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Page 12 of 15 Brolese et al. Hepatoma Res 2020;6:34 I http://dx.doi.org/10.20517/2394-5079.2020.15

[20]
Amato et al. wrote that the main factor that would contribute to decreased blood loss might be the tumor
position in anterior segments. Challenge segment resection in their series was performed only with the open
approach. This selection might have had significant effects in reducing severe bleeding risks, but the robotic
[52]
approach can represent the ideal overlap technique to overcome the bias in their study .
Pulmonary and cardiovascular failure after liver resection might be very dangerous in the elderly. The
[53]
incidence range has been reported to be from 10% to 20% , and they are related to functional changes
[53]
in old age [54,55] but also to intraoperative fluid overload . Some conditions such as a lower morbidity rate
or a lower intraoperative blood loss in the MILR group might contribute to reduced fluid administration
during liver resection. Thus, the absence of large abdominal incision might increase thoracic cage excursion
and decrease the pain without respiratory distress. This might be associated with enhanced postoperative
recovery and shorter hospital stay.

MILR reduces LOS rate because the absence of large abdominal incision and preservation of postoperative
[56]
pulmonary function may explain less minor postoperative complications in the MILR group . However,
careful patient selection about assessment of liver function is the most important factor in morbidity
prevention.

This report reveals that operative time in the MILR group was longer than OLR group. The learning curve
was associated with experience of surgeons and might be a significant factor contributing to the difference
in operative time for the mini-invasive group. The robotic approach, in the MILR group, was associated
with longer operative time. This can be explained by the large proportion of major hepatectomy or challenge
segment approach, and especially for additional time required for docking and de-docking of robotic system.
[57]
Tsung et al. found that operative time decreased significantly as the number of cases accumulated and
increase of experience with robotic liver surgery.

Oncological outcome such as tumor recurrence and survival did not differ significantly between the two
groups, but this outcome was investigated in only half of studies [18,24,25] . Recurrence rate is a very important
prognostic element. It is essential for improving long-term prognosis, and it is related to tumor-free margins
in oncological surgeries, because histologically negative margins could result in a better outcome after
[38]
HCC resection . For patients with HCC, clinical and oncological outcomes are conditioned by tumor
[58]
invasiveness and underlying liver disease . The risk of recurrence of HCC after liver resection is always a
concern and is common with the diseased liver remaining in situ. Perhaps not surprisingly, recurrence and
survival after surgery for HCC has been shown to be shorter in patients with advanced cirrhosis compared
with patients with early disease. The higher recurrence rate during the worsening of the disease probably
reflects the carcinogenic effect of advanced cirrhosis, being more prominent than in less cirrhotic livers or in
[59]
chronic hepatitis, which is well established in the literature . Therefore, MILR for HCC provided long-term
outcomes that were comparable with OLR and did not generate unusual HCC recurrence patterns.

Study limitation
There were several limitations in this systematic review. First, the literature search was only done on the
two most relevant scientific databases for medical practice (PubMed and Cochrane Library). Second, the
review was limited by the lack of randomized controlled studies or prospective studies regarding comparable
populations. Indeed most of the studies on this topic were observational and retrospective, although some of
them [18,21,23,25] minimized selection bias, performing a matching of the populations studied.

Due to no events in small sample size papers, or outcomes not available in the primary studies, few studies
were available in some of the meta-analyses, thus limiting the strength and trustworthiness of our results.

Meta-analyses are characteristically limited by the presence of heterogeneity between studies. Sources of
heterogeneity in this review were different patient’s age cut-off, different percentages of HCC patients, and