Hepatocellular carcinoma (HCC) is a primary malignancy of the liver. Most cases of HCC are secondary to either a viral infection (hepatitis B or C) or cirrhosis (alcoholism is the most common cause of hepatic cirrhosis).
On CT, HCC can have three distinct patterns of growth:
1. A single large tumor
2. Multiple tumors
3. Poorly defined tumor with an infiltrative growth pattern
The usual outcome is poor, because only 10 - 20% of hepatocellular carcinomas can be removed completely using surgery.
A new tyrosine kinase receptor inhibitor, sorafenib has been shown in a Spanish phase III clinical trial to add two months to the lifespan of late stage HCC patients with well preserved liver function. Sorafenib is a small molecular inhibitor of several Tyrosine protein kinases. A protein kinase is a kinase enzyme that modifies other proteins by chemically adding phosphate groups to them (phosphorylation). Phosphorylation usually results in a functional change of the target protein (substrate) by changing enzyme activity, cellular location, or association with other proteins. Tyrosine-specific protein kinases phosphorylate tyrosine amino acid residues, and like serine/threonine-specific kinases used in signal transduction. They act primarily as growth factor receptors and in downstream signaling from growth factors. Sorafenib is unique in targeting the Raf/Mek/Erk pathway (MAP Kinase pathway). The MAPK/ERK pathway is a signal transduction pathway that couples intracellular responses to the binding of growth factors to cell surface receptors. This pathway is very complex and includes many protein component.
HCC presents radiographically as a spectrum, from large dominant hypervascular masses to diffuse, infiltrative, poorly visualized lesions. Because of this imaging for assessing treatment response in HCC with current modalities is challenging. New imaging modalities for following HCC responses, especially to the new biologic therapies, must be developed. Routine use of liver biopsy to conduct correlative studies is too risky . Diffusion weighted MR imaging may serve as an early biomarker of HCC response. Perfusion MRI is also being evaluated.
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Diffusion-weighted MR imaging for determination of hepatocellular carcinoma response to yttrium-90 radioembolization. Deng J, Miller FH, Rhee TK, Sato KT, Mulcahy MF, Kulik LM, Salem R, Omary RA, Larson AC. J Vasc Interv Radiol. 2006 Jul;17(7):1195-200.
