New Replacement Procedure Preserves More of the Hip
 Brain Stimulation Techniques Enhance Psychiatric Treatment
 Cancer Drug for Children Shows Promise



New Replacement Procedure Preserves More of the Hip

By Adar Novak
Patient X-ray
Patient X-ray showing a left total hip arthroplasty (right side of image) with ceramic on ceramic articulation and bone-preserving right total hip resurfacing (left side of image) with a metal on metal articulation
An avid outdoorsman, Larry S. was afraid he would have to give up hunting, fishing, cycling, and whitewater rafting when he learned he needed surgery on his right hip. After being referred to William Macaulay, M.D., associate professor of clinical orthopedic surgery and director of Columbia’s Center for Hip and Knee Replacement, in December 2005, Mr. S. was told he would be able to continue his active life.
   Rather than a total hip replacement — which Mr. S. had on his other hip several months earlier — he opted this time for a new procedure called a total hip resurfacing. The decision put Mr. S. back on the path to adventure in less than four months.
   Total hip resurfacing preserves more of the body’s natural bone structure. A total hip replacement involves the removal of the entire femoral head and neck; resurfacing involves the reshaping and then capping of the bone of the femoral head, leaving the neck untouched. This procedure enables people to return more quickly to an active lifestyle.
   The all-metal implant used in resurfacing is much larger than the one used in total hip replacement (in some cases doubles the diameter) to allow greater stability and almost obviating the possibility of dislocation. It requires a slightly larger incision to work around the femoral head and neck so that more of these structures can be saved.
   While awaiting FDA approval for the operation, Dr. Macaulay was able to perform the procedure on many patients after receiving approval for compassionate use from Columbia’s institutional review board. The FDA approved the procedure in May 2006; since then Dr. Macaulay has performed more than 30 additional total hip resurfacing operations. All of the operations have had excellent outcomes.
   “Total hip replacement is still the gold standard, and the resurfacing technique has to be chosen for just the right patients,” Dr. Macaulay says. “We anticipate that about 20 percent of the patients who come in for a total hip replacement will be suitable candidates for this procedure.”
   The ideal patient for total hip resurfacing is someone relatively active and under 60 years old who suffers from arthritis, dysplasia, or avascular necrosis of the hip. The implant can be used only in patients whose bone quality is strong enough to support it. Dr. Macaulay adds that the procedure has been successful because the patients — like 37-year-old Mr. S. — are relatively healthy and active at the start. Mr. S. underwent the total hip resurfacing procedure as part of the compassionate use program.
   “While the total hip replacement on the left side was successful, my right side is much stronger than my left,” Mr. S. says. “I don’t have constant pain because I’m walking around with more of my original parts. I only wish I could have had it done on both sides.”
   He adds that the recovery time was shorter when he had his hip resurfaced, and the rehabilitation was faster. Dr. Macaulay is the only Columbia surgeon performing total hip resurfacing, but he plans to train his colleague, Jeffrey Geller, M.D., assistant professor of orthopedic surgery, to do the procedure. Dr. Macaulay is also an official surgeon trainer for Smith & Nephew, the company that manufactures the implants. Many patients who have learned of the resurfacing technique have approached Dr. Macaulay, who urges a careful approach.
   “My hope would be that both surgeons and patients continue to use it prudently, that surgeons get adequate training, and that potential patients receive enough opinions from highly trained surgeons to make the appropriate choice,” he says.

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Brain Stimulation Techniques Enhance Psychiatric Treatment

By Adar Novak
The use of brain stimulation to aid treatment-resistant depression burst into the national news several months ago with a book by Kitty Dukakis, former first lady of Massachusetts, in which she describes her success with electroconvulsive therapy (ECT). Her experience — and that of tens of thousands of others who have undergone the treatment — would not have been possible without the research conducted at the Division of Brain Stimulation and Therapeutic Modulation at the New York State Psychiatric Institute, which has made Columbia a clear leader in the field. These efforts could lead the way to help the approximately 8.5 million Americans suffering from treatment-resistant depression.
  Columbia has opened a new clinical service, the Brain Stimulation Service, that offers expert consultations, treatment, and research into innovations in therapeutic brain stimulation.
  “Of the nine types of brain stimulation used in the United States, Columbia is a leader in six of them, and several of those were either invented at the Psychiatric Institute or were strongly influenced in their design by work conducted at Columbia,” says Harold Sackeim, Ph.D., professor of psychiatry and radiology. “We’re seeing the beginning of a new class of therapeutics.”
  Led by Sarah H. Lisanby, M.D., associate professor of clinical psychiatry and director of the Division of Brain Stimulation and Therapeutic Modulation at the NYSPI, and Dr. Sackeim, researchers are treating patients with ECT and vagus nerve stimulation and are studying several other techniques, including magnetic seizure therapy that was developed at Columbia. The advantage of brain stimulation, Dr. Sackeim says, is that it allows doctors to directly affect and change the functioning of the brain. Unlike the use of pharmaceuticals, which for many is either of little help or can cause side effects in other parts of the body, brain stimulation can be targeted to the specific neural circuitry underlying the disorder.
  Though a stigma has been attached to the use of ECT over the years, Columbia researchers have transformed the technique. They recognized a decade ago that the electrical dosages commonly used in the treatment were excessive, Dr. Sackeim says. Briefer electrical pulses and electrode placements used now cause fewer side effects. The most common side effect, cognitive memory loss, is much less pronounced with modern usage.
  Already approved by the FDA to treat epilepsy, vagus nerve stimulation was approved in November 2005 for the treatment of major depression. It entails surgically implanting a pacemaker-like device in the soft tissue of the chest. An electrode sends impulses to the vagus nerve in the neck to modulate brain function. A psychiatrist trained in the use of VNS controls the stimulation parameters, which can be adjusted in follow-up visits. VNS is an adjunctive treatment for the long-term management of chronic medication-resistant depression, Dr. Lisanby explains, adding that the most common side effect may include hoarseness, since stimulation can affect a nerve that controls the vocal chords.
  Dr. Lisanby also is Columbia’s principal investigator in a 23-center clinical trial of approximately 300 patients undergoing transcranial magnetic stimulation. TMS uses a compact electromagnetic coil to apply magnetic fields to the head. The magnetic fields are turned on and off rapidly to induce small electrical impulses in the brain to stimulate or inhibit brain function. TMS can focus on small regions in the brain, allowing doctors to target specific brain structures.
  “TMS is already approved in Canada and is awaiting an FDA panel review for use in the treatment of depression,” Dr. Lisanby says. “This is an exciting development because TMS could represent a less invasive alternative for depressed patients when medications fail them. Promising work is also under way using TMS in schizophrenia, neuron-rehabilitation, and other disorders.”
  More information about brain stimulation treatment is available by email (depression@columbia.edu), online (www.columbiapsychiatry.org/cs/bss.html), or phone (212-543-5558).

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Cancer Drug for Children Shows Promise

By Susan Conova
Cancer Drug for Children Shows Promise A new type of therapy could be on the way for children suffering from hard-to-treat solid cancers, including Wilms tumor, a cancer of the kidney, and neuroblastoma, a cancer of nerve cells. P&S oncologists working with the National Cancer Institute and the Children’s Oncology Group are poised to begin a multi-center phase II trial for bevacizumab in children. Bevacizumab — the first drug approved by the FDA designed to attack a tumor’s blood supply — has been shown to extend the lives of adults with metastatic colon cancer and other tumors.
  “Our hope is to provide a new agent with which to treat childhood cancers by exploiting the recent discoveries of the crucial role of the blood supply to growing cancers,” says Jessica Kandel, M.D., associate professor of surgery. “We felt that bevacizumab had promise because it was aimed at the molecule that is critical to blood vessel growth and maintenance and is therefore essential to growing tumor masses.”
  The idea of targeting a tumor’s blood supply grew from the theory of angiogenesis, developed by Judah Folkman, M.D., director of Harvard Medical School’s Vascular Biology Program, in 1971.
  He hypothesized that because a blood supply is required for a tumor to grow, the tumor might not grow or spread if that supply is cut off. Other researchers discovered later that a molecule called vascular endothelial growth factor (VEGF) helps tumors create their own blood supply. In 1998, Dr. Kandel and Darrell Yamashiro, M.D., Ph.D., the Irving Assistant Professor of Pediatrics and assistant professor of pathology, founded the Pediatric Tumor Biology Laboratory, where they were the first to show that blocking VEGF suppresses the growth of pediatric tumors implanted in mice. Bevacizumab, approved by the FDA in 2004 for use in colon cancer, inhibits VEGF.
  The new Phase II trial is being led by Julia Glade Bender, M.D., assistant professor of pediatrics, who is a member of the Pediatric Tumor Biology Laboratory. Dr. Glade Bender also led a Phase I trial of bevacizumab that ended in September 2005. Both trials are being conducted through the Children’s Oncology Group, an NCI-supported cooperative of more than 5,000 cancer researchers.
  Because of the inhibitory effect bevacizumab has on blood vessels, possible side effects of the treatment include hypertension, thrombosis, bleeding, proteinuria, gastrointestinal perforation, and delayed wound healing. Fortunately, Dr. Kandel says, these adverse effects have not proved common or severe enough to limit the use of the drug.
  “Since children’s diseases often don’t get the attention that adult diseases do, this is a particularly exciting trial,” she says. “Children are frequently at the end of the line when it comes to new agents, because there are fewer pediatric cancer patients than adult cancer patients. Also, their tumors have a different biology, usually stemming from errors of development, rather than chronic exposures to carcinogens. Since pediatric cancers require new blood vessels, however, angiogenesis can be a common target in pediatric and adult tumors.”
  Dr. Kandel’s next step in the laboratory is to understand why tumors can adapt to the blockade of VEGF. “While bevacizumab can be effective treatment, it is not a cure,” Dr. Kandel says. “Tumors can eventually acquire a resistance, so we have a long road ahead.”



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