Simultaneous transcatheter arterial chemoembolization and portal vein embolization for patients with large hepatocellular carcinoma before major hepatectomy

BACKGROUND Sequential transarterial chemoembolization(TACE)and portal vein embolization(PVE)are associated with long time interval that can allow tumor growth and nullify treatments'benefits.AIM To evaluate the effect of simultaneous TACE and PVE for patients with large hepatocellular carcinoma(HCC)prior to elective major hepatectomy.METHODS Fifty-one patients with large HCC who underwent PVE combined with or without TACE prior to hepatectomy were included in this study,with 13 patients in the simultaneous TACE+PVE group,17 patients in the sequential TACE+PVE group,and 21 patients in the PVE-only group.The outcomes of the procedures were compared and analyzed.RESULTS All patients underwent embolization.The mean interval from embolization to surgery,the kinetic growth rate of the future liver remnant(FLR),the degree of tumor size reduction,and complete tumor necrosis were significantly better in the simultaneous TACE+PVE group than in the other groups.Although the patients in the simultaneous TACE+PVE group had a higher transaminase levels after PVE and TACE,they recovered to comparable levels with the other two groups before surgery.The intraoperative course and the complication and mortality rates were similar among the three groups.The overall survival and disease-free survival were higher in the simultaneous TACE+PVE group than in the other two groups.CONCLUSION Simultaneous TACE and PVE is a safe and effective approach to increase FLR volume for patients with large HCC before major hepatectomy.

Kinetics of remnant liver volume and function after a major hepatectomy

Liver regeneration after a major hepatectomy(MH)is crucial for the patient postoperative recovery,with the first postoperative month(1M)being a critical period for the liver regeneration course.The risk of post hepatectomy liver failure(PHLF),which is the leading cause of death,is usually anticipated in the preoperative period by the measurement of the future remnant liver volume(RLV)via computed tomography(CT)with volumetry.

Current strategies to induce liver remnant hypertrophy before major liver resection

Hepatic resection is the gold standard for patients affected by primary or metastatic liver tumors but is hampered by the risk of post-hepatectomy liver failure.Despite recent impro-vements,liver surgery still requires excellent clinical judgement in selecting patients for surgery and,above all,efficient pre-operative strategies to provide adequate future liver remnant.The aim of this article is to review the literature on the rational,the preliminary assessment,the advantages as well as the limits of each existing technique for preparing the liver for major hepatectomy.

Cyclin-dependent kinase inhibitors p21 and p27 function as critical regulators of liver regeneration following 90%hepatectomy in the rat

BACKGROUND Liver reduction is the main curative treatment for primary liver cancer,but its use remains limited as liver regeneration requires a minimum of 30%functional parenchyma.AIM To study the dynamics of the liver regeneration process and consequent behavior of cell cycle regulators in rats after extended hepatectomy(90%)and postoperative glucose infusions.METHODS Post-hepatectomy liver failure was triggered in 84 Wistar rats by reducing their liver mass by 90%.The animals received a post-operative glucose infusion and were randomly assigned to two groups:One to investigate the survival rate and the other for biochemical analyses.Animals that underwent laparotomy or 70%hepatectomy were used as controls.Blood and liver samples were collected on postoperative days 1 to 7.Liver morphology,function,and regeneration were studied with histology,immunohistochemistry,and western blotting.RESULTS Postoperative mortality after major resection reached 20%and 55%in the first 24 h and 48 h,respectively,with an overall total of 70%7 d after surgery.No apparent signs of apoptotic cell death were detected in the extended hepatectomy rat livers,but hepatocytes displaying a clear cytoplasm and an accumulation of hyaline material testified to changes affecting their functional activities.Liver regeneration started properly,as early events initiating cell proliferation occurred within the first 3 h,and the G1 to S transition was detected in less than 12 h.However,a rise in p27(Kip1)followed by p21(Waf1/Cip1)cell cycle inhibitor levels led to a delayed S phase progression and mitosis.Overall,liver regeneration in rats with a 90%hepatectomy was delayed by 24 h and associated with a delayed onset and lower peak magnitude of hepatocellular deoxyribonucleic acid synthesis.CONCLUSION This work highlights the critical importance of the cyclin/cyclin-dependent kinase inhibitors of the Cip/Kip family in regulating the liver regeneration timeline following extended hepatectomy.

Liver resection and metabolic disorders: An undescribed mechanism leading to postoperative mortality

AIM: To investigate the mechanism leading to perioperative mortality in patients undergoing major liver resection and presenting with metabolic disorders.

Extent of liver resection modulates the activation of transcription factors and the production of cytokines involved in liver regeneration

AIM： To investigate the molecular events involved in liver regeneration following subtotal hepatectomy （SH） as previous studies have largely focused on partial hepatectomy （PH）. METHODS： Male Wistar rats were subjected to 70% PH or 90% SH, respectively, and sacrificed at different times after surgery. Untreated and sham-operated animals served as controls. Serum and liver samples were obtained to investigate liver function, apoptosis （TUNEL assay） and transcription factors （NF-KB, Stat3; ELISA） or cytokines （HGF, TNF-α, IL-6, TGF-α, TGF-β; quantitative RT-PCR） involved in liver regeneration. RESULTS： Serum levels of ALT and AST in animals with 70% PH differed significantly from sham-operated and control animals. We found that the peak concentration 12 h after surgery returned to control levels 7 d after surgery. LDH was increased only at 12 h after 70% PH compared to sham. Bilirubin showed no differences between the sham and 70% resection. After PH, early NF-kB activation was detected 12 h after surgery （313.21 ± 17.22 ng/mL）, while there was no activation after SH （125.22 ± 44.36 ng/mL） compared to controls （111.43 ± 32.68 ng/mL） at this time point. In SH, however, NF-kB activation was delayed until 24 h （475.56 ± 144.29 ng/mL）. Stat3 activation was similar in both groups. These findings correlated with suppressed and delayed induction of regenerative genes after SH （i.e. TNF-α 24 h postoperatively： 2375 ± 1220 in 70% and 88 ± 31 in 90%; IL-6 12 h postoperatively： 2547 ± 441 in 70% and 173 ± 82 in 90%）. TUNEL staining revealed elevated apoptosis rates in SH （0.44% at 24 h; 0.63% at 7 d） compared to PH （0.27% at 24 h; 0.15% at 7 d）. CONCLUSION： The molecular events involved in liver regeneration are significantly influenced by the extent of resection as SH leads to suppression and delay of liver regeneration compared to PH, which is associated with delayed activation of NF-kB and suppression of proregenerative cytokines.

Morbidity analysis of left hepatic trisectionectomy for hepatobiliary disease and live donor

Background:Despite remarkable advances in surgical techniques and perioperative management,left hepatic trisectionectomy(LHT)remains a challenging procedure with a somewhat high postoperative morbidity rate compared with less-extensive resections.This study aimed to analyze the short-and long-term outcomes of LHT and identify factors associated with the postoperative morbidity of this technically demanding surgical procedure.Methods:The medical records of 53 patients who underwent LHT between June 2005 and October 2019 at a single institution were retrospectively reviewed.The independent prognostic factor of postoperative morbidity was analyzed using the logistic regression model.Results:Hepatocellular carcinoma was the most common indication for surgery(n=21),followed by hilar cholangiocarcinoma(n=14),intrahepatic cholangiocarcinoma(n=10),and other pathologies(including colorectal liver metastasis,hepatolithiasis,gallbladder cancer,living donor,hemangioma,and multilocular biliary cyst;n=8).The rates of postoperative morbidities of Clavien-Dindo grade 3 or higher and 90-day mortality were 39.6% and 1.9%,respectively.The 1-,3-,and 5-year overall survival rates were 81.1%,61.4%,and 44.6%,respectively.Multivariate analysis revealed that preoperative jaundice[hazard ratio(HR)=6.15,95%confidence interval(CI):1.57-24.17,P=0.009]and operative time>420 min(HR=4.66,95%CI:1.27–17.17,P=0.021)were independent predictors of postoperative morbidity.Conclusions:The in-hospital mortality of LHT surgery can be minimalized by a reliable preoperative evaluation of liver function and selection of the dominant anatomic features of right posterior sector,active and appropriate preoperative management for obstructive cholangitis and compensatory hypertrophy of the future remnant posterior sector,and the experience of the surgeon.