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have tumor marked with vascular invasion and extra-hepatic beads for end capillary embolization and the larger for arterial
spread with decompensated cirrhosis (Child-Pugh Class C), embolization both designed to deliver up to 150 Gy of beta
poor functional status (PS > 2). radiation. Both have relative complications related to their size,
[57]
embolization stasis methods and radiation intensity. Elevated
TREATMENT OPTIONS bilirubin and portal vein thrombosis have become relative
contraindications using selective and super-selective approaches.
Surgical resection is an excellent option but has a limited Y-90 has a median survival of 17.2 months in Child-Pugh A
utility due to advanced cirrhosis and is employed in < 5% of cirrhotics and 7.7 months in Child-Pugh B cirrhotics. [58]
patients. Candidates for resection include: (1) Child-Pugh
[46]
Class A; (2) hepatic venous pressure gradient < 10 mmHg; Trans-arterial chemoembolization (TACE) is a widely adopted
(3) platelet count > 100,000; (4) future remnant > 25% therapy for HCC embolizing tumor’s arterial supply with or
(non-cirrhotic); and (5) 50% (cirrhotic) resulting in a 70% without doxorubicin. TACE has a survival advantage at 1 year (82%
5-year survival. [47,48] The future remnant can be augmented vs. 63%) and 2 years (63% vs. 27%) compared to controls. [59,60]
by pre-operative portal vein embolization. Unfortunately, the Increased bilirubin (> 2.5 mg/dL) and portal vein thrombosis
majority of patients develop either new HCC or recurrent tumor are no longer an absolute contraindications utilizing a selective
[61]
within 5-year exceeding 70% but if the tumor burden remains or super-selective approach to tumors. Drug-eluting beads
within Milan they are candidates for salvage transplant. [49,50] have been developed to provide stable and prolonged delivery
to decrease doxorubicin toxicity resulting in higher rates of
Liver transplantation is reserved for unresectable or complete response. [62,63] Chemoembolization results in the
decompensated cirrhotics with HCC within the Milan criteria: tumor ischemia and hypoxia, which stimulate angiogenic growth
(1) One lesion ≤ 5 cm and (2) three lesions ≤ 3 cm could provide factors including vascular endothelial growth factor (VEGF), which
a > 70% 5-year survival. Current organ allocation in the United potentially-induce tumor angiogenesis and tumor recurrence. [64]
[51]
States is performed utilizing Model for End-stage Liver Disease
with HCC receiving exception point varying from 22 to 34 Sorafenib is a tyrosine kinase inhibitor that was shown to
points while patients that exceeding Milan are required to be have a survival benefit over best supportive care in two pivotal
downstaged by pre-transplant locoregional to reduce dropout studies: (1) sorafenib in patients with advanced HCC and Asian
and potentially post-operative recurrence. [52,53] European centers Pacific trials in patients with Child-Pugh Class A cirrhosis, and (2)
take an alternative approach whereby laparoscopic resection advanced HCC compatible with Stage C. [65,66] Sorafenib is currently
is liberally employed, and those patients with the highest risk the primary chemotherapeutic agent for the treatment of
for recurrence are sent for the liver transplant. These factors unresectable or recurrent HCC. Multiple adjuvant trials are under
include lymphovascular invasion and nonencapsulated tumors. way to evaluate the synergistic effects of sorafenib post-resection
and ablative therapies. Brivanib is an oral selective dual inhibitor
Locoregional therapies include: (1) percutaneous ethanol of the fibroblast growth factor and the VEGF pathway, which is
injection; (2) cryotherapy; (3) radiofrequency ablation; being evaluated as a second-line therapy for the management of
(4) microwave therapy; (5) irreversible electroporation (IEP); VEGF stimulation. Other agents under investigation include:
[67]
and (6) yttrium. Percutaneous ethanol is the least expensive erlotinib, bevacizumab, lapatinib, gefitinib and cetuximab.
and frequently performed in the office with ultrasound.
Thermal ablation is more complex but very effective in smaller CONCLUSION
tumors (2-3 cm): 70-80% and intermediate tumors (3-5 cm): 50%.
Radiofrequency ablation, microwave ablation, and IEP all result Hepatocellular carcinoma is the third leading cause of cancer
in thermal injury, tissue necrosis and apoptosis propagation. [54,55] mortality world-wide preferentially afflicting lower socioeconomic
patients. Dramatic advances have been made to reduce the
Several drug delivery systems have been introduced including incidence of HBV and HCV including HBV immunization strategies
ThermoDox and Delcath a percutaneous intrahepatic, and the introduction of new direct acting antiviral drugs for the
®
®
®
hepatic perfusion device. ThermoDox is a liposomal delivery treatment of HCV. With eradication strategies for HBV and HCC,
system for doxorubicin triggered by heat delivered by an NAFLD and NASH will become the principle etiology for HCC.
ablation device. The Delcath device delivers high doses HCC will become a disease of the obese.
[56]
®
of chemotherapy to the liver in an isolated circuit under
hyperthermic conditions. Obesity itself will complicate HCC management particularly
surgical interventions including resection and liver transplantation.
Radioembolization or Y-90 is the radiation delivered through Concentrated efforts should be placed on early diagnosis. Early
microembolization beads. Two versions of Y-90 exist, smaller diagnosis not only improves patient survival and is far more cost

Hepatoma Research | Volume 1 | Issue 1 | April 15, 2015 3