Renal cell carcinoma

Renal cell carcinoma
Classification and external resources

Micrograph of the most common type of renal cell carcinoma (clear cell) - on right of the image; non-tumour kidney is on the left of the image. Nephrectomy specimen. H&E stain.
ICD-10 C64.
ICD-9 189.0
ICD-O: M8312/3
OMIM 144700 605074
DiseasesDB 11245
MedlinePlus 000516
eMedicine med/2002

Renal cell carcinoma (RCC, also known as hypernephroma) is a kidney cancer that originates in the lining of the proximal convoluted tubule, the very small tubes in the kidney that filter the blood and remove waste products. RCC is the most common type of kidney cancer in adults, responsible for approximately 80% of cases.[1] It is also known to be the most lethal of all the genitourinary tumors. Initial treatment is most commonly a radical or partial nephrectomy and remains the mainstay of curative treatment.[2] Where the tumour is confined to the renal parenchyma, the 5-year survival rate is 60-70%, but this is lowered considerably where metastases have spread. It is resistant to radiation therapy and chemotherapy, although some cases respond to immunotherapy. Targeted cancer therapies such as sunitinib, temsirolimus, bevacizumab, interferon-alpha, and possibly sorafenib have improved the outlook for RCC (progression-free survival), although they have not yet demonstrated improved survival.

Contents

Signs and symptoms

A wide range of symptoms can be present with renal carcinoma depending on which areas of the body have been affected.[3] The classic triad is hematuria (blood in the urine), flank pain and an abdominal mass. This triad only occurs in 10-15% of cases, and is generally indicative of more advanced disease. Today, the majority of renal tumors are asymptomatic and are detected incidentally on imaging, usually for an unrelated cause.

Signs may include:

Patients may also experience the following symptoms:

Classification

Micrograph of clear cell renal cell carcinoma. Nephrectomy specimen. H&E stain.
Micrograph of papillary renal cell carcinoma, showing vascular papillae with foam cells. H&E stain.
Micrograph of chromophobe renal cell carcinoma oncocytic variant. H&E stain.

Recent genetic studies have altered the approaches used in classifying renal cell carcinoma. The following system can be used to classify these tumors:[10][11][12]

Renal epithelial neoplasms have characteristic cytogenetic aberrations that can aid in classification.[13] See also Atlas of Genetics and Cytogenetics in Oncology and Haematology.

Array-based karyotyping can be used to identify characteristic chromosomal aberrations in renal tumors with challenging morphology.[14][15] Array-based karyotyping performs well on paraffin embedded tumors[16] and is amenable to routine clinical use. See also Virtual Karyotype for CLIA certified laboratories offering array-based karyotyping of solid tumors.

Other associated genes include TRC8, OGG1, HNF1A, HNF1B, TFE3, RCCP3, and RCC17.

Epidemiology

The incidence of renal cell cancer has been rising steadily. Nearly 51190 new diagnoses and 12890 deaths reported in the United States in 2007. It is more common in men than women: the male-to-female ratio is 1.6:1 and has been decreasing over the last decade. Blacks have a slightly higher rate of renal cell cancer than whites. The reasons for this are not clear.[17] Note: in epidemiology, RCC is registered together with renal pelvis carcinoma, which is predominantly transitional cell type.

In Europe the incidence of RCC has doubled in the period from 1975 to 2005.[18] RCC accounted for 3777 deaths in the UK in 2006; male 2372, female 1820.[19][20][21]

Risk factors

Cigarette smoking and obesity are the strongest known risk factors. Hypertension and a family history of the disease are also risk factors.[22]

Dialysis patients with acquired cystic disease of the kidney showed a 30 times greater risk than in the general population for developing RCC.[23]

Exposure to asbestos, polycyclic aromatic hydrocarbons, gasoline has not been shown to be consistently associated with RCC risk.[24]

Patients with certain inherited disorders such as von Hippel-Lindau disease, hereditary papillary renal cancer, a hereditary leiomyoma RCC syndrome and Birt-Hogg-Dubé syndrome, show an enhanced risk of RCC.[25][26][27]

Hysterectomy is associated with an approximately doubled risk. Hormonal factors or injury of the ureter during surgery were considered as possible causes.[28][29]

Diagnosis

An accurate diagnose may be difficult to establish given that the early stages of renal cancer are asymptomatic. However, the first steps taken in order to diagnose this condition are observing the signs and symptoms and an anamnesis (the detailed medical review of past health state).

By Signs and symptoms But unfortunately, early kidney cancers do not usually cause any signs or symptoms, but larger ones may.

Anamnesis (detailed medical review of past health state)

Physical examination The physical examination may be useful in providing information about the signs of kidney cancer. During a physical exam, the doctor evaluates general signs of health and tests for fever and high blood pressure. The palpitation of the abdomen may reveal the presence of a mass or an organ enlargement.[30] The doctor also checks general signs of health and tests for fever and high blood pressure.

If a patient has symptoms that suggest kidney cancer, the doctor may perform one or more of the following procedures:

Lab tests Lab tests are not usually used to diagnose kidney cancer, but they can sometimes give the first hint that there may be a kidney problem. They are also done to get a sense of a person’s overall health and to help tell if cancer may have spread to other areas.They can help tell if a person is healthy enough to have an operation. The laboratory tests may provide information whether there are signs of cancer or, if its presence is confirmed, they can show if cancer has spread. Urine tests such as the urine cytology and the urinalysis and blood tests complete blood count and serum calcium) may reveal abnormalities in the kidneys functioning.[31]

Urinalysis(Urine tests) These set of tests check for several indicators of the cancer such as blood, sugar, proteins, and bacteria.

Complete blood count A complete blood count can detect findings sometimes seen with renal cell cancer.

Blood chemistry tests Blood chemistry tests are usually done in people who may have kidney cancer, as it can affect the levels of certain chemicals in the blood.

Imaging tests Imaging tests use x-rays, magnetic fields, or radioactive substances to create pictures of the inside of your body. imaging tests can give doctors a reasonable amount of certainty that a kidney mass is (or is not) cancerous. Unlike most other cancers, doctors can often diagnose a kidney cancer fairly certainly without the need for a biopsy. In some patients, however, a biopsy may be needed to be sure. The imaging tests are a reliable source of information for doctors because they provide clear pictures of the organs and tissues of the body. The main imaging tests performed in order to establish a renal carcinoma are the abdominal CT scan, ultrasound test of the abdomen and kidneys, renal angiography, MRI scan or an intravenous pyelogram (IVP).

Computed tomography (CT) scans, magnetic resonance imaging (MRI) scans, intravenous pyelograms, and ultrasound can be very helpful in diagnosing most kinds of kidney tumors, although patients rarely need all of these tests.

Computed tomography(CT) This imaging test is similar with an x-ray test, and creates a detailed cross-sectional image of the body. Instead of taking one picture, like a regular x-ray, a CT scanner takes many pictures as it rotates around you while you lie on a table. The pictures of the patient's kidneys show if there is a kidney tumor or not. It is a test similar to the x-rays in which is used a contrast agent and the diagnosis is made based on the pictures taken before the contrast agent is injected compared to the pictures taken after the contrast agent was administrated.

The abdominal CT scan consists in taking clear pictures of the patient's kidneys, showing if there is a kidney tumor or not.CT scanning is one of the most useful tests for finding and looking at a mass inside your kidney. It is also useful in checking whether or not a cancer has spread to organs and tissues beyond the kidney. The CT scan will provide precise information about the size, shape, and position of a tumor, and can help find enlarged lymph nodes that might contain cancer.

Magnetic resonance imaging(MRI) magnetic resonance imaging (MRI) scans provide detailed images of soft tissues in the body; however, magnetic fields are generated rather than ionizing radiation. These tests may be performed in preference to CT scans if the patient has a contrast allergy.

Ultrasound or ultrasonography Ultrasound imaging is a safe, noninvasive and brief test that can detect tumors. Ultrasound imaging is a medical technique that uses high-frequency sound waves to create an interior image of the body on a special computer screen. For this test, a small, microphone-like instrument called a transducer is placed on the skin near the kidney. Ultrasound can be helpful in determining if a kidney mass is solid or filled with fluid. The echo patterns produced by most kidney tumors look different from those of normal kidney tissue. If a renal carcinoma is suspected, the doctor will examine the kidneys, ureters and the bladder. The image created by an ultrasound is actually formed by echoes of the sound waves on the surface of the organs but the abnormal tissue masses and organs reflect sound waves differently and this is why the ultrasound may be useful in diagnosing renal carcinoma.[32]

If a kidney biopsy is needed, this test can be used to guide a biopsy needle into the mass to obtain a sample.

If cancer was already diagnosed, the evolution of the disease must be closely observed. The tests that can provide information on the evolution of the condition are the PET scan, chest x-rays, biopsy and the bone scan.

Positron emission tomography(PET scan) This is a very specialized imaging technique that provides useful information about the tumor location and how far the cancer has spread. The Pet scan uses radioactive glucose (known as fluorodeoxyglucose or FDG) to locate the cancer, because the cancerous cells absorb a higher amount of this substance than normal tissues.

This test can be useful to see if the cancer may have spread to lymph nodes near the kidney. PET scans can also be useful if your doctor thinks the cancer may have spread but doesn’t know where.

Intravenous pyelogram(IVP) The doctor injects dye into a vein in the arm. The dye travels from the bloodstream into the kidneys and then passes into the ureters and bladder. The dye makes them show up on x-rays. An IVP can be useful in finding abnormalities of the urinary tract, such as cancer, but you might not need an IVP if you have already had a CT or MRI.

Angiography Like the IVP, this type of x-ray also uses a contrast dye. The renal angiography may be required in order to examine the blood vessels in the kidneys. The test implies using a contrast agent which is injected into the renal artery and which is absorbed by the cancerous cells.This contrast agent is absorbed by the cancerous cells and displayed on an angiogram. Because angiography can outline the blood vessels that supply a kidney tumor, it can help a surgeon plan surgery in some patients who need blood vessels mapped before the operation. Angiography can also help diagnose renal cancers since the blood vessels usually have a special appearance with this test. .An intravenous pyelogram (IPV) can reveal the presence of an abnormal mass which can develop within the kidneys. In order to get clear images of the urinary tract, a dye substance is administrated into the patient's arm vein.

Other tests described here, such as chest x-rays and bone scans, are more often used to help determine if the cancer has spread (metastasized) to other parts of the body

Chest x-rayThe chest x-rays may determine if the cancer has spread to the other organs by using high energy electromagnetic radiation. A bone scan can show whether the cancer has spread to the bone tissues or not.

Bone scan

Biopsy Biopsies are not often used to diagnose kidney tumors. Imaging studies usually provide enough information. But, biopsy is sometimes used to get a small sample of cells from a suspicious area if imaging test results are not conclusive enough to warrant removing a kidney. Biopsy may also be done to confirm the diagnosis of cancer if a person’s health is too poor for surgery and other local treatments (such as radiofrequency ablation, arterial embolization or cryotherapy) are being considered. (10 questions to ask your doctor before a Biopsy) In many cases, the biopsy is the most accurate procedure that can confirm if the tumor or abnormal growth is a malignant tissue or not. This procedure consists in the removal of a sample of tissue from the abnormal tumor of mass. It can be performed in two different ways, either by a fine needle aspiration either by a core needle biopsy.

Fine needle aspiration This procedure involves taking a sample of tissue from the tumor by using a thin needle attached to a syringe. Fine needle aspiration is performed only if the tumor can be easy reached. In kidney cancer patients, fine needle aspiration is the most used procedure of removing a sample of tissue.

Core needle biopsy This procedure is performed under local anesthesia and involves removing a small cylinder of tumor tissue.

Fuhrman grade The Fuhrman grade is determined by looking at kidney cancer cells (taken during a biopsy or during surgery) under a microscope. It is used by many doctors as a way to describe how aggressive the cancer is likely to be. The grade is based on how closely the cancer cells’ nuclei (part of a cell in which DNA is stored) look like those of normal kidney cells.

Renal cell cancers are usually graded on a scale of 1 through 4. Grade 1 renal cell cancers have cell nuclei that differ very little from normal kidney cell nuclei. These cancers usually grow and spread slowly and tend to have a good outlook (prognosis). At the other extreme, grade 4 renal cell cancer nuclei look quite different from normal kidney cell nuclei and have a worse prognosis.

Although the cell type and grade are sometimes helpful in predicting a prognosis, the cancer’s stage is by far the best predictor of survival. Staging is explained in Kidney cancer staging.[1]

Pathology

Renal cell carcinoma
Renal cell carcinoma

The gross and microscopic appearance of renal cell carcinomas is highly variable. The following describes a typical clear cell carcinoma, which is the most common type.

The renal cell carcinoma may present reddened areas where blood vessels have bled, and cysts containing watery fluids.[33] The body of the tumor shows large blood vessels that have walls composed of cancerous cells.

Gross examination often shows a yellowish, multilobulated tumor in the renal cortex, which frequently contains zones of necrosis, hemorrhage and scarring.

Light microscopy shows tumor cells forming cords, papillae, tubules or nests, and are atypical, polygonal and large. Also, the cells that make up a renal carcinoma may be clear, granular, mixed clear and granular or sarcomatoid or spindle type. Recent studies have brought to attention that the type of cancerous cells and the aggressiveness of the condition are closely related.Because these cells accumulate glycogen and lipids, their cytoplasm appear "clear", the nuclei remain in the middle of the cells, and the cellular membrane is evident. Some cells may be smaller, with eosinophilic cytoplasm, resembling normal tubular cells. The stroma is reduced, but well vascularized. The tumor compresses the surrounding parenchyma, producing a pseudocapsule.[34]

The clear cells are thought to be the least likely to spread and usually respond more favorably to treatment.[35] However, most of the tumors contain a mixture of cells. The most aggressive stage of renal cancer is believed to be the one in which the tumor is mixed, containing both clear and granular cells.

Secretion of vasoactive substances (e.g. renin) may cause arterial hypertension, and release of erythropoietin may cause erythrocytosis (increased production of red blood cells)[4] (see the Signs and symptoms section).

Radiology

The characteristic appearance of renal cell carcinoma (RCC) is a solid renal lesion which disturbs the renal contour. It will frequently have an irregular or lobulated margin. Traditionally 85 to 90%% of solid renal masses will turn out to be RCC but this number may be decreasing as renal masses are being found at smaller and smaller sizes with larger numbers of benign lesions. 10% of RCC will contain calcifications, and some contain macroscopic fat (likely due to invasion and encasement of the perirenal fat). Following intravenous contrast administration (computed tomography or magnetic resonance imaging), enhancement will be noted, and will highlight the tumor relative to normal renal parenchyma.

In particular, reliably distinguishing renal cell carcinoma from an oncocytoma (a benign lesion) is not possible using current medical imaging or percutaneous biopsy.

Renal cell carcinoma may also be cystic. As there are several benign cystic renal lesions (simple renal cyst, hemorrhagic renal cyst, multilocular cystic nephroma, polycystic kidney disease), it may occasionally be difficult for the radiologist to differentiate a benign cystic lesion from a malignant one. A classification system for cystic renal lesions that classifies them based specific imaging features into groups that are benign and those that need surgical resection is available.[36]

At diagnosis, 30% of renal cell carcinoma has spread to that kidney's renal vein, and 5-10% has continued on into the inferior vena cava.[37]

Percutaneous biopsy can be performed by a radiologist using ultrasound or computed tomography to guide sampling of the tumor for the purpose of diagnosis. However this is not routinely performed because when the typical imaging features of renal cell carcinoma are present, the possibility of an incorrectly negative result together with the risk of a medical complication to the patient make it unfavorable from a risk-benefit perspective. This is not completely accurate, there are new experimental treatments.

Treatment

If it is only in the kidneys, which is about 40% of cases, it can be cured roughly 90% of the time with surgery. If it has spread outside of the kidneys, often into the lymph nodes or the main vein of the kidney, then it must be treated with adjunctive therapy, including cytoreductive surgery. RCC is resistant to chemotherapy and radiotherapy in most cases, but does respond well to immunotherapy with interleukin-2 or interferon-alpha, biologic, or targeted therapy. In early stage cases, cryotherapy and surgery are the preferred options.

Watchful waiting

Small renal tumors (< 4 cm) are treated increasingly by way of partial nephrectomy when possible.[38][39][40] Most of these small renal masses manifest indolent biological behavior with excellent prognosis.[41] More centers of excellence are incorporating needle biopsy to confirm the presence of malignant histology prior to recommending definitive surgical extirpation. In the elderly, patients with co-morbidities and in poor surgical candidates, small renal tumors may be monitored carefully with serial imaging. Most clinicians conservatively follow tumors up to a size threshold between 3–5 cm, beyond which the risk of distant spread (metastases) is about 5%.

Surgery

Micrograph of embolic material in a kidney removed because of renal cell carcinoma (cancer not shown). H&E stain.

Surgical removal of all or part of the kidney (nephrectomy) is recommended.[2] This may include removal of the adrenal gland, retroperitoneal lymph nodes, and possibly tissues involved by direct extension (invasion) of the tumor into the surrounding tissues. In cases where the tumor has spread into the renal vein, inferior vena cava, and possibly the right atrium, this portion of the tumor can be surgically removed, as well. In cases of known metastases, surgical resection of the kidney ("cytoreductive nephrectomy") may improve survival,[42] as well as resection of a solitary metastatic lesion. Kidneys are sometimes embolized prior to surgery to minimize blood loss[1] (see image).

Surgery is increasingly performed via laparoscopic techniques. These have the advantage of being less of a burden for the patient and the disease-free survival is comparable to that of open surgery.[2] For small exophytic lesions that do not extensively involve the major vessels or urinary collecting system, a partial nephrectomy (also referred to as "nephron sparing surgery") can be performed. This may involve temporarily stopping blood flow to the kidney while the mass is removed as well as renal cooling with an ice slush. Mannitol can also be administered to help limit damage to the kidney. This is usually done through an open incision although smaller lesions can be done laparoscopically with or without robotic assistance.

Laparoscopic cryotherapy can also be done on smaller lesions. Typically a biopsy is taken at the time of treatment. Intraoperative ultrasound may be used to help guide placement of the freezing probes. Two freeze/thaw cycles are then performed to kill the tumor cells. As the tumor is not removed followup is more complicated (see below) and overall disease free rates are not as good as those obtained with surgical removal.

Percutaneous therapies

Percutaneous, image-guided therapies, usually managed by radiologists, are being offered to patients with localized tumor, but who are not good candidates for a surgical procedure. This sort of procedure involves placing a probe through the skin and into the tumor using real-time imaging of both the probe tip and the tumor by computed tomography, ultrasound, or even magnetic resonance imaging guidance, and then destroying the tumor with heat (radiofrequency ablation) or cold (cryotherapy). These modalities are at a disadvantage compared to traditional surgery in that pathologic confirmation of complete tumor destruction is not possible. Therefore, long-term follow-up is crucial to assess completeness of tumour ablation.[43][44]

Medications

RCC "elicits an immune response, which occasionally results in dramatic spontaneous remissions." This has encouraged a strategy of using immunomodulating therapies, such as cancer vaccines and interleukin-2 (IL-2), to reproduce this response. IL-2 has produced "durable remissions" in a small number of patients, but with substantial toxicity. Another strategy is to restore the function of the VHL gene, which is to destroy proteins that promote inappropriate vascularization. Bevacizumab, an antibody to VEGF, has significantly prolonged time to progression, but phase 3 trials have not been published. Sunitinib (Sutent), sorafenib (Nexavar), and temsirolimus, which are small-molecule inhibitors of proteins, have been approved by the U.S. F.D.A.[45]

Treatment with tyrosine kinase inhibitors including nexavar, pazopanib, and rapamycin have shown promise in improving the prognosis for advanced RCC since 2004.

Sorafenib, a protein kinase inhibitor, was FDA approved in December 2005 for treatment of advanced renal cell cancer.

A month later, Sunitinib was approved as well. Sunitinib—an oral, small-molecule, multi-targeted (RTK) inhibitor—and sorafenib both interfere with tumor growth by inhibiting angiogenesis as well as tumor cell proliferation. Sunitinib appears to offer greater potency against advanced RCC, perhaps because it inhibits more receptors than sorafenib. However, these agents have not been directly compared against one another in a single trial. [2][3]

Recently the first Phase III study comparing an RTKI with cytokine therapy was published in the New England Journal of Medicine. This study showed that Sunitinib offered superior efficacy compared with interferon-α. Progression-free survival (primary endpoint) was more than doubled. The benefit for sunitinib was significant across all major patient subgroups, including those with a poor prognosis at baseline. 28% of sunitinib patients had significant tumor shrinkage compared with only 5% of patients who received interferon-α. Although overall survival data are not yet mature, there is a clear trend toward improved survival with sunitinib. Patients receiving sunitinib also reported a significantly better quality of life than those treated with IFNa.[46]

Temsirolimus (CCI-779) is an inhibitor of mTOR kinase (mammalian target of rapamycin) that was shown to prolong overall survival vs. interferon-α in patients with previously untreated metastatic renal cell carcinoma with three or more poor prognostic features. The results of this Phase III randomized study were presented at the 2006 annual meeting of the American Society of Clinical Oncology (www.ASCO.org).

Date of Approval: March 30, 2009 Company: Novartis AG Treatment for: Renal Cell Carcinoma Afinitor (everolimus) is an oral once-daily inhibitor of mTOR indicated for the treatment of patients with advanced renal cell carcinoma (RCC) after failure of treatment with sunitinib or sorafenib. Afinitor approved in US as first treatment for patients with advanced kidney cancer after failure of either sunitinib or sorafenib - March 30, 2009 Thalomid and Revlimid have been studied in the treatment of renal cell carcinoma.[47]

Chemotherapy

Most of the currently available cytostatics are ineffective for the treatment of RCC. Their use can not be recommended for the treatment of patients with metastasized RCC,as response rates are very low,often just 5-15%,and most responses are short lived.[1] The use of Tyrosine Kinase (TK) inhibitors, such as Sunitinib and Sorafenib, and Temsirolimus are described in a different section

Vaccine

Cancer vaccines, such as TroVax, have shown promising results in phase 2 trials for treatment of renal cell carcinoma.[48] However, issues of tumor immunosuppression and lack of identified tumor-associated antigens must be addressed before vaccine therapy can be applied successfully in advanced renal cell cancer.[49]

Prognosis

The five year survival rate is around 90-95% for tumors less than 4 cm. For larger tumors confined to the kidney without venous invasion, survival is still relatively good at 80-85%. For tumors that extend through the renal capsule and out of the local fascial investments, the survivability reduces to near 60%. If it has metastasized to the lymph nodes, the 5-year survival is around 5 % to 15 %. If it has spread metastatically to other organs, the 5-year survival rate is less than 5 %.

For those that have tumor recurrence after surgery, the prognosis is generally poor. Renal cell carcinoma does not generally respond to chemotherapy or radiation. Immunotherapy, which attempts to induce the body to attack the remaining cancer cells, has shown promise. Recent trials are testing newer agents, though the current complete remission rate with these approaches are still low, around 12-20% in most series. Most recently, treatment with tyrosine kinase inhibitors including nexavar, pazopanib, and rapamycin have shown promise in improving the prognosis for advanced RCC since 2004.

History

Historically, RCC was also known as nephrocellular carcinoma.[50] Paul Grawitz first described renal cell carcinoma in 1883.

Metastatic renal cell carcinoma

The metastatic stage of the renal cell carcinoma occurs when the disease invades and spreads to other organs. It is most likely to spread to neighboring lymph nodes, the lungs, the liver, the bones, or the brain.[51] Metastatic renal cell carcinoma presents a special challenge to oncologists, as about 70% of patients with renal cell carcinoma develop metastases during the course of their disease, and 5 year survival for patients with metastatic renal cell carcinoma is between 5-15%,though it is much improved if metastatectomy and nephrectomy to remove all visible disease is performed. even if metastases are not removed,cytoreductive nephrectomy is sometimes used in the treatment of metastatic renal cell carcinoma,and at least 1 study has supported the use of cytoreductive nephrectomy in "some cases" of metastatic renal cell carcinoma,citing improved response rates to interleukin-2 immunotherapy and modestly prolonged survival.

Radiotherapy and chemotherapy have less of a role in therapy of renal cell carcinoma then in other malignancies; but they are still sometimes used in treatment of metastatic renal cell carcinoma. Radiotherapy is used in bone metastases from renal cell carcinoma to reduce pain and lower the risk of pathologic fracture, in patients with brain metastases, and to palliate symptoms of metastatic disease to the liver, adrenals, or lungs from renal cell carcinoma. Interleukin-2, has been the standard of care since the 1990s in metastatic renal cell carcinoma, as although response rates are low [7-16%], about half of patients that respond have long term disease free survival, and some of these patients may be cured of their disease. However,the side effects of interleukin-2 are very severe, including decreased neutrophil function, increased risk of dissemenated infection, including central venous catheter infections, septicaemia, and bacterial endocarditis, capilary leak syndrome, which can result in myocardial infarction, renal failure, angina, hypotension, reduced organ perfusion, altered mental status, pulmonary failure requiring intubation, cardiac arrhythmias, edema, and gastrointestinal bleeding. Proleukin also can result in lethargy and somnolence; if interleukin-2 therapy is not discontinued lethargy may progress to coma. Interleukin-2 can also worsen pre-existing autoimmune diseases.exacerbation of scleroderma, diabetes mellitus, thyroiditis, inflammatory bowel disease, myesthinisa gravis, nephritis, and other autoimmune diseases have been reported. Neurological side effects can also occur, and include ataxia, cortical blindness, hallucinations, psychosis, speech problems, and coma. Other side effects include abdominal pain, rigors, fever, malaise, asthenia, acidosis, tachycardia, vasodialation, diarrhea, vomiting, mouth sores, loss of appetite, dermatitis, dyspnea, thrombocytopenia, and anaemia. Also, patients must be in good health with normal cardiovascular, hepatic, pulmanary,and neurological function to be treated with interleukin-2.

Recently, targeted therapies including torisel, nexavar, sutent, and bevacizumab have been developed, and all are now approved for the treatment of metastatic renal cell carcinoma. Also, votrient [pazopanib] was approved for the treatment of metastatic renal cell carcinoma in October 2009. This is the sixth drug to be approved for metastatic renal cell carcinoma since 2005. The last 3–5 years have seen dramatic improvements in treatment for those with metastatic renal cell carcinoma, Richard Pazdur, MD, director of the office of oncology drugs at the U.S. Food and Drug Administration (FDA). However, despite these improvements in therapy, overall survival in metastatic renal cell carcinoma remains quite poor.

Currently, tumor vaccines and chemotheraputic, biologic, and immunologic agents are being researched in the treatment of metastatic renal cell carcinoma, and some appear promising. It is not known whether or not detecting metastatic renal cell carcinoma earliar improves survival or response to treatment. Symptoms of metastatic renal cell carcinoma are often mistaken for other, less severe illness,and include: for bone metastases, pain, stiffness, bruit, and pathologic fracture; for liver metastases, abdominal pain, jaundice, elevations in AST and ALT, and vomiting, for lung metastases, cough, dyspnea, and abnormal chest radiograph. Brain metastases produce diplopia, personality changes, headache, ataxia, vertigo, and seizures. Systemic symptoms occur in some people with metastatic renal cell carcinoma, and include anorexia, fatigue, fever of unknown origin, weight loss, and malaise. Given that many diseases can cause these symptoms, extensive testing is typically required to diagnose metastatic renal cell carcinoma. Differential diagnoses include leukaemia, arthritis, any other neoplastic disease, locomotor ataxia, Lyme disease [in the case of unexplained malaise, fatigue, and bone pain], and other chronic infections.

Adjuvant therapy in renal cell carcinoma

Adjuvent therapy is typically a secondary treatment that is administerted after all visible cancer has either been surgically excised, radiated or otherwise eliminated, in order to prevent any new (metastatic) cancer growths from re-appearing. The re-appearance of cancer typically occurs after micro-cancerous cells remain in the body after the primary cancer has been removed.

There is currently no established adjuvant therapy for renal cell carcinoma, although there have been a number of clinical trials exploring the effectiveness of various potential treatments.

The use of non-specific cytokines has so far been shown to be ineffective. Unlike most other cancers, renal cell carcinoma is resistant to most cytotoxic and cytostatic agents,which severely limits possible effective adjuvant therapy. Trials of "cancer vaccines", radiotherapy, chemotherapy, immunotherapy, or biologic therapies (i.e. nexavar, sutent) have been met with little success,and currently the standard of care for completely resected high-risk renal cell carcinoma is close observation with no other therapy. There does appear to be some evidence that if there cancer is incompletely resected (positive surgical margins,adrenal involvement,vena caval involvement) radiotherapy reduces the risk of invasive local disease,but data is lacking on that as well.

There have also been a number of trials of Autolymphocyte therapy (ALT) which have shown varying degrees of efficacy.[52][53][54][55][56]

ALT is a form of outpatient adoptive immunotherapy utilizing autologous ex vivo activated T-cells accompanied by high dose cimetidine.

See also

References

  1. ↑ 1.0 1.1 1.2 Mulders PF, Brouwers AH, Hulsbergen-van der Kaa CA, van Lin EN, Osanto S, de Mulder PH (February 2008). "[Guideline 'Renal cell carcinoma']" (in Dutch; Flemish). Ned Tijdschr Geneeskd 152 (7): 376–80. PMID 18380384. 
  2. ↑ 2.0 2.1 2.2 Rini BI, Rathmell WK, Godley P (May 2008). "Renal cell carcinoma". Curr Opin Oncol 20 (3): 300–6. doi:10.1097/CCO.0b013e3282f9782b. PMID 18391630. 
  3. ↑ "Renal Carcinoma or hypernephroma". http://www.renalcarcinoma.net/. Retrieved 2010-03-31. 
  4. ↑ 4.0 4.1 4.2 4.3 4.4 Kumar, Parveen & Clark, Michael, eds (2005). Clinical Medicine (Sixth ed.). London: Elsevier. pp. 683–648. ISBN 0-7020-2763-4. 
  5. ↑ Motzer RJ, Bander NH, Nanus DM (September 1996). "Renal-cell carcinoma". N. Engl. J. Med. 335 (12): 865–75. doi:10.1056/NEJM199609193351207. PMID 8778606. http://content.nejm.org/cgi/pmidlookup?view=short&pmid=8778606&promo=ONFLNS19. 
  6. ↑ "Renal Cell Cancer". http://www.cancercompass.com/renal-cell-cancer-information/symptoms.htm/. Retrieved 2010-03-31. 
  7. ↑ "Renal Cell Carcinoma". http://www.omnimedicalsearch.com/conditions-diseases/renal-cell-carcinoma-symptoms.html. Retrieved 2010-03-31. 
  8. ↑ "Causes". http://www.nlm.nih.gov/medlineplus/ency/article/000516.htm. Retrieved 2010-03-31. 
  9. ↑ "Kidney Cancer Symptoms (Renal Cell)". http://cancer.about.com/od/kidneycancerrenalcell/a/kidneysymptoms.htm. Retrieved 2010-03-31. 
  10. ↑ Reuter VE, Presti JC (April 2000). "Contemporary approach to the classification of renal epithelial tumors". Semin. Oncol. 27 (2): 124–37. PMID 10768592. 
  11. ↑ Bodmer D, van den Hurk W, van Groningen JJ, et al. (October 2002). "Understanding familial and non-familial renal cell cancer". Hum. Mol. Genet. 11 (20): 2489–98. doi:10.1093/hmg/11.20.2489. PMID 12351585. http://hmg.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=12351585. 
  12. ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease. St. Louis, Mo: Elsevier Saunders. p. 1016. ISBN 0-7216-0187-1. 
  13. ↑ van den Berg E, Storkel S . Kidney: Renal cell carcinoma. Atlas Genet Cytogenet Oncol Haematol. June 2003.
  14. ↑ Hagenkord JM, Parwani AV, Lyons-Weiler MA, et al. (2008). "Virtual karyotyping with SNP microarrays reduces uncertainty in the diagnosis of renal epithelial tumors". Diagn Pathol 3: 44. doi:10.1186/1746-1596-3-44. PMID 18990225. 
  15. ↑ Monzon FA, Hagenkord JM, Lyons-Weiler MA, et al. (May 2008). "Whole genome SNP arrays as a potential diagnostic tool for the detection of characteristic chromosomal aberrations in renal epithelial tumors". Mod. Pathol. 21 (5): 599–608. doi:10.1038/modpathol.2008.20. PMID 18246049. 
  16. ↑ Lyons-Weiler M, Hagenkord J, Sciulli C, Dhir R, Monzon FA (March 2008). "Optimization of the Affymetrix GeneChip Mapping 10K 2.0 Assay for routine clinical use on formalin-fixed paraffin-embedded tissues". Diagn. Mol. Pathol. 17 (1): 3–13. doi:10.1097/PDM.0b013e31815aca30. PMID 18303412. 
  17. ↑ American Cancer Society. Cancer facts & figures 2007. American Cancer Society; 2007.
  18. ↑ Ferlay J, Autier P, Boniol M, Heanue M, Colombet M, Boyle P (March 2007). "Estimates of the cancer incidence and mortality in Europe in 2006". Ann. Oncol. 18 (3): 581–92. doi:10.1093/annonc/mdl498. PMID 17287242. 
  19. ↑ Office for National Statistics, Mortality Statistics: Cause England & Wales, 2006. Vol. DH2 No.32. 2006: TSO.
  20. ↑ GRO for Scotland Registrar General's Annual Report, 2006.
  21. ↑ Northern Ireland Cancer Registry, Cancer Mortality in Northern Ireland, 2006. 2006.
  22. ↑ Lipworth L, Tarone RE, McLaughlin JK (December 2006). "The epidemiology of renal cell carcinoma". J. Urol. 176 (6 Pt 1): 2353–8. doi:10.1016/j.juro.2006.07.130. PMID 17085101. 
  23. ↑ Brennan JF, Stilmant MM, Babayan RK, Siroky MB (April 1991). "Acquired renal cystic disease: implications for the urologist". Br J Urol 67 (4): 342–8. doi:10.1111/j.1464-410X.1991.tb15158.x. PMID 2032071. 
  24. ↑ McLaughlin JK, Kidney Cancer, Oxford University Press, Oxford, 2006, pp. 1087–1100.
  25. ↑ Lamiell JM, Salazar FG, Hsia YE (January 1989). "von Hippel-Lindau disease affecting 43 members of a single kindred". Medicine (Baltimore) 68 (1): 1–29. PMID 2642584. 
  26. ↑ Pavlovich CP, Schmidt LS (May 2004). "Searching for the hereditary causes of renal-cell carcinoma". Nat. Rev. Cancer 4 (5): 381–93. doi:10.1038/nrc1364. PMID 15122209. 
  27. ↑ Washecka R, Hanna M (April 1991). "Malignant renal tumors in tuberous sclerosis". Urology 37 (4): 340–3. doi:10.1016/0090-4295(91)80261-5. PMID 2014599. 
  28. ↑ PMID 10566555 (PubMed)
    Citation will be completed automatically in a few minutes. Jump the queue or expand by hand
  29. ↑ PMID 18711701 (PubMed)
    Citation will be completed automatically in a few minutes. Jump the queue or expand by hand
  30. ↑ "Renal cell carcinoma". http://www.nlm.nih.gov/medlineplus/ency/article/000516.htm/. Retrieved 2010-03-31. 
  31. ↑ "Symptoms of kidney cancer". http://www.medicinenet.com/kidney_cancer/page3.htm#symptoms/. Retrieved 2010-03-31. 
  32. ↑ "Renal Cell Carcinoma". http://www.omnimedicalsearch.com/conditions-diseases/renal-cell-carcinoma-tests-diagnosis.html. Retrieved 2010-03-31. 
  33. ↑ "Clear-cell Carcinoma, Hypernephroid Tumour, or Hypernephroma". http://www.britannica.com/EBchecked/topic/497921/renal-carcinoma. Retrieved 2010-03-31. 
  34. ↑ "pathologyatlas.ro". http://www.pathologyatlas.ro/renal-cell-carcinoma-grawitz-tumor-kidney-pathology.php. Retrieved 2007-12-29. 
  35. ↑ "PathologyPathology". http://www.urologychannel.com/kidneycancer/pathology.shtml. Retrieved 2010-03-31. 
  36. ↑ Israel GM, Bosniak MA (August 2005). "How I do it: evaluating renal masses". Radiology 236 (2): 441–50. doi:10.1148/radiol.2362040218. PMID 16040900. 
  37. ↑ Oto A, Herts BR, Remer EM, Novick AC (December 1998). "Inferior vena cava tumor thrombus in renal cell carcinoma: staging by MR imaging and impact on surgical treatment". AJR Am J Roentgenol. 171 (6): 1619–24. PMID 9843299. http://www.ajronline.org/cgi/pmidlookup?view=long&pmid=9843299. 
  38. ↑ Novick AC (September 1998). "Nephron-sparing surgery for renal cell carcinoma". Br J Urol 82 (3): 321–4. PMID 9772865. 
  39. ↑ Herr HW (January 1999). "Partial nephrectomy for unilateral renal carcinoma and a normal contralateral kidney: 10-year followup". J. Urol. 161 (1): 33–4; discussion 34–5. doi:10.1016/S0022-5347(01)62052-4. PMID 10037361. 
  40. ↑ Van Poppel H, Bamelis B, Oyen R, Baert L (September 1998). "Partial nephrectomy for renal cell carcinoma can achieve long-term tumor control". J. Urol. 160 (3 Pt 1): 674–8. doi:10.1016/S0022-5347(01)62751-4. PMID 9720519. 
  41. ↑ Mattar K, Jewett MA (January 2008). "Watchful waiting for small renal masses". Curr Urol Rep 9 (1): 22–5. doi:10.1007/s11934-008-0006-3. PMID 18366970. 
  42. ↑ Flanigan RC, Mickisch G, Sylvester R, Tangen C, Van Poppel H, Crawford ED (March 2004). "Cytoreductive nephrectomy in patients with metastatic renal cancer: a combined analysis". J Urol. 171 (3): 1071–6. doi:10.1097/01.ju.0000110610.61545.ae. PMID 14767273. 
  43. ↑ Mogami T, Harada J, Kishimoto K, Sumida S (April 2007). "Percutaneous MR-guided cryoablation for malignancies, with a focus on renal cell carcinoma". Int. J. Clin. Oncol. 12 (2): 79–84. doi:10.1007/s10147-006-0654-6. PMID 17443274. 
  44. ↑ Boss A, Clasen S, Kuczyk M, Schick F, Pereira PL (March 2007). "Image-guided radiofrequency ablation of renal cell carcinoma". Eur Radiol 17 (3): 725–33. doi:10.1007/s00330-006-0415-y. PMID 17021704. 
  45. ↑ Michaelson MD, Iliopoulos O, McDermott DF, McGovern FJ, Harisinghani MG, Oliva E (May 2008). "Case records of the Massachusetts General Hospital. Case 17-2008. A 63-year-old man with metastatic renal-cell carcinoma". N Engl J Med. 358 (22): 2389–96. doi:10.1056/NEJMcpc0802449. PMID 18509125. http://content.nejm.org/cgi/content/full/358/22/2389. 
  46. ↑ Motzer RJ et al. (2007). "Sunitinib versus interferon alfa in metastatic renal-cell carcinoma". N Engl J Med 356 (2): 115–124. doi:10.1056/NEJMoa065044. PMID 17215529. 
  47. ↑ http://professional.cancerconsultants.com/oncology_renal_cancer_news.aspx?id=42229
  48. ↑ "Vaccine for kidney and bowel cancers 'within three years'". Daily Mail (London). 2006-11-13. http://www.dailymail.co.uk/pages/live/articles/news/news.html?in_article_id=416006&in_page_id=1770. 
  49. ↑ Amato RJ (September 2008). "Vaccine therapy for renal cancer". Expert Rev Vaccines 7 (7): 925–35. doi:10.1586/14760584.7.7.925. PMID 18767943. 
  50. ↑ Vasil'eva NN (1975). "[Patho-anatomical characteristics of renal cell cancer]" (in Russian). Arkh. Patol. 37 (10): 11–8. PMID 1225265. 
  51. ↑ "Renal Cell Cancer". http://www.emedicinehealth.com/renal_cell_cancer/article_em.htm/. Retrieved 2010-03-31. 
  52. ↑ Randomized, controlled trial of adjuvant therapy with ex vivo activated T cells (ALT) in T1-3a,b,c or T4N+,M 0 renal cell carcinoma'
  53. ↑ Biotherapy of advanced cancer by infusion of in vitro activated'
  54. ↑ x vivo activated memory T-lymphocytes as adoptive cellular therapy of human renal cell tumour targets with potentiation by cis-diamminedichloroplatinum(II).'
  55. ↑ Treatment of metastatic renal cell carcinoma with autolymphocyte therapy'
  56. ↑ Effect of autolymphocyte therapy on survival and quality of life in patients'
  57. ↑ Valladares Ayerbes M, Aparicio Gallego G, Díaz Prado S, Jiménez Fonseca P, García Campelo R, Antón Aparicio LM (November 2008). "Origin of renal cell carcinomas". Clin Transl Oncol 10 (11): 697–712. doi:10.1007/s12094-008-0276-8. PMID 19015066. 
Tumors: urogenital neoplasia: urinary organs (C64-C68/D30, 188-189/223)
Abdominal
Kidney

Glandular and epithelial neoplasm: Renal cell carcinoma · Renal oncocytoma

Complex and mixed tumor: Wilms' tumor · Mesoblastic nephroma · Clear-cell sarcoma of the kidney · Angiomyolipoma · Cystic nephroma · Metanephric adenoma

by location: Renal medullary carcinoma · Juxtaglomerular cell tumor
Ureter
Ureteral neoplasm
Pelvic
Transitional cell carcinoma · Inverted papilloma · Squamous cell carcinoma
Urethra
Transitional cell carcinoma · Squamous cell carcinoma · Adenocarcinoma · Melanoma
Retroperitoneum
Malignant fibrous histiocytoma

: URI

anat/phys/devp/cell

noco/acba//tumr, sysi/, urte

proc/itvp, drug (G4B), blte,
Glandular and epithelial neoplasms (ICD-O 8010-8589)
Epithelium
Papilloma/carcinoma
(8010-8139)
Small cell carcinoma · Verrucous carcinoma · Squamous cell carcinoma · Basal cell carcinoma · Transitional cell carcinoma · Inverted papilloma
Glands
Adenomas/
adenocarcinomas
(8140-8429)
Gastrointestinal

tract: Linitis plastica · Familial adenomatous polyposis

pancreas (Insulinoma, Glucagonoma, Gastrinoma, VIPoma, Somatostatinoma)

Cholangiocarcinoma · Klatskin tumor · Hepatocellular adenoma/Hepatocellular carcinoma
Urogenital
Renal cell carcinoma · Endometrioid tumor · Renal oncocytoma
Endocrine
Prolactinoma · Multiple endocrine neoplasia · Adrenocortical adenoma/Adrenocortical carcinoma · Hurthle cell
Other/multiple
Neuroendocrine tumor (Carcinoid) · Adenoid cystic carcinoma · Oncocytoma · Clear cell adenocarcinoma · Apudoma · Cylindroma · Papillary hidradenoma
Adnexal and
skin appendage (8390-8429)
sweat gland (Hidrocystoma, Syringoma) · Syringocystadenoma papilliferum
Cystic, mucinous,
and serous (8440-8499)
Cystic general
Cystadenoma/Cystadenocarcinoma
Mucinous
Signet ring cell carcinoma (Krukenberg tumor) · Mucinous cystadenoma/Mucinous cystadenocarcinoma (Pseudomyxoma peritonei) · Mucoepidermoid carcinoma
Serous
Ovarian serous cystadenoma/Pancreatic serous cystadenoma/Serous cystadenocarcinoma/Papillary serous cystadenocarcinoma
Ductal, lobular,
and medullary (8500-8549)
Ductal carcinoma
Mammary ductal carcinoma · Pancreatic ductal carcinoma · Comedocarcinoma · Paget's disease of the breast/Extramammary Paget's disease
Lobular carcinoma
Lobular carcinoma in situ · Invasive lobular carcinoma
Medullary carcinoma
Medullary carcinoma of the breast · Medullary thyroid cancer
Acinar cell (8550-8559)
Acinic cell carcinoma
Other
Complex epithelial (8560-8589)
Warthin's tumor · Thymoma

: NEO

tsoc, mrkr

tumr, , para

drug (L1i/1e/)