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Page 10 of 15 Brolese et al. Hepatoma Res 2020;6:34 I http://dx.doi.org/10.20517/2394-5079.2020.15

demonstrated a risk reduction of 45% for the mini-invasive group with respect to the open one, although not
2
significant (P = 0.06) and with moderate heterogeneity (I = 57%). However, the number of studies for each
outcome was too low to evaluate publication bias.

DISCUSSION
The management of HCC in elderly patients is multidisciplinary with a wide range of treatment options
ranging from liver resection, liver transplantation, loco-regional therapies including ablation and
[26]
transarterial-chemoembolization, to molecular-targeting therapies . The right patient allocation is
determined by many factors including clinical characteristics, tumor burden, and multidisciplinary staff
[27]
expertise . Elderly patients have increased comorbidities including cardiovascular disease, pulmonary
disease, diabetes mellitus, and renal insufficiency: these are conditional factors for outcome after surgical
[28]
therapy as compared to the younger population . Mini-invasive liver surgery represents a particular
challenge for elderly patients affected by cardiopulmonary disease. Carbon dioxide pneumoperitoneum
[29]
may result in acid-base disturbance with acidosis and the increase of intra-abdominal pressure may result
in a decrease in lung compliance, vital capacity, venous return and vascular perfusion of intra-abdominal
[30]
organs .

In the last 10 years, improvement of perioperative care, careful patient selection and the presence of
strong clinical evidence of benefits have increased the application of laparoscopic procedures in elderly
patients. Several studies have reported on the safety and reduced postoperative morbidity and mortality in
laparoscopic surgery in elderly patients [31,32] . Randomized trials, multicenter trials, systematic reviews, and
meta-analyses about laparoscopic colorectal resection in the elderly indicate a real benefit in terms of lower
risk of blood transfusion, postoperative complications and oncological outcome. Longer operative time and
pneumoperitoneum seem to promote short-term pulmonary and/or cardiac complications [33-36] .

Surgical resection is a potentially curative option for the elderly patient. Several meta-analyses [37,38] have
shown that laparoscopic and robotic liver resection is associated with faster recovery, less postoperative pain
and shorter hospital stay when compared with open liver resection.

Although the elderly could have a more complex clinical profile and a number of fragilities, age is not
an absolute contraindication to liver surgery. The Barcelona Clinic Liver Cancer staging and treatment
algorithm recommend surgical resection as elective treatment without difference between young or
[39]
elderly . Nevertheless, the correct determination of which patients in the elderly group would benefit from
surgical therapy is the most important clinical challenge. Poor liver function, portal hypertension, important
comorbidities and cirrhosis stage are the true selection criteria for the right therapy and are helpful for
identifying unfit patients.

Many studies have already demonstrated the feasibility of liver resections by the open approach in elderly
[40]
patients including those suffering from other concomitant diseases , but the role of the mini-invasive
approach (laparoscopic or robotic) in the surgical management of HCC is under investigation.

This systematic review focused on the elderly population affected by HCC to assess if MILR may be safe
and feasible in this group of fragile patients. In this study, we included eight primary studies with a total of
3051 patients undergoing liver resection; 950 were treated by MILR and 2101 by OLR. Using these data, we
performed twenty-one meta-analyses investigating the main clinical and oncological outcomes of relevance.
Regarding the functional selection criteria for MILR or OLR in HCC patients, all papers [18-25] reported that the
only patients considered eligible were those with well-compensated cirrhosis or liver function without severe
portal hypertension or bilirubin level out of normal range. They were essentially identical in both groups (OLR
and MILR), because a careful patient selection and a complete liver function assessment were mandatory
in these patients. Of all meta-analyses investigated, only 8 patients in the OLR group [18,19,22,24] and only 2