Evaluation of the clinical value of contrast enhanced ultrasound in the diagnostic and follow-up of renal cell cancer

Kindney cancer accounts for 3% of all new cancers in the world. Of these kidney
cancers 85% are carcinomas derived from the epithelium (renal cell carcinomas).
The incidence of renal cell carcinoma (RCC) is steadily rising. In the United
States 51190 new cases and 12,890 deaths are expected in 2007.
Diagnostic of RCC is based on radiological features and once the suspicion is
arised, surgery (radical or nefron sparing) remains the strategy of choice.
Although most of these tumors are initially found by ultrasound (US), the
gold-standard for imaging kidney tumors is a four-fase contrast enhanced
abdominal CT-scan (CE-CT). Main disadvantage of this exploration is the
radiation exposure and the possible adverse effects of the contrast, mainly
allergy and nefrotoxity. For patients in whom formal contraindication exists
for CE-CT, contrast enhanced magnetic resonance imaging (CE-MRI) is the
modality of choice. However CE-MRI is expensive and time consuming and limited
by physical patient conditions. CE-CT is also regularly performed in the
follow-up of patients having received a nefron sparing surgery .
Since 1968 contrast agents are being developed to be used with ultrasound10.
These contrast agents are intravenously administered, well tolerated and
non-nephrotoxic. These contrasts are vascular selective and consists of
microbubbles of inert gases encased in a biodegradable phospholipids shell.
They are smaller than the erythrocytes and able to circulate in vessels of 2
*m. The newest CE-US methods are based on the characteristics of the nonlinear
bubble behavior offering a high sensitive en selective imaging of the contrast
agent. Some techniques enable distinction between the non-linear signals
reflected by the contrast agent and the linear responses of the normal tissue.
This makes simultaneous viewing of tissue-only and contrast-only images
possible. One of these methods is described in detail in a publication by
Phillips. Various microbubble contrast agents have been registered for use in
Europe; in the Netherlands, Sonovue® (Bracco) is approved for general use.

Contrast enhanced ultrasound (CE-US) is performed in diagnostic and
experimental settings in various institutions throughout the world. In oncology
CE-US is mainly used for the characterization and detection of hepatic masses.
Its use in kidney, spleen and pancreas are currently under investigation. In
our institute we are investigating the use of CE-US in the diagnostic of
prostate cancer. The preliminary results are promising.

Experience with CE-US in Renal Masses
The use of CE-US for imaging of renal masses was first described in 199420 in
patients with renal cell carcinoma (RCC) and renal insufficiency. However for
detection and characterization of renal cell cancer, only small studies are
available. All authors conclude that differentiation between benign and
malignant renal masses could be possible using ultrasound after the injection
of microbubbles.

We would like to investigate the role of CE-US with Sonovue (Bracco) in
patients with RCC.
Our primary objective is to establish the diagnostic accuracy of CE-US in renal
masses suspicious for RCC.
Our secondary objective is to establish the pattern of vascularisation in the
different sub-types of RCC.

We will preform CEUS at 100 patients with renal cell carcinoma who will be
treated by either (partial) nefrectomy or cryosurgery. Patients treated with
nefronsparing therapie will also be followed-up with CEUS.
Patients with complicated cysts who will be followed-up by CT or MRI a CEUS
will be performed on their next visit to the out-patient clinic. The images
gained with the CEUS will be stored and descriped. These images will be
compered with the CT and the histology. On basis of this we will make a
classification.

Patients will be asked to undergo 1 or more CE-US investigations before and
after treatment for renal cell cancer. Investigations will be planned together
with hospital visits or carried out during hospital admission as much as
possible. This imaging tool is part of standard patient care in various
institutions and the microbubble agent is marketed for general use in the
Netherlands. Furthermore, ultrasound is considered a safe investigation because
of the use of non-ionizing radiation. The side effects of the microbubble
contrast agent are minimal, as described above. All investigations will be
carried out according to the recommendations in the published