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Page 2 of 15 Brolese et al. Hepatoma Res 2020;6:34 I http://dx.doi.org/10.20517/2394-5079.2020.15

analyses provided pooled relative risks and mean differences for these outcomes. Cut-off for “elderly age” was set
at 65 years old.

Results: Eight studies that evaluated 3051 patients who underwent liver resection for HCC, with 950 undergoing
MILR and 2101 OLR, were included after the screening process. Blood loss, morbidity, and LOS showed statistical
significance in favor of MILR. In particular, with respect to OLR, MILR decreased on average blood loss by 161.43 mL
(95%CI: 250.24-72.61), risk of morbidity by 42% (P < 0.01), LOS by 4 days (95%CI: 7-2), postoperative mortality
risk by 47% (although not significantly, P = 0.06). Major resections were significantly more common in the OLR
group (P < 0.0001). Recurrence, although not significant (P = 0.06), must also be emphasized. The two surgical
approaches were comparable with regard to the other outcomes investigated.
Conclusion: Meta-analyses confirmed the advantages of MILR in terms of short perioperative outcomes, where
it may promote the extension of liver resection to HCC patients with borderline liver function. MILR may be
considered an important treatment option with significant benefits in the elderly and fragile patients. However,
large well-designed prospective comparative studies or randomized controlled trials would be necessary to further
confirm our conclusions.

Keywords: Hepatocellular carcinoma, HCC, mini-invasive liver resection, laparoscopic liver surgery, robotic liver
surgery, open liver surgery, meta-analysis

INTRODUCTION
Hepatocellular carcinoma (HCC) is the most common primary liver neoplasm: it is the second leading
[1,2]
cause of cancer-related deaths worldwide and sixth for cancer-related deaths in developed countries . With
regard to Italian data, HCC accounts for 79% of primary liver cancer, and it is among the first five causes of
[3]
cancer-related deaths (7% global population) .

The elderly rate in Italian and Western populations has increased for reduced newborn/year and the
progressive increasing of mean age. The risk of developing cancer is age-dependent. In Italy, patients over 75
years old have a 25% higher relative risk than the 60-74 age group (147/100,000 vs. 106/100,000), and it is 5
[4]
times higher than the 45-59 age group . In the next years, the true incidence of HCC will be directly related
[5]
to population age up to rates of 51 cases/100,000 in males and 119 cases/100,000 in females , according
[6]
to EUROCARE report . Therefore, the number of elderly patients requiring treatment for primary and
metastatic liver cancer is constantly rising and, despite a limited life expectancy, the use of liver surgery has
[7,8]
been found by many authors to be a safe and effective treatment for these patients .

Laparoscopic liver resection for HCC in selected patients has shown very good results [9,10] with regard to
oncological outcomes, morbidity, mortality, length of hospital stay (LOS) and fast postoperative recovery.
This is important after oncological surgery, because complications may negatively impact on short-term
[11]
outcomes, long-term survival and recurrence . The robotic approach has been introduced to overcome
some limitations of conventional laparoscopy, such as improved range of movements and enhanced
instrument dexterity, a 3-dimensional view of the surgical field, a reduction in surgeon tremors and
shortened learning curve.

[12]
The effect of age on cancer treatment allocation is controversial . Mini-invasive surgery is a new goal in
the treatment of HCC because it has made a great impact on surgical practice and on liver surgery. The
management of elderly patients with HCC is becoming routine in clinical practice, but it is substantially more
complicated than with younger patients because of comorbidities such as cardiovascular and respiratory
disease, diabetes, renal failure and fragility. Age may not represent a limiting factor for liver resection, but it
is still unclear if elderly patients can benefit from minimally invasive surgery. The most common concerns