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Page 2 of 12 Hiyama et al. Hepatoma Res 2021;7:44 https://dx.doi.org/10.20517/2394-5079.2021.21

90.9% in those (n = 22) with microMPR, respectively. The EFS, but not OS, was significantly lower (P < 0.05) in
patients with microMPR vs. complete resection. The local recurrence rate was significantly different (chi-square =
12.11, P < 0.01) between the two groups.

Conclusion: In patients administered cisplatin/pirarubicin-based chemotherapy, the presence of microMPR
influenced local recurrence but not outcome. Advance of liver surgery including LT correlated with improving of
resection rates. The presence of microMPR influenced the local recurrence but not the outcome in the JPLT-2
study. The outcome of patients with microMPR might depend on the postoperative treatment and/or tumor
biology rather than occurrence of recurrence.

Keywords: Hepatoblastoma, surgical margin, outcome, surgery, chemotherapy, microscopic positive

INTRODUCTION
Hepatoblastoma (HB), the most common childhood liver tumors, is usually detected in the children under 5
[1]
years old. The incidence of this tumor is 3-5 per 100,000 children less than 15 years of age . In multicentric
clinical trials of pre- and postoperative chemotherapy (CTx) with surgery including liver transplantation
[2-6]
(LT), the five-year overall survival (OS) rate of HB patients has improved from 60% to 80% . However, the
survival outcomes of patients with advanced HB remain poor . A favorable outcome requires total
[3]
removal/shrinkage of the primary and metastatic tumors by surgery and the appropriate CTx. Patients
whose lung metastasis has been cleared by SIOPEL4 high-dose cisplatin regimen showed favorable
[7]
outcome . Therefore, the poor survival outcome of HB might be associated with residual or unresectable
tumors . Therefore, to ensure satisfactory resection, liver transplantation may be considered post-CTx for
[3,8]
patients with POST-Treatment EXTent of disease (POST-TEXT) IV or III tumors with positive annotation
factors such as multifocality, encasement, or obliteration of the main and/or both left and right branch of
portal veins and/or all three major hepatic veins, especially with tumors that are less responsible to CTx
which, might reflect unfavorable tumor biology [9-12] . Primary LT is an effective treatment for patients with
unresectable HB, with long-term survival rates of 78%-90% [12,13] . Recently, the advanced cases whose lung
disease has responded completely to chemotherapy or has been cleared by surgery are also eligible for LT,
and their survival is also satisfactory [14,15] . However, patients with residual metastases or other
contraindications, as well as those whose family decides against the procedure, are ineligible for LT and
instead undergo extended liver resection. In previous studies, extensive liver resection has been effective for
treating patients with advanced HB, but the correlation between microscopically margin-positive resection
(microMPR) and survival remains unclear [16-18] .

In Japan, the survival of patients with HB has improved due to the results of the JPLT-1 and JPLT-2 clinical
trials, which were conducted by the Japanese pediatric liver tumor study group and evaluated the use of
cisplatin/pirarubicin-based CTx combined with surgical resection for HB [12,13] . In this study, the primary aim
was to compare the outcomes of HB patients from the JPLT-2 trial who underwent microMPR with those
who received microscopically margin-negative resection (microMNR).

METHODS
Patients
We aimed to clarify whether microMNR was correlated with the prognosis of HB patients from JPLT-2
(1999-2012) for evaluating first line CTx (CITA: cisplatin/pirarubicin-based regimen) and second line CTx
(ITEC: ifosfamide, pirarubicin, etoposide, and carboplatin regimen) combined with surgical resection for
histologically diagnosed HB in children under 14 years old [3,19] . Of the 361 HB patients, 4 died before
surgery, 14 were inoperative following preoperative CTx, and 6 underwent macroscopically positive