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Brolese et al. Hepatoma Res 2020;6:34 I http://dx.doi.org/10.20517/2394-5079.2020.15 Page 5 of 15

Table 1. Characteristics and quality assessment of studies included in the systematic review
Study Year Country Study design Surgical group Number Quality assessment**
Badawy et al. [18] 2017 Japan Retro + PMS* MILR 40 M
OLR 40
Chan et al. [19] 2014 China Retro MILR 17 L
OLR 34
Amato et al. [20] 2016 Italy Retro MILR 11 M
OLR 18
Nomi et al. [21] 2020 Japan Retro-multicenter MILR 221 H
OLR 409
Wang et al. [22] 2015 China Retro MILR 30 M
OLR 60
Tee et al. [23] 2019 USA Retro-multicenter MILR 487 H
OLR 1282
Wang et al. [24] 2018 Taiwan Retro MILR 63 M
OLR 177
Chen et al. [25] 2017 Taiwan Retro + PMS* MILR 81 H
OLR 81
*PMS: propensity match score; **quality assessment evaluated by Critical Appraisal Skills Programme (2018). CASP Case Control Study
Checklist (L: low quality; M: medium quality; H: high quality). MILR: mini-invasive liver resection; OLR: open liver resection

by Chi2, I2, and Tau2 statistics, which were determined by an inverse-variance fixed-effect model. Funnel
plots graphically assessed publication bias.

A 2-tailed P value < 0.05 indicated statistical significance. All analyses were performed using the Cochrane
Collaboration Software Review Manager 5 (version 5.2).

RESULTS
Study characteristics and population
The flow diagram for article selection for systematic review is shown in Figure 1 according to the PRISMA
guidelines. The initial search yielded 19,558 reports but only 17,717 were in English. After examining the
titles and key words, we excluded 15,852 citations because of irrelevance, and after abstract screening,
we removed 1836 other records because of incongruences on population or outcomes. The 29 remaining
studies were assessed for eligibility by a full-text examination. Finally, eight studies [18-25] were included in
this systematic review for the quantitative synthesis, five of which compared laparoscopic liver resection and
open approach, two robotic vs. open liver resection and one both laparoscopic and robotic vs. open approach
[Table 1].

A total of 3051 patients who underwent liver resection for HCC from 8 studies were included, with 950
undergoing MILR and 2101 OLR. All the selected studies were retrospective (5 case-control and 3 case-
matched). The cut-off age for elderly was 75 years old in 2 studies and 70 for 5 studies and median age was > 65
[18]
for 1 study. Percentages of HCC patients were 100% for all the included studies with exception of Badawy et al.
[19]
and Chan et al. . For these two studies percentages of HCC patients in both mini-invasive and open groups
were greater than 50%, therefore we included the studies in the review and in the statistical analyses. The
overall quality assessment of each of the studies included is given in Table 1. One study was assessed as low
[19]
quality , four studies as moderate quality [18,20,22,24] and three studies as high quality [21,23,25] .

Primary outcomes
Meta-analyses of the considered outcomes are reported in Figure 2A and B, Table 2 and Table 3. No
significant differences in preoperative characteristics were noted between the groups for liver assessment
and function, including Child-Pugh score, serum total bilirubin level, comorbidities, presence/absence of
cirrhosis. Major resections were significantly more common in the OLR group compared to the MILR group;
indeed, the relative risk for MILR was reduced by 42% (RR = 0.58, 95%CI: 0.34-0.97), but this result was
2
affected by substantial heterogeneity (I = 86%). Segmentectomies and wedge resections were significantly