Recent advances in the surgical treatment of hepatocellular carcinoma

Table 1 Treatment options for hepatocellular carcinoma within injured liver

Local ablation therapy	Only for small tumors (in size and number)
Liver resection	Most available and efficient treatment
	Applicable to < 30% of all HCC patients
	5-yr survival of 38%-61% depending on the tumor stage
	80% of patients recur within five years after resection
Liver transplantation	Ideal treatment for removal of existing tumor and underlying injured/preneoplastic tissue
	Tumor progression while on waiting list
	Patients with advanced/extensive HCC have very poor outcomes

HCC: Hepatocellular carcinoma.

Table 2 Summary of recent advances in liver resection for hepatocellular carcinoma

Established

Screening and early detection for high-risk patients (i.e., with HCV or HBV infection, alcoholic, metabolic chronic liver disease, etc.)

Diagnosis with contrast-enhanced imaging for the detection of early lesions

Assessment of liver function (Child-Pugh classification, indocyanine green retention test, MELD score)

Modulation of residual liver function with preoperative portal vein embolization

Anatomic resection removing undetectable disseminated tumor foci in the same portal territory

Under discussion

Three dimensional-CT-assisted preoperative surgical planning facilitates:

Unconventional types of liver resection

Laparoscopic liver resection could be beneficial:

For patients with severe liver dysfunction with lower morbidity

For repeat resection

As a bridging therapy for liver transplantation

Under trial or proposal

Adjuvant and/or combined therapy for advanced tumor

Sorafenib

Intraarterial 5-FU plus IFN therapy for hepatocellular carcinoma with VTT

CT: Computed tomography; HBV: Hepatitis B virus; HCV: Hepatitis C virus; IFN: Interferon; MELD: Model for end-stage liver disease; VTT: Venous tumor thrombosis; 5-FU: 5-Fluorouracil.

Table 3 Summary of recent advances in liver transplantation for hepatocellular carcinoma

	Established	Under discussion	Under trial or proposal
Criteria for listing candidate	The Milan criteria: Solitary tumor of ≤ 5 cm or up to 3 nodules ≤ 3 cm 5-yr survival of 70% with recurrence in less than 10%	The UCSF criteria: Single tumors ≤ 6.5 cm or 2–3 tumors ≤ 4.5 cm, with a total tumor diameter ≤ 8 cm	Add parameters for biologic features of tumors related to risk of recurrence (AFP, PIVKA-II, etc.) Expansion of criteria for living donor-LT
Management on the waiting list (about 40% dropout rate at 12 mo)	Local ablation therapy and TACE are performed without solid evidence	Different models have been developed to quantify the risk of death in neoplastic and non-neoplastic patients Association with liver resection: "bridging resection" to transplantation and "salvage transplantation" following resection	Application of living donor-LT to shorten the waiting time Candidate selection with information from precedent therapy (histologic specimen, response to locoregional therapy, etc.)

AFP: α-fetoprotein; PIVKA: Protein induced by vitamin K absence; LT: Liver transplantation; TACE: Transarterial chemoembolization; UCSF: University of California, San Francisco; HCC: Hepatocellular carcinoma.

Table 4 Overview of current outcomes of liver resection and liver transplantation for hepatocellular carcinoma

Liver resection
Overall survival after liver resection
1 yr	3 yr	5 yr
87.8%	69.2%	53.4%	(Japanese registry, n = 27062)[16]
			90% 72% 56% (Multi-center study of the HCC East-West Study Group, n = 2046)[5]
Disease free survival after liver resection
67%	38%	23%	(Multi-centrer study of the hepatocellular carcinoma (HCC) East-West Study Group, n = 2046)[5]
90 d mortality rate: 2.7% Morbidity rate: 42% (Multi-central study of the HCC East-West Study Group, n = 2046)[5]
Overall survival of the patients with massive portal vein invasion after liver resection
50.4%	25.8%	18.4%	(Japanese registry, n = 976)[16]
Liver transplantation
Overall survival after liver transplantation
1 yr	3 yr	5 yr
Within Milan
91%	85%	79%	(72% of 5 yr DFS, UCLA, n = 467)
		60.1%	(Multi-centrer study of 14 French institutes, n = 479)
Beyond Milan and Within UCSF
88%	74%	64%	(64% of DFS, UCLA, n = 467)
		45.6%	(Multi-center study of 14 French institutes, n = 479)
Beyond UCSF
71%	49%	41%	(UCLA, n = 467)
		34.7%	(Multi-central study of 14 French centers, n = 479)
30 d mortality rate: 5.3% Re-transplantation rate: 4.2% (UCLA, n = 467)

DFS: Disease free survival; Milan: Milan criteria = Solitary tumor of ≤ 5 cm or up to 3 nodules ≤ 3 cm; UCSF: University of California: San Francisco Criteria = Single tumors ≤ 6.5 cm or 2 – 3 tumors ≤ 4.5 cm, with a total tumor diameter ≤ 8 cm; UCLA: Single center study from University of California, Los Angeles.