9 Hepatocellular Carcinoma


9 Hepatocellular Carcinoma

Douglas M. Coldwell


Overall, hepatocellular carcinoma (HCC) is the fifth most common cancer in the world and the second most common cause of cancer death in the world. It is the fifth most common cancer in men and seventh in women worldwide. Causes are well known with hepatitis B and hepatitis C (HCV) and ethanol abuse causing cirrhosis leading to the formation of HCC in approximately 10 years. Asian and sub-Saharan Africa rates are declining due to hepatitis immunization but U.S. rates are rapidly increasing due to immigration from high incidence areas as well as increasing drug abuse resulting in HCV infection. 1



HCC is caused by alterations in 140 genes belonging to 12 signaling pathways that regulate core cellular processes. New microarray technology will be able to pinpoint more specific “druggable” mutations. 2 Not only the genetic alterations, but also the epigenetic alterations such as DNA methylation are being studied. These changes are thought to be early events in the evolution of HCC. The global hypomethylation can be categorized as to the origin of the HCC and correlate well with subsets of patients. 3 , 4 HCC develops on a background of chronic liver disease and more than 80% demonstrate cirrhosis. Beta-catenins and TP53 are the most frequently mutated oncogene and tumor suppressor genes in HCC. 5 , 6 A low-grade dysplastic nodule develops in the cirrhotic liver, which then undergoes oxidative stress and transforms into a high-grade dysplastic nodule. With progressive activation of adverse signaling pathways and immune response, this high-grade nodule becomes an early HCC and begins proliferation. This is progressive loss of differentiation and activates the Myc gene, Pi3K (phosphoinositide-3 kinase) and TGF-β (transforming growth factor-β) signaling, and epithelial mesenchymal transition with metastases development. 7 , 8

Staging 9


T1 = Solitary tumor without vascular invasion.

T2 = Solitary tumor with vascular invasion or multiple tumors less than 5 cm in diameter.

T3a = Multiple tumors greater than 5cm in diameter.

T3b = Tumor involving major branch of the portal or hepatic veins.

T4 = Tumor with direct invasion of adjacent organs or perforation of visceral peritoneum.

Lymph Nodes

N0 = No regional lymph node (LN) metastasis.

N1 = Regional LN metastasis.


M0 = No distant metastasis.

M1 = Distant metastasis.

Stage I = T1 N0 M0.

Stage II = T2 N0 M0.

Stage IIIA = T3a N0 M0.

Stage IIIB = T3b N0 M0.

Stage IIIC = T4 N0 M0.

Stage IVA = T1/2/3/4 N1 M0.

Stage IVB = any T any N M1.


Untreated HCC has a 5-year survival of less than 10%.


Liver resection is preferred for patients with noncirrhotic HCC or with Child–Pugh A patients. Patients with a greater degree of liver dysfunction are not candidates since they do not have enough normal hepatocytes to maintain normal function. After liver resection, the patient needs to have at least 30% of the volume of the normal liver to maintain normal function. If this fraction is borderline, the portal vein (PV) of the segments to be resected may be embolized with particles and coils to shift the flow of the PV to the anticipated remnant fraction. The PV is accessed transhepatically, then each segment is to be removed and embolized with particles and coils. This procedure will enlarge the remnant fraction by 5 to 15% and may allow the HCC to be resected. 10 , 11 The 5-year survival of resected HCC is between 50 and 60% with perioperative mortality around 2 to 7%. 12 , 13 The two prognostic factors associated with improved survival are lower T stage with smaller tumor size and an R0 resection with a 2-cm margin. The larger the HCC, the more likely it is that satellite tumors are present in the liver; a 2-cm margin is difficult to obtain and micrometastatic disease will likely be present. Without clear margins and a 2-cm tumor-free area around the tumor, the likelihood of recurrence as well as development of metastatic disease is increased. 14

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May 21, 2020 | Posted by in ONCOLOGY | Comments Off on 9 Hepatocellular Carcinoma
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