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Tsutsui et al. Hepatoma Res 2018;4:13 I http://dx.doi.org/10.20517/2394-5079.2018.20 Page 3 of 11

Another 36 patients who met the inclusion criteria, between January 2003 and May 2009, had a curative
hepatic resection (control group). This was a retrospective study of HCC patients at Yame General Hospital.
The institutional review board approved this study, and written informed consent was obtained from the
treatment group. Regarding the control group, the Ethics Committee waived the requirement for ethical
approval and informed consent due to the retrospective nature of the study.

Preoperative evaluation
Baseline imaging examinations [CT angiography, dynamic CT, or/and dynamic contrast-enhanced magnetic
resonance imaging (MRI)] were performed before surgery. HCC was confirmed when at least 2 radiographic
images revealed the hallmarks of HCC or 1 radiographic image revealed the hallmarks of HCC together with
[1]
AFP levels > 400 ng/mL . HCC staging was performed according to the Barcelona clinic liver cancer (BCLC)
staging classification [21,22] and the 6th edition of the American Joint Committee on Cancer staging system of
tumor nodes metastasis. Laboratory blood tests, including tests for hepatitis B surface antigen, hepatitis C
virus antibodies, serum AFP, serum des-gamma-carboxyprothrombin (DCP), serum albumin, serum total
bilirubin, serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), prothrombin
time, C-reactive protein, and platelet counts, were performed.

Neoadjuvant hepatic arterial infusion chemotherapy protocol
[23]
In the treatment group, a temporary indwelling catheter system was implanted via the left brachial artery
under fluoroscopic guidance and was used for HAIC. A polyurethane-covered catheter, called anthron P-U
catheter (APUC), 5 Fr (100 cm) (Toray Medical Co., Ltd., Tokyo, Japan) with a tapered tip (5- and 3.3-French
outer diameters of the shaft and tip, respectively, and 0.035-/0.021-in inner diameters of the shaft and tip,
respectively) was used as the indwelling catheter. This catheter was 100-cm long and tapered to a 3.3-French
microcatheter 60 cm from the tip. The tip of the catheter was inserted into the right or left hepatic artery,
corresponding to the side on which the main tumor was located, via the celiac artery. In the case of multiple
tumors, one or two side holes were manually created with a surgical knife to supply the rest of the tumor
with chemotherapeutic agents.

The treatment regimen included low-dose 5-fluorouracil (5-FU) and cisplatin (low-dose FP), specifically,
the regimen featured daily administration of cisplatin (10 mg for 30 min) and a subsequent infusion of
5-FU (250 mg for 3 h) on days 1-10. We named this treatment regimen as 2 weeks of low-dose FP. After the
administration of chemotherapeutic agents, the catheter was removed under fluoroscopic guidance. No
prophylactic antibiotics were administered during the catheter placement.

Laboratory variables were assayed once in several days, and the tumor marker was measured before and
after the treatment regimen. HAIC was discontinued or reduced in case of adverse events higher than grade
3/4 of the common terminology criteria for adverse events (CTCAE).

Surgical procedure
Curative liver resection was performed after a mean delay of 24 ± 12 days after catheter removal. A
single surgeon performed all surgeries. Anatomic resection was defined as hemihepatectomy, extended
hemihepatectomy, sectionectomy, or segmentectomy, and all other non-anatomic resections were classified
as partial resections.

To determine the operative outcome, data regarding the operative time, intraoperative blood loss, red blood
cell transfusion, complications, type of resection, hospital mortality, and hospital stay were collected for both
groups.

Pathologic assessment
Two senior pathologists reviewed each specimen for histologic confirmation of the diagnosis. Clinicopathologic
data such as tumor size recorded as the maximum diameter, vascular invasion, intrahepatic metastasis, gross