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Page 4 of 15 Brolese et al. Hepatoma Res 2020;6:34 I http://dx.doi.org/10.20517/2394-5079.2020.15

The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement checklist was
[13]
used to report selection .

Study inclusion criteria
In this section, we report the selection criteria to identify eligible studies for this review that aimed to
compare studies on the effects of MILR vs. OLR for HCC in elderly patients. Different cut-offs for “elderly
age” were considered in most studies. In the present study, the cut-off was set at 65 years old. Different
resections, major or minor, were included. Study selection criteria were defined according to the PICOT
framework [Figure 1]. Three different searches were identified: type 1, comparing open and laparoscopic liver
resections; type 2, comparison in elderly between open and robotic liver resections; and type 3, comparison
between laparoscopic and robotic liver resections. The following studies or data were excluded: case report,
abstract, review, editorial letter, study without control group, and comparative study with population less
than 10 patients for each group. The quality assessment of the primary studies did not represent exclusion
criteria.

Outcomes
Primary outcomes of all eligible studies included Child-Pugh score, serum total bilirubin level, comorbidities,
presence/absence of cirrhosis, minor/major resection, challenge segment approach, operative time, estimated
[14]
intraoperative blood loss, liver failure rate, morbidity according to the Clavien-Dindo classification , LOS,
and postoperative mortality. Operative time was defined as the time from skin incision to wound closure.
Postoperative mortality was defined as death during the same hospital admission or within 30 days after
liver resection. Major resection was defined as a liver resection of three or more contiguous segments in all
papers under investigation. Challenge segments were posterolateral segments (Sg6 and Sg7), posterosuperior
segments (Sg8 and Sg4a) and caudate lobe. Secondary outcomes included tumor size, number of lesions
(single/multiple), readmission rate, recurrence rate and survival at 1, 3 and 5 years after operation.

Data extraction and quality assessment
Two reviewers (F.C. and M.R.) independently screened titles, abstracts, full texts, and extracted the
demographic and clinical outcome data from the selected studies. When disagreement occurred, they
reviewed the papers together to reach joint conclusions. The methodological quality of the studies was
evaluated by applying the Critical Appraisal Skills Program - CASP Checklists for Case Control Study
(Critical Appraisal Skills Programme (2018). CASP Case Control Study Checklist. Available at: https://casp-
uk.net/casp-tools-checklists/). The overall quality of the primary studies was assessed as low, moderate or
high quality.

Statistical analyses
All the analyses were performed with the data originating from the included studies. When available, patient
characteristics and outcomes were expressed as numbers or percentages, mean ± SD or median (interquartile
range or range), as reported in primary studies.

Some of the included studies reported the continuous variables with means and standard deviation, other
studies with median and range or interquartile range. For continuous outcomes (i.e., operative time,
estimated blood loss, and LOS), mean ± SD for some primary studies were estimated from median, range,
[16]
[15]
and interquartile range following the approach by Hozo et al. and Deeks et al. . For mortality at 1, 3 and
5 years, row data (i.e., counts) were calculated by simple proportions by the given percentages of survivors in
whole population of each primary study.

Eleven meta-analyses were performed, one for every outcome considered. A random effects model based on
[17]
the method used by DerSimonian and Laird was used to estimate pooled risk ratios (RRs), pooled mean
differences (MDs) and 95% confidence intervals (95%CIs). Data heterogeneity between studies was estimated