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Reporting from Rio
See special news about pregnancy and hearing tests
In October, it is springtime in Rio de Janeiro. This beautiful port city on the east coast of Brazil in South America is situated on Guanabara Bay, so wide and deep that the Portuguese sailors who first visited thought it was a river. In fact, it is a bay which they named the River of January. In the bay are scattered granite monolith mountains reaching high up out of the sea and into the sky. In the unique logo created for this conference, you will see Copacabana Beach stretching as a crescent to the right, Sugar Loaf Mountain, and “Christo”, a statue of Jesus Christ the Redeemer, as high as a football field is long, standing atop another of the monoliths, dominating the view of the harbor. We met in one of the hotels that line Copacabana Beach. Right across the street from wonderful white sand beaches the city is bustling with all the myriad activities of a city of 6 million people in a metropolitan area of 12 million people, with twice as many people per square kilometer as in New York or London. Rio is the second largest city in Brazil (after Sao Paolo), and the third in South America. The first day of the conference was dedicated to understanding the molecular genetics of VHL, an essential element in the life of the cell in organisms from yeast to humans. Inside the cell, there is a complex system of sensors and controls that keep all the body’s activities in balance and respond to changes in circumstance and environment. Each time we meet, there is a deeper understanding of the normal role of the VHL protein in the cell and of the chain reaction that occurs when the VHL protein is not present or not doing its job properly. It’s not just a simple single-file process; it’s a complex waterfall of events. The abstracts, or short summaries, of the presentations are contained in the Program from the conference. See http://vhl.org/conf2010. I will give a brief overview of the presentations on the second and third days of the conference, which were devoted to the more clinical aspects of VHL and to the family experience of VHL. These issues are of course more familiar and more immediate for most of us. On Saturday we heard from experts from all over the world; on Sunday we heard from Brazil itself.
Dr. Hiroshi Kanno (Japan) shared his series of 62 central nervous system (CNS) hemangioblastomas in 34 patients from 1992 to 2010. Laboratory data often revealed polycythemia due to secretion of erythropoietin from the tumor. Most results were quite good. Larger tumors tended to have less good outcomes (>4 cm in the brain or >2 cm in the spinal cord). He found that SRS did not always control the tumor. His recommendation was to operate earlier rather than later in order to avoid deterioration of neurological function. Dr. Eric Jonasch (USA) presented a progress report concerning three clinical trials in progress at MD Anderson Cancer Center in Houston. Sunitinib has gotten a significant response in kidney tumors, but not in CNS. He will be treating 14 VHL patients with VHL and hemangioblastomas with TKI258, a small molecule inhibitor of FGFR and VEGFR. He will also be opening a multicenter 40-patient study treating VHL patients with pazopanib, a well tolerated small molecule VEGFR inhibitor. Several presentations from Germany, France, and Brazil described a number of studies of kidney cancer, searching for biomarkers that would give us a good “measure” of the level of tumor activity in the kidney without going to the cost and trouble of getting an image. While there are no confirmed biomarkers yet, there is a great deal of activity in this race. Dr. Karel Pacak (USA) presented his extensive work on pheochromocytomas, not only caused by VHL but also by any of five other genetic flaws. While VHL is the largest of these genetic promoters of pheochromocytoma and paraganglioma, all genetic causes so far account for only 30% of the pheos there are—70% are sporadic in the general population or have other genetic causes we have not yet identified. The tools to diagnose a pheo exist—the biggest hurdle is finding a doctor who will believe that the patient is not crazy, run the tests, and take the time to learn what the resulting numbers mean. There is a protocol open now at the US-NIH to assist in arriving at a diagnosis, and to help us learn as a community how we can move more quickly to a diagnosis. See http://vhl.org/pheo. Dr. Surena Matin (USA) presented his experience in treating VHL renal tumors. He has found the 3 cm strategy to be quite effective. Open partial nephrectomy is the primary modality he uses, but each successive surgery becomes more difficult. Dr. Ian McCutcheon (USA) presented a series of cases where he worked with five people with VHL who suffered intractable nausea from a hemangioblastoma located in or near the distal medulla. Relief in all cases occurred within one week following removal of the tumor. While nausea can be caused by other conditions associated with VHL (e.g., pancreatic cysts or tumors), this symptom should trigger a search for a hemangioblastoma of the distal medulla, which should be clearly seen on an MRI. Dr. De Campos (Spain) presented a series of 62 patients with a total of 291 diagnosed tumors from 30 families in Spain, and followed in the Spanish national health system their whole lives, in which they tracked the age of onset of the first symptom and the course of the disease. They demonstrated that in 10% of the cases the first issue arose before age 19. Having an early symptom did not predict an aggressive clinical course for subsequent tumors. He is happy to see the recommendations for early DNA testing and regular screening in order to find and address any early tumors in a timely manner. Dr. Sven Gläsker (Germany) reported that he is using color Doppler ultrasound during neurosurgery to guide the surgical approach and resection of CNS hemangioblastomas. Dr. Valérie Krivosic (France) presented the work of Dr. Alain Gaudric on the role of vitreoretinal surgery in the management of advanced retinal capillary hemangioblastomas (RCH) of VHL. While he was able to treat the RCH successfully and save the eye, in most cases there was a high rate of vision-threatening RCH recurrence in the long run.
Pregnancy and VHLFrom the earliest days of the VHL Family Alliance, families have been asking whether pregnancy promotes tumor growth. Dr. Caroline Abadie (France) reported that the French team has recently completed the first scientific study of this important topic. They went back through the records in the French National VHL clinical database to study 269 women from 172 families. Their aim was to analyze the onset of new hemangioblastomas and potential tumor complications in patients compared to their pregnancy status. They collected follow-up data on CNS and retina for 176 women with at least one pregnancy (Group 1) and 93 women with VHL who have had no pregnancies (Group 2). More complications of hemangioblastomas were found in Group 1. Because of this finding, the French VHL Study Group now recommends an MRI without contrast in the fourth month of pregnancy to check on the health of the mother. This is especially important for women with a previously identified CNS lesion.
Hearing Testing and ELSTWe know that if there is a significant drop in hearing, we should immediately suspect an ELST. For that reason, we include in the annual screening recommendations an audiology test to quantify the hearing and allow us to compare year over year. Before 2009, none of the 42 people with VHL in Denmark had ever been diagnosed with an ELST. Since the international averages indicated that 11–16% of people with VHL can have ELST’s, the Danish team asked all their patients to be examined for ELST. So far, they have identified 2 out of 39 people (5%) who have ELST’s. One had hearing and balance symptoms, while the other had no symptoms but an ELST can be seen on the MRI. We do not yet know whether there are more subtle early signs of trouble that might be learned from an audiology report. The Danish team proposes to study these annual audiology reports and would like to invite patients and physicians throughout the world to contribute to this important learning. Please contact Marie Louise Poulsen, Genetic Counselor, University of Copenhagen, Denmark. On Sunday we focused on Brazil—reviewing for Brazilians with VHL and their families what VHL is, the genetics, DNA testing, and management. Dr. Claudio Casali da Rocha is the geneticist who has introduced DNA testing for VHL into Brazil and has made it possible for each of these families to finally learn the name of their disease—sometimes after three generations of mysterious and devastating medical problems. Brazil is a large country with some outstanding medical centers and a lot of local hospitals with limited facilities. They are still working to set up a chain of information and escalation of problem cases to support doctors throughout Brazil in managing the health of their patients with VHL. The VHL Family Alliance in Brazil (ABVHL), under the presidency of Jamila Mansour Najar, is providing coaching by e-mail and telephone to help people get the best care. Joyce Graff spoke about VHL in the world and the progress we have made in the last 20 years. She remarked that what Brazil is going through now is where we all were in 1993—few people with diagnoses, few doctors who remembered more than one paragraph from medical school about VHL, and very little information available on the ground. Today we have a good base of information available in the world and on the internet, and we have the tools to tap that knowledge for people in Brazil. While many people in Brazil can read or speak Spanish or English, it would be best if the Handbook were in Portuguese. Claudio and Jamila are working to make that happen. Also, all the other Family Alliance groups around the world stand ready to assist people in Brazil in getting the best information possible to help in a particular situation. There were many very moving presentations from Brazilian families about the difficulties they had gone through in trying—sometimes for decades—to find out what was happening and find competent care. There is a temptation to want to fly your child anywhere in the world to find that care. Joyce said, though, that while in some cases that might be the right approach for a very specialized problem, for most people most of the time, the best place to get care is right where you are, with your own local doctor. The Handbook is designed to help you and your doctor learn together, find things early, understand what choices exist for treatment, and with whom to discuss the problems. In Brazil today, that starts with Dr. Casali, Dr. Bruno Vilhena, Dr. Marcelo Reis, Dr. Renato Faria, Dr. Leonardo Machado, Dr. Yonder San, Dr. Cristiano Guedes, and all the other physicians and researchers from Brazil who participated in this meeting. Even more than that, it starts with every patient and every family member. You spend more time with your own body than any doctor ever will. You need to understand what to watch for, what you can do to keep your body and its own immune system strong, and how to seek the help you need when you need it. It was a very emotional day. We applauded our translators who kept us all in the conversation by providing excellent simultaneous translation throughout the day, and the head of the translation team tearfully hugged Joyce at the end of the day as she was so moved by all the family stories and the compassionate exchange she had witnessed. All of us from US and Europe went away grateful for what we have learned together in the last 18 years and the progress we have made ourselves. We all need to remember that there are lots of other families out there struggling to get a diagnosis. Some are in foreign countries and some are right in our own towns. While in the past it took tumors in at least two organ systems before anyone would have considered a diagnosis of VHL, today there is DNA testing to confirm a diagnosis in a younger person with only one kind of tumor and get them into a surveillance program that will hopefully save them a great deal of suffering in their lifetime. Will the doctor think to check for it? Will the family find the clues on the internet? And will we be ready to hug them too?
As printed in the VHL Family Forum 19:1, January/February 2011. For permission to reprint, please contact VHL Family Alliance, editor@vhl.org. Further information is available from the VHL Family Alliance, info@vhl.org. |
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