Our Amazing Skin

From the Summer 2018 edition of Vanderbilt Medicine Magazine

Photo by istockphoto.com

Skin is the human body’s largest organ accounting for 8 pounds and 2 square meters on an adult. It is our fiercest protector, an impervious shield that plays a major role in keeping us alive. Since a substantial portion of our immune cells live in our skin, it teaches our body to fight off infections. It regulates our body temperature, constantly cooling us, and protects us from the sun’s harmful rays. It cleanses our body by secreting our toxins. It is the body’s storeroom for water, fat and metabolic products. It helps our body maintain homeostasis — a stable, relatively constant internal environment.

Its importance cannot be overstated. We would dehydrate with even a small reduction in its ability to prevent evaporation of our internal water supplies.

“The skin is a very exciting, incredibly complex and diverse organ, which helps explain why there are more than 3,000 diseases of the skin. For me, as a physician-scientist, the skin is an endless source of curiosity and discovery. Take for example the recent astounding finding of olfactory receptors in the skin — who would have thought the skin has a sense of smell? The more details we learn about the function of the skin, the more we can help people when it’s not working properly,” said Eric Tkaczyk, MD, PhD, assistant professor of Dermatology and Biomedical Engineering.

• • •

Comfortable in Her Own Skin

Surgery boosts confidence after weight loss

Photo by John Russell

After undergoing gastric sleeve surgery for weight loss at Vanderbilt University Medical Center in October 2016, Denise Stevenson was ecstatic with the results, but she realized during a yoga class 10 months later that her weight loss journey was not over.

“I knew there was a good chance after a significant weight loss that I could have loose skin,” said Stevenson, who shed 105 pounds in a year. “But the extra skin really impacted my confidence. Mostly I was very self-conscious that if I moved a certain way my skin would be exposed.”

It was while attempting an inverted position during a yoga session that her worst fear was realized.

“I would describe my skin like liquid — it would just flow out from the edges of my clothing,” she said. “If I laid on my side, it would puddle next to me. On this day in yoga class I was trying to kick up into a handstand; I nearly had a wardrobe malfunction.

“I knew right then I had to get my skin fixed.”

Stevenson was one of 540 patients to undergo a bariatric surgical procedure at the Vanderbilt Center for Surgical Weight Loss that year.

“I have struggled with my weight all my life,” she said. “I yo-yoed for years. And as I began to age, I realized that it was getting harder and harder to lose the weight. I didn’t want to be sitting around with my knees hurting, with high blood pressure or diabetes because I was overweight. I wanted a good quality life and to continue being active.”

In 2014 she tore her anterior cruciate ligament (ACL) while skiing and then broke her ankle in 2016 during a training run. Both injuries sidelined her from exercise, and she continued to gain weight.

During the recovery in 2016, she caught an episode of “Dr. Oz” on bariatric surgery. She began researching the Vanderbilt program, completed an online questionnaire and attended an orientation for the surgical weight loss options, which include the Roux-ex-Y gastric bypass or the vertical gastric sleeve.

Stevenson, who weighed 240 pounds prior to the surgery, set a goal to lose between 80 and 90 pounds. Prior to surgery she wore size 18-20 clothing. Today she is a size 4.

“Once I reached a size that I was perfectly happy with, I wanted to make sure my weight was stable, my body was used to the weight loss and that I could maintain my weight.”

In May 2018 Stevenson, 54, had a belt abdominoplasty or circumferential body lift, breast augmentation and breast lift.

Galen Perdikis, MD, FACS, professor and chair of the Department of Plastic Surgery, was Stevenson’s surgeon. He sees multiple new patients monthly post weight loss.

“This specialty [skin repair] has grown over the past 15 years as weight loss surgeries have become safer and more prevalent,” said Perdikis. “Our patient volume continues to increase and the patients span all ages.”

Perdikis and his team remove excess skin from all parts of the body, but the most common skin repair procedures are the tummy tuck and breast surgeries. Most procedures are done on an outpatient basis or may occasionally require an overnight observation. Patients are evaluated carefully to ensure safety and the best outcomes possible.

“Our surgical weight loss center’s team members are excellent and a big help to us,” said Perdikis. “Once the patients come to us, they have already been informed and educated about the possibilities. After assessing them thoroughly in our plastic surgery clinic, we educate them about their options including what to expect the day of surgery and post operatively during recovery. Our team will also discuss the financial aspects of the non-covered procedures.”

Insurance companies will not cover most skin removal surgeries unless there is a health issue that causes an interference in perineal hygiene or if skin rashes or infections occur because of the excess skin. Removing skin from the lower abdomen is the most commonly covered procedure for the above reasons, he said.

“For many of our patients who lost weight, the journey is not over. They have loved losing the weight but they hate all the loose skin. They feel like a trick has been played on them. Their bodies have been deflated with all the fat gone. They are excited to get to the next point and get rid of all the excess skin.”

Stevenson said she was “absolutely giddy at times” over the change in her body since the skin removal procedure.

“This was kind of my final part of the journey,” she said. “I don’t have to worry about the shoulder-to-knee length Spanx anymore. I can wear prettier clothes and I don’t look like I am carrying an inner tube around all day. But the biggest change for me post skin removal, besides being firmer in my clothes, is that I am not tentative about people touching me.”

Prior to her skin repair, Stevenson said she felt “squishy” all over and didn’t want people to feel the loose skin.

“I just kept my distance and tried to avoid allowing people to touch me. Not so much anymore.”

She is also easing back into yoga, but said it’s a slow process after surgery. She is jumping into other activities that her previous weight prohibited, such as hang gliding.

“There’s a weight limit [for hang gliding] and I would not have been able to do that before,” she said. “I love being active. The weight loss has allowed me to do more and the skin repair returned my confidence.

“If someone has invested enough in themselves to have the weight loss surgery, and the excess skin takes away their confidence and keeps them from living a full life, then I would encourage them to take the final step. You’ve worked hard to get to that point and you deserve to live your best life,” Stevenson said.

Seeing patients during the follow-up appointments is very satisfying, Perdikis said, smiling.

“These are some of the happiest patients and we get a lot of satisfaction from helping them. Surgery for them is a silver lining of a journey they have completed.”

– by Jessica Pasley

• • •

From Hurt to Healed

Collaboration key to wound care

Every year in the United States, an estimated 8 million people seek medical help for wounds that just will not heal, and at Vanderbilt University Medical Center the teams that care for these patients look beyond the wound to find the ‘why.’

A litany of issues can cause a poorly healing wound including severe trauma, burns, obesity, vascular diseases, lymphedema, diabetes, smoking, poor nutrition and a weakened immune system. And when a combination of these issues is present, the body’s natural ability to heal can be greatly impaired.

“At some institutions, a patient will see a wound care specialist and that’s the only medical provider they see for a chronic wound,” said Wes Thayer, MD, PhD, a plastic surgeon who was named VUMC’s Wound Care director in late 2017. “At Vanderbilt, we have a powerful system of referrals so we can take a much more comprehensive, coordinated approach to wound care.

“That’s important because wounds aren’t all the same. When we have a patient come to us with a chronic wound, we work quickly to identify the cause. Then, in addition to providing the highest standard of care for the wound, the appropriate topical product and dressing, as well as wound care follow-up, we can refer them to other specialists at Vanderbilt who can help manage the pathology that initially led to the wound or prevented its healing.”

If a wound hasn’t made normal progress toward healing, with restored function and mobility, after three months, it’s typically classified as a chronic wound. A chronic wound can greatly compromise an individual’s quality of life, impair movement and increase the risk of both localized and systemic infection, Thayer said.

In addition to impacting an individual’s health, chronic wounds are costly. In a 2018 study that analyzed 2014 Medicare reimbursements, a conservative estimate of the annual cost of treating chronic wounds for Medicare recipients alone was nearly $32 billion. The study was published in Value in Health, the journal of The International Society for Pharmacoeconomics and Outcomes Research.

Because a team approach is vital for successfully treating chronic wounds and establishing preventive care to ward off future wounds, Thayer is working with other clinical leaders to establish a comprehensive, multidisciplinary wound care center at VUMC.

The care of a patient with a chronic wound, especially one that is the result of severe trauma or burn, can involve a large cast of caregivers, such as trauma, plastic and orthopaedic surgeons, cardiologists, endocrinologists, nursing staff, physical and occupational therapists, nutritionists, psychologists and other care providers. The goal is to improve healing, prevent scarring, increase mobility and function, and provide long-term support as a patient heals.

These providers would be readily available and coordinated through the planned wound care center, Thayer said. In addition, the center would treat not just Vanderbilt patients, but would also serve as a referral center for a multi-state region. The center is still in planning stages, but he hopes to begin seeing patients no later than summer 2019.

“Most chronic wounds are associated with conditions more common in older individuals, including vascular disease and diabetes,” said Thayer. “Also, as our population ages, and we’re living longer, more seniors are undergoing surgery. Older patients are at higher risk of surgical site wound complications. We need to make sure we’re ready to meet the needs of this growing population.”

Complex wounds from burns

Severe burn injuries are complex and challenging to heal because they don’t affect the skin uniformly in severity, can also damage bones and internal organs, can cover large areas of the body, and can be caused by a wide range of environmental factors, said VUMC plastic surgeon Blair Summitt, MD, medical director of acute burn services.

And time is of the essence when working to heal open wounds caused by burns, he said. Without the skin’s shielding protection, burn wounds can quickly develop bacterial and fungal infections.

“You also have to get the burned tissue off or debrided, ideally no more than a week after the injury,” Summitt explained. “The burn itself can drive a multi-system inflammatory response in the body, so the goal is to get that dead tissue off and at least get temporary coverage on the wound.

“You have to come up with a long-term strategy to get the patient back to functionally living their life. The problem we often run into with patients who have very large burns is that we only have so much healthy skin remaining that we can use to make repairs.”

If a patient has unharmed skin available, that skin can be used as a graft or skin transplant to cover the burned areas. There are two types of autologous (from the same individual) skin grafts: split-thickness grafts in which just a few layers of outer skin are transplanted and full-thickness grafts, which involve using all the layers.

The graft is placed on the area needing covering and is secured by stitches or staples and a dressing. Recovery time for a donor site used for a split-thickness skin graft is quick — often less than three weeks. Full-thickness skin grafts take longer to heal, said Summitt. In a few days new blood vessels typically begin growing outward from the body into the transplanted skin in a process known as capillary inosculation.

If a patient has large burn areas, their unharmed skin is used as graft material first on the face, neck and hands for the least amount of scarring on the most visible parts of the body, he added.

If a burn site is larger than an individual’s remaining healthy skin, a technique called meshing can be used to enlarge a segment of donor skin to cover a bigger area, he said. Meshing involves running a harvested sheet of skin through a machine that cuts rows of small slits in the tissue so it can expand, much like fishing net. The expanded, meshed tissue is secured in place over the open wound in order to spur new skin growth.

Because meshed skin tends to contract as the area heals, leading to restrictive bands of scarring, the healing must be monitored closely, Summitt said. Also, the meshing process can lead to an uneven skin surface once it heals. Laser treatments have become increasingly crucial in minimizing both the discoloration and uneven textures that can often occur after severe burns that require grafts, he added.

Cadaver skin or homograft can also be used as a temporary skin graft. Sterilized skin grafts from animals such as pigs, called heterografts or xenografts, can also serve as temporary biologic dressings to reduce infection and reduce fluid loss in the open wound.

The ReCell system, currently in clinical trials in the United States, is another innovation that may speed severe-wound healing, particularly burns. In the ReCell process, a graft of a patient’s healthy skin is processed into a solution that is then sprayed on the area of the body needing skin coverage. This treatment is already in use in England.

“A patient with very large burns is typically my patient for life,” Summitt said. “I’ll work with them for years trying to make things better for them.”

– by Jill Clendening

• • •

Melanoma Meets Its Match

Better options mean longer lives

Photo by Daniel Dubois

Two years after being diagnosed with metastatic melanoma that had spread to his brain, lungs and pancreas, Luke Simons just returned from a vacation in Alaska where he kayaked across the fjords with his wife Susan and watched the whales with their grandchildren.

It was a dream vacation, a miraculous recovery, and immunotherapy made it possible.

“As far as we know, I am clean and clear of cancer,” Simons said. “Every quarter, I go for a scan to check. If the next one is clear, I will just have to go every six months.”

Simons received infusions of pembrolizumab, an immunotherapy approved the U.S. Food and Drug Administration (FDA) in 2014 and marketed as Keytruda. It’s an antibody that blocks a protein that hides cancer cells from the immune system. It removes the armor around cancer so patient’s immune systems can unleash T cells to attack the disease.

After Simons received his first four infusions of pembrolizumab following surgery to remove the brain tumor in 2016, the tumor in his lung shrank by half. After the next round, it shrank even more. The tumors on his pancreas disappeared.

Oncologists now have an expanding arsenal of new treatment options, immunotherapies and targeted therapies, for metastatic melanoma, a disease that previously came with a bleak prognosis. While melanoma accounts for about 1 percent of skin cancer, it causes a large majority of skin cancer deaths.

“There has been a huge amount of progress over the last five to seven years in the treatment of metastatic melanoma. We have moved from essentially no treatments that had ever improved survival for patients to now having over 10 different treatments,” said Douglas Johnson, MD, MSCI, clinical director of melanoma at Vanderbilt-Ingram Cancer Center and assistant professor of Medicine at Vanderbilt University. “It has been a remarkable amount of progress in the last few years.”

Simons is an immunotherapy responder, but not all patients are. Johnson and colleagues are developing and testing new treatments as well as combinations of existing ones so more patients with metastatic melanoma can enjoy fuller lives.

“About 60 percent of patients will respond to the most aggressive immunotherapy regimen,” Johnson said. “These are patients who previously would have had essentially no treatment options. Now, over half of patients are responding. The vast majority of these patients are still alive and doing well at three years, even five years, later. These patients are actually getting long-term and durable responses that are probably going to translate into a cure.”

Long before his diagnosis, Simons and his wife Susan had a strong connection to Vanderbilt-Ingram, having provided philanthropic support for research on melanoma therapies that led to the treatment now benefiting him. His illness has strengthened the couple’s commitment; Susan now serves on the VICC Board of Overseers.

Simons’ diagnosis occurred in July 2016 when he had originally planned to take that Alaska vacation. It was a quirk of fate that changed those plans. He slipped on a slick hardwood floor and hit his head the day before he was supposed to fly out. Emergency room scans showed a lesion on his brain. Weeks later, after a biopsy following brain surgery revealed he had metastatic melanoma, he doubted if he would ever get to take his grandchildren to Alaska. But he held onto to hope because Johnson told him he would be getting the same immunotherapy as former U.S. president, Jimmy Carter.  Carter also had metastatic melanoma that had spread to his brain, but he had fought back the cancer.

“That gave me the emotional incentive,” Simons said. “I had the attitude of ‘OK, let’s get on with it. It’s going to work.’ I didn’t really know what the odds were. It wasn’t a walk in the park, but that one story helped me more than anything.”

Not all patients with metastatic melanoma respond to immunotherapy, and researchers are looking for biomarkers that might explain why they don’t. One clue might be the number of mutations in a tumor.

“The more mutations a tumor has, the more foreign it looks to the immune system,” Johnson said. “Therefore, the more likely those patients are to respond to immune therapy. We can test this in the clinic to help guide how we treat patients.”

Another clue might be a molecule biomarker called MHC-II. Research from Vanderbilt-Ingram Cancer Center (VICC) identified the molecule as a possible predictor of response to immunotherapy. A clinical trial at VICC will screen patients for the molecule. Johnson is working with Justin Balko, PhD, PharmD, assistant professor of Medicine, on the initiative.

“If patients are positive for MHC-II, they will get a new immunotherapy combination — nivolumab plus relatlimab,” Johnson said. “Relatlimab is not FDA-approved yet. It’s an experimental combination. If patients are negative, they are going to get the most aggressive currently-available regimen — nivolumab plus ipilimumab.”

VICC participated in another clinical trial that compared the effect of pembrolizumab in patients to pembrolizumab in combination with another immunotherapy, talimogene laherparepvec (T-VEC), a genetically modified virus injected directly into tumors on the skin or in the lymph nodes.

“That seems to work better than either treatment alone,” Johnson said. “T-VEC alone treats superficial tumors effectively but cannot reach internal tumors. However, it seems as though treating the superficial tumors actually makes the treatment of the internal tumors work more efficiently. Using the two drugs together allows you to stimulate the immune system in multiple complementary ways.”

Immunotherapies are not the only new treatments that have been shown to work better in combination. Targeted therapies — drugs that block the molecules that allow cancers to grow and spread — have also proven to be more effective in some melanoma patients. One combination approved in 2018, dabrafenib with trametinib, has been shown to dramatically decrease the risk of recurrence and improve the cure rate for patients with high-risk, stage III melanoma.

“The advantages to that approach are to avoid the really devastating complications of metastatic disease,” Johnson said.

At this point in time, surgery remains the treatment protocol for early stage melanoma.

“Early stage melanomas treated with surgery alone are certainly much lower risk, but they actually represent ultimately the majority of patients who develop metastatic disease because they are so much more common,” Johnson said. “That’s still a real gap in our knowledge of how to predict those patients who will develop metastatic disease and then try to prevent that with some of these treatments. That’s certainly a big area of research to look at the genes in the tumor, to look at the different proteins and to understand which patients are at the highest risk.”

– by Tom Wilemon

• • •

A different direction for dermatology

Meg Chren, MD, takes the helm of the new department

Photo by John Russell

Mary-Margaret “Meg” Chren, MD, the Buchanan and Lancaster Professor and Chair of Dermatology, joined the VUSM faculty in January to become the inaugural chair of the new Department of Dermatology. Chren was formerly professor of Dermatology at the University of California, San Francisco (UCSF).

What is the advantage to establishing Dermatology as its own department?

As a department, we will be responsible for not only the quality and solvency of our clinical and educational activities, but for building and growing as a vital part of the larger Medical Center. So this transition is a business, organizational and conceptual change. In fact, this fall we will come together as a department in a formal strategic planning process to articulate explicitly our vision, and how we want to move forward for the next five to 10 years.

What is the strategic vision for the department?

Our faculty are here because they are committed to the academic environment, and as a group we’ve been thinking a fair amount about what it means to be “academic.”  I define it as a culture of inquiry and curiosity, and I hope we will build around that idea. We want to be firmly embedded in the institution’s clinical goals, the things that uniquely characterize Vanderbilt — exceptional quality of care and expanding to serve the region and the state. Teaching is extremely important; we have a sought-after residency and plans to expand with new educational opportunities such as teledermatology. Finally, we will build our research portfolio both in basic and clinical research, which will be very exciting given the richness of the broader Vanderbilt investigative environment.

What intrigued you about dermatology early in your career?

I trained in internal medicine first and was an internist in a small practice outside of Boston. That experience was pivotal for me. It exposed me to the care of people with chronic conditions who are living with their illnesses. It also showed me the pleasures of practicing in a well-run environment so clinicians can focus on patients. I also learned I had the mentality of a specialist; I’m someone who does better focusing on one part of the human body and patient experience, so I knew I would specialize and do a fellowship. For me, a few pivotal patients with serious skin conditions shaped my career, and getting to know their dermatologists made me want to be as scholarly as they were.

How has dermatology evolved and been impacted by cosmetic advances?

In the past there was concern that an emphasis on cosmetic procedures might erode the mission of academic dermatology. In fact, these concerns were unfounded and academic dermatology is thriving.  Our faculty and doctors-in-training want to care for people with all types of skin conditions that affect their health and well-being. Skin problems can affect patients in many ways. For example, a child may have very itchy eczema, or a woman with psoriasis of the hands may no longer be able to perform her job, or a man with skin cancers may need multiple surgeries. But in addition, skin conditions — because they are often visible — can also affect patients emotionally because of their effects on appearance. Caring for patients’ cosmetic concerns is one way — of many — in which we can take better care of people with all types of skin conditions that affect their health and well-being.

What are your research interests?

After my dermatology residency, I did a research fellowship in clinical epidemiology and outcomes research. The vast majority of our dermatology patients have chronic conditions, and to improve our care we need to understand how to measure the outcomes of that care. I began by focusing on the patient’s quality of life as an outcome for skin conditions. My group developed, tested, and perfected a quality-of-life tool for skin disease called Skindex, and we have used that tool to measure and compare outcomes of treatments for a variety of skin conditions. I’m very excited to continue this work in the wonderful research environment at Vanderbilt. Our current studies focus squarely on the experience of a patient with a skin condition — how it affects his or her well-being — which we call the Skin Vital Signs. We have developed a user-friendly mobile tool to measure the patient’s experience, and will learn if giving this information to clinicians in easy, quick ways can improve care. Stay tuned!