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Page 2 of 11 Tsutsui et al. Hepatoma Res 2018;4:13 I http://dx.doi.org/10.20517/2394-5079.2018.20

Conclusion: Neoadjuvant HAIC decreased the risk of recurrence and improved survival in patients with HCC with
high malignant potential.

Keywords: Hepatocellular carcinoma, transcatheter arterial chemoembolization, hepatic arterial infusion
chemotherapy

INTRODUCTION
Surgery is the standard treatment for hepatocellular carcinoma (HCC), which offers a chance of cure with
[2]
[1]
preservation of liver function and achieves the best outcome (5-year survival rate of 33%-60%) . However,
after curative liver resection for HCC, the incidence of recurrence in the remnant liver is as high as 60%
[3-5]
within 3 years . Among all cases of recurrence, approximately 90% are intrahepatic recurrences, which
[6-9]
contribute to the high mortality rate in patients with HCC . The risk factors for early-phase recurrence
of HCC depend on the malignant potential of the tumor, including the presence of microscopic vascular
invasion (MVI), serum alpha-fetoprotein (AFP) levels, tumor number, and tumor size [3,10,11] . Among these,
the presence of MVI is an important risk factor affecting survival throughout the entire postoperative
[13]
[12]
period , and the gross classification of HCC predicts the presence of MVI .
Some studies demonstrated that preoperative transarterial chemoembolization (TACE) improved prognosis
in select patients, such as those with preserved liver function and advanced-stage HCC [14-17] . However,
according to the 2012 European Association for the Study of the Liver (EASL) and European Organization
for Research and Treatment of Cancer clinical practice guidelines, neoadjuvant chemoembolization has not
[1]
proven to improve the outcomes of patients who underwent resection . Additionally, neoadjuvant TACE is
associated with the disadvantages of delaying surgery and increasing complications during surgery because
of inflammatory pediculitis, perihepatic adhesions, or arterial thrombosis; moreover, if the tumor fails to
respond to therapy, it continues to grow and becomes incurable [18,19] . Moreover, TACE also has the potential
to cause adverse effects on liver function. Hepatic arterial infusion chemotherapy (HAIC) may sometimes be
chosen as a therapeutic option for advanced HCC because of poor liver function. It allows the direct delivery
of high doses of chemotherapeutic agents to the tumor site and reduces the systematic concentration of
chemotherapeutic agents to a low level, which may result in a lower incidence of adverse drug reactions and
early appearance of the chemotherapeutic effects in the early stage of treatment.

In this retrospective study, we evaluated the safety, feasibility, and surgical complications of neoadjuvant
HAIC, and investigated the effect of it on survival without recurrence after resection of the lesion.

METHODS
Patients
Between January 2003 and January 2014, 80 patients underwent hepatic resection for HCC at our hospital.
Of these patients, we investigated 49 patients who met the following inclusion criteria: (1) preserved liver
function (Child-Pugh A); (2) resectable HCC (≤ 3 nodules, regardless of the size); and (3) HCC with high-
grade malignant potential. High-grade malignant potential refers to HCC with MVI. The patients were
diagnosed on the basis of fan-shaped portal perfusion defects, which appeared in the periphery of the tumor
on computed tomography (CT) scans during arterial portography and showed tumorous arterioportal
shunts caused by microscopic portal vascular invasion. In terms of gross appearance, the simple nodular

type with extranodular growth or confluent multinodular typepredicted the presence of MVI [13,20] .
Of the 49 patients, 13 patients who were preoperatively diagnosed as having HCC with high-grade malignant
potential, between June 2009 to January 2014, were treated with neoadjuvant HAIC (treatment group).