Page 67 - Read Online

Page 2 of 17 Calinescu et al. Hepatoma Res 2021;7:59 https://dx.doi.org/10.20517/2394-5079.2021.26

Keywords: Pediatric liver transplantation, hepatoblastoma, hepatocellular carcinoma

INTRODUCTION
Despite initial concerns about the risks of exposing oncological patients to immunosuppression, many
series have confirmed that the outcome can be excellent even though these children are exposed to
immunosuppression after total liver resection and liver transplantation (LT). As a result, LT has expanded
as a possible cure and its role has become increasingly important in the management of pediatric liver
malignancies. Overall, pediatric liver malignancies account for a tenth of all pediatric LT performed in the
[1]
United States ; in Europe, 6% of all pediatric liver transplantations are performed for an oncological
[2]
indication within the European Liver Transplant Registry . By far, the most frequent pediatric liver
[3]
malignancies proposed to LT are hepatoblastoma (HBL) and hepatocellular carcinoma (HCC) . Although
the place of LT is growing in the pediatric liver oncology setting, determinants of long-term survival are not
very clear yet .
[4]
Unresectable HBL and HCC have as the only curable alternative total hepatectomy and orthotopic LT; it is a
conclusion that was readily available in the early 1990s, with the advent of the first LT for unresectable
[6]
pediatric liver malignancies . The first study providing results for survival was SIOPEL 1 : it highlighted
[5]
the importance of proposing LT as a primary strategy and avoiding using it as a last option or as a rescue of
previous (failed) surgical attempts; while the former strategy provided excellent results, the latter was
associated with poorer prognosis.

Tumor biological behavior has been shown to be not only an important parameter for patient selection but
[7]
also an essential predictor of the outcome after LT . Although 60%-80% of the patients presenting with
HBL are unresectable at presentation and diagnosis , most respond so well to cisplatin and doxorubicin
[8,9]
neoadjuvant chemotherapy that they become “resectable” (up to 85% of the initially “unresectable” tumors
[3]
ending resected). Recent series have evidenced that in fact only 20% of the newly diagnosed patients with
HBL eventually will need a LT [10-13] ; for these patients, total hepatectomy and LT is the only option and
possible cure, with standard/extreme resection less likely to be curative. More interestingly, even in these
[7]
unresectable cases proposed to LT, it was suggested in 2002 and confirmed later that good responders to
chemotherapy [as judged by dropping levels of alpha-fetoprotein (AFP) and reduction of tumor mass] have
a better outcome after LT - this is common sense and can be used as a selection criterion.

HCC in children is rare and has a different biological behavior compared to HBL. In children, it also has a
different physiopathology and behavior compared to that in adults, who present HCC mostly on cirrhotic
liver, while in children HCC is usually a primary tumor on healthy liver. HCC in children is often
unresectable at diagnosis (80%) ; however, multimodal treatment (i.e., chemotherapy and transarterial
[14]
[15]
chemoembolization) has limited effect on HCC, with only 50% of HCC patients proposed for resection ,
and up to 25% will eventually need a LT [15,16] .

THE ROLE OF LIVER TRANSPLANTATION IN HEPATOBLASTOMA
Indications and contraindications in liver transplantation for hepatoblastoma
Indications
Based on SIOPEL (International Childhood Liver Tumour Strategy Group), indications for LT in HBL
patients include: