpected turns and at times seem stalled. Getting to the right answer often requires the combined knowledge and effort of a team of experts—and the patient.

Written by Anne Makeever

Initial injury When Doug McTall stepped off the curb and landed funny, injuring his right knee, he couldn’t have known that he had just taken the first step of a difficult journey— one that for him would take many months, and many doctors, to complete.

McTall and his wife, Donna, live in a small town in southern Illinois, where he works as a regional truck driver and dock worker. The injury happened while he was at work, in April 2013, but it wasn’t anything he thought a doctor needed to treat. Then in June, climbing into the cab of his truck, he reinjured his knee. This time, pain and swelling in his lower leg forced him to a local clinic.

An exam suggested that something more serious than a hyperextended knee was going on, and McTall was quickly referred to the local hospital. There, he learned he had high levels of M-protein, a substance in the blood that is sometimes a sign of cancer. Doctors also told him he had deep vein thrombosis (DVT), essentially a blood clot, affecting his right thigh and the area behind his knee, and started him on anti-clotting drug therapy.

Complications While hospitalized, new symptoms cropped up: joint pain and then a rash, which began on his back and soon spread to cover his body. Next came chills and sweats, but there was no cough, no loss of appetite, no nausea. The couple wondered if a reaction to medication was the cause.

McTall left the hospital eight days later with his DVT under control but without an explanation for his new symptoms. He then saw a hematology and oncology specialist to learn more about his elevated M-protein. The resulting diagnosis: a blood disorder called monoclonal gammopathy of unknown significance, or MGUS, and a mutation in a particular gene that, when deficient, can contribute to many serious conditions. The doctor told him he didn’t have cancer but would need medication and periodic checkups. These diagnoses, however, didn’t explain the reason for the range of symptoms that had plagued McTall and that continued, unchecked.

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New strategy Jerry Beguelin, MD, McTall’s primary care physician, saw McTall in his office in August. Thinking the symptoms might be related to toe pain McTall had five years prior, caused by an elevated uric acid level that indicates gout, he prescribed an appropriate drug. But the tests for gout were negative, and the treatment was stopped. McTall’s symptoms continued unabated; he decided to track them by keeping a daily journal.

Next, Beguelin prescribed a steroid treatment that tapered in dosage each day. When taking the maximum dose, McTall’s joint pain and rash eased. But as he neared the end of treatment and was taking fewer steroid pills, the pain and rash returned, as did chills and sweats.

And then hot flashes appeared.

In January 2014, Beguelin prescribed another course of steroid treatment.

Again, the treatment helped ease symptoms at first, then became ineffective. The symptoms returned with a vengeance.

By this time, the sum of McTall’s health problems had altered his life at work and at home. He found simply walking around the house or getting in and out of bed was extremely difficult on his worst days. And he couldn’t go to the store with his wife without needing two days afterward for recovery.

The last referral In February, Beguelin told McTall he’d found a specialist who might be able to solve the puzzle: John Atkinson, MD, a Washington University rheumatologist and autoimmune disease specialist at Barnes-Jewish Hospital. When Atkinson received McTall’s medical records, he got to work, discussing the details with his colleagues. When Doug and Donna McTall met with Atkinson, they gave him McTall’s journal and photographs Donna had taken of her husband at various times throughout their ordeal. During the exam, Atkinson told McTall he had specialists on the case. When the couple left that day, he promised them an answer.

Atkinson has a reputation for diagnosing the difficultto-diagnose. He brought dermatologists, hematologists and radiologists into the process, and he delivered a challenge to a fourth-year medical student, who saw McTall in the consultation clinic during his appointment with Atkinson: See if you can come up with a diagnosis in 24 hours.

Confirmation and treatment Atkinson asked the McTalls to do a little research on their own to see if they thought the diagnosis fit. The McTalls discovered that Schnitzler syndrome can manifest itself through the following symptoms, among others: > Deep vein thrombosis > Presence of M-protein in the blood > Rash > Joint pain or arthritis > Fever and/or night sweats The McTalls knew they had their answer. To confirm the diagnosis, and to rule out any cancer of the blood (which can develop with Schnitzler syndrome), McTall returned to Barnes-Jewish Hospital for a series of tests. His bone marrow biopsy was negative for cancer, though he will need periodic testing.

The drug anakinra can be effective in treating Schnitzler syndrome, but it requires a daily injection and is very expensive. In search of an alternative treatment, Atkinson turned to Washington University dermatologist Milan Anadkat, MD, who knew of a clinical trial looking at the effectiveness of a drug called gevokizumab. Participants in the trial receive medication at no cost. Anadkat began the process required to get McTall accepted into the study.

The student went home that night to have dinner with his wife, a dermatology resident at Barnes-Jewish Hospital.

During the meal, they discussed Atkinson’s challenge. By the end of the evening, she had a rare disease in mind she had come across while studying for her medical-board examination. In the morning, the med student delivered their answer to Atkinson, who confirmed they had gotten it right.

On March 5, 2014, Atkinson made a phone call to the McTall home to relay the diagnosis: Schnitzler syndrome.

He told the McTalls that the elevated M-protein, discovered earlier in the course of his illness, might have created an inflammatory reaction that caused the syndrome.

Named for French dermatologist Liliane Schnitzler, the syndrome was first described in 1974. Since then, fewer than 100 people have been diagnosed with the disease.

Some conclusions “These kinds of cases,” says Atkinson, “are often best diagnosed at large academic medical centers like ours. We have a wealth of resources, including access to clinical trials. In this case, very bright students, residents and fellows as well as experienced physicians from multiple specialties applied themselves to the task of finding an answer.” Atkinson notes that most patients who have Schnitzler syndrome respond well to available treatment. “I’m pleased we are able to help Doug and Donna McTall.”

The McTalls are pleased, too, and eager to thank those who never gave up. “Dr. Beguelin was determined to put me in touch with a specialist who could help,” McTall says. “I guess Dr. Atkinson’s job is to figure out every strange case that comes his way.

And Dr. Anadkat has jumped through hoops to get me approved for the trial.”

And then there’s Donna McTall, an essential part of solving the diagnosis equation. She called doctors, set appointments, managed insurance and workman’s compensation tangles. For the past year, her husband’s health has been her full-time job, all day, every day. Her husband says, “I love her. And I wouldn’t have made it through this past year without her.”

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U.S. Department of Agriculture / Eric Young

WRITTEN BY GAIA REMEROWSKI

Trillions of microbes live in the human gut. Some promote health and fight disease; others, like the bacterium Enterococcus faecalis, shown here in different colors, can cause life-threatening infection.

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Centers for Disease Control and Prevention

The microbe E. faecalis is commonly found in the gut.

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C. difficile is a common cause of antibioticassociated diarrhea.

including obesity, malnutrition and possibly even brain disorders such as anxiety and depression.

Treating dangerous diarrhea Though scientists still aren’t sure what microbial mix makes up a healthy gut, they do know there are some nasty bugs that, left unchecked, can wreak havoc with digestion. One of these is the bacteria C. difficile, or C. diff, which can cause severe diarrhea.

“C. diff is virtually everywhere,” says Erik Dubberke, MD, a Washington University infectious disease specialist at Barnes-Jewish Hospital. “It’s been found in our homes, our drinking water, even our food.” Those of us who are older adults, and those who are hospitalized, are especially susceptible to this type of infection, which causes more than 14,000 deaths per year in the United States.

Sometimes, we become susceptible to C. diff when we take an antibiotic, which can destroy the good bugs that normally protect our guts from the infection this little pathogen causes.

Once C. diff has taken hold, it’s hard to get rid of; in up to 30 percent of

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patients, the infection returns at least once—and sometimes multiple times.

As many as 10 percent of those made sick by C. diff cannot get rid of these recurrent infections. To help these individuals, Dubberke performs fecal transplants, a transfer of fecal matter from a healthy gut to an infected gut.

If all goes well, the healthy microbes take up residence and go to work, preventing C. diff from returning. To qualify for such treatment, patients who are referred to Dubberke first must meet strict criteria; often, they have exhausted all other forms of treatment.

Although such transplants are in some ways still the “Wild West,” says Dubberke, scientific literature reports an 80 to 85 percent success rate for stopping recurrent infections. But Dubberke says there are still challenges: “We don’t yet have an ideal method for choosing donors, and we don’t know which bacteria are the best to use in the transplant.”

He and his collaborators are working on identifying the most protective microbes and to commercialize preparation of prescreened, healthy fecal samples.

Radiation protection Another way gut function can be disrupted is through radiation therapy for abdominal cancers.

Matthew Ciorba, MD, a Washington University gastroenterologist at BarnesJewish Hospital, explains it this way: “The epithelial cells that line the gut’s inner surface often are part of the ‘collateral damage’ of radiation cancer continued on page 22

Matthew Ciorba, MD

contain tens of trillions of microbes.They outnumber the body’s cells 10 to one.

This community of microbes, known as the gut microbiota, affects all of us—for better and for worse—in ways scientists are now more fully appreciating.

On the positive side, these bugs are a key part of maintaining our well-being; not only do they help us absorb and make essential nutrients, they also boost our immune system and protect us against harmful pathogens—the bugs that can cause disease. But they can also contribute to many undesirable conditions, including inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS).

Researchers at Washington University are pioneering the study of the bugs that live in and on us to learn more about how our microbiota shapes health and disease, to define what makes up a healthy gut and to understand how to alter the gut microbiota to restore us to health or keep us from getting sick.

The work these scientists are engaged in has global implications for addressing major human health problems,

Centers for Disease Control and Prevention

Our guts

Which probiotics actually work?

Probiotics Report Card Gastroenterologist Matthew Ciorba, MD, published a review of the probiotic products available in the marketplace based on clinical trials that evaluated their effectiveness in treating a number of digestive disorders. In his report, he notes that, though research in the field of probiotics continues to evolve, it is possible to evaluate the available products for their ability to treat or prevent problems. This report also notes that probiotics have a limited ability to address symptoms and that “not all probiotics are right for all diseases.”

Grade*

Condition

Probiotic Name

Preventing diarrhea while taking antibiotics

Culturelle A Danactive A Florastor A

Treating infectious diarrhea

BioGaia A Culturelle A Florastor A

Treating symptoms of irritable bowel syndrome

Activia C Align B BioGaia C Culturelle B/C VSL#3 B/C

*Grades: A = Strong evidence

B = Moderate evidence C = Inadequate evidence

Source: A gastroenterologist’s guide to probiotics. Ciorba MA. Clin Gastroenterol Hepatol. 2012 Sep;10(9):960-8. doi: 10.1016/j.cgh.2012.03.024.

Epub 2012 Apr 10. Review. PMID: 22504002

Tim Mudrovic

> To read the report in its entirety, visit: wumcnews.org/probio.

Matthew Ciorba, MD

Current research is considering the probiotic Lactobacillus GG (shown at top) and its ability to protect the lining of the small intestine from radiation injury caused by cancer treatment.

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continued from page 20

Robert Boston

treatment.” When that happens, patients suffer from diarrhea, stomach pain and Sharing microbes: fat mouse, thin mouse nausea. Sometimes their symptoms are Mice fed microbes from obese people tend to gain fat. so severe that radiation therapy must be Microbes from lean people protect mice from excessive weight gain. stopped. And that delay can compromise their cancer treatment.

In response to this potentially harmful chain of events, Ciorba and colleagues are evaluating probiotic therapy, the introduction of live and “helpful” microorganisms to the body. microbes Low-fat, Obese Recipient Mouse high-fiber diet Microbe Donor mouse gets fatter Specifically, their research is considering the benefits of taking live bacteria in pill form as a way to protect intestinal cells and help patients complete radiation therapy with fewer side effects. So far, researchers have shown that the probiotic Lactobacillus GG (LGG) Lean microbes Recipient Low-fat, Mouse does protect against radiation damage Microbe Donor mouse high-fiber diet stays thin in mice. Their next step is to test LGG in humans. They plan to recruit 20 patients with rectal, pancreatic and anal cancers for a safety trial that has been revealing an intimate connection from the lean twin invaded the guts of Low-fat, Lean twin mouse Mousethin stays thin approved by the U.S. Food and Drug among gut microbes,microbes diet and nutrition.reg mice with high-fiber the obesediet twin’s microbes, & arrowweight gain and arrow Administration. Each study participant Studies performed by&Gordon’s lab havemousewhich prevented will receive the commercially available shown that people who are obese have metabolic problems. But this only LGG probiotic Culturelle before a less diverse collection of microbes occurred if the mice ate healthy human radiation therapy starts. than those who maintain a healthy diets that were low in saturated fats and “Patients ask me every day what they weight. The lack of certain microbes in high in fruits and vegetables. can do and what they can take in terms obese people’s gut communities may “Eating a healthy diet encourages of nutrition and wellness to help them contribute to disease. microbes associated with leanness to > through their cancer treatment,” says To investigate a potential relationship Parag Parikh, MD, radiation oncologist between the gut microbiota and obesity, at the Alvin J. Siteman Cancer Center at Gordon and fellow researchers recruited Barnes-Jewish Hospital and Washington pairs of human twins, one obese and one University School of Medicine, who lean.They transplanted gut microbial is helping Ciorba run the trial. Parikh communities from each twin into germhopes to soon have the scientific free mice.The results of their study evidence to recommend probiotics as show that mice receiving transplants an option for certain patients getting from the obese twin developed obesity radiation therapy. and metabolic problems; mice receiving transplants from the lean twin did not. In Jeffrey Gordon, MD, and Vanessa Ridaura are Fighting obesity and malnutrition the next phase of the study, researchers studying the ways gut microbes influence weight.

Pioneering research led by Jeffrey repeated transplants and placed mice As shown in the illustration at top, altering the mix Gordon, MD, director of the Center carrying obese microbial communities of gut microbes in mice prevents obesity, but diet for Genome Sciences & Systems into the same cage with mice carrying remains a key factor.

Biology at Washington University, is lean microbial communities. Microbes

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f

quickly become incorporated into the gut,” says Gordon. “These findings are important as we look to develop nextgeneration probiotics as a treatment for obesity,” he adds.

Although some microbes may make us too fat, others may contribute to the opposite problem—malnutrition, the leading cause of child mortality worldwide.

Our gut microbiota are established at birth and continue to change for the first three years of life. Gordon is leading an international team of scientists studying malnutrition in children from Malawi during those early years. Their work with 317 pairs of twins finds that gut microbiota in malnourished children do not mature normally and may prevent some children from proper growth even when given therapeutic foods.This research suggests that successful treatment of malnutrition requires not only food-based therapies, but also long-lasting repair of the disrupted microbiota.

Microbial who’s who A good deal of the research focused on microbial communities and their genes—the microbiome—has concentrated on illness.We still don’t know what bugs make up a healthy microbiota. Researchers at Washington University’s Genome Institute are gathering information on the species, genetics and function of the microbiota in our bodies; they hope to establish a baseline for health so they can then look for abnormalities associated with disease.

Their studies include characterizing all the various types of microbes residing in the human body, including bacteria, viruses, fungi and other lower organisms.

“Our most immediate focus is to assemble a pipeline to complete

microbiome projects more quickly,” says infectious disease genomics researcher Makedonka Mitreva, PhD, who is also assistant director at The Genome Institute. “Our ultimate goal is to use this information in the clinic to detect and trace disease outbreaks, and diagnose and treat patients with a wide range of health problems.”

Gut microbes and the brain Often when we’re nervous, we feel it in our gut—that familiar and disconcerting butterflies-in-the-stomach sensation. So it’s not surprising that science is revealing links among our gut, gut microbiota and brain. “I think in many conditions such as anxiety and depression, a very logical place to look for answers is in the gut,” says Ciorba.

We have more nerve endings in the gut than in the brain.The gut is also home to 95 percent of the body’s serotonin—a hormone often associated with anxiety and depression. And studies suggest that gut microbes may alter the levels of many hormones that affect the brain.

Ciorba and his colleagues have shown that mice with gut inflammation UP FRONT show symptoms of anxiety and

Makedonka Mitreva, PhD, is assistant director at The Genome Institute, where researchers are gathering information on the species, genetics and function of the human microbiome.

depression.This group is now researching IDO, an enzyme that is activated by gut microbes and interferes with serotonin production. Ciorba and his colleagues are looking at whether IDO may be a factor in the anxiety and depression often suffered by patients with IBD. Studies in this area offer hope that certain dietary supplements that interact with the gut microbiota may help restore these hormones to healthy levels and alleviate brain-related symptoms, says Ciorba.

It is still the early days for this research, but so far, science has made it clear that our gut microbiota play a much bigger role in our health than once thought. And whether it’s through fecal transplants, probiotics, diet or drugs, cultivating and nurturing our gut communities have become a key focus in the search for understanding disease and health. n

FOR THE CURIOUS: > For more information about the probiotics and radiation therapy trial, visit: Clinicaltrials.gov; type NCT01790035 in the search box, then click on the search button.

> To hear a TEDX talk by Jeffrey Gordon, MD, visit: Tedxgatewayarch.org; click on TEDX Talks, then on Gordon’s talk, titled Gut Microbes and Children Under Nutrition.

>T o view an animated video about research that suggests a link between gut microbiota and obesity, visit: wumcnews.org/gut-animation.

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Personalized medicine:

how genetic research is transforming cancer care Written by Jim Goodwin

W

hen it comes to cancer care, it is clear that a one-size-fits-all approach is not ideal.

Today, armed with growing data from genetic research, physician-scientists are ushering in a new era in which cancer care is tailored to the individual.

The ultimate goal: to make cancer a manageable, if not a curable, disease.

Cancer, however, isn’t just a single disease; it comes in countless forms and appears throughout the body. No two cases of cancer are exactly alike.That complication poses a major challenge for physicians trying to choose the best treatment for each patient and for researchers working to develop better approaches to care.

For answers, physician-scientists at Washington University are looking

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to our genetic code. Conducting one of the world’s largest research efforts of its kind—understanding cancer genomics—these men and women are uncovering the roots of cancer and using what they learn to tailor treatment based on the genetic signature of each patient’s tumor—an approach called personalized medicine.

“Cancer care is undergoing a great shift,” says Timothy Eberlein, MD, director of the Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine. “We want to deliver effective, tailor-made treatment to each patient based on his or her unique situation.”

Considering our genes Personalized medicine is grounded in our growing understanding of DNA,

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the material within all human cells that directs development and growth throughout life. Our genes are the working subunits of DNA; an organism’s entire set of genetic material is called its genome. Genomic medicine is trying to understand how genes interact with each other and the environment in ways that are relevant to health and disease.

Gene mutations—abnormalities that are either inherited or caused by environmental factors—can accelerate cell division and eventually lead to cancer. Scientists study the differences between genes in normal cells and those in cancer cells to identify cancer-causing mutations, learn what causes them and determine how to stop them.

Major technological advances in recent years—many developed at Washington University’s world- >

renowned Genome Institute—have made genome analysis significantly faster and more economical, in turn fueling research on the genetic basis of disease.

Breaking ground Cancer genome sequencing was pioneered by a team of researchers at The Genome Institute. In 2008, they sequenced the first-ever complete genome of a cancer patient, an individual with acute myeloid leukemia (AML), a cancer of the blood and bone marrow.

In 2013, a subsequent Washington University study involving some 200 patients and nearly 150 researchers revealed virtually all of the major mutations driving AML. “We now have a genetic playbook for this type of leukemia,” says study coleader Timothy Ley, MD, a Washington University oncologist at Siteman Cancer Center. “This information can help us begin to understand which patients need more aggressive treatment right up front and which can be treated effectively with standard chemotherapy.”

The field continues to mushroom at Washington University and beyond. Genome Institute scientists, working with Siteman Cancer Center oncologists, have conducted studies similar to the AML project for breast, ovarian, lung, uterine and other cancers.

And the results are beginning to make a difference in patient treatment.

Washington University’s Genomics and Pathology Services (GPS) now

offers testing for 42 known cancerrelated gene mutations—the results of which physicians can use to tailor treatment, says Jon Heusel, MD, PhD, chief medical officer of GPS and medical director of clinical research genomic testing at The Genome Institute.

“GPS is bringing the promise of human genomics to physicians and the clinic,” says Karen Seibert, PhD, its director. “We use the latest genesequencing technology and crossreference the results to known treatment options for a patient’s particular mutations. In addition to patient care, our labs support clinical trials aimed at identifying new ways to diagnose and treat disease.”

Genetic Services Genetic testing Genomics and Pathology Services at Washington University offers a Comprehensive Cancer Test that evaluates 42 genes for mutations linked to: > Solid tumors: brain, breast, colon, gastrointestinal stromal, head and neck, liver and biliary structures, lung, ovary, pancreas, prostate, skin, thymic, uterus and many others. > Blood cancers: acute myelogenous leukemias, lymphocytic leukemias, lymphocytic lymphomas and others.

Results of genetic testing can, but do not always, suggest targeted or personalized therapies. You may request genetic services through your physician; many insurance plans cover the cost.

Improving tumor classification Ongoing research is transforming the process of defining types of cancer tumors—information that is key to choosing treatment.Traditionally, this work is done by looking at tissue under a microscope; but categorizing some tumors this way is difficult, and pathologists don’t always agree on what they see. Gene testing provides a more >

Genetic counselors At Siteman Cancer Center, patients can speak with counselors about hereditary cancer risk and genetic mutations identified through testing. Call 800-600-3606 or visit siteman.wustl.edu for information.

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Tim Parker

detailed picture, allowing physicians to classify tumors based on their genetic signatures in addition to their location in the body. According to early clinical studies, the results may alter the course of treatment for some patients.

A recent study of endometrial cancer is a case in point. Clinically, endometrial cancers, found in the lining of the uterus, fall into two types, one more aggressive

From left to right: Richard Wilson, PhD; Timothy Ley, MD; and Elaine Mardis, PhD; in the The Genome Institute’s 16,000-square-foot data center

than the other. Using a genetic analysis of tumor samples from 373 women with endometrial cancer, researchers have identified four additional tumor subtypes. What’s more, one of those subtypes, identified as the less aggressive form through pathology tests alone, actually is genetically similar to the more aggressive type and requires more rigorous treatment.

“We are entering an era when tumors can be evaluated from a genomics standpoint, not just by looking at cells under a microscope,” says Elaine Mardis, PhD, co-director of The Genome Institute and project co-leader for the study. “This more comprehensive approach provides a clearer idea of how particular endometrial cancers will behave and will be important to gynecological oncologists who treat this disease.”

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Such testing has already proven its merit in breast cancer—the cancer type at the forefront of personalized medicine.

In one study of 77 postmenopausal women with an advanced form of the disease, Mardis and colleagues identified distinct genetic signatures that accurately predict which patients are most likely to benefit from estrogen-lowering drugs.The drugs can reduce the size of breast tumors, enabling many women to receive breast-conserving surgery rather than a mastectomy.

“This is among the earliest cancer genomics studies to use mutations to accurately predict a patient’s response to treatment,” says Mardis, the study’s lead researcher. “If our results are validated in larger studies, we think genomic information will be one more thing for physicians to consider when they select UP FRONT among several treatment options for their patients.”

Siteman Cancer Center coordinates patient enrollment into clinical trials, where access to experimental treatments like this is available for many cancer types. These trials are key in learning which tests and treatments are beneficial and should become mainstream care.

New applications for existing drugs Surprisingly, some studies reveal genetic kinship among tumors in distinct sites of the body, and the implications are far-reaching. Mardis’ endometrial cancer study showed that some endometrial cancers are genetically similar to deadly subtypes of ovarian cancer and basallike breast cancer. And in patients with breast cancer, researchers have found numerous gene changes associated with leukemia and prostate, colorectal, lung, skin and other cancers. Patients with these mutations may benefit from drugs already in use for those cancer types. >

Seeking Treatment for Cancer The American Society of Clinical Oncology suggests that patients ask their doctors the following questions to learn more about available personalized cancer care: > What are my treatment options? > What clinical trials are open to me? > Are there tests available that can help guide treatment choices? > Is this treatment considered an example of personalized medicine? If so, how? > What are the benefits of this treatment? > What are the potential side effects of this treatment? > What is my chance of recovery?

Siteman Cancer Center is the only National Cancer Institute-designated comprehensive cancer center within a 240-mile radius of St. Louis. The center offers personalized medicine options, excellence in cancer care and a wealth of patient resources. >T o learn more about clinical trials available nationwide, visit: clinicaltrials.gov. > F or a list of clinical trials available at Siteman Cancer Center, visit: siteman.wustl.edu/ FindProtocol.aspx. >T o learn more about Siteman Cancer Center and its approach to cancer care, visit: siteman.wustl.edu.

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potential value of testing even a single gene of interest, says Ron Bose, MD, PhD, a Washington University medical oncologist at Barnes-Jewish Hospital.

“If we can identify mutations that we can act on, that information will help us better guide treatment,” he says. “In this case, we don’t even have to develop new drugs against HER2 mutations. It’s just a matter of finding the patients who can benefit.”

Robert Boston

In another study,Washington University researchers found that some women with HER2-positive breast cancer may benefit from antiHER2 drugs even though standard tests don’t indicate they are candidates for the drugs.The study shows the

John DiPersio, MD, PhD, speaks with patient Elzy Bannister. DiPersio, deputy director of Siteman Cancer Center, is known for his achievements in cancer genome sequencing and stem cell research.

Looking ahead Gene sequencing may also help map the genetic evolution of an individual’s disease. Much like bacteria, whose habit of continually mutating can render them resistant to antibiotics, tumors also constantly change, including in response to treatment. Genetic surveillance might allow physicians to monitor patients’ response to treatment and signal when it is time to try a different approach.

As research continues, cancer physician-scientists envision a brighter future.

“Already, we can treat patients with cancer more effectively and use the word ‘cure’ more often,” says Ryan Fields, MD, a Washington University surgeon at Barnes-Jewish Hospital and

Genetic surveillance might allow physicians to monitor patients’ response to treatment and signal when it is time to try a different approach.

a Siteman Cancer Center member. “But even if we’re not using the word ‘cure,’ we are converting cancer into a more chronic disease, so it’s more like having high blood pressure or high cholesterol— something that can be managed over time with different regimens, improving the treatment but also maximizing the patient’s quality of life.” n

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BrainwOrks YOUr MIND ON LIFE

Understand life and the human brain. Like never before.

SATURDAY, DEC. 6, 2014 | THE SHELDON CONCERT HALL

Barnesjewish.org/Brainworks2014 30

Innovate | fall 2014, vol. xix | Barnes-Jewish Hospital and Washington University Physicians

Fighting the flu David Haley, police chief in Carlinville, Ill., says a cough was the first sign that he wasn’t his usual healthy self. Next came fever, which spiked to 105 degrees. Sick enough to seek care at a Springfield, Ill., hospital, where he was admitted, Haley found himself engaged in a fight not covered in standard police training.

And he says he very nearly lost.

According to the Centers for Disease Control and Prevention (CDC), the 2012-2013 flu season resulted in 79,000 hospitalizations in the United States. In January, with the season still active, Barnes-Jewish Hospital reported 320 diagnosed cases, including 35 with severe symptoms being treated in intensive care units and nine deaths in patients ranging in age from mid20s to mid-60s.

Influenza, or flu, is an infection of the respiratory system caused by virus. And it’s highly contagious; airborne droplets from the sneeze or cough of an infected person can reach someone standing as far as six feet away.The CDC reports the H1N1 influenza strain that dominated the 2013-2014 flu season can cause, among other symptoms, fever, cough, sore throat, body aches and chills. Even in healthy people, the flu can cause serious complications or even death.

Haley was transferred to Barnes-Jewish Hospital but doesn’t remember much about his stay. His wife, Missy, however, remembers clearly the efforts made to keep her husband alive.

Because Haley’s lungs were damaged by influenza, and he

Detailed rendering of the H1N1 virus

wasn’t responding to other interventions, his team of health care professionals chose to use ECMO, or extracorporeal membrane oxygenation, a procedure that can benefit patients with severe cases of flu or other illness affecting the lungs. Essentially, ECMO replaces the lungs’ function: a patient’s blood runs through the ECMO machine, which removes carbon dioxide and adds oxygen, then returns the blood to the heart.With their workload temporarily halted, the lungs can rest and heal.

When Haley recovered and was able to leave the hospital, he had lost 42 pounds, and he needed dialysis three times a week as a result of kidney damage. He and his family honored Christmas a few weeks late, happy to have another good reason to celebrate.

Haley says he didn’t take time out of his busy schedule to get a flu vaccination last fall, and he wants to make sure others don’t make the same mistake.

The CDC estimates that in the 2012-2013 season, the flu vaccine helped 3.2 million people avoid influenza.

— A. Makeever

Get Vaccinated Flu shots are available throughout the region—in drug stores, big box stores and outpatient clinics. To make an appointment with a physician for your vaccination,

call 314-TOP-DOCS or 866-867-3627 (toll free).

The CDC recommends that virtually everyone older than six months of age, including seniors, teens, young adults and pregnant women, get vaccinated against influenza.* It takes about two weeks after vaccination for the body to develop the antibodies that provide protection against the flu. *See: cdc.gov/flu/protect/keyfacts.htm

barnesjewish.org | fall 2014, vol. xix | Innovate

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One Barnes-Jewish Hospital Plaza Mailstop 90-75-585 St. Louis, MO 63108

As a triathlete, Brad Eastman never thought he’d have cancer. So when a brain tumor the size of a fist was found, he placed his trust in our care.

At Barnes-Jewish Hospital, a Washington University neurosurgeon used intraoperative MRI to scan Brad’s brain during surgery and remove as much

of the tumor as possible without damaging his healthy brain cells.

Today, Brad is training again, while we continue to advance the science of care. Learn more about his story at BarnesJewish.org/Brad or call 314-747-2350 to find a doctor or schedule an appointment.

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