Rat Model of the Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) Procedure

Abstract

Recent clinical data support an aggressive surgical approach to both primary and metastatic liver tumors. For some indications, like colorectal liver metastases, the amount of liver tissue left behind after liver resection has become the main limiting factor of resectability of large or multiple liver tumors. A minimal amount of functional tissue is required to avoid the severe complication of post-hepatectomy liver failure, which has high morbidity and mortality. Inducing liver growth of the prospective remnant prior to resection has become more established in liver surgery, either in the form of portal vein embolization by interventional radiologists or in the form of portal vein ligation several weeks prior to resection. Recently, it was shown that liver regeneration is more extensive and rapid, when the parenchymal transection is added to portal vein ligation in a first stage and then, after only one week of waiting, resection performed in a second stage (Associating Liver Partition and Portal vein ligation for Staged hepatectomy = ALPPS). ALPPS has rapidly become popular across the world, but has been criticized for its high perioperative mortality. The mechanism of accelerated and extensive growth induced by this procedure has not been well understood. Animal models have been developed to explore both the physiological and molecular mechanisms of accelerated liver regeneration in ALPPS. This protocol presents a rat model that allows mechanistic exploration of accelerated regeneration.

A preliminary study of associating liver partition and portal vein ligation for staged hepatectomy in a rat model of liver cirrhosis

“…1A). According to previous experimental studies (17,19,20), liver sections account for the following total liver volumes: LML, 10%; LLL, 30%; RML, 30%; RL, 22%; and CL, 8%. The median lobe is supplied by two portal branches: The right branch and the left branch.…”

“…The branch of the portal vein and branches of the lobes were exposed and prepared for ligation to remove the peripheral ligaments of the liver. A bulldog clamp was briefly applied near the hepatic pedicle (pringle maneuver) (20) to reduce the amount of blood loss during the parenchymal transection. After the operation, rats were re-warmed with an electric blanket at 36°C until they awakened and were then returned to their cages in the laboratory.…”

Hypoxia sensing by hepatic stellate cells leads to VEGF-dependent angiogenesis and may contribute to accelerated liver regeneration

“…The right middle lobe (RML, 25% of the total liver volume) was used as FLR in models of PVL and ALPPS with 25% future liver remnant which have been established in this laboratory and were previously described Fig. 1A-C 13,20 . Control animals for PVL+DMOG, the prolyl-hydroxylase inhibitor dimethyloxalylglycine (DMOG) was injected intraperitoneally 12 h prior to PVL (Fig.…”

“…Rat models of PVL and ALPPS have been established previously 37,[42][43][44] . The RML was used as the FLR, and PVL as well as ALPPS were performed according to previous experiments 13,20 . For PVL+DMOG, 200 µg/g body weight of the PHI DMOG (Frontier Scientific, Newark, DE, USA), was injected intraperitoneally 12 h prior to PVL.…”

Laparoscopic left hemihepatectomy in small dogs: an easy and effective new technique

“…Hepatectomy is widely used in medical research and experimental surgery, for studying liver failure (Imai et al 2019;Meyer et al 2019;Shirata et al 2019), regeneration (Schadde et al 2017;Tsai et al 2018), and transplantation (Etheredge et al 2019;Lué et al 2019;Majd et al 2019), and is one of the common hepatic procedures performed on companion animals (Boothe 2015;Zhang et al 2014). Thus, an animal model of hepatectomy is an extremely important research tool for evaluating liver regeneration after various treatments (Bernat Córdoba-Jover 2019;de Miguel et al 2019;Lee et al 2019).…”