The kidneys are an essential part of the body's urinary system. Each kidney is composed of about one million microscopic "filtering packets" called glomeruli. The glomeruli remove uremic waste products from the blood. Each glomerulus connects to a long tube, called the tubule. Urine made by the glomerulus moves down the tubule. Together, the glomerulus and the tubule form a unit called a nephron. Each nephron connects to progressively larger tubular branches, until it reaches a large collection area called the calyx. The calices form the funnel-shaped portion of the upper ureter (renal pelvis). Urine moves from the renal pelvis to the ureters, the large tubes that connect the kidney to the bladder.
The kidneys produce three important hormones: erythropoietin (EPO), which triggers the production of red blood cells in bones; renin, which regulates blood pressure; and vitamin D, which helps regulate the body's metabolism of calcium necessary for healthy bones.
Renal Cell Carcinoma
Early diagnosis is critically important. As with most cancers, the earlier kidney tumors are discovered, the better a patient's chances for survival. Tumors discovered at an early stage often respond well to treatment. Survival rates in such cases are high. Tumors that have grown large or metastasized (spread) through the bloodstream or lymphatic system to other parts of the body are much more difficult to treat and present a greatly increased risk for mortality.
Other Types of Kidney Cancer
The symptoms of transitional cell carcinoma are quite similar to those of RCC, and include hematuria and back or flank pain.
If found early, these cancers have a 90% cure rate. Treatment usually involves surgical removal of the kidney, ureter, and portion of the bladder connecting to the ureter. Depending on the stage of the cancer, chemotherapy and radiation may be used as adjuvant treatments.
The prognosis for cure declines sharply when the cancer invades the ureter wall or penetrates the kidney. Regular follow-up examinations after surgery are important, as transitional cell carcinoma is prone to recurrence.
Wilms' tumor can arise anywhere within the kidney's tissues. Untreated, it can spread to the veins, lymph nodes, adrenal glands, large or small bowel, and liver. Fortunately, advances in radiation and chemotherapy over the past few decades, pediatric anesthesia, and surgery have made Wilms' tumor one of the most curable of all childhood cancers. Today the 5-year survival rate approaches 90%.
Such tumors will grow and spread to adjacent organs, bones, and lymph nodes if left untreated. The only potentially curative form of treatment is surgery, usually radical or partial nephrectomy, sometimes with radiation or chemotherapy.
According to the National Cancer Institute, the highest incidence of kidney cancer occurs in the United States, Canada, Northern Europe, Australia, and New Zealand. The lowest incidence is found in Thailand, China, and the Philippines.
In the United States, kidney cancer accounts for approximately 3% of all adult cancers. According to the American Cancer Society, about 32,000 new cases are diagnosed and about 12,000 people die from the disease annually. Kidney cancer occurs most often in people between the ages of 50 and 70, and affects men almost twice as often as women.
Smokers develop renal cell carcinoma about twice as often as nonsmokers and develop cancer of the renal pelvis about 4 times as often. Not smoking is the most effective way to prevent kidney cancer and it is estimated that the elimination of smoking would reduce the rate of renal pelvis cancer by one-half and the rate of renal cell carcinoma by one-third.
Wilms’ tumor accounts for about 6% of childhood cancers and it is the most common type of kidney cancer in children. Incidence of Wilms’ tumor is higher in girls younger than the age of 5 and in African Americans.
Research has revealed several risk factors that appear to be associated with the renal cell carcinoma.
Overuse of Painkillers
Other genetic mutations are thought to be responsible for two rare forms of kidney cancer: von Hippel-Lindau syndrome, a disease that causes multiple tumors of the brain, spine, eyes, adrenal glands, pancreas, inner ear, testicles, and kidneys; and tuberous sclerosis, a disease characterized by small tumors of the blood vessels, resulting in numerous bumps on the skin; mental retardation; seizures; and cysts in the kidneys, liver, and pancreas and; in some cases, RCC.
Other Risk Factors
These are the primary symptoms of RCC : Abdominal mass or lump in the belly Blood in the urine (hematuria) Fever not caused by a cold or flu High blood pressure Pain in the flank (side) or lower back not associated with injury Persistent feeling of fatigue Rapid, unexplained weight loss Swelling of the legs and ankles While these symptoms are usually caused by other illnesses, they may indicate the presence of RCC. People who have any of these symptoms should see their urologist or family doctor as soon as possible.
The grade of a cancer cell is an assessment of its appearance compared to that of a normal, healthy cell. Grading is done on a scale of 1 to 4: Grade 1 RCC cells differ little from normal kidney cells, typically spread slowly, and have a good prognosis for treatment. Grade 4 RCC cells look extremely different and indicate an aggressive cancer with poor prognosis.
Although grading and the identification of cancer cell types help determine a patient's prognosis, most doctors believe that the cancer's stage is a better indicator of a patient's survivability.
Staging allows a physician to gauge the size and location of tumors by using information gathered from imaging studies such as CT scans and MRIs, and from pathology tests and physical examinations.
Staging factors that influence a patient's prognosis are:
There are two staging systems for RCC, Robson and TNM.
The Robson system classifies tumors as stages.
The TNM system stages RCC tumors at four intervals:
The TNM system also uses alphanumeric subcategories to define areas and degrees of invasion. These are as follows:
If the physician suspects that symptoms are caused by RCC, the patient will undergo a series of examinations, procedures, and laboratory tests to confirm the diagnosis. The process usually starts with a thorough physical examination to assess the patient's health and to gather as much information as possible about his or her symptoms. A medical history is taken to determine if there are any risk factors associated with RCC.
In some cases, the physician may request an arteriogram or venacavagram (IVPs of the blood vessels that supply the kidneys) to look for tumors in the connecting arteries and veins.
Fine Needle Aspiration
Physicians usually avoid performing needle biopsies of suspected kidney tumors because of the risk for bleeding or other complications. Some tumors contain a fluid-filled cyst. A small amount of this fluid can be drawn out of the cyst for examination by a pathologist, who will look for and identify the cancer cells. This can help the physician determine an appropriate treatment plan. While no longer common, a similar technique can be used to collect a sample of solid tissue from a noncystic tumor.
Most studies suggest that the type of cancer cell indicates the relative aggressiveness of the disease.
Under a microscope, clear cell cancers are the least abnormal-looking -- they are round or polygon-shaped and contain an abundance of fat and sugar. The tumors they produce are yellow to orange in color. Clear cell cancers are thought to be the least aggressive (likely to spread) and respond more favorably to treatment.
Few tumors contain only clear cells, however. Darker granular cells usually are present to some degree. These have a larger, darker nucleus and are full of tiny pink granules called mitochondria. The tumors they produce tend to be gray to white in color. Mitochondria are small, oval bodies that provide energy for cell growth. Their presence indicates a more aggressive form of cancer.
Tumors that contain both clear and granular cells are considered mixed. This is the most common form of RCC and indicates the most aggressive form of kidney cancer.
Mixed tumors that contain spindle shaped, sarcomatoid cells have the least favorable prognosis. Although tumors composed exclusively of spindle cells are uncommon, the presence of sarcomatoid cells indicates a form of cancer that grows and spreads quickly.
Once a diagnosis of renal cell cancer has been confirmed and the disease's stage determined, doctor and patient decide on a plan for treatment. Factors to consider in this decision include the patient's age and overall health, the extent to which the cancer has spread, and any other physical conditions that might affect the patient's survivability. For example, a patient with one healthy, functioning kidney and one afflicted with an aggressive Stage 2 RCC would be a more likely candidate for radical surgery than a person with only one kidney and a less aggressive Stage 1 cancer.
It is important that the patient and physician make an informed decision together after considering all possible options, side effects, and outcomes. It is imperative that the decision to proceed with a particular treatment be as free from doubt as possible. A confident, positive outlook can help the patient cope with the physical demands surgery and/or therapy will impose on the body and can improve the chances for a speedy recovery.
A second opinion can provide additional information in the decision-making process and help the patient feel that he or she has made the right choice. (Some insurance companies require a second opinion before they approve payment for treatment.)
In general, there are five treatment options for the patient with RCC:
Two or more forms of treatment may be used jointly, such as surgery to remove a primary tumor followed by radiation treatment or chemotherapy to kill any cancer cells that may remain in the body.
A sixth form of treatment, gene therapy, is now being explored by researchers who think inherited genetic mutations may cause many cases of RCC. Eventually, a process that uses normal genes to overcome or reverse the cancer-causing process may be developed. Currently, however, gene therapy is not a treatment option.
Surgery usually is required to treat RCC. Without it, most patients' chances for survival are poor. Several surgical options are available to the patient and physician; which is most appropriate depends on the patient's condition and the cancer's stage.
The most common form of surgery for RCC, radical nephrectomy involves removal of the entire kidney, often along with the attached adrenal gland, surrounding fatty tissues and nearby lymph nodes (regional lymphadenectomy), depending upon how far the cancer has spread.
It may be possible to remove only the cancerous tissue and part of the kidney if the tumor is small and confined to the very top or bottom of the kidney. A partial nephrectomy may be the procedure of choice for patients with RCC in both kidneys and for those who have only one functioning kidney.
This procedure usually is reserved for patients whose health does not permit surgery, such as those with heart or lung disease. In arterial embolization, a catheter (very small tube) is inserted through a blood vessel in the groin and passed up to the kidney. A small piece of gelatin sponge is then injected into the artery that supplies blood to the cancerous kidney. This cuts off the flow of blood to the kidney and the cancerous tumor, and both die. The kidney usually is surgically removed at a later date, if and when the patient's health permits.
Any form of invasive surgery carries certain risks. Patients contemplating kidney surgery should be advised of the possibility of experiencing complications, such as the following:
The natural course of renal cell cancer is more unpredictable than that of most tumors. It is the second most common tumor to undergo spontaneous regression following removal of the primary lesion; this occurs about 0.5% of the time. Another unusual characteristic of RCC is the variability in the growth of the primary tumor.
Once distant disease occurs, survival depends on the extent of the spread and the interval between appearance of metastases and the removal of the kidney.
Overall, the 5-year survival rate for RCC -- all stages combined -- is about 40-45%.
Follow-up Care and Recurrent Kidney Cancer
Some patients who undergo surgery to remove a cancerous kidney or kidney tumors experience a recurrence of the disease. For this reason, patients usually undergo a regimen of follow-up examinations after surgery, typically at 3-month intervals for the first year. These examinations include a complete physical examination, a chest x-ray, complete blood tests, and assessments of liver and kidney function.
If the disease recurs but remains confined to a few small areas, additional surgery may be recommended. Radiation, biological, or chemotherapy also may be tried as an adjuvant or palliative (relief-giving) treatment.
Chemotherapy uses chemical agents to kill cancer cells throughout the body. Unfortunately, RCC has proven to be particularly resistant to chemotherapy. Research to develop more effective chemical compounds to treat RCC is ongoing, however, and a number of them are currently being tested.
The use of radiation, either in the form of x-rays or other high-energy rays, to shrink and kill cancer cells is used to treat some kidney cancer patients. The radiation may be delivered as a focused beam (external therapy) that is projected into the body or in the form of radioactive materials placed at the site of the cancer through thin plastic tubes (internal therapy). Radiation therapy is used often as an adjuvant (follow-up) therapy to kill any cancer cells that may remain in the body after a radical or partial nephrectomy. It also may be used as palliative therapy to lessen pain or bleeding in patients with inoperable or widespread metastatic RCC. In such cases, there is no expectation of cure; the object is simply to ease the dying patient's discomfort. Radiation therapy alone has a relatively low success rate in treating RCC, and often produces unpleasant side effects:
Agents such as estrogen, progesterone, and tamoxifen have been used with varying degrees of success to stop some types of cancer from growing. There is little evidence, however, that hormone therapy, either primary or adjuvant, is effective when used to treat RCC. Some recent studies show success rates of 5% to 10%. At best, it remains a subject for future research.
Over the last 10 years, there has been much interest in the use of biological agents, primarily interleukin and interferon, to boost, restore, or direct the patient's immune system to fight RCC in the same way it would fight an infection. There are data to suggest that these agents effectively treat this disease and can at times produce complete remissions. Both interleukin and interferon are approved by the FDA for treating metastatic RCC.
Some recent studies suggest that combining biological therapy with chemotherapy (chemobiological) therapy produces significantly higher response rates than biological therapy alone, although the data need to be confirmed in a larger study. The side effects of chemobiological therapy include, but are not limited to the follwing:
A benign tumor is one that is noncancerous. Most are asymptomatic and are discovered incidentally. While not immediately life threatening, many benign tumors can become cancerous if allowed to grow. For this reason, the discovery and identification of a benign kidney tumor is regarded a fortunate finding. These growths are evaluated and treated as an early form of cancer.
Renal adenomas are the most common form of benign, solid kidney tumor, and are typically small, low-grade growths. Their cause is unknown. Because they usually are asymptomatic, their incidence in the live population is unknown, although one study found them present in 7% to 22% of autopsy cadavers. In rare cases, where they have grown large enough to erode the function of the kidney or adjacent vessels, symptoms similar to those of RCC have been known to occur.
Adenoma cells look much like low-grade RCC cells under a microscope. In fact, while they are considered benign, there is presently no known cellular classification to differentiate them from RCCs. Many researchers and physicians regard them as early stage precancers, to be treated accordingly.
Oncocytoma is a benign, usually asymptomatic tumor that can grow quite large. They can develop throughout the body and are not unique to the kidneys. Their cause is unknown, and they appear with greater frequency in men than in women. Typically, they are discovered incidentally by ultrasound, IVP, CT, or MRI scan during an examination for some other health problem.
Under a microscope, many oncocytomas resemble early-stage RCCs. Many physicians regard them as precancerous growths to be surgically removed unless the patient's age or overall health condition dictates otherwise.
Also known as renal hamartoma, angiomyolipomas are rare benign tumors usually caused by an inherited genetic mutation. They can occur on an isolated, individual basis, but most often are associated with the rare genetic disease called tuberous sclerosis, an affliction characterized by small tumors of the blood vessels, resulting in numerous bumps on the skin; mental retardation; seizures; cysts in the kidneys, liver, and pancreas; and, in some cases, RCC. About 80% of persons diagnosed with tuberous sclerosis also have angiomyolipoma.
In patients without tuberous sclerosis, these tumors most often occur in middle-aged women. Most cases are discovered when the patient undergoes a CT scan for an unrelated abdominal problem, suffers gastrointestinal discomfort, or suffers a sudden hemorrhage caused by the rupture of a large tumor.
Management of the condition depends on the size of the tumors and the severity of the symptoms they produce. Asymptomatic patients and those with small tumors usually are not treated; instead, they are observed periodically with an eye toward surgery if the tumors grow or produce symptoms. Because of the potential for spontaneous rupture and life-threatening hemorrhage, patients with large tumors usually are considered candidates for some form of surgical treatment, ranging from partial nephrectomy to arterial embolization.
Fibromas are tumors of the fibrous tissue on, in, or surrounding the kidney. They are rare and most often found in women. Their cause is unknown. Usually they grow on the periphery of the kidney and can become large before becoming clinically obvious. Most are asymptomatic. While generally benign, these tumors have no special characteristics to differentiate them from other malignant tumors of the kidney. Because of this uncertainty of diagnosis, most physicians treat them surgically. Partial or radical nephrectomy is the standard approach.
Lipomas are rare renal tumors that appear to originate in the fat cells within the renal capsule or surrounding tissue. They typically occur in middle-aged women, can grow very large, and produce pain and hematuria. Like many benign tumors, they are suspected of harboring potential for becoming cancerous and usually are treated with total nephrectomy.