AIM: To compare the surgical outcomes between laparoscopic liver resection (LLR) and open liver resection (OLR) as a curative treatment in patients with hepatocellular carcinoma (HCC).

METHODS: A PubMed database search was performed systematically to identify comparative studies of LLR vs OLR for HCC from 2000 to 2014. An extensive text word search was conducted, using combinations of search headings such as “laparoscopy”, “hepatectomy”, and “hepatocellular carcinoma”. A comparative study was also performed in our institution where we analysed surgical outcomes of 152 patients who underwent liver resection between January 2005 to December 2012, of which 42 underwent laparoscopic or hand-assisted laparoscopic resection and 110 underwent open resection.

RESULTS: Analysis of our own series and a review of 17 high-quality studies showed that LLR was superior to OLR in terms of short-term outcomes, as patients in the laparoscopic arm were found to have less intraoperative blood loss, less blood transfusions, and a shorter length of hospital stay. In our own series, both LLR and OLR groups were found to have similar overall survival (OS) rates, but disease-free survival (DFS) rates were higher in the laparoscopic arm.

CONCLUSION: LLR is associated with better short-term outcomes compared to OLR as a curative treatment for HCC. Long-term oncologic outcomes with regards to OS and DFS rates were found to be comparable in both groups. LLR is hence a safe and viable option for curative resection of HCC.

Hepatocellular carcinoma (HCC) is the sixth most prevalent cancer and the third most frequent cause of cancer-related death, with about 750000 new cases diagnosed and approximately 700000 deaths worldwide each year[1,2]. Potentially curative treatment options for HCC include surgical resection[3], liver transplantation[4], and local ablation[5]. Surgical resection remains the standard treatment, and provides the best outcomes, for candidates who are eligible for resection[6]. In 1991, Reich et al[7] performed the first laparoscopic hepatic resection (LLR) for a benign liver tumour; subsequently, Hashizume et al[8] reported the first LLR performed for HCC. However, many barriers have hindered the popularity of LLR, including concerns of uncontrollable bleeding, resection margins, tumour seeding, and port-site metastases. LLR may also be perceived as a challenge especially in cirrhotic patients, who are at increased risk of complications related to underlying synthetic and metabolic dysfunction[9]. Nevertheless, over the past 2 decades, it has become a widely accepted mode of curative resection for HCC by being established as both safe and feasible. It has also evolved to encompass more difficult anatomic resections.

A number of comparative studies have been published on the surgical outcomes of LLR vs open liver resection (OLR) as a curative treatment for HCC, and most suggest that while LLR and OLR both have similar overall survival (OS) and disease-free survival (DFS) rates, LLR confers the additional advantages of shorter duration of hospitalization and lower complication rates. To our knowledge, there has been so far no prospective, randomized controlled study done on this subject.

In this review article, we systematically reviewed 17 comparative studies from 2001 to 2014 to look at the surgical outcomes of LLR vs OLR for curative resection of HCC. We also conducted our own comparative study by analysing data from 152 patients who underwent surgical resection of HCC from 2005 to 2012 at the National University Hospital (Singapore) and compared our results to those of the 17 comparative studies.

A PubMed database search was performed systematically to identify comparative studies of LLR vs OLR for HCC from 2000 to 2014. An extensive text word search was conducted, using combinations of search headings such as “laparoscopy”, “laparoscopic”, “minimally invasive surgery”, “hepatectomy”, “hepatic resection”, “hepatic lobectomy”, “liver resection”, “hepatocellular carcinoma”, “HCC”, and “primary liver cancer”. The search was restricted to comparative studies and human studies only. All studies identified for screening were manually reviewed. References from these articles were also searched for relevant studies. The most recent search was conducted on 6 June 2014 (Figure 1).

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Figure 1 Flow chart illustrating the screening and selection process. LLR: Laparoscopic liver resection; OLR: Open liver resection; HCC: Hepatocellular carcinoma.

Studies were included in the analysis if they: (1) were comparative studies on humans and in the English language; (2) focused on outcomes of LLR vs OLR for HCC; (3) had more than 10 patients in each group included in the study; and (4) if multiple studies were reported by the same institution or authors, the most recent publication was included. Studies were excluded from the analysis if they: (1) were reviews lacking original data, abstracts, editorials, or expert opinions; (2) did not show clear comparisons between outcomes on LLR vs OLR; and (3) included resections of benign tumours or metastatic lesions other than HCC. Our own series was analysed together with the selected studies.

Intraoperative bleeding is a significant problem faced during liver resection, and is frequently the most common reason for conversion from laparoscopic to open hepatectomy[27,28]. The number of transfusions required intraoperatively has also been shown to be an independent risk factor for a worse post-operative prognosis[29,30]. The worldwide acceptance of LLR was delayed due to concerns of the technical difficulties of controlling hemorrhage and obtaining hemostasis. However, our study showed that intraoperative blood loss and the number of patients requiring transfusion were significantly lower in the laparoscopic arm. Reasons for this include image magnification during LLR, usage of intra-operative ultrasonography to visualize the tumour and surrounding intrahepatic vessels and equipment such as ultrasonic laparoscopic coagulation shears and argon beam coagulators to provide rapid hemostasis in the event of hepatic hemorrhage. The pneumoperitoneum in LLR results in increased intra-abdominal pressure, which also reduces visceral blood flow, in turn decreasing blood loss[31,32].

Another major concern regarding LLR for malignant lesions is difficulty assessing resection margins, due to the lack of tactile sensation and distance perception in laparoscopic resection. However, our study showed that there was no difference in resection margins in both series. We are able to make up for the lack of palpation in LLR and hence achieve the intended margins laparoscopically, with pre-operative surgical planning using a variety of imaging techniques and the use of intra-operative ultrasonography to demarcate surgical margins.

Our analysis of the 17 studies showed that the rates of postoperative complications were significantly lower in patients who underwent LLR. Possible reasons for this include less mobilization and manipulation of the liver and other intra-abdominal organs, avoidance of long incisions and division of the abdominal muscles hence minimizing disruption to the abdominal wall collateral circulation, less severe pain, earlier ambulation and oral food intake, and more post-operative cough and expectoration. However, the findings in our comparative study were not significant. Nevertheless, it is worthy to note that even though there was a significantly higher number of co-morbidities in patients in the LLR group, and a significantly greater number of patients found to have cirrhosis in the LLR group, the LLR cohort experienced fewer postoperative complications, though this result was not statistically significant.

Liver resection in HCC patients with chronic liver disease (CLD) or cirrhosis has been a major issue due to the high rates of postoperative morbidity from decompensation due to their underlying liver disease. In these patients, portal hypertension is a major risk factor for development of postoperative decompensation[33,34]. The studies we analysed which were specific to HCC patients with underlying CLD or cirrhosis showed that LLR resulted in fewer postoperative complications compared to OLR. Belli et al[15] showed that a significantly decreased postoperative morbidity rate in the laparoscopic group. The studies by Laurent et al[11] and Truant et al[21] showed lower rates of post-operative ascites and liver failure in the LLR group as well. Overall, fewer complications in the LLR group result in a shorter length of hospital stay. Furthermore, from our own comparative study, the rates of prolonged ascites and liver failure in both groups were not significantly different despite a significantly larger number of patients with cirrhosis in the LLR group.

Laparoscopic hepatectomy has not been shown to increase the risk of tumor recurrence and affect the oncologic outcomes (in terms of overall survival and disease-free survival). However, in our study, there was a significant increase in disease-free survival rates in the LLR group; this could be attributed to the higher incidence of microscopic vascular invasion found on histology in the OLR group, which is a significant underlying risk factor for tumour recurrence.

Although LLR has been shown to be superior to OLR in terms of surgical outcomes, the clinical significance of these results should be interpreted keeping in mind that they were based on selected patients who fulfill certain criteria. The size and location of the tumour are important considerations that influence a surgeon’s decision to perform an open or a laparoscopic resection. As a general rule, small (< 5 cm) tumours, in superficial or peripheral locations, far away from major vessels, are considered for LLR. Large tumours and cases requiring vascular or biliary reconstruction are usually indications for open resection. Nevertheless, with improvement of the laparoscopic technique and new advances in technology over the past 2 decades, LLR is being performed more frequently and for more complex cases with tumours in difficult anatomical locations[22,35,36].