Right hepatectomy for hepatocellular carcinoma: is the anterior approach superior to the conventional approach?

To the Editor: We read with great interest the article by Liu et al comparing the results of a right hepatectomy for the treatment of large hepatocellular carcinoma (HCC) via the anterior approach, where the liver parenchyma is transected before the full mobilization of the right liver and the division of the right hepatic vein, and the conventional approach. Congratulations to the authors for completing this large prospective randomized study. Liu et al hypothesized that the anterior approach for performing a right hepatectomy had beneficial effects on operative and survival outcomes for patients with large HCC because such an approach does not require liver mobilization, which could increase the risks of massive bleeding from hepatic vein avulsion, prolonged ischemia in the remnant liver, and the spillage of the cancer cells into the systemic circulation. In their study, the anterior approach was superior to the conventional approach with regard to the incidence of massive blood loss of 2 L (8.3% vs. 28.3%, P 0.005) and transfusion requirements (6.7% vs. 28.3%, P 0.003). The median overall survival period was also better in the anterior approach group than in the conventional approach ( 68.1 vs. 22.6 months, P 0.006), whereas the median disease-free survival was similar (15.5 vs. 13.9 months, P 0.882). Nevertheless, their conclusion that the anterior approach “is the preferred technique for major right hepatic resection for large HCC” is questionable. First of all, the disease-free survival period was similar between the 2 approaches, yet the conventional approach supposedly increased the risk of tumor cell dissemination. Liu et al speculated that the additional tumor manipulation in the conventional approach did not lead to a lower disease-free survival period but caused “more widespread metastases. ” Indeed, in the subgroup of patients with AJCC stage II disease, localized and solitary recurrences were more common in the anterior approach group (80%) than in the conventional approach (17%). However, their consideration is unconvincing because the incidence of localized and solitary metastasis was not different in stage III patients, who would be at a similar or even higher risk of tumor cell dissemination, compared with stage II patients. The locations of recurrence (intrahepatic and/or extrahepatic) were also similar between the 2 groups. Second, Liu et al attributed the lower overall survival period in the conventional approach group to the unavailability of effective treatments for the more widespread metastases. However, it seems that the major contributing factor to the difference in overall survival may have been the higher hospital mortality in the conventional approach group, compared with the anterior approach (10% vs. 1.7%). In the overall survival curves presented by Liu et al, the decrease in the conventional approach group paralleled that in the anterior approach for the first 20 months after surgery, keeping the difference in the hospital mortalities. The subsequent difference in overall survival is rather uninformative, because the median follow-up duration was only around 20 months. Third, their reported rate of hospital mortality in the conventional approach group (10%, 6 hospital deaths related to liver failure) is unacceptably high, compared with the reported mortality rate of 0% to 5% among patients undergoing a major hepatectomy for the treatment of advanced HCC. Liu et al speculated that the high incidence of liver failure in the conventional approach group was associated with the prolonged ischemia in the remnant liver during mobilization. In contrast, remnant liver volume is acknowledged to be the major predictor of postoperative liver failure. When the remnant volume is estimated to be inadequate, preoperative portal vein embolization is effective for increasing the functional volume of the future remnant and minimizing the risk of liver failure after HCC resection. We wonder whether the authors preoperatively assessed the remnant liver volume and considered the application of portal vein embolization. Finally, Liu et al considered the increase in plasma albumin mRNA levels during surgery in the conventional approach group as evidence of tumor cell dissemination caused by liver mobilization. However, molecular markers like albuminand alpha-fetoprotein mRNA have been shown to be not specific for HCC cells if the blood samples are taken during surgery, because surgical intervention induces the release of non-neoplastic liver cells into the circulation. We previously demonstrated that HCC recurrence could be predicted by detecting the alpha-fetoprotein mRNA in the peripheral blood 1 week after surgery, once the liberated non-neoplastic cells had supposedly been filtered from the blood system. The intraoperative albumin-mRNA level, as assessed by Liu et al, would probably be less informative than the postoperative values for evaluating the risk of tumor cell dissemination during surgery. We agree with the comment of Liu et al that “the anterior approach can potentially be dangerous” because “torrential bleeding can occur at the deeper plane of parenchymal transection” and “without prior mobilization of the right liver and the tumor, and control of the right hepatic vein, bleeding can be substantial and difficult to control. ” In principle, we prefer the conventional approach to the anterior approach, irrespective of the tumor size, because we consider bleeding control during liver transection to be most important. Our methodology for the conventional approach has been described previously. Briefly, a thoracophrenolaparotomy is mandatory for providing a good view around the vena cava, whereas Liu et al added this procedure in only 23% of their patients in the conventional approach group. The right adrenal gland is dissected from the liver after the division of the medial side of the gland from the vena cava to pass a thick suture, which should be ligated in the case