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Page 8 of 14 Cullen et al. Hepatoma Res 2020;6:76 I http://dx.doi.org/10.20517/2394-5079.2020.69

long-term survival outcomes among carefully selected patients under specific criteria such as: (a) PVTT
in a segmental branch, (b) AFP level < 100ng/mL, (c) low AP score, and (d) patients with HCC and PVTT
who were successfully downstaged [36,42,43] .

[36]
In a paper in 2017, Choi et al. evaluated PVTT recurrence, disease-free survival (DFS), and overall
survival (OS) in a cohort undergoing LDLT to treat HCC. Among the 242 patients, microvascular invasion
was apparent in two patients, segmental PVTT was noted in 27, while lobar PVTT was seen in 7 patients.
The authors aimed to define the branch level in which PVTT presence was acceptable in LT and found no
difference in DFS rate between microvascular invasion and segmental PVTT group, while those with lobar
PVTT exhibited poorer DFS and OS. No significant difference in the maximal or total tumor diameter or
tumor number was detected between groups. The authors found that in the segmental PVTT group, the
5-year DFS and OS rates were 63.9% and 50.3%, respectively, and did not differ significantly from those of
the microvascular invasion group. Based on these results and similar 5-year survival rates between patients,
transplantation should not be restricted, and mutual donor and recipient interest should guide decisions to
proceed with transplantation.

[43]
Other LDLT experiences with patients with vascular involvement include the one by Lee et al. , which
reported successful LDLT in 11 HCC patients with macrovascular invasion. Recurrence-free survival at
5 years was 45.5%, and 5-year overall survival was 63.6%. The authors found tumor thrombus extension
into the main portal vein, elevated AFP, and tumor size greater than 7 cm to be independent risk factors
for recurrence. In the largest study to date, 46 patients with PVTT underwent LDLT after a downstaging
protocol using stereotactic body radiation in combination with transarterial chemo-embolization or
[42]
transarterial radio-embolization . Five-year recurrence free survival and overall survival rates were
51% and 57%, respectively. Furthermore, the authors found several favorable prognosticators, including
lower initial AFP levels, significant decrease in AFP after downstaging, and low tumor grade. The authors
proposed offering their downstaging protocol to “all comers” with HCC and PVTT without extrahepatic
disease or extensive thrombosis of the main portal or superior mesenteric veins. Once again, this offers
the surgeon an opportunity to maximize the benefit of LDLT by allowing timing of the operation when the
disease is most under control and when it is most likely to be successful for the recipient.

Strategies before and after LDLT in advanced HCC patients
Downstaging and adjuvant therapy administration are commonly used strategies in advanced HCC
[44]
patients [44,45] . The goals of each vary depending on the treatment modality to be performed . When
applied before transplantation (versus before resection), downstaging strategies are used to convert a
patient outside accepted criteria for transplantation into an acceptable candidate, by reducing tumor
burden. It is also used as a way to select patients with low rates of recurrence among those who would
have been excluded based on current criteria. On the other hand, adjuvant therapy is used in patients
following surgical management to help decrease the incidence of HCC recurrence, and thus, improve their
outcomes [30,44,45] .

Locoregional therapies
Locoregional therapies provide several benefits: tumors outside Milan can be downstaged or downsized
so that criteria are met, patients within Milan with disease progression can be bridged to avoid waitlist
dropout, and tumor necrosis can be induced which reduces intraoperative tumor spread. Additionally,
response to these therapies reflects favorable disease biology and indicates recurrence risk.

The most commonly used locoregional techniques are stereotactic body radiation, transarterial chemo-
embolization, transarterial radio-embolization, and radiofrequency ablation. Aravinthan et al. reported
[46]
their outcomes after liver transplantation in patients with advanced HCC within extended Toronto Criteria.