ATLANTA-What do 30 doctors, 20 nurses, 100 patients, and one magician have in common? A desire to make VHL stand for “Very Happy Life” as well as von Hippel-Lindau disease. These 150 people, including illusionist The Amazin’ Grayson (Grayson Smith of Memphis), attended the Sixth International Patient/Provider Conference on VHL, a 3-day meeting to build teamwork for management of VHL.
ATLANTAWhat do 30 doctors, 20 nurses, 100 patients, and one magician have in common? A desire to make VHL stand for Very Happy Life as well as von Hippel-Lindau disease. These 150 people, including illusionist The Amazin Grayson (Grayson Smith of Memphis), attended the Sixth International Patient/Provider Conference on VHL, a 3-day meeting to build teamwork for management of VHL.
Named for the two European doctors who first described it, von Hippel-Lindau disease is now understood to be caused by the loss of a tumor-suppressor gene, known as the VHL gene, which allows tumors to form in the retina, brain, spinal cord, kidney, pancreas, and adrenal glands. It is thought to affect one in 34,000 people worldwide and appears in every ethnic group.
Like so many rare disorders, VHL is not always recognized and is widely underdiagnosed. Even when it is properly diagnosed, it is still a challenge to get optimal care because of the lack of information on this disease among medical professionals.
Six years ago a group of affected peoplepatients, parents, spouses, and friendscame together to form the VHL Family Alliance (VHLFA), with the express purpose of improving the diagnosis, treatment, and quality of life for individuals and families affected by von Hippel-Lindau disease.
At the Annual Meeting of the VHL Family Alliance, Maria Shipton of Pennsylvania was elected to the Board of Directors and awarded the VHL Chapter Chairperson of the Year for her work in public relations concerning Jay Platts hike (see below). Mr. Platt was honored as the Volunteer of the Year for his extraordinary effort in hiking the Appalachian Trail.
New officers of the Board of Directors were announced at the meeting. Altheada Johnson of New York continues as chairman of the board. Peggy Marshall of Mississippi continues as chairperson of the Alliance, essentially the chief operating officer of the VHLFA. She will be assisted by vice chairpersons Don Marshall (Mississippi) and Kathy Braden (Indiana), secretary Melissa Minster (Delaware), and treasurer Kelly Heselton (Minnesota).
When the VHLFA was founded, the bylaws were written to include a provision that no one person could serve more than two consecutive terms on the Board of Directors. Thus, Joyce Graff retired from the Board after two consecutive
3-year terms, as chairman or co-chairman. Ms. Graff was given a plaque naming her Founder Emeritus of the VHL Family Alliance.
To achieve this goal, the group set out to educate both the consumers and providers of health care for VHL. We seek out physicians who have treated large numbers of patients for one or more decades and bring them together at meetings and on the Internet to grapple with the tricky problems the disease presents.
This years conference was co-sponsored by Emory University School of Medicine, Division of Medical Genetics, and the VHL Family Alliance. Louis J. Elsas II, MD, chief of genetics at Emory, and Eva Logan, VHLFA Georgia Chapter chairperson, co-chaired the event.
In the opening session of the VHL conference, Joseph A. Jay Platt, Gunnery Sergeant (ret), US Marine Corps, gave an inspiring talk about his experience hiking the Appalachian Trail, and the lessons he learned through that experience about self-discipline, motivation, and the courage and perseverance to see a difficult task through to completion.
Mr. Platt is one of only about 300 people who have succeeded in hiking the 2,160 miles of mountain trail southbound from Maine to Georgia. More people complete the trail northbound, but most southbound hikers are discouraged by the more difficult northern end.
I was a Marine. I thought I knew how to get through tough conditions, Mr. Platt said. But 100 miles between towns in Maine was lonely, and I ran out of food. Two days on the shale of Pennsylvania and my boots were in ribbons. Walking for weeks through Virginia brought on the Virginia blues. Its a test of the strength of your mind even more than of your body.
Not unlike living with a chronic disease like VHL, which presents people with a series of life challenges, he said.
In a session on genetics, Debra Collins, a genetic counselor at the University of Kansas Medical Center, discussed the issues surrounding DNA testing for VHL. DNA testing comes with a set of social and emotional issues that require careful consideration and discussion with genetics professionals and among family members, she said. This test will determine whether a family member carries a genetic alteration in the VHL gene and thus whether he or she is at risk for developing the tumors and other medical problems of VHL.
With a condition like VHL, where testing can help to prevent serious damage, there are sound medical reasons for testing children from about age 5, Ms. Collins said. If the family chooses not to test children until they are older teenagers and can participate in the decision, then the children must be screened as if they were known to have VHL.
Thomas D. Rodenberg, Esq, an attorney from Kansas City, Missouri, shared his experiences in dealing with insurance companies as the family negotiator for a large VHL kindred in Missouri.
He presented excellent tactics for dealing with refusals to pay. In short, he said, never give up. If the insurer turns you down, appeal the decision. Insurance companies often turn everything down on the first round, hoping you will give up, he said.
During the neurology panel, Edward H. Oldfield, MD, chief of surgery at the National Institute for Neurological Disorders and Stroke, outlined the points he weighs in making a decision whether to operate on VHL patients with brain and spinal hemangioblastomas. It is rarely a clear-cut decision, he said. Most of the time it is a careful balancing of pros and cons, determining what course of action will produce the best patient outcome.
Daniel Choo, MD, of the Department of Otolaryngology, Childrens Hospital Medical Center, Cincinnati, presented highlights of the work he has done at NIH and Cincinnati on the endolymphatic sac tumors of VHL, which can cause hearing loss. They are difficult to find and are often misdiagnosed as Ménières disease, he said.
Dr. Choo explained the screening process he and his colleagues devised to determine the progress of such a tumor and the approaches he has used to remove the tumor and save the hearing. Left untreated, these tumors lead to progressive hearing loss over time and sometimes sudden hearing loss.
Dheerendra Prasad, MD, of the University of Virginia, presented his work with the Gamma Knife machine doing stereotactic radiosurgery on a variety of tumors, including hemangioblastomas. While he was very enthusiastic about the capabilities of this technology, he was also very straightforward in presenting the limitations of the technology. Not all tumors are good candidates for stereotactic radiosurgery, he said. It has to be used with caution, in order to avoid secondary complications that can be at least as damaging as open surgery.
Saving the Eye
In the ophthalmology panel, Emily Chew, MD, of the National Eye Institute, discussed the ocular manifestations of VHL. Dr. Chew has now seen more eyes with VHL than any other single ophthalmologist and has a unique perspective on treatment.
Hans E. Grossniklaus, MD, of Emory University, talked about his research in retinal disease, some of which was done in conjunction with Dr. Chew. The goal is always to save vision and to save the eye. In some circumstances, however, it is not possible to save the eye. Once the retina is gone, the eye tends to atrophy over some years, eventually becoming painful and requiring removal.
Robert A. Thomas, an oculist from Memphis, Tennessee, presented a series of photographs of artificial eyes and facial and eye restorations, showing that people can look completely natural with a well-made ocular prosthesis (see photographs). After the eye socket has healed, the oculist fits the prosthesis. It is similar in many ways to making dentures, Mr. Thomas said. He stressed that patients facing enucleation should have at least one meeting with a board-certified oculist prior to the surgery.
The urology panel was headed by Hartmut Neumann, MD, of Albert-Ludwigs University, Freiburg, Germany. Dr. Neumanns study of kidney tumors in VHL patients is the largest and longest in Europe. He was the first to propose delaying operation on VHL kidney cancer tumors.
Dr. Neumann and Walter Rayford, MD, of Louisiana State University, New Orleans, described their workDr. Neumanns in Germany and Dr. Rayfords at the NIHand the issues they weigh in deciding when to operate on a kidney and how long one can watch the tumor without actually taking action.
In general, they apply the 3-cm rulewatch tumors until they become 3 cm in diameter and then surgically remove as many tumors as possible, leaving as much functioning kidney tissue as possible. VHL kidney tumors tend to be very well encapsulated, so there is no need to take a wide margin, they said. It is more important to keep the kidney working. The goal in all cases is to maintain normal organ function while avoiding metastatic cancer.
Steven K. Libutti, MD, of the National Institutes of Health, headed the endocrinology panel and gave a talk on pancreatic lesions in VHL. These pancreatic lesions have been poorly understood, leading some physicians to overtreat and others to undertreat. Dr. Libutti said that there are no tumors in VHL that produce chemical tracers that can be seen in the urine. Instead, clinicians must rely on imaging and on knowledge derived from studying many pancreatic tumors over the years to determine which tumors can be watched and which ones require immediate removal.
The NIH has come to apply the 3-cm rule for kidney tumors to most tumors in the pancreas. If the tumors are in the head of the pancreas, the NIH advises watching the tumors until they reach 2 cm in size and then removing them. If the tumors are producing symptoms or if they are growing at a particularly fast rate, the NIH physicians move more quickly to remove the tumors.
McClellan Walther, MD, chief of the Neurodynamics Laboratory at the National Institutes of Health, spoke about pheochromocytomas (pheos) in VHL. Pheos can grow anywhere along the sympathetic nervous system, in a line from the base of the skull to the bladder. Very few (1.6%) metastasize in VHL, but all pheos can be dangerous because of their effect on the cardiovascular system.
He noted that the NIH has developed a new biochemical test of free meta-nephrines to detect pheos that is much more sensitive, reliable, and easier to administer than a 24-hour urine collection.
The last panel included five research scientists, three of whom have received funding from the VHL Family Alliance. The panel members reported their work in the biochemical study of the VHL gene and the VHL protein.
The VHL gene functions as a tumor- suppressor gene and produces the VHL protein (pVHL). When normal levels of pVHL are present in the cell, cell division starts and stops normally. When pVHL is missing, cell growth can go out of control. Although the exact mechanisms of uncontrolled cell growth in this situation are not understand, one result of missing pVHL is the overproduction of vascular endothelial growth factor (VEGF), which is implicated in the growth of new blood vessels. In VHL, this overproduction of VEGF results in hemangiomas.
The key take-away message from this session was that there is progress in understanding the function of the normal VHL protein in the cell, and once this is understood, it will be easier to talk about ways to restore normal function.
Jeffrey Humphrey, MD, of Bristol-Myers Squibb, said that his company has an antiangiogenesis agent going into clinical trials soon. Othon Iliopoulos, MD, of the Dana-Farber Cancer Institute, described his work with Dr. William Kaelin using antiangiogenic drugs from Novartis and Sugen. Trials of these agents in VHL are just beginning, he said.
Although it will be some years before these drugs come up for approval, the researchers left the audience with hope that there will someday be drugs to emulate the function of the VHL gene or to go around the VHL function and control VEGF levels directly, as well as possible methods of gene therapy.