Correct Diagnosis is Key to Successful Treatment

Penn Medicine’s excellent diagnostics and expert physicians provide patients with the best chance of a successful outcome.  Effective medical treatment is based on an accurate diagnosis of each patient’s disease.  As one of the nation’s top medical centers, Penn Medicine offers patients the latest, state-of-the-art diagnostic tools and tests. But technology is only as good as the people using it, and Penn physicians are experts at reviewing and interpreting test results. In fact, Penn physicians and researchers invented much of the current diagnostic technology and continue to look for ways to expand its uses.

Advances in Imaging

Medical care and treatment depends on the ability to see inside the body quickly and accurately. At Penn, the radiologists interpreting these images often specialize in just one field—such as heart images, brain images, or gastrointestinal images. Because Penn radiologists specialize in a specific area, readings are more accurate. In addition, because of this specialization, Penn radiologists are looking for physiological and molecular changes in the body, such as blood flow and glucose metabolism, as well as anatomical changes.   Penn has a long history of excellence in imaging. The Hospital of the University of Pennsylvania is home to the first department of radiology in the United States. Many imaging technologies now in use were developed and perfected at Penn.

Radiologists continue to look for new ways to see what is happening inside the body—and why.  Right now, Penn radiologists are working to advance several technologies.

• Arterial spin labeling (ASL). This technology developed at Penn is now being licensed around the world as a non-invasive method for viewing cerebral blood flow in the brain.
• Spiral CT (see related article about diagnosing lung cancer on page 4).  Helical CT images provide high-resolution views with less radiation exposure to patients. Along with lung cancer, this technology is being used to diagnose vascular abnormalities and diseases. 
• Positron emission tomography (PET) for detecting Alzheimer’s disease (see related story on page X). A compound developed at Penn helps detect brain plaques associated with Alzheimer’s disease.

“Penn has traditionally emphasized research in addition to clinical care,” said R. Nick Bryan, MD, PhD, chair of Penn Radiology. “As one of the leading research institutes in the country, we are leaders in developing new imaging technology as well as bringing in the latest technological advances to help make difficult diagnosis in our patients.”

Developing Personalized Diagnostics

The Human Genome Project, an international scientific research project, identified and mapped the approximately 20,000 to 25,000 genes in human DNA, and determined the sequences of the 3 billion chemical base pairs that make up the human genome. The project ushered in a revolution in personalized medicine, and nowhere is that more apparent that at Penn Pathology and Laboratory Medicine.
“By finding and studying gene mutations, we will eventually have information that helps us identify cancer causing mutations and how they react to treatment for every cancer patient. It will be a terrific resource,” said David B. Roth, MD, PhD, chair of pathology and laboratory medicine at Penn. Additionally, predictive testing for mutations in genes that may predispose individuals to disease will provide more accurate risk assessment and has the potential for great impact on prevention, early detection and early intervention.
The Penn laboratory where the Philadelphia Chromosome was discovered is expanding to include a new Center for Personalized Diagnostics. Both a research and patient care center, its plans are to provide diagnostic gene sequencing and other genome-wide diagnostic tools for patients.  The goal is to provide clinicians with information regarding their patient’s disease, so that a customized treatment regimen can be directed to the driving mutations specific for their patient.

“Personalized diagnostics are an important part of personalized medicine,” said Dr. Roth, “and Penn has the vision to see that this is next step in providing the best outcomes for patients. Large-scale gene sequencing is a laborious process, but the enormous results are worth it.”

For more information or to schedule an appointment with a Penn Medicine physician, visit PennMedicine.org or call 800-789-PENN (7366).

Gene Researchers: Curing Blindness

As one of the premier patient care, teaching and research ophthalmology departments in the country, Scheie is a world leader in research and consistently ranks among the top five programs in the nation in funding by the National Eye Institute.

“Scheie one the of the top-funded eye research programs in the country,” said Joan O’Brien, MD, chair of ophthalmology, “but almost all of our scientists are physician/scientists who bring this research back to their patients. Marrying the science to patient care allows us to treat vision loss in a personalized manner.”

Gene therapy is just one of the areas of focus for researchers at Scheie. With the rapidly expanding knowledge about genetic diseases, researchers can target the biology of eye diseases and develop personalized treatment for patients.

Using Gene Therapy to Cure Blindness

The work of Penn researchers received a great deal of publicity after they brought sight to children who suffer from inherited retinal diseases. Leber congenital amaurosis (LCA) is a group of inherited blinding diseases that damages light receptors in the retina. It usually begins stealing sight in early childhood and causes total blindness by the time patients reach their 20s or 30s.

Clinical trials conducted at The Children’s Hospital of Philadelphia (CHOP) have shown that gene therapy safely restored vision in young people with this rare form of congenital blindness. The treatment consists of injecting one eye with a virus genetically engineered to carry a normal version of the gene that causes LCA.

Although the patients have not achieved normal eyesight, their vision improved from detecting movements to reading lines on an eye chart. Three children, who previously sat at the back of the class relying on electronic screens and assistance from teacher aides, now, sit in the front of the class. One joins classmates on the playground for a game of softball and another joins them for soccer.

“For children and young adults with congenital blindness gene therapy is the best chance for restoring and improving their sight,” said Jean Bennett, MD, PhD, and lead author of the study. “With the success we have had in treating one eye, we are cautiously preparing to begin treatment of the other eye. Penn and CHOP are leaders in developing ocular gene therapy and are poised to move forward quickly with this promising research.”

Providing World-Class Care

Along, with their research, Penn Eye Care specialists provide the most up-to-date methods of treatment for the full range of eye disorders, from routine eye examinations to the most advanced ocular surgery.

For more information about eye care and ophthalmology research at Penn Medicine or to schedule an appointment with a Penn ophthalmologist, please visit PennMedicine.org or call 800-789-PENN (7366).

Watch a video of study participants before and after treatment.

Focusing on Vision

At Scheie Eye Institute and the F.M. Kirby Center for Molecular Ophthalmology, scientists investigate the causes of important eye conditions including macular degeneration, diabetic retinopathy, hereditary retinal degenerations, cataract and severe myopia that may be treatable with molecular therapies.

In addition to the gene therapy work being done by Jean Bennett, PhD, and Albert Maguire, MD, nearly 50 physician/scientists are involved in translational ophthalmology research at Penn, many of them bringing their research directly to the patients they treat.

Alexander Brucker, MD

Dr. Brucker is one of the most prolific investigators at Scheie Eye Institute. As a retina specialist, Dr. Brucker’s research focuses on medications and treatments for diabetic retinopathy, diabetic macular edema and age-related macular degeneration. He is also a member of the executive committee of the Diabetic Retinopathy Clinical Research Network (DRCRnet), the NEI-sponsored collaborative network dedicated to facilitating multicenter research of diabetic eye conditions.

Vatinee Y. Bunya, MD

Dr. Bunya is currently the principal investigator for several dry eye studies focused on studying different components of the tear film. In addition, she serves as a co-investigator for an international Sjogren’s syndrome study and is part of a multidisciplinary team working on the development of a new blepharitis reading center. She will soon begin her K12 research training grant, which focuses on the development of new topical therapies for dry eye disease.

Joshua Dunaief, MD, PhD

Dr. Dunaief is the recipient of the prestigious Cogan Award from the Association for Research in Vision and Ophthalmology. His research and clinical practice focus on age-related macular degeneration (AMD), a common cause of irreversible blindness in the U.S. Evidence suggests that cumulative oxidative damage contributes to AMD and aging in general and his research has found that AMD retinas have iron overload, which can increase oxidative stress. Dr. Dunaief’s lab is working to understand retinal iron homeostasis and how it may lead to treatments for AMD. His lab has found that treating genetically engineered mice with an oral iron-binding drug prevents both retinal degeneration and a Parkinson’s disease-like movement disorder.

Juan Grunwald, MD

Dr. Grunwald is world renowned for his research on blood flow in the retina. Currently, he is photographing the retinas of patients with kidney disease to identify retinopathy. The tiny blood vessels in the retina reflect vascular issues throughout the body and the photos provide a non-invasive way to obtain information about vascular disease. Dr. Grunwald is also an investigator on the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT) and the Retinopathy in Chronic Renal Insufficiency Cohort study (RCRIC).

John Kempen, MD, MPH, MHS, PhD

Known nationally and internationally as an expert in ocular inflammatory diseases—such as uveitis, scleritis, and others—as well as ocular complications of AIDS, Dr. Kempen is the principal investigator for the Systemic Immunosuppressive Therapy for Eye Diseases (SITE) Cohort Study, the first NIH-sponsored multicenter clinical research study in the field of uveitis. Following up on the results of the study, Dr. Kempen is now expanding his research to examine cancer-related mortality among patients with ocular inflammation who are being treated with immunosuppressive drugs.

Alan M. Laties, MD

Dr. Laties’ lab focuses on understanding the mechanisms of hereditary retinal degenerations and age-related macular degeneration (AMD), to perform pre-clinical evaluation of drug therapies, and to fast track laboratory results to patient care.

Maureen G. Maguire, PhD

As director of the Center for Preventive Ophthalmology and Biostatistics, Dr. Maguire’s current research projects include directing the coordinating center for the NIH-funded Comparison of Age-related Macular Degeneration Treatments Trials, a multicenter, randomized clinical trial involving 1,200 patients with choroidal neovascularization.

Eydie G. Miller-Ellis, MD

As a glaucoma specialist and director of the glaucoma service, Dr. Miller-Ellis’ research interests include medical and surgical interventions for glaucoma, and diagnostic techniques for the evaluation of glaucoma. She was the principal investigator for the Advanced Glaucoma Intervention Study and the Ocular Hypertension Treatment Study, two pivotal multicenter clinical trials sponsored by the National Institutes of Health that helped define glaucoma management. She is also the principal investigator for an upcoming multicenter clinical trial that will evaluate the relative efficacy of medical and surgical management of glaucoma.

Kenneth S. Shindler, MD, PhD

Dr. Shindler’s research area is optic neuritis, an inflammatory disease of the optic nerve that often occurs as part of the neurodegenerative disease multiple sclerosis. (MS). Dr. Shindler’s studies are helping to identify new drug therapies and drug combinations to prevent nerve damage in MS, and such therapies will also likely have benefits for other neurodegenerative diseases.

Dwight Stambolian, MD, PhD

Dr. Stambolian’s lab focuses on gene discovery of complex and single-gene disorders. His research projects include searching for the genes for myopia (near-sightedness), age-related macular degeneration (AMD), Nance Horan Syndrome (a disorder linked to the X-chromosome causing eye and dental abnormalities) and Tcm gene causing microphthalmia or small eyes.

Kalliopi Stasi, MD, PhD

As a cornea specialist and a clinician scientist, Dr. Stasi’s current research project, in collaboration with Penn’s Institute for Regenerative Medicine, focuses on establishing a method for culturing cornea/limbal stem cells and studying their properties in a way that they can be used in the future for transplantation in order to treat limbal stem cell deficiency from a variety of ocular conditions, from ocular burns to post-cancer to congenital diseases.

Richard Stone, MD

Dr. Stone is director of the Applied Ophthalmic Neurobiology Laboratory, studying control mechanisms regulating ocular physiology and development. His studies have addressed the mechanisms responsible for myopia (near-sightedness). His studies have identified several signaling pathways that appear to be involved in controlling eye development, a number of which have now been extended to children. These include the identification of a drug-inhibiting myopia progression in children, the first such clinical innovation in several centuries, and the idea that the daily light-dark cycle might influence eye development.

Gui-shuang Ying, PhD

Dr. Ying is the principal investigator of the Data Coordinating Center for a multicenter study “Telemedicine Approaches to Evaluating Acute-phase Retinopathy of Prematurity (e-ROP)”, a four-year study funded by the National Eye Institute. Retinopathy of prematurity (ROP) is the leading cause of treatable childhood blindness, but is becoming an increasing problem in underserved areas of the U.S. and Canada, and epidemic rates are being found in rapidly developing countries The e-ROP study evaluates the validity, reliability, feasibility and cost-effectiveness using telemedicine to examine the eyes of at-risk babies. The study will enroll 2,000 babies with birth weight of 1250 grams (2.76 pounds) or less from 10 neonatal intensive care units in the United States. The study hopes to greatly reduce the number of examinations needed to be performed by specially trained ophthalmologists, and significantly increase the number of babies who receive appropriate timely evaluations.

Penn Provides Specialized Care for Pituitary Disease

The symptoms can be vague. Headaches, weight loss or gain, fatigue, and cold intolerance: Symptoms that might be dismissed as menopause or stress. But these symptoms can sometimes mask pituitary disease.

The Penn Pituitary Center was created to diagnose and treat people with pituitary disease. The center's multidisciplinary team of endocrinologists, neurosurgeons, radiation oncologists, neuroradiologists, interventional radiologists and neuro-opthalmologists are recognized internationally for their expertise in the diagnosis and treatment of neuroendocrine diseases.

The pituitary gland is about the size of a pea and sits in a small cavity at the base of the brain. It produces major hormones that control bodily functions.

“If the pituitary gland’s functions are compromised by disease or a tumor, hormone production is impaired and an individual will experience symptoms,” says endocrinologist Julia Kharlip, MD.

"The symptoms may go unexplained for months or sometimes years until the problem is uncovered by an astute clinician or when the patient’s peripheral vision begins to be affected by a growing pituitary tumor," Dr. Kharlip continues. "The good news is that although these diseases are insidious, once diagnosed, they can be treated successfully, restoring quality of life and preserving vision.”

The Penn Pituitary Center provides the latest specialized care for patients with pituitary disease including:

• Acromegaly
• Cushing's disease
• Hyperprolactinemia
• Gonadotroph and other clinically nonfunctioning pituitary adenomas
• Pituitary and hypothalalmic lesions
• Hypopituitarism
• Diabetes insipidus

Because these are complex disorders, care of one patient involves multiple specialists.

“Seeing so many doctors may sound daunting, but our center coordinator makes navigating the multiple visits easier for families, often scheduling all appointments on the same day. All physicians at Penn have access to electronic medical records and images. Once a patient starts their journey, there is no more logging of the bulky stacks of handwritten notes or image envelopes from visit to visit," Dr. Kharlip said.

“Once all of us had a chance to evaluate the patient individually, the specific case is discussed among the team at a conference, where we can form a consensus of opinion about treatment plans from all disciplines,” says Dr. Kharlip. "When several treatment options are reasonable, we involve the patient in choosing the approach that is best for him or her."

Every person’s experience with pituitary disease is unique and deserves a treatment plan tailored to their needs. Consequently, patients with pituitary disease benefit from the observations and expertise of many medical fields including endocrinology, ophthalmology and neurosurgery.

“We can offer patients advanced care that community hospitals may not be able to offer because we have the expertise and technology only an advanced academic institution like Penn Medicine has,” says Dr. Kharlip.

Surgical expertise

Pituitary disease affects nearly 22 percent of the U.S. population. It is often caused by a tumor and surgery is almost always part of the treatment plan. The good news is most pituitary tumors are benign, or non-cancerous.

“Having surgery when the pituitary is damaged can be dangerous. Before surgery, the endocrinology team works with patients to make sure their hormones are at safe levels,” said Dr. Kharlip.

Sean Grady, MD, is the chairman of the department of neurosurgery at Penn Medicine. He says the procedure to remove pituitary tumors is straightforward, but its complications can be substantial.

“Pituitary tumors are usually removed with minimally invasive techniques through a patient’s nasal cavity,” says Dr. Grady. “It requires no incisions, and patients usually go home within three days.”

But because of the tumor’s location within the brain, it’s important for patients to have their surgery performed by a team whose experience and expertise ensures the best possible outcomes.

“We perform two to three surgeries like this per week,” says Dr. Grady. “Not only does our surgical team have vast experience with this type of procedure, the entire team within Penn’s Pituitary Center is aware of the alternatives to surgery when surgery may not be the best option.”

After surgery, patients may receive radiation treatment to prevent recurrence or shrink any part of the tumor that could not be surgically removed.

“Penn offers patients the latest approaches in radiation treatment,” says Dr. Kharlip. “From Gamma Knife® radiation therapy, which delivers a single high dose of gamma radiation to the tumor, to proton therapy which is only offered in a handful of locations within the country, to traditional radiation therapy, patients have the benefit of Penn’s expertise throughout their entire treatment.”

For more information about the Penn Pituitary Center, or to make an appointment, please call 800-789-PENN (7366) or visit PennMedicine.org.

Advanced Neuro Critical Care

It might look like every other intensive care unit (ICU) in a hospital, but Penn Medicine’s Neuro ICU is a highly specialized unit with experts trained to monitor, treat and rehabilitate patients with neurological issues.

W. Andrew Kofke, MD, specializes in anesthesiology and critical care and is co-director, with Joshua Levine, MD, of the 22-bed unit.

“While we act very similar to a regular ICU, our staff is trained and specialized to look for specific issues and complications neurosurgery and neurology patients may encounter as they recover,” says Dr. Kofke.

The Neuro ICU is part of the Penn Comprehensive Neuroscience Center. It is a level I trauma center and acute brain injury center, treating and monitoring patients who have experienced head trauma, spinal cord injuries, epilepsy, brain infections, strokes and patients who have had neurosurgery, including removal of tumors on the pituitary gland.