Christopher W Mangieri1,2, Jason C McCartt3, Matthew A Strode3, John E Lowry3, Prasad M Balakrishna3. 1. General Surgery Department, 300 East Hospital Road, Fort Gordon, GA, 30905, USA. christopher.w.mangieri.mil@mail.mil. 2. , 207 Sunbury Drive, Evans, GA, 30809, USA. christopher.w.mangieri.mil@mail.mil. 3. General Surgery Department, 300 East Hospital Road, Fort Gordon, GA, 30905, USA.
Abstract
BACKGROUND: As hepatic surgery has become safer and more commonly performed, the extent of hepatic resections has increased. When there is not enough expected hepatic reserve to facilitate primary resection of hepatic tumors, a clinical adjunct to facilitating primary resection is portal vein embolization (PVE). PVE allows the hepatic remnant to increase to an appropriate size prior to resection via hepatocyte regeneration; however, PVE is not always successful in facilitating adequate regeneration. One of the strongest trophic factors for hepatocyte regeneration is hepatocyte growth factor (HGF). The purpose of this study was to improve hepatic regeneration with perioperative HGF infusions in an animal model that mimics PVE. METHODS: Portal branch ligation (PBL) in rodents is equivalent to PVE in humans. We performed left-sided PBL in Sprague-Dawley rodents with the experimental group receiving perioperative HGF infusions. Baseline and postoperative liver volumetrics were obtained with CT scanning methods as performed in clinical practice. Baseline and postoperative liver functions were assessed via indocyanine green (ICG) elimination testing. RESULTS: HGF infused rodents had statistically significant increase in all postoperative liver volumetrics. Most clinically relevant were increased right liver volumes (RLV), 14.10 versus 7.85 cm3 (p value 0.0001), and increased degree of hypertrophy (DH %), 159.23 versus 47.11 % (p value 0.0079). HGF infused rodents also had a quick return to baseline liver function, 2.38 days compared to 6.13 days (p value 0.0001). CONCLUSION: Perioperative HGF infusions significantly increase hepatic regeneration following PBL in rodents. Perioperative HGF infusions following PVE are a possible adjunct to increase the amount of patients able to successfully undergo primary resection for hepatic tumors. Further basic science is warranted in examining the use of HGF infusions to increase hepatic regeneration and translating that basic science work to clinical practice.
BACKGROUND: As hepatic surgery has become safer and more commonly performed, the extent of hepatic resections has increased. When there is not enough expected hepatic reserve to facilitate primary resection of hepatic tumors, a clinical adjunct to facilitating primary resection is portal vein embolization (PVE). PVE allows the hepatic remnant to increase to an appropriate size prior to resection via hepatocyte regeneration; however, PVE is not always successful in facilitating adequate regeneration. One of the strongest trophic factors for hepatocyte regeneration is hepatocyte growth factor (HGF). The purpose of this study was to improve hepatic regeneration with perioperative HGF infusions in an animal model that mimics PVE. METHODS: Portal branch ligation (PBL) in rodents is equivalent to PVE in humans. We performed left-sided PBL in Sprague-Dawley rodents with the experimental group receiving perioperative HGF infusions. Baseline and postoperative liver volumetrics were obtained with CT scanning methods as performed in clinical practice. Baseline and postoperative liver functions were assessed via indocyanine green (ICG) elimination testing. RESULTS:HGF infused rodents had statistically significant increase in all postoperative liver volumetrics. Most clinically relevant were increased right liver volumes (RLV), 14.10 versus 7.85 cm3 (p value 0.0001), and increased degree of hypertrophy (DH %), 159.23 versus 47.11 % (p value 0.0079). HGF infused rodents also had a quick return to baseline liver function, 2.38 days compared to 6.13 days (p value 0.0001). CONCLUSION: Perioperative HGF infusions significantly increase hepatic regeneration following PBL in rodents. Perioperative HGF infusions following PVE are a possible adjunct to increase the amount of patients able to successfully undergo primary resection for hepatic tumors. Further basic science is warranted in examining the use of HGF infusions to increase hepatic regeneration and translating that basic science work to clinical practice.
Authors: Claudia Mitchell; Mary Nivison; Leslie F Jackson; Richard Fox; David C Lee; Jean S Campbell; Nelson Fausto Journal: J Biol Chem Date: 2004-11-08 Impact factor: 5.157
Authors: Na Chang; Lei Tian; Xiaofang Ji; Xuan Zhou; Lei Hou; Xinhao Zhao; Yuanru Yang; Lin Yang; Liying Li Journal: Cells Date: 2019-09-11 Impact factor: 6.600