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Page 2 of 9 Calinescu et al. Hepatoma Res 2021;7:54 https://dx.doi.org/10.20517/2394-5079.2021.25

[3]
Laboratory findings are usually not specific (i.e., normal liver tests and negative neoplastic markers) .
Radiological diagnosis might be difficult because of overlapping features with other pediatric liver masses;
ultrasound may show a mass with mixed solid and cystic components and computed tomography usually
[3-5]
depicts a large hypodense mass with multiple septations and solid nodules . The cystic appearance might
be misleading, causing delayed management . UESL is often larger than 10 cm at diagnosis, with 75% of the
[3]
[3,6]
cases located in the right liver lobe, 10% in the left lobe, and 15% in both lobes . Pathological examination
and immunohistochemical analysis of biopsy specimens, as well as of the surgical resection material, is the
[7]
mainstay of diagnosis for UESL . In contrary to other liver tumors such as hepatoblastoma and
hepatocellular carcinoma, there is no universally agreed treatment of UESL. But two elements are constant
and acknowledged within the worldwide used protocols: UESL is a chemo-sensitive tumor and complete
surgical resection is of utmost importance. The aim of this perspective is to discuss the state-of-the-art
surgical strategy of UESL as well as the necessity to define a new risk stratification grouping system for this
particular pediatric liver malignancy.

TREATMENT PROTOCOLS
Treatment for UESL evolved from a surgery-only based treatment in the early 1980’s, when chemo- and
radiotherapy was used only occasionally, to a multimodal treatment management plan including
[8]
(neo)adjuvant chemotherapy . But still, and as mentioned above, the management for UESL varies within
different oncological societies, as further addressed below [Table 1]. Nonetheless, the general agreement is
as follows: if the mass is resectable, an upfront surgical resection followed by adjuvant chemotherapy is
advised; however, if the mass is deemed an unresectable mass, a neoadjuvant chemotherapy, reassessment,
surgical resection or liver transplantation, and subsequent chemotherapy is recommended [Figure 1] [9,10] .

As for the timing of surgery after neoadjuvant chemotherapy within the different protocols of the different
societies, the “European” treatment of UESL initially, between 1995 and 2005, followed the rules of the Socié
té Internationale d’Oncologie Pédiatrique (SIOP) using the “Malignant Mesenchymal Tumors Protocol
SIOP-MMT95”; from 2005, the protocol has changed to the RMS2005 EpSSG that evaluates surgical
[9]
feasibility after the 3rd course and actually performs it after the 4th course . The German CWS
(Cooperative Weichteilsarkom Studie) also evaluates treatment response after 3 courses of chemotherapy,
and if deemed feasible a definitive delayed surgery is performed after the 4th course; within both protocols,
abdominal irradiation is recommended only if local control cannot be achieved otherwise . The American
[11]
Children Oncology Group (COG) uses different protocols; within the “soft tissue sarcoma protocol”, 5
[10]
courses of neoadjuvant chemotherapy are employed .
As for radiotherapy, the role and average dose in UESL is not well-defined . Radiotherapy might help in
[11]
preventing recurrence but its effectiveness as well as impact on survival is unknown yet . Reports of its use
[12]
in peritoneal dissemination confirm its feasibility but data is still scarce . But still, the use of radiation
[13]
therapy is reported to be as high as in 15% of the patients [12,14] .

A case series dating from 2000, evaluating the role of transhepatic arterial chemoembolization (TACE) in
liver tumors, showed that in two children with UESL TACE did not show any response to this type of
[15]
therapy . However, in a recent report of two cases, TACE combined with neoadjuvant chemotherapy with
reduced dosage, allowed for significant reduction of tumor size. Zhao et al. consider that TACE might be
[16]
used as a preoperative therapy in pediatric UESL where the tumor is initially deemed unresectable.

Unresectable tumors might benefit from the transarterial radioembolization as a bridge to resection or
[17]
transplantation or as a less toxic, palliative treatment alternative . Minimal data exists for this treatment