A Report of Stewardship
to
Reid's Lemon-aid
on advances
within the
Division of Neurosurgery
and
The Falk Brain Tumor Center
at
Children's Memorial Hospital
and
Children's Memorial Research Center
September 2007
Your Support Makes an Impact for Families at Children's Memorial
Children with aggressive brain tumors, spina bifida, hydrocephalus and other complex conditions that affect the brain and nervous system are beating the odds in greater numbers than ever before because of huge strides in pediatric neurosurgery. New technologies, less invasive surgical techniques and safer therapies are revolutionizing how we diagnose and treat children today. Overall, research has been and will continue to be the key to unraveling the complexities of these disabling and often life-threatening disorders and achieving breakthroughs that can transform children's lives far into the future.
We deeply value Reid's Lemon-aid's support of the Division of Neurosurgery and The Falk Brain Tumor Center at Children's Memorial. Thanks to your generous philanthropy, Tadanori Tomita, MD, and his colleagues have the opportunity to bring about advances and opportunities in the field that were never before possible. New therapies emanating from the work they are doing today may hold the key to a vastly different, and better, future for our young patients who need and deserve outstanding neurosurgical care. And, because of your commitment, as powerful new tools and technologies continue to become available, they have the resources they need to further advance their medical knowledge and clinical practice in pediatric neurosurgery.
Philanthropic support has and always will play a critical role in helping to support the division's highest priorities--educational programs, clinical and basic research projects and participation in several national and international presentations and conferences. In appreciation of your support, we are pleased to provide you with this overview that highlights some of the most prominent clinical and research efforts being advanced today within the Division of Neurosurgery and the Falk Brain Tumor Center, which we hope will give you a sense of the vast promise that this work represents for so many of the sick children in his care.
As we look to the future, more children than ever before will continue to seek out our care. As you read on, please know that because of your support, we can continue to offer our patients and their families the absolute best care backed by cutting-edge research and an unmatched commitment to compassion.
A Remarkable History of Providing Outstanding Care and Compassion
Children's Memorial's highly regarded Division of Neurosurgery, headed by Tadanori Tomita, MD, Yeager Professor of Pediatric Neurosurgery, and Director, Falk Brain Tumor Center, continues to make important strides in the treatment and care of children affected by a range of difficult and disabling neurological disorders. With decades of clinical and research experience, our Division of Neurosurgery has brought together the talented team of experts, clinical population and investigative agenda needed to extend the boundaries of care for children and their families in need.
For example, Dr. Tomita leads an interdisciplinary team of medical professionals, rehabilitation specialists and educational experts who are committed to improving outcomes for patients with all forms of hydrocephalus, and has built our reputation as one of the region's leading programs for the diagnosis, treatment and ongoing management of hydrocephalus. Many of our patients experience hydrocephalus as a consequence of brain tumors, trauma, congenital spinal disorders and vascular malformations. As a result, each year, we care for more than 1,500 children on an inpatient basis and record as many as 5,000 outpatient visits related to the ongoing management of hydrocephalus. In addition, the division annually performs between 500 and 600 hydrocephalus-related surgical procedures, including shunt placements and revisions. We continue to achieve excellent clinical results, and the opportunity to further improve the treatment of hydrocephalus for these patients has never been more within our reach.
Furthermore, to improve the care we provide for our patients who suffer from epilepsy, we brought together Drs. Arthur DiPatri and Tord Alden, to create our outstanding Epilepsy Surgery Program, the first pediatric program of its kind in the Chicagoland area. Dr. DiPatri also currently provides surgical services and an outpatient clinic at Shriner's Hospital for their growing patient population who require our exceptional surgical expertise and care.
In the coming year, Dr. Tomita looks to further expand our neurosurgical services through increased outreach efforts to several suburban locations. He also seeks to establish a formal partnership with Shriner's Hospital to conduct craniofacial surgery research.
The 13th International Symposium on Pediatric Neuro-Oncology
It is with great pleasure and enthusiasm that we share the news that both Dr. Tomita and
Dr. Stewart Goldman have been chosen to chair the 13th International Symposium on Pediatric Neuro-Oncology. This biannual event will be held in Chicago June 29th thru July 2nd, 2008. The symposium is a unique event that brings together a large group of physicians, scientists, and allied health professionals from around the world who are experts in the treatment of pediatric brain tumors.
Advancing Neurosurgical Care in a New Children's Hospital
While we can offer outstanding care for our patients, as you know, we can no longer accept the constraints of an aging hospital facility with inadequate space for the growing number of families who come to us in need. Today, our flexibility is severely hindered by the lack of an infrastructure that can support the most advanced technology and standard of care. For these reasons, the leadership of Children's Memorial has launched a historic $400 million campaign to place exceptional care within a 21st century hospital. To do any less would be to step back from our responsibility to the children who need our help.
The new Children's Memorial Hospital will be a state-of-the-art facility where more lives will be saved and an improved quality of life can be achieved for more families. To help us achieve this goal, Dr. Tomita is seeking philanthropic support to establish intraoperative MRI services in the new facility, which will allow him to provide more advanced diagnostic care for his patients
Currently, to assess whether a tumor has been completely removed during surgery, we use ultrasound technology to view the tumor site, which offers a good, although comparably low resolution image. After surgery, the patient is typically sent for a follow-up MRI later that day or the next day.
The two foremost benefits of the intraoperative MRI system is that it will allow the patient to experience less trauma, while offering a greater chance at a higher success rate because it can be performed during surgery and because of the high resolution imagery that it can generate. For example, if the intraoperative image indicates that a small piece of tumor remains at the site, the surgeon is able to resect the tumor immediately before closure, negating the need for a second surgery based on a follow-up MRI.
Today, there are only six pediatric centers in the US utilizing intraoperative MRI with the magnetic field strength necessary to generate the kind of high-quality images needed to truly improve diagnostic care. For the benefit of our young patients, Children's Memorial must be next on that list.
The cost to acquire and install the most highly advanced system in our new facility is approximately $10 million, which will require a significant commitment from our philanthropic community to make this service a reality for our patients and their families. We stand confident that our dedicated donors will ensure that it does.
By 2012, the new Children's Memorial will be a catalyst for healing on the frontiers of innovation and compassionate.
The Healing Power of Research
In general, scientists have learned nearly 90 percent of what they know about the brain in the just the past 10 years, thanks to revolutionary advances in molecular biology, biomedical imaging, structural chemistry, immunology, psychology and computer science. The ability to explore, analyze and direct biological events in a controlled fashion at the cellular level is opening up infinite opportunities to cure disease, restore function and improve the health of children who suffer with neurologic disorders ranging from epilepsy to traumatic brain injury. In an era of unprecedented advances in neurology and neurosurgery, gifted physician-scientists are better positioned than ever before to unlock the deep mysteries of the human brain and develop revolutionary therapies and techniques that may one day prevent these disorders altogether.
Children's Memorial recognizes the importance of research in our institution's national stature. This is evidenced by fact that we have invested more in pediatric research than any other hospital in the region-$233 million over the last six years-a commitment far beyond the usual limits of patient care. Our growing research endeavors have earned the distinction of being awarded $9.7 million in funding from the National Institutes of Health (NIH) in the current year, up from just $3.2 million in 1995. While we are currently ranked eighth in the nation among pediatric institutions receiving NIH funding, we continue to strive to be among the top five recipients in the United States.
This strong level of institutional commitment is a testament to our belief that research is the key element that will propel our Falk Brain Tumor Center from one of the nation's premier programs to one of unparalleled academic excellence. Today, our major areas of research are focused on hydrocephalus, spina bifida and brain tumors, including interstitial studies and nanotechnology.
Understanding Brain Tumors to Treat Patients Better
To improve patient care and outcomes, our Division of Neurosurgery is firmly committed to research that will translate into a better understanding of pediatric brain tumors. Dr. Tomita, for example, serves on numerous national and international committees. The Falk Brain Tumor Center is a full member of the Pediatric Brain Tumor Consortium (PBTC). Only 10 pediatric centers in the country have been chosen to join this prestigious group, formed by the National Center Institute (NCI), which provides access to the most advanced experimental treatment protocols.
Throughout his career, Dr. Tomita has contributed to the advancement of pediatric neuro-oncology in more than 200 peer-reviewed papers. He was among the first to compare the results of partial versus total resection in childhood medulloblastoma, and to report on the long-term neurocognitive outcomes in this group of patients, and he technique of intraoperative neurosurgical ultrasound localization of brain tumors for infants and children, that is now a regular part of a pediatric neurosurgery practices. Dr. Tomita also has been involved in innovative studies using hyperfractionated radiation in brain stem gliomas, and has investigated multi-drug-resistant gene expression in childhood medulloblastoma and ependymomas and its correlation with clinical outcome.
Another major advancement in our ability to undertake research at the frontiers of medical science was the recruitment of internationally renowned scientist, Dr. Marcelo Bento Soares, who joined our brain tumor team last June. Mary J.C. Hendrix, PhD, President and Scientific Director of Children's Memorial Research Center (CMRC), and Dr. Tomita selected Dr. Soares to lead the Cancer Biology and Epigenomics Program at the CMRC, and he was appointed to serve as Scientific Director of the Falk Brain Tumor Research Program.
Dr. Soares' work focuses on understanding the biology of cancer cells in order to speed the development of novel treatments, custom-designed to target the specific tumor of a particular individual. For example, one of his current projects could lead to the creation of a new diagnostic and predictive tool that would provide a fingerprint of cellular cancer activity. This distinctive profile would then serve as a guide for physicians as they make decisions concerning the best possible treatment for a particular cancer at a specific time. Given that cancer is a rapidly changing and differentiating condition within the patient, this type of medical guidance would be invaluable to refine treatment protocols for our patients. Overall, new knowledge about how cancers arise, grow and spread on the molecular level has led to an exponential growth in the development of targeted cancer therapies designed to interrupt abnormal gene activities, restore normal cellular functions and counteract drug resistance. Dr. Soares is working at the forefront of this specialized field of cancer research.
Offering New Treatments for Patients Who Need Them Today
Clinical trials continue to be a major focus of the Falk Brain Tumor Center. We currently offer a number of innovative institutional protocols including up front therapy for brain stem gliomas, treatment of neurofibromatosis, protocols involving stem cell rescue, as well as therapies for recurrent tumors. Two additional developments have hastened our ability to conduct significantly more clinical trials. Dr. Goldman was recently appointed to serve as Director of the Center for Clinical Trials Research for the CMRC. In this role, he provides leadership for our clinical research enterprise and will further develop the infrastructure necessary to support this growing effort. We also were successful in recruiting Jason Fangusaro, MD, a prominent neuro-oncologist from Children's Hospital Los Angeles, who brings extensive clinical trials experience to our team. Altogether, we now operate a four person brain tumor service, including Joanna Weinstein, MD, and Amy Rosenthal, MD, who is training through our dedicated clinical neuro-oncology fellowship.
Neurosurgery also benefits from an international fellowship program which brings two fellows to the hospital each year to receive an additional year of training, including research, after which they return to their home country to practice and improve neurosurgical care throughout the world. Our fellows help to analyze brain tumor samples, conduct drug studies and perform animal dosage testing, like Yaichi Tange, MD, who currently leads a novel research investigation of a highly experimental method that will be the first of its kind in the world. Convection-enhanced delivery of interstitial chemotherapy, a process that delivers a very small amount of chemotherapy directly into the tumor over a prolonged time period, appears to work, at least in part, through a mechanism which causes apoptosis or cell death, another highly promising area of cancer research. Dr. Tange is performing studies to examine the neurotoxicity and efficacy of administering various chemotherapeutic agents interstitially. His studies are underway and are already producing promising results. Another aspiring physician-scientist, Akihide Kondo, MD, arrived this year and is currently training alongside Dr. Tange to take over his research studies this fall.
Advancing Spina Bifida Care at Children's Memorial
As Medical Director of Children's Memorial's Spina Bifida Program for over 30 years, David McLone, MD, PhD, continues to set the standard for excellence and academic leadership for the Division of Neurosurgery at Children's Memorial.
Dr. McLone oversees Children's Memorial's Spina Bifida Genetic Research Project, which continues to collect genetic samples from patients' family members in an attempt to identify abnormal gene sequences. Looking to the future, we know that the identification of the specific gene cluster or genetic pathway(s) that are involved in the development of neural tube defects is critical to developing better treatment options and finding ways to prevent spina bifida. Likewise, identification of the genes that place families at risk might help reduce the incidence of neural tube defects or make early intervention more feasible.
In the laboratory, Dr. Shekhar Mayanil, MD, has uncovered important new findings over the past year regarding the critical role of specific genes during the early stages of human development that form the neural tube. He continues to make important strides in understanding the complex series of events that result in the failure of the neural tube to close, leading to spina bifida. Dr. Mayanil's hope is to use his findings to better help kids heal.
While environmental factors- including maternal toxin exposure, inadequate folate status and hyperglycemia-may account for 70 percent of neural tube defects, genetic factors are known to play an important role. Although researchers have identified nearly 100 genes that influence neural tube defects in mouse models, no single gene has been clearly linked to these defects in humans.
Much of the work that Dr. Mayanil continues to focus on today is related to the Pax3 gene, which belongs to a family of genes that appears to play a critical role in the formation of the neural tube during embryonic development. Other genes that also show a relationship to neural tube defects are TGFß2, Hairy and enhancer of split (Hes1) and Neurogenin2 (Ngn2). Although mutations in all four genes lead to neural tube defects, it is largely unknown if these genes work independently or through mutual regulation.
Dr. Mayanil also leads a novel nanomedicine initiative that was launched in January 2007. The objective of the study is to use magnetic nanoparticles (MNP) for the delivery of drugs and/or genes to the cell structures that are responsible for neural tube closure. In his preliminary studies, Dr. Mayanil was able to target the MNP-FITC (a fluorescence marker) to the nucleus of cells in culture. This initial experiment provided proof of principle for this novel mode of delivery to target cells, particularly to the cell nucleus for neural tube repair. Working alongside Dr. Mayanil, Shurisuke Ichi, MD, a highly talented neurosurgeon from Japan, currently holds the neurobiology research fellowship. His research interests are focused on neural tube defects and hydrocephalus. Together with Dr. Tomita, Dr. Mayanil's laboratory is conducting hydrocephalus research at the molecular level. In particular, the role of aquaporin, a protein present in nervous systems cells, is investigated to determine if it can be altered to reduce the excessive production of water in the brain.
Over the past year, Dr Mayanil submitted two grants to the NIH and the NSF, both of which received high marks, but owing to the current paucity of funds, they did not receive funding. However, he is hopeful that the funding situation will be more optimistic in the next fiscal year.
Realizing the Impact of Your Support
Today, with your help, Children's Memorial is poised to make a significant and lasting difference in the fight against pediatric brain cancer. The number of patients coming to us continues to grow; the synergistic energies of clinicians, clinical researchers and laboratory scientists are combining to yield positive outcomes for the children in our care; the potential for translating the results of scientific inquiries and clinical trials into earlier diagnoses, prevention and better and safer treatment is enormous; and the implications for improving the quality of life for children who suffer from this devastating disease are stunning. As a result, our Division of Neurosurgery and the Falk Brain Tumor Center stand as two of the premier pediatric programs in the country, resolutely establishing Children's Memorial as the place where kids come first.
The tremendous progress we have made and will continue to make can be largely ascribed to high-caliber recruitments and innovations in research - none of which would have been possible without strong philanthropic support. Advances in pediatric neurosurgical care, such as those made by Dr. Tomita, have placed us at the forefront of a transformational moment in medicine. With a 21st century facility anchoring our ability to provide world-class care, the outlook for what we can accomplish in support of our mission to help children thrive is limitless.
Your investment today truly helps to shape the programs and services we can offer, and energizes our quest for new knowledge, all of which benefit children and families through Chicago and beyond-today, and far into the future.
The remarkable courage of our patients and their families motivate us to reach for new heights of excellence every day. As such, Reid's Lemon-aid's partnership will continue to be a crucial ally in our efforts to develop and implement the innovative programs at Children's Memorial that impact families so that they can have the best chance to achieve healthy, happy lives.
Please know that the children and families in our care benefit every day from your heartfelt generosity and compassion.
Thank you.