Cancer of Kidney

     Kidney cell carcinoma is about 85% of kidney cancer and around 3% of adult cancers. Twice more frequent in men than in women, its incidence is increasing. Incidental finding most of the time, this cancer benefits form imaging technology. We can therefore think about an earlier diagnosis of this carcinoma, without any clinical signs, therefore improving the prognostic.

      At all stages of the disease, a better analysis of hereditary predispositions, elaboration of tool and scores to follow up on evolution, progresses of surgical techniques, allow nowadays a better care for renal cell carcinoma. However, advanced stage kidney cancers still have a poor prognosis even though Interleukin 2 and Interferon alpha were introduced. But research continues and develops new therapeutic weapons, especially in the care of metastatic disease

     The discovery of molecules acting against angiogenesis represents an important step forward. The diversity and the intensity of research that finally lead to discoveries ensue into hope in a near future.

Epidemiology

     Renal cell carcinomas are the most common primitive cancers. They represents 85% of total kidney cancer, and around 3% of all adult cancers. In 2000, the number of news cases in France is estimated to be 8293. In france, the highest incidence rate are found in the North East (Haut Rhin, Bas Rhin) and the lowest rates in south regions (Isere, Herault, Tarn).

     This cancer is twice more common in men than in women. He standardized incidence rate are of 12.2 in men, and 5.7 in women. The incidence has increased in men along the two last decades. This effect is principally due to the aging of the population. The index rate increases around 35 years old to reach a maximum at 70 years old.

     In 2000, the median age at diagnosis was 67 years old in men, and 70 years old in women. However, this increase is associated with an improvement of survival in the USA as well as in other Europeen countries.

Risk factors

     The numerous epidemiological studies allowed shedding light on various risk factors for kidney cancer, some of which are not clearly identified. In the general population of kidney cancers can be attributed to 3 modifiable risk factors: obesity, tobacco use and arterial hypertension.

     The obesity influence on the increase of risk of kidney cancer is confirmed in both men as well as women. The cessation of tobacco use leads to a linear decrease of risk of kidney cancer, but 20 years are necessary to be back to the normal risk.

     Many studies have evidenced relative risk factors in which the environment plays a more and more probable role. Some alimentary habits and food products, some professional exposures, the lack of physical activity, chronic urinary infection, are also risk factors being discussed. Kidney tumors prevalence is more elevated in patient with end stage kidney failure than in the normal population.

In a study conducted on 2372 transplanted patients, 6.5% have developed a cancer and 0.5% have developed a renal call carcinoma
Similarly, in a dialysis population of 260 patients, the occurrence was of 4.2%. This rate is 100 times superior to the one in the general population.

The average time between end stage renal failure and tumor appearance is between 6 to 10 years. The growth rate of the tumor is unknown.

Hereditary predisposition and carcinogenesis

Hereditary forms of kidney cancer, even though they are rare (1 to 2% of all cases), deserve to be known for their clinically peculiarity, for their follow up and as well as for genetical consult for members of the same family. Familial forms of kidney cancer can be divided into different entities according to their histological nature (clear cell carcinoma, tubulo papillary carcinoma…) and their association or not with other cancers. We also distinguish, on one side the kidney cancers that are part of a familial hereditary tumor syndromes:

Von-Hippel Lindau Disease (the most frequent form),

Birt-Hogg-Dube syndrome,

Familial cutaneous leiomyomatosis,

Bourneville tuberous sclerosis.

And on the other side the familial kidney cancers (clear cell and tubullo-papillary) that are not part of a syndrome. Kidney cancer part of the Von Hippel Lindau disease. Extremely rare, this hereditary disease affects around 1500 persons in France. It is an autosomal dominant disease, with high penetrance, for which only one gene is affected: VHL gene on the short arm of Chromosome 3. Risk of renal cell carcinoma in VHL disease is less than 70% after 60 years old.

The kidneys can be affected through

- multiple and bilateral cysts (that alter renal function),

- clear cell adenocarcinoma that is responsible for 50% of death

Here, the metastatic potential of renal cell carcinoma is inferior compared to the sporadic forms, with a metastatic frequency of 8% against 50% sporadic forms. Patients affected by VHL disease live on average up to 40 to 50 years old. The prognosis has been improved by the mortality reduction thanks to the treatment of cerebellar hemangioblastomas. Kidney cancer part of familial tumor syndromes other than VHL.

Once diagnosed, these syndromes require specialized care. A genetic diagnosis is possible for Bourneville’s tuberous sclerosis (mutation of TSC1 and 2 genes), Birt Hogg Dube syndrome (mutation of BDH gene) and familial cutaneous leimyomatosis (mutation of FH gene) Clinically, renal cell carcinoma associated with familial cutaneous leimyomatosis are distinguished from other cancers that re usually unifocal and very aggressive with early metastatic risk.

Screening

     In general, the prognosis of symptomatic tumors is less favorable than tumor diagnosed by screening. That is why early screening is extremely important. Recommendations on screening modalities have been established, especially for populations at risk for the cancer.

With renal failure, on dialysis or tansplanted
     Ultrasound and Ct scan (especially spiral CT) are efficient surveillance techniques (whereas MRI role in these patients is not established). At least an annual renal ultrasound is recommended, with additional tomodensitometry in case of abnormalities suggestive of tumor. The role RMN imaging is not established.

     Signs of VHL disease must be systematically looked for. If no signs of VHL disease are found, the screening for renal cancer must be done through ultrasound every two years. In people with family history of VHL gene mutation, screening can be started as early as 30 years old, or 10 years before the age of the earliest person diagnosed in the family.

Advances in imaging techniques

Renal cell carcinoma appearance on imaging is not uniform. Its appearance can considerably vary from one tumor to another, especially relative to:

its size,
its histological architecture
its vascularization,
the presence or not of hemorrhagic-necrotic changes

     Renal cancer diagnosis is bases on CT scan (tomodensitometry) and ultrasound. Ct scan with contrast is the standard technique for diagnosis: its sensitivity (94%) is superior to any other technique. Among renal masses smaller or equal to 5mm in diameter, CT scan detects 50% of renal cell carcinoma, and 75% of masses less than 15mmThe best results are obtained with a spiral CT associating the results after contrast with arterial and tubular phase. Ultrasound is more used as a screening tool for occult renal cell carcinoma.

     During any routine abdominal ultrasound, time accredited to the investigation of both kidneys allowed for a better screening ability with 83% of incidental discoveries of renal cell carcinoma. This screening tool has allowed for discoveries of tumors of smaller sizes (average diameter decreased from 8 to 5mm) at the time of diagnosis, and consequently improved the locoregional extension and the prognosis. MRI can be indicated in case of contra indiaction for CT scan (renal insufficiency, pregnancy or allergy to the contrast)

     Having a better contrast resolution, MRI can give other information in certain atypical type of renal cell carcinoma (especially cystic types) or when diagnosis is difficult. MRI performances using surface antenna (phased network antenna) and a very recent technique (especially apnea dynamic sequencing with saturation of fat signal) are today comparable to CT scan.

Arteriography have no diagnostic role

In the view of a pre-operatory work up, arteriography tends to be replaced by CT angio, giving a precise pedoncular arterial and venous anatomy. Pet scan is an imaging system that should allow great advances in the care of patients, at the initial diagnostic level as well as for the invasion work up and therapeutic follow up. This system associated a camera with positrons, that detect early tumor areas, and an X ray scanner that would allow anatomical localization. Therefore functional and anatomic pieces of information are obtained on the same image. The tumor is localized and its behaviour is visualized. Images allow characterisation of clear cell carcinoma In the vast majority of cases, the typical shape of a renal cell carcinoma corresponds in images to a regular large clear cell carcinoma (more than 4cm)

The tumor is well circumscribed (encapsulated) and heterogeneous (association of a solid hypervascularized tissue with an avascular necrotic/necrotic-hemorrhagic tissue).

ontrast product injection typically shows an increase in early density and intensity of the vascular part. An increase of more than or equal to 84 Hounsfield units in arterial phase is characteristic of a standard renal cell carcinoma, with 100% specificity and 76/ sensitivity

Some inconsistent but characteristic elements can also be found :

- Calcification within the tumor (about 30% of renal cell carcinoma),
- Renal vein invasion (23% of renal cell carcinoma),
- Inferior vena cava invasion (7% of renal cell carcinoma)

There are also renal cell carcinoma types where the diagnosis is difficult

- Small size (less than 4mm),
- Hypovascular and solid,
- Hemorrhagic,
- Cystic

Rarely, atypical forms of renal cell carcinoma can present as multiple and bilateral, infiltrative forms, and fatty components may be present. Cystic renal cell carcinoma have a classification of their own.

Diagnosis of a cystic tumour is primarily based on the presence of a solid component (wall, vegetation, nodule) that is vascularized (increase with contrast) that must allow classification of the lesion within one of the 2 Morton Bosniak categories (type 3 and 4).