Ablative Liver Partition and Portal Vein Embolization (ALPPVE): Proof of Concept in a Rabbit Model

PURPOSE: Portal vein embolization (PVE) is the standard of therapy for future liver remnant (FLR) growth induction prior to hepatectomy. Associated liver partition and portal vein ligation (ALPPS) is an alternative 2-step surgery involving portal vein ligation and hepatic transection followed by resection at a later date. ALPPS may result in more rapid FLR growth compared to PVE, but has higher morbidity/mortality. Combining these procedures to retain the minimal invasiveness and safety of PVE and exploit the regenerative capacity of ALPPS may allow high FLR growth rates with low adverse events. This proof-of-concept study examined the feasibility and efficacy of a novel modified approach combining PVE with microwave ablation — termed Ablative Liver Partition and Portal Vein Embolization (ALP-PVE) —in an animal model. METHODS: Sixteen New Zealand White rabbits underwent PVE (n=8) or ALP-PVE (n=8). They represent a suitable pre-clinical model given their favorable anatomy and rapid hepatic hypertrophy. All rabbits underwent laparotomy for PVE to 3 cranial liver lobes; the portal vein to the caudal lobe FLR was spared. In the ALP-PVE cohort, the parenchyma connecting cranial and caudal lobes was ablated utilizing microwave ablation. Animals were sacrificed and livers harvested on post-procedure day 7. Caudal/cranial liver lobes were weighed immediately after harvest and after drying for 4 weeks. Liver masses were standardized to rabbit mass and liver mass before comparison. Immune histochemical staining with Ki-67 was also performed. Data was compared utilizing the 1-tailed Student’s t-test. RESULTS: The final cohort included 15 rabbits; 1 ALP-PVE rabbit died on post-procedure day 2 secondary to mesenteric ischemia and was excluded. The caudal lobe to whole liver mass ratio was higher for ALP-PVE vs. PVE (.313 ± .052 vs. .267 ± .032; p = 0.029). After drying, there is still a difference but it is no longer significant (.309 ± .047 vs. .276 ± .039; p = .081). This difference became statistically significant when the first 2 rabbits in each group (constituting the procedure learning curve) were excluded (0.323 vs. 0.266, P=0.029), with ALP-PVE caudal lobes showing a 6% greater degree of hypertrophy. The cranial liver lobes (embolized liver lobes) were significantly smaller in the ALPPVE cohort for both the wet and dry absolute masses and when standardized by rabbit weight and when calculating data excluding initial 2 rabbits in each cohort. All samples displayed Ki-67 staining. The percentage of Ki-67 positive cells was significantly greater in the ALP-PVE caudal lobes (14± 6.3%) compared to that of the PVE cohort (9.3± 5.7%, p = 0.078) and this almost reached statistical significance when excluding the initial 2 cases from each cohort (16.4± 4.5% vs. 10.6± 6.1%, p = 0.054). CONCLUSION: The results of this study suggest that ALP-PVE results in faster and more robust growth of the FLR compared to PVE alone when comparing, absolute caudal masses, both wet and dry, and caudal percentage of total liver mass between cohorts. The greater number of Ki-67 positive staining cells in the ALP-PVE caudal group compared to the PVE caudal group supports this and provides evidence of increased proliferation. The study was limited by a small sample size, initial procedural learning curve, and presence of only a single time point post intervention. The clinical utility of ALP-PVE requires further evaluation including providing evidence that ALP-PVE can be performed minimally invasively, as well as performing the procedure in an animal model more closely related to humans anatomically and physiologically.