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Kidney Cysts, Renal Cell Carcinoma

excerpts from VHL Handbook

The kidneys are organs located in the back of the abdominal cavity which are about  12 cm (4 inches) long, or about the size of the fist. VHL in the kidney may cause cysts or tumors to form. It is common for any adult in the general population to have an occasional kidney cyst. VHL cysts are usually multiple. The presence of one or more simple cysts is not a problem in itself. However, each cyst may contain a small tumor, and it is possible for these tumors to become renal cell carcinomas (RCC), one kind of kidney cancer, formerly known as hypernephroma.

There are generally no specific physical signs to indicate the presence of kidney cysts and tumors early, so it is critically important to begin monitoring the kidneys long before any obvious physical symptoms or signs occur. The kidneys continue to function while these structural changes are occurring without physical symptoms, and with normal blood and urine tests.

Think of it as having a mole on your skin, except that you cannot see that it is growing. When it is very small there may be no cause for alarm. When the mole begins to grow or change in suspicious ways, your doctor would recommend that it be removed.

Similarly, when a kidney tumor is quite large when discovered, if it changes shape, size, or the rate of growth becomes suspicious, your medical team may recommend surgery. Not all kidney tumors require immediate surgery. Based on characteristics such as density, size, shape, and location, your medical team will recommend either a time to repeat the imaging tests or surgical resection (removal of the tumor). Once VHL kidney tumors appear, they act like Clear Cell Renal Cell Carcinoma (ccRCC) which represents 75%–80% of sporadic RCC occurring in the general population. The biggest difference is that in VHL there is the opportunity to find them earlier than people who have sporadic kidney cancer. That provides better options for dealing with the tumor early and allowing the kidney to function as long as possible while avoiding the worst consequences of cancer—metastasis. Knowing that someone with VHL is at risk for RCC, the tumors can be found at much earlier stages. If you wait for symptoms, the tumor will usually be at a much later and more dangerous stage when it is found.

There is widespread agreement on the optimal approach to dealing with VHL kidney tumors. In VHL, a person with kidney involvement typically has a series of tumors on both kidneys which develop over the course of several decades. Clearly, one cannot remove every little tumor, since that would be too many surgeries for the person, and this small organ, to endure. The goal is to maintain the patient’s own kidney function throughout his or her lifetime, to minimize the number of surgeries, and remove tumors before they metastasize and cause the cancer to grow in other organs. The tricky part is to choose the right moment to operate—not too early and not too late.

The objective is to track the progression of the cells from harmless (benign) to the point before they become capable of spreading (metastatic). Think of a dandelion. It begins as a bud, becomes a yellow flower, turns white, and one day the white seedlings are carried off on the wind to seed the lawn. If you pick the yellow flowers, the seeds are not mature and cannot spread. The cells have to mature to the point where they are able to seed themselves in the lawn. The trick to living with dandelions is to pick them while they are yellow.

There is a similar transition in cancer. Cancer researchers have identified a series of distinct steps that the cells go through before they are even capable of metastasizing.

It would be ideal if there were some easy blood or urine test—some biomarker—to check on the cell progression. There is no such test at this time though there is a great deal of research effort to find one. Meanwhile, clinical research has shown that the size of a solid tumor is one relatively crude but fairly reliable sign of its progress.

Biopsies are usually not called for in this case, since with a diagnosis of VHL one is pretty certain what the structure will contain. There will be cancer cells even in very small tumors. The question is: what is their level of progression? This is not a question that can be answered accurately through a biopsy.

Cysts are generally not considered sufficient cause for to operate. In the rare event a tumor is present in the wall of a cyst, it will be important to watch the size of that tumor, not of the cyst. MRI imaging of the kidneys both with and without contrast agents as detailed in the VHL Active Surveillance Guidelines is a reliable way to follow these tumors.

The consensus from the VHL International Medical Symposium meeting in 1994 (Freiburg, Germany) was to recommend surgery only when the largest tumor is larger than 3 cm. This recommendation was verified by a multi-center study led by the late Dr. Andrew Novick. All the VHL study teams, worldwide, now concur with this guideline. After nearly 20 years of experience using these guidelines, there are only three verified reports of metastasis from tumors smaller than 4 cm; all of which were  at or greater than 3 cm.

In summary, the best practice in caring for VHL patients is to minimize the number of surgeries while preventing metastatic disease in order to allow the kidneys to continue to function. In addition to the 3 cm guideline for the longest tumor diameter, your doctor will look at the size of the tumor over time in order to determine its growth rate. A faster growth rate may indicate the need for surgery to remove a smaller tumor. Tumors typically grow in steps, with periods of little to no growth followed by periods of rapid growth. Looking at tumor growth over a number of years, NIH has found the average growth rate is 3–4 mm per year.

In watching the kidneys, your medical team is working to evaluate whether there are cysts or solid tumors. Magnetic resonance imaging (MRI) or computed tomography (CT) are the best methods of medical screening. The doctors will watch the tissue density, the position of the tumors, their size, and the rate of growth. MRI is preferred in most cases as it does not use radiation and can detect even those tumors located within a cyst.

It is important that you understand in as much detail as you can the medical findings about which your physicians are concerned. This will allow you to participate in determining the right timing and treatment. Do not hesitate to get a second opinion. The distinction between a cyst and a tumor can be debatable depending on the clarity of the image and the experience of the radiologist who reviews the VHL tumors. Even among experts, there can be differences of opinion. This is an area where the perspective of one or more physicians with significant experience in VHL can make a world of difference. Films or compact discs (CDs) can easily be sent to a consulting physician far away, even in another country. Contact a VHL Clinical Care Center or the VHL Alliance for assistance in locating an expert who can assist you.

Decisions about when to operate and the extent of the procedure need to be made by the entire team. This should include the patient with full disclosure of all information. All points of view, the location of the tumor, the patient’s level of stamina and health, and even the possible desire of the patient to be free of the tumor, all play a role.

In cases where the last remaining kidney must be removed, VHL patients have been proven to be good candidates for kidney transplant. VHL tumors grow from abnormalities within the cells of the kidney, itself. Since the new kidney has the donor’s genetic structure and two healthy copies of the VHL gene, it is not at risk for VHL tumors. Immune suppression for transplantation has not been seen to increase the growth of VHL tumors in other organs.

Imaging Considerations with Reduced Kidney Function

People with low creatinine clearance (due to reduced kidney function) need to be protected from any side effects of the contrast dyes used in contrast-enhanced CT scans and MRIs. The principal goal is to ensure that the patient has sufficient fluid in the body to flush the contrast dye out in a timely manner. Typically, for patients with an estimated glomerular filtration rate (GFR) of less than 60 and greater than 45 undergoing CT scans, fluids are given to flush the kidneys. CT scans require iodine contrast which can harm kidneys when the estimated GFR is less than 40–45, so iodine contrast is not given to those patients. For MRI, the gadolinium contrast does not harm the kidneys, but in those with much reduced kidney function can cause skin side effects. Therefore for patients with an estimated GFR of less than 60 and greater than 30, hydration with 1 liter of bicarbonate solution infused over the course of one hour immediately prior to when IV contrast injection is performed. For those on long-term surveillance and esti mated GFR over 60, a full dose of gadolinium is used, for estimated GFR of 30–60, ½ dose, and no contrast agent is used if estimated GFR is less than 30. People with renal failure (estimated GFR less than 30) can be followed without use of contrast agents using non-contrast MRIs with T1, T2, and fat suppression sequences, which can help partially make up for the lack of contrast.

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