Keywords

1 Introduction

Laparoscopic liver resection (LLR) was born in 1991 and gradually expanded during the following thirty years [1]. Even extremely complex procedures are performed in centers with adequate experience [2, 3].

Curative treatments for hepatocellular carcinoma (HCC) include liver resection (LR) and local ablation therapy, which can now be performed using the laparoscopic technique. Moreover, laparoscopy is increasingly being used to expand the indications for surgical treatment for HCC patients, being able to overcome some of the limits or issues linked to traditional open LR.

2 Short-Term Outcomes

Many studies have documented the feasibility and safety of LLR and reported advantages with respect to perioperative outcomes. Among the most frequent are the reduction of blood loss, transfusion needs, complications, and length of hospital stay, as well as earlier recovery of physiological functions and patient’s autonomy. This is extremely important for HCC, since hepatectomy in cirrhosis is associated with higher complication rates than other conventional settings. In many studies focusing on HCC, the benefits of laparoscopy have been particularly evident and often associated with specific advantages. Of particular interest is the reduction of ascites, a very fearful and frequent complication in the cirrhotic patient, which laparoscopy is able to contain by avoiding large abdominal incisions, thus allowing the surgeon to preserve the parietal circulation and lymphatics and to limit the dispersion of fluids [4, 5]. Also, the incidence of postoperative liver failure was shown to be reduced by many studies [6]. These results have been supported by various meta-analyses including a large number of HCC patients. In 2018, Chen et al. performed a systematic review of high-quality case-matched studies: regardless of whether the patients underwent minor or major hepatectomy, ascites was less in LLR than in open LR, and patients undergoing laparoscopy were less likely to suffer liver failure [7].

3 Long-Term Outcomes

Most of the studies and meta-analyses showing the short-term advantages of LLR for HCC have also revealed long-term results similar to those of open LR [8]. Few recent publications reported improved survival rates, suggesting a possible long-term advantage on the oncological side. A meta-analysis of 888 HCC patients showed higher 1-, 3- and 5-year overall survival rates and 1-year disease-free survival rate for LLR than for open surgery; moreover, tumor recurrence was also lower [9]. The improved long-term outcomes of LLR are explained by the authors as likely due to decreased blood loss and higher rates of negative surgical margins. In 2021, Sun et al. performed a meta-analysis based on reconstructed time-to-event data of propensity score studies. The results suggested that laparoscopy can improve recurrence-free survival in HCC patients undergoing minor hepatectomy [10].

4 Advanced Cirrhosis and Portal Hypertension

Laparoscopy is increasingly used to push the limits for LR to those categories of HCC patients for whom open surgery entails a significant risk of major complications and mortality, i.e., to patients with advanced cirrhosis and portal hypertension.

One study reported that Child A and Child B patients receiving LLR had a similar perioperative course as there was no difference in blood loss, blood transfusions, overall morbidity, postoperative mortality, or liver-specific complications, such as ascites decompensation and liver failure [11]. Moreover, clinically significant portal hypertension was not a risk factor for major morbidity. Some retrospective studies explored the perioperative and long-term effect of LLR on HCC patients with clinically significant portal hypertension, showing comparable overall survival to non-portal hypertension groups [12, 13]. Thus, laparoscopy may offer a protective effect with regard to postoperative liver failure, ascites and major complications even in Child B patients, and its role in extending the candidacy to LR is currently being further investigated on the basis of fresh promising evidence [14].

5 Major Hepatectomies

Major LLR were first performed in 1998 but have undergone a slow diffusion due to their technical difficulty and fears of poor bleeding control [15]. Even today, despite their proven safety and feasibility, it is recognized that major LLR must be carried out in the presence of high levels of expertise and experience [16].

In 2019, a multicenter propensity score-based comparative study of 1355 patients reported that major LLR were associated with reduced blood loss, postoperative stay and morbidity than open LR, also in the setting of malignant disease [17].

In the last few years, the results of single-center studies on major LLR have disclosed favorable results for HCC, further confirmed by more than one systematic review. In a meta-analysis of 780 patients, Chen et al. found major LLR to be associated with less intraoperative blood loss and morbidity and shorter postoperative stay despite longer operative times, concluding that it may serve as a promising alternative to open LR [18]. In 2019, Wang et al. considered 1173 HCC patients who underwent laparoscopic and open major hepatectomies, obtaining similar results [19]. Thus, major LLR can be performed safely in patients with HCC, who are often affected by large lesions [20]. Especially in these settings, the anterior approach can be applied to respect the no-touch principles of oncological surgery [21].

6 Repeat Surgery

Most HCC arise on a background of chronic liver disease, which can cause intrahepatic recurrence after a first LR and consequently expose patients to the need for repeated hepatectomies. The operative advantage that can derive from a first surgery performed by laparoscopy is the benefit on intra-abdominal adhesions thanks to the limited manipulation of organs [22, 23]. By decreasing the need for adhesiolysis, the surgical time of repeated LR after a first laparoscopic surgery has been shown to be reduced compared to a first open surgery [24]. It should be emphasized that, although repeated LR are complex operations due to the distortion of the parenchyma that follows previous resections and the consequent alteration of the original anatomy, they are nevertheless still associated with perioperative advantages for patients. In 2021, the results of an international multicenter study evaluating the surgical results of repeated LLR for relapsed HCC revealed reduced intraoperative blood loss and complications for the laparoscopic group [25].

7 Elderly Patients

The laparoscopic approach has also yielded interesting results for the treatment of patients with advanced age [26]. For HCC, Nomi et al. disclosed the results of a multicenter retrospective propensity-based study on 630 HCC patients aged ≥75 years. As compared to open surgery, intraoperative blood loss, transfusion and morbidity were lower for LLR, including major, cardiovascular and pulmonary complications as well as 180-day mortality for causes other than HCC- or liver-related causes. Moreover, for octogenarians, laparoscopy was associated with decreased major morbidity and length of stay [27]. In 2021, a multicenter propensity-matched study including 184 HCC patients aged >70 years undergoing laparoscopic or open major LR was performed. Laparoscopy was confirmed to be associated with reduced complications and duration of stay with mortality comparable to open surgery [28]. Hence, age should not be considered a contraindication to LLR for HCC, even for major resections, since the benefits of minimal invasiveness are also confirmed for this category of fragile patients.

8 Difficulty Scores

The concept of difficulty is crucial in guiding safely the development of LLR expertise and learning curve. Particular attention has been given to the many factors influencing the complexity of an operation, some related to the topography and nature of the liver injury, others intrinsic to the type of operation, others related to the characteristics of the patient. As a result, various difficulty scoring systems (DSS) to predict surgical difficulty have been produced in recent years. The most popular are the IWATE-DSS, Halls-DSS, Hasegawa-DSS, and Kawaguchi-DSS [29,30,31,32].

Lin et al. conducted a single-center study specifically designed to validate these scores in HCC patients [33]. They found significant distributions of applying bleeding control, surgical time, estimated blood loss, postoperative major complications and hospital stay among different groups of each system, and that the IWATE-DSS was also able to predict conversion.

Additionally, in 2020 Goh et al. raised attention regarding the effect of cirrhosis on the difficulty of a LLR, given that none of the four existing DSS included its presence/absence as a determinant factor (only the IWATE-DSS considered Child B cirrhosis as a significant factor, but without distinguishing between patients with Child A liver function and patients with non-cirrhotic livers) [34].

In general, all the DSS show different profiles of utility. As a reasonable approach, we have made the proposal to use the “Kawaguchi-, IWATE-, and Halls-DSS” order for: a first assessment based on the type of operation and exclusion if the learning curve has not yet been overcome; a second stratification within procedures of the same complexity to guide towards progression to the next phase of difficulty; a final evaluation to estimate intraoperative complications and adequately prepare the equipment and team [35].

9 Laparoscopic Approach for Local Ablation Therapy

With the accumulation of evidence on its efficacy, ablation has become a viable treatment for HCC and liver malignancies. For HCC, it has moved from palliative to potentially curative treatment in selected patients [36]. The spread of laparoscopy has allowed its adoption for ablations, especially in the presence of limitations due to the percutaneous approach (mainly unfavorable localizations). Furthermore, laparoscopy has the clear advantage of providing real-time monitoring of the ablative process and hemostasis. Some studies have indeed reported a lower complication rate and shorter length of stay for laparoscopic compared with percutaneous ablations [37]. One study also reported comparable local tumor progression rates [38]. However, definitive conclusions on the oncological non-inferiority of laparoscopic ablations are still awaited, as well as validation of their role as a first-choice curative treatment for selected patients.

10 Conclusion

LLR has been performed worldwide with oncologic outcomes for HCC comparable to open surgery. The evidence is based on case-control studies, propensity score-matched studies and meta-analyses. Although most of the reports of LLR refer to Child A cirrhotic patients, some studies have demonstrated the feasibility of LLR in selected patients with advanced cirrhosis, for which laparoscopy can extend the indications for surgery. Future studies will need to clarify further which patients with advanced cirrhosis and HCC are most suitable for a minimally invasive approach and elucidate the role of laparoscopy for laparoscopic ablations.