Impact of minimally invasive approach surgery in hepatocellular carcinoma

Liver cancer is the fifth most common and the second most frequent cause of cancer-related death globally. Hepatocellular carcinoma (HCC) represents about 90% of primary liver cancers and constitutes a major global health problem. According to the World Health Organization (WHO) the incidence rate of HCC has increased in the last three decades and will maintain this trend in 2030. In accordance with the last published world record, 854.000 new cases and 810.000 deaths are diagnosed every year, representing 7% of all cancer’s deaths. The prognosis of the response to treatment is different depending on the type of HCC and its status at the time of diagnosis. For this reason, HCC classification and choice of the most suitable treatment is relevant for a successful response. Surgical approach is the first treatment option in patients with very early-stage and preserved liver function with a 5-years OS rate around 60-80%. Under the EASL guidelines surgical resection is recommended as the treatment of choice in patients with HCC arising on a non-cirrhotic liver. Indications for resection of HCC in cirrhosis should be based on a multiparametric composite assessment of liver function, portal hypertension, extent of hepatectomy, expected volume of the future liver remnant, performance status and patients’ comorbidities. In patients with chronic liver disease or cirrhosis, the choice of surgical resection should be more debated and, in certain cases, discarded. Liver Transplant (LT) is recommended as the first-line option for HCC within Milan criteria but unsuitable for resection. Laparoscopic liver approach is now a standard of practice for several procedures and has overpassed the tip point from pioneers to being currently widely adopted by several groups. Because of cirrhotic-associated complexity, laparoscopic liver resection for HCC may be more complex due to different factors: liver failure, coagulopathy, collateral circulation, and parenchymal stifness. The current situation is a trend towards the expansion of laparoscopic surgery in both simple resection and complex hepatectomies. The early diffusion of this approach made the current Guidelines Meeting in Laparoscopic Liver Surgery another landmark in the field. The alternative hypothesis proposed for our study was if laparoscopic hepatic surgery offers advantages compared to open surgery in the management of Hepatocellular carcinoma. The aim of this study was to perform a systematic review and meta-analysis comparing the short- and longterm outcomes of laparoscopic and open liver resections for hepatocellular carcinoma. To evaluate if considering severe morbidity, including liver-specific posthepatectomy liver failure and 90-days mortality, laparoscopic approach offers benefits against the open. To evaluate if laparoscopic approach has an impact on long-term outcomes considering overall survival and disease-free survival. To demonstrate whether laparoscopic approach for the treatment of hepatocellular carcinoma may be considered as the first option and in which cases it could be considered as standard of practice. To identify all the comparative manuscripts reporting on laparoscopic and open liver resection for HCC, all published English-language studies with more than 10 cases were screened. In addition to the primary metaanalysis, four specific subgroup analyses were performed on patients with Child–Pugh A cirrhosis, resections for solitary tumors, and those undergoing minor and major resections. The manuscripts included in the meta-analysis are subjected to a double-check quality analysis. That assessment was performed first under the Scottish Intercollegiate Guidelines Network (SIGN) methodology criteria and then in accordance with the Newcastle-Ottawa Quality Assessment Scale (NOS) for cohort and casecontrol studies (Ottawa Hospital Research Institute). This double assessment of each manuscript included is performed to reduce the risk of biases and thus enhance the quality of their results. Once the first step is completed, the evidence level on the topic is produced based on the quality of the available literature assessed at the previous step. The next step, once the evidence tables of each manuscript have been made, is to produce recommendations according to the evidence found in each one of them for the elaboration of guidelines of liver laparoscopic surgery. From the initial 361 manuscripts, 28 were included in the meta-analysis. Five of these 28 manuscripts were specific to patients with Child–Pugh A cirrhosis (321 cases), 11 focused on solitary tumors (1003 cases), 16 focused on minor resections (1286 cases), and 3 focused on major resections (164 cases). Three manuscripts compared 1079 cases but could not be assigned to any of the above subanalyses. In general terms, short-term outcomes were favorable when using a laparoscopic approach, especially in minor resections. The only advantage seen with an open approach was reduced operative time during major liver resections. No differences in longterm outcomes were observed between the approaches. Our exhaustive literature review, and assessment of current evidence by SIGN methodology has been the basis for the development of the European Guidelines Meeting on Laparoscopic Liver Surgery and for the eachievement of consistent, reliable and evidence-based statements in the application of minimally invasive approaches for the treatment of hepatocellular carcinoma. - According to the results of our updated meta-analysis, a minimally invasive approach might be more beneficial compared to an open approach as it may offer a lower rate of complications, blood loss, transfusion rate and postoperative hospital stay for patients with Child-Pugh A cirrhosis, solitary tumors and those undergoing minor resections. - Considering severe morbidity including liver-specific posthepatectomy liver failure and 90-days mortality, laparoscopic approach was not different compared to open approach. - Laparoscopic approach does not have an impact on short-, mid- and long-term outcomes considering overall survival. A trend towards better disease-free survival when laparoscopic approach is used was observed but no robust conclusions may be obtained. Its impact on re-do hepatectomies or on feasibility of rescue or salvage transplantation procedures remains unresolved. - Considering the optimal results obtained from laparoscopic approach, its use for the treatment of hepatocellular carcinoma should be considered as first option and standard of practice in selected patients from high-volume centers in which a multimodal strategy can be offered to these complex patients.

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