PHILADELPHIA INTERNATIONAL MEDICINE® NEWS BUREAU
Contact: Leonard N. Karp
lkarp@philadelphiamedicine.com
215-735-3989
January 28, 2004

In this month's edition:

1. Temple Doctors Use Removable Filter Device to Prevent Life-Threatening Blood Clots
2. Fox Chase Researchers Demonstrate Ability to Detect Kidney Cancer through Urine
3. New Drug May Help Cancer Patients in Need of Stem Cell Transplants, Jefferson Trial Shows
4. Marian S. Ware Alzheimer Program Established at PENN Medicine with a $6 Million Gift

Editor’s Note: Philadelphia International Medicine® hospitals are making news with new research, journal articles and new services. This month’s news bureau edition brings you several examples.

Temple Doctors First to Use Removable Filter Device to Prevent Life-Threatening Blood Clots

Philadelphia – Doctors at Temple University Hospital are the first in Philadelphia to use a new removable filter that helps prevent blood clots from forming and traveling to the lungs, a serious condition that causes as many as 150,000 deaths each year.

The new retrievable filter, called the Recovery® vena cava filter, is inserted into a major vein. It protects patients at high risk for developing deep vein thrombosis (DVT) of the legs and pulmonary embolism that cannot be treated with routine blood thinners.

Up to now, only filters that could stay in the body no longer than 2 weeks had been available for use. The new filter, which can be left in the body as long as the physician deems warranted, allows physicians more flexibility in protecting patients against life-threatening clots. The new filter received FDA approval as a permanently placed device in November 2002 and recently was cleared to allow for removal, as well.

The filter is implanted through a small needle usually inserted in a vein in the groin. Using x-ray imaging techniques, the filter is placed in the inferior vena cava (IVC) at a point that is protective of clots that could travel from the legs to the heart and lungs.

Removal is performed on an outpatient basis, using a newly-developed technique in which angiography and x-rays are used to visualize the filter and grab it with a unique conical retrieval device. The procedure takes about 30 minutes and patients experience a quick and easy recovery.

This new method of removal is ideal for young patients with thrombosis of the legs, or patients recently post-partum with DVT who require short-term safeguards like this one. Also, the obese population and orthopedic population can benefit from having a filter that can be easily inserted and

removed. Cancer patients and those undergoing surgery, including orthopedic and neurosurgical procedures, risk developing venous thrombosis and pulmonary embolism as well.

“We are extremely pleased to be able to bring this new technology to our patients,” says Gary Cohen, MD, associate professor, chief of Vascular/Interventional Radiology and vice chairman of Radiology at Temple University Hospital. “I believe this is an important advance in the treatment of patients with potentially lethal deep vein thrombosis of the pelvis and legs. We can now comfortably insert a device that protects patients from fatal pulmonary embolism but feel confident that we can remove it when the risk of anticoagulation and DVT are no longer present. We will see a large role for this new FDA-cleared technology in a significant percentage of the DVT population.”

Fox Chase Researchers Demonstrate Ability to Detect Kidney Cancer in Urine

Laboratory researchers and urologic oncologists from Fox Chase Cancer Center have demonstrated the ability to identify kidney cancer, including localized (stage I) cancer, in the urine of affected patients. The research is published in the Dec. 15 issue of the journal Cancer Research.

As with other cancers, an early diagnosis of kidney cancer can result in curative treatment whereas the prognosis for advanced kidney cancer is poor. The challenge in diagnosing cancer early is developing an inexpensive, noninvasive, accurate and simple screening test. The researchers say a urine test meets these standards. Currently, kidney cancer is diagnosed after radiographic imaging of the kidney, which may include an ultrasound, CT scan and/or MRI. Biopsy of a kidney mass is often difficult to interpret or may give a false negative result and therefore currently confirmation of radiographic results is primarily after surgical excision. There is no protein marker test for kidney cancer as there is for prostate cancer with the PSA test.

“We used a common laboratory procedure to test the urine of 50 patients with kidney cancer,” explained Fox Chase molecular biologist Paul Cairns, PhD, lead author of the study. “Forty-four of the 50 tests showed gene changes in the urine that were identical to the gene changes found in the tumor samples taken at the time of surgery.”

When the same test was conducted on the controls – urine from people without cancer – none showed the relevant gene alterations that were found in the urine from people with cancer.

“The test is remarkably accurate with no false-positives in this study,” said Robert G. Uzzo, MD, a urologic surgeon at Fox Chase and co-author of the paper. “In addition, one of the most impressive outcomes of this research is that the test also identified 27 of the 30 patients with stage I disease. Finding these cancers early means earlier treatment and better prognosis.”

The researchers used a molecular DNA-based test called methylation-specific PCR (polymerase chain reaction) to detect genetic alterations that initiate and fuel the onset of cancer. The test searched for six cancer specific tumor-suppressor genes that were altered – causing them to falter in their critical role of preventing errant cell growth. These six genes are usually identified only after a pathologist’s review of tumor tissue.

“If these results are confirmed in larger studies, this urine-based test may play a vital role in kidney cancer diagnosis,” said Cairns.

New Drug May Help Cancer Patients in Need of Stem Cell Transplants, Jefferson Trial Shows

A new drug may help patients restore their blood-forming system after high-dose chemotherapy, according to results from a clinical trial at the Kimmel Cancer Center at Thomas Jefferson University Hospital in Philadelphia.

In the phase II trial, which is being conducted at several centers in the United States, researchers are attempting to determine if patients with multiple myeloma or non-Hodgkin’s lymphoma who receive the drug AMD-3100 along with the standard drug G-CSF have more stem cells available for transplantation as compared to those who receive only G-CSF.

AMD-3100 blocks a specific cellular receptor, triggering the movement of stem cells out of the bone marrow and into the circulating blood, boosting the supply of stem cells from the bone marrow to be used in transplantation. Stem cell transplantation entails collecting certain types of cells known as hematopoietic stem cells from patients who receive treatment with high-dose radiation and/or chemotherapy for cancers such as leukemias, lymphomas and multiple myeloma, all of which involve the blood and immune system. The cells, once returned to the body, help restore the blood-forming system within the bone marrow – and the body’s immune system, which is severely damaged if not destroyed by high-dose chemotherapy and/or radiation.

To date, every one of 19 patients given the drug combination were able to mobilize stem cells from the marrow to the bloodstream better than those who had G-CSF alone, says Neal Flomenberg, M.D., professor of medicine and director of medical oncology at Jefferson Medical College of Thomas Jefferson University, who oversees the trial at Jefferson. Dr. Flomenberg presented the trial’s interim results December 7 at the American Society of Hematology’s 45th Annual Meeting.

As a result, he said, there were fewer stem cell collections necessary and more stem cells retrieved. “This is the first time the drug combination has been tested in patients who have undergone chemotherapy, whose marrows have already been somewhat beaten up from prior treatment,” Dr. Flomenberg says. “This is the acid test. These are the first patients whose cell products are being used for transplants.”

Most patients undergo standard chemotherapy for four to eight months before they have a stem cell transplant, he explains. Some patients won’t have a transplant until their disease relapses and treatment once again puts them back in remission. These treatments sometimes make subsequent stem cell collection difficult.

According to Dr. Flomenberg, stem cell transplantation is “front line therapy for multiple myeloma, or cancer of the bone marrow, and for high-risk lymphoma patients.”

Approximately 25 percent to 35 percent of transplant patients have trouble moving stem cells from their bone marrow into the bloodstream using the standard drug, G-CSF. “Some patients with the standard approach don’t mobilize well, meaning more collections and often a poor or unusable cell product,” he says.

Dr. Flomenberg explains that based on results to date, the drug holds promise to cut down the number of stem cell collections patients need. The drug combination may both increase the number and improve the quality of cells collected. The greater the number of available stem cells, the more likely transplantation will be successful. In some cases, this can mean the difference between a patient being able to receive a transplant or not. The drug has little toxicity.

Marian S. Ware Alzheimer Program Established at PENN Medicine with a $6 Million Gift

The University of Pennsylvania today announced the establishment of the Marian S. Ware Alzheimer Program, comprising a set of collaborative initiatives between PENN Medicine and the University of Pennsylvania School of Nursing to advance drug discovery, clinical research and patient care related to Alzheimer’s disease. The Program is created through a $6 million gift from Marian S. Ware, a long-time supporter of the University and advocate for progress in medical research and treatment for Alzheimer’s disease.

The Marian S. Ware Alzheimer Program will uphold a three-part mission: drug discovery, identifying and evaluating novel therapeutics; clinical research, particularly in developing and testing biomarkers to identify patients with Alzheimer’s disease; and patient care, formulating best practice models that coordinate the complex care needs of patients and their family members.

“With our aged population projected to expand dramatically in the coming years, and with Alzheimer’s disease research showing great potential, now is the time to focus increased resources and energies on uncovering the mysteries of this devastating disease and offering new hope to its patients and their loved ones,” said Dr. Arthur H. Rubenstein, executive vice president of the University of Pennsylvania for the Health System and Dean of the School of Medicine. “The timely and extraordinarily generous gift from Marian S. Ware will be invaluable to advancing Penn’s contributions to several realms of this vital work.”

The Marian S. Ware Alzheimer Program will build on the recognized expertise and research strengths at Penn’s Alzheimer’s Disease Center, the Center for Neurodegenerative Disease Research, and collaborating faculty and centers within the University of Pennsylvania Schools of Medicine and Nursing.

In the last decade, Penn researchers have identified potential targets of therapy for Alzheimer’s disease. The drug discovery component of the program will capitalize on these recent discoveries by attempting to identify novel compounds that may prevent or ameliorate the onset or progression of Alzheimer’s disease. This work will be led by Center for Neurodegenerative Disease Research Director Virginia M.Y. Lee, PhD, MBA, and co-director John Q. Trojanowski, MD, PhD.

The clinical research initiative addresses another goal within the Alzheimer’s disease medical community: developing a reliable, easily administered, and safe test to both detect Alzheimer’s disease pathology and measure changes in disease progression. The assay would facilitate clinical research and improve a physician’s ability to identify patients with Alzheimer’s disease who might benefit from treatment. This work will be led by Christopher M. Clark, MD (Department of Neurology) and Jason H. Karlawish, MD (Department of Medicine: Division of Geriatrics), of Penn’s Alzheimer’s Disease Center Memory Disorders Clinic.

The third main piece of the program focuses on developing a comprehensive, coordinated and cost-effective model of care management for Alzheimer’s patients, who often have multiple chronic illnesses and must navigate through an intricate, disjointed health care system.

A recently completed pilot study, led by Mary D. Naylor, PhD, RN, the Marian S. Ware Professor in Gerontology at the University of Pennsylvania School of Nursing, and funded by the Alzheimer’s Association, demonstrated the potential of an innovative, evidence-based model of care management for high-risk elders and their caregivers, one implemented by advanced practice nurses in collaboration with patients’ physicians and other health team members.

“Managing the progression of Alzheimer’s in patients and providing nursing support for them and their family members is ultimately as critical as managing the disease itself. In order to best care for Alzheimer’s patients, we must be continuously working to develop, test, and apply cutting-edge models of care management, “ said Dr. Afaf Meleis, Dean of the School of Nursing.

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