Primary liver cancer is one of the most common malignancies that occurs worldwide, and the vast majority of primary liver cancers are hepatocellular carcinoma (HCC) (1). Numerous studies have examined survival in patients with HCC treated by transcatheter arterial chemoembolization (TACE), with chemoembolization showing no clear benefit to survival (2–5). However, patients receiving chemoembolization in these studies included cases with unresectable HCC and poor liver function.

Solitary HCC with good liver function is usually treated by hepatic resection, but not chemoembolization. However, a small number of studies have described the results of chemoembolization for patients with resectable HCC and good liver function (6).

Findings of this study showed survival rates for patients with resectable HCC who received chemoembolization in comparison to those of HCC patients who underwent hepatic resection. To reduce selection bias from our database, patients selected had solitary HCC and liver function of Child-Pugh A or B and were stratified according to the Cancer of the Liver Italian Program (CLIP) (7), the International Union Against Cancer (UICC) T factor (8) and the Milan criteria (9).

Previous reports showed that the treatment modalities offering a cure of HCC include surgical resection (17,18), PEIT (19), RFA (20) and liver transplantation (21). However, chemoembolization has yet to be considered as a curative treatment of choice for HCC. The reason for this is that numerous studies have been unable to demonstrate any improvement in survival for the chemoembolization treatment of HCC (2,22).

Chemoembolization involves mixing iodized oil and one or more anticancer drugs, such as doxorubicin hydrochloride, epirubicin hydrochloride, mitomycin C, cisplatin, neocarzinostatin or floxuridine; injecting the mixture into tumor-feeding vessels; and embolizing the vessels with gelatin sponges (3,6,11,14–16,23–33). In our series, the main anticancer drug used in chemoembolization was epirubicin hydrochloride. According to the latest nationwide report by the Liver Cancer Study Group of Japan, anticancer drugs used for chemoembolization in Japan include doxorubicin hydrochloride, epirubicin hydrochloride and cisplatin (33). However, strict dose criteria for anticancer drugs and lipiodol have yet to be determined. The objective of chemoembolization is to accumulate lipiodol in the liver tumor as compactly as possible (4,6,13,15,24,34). Almost all patients in our study undertook CT approximately 1 week after chemoembolization. When the accumulation of lipiodol in the tumor was insufficient, additional chemoembolization was performed. Lee et al reported favorable survival rates for patients with HCC who received chemoembolization when lipiodol was compactly retained (6).

Chemoembolization has been used as a palliative therapy for unresectable HCC. Previous reports showed that eligible candidates for chemoembolization are patients with unresectable HCC and poor liver function, multiple liver tumors (>3) or large tumor size (>10 cm) (4,5,16,22,30,32,35).

An initial randomized controlled trial of chemoembolization did not identify superior survival by chemoembolization compared to palliative therapies (2,22,36,37). However, previous randomized control trials showed that chemoembolization is superior to symptomatic treatment in terms of the 2-year survival rate (38,39).

Resected specimens following chemoembolization have shown a high correlation between complete retention of lipiodol in the tumor and pathological necrosis (11,14,24,34,40). In those studies, patients had good liver function and a solitary liver tumor. Therefore, the possibility of a favorable prognosis exists after chemoembolization in selected patients with operable HCC. Choi et al (24) stated that chemoembolization was performed to reduce the possibility of tumor recurrence and to decrease tumor size in operable cases of HCC. Takayasu et al (15) reported a correlation between lipiodol accumulation in the HCC and survival rate. These authors showed that survival rates of 1, 2 and 3 years after TACE were 93.3, 77.1 and 77.1%, respectively. In comparison, our results demonstrated that survival rates of 1, 2 and 3 years after TACE were 80.9, 68.2 and 59.3%, respectively. However, Takayasu et al used the inclusion criterion for chemoembolization of one main lesion (<5 cm) associated with no more than two lesions (<3 cm) (15), and patients with solitary HCC underwent surgery. In addition, few studies have compared hepatic resection and chemoembolization in patients with solitary HCC and good liver function (6).

Numerous criteria have been proposed for an HCC staging system (41–46). Among these criteria, the most frequently used are the Okuda staging system (47), the Child-Pugh staging system (48), tumor node metastasis (TNM) staging (8) and CLIP score (7). Although a number of obstacles and limitations exist with these proposed criteria, Georgiades et al (42) reported Child-Pugh staging as the most accurate of 12 liver staging systems for predicting results in unresectable HCC patients. We applied the Child-Pugh staging system, TNM staging and CLIP score as liver staging systems for our patients.

The present results showed that the survival rate did not differ significantly between the hepatic resection and chemoembolization groups for UICC T1-2 HCC, while a significant difference was apparent for UICC T3 HCC. UICC T3 indicates multiple tumors larger than 5 cm or a tumor involving a major branch of the portal or hepatic veins. Previous reports indicated tumor size, number of tumors, serum α-fetoprotein levels, liver function and portal vein involvement as prognostic factors of HCC (16). In our study, no significant differences in the number of tumors and liver function were noted between the two groups. However, portal vein involvement was not thoroughly considered in the T3 HCC subgroup between treatments. Portal vein involvement may thus be one source of survival bias.

The Milan criteria are used in patient selection for liver transplantation (9), which is considered to be the optimal treatment of small HCC. Bridge treatments, including hepatic resection, TACE and RFA, are necessary for patients anticipating organ transplantation (50,51). Roayaie et al (51) reported that patients with HCC measuring more or equal to 5 cm achieve long-term survival after liver transplantation combined with TACE. Belghiti et al (50) reported that liver resection prior to liver transplantation does not increase the morbidity nor impair long-term survival following liver transplantation in patients with Milan criteria. Our results showed that there was no significant difference between chemoembolization and hepatic resection in patients both within (<5 cm) and beyond (>5 cm) Milan criteria. We suggest that patients eligible for liver transplantation should be managed by hepatic resection or TACE until such time organ transplantation occurs.

Limitations were noted in this study. The study design was retrospective and showed selection bias. Furthermore, the backgrounds of chronic liver damage varied. The majority of background disease was hepatitis B or C, but the two diseases exhibit different characteristics (41,45). The background bias should therefore be considered. In conclusion, chemoembolization appears to be as effective as hepatic resection in treating solitary HCC and in subpopulations with UICC T1-2N0M0 or CLIP 0-2 HCC with adequate liver function. However, hepatic resection is preferable for treating the subgroup of patients with UICC T3N0M0 HCC.