The role of associating liver partition and portal vein ligation for staged hepatectomy in the management of hepatocellular carcinoma

Abstract

Motivation Insufficient future liver remnant (FLR) is a common reason that precludes patients from major curative liver resection for hepatocellular carcinoma (HCC). Augmentation of the FLR is therefore required and the standard approach is portal vein embolization (PVE). Nonetheless, PVE is associated with a 12% risk of adverse events that would deter the chance for hepatectomy, and in our experience over the past decade, around 30% of the patients failed PVE because of tumor progression while waiting for liver hypertrophy or procedure-related complications. Based on this rationale, we were eager to explore alternative approaches that would enhance the chance for curative resection in patients with insufficient FLR. In 2012, Schnizbauer and co-workers from Germany reported their experience of right portal vein ligation followed by in-situ split in a cohort of patients with liver metastasis or non-hepatitis related primary liver cancer. The procedure was later termed ‘Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS).’ The development of this novel procedure has aroused our interest in its application to patients with chronic hepatitis and cirrhosis. Hence, I hereby report our 5-year experience of ALPPS in patients with HCC. Methods Our first pediatric and adult experience in ALPPS was described. Cumulative experience over the past 5 years was evaluated after reviewing prospectively collected data including clinicopathological details, portal hemodynamics and oncological outcomes. Tumor immunohistochemistry for PD-1, V-EGF and alpha-fetoprotein was evaluated in ALPPS and compared with PVE and upfront hepatectomy. Results From 2002 to 2018, 115 patients with HCC (hepatitis B: n=103, 89.6%) underwent FLR modulation (ALPPS, n=46; PVE, n=69). They were included for analysis. Of these, 65 patients (56.5%) had cirrhosis. ALPPS induced FLR volume increment by 48%, or an additional 12.3% of FLR over estimated total liver volume over 6 days. No difference in morbidity (20.7% vs. 30.4%, p=0.159) and mortality rates (6.5% vs. 5.8%, p=1.000) with PVE were observed. ALPPS induced substantial FLR portal flow increment from 70.2ml/min/100gm to 183.2ml/min/100gm (p<0.001) at stage I and decreased to 87.4ml/min/100gm at stage II operation (p<0.001). Chronic hepatitis and intraoperative indocyanine green clearance rate </=39.5% favored adequate FLR hypertrophy in ALPPS. Five-year overall survival rates for ALPPS and PVE were 46.8% and 64.1% (p=0.234) respectively. No difference in tumor expression of PD-1, V-EGF and alpha-fetoprotein between ALPPS, PVE and upfront hepatectomy was observed. Discussion ALPPS was effective for FLR augmentation in hepatitis-related HCC without compromising the oncological outcome of hepatectomy. Intraoperative indocyanine green clearance test was helpful to predict FLR hypertrophy and offered guidance to timing of stage II operation. Significance Our cohort represented one of the largest single-center experience in ALPPS for hepatitis-related HCC. It showed that ALPPS was safe and feasible for chronic hepatitis or cirrhosis with comparable survival outcome to standard treatment. Given its effect on rapid liver regeneration, it would be most appropriately applied when the FLR occupied <30% of the estimated total liver volume and should be included into the treatment algorithm for HCC.