University of Pittsburgh

Summer 2015

3000 Patients Treated at Center for Skull Base Surgery On a Wednesday in early December 2015, when James Demaria had a pituitary tumor removed endoscopically, a landmark was reached in the Center for Skull Base Surgery—James became the 3000th patient to have a tumor removed via the endoscopic endonasal surgical approach. Since the Center was formally initiated three decades ago, University of Pittsburgh surgeons have continued as trailblazers in minimally invasive procedures for brain tumors, sparing more and more patients the morbidities associated with disrupting the brain during surgery. While living and working in Ohio, James experienced a succession of perplexing health issues—he was increasingly fatigued, had gained 50 pounds over a 5-month period, and had bouts of double vision. His primary care physician

diagnosed James with stress; the antidepressants prescribed, says James, “made me feel so much worse. So my primary care referred me to a neurologist. The neurologist did numerous tests, results of which were all negative.

James Demaria

They then ordered an MRI, which clearly showed a very noticeable tumor in my brain. That led me next to a neurosurgeon who did not want to do surgery until the tumor was smaller; he was concerned with its large size and location. So, next I was referred to an endocrinologist who prescribed medications to shrink the tumor and get my hormone levels in line.” At 6-month followup, James’ tumor shrunk by 30% with no change in his hormone levels. “I was still fatigued, still couldn’t lose weight, and I still was having double vision. I was not feeling better; at 40 years old, I shouldn't have been feeling like this.” It was his parents’ health issues that ultimately led James to Pittsburgh. His mother’s diagnosis of cancer and his father’s challenges with spinal stenosis prompted James to leave Ohio to care for his parents full time at their home in West Virginia. While in West Virginia, James consulted with a neurosurgeon who directed him to Dr. Paul Gardner. “I liked Dr. Gardner right away” says James, “he was very informative. He was the first doctor I talked to who had the same thought pattern I did. Dr. Gardner felt like I did, ‘let’s get the tumor out, then get hormone levels inline.’ Dr. Gardner recalls, “James was still very symptomatic from his tumor which was not well controlled with medication. Despite the challenge of the large tumor, I felt our Pittsburgh skull base team could provide James a cure because of our extensive experience and improved outcomes with the endoscopic endonasal approach.” James reports, “I feel better—I have such a greater sense of well being – I’m not back to all activities yet. I just feel so much better; I started my new job 2 weeks after the surgery and I’m looking forward to exercising again. If I were to advise other people with my condition, I would say ‘go forward with surgery.’ 3000! That’s the number of minimally invasive endoscopic skull base procedures performed by the UPMC Center for Cranial Base Surgery, making them one of the most experienced centers in the world. The surgical team continues to develop new surgical approaches and techniques, explore new therapies, and strive to optimize outcomes for all patients. Some of the surgeons’ clinical studies are highlighted in this issue. Dr. Carl Snyderman’s slide presentation and talk on the evolution of skull base surgery can be viewed at: http://www.upmcphysicianresources.com/cme-course/cranial-base-surgery/item/2

Clinical Studies at the Center for Skull Base Surgery

Quality of Life in Skull Base Surgery

Endoscopic Perfusion with ICG Fluorescence Technology

Nasal Dorsum Collapse Following Endoscopic Endonasal Surgery

Effect of Sidedness of Nasoseptal Flap Elevation on Dominant Olfaction

Extraocular Cranial Nerve Monitoring with Minimally Invasive Electrodes

Acoustic Patterns of Bone Drilling

Vidian Nerve Function following Endoscopic Endonasal Surgery

Genomic Sequencing of Skull Base Tumors

Leaders of the Center for Skull Base Surgery at the University of Pittsburgh conduct numerous clinical studies related to improving the diagnosis, treatment, and outcomes of skull base surgery. Dr. Eric Wang, Assistant Professor, states, “Outstanding clinical care is our ongoing purpose at the Center for Skull Base Surgery. Each of us has as our first goal always to provide care to enable the healthiest life possible for our patients. As is true of all of us in the Center, I never forget the many patients who entrust us with the privilege of providing their care. As leaders in skull base surgery, we are uniquely positioned to study uncommon skull base pathologies, the consequences of our surgical interventions, and emerging technologies, all with the goal to answer questions that improve the care of patients.” “Our clinical trials and research are accomplished with the help of past and current patients,” Dr. Wang emphasizes. “Each patient who takes part in our research contributes to improved outcomes for themselves and for all patients who come to us. In our Center, we look upon it as our responsibility to share findings with colleagues in medical centers throughout the world.”

Quality of Life What does the patient experience after undergoing surgery for skull base tumors? Dr. Carl Snyderman leads this clinical study to determine how life changes for a person who undergoes skull base surgery. In conjunction with skull base surgeons at the University of Toronto, the Pittsburgh skull base team is developing a new tool that will more accurately assess quality of life issues in patients undergoing endoscopic skull base surgery. The study also will compare different surgical approaches to see how they affect patients.

Endoscopic Perfusion Utilizing ICG Fluorescence Technology How does the surgeon accurately differentiate tumor from normal healthy tissue so that the entire tumor and only the tumor is removed? How can the surgeon effectively treat a brain aneurysm? Indocyanine green (ICG) is a dye that has been used to assess blood flow through vessels during brain surgery. When injected into the bloodstream, first the vessels, then the tissue glow a bright fluorescent green color. Using a special fluorescent light source, Dr. Paul Gardner is working closely with industry to test the applications of the ICG dye during a variety of skull base surgeries. In additio n to detecting vessels so that injury can be avoided, the surgeons hope that the dye can be used to detect tumor margins more precisely.

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Nasal Dorsum Collapse following Endonasal Endoscopic Surgery What happens to the shape of the nose after endoscopic endonasal surgery? The skull base team at UPMC was the first to discover that endoscopic approaches to the skull base can alter the shape (profile) of the nose in a small percentage of patients. In order to better understand the factors that play a role, Dr. Carl Snyderman and his team are conducting a rigorous analysis of operative data. This study will allow surgeons to avoid this complication and better counsel patients about the risks of University of surgery.

Pittsburgh Effect of Sidedness of Naso-Septal Flap Elevation on Olfaction

Can a person still “smell the roses” after skull base surgery? Is a person’s sense of smell altered following surgery ? The sense of smell (olfactory region), is located high in the nasal cavity and can be diminished following surgery. Dr. Eric Wang is conducting a study to better understand why some patients are less affected than others. By measuring olfactory ability before surgery on each side of the nose, the surgeons hope to plan their surgeries to maximize preservation of the sense of smell so that patients can continue to smell the roses and savor the complex bouquet of wine.

Extraocular Cranial Nerve Monitoring with Minimally Invasive Electrodes How can surgeons remove tumors that are wrapped around nerves without losing nerve function? The nerves that move the eye are often affected by tumors such as pituitary tumors, meningiomas, and chordomas. Injury to these nerves causes double vision. Currently, small needles are inserted into the tissues around the eye to monitor and protect these nerves during surgery. Dr. Paul Gardner and his team are working with neurophysiologists to improve the monitoring technique to simplify the process and improve the monitoring of nerve signals. This research will make it possible for all surgeons to monitor nerve function more effectively.

Acoustic Patterns of Bone Drilling From a multiple choice list, we might be tempted to select “sense of sight” and “sense of touch” if we were asked what senses the surgeon needs and uses most. No doubt we would add “sense of hearing” or even “musical training” upon learning of Dr. Carl Snyderman’s team’s research into acoustic analysis of bone drilling. While imaging systems guide surgeons in the operating room, the most adept, experienced surgeons learn to listen for a pitch change that occurs when the drill reaches thinner bone that indicates soft tissue is near. Snyderman and his team have discovered a way to monitor the sounds of bone drilling and predict with 95% accuracy when the bone is getting very thin. This has wide application for cranial and spine surgery and will allow surgeons to drill more safely and avoid injury to tissues next to the bone.

Vidian Nerve Function following Endoscopic Endonasal Transpterygoid Approach Excessive “dry eye” discomfort can be a result of a particular surgical approach when it involves dissection of the vidian nerve. Loss of “emotional” tearing (crying, laughing) can cause dry eye problems for patients who already have decreased tear production. The nerve responsible for emotional tearing, the vidian nerve, may be injured with some surgical approaches. Dr. Eric Wang is directing a study to measure the function of this nerve before and after surgery to better understand the impact of surgery on tear production.

Genomic Sequencing of Skull Base Tumors When surgery and medical therapies do not stop a skull base tumor, what are the next steps? When tumors occur rarely, physicians have limited data to guide them in eradicating relentlessly occurring disease. Emerging genomic information provides a hopeful option to understand rare skull base disease. Dr. Paul Gardner and his team are studying patients who have been diagnosed with a chordoma, a generally slow -growing tumor with a tendency to recur after treatment. The tumor’s proximity to critical anatomic structures, such as the spinal cord, brainstem, and nerves, makes chordoma especially difficult to treat. The team is analyzing tumor tissue using the most current molecular techniques to better understand and reveal the development of these tumors.

His rare tumor drives him to find answers . . Josh Sommer’s story is on page 5

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Dr. Fernandez-Miranda NIH Grant for Neuroplasticity It wasn’t that long ago—about 30 years – that the word “Neuroplasticity” came into use in medical terminology. The concept of neuroplasticity dashes long-held belief that the brain has a finite number of neurons and that connections between neurons weakened and lost with injury and age. With new understanding that the brain retains its plasticity in retaining and building neuronal pathways throughout the life span, neuroplasticity is being studied from many aspects.

Language Connectivity Pathways and Neuroplasticity in Aphasic Stroke Patients is the subject of the grant for which Dr. Juan Fernandez-Miranda was awarded $1.8 million from the Eunice Kennedy Shriver National Institute of Child Heath & Human Development and by the National Institute on Deafness and other Communication Disorders. Dr. Fernandez-Miranda, Associate Director of the Center for Skull Base Surgery at the University of Pittsburgh, is the Director of the Surgical Neuroanatomy Lab and the Fiber Tractography Lab at the University of Pittsburgh; he and his lab team are working to understand and visualize neuroplasticity via fiber tractography with the goal of enabling clinicians to better manage quality of life for patients. Fiber Tractography

Clinical Research Director in Center for Skull Base Surgery With so many important research activities underway with the surgeons of the Center for Skull Base Surgery, doing the work of identifying potential study participants through signing up patients, getting studies approved, and compiling research results is a job unto itself. Benita Valappil, MPH, CHES is the Clinical Research Director for the Center for Skull Base Surgery who does this essential work. Benita holds a Master’s Degree in Public Health from the University of Pittsburgh. Prior to her current work with the Center, she was engaged with a number of research projects at Magee Women’s Hospital and the Graduate School of Public Health; she also served as a project director in the School of Dental Medicine. When describing her work with the Center for Skull Base Surgery, the first thing Benita talks about is, “The patients! The patients are amazing. The medical challenges they face are so tough, yet they don’t hesitate to say ‘yes’ to be part of a study that will help others with skull base tumors.” Benita reflects, as she describes what is involved in clinical case studies, that it is Benita Valappil her genuine passion for patients that enables her to connect, gaining compliance of 98% of the patients she approaches to enroll in clinical studies. “And, of course, their surgeons have enormous impact; the patients respect their doctors and feel good about knowing they can help them by enrolling as study participants.” The bottom line is . . there were, in fact, several noteworthy “bottom lines” as Benita tried to encapsulate the value she finds in her work with the Center:  “Quality of life improvement for patients is truly the end goal of all the studies, no matter what the focus is. How great to be involved with that!”  “If it weren’t for patients, research studies would not exist; patients who take part advance surgeons’ knowledge.”  The Center’s surgeons are brilliant; they are an incredibly dynamic group who see a large number of patients and they are always striving to do better for each and every one.”

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First Clinical Guidelines for Chordoma An 18-year old engineering student from Duke University came to the University of Pittsburgh Medical Center (UPMC) for endonasal surgery to remove a skull base chordoma, a rare malignant tumor at the base of his skull. The surgical team, including Dr. Carl Snyderman, performed the successful 10-hour operation. Ten years later that student, Josh Sommer, has built the Chordoma Foundation, the first organization of its kind to promote research and clinical trials for this rare disease. Ten years later the neurosurgical fellow involved with Josh’s care, Dr. Paul Gardner, is contributing to chordoma research through projects at the UPMC and as a medical advisory board member of the Foundation. Dr. Gardner participated in the Foundation’s Consensus Meetings, the outcome of those meetings culminating in the publication of the first clinical guidelines for the comprehensive management of chordoma. These guidelines represent the work of a global and multidisciplinary group of physicians that Josh has assembled in his mission to help chordoma patients. “It’s a lonely, challenging journey for patients with chordoma,” say Josh. “Physicians can’t possibly meet all of the needs of chordoma patients; the Foundation is here to help patients get educated about chordoma, find appropriate treatments, and get support from peers.” Josh makes annual visits to the UPMC for medical follow up. He says, “Dr. Snyderman and Dr. Gardner have a rare combination of talent and compassion for their patients. As a patient, to me It’s evident that they have these qualities. They are thought leaders and pushing the boundaries of skull base surgery. And Dr. Gardner has participated in all of the Foundation’s conferences, that demonstrates genuine commitment.” The Foundation has a partnership with the University of Pittsburgh Medical Center, one of four hospitals in the United States, to access its biobank – tissue donated for research. “It’s a very critical resource for researchers due to scarcity of tumor tissues,” says Josh. If a patient comes to UPMC with a chordoma, the team discusses tissue donation with the patient to expand research for the benefit of all chordoma patients. www.Chordomafoundation.org

Royal Society of Medicine Award to Carl Snyderman At the Semon lecture for Britain’s Royal Society of Medicine in London, Dr. Carl Snyderman presented his insights into “Paradigm shifts in skull base surgery and the creative process." He discussed the central role of creativity in driving innovation in surgery, drawing upon his personal experience with the development of skull base surgery. Acknowledged by the Society members as a world leader in endoscopic skull base surgery, Dr. Snyderman was presented with the Society’s commemorative bronze medal. Established in 1912, the Semon lecture honors the memory of Britain’s greatest laryngologist and is annually bestowed upon someone who exemplifies "the best work in the treatment of diseases of the throat and nose.” Few physicians outside of Britain have received this award. The Royal Society of Medicine, established in 1805, has hosted such luminaries as Charles Darwin, Louis Pasteur, Sir Thomas Paget, Joseph Hodgson, Thomas Addison, and other widely recognized leaders in medicine and research. Dr. Carl Snyderman 5

Center for Skull Base Surgery University of Pittsburgh 203 Lothrop Street Suite 500 Pittsburgh, PA 15213 Directors: Paul A. Gardner, MD gardpa@upmc.edu Carl H.Snyderman, MD snydermanch@upmc.edu

In future newsletters, you will hear about some of the new exciting educational projects initiated at the Center for Skull Base Surgery. Your support is essential.

If you would like to learn more about our activities or sponsor a project, please contact the Eye & Ear Foundation.* To support the Center for Skull Base Surgery, please use the enclosed envelope or visit eyeandear.org. If sending a check, please make payable to the Eye & Ear Foundation.

The University of Pittsburgh Skull Base Team is pictured above.

Additional information about the educational and clinical work of the Surgeons of the Center for Skull Base Surgery is found at: UPMC.com/skullbasesurgery

www.eyeandear.org 203 Lothrop Street Suite 251 EEI Pittsburgh, Pennsylvania 15213 Tel: 412 864 1300 *The Eye & Ear Foundation is a non-profit (C)(3) organization created solely to support the educational and research efforts of the Departments of Otolaryngology and Ophthalmology at the University of Pittsburgh.

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