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Page 2 of 6 Cassese et al. Hepatoma Res 2022;8:24 https://dx.doi.org/10.20517/2394-5079.2022.15

the reduced invasiveness of MILS minimizes liver manipulation, with the lack of a big incision that
[7]
preserves the collateral vessels and the muscles of the abdominal wall . Finally, an international propensity
score-matched study involving high-volume centers reported the superiority of LLR in terms of reduced
blood loss, morbidity, and major complications, also in Child-B cirrhotic patients, for whom MILS was
previously considered contra-indicated .
[8]
Randomized controlled trials investigating the outcomes of LLR specifically for HCC treatment still do not
exist. However, in 2015, we published very encouraging results from a propensity score-matched study on
389 patients undergoing LLR, showing a significantly shorter length of hospital stay and lower complication
rate after LLR when compared to OLR, with similar disease-free survival and overall survival at one, three,
and five years . These outcomes encouraged further comparative studies, with another propensity score-
[9]
matched study by Sposito et al. that found the laparoscopic approach as the only independent factor in
reducing the complication rate in minor liver resections for HCC . At the same time, a wide metanalysis
[10]
confirmed that LLR for HCC treatment is associated with reduced blood loss, transfusion rate,
postoperative ascites, liver failure, and hospital stay with comparable recurrence rates, disease-free margins,
and operation time [11,12] . The learning curve for LLR is a key point to reaching the aforementioned results. It
has been widely investigated over the last years, and 60 procedures have been proposed to be necessary to
achieve proficiency with minor LLR , with a further 50 procedures considered necessary to complete the
[13]
learning curve of major LLR . However, these data come from single-center experiences, including
[14]
different surgeons. Tomassini et al. evaluated the single-surgeon learning curve for LLR, concluding that at
least 160 cases were needed . According to the literature and our experience, heterogeneity across not only
[15]
different centers but also within a single, high-volume center is a fact, with the center’s experience also
playing an important role. The learning curve must be a stepwise process, during which accurate patient
selection is essential.

A further specific concept of the surgical treatment of HCC is the need to perform anatomical resection
(AR). This concept was suggested by Makuuchi in 1985, and it aims to remove the entire hepatic
parenchymal tissue supplied by the portal venous system draining the lesion , based on the concept that
[16]
HCC invades the portal branches, spreading tumor cells into the portal flow and creating satellite
[17]
nodules . Large reports show an advantage in terms of local recurrence when comparing AR and non-
anatomic resection (NAR), in particular for solitary tumors without microvascular invasion [18-20] .
Furthermore, an unintentional injury to a segment’s inflow or outflow can easily result from NAR, leading
to ischemia of the tissue supplied by the damaged vessel. This remnant liver ischemia has been shown to be
associated with worse oncological outcomes . In addition, selective inflow control can avoid splanchnic
[21]
stasis and fluid replacement, instead of a total inflow control such as the non-selective Pringle maneuver .
[22]
Even if technically more challenging, because of the absence of a clear demarcation of the hepatic segments
during parenchymal transection, AR can also be carried out using the minimally invasive approach liver
resection (MIALR). The study group of Precision Anatomy for Minimally Invasive Hepato-Biliary-
Pancreatic surgery (PAM-HBP) confirmed the safety and feasibility of MIALR, concluding about several
advantages of the Glissonean approach compared to the conventional hilar approach [23,24] . In particular,
according to our experience, the improvements in imaging technologies, with their magnification, flexible
scopes, and 3D vision, can help to understand the anatomical concepts of Laennec’s capsule and its
relationships with Glissonean pedicles , which is the basis for the technical standardization of the
[25]
[26]
technique for MIALR . In addition, indocyanine green (ICG) fluorescence can be a useful tool for the
[27]
surgeon during MIALR. To perform a AR with the Glissonean approach , a negative contrast delineation
(counterstaining) of the transection line can be achieved through an intravenous systemic ICG injection
after the selective dissection and clamping of the segmental branch .
[28]