Anatomical liver resection for hepatocellular carcinoma appears to be the preferred surgical technique

We greatly appreciated the editorial “Anatomical or non-anatomical resections for hepatocellular carcinoma: a never-ending debate” by Berardi et al. (1), recently published in HepatoBiliary Surgery and Nutrition.

Prof. Ettorre’s group presented a concise yet comprehensive narrative on the comparison of outcomes between anatomical resection (AR) and non-anatomical resection (NAR) for hepatocellular carcinoma (HCC), as currently documented in the literature (1). They also shared interesting epidemiological, anatomical, and histopathological data, along with personal reflections on the topic of interest (1). The authors emphasized the lack of evidence A that could justify the recommendation of AR in the surgical treatment of HCC (1). In particular, they highlighted the absence of advantages in terms of overall survival (OS) in the AR group, especially considering the results of the two randomized control trials (RCTs) currently available (2,3).

However, several recent high-quality studies appear to strongly tip the balance of the debate in favor of AR.

In addition to the two RCTs cited by Berardi et al. (1), Liao et al. recently presented their results (4). The authors randomized 385 patients undergoing laparoscopic liver resection (192 AR versus 193 NAR) for HCC and having (I) Child-Pugh A or B; (II) retention rate of preoperative indocyanine green 15-min (ICGR15) <10%; (III) a future liver remnant (FLR) >40%; (IV) a single HCC <10 cm; (V) absence of invasion or thrombosis in major vessels, and intrahepatic or extrahepatic metastases (4). Liao et al. identified a significantly higher 5-year recurrence-free survival (RFS) in the AR group (P=0.009), in the absence of statistically significant differences in terms of OS and postoperative complications, when compared to the NAR group (4). Furthermore, they identified significantly lower overall recurrence (P<0.001) and intrahepatic ipsilateral recurrence (P=0.003) rates in the AR group (4). Considering the microvascular invasion (MVI) subgroup, AR was associated with statistically better 1-, 3-, and 5-year RFS than NAR (P=0.003) (4).

Despite the fact that only three existing RCTs on the topic of interest, numerous observational studies were published over the years. To enhance the statistical significance of the results by reducing biases, Shin et al. recently performed a meta-analysis of 22 retrospective propensity score-matched (PSM) studies, involving a total of 5,086 patients with HCC without extrahepatic disease or macrovascular invasion (5). The pooled population analysis showed better 3-year [hazard ratio (HR) =0.82, P=0.008] and 5-year (HR =0.84, P=0.009) OS and 1-year (HR =0.81, P=0.001), 3-year (HR =0.80, P<0.00001) and 5-year (HR =0.80, P<0.00001) RFS in the AR group compared to the NAR group (5). Considering subgroup analyses, the authors identified better 3- and 5-year OS and RFS in the group undergoing AR for lesions smaller than 5 cm, and a better 3-year RFS in the group undergoing AR for lesions larger than 5 cm, compared to the NAR group (5). Patients undergoing AR had a significantly lower incidence of intrahepatic and extrahepatic recurrences. Furthermore, AR significantly reduced the rate of local recurrences as well as multiple intrahepatic recurrences compared to NAR (5). MVI patients undergoing AR had better 2-, 3-, and 5-year RFS compared to the MVI group undergoing NAR (5). However, population heterogeneity may have significantly influenced the results obtained (5). In particular, the authors point out that: (I) AR was more frequently performed in patients with well-preserved liver function; (II) inclusion criteria regarding tumor stage, tumor size, number of lesions, and presence of vascular invasion varied among the included studies; (III) no standardized technique or definition of AR and NAR was found (5).

Given the limited availability of organs, liver resection is the cornerstone of curative treatment for HCC (5). The ideal surgical approach should optimize locoregional control of the disease while preserving as much healthy liver parenchyma as possible, and reduce the risk of non-transplantable recurrence (NTR), given that treatment options for NTRs are limited and burdened by high mortality rates (6-8). In particular, approximately 40% of patients undergoing upfront liver resection for HCC develop a NTR that excludes the possibility of salvage transplantation (9). Although repeat resection is the best alternative therapeutic option, it is associated with a poor prognosis (9).

To date, the risk of NTR after AR or NAR is poorly understood (9). Kawashima et al. recently conducted an international multicenter study aimed at clarifying the above-mentioned issues (9). The authors demonstrated that AR was associated with a lower risk of NTR after adjusting for patient and tumor characteristics using inverse probability of treatment weighting (IPTW) on the basis of a PSM (P=0.01) (9). In addition, patients with medium tumor burden score (TBS) undergoing AR showed a markedly lower risk of NTR compared to patients with medium TBS undergoing NAR (3-year NTR 10.9% versus 19.1%; P=0.04) (9). There was no significant difference between the two groups when considering only patients with low TBS (9). A higher incidence of peritumoral micrometastases and portal tumor tracking among patients with higher TBS would make AR a better option (9).

One of the main causes that makes it difficult to truly identify the pros and cons of the two techniques is the lack of standardization of the techniques themselves. In particular, NARs are more affected by heterogeneity. Recently, Garancini et al. introduced the SegSubTe classification, which details the appropriateness of the surgical section level (segmental, subsegmental, or terminal next to the tumor) of the Glissonean pedicles feeding HCCs (10). The authors aimed to investigate whether the SegSubTe classification could be a useful tool to stratify patients undergoing NAR in terms of tumor recurrence and long-term survival (10). The relationship between the tumor and the Glissonean feeding pedicles, as well as the vascular level of the tumor’s feeding pedicles, were used to classify HCC patients (1). The authors identified that patients who underwent an appropriate level of sectioning of the Glissonean feeding pedicles of HCC during NAR had a significantly lower overall (P=0.006), local (P=0.003), and cut-edge (P=0.02) recurrence rate, as well as a significantly better 1-, 3-, and 5-year RFS compared to patients who underwent NAR with poor sectioning levels close to the tumor (81%, 58%, 35% in the SegSubTe-IN group versus 46%, 21%, 11% in the SegSubTe-OUT group; P<0.001) (10).

Identifying a technique that can have a greater impact on another in terms of OS is certainly of fundamental importance, as emphasized by Berardi et al. (1). However, since HCC is a disease with a very marked predisposition to recurrence, we believe that RFS should be considered a long-term outcome of equal relevance.

Berardi et al. concluded that the choice to perform AR or NAR depended on the patient’s presentation, liver function, tumor burden, location of disease, and any available alternatives in case of recurrence (1). Among the aforementioned characteristics, the location of the disease plays a significant role in the surgical decision. In fact, AR is generally the preferred choice, if not mandatory, in cases of large lesions located deeply or closely adjacent to major vessels (1). Instead, NAR is the most convenient and popular option for small and/or superficial lesions (1). We believe that if the patient’s clinical conditions and liver function are permissive, AR should be strongly suggested for HCC patients with a high risk of MVI and medium TBS, and preferred for HCC patients with a low risk of MVI and low TBS.

However, we understand that differences in general patient characteristics, primary liver disease status, and histopathological parameters of the HCC lesion between the examined populations make it difficult to closely compare the two surgical methods and consequently achieve strong evidence.

Therefore, further well-designed randomized trials based on standardized anatomical and non-anatomical liver resections may help the hepatobiliary surgical community identify HCC patients who would benefit most from AR versus NAR.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was a standard submission to the journal. The article has undergone external peer review.

Peer Review File: Available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-2025-492/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-2025-492/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Local ethics committee (Comitato Etico dell’Area Vasta Emilia Nord, Sede presso la Azienda USL – IRCCS di Reggio Emilia, Edificio Spallanzani, Viale Umberto I n. 50, 1° piano – Infrastruttura Ricerca e Statistica, Italy) ruled out any need for formal ethics approval.

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