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Page 4 of 10 Yamaguchi et al. Hepatoma Res 2018;4:50 I http://dx.doi.org/10.20517/2394-5079.2018.68

Hepatectomy or RFA is recommended for the patients with 2 or 3 tumors 3 cm or smaller, based on the data
examined by Hasegawa et al. . Huang et al. compared hepatectomy and RFA for HCC patients under
[19]
[18]
the Milan criteria and showed a better survival rate in patients undergoing hepatectomy. However, since
the patient characteristics in their study were very different from those in Japan, a randomized controlled
trial (SURF trial, UMIN000001795) comparing hepatectomy and RFA in Japanese HCC patients under the
Milan criteria has been conducted in Japan. The trial has not reported a high level of evidence for surgical
resection and RFA in HCC patients with 4 or more tumors, and recommends transcatheter embolization/
chemoembolization (TAE/TACE) as the first treatment option and hepatic arterial infusion chemotherapy
and molecular targeted drug therapy as the second treatment option for those patients.

Indications for hepatectomy (vascular invasion)
The indications for surgery for HCC with vascular invasion are described here. The 5-year survival rate for
HCC patients with portal vein invasion and undergoing hepatectomy was found to be 1% to 38%, which
showed a survival benefit [20,21] . Kokudo et al. reported that the prognoses of patients with Child-Pugh
[21]
score A and undergoing hepatectomy were strongly favorable and that hepatectomy was effective in patients
with localized invasion in the first branch of the portal vein. TACE, molecular targeted drug therapy, and
hepatic arterial infusion chemotherapy for HCC patients with vascular invasion were also reported [22-24] , but
a consensus on these treatments has not yet been reached in Japan. Therefore, hepatectomy, embolization
therapy, hepatic arterial infusion chemotherapy, and molecular targeted drug therapy are recommended
equally at present in Japan as treatments for HCC patients with vascular invasion.

The AASLD guidelines suggest that adults with Child-Pugh class A cirrhosis and resectable T1 or T2
[25]
HCC undergo resection rather than radiofrequency ablation. These patients are indicated for resection. Most
studies define patients with resectable HCC as those: (A) with one to three unilobar lesions, with an upper
size limit of 5 cm for single lesions and 3 cm for more than one lesion; (B) without radiographic evidence of
extrahepatic disease of macrovascular invasion; and (C) occurring in the setting of minimal or no portal
hypertension and in the absence of synthetic dysfunction. It is different from Japanese guidelines. The
Chinese guidelines similarly define general surgical indication for cases with less than three tumors. But,
[26]
it is different from AASLD guidelines at the point about including resection of portal vein tumor thrombus
(PVTT) and concomitant splenectomy for cases with portal hypertension.

In Europe and the US, the use of molecular targeted drug therapy is recommended for HCC patients with
vascular invasion at BCLC stage C.

HEPATECTOMY PROCEDURE
Since HCC is known to spread through veins into the liver, systematic removal of the tumor-bearing portal
territory is advisable, if possible. Some recent literature has reported that patients undergoing systematic
resection had better prognoses than those undergoing nonsystematic resection (segmental resection) [27-31] .
However, many patients develop HCC in the background of chronic liver diseases, and some of them may not
undergo systematic resection at present due to poor hepatic reserve. Therefore, the indication for surgery and
the surgical procedure are often determined upon consideration of the balance between tumor conditions
and liver function conditions. While systemic resection is anatomic resection of the tumor-bearing portal
territory with consideration to HCC development through the portal vein, nonsystematic resection is
resection of the tumor with some surgical margin regardless of the anatomy of the vessels. Some studies
have reported that a comparison of surgical outcomes between systematic resection and nonsystematic
resection showed no significant difference in cumulative survival rate and relapse-free survival rate [32-34] . It is
recommended in Japan to choose either a small range of systematic resection or nonsystematic resection as