DukeMed Magazine

Duke Medicine's Plan to Expand

Mon, 23 Nov 2009 14:03:59 -0500

Cranes, bulldozers, and a corps of construction workers have swarmed onto the Duke University Medical Center campus, signaling the start of an ambitious expansion project designed to dramatically enhance the experience of patients, families, students, and staff at Duke for decades to come.

Following rigorous rounds of project reviews and approval by the State of North Carolina, Duke Medicine leaders announced in August 2009 their decision to move ahead with the historic initiative, which has been on the drawing board for several years.

"Duke Medicine is all about people -- it's about the patients we serve, it's about the people who work here to deliver the best care, discover new things, and train the next generation," says Victor J. Dzau, MD, chancellor for health affairs.

"To support those people in the years to come, we must make sure that we have the state-of-the-art facilities we need to provide the best care and the best environment to work and learn in."

This vision is now becoming a reality with the official start of two landmark buildings. Together, the new Duke Medicine Cancer Center and the Duke Medicine Pavilion, along with related renovations, will add more than 800,000 square feet of space, with 160 intensive- and intermediate-care inpatient rooms, 16 new operating suites, 130 exam rooms and 75 infusion spaces dedicated to cancer care, and expanded and updated imaging platforms. Total project costs are estimated at more than $700 million.

Planning is also under way for a new School of Medicine learning center that will provide an optimal environment for medical student and interdisciplinary team training. The larger, modernized facilities are greatly needed not only to accommodate an increasing demand for patient care, but also to support the broader vision for medicine at Duke, according to administrators.

The new facilities are thoughtfully designed to:

Improve the patient experience by making clinic visits more efficient, increasing inpatient room size, better accommodating visitors and family members, and providing amenities such as resource centers, healing and spiritual spaces, and green spaces
Support multidisciplinary care by co-locating a wide range of providers within fast-growing specialty services such as cancer and heart
Accommodate leading-edge clinical technologies including advanced imaging and diagnostic equipment and linear accelerators for cancer radiation therapy
Enhance education and research by providing state-of-the-art facilities that support training, facilitate study of new techniques and treatments, and bring clinical research teams closer to patients
Incorporate advances in information technology to improve communications between clinical teams and individual patients -- not only within each building, but across the continuum of Duke Medicine services and sites

Although the global economic crash in 2008 diminished Duke’s capital reserves,
Duke Medicine leaders remained committed to moving ahead -- describing the efforts as a mission-critical investment in the future.

"Without expansion and modernization, the quality of our patient care could suffer and our long-term goals could be significantly stunted," Dzau says.

"Years of conservative and prudent fiscal management, combined with careful cost-cutting measures, have put us in a strong position to move forward with these projects -- which we believe are essential to our ongoing ability to meet the growing demand for patient care services and to conduct cutting-edge research and training in an era of population growth and accelerating innovation.

"At heart, we believe we have a responsibility to meet our patients' needs for high-quality health care in the years ahead."

In addition to institutional investment, fund-raising initiatives have been launched to raise $75 million toward the costs of the Duke Medicine Cancer Center, $50 million toward Duke Medicine Pavilion, and $15 million toward the learning center, which is also supported by a $35-million gift from The Duke Endowment.

"The vision for the future of the campus is to continue to support what makes
Duke Duke: excellence in clinical care, teaching the next generation of all kinds of providers, and generating innovations that we can push through the enterprise," says Kevin Sowers, RN, MSN, CEO of Duke University Hospital.

"It's about supporting incredible people who work here every day and do incredible things in people’s lives, by giving them facilities designed to enhance their efforts to care for Duke's surrounding communities, the residents of North Carolina, and beyond."

Training Spaces

Besides serving hundreds of thousands of patients every year, Duke University Medical Center is also home base for one of the country’s largest health-care training programs, with more than 900 medical residents and fellows on the house staff, plus more than a thousand students in the medical, nursing, physical therapy, and physician assistant programs. The planned campus expansion will benefit these next-generation caregivers as well as the patients they’ll serve:

State-of-the-art technology from new linear accelerators in the cancer center to interoperative imaging technologies in Duke Medicine Pavilion’s surgical platform will allow clinicians to better practice -- and therefore teach -- to their full potential, facilitate research that will improve care and support training of academic physicians, and enable trainees to gain experience in cutting-edge care.
A School of Medicine learning center located in the heart of the medical center campus -- the first new building dedicated to medical education since 1930 -- is being planned to provide the team-oriented, technology-based experiences today’s curriculum demands. “New learning space for our students was the top priority for our own leadership and the main recommendation during our recent accreditation process,” says Dean Nancy Andrews, MD, PhD. “Medical education has changed dramatically since our current facilities were built. The vision for this new space is to provide our students with the laboratories and training facilities that will best help them prepare for their future careers.”

The new buildings have been preceded by new facilities for the School of Nursing (completed 2006) and the physician assistant program, which in early 2009 moved into a freshly renovated building designed to accommodate future growth.

Read more about the planned learning center in the summer 2009 issue of DukeMed Alumni News, online at medalum.mc.duke.edu.

Duke Medicine Pavilion: Answering Demand for Surgical and Intensive-Care Services

Since its current bed tower opened in 1980, Duke University Hospital has grown not only in patient volume but also in reputation as one of the most advanced hospitals in the country. And frankly its success has the 29-year-old building bursting at the seams.

From Monday through Friday, the hospital fills at least 90 percent of its 924 inpatient beds, many of them with critically ill patients sent here for the best medicine has to offer.

A 2005 study showed Duke's OR usage to be 93 percent -- compared to 80 percent for the average academic medical center. And with every upgrade to new technology, Duke electricians and IT experts have to figure out how to rearrange the guts of the building to support the state-of-the art tools in play.

The plans for the new Duke Medicine Pavilion -- a 580,000-square-foot addition to the hospital housing OR suites, intensive care units, step-down units, and diagnostic facilities -- have focused on maximizing flexibility of space and technology, leaving Duke Medicine room to grow.

Operating Space

The 16 new OR suites will be larger than the current operating rooms in order to accommodate advances in technology that enhance precision and safety. The new suites are designed to be flexible, allowing both multipurpose and specialized use: interoperative MRI and CT are located between suites, for instant access that won’t crowd the room when not in use.

A hybrid OR is already under construction in the current hospital, and will open in 2010; it will allow interventional cardiologists and surgeons on-the-spot, highly detailed vascular imaging capabilities -- and enable easy transition between catheter-based, minimally invasive, and open procedures within the same space.

Built-in technology will enable the surgical team to review critical information without going to multiple places or even stepping away from the table: multiple plasma screens will allow surgeons to review x-rays and other imaging studies, as well as pathology specimens.

"Duke’s surgical faculty are nationally and in many cases internationally respected, and demand for their services is exhausting our current facility," says Danny Jacobs, MD, MPH, chair of the Department of Surgery.

"The Duke Medicine Pavilion will be critically important to our ability to meet surgical demand and train the next generation of surgical leaders."

Roomier Rooms

Duke Medicine Pavilion’s 96 critical-care and 64 intermediate-care beds won’t just add more space, but better space -- reflecting dramatic changes in care since the hospital’s Anlyan bed tower was built.

Then, patients arrived for surgery the night before the procedure; their families awaited results in the waiting rooms and sat with their loved ones in brief stints during visiting hours. Today families want to stay with patients around the clock, and the new patient rooms are designed to accommodate more people -- clinicians and family alike.

These and other features of Duke Medicine Pavilion reflect input from current patients, families, physicians, nurses, and other staff, says Mary Ann Fuchs, RN, Duke University Health System's chief nursing officer.

"The building’s entire layout will allow patients much more access to their families, allow the staff more interaction with patients, and allow the staff to work in a more streamlined fashion. We strove to create a place where multidisciplinary teams could work well together and where patients could feel comfortable and cared-for."

High-Tech Hospital

In addition to upgrades in the OR, a high-tech, centrally located imaging center will streamline access to MRI, CT, and nuclear testing for patients and clinicians. The building will also accommodate new tracking and electronic medical record (EMR) technology, enabling better coordination of care within the hospital, across the health system, and beyond Duke.

"Most medical errors and patient safety issues emerge when a patient transitions from a hospital to a primary care setting," says Asif Ahmad, chief information officer for the health system.

"Our EMR technology already coordinates a patient’s information among all three of our hospitals; our plan for this building is to go ‘EMR-plus’—to use technology to improve patient education and help prevent glitches in the translation of information when they leave the hospital."

Patients -- and Providers -- in Motion

The layout of the hospital -- as well as the cancer center -- began with studying all the traffic that flows through current service areas, from shift changes to patient transport.

For example, neurology patients have to go for CT scans frequently, so designers worked to locate the neurology ICU near CT. And all heart services throughout Duke University Hospital will be located on the same level, regardless of what building they are in.

A two-story concourse -- just about the same width as an airport concourse -- will be the "Main Street" that connects Duke Clinic to Anlyan Tower. The totally enclosed and climate-controlled concourse will simplify the journeys of patients and staff as they move around the medical center.

Healthful and Healing Spaces

Great care is being taken to create an environment that is pleasant and supportive for patients and their families. A major component of that philosophy is linking patients to the world beyond the facility walls -- by providing green spaces that can be seen from patient rooms and waiting rooms alike.

The Duke Medicine Quadrangle: The doors of the cancer center and the new hospital addition will open onto a park designed by Laurie Olan, the landscape architect who redesigned both Columbus Circle in New York City and Philadelphia’s Independence National Historic Park. Similarly designed courtyards within the hospital will provide more green views for patient rooms.

Patient resources: The main doors of the hospital addition will open into a two-story entryway that leads visitors to a patient library, a café, and a quiet meditation or reflection space.

Letting the sunshine in: The overall facility design brings natural light into staff and patient-care areas. "That actually is really helpful to patient and staff morale," says Fuchs, "just having a pleasant environment in which to do our work."

Green in more ways than one: Besides its visual connection to the outdoors,
Duke Medicine Pavilion -- targeted for LEED Silver status -- is designed to be environmentally friendly, with green roof space, sustainable building materials, and energy-efficient mechanical systems.

Duke Medicine Cancer Center: Creating the Optimal Experience for Cancer Patients

When Harry Rhoads was diagnosed with stage 4 melanoma three years ago, his Duke oncologist told Rhoads he most likely had about 11 months to live -- but that he could join a clinical trial of a promising new interleukin drug.

The treatment schedule would be difficult: two weeks of treatment and two weeks off, for a total of six treatments. Each round of interleukin was followed by "six days of hell," Rhoads says -- nausea, vomiting, hallucinations.

"I was scared."

But PET scans showed that the tumors were shrinking with each session. Despite a few setbacks, Rhoads is cancer-free today.

Rhoads’s experience of cancer treatment isn’t representative of all cancer patients; as every tumor type is unique, every cancer patient has his or her own treatment experience. But in many ways, Rhoads says, "every patient goes through the same thing" -- a complex balancing act of fear and faith, suffering and grace.

Rhoads lives near Washington, DC, so his choosing Duke for his treatment went beyond the considerations of distance and convenience.

William J. Fulkerson Jr., MD, Duke Medicine’s senior vice president for clinical affairs, says patients like Rhoads travel to Duke for access to world-class specialists and the promise of the newest and most comprehensive treatments for the disease that threatens their lives.

As one of only 40 National Cancer Institute-designated Comprehensive Cancer Centers in the nation, Duke offers options that simply aren’t available in many hospitals.

"There are two things that set academic medical centers like Duke apart from other health care organizations," says Fulkerson. "One is that highly focused specialists from many disciplines work together under one roof to provide comprehensive care; the other is that academic medical centers are in the business of bringing innovation to the table as quickly as possible."

The impetus for building Duke Medicine’s new cancer center facility, say its leaders, is to continue to deliver on that promise to an ever-growing number of patients. By more closely integrating clinician and clinical research teams, the design of the building seeks to promote the best of academic medicine’s multidisciplinary and research-driven nature.

In addition, the space must provide the most healing, patient-centered environment possible to support patients like Rhoads as they go through the journey of fighting, living with, and surviving cancer.

Combining these mandates of form and function is a tall order -- and that's why the vision for the project goes far beyond adding square footage. In fact, leaders say, the goal is nothing less than to create the best possible cancer treatment experience.

What Makes "Multi-D" Work?

A key part of that is enhancing the multidisciplinary approach that distinguishes cancer care at Duke -- and that studies show is associated with better patient outcomes. But the buzzword multidisciplinary has multiple meanings.

Depending on the cancer type, multidisciplinary care at Duke might mean having different specialists working in the same space on parallel schedules for easy "collaboration on the fly," or it might mean scheduling clinicians around each patient -- such as in the Duke Prostate Center, in which a newly diagnosed patient is visited by a surgeon, radiation oncologist, and medical oncologist who confer with each other to develop a coordinated, comprehensive care plan.

And then there is the expertise of specialized nurses, nutritionists, psychologists, social workers, and physical therapists, all of whom work in concert to provide Duke cancer patients with whole-person care.

If the fuel that powers these many modes of multidisciplinary care is the talent pool of the clinicians on staff, then the rate-limiting factor is space -- which in Duke’s current buildings is growing tighter due to swelling patient volume and the continual introduction of new and better imaging and radiotherapy technology.

This is why the most talked-about feature of the new building is space: 267,000 square feet of it, including ample room to bring clinicians, counselors, and research staff from their current far-flung locations into dedicated space closer to patient exam rooms.

"Physicians want their patients to have multidisciplinary care that doesn’t require coming to Duke three or four times to see different doctors," says Carolyn Carpenter, the health system’s associate vice president for oncology services.

"Adding space to our facility will allow us to schedule patients and clinicians in a way that's more efficient -- and that will lead to a better experience for the patient."

Designed to Heal

Not only the exam rooms but the entire building is designed to deliver an ideal patient experience. Planners began by mapping out all the stops cancer patients have to make during a visit to Duke, from registration and the pharmacy to mammography, MRI, labs, chemotherapy, or radiation therapy.

"Then we went to focus groups [of Duke cancer patients] and said, 'Here’s what we think the experience is like. Do we have it right? And what would you change?'" says Sowers.

The central premise behind every focus group -- and there were several -- was how to make cancer care revolve around the patient instead of the patient's disease.

In the case of radiology, for example, patients didn’t want to have to walk to one part of the building to get a CT and then another to get an MRI, as they do in the current facility; in the new building a full floor of the cancer center hosts all of the radiology platforms in one consolidated area.

When patients enter the new building, they'll be welcomed by a resource center -- no long registration queues or full waiting rooms in sight. The boutique, food court, and outdoor spaces are designed to provide pleasant options for patients who are waiting before or between appointments.

And the waiting areas themselves are designed to accommodate comfortably both the patients and the family members who travel with them.

"We did studies of how many people typically accompany a clinic patient and an infusion patient," says Carpenter. "And we used that information to determine how big our waiting areas should be."

Betty Lamar, a member of Duke Comprehensive Cancer Center’s Citizens Advisory Council, says the intangible effects of a patient-friendly atmosphere make all the difference -- and she should know. Her first husband died of leukemia, while her second had bladder cancer, and she experienced the full spectrum of cancer care in a variety of clinical settings.

As a veteran caregiver, Lamar says she’s seen how cancer treatment has shifted over the years to a patient focus.

"At Duke they are now really treating the whole person and not the disease," she says. "It didn’t use to be like that, it was all focused on the disease."

Lamar serves as a volunteer at Caring House, a home away from home for many Duke cancer patients. She says she has seen many patients and families who reflected her own experience.

"They would arrive so afraid and anxious," she says. "They came from all over the country and world. They were desperate for help."

Room to Advance

The draw for these patients is often the clinical trials offered at Duke, such as the interleukin trial Rhoads is part of. In fact, Duke is currently conducting more than 700 cancer trials.

"Cancer care, almost more than anything else that we do at Duke Medicine, is a fast-evolving field -- new treatments and new understandings emerge all the time," says Fulkerson.

Clinical trials are what drive these discoveries into cancer care practice, and the studies are "fundamentally intertwined with clinical care," says breast oncologist P. Kelly Marcom, MD.

"We need efficient clinical space to ensure a seamless approach to clinical research, as well as patient care. With the new building, we will have additional space to educate patients about clinical trials and accrue individuals to participate in these trials."

The new building will include dedicated space for clinical trial consultation and coordination, making standard what was previously a rare luxury for clinical trial coordinators -- complete privacy and uninterrupted quiet space near patient exam rooms to discuss clinical trials, informed consent, and any questions a patient has about clinical research.

Also, says radiation oncologist and Duke oncology services medical director Christopher Willett, MD, the new building will house brand-new, first-in-world imaging and radiotherapy technologies that will supplement both patient care and research.

"In addition to expanding the space and bringing in more tools, we are intensifying our focus on the patient’s experience. The new building will be more efficient for them and for us -- and very user-friendly. I think that all of us feel extraordinarily positive about the plans for it."

Lamar made the first gift to the Cancer Center building fund, which Duke hopes will raise $75 million toward the project’s estimated $220-million cost.

"Where you're treated is a very important part of treatment and cure -- it's important to be in a happy place," she says. "And the new building will really make you feel that way.

"It’s a place that makes you realize that you’re being considered as a whole person."

This article was first published in the Fall 2009 edition of DukeMed Magazine.

Dueling Guidelines

Mon, 23 Nov 2009 13:41:17 -0500

Erik Paulson, MDAlthough colon cancer has been well-publicized as the second leading cause of cancer deaths in the United States, only about half of the people who should get screened for the disease actually do.

It’s not hard to imagine why: colonoscopy, the current gold standard for screening, is no fun. The rigors of “bowel prep.” Sedation. An endoscope inserted into the colon. But in 1993 a less invasive option came on the scene -- "virtual colonoscopy," or CT colonography, which involves the same bowel prep as colonoscopy, but neither sedation nor scope.

"We insufflate the colon with carbon dioxide, and in a single breath-hold take a CT scan of the abdomen," says Erik Paulson, MD, chief of abdominal imaging at Duke.

"Then the study is over. After the procedure, patients can return to work."

Physicians at Duke offer CT colonography as a clinical option, participate in its development, and train physicians in its use. Some studies suggest that CT colonography is comparable with colonoscopy in terms of effectiveness for most patients, especially when weighed in terms of its comparative ease.

But it isn’t perfect; even the major organizations that promote colon cancer screening have not yet recommended it as the procedure of choice for routine screening for average-risk adults.

In 2008, in the first-ever joint guidelines for colon cancer screening, the American College of Radiology, the American Cancer Society, and the U.S. Multi-Society Task Force on Colorectal Cancer specifically included CT colonography among several recommended options for screening and prevention in average-risk adults.

These guidelines differ from those issued that same year by the U.S. Preventive Services Task Force, which express doubt about the widespread accuracy of CT colonography because most physicians still have little experience with it.

A Big Change in Coverage

For some patients, the dueling guidelines won’t matter because of a practical issue -- payment. Medicare and Medicaid, as well as some insurance companies, still do not cover CT colonography for patients at average risk for colon cancer.

Medicare and Medicaid pay for the procedure only for patients whose condition makes a standard colonoscopy riskier than usual, such as if they’re taking anticoagulants or can’t be sedated for some reason. It may be covered for patients who have had an attempted colonoscopy that wasn’t completed because of bowel blockage.

Those rules aren’t likely to change soon. In a final decision released in May 2009, Medicare and Medicaid announced they would not cover CT colonography for routine screening. But some private insurance companies have begun paying for CT colonography for routine screening for patients 50 and older.

"That’s a big change," Paulson says. Multiple studies showing that CT colonography rivals colonoscopy are what have turned the tide.

Paulson points in particular to a multi-institutional trial published September 18, 2008, in the New England Journal of Medicine.

"That study showed that the sensitivity and specificity of CT colonography is competitive with colonoscopy," Paulson says.

In the study, 2,800 patients underwent CT colonography and then a colonoscopy, and the CT version identified 90 percent of patients with polyps or cancers that were 10 millimeters or more in diameter.

Some previous studies, including one at Duke in which Paulson was involved (published in Lancet in 2005), showed that while CT colonography was good at detecting actual cancers, it was not as good as colonoscopy at detecting polyps.

But Paulson says the technology has since made big leaps thanks to advances in bowel preparations, the three-dimensional technology used to interpret the scans, computer-aided detection software which increases the accuracy of interpretation, and the ability to label residual fecal matter in the colon so it doesn’t show up on the test.

He and other Duke researchers continue to study the technique -- leading research including multi-institutional clinical trials, the causes of false-negative and false-positive interpretations, and evaluation of computer-aided detection software.

Duke Radiology has for the past five years offered CT colonography as part of its routine clinical practice.

"We have six radiologists in our department who are skilled and experienced at CT colonography," Paulson says. "We’re doing more of them now than we’ve ever done."

Colonoscopy: Still the Gold Standard

Joanne Wilson, MDDuke gastroenterologist Joanne Wilson, MD, does think that less-invasive tests can increase screening rates.

"Definitely the biggest impact something like CT colonography will have is getting more people screened who are at average risk," Wilson says.

But she sees the technology as one that’s not ready to be widely implemented.

"CT colonography has promise, but there probably needs to be some further development of the technology," she says.

Also, many current physicians aren’t prepared to offer the procedure.

"One of the points raised in the literature is that radiologists who were trained just in standard CT would need to gain additional training in order to conduct and read CT colonographies," Wilson says.

"When new technology is introduced, there’s always a concern about how you’re going to train currently practicing physicians."

Wilson also points out that if alternative tests such as CT colonography or stool tests come back positive, the patient likely will have to have a colonoscopy anyway in order to remove or sample the lesion.

"The colonoscopy is both diagnostic in the sense that you can see polyps, and it’s therapeutic because you can take them out, or you can mark them or sample them. The final diagnosis of cancer is a histological diagnosis; you want to look at the tissue with the microscope," she says.

She also emphasizes that colonoscopy will remain the recommended test for patients at high risk for colon cancer -- those with a prior history of colon polyps and colon cancer and those with a family history of polyps and cancer.

Paulson acknowledges that colonoscopy is still the tried-and-true gold standard.

"There’s no doubt that colonoscopy is a great test," he says. "For many people it makes all the sense in the world. But as good as it is, it has some risk and requires sedation and is more invasive."

And, he says, while colonoscopy is a mature technology, the virtual version can be expected to continue to make technological leaps.

This article was first published in the Fall 2009 edition of DukeMed Magazine.

New Angles on AFib

Mon, 23 Nov 2009 13:39:51 -0500

Atrial fibrillation is the most common heart arrhythmia. It’s also among the most challenging to control -- first-line therapies don’t work for up to half of patients, raising their risk of heart failure and stroke.

By pinpointing the often-mysterious origins of AFib, fine-tuning drug strategies, and pushing the boundaries of catheter ablation, physicians in Duke’s new Center for Atrial Fibrillation are now restoring healthy heartbeats in more than 90 percent of patients -- and counting.

The heart’s beat begins with an impulse. The sinoatrial node -- our natural pacemaker -- generates electrical signals that travel through the atria and into the ventricles.

These signals set off synchronized contractions in each chamber of the heart, creating the comforting lub-dub sound of the heart’s pumping as it trades spent blood for a freshly oxygenated supply.

Atrial fibrillation (AFib) is the most common disruption of this powerful rhythm, affecting around 2.2 million Americans. It can stem from coronary artery disease, high blood pressure, structural heart defects, or even arise seemingly out of the blue.

Whatever the cause, abnormalities in the heart’s electrical system make the atrial chambers contract too quickly -- up to 350 times per minute. This quivering in the atria causes chaos in the ventricles, which react with a flurry of rapid, irregular beats. The lub-dub becomes more like a pitterpat -- one that is disconcerting at best, life-threatening at worst.

For some patients, AFib is barely noticeable: they have mild symptoms, such as fatigue, or no symptoms at all.

Others feel their hearts racing or experience frightening episodes of heart palpitations. These individuals often live in dread of such events: they don’t want to travel or go to work or school. Others give up exercise and other activities that could trigger the irregular beats.

"AFib symptoms and the anticipation of the episodes are so dramatic for some patients that it almost turns their lives upside down," says James Daubert, MD, the new director of the Duke Heart Center’s electrophysiology (EP) program.

Even worse than unpleasant symptoms, says Daubert, the irregular rhythm can contribute to heart failure, while ineffective pumping allows blood to pool in the ventricles and atria -- turning the chambers of the heart into a breeding ground for blood clots.

In fact, atrial fibrillation is responsible for about 15 percent of strokes.

Managing these symptoms and sequelae has long been a hit-or-miss proposition. The usual front lines of defense -- drug therapy to alleviate the arrhythmia and prevent stroke -- are often ineffective or fraught with complications.

But recent advances in understanding the physiology of AFib are leading to new treatment strategies, including safer, more effective medical management and sophisticated catheter ablation techniques that are providing a new alternative to drug treatment.

At Duke, electrophysiologists, cardiologists, cardiovascular surgeons, and other specialists on the forefront of these efforts are banding together to mount a new attack on AFib -- the Duke Center for Atrial Fibrillation (DCAF).

"The spectrum of therapies necessary to treat AFib today falls under different specialties, and we created the DCAF to draw on our depth of resources," says the center’s director, electrophysiologist Tristram Bahnson, MD.

"As treatment for AFib becomes more precise and personalized, we are bringing together a convergence of specialists to formulate how best to care for each individual patient."

A New Aproach to AFib

Treatment of AFib usually begins with a constellation of drugs, each selected to slow the heart rate, restore the heart’s normal rhythm, or prevent stroke. But medical management of AFib can be problematic.

More than half of patients treated with antiarrhythmic drugs report recurrences of atrial fibrillation within a year of the start of treatment, according to several nationwide studies. And when not used carefully, these drugs can actually trigger dangerous heart rhythms or other serious side effects.

For example, one of the most effective antiarrhythmics, amiodarone, can produce side effects such as skin discoloration, photosensitivity, thyroid imbalance, liver inflammation, or decreased lung function in as many as 30 percent of patients who take the drug for long periods. It also can interfere with the action of anticoagulant drugs, which most AFib patients should take to help prevent stroke.

And while antiarrhythmic drugs may improve symptoms, they do not improve mortality rates compared with those of AFib patients treated with rate-control drugs such as beta-blockers.

Catheter ablation, which cauterizes and neutralizes small spots of heart tissue that generate abnormal electrical patterns, is gaining ground as a strategy to help AFib patients who don’t respond to antiarrhythmic medication. According to a collective review of six smaller studies published in 2003 and 2004, roughly 80 percent of patients in their 50s and 60s who received the minimally invasive procedure were free from recurrent episodes.

"In the past, people who could not get good control of their AFib with medication just had to suffer the symptoms as best they could or perhaps undergo major surgery," says Bahnson.

Today, with catheter ablation as a proven alternative for patients who have failed drug therapy, the Duke team is able to control symptoms in more than 90 percent of people seeking treatment, he says. The DCAF currently performs the highest volume of AFib catheter ablations in North Carolina, and Bahnson expects the procedure’s popularity to grow.

Although it’s just coming into its own as a treatment for AFib, ablation to treat other abnormal heart rhythms has been around for several decades. In fact, cutting or removing pieces of heart tissue to cure arrhythmia was pioneered at Duke.

In 1968, a Duke team performed the first successful ablation surgery to treat abnormal heartbeats in a 32-year-old fisherman who had Wolff-Parkinson-White syndrome -- a disorder that causes AFib or other fast heart rhythms.

In 1987, James Cox, MD, a cardiothoracic surgeon at Barnes-Jewish Hospital in St. Louis who had trained at Duke, showed that he could cure AFib by making and then suturing multiple incisions in a grid-like pattern of lines through the atrial chamber walls -- a technique known as the Cox maze procedure, or simply "maze."

The idea was that the incisions would leave lines of scar tissue that could act as barricades, blocking impulse propagation in the heart chamber and preventing AFib from being sustained. Maze surgery is still performed to treat AFib, but usually in conjunction with other major open-heart surgery.

The maze surgery was complex and daunting to imitate with a catheter, says Daubert, who was in training at Duke around that time. When Cox introduced the surgery, many assumed that the electrical source of atrial fibrillations originated within the atria itself.

That idea was challenged as other doctors tried maze and discovered that the pulmonary veins were usually "the money spot" for the origin of the abnormal heartbeat.

"The discovery that it was coming from the pulmonary veins made catheter-based treatment a more feasible target," Daubert says.

Other strategies were also being tested, such as the use of implantable cardioverter defibrillators, or ICDs, to shock the heart and restore normal rhythms. For patients with ventricular arrhythmias, which are sometimes accompanied by atrial fibrillation, ICDs are commonly used, and the devices have been shown to reduce the incidence of sudden cardiac death in patients with heart failure.

In the late 1990s, researchers tried ICDs as a therapy for atrial fibrillation. While the devices worked to shock the heart back into normal rhythm and to reduce the frequency of AF episodes, the shocks were painful and were needed too often to make the treatment practical, Daubert says.

In the late 1990s, Daubert and others did their first catheter ablations to treat atrial fibrillation. It was slow going in this early stage of the technique: they would put the catheters in the heart and wait for the first signs of abnormal activity. Was it coming from the left pulmonary vein, or the right? The doctors would leave the catheters in different regions of the heart, sometimes for hours.

They tried to speed the process along by artificially pacing the heart into AFib and then restoring normal rhythm with a shock, hoping to stir up the sites that led to a recurrence of AFib.

"The problem was that sometimes [the fibrillation] wouldn’t happen during that procedure," Daubert says. "Sometimes, it would come from one vein and we’d ablate there, but another day it would come from a different vein and we hadn’t ablated there."

Over the next few years, it became clear that electrophysiologists needed to ablate around all four pulmonary veins, regardless of where initiating arrhythmias were observed. By then the potential benefits of the treatment began to crystallize.

Better Ablation

Bahnson is also encouraged by the rapid development of ablation and the potential for the technique to improve lives. In fact, the results are so promising that they raise the question of whether ablation could become a first-line therapy for atrial fibrillation.

However, Bahnson cautions, a few important unknowns remain about the procedure’s long-term effectiveness. Bahnson is one of the principal investigators of a large, multi-site investigation coordinated by the Duke Clinical Research Institute that will compare catheter ablation with drug therapies for initial treatment of atrial fibrillation.

"This study will likely be a definitive one to determine whether mortality or stroke rates in AFib patients are improved by catheter ablation as compared to treatment with medications only," says Bahnson.

Meanwhile, Daubert is beginning research that will look at outcomes of ablation treatment in older patients.

"Most patients with AFib are in their 70s or even 80s," he says. "We don't have a lot of data as to whether the ablation is as safe or effective in this group as it is in younger patients."

Catheter ablation does come with risks and challenges. For example, in rare cases, the ablation procedure itself can cause blood clots and subsequent stroke. In other rare instances, parts of the body, such as the esophagus, can be injured during the procedure.

Researchers in the DCAF are investigating a range of novel technologies to make catheter ablation safer and more effective. For example, Duke recently began working with a new system, Hansen Medical’s Sensei X Robotic Catheter System, which allows catheters to be manipulated with greater control and precision within the heart. Outcomes research is under way to establish the value of this system and develop it further.

Other DCAF research is testing arrhythmia-mapping techniques to identify areas that should be targeted for ablation and to determine when enough ablation energy has been delivered at any given site within the heart.

"A big question in the catheter-ablation arena is how do you know when you’ve created a lesion in the heart that’s sufficient?" says Bahnson.

The DCAF group is now assessing catheter-created lesions in real time, working with Duke bioengineers on intracardiac ultrasound techniques that image the heart from within.

Various types of catheters in development might also make ablation safer and easier. Duke physicians are working on one new type that freezes heart tissue instead of cauterizing it, as with radiofrequency ablation. Daubert says the technique, called cryoablation, may make ablation safer than with traditional methods.

"If we’re ablating too close to the pulmonary vein, we could cause it to scar or narrow," Daubert says. "With the cryoablation, that problem is almost completely eliminated."

Another new type, an irrigated catheter, has six pin-sized holes at the tip that can be flushed with saline to prevent the catheter tip from overheating, thereby reducing the risk of blood clots. Both new catheter types, Daubert says, may help minimize the risk of stroke.

New techniques may also make catheter ablation for AFib more efficient. Daubert is currently experimenting with inflating a balloon at the opening of the pulmonary vein, which allows physicians to ablate all the way around the vein using radiofrequency energy or freezing techniques, rather than having to make small lesions, point by point, sometimes over the course of several treatments.

Personalized Rhythms

Despite the impressive advances in catheter ablation, the procedure may not be necessary or appropriate for all patients.

"There are so many players that act in the development and continuation of AFib," says Patrick Hranitzky, MD, director of the EP fellowship program at Duke, who is leading research to better understand the condition.

"It’s very difficult to decipher what all the contributors are," which can make it tough for physicians to select the best treatment.

For example, Hranitzky says, "There’s a clear difference in the mechanism of AFib in a 30-year-old marathon runner as opposed to an 80-year-old with a long-standing history of hypertension -- these differences involve not only what sustains it but what initiates it."

In the marathoner, extreme physical stress can cause changes in electrical properties within the heart, triggering episodes of AFib in athletes predisposed to the condition.

In contrast, an elderly person might develop AFib because of age-related structural changes in the heart muscle. The heart becomes less flexible, and can develop tiny scars or fibrosis that can worsen with time, especially if high blood pressure is not controlled. This fibrosis can cause atrial fibrillation.

For the marathoner, doctors aim to prevent the triggering of the arrhythmia, Hranitzky says. If the triggers can be identified -- usually they are found near the junction of the pulmonary veins and the left atrium of the heart -- the arrhythmia can often be effectively treated with antiarrhythmic medications that abate the triggers, or cured with catheter ablation.

The elderly person, however, has a more complex situation. His heart cells have undergone a process of “remodeling,” and merely eliminating the triggers does not suffice.

"We must also alter the remodeled substrate," Hranitzky says, using either drugs or ablation to target the affected heart tissue.

The researchers are now probing deeper into what makes AFib different in each person.

"Clearly there are people who have genetic predispositions to AFib," says Hranitsky, but "it’s not going to be a single gene that determines whether someone will have AFib or not."

To help untangle the complex causes of the condition, Hranitzky and his colleagues began assembling a biorepository and clinical database for arrhythmia research in 2006 -- collecting DNA, messenger RNA, and protein from consenting patients in the electrophysiology lab.

By identifying alterations in these molecules, the researchers hope to find new clues about the underlying mechanisms of atrial fibrillation. They plan to look for genetic or molecular predispositions based on gender, age, and race differences, as well as for differences in the way individuals respond to treatment. The findings could lead to better prevention strategies and more targeted treatments. Researchers at other institutions are working on these same types of studies.

"In reality it’s going to take a collaborative effort among many centers," Hranitzky says. "We’re not going to have all the answers, but personalized treatment for arrhythmias is something that we’re moving toward."

Daubert, who created and led the University of Rochester’s heart rhythm program until he returned to Duke this summer, says the range of new AFib treatment techniques and technologies introduced over the course of his career is heartening -- just a decade ago, for his patients with AFib that didn’t respond to medical therapy, he could do little more than watch their hearts quiver. He says he’s pleased to be back at his alma mater to tackle the next frontiers in atrial fibrillation.

"Coming back to head up the program that pioneered some of these ideas that have brought us this far is really an awesome opportunity. This is a team with the expertise and drive to truly make a difference in people’s lives."

This article was first published in the Fall 2009 edition of DukeMed Magazine.

Outside Influences

Mon, 23 Nov 2009 14:01:04 -0500

H. Kim Lyerly, MD, director of the Duke Comprehensive Cancer Center (left), and William Chameides, PhD, dean of Duke’s Nicholas School of the Environment.She was standing at the kitchen sink, washing dishes, just as she had dozens of times in my childhood when I had walked in with a question about something I didn’t understand.

But the question we were discussing was not one between a young mother and a curious kindergartner; it was between a 50-year-old woman whose breast cancer had been in remission for a year and her college-aged daughter who wondered what sort of fortunes might await her own body, yet to be told.

My mother was convinced that stress -- losing her father, moving to a new state -- had caused her disease, for there was no history of it in our family. I was thinking about the other tapestries of her life: the coal mining she grew up around; the chemical plants that billowed clouds of smoke and dotted the landscape of the region where we made our home for the first 16 years of my life.

Could any or all of these factors have caused her cancer? Would they one day haunt me or my children?

For most of us -- even for many researchers -- the relationships between nature and nurture remain murky.

But scientists at the Duke Comprehensive Cancer Center and the Nicholas School of the Environment believe that such questions are answerable, that our lifestyles, our environments, even the possible effects of what’s stored underneath that kitchen sink, can be shrunk from imposing questions to understandable relationships, from theory to therapy, from perhaps to prevention.

The partnership is one-of-a-kind: No other institution in the country boasts such a level of collaboration between environmental and cancer researchers.

The effort began in 2005, seeded with a series of joint projects funded by Fred and Alice Stanback of Salisbury, North Carolina (who have since contributed an additional $6 million to the cause).

Over the years the initiative has grown and given rise to new research in both domains, with scientists coming together to explore questions that once ended where another discipline’s research lab began.

Researchers are visiting their neighboring schools, borrowing the proverbial cup of sugar, and getting personal -- just like the disease itself.

"You can find the big answers if you have the culture and the willingness to work together," says William Chameides, PhD, dean of the Nicholas School. "You have to be willing to say, 'Yeah, I’m going to stretch a little bit, and I’m going to get a little bit out of my element, because I see the big payoff.'"

In pinpointing our environmental enemies more precisely, the eventual payoff could indeed be huge -- and more than a little alarming.

"I have three kids: an eight-year-old, a six-year-old, and a four-year-old," says H. Kim Lyerly, MD, director of the Duke Comprehensive Cancer Center. "So there’s stuff in the backseat of the car. There are plastic drinking cups, toys, balls, and other man-made things."

To contemplate the spectrum of dyes, paints, and coatings on the endless odds and ends that we dig out from between the car seats and behind the sofa cushions, all the materials that end up on our skin or -- more likely -- in our children’s mouths, it’s easy to spin into paranoia or a sense of futility.

But the goal, says Lyerly, is not to "panic about the things we find; it’s to discover what kind of impact they have. If something is harmful, we want to know why. We want to link actual biology with detection in the environment.

"Let’s say we find a new type of molecule that causes cells to duplicate themselves uncontrollably," he explains.

"That’s a new insight that might help us understand cancer and therapies for the disease. But it’s also an insight we can give to the Nicholas School and say, 'Do you find this molecule in populations that are at greater risk based on your screening?'"

Mapping Cancer Risk

Marie Lynn Miranda, PhD and Amy Abernethy, MD are using Miranda’s mapping techniques to track cancer incidence in North CarolinaNew tools such as geospatial mapping are making these collaborations efficient for both sides. Researcher Marie Lynn Miranda, PhD, who leads the Nicholas School’s Children’s Environmental Health Initiative, has helped advance this mapping technique -- which uses a range of spatial data layers -- in North Carolina and nationally through her work on environmental contributors to maternal and child health.

Now, geospatial mapping is being expanded to other fields as well, including cancer.

The mapping tools herald an age of "personalized environmental health," paving the road to a better grasp on where cancers occur and why, says Amy Abernethy, MD, associate director for IT and informatics at the Cancer Center, who often works with Miranda.

Using a database of Duke cancer patients, Abernethy says, researchers are compiling where patients with different kinds of tumors live and then correlating their information with geographic maps of known heavy metals or other kinds of exposures considered potential carcinogens -- arsenic, radon, and even the sun itself.

As more and more information is gathered and other databases are folded in, those maps will be not only heavy-duty tools for research, says Abernethy, but eventually clinical tools to help drive home the importance of proper screening. Like the old picture of lungs blackened from smoking, physicians can pull out a map during an office visit that details their patients’ risk based on geography.

"It allows people to see that, 'Wow, I live in Johnston County and these are the things that I need to worry about, and this is based on real-life data,'" Abernethy says. "It becomes much more meaningful.

"I think ultimately we'll become more and more sophisticated in our risk-modeling.
We'll be saying: 'This is a 33-year-old woman living in Johnston County, near Highway 242, who has lived in Wake and Durham counties at prior points in her life, and her risk of having this type of cancer by the time she turns 70 is x.' And it may influence the screening we recommend."

What’s in the Water

Avner Vengosh, PhDCancer is an intimate foe; when you have it, and even when you no longer do, reminders of its presence pockmark your body and your psyche.

And many of the environmental insults that are linked with oncogenesis, as Nicholas School professor Avner Vengosh, PhD, knows, also pockmark the landscape that surrounds us.

Vengosh is a geochemist who is known internationally for his expertise on the chemical and isotopic composition of water contaminants, developing tracers for contaminants in water supplies from the Middle East to the mountains of western North Carolina, where harmful radon in groundwater was exposed.

He has collected samples of the coal-ash waste that spilled from the Tennessee Valley Authority’s Kingston coal-burning plant on December 22, 2008, covering 300 acres of land and water with sludge and damming a tributary of the Emory River there.

Coal ash has relatively high levels of toxic elements such as radium and arsenic; long-term exposure to either has been deemed a cancer risk by the Environmental Protection Agency.

"The massive coal-ash spill contaminated associated surface water -- specifically with arsenic—but the good news is, we detected only trace amounts of arsenic in waters beyond the dammed tributary," Vengosh says.

"The data suggest that river flow has diluted the arsenic content. The river is relatively clean, but the water from areas like the dammed tributary, where the coal ash accumulated, still contains high arsenic levels."

The Tennessee coal-ash spill is a wake-up call, as about 70 million tons of coal ash are stored around the United States.

Avner and fellow Nicholas School investigators worked with Julia Kravchenko, MD, PhD, of the Cancer Center on a paper (published in May in Environmental Science & Technology) that examines the link between environmental contaminants found in the Kingston coal ash, contaminated water, and health risks -- the first of several planned studies of the biomedical implications of environmental disasters.

Chameides is particularly interested to see what the Vengosh team finds as its research into these links unfolds during the coming year; hundreds of coal-ash retention ponds exist in the United States, he says, and if high levels of carcinogens are found in Tennessee, those data could ultimately unlock clues about cancer incidence in other areas of the country.

"If you try to understand in general the impact of environmental pollution on human health,” Chameides says, “it’s sometimes useful to look at places where you see a really high impact, a larger signal such as the coal-ash spill, and then work backward from that to see what’s happening in a more subtle way in other places."

The Hopeful Science

Duke epigenetics expert Randy Jirtle, PhDIn 2003, Duke epigenetics expert Randy Jirtle, PhD, proved that while our genome is fixed when we’re born, our epigenome -- the collection of chemical switches that tell the genes what to do -- is not.

If the genome is the hardware of our bodies, the epigenome is the reprogrammable software capable of yielding to outside influences, says Jirtle.

In his study, baby mice suffered from a flawed gene that led to increased susceptibility to obesity, diabetes, and cancer -- except among those whose mother had been fed a prenatal diet including folic acid.

In that group, the extra nutrients acted at the molecular level to latch onto the troubled gene, resulting in its appropriate regulation. Those mice were born healthy.

Jirtle reported a similar finding last year on folic acid countering the negative effects of BPA, a chemical found in many plastics.

What’s more, says Jirtle, once this good-guy methylating gang does its work in the embryo, the genomes of those mice’s offspring are permanently mended, carrying the good alteration throughout the individual’s life. It is, he says, a hopeful new way of looking at life, and at medicine.

Of course, it also means that, as more is learned about the epigenomic switches, clinicians will have to ask their patients to sidle up to the responsibility trough and get smart about their lifestyle and environment choices based on the findings.

"What you eat, what you drink, and so on can affect not only yourself, but generation upon generation after you," Jirtle says.

That is why, although researchers continue to study the effects of nutrition and lifestyle on cancer incidence, Jirtle believes doctors should urge their pregnant patients -- and women thinking of starting a family -- to start limiting their exposure to BPA now by avoiding food from cans coated in plastic and water from plastic containers made from BPA, which may mimic estrogen(s) in the body.

Along with oncologist Victoria Seewaldt, MD, Jirtle also is working with a subset of our genome called "imprinted genes" to learn more about the influence of environment on breast cancer.

Unlike other genes we’re born with, in imprinted genes, only one of the two copies inherited from the mother and the father works. This nonworking gene is epigenetically switched off, or methylated, in a normal gene. But, if either both copies or no copies are working, susceptibility to disease increases.

Jirtle estimates that only about 200 of the 25,000 genes in our makeup are imprinted, but these are the ones Jirtle believes will unlock the mysteries behind many diseases, especially cancer.

The researchers are looking at people with a high risk of breast cancer to see if there are epigenetic changes in the KCNK9 imprinted gene, a potassium channel that has been shown in previous studies to result in breast cancer when overexpressed. Jirtle says they have already seen some evidence of a relationship at the epigenetic level.

Jirtle’s studies even investigate how the environment within the body may affect the epigenome -- specifically, he’s researching the link between neurological disorders and cancer, because patients with schizophrenia are known to have low incidence of cancer.

He believes that one day, when these ties are better understood, therapies might be introduced to turn off disease-causing genes and turn on protective mechanisms at the cellular level.

"With epigenetics," he says, "for the very first time, the word prevention comes into cancer. To get to the answers, though, you have to bring together groups of people that possibly have never been brought together before; and in fact, that’s what’s happening right now between the Nicholas School and the Cancer Center."

Disrupting the Status Quo

Donald McDonnell, PhDBPA is one of several known endocrine disruptors -- though it has received by far the most attention, causing certain plastic water bottles, baby bottles, and other goods to be shunned almost overnight.

But Jirtle’s colleague, Duke molecular cancer biologist Donald McDonnell, PhD, discovered startling information regarding endocrine disruptors and pharmaceuticals that should give pause to doctors prescribing medications with hormonal components.

McDonnell’s team showed why a common solvent used in industrial cleanrooms and one of the most popularly prescribed drugs in the country could lead to increased risk of cancer in some individuals.

His team tested a cleaning agent known as ethylene glycol methyl ether (EGME) that’s used in varnishes, paints, dyes, fuel additives, and the semiconductor industry; and valproic acid (Depakote), a drug with a similar chemical makeup that is prescribed for migraines, seizures, and attention deficit and bipolar disorders.

They discovered that EGME, when metabolized, and valproic acid both act as hormone sensitizers—they enhance progesterone and estrogen activity inside cells.

When that hormonal activity is accelerated in a person who is already ingesting a drug that contains synthetic progestin and estrogen (such oral contraceptives or hormone replacement therapy), the extended, double exposure of hormones in the body is likely to increase cancer risk.

McDonnell says the results are a break from more traditional thinking on the work of endocrine disruptors, where the focus has been on agents that mimic estrogen in the body rather than those that change the way cells see estrogen.

That mimicking also has been the main focus of drug testing for such disruptors, and until testing strategies take this new mechanism into account, he says, physicians need to act cautiously before prescribing any drug in combination with hormone-containing pharmaceuticals.

"This adds fuel to the debate as to the effectiveness of the currently used tests for endocrine disrupters," says McDonnell. "The drug-testing programs are outdated and do not adequately incorporate our current understanding of hormone action."

McDonnell suggests taking particular caution with tamoxifen, which is widely used in the treatment and prevention of breast cancer but is chemically altered from an antagonist to an agonist in the presence of EGME and valproic acid.

And while he has received some feedback from oncologists who do check with their patients about valproic acid use, for the most part, he says, "the message hasn’t yet hit home" in the medical community.

McDonnell adds that there’s no doubt in his mind that the environment contributes in a very significant manner to cancer susceptibility.

"Endocrine disruptors have received a lot of attention of late but there are likely to be hundred of other types of agents in the environment that impact cancer risk."

Ready for Its Close-up

Environmental effects on cancer are taking center stage in the medical research community and likely will become a greater topic of conversation around dinner tables, too.

It’s precisely that growing curiosity among the public about what’s safe around us and what isn’t that is fueling the partnership between the Nicholas School and the Cancer Center.

Patients want answers; researchers want to give doctors the right tools to provide those answers.

In the coming months, Lyerly and Chameides will see the connections they’re making at Duke unfold nationally. The President’s Cancer Panel, a group Chameides spoke to last fall which is tasked with appraising the National Cancer Program, will focus its annual report to President Barack Obama on the links between the environment and cancer.

Lyerly and Chameides also are co-chairs of a state cancer-plan task force on the same topic, and the foundation Susan G. Komen for the Cure also will be putting a brighter spotlight this year on environmental links to breast cancer.

"When I first called Bill to get directions to his office, he told me, 'Just follow the
Birkenstocks to the Levine Center,'" Lyerly says.

Now that trail has becoming a well-beaten path -- and a road that the two hope others may follow.

"The more we work with the School of the Environment, the more we understand that there are few people at the Cancer Center who couldn’t find ways to interact with their expertise," says Lyerly. "We’re hoping this will be a model for other places, for balancing individual research accomplishments with the collective good.

"We can find the answers if we work together."

This article was first published in the Fall 2009 edition of DukeMed Magazine.

Born in the Blood

Tue, 24 Feb 2009 11:56:35 -0500

One of Duke oncologist Sandeep Dave’s favorite stories is that of a professor at his medical school. “He was the kind of guy who could run up the stairs and leave all the young students huffing and puffing behind him,” Dave says.

Unbeknownst to most of these winded students, the physician was also suffering from follicular lymphoma, which he was monitoring without treatment, according to his oncologist’s recommendations.

One day on rounds the doctor suffered a heart attack and underwent emergency bypass surgery. “The recovery was terrible,” says Dave -- infection set into his chest incision; he was “essentially at death’s door” and remained hospitalized for three months. He eventually recovered and returned to work -- and when he visited his oncologist a few months after the ordeal, bloodwork showed that his lymphoma had completely resolved.

Spontaneous remission can occur in a small minority of patients with follicular lymphoma -- somehow the body’s immune system wins the duel with the lymphoma cells that are attempting to overtake normal, healthy white blood cells in the lymph nodes and elsewhere.

But a number of patients with the same disease will die within months of diagnosis. This sort of slippery prognosis makes the term liquid tumors -- which includes leukemias, lymphomas, and multiple myeloma -- especially apt.

These hematologic cancers develop in the marrow of our bones, inexorably squeezing out the healthy cells in the blood that nourishes every tissue in our body. They can’t be excised by surgery; there are no known effective screening methods or reliable ways to reduce one’s risk. And the number of patients with these cancers is rising.

Duke hematologic clinicians have achieved many of the greatest successes in liquid tumor treatment, from improving bone marrow and cord blood transplantation to testing targeted drug therapies such as imatinib (Gleevec). Meanwhile, Duke’s discovery of the breast cancer mutation on the BRCA-1 gene and the development of the Institute for Genome Sciences & Policy have put Duke at the forefront of genetic cancer research.

Nationally respected hematologic clinicians like Joseph Moore , MD, have built a sizeable patient base, while hematologic researchers like J. Brice Weinberg, MD, have built vast stores of tumor samples for analysis. “We’ve had excellent research and excellent clinical care,” says Duke hematologic malignancy program director David Rizzieri , MD, “but we haven’t always had a good bridge between the two.”

Over the last 10 years, though, the program has worked to link its large patient population with its prolific bench research. Much of this translational bridge has been built over the ever-swelling current of genomic discovery: a broadening understanding of exactly what genes are aberrantly active, or overexpressed, during the genesis of cancer.

This type of analysis paints a portrait of a tumor in detail previously unavailable to researchers; for each tumor, it unveils a palette of overactive cellular processes, or pathways, that essentially make that tumor tick.

Dave says genomics makes possible the blueprint for personalized medicine: cancer treatment that begins with genomic profiling, so that patients receive only the therapies to which they are likely to respond. “It seems very commonsense,” Dave says, “but it’s far from the standard right now. The standard practice is that if the patient fails one treatment, he gets something else, then something else, then something else. And the results are highly variable -- in many cases they are quite, quite poor.”

Several years of genomic research have brought oncology to a watershed moment, Rizzieri says, with clinical trials of genomic-based therapies popping up in program after program. Now the youngest generation of liquid-tumor researchers at Duke carries the charge of walking this line between the bench and the bedside, to speed the translation of discovery into therapy.

Bettering the Best

Chronic myelogenous leukemia, or CML, made headlines when Gleevec hit the streets in 2001. Hailed as a miracle worker, Gleevec (imatinib) has been quite effective in many patients by blocking a certain chemical pathway. But the drug is no panacea -- it is not curative and a significant number of patients grow resistant to its effects.

One of the drawbacks to Gleevec, says Duke cancer biologist Tannishtha Reya, PhD, is that even in patients who don’t develop resistance to the drug, it doesn’t affect the cancer stem cells, which are the cells that propagate the cancer. “So you always have to be on the drug,” says Reya.

Her team has been searching for a new chemical pathway that could be targeted to attack the cancer stem cells and sidestep the biologic roadblock that halts Gleevec’s usefulness in some patients. And they’ve hit a potential treatment jackpot: a pathway called Hedgehog, which is known to be active in many solid tumors.

“There are currently several drugs in development that can block this pathway in solid tumors,” Reya says, “so it was a really unique opportunity to see if the approach would be effective in leukemia.”

First the team studied mice that were genetically altered to lack the Hedgehog pathway at birth. The mice had a significantly reduced incidence of CML, and those who did develop CML showed both delayed disease progression and a reduced number of cancer stem cells.

Reya’s team then tried blocking Hedgehog in normal mice using a drug called cyclopamine, a small molecule inhibitor that can be delivered easily into the body. Half of the mice treated with cyclopamine survived the cancer, while all of the mice that were not treated succumbed to the tumor.

So Reya’s group worked with David Rizzieri and John Chute , MD, to test the effects of cyclopamine on tumor samples from human patients who were in an advanced phase of CML. “The human samples have been remarkably responsive,” she says, and the team is now planning to further test Hedgehog inhibitors; if the studies bear out, she says, they could open a new window to therapies not only for CML but also for other liquid tumors.

Examining the Anomalies

The CML treatment successes of the last decade grow more impressive when compared to current therapies for other forms of leukemia, many of which have been idling essentially unchanged since the late 1960s.

The standard therapy for patients with acute myelogenous leukemia, or AML, is what’s called the 7 and 3 regimen: a strategic pairing of two powerful chemotherapies to create a treatment that is aggressive, toxic -- and in many cases simply ineffective.

“We’ve been getting the same abysmal results for years,” says oncologist Arati Rao , MD. Only one in five patients diagnosed with AML lives five years after diagnosis; most die within a year or two. The prognosis is even worse for older people, who make up the bulk of AML patients and who have a two-year disease-free survival rate of less than 10 percent.

Rao is working to get to the biological bottom of what makes older AML patients so much tougher to treat. She and colleagues in the Netherlands and Germany gathered a cohort of 425 patients and studied patients who were 45 and younger and 55 and older.

The clinical differences between the two groups were considerable: most patients in the younger group responded to therapy, and they typically lived three times as long as the older group.

When gene-expression studies were applied to these patients, distinct clusters of patients began to emerge, based on their tumor biology, how the tumors developed, and their responsiveness to chemotherapy.

The tumor cells in older patients, regardless of their other biologic traits, were uniformly unresponsive to therapy; for these patients there is no biologic opportunity for the merciless 7 and 3 regimen to work. That, combined with normal age-related health changes and complications, says Rao, might be the reason for these patients’ poor prognosis.

Rao is collaborating with other institutions to amass a total of 1,200 patient samples. “We already have drugs that target some of the overexpressed pathways found in older AML patients’ tumors,” she says, so if the initial results hold true, “we will be in a position to actually design clinical trials that are individualized,” selecting new therapies to try based on the genomic makeup of each patient.

At the very least, she says, physicians will be able to spare patients the risks and side effects of regimens like 7 and 3 when they are genetically destined to have no treatment benefit.

Pattern Hunting

Guessing a tumor’s destiny has become easier over the last 10 years. As techniques such as high-throughput sequencing have become more widely available, researchers have been able to create genetic sketches of one malignancy type after another -- and in the class of liquid tumors, the subtypes of leukemia, lymphoma, and myeloma are legion.

“The idea is simple,” says Sandeep Dave, pointing to a computer screen displaying a grid of jumbled green and red blocks. The grid maps the expression of 20 genes (a selection out of 25,000) in a group of patients with diffuse B-cell lymphoma -- one of the most aggressive forms of lymphoma, and one of the first tumor types to be examined genomically.

“Two samples of this type of tumor could look absolutely identical under the microscope and have two very different outcomes,” explains Dave. “No one could understand why there was so much heterogeneity in these patients.”

Genomic technology was able to turn the gene jumble on his screen into a very clear pattern. “A technique called hierarchical clustering groups together the samples with the most similar genetic makeup,” he says, clicking to the next screen, where the jumbles are rearranged into a patchwork pattern -- several patients who share a high-low expression pattern followed by several more who share a low-high pattern.

The small sample of each patient’s intricate genetic quilt shows that while no two tumors are exactly alike, there are definitely ways to classify them into similar groups. And the clinical outcomes of these groups could be predicted based on their genetic expressions.

When Dave applied this same technique to follicular lymphoma, the disease that struck his med-school mentor, he looked for gene expression patterns that might explain the disease’s widely variable prognosis -- and he found them, though not where he thought he would.

“We found genetic signatures in the patients’ immunologic makeup that are associated with survival,” he says, and these signatures are more predictive of positive outcomes than any clinical factors such as age and stage at diagnosis.

This type of genomic profiling is taking place throughout the field of oncology, in solid and liquid tumors alike -- Duke’s Institute for Genome Sciences & Policy has already initiated clinical trials in breast, lung, and prostate cancers, all based on genomic research. Led by Joseph Nevins, PhD, Anil Potti , MD, and Phillip Febbo , MD, the trials use genetic profiling of tumors as a means of selecting chemotherapy for participating patients.

But Dave says that the hematologic research goes beyond predicting which existing chemotherapy will work best. “Chemotherapies in nearly every combination have been tested in almost every hematologic malignancy,” he says.

Instead, he believes that the patterns he finds can help focus research resources on the experimental models that are most likely to work. “There are over a hundred biotech companies trying to create new cancer drugs, in addition to the usual drug companies,” says Dave. “So the question is, what molecules are most likely to have an effect on which types of liquid tumor?”

An Army of Trials

Dave’s work to answer that question supports clinical investigators such as Anne Beaven , MD, who are launching an array of new, genomically based trials for liquid tumor patients. Beaven will lead the lymphoma trial at Duke that tests whether the genetic patterns found by Dave correlate to clinical response to therapy; if successful, another wave of trials will use these patterns to pair patients with treatments.

“It’s the first lymphoma trial of this kind at Duke,” Beaven says, that takes a patient-by-patient approach. “These aren’t going to be the therapies where 80 percent of all people with diffuse B-cell or follicular lymphoma will respond; we’re looking for agents that will work in 80 percent of a particular selection of patients.”

Beaven’s goal is to have clinical trials open for every major type of lymphoma. “It’s important, as an academic medical center, that we offer that kind of availability,” she says. Oncologist Cristina Gasparetto , MD, a specialist in multiple myeloma, agrees. “At Duke we’re trying to offer lots of options to patients and their physicians,” she says, from proper staging of the disease to experimental approaches for high-risk or relapsed patients.

One option that is continually being improved at Duke is stem-cell transplant -- currently the best treatment bet for many patients with multiple myeloma and other hematologic malignancies. Duke researchers Nelson Chao , MD, and Joanne Kurtzberg , MD, are among those who have made transplantation a feasible, survivable therapy for an ever-growing number of cancer patients in an ever-widening age range, but the process is still a toxic one, and often frail patients are not good candidates.

Gasparetto is investigating ways to improve transplantation and expand the number of patients who are eligible for the procedure. “We are testing new, powerful pre-transplant therapies that have lower toxicity,” she says, noting that these therapies are also being examined in patients who are not transplant candidates.

Last year Gasparetto was part of a Duke team, led by David Rizzieri, that published the largest study yet to demonstrate the effectiveness of mismatched adult immune-system (blood) transplants. “If we look at the reasons that transplants fail patients,” says Rizzieri, “it’s because of either relapse, infection, or not having donor matches.”

And as the success of mismatched transplantation improves, “you broadly expand those who have a donor to include almost everyone,” he says. “That, combined with a well-tolerated preparative regimen for transplant, would significantly decrease the toxicity of the approach -- and allow us to offer this therapy to patients who otherwise wouldn’t have a meaningful chance of cure.”

A Better Watch-and-Waiting Game

For patients with aggressive, quickly fatal malignancies such as multiple myeloma, clinical trials can offer promise where previously there was none. For patients with less aggressive cancers, such as chronic lymphocytic leukemia (CLL), this new wave of genomic clinical trials helps refine both treatment options and the decision of whether to treat at all.

CLL is one of the most common leukemias, and according to several studies it is one of the most strongly heritable diseases period. Survival of CLL patients ranges wide, and in many cases patients can live for years before symptoms or disease progression mandates treatment.

Oncologists Daphne Friedman , MD, and Mark Lanasa , MD, PhD, are building a CLL clinic at Duke that will both treat CLL patients and help sort out what genes are involved in the development of the disease.

From a research perspective, Friedman says that because CLL is such an indolent disease in many patients, it’s an excellent model to study genetically. “Patients live for a long time, often without needing aggressive therapies. They come in again and again, so we can take repeated samples and look at how things change” -- because the initial genetic trigger of CLL in a patient may not be what promotes tumor cell survival during the course of treatment or in cases of relapse.

Understanding how the disease changes genetically will help physicians choose therapies wisely for CLL patients. “There are about five drugs that could be applied to CLL patients,” says Friedman, “but there aren’t a lot of ways to forecast which one -- if any -- is likely to have an effect.” Also, she says, understanding changes in oncogenesis can have a significant impact in many other types of cancer.

Lanasa treats patients in the CLL clinic and also collects data -- from both the patients and their families. He is part of a national collaboration gathering data from families with high incidence of CLL to help sort out what group of genes causes the cancer.

Unlike cancer-causing gene mutations such as that of BRCA-1, which have a high “penetrance” -- meaning that if you have the mutation you are highly likely to develop the disease in your lifetime -- CLL seems more likely to be the result of an unruly set of low-penetrance genes. “There are probably five or 10 genes that are involved,” says Lanasa, “but you need lots of families to figure this out for sure.”

Lanasa and Friedman’s work is a continuation of their fellowship research, which they both completed last year under J. Brice Weinberg. Their new clinical initiatives, like those of Dave, Beaven, Gasparetto, Rao, and Reya, illustrate how the journey of potential new therapies from laboratory bench to bedside is growing steadily shorter.

For some patients this offers new hope for effective treatment. But Lanasa says that even for patients whose cancer is being followed but not treated, clinical studies can provide a much-needed mental benefit. “Watching and waiting can be frustrating; it can feel passive to people,” he says. “When patients can participate in clinical trials, it’s something active they can do about their disease.”

To learn more about Duke hematologic malignancy clinical care programs, call 919-684-8964. To learn more about clinic trials for lymphoma, leukemia, and myeloma, call 919-681-4769.

This article was first published in the Winter 2009 edition of DukeMed Magazine.

Sound Plans

Tue, 24 Feb 2009 16:33:35 -0500

Rachael Ragin was 45 years old before she knew that fizzy soda bubbles make noise.

Profoundly hearing-impaired from infancy, Ragin, of Cary, North Carolina, successfully navigated the hearing world for years with the help of two powerful hearing aids, despite being able to understand only 8 percent of the words spoken in a soundproof auditory booth. But when she entered college, her hearing deficit became increasingly difficult to overcome.

“My hearing was so bad that in addition to wearing hearing aids, I learned sign language and started relying on an interpreter,” which she did for the next two and half decades, Ragin says.

The mother of two was in her early 40s when she began investigating cochlear implants, the only auditory prosthetic devices proven effective for treating severe hearing impairment and deafness.

Debara L. Tucci, MD, MS

In 2003, Ragin underwent cochlear implant surgery, performed by Duke neurotologist Debara L. Tucci, MD. Within several weeks, Ragin’s hearing comprehension had soared to 95 percent.

“The world became magical with all the sounds it made,” Ragin says. “Being able to better communicate with my family, hearing the wind in the trees, listening
to rain fall…it was thrilling.”

While Ragin says the decision to use auditory prostheses is a personal one -- and that she, like many of the two million Americans who are deaf or profoundly hard of hearing, continues to take great pride in deaf culture -- she is delighted to have opted for cochlear implantation.

“I live and work in a hearing world,” says Ragin, a doctoral-level consultant who works with deaf and hearing-impaired children for the North Carolina Department of Public Instruction. “My implants allow me to negotiate that world as well as I do the deaf world.”

A Flat Miracle

The cochlear implant is arguably the most significant advance to date in the treatment of hearing loss -- a widespread condition that the World Health Organization consistently ranks among the top 15 medical concerns in terms of human suffering and economic cost.

In the United States, about 10 percent of the population is deaf or hard of hearing, with some 28 million people -- about half of them aged 65 and older -- experiencing hearing loss significant enough to impact their quality of life.

“Thirty years ago, there were no options, simply no treatments, for someone who was deaf or had a severe hearing loss,” says Duke-trained electrical engineer Blake S. Wilson, an adjunct professor in otolaryngology who also serves as the chief strategy advisor for MED-EL GmbH of Innsbruck, Austria, a leading developer and manufacturer of cochlear implants.

Wilson has been associated with Duke otolaryngology since 1984, when he and Duke otolaryngology chief emeritus Joseph C. Farmer Jr., MD, established the Duke Cochlear Implant Program as one of the nation’s first. Tucci has led the program since coming to Duke in 1993.

“Cochlear implants have enabled us to come a very long way in a relatively short time in terms of treating profound hearing loss,” says Wilson. “Most of today’s implanted patients can understand everyday speech with hearing alone, without lip reading -- many in noisy environments, some even on the telephone. To me, that’s a flat miracle.”

While technological advances have opened a new world of sound for many, a host of challenges remains. Not everyone with hearing loss is a candidate for cochlear implants, and outcomes vary widely among recipients -- for reasons that aren’t fully understood. And for many millions of children and adults worldwide, affording or even accessing the technology remains out of the question.

Not all people with profound hearing loss consider it a disability; many people who were born deaf or severely hard of hearing -- or who became so early in life -- find deep fulfillment and great pride in deaf culture. But for many others with untreatable or undertreated hearing loss, the economic and emotional costs can be enormous.

For those who became deaf before they learned to speak, experts estimate a lifetime cost of more than $1 million per person to address hearing-related challenges. Many of these people say their hearing deficit makes them feel disconnected, socially isolated, and discriminated against.

On January 29, Duke’s efforts to help these individuals were galvanized in a new way with the official launch of the Duke Hearing Center. This major interdisciplinary initiative is designed to harness Duke’s scientific and clinical strengths to alleviate the massive global toll of hearing loss.

Synthesizing the Science

Part of the plan for the new center, says Wilson, is to take advantage of an “explosion of knowledge” that’s occurred in the fields of otology, neurotology, and engineering, particularly in the past 10 years.

“Duke has awesome resources and capabilities across the spectrum needed to develop new treatments for hearing loss, and we’re highly unusual in that respect,” Wilson says. “The combination of all these capabilities is what’s so powerful, and a large part of the rationale for the hearing center is to bring that strength to bear on such an important societal problem as hearing loss.”

Co-directed by Tucci and Wilson, both of the Department of Surgery’s Division of Otolaryngology-Head and Neck Surgery (OHNS), the center will foster collaborations among faculty within the School of Medicine, the Pratt School of Engineering, the Duke Center for Cognitive Neuroscience, the Division of Neurology, the Duke Global Health Institute, and the Duke Institute for Genome Sciences & Policy.

Nancy Andrews, MD, PhD“It’s very important for investigators at Duke to work on solving problems that have a major patient impact, and the center’s multidisciplinary approach will be critical to this effort,” says Nancy Andrews, MD, PhD, vice chancellor for academic affairs and School of Medicine dean, who granted the program “center” status in July.

Andrews herself has a personal interest in otology, and recently made a serendipitous discovery of a gene in mice that may play a role in determining how genes are expressed in developing inner-ear cells in humans.

“Hearing loss is a large problem, but it’s one for which we have real hope that modern science will lead to solutions,” she says. “Many causes of hearing impairment are preventable, and understanding those will help in the short term. In the long run, scientific investigation will eventually help people preserve their hearing.”

For example, says Wilson, “about 60 percent of congenital hearing loss is caused by genetic defects, and there’s huge potential to identify additional defects that lead to hearing loss and develop molecular repairs for them.”

Another area of investigation the center plans to pursue is cellular-regeneration therapies, which take a cue from the animal kingdom -- some aquatic animals and birds regenerate their damaged inner-ear receptor cells with the help of nearby cells that act as stem cells.

“We hope to build upon a rapidly growing body of knowledge to better understand the biology of the mammalian inner ear, with the goal of inducing hair-cell and neural regeneration and thereby restoring hearing,” Tucci says. “This field of cell biology holds great promise for the treatment of sensorineural hearing loss, for which there is no direct treatment at present.”

Improving the Implant

In addition to pursuing basic-science and translational research, center faculty will work to improve existing treatments for hearing loss, including the groundbreaking cochlear implant.

Much of this work will build upon a longtime collaboration between OHNS and the Research Triangle Institute (RTI) Center for Auditory Prosthesis Research -- which Wilson, who is internationally recognized for inventing many implant components, led from 1994 to 2002.

This partnership has produced a number of breakthroughs in cochlear implant design, as well as the signal- and speech-processing strategies used in cochlear implants, hearing aids, and other devices used to improve hearing.

More than 130,000 people worldwide have received cochlear implants since they became widely available in the early 1980s -- and thanks to constant improvements in the devices, many more people now stand to benefit from them than ever before. In fact, says Tucci, “In our state alone, many, many people are candidates and don’t know it.”

Many insurers now cover at least one implant -- including Medicare and, for children, Medicaid -- and there are no real age restrictions for getting them, she adds. Although about a third of the division’s patients are children from one to 18 years old, “we’ve implanted patients as old as 86 who have done very well,” Tucci says.

However, Wilson points out, there’s still much work to be done to help cochlear implantation reach its true potential -- and transform the lives of even more deaf and hearing-impaired people.

Unlike hearing aids, which amplify sound so it is loud enough for damaged ears to hear it, cochlear implants reroute sound around damaged parts of the ear, directly to the auditory nerve, which stimulates the area of the brain that receives and makes sense of auditory input.

At present, the best candidates for cochlear implants are young children and people whose auditory brains have received at least some ongoing stimulation -- such as those who regularly wear hearing aids. That’s because connections among neurons and auditory pathways erode as the brain is deprived of input, and it’s easier to successfully establish or re-establish ear-brain connections when they haven’t been idle for a prolonged period.

Hearing Center researchers will explore ways to overcome that obstacle, and also address the differences in outcomes among recipients, which Wilson says are still not completely understood.

“A leading theory [as to why implants work better for some people than others] is that it’s due to individual differences in auditory brain function,” which can vary widely among people who have suffered from different degrees of hearing loss for different lengths of time.

“The brain is the tail that wags the dog in determining cochlear implant outcomes,” he says, “and we need to figure out why and what we can do about it.”

Because hearing-impaired people who are not candidates for cochlear implantation can benefit significantly from other devices, Hearing Center faculty will also work to improve auditory prostheses across the board, says Wilson. These devices include hearing aids and the hearing aid-cochlear implant hybrid -- both for people with some residual hearing -- as well as the central auditory implant (CAI), a device, still in the early stages of development, that is designed to stimulate brain structures central to the auditory nerve.

Addressing a Global Crisis -- At Home and Abroad

To speed the delivery of these advances in technology and research to the people who need them, Duke Hearing Center faculty plan to grow a statewide network of sites for clinical trials and patient care.

“One of our overarching goals is to integrate clinical research with treatment,” says Tucci, who is currently working with David L. Witsell, MD, director of the Duke Voice Care Center, on an NIH grant to develop a network of clinical research sites within academic centers and community-based private practices.

“The idea is to see which interventions work best in treating patients with otologic disease -- and for the Duke Hearing Center to have a presence in most North Carolina communities in the next five to 10 years.”

But the Hearing Center’s vision extends far beyond North Carolina. Tucci explains that the center’s mission includes fighting hearing impairment globally, where it may be an even greater problem than in the United States.

Roughly 60 million people in India suffer from significant impairments in hearing, for example, many due to congenital rubella -- which is preventable by vaccination. And in China, more than seven million people are completely deaf, an incidence due largely to widespread use of ototoxic over-the-counter antibiotics administered by the “barefoot doctors” during the country’s cultural revolution.

As part of a partnership between the Department of Surgery’s Global Health Initiative and the Duke Global Health Institute, Tucci and Wilson have traveled to India to investigate opportunities for clinical outreach and research collaboration. They also are working with Samuel L. Katz, MD, internationally known chairman emeritus of the Duke Department of Pediatrics, to create an infrastructure to prevent and treat hearing loss in India.

“We’re working with [our counterparts] there to establish rubella vaccine and hearing screening programs, to facilitate the care people need, and to make low-cost cochlear implants accessible to patients who are candidates for them,” Tucci says.

Whether it affects a child in an impoverished nation, a middle-aged American professional, or Grandma, smiling as her family shares stories around the holiday dinner table, not hearing a word, “hearing loss can be isolating and tragic, and that’s the real impetus for creating the Duke Hearing Center,” Tucci adds.

“By bringing together researchers in many areas related to hearing science and hearing health care and working to broaden our clinical outreach in the community, in the U.S., and globally, we will be able to make a tremendous difference in many people’s lives.”

Rachael Ragin is living proof of that. “Sound and communication are at the core of human society, and people with profound hearing loss often struggle to be a part of that -- particularly children, who rely on effective communication to learn,” Ragin says. “I truly believe that efforts to reduce the prevalence and the impact of hearing loss are efforts to diminish a serious human-rights concern.”

To learn more about the Duke Hearing Center, visit hearing.surgery.duke.edu and dukehealth.org/hearingcenter.

To make a referral, call the Duke Consultation and Referral Center at 1-800-MED-DUKE (1-800-633-3853).

This article was first published in the Winter 2009 edition of DukeMed Magazine.

Rationing Health Care: Why We Shouldn't Always Get What We Need

Mon, 16 Nov 2009 13:26:06 -0500

Gopal Sreenivasan, PhDHealth care reform has been debated for decades, but an ailing economy, aging population, and new administration are bringing a renewed sense of urgency to the discussion of how to manage the costs and provision of health care in the United States.

Bioethicist Gopal Sreenivasan, PhD, asserts that a seemingly severe approach -- rationing -- is not only part of a workable solution, but a moral duty.

Most people believe that health care systems should ideally provide citizens who are sick with whatever health-related goods and services they need. While this model may appear at first glance to be the equitable way to meet people’s health care needs, it is not really morally defensible on a national scale.

This is because a nation’s health is not the only important good with a claim to the finite pool of social resources -- there are also education, defense, transportation, and infrastructure, to name just a few others.

The more society allocates to health-related goods and services, the less it can allocate to anything else.

In other words, when access to every medically necessary good and service leads to overspending on health care, a country is forced to underspend on schools, roads, and other critical services. This is incompatible with justice, which forbids robbing Peter to pay Paul.

Countries are therefore morally obligated to observe a strict limit on health care spending. In effect, they must fix a ceiling on their annual health care budgets before knowing the total cost of the medically necessary care required by their population over the year.

By supporting this approach, a nation commits itself to rationing the health care goods and services it provides its citizens.

Building the Case for Rationing

Since rationing means that citizens will be denied some medically necessary care, people are often understandably uncomfortable with this notion. Most don't want to say it's acceptable to withhold health care benefits or to settle for anything less than what is, at least in principle, possible.

It seems uncompassionate, even unfair.

Still, the evidence is clear and mounting that we must set limits on health care expenditures. Already, the United States spends more on health care -- both absolutely and as a percentage of the gross domestic product (GDP) -- than nearly every other country by far.

Even worse, in America, the growth rate of medical spending has consistently surpassed the growth rate of the GDP in recent years.

In fact, the share of the GDP the U.S. spends on health care -- about 16 percent -- is projected to reach nearly 20 percent by 2017. (The average for countries in the Organisation for Economic Co-operation and Development is 9 percent.)

When the percentage of GDP spent on health is rising, that means that health care spending is gobbling up resources that were previously spent on other goods. As long as the growth rate in health care spending outstrips the growth rate in GDP itself, this diversion of resources from other legitimate expenditures only gets worse.

At current growth rates, health care spending will eventually cross the line into claiming resources that should be spent on other goods, no matter where you draw that line. Since it is difficult to defend a more-than-15-percent share of GDP designated for health care, that line may have already been crossed.

Of course, it's hard to suppress the thought that if only we could eliminate all the waste and inefficiency in the health care system, we really could have it all -- and not have to settle for rationing medically necessary services.

Yet while every little bit helps, it's highly unlikely that improving efficiency and eradicating waste would allow us to cover everything, as the "Growth in national health expenditures under various scenarios" chart makes clear.

The three lines represent projections of health spending under different assumptions about possible cost savings. The top line (baseline national health expenditures) projects current growth trends without any cost savings. The "one-time savings scenario" assumes significant initial savings (e.g., from eliminating waste), but no change in the underlying growth trend. The "slowing trend scenario" assumes the reverse: no significant initial savings, but a smaller underlying growth rate.

Even the best-case scenario (slowing trend) has health care spending almost doubling between 2005 and 2015. That is because new technology, rather than waste or inefficiency, is the fundamental driver of growth in health care spending.

Asking the Tough Questions

But how do we decide where to cut costs? The first step is to establish a firm limit on health care spending that is independent of (and less than) what is technically possible to spend on health care, even when spending is restricted to medically necessary services and all waste is eliminated.

However, this does mean accepting that some medically necessary and beneficial services will not be covered, because we cannot reasonably afford it.

The next step is to develop adequate measures of the comparative cost and effectiveness of different effective medical interventions. The goal would be to have a rational and accountable method of deciding which interventions are most worthwhile to cover with a limited budget and which ones, regrettably, must be left out. But this is another topic for another day.

The questions of how to ration health care, and how much care we as a country can reasonably afford to pay for, will not be easy to answer. But accepting rationing as a necessary and moral approach remains the first step toward resolving those questions -- and creating a more just health care system.

Gopal Sreenivasan, PhD, is the Lester Crown University Professor of Ethics and a professor of philosophy in Duke's Trent Center for Bioethics, Humanities, and History of Medicine. His research in bioethics largely focuses on the broad notions of health and justice.

This article was first published in the Winter 2009 edition of DukeMed Magazine.

Robots in the OR

Mon, 16 Nov 2009 14:53:12 -0500

Urogynecologist Anthony Visco, MD, readies a robot for surgery.When he decided to become a surgeon, Anthony Visco, MD, entered one of the most hands-on of professions. But nowadays he does some of his best work when sitting eight feet away from his patient.

To repair pelvic prolapse, for instance, the gynecologic surgeon begins by making dime-sized incisions in the patient's abdomen, through which four hollow instruments called trocars are placed.

He then steers a state-of-the-art surgical robot over to the patient's belly. The robot's four arms are docked -- attached to the trocars -- and then used to insert a camera and specialized robotic instruments such as forceps, scissors, a scalpel, or a needle holder into the patient's body.

Sitting at the robot console, Visco operates the instruments and camera using hand controls and foot pedals. His face rests in a viewer with left and right eyepieces. The views from the robot's two cameras merge to give a three-dimensional view of the operating field that rivals that of open surgery.

"You can zoom in closer than you can with your own eyes," Visco says.

As for the arms, there's little comparison -- the robotic instruments can rotate much like the human hand, but with a greater range of motion and on a much smaller scale, enabling doctors to perform intricate maneuvers through keyhole incisions.

Engineered for dexterity, surgical robots have opened up new possibilities in the OR since they arrived on the scene less than a decade ago -- enabling surgeons to give patients a minimally invasive option for some of the most complex procedures.

Currently only one robotic surgical system is sold commercially in the United States, Intuitive Surgical's da Vinci Surgical System, which was approved by the Food and Drug Administration for use in general surgery in 2000. Since then it's been approved for a variety of cardiac, thoracic, urologic, and gynecologic procedures.

Urology and gynecology appear to be the biggest users of robotics; a 2008 financial filing from the company notes that robotic prostatectomies and hysterectomies make up 79 percent of the procedures performed with its system.

David M. Albala, MDUrologic surgeon David Albala, MD, says that data from the company show that in 2007, over 60 percent of prostatectomies in the United States were performed using the robot, up from some 40 percent in 2006.

Robotic surgery has been steadily gaining ground at Duke, too. Since the medical center acquired its first robot in 2002, hundreds of patients have come here from around the state and the country to have robotic surgeries.

Today Duke doctors have the most experience in North Carolina in robotic prostatectomies and the most experience in the world in robotic sacrocolpopexy (the procedure to repair pelvic prolapse).

But surgeons point out that while calling such procedures "robotic surgery" may sound cutting-edge, in truth they are robotically assisted; the robotic arms are just extensions of the surgeon's hands.

"Robotics isn't going to take a mediocre surgeon and make him a great surgeon," says Visco, chief of the division of urogynecology in the Department of Obstetrics and Gynecology.

The field has its critics, too; some surgeons at Duke say that robotics simply isn't for them.

But there's no denying that robotics is making a major impact on the surgical scene -- and at Duke, proponents and skeptics alike are leading efforts to define just what its place should be.

Writing the Book on Sacrocolpopexy

Developed at Duke in the 1960s, sacrocolpopexy, in which a mesh is attached from the vagina to the sacrum, is considered the gold standard for repair of pelvic prolapse -- a sagging of the pelvic floor tissues which can happen after menopause, childbirth, or a hysterectomy.

One of the procedure's progenitors taught it to Visco during his urogynecology fellowship at Duke in the late 1990s; Visco first learned to perform the open surgery, then the laparoscopic technique -- in which surgery is performed through small incisions using specially designed handheld instruments.

"I did a lot of open colpopexies. I believed in minimally invasive surgery. When I was exposed to the robot, it seemed like an obvious extension of what I was already doing," he says.

Now he has literally written the book on performing them robotically -- he authored the colpopexy training manual for the da Vinci system, regularly hosts courses at Duke, and provides live broadcasting of the surgery, so that surgeons and urogynecologists around the country can learn about the technique.

Visco expects the need for sacrocolpopexy to increase as the baby boomers age. And he now considers robotics the gold standard for performing that surgery in a minimally invasive way.

Because colpopexy requires intricate steps such as attaching mesh, the laparoscopic version is just too hard for many surgeons to learn. "There are a limited number of people who can actually perform a laparoscopic colpopexy," Visco says.

Tying knots and suturing is difficult with laparoscopic instruments because they're straight "like a pair of long, skinny needle-nose pliers," Visco says. And they don't bend. Urologic surgeon David Albala, MD, likens using laparoscopic instruments to operating with a pair of chopsticks.

Visco and colleagues have documented that robotic colpopexy does provide the short-term benefits that patients are looking for. They found that compared with the open procedure, robotic sacrocolpopexies provided similar short-term surgical outcomes, but the robotic group had significantly shorter hospital stays (1.3 days on average versus 2.7 days for open), and their blood loss was significantly less (103 ml versus 255 ml).

Duke owns four different robots, two at Duke University Hospital and one each at Duke Raleigh and Durham Regional hospitals, which are used to perform a variety of procedures.

Like Anthony Visco, Duke urogynecologists Alison Weidner, MD, and Jennifer Wu, MD, perform robotic sacrocolpopexy and other robot-assisted procedures, while Cindy Amundsen, MD, offers other minimally invasive options for the treatment of pelvic prolapse.

Gynecologic oncology surgeon Fidel Valea, MD, uses the robot mostly for radical hysterectomy, which requires a lot of dissection. Craig Sobolewski, MD, chief of the Division of Minimally Invasive Gynecologic Surgery, uses the robot mostly for myomectomy (fibroid removal), which involves a lot of suturing.

"The robot is much more capable of mimicking what we do with open surgery if you're putting in a lot of sutures," Sobolewski says. But he doesn't do simple hysterectomies robotically because he mastered the laparoscopic version years ago. As all these surgeons point out, they don't dabble; for each procedure, most of them pick one method, then perfect it.

In urology, Albala performs nearly all of his radical prostatectomies robotically. Other surgeons who offer the robotic procedure are Phil Walther, MD, Thomas Polascik, MD, Cary Robertson, MD, and Brant Inman, MD.

Combined, these Duke surgeons now perform 300 to 350 robotic prostatectomies per year. Albala trains urologists from across the country in the procedure, helping to disseminate the new approach even more widely.

Climbing the learning curve

All these seasoned surgeons learned robotics in the midst of their careers, most using a training robot. The magnified view took some getting used to. So did keeping all three robotic instruments in view at all times.

"If you can't see one of them, and your hands are in the cradles, you could make it do something you don't want it to," Valea says. Then it's a matter of practice to get familiar with the power and sensitivity of the controls, and to learn to take full advantage of the wristed instruments.

When Visco was in medical school, he would take suture material home and put stitches in his scrubs, to practice tying knots. He and colleagues did the same type of practice with the robotic instruments.

Visco also videotaped his first robotic cases and spent time reviewing them, to find places where he could have tied a knot or made a cut more efficiently.

Though Albala's first few robotic prostatectomies took seven or eight hours, his speed increased as he got his bearings in the magnified view of the operating field. "Now, I feel like I'm in total control during the case. I know my landmarks. Once you learn how the robot moves, I think the surgery is simplified," he says.

Surgeons seem to like the increased autonomy of the console; if they want to cauterize something, often they don't ask an assistant, they just press a foot pedal. And the 3-D, close-up visualization of the surgical field is considered by some to be better than they can get with their own eyes.

"It's almost as if I've stepped inside the patient," Albala says.

First a dry lab, then you fly

When the two robots at Duke University Hospital aren't in surgery, they reside in a hallway outside the operating room.

There, residents use petri dishes of coins and multicolored dollops of silicone to conduct their "dry lab" with the robotic instruments. Valea, who directs the Residency Program in Obstetrics and Gynecology, puts some of the residents through their paces.

"I may tell them, pick up this coin, turn it over, put it in your other [robotic] hand, turn it over again," Valea says. "That's a great exercise because it teaches them transfer and it teaches them rotation of the hand." They'll also practice stitching the silicone dollops together.

In the OB-GYN residency, robotics isn't yet required, but most residents are proactive about learning it, Valea says. They learn to do robotic hysterectomies, myomectomies, and pelvic floor reconstruction.

They take it in small steps, observing or assisting in surgeries first, then, when they've shown proficiency in dry lab, performing part of an operation, such as sewing up the vaginal cuff after a hysterectomy. Once they've shown they can "fly," they move on to perform other parts and then a whole operation under supervision.

"We're not putting first-year residents in there. They will have done the case open many times before they try it on the robot," Valea says.

He doesn't set a certain number of cases as a criterion for moving on; each resident's competency is judged by the faculty, and that is how he or she is deemed proficient. He notes that's a trend in surgical training in general -- using competency-based measures.

In urology, Albala uses a formal procedure to teach robotic prostatectomies. Residents assist a senior surgeon for 10 cases before actually working at the robot console.

For training purposes, the procedure is divided into three parts. Trainees first perform the third part of the procedure, which consists mostly of suturing, for 10 cases or until they become proficient. Then they do the second part of the procedure for 10 more cases, and only then do they take on the responsibility of performing two or more parts of the operation.

"It's very regimented, and I'm in the room monitoring," Albala says.

In a study published April 2008 in the journal Urology, Albala and colleagues found that outcomes -- blood loss and rate of positive margins -- for 383 patients at Duke were the same whether the experienced surgeon performed the robotic prostatectomy or the resident performed it.

"One of the things we're very proud of at Duke is we've trained 16 different surgeons in urology at this point in how to do robotics safely and with good outcomes," Albala says.

Are the benefits overhyped?

Judd W. Moul, MDLike most of these surgeons, Judd Moul, MD, chief of the Division of Urology in the Department of Surgery, sees robotics as part of a trend toward minimally invasive procedures that will only keep growing.

But he expresses concern that some hospitals acquire robots just to keep up with the Joneses, and others hype them so much that some patients think the robot is more than what it really is -- a tool that needs the skill of a surgeon.

In a study published October 2008 in European Urology, Moul and Albala found that patients who underwent robotic-assisted prostatectomy were more likely to report being regretful and dissatisfied, possibly because they had higher expectations that they were receiving an innovative procedure.

The study points to the need for doctors to make sure patients know all the risks and benefits of the procedures they may choose, Moul says. For radical prostatectomy in particular, Moul wants to see more data to show that robotics is superior to open surgery.

For both procedures, the rate of complications, such as incontinence or sexual dysfunction, is the same. The smaller incisions possible with the robot do result in less blood loss, but at Duke it's not enough to cause a difference in transfusion rates, he says.

Moul also points out that the incisions made for the robot are in the abdomen, higher on the body than the incision for an open prostatectomy.

"It's important for patients to understand that the robotic prostatectomy is going through a cavity that wouldn't normally be entered for this surgery," Moul says. "Open surgery stays below the intestines, so there's a slightly lower chance of intestinal injury."

Albala counters that studies from other institutions find that patients who have the robotic procedure show decreased blood loss, decreased transfusion rates, shorter hospitalization, decreased pain, and decreased analgesia use when compared to patients undergoing open procedures.

"It's an evolving field," he says. "There are over a thousand robots in use now, and groups around the world are constantly improving the outcomes. We're continually modifying our practice based on new evidence in the literature."

And he thinks that patients will drive increased demand for robotics. "With a robotic prostatectomy, the patient will leave the hospital the next day. The catheter will stay in place for about a week to 10 days. The patients like that," he says.

Even Moul says the use of the robot has inspired him and other urologic surgeons to refine procedures. "We're a competitive bunch. When the robotic guys came in and said 'We can get patients discharged on day one,' we open guys changed our techniques. We started using long-acting local anesthesia in the incision and tweaked this and tweaked that, and said 'Okay, now we can get our patients out on post-op day one.' It's pushed us to reassess our whole practice pattern for radical prostatectomy and try to do a better job for all patients."

Such efficiency translates into the intangible benefit of a calmer operating room. As with standard surgeries, the robotic operating team is honed so that everyone has a defined role to execute.

"Even though the robot affords a lot of autonomy to the console surgeon performing the operation, it really is a team approach," Visco says. "We owe a lot to the nurses and the OR and anesthesia staff. We've become very efficient at setting up the robot, for example. You need a group of people who are really committed."

Adds Albala, "Duke is one of the few places where everyone in the OR, from the anesthesiologist to the nursing staff, is dedicated to robotic procedures -- so patients are benefiting from having not just an experienced surgeon, but an experienced team."

A Robot for Every OR?

Visco predicts that more and more doctors will adopt robotics because it provides a minimally invasive tool for surgeons who find laparoscopy too difficult. Laparoscopy has been around for more than 20 years, but Visco, Wu, and colleagues reviewed 2003 data showing that only 11 percent of hysterectomies in the United States were performed laparoscopically.

"I think robotics is going to allow minimally invasive surgery to be an option for a greater number of patients," he says. But will robotics completely replace traditional laparoscopy? Duke surgeons aren't sure.

Valea thinks that laparoscopy will remain very popular as the current generation of surgeons with advanced laparoscopic training enters the field. "We're infusing graduates from our training programs who are truly capable of performing advanced laparoscopy," he says.

He also predicts that the cost of the robot (more than $1 million to purchase, plus $100,000 or more in yearly upkeep costs) will prevent it from becoming an everyday tool. "I think hospitals will reserve it for the most technically challenging cases. Otherwise you will need more robots, and that will just drive the cost of medical care even higher," he says.

Open surgery will probably always be around, for several reasons.

Some patients, because of weight or prior complications in the abdomen, aren't eligible for robotic surgery -- although, Albala notes, as surgeons gain experience, they are able to offer the procedure to more and more such patients.

And some hospitals don't have the volume of cases needed to make the expense of the robot worthwhile and to enable their surgeons to become proficient at robotics, Albala says. It takes 25 robotic cases to get really comfortable and maybe 250 to become a master, but a surgeon at a community hospital may perform only 10 prostatectomies a year.

"Many community-based urologists refer patients to us for robotic surgery, and then we transfer them back for follow-up care," says Albala. "Since we were the first in the state to offer robotic prostatectomies, we've been able to build strong relationships with community physicians across the region, and we're grateful for that."

Visco thinks the ideal way to grow robotics is the same way he and his colleagues have perfected their skill with it -- purposefully and carefully. "I think there is probably a pressure to offer this kind of new technique for patients," he says.

"But we still want to do the fundamental things -- take care of patients, get them home in a reasonable period of time, have few complications if any, and give them good long-term outcomes. "If we can do that with a minimally invasive approach? Great."

Note of disclosure: Visco consults for Intuitive Surgical, manufacturer of the da Vinci Surgical System.

This article was first published in the Winter 2009 edition of DukeMed Magazine.

Finding Freedom from Back Pain

Thu, 10 Jul 2008 08:33:54 -0400

When patients talk to Paul Tawney, MD, about their aching backs, they can be sure he knows the lay of the land.

His own journey with back pain began in college, when he was in the gym lifting 365 pounds.

"My foot slipped about half an inch, and I felt pain in my back, the back of my thigh, and my calf," says Tawney, assistant professor of orthopaedic surgery at Duke.

"I put the weight down and I passed out."

Doctors told him he was fine neurologically, but later, his foot started giving way whenever he'd get out of his car.

Imaging studies showed that Tawney had a ruptured disc and previously undiagnosed congenital spinal stenosis (narrowing of the spinal canal). Surgery to remove the disc and correct the stenosis helped, but didn't heal all. Tawney's back has gone out several times, including while he completed a surgery rotation in medical school. During a marathon operating room session, Tawney spent hours with his arms in one position, holding up a retractor.

"I twisted to wheel the patient out of the operating room, and that was it," he says. He was bent over for days.

Tawney decided the physical demands of being a surgeon were too much for his back.

"So I researched a bunch of different therapy protocols and found the field of physical medicine and rehab," he says.

Today Tawney still has flare-ups but controls them mostly with exercise.

"I feel it's most under control when I'm staying on top of my workouts, running as well as keeping my core muscles strong," he says.

As Tawney's experience shows, no single treatment, not even surgery, is a cure-all for back pain. And if you haven't yet had your own experience with it, chances are you will. Eighty to 90 percent of adults will have at least one episode that limits their activity for at least 24 hours.

The good news is that it will be brief -- most of us will return to normal within six to eight weeks, no matter what the treatment. But we spend a lot of money on the problem. According to a 2004 Duke study, patients with back trouble rack up over $90 billion in health-care expenses annually, with approximately $26 billion of that directly attributable to treating the pain.

A 1991 study from researchers at the University of Vermont showed that most of the money is spent on those few who have chronic back pain (that which lasts for more than three months).

"Part of the art of taking care of people with back pain is identifying that small group of people who may have something truly, seriously wrong.

"And for the group of folks who have traditional back pain, it's helping them to be as comfortable and functional as possible while they're recovering, while at the same time trying to not inappropriately use health care resources," says Joe Minchew, MD, assistant professor of orthopaedic surgery.

Duke's physical medicine doctors, orthopaedists, physical therapists, anesthesiologists, and neurosurgeons work together to guide people through back trouble. For most patients, the focus is temporarily relieving pain so they can get moving -- and healing. Patients with chronic, hard-to-treat pain can get advanced pain therapies at Duke that are available at few other places.

And for the few conditions that respond well to surgery, Duke offers traditional procedures as well as minimally invasive ones that can get patients out of the hospital in just a few days.

Pictures don't always show the way

Tracing the spine's parts, it's easy to see why they're vulnerable to wear. Each of the 33 vertebrae has two joints, one on each side. Just like your hip or knee, these facet joints can develop arthritis. Or the vertebrae can enlarge over time, which narrows the spinal canal and puts pressure on nearby nerves (spinal stenosis).

The discs that cushion the space between each vertebra can age too. They're made of a tough outer coating and an inner jelly-like material that can take in and release water. But over time the disc loses some of that ability to absorb water, so it doesn't cushion so well anymore. And as a disc wears, it can bulge like a lip bruised from a punch, putting pressure on spinal cord nerves and causing pain, says Winston Parris, MD, director of Duke's Pain Clinic.

All the fancily named back problems -- facet joint disease, spinal stenosis, disc degeneration -- are not really diseases, but a normal part of aging, Minchew says.

If people were randomly given an MRI at age 25, a quarter of them would show aging-related changes in their discs. By age 65, 85 percent of people would show changes in their spine that a radiologist would label "not normal," Minchew says.

If an MRI shows such changes, but your pain doesn't come from that particular area, then your "disease" probably isn't what's causing your pain.

"Nine times out of 10 you cannot look at an x-ray or an MRI or any other test and tell the patient with any absolute certainty why they're having back pain," Minchew says.

William Richardson, MD, professor of orthopaedic surgery, says that in their first weeks of back pain, most people don't even need an x-ray.

"Imaging is not indicated in the first six weeks of pain unless you have some suggestions that the person has had trauma, has a fever suggesting infection, has a major neurologic deficit, or has any history of a tumor or suggestive of a tumor, such as weight loss," he says.

Studies show that 70 percent of people get better in the first six weeks, and 90 percent in the first 12 weeks, he says.

Because imaging can be inconclusive, the dialogue between doctor and patient can be just as important as an x-ray or an MRI. In many cases, non-operative doctors steer patients toward using medications and adjunctive treatments that will relieve the pain enough that patients can do the physical therapy that will help the body heal itself.

Physical therapy paves the road to healing

While physical activity may seem daunting to someone whose back twinges or throbs with every movement, doing appropriate exercises as soon as possible can be very effective.

"We try to enable the patient to achieve early success," says Matt Roman, PT, practice manager for Duke Physical Therapy. "We tend to have people do a very high frequency of activity, but at low intensity, so they're not provoking symptoms."

Physical therapy eases back pain in three major ways.

Low-impact aerobic activity promotes fresh blood flow to the tissues and flushes out waste products. Strengthening core muscles such as the abdominals builds a strong foundation for the spine. And flexibility exercises help people go about their days without stressing their backs.

"If you bend over to reach a box, and your leg muscles aren't flexible enough to allow you to get there, the motion will occur through your spine where it shouldn't," Roman says.

Duke physical therapy researchers are working to fine-tune such interventions; researcher Chad Cook, PT, PhD, and colleague Adam Goode, PT, DPT, are testing a new scale that measures the outcomes of various physical therapy interventions for lumbar and cervical spine pain, in terms of how well these tactics improve patients' ability to go about their daily activities with ease.

Karyn Rahn, MD, an occupational medicine physician in the Division of Orthopaedic Surgery, says that physical therapy is as important as medication in treating back pain.

In fact, she says exercise therapy proved to be the magic ingredient for her patient Donald Hendrix, 79.

Because spinal stenosis made it painful to walk, Hendrix was using a walker all the time, and, for longer distances -- such as when he came for appointments at Duke -- a wheelchair.

In addition to spinal injections, Rahn suggested water therapy.

"I said, 'Look, water takes the weight away, you can work your body out and not put that pressure on your spine,'" Rahn says.

Now, Hendrix spends an hour in the pool each day doing back exercises, and another 30 minutes walking in the pool for aerobic benefit. He says he feels the best just after exercising.

"I felt so good last Tuesday, I got the lawnmower out and cut the grass, edged the yard, and blew the clippings off the driveway," he says.

Hendrix no longer needs a wheelchair or a walker.

"I've come a long way, thanks to Dr. Rahn and her encouragement," he says. Gloria Liu, MD, assistant professor of orthopaedic surgery, also emphasizes getting active early, before patients start to lose balance and sensation.

"I'm a rehab doctor," Liu says. "I want to help people get their lives back."

She also offers adjunctive therapies to ease pain, including acupuncture (two 2005 studies showed that acupuncture is moderately effective against chronic lower back pain).

Liu, Tawney, and others offer a variety of spinal injections to reduce inflammation and pain.

"If you can manage a patient with medications and physical therapy, then you don't really need to do an injection. But if they're still uncomfortable, and you want to try and calm down the nerve, then an injection is a reasonable thing to offer," Tawney says.

For patients with disc herniation or stenosis, epidural injections send steroids or anesthetic (or a combination) into the entire space around the spinal cord.

Such medications can also be injected into a specific facet joint under the guidance of fluoroscopy. Botox injections, which Liu performs, can temporarily stop the nerve signals that lead to painful muscle contractions.

Selective nerve root blocks (injecting steroids and anesthetics into a specific nerve where it exits the space between the vertebrae) can confirm the source of the pain as well as relieve it.

These blocks are performed by Liu as well as Duke interventional radiologists, who offer these outpatient spinal injections guided by CT scan. Imaging helps the injectionist place the needle precisely at the nerve or disc that shows degenerative changes.

Rahn says that these injections can aid in diagnosis if a patient may have problems in more than one area of the spine and the doctor wants to know which is causing the most pain.

"If an injectionist does a nerve-root block on one level and you don't get any relief, but on a different level you do, then that can provide some clues," Rahn says. "We're very lucky that we have several providers here who can perform this service."

A destination for tough-to-treat pain

For pain that doesn't respond to such treatments, patients can get comprehensive evaluation at Duke's Pain Clinic, which offers pain management specialists, neurologists, neurosurgeons, interventional anesthesiologists, psychiatrists, and psychologists under one roof.

Many of the patients seen at the clinic have "failed back surgery syndrome" -- persistent post-operative pain.

One of the causes is scar tissue that puts pressure on a nerve, says Parris, the clinic's director.

"Surgeons can't control the accumulation of scar tissue," Parris says. "Different people produce different amounts of scarring."

For such patients, the clinic offers specialized therapies, including a new procedure offered at only a handful of places -- percutaneous neuroplasty.

For patients with spinal stenosis and failed back surgery, this treatment involves injecting a 10 percent saline solution (hypertonic saline) that may dissolve scar tissue. Guided by fluoroscopy, the doctor injects the precise disc affected.

At the October 2007 meeting of the American Society of Anesthesiologists, Parris and colleagues presented results of a small study demonstrating the efficacy of this procedure [abstract available at www.asaabstracts.com].

Other treatments circumvent the nerve signals that cause pain.

For instance, Prialt (ziconotide) is administered directly into the spinal cord fluid through an implanted or external pump. Prialt is for patients who haven't responded to narcotics or for whom narcotics are contraindicated because of allergies or addictions, Parris says.

The clinic also offers nerve ablation for patients who have failed more conservative therapies, and for patients with nerve injuries, the clinic can implant a spinal cord stimulator that blocks pain "messages" using a small electrical stimulation that the brain doesn't perceive as painful.

"This is not for everybody," Parris cautions. "In the wrong patient it could be harmful."

In addition, psychiatrists and psychotherapists at the clinic treat the depression that can accompany chronic pain, and biofeedback is also offered.

"It's a very good adjunct therapy, to learn how to relax, how to cope with the pain," says Billy Huh, MD, PhD, associate professor of anesthesiology.

"The mind is a very important part of pain management."

Surgery: The path less traveled

Patients shouldn't enter surgery territory until they've tried conservative therapy for at least three months, and more likely six, without success.

Even then, doctors reserve surgery for those with classic symptoms of particular conditions that also show up on imaging studies.

"Surgery can be very effective for back pain, but it needs to be directed to the diagnoses that clearly improve with surgery" -- such as spinal stenosis, adult scoliosis (curvature of the spine that's not congenital), and degeneration of a single disc, says neurosurgeon Rob Isaacs, MD, assistant professor of surgery and director of spine surgery.

To address the full range of patient needs, Duke's multidisciplinary spine surgery team includes both neurosurgeons, such as Isaacs, Michael Haglund, MD, PhD, and Carlos Bagley, MD, as well as orthopaedic surgeons such as Minchew, Richardson, and Christopher R. Brown, MD.

Brown, an assistant professor of orthopaedic surgery, says that the pool of surgical candidates has narrowed in the last 10 to 15 years.

"I don't do surgery for back pain. I do surgery for spinal instability," he says.

That's a broad term for any condition that causes the vertebrae and discs to interact abnormally, for instance when one vertebrae slips upon another (called spondylolisthesis). Patients with instability will often have pain that radiates into the legs and impedes walking.

A patient with a badly degenerated disc may be a candidate for fusion surgery, in which doctors remove the disc, then graft on bone and sometimes insert screws. The procedure stops the movement and reduces the pain caused by the lack of cushioning between the vertebrae.

The best candidate for a fusion is someone with degeneration in only one disc (single-level disease). Fusion does carry the risk that patients will later develop adjacent-level disease; by stopping natural movement of one vertebrae, the stress may be transferred to an adjacent one.

Artificial discs attempt to eliminate that side effect.

Disc replacements are approved by the Food and Drug Administration, and Duke does offer them, but many insurance companies won't pay for them.

Brown has performed one lumbar (lower back) disc replacement at Duke. But studies have shown that such disc replacement is only as effective as, not better than, disc fusion, he says.

Study results are better with disc replacements in the cervical spine (neck), but insurance companies often refuse payments for those as well, Brown says.

To provide more options for future patients, Richardson works with Lori Setton, PhD, professor of biomedical engineering and associate research professor of orthopaedic surgery, to engineer cells similar to the body's own that could be used to help regenerate discs.

And the researchers are trying to merge anti-inflammatory medications with proteins that will cause medications to gel around discs and stay there, reducing systemic side effects.

Richardson advises on the design of these experiments from a surgeon's perspective. But the use of such treatments is probably years away, he says.

Mapping the best route in the operating room

Isaacs and Richardson help patients now by offering minimally invasive procedures for virtually all back problems that respond to surgery, from disc degeneration to spinal stenosis.

While some traditional procedures require such drastic measures as collapsing a lung, minimally invasive surgery can be done with a few small incisions. That means fewer complications and a shorter hospital stay for patients.

"The short-term morbidity is dramatically less with minimally invasive procedures. The risk of being transfused is less, the risk of having a major medical complication is dramatically lower," Isaacs says.

Isaacs works to improve outcomes for all procedures through Duke's participation in the Degenerative Spine Study Group.

"We're linking up thousands of patients undergoing a certain procedure in the United States, and looking at the outcomes," Isaacs says.

Every time a patient has spine surgery at Duke, information about the procedure and outcomes are collected, along with that of patients at 30 centers around the country.

The data will tell surgeons whether minimally invasive procedures result in better long-term outcomes than traditional ones, and how to best perform procedures, such as whether to operate from the back or from the front.

Learning about Duke's minimally invasive procedures persuaded Carol Smith to take steps to stop hurting sooner.

She began having aching back pain around 1997. After an initial diagnosis of muscle spasms, an x-ray showed a curve in her spine.

Smith has adult scoliosis, which occurs more often in women and often worsens with age. As her curvature got worse -- in nine years it progressed from a 13-degree curve to a 33-degree curve -- the pain made it hard for her to walk and to do everyday things like shopping.

Another doctor had suggested a traditional procedure in which he'd have to cut along her spine and use a metal rod, screws, and bone grafts.

"It sounded horrendous to me," she says. "If there was no other option I probably would have gone that route, but not anytime soon."

Fortunately, she found an alternative -- and turned to Isaacs for a fusion surgery that required only three incisions in her side.

She had the procedure on a Monday and went home that Friday. Her predicted recovery time is three to six months, half the time predicted for the traditional procedure.

"Just thinking about the description of the other treatment, there's not a lot of comparison," Smith says.

"I'm so glad to have gotten it fixed. I was just really tired of hurting."

For more information about Duke's services for back pain, call 1-888-ASK-DUKE (patients) or 1-800-MED-DUKE (physicians).

This article was first published in the Summer 2008 edition of DukeMed Magazine.

Duke Transplant Center: A Matter of Life and Breath

Thu, 10 Jul 2008 08:44:36 -0400

Respiration has two parts: inspiration and expiration.

Air flows in and out of the lungs, taking sustenance into our bodies and delivering our leftovers back to the world. The flow of our breath, from our first cry to our last exhale, is our most basic function, connecting heart and brain to life as we know it.

Gordon Weeks goes with the flow. Or, at least, he does when it comes to matters of life and breath.

But he is also a survivor, which is why on April 12, at age 56, he celebrated his first rebirthday. It marked a year of living on someone else's lungs, a year since he was snatched back from the foggy line where life rubs shoulders with death.

His story is one of hundreds in the Duke Transplant Center, where the model of moving bench discoveries to bedside care takes on a new speed.

Thanks to the interchange of clinical practice and research innovation, patients for whom transplant wasn't possible a decade ago are now surviving longer and thriving after surgery.

Mr. Weeks goes south

Weeks and his wife, Shauna, live with their 10-year-old daughter on Cape Cod, Massachusetts, where Gordon used to spend much of his free time surfing.

Then one day he just stopped.

"I couldn't paddle out anymore," he says. "Didn't have the drive." He had no idea that the problem was his lungs -- as for many people with idiopathic pulmonary fibrosis, or IPF, it took years to make that diagnosis.

In November 2006, Weeks's brother Doug died from IPF. At that point Gordon himself had already been battling the disease for at least 10 years, and he and Shauna began to search for their only hope for meaningful treatment: lung transplant.

They applied to the transplant program at a hospital in nearby Boston, but waiting list was too long.

"They basically told us there wasn't anything they could do for [Gordon]," says Shauna, so the couple set out to find someone who could.

"I looked up Duke's outcomes online and they were the best. So I put Gordon and my daughter in the car and we drove to North Carolina."

That was March 19, 2007 -- one of the last days of winter. Gordon wouldn't see Cape Cod again until after midsummer.

The drive was tough, says Gordon.

"Shauna drove straight through -- 13 hours, and at one point we had to pull off of I-95 in the middle of Washington, DC, because I was so sick. Shauna had no idea what was happening to me."

What was happening was an escalating collapse of Gordon's respiratory system.
In the lungs of people with IPF, something -- no one yet knows what -- upsets the healing and repair processes in certain cells of the alveoli sacs. This thin, delicate tissue is gradually but inexorably scarred, and ultimately the alveoli can no longer broker the blood's precious exchange of oxygen for carbon dioxide.

The prognosis for IPF is always poor, but the process can take decades to reach a life-threatening stage; Gordon calls the disease a "sneaky one, a faker."

There's no pain, and no sensation that you aren't getting enough air (at least early on). Mostly, he says, it's a disease of frustration.

"You just sit around a lot more than you used to." And then, sometimes all at once, "the disease can just slam you."

In the lobby of the Millennium Hotel in Durham, where Shauna was checking in the road-weary family, that's what happened.

"I started shaking all over," says Gordon.

EMTs were called and he was admitted to Duke University Hospital, where the transplant team took over.

"I basically appeared to them out of nowhere, essentially waltzed in off the street totally unannounced," says Gordon, "but they immediately took me in and started rooting for me."

Gordon was stabilized and then spent the next week undergoing the rigorous physical and psychological evaluation for transplant.

"I remember that the whole transplant team gathered around Gordon's bed," says Shauna. "I was so sure they were coming to tell us that they couldn't do the transplant.

"And then one of the team members said, 'Mr. Weeks, you're having a very bad air day, and you needed a lung transplant yesterday. We're here to help."

Gordon then began the pre-transplant rehabilitation program at Duke's Center for Living, which helps lung transplant patients get strong before their surgeries. All transplant patients are required to do four hours of cardiovascular rehab training, every day, for 24 days prior to their operation and for 24 days afterwards.

"The whole Duke team is really adamant about exercise," Gordon says.

So, as the Weeks family awaited a pair of lungs, Gordon hit the gym.

At this point, no one knew just how close he was to dying.

Waiting for the call

"We were desperados in desperate times," Gordon says of his peers awaiting lung transplant.

Particularly, he says, at the Center for Living gym, where patients walk the treadmills, ride bikes, and lift weights, always with oxygen tanks in tow.

Those awaiting transplant range from young people with cystic fibrosis -- some of whom get multi-organ transplants -- to older people with emphysema and IPF patients like Gordon.

One woman Gordon got to know had a disease that actually turned her blue. She, Gordon says, waited several weeks for her transplant -- but that's an exception to the rule.

The waiting time of lung transplant patients at Duke is unusually short -- about two weeks, in most cases.

Robert D. Davis, MD, a cardiothoracic transplant surgeon and director of the Duke Transplant Center, says the short wait is made possible by the program's ability to procure about three times more lungs from donors than most other American programs.

"A lot of that has to do with the fact that we'll consider organs that other people won't," says Davis.

That doesn't mean that they take lungs that are sub-par, he says, but that they have the resources and manpower to travel to a hospital that has a potential donor match.

Davis says that when surgeons physically go to look at potential donor organs, "you can do things to optimize the lung function before procurement. It allows us to use a lot of organs that are viable, but might not sound so over the phone."

The national standards for allocating donor lungs were changed in May 2005.
Originally the allocation was done on a sort of first-come, first-served basis, but the revisions now give highest preference to patients whose odds of survival after transplant are good and whose survival without transplant is dire.

And there wasn't much about the Weeks case that wouldn't turn out to be dire. On the fourth morning of his rehab training, Shauna called the paramedics.

As Gordon puts it, "I was tanking."

"Mr. Weeks's illness had progressed to the point that the trip and the transplant evaluation were too much stress on him," says Duke pulmonologist Scott Palmer, MD, who is medical director of the lung and heart-lung transplant teams.

"By the time he got to us, his survival could have been measured in weeks."

Back in the hospital, Gordon was put on a ventilator to help him breathe. But the ventilator quickly proved inadequate; it was giving Gordon oxygen, but his lungs couldn't do anything with it.

"They called my wife and more or less said, 'Please come quickly, your husband is about to die,'" says Gordon.

But he wasn't afraid at any point in those last moments of consciousness. "I really went through the whole thing like a piece of wood floating in a river," he says.

"I just thought, well, I'm putting myself in their hands and God's, and it's going to be fine, one way or another."

Uncharted waters

"The first time I met the transplant surgeon, they had just coded my husband," says Shauna.

Davis told her that they were entering uncharted waters: most patients who are at this stage of IPF are no longer good transplant candidates.

But, Davis said, if lungs became available in the next five days, they would perform the surgery.

Meanwhile, Gordon would have to be put on ECMO -- extracorporeal membrane oxygenation, which is essentially a last-resort therapy for patients whose lungs are simply unable to function.

It's a rather gruesome-looking scenario: large catheters are run in through the neck and out through the groin, so that they can capture blood from the large veins and run it through the machine's belly.

Much like a heart bypass or dialysis machine, ECMO is the mechanical means to do what the body's own system cannot -- in this case, to filter the blood's carbon dioxide and replace it with oxygen.

ECMO can be a lifesaving tool for some patients, particularly premature babies with still-forming lungs, because it provides a bridge to keep the body going if the lungs simply need to go off-duty for a while. But Gordon's lungs weren't going to get any better -- his lungs were gone.

Gordon meets his match

"I'm still not sure what it was about me that made them decide to do the transplant -- I was so sick," Gordon says.

Davis explains that such a choice is made by gestalt: The weeklong evaluation gives the team -- which includes surgeons like Davis, pulmonologists like Palmer, nurses, transplant coordinators, and social workers -- a chance to assess a variety of physical, psychological, and social support factors that help them determine whether the patient has a reasonable chance for a successful recovery after transplantation.
Lung transplant surgery is a huge commitment, on the part of the patient, the patient's family, the hospital, and the organ donation service.

Ideally, Davis says, the final decision to go through with a transplant isn't made in an emergency situation, but in those cases "it often has a lot to do with how healthy the patient was before the crisis," he says.

"Gordon was in reasonably good physical condition before he took the sudden downhill turn."

The fact that Gordon suffers from IPF also made transplantation a clearer choice, according to Palmer.

"We knew we were giving him a survival benefit, because he had no survival left with his lungs. There are other diseases where we really debate about how much of a benefit we're offering."

For example, the number of emphysema patients receiving transplants has gone down in the last five years, for two reasons: first, emphysema patients are not as sick as patients with illnesses such as IPF, and second, it's not as clear whether their survival and quality of life will be better if they are transplanted sooner rather than later.

"We want to maximize everyone's life expectancy," says Palmer, "so we want to time the transplant so that they really are at the end of the road with the lungs they have, and that they can have a good recovery and good quality of life after transplant.

"There's no crystal ball to it, and sometimes it's hard to know what's best."

After all, the surgery is no small affair.

"To make the recovery easier, they make the incision from armpit to armpit; they open you up like a clam," says Gordon.

His own turn on the table came after four days on ECMO -- Shauna says it was just as he was starting to look "really bad," if it was possible to look worse than he already did.

Gordon's surgery was as arduous as the family's drive from Cape Cod three weeks before: it took 14 hours and, when Gordon began to hemorrhage at one point, more than 100 units of blood.

Kidney envy

Even from his most precarious moments in surgery, Gordon had great odds. Fifty percent of Duke lung transplant patients survive at least eight years following their surgery (the national figure is four years).

Davis attributes these outcomes to a number of factors: only double-lung transplants are performed (their outcomes are better than single-lung transplants); the team does a large volume of transplants (also associated with better outcomes); and they employ a clinical protocol to help prevent the new lungs from injury due to gastric reflux.

"Some of it is also the sum of all sorts of little processes," Davis says. "The expertise and dedication of the physicians, the coordinators, the team aspect of delivering care -- we're still doing the same protocol as institution X, but we're doing it better."

But as good as Duke's lung stats are, they still aren't as good as the average successes for heart, or kidney, or liver transplants, which function successfully for up to 14 years.

Palmer notes that, worldwide, lung transplants have the lowest numbers in terms of both incidence and successful outcomes.

"But to me, that means we have the most opportunity to make an impact," he says.
"We don't want to just do more lung transplants. We want to extend the longevity and quality of our transplants."

Most lung transplant patients eventually succumb to either infections or, most commonly, chronic transplant rejection: at some point, the immune system registers that the transplanted organ is foreign material.

Thinking it's doing its duty, it sends its cellular troops to attack the infidel. Immunosuppressive drugs are used to keep this response in check, but often the body's impulse to defend itself simply takes over.

"Kidneys now have about a 10 percent acute rejection rate at six months," says Palmer, "and we still have about 50 percent acute rejection at six months."
He explains that, for lungs, the current immunosuppressive medications aren't making the grade.

"Lung transplant has basically just been borrowing all the drugs from kidney transplant, because they're all we've got. But the reality is that they don't work as well for us."

Some other mechanisms are at play in lung transplant failure -- the question that preoccupies Palmer and Davis, who each lead research teams on lung rejection, is what these mechanisms are, and how they can be dampened down to keep patients like Gordon alive.

Innate impulses

Why transplanted lungs succumb to rejection faster than other solid organs is a tricky question.

At first glance, the immune response makes no sense: of all the solid organs, our lungs are designed to deal with foreign matter.

The average person inhales about 26,000 times a day, taking in about 14,000 liters (or 150 bathtubs' worth) of air. With every inhale, we breathe in foreign materials along with our essential oxygen -- gasses and chemicals, particulates and microbes of varying sizes. And our lungs are set up to capture all this foreign material while not overreacting to it.

"The normal process is that the immune system operates to just get rid of the junk -- swallow it up in macrophages and dispose of it," Davis says.

But in a transplanted lung, because the lung itself is not 'self,' these injuries that otherwise would not have any consequence trigger an immune reaction that could degrade the lung and ultimately cause failure.

"We get what seems on the surface to be classic immunologic rejection," says Davis.

When a transplanted heart, lung, or liver is rejected, it's taken down by the body's adaptive immune system: T cells and antibodies are sent out specifically to attack any cell that registers as this foreign type.

Palmer says that in the lungs a different sort of immune rejection may be at work.
"Because the lungs are constantly exposed to the environment, they have an intrinsic set of defense mechanisms that are there to deal with all the stuff you're breathing in."

This is known as innate immunity, and it's a more generic immune response, involving inflammation, a cascade of antagonizing proteins, and a flood of white blood cells.

"My idea is that this facet of the immune system plays a central role in orchestrating and regulating rejection in lung transplant."

It's a new idea, and one that will take time to prove. Palmer is currently looking at how genetic variations correlate to innate immune responses and rates of rejection after transplant.

"The hope would be that someday we could better gauge your risk for rejection after transplant based on some of these genetic variations in your innate immune system," perhaps clearing up the crystal ball to help select which patients might benefit most from transplantation.

Gut reactions

Any toxins, pollution, and infections that a lung transplant patient breathes in have the potential to trigger lung injury and rejection episodes.

But the battle most often begins with the gut.

Lung transplant patients have a high incidence of gastric reflux disease, which puts them at high risk for aspiration events, in which reflux travels into the lungs, sounding the immune system's alarms.

Davis says the high rate of reflux is in large part because the vagus nerve -- which, among many other things, regulates gastric function -- takes a beating during a lung transplant surgery.

Also, patients with end-stage lung disease have a greater amount of reflux in general.

"It may result from coughing and changes in pressure in the abdominal cavities at this stage of disease," he says.

"And the reflux may contribute to the lung disease by injuring the lungs when it's inhaled. We know it's related, and it could also be causative."

Davis's research includes investigating what happens at the point of injury.

"There's a certain amount of bacteria in the aspirate material," he says. "We're looking at whether the protein coats of these bacteria are what's triggering the immune attack on the lung."

Though conclusive explanations of the hows and whys of reflux and aspiration injury are still being fleshed out, it's inarguably a condition that lung patients want to avoid.

Duke has developed very aggressive clinical procedures to prevent aspiration injuries, says Davis, including a surgical stomach-wrapping procedure -- just as it sounds, the stomach is wrapped around the esophagus to prevent reflux from moving into the lungs.

"Our protocol seems to play a large part in our outcomes," Davis says, "and we're taking the observations we're seeing in the clinics back to the laboratory, so that we can use basic research to answer some of the still-unanswered questions."

All hail the inhale

The first breaths Weeks took with his new lungs were not his own; they were the mechanized inspirations and expirations of the ventilator, to which he remained connected for four days after his surgery.

"It was really frustrating," he says. "I'd look over and see that my oxygen level was good, but it felt like I wasn't breathing at all. As Dr. Davis puts it, it takes some time for the lungs to fly."

Weeks spent six more weeks in intensive care, beginning to recover from extreme muscle weakness and adjust to the immunosuppressive drugs that will be his lifelong companions.

"Getting up [for the first time after surgery] was probably the hardest thing ever," he says.

Not because of pain, but because of sheer weakness: before his downward spiral, Gordon was a tall, strong 250 pounds; when he left North Carolina he was down to 160.

"Every day is a different healing," he says. "There are definitely steps in the healing process, and for me it's been a long staircase."

Gordon left the hospital the weekend of July 4, 2007, and went back to the rehab at the Center for Living he'd left so abruptly in April.

He says the staff there taught him -- firmly -- how to bring his body back to life after such a close courtship with death.

"I was so weak that I showed up [to rehab] in a wheelchair. And David Best said to me, 'You're not coming in on a wheelchair anymore. Get yourself a walker if you need to.'

"And so I did, and I used it for a while. Then one day he said, 'Get rid of that walker!' So I kicked it to the side as I walked in the door, and that's where it stayed."

Scott Palmer has two pictures of Gordon Weeks: one taken when he was on ECMO -- about as far from the New England surf as he could be -- and one taken recently at his home in Cape Cod, where he's built back up to 190 pounds and is able to spend most days on the job, which for him is splitting wood -- about as far from ECMO as one could imagine.

Palmer says that, though Gordon's story is particularly hair-raising at times, it's still typical of the everyday miracles he sees in the Duke Transplant Center.

"When I started doing lung transplant," he says, "I told my patients that they have a 50 percent chance of living five years.

"Now I tell them eight years, and it's pretty amazing to see that change in 10 years."

"It's not for the faint of heart," says Gordon of this process of surgical rebirth. "But the drive to live is so strong -- you don't want to let go. And as much as it hurts, and as weak as you are, there is always tomorrow to heal, to get better. Every day you do get stronger."

And his lungs, so far, have kept him flying. "I like to talk to them -- thank them, and thank the person who gave them, even though I don't know who that person is.
"I keep going back to how incredible that part of it is. One forfeits his or her life, but gives life to another, and there are people here who can make it happen."

For more information about organ transplant services at Duke, call the transplant office at 919-684-5926.

Gordon and Shauna Weeks found Duke's transplant outcomes information (and that of other hospitals) on the Web site for UNOS, the United Network for Organ Sharing.
Read more about that organization at unos.org

This article was first published in the Summer 2008 edition of DukeMed Magazine.

Multi-Vessel Heart Disease

Thu, 10 Jul 2008 13:54:42 -0400

Hundreds of thousands of Americans are diagnosed each year with coronary artery disease (CAD), a life-threatening narrowing or blockage in any of the four arteries that feed the heart.

The leading cause of death among both women and men, CAD claims some 500,000 lives in the United States each year -- and comprises more than 70 percent of all heart disease mortality.

While some patients experience no symptoms until they suffer a heart attack, coronary disease often causes symptoms such as chest pain (angina), shortness of breath, fatigue, lightheadedness, and nausea, with patients becoming increasingly weak and debilitated as the heart is starved of oxygen.

Untreated, CAD usually means fewer years of life -- and less quality to those years. In general, the more arteries involved, the sicker the patient. People with multi-vessel disease are often scared, confused, and overwhelmed.

Nearly all say that they just want to get it "fixed."

That's where things can get tricky.

So tricky, in fact, that the first annual Thomas Ryan, MD, Duke Heart Center Lecture, held at Duke in late 2007, was dedicated to debating this important issue.

Entitled "Multi-Vessel Coronary Disease: PCI, Surgery, or Maybe Both Are Wrong?," the event began with the presentation of a case study by moderator Mark F. Newman, MD, chair of anesthesiology.

Newman reported the particulars of patient "Mr. G," as well as his angiogram results, which revealed coronary disease in three arteries.

The case was then discussed by Peter K. Smith, MD, chief of the Division of Cardiovascular and Thoracic Surgery, and Robert M. Califf, MD, and E. Magnus Ohman, MD, both of the Division of Cardiology.

Each spoke primarily in favor of a different intervention for patients who, like Mr. G, suffer from multi-vessel disease, their positions reflecting the larger ongoing debate within the medical community.

Those interventions fall under three main categories:

Percutaneous coronary intervention (PCI)
"Surgery," which typically refers to the coronary artery bypass graft (CABG or "cabbage")
Medical management

DukeMed Magazine asked Smith, Califf, and Ohman to recap their remarks on this controversial topic.

PCI: Minimally invasive, widely performed

PCIs are aggressive, non-surgical procedures used to clear narrowed or blocked coronary arteries.

These minimally invasive procedures include angioplasty -- in which a balloon-tipped catheter is inserted into a blocked coronary artery and then inflated to clear the vessel of debris -- and the placement of stents, minuscule mesh-like tubes that hold arteries open.

The two procedures are commonly performed together.

The immediate risks of complications and infection associated with PCI are significantly lower than those of open surgery.

There's less post-procedure pain, recovery is quicker, and the risk of cognitive decline sometimes associated with CABG surgery is eliminated.

The preferred intervention for people in the midst of heart attacks, PCI gets blood flowing to the heart within 90 minutes, as opposed to the approximately three hours it takes with surgery.

PCI -- in particular, stenting (also known as percutaneous transluminal coronary angioplasty, or PTCA) -- has also been widely criticized.

Plagued by safety and efficacy concerns, stenting has been the topic of an ongoing debate comparing bare-metal stents (BMS) to drug-eluting stents (DES).

BMS have seen a high rate of in-stent restenosis -- plaque buildup inside a stent, which renders it useless.

DES, developed to remedy this issue, were viewed as a great advance. But when studies(1) showed an increased risk of DES-related heart attacks due to in-stent thrombosis (a blood clot that develops inside the stent), many physicians went back to BMS.

Recent findings may cause them to reconsider -- again.

A study(2) of the National Heart, Lung, and Blood Institute Dynamic Registry examined the data of 1,460 DES patients and 1,763 BMS patients one year after their stent placements.

DES patients had a 15.5 percent risk of suffering a major cardiac event compared to BMS patients' 20.9 percent.

In addition, DES patients had a 43 percent less chance of needing post-stent angioplasty or bypass surgery than those with BMS. And the rate of in-stent thrombosis among DES patients was only 1 percent -- down from previous studies. A study(3) of a Massachusetts registry of 21,024 patients had similar findings two years post-stenting.

"PCI has evolved a lot and continues to evolve -- from standard balloon angioplasty to BMS to DES and now to newer forms of DES," says Ohman, who specializes in performing PCI and leads the Duke Heart Center's Program for Advanced Coronary Disease.

"It provides a new way forward for patients -- especially older patients and those with more complex disease -- by lowering the risk of recurrence and offering a tremendous reprieve from their symptoms."

PCI isn't for everyone, but for many patients, it's "a great option that's associated with fewer symptoms and a higher quality of life," Ohman says.

"When a patient is a candidate for both PCI and bypass surgery, I think it makes sense to offer the less invasive PCI as the first line of defense."

Smith, the surgeon, agrees that because PCI isn't as physically traumatic for patients as bypass surgery, it's sometimes the better option for patients who may not be well enough to survive surgery -- such as those with advanced age or prior cardiac surgery, and even some with three-vessel disease.

But, Smith believes, "It's not fair to recommend PCI for a patient and say, 'You can always have surgery later if this doesn't work.' The public gets the idea that surgery and PCI are equivalent -- which isn't true for patients with three-vessel disease, for whom surgery is life-prolonging compared to PCI," he says.

"Proponents of PCI are basically saying, 'We never said it would save anybody's life; we just wanted to improve their symptoms.' And they should acknowledge that this is the case when they discuss options with patients who have life-threatening coronary disease."

So how long must a patient feel better before "improving symptoms" can be called "saving a life"?

The randomized ARTS II trial(4), the largest follow-up study of its kind to compare surgical and PCI patients, looked at 607 patients one year out.

ARTS II showed that "the drug-eluting stent is every bit as good as bypass surgery for treating multi-vessel disease," Ohman says.

Despite the ongoing controversy, PCI continues to be the most commonly used intervention for coronary artery disease.

The American Heart Association (AHA) reports that 1,265,000 PCIs were performed in the United States in 2005 -- approximately two-thirds in men and one-third in women. (Duke cardiologists perform more than 1,300 PCIs every year.)

But while data show that stents have gotten safer, the overall use of angioplasty appears to be waning, according to a recent analysis conducted by the National Cardiovascular Data Registry.

"The rise of angioplasty procedures has leveled off and appears to be on the decline," Duke cardiologist Eric Peterson, MD, told USA Today after reviewing the data.

This could be because some believe that PCI in general is an overused strategy for treating multi-vessel disease that would be more effectively treated with CABG surgery and/or medical management.

Bypass surgery: Tried and true

A second approach to treating CAD is the coronary artery bypass graft, an open revascularization procedure in which arteries are surgically rerouted to allow unrestricted blood flow around narrow or blocked spots.

Because it entails opening the breastbone, spreading the rib cage, and hooking patients up to a heart-lung machine, CABG is major surgery.

Patients face months of recovery time, a large external scar, and increased risk of stroke.

"The risk of stroke associated with CABG is about 10 times that associated with PCI, and strokes occur very rarely as a result of PCI," Ohman says, adding that most patients fear that CABG will result in neurological complications, as well.

Although many patients opt for PCI to avoid these risks, the AHA reports that approximately 470,000 CABG surgeries were performed in the United States in 2005 -- some 325,000 in men and 145,000 in women.

Duke Heart Center surgeons alone performed over 600 bypass surgeries annually between 2003 and 2007.

Smith says that's because the procedure is tried and true, with proven benefits and very low mortality and complication rates.

"The advantage of surgery is that it's definitive, it's durable, and evidence shows that in almost all cases, it is effective," says Smith, who specializes in performing the procedure.

"CABG completely bypasses the disease, and in many cases, it simply doesn't come back" -- particularly with artery grafting, he adds, although the disease can return with vein grafts.

A 2006 Duke analysis(5) of outcomes from more than 18,000 heart patients found that patients who received bypass surgery lived an average of 5.3 months longer than those treated by angioplasty -- and that both bypass surgery and angioplasty provided more benefit for patients than medicine alone.

Because bypass surgery has shown the greatest longevity benefit in treating three-vessel disease -- "potentially the most lethal form of heart disease," says Smith -- "it's the clear winner for many of those patients."

Ohman concurs. "CABG certainly offers the best long-term solution for some people. The more severe the disease and the more vessels are involved, the more appropriate surgery becomes."

"Select patients do require intervention beyond medical management," Califf says. "In those cases, it's the doctor's responsibility to make sure those patients understand the potential benefits and risks of the procedure they're being offered."

Medical management: A solid foundation

Because it is recommended as both a singular strategy and for use in conjunction with PCI and surgery, medical management actually transcends and supplements all other multi-vessel disease interventions.

Medically managing CAD means treating the condition with non-surgical methods that include drug therapies and/or modification of lifestyle factors such as diet, exercise, smoking, and stress management.

These strategies also help prevent further deterioration of the heart muscle in patients with existing damage.

"Medical management is the bedrock of treating coronary disease," says Califf. "Regardless of anything else patients have done, medical treatment should be the standard of good medical therapy and the first option we offer our patients.

"The Duke data(6) show that patients who are on multiple effective treatments -- which can be a first-rate aspirin, beta-blocker, and statin, available for four bucks a month from Wal-Mart -- have about a twofold reduction in their risk of death compared to patients who do not adhere to their medication regimens.

"The issue is that the real benefit is in medical therapy," Califf continues.

"PCI doesn't prolong survival in most patients, so you're not losing anything there by going with medical management, and CABG obviously has a higher risk than medical treatment."

"If we cardiologists could just do our jobs in our own treatment environment and give patients simple four-dollar-a-month plans, we would save literally thousands of lives," he says.

"We need to give patients the important treatments first, and if those fail, then try the expensive and risky treatments."

Smith agrees that medical management plays an important role for surgical patients, and its use as an alternative to both PCI and CABG may be underutilized.

"Advances in medical therapy have led to more promising results than anticipated in treating patients with one- and two-vessel disease, whom the COURAGE trial(7) showed aren't being helped as much with PCI."

The key to the best outcome? Honest dialogue.

Since each multi-vessel disease intervention has its pros and cons, how does one decide which is likely to have the best outcome for a given patient?

By having a truthful and thorough doctor-patient conversation, these experts say.

"Many doctors tell their patients, 'You've got bad blockages, and we need to bypass or dilate those blockages because if we don't, you're going to have a heart attack or die,'" Califf says.

"And that's simply not validated by the randomized trials; it's not true. But it's something we frequently tell our patients because it avoids a much longer discussion about what's really going on in terms of the risks versus the benefits of these various interventions."

Risks versus benefits

Many people assume, for instance, that minimally invasive procedures are inherently safer -- and therefore always "better" -- than open surgeries.

Take the surgery-versus-PCI issue, for example.

"Surgery has risks like pain, infection, and recovery time that people understand up front," Smith says.

"But multi-vessel coronary disease patients should understand that PCI's ongoing cumulative risk of restenosis is less obvious, with studies showing that surgery compares more favorably to PCI the longer patients are followed."

Patients may have different perceptions of risk when considering medical management, as well.

Some may perceive this strategy as having the lowest risk because it doesn't involve any type of surgery. Others may see it as being more risky than the other options because they don't believe medication and lifestyle changes can successfully treat their heart disease.

"It's only natural for patients to think that if they have a stent placed or undergo a bypass that their disease is 'fixed' -- and doctors can easily get away with saying, 'It's lucky we found this blockage; now we can fix it,'" Califf says.

"A doctor who offers patients a potentially risky procedure must be able to show that it's likely to help them."

Another issue, Califf says, is that many patients have difficulty translating probability into risks that are meaningful to them.

For example, when comparing a treatment said to have a 10 percent risk of death with one said to have a 90 percent survival rate, people are more likely to choose the second option, even though the actual degrees of risk are equal.

Patient factors

Patient factors that figure into the risk-versus-benefit equation commonly include:

Age and health status: A patient may be too elderly or ill to withstand surgery, for example -- or to wait for the effects of medical intervention.

Medical management alone or in conjunction with PCI may be the most appropriate choice for someone with minimal disease.

Goals, values, and concerns: A big issue is quality versus quantity of life. Some people prefer better years to more years; some, the opposite.

Patients might think about what they hope to achieve through treatment. The stamina to keep running marathons? The ability to perform daily activities and play with the grandchildren? Relief from debilitating symptoms?

Other factors can include patients' affinities for (and aversions to) particular treatments, insurance or financial concerns, and so on.

Lifestyle and compliance: Some patients follow their doctor's instructions to a tee; others don't.

Some aren't likely to quit smoking, take up regular exercise, or improve their diets; others view their condition as a call for meaningful lifestyle change. Some are very self-motivated; others might benefit from working with a health coach.

Additional factors

Other factors also can come into play when choosing a treatment for multi-vessel disease.

"The patient made me do it" phenomenon: While patients are encouraged to educate themselves and take a proactive role in their own health, they are increasingly arriving at their initial cardiologist visits with Internet printouts in hand and a treatment in mind -- without having discussed their individual risks and benefits with their doctors, and frequently armed with data that are murky at best.

Unclear and/or biased data: Unfortunately, the large body of existing research data about treating multi-vessel CAD can lead to confusion, not clarity. The length and type of the study, as well as the number of participants, obviously influence the quality and meaning of the data.

And different uses and interpretations of the word "multi-vessel" -- which can mean two, three, or four vessels -- mean that data from studies of patients with different degrees of disease may be combined, accounted for multiple times, and/or simply unclear.

"Most 'multi-vessel' CAD studies have in fact looked only at patients with two-vessel disease -- not three- or four-vessel disease -- and the distinctions are critical in terms of both compromised patient health and the interpretation of the data," Smith says.

"People can take these results to mean what they want them to mean when making a case for or against a particular therapy."

Physician expertise and bias: A physician or hospital's experience with and/or bias toward particular treatments plays a role in which strategies are recommended to people with heart disease.

"It's one thing for doctors to advocate for the procedures they do, but it can be an entirely different thing for them to advocate for their patients," Smith says.

"We should help our patients develop a perspective beyond what happens today, present them with information honestly, and never present a procedure as an option when another one would be more appropriate."

Califf agrees. "Let's have the courage to tell our patients the truth about what we know about each of these treatment strategies, and take the time to explain all of the risks and benefits."

While the morbidity and mortality associated with coronary artery disease is devastating, both doctors and patients can thank ongoing advances in medicine for the variety of lifesaving treatment options available today.

Selecting the right one to treat a patient's multi-vessel disease means working together to make a carefully informed, patient-centered decision.

Robert M. Califf, MD, is the Donald F. Fortin, MD, Professor of Cardiology, vice chancellor for clinical research, and director of the Duke Translational Medicine Institute.

E. Magnus Ohman, MD, is a professor of medicine and director of Duke Heart Center's Program for Advanced Coronary Disease.

Peter K. Smith, MD, is a professor of surgery and chief of cardiovascular and thoracic surgery at Duke.

This article was first published in the Summer 2008 edition of DukeMed Magazine.

Footnotes

1, 3 N Engl J Med. 2007 Mar 8;356(10):1009-19. Epub 2007 Feb 12.
2 J Am Coll Cardiol. 2007 Nov 20;50(21):2029-36.
4 Heart. 2004 September; 90(9): 995-998.
5 Ann Thorac Surg. 2006 Oct;82(4):1420-8; discussion 1428-9.
6 Circulation. 2006 Jan 17;113(2):203-12. Epub 2006 Jan 9.
7 N Engl J Med. 2007 Apr 12;356(15):1503-16. Epub 2007 Mar 26.

A New Normal for Cancer Survivors

Mon, 16 Nov 2009 16:02:11 -0500

One morning each week, the waiting room of the Duke Breast Cancer Survivors Clinic fills up with half a dozen women.

They make their way to the blood pressure gauge, pumping, listening, and writing down their own readings. They take their own pulses, check their weight. They even use notepad computers to answer questions about their physical, emotional, and psychological well-being.

The one thing the women don’t do in that waiting room is wait.

"It's so nice to talk to other people going through similar things," says Martha Hall, who's been cancer-free for four years and recently attended the clinic for her annual checkup.

What's more, after the women fill out their materials, instead of hanging around avoiding eye contact, they meet with nurse practitioner Kathy Trotter -- as a group. They discuss issues they face as cancer survivors: bone density, depression, weight gain, nutrition, exercise, and what they can do to take care of themselves.

The Survivors Clinic represents a new, empowering model of care -- very different from the suspense-filled annual mammogram surrounded by two hours of waiting that most survivors are familiar with.

"The focus is keeping you healthy, it's not 'You're so sick,'" Hall says. It's an affirmation of just how far these women have come -- and of how much things change after cancer treatment ends.

"You've been in the womb of care," says Bebe Guill, director of survivorship programs and services at Duke's Preston Robert Tisch Brain Tumor Center. "You've been encircled by these people who talk to you every day, every week, and all of a sudden they're gone. And you're left with this terrifying fear of, 'Who am I now? What is my life about now? And what happens if this comes back?'"

Add in that you will likely experience physical side effects (which can range from muscle wasting to infertility and even heart disease) or emotional side effects (like anxiety and depression), and a cancer survivor is faced with a new crisis: "The challenge," Guill says, "is finding a new normal."

That goes for caregivers as well as their patients.

Throughout the Duke Comprehensive Cancer Center, clinicians and researchers are figuring out how care should evolve as more and more people survive cancer longer and longer, creating a new class of patients that once would have been an oxymoron: cancer survivors.

Tina Piccirilli (left), director of the Duke Center for Cancer Survivorship, pictured with Bebe Guill of the Preston Robert Tisch Brain Tumor Center at Duke.There are now 10 million cancer survivors in the United States, says Tina Piccirilli, director of the Duke Center for Cancer Survivorship, founded in 2005. Trends suggest North Carolina will have more than 60,000 new cancer cases by 2030 -- which at the current five-year survival rate of 64 percent means a good 40,000 new cancer survivors five years after diagnosis.

As the population of survivors has increased, survivorship has emerged as a distinct field of care. There are now a dozen or so cancer survivor centers nationwide, Piccirilli says, and new ones are being created each year.

Duke's program seeks to develop care that meets the needs of survivors -- and conduct the research that will identify just what those needs are.

In the 15 years she has been with Duke, Bebe Guill has seen the shifting tides of survivorship firsthand.

Cancer, she says, "is not a linear process, the way we used to think about it: you get the diagnosis, you get a little treatment, either you're cured or you die. Cancer is becoming a chronic disease."

That's why, Piccirilli says, the Duke Comprehensive Cancer Center has adopted the National Coalition for Cancer Survivorship's definition of cancer survivor: "You're a survivor from the day you're diagnosed -- which is a hugely positive message."

Care is changing to reflect that attitude. At the brain tumor center, clinicians and patients begin creating a survivorship plan from the start of treatment. Caregivers discuss the long-term effects of brain cancer and various treatment options as clinical decisions are made, and offer both medical and psychosocial resources throughout treatment to help patients manage or adapt to those outcomes.

With brain tumors, cognitive deficits are a frequent result of the tumor or its treatment -- the ability to solve problems, to pay attention, to multitask.

"Short-term memory loss," Guill says, "is common in our patients and can make day-to-day life very difficult and frustrating."

So patients need not just medical care but the kind of support services that will help them adjust to changes in their relationships, their earning status, their independence.

This fall, the brain tumor center is launching a new survivorship clinic that will pull together a range of resources to help survivors cope with their changed status.

In addition to offering clinical surveillance and preventive care, and recommending interventions for effects such as neurocognitive deficits, sexual dysfunction, or vision and hearing problems, the clinic will offer guidance for practical concerns -- such as returning to work or coping with an inability to drive -- and connect survivors with wellness resources to aid their recovery.

A key part of that is support from others who are going through similar experiences, says Guill -- so the clinic will incorporate a patient and family support group, as well as a "lunch and learn" group where experts will discuss vital topics such as managing fatigue and depression or coping with behavioral changes.

Other specialized clinics for survivors are also popping up around Duke -- including programs in the works for prostate and other cancer types, in addition to the Breast Cancer Survivors Clinic, launched in February -- to better meet survivors' broad range of needs.

In the action-packed breast cancer clinic, for example, patients benefit from the self-assessment of weight, pulse, and blood pressure, plus facilitated group discussion and education.

Then they go on to individual appointments, whether for mammograms or bloodwork, nutrition consults or physical therapy, or one-on-one time with nurse practitioner Kathy Trotter, where they complete a long-term care plan to share with their primary care physician.

When necessary, they schedule appointments with the oncologist as well. Each woman ends up spending the same few hours she would have devoted to her checkup, but she’s seen multiple practitioners and wasted no time.

"This may be the first survivorship clinic in the United States to combine both group and individual support, assessment, and education within a single visit," says Trotter, adding that she hopes it will serve as a national model. "It's designed to empower survivors -- and they love it."

Plus, adds clinic medical director Kelly Marcom, MD, the new clinic benefits women through not just how they spend this time but where they don’t spend it: in the oncologist’s waiting room.

"Not to sound callous, but if you've been treated for early-stage breast cancer and are hopefully cured, you don't necessarily want to be in a clinic with people who have had a recurrence," Marcom says.

Hall agrees: "I just said to a friend, every time I go in [to the oncologist] I cry -- it just brings it all back like it was happening today."

"It's a symbolic moving on in their lives," Marcom says. "We can overmedicalize their lives -- that's not a good thing.”

From Patient to Person

Amy P. Abernethy, MD That is a growing consensus, says Amy Abernethy, MD. Abernethy directs the Duke Cancer Care Research Program, which "tries to move the philosophy of whole-person care into real clinical space" at every stage of survivors' care.

"We are systematically developing new models of care to do a better job of taking care of the individual patient," Abernethy says.

She looks at what she calls the "misery line," a representation of the cumulative effects of cancer and treatment: pain, fatigue, difficulty getting around, nausea. "If you plot this across time, this is a volume of misery, and my job is to decrease the misery line."

The first job is to measure that misery, via clinical trials that focus on quality of life. Abernethy cites as example a trial now under way in the sarcoma clinic, where patients answer a computerized series of questions regarding their physical, psychological, and emotional states:

Are they in pain? Depressed? Functioning poorly or well?

Those data can be tracked over time as they progress through treatment -- and then compared with therapeutic actions taken to see what seems to be working.

"We're just at the starting point of identifying trends in the data, looking at what happens to things like pain or depression over the course of treatment," Abernethy says.

"Then we bundle that information and report it back to the clinicians so they understand what kind of things people are dealing with. And as soon as we've got a sense of that, we can start bringing in new services, new products to help them cope."

This data-gathering helps make a whole of both patients and their care.

"It doesn't really help if I just take care of pain, or of nausea and vomiting. Those are isolated events in a whole person," Abernethy says.

"How do we wrap it all together? That's my ultimate goal."

Preserving Fertility

Susannah D. Copland, MD, MSAs survivors pass from active treatment to one, three, five or more years of remission, new concerns arise -- many that might not even be on the patient's radar screen at the time of diagnosis.

Consider oncofertility, the relatively new arena addressing the effects of cancer treatment on fertility.

"When people weren't surviving their cancer, nobody cared whether they would have been fertile," says Susannah Copland, MD, of the Duke Fertility Center. Today, it's a vital question for young people facing a cancer they can legitimately hope to survive.

So Duke oncologists have added a question to their intake survey to trigger the conversation, and if a patient expresses interest in future fertility, Copland is called in to discuss their options before, during, and after potentially damaging chemotherapy.

Male adults face relatively few problems, Copland says: "Sperm freezing is one of the most established methods of fertility preservation." Even if radiation or chemotherapy leaves a man sterile, his own sperm can be collected beforehand for use in in vitro fertilization (IVF).

For women, the obstacles are greater.

"The first question we ask is, do we have time?" Copland says. If a woman has a little time and a partner, her eggs can be gathered and fertilized and the embryos frozen. The largest group of such patients are women with breast cancer who have had surgery and are waiting to heal before they start chemotherapy.

That healing time can be used for IVF, though since IVF raises estrogen to many times its usual levels and some breast cancers are hormonally responsive, Copland works closely with patients' oncologists.

"We can take the medication to a level where the estrogen is only twice the woman's normal level," which oncologists find less worrying.

The embryos created through IVF can then be frozen -- a well-established practice -- until the woman makes her decisions about pregnancy. Some forms of chemotherapy leave women menopausal afterwards, so women without partners or donors may consider freezing eggs.

Duke is initiating a clinical trial to offer the investigational procedure, which is newer than embryo freezing and has lower pregnancy rates.

"All those freezing options require time [for stimulating and gathering eggs] and the comfort of her oncologist with increased hormone levels," Copland says. "What does not is freezing ovary tissue. If a woman is at exceedingly high risk of losing ovarian function, we can do a laparoscopic surgery to remove one ovary and freeze it."

Duke is in the process of joining the National Physicians Cooperative to Preserve Fertility for Female Cancer Patients, a multi-center study of ovarian tissue freezing, which is a more invasive and experimental procedure. It has generated babies only in women who also still had the other ovary, so it does not definitively work.

"You are investing in hope," Copland says.

Should a woman who has not chosen any of the freezing procedures turn out menopausal after treatment, she's still not out of options: she can try IVF using an egg donor. "I think for many women it's a relief to hear there are options afterwards," says Copland.

Copland and other Duke researchers are also studying the root causes of ovarian dysfunction after chemotherapy. Copland is collaborating on a grant to fund a study to follow patients through their treatment, measuring ovarian function markers to learn more about what's happening to their ovaries.

"That will give us better information than just 'this woman took chemo and didn’t get her period back, and this is how old she was.'"

Helping Hearts

Pamela S. Douglas, MDAcross the medical center, Pamela Douglas, MD, Ursula Geller Professor of Research in Cardiovascular Diseases, is studying heart disease in cancer survivors.

Anthracyclines, used in chemotherapy, cause heart weakening in many patients: "They can damage the heart muscle," Douglas says, "and can also damage blood vessels, leading to hypotension or kidney failure."

Newer targeted cancer therapies such as bevacizumab (Avastin) and trastuzumab (Herceptin) have also been linked to an increased risk of high blood pressure and heart disease.

Studies have shown that up to 4 percent of breast cancer patients taking trastuzumab have symptomatic heart failure and 10 percent have reversible heart problems.

Douglas is leading clinical studies to better understand the connection between cancer treatment and heart disease. "We have fairly crude measures" of the cardiac effects of chemotherapy, she says. "Heart failure is not the way anyone would like to diagnose a side effect."

So she's testing novel uses of echocardiography -- a noninvasive test that doesn't use radiation -- to see whether it does well at predicting which cancer patients might go on to heart failure.

More general trials include detailed cardiac monitoring of current cancer survivors to build up a database that could be mined for more evidence about which cancer patients develop heart disease and why.

Part of the reported increase in heart disease among breast cancer survivors may be simply a matter of numbers, Douglas believes: "Because the cancer cure rate is so high, people who survive are going to die of the kind of diseases that women who don't have cancer get."

The Exercise Connection

Lee Jones, PhD, co-director of Duke’s Tug McGraw Research Center, is studying a simple approach that could stave off the muscle atrophy that often accompanies cancer treatment—and possibly even cancer itself: exercise.Lee Jones, PhD, co-director of Duke's Tug McGraw Research Center, is studying an approach that could be used to stave off not only heart problems, but the muscle atrophy that often accompanies cancer treatment -- and possibly even cancer itself.

The miracle treatment? Good old-fashioned exercise.

Many cancer patients take catabolic steroids, which cause muscles to waste away, with major effects on their quality of life -- though "believe it or not we haven't got a good handle on how to quantify that," Jones says.

So, in a study funded by the National Cancer Institute, he is conducting strength testing and muscle measurement to study those effects over time among individuals with primary brain tumors.

"The next step will be to do biopsies and genetic screening" to isolate genetic markers for patients most likely to suffer severe wasting.

The data will also show when the wasting becomes most severe: "This will inform the timing and type of intervention that may have the most benefit," says Jones. "Say, we know this patient's going to experience muscle dysfunction, then we can be proactive and intervene before dysfunction occurs."

Regarding the cardiac disease so many survivors get, Jones is collaborating with Douglas to investigate whether exercise can prevent heart damage associated with certain types of chemotherapy and reduce the risk of cardiovascular disease in long-term survivors of breast and prostate cancer.

In a study funded by the Lance Armstrong Foundation, Jones is also examining the effects of exercise in patients undergoing active treatment for early-stage lung cancer, and says, "They're doing better, and they're feeling better."

The next study will investigate which type of exercise is most beneficial for these patients and whether exercise can impact long-term quality of life as well as overall survival.

But Jones is most excited about whether exercise can itself help shrink tumors: "Put a tumor in a mouse, exercise the mouse, and the biology of the tumor will change."

He's now working with breast cancer patients in a novel study investigating whether exercise can improve chemotherapy's effectiveness in killing breast cancer cells. "This will be the very first study to look at the effect of exercise on the tumor itself in a human," says Jones.

"If exercise can help chemotherapy work better but also protect your heart and the rest of your body from the harmful effects of the chemo at the same time, it would be just fantastic."

It would also be a great example of the direction in which cancer care is going -- with care focused on not only beating the disease, but helping people continue to triumph in the many battles, small and large, they will face in the months and years after their diagnosis.

And as Jones and his fellow clinicians and researchers transform the landscape of care for a new generation of cancer survivors, they are helping patients close in on the goal every one of them has held since the beginning: surviving -- as well and as long as possible.

This article was first published in the Summer 2008 edition of DukeMed Magazine.

Sleep Chasers

Thu, 21 Feb 2008 16:23:39 -0500

Move over, Manhattan. It used to be that, outside of the world's most urban areas, the night belonged only to stoics like doctors on call, cops, and truck drivers.

But now that so much of modern culture and commerce aspires to 24/5/365, the sleepless most anywhere in America can pass the night from the 24-hour Wal-Mart to the 24-hour Kinko's to their 300-channel cable TV and the World Wide Web, where it's always daylight somewhere.

Want to wake up in a city that never sleeps? You probably already do.

Perhaps that’s why sleep medicine, once something of a backwater specialty, is now experiencing an unprecedented heyday. In a clear sign that the specialty has arrived, the American Board of Medical Specialties began offering physicians board certification in sleep medicine just last year.

“I think sleep is in the public consciousness,” says psychiatrist Andrew Krystal, MD, who directs the sleep research program at Duke. “It’s hard for me to believe that people are sleeping worse now than they were a few decades ago, but it seems that people are talking about it more. Ambien is a household word now, like Prozac.”

In the Triangle, while growing ranks of insomniacs fill clinicians’ offices, sleep labs are running ever-more recordings of the squiggles and lines that describe the landscape of nightly repose—or the fitful lack thereof. The Duke Sleep Disorders Center—one of the country’s oldest, and one of the few in the nation that offer faculty expertise in neurology, pulmonology, psychology, and psychiatry—moved its clinical sleep laboratory to Durham’s Millennium Hotel in November 2005.

The new setting not only provided patients with a less hospitalized and more amenitized way to undergo a sleep study, but also upped the number of beds, in order to accommodate increasing referrals from physicians and patients themselves. It seems that the long-sung refrain of sleep medicine experts is finally catching on: How can we ignore any chronic disruption in something that all of us are wired to spend a third of our lives doing?

A Strategy for the Bed Battlefield

By far, the number-one disorder of sleep is its painful absence. We live in a sleep-deprived culture, but beyond our self-imposed sleep debt, on any given night at least a fifth of our populace is watching the alarm clock in waking misery. There is good news for those with chronic insomnia: there’s a well-proven, drug-free treatment that works well for the majority of patients. The bad news? Only about 100 psychologists in the country are trained and board-certified to provide it.

Andrew Krystal, MD, (left) and Jack Edinger, PhDOne of them -- Duke sleep psychologist Jack Edinger, PhD -- pulls a dust-covered briefcase from the corner of his office in the Durham VA Medical Center, opening it to display a tool from the early days of this now-proven prescription for insomnia, cognitive behavioral therapy (CBT).

“It’s a timer with an alarm on it, and a tape recorder,” Edinger says of the circa-70s machine. “It was set up to beep, very softly, several times throughout the night; when it beeped it would turn on the tape recorder, and the patient had 10 seconds to say ‘I’m awake.’ Then in the morning you could reconstruct the night of sleep or wakefulness.” The device was among the tools used by a small group of researchers, including Edinger, to develop and prove the effectiveness of CBT for insomnia.

“It’s not rocket science,” says Edinger of his craft, but it is one that was painstakingly designed to target and disengage the behaviors and anxieties that can perpetuate sleeplessness. Most people with chronic insomnia are stuck in a self-perpetuating loop: their anxiety about not getting enough sleep keeps them hyper-aroused at night, both mentally and physically. Meanwhile, they’ve altered their sleeping habits -- napping, fiddling with their bedtimes, and so forth -- in an effort to coax more sleep out of their days. This sort of sleep-chasing ultimately interrupts the homeostatic drive of the body’s sleep system.

“CBT helps them right the ship again,” Edinger says. “And once they are in treatment, it’s easy for the patients to see what they need to change. Conceptually, it’s not a tough disorder to treat.” A recent study at the Durham VA Medical Center showed that people with primary insomnia who undergo cognitive behavioral therapy have excellent success rates -- 75 percent experience remission.

The caveat is that sleep research to date -- and this goes for both CBT and pharmacologic research, notes Edinger -- has focused almost exclusively on primary insomnia, meaning insomnia that occurs in the absence of other illnesses, chronic pain, and substance abuse. While people with this type of insomnia number large, they comprise only about 20 percent of all insomnia sufferers.

Edinger and other sleep psychologists at Duke are working to tweak the CBT model for patients whose insomnia is confounded by other conditions. According to current research, including three studies at Duke, the management of one hinges on the other. “If you look at people with depression, those with prominent comorbid insomnia problems are generally more difficult to manage and treat,” Edinger says.

“They also have a greater propensity toward suicide, and if you treat the depression effectively but there is residual insomnia, they’re more likely to relapse.” Conversely, treating insomnia along with depression seems to vault a patient’s progress forward. Research shows that both anxiety disorders and chronic pain are also linked with insomnia in this way: to treat any of the conditions effectively, you must treat them all.

Tangles in the Bedsheets

But there are times, says Duke neurologist Aatif Husain, MD, when a patient complaining of insomnia may actually have an entirely different sleep disorder. Husain is one of the physicians who read sleep studies at Duke’s lab at the Millennium Hotel -- one of the few in the area staffed entirely by physicians who are board-certified in sleep medicine.

In many cases, he says, the real culprit is another of the wide range of sleep-disrupting problems patients present with. Some suffer from REM behavior disorders, in which sleepers act out fearful, violent dreams at great peril to themselves and their bed partners (and which has now been linked to a subsequent onset of Parkinson’s disease).

Others have narcolepsy, which often plagues patients for 10 years before they get a proper diagnosis. That’s because most of the time its main symptoms -- fatigue and daytime sleepiness -- start in the teenage years, when fatigue and sleepiness are likely to be glossed over as the throes of adolescence or treated as symptoms of depression.

“Unless a diagnosis is made early on, it can have long-lasting consequences for these patients’ lives,” says Husain, “since they may underachieve during important academic years in high school and college.” He says that a physician can spot signs of narcolepsy in the patient history: if someone says she doesn’t sleep well at night and reports having dreams during short naps (15 to 30 minutes), she may need further evaluation.

A more common cause of sleep disruption is restless leg syndrome (RLS). Hallmarked by nighttime movement of the legs and a creepy-crawly sensation that can torment patients trying to sleep, RLS may be a disorder of dopamine levels in the brain -- much like Parkinson’s disease. In fact, Husain notes that many Parkinson’s disease patients have restless leg syndrome -- though the converse is far from true.

Husain participated in the international testing of the two medications currently approved for the treatment of restless leg syndrome, both of which are also prescribed for many Parkinson’s disease patients, although at a much higher strength. In some cases, the treatment can be as simple as an iron supplement, because there is a high incidence of low iron levels among patients with RLS. “Patients really see a significant day-to-day benefit from these treatments,” says Husain.

Breathless Nights

Even more common than RLS in patients visiting sleep labs is obstructive sleep apnea, says neurologist Rodney Radtke, MD, medical director of the Duke Sleep Disorders Center. Sleep apnea affects about one out of every 10 people, and because obesity often triggers the condition, that number could be on the rise. But Radtke emphasizes that it is not strictly a disorder of obesity: “One 300-pound man may have it while another doesn’t. And a 170-pound man may have it while a 300-pound person doesn’t.”

The toll obstructive sleep apnea takes on a sufferer of any weight can be extreme, and sleep-study footage of the condition is almost painful to watch: Over and over, the sleeping patient stops breathing; then, as the oxygen levels in his blood drop, he rouses from sleep with a jarring gasp, his heart rate leaping high as he hyperventilates. The same episode repeats and repeats, eerie quiet followed by frantic gasping.

What’s unseen on film, says Duke pulmonologist Ambrose Chiang, MD, is how this grim cycle triggers the body’s sympathetic system and increases oxidative stress, leading to endothelial cell dysfunction and systemic inflammation. This is why sleep apnea not only strains the heart but also can play a role in atherosclerosis, insulin resistance, and glucose intolerance, as well as a host of cardiovascular complications from refractory hypertension to atrial fibrillation.Aatif Husain, MD, Rodney Radtke, MD, and Ambrose Chiang, MD

“It’s such an important disease, and it affects so many organ systems,” Chiang says, noting that it’s also among the most common causes of motor vehicle accidents in which drivers fall asleep at the wheel.

The condition also brings with it a buffet of unpleasant complications that can raze the sufferer’s quality of life, from headaches and acid reflux to erectile dysfunction and nocturia (frequent nighttime urination), which is triggered by the heart’s chemical release when the body strains to breathe against a closed airway. But because it is usually these accompanying complaints that drive patients to the practitioner, most of the time, Chiang says, the sleep apnea is not picked up. “Nocturia in particular is often misattributed to fluid intake, diuretics, or bladder or prostate problems,” he says. “Many physicians don’t know that it can be a sign of sleep apnea.”

Test of the Evil Tongues

In many cases, people who seek treatment specifically for sleep apnea are those whose bed partners have lain awake beside them, listening for their absent breathing. Chiang believes that certain patients should be screened for sleep apnea as a routine.

“Though we don’t have the studies to support this yet, it’s my opinion that every cardiac inpatient should be evaluated for sleep apnea before they are discharged,” he says. “When folks come in for an acute cardiac event and we send them home without catching their sleep apnea, they may wind up coming back.” Likewise, he says, every hypertensive patient, every obese patient, and every insomnia patient should be screened. “ It makes good clinical sense to assess the possibility of sleep apnea in these patients -- because there are a lot of patients that we could be treating that we’re not.”

But all of these patients can’t just grab a sleep study on their way home, so Chiang hopes to improve in-office diagnostic tactics. He is working to devise an easy-to-use scoring system that could flag possible obstructive sleep apnea patients, based on the patient’s history, symptoms, craniofacial profile, and a good physical exam of the upper airway.

“If we do it right, a user-friendly scoring system could make it possible for a sleep apnea screening to be done by a physician’s staff, or nurses in a hospital,” says Chiang. “And if we can achieve this, then we’ll be able to pick up these sleep apnea patients early instead of 10 years down the line.”

Chiang shows a slide to illustrate how clearly some of the physical characteristics of sleep apnea can be identified. The slide, which he titled “The Evil Tongues,” shows six pinkish tongues displayed dragon-style, whose edges look nearly the shape of a piecrust. This kind of noticeable tongue scalloping suggests that the tongue may be too big for the mandible, and therefore likely to shut off the airway when that person sleeps.

Similar physical signs of apnea can be seen in the narrowness of a patient’s posterior pharynx or the size of his uvula or tonsils. Even facial features such as a small, receding chin or a pronounced overjet (overbite) can signal a potential obstructive apnea. “The upper airway examination has traditionally been ignored,” says Chiang. “A brief, focused upper-airway examination can be very enlightening, and it takes no more than two minutes to do.”

Patients Unmasked

While weight is a significant contributor to obstructive sleep apnea, it usually takes major weight loss to have a significant impact, Radtke says. But like insomnia, obstructive sleep apnea already has an interventional therapy that works for most people: nasal CPAP (continuous positive airway pressure) delivered via a soft plastic mask that fits over the nose.

“If you wear it, it works,” says Radtke. “CPAP became commercially available in 1985, and we have people who have been on it for 22 years. They’ll jokingly say things like, ‘You can have my wife, but you can’t have my machine.’ It really brings a marked benefit to their lives.”

In fact, the only patients who don’t benefit from CPAP are those who don’t wear the mask. “People who have severe apnea are remarkably compliant, because of the change in their ability to stay awake and energetic during the day,” says Radtke. “They get the immediate reinforcement of feeling great. But in the mild apnea patients, who get only a modest benefit in terms of how they feel, it can be hard to put up with the aggravation of CPAP over the long haul.”

Radtke says that in these mild cases compliance is only 70 percent at best, and sometimes as low at 30 percent. “Most 40-year-olds don’t like the vision of themselves going to bed every night with a mask on.”

Husain says that the more a patient understands about the health implications of stopping breathing 50 times an hour, the better his CPAP compliance becomes. Duke’s year-old sleep apnea/CPAP clinic was developed in part to make sure that these patients understand the importance of what the perhaps ungainly equipment is doing for them.

“Our sleep technologist works with patients to make sure they have the best-fitting mask and to solve any issues of discomfort, as well as to provide education,” Husain says. The clinic also streamlines the CPAP process for both patient and referring physician. “We arrange for the CPAP equipment to be sent to the patient’s home, and we conduct follow-up appointments and further testing when needed,” he says -- which serves the patient and saves the primary care physician potential logistical nightmares.

“When I order CPAP I have to send a prescription to a home health company, and they get the machine to the patient. But different insurance companies deal with different home health care companies, and most physicians don’t have any cause to know which works with which. It can take a lot of navigation to sort it all out.”

Educating More Bedfellows

For both apnea and insomnia, the greatest challenges aren’t in discovering treatment, but in getting the treatments to more patients. “Most patients who seek treatment for insomnia do so in a primary care setting,” says Edinger, “where the most they are likely to get is a sleep medication. Ultimately we want a model of CBT that would be practical for primary care physicians to use.”

He says there are now studies under way to look at different ways of providing CBT through nurse providers, physician assistants, or even Internet delivery systems. “In Holland they did behavioral interventions via TV,” he says. “That kind of delivery isn’t as effective as one-on-one CBT in a clinic setting, but for what it was they actually did fairly well -- and they reached thousands of people.”

Krystal is trying another tactic: educating physicians online. “We know that physicians can improve how they manage their patients in general when they improve how they manage their patients’ sleep,” he says, but clinicians in the field currently don’t get much in the way of training to do so.

To remedy that, Krystal and two colleagues, Thomas Roth, PhD, at Detroit’s Henry Ford Hospital and Daniel Buysse, MD, at the University of Pittsburgh, formed the Sleep Medicine Education Institute, a non-profit organization that disseminates sleep medicine research findings and provides continuing medical education credit on insomnia, restless leg syndrome, and sleep apnea. The organization is funded in part by pharmaceutical companies, but the content of the information is not influenced by industry.

“It’s a means of education in which the educator is in no way compromised by commercial interests,” he says. “It allows physicians to hear from the people who are actually doing the research.”

Krystal hopes that this and similar education venues will help improve care for the hordes of patients still awaiting a consistent night’s rest. “Sleep medicine is still an area where we’re not getting any better at making the problems go away,” he says. “But we are getting better at treating it. There are effective methods out there to help people with sleep problems -- we just need more people who are trained to provide them.”

This article was first published in the Winter 2008 edition of DukeMed Magazine.

Mending Hearts

Wed, 30 Jan 2008 16:15:55 -0500

For years, Deloris Gibson had felt tired -- exhausted, really. Her doctors thought it might be allergies. Then, four years ago, when Gibson was 64, her problem worsened. “To get the dishes done, I’d do one pan and stop for an hour and rest, then do another one,” she says.

She went to a pulmonary specialist, and bought a home oxygen saturation monitor. She found that her oxygen level was at times dropping to a dangerously low 70 percent (a level greater than or equal to 90-94 percent is considered normal). She had a diagnostic catheterization, but it revealed nothing definitive. Her doctors put her on home oxygen.

In 2006, Gibson was at her sister’s house, making the Thanksgiving dressing, when she felt especially tired. “I measured my oxygen, and it was 68,” she says. She slept through Thanksgiving and two days beyond, waking only to eat. Her family wanted to hospitalize her, but she waited until she returned home to North Carolina and went back to a pulmonary specialist, then to a cardiologist, and had another diagnostic catheterization.

Gibson’s cardiologist referred her to Duke because he suspected her problem was caused by a heart defect called a patent foramen ovale (PFO). “The best way to think about it is as a trap door in the wall in the heart,” says John F. Rhodes Jr., MD, chief of clinical cardiology in Duke’s Department of Pediatrics. The opening should close sometime after birth, but in 25 to 30 percent of people it remains open.

PFOs often go unrepaired because they are considered normal. “Unfortunately, in some people, PFOs can become pathologic,” Rhodes says. “In people with hypoxemia [low levels of oxygen in the blood] we think the hole opens up, and all the blue blood goes across, causing the pink blood to be unoxygenated.”

John F. Rhodes Jr., MDFor Gibson, Rhodes performed a catheterization to close the PFO with a Dacron-and-metal patch about the size of a quarter. Today, for the first time in years, she doesn’t depend on supplemental oxygen. “Dr. Rhodes thought I might be on oxygen part-time, but I don’t need it,” she says. In addition, she’s been able to have knee surgery that her doctors previously considered too dangerous because of her low oxygen levels.

Gibson gets tears in her eyes when she talks about all the things she can do now -- paint her kitchen, mow her one-and-a-half-acre lawn with a riding mower, and travel. “I thank the doctors and everyone at Duke with all my heart -- including the patch over it,” she says.

From Surviving to Thriving

Fortunately, most patients with congenital heart defects don’t have to wait as long as Gibson did to reap the rewards of detection and treatment. In fact, the average age at which treatment begins has steadily dropped over the years -- and many heart abnormalities are now being identified before babies are even born.

Even better news for the estimated 40,000 infants born with heart defects each year in the United States is that improved diagnostic and repair techniques have enabled defects previously associated with high mortality to be successfully treated. From 1993 to 2003, death rates for congenital cardiovascular defects declined 31 percent, according to the American Heart Association.

“A number of heart defects that were previously considered fatal can now be treated surgically with good results,” says James Jaggers, MD, associate professor of surgery. For example, for children with single ventricle defects, in which one of the heart’s pumping chambers is underdeveloped, the survival rate 10 to 15 years ago was less than 50 percent. Today, the survival rate has risen to 85 to 90 percent.

Now that mere survival isn’t a luxury, many patients grow up with their cardiac team. Today, care focuses on helping patients of any age to thrive. At Duke, patients benefit from physicians’ experience in the most complex cases, access to a steady stream of new treatments and devices available only through clinical trials, and a team that follows a patient for as long as it takes -- often into adulthood.

Diagnosing Defects Before Birth

At Duke, physicians use ultrasound routinely to detect birth defects before babies are born. “If defects are identified early, then the baby’s delivery can be coordinated at a tertiary care center, where ICUs and neonatal and cardiology support are available,” says Jennifer Li, MD, chief of cardiovascular research in the Department of Pediatrics and an associate professor of pediatrics. “It’s also easier on the family because they learn earlier what is going on with their child and can have a consultation to find out if there are other abnormalities.”

Angelo Milazzo, MD, of Duke Children’s Cardiology of Raleigh, uses telemedicine to provide answers for expectant mothers and other patients as soon as possible. While an ultrasound or echocardiogram is performed in the Raleigh office, colleagues at Duke can see the images in real time and discuss them with Milazzo and the sonographer. Milazzo also uses telemedicine to consult live with doctors whose patients are having these tests performed at outlying community hospitals.

“Fetal ultrasounds are very complicated, technically difficult studies to do because you’re at the mercy of the position of the baby and several other factors,” Milazzo says. This is especially true when a baby is suspected to have a complex condition such as hypoplastic left heart syndrome, which represents a spectrum of different but related kinds of heart disease. “No two of these patients are alike, and it can be very difficult prenatally to determine exactly what variant the baby may have,” Milazzo says.Angelo Milazzo, MD

“We’re a full-service pediatric cardiology office, and we’re able to do the test and give the results that day. But if we have a very complicated case or a clinical question that we feel needs multiple opinions, by using telemedicine, we can do that at the time of the visit. We don’t have to say, ‘I want to discuss this with my colleagues, so I’ll bring you back in a month.’ That’s very helpful because these women are often scared to begin with because they’ve been told there may be something wrong with their baby’s heart. It’s important to give them information because they may have to make difficult decisions,” Milazzo says.

Improving Outcomes

After a defect is detected, often it is repaired through either cardiac catheterization or surgery. Duke has become a leader in both methods. Duke’s pediatric interventional catheterization lab is the busiest in North Carolina, performing 600 procedures in 2006. The pediatric surgical program has the highest volumes in the state, performing 380 surgeries in 2006.

And though Duke often handles complex cases, outcomes are superb. Out of dozens of U.S. programs involved in the Society of Thoracic Surgeons congenital heart national surgical database, Duke has one of the most complex patient populations but still has one of the lowest mortality rates, Rhodes says: “Our outcomes are as good as anywhere.” Adds Jaggers, “We specialize in taking care of the most complicated cases with excellent results that rival anyone in the country.”

One factor in that success is the ability to perform more complete repairs when patients are babies. “We do a significant number of operations on premature infants -- children as small as three-and-a-half pounds with very complex heart defects,” Jaggers says. In the past, doctors would perform smaller, temporary repairs early in life, then bring the patient back later for a bigger surgery. “Now, we tend to do a definitive repair at an earlier age,” Jaggers says.

In addition, Rhodes and Jaggers point to improved management in both the operating and recovery rooms. Developing best practices that are uniformly used has meant that patients spend less time on the breathing machine and suffer fewer side effects from surgery, such as strokes or neurological injury. “We’re interested in not only getting kids through surgery, but getting them through functional and whole,” Jaggers says.

Jon Meliones, MD, director of the pediatric ICU at Duke, has led these efforts, including a formalized procedure for transferring patients from the operating room to the ICU. First the surgeon conveys the results of the procedure, then the anesthesiologist gives a report, then the nurse repeats the information back, and the ICU physician clarifies with questions.

“Before, people would begin talking without having a plan of what they were going to say,” Meliones says. “Now, the team comes in, and we do the handoff using very scripted, stylized communication, and it happens the same way every single time.” The procedure is modeled on those used in the aviation industry to reduce crashes. Duke has won several awards for quality for this procedure, including a scientific award from the Society for Critical Care Medicine. Articles on these procedures have been accepted for publication by the Agency for Healthcare Research and Quality.

Though repair of defects is the mainstay of treatment, care does not end there. Duke’s team of nurses, genetic counselors, doctors, and others work to treat the whole patient. “We’re looking more comprehensively at patients and thinking about the genetic causes of their heart disease, their neurodevelopmental outcomes, and how we can help maximize their developmental potential,” says Stephanie Wechsler, MD, who runs Duke’s specialized cardiovascular genetics clinic. “We are moving well beyond just survival to look at what we need to do to help these kids have as full a life as possible.”

Stephanie Wechsler, MD Wechsler sees patients with congenital heart disease that accompanies other birth defects, patients with cardiomyopathies that may have a genetic basis, and patients who may have a connective tissue disorder such as Marfan syndrome. Children with congenital heart disease as well as other congenital anomalies can often benefit from finding out if they have a named genetic syndrome or chromosomal abnormality.

“That can be helpful both for planning care for the child and for letting the family and pediatrician know about other health problems that might come up in the future,” Wechsler says. In addition, Wechsler and clinic coordinator Elizabeth Melvin, a certified genetic counselor, counsel families about the possibility that current or subsequent siblings may also have congenital heart disease.

Additional support comes from nurses, social workers, and even parents of other patients. Robin Wilson, a pediatric cardiology nurse at Duke, helped start a Triangle-area chapter of Mended Little Hearts, a support program for families of children with congenital heart disease. At weekly meetings held at Duke, parents receive support from each other as well as information from a guest, such as a dentist who provided heart-healthy dental care tips.

Watching Patients Grow

As treatment has improved, more and more patients with congenital heart disease are growing into adulthood. Ronald J. Kanter, MD, who specializes in treating heart rhythm problems, has followed some patients for as long as 20 years. For one patient, who first came to Duke when he was 15, Kanter has implanted three pacemakers over 15 years. “He’s now married and has a kid,” Kanter says.

For such patients, Duke offers one of the nation’s few specialty clinics providing comprehensive treatment for adult congenital heart disease. The clinic includes pediatric cardiologists such as Kanter and Rhodes, adult cardiologists, cardiovascular surgeons, and other specialists in adult congenital heart disease. Patients include a few who, like Gibson, have heart defects that were not repaired in early life.

But many have had complex defects repaired during childhood and still need ongoing care. Such patients may have recurring or new problems that can require additional surgeries or procedures to repair valves, blood vessels, or holes in the heart using new non-surgical techniques in the cardiac catheterization laboratory. They can also develop heart rhythm problems related to scars from prior surgeries, which may also be treated with catheter-based procedures, Kanter says. And, adds cardiologist Thomas Bashore, MD, “As patients get older, they may develop heart problems that affect everyone, such as hypertension, coronary artery disease, or diabetes. These issues can further complicate their overall care.”

The clinic offers services such as genetic counseling, referrals for vocational counseling, management of issues that might arise during pregnancy, clearance to participate in sports, and comprehensive imaging techniques, such as echocardiography, cardiac CT, and cardiac MRI, to diagnose and follow these patients. Specialized services also include the newest treatments for pulmonary hypertension offered in collaboration with Duke pulmonologists.

Kanter remembers having to tell a high-school senior that he had to stop playing on his school’s basketball team. “When I met with him, I realized he had a valve disease that made it unsafe for him to continue to compete at high-level sports until we dealt with it either with a catheter-based procedure or surgery,” Kanter says.

But the teenager desperately wanted to play in his homecoming game. Kanter, despite his reservations, trekked down to the gym with a portable defibrillator to supervise while the teen played in one last game. “I felt we could take whatever minimal risk there was, and let him play, and I could be there in case he had a life-threatening heart rhythm episode,” Kanter says. Fortunately, Kanter didn’t need to use the defibrillator -- and the boy’s team won.

“I realized that like many things, in medicine there is opportunity for compromise,” Kanter says. “We have to take into account more about the patient than just their physical problem; we have to take into account their developmental level and emotional status as well.”

For more information on congenital heart disease treatment at Duke, call 919-681-2916 (general information) or 919-668-4000 (appointments and referrals).

This article was first published in the Winter 2008 edition of DukeMed Magazine.

The Sports Team

Mon, 11 Feb 2008 15:55:52 -0500

One youth chases another at furious speed, and when he catches his quarry grabs him by the shoulders and flings him mercilessly to the hard earth. The contact between boy and ground creates a sound so clear you can envision it in large, bright letters: THUNK! MMMMPH!

The tackled boy, being an adolescent and thus immortal, rolls, jumps up, and trots back to his team’s huddle, probably with a smile hidden inside his football helmet that says, “Hit me as hard as you want. That was 30 yards, and I’m about to get 30 more.” And so the running, hitting, falling, twisting, and blocking -- the continuous, jarring impact -- rolls on into a cold autumn night as boys from Charles E. Jordan High School in Durham and Garner High School battle for glory in the state’s high-school football playoffs.

On the sidelines pace a number people who understand the possible consequences of that impact, have helped the boys prepare for it, and are ready to respond if a boy can’t jump up from a blow.

Claude T. Moorman, MD -- who goes by his middle initial -- is the director of the Duke Sports Medicine Center and an associate professor in the Division of Orthopaedic Surgery. Claude T. Moorman, MD, at the Jordan vs. Garner high school football gameJust before halftime, he squats before a boy on the bench who had come out of the game with a neck “stinger” several minutes earlier. He supports the boy’s wrists lightly and has the boy raise his arms to shoulder level, with his elbows at horizontal 90-degree angles. The boy doesn’t wince, but he looks tired and disappointed. Moorman gives him the OK, and the boy trots to the locker room with his teammates.

Duke Doctors, Local Athletes

Seven years ago, Moorman helped create Duke’s outreach into area high school athletic teams. Duke supplies them with orthopaedic physicians, primary care physicians, and certified athletic trainers or physical therapists, for free. Depending on the needs of the school, they might consult with coaches and school-based certified athletic trainers during the week, but at the least every Friday night in autumn they’re at football games, either at home or away, and they often attend the home games of a school’s other sports.

The program now reaches nine high schools in Durham County and one each in Orange and Wake, and Duke certified athletic trainers are at Durham middle school football games every Wednesday during the fall. Duke also supplies physicians for North Carolina Central University games -- and, of course, for the Blue Devils.

Usually orthopaedic residents also attend the high school games, but on this night the residents are studying for their training exam the next day. It’s a rare night off -- they must serve at 20 sporting events during their residency year, whether or not they intend to practice sports medicine as a subspecialty. Why? It’s simultaneously a service to the community, a living lab of bone-jarring impact, and way to form connections between Duke and the world beyond its walls. It’s also good preparation for the sports-related injuries the residents will likely see in their future practices.

“Hit ’em again, harder,” chant the cheerleaders to a cold crowd, as if to remind the absent doctors that they will have no shortage of patients.

The K Factor

The Duke Sports Medicine Center is built around four pillars: a sports medicine clinic, physical therapy services, a sports performance program, and research in the Michael Krzyzewski Human Performance Lab -- the K-Lab. The center, in various forms, dates back 70 years and has pushed the boundaries of orthopaedic medicine through its focus on people placing maximum stress on their musculoskeletal systems. In recent years it has greatly expanded its efforts along a continuum that ranges from research through clinical treatment to sports performance training.

Among its newer components is the 10-year-old K-Lab, directed by Robin Queen, PhD. On this particular day, participants in a K-Lab study are preparing to perform simple exercises, such as climbing a step. Small reflective markers are attached to the outsides of their knees, ankles, and hips. Eight cameras around the room capture the movement from the markers and feed computers that create digital representations of the motion of their joints.

Queen, with a doctorate in biomechanics, and researchers from Duke University Medical Center are studying several orthopaedic issues in the K-Lab. For example, three Duke specialists in hip replacement surgery utilize three different surgical approaches for reaching the hip: posterior, direct lateral, and modified anterior lateral. Each involves cutting different muscles. Outcome studies to date -- by various researchers around the country -- have been based on patient satisfaction surveys.

Improving Patient Outcomes

In this study, for which Queen serves as the principal investigator, patients who have undergone hip surgery will be examined to determine whether they have returned to walking normally. Their movement will be compared to that of a control group measured in the K-Lab. Members of the control group have been chosen to match the age, weight, gender, and other characteristics of the group that has undergone surgery.

Initially, Queen’s group is looking at patients post-surgery, but eventually the gait and movement of patients will be examined before surgery in order to compare movement before and at several milestones after the operations.

The logic is as clear as the sound of high-school athletes hitting hard ground. Patients will be compared to healthy, normal controls in order to evaluate the success of their operation in returning them to normal movement. “We’re looking at what the numbers say in addition to what the patients say,” Queen says.

Few if any similar studies have been undertaken anywhere -- likely, as Queen notes, because scientific disciplines often operate independently. “It’s a novel concept to combine biomechanics with clinical outcomes,” she says.

The same idea drives studies of hip resurfacing. Patients who have undergone either hip replacement or hip resurfacing will be compared to healthy controls, with researchers examining such indicators as hip flexion angle, range of hip flexibility, and degree of hip hike.

A similar study is evaluating ankle replacements. And as the K-Lab builds databases of movement of various aspects of the musculoskeletal system, they could be applied to future studies.

The K-Lab also plays a vital role in collecting kinematic and kinetic movement data on patients who have knee osteoarthritis in an attempt to understand how the disease alters movement patterns. “We’re looking at gait mechanics as a functional outcome following a clinical intervention of weight loss and pain management,” says Queen. This work is part of a larger NIH-funded Program Project Grant directed by Farshid Guilak, PhD, who heads Duke’s Orthopaedic Bioengineering Lab.

The knowledge generated by these studies is published in scientific journals and makes its way into the practice community through traditional routes. But the K-Lab itself also is used for immediate clinical applications, such as assessing athletes to help them improve sports performance. (see article: The Science of Sports Performance)

Not Just for Pros

With the attention paid to athleticism at Duke Sports Medicine -- and its location in the heart of the Duke athletics complex, right next to Wallace Wade Stadium -- it is almost a surprise to walk through the clinic, with its standard-looking examining rooms, nurses’ station, and x-ray rooms. But while the Center has an obvious focus on sports-related medicine, it is not just for competitive athletes -- the team here can help anyone with musculoskeletal injury or pain who seeks to be more active than his or her medical condition currently allows.

In addition to straightforward sports-related orthopaedic services, the medical and therapeutic staff provide services specifically focused on women’s sports medicine, pediatric sports medicine, sports psychology, primary care, and rheumatoid arthritis treatment, plus an extensive on-site physical therapy program that enables seamless post-surgical care and rehabilitation.

In fact, the majority of the patients seen here aren’t professional athletes, or even necessarily serious amateurs. Most patients are self-referred, many of them simply active people who have injured themselves or people looking for help with medical problems such as osteoarthritis. On a recent day an older man with a leg brace was leaving his appointment while a young father with his elementary-school age boy were checking in.

“We’re somewhat like a ‘space program’ for orthopaedics,” says Moorman from his office overlooking the football stadium. “Athletes are always looking to break barriers that you and I don’t generally approach, and in sports medicine you get to work with problems and treatments at the edge of the scientific field. One of the results is that sports medicine has driven the development of treatments that have eventually become the gold standard for the rest of us, like minimally invasive surgical techniques and early motion, minimal stress recovery therapies.”

For example, recovery from ACL repair once took a year but now takes three to four months, thanks in many ways to practices developed for athletes. Sports medicine has also supported advances in soft-tissue healing, such as contributing to findings that the body overshoots the mark in healing and causes overinflammation, which can be mediated by anti-inflammatory agents.

Some sports medicine research even makes its way into the commercial arena. The K-Lab, for example, has provided data to help Nike improve the safety and performance of cleats and other athletic footwear. And recently Duke Sports Medicine has been involved in testing a new way to deliver electrolytes -- via an oral strip against the gums.

“When you’re active, your blood goes to your extremities, away from your GI tract, which cuts down on your body’s efficiency in absorbing electrolytes delivered through drinks -- which, of course, is the way they’ve traditionally been delivered,” explains Moorman. “People have wondered if there was a more efficient way of delivering them so that they would spread to your muscles more effectively. This strip appears to do that and decreases cramping significantly.”

The need for better delivery systems for professional athletes, who spend hours in intense activity, seems self-apparent, but the same need may exist among boys and girls who are physically active, especially those in warm climates. The number of school-age athletes has doubled over the past 10 to 15 years, says Moorman, due in large part to the influx of young women into sports.

Focus on Women

That growing population of young female athletes has resulted in the need for more sports-medicine research and treatment focused on women. Just down the hall from Moorman’s office is the office of Alison Toth, MD, who launched Duke’s Women’s Sports Medicine Program in August 2001.

The program quickly became a national hub for the growing movement to teach women and clinicians to recognize and prevent problems that plague active females -- whether they’re young Olympic hopefuls or senior citizens who want to resume a walking program after a fracture. The Duke program was one of the first three in the country to focus specifically on women in sports and has the capability to diagnose and treat injuries that are unique to women, that manifest themselves differently in women than they do in men, or that require interventions specific to women.

Like the rest of Duke Sports Medicine, the Women’s Program isn’t just for jocks. “Our practice is for anyone who has musculoskeletal problems and wants to stay active, whether through sports, walking for exercise, or simply being able to reach overhead and comb her hair,” says Toth. “We can help people maximize their ability to stay active and remain injury-free.”

That’s the common thread among people who come to Duke Sports Medicine, it seems, whether they’re pro athletes, active seniors, or soccer-crazy kids. All seek to improve their physical capabilities in an atmosphere that helps them push their limits.

Friday Night Lights

On the football field, boys are pushing their limits in order to keep their season alive, one game at a time. Ron Olson, MD, walks the sidelines of the field on that cold Friday night. Olson, the Duke primary care physician working the game this evening, has a long history in sports and sports medicine and describes himself as a semi-serious athlete. In addition to helping with the outreach program and the Duke primary care sports medicine fellowship, he looks after a few other teams and travels with the U.S. Ski Team to Europe for a week each year. As Moorman attends to a player on the bench, Olson jokes, “We let the orthopaedics people be the first responders at these games.”

Ron Olson, MD Not far away is Alanna Cooley, a Duke physical therapist and certified athletic trainer assigned to the Jordan teams. In the mornings she sees physical therapy patients at the Duke Sports Medicine Center, but afternoons are often spent at the large Durham high school, working with Jordan’s athletic trainer, Gail McMurry. At the game, both she and McMurry carry packs containing bandages, tape, scissors, gloves, and other tools to take care of small injuries.

This evening all the injuries are minor. The staff get to enjoy the game. Jordan loses, however, and so its season -- and the Duke staff’s attendance at its Friday night games -- are over for the year.

But basketball season is starting. And wrestling.

“We may even see some of these kids at the Saturday clinic tomorrow,” says Moorman as the game winds down.

Then his own team packs up and heads home for the weekend.

This article was first published in the Winter 2008 edition of DukeMed Magazine.

Meet the Dean: Nancy C. Andrews, MD, PhD

Tue, 17 Nov 2009 11:16:28 -0500

From the legendary Wilburt C. Davison to the recently promoted R. Sanders Williams, the six former deans of Duke University School of Medicine have, to a man, been exceptionally talented physician-scientists, educators, and leaders -- passionate advocates for the advancement of medicine in general and Duke medicine in particular.

Dean No. 7 is no exception.

Called "a leader who is able to take programs, organizations, and people to new heights" by her mentor David Nathan, MD, president emeritus of Dana-Farber Cancer Institute, "one of the nation's most accomplished physician-scientists," by Williams, now senior vice chancellor for academic affairs at Duke, and "the best candidate in the country for this position," by Chancellor Victor J. Dzau, MD, Nancy C. Andrews brings to her new post a record of experience and accomplishment that clearly establishes her place in the pantheon of Duke Med deans.

There is, of course, one notable difference between this dean and her predecessors: she's a woman.

As the first female dean not only of Duke’s medical school, but at any top-10 medical school in the United States, her appointment created a buzz that expanded beyond academic circles to over 200 media outlets nationwide, from the Wall Street Journal to NPR.

DukeMed Magazine recently talked with Andrews about all the attention -- and where she’ll be focusing her attention as Duke’s next dean.

After two decades at Harvard and inquiries about deanships at other institutions, why did you decide to accept the position at Duke?
"From my first visit, it was clear that Duke has a very special character -- a real spirit of innovation and entrepreneurialism. I had the feeling that this was a place where big things could happen -- where somebody could have a great idea and if it was compelling, something would come of it.

"Some of the large New England schools are so big and there's so much process around everything that it can be hard to start new initiatives. It’s like trying to change the direction of the Titanic. Here, doing new things seems to be part of the culture.”

Were you surprised at the level of media attention your appointment received?
"Kind of -- initially, I don't think any of us had really thought about my being 'the first.'

"I think it's another wake-up call for academic medicine. Women and members of underrepresented minority groups are still not on equal footing at the highest levels, even though medical school classes are more representative. I hope that it will help to have more women leaders who not only understand what the issues are for young female faculty, but are also in a position to do something about them."*

You've gotten to know Duke better since becoming dean in October. What do you see as this institution's differentiating strengths -- and its major challenges?
"Duke has a great tradition of collaboration, especially across traditional academic boundaries. Duke has remarkably strong clinical research and basic science engines, and is ready to take full advantage of where they intersect to do translational work.

"Duke also has a strong core value of being of service to society, which I think is really important. I like the fact that Duke is aggressively thinking about its global role, and reaching out to establish collaborations with academic and industry partners and other countries and governments.

It is always a challenge when there are more great ideas than there are resources to support them in terms of building space and money. So we're not in a position to do all the things that we’d like to. It's unfortunately a fact of academic life right now, especially while the NIH budget is in so much trouble."

What are your main priorities as dean?
"Education always has to be a top priority for our medical school. I want to put a lot of my attention early on into strengthening the MD/PhD program. We have very fine students and committed faculty, but we need to continue to increase the size and quality of our applicant pool, diversify the kinds of research experiences students choose, and bring more visibility to the physician-scientists who are role models for those students.

"We also want to be continuously rethinking education for all of our students, because the needs change over time.

"Another priority is to find better mechanisms and incentives for interdisciplinary work. The traditional departmental structure can pose logistical barriers for interdepartmental collaborations, and if we can fine-tune ways to manage these intersecting enterprises, that will be important not only to Duke but on a national scale.

"We'll also be working on the goals identified in the [2006] strategic plan, exploring possibilities for a new student learning center, research building, and imaging facility and contributing to Duke's initiatives in global health, genomics, translational medicine, brain sciences, and others.

"We want to make sure Duke is well-positioned not only for what’s hot today but also for the next waves in medicine."

*For more perspectives, see Dean Andrews’s editorials "The other physician-scientist problem: where have all the young girls gone?" (Nature Medicine, May 2002) and "Climbing through Medicine's Glass Ceiling" (New England Journal of Medicine, November 8, 2007).

This article was first published in the Winter 2008 edition of DukeMed Magazine.