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Calinescu et al. Hepatoma Res 2021;7:59 https://dx.doi.org/10.20517/2394-5079.2021.26 Page 3 of 17

(1) Multifocal PRETEXT IV tumors are the typical indication for LT, as by definition all liver sectors are
invaded by the tumor or at least by one tumor node. In these cases, the concept of radical resection imposes
total hepatectomy; the latter strategy is based on the fact that, although a tumor node (or metastasis) can
clear on imaging, viable microscopic tumor residues may persist at the very site that seems “cleared” on
imaging. In the latter situation, the only adequate strategy is to radically resect all liver segments that were
positive for nodes at diagnosis - although they may be negative on POSTTEXT staging. Controversy persists
about the former strategy, with some groups advocating the “pulmonary metastasis” approach, where the
clearance of metastatic nodes after chemotherapy allows a “wait and see” policy - allowing to consider liver
replacement and transplantation, as metastasis clearance is then considered “absence of active extrahepatic
disease” [17-23] . In that context, proceeding with partial resection instead of total hepatectomy for PRETEXT
IV HBL (and leaving in place liver segments that were positive at diagnosis but cleared during
chemotherapy) made sense to a few teams in the last decade. Initial reports were rare and anecdotical (2
[18]
[20]
cases by Baertschiger et al. in 2010 and 5 cases by Lautz et al. in 2011); in the latter series, the only
patient who died had partial hepatectomy in the absence of history of metastasis, and one emergency
transplant was lifesaving for a child with ischemia after resection. Two other, larger series were reported
recently (12 and 21 cases, respectively) (de Freitas Paganoti et al. in 2019 and Fahy et al. in 2020). In the
[19]
[21]
de Freitas Paganoti series, 5/12 had partial hepatectomy (only 1/5 had an extensive hepatectomy), which was
followed by a 31.0% recurrence within three years . In the Fahy series, although the outcome is, generally
[19]
speaking, satisfactory, the cohort description is insufficient to come to a precise conclusion about the
[24]
children with a PRETEXT IV condition . In a recent paper, Uchida et al. reported a series of 24 HBL (22
[21]
POSTTEXT II or III and 2 POSTTEXT IV) who were proposed for resection (N = 12) or LT (N = 12) on the
basis of a local algorithm based on pre- and peri-operative imaging. Overall, recurrent disease was observed
in 2/12 cases after LT and 5/12 cases after resection (2/5 received rescue LT successively), while overall
survival was 100% after LT and 91.7% after resection (recurrence-free survival being 91.7% and 58.3%,
respectively).

Initial reports of non-transplant approach for PRETEXT IV cases triggered comments from many expert
surgeons, worldwide, highlighting the risk of encouraging fewer expert teams to proceed with inappropriate
[23]
surgical strategies when extreme surgery is associated with higher technical complications rates . This has
been followed by a series of reports in recent years where there is evidence that:

- PRETEXT IV stage is one of, or “the”, most negative prognostic factor for HBL patients [22,25,26] .

- Radical resection and efficient chemotherapy are both essential for the cure of HBL, which supports the
role of LT for complete disease removal in the case of PRETEXT IV at diagnosis, in order to avoid local
recurrence [17,25-27] .

- Liver transplantation played an important complementary role in managing HBL children and
contributed to the recent increase of survival [24,28,29] .

- Although transplantation might be viewed as an “over-treatment” in some cases, it is associated with
excellent outcome, while late rescue transplantation (for local recurrence of disease) is the worst scenario,
[6]
with very poor outcome .
The debate is still active [17,24,30,31] , and only dedicated structured prospective studies will be able to answer this
delicate question, which cannot be answered at the level of single centers. This might be addressed in the
future by the upcoming international protocol “Pediatric Hepatic International Tumour Trial” (PHITT) .
[32]