PHILADELPHIA INTERNATIONAL MEDICINE® NEWS BUREAU
Contact: Leonard N. Karp
215-575-3720
lkarp@philadelphiamedicine.com
April 27, 2006
For immediate release:
In this month's issue:
- Live on the Web—Jefferson Surgeons Perform Leading Edge Minimally Invasive Surgery to Remove Pituitary Tumor
- Therapeutic Prospects Beyond Vioxx: Penn Study Suggests New Class of Anti-inflammatory Drugs that Might Lessen Chance of COX-2 Cardiovascular Problems
- New Rotavirus Vaccine Traced Back to Three Scientists Associated with Children’s Hospital
Editors note: Research, new techniques and improved facilities by Philadelphia International Medicine hospitals and physicians may lead to new ways to treat some of our most challenging diseases. Below are just some examples from our hospitals.
Live on the Web — Jefferson Surgeons Perform Leading Edge
Minimally Invasive Surgery to Remove Pituitary Tumor
Philadelphia – Thomas Jefferson University Hospital will host a Webcast featuring the newest approach for the removal of pituitary tumors – minimally invasive endoscopic pituitary surgery – at 4:30 p.m. Tuesday, May 23, 2006. Viewers also will be able to ask questions online of the surgical team during the surgery.
Jefferson experts in neurosurgery and otolaryngology will perform this procedure through the nasal passages and sinus cavities without external incisions. New state-of-the-art technology has allowed for improved visualization and access to these difficult tumors, resulting in a shorter hospital stay, a faster recovery and improved outcomes. To participate in the Webcast, please email Lucia Rosenberg, director of the PIM Institute of Education, lrosenberg@philadelphiamedicine.com.
The Jefferson Center for Minimally Invasive Cranial Base Surgery and Endoscopic Neurosurgery is the first comprehensive center in the region where surgeons are able to remove skull-based tumors through nose and nasal sinuses instead of the traditional, more invasive surgery which required opening up the brain and skull.
Marc Rosen, MD, Otolaryngology--Head and Neck Surgery, Jefferson Medical College of Thomas Jefferson University, and James Evans, MD, Neurosurgery, will perform the procedure. David W. Andrews, MD, professor and vice chair of Neurosurgery, will narrate. Drs. Evans and Rosen have been working together for several years and have performed at least 150 similar endoscopic tumor surgical procedures to date.
"The Webcast will allow both patients and colleagues to see this leading edge surgical technique that gives us a new way to treat patients with benign and malignant brain, cranial base and sino-nasal tumors, many of which were previously untreatable," said Dr. Rosen.
"Our multidisciplinary team of medical experts has been able to dramatically improve patient outcomes and reduce the length of hospitalization using this new technique," said Dr. Evans. "This is sure to become the standard of care. Through this Center, our multidisciplinary team of medical experts will be able to dramatically improve patient outcomes. Patients can also begin radiation and chemotherapy sooner than they would be able to with conventional surgical procedures."
"Jefferson’s innovative program combines neuro-navigation, endoscopic technology and minimally invasive approaches to effectively treat many cranial base and intracranial tumors previously requiring lengthy and often destructive procedures," said Dr. Rosen. "Better visualization and access to these difficult lesions has enabled improved resection, preservation of function, decreased post-operative morbidity, decreased hospital stay and fewer complications."
The new center has minimally-invasive operating suites, each equipped with state of the art computer navigation systems, and new endoscopic instrumentation, including image guidance capture systems, state-of-the art robotic technology, CT/MRI fusion and plasma monitors. These procedures are also complemented by the Department of Neurosurgery’s Division of Neuro-Oncologic Neurosurgery and Stereotactic Radiosurgery. The Jefferson Hospital for Neuroscience is equipped with both a Novalis® Shaped Beam radiosurgery unit, and gamma knife radiosurgery unit, representing the first configuration of its kind in the region.
Traditionally, cranial-based tumors have been removed through large surgical openings in the patient’s skull or by removing facial bones. Instead, Jefferson’s surgeons first use a thin endoscope with a camera attached to enter a patient’s nose and sinuses, allowing them to view the tumors magnified on plasma screens without external incisions.
Guided by the endoscope and enhanced computer navigation, the surgeons open small holes in the base of the skull and membrane covering the brain.
Jefferson’s surgeons are finding that better visualization and access to these difficult lesions has enabled improved resection, preservation of function, decreased post-operative morbidity, decreased hospital stay and fewer complications.
In addition to pituitary tumors, other conditions that may be effectively managed by minimally invasive endoscopic techniques include: craniopharyngioma (brain tumor that mostly affects children); chordoma (a malignant tumor that occurs along the spine especially attacking the bones at the base of the skull or near the coccyx); chondrosarcoma (malignant neoplasm derived from cartilage cells and occurring most frequently in pelvic bones); meningioma (slow-growing tumor of the meninges, occurring most often in adults); sino-nasal malignancy; juvenile nasal angiofibroma; cerebrospinal fluid leak; and others.
Therapeutic Prospects Beyond Vioxx: Penn Study Suggests New Class of Anti-inflammatory Drugs that Might Lessen Chance of COX-2 Cardiovascular Problems
Researchers at the University of Pennsylvania Medical Center have clarified the mechanism by which drugs like Celebrex and Vioxx cause heart problems, in multiple animal models. The findings offer the prospect of a new generation of anti-inflammatory drugs that by-pass this issue, as reported in the May print issue of "The Journal of Clinical Investigation."
"Although these results are in mice, not people, they raise an exciting possibility which can be tested in humans," says senior author Garret FitzGerald, MD, director of Penn’s Institute for Translational Medicine and Therapeutics.
Ever since the association of selective inhibitors of COX-2 - Vioxx, Bextra and Celebrex - with an increased incidence of heart attack and stroke, there has been intense interest in understanding the mechanism involved. Clarification of this issue offers the prospect of conserving the clinical benefit of these drugs for patients with arthritis, while managing the risk.
Almost 10 years ago, FitzGerald noticed that both Celebrex and Vioxx depressed in healthy individuals a protective fat called prostacyclin, while leaving unaltered a harmful one called thromboxane. This led him to predict that drugs in this class might confer a cardiovascular risk before either reached the U.S. market.
In the present studies, the investigators used multiple genetically manipulated mice - including mice that mimicked the impact of either COX-2 inhibitors or low-dose aspirin and compared them with treating healthy mice with COX-2 inhibitors, such as Celebrex. They found that genetic disruption of COX-2; inhibition of the enzyme by different inhibitors; and disruption of prostacyclin’s effects by removing its receptor all had the same effect - a predisposition to clotting and an elevation of blood pressure. "This provides compelling evidence in support of the original hypothesis," says co-author Colin Funk, PhD, who has collaborated with FitzGerald at Penn over the last decade on this line of research. Funk is now the Canada Research Chair of Physiology at Queen’s University, Ontario. "One does not need additional explanations to understand what we have seen in clinical trials. COX-2 inhibitors confer a small but absolute cardiovascular risk using the same mechanism by which they relieve pain and inflammation."
The investigators also addressed the likely benefit of adding aspirin to diminish this effect of the inhibitors. Surprisingly, this appeared to reduce not only the clotting response, but also the rise in blood pressure caused by drugs like Celebrex.
"Despite some chatter to the contrary, this issue of an aspirin effect has not been addressed directly in any of the clinical trials of COX-2 inhibitors," says FitzGerald. "However, although these studies indicate that it would limit the cardiovascular risk, it would also be expected to add to the risk of stomach problems, undermining the reason for choosing COX-2 inhibitors in the first place."
A surprising finding came when the investigators turned to a drug target that might substitute for COX-2 - an enzyme called microsomal prostaglandin E synthase (mPGES)-1. Other investigators had shown previously that deletion of this enzyme seemed as effective as treatment with NSAIDs in models of pain and inflammation. This has prompted several large pharmaceutical companies to develop drugs targeting this enzyme. Such inhibitors will soon enter human trials.
FitzGerald and his colleagues showed that deletion of mPGES-1, in contrast to deletion or inhibition of COX-2, did not predispose the animals to thrombosis or elevate blood pressure. A clue to this surprising finding was that while mPGES-1 deletion suppressed profoundly another product of the COX-2 pathway called PGE2, the deletion of mPGES-1 actually elevated prostacyclin, the complete reverse of what was observed with COX-2 inhibitors. "Selective inhibitors of mPGES-1 may retain much of the benefit of drugs like Vioxx and Celebrex, while diminishing the risk of heart attack and stroke by having precisely the opposite effect on prostacyclin," says FitzGerald.
Co-authors are research associate Yan Cheng and postdoctoral fellows Ying Yu and Miao Wang, all from Penn. This work was supported by grants from the National Institutes of Health and, in part, a grant from Merck.
PENN Medicine is a $2.9 billion enterprise dedicated to the related missions of medical education, biomedical research, and high-quality patient care. PENN Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation’s first medical school) and the University of Pennsylvania Health System. Penn’s School of Medicine is ranked #2 in the nation for receipt of NIH research funds; and ranked #3 in the nation in U.S. News & World Report’s most recent ranking of top research-oriented medical schools. Supporting 1,400 fulltime faculty and 700 students, the School of Medicine is recognized worldwide for its superior education and training of the next generation of physician-scientists and leaders of academic medicine.
New Rotavirus Vaccine Traced Back to Three Scientists Associated with Children’s Hospital
The federal agency that oversees childhood vaccinations recommended a new vaccine for routine use against rotavirus infection, a common childhood illness that is the single largest infectious disease killer of infants and young children worldwide. Three scientists associated with The Children’s Hospital of Philadelphia and The Wistar Institute are co-inventors of the vaccine, based on research dating to 1980.
The Advisory Committee on Immunization Practices (ACIP), an expert panel selected by the U.S. Department of Health and Human Services, added the new RotaTeq(R) vaccine, manufactured by Merck & Co., Inc., to its list of routinely recommended childhood immunizations. The recent decision follows the vaccine’s approval for licensing by the U.S. Food and Drug Administration.
Rotavirus affects nearly all children at some point, often with mild symptoms, but in other cases with severe and potentially life-threatening diarrhea and dehydration. It causes tens of thousands of hospitalizations in the U.S. each year, and throughout the world, hundreds of thousands of child deaths.
The new vaccine was invented by three Philadelphia scientists: H. Fred Clark, DVM, PhD; Paul A. Offit, MD; and Stanley A. Plotkin, MD, all of whom led laboratory studies of the vaccine at The Children’s Hospital of Philadelphia and The Wistar Institute between 1980 and 1991. Since 1991, the vaccine has been developed for commercial use by Merck, which conducted extensive clinical trials.
Dr. Offit is currently chief of Infectious Diseases, Maurice R. Hilleman Endowed Chair in Vaccinology, and director of the Vaccine Education Center at The Children’s Hospital of Philadelphia. Dr. Clark is a research professor of Pediatrics at Children’s Hospital. Dr. Plotkin, an emeritus professor at Wistar and a former director of Infectious Diseases at Children’s Hospital, developed a number of previous vaccines, including the vaccine that has eradicated rubella (German measles) in the United States.
"This vaccine against a major childhood killer will impact the lives of children around the world," said Steven M. Altschuler, MD, president and chief executive officer of The Children’s Hospital of Philadelphia. "The addition of this vaccine to the roster of childhood immunizations is the culmination of decades of work and represents a significant milestone in public health. It brings us a step closer to our ultimate goal of eliminating childhood disease."
Nearly every child experiences infection with rotavirus, usually as gastroenteritis. In the United States, children under age five experience an estimated 2.7 million episodes of rotavirus gastroenteritis each year, resulting in 250,000 emergency room visits and an estimated 70,000 hospitalizations. In developing countries, where appropriate medical care may be unavailable, rotavirus kills as many as 600,000 children annually. Merck conducted clinical trials of RotaTeq in more than 70,000 infants in 11 countries - one of the largest clinical trials to be performed by a pharmaceutical company. The company’s data showed that the vaccine prevented 98 percent of severe cases of rotavirus gastroenteritis and 74 percent of routine cases, compared to a placebo. Furthermore, the vaccine showed no increased risk of intussusception, a telescoping of the bowel that had been associated with a previous, discontinued rotavirus vaccine produced by another manufacturer in the 1990s.
Currently the only vaccine available in the U.S. to prevent rotavirus gastroenteritis, the new vaccine will be delivered by mouth, in three doses, at well-baby visits at ages two, four and six months. Merck has expressed a commitment to working with the global public health community to make the RotaTeq vaccine available to infants and children worldwide.