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Brolese et al. Hepatoma Res 2020;6:34 I http://dx.doi.org/10.20517/2394-5079.2020.15 Page 11 of 15

patients in the MILR group [18,24] were identified as Child-Pugh score B. These data, as shown in Figure 2A,
however represented a study limitation since the present meta-analysis was not able to find statistically
significant results.

Meta-analyses demonstrated that in elderly patients MIRL had similar organ failure, mortality and
readmission rate as compared to the open approach. MILR can be safe in the elderly because it requires
less sacrifice of liver tissue and has better bleeding control and lower rate of intermittent Pringle maneuver
and because it can treat multiple lesions at the same time, especially in anterior segments. However, there
are cases where complete MILR is not possible and use of ablative therapy combined with surgery increase
[41]
oncological outcome .
[21]
Nomi et al. demonstrated in their series that MILR was safer and more feasible when compared with
OLR, even in octogenarian patients. This study was the first multicenter, propensity score-matched study to
show better short-term outcomes with MILR than with OLR in elderly patients with HCC. These authors
performed a subgroup analysis according to patient’s age (group 75-79 compared with group > 80) and
dividing patients in relation to treatment (MILR - 78 patients and OLR -147 patients). In the cohort > 80, the
major complication rate and LOS were significantly lower in the MILR group than OLR group. Furthermore,
in the MILR group, the study reported both a 90-day mortality rate and transfer to rehabilitation facility
rate of 0% in the MILR group. These data suggested that mini-invasive surgery was less invasive and was
associated with early recovery in elderly patients.

In our analysis, morbidity rate according to the Clavien-Dindo classification, LOS and intraoperative blood loss
were lower in the mini-invasive group with high statistical impact. These findings were consistent with many
studies and meta-analyses on major resection [42-44] . The Southampton Guidelines reported that the laparoscopic
[45]
approach was found to be the only independent factor to reduce the complication rate in resections for HCC .
In cirrhotic patients, the laparoscopic approach reduces the incidence of postoperative ascites, liver failure and
morbidity assessed in terms of ‘‘Comprehensive Complication Index” [45-47] . Blood loss and transfusion rate are
[48]
very important prognostic factors in liver surgery . Morbidity rate reduction demonstrated by our meta-
analysis in patients undergoing MIRL could be explained by many factors. First, pneumoperitoneum with
abdominal negative pressure decreased portal flow rate and reduced the small and continuous venous bleeding
[49]
during the parenchymal transection phase . Second, the use of an energy instrument for transection of liver
[50]
parenchyma has proved to be highly effective for hemostasis . Moreover, the absence of a large abdominal
skin incision reduces muscle wall bleeding, and finally, laparoscopy and robotic technology offer an optimal
magnified and three-dimensional view, which are important surgical factors for meticulous hemostasis as well
[51]
as for greatly facilitating parenchymal transection in cirrhotic livers .
However, one of the major limitations of our meta-analysis could be that surgical indications to MILR were
selected at the center’s discretion according to surgical procedure complexity rather than by defined criteria.
All authors included in this meta-analysis always reported the principles guiding patient selection to undergo
MIRL were according to the International Position on Mini-Invasive Liver Surgery agreement of Louisville
[24]
(2008) or Morioka Guidelines (2014) [9,10,24] , tumor size and tumor location [18,19,20,22,24] . An important point
that needs to be investigated is that all papers reported many minor liver resections in the MILR group rather
than in the OLR group. However, it remains uncertain if the same short and long benefits could be extended
to elderly patients with major anatomical resection involving larger parenchymal transection area or longer
[24]
operative time. Wang et al. found in their study that 38% of HCC cases in the robotic assisted group were
located in challenge segments, but they never performed a major hepatectomy in the MILR group. The large
number of minor resections, wedge or segmentectomies, suggested that a parenchymal sparing strategy and
R0 resections are however basic and main guidelines for treatment when using a mini-invasive technique.
This means that the mini-invasive cohort included in this paper was certainly not previously highly selected
because all authors, as stated, followed international guidelines.