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Hiyama et al. Hepatoma Res 2021;7:44 https://dx.doi.org/10.20517/2394-5079.2021.21 Page 7 of 12

pirarubicin); LC: low CITA regimen; I: ITEC regimen (ifosfamide, pirarubicin, etoposide, and carboplatin); local: local recurrence in liver; lung: lung metastasis; CTx: chemotherapy; LT: liver transplantation; CPT-11:
irinotecan; metastasec, lung metastasectomy; m: months after diagnosis.

additional CTx (n = 4), CTx plus radiation therapy (n = 1), and high-dose CTx with stem cell transplantation (n = 1). Among them, one case died of secondary
malignancy at 7 years 10 months after diagnosis regardless the remission of recurrence (Case 6 in Table 1).

Forty patients received up-front resection (Stratum 1 in Figure 1). Ten with ruptured tumors underwent emergent resection to achieve hemostasis. The

remaining 30 patients included 14 with PRETEXT I tumors without annotation factors and 16 with PRETEXT II tumors who underwent Stratum 1 treatment
by institutional decision. Of these 30 patients, all achieved microMNR except for one (aged one month) who underwent partial resection for a tumor involving
Segments 5-8 with microMPR (Case 9 in Table 1). This patient achieved five-year EFS, but another patient (aged 16 months) who underwent right
hepatectomy for a large tumor involving Segments 5-8 with right hepatic vein invasion died from surgical complications regardless of microMNR.

DISCUSSION
HB is usually diagnosed as a large abdominal tumor involving 3 or 4 segments of the liver and compressing the portal and/or hepatic vein. Even if the tumor is
PRETEXT I or II, it usually involves the middle hepatic vein such that surgical resection with a sufficient margin is difficult in most cases. Although LT has

become a safe and effective treatment for children with advanced HB, it is sometimes delayed for several reasons, such as residual metastatic lesions, the
difficulty of donor selection for living donor LT, and issues with post-surgical administration of immunosuppressive drugs. Therefore, surgeons may choose
extensive liver resection to treat children with advanced HB who might be indication of LT. However, in patients with large tumors undergoing aggressive

hepatic resection, attention must be paid to the remaining liver volume and to preservation of the vital vessels attached to or encased by the tumor. In such
cases, even if the tumor is removed macroscopically by cautious resection, microscopic residual tumor is sometimes detected at the margin of the resected liver
by histologic examination, consequently resulting in microMPR. In fact, in the present study, the extended right or left hepatectomy had a significantly high
rate of microMPR. In these cases, attention must be paid to avoid microMPR due to large existing tumor and the viable cells remaining by less chemo-

responsiveness.

The correlation between microMPR and the survival rates of children with HB remains controversial [16,18] . The analysis of SIOPEL studies presented similar
outcomes between children with microMPR and those with microMNR, especially in those whose tumors showed effective responses to preoperative CTx [16,27] .
In a retrospective study of patients from a single Asian institution, the five-year OS and EFS rates were lower in the microMPR cases compared to JPLT-2 and
[18]
SIOPEL studies . In that report, there was no significant difference in the rate of hepatic recurrence between the two groups of complete and microMPR
resection cases, even after adjustment for the response to neoadjuvant CTx. Their explanation for this result is that the outcome might depend on HB
chemosensitivity. Neoadjuvant and adjuvant CTx can shrink the size of the tumor and diminish small pulmonary metastases, but it might also control the
microscopic residual tumor at the margin. Another possibility could be the use of energy-based surgical instruments, such as high-frequency electrotomes and