PHILADELPHIA INTERNATIONAL MEDICINE® NEWS BUREAU
Contact: Leonard N. Karp
lkarp@philadelphiamedicine.com
215-735-3989
August 26, 2005

For immediate release:

In this month's issue:

1. Fox Chase-Temple Bone Marrow Transplant Program Increases Capacity, Services
2. Jefferson Neurosurgeons, Radiation Oncologists Wrap Radiation Around Spine to Provide Cancer Pain Relief
3. Jefferson Surgeons to Perform Immediate Breast Reconstruction Surgery Live on Internet Sept. 29
4. MossRehab Welcomes Michael F. Saulino, MD, PhD and Theera Vachranukunkiet, MD as Attending Physicians
5. Penn Study Finds a New Role for RNA in Human Immune Response Penn Findings Could Lead To New Types of Therapeutic RNAs for Cancer, Genetic Diseases

Editors note: Research by Philadelphia International Medicine physicians may lead to new ways to treat some of our most challenging diseases. Below are some examples from our hospitals.

Fox Chase-Temple Bone Marrow Transplant Program Increases Capacity, Services

Philadelphia – The Fox Chase-Temple Bone Marrow Transplant (BMT) program has substantially increased its capacity in order to offer complete continuity of care for the treatment of patients with acute leukemia. With this added capacity, the Fox Chase-Temple BMT Program can now admit patients with acute myelogenous and acute lymphoblastic leukemia at the time of diagnosis.

This expanded service complements highly successful autologous and allogeneic transplant programs in myeloma and lymphoma, and a mini-allogeneic transplant program. The growing BMT program, in its 18th year of operation, now occupies an entire wing of Jeanes Hospital in Northeast Philadelphia.
At the Fox Chase-Temple BMT program, a multidisciplinary team cares for leukemia patients, ages 16 to 70, from the time of diagnosis through initial induction and consolidation chemotherapy. Following initial chemotherapy, leukemia patients are taken to an autologous or allogeneic stem cell transplant with curative potential.

“Induction therapy is a very intense and lengthy process that can take four to six weeks,” says program director Kenneth F. Mangan, MD, F.A.C.P. “It requires the type of unique supportive care that we offer in the Bone Marrow Unit.”

A three-to-one patient-to-nurse ratio ensures that acute leukemia patients receive focused care. The BMT team is expert at administering chemotherapy, caring for central Hickman catheters and working with blood and platelet transfusion patients. Private rooms have special air filtration to protect patients from infection.
The vast majority of acute leukemia patients who are younger than 65 and go into remission are transplant candidates. “It makes sense for us to see these patients at diagnosis, get them into remission with induction therapy, and then ultimately transplant them,” says Dr. Mangan. “A truly seamless transition, from pre-transplant therapy to transplant therapy, is best for the patients.” This continuity of care expedites the transition to transplant, minimizing the risk of relapse before transplantation can occur.

The Fox Chase-Temple BMT Program is a fully accredited adult transplant and stem-cell collection center for the National Marrow Donor Program. In addition, the Foundation for Accreditation of Cellular Therapy awarded the program its’ prestigious Level I status in 2000. It is one of the first programs in the country to achieve and maintain such status.

The Program offers autologous, allogeneic and unrelated allogeneic bone marrow/blood stem cell transplants for most hematologic malignancies, aplastic anemia, amyloidosis and selected solid tumors. The BMT team has performed more than 850 transplants since the Program’s inception in 1988 and has taken a leadership role in the innovative use of high-dose chemotherapy and autologous and allogeneic stem cell transplants.

The program team has performed over 90 low-intensity, or “mini” allogeneic transplants. Since 1999, Fox Chase-Temple transplant physicians have treated older patients with hematologic malignancies and metastatic renal cell cancer using a low-intensity “mini” allogeneic blood stem-cell transplant. Studies have shown that by using matched related and matched unrelated donors, 40 to 50 percent of patients may obtain complete or partial responses due to a graft vs. renal-cell cancer effect. Up to 80 to 90 percent of patients with hematologic malignancies may benefit from a graft vs. tumor effect.

“We’ve done approximately 90 donor transplants in patients in their late 50s and 60’s –a group that we were not previously able to treat,” says Mangan. “Because we’ve reduced the intensity of the preparation regimen and subsequent treatment-related mortality, we’re now able to offer this type of transplant to patients in the older age group where these diseases are more common.”

With increased capacity comes the need for additional staffing. Mary Ellen Martin, MD, who has a research interest in acute lymphoblastic leukemia, has joined the BMT team. Within the next year, two additional physicians, three physicians assistants and eight new nurses will round out the growing team of expert caregivers.

Jefferson Neurosurgeons, Radiation Oncologists Wrap Radiation Around Spine to Provide Cancer Pain Relief

Using the most advanced radiation technology currently available in the region, neurosurgeons and radiation oncologists at the Jefferson Hospital for Neuroscience and Thomas Jefferson University Hospital have for the first time wrapped beams of radiation around a patient’s spine, relieving pain from several cancerous tumors there while avoiding the spinal cord.

The technology, called shaped beam surgery, relies on sophisticated computers to tailor the shape and intensity of radiation beams to fit the exact size and shape of the tumor ¬– all while sparing healthy tissue. It enables doctors to treat a range of hard-to-reach benign and malignant tumors in the brain and spine they couldn’t treat before, often avoiding invasive surgery and speeding the patient’s recovery.

David Andrews, MD, professor of neurosurgery at Jefferson Medical College of Thomas Jefferson University and director of the Division of Neuro-oncologic Neurosurgery and Stereotactic Radiosurgery at Thomas Jefferson University Hospital, used shaped beam surgery to treat the patient, a 46-year-old, who had two tumors on her spine that had spread from another cancer elsewhere in the body. One tumor was pressing on the spinal cord, causing considerable pain. Treating the tumors with standard radiation was impossible because she had already received spine radiation more than 20 years earlier for non-Hodgkin’s lymphoma.

According to one of her physicians, neurosurgeon Ashwini Sharan, MD, assistant professor of neurosurgery at Jefferson Medical College, the woman would have needed three separate surgeries, including abdominal surgery to reach the cancer in her lumbar spine, and back surgery to reconstruct her spine with medical screws.

He explains that cancer in the spine is almost invariably considered advanced metastatic disease, and patients usually have an uncertain prognosis. “The only other option besides radiosurgery is reconstructive spinal surgery. Recovery from a spine operation and reconstructive surgery is three to six months, and surgeons and patients with spine cancer must weigh the costs and benefits because of the trauma and pain involved with surgery. “The goal is to keep patients independent, pain-free and ensure a good quality of life,” says Dr. Sharan. The patient, he notes, avoided a six-week hospital stay and was able to be at home and relatively pain-free.

“We can wrap doses around structures such as the spinal cord, and can create a very high dose of radiation and leave the cord untouched,” says Dr. Andrews, who is director of the Radiosurgery Units at the Jefferson Hospital for Neuroscience. “There’s no other technology out there that can do this.”

“Shaped beam surgery is a new tool for selected patients,” says Walter J. Curran Jr., MD, professor and chair of Radiation Oncology at Jefferson Medical College and clinical director of the Kimmel Cancer Center at Jefferson. He notes that the technology provides an improved ability to specifically target a tumor with real-time imaging.

“As oncologists continue to improve treatments and enable many individuals with metastatic cancer to live longer, more productive lives, expectations and quality-of-life issues become paramount,” notes neurosurgeon James Harrop, MD, assistant professor of neurosurgery at Jefferson Medical College and neurosurgery director of the Regional Spinal Cord Injury Center of the Delaware Valley at Thomas Jefferson University. More patients with metastatic breast cancer, for example, are living longer, healthier lives than ever before.

“As we move forward in using this technology for spinal cancer patients, we will continue to focus on treating the individual’s pain,” Dr. Andrews says. “One of the promises of this technology is more rapid relief of spinal cord pain and more rapid disease control.”

Jefferson Surgeons to Perform Immediate Breast Reconstruction Surgery Live on Internet Sept. 29

Women with breast cancer often seek immediate breast reconstruction after a mastectomy to help them regain a semblance of their body and for their psychological peace of mind.

One of the most often performed breast reconstruction surgical procedures, using muscle tissue from a patient’s back, will be demonstrated live on the Internet by surgeons at Thomas Jefferson University Hospital, in advance of Breast Cancer Awareness Month, which begins in October.

Jefferson surgeons who specialize in treating breast cancer will perform immediate breast reconstruction after mastectomy at 4:30 p.m. on Thursday, September 29, in a webcast from Jefferson University Hospital. For information on viewing the Webcast, contact Lucia Rosenberg, director of the Philadelphia InternationalMedicine Institute of Education at lrosenberg@philadelphiamedicine.com , or call her at 215-735-3269.

The 60-minute webcast will not only include the live reconstruction, but cover the entire medical path that a patient diagnosed with breast cancer takes during diagnosis and treatment, from an abnormal mammogram, MRI and other diagnostic imaging, to genetic testing and risk assessment, a biopsy, sentinel node biopsy and mastectomy, said breast surgeon Anne Rosenberg, MD, clinical associate professor of Surgery, Jefferson Medical College of Thomas Jefferson University.
“We want to present women with the latest and best options for diagnosing and treating breast cancer,” said Dr. Rosenberg. “This webcast will demonstrate simply and clearly what a patient can expect if she is diagnosed with breast cancer.” Dr. Rosenberg will host the webcast with plastic surgeon Steven Copit, MD, clinical assistant professor of Surgery, Jefferson, who will perform the reconstruction.

The Jefferson surgeons will demonstrate latissimus dorsi flap surgery, in which tissue, sometimes including underlying fat and muscle, is taken from the back and tunneled to create a breast mound to reconstruct the breast.

“So when the patient wakes up from surgery, there is a breast mound already in place and the patient is spared the experience of seeing herself with no breast at all,” said Dr. Copit. “It looks better [to the patient] and offers them a psychological advantage.”

Once the shell is in place, the plastic surgeon uses an expander, a balloon-like object, underneath the chest muscles. The expander is inflated to try to stretch the skin and to maintain the new breast’s shape until an implant — possibly a silicone container filled with saline solution -- can be put in about three months later, Dr. Copit said.

“This type of reconstruction also allows a breast cancer patient to receive radiation therapy and chemotherapy,” Dr. Rosenberg noted.

The patient is typically under general anesthesia for a total of four hours during both the mastectomy and reconstruction procedures.

Three months following the implant procedure, another procedure is performed to recreate the breast’s nipple, Dr. Copit said. The surgeon may reconstruct the nipple and areola with tissue from the reconstructed breast or with a graft of skin from the underarm. Sometimes tattooing is done instead of, or in addition to, the tissue graft.

Dr. Copit said that not every patient is a good candidate for breast reconstruction using back tissue; it depends, for one thing, on the amount of tissue available to recreate the breast. The patient may be in the hospital for three to six days after surgery, and it may take three to four weeks for her to heal completely.

Prior to seeing the reconstruction procedure live, webcast viewers will see patients undergoing procedures including:

A breast biopsy -- the removal of breast tissue through surgery or by withdrawing tissue through a needle for examination by a pathologist. A biopsy is recommended when a significant abnormality is found either on physical examination and/or by an imaging test. Examples of abnormality can include a breast lump felt during physical self-examination or tissue changes noticed from a mammogram. Before a biopsy is performed, it is important to make sure that the threat of cancer cannot be disproved or ruled out by a simpler, less invasive examination. A lump may be determined to be harmless when examined by ultrasound. If this result is not decisive, the presence of cancer or a variety of benign breast conditions can be determined using a biopsy.

Genetic testing or risk assessment -- providing individuals with information and guidelines based on their family history and/or genetic test results that will assist them and their families in the prevention of cancer occurrence and in the early detection of cancer. Family history is the primary indicator of an inherited risk for cancer. The staff of the Hereditary Cancer Program at Jefferson, for example, evaluates a person’s family history and develops a written risk assessment and a cancer screening program for each individual and their at-risk family members. The Jefferson Hereditary Cancer Center takes a multidisciplinary approach to cancer risk evaluation and is one of few centers that offer cancer risk counseling for any type of cancer. Sentinel node biopsy -- to determine whether cancer has spread to the lymph nodes. Sentinel node dissection involves injecting a radioactive isotope and/ or blue dye into a patient’s breast before her surgery. This marker follows the same path that malignant cells would follow as they might spread from the tumor in the breast to the nodes. The surgery begins as the dye reaches the first layer of nodes. This first or sentinel node is identified and removed, and examined for any signs of cancer.

Mastectomy -- There are several types of procedures for surgery of the breast where cancerous tumors are found. One is a total (or simple) mastectomy, in which the surgeon removes the entire breast and may also remove some of the lymph nodes under the arm, also called the axillary lymph glands. Often, breast cancer spreads to these lymph nodes, thereby entering the lymphatic system allowing the cancer to spread to other parts of the body. Another type is a modified radical mastectomy in which the surgeon removes the entire breast, some of the lymph nodes under the arm and the lining over the chest muscles. In some cases, part of the chest wall muscles is also removed.

Jefferson’s Kimmel Cancer Center is a National Cancer Institute (NCI) designated cancer center. This recognition for excellence in cancer research and treatment allows patients access to the very latest in care. Doctors at Thomas Jefferson University Hospital have been cited as among the nation’s best for cancer treatment by “Best Doctors in America.”

Jefferson’s breast surgeons have also made important contributions to the lumpectomy procedure and to overall guidelines for surgical care of breast cancer.

MossRehab Welcomes Michael F. Saulino, MD, PhD and Theera Vachranukunkiet, MD as Attending Physicians

Michael Saulino, MD, PhD, earned his medical degree and doctorate in Neuroscience at the Hershey Medical Center. Following an internship at Mercy Catholic Medical Center, he completed residency training in Physical Medicine and Rehabilitation at Thomas Jefferson University Health System. Dr. Saulino is board certified in Physical Medicine and Rehabilitation, Pain Medicine, and Spinal Cord Injury Medicine.

Prior to joining MossRehab, Dr. Saulino was an attending physician at Magee Rehabilitation Hospital and residency program director, Department of Rehabilitation Medicine at Thomas Jefferson University. His clinical interests are spasticity management, pain management, swallowing disorders and spinal cord injury.

Dr. Saulino has been appointed Clinical Director, Outpatient Services at MossRehab at Elkins Park and Director, MossRehab Adult Spina Bifida Program. Services he will provide include rehabilitation consultations, Intrathecal Pump Management, Neurolytic Blockage Procedures and Electrodiagnostic studies.

Theera Vachranukunkiet, MD, earned her medical degree at the University of Pennsylvania. She completed an internship in the Department of Internal Medicine at Abington Hospital. Her residency training in Physical Medicine and Rehabilitation was completed at Thomas Jefferson University Health System, where she was chief resident. Most recently she completed Fellowship training in Gait and Motion Analysis at MossRehab.

Dr. Vachranukunkiet will provide inpatient and outpatient services in the MossRehab Amputee program, including prosthetic prescriptions. Additional services she will provide include rehabilitation consultations, Gait Lab and upper limb Motor Control Lab evaluations, botulinum toxin neurotherapy, orthotic prescriptions, EMG/Nerve Conduction studies, and ambulatory services for patients with Musculoskeletal pathologies.

Penn Study Finds a New Role for RNA in Human Immune Response Penn Findings Could Lead To New Types of Therapeutic RNAs for Cancer, Genetic Diseases

Researchers at the University of Pennsylvania Medical Center have published the first study to test the role of RNA chemical modifications on immunity. They have demonstrated that RNA from bacteria stimulates immune cells to orchestrate destruction of invading pathogens. Most RNA from human cells is recognized as being self and does not stimulate an immune response to the same extent as invading bacteria or viruses. The researchers hypothesize that if this self-recognition fails, then autoimmune diseases such as systemic lupus erythematosus could result.

The research was a collaborative work led by Drew Weissman, MD, PhD, of the Division of Infectious Diseases and Katalin Karikó, PhD, of the Department of Neurosurgery. The investigators published their findings in the August issue of Immunity. “We think this study will open a new area of research in understanding how our immune systems protect us,” says Dr. Weissman.

“One application of our findings is that scientists will be able to design better therapeutic RNAs, including anti-sense or small-interfering RNAs, for treating diseases such as cancer and single-gene genetic diseases,” says Dr. Karikó.

RNA is the genetic material that programs cells to make proteins from DNA’s blueprint and specifies which proteins should be made. There are many types of RNA in the cells of mammals, such as transfer RNA, ribosomal RNA, messenger RNA, and all of them have specific types of chemical tags, or modifications. In contrast, RNAs from bacteria have fewer or no modifications.

Another type of RNA in mammalian cells is found in mitochondria, the powerhouses of cells. Mitochondrial RNA is thought to have originated from bacteria millions of years ago. Similar to RNA from bacteria, mitochondrial RNA has fewer chemical tags. It is the absence of modifications that causes RNA from bacteria and mitochondria to activate the immune response. The researchers suggest that these modifications have evolved in animals as one of the ways for the innate immune system to discriminate self from non-self.

When a tissue is damaged by injury, infection, or inflammation, cells release their mitochondrial RNA. This RNA acts as a signal to the immune system to recognize the damage and help defend and repair the tissue.

Conversely, the presence of the modifications on the other types of RNA does not activate an immune response and thus allows the innate immune system to discriminate self from non-self. “We showed that special proteins on the surface of immune cells, called Toll-like receptors, are instrumental in recognizing bacterial and mitochondrial RNA,” explains Weissman. The amount of modification on the RNA is important because as little as one or two tags per RNA molecule could prevent or suppress the immune reaction.

The authors concluded that the potential of RNA to activate immunity seems to be inversely correlated with the extent of its chemical modification and may explain why some viral RNA that is overly modified evades immune surveillance. The authors plan to investigate whether longer RNAs with specific tags will be useful for delivering therapeutic molecules to diseased cells.

This study was funded by the National Institutes of Health. Co-authors are Michael Buckstein and Houping Ni, both from Penn.

Philadelphia International Medicine is an organization that provides medical and patient support services to international patients. It also provides continuing medical education and health care training and education to international physicians, administrators and other practitioners. As the international department of several Philadelphia-area hospitals, international patients gain access to physicians and hospitals rated among the best in the world through one telephone call to PIM. You can reach PIM by calling 1-215-735-3575; fax, 1-215-790-1267; or e-mail, physicians@philadelphiamedicine.com . You can find out more about PIM through its Website at www.philadelphiamedicine.com .