VHL (von Hippel-Lindau disease) is a rare genetic disease that can cause tumors, both benign and malignant, to develop in up to ten different organs throughout a patient's life. We invite you to join Roswell Park Comprehensive Cancer Center’s VHL Clinical Care Center's lead physician, urologic-oncologist Eric Kauffman, MD, as he discusses the disease, its risk factors and the collaborative, multidisciplinary approach necessary to manage a patient's care.
Hi, my name is ERic Kaufman. I'm a urologic oncologist at Roswell Park Comprehensive Cancer Center and I have a sub specialized focus in kidney cancer. And I'm here today to answer questions about the V. H. L. Syndrome, which is a complicated hereditary syndrome that you as a primary care physician may have some questions about what is von hippel lindau disease and what is its cause? Von hippel lindau disease is a hereditary syndrome characterized by tumors and cysts in multiple organs throughout the body as a result of an inherited mutation in the von hippel lindau or V. H. L. Gene. The V. H. L syndrome is the most common cause of hereditary kidney cancer and although it is responsible for about one out of every 100 kidney cancers diagnosed, it is very common cause of kidney cancers in younger patients, Particularly those who are in their early 40s, 30s, 20s or even teenage years. In addition to kidney cancers, V HL patients also have high risk to develop tumors in other specific body parts, including the eye, ear, cerebellum, spinal cord, adrenal, gland pancreas and reproductive organs. As with V. H. L. Kidney cancers. V. HL tumors and other organs tend to occur at a young age and are often multiple nature and additionally they tend to involve multiple organs at once. So as mentioned, the V. H. L. Syndrome results from an inherited mutation in the V. H. L. Gene. The V. H. L. Gene was actually among the very first tumor suppressor genes ever discovered over 30 years ago, back when the field was really first learning about the link between mutations and cancer, interestingly. The normal function of the V. H. L. Gene is to sense drops and oxygen and iron levels in body cells and to orchestrate the normal physiologic response in these cells. The loss of a normal V. H. L. Gene results in high levels of certain proteins called hypoxia induced herbal factors and their accumulation somehow helps trigger cancers. But even with this knowledge in hand, for the past several decades, we still don't really understand why these molecular changes ultimately lead to cancers and in only certain specific body organs. So how is V. H. L. Diagnosed? And when should I recommend that a patient be screened? A diagnosis of V. H. L. Syndrome is often suggested clinically but ultimately requires genetic testing for definitive confirmation. Often symptoms and signs of V. H. L. Are first brought to the attention of their primary care physician. So what are some of these signs and symptoms? Well occasionally patients may present with him a jury a due to an underlying kidney cancer, but probably the most common presentation is visual symptoms including blindness at an early age, which is due to retinal tumors as with other organs involved in V. H. L. Retinal tumors tend to be multifocal and may manifest as macular oedema, retinal detachment or neo vascular glaucoma. Another common presentation of V. H. L. Syndrome is neurologic symptoms that localized to the cerebellum such as ataxia. In this case A C. T. Or M. R. I may reveal a cerebellum human glioblastoma, which is the characteristic benign central nervous system tumors of the HL syndrome. Other less common presentations of V. H. L. Syndrome include hearing loss from invasive and the lymphatic sac tumors of the ear or probable tumors of the epidemics gland on scrotal exam or ultrasound, which may also present as male infertility when bilateral. That all said, given the uprising cT scanning to work up non specific abdominal symptoms and increasingly common clinical presentation of V. H. L. Syndrome in the contemporary era is the incidental discovery on CT scan obtained for other reasons that ends up showing tumors or cysts in different organs. For example, a patient who undergoes a CT scan for constipation related pain and is incidentally found to have both a kidney tumor and a pancreas tumor or perhaps an adrenal or spinal cord with sis also found on the pancreas or kidney. Multifocal tumors of the kidney in particular are quite common in V. H. L. Syndrome, compared to only about 10% of sporadic kidney cancer cases. Hence, a patient with more than one kidney tumor should also raise clinical suspicion for V. H. L. Syndrome. Finally the only sign of V. H. L. Syndrome might simply be a family history involving multiple family members with tumors in these organs mentioned in particular, a diagnosis of kidney cancer and more than one family member whether including the patient or not should trigger suspicion for V. H. L. Syndrome even if the patient has no detectable tumors. If the diagnosis of V. H. L. Syndrome is clinically suspected, a patient should undergo genetic testing to either confirm or rule out the diagnosis. This involves a referral to a genetic counselor like those at Roswell Park who will interview the patient and if appropriate, order a simple blood test to check for the presence of a germ line that is inherited mutation in the V. H. L. Gene. I have a patient who has been diagnosed with DHL. What should my next steps be? The next step would be to refer the patient to a V. H. L. Clinical care center like Roswell Park Comprehensive Cancer center, of which there are approximately three dozen currently located throughout the U. S. Suspicion for V. H. L. Diagnosis should be mentioned during the referral and a patient navigator will contact the patient to discuss the details of upcoming visits such as the need for genetic counseling and a variety of specialist visits to follow. More information on scheduling. A consultation can be obtained from the websites of Roswell Park Comprehensive Cancer center or the V. H. L. Alliance. So why is it important for V. H. L. Syndrome patients to be managed at a V. H. L. Clinical Care center? The management V. H. L. Patients is very complex and deviates from guidelines typically followed for sporadic or non inherited as a result, the international organization known as the V. H. L. Alliance has recommended a certain level of expertise resources and multidisciplinary infrastructure be available at a clinical care center to meet the needs of a VHS patient there right now. About three dozen V. H. L. Clinical care centers in the U. S. Recognized by the V. H. L. Alliance and Roswell Park Comprehensive Cancer Center is currently one of four new york state and the only one in Western new york. There are three important reasons that DHL patients should be managed at A V. H. L. Clinical care center whenever possible. First has touched upon V. H. L. Cancers require a unique specialized treatment approach that is the recommended management of the HL tumors for each particular organ often deviates from the typical management of non hereditary tumors that form in the same organs. Let's take kidney cancer management. As an example, kidney cancers in the V. H. L. Syndrome tend to pop up repeatedly in both kidneys throughout a patient's life and this feature carries an increased long term risk for dialysis due to the lifetime need for repeated bilateral kidney surgeries and healthy kidney tissue resection. To reduce the risk for dialysis. It is critical in V. H. L. Patients that partial gastrectomy be performed preferentially over radical mastectomy even when tumors are on the large side. Furthermore, certain specialized techniques are recommended for V. H. L. Patients during the partial gastrectomy, such as the use of zero margin and new creation approach, which minimizes resection of healthy kidney tissue around the tumor or in the case of several tumors within the same kidney. And a typical surgical approach called off clamp resection is often needed that is removing the tumor without first clamping off the renal artery, which is otherwise the usual approach. The alternative approach requires a high level of expertise and spares more renal function but involves high inter operative blood loss and critical post operative recovery is often required to further reduce the dialysis risk. The nonsurgical management approach known as active surveillance or monitoring with an intent to safely delay time to treatment plays a particularly important role in V. H. L. Syndrome, kidney cancer management. This is because each additional surgery on the same kidney carries a higher risk than the prior surgery for conversion from partial to radical naff rectum E due to increasing amounts of scar. Currently, active surveillance is therefore recommended preferentially over surgery for all v. H. L. patients whose largest kidney tumor is less than three cm which is different from recommendations for sporadic kidney tumors, Where surgery has a first line role, even at small sizes below three centimeters, the metastatic risk in V. H. L. Kidney cancers appears to be potentially zero and surveillance is not only an ecologically safe. It is actually critical to reduce long term dialysis risk. Further more recently, a drug called well a rag has been FDA approved to reduce kidney cancer growth specifically in V. H. L. Patients. And this provides another treatment options for V. HL patients that is not available for sporadic kidney cancer patients. And finally per cutaneous thermal ablation such as cry ablation should really be used more sparingly in V. H. L. Patients as the amount of adjacent kidney tissue lost and the amount of scar acquired is relatively high and this increases the likelihood of radical mastectomy conversion and future surgeries and potentially speeding up time to dialysis. Thus, to summarize when compared with typical kidney cancers. The lifelong multifocal allergy risk of V. H. L. Kidney cancers requires a greater role for active surveillance, specialized partial gastrectomy approaches and primary drug therapy and a lesser role for radical mastectomy and probably thermal ablation which overall makes the management of E. HL patients quite unique and complex, which is why these patients require a specialized center with dedicated expertise in V. H. L. Syndrome care. A second important reason for referral to V. H. L. Clinical care center is to implement early detection and screening for tumors. Many V. HL tumors even when not cancerous can cause loss of organ function or injure the patient in other ways such as blindness from retinal tumors, stroke from sarah bell or tumors or adrenal field chroma site. Omagh's that can cause hypertensive crisis or infertility with epidermal tumors in many cases these effects can be irreversible. So early detection with screening under specialist care is very important to prevent these complications. How often and for how long the screening is performed depends on the organ site. But in many cases screening will be for life. A third reason that is important for V. H. L. Patients to be managed at A V. H. L. Clinical care center is the need for carefully coordinated multidisciplinary care. Given the complexity of multi organ involvement with the V. H. L. Syndrome is important that the care of the syndrome be carefully integrated in a multidisciplinary manner among a variety of different subspecialties. Because B. H. L. Can affect so many different organs. It takes communication and planning between numerous experts across multiple disease sites to keep track of a patient's care plan and know what the other physicians are doing. For example, before a V. H. L. Patient with a kidney cancer can be taken to surgery, the patient needs to be appropriately cleared from a neurosurgeon to make sure that a central nervous system, tumors isn't going to trigger a neurovascular event during surgery or cleared with the help of an endocrinologist to ensure that a functioning feel chromosome toma won't trigger a hypertensive crisis during the surgery, failure to a pro appropriately account for these tumors in other organs. Could lead to life threatening complications during the kidney surgery at a clinical care center. The infrastructure is in place to ensure the proper ongoing communication between physicians of different organ sites aided by a dedicated patient. Navigator and nurse coordinator who facilitate these interactions. Furthermore family dynamics and psychosocial aspects of V. H. L. Syndrome diagnosis can be quite complex in A. V. H. L. Clinical care center also includes a psychosocial support team and genetics counselor to ensure this holistic care to the patient. What factors makes a patient eligible for a consult at the V. H. L. Clinical care center at Roswell Park. The main factors that one should look out for to trigger a referral to the V. H. L. Clinical care center can be summarized as one kidney cancer diagnosis before the age of 50 to kidney cancer in at least two blood related family members. Whether or not these two individuals include the patient three a diagnosis of certain atypical tumors including commando blast, Omagh's of the retina, cerebellum or spinal cord and a lymphatic sac tumors of the ear vo chroma site Omagh's of the adrenal gland, pancreatic neuroendocrine tumors or peanuts or assist adenomas of the epidermis gland in males and broad ligament in females. And for if the type of tumor is not yet known suspicion for V. H. L. Syndrome should still be triggered if there are multifocal tumors involving any of the following organs, particularly if more than one organ is involved. The brain, eyes, ears, kidney, pancreas, adrenal gland, epidemics and males or broad ligament and females. This is especially the case of the page is young but also even if the patient is elderly. If a patient has any one of these four categories of risk factors then a referral to a V. H. L. Clinical care center such as that at Roswell Park is recommended if there is any question we encourage people to still make an appointment at Roswell Park to be evaluated by our V. H. L. Care team. Which addition to meeting with physician experts will include a consultation with genetic counselors who have expertise and when to test for V. H. L. And how to interpret the test result. So what types of screenings can a patient expect at their visit for V. H. L. Care once a patient is referred to a clinical care center such as that at Roswell Park Comprehensive Cancer center, the patient will be set up with a genetic counselor who will interview the patient and if appropriate proceed with screen for an inherited V. H. L. G. Mutation with a simple blood test. If a V. H. L. Mutation is detected, the patient will then be set up to initiate screening with a variety of specialists such as a urologic oncologist, ophthalmologist, otolaryngologist, neurosurgeon, endocrinologist and a pancreatic surgeon. Each will evaluate for current tumors of different organ sites and individually discuss the longer term screening plan with the patient. So what is the V. H. L. Patients risk of developing kidney cancer and how can I as a medical professional mitigate this risk. Once a patient is diagnosed with DHL syndrome precise risk of developing a kidney cancer is estimated to be about 30 to 50% lifetime risk. Thus close to about half of all V. HL patients will likely develop kidney cancer screening. And DHL patients includes lifelong annual cross sectional abdominal imaging with CT or M. R. I. But M. R. I. Is strongly preferred due to its lack of radiation exposure. In patients who are otherwise getting repeated imaging for a long period. V. H. L. Patients are advised to avoid other well established risk factors for kidney cancer namely tobacco usage, lifestyle interventions are also recommended that prevent hypertension, obesity and diabetes which are all kidney cancer risk factors. At what point should surgical intervention be considered? Surgical intervention is driven by different factors for each organ site. For example, for kidney cancers, surgery is not considered unless a tumor surpasses three centimeters at smaller sizes. The cancer has minimal to no oncological risk and should be surveyed with or without the addition of a recently approved oral pill for V. H. L. Kidney cancer. Caldwell a rig that targets hypoxia induced factor accumulation, which is the cellular alteration that results from the loss of the V. H. L. Gene. Are there any other rare hereditary cancer syndromes you treat? Yes. Although the Roswell Park V. H. L. Clinical care center focuses on the V. H. L. Syndrome as the most common hereditary kidney cancer syndrome are clinical care center also oversees multidisciplinary care for other more rare hereditary kidney cancer syndromes such as hereditary leo, mayo mitosis and renal cell carcinoma, or H. L. R. C. C. And BIrt Hogg Dube A syndrome, or BhD, which are both associated with a risk for certain skin tumors for which a dermatologist is included in the clinical care team, as well as a gynecologist. Since HL RCC often presents with symptomatic fibroids in women at a young age, a genetic counselor considers all of these other syndromes when meeting with a potential DHL syndrome patient.