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Page 10 of 12 Hiyama et al. Hepatoma Res 2021;7:44 https://dx.doi.org/10.20517/2394-5079.2021.21

[16]
rates were 67% in SIOPEL-2 and 74% in SIOPEL-3 , which were equivalent to those in JPLT-1. The recent
developments in surgical treatment strategies, including extreme hepatic resection techniques and LT,
which exhibit good safety and liver function preservation, may have contributed to the better resection rates
in JPLT-2. In particular, the resectability rate for non-metastatic PRETEXT IV cases was significantly better
in JPLT-2 than in JPLT-1 (73.2% vs. 40.0%) (chi-square = 6.814, P = 0.009). In contrast, the five-year EFS
and OS rates were poor in both trials (40.2% and 57.9% vs. 40.6% and 38.9% in JPLT-2 vs. JPLT-1). Of the
current surgical options for HB, complete tumor resection remains the cornerstone of therapy, as it offers
the only realistic chance of long-term disease-free survival [30-32] . In our series, patients who underwent
incomplete resection had a significantly higher rate of relapse, suggesting that complete resection
(microMNR) is necessary for improved outcomes. Moreover, 13 cases of recurrence among 31 cases with
positive margins underwent extended or massive hepatectomy, and 10 of them were diagnosed between
2000 and 2005, suggesting that LT might be indicated in these cases. In liver surgery, developments in
imaging procedures such as CT and MRI provide three-dimensional images that can reveal vascular
remodeling and the exact residual volume after liver resection. In addition, technical developments in
surgical liver transection such as ultrasonic dissectors and clamp crushing with intraoperative ultrasound,
use of vascular staplers, and low central venous pressure anesthesia have resulted in increased eligibility for
liver resection. Consequently, the number of cases undergoing liver resection has increased, thereby
increasing the rate of microMPR. Therefore, currently, we should reconsider the evaluation of microMPR in
hepatic resection for HB. Complete resection with LT might decrease the total dose of adjuvant CTx needed
[3]
and the requirement for additional surgery, resulting in a decreased rate of late complications .
Patients with advanced HB are usually candidates for primary LT and aggressive hepatic resection. The
benefits and disadvantages of LT and hepatic resection should be discussed by the hepatic surgery team
involving LT surgeons. The marginal positive resection should be discussed as one of the disadvantages of
aggressive hepatic resection.

The present study has several limitations. First, as described in the previous paragraph, the JPLT-2 study
was conducted over more than 10 years, during which the indication and outcome of LT for children had
dominantly changed. The extensive resection in the early era when LT was difficult caused high incidence of
marginal positive resection. Second, the biological characteristic of tumor cells was not evaluated in this
study. There is a possibility that highly malignant HBs might form more invasive tumors, resulting in high
incidence of marginal positive resection and increasing recurrence. To consider these possibilities,
prospective studies on extensive hepatectomy and LT for advanced HB and biological analysis of recurrence
or refractory HB including tumor with microMPR are needed in the future.

In conclusion, after effective CTx, microMPR was associated with worse EFS in children with HB
undergoing surgical resection.

DECLARATIONS
Acknowledgments
The authors would like to thank all members of the liver tumor committee of the Japan Children’s Cancer
Group for their contributions to this paper and the JPLT-2 study.

Authors’ contributions
Made substantial contributions to the conception and design of the study and performed the data analysis
and interpretation: Hiyama E, Hishiki T, Watanabe K, Ida K, Yano M