Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide [
1]. Liver resection remains the mainstay of curative treatment for HCC due to the current donor shortage of liver transplantation [
2]. Unfortunately, the majority of the HCC patients are suffered from liver cirrhosis, making hepatectomy more complex and risky in the setting of elevated portal pressure and impaired coagulation, particularly for patients requiring major hepatectomy [
3‐
7].
As a less invasive surgical approach, laparoscopic liver resection (LLR) was first introduced in 1990s, and since then this technique has gained attention worldwide [
8,
9]. In the statement by the First International Consensus Conference for Laparoscopic Liver Resection, laparoscopic left lateral segmentectomy was considered to be the gold standard approach with reported reduced blood loss, decreased rates of postoperative complications, and shorter hospital stays compared with traditional open liver resection [
10,
11]. However, the progress of laparoscopic major hepatectomy (LMH) has been very slow worldwide because of its inherent technical difficulties and fear of uncontrollable bleeding during parenchyma dissection. By 2014, the Second International Consensus Conference for Laparoscopic Liver Resection was convened in Morioka, and laparoscopic minor hepatectomy was considered to be a standard surgical practice (IDEAL 3), while LMH was deemed only to be the “Exploration” stage as there is still risk associated with novelty (IDEAL 2b) [
12,
13].
Over the past few years, advances in laparoscopic devices and experience have gradually expanded the indications for LLR and resulted in several centers reporting good outcomes after LMH [
14‐
16]. What is more, for patient with liver cirrhosis, comparative studies have also proved the feasibility of this technique with good short- and long-term outcomes [
3,
4,
7]. However, most of the published literatures focusing on cirrhotic patients were based on the laparoscopic minor resections, while the LMH for patients with cirrhosis have been performed only in a related small number of cases, making it remaining a debatable issue.
The aim of the present study is to analyze our initial experience with LLR and compare outcomes following purely LMH with open major hepatectomy (OMH) for HCC in patients with cirrhosis.
Discussion
Hepatectomy remains the first-line treatment option for early- and intermediate-stage HCC due to the extremely limited number of donor supply worldwide [
2]. Although recent advances in laparoscopic instruments and technique have greatly promoted the development of LLR, this procedure is still associated with challenge and technological complexity, especially for cirrhotic patients requiring major liver resection [
3‐
5,
14].
The first laparoscopic liver surgery performed in our center was local resection for lesion positioned in segment III in 2009, and since then an increasing number of laparoscopic minor hepatectomy was introduced, mainly for left lateral section ectomy and wedged resection. Up to 2015, more than 40 cases of LLR were performed including both benign and malignant tumors and the first case of laparoscopic right hemihepatectomy was successfully operated, making the indications for LLR more expanded in our center. As it has been proved that this relatively novel technique is associated with a steep learning curve about 45–75 cases, the current study included patients underwent LLR only after 2015 to limit the influence of learning curve as less as possible [
26‐
28]. As far as we are concerned, for safely starting the LLR, a comprehensive understanding of liver anatomy, basically learning of laparoscopic techniques in other abdominal surgery, knowledge of the merits and faults of different energy devices, and extensive open liver resection experiences are of great importance. Mastering each of these factors is a challenging task, and the requirement for combining all of them in LLR will no doubt contribute to the steep learning curve of LLR. Moreover, such a steep learning curve could be more obvious in LMH, which often requiring more laparoscopic minor liver resection and open major resection experiences. In our center, the comparison of LMH between 2015 and 2016 showed that even though patients in 2015 were associated with longer operative time and more blood loss compared with those in 2016, the results did not reach significant differences, indicating that the effect of learning curve was mitigated.
In the present study, our results suggested that the blood loss and the intraoperative transfusion requirement in the LMH group tended to be less than the OMH group, even though the comparable result was noted after PSM. Control of bleeding is of great concern in the field of liver surgery, particularly for LMH. Besides the meticulous dissection and maintaining low level of the central venous pressure during the liver parenchyma dissection, we routinely applied intermittent Pringle maneuver to control surgical blood loss. Differ from the previous series reported, the Pringle maneuver was performed occasionally in the event of major bleeding [
29,
30], we adopted this technique as routine use because parenchyma transection in the setting of elevated portal pressure and impaired coagulation in cirrhotic patients can be extremely difficult. Under the magnified vision during laparoscopic hepatectomy, a clean surgical field with less blood loss is associated with shorter operative duration. Usually, the use of CUSA or harmonic scalpel in the setting of bleeding can easily stain the laparoscope, which may in turn affect the fluency of surgery and prolong the operative time. Therefore, the routine use of Pringle maneuver can sometimes be advantageous and help surgeons to control bleeding.
The relatively longer operative duration in the LMH group than that of OMH group could be attributed to the wide application of Pringle maneuver during parenchyma transection. What’s more, the effect of learning curve may still serve as an important role for the slow-gestating of LLR in our center compared with more than one thousand open liver resection experience over the past few years.
With respect to postoperative morbidity, the LMH group tended to be more superior than OMH group even though there were no statistical differences in the rates of overall complications, major complications, and liver-specific complications after PSM. Considering the liver-specific complications, the high rates of posthepatectomy liver failure and ascites were encountered after major hepatectomy which in line with the reported literatures [
14,
29]. In current study, the proportion of liver failure did not differ between the two groups, while the incidence of ascites was significantly less in the LMH group than in the OMH group both before and after PSM, which also in compliance with the previous studies [
14,
31]. Instead of making the large subcostal incision, the LMH simply put four or five trocars in the upper quadrant of abdomen, resulting in minimizing the destruction of the collateral circulation of the abdominal wall and lymphatic flow of the diaphragm in the setting of liver cirrhosis hence decreased the incidence of postoperative ascites.
It has been reported that LLR decreased the rates of infectious complications in the postoperative course [
32]. In the current study, the OMH group seems more vulnerable to such complications, although there was no statistically significant difference in the incidence of general complications according to respiratory infection, wound infection and pleural effusion between the two groups before and after PSM. The hospital stay and 90-day mortality were comparable between the groups, while the cost of laparoscopic surgery was much more expensive compared with traditional open liver resection, which can be explained by the relatively new developed devices applied in the LMH such as LigaSure, high-definition laparoscope, and endoscopic stapler.
Based on the current study, the comparable oncological outcomes between the LMH group and the traditional open surgery group were observed after PSM. As it has been proved that the prognosis of HCC patients could be extremely influenced by the biological behavior of the hepatic tumors [
33,
34], the results of pathological characteristics between the compared groups showed no statistically significant differences with respect to the R0 resection, microvascular invasion, capsular invasion, satellites present and poor differentiation, which certified the reliability of oncological outcome analysis of the current study.
There are some limitations in the present study. The small sample size, retrospective nature, and absence of randomization may limit the strength and validity of the results. However, given the fact that the LMH for cirrhotic patients is associated with novelty and unpredictable risk, the current study enrolled the relatively large number of cases compared with a lack of published data regarding this special cohort of patients. Although a randomized controlled trial may provide the most robust evidence for clinical study, it is sometimes extremely difficult to carry out as there is no accurate evaluation for the severity of liver fibrosis preoperatively, and it is unlikely to recruit patients when the two techniques are associated with obviously different cosmetic effect. To overcome the selection bias arising from lack of randomization, we performed the PSM analysis which is deemed as the most effective method to balance the covariates and thus reducing bias in the retrospective studies. Despite this, it could lead to the reduction of the original small number of cases and the inevitable loss of information. Further studies with large sample size are definitely warranted.
In conclusion, the current study demonstrated that LMH for HCC patients with liver cirrhosis showed comparable results in terms of postoperative morbidity and oncological outcomes compared with traditional open procedure. LMH may serve as a safe and feasible alternative for selected HCC patients with cirrhosis.