Cancer of the kidneys

belongs amongst oncology kidney diseases. The kidneys are two organs, on the surface uniformly reddish brown in colour, are placed on the sides of the lumbar spine. Seen from the front they have a characteristic bean like shape. They are located closer to the rear than the front side of the body. At kidney the malignant cells grow uncontrollably and form a tumour masses.

Kidneys filter blood and remove waste products, molecules containing nitrogen and sulfur, excess salt and water. Through the renal capillaries 180 liters of blood plasma is filtered daily and every minute 120 ml of ultrafiltrate is created. These organs also produce hormones, which control blood pressure, red blood cell creation and other functions. Each kidney functions independently of the other. With the assistance of instrument dialysis, which is a mechanical process of filtering waste products of metabolism outside the patient’s body, it is possible to live without kidneys.

include several types:

• Clear cell carcinoma accounts for about 85% of cases of renal tumors. This type arises from the epithelium of the renal glomeruli and tubules renal parenchyma.
• Carcinoma from the transitional urothelial cells grows from the renal pelvic epithelium, where the created urine flows before it gets into the bladder. This type of tumour is similar to bladder and is therefore treated by the same procedure.
• Wilms’ tumour occurs mainly in children. Its method of treatment is different, as the treatment for kidney in adults. For more , see the section tumours in children: Wilms’ tumour.
• Papillary renal carcinoma was found in 10% to 15% of patients. Genetically it is different from the clear cell type and is also treated differently.

Determining the exact type of tumour cells help doctors to plan a treatment strategy. In the case of renal cell carcinomas we can consider four different types of cells, of which two are particularly important:

• Clear (bright) cell type is the most common, it is found in 85% of cases of renal cell carcinoma
• Sarcomatoid cell type is rare, occurs in sarcoma tumours that grow from the kidney fat or sheath.

Surgical procedure by which the kidney tumour is removed, or the entire kidney, gives a fair chance to cure , if this has not spread to other areas yet. If the has advanced beyond the kidney and metastases are present, it is difficult to treat it successfully. Whereas approximately one percent of all cases of kidney , the tumour sometimes spontaneously (by itself) is reduced, or even completely disappears, experts in this field have focused on the support of the immune system as an effective tool for the treatment of advanced renal cell carcinoma, which likely plays a role in suppression of tumour growth.

Statistics

in men is the seventh most common , and the tenth most common cause of death from . The percentage of five-year survival is in people with kidney about 63%.

Statistics on should be interpreted with extreme caution. It is not possible to accurately determine in the patient how long he will live with and acquaint him with an average survival of patients with the same disease and the stage of cases without knowing that the figure is only an average statistical number obtained by monitoring a large group of patients and from the actual length of survival in his case may also vary considerably. Since the survival statistics are evaluated at five-year intervals (sometimes even one year) may not capture the most recent advances made in the treatment or diagnosis of this type of .

Risk factors and prevention

The cause of kidney is not known, but a number of risk factors that may participate in malignant transformation of cells were identified. Some of them, such as age or sex can not be affected, others can be affected.

There are not enough facts know about the kidney in to say for certain how to prevent their formation. There are certain options that can decrease the risk of tumour formation, such as: to quit smoking, control high blood pressure, keep body weight under control, eat lots of fruits and less fat.

Risk factors for renal cell carcinoma are as follows :
Smoking. Smoking doubles the risk of developing renal cell carcinoma. It seems that the smoking causes 30 % of cases of kidney in men and about 25 % in women.
Gender and race. occurs two to three times more often in men than in women. The occurrence of kidney is high among the population with dark skin.
Age. is usually a disease of adults , and is most often diagnosed in people between 50 -th and 70 -th year of life.
Catering and body weight. Researches have consistently confirmed the link between renal and obesity, caused by the intake of food high in fat.
Hypertension (high blood pressure). The link between high blood pressure and renal has been confirmed in some research works.
Excessive use of certain drugs. Painkillers, containing phenacetin, are not used today as the connection in their use with the occurrence of renal cell carcinoma was proved. Excessive use of other drugs from the group of diuretics (water pills) and analgesics (painkillers), may also have a connection with the occurrence of renal cell carcinoma.
Exposure to asbestos and cadmium. Some studies have shown a connection between asbestos exposure and renal . Effect of cadmium metal element while working with products such as batteries, paints, welding materials, may also increase the risk of , which is multiplied if the smoker is exposed to cadmium.
Long-term dialysis. In patients, who are long-term dependent on dialysis, cystic formations may occur in the kidneys. These cysts are not usually detected early and can be removed before they succumb to malignant transformation.
Genetic risk and inheritance. The risk of heredity was confirmed in kidney , but only a few specific genes that increase this risk were discovered. One of these genes is responsible for the hereditary genetic disease, called von Hippel – Lindau disease. Renal cell carcinoma of the clear cells occurs in about 50 % of patients with this syndrome.
Two other genetic syndromes have recently been discovered, associated with renal cell : a Birt-Hogg-Dube syndrome and hereditary syndrome of Leiomyomatosis.
The presence of other diseases. In patients with tuberous sclerosis, complex genetic disease there is an increased risk of renal cell carcinomas, similar to people with von Hippel-Lindau syndrome (see above: a genetic risk).

Symptoms

Many cases of renal tumors are discovered accidentally, when the patient is subjected to X-ray, or ultrasound scans for other reasons. In these early stages the kidney does not cause any pain. Several warning signs of malignancy, such as the presence of blood in the urine, may be due to other causes (inflammation, cysts). Tumour symptoms usually appear only when the tumour is large enough and tends to overgrow nearby organs.

Symptoms of renal tumours are as follows:

• blood in urine
• pain or a feeling of pressure on the side or on the back
• swelling or lump on the side or on the back
• swollen ankles and feet
• high blood pressure, or anemia (anemia, decreased red blood cell count)
• fatigue
• loss of appetite
• weight loss
• recurrent fever, the cause of which is not inflammatory

Diagnostics

There are no simple tests that would straight away reveal the early stages of kidney tumour. Doctors may suggest that people at high risk of the disease undergo more frequent control examinations of urine presence in blood or ultrasound of the kidneys.

Medical examination.In the diagnosis of kidney the physician must medically examine the patient and palpate the patient’s abdomen and also other areas, whether he finds by palpation suspiciously raised points on the body.

Blood tests. Several laboratory tests are performed, including blood counts, where the number of red blood cells and urine for the presence of blood, bacteria, or cells is determined.

Imaging examinations:

Intravenous exclusion pyelography (IVP). Liquid contrast agent is administered into the bloodstream through a vein that is excreted by the kidneys and enhances on the X-ray both kidneys, urinary pelvis, ureters, bladder or urethra as well. The X-ray may show changes in renal size and deformation of renal calyces and pelvis in the case that the tumour is present.

Arteriography.Contrast agent is injected into a large artery that supplies the kidney with arterial blood. Atypical arteries that nourish the larger tumour are well displayed at such examination.

Ultrasonography. Ultrasonography may show the presence of the tumour using ultrasound waves, which are transmitted and reflected back through the sonographic sensor. Sometimes, on the ultrasound, kidney tumour may be detected also in the case where the patient was sent for the examination of another urological diagnosis.

Computed tomography (CT) and magnetic resonance imaging (MRI).Computed tomography (CT) processes X-rays from different angles and using the computer creates a cross-sectional view of the body inside. Sometimes, for the detail view, a contrast agent is also injected into a vein. Magnetic resonance imaging (MRI) is not used to create the image of X-rays, but the induced magnetic field. The processing principle of cross-cutting image inside the body is similar to the CT scan.

Chest and bone X-ray (RTG). These tests help to detect metastatic lesions on the lungs and bones.

Positron emission tomography (PET). PET scans is used as a new method of diagnosis of in ambiguous cases. This examination makes the use of a low dose of radiation isotope-labeled sugar (glucose) to determine the metabolic activity of the cells. It is able to differentiate between malignant and benign tumours. Although this method is quite new, doctors may recommend it in certain situations. Positron emission tomography can be recommended as a supplementary examination to CT and MRI.

Biopsy At biopsy the doctor removes a sample of tissue for histological examination. Biopsy sample is sent to the laboratory where an experienced pathologist checks the presence of cells in the examined tissue. If the biopsy is positive, it can confirm . If the biopsy is negative, it is necessary to conduct further investigations. A biopsy is not necessary if the tumour is clearly confirmed by computerized tomography.

In rare cases, of the renal pelvis can be done by special examination – cystoscopy and nefroureteroskopia. At these examinations, the patient under sedatives (tranquilizers) an endoscopic sensor with a light source and optics is inserted through the urethra into the bladder and then through the mouth of the ureter to the renal pelvis. This device can take sample cells from suspicious locations, and in some cases remove small tumours.

Stages

The next step after the detection of the presence of tumour is to determine to what extent the tumour is advanced and whether it has not spread to other parts of the body in the form of metastases. This process is called stage determination.

Doctors often use to determine the stage of renal tumors a TNM classification system.

This system takes, when assessing the stage of , three criteria into account: the tumour itself, lymph nodes around it and the presence of metastases. The combination of resulting findings determines the stage of in particular patient.

Knowing the stage helps the doctor plan the optimal treatment strategy and determine the prognosis of the patient. The stage of the renal carcinoma is dependent on the size of the primary tumour, its growth into the surrounding tissues and also on knowledge, how intensively it grows into the vascular system of the kidney.

Categorization of stages of kidney according to the TNM

TNM is an abbreviation: tumour – T, node (Latin nodus) – N and metastasis – M. To determine the stage of , doctors take into account the following three factors:

• How large is the primary tumou ?(T – tumour)
• Has the tumour spread to the lymph nodes? (N – nodus)
• Has the spread (metastasized) into other parts of the body?(M – metastáza)

T – Ttumour

T – Tumour
Using the TNM system, the symbol “T” in conjunction with another letter or number (0-4) is used to describe the extent stage and the location of the primary tumour. Some stages are divided into smaller groups that can provide more detailed data update. This helps doctors to suggest the best treatment plan for the patient. If there are more tumours, the category “T” is added with the letter “m” (multiple).
TX: primary tumour can not be assessed.
T0: there is no evidence of a primary tumour in the kidney, with no evidence of primary tumour.
T1: Tumour of 7 cm or less in the greatest extent, limited to the kidney.
T1a: tumour has more than 4 cm in the greatest extent, limited to the kidney.
T1b: tumour has more than 4-7 cm in the greatest extent, limited to the kidney.
T2: tumour larger than 7 cm in the greatest extent, limited to the kidney.
T3: tumour grows into the main renal arteries, or affects the adrenal gland (a gland in the upper pole of each kidney, which produces various hormones and adrenaline, which regulate heart rate, blood pressure and other bodily functions), or perinephric tissues (adipose connective tissue around each kidney) . The tumour does not exceeds Gerota renal fascia (membranous cover of each kidney).
T3a: tumour invades adrenal gland or surrounding tissues, but does not exceeds Gerota fascia
T3b: tumour spreading into renal (kidney) vein (veins) or into vena cava (the vena cava, which leads the blood to the heart) below the diaphragm.
T3c: tumour spreading into the vena cava above the diaphragm.
T4: tumour does not grow beyond Gerota renal fascia.

N – Regional Lymph Nodes
“N” in the TNM abbreviation indicates a nodule. Lymph nodes are small nodules of a bean shape, located throughout the body that normally help fight infections and growth as part of the human immune system. The regional lymph nodes (hilar, abdominal, paraaortal and paracaval) are located near the kidneys, and in other parts of the body are due to kidney distant lymph nodes.
NX: regional lymph nodes can not be assessed.
N0: without metastases in regional lymph nodes.
N1: metastasis in a single regional lymph node.
N2: metastasis in more than one regional lymph node.

M – distant metastasis
“M” in the TNM abbreviation indicates whether the tumour spread (metastasized) also into other parts of the body. At kidney there are frequent sites of metastases in bone, liver, lungs, brain and distant lymph nodes.
MX: presence of distant metastases can not be assessed.
M0: distant metastases are absent.
M1: distant metastases are present.

Categorization into stages I, II, III and IV
When the patient’s condition data are collected according to the TNM categorization, doctors, with the combination of these data will determine the stage, in which the disease is. Under this classification, physicians specify precisly the stage of renal cell carcinoma by stage number I, II , III and IV.
Stage I: The tumour has the most 7 cm in the greatest size and is limited to the affected kidney. It has not spread to lymph nodes or to distant parts of the body (T1, N0, M0).
Stage II: The tumour is larger than 7 cm and is limited to the affected kidney. It has not spread to lymph nodes or to distant parts of the body (T2, N0, M0).
Stage III: This includes the following options:

• Tumour has spread into a single regional lymph nodes, but not to distant lymph nodes or other organs (T1, T2 , T3 , N1 , M0).
• Tumour grows into the fatty tissue around the kidney and / or renal (kidney) vein, but does not affect any lymph nodes or other organs (T3, N0, M0).

Stage IV: Any of the following options:

• The tumour has spread directly through the fatty tissue and fascia (the membrane that encloses the kidney), perhaps even into a single regional lymph node, but will not affect other parts of the body (T4, N0, N1, M0).
• The tumour has spread into more than one regional lymph nodes near the kidney, but not in other parts of the body (any T, N2, M0).
• The tumour has spread into any of distant organs such as lungs, bones, or brain (any T, any N, M1).

Recurrent (repetitive)

Recurrent kidney means that , after stopping treatment, returned again. New tumour can occur in the remaining kidney, or in other body parts.

Treatment

A team of experts is responsible for the selection of appropriate treatment, which may be represented by a urologist, clinical oncologist, histo-pathologist, radio-diagnostician, radiation oncologist and other experts. Determining the treatment strategy depends on the subtype of tumour cells (histology) and on the progress of the tumour (stage).

If the is localized and does not spread outside of the kidney, surgery gives a considerable chance to the full cure, during which the entire tumour is removed, or all of the kidney, and if possible, also the surrounding tissue and regional lymph nodes.

If the is advanced by its growth and grows into nearby organs or metastases, radiation therapy can help (at regional spreading) or so called systemic therapy (at distant metastases), among which we count immunotherapy and chemotherapy. So far the best results at metastatic renal was brought by immunotherapy that can support the patient’s immune system in suppressing .

Surgical Treatment
Surgical procedure that removes the entire tumour and surrounding tissue is called a nephrectomy. At radical nephrectomy the entire affected kidney is removed. If the tumour affected also the surrounding tissue and regional lymph nodes, the radical nephrectomy with dissection (removal) of the lymph nodes follows. If the tumour grows into the adrenal glands then the affected adrenal gland can also be removed as so called adrenalectomy. If the grows into the surrounding blood vessels, surgeons may remove part of these vessels during surgery. Partial nephrectomy is such a surgical procedure, at which the entire tumour is actually removed, but the most possible healthy part of the affected kidney is kept.

During the laparoscopic surgical approach surgeon performs only a few small incisions into the skin, as opposed to 25 cm abdominal incision at the classic surgery, opening the abdominal wall (laparotomy). Surgeon uses, during laparoscopy, a special telescopic device with a light source and optics to remove the entire kidney, or the entire tumour from the kidney is just excised just as is smaller. Laparoscopic surgery takes longer than laparotomy, but it is less painful and the patient recovers faster. After this treatment, the patient is usually in hospital for a shorter period, there also tends to be lower risk of complications and faster recovery leads to health.

Radiotherapy
Radiotherapy (radiation therapy) uses high-energy x-rays to destroy cells and as an independent method of treatment it is not considered effective at renal cell carcinoma. It is rarely used as a therapeutic option for kidney , because the rate of kidney healthy tissue damage by irradiation is very large. In addition, this type of tumour is not very sensitive to radiation therapy. It is only approached if it is not possible for the patient, from different reasons, to undergo a surgery. Most often the radiation therapy is used in cases, where the tumour has spread, in the form of bone or brain metastases, here it may improve certain symptoms of the diseases such as bone pain, or swelling of the brain.

The latest Advanced Therapies in radiotherapy include stereotactic radiosurgery, which is designed to optimize the dose of radiation only into the specific area of the tumour without damaging the surrounding healthy tissue.

External radiation (external radiotherapy) can cause on the skin on places of the irradiation field a reaction similar to sunburn. Other side effects may include: nausea, vomiting, diarrhea and fatigue. Internal radiation therapy (internal radiotherapy, brachytherapy) can cause bleeding, infection and possible injury to the surrounding tissue.

Chemotherapy
Chemotherapy uses effects of special drugs (cytostatics) that destroy malignant tumour cells. It is well effective for a large number of patients, but most cases of kidney is resistant to all chemotherapeutic drugs. Therefore cytostatic therapy in renal cell carcinoma fails and does not lead to satisfactory results. Experts continue to research and look for new more effective drugs and new combinations of cytostatics.

Immunotherapy
Unlike most other types of , the advanced renal cell carcinoma responds poorly to chemotherapy, but surprisingly well to the so-called immunotherapy, which places it into the position of the first treatment choice. It was shown that the renal cell carcinoma is one of the few types of tumours with which the human body is able to fight through the immune system. Immunotherapy (also called biological therapy) is designed to stimulate the patient’s own immune system. It uses substances created by organic body, or artificially in the laboratory to support, provide guidance, or restore immune defense functions.

Immunotherapy is currently the most effective treatment for metastatic renal cell carcinoma. Together with this treatment preparations are used, which support the activity of cell and antibody immunity.

High doses of these preparations may produce severe side effects, such as too low blood pressure, fluid stagnation in the lungs, kidney damage, heart attacks, bleeding, chills and fever with chills. Therefore, some patients must, during the treatment, remain in the hospital for the purpose of health observation, sometimes for longer period. If these side effects are very strong, then the patients, who are intolerant of high doses, receive a treatment with lower doses.

Treatment of immunotherapy and chemotherapy is sometimes combined and administered simultaneously.

Follow-ups
After finishing the treatment of , patients should be regularly checked for his blood parameters of kidney functioning, chest X-ray, CT of abdominal and thoracic cavities, and also some other screening tests that can detect whether the disease is not returning, or distant metastases or a new tumour in place of the original do not recur after the surgery. The checks should be carried out every three months during the first year, every four months during the second to fifth year and then annually.

Generalized (metastatic) renal cell carcinoma
In the most advanced stage (IV), the tumour cells are separated from the original tumour and travel through the lymphatic system and bloodstream into other distant parts of the body, where they begin to grow and form metastatic foci (metastases). The most common site for metastases are the lungs, but tumour may spread also into the opposite kidney, bones, liver, brain, skin, and other locations.

Current research

Because kidney does not respond well to traditional chemotherapy, when treating it the emphasis is placed on testing new and original drugs, immunotherapy and other biological therapies.

Tumour vaccines are experimental therapy s the patient’s own immune system to fight . Doctors are testing the effect of a number of different types of vaccines in people with generalized renal cell carcinoma, in to prevent the growth of and try to at least stabilize the patient’s condition. Some vaccines are prepared from the patient’s tumour tissue itself and are then administered after surgery, while others are made ​​of proteins, which are located on the surface of tumour cells or tumour infiltrating dendritic cells.

Allogeneic transplantation of stem cells, or “mini-transplantation” is another example of immunotherapy. Patients first undergo chemotherapy, which suppresses their immune system and subsequently the stem cells from an HLA-identical donor (usually a patient‘s sibling) are transplanted into the sick person. Other highly effective drugs are then administered to suppress the patient’s existing immune system until the donor stem cells do not settle and create a new immune system (engraftment). New cells from the donor’s immune system fight against a current patient’s tumour cells and this reaction is called “graft-versus-tumour”. New immune system can also affect the patient’s healthy tissues and cause illness “graft versus host”. Such a state can be controlled by special medication – immunosuppressive agents that can hinder a strong immune reaction.

Neovascularisation inhibitors and other drugs of the targeted therapy prevent the formation of new tumour blood vessels that the tumour needs to supply oxygen and nutrients in to grow and expand. A further possibility is the use of monoclonal antibodies against receptors that are found on tumour cells of renal cell carcinoma