Abstract:

Objective: To investigate the efficacy of using liver hanging maneuver (LHM) in associating liver partition and portal vein ligation for staged hepatectomy (ALPPS). Methods: The clinical data of 4 patients with primary liver cancer undergoing ALPPS procedure were retrospectively analyzed. Of the patients, 3 cases had tumor in the right lobe and one case in the caudate lobe. All patients underwent first-stage operation of in situ splitting of the liver parenchyma and right portal vein ligation guided by LHM, and a second-stage of complete tumor removal. Results: In all the 4 patients, the prior hepatic transection, hanging tape positioning and second-stage liver resection were performed successfully. In the first-stage operation, the operative time was 195–273 (232.2±35.3) min, intraoperative blood loss was 420–1 210 (735±344.3) mL, and bile leakage occurred in one case; in the second-stage operation, the operative time was 98–186 (139.5±36.6) min, and intraoperative blood loss was 100–320 (197.5±95.3) mL. No operative death occurred. The patients were followed-up for 3 months, at which time 3 patients were in good condition, and one patient had died of recurrence 2 months after operation. Conclusion: LHM is effective for inferior vena cava protection and clear exposure of the intrahepatic blood vessels and ductal system, so it can be routinely used in ALPPS procedure.

Abstract:

Objective: To compare the clinical efficacies of three hepatic inflow occlusion methods in hepatectomy for large hepatocellular carcinoma. Methods: The clinical data of 218 patients undergoing hepatectomy for large hepatocellular carcinoma (>5 cm) from January 2011 to March 2013 were retrospectively analyzed. During surgery, 88 cases were subjected to intermittent hepatic inflow occlusion with Pringle maneuver (portal occlusion group), 51 cases underwent selective hemihepatic blood flow occlusion (hemihepatic occlusion group), and 79 cases received infrahepatic inferior vena cava (IVC) clamping plus Pringle maneuver (combination occlusion group). The relevant clinical variables among the three groups of patients were compared. Results: There were no significant differences in preoperative conditions, operative time, inflow occlusion time and liver resection volume among the three groups (all P>0.05). In either hemihepatic occlusion group or combination occlusion group, the intraoperative blood loss, blood transfusion volume and blood transfusion rate were all significantly lower than those in portal occlusion group, and the blood transfusion volume and blood transfusion rate in combination occlusion group were also significantly lower than those in hemihepatic occlusion group (all P<0.05). All liver function parameters showed no significant difference among the three groups on postoperative day (POD) one, but the transaminase and total bilirubin levels in both hemihepatic occlusion group and combination group were significantly decreased compared with portal occlusion group on POD 3 and 7 (all P<0.05). No significant difference was noted in incidence of postoperative complications among the three groups (P>0.05). Conclusion: In large liver cancer resection, hepatic inflow control with combination of infrahepatic IVC clamping and Pringle maneuver can not only effectively reduce intraoperative blood loss, but also be advantageous for recovery of postoperative liver function.

Abstract:Objective: To assess the efficacy and safety of percutaneous radiofrequency ablation (RFA) in treatment of recurrent hepatocellular carcinoma (HCC). Methods: The clinical data of 79 patients with recurrent HCC undergoing percutaneous RFA from May 2008 to March 2014 were retrospectively analyzed. There were a total of 106 recurrent lesions in the 79 patients, and the tumor size ranged from 0.8 to 5.0 cm with an average of (2.8±1.0) cm. Results: The success rate of ablation was 98.1% and a complete tumor ablation rate reached 94.2%. The common post-ablation adverse reactions were fever (72.7%), pain in hepatic region (90.9%), gastrointestinal symptoms (20.8%), and jaundice (6.5%). No severe complications such as liver failure, bile leakage, infection, and bleeding occurred, and no perioperative death occurred as well. The length of postoperative hospital stay was 1 to 5 d with an average of (2.2±1.0) d. Follow-up was conducted for 7 to 64 months with an average of (38±14) months, post-ablation recurrence occurred in 54 cases, and the recurrence rate was 70.1%. The 1- and 3-year post-ablation survival rate was 89.6% and 66.2%, respectively. Conclusion: Percutaneous RFA is a safe, effective and minimally invasive treatment method for small recurrent HCC, and should be considered as a preferential alternative for this condition.

Abstract:Objective: To systematically assess the short- and long-term efficacy and safety of laparoscopic liver resection (LLR) and open liver resection (OLR) for liver cancer. Methods: The case-controlled studies comparing LLR and OLR for liver cancer were collected by searching the relevant databases covering scholarly journals, materials, conference proceedings, and dissertations. Data from selected studies were analyzed according to the MOOSE guidelines. After data extraction, a Meta-analysis was performed using RevMan 5.3 software. Results: Fifteen case-controlled studies were finally included, involving 1 246, with 499 cases in LLR group and 747 cases in OLR group. The results of Meta-analysis showed that there was no significant difference between LLR group and OLR group in operative time, 1-, 3-, and 5-year survival rate, 1-, 3-, and 5-year disease-free survival rate and 3-year recurrence rate (all P>0.05), while the intraoperative blood loss, incidence of postoperative complications, perioperative mortality and length of postoperative hospital stay were significantly reduced in LLR group compared with OLR group (all P<0.05). Conclusion: LLR offers the same radical resection for liver cancer as does OLR, with a similar short- and long-term efficacy but reduced perioperative adverse events.

Abstract:Objective: To evaluate the clinical significance of determination of the preoperative level of total bile acid (TBA) in hepatocellular carcinoma (HCC) patients. Methods: The clinical data of 176 HCC patients undergoing surgical treatment were retrospectively analyzed. Of the patients, 173 cases had Child-Pugh A and 3 cases had Child-Pugh B liver function. The sensitivity of the preoperative TBA level and other liver function indexes in estimating liver cirrhosis, and the relationship between preoperative TBA level and operative complications were analyzed. Results: Eighty-eight patients were diagnosed with liver cirrhosis and 6 cases among the non-cirrhotic patients were diagnosed as Knodell stage S4 by postoperative pathology, and surgery-associated complications occurred in 27 patients (15.3%) in the entire group. Compared with non-cirrhotic patients, the preoperative TBA level in patients with liver cirrhosis was significantly increased (P<0.05), while parameters irrelevant to liver function showed no significant difference (all P>0.05), and in non-cirrhotic patients, the preoperative TBA level were significantly higher in cases with Knodell stage S4 than that in those with Knodell stage S1 to S3 (all P<0.05). The incidence of operative complications in patients with preoperative TBA level ≥10 μmol/L was significantly higher than in those with preoperative TBA level <10 μmol/L (P<0.05). Conclusion: Preoperative TBA level is a sensitive indicator for assessing liver function in HCC patients, and in those with preoperative TBA ≥10 μmol/L, uni-segmental or local hepatectomy should be considered.

Abstract:

Objective: To investigate the expressions of Numb and vascular endothelial growth factor (VEGF) in primary hepatocellular carcinoma (HCC), and the clinical significance. Methods: The Numb and VEGF expressions in the surgical specimens of HCC tissue along with tumor adjacent tissues from 60 HCC patients, and normal liver tissues from 27 cases with liver injury or hepatic hemangioma were determined by immunohistochemical staining. The relations of Numb and VEGF expressions with the clinicopathologic factors and prognosis of the HCC patients were analyzed. Results: Compared with normal hepatic tissue and tumor adjacent tissue, the positive Numb expression rate was significantly decreased, while the positive VEGF expression was significantly increased in HCC tissue (both P<0.05), further, there was a negative relation between Numb and VEGF expression in HCC tissue (r=–0.5248, P=0.01). Both Numb and VEGF expressions were significantly associated with TNM stage, and Edmondson grade, and the presence or absence of portal cancer embolus and tumor capsule (all P<0.05). The overall survival period in patients with negative Numb expression was significantly shorter than in those with positive Numb expression, but the finding for VEGF expression was the opposite of that (both P<0.05). Conclusion: Numb expression is decreased and VEGF expression is increased in HCC tissue, and waxing and waning between them may closely relate to the invasiveness and poor prognosis of HCC.

Abstract:Objective: To investigate the general properties of the complexes of VEGF siRNA-loaded RGD-conjugated gold nanoparticles (GNPs) (GNPs-TyrRGD-VEGFsiRNA) and their impact on necrotic effect of radiofrequency ablation (RFA) in the liver. Methods: GNPs-TyrRGD-VEGFsiRNA complexes were synthetized by chemical and electrostatic adsorption methods and the discreteness of the complexes was examined by electron microscope. The stability of the VEGF siRNA in the complexes was tested by gel electrophoresis, the cytotoxicity of complexes to normal hepatic cells was determined by CCK-8 assay, the binding capacities of the complexes to normal hepatic cells and liver cancer cells after co-incubation were analyzed by using electron microscopy, and the impact of the complexes on the necrotic effect of RFA were observed in the in-vitro pig liver. Results: The complexes showed a higher discreteness than the naked GNPs and the content of VEGF siRNA in the complexes was approximately equal to the initially loaded content. Both the complexes and naked GNPs exhibited almost no cytotoxicity to the normal hepatic cells at a concentration below 30% and the binding ability of the complexes to the liver cancer cells was significantly greater than that to the normal hepatic cells (P<0.05), but the naked GNPs showed no difference between binding ability to the two types of cells (P>0.05). The lesion diameter induced by RFA with the complexes injected through radiofrequency needle was significantly larger than that in control group with saline injection [(2.19±0.24) cm vs. (1.71±0.14) cm, P<0.05]. Conclusion: GNPs-TryRGD-VEGFsiRNA complexes can integrate targeted concentration and targeted therapy as a whole, and may also be helpful for enhancing the efficacy of liver cancer RFA treatment.

Abstract:Objective: To investigate the drug resistance reversing effect of gold nanoparticles (GNPs) on drug-resistant human hepatocellular carcinoma cell line. Methods: GNPs were synthesized by reducing hydrogen tetrachloroaurate using tri-sodium citrate, and identified. Adriamycin (ADM)-resistant hepatocellular carcinoma HepG2/ADM cells were treated with GNP and adriamycin (ADM), alone or in combination, using HepG2/ADM cells without any treatment as a control, and then the cell proliferation and apoptosis were determined by MTT assay and flow cytometry, respectively. The intracellular ADM concentration of HepG2/ADM cells after exposure to ADM alone or GNP plus ADM were determined by ultraviolet-visible spectrophotometer. Results: Compared with control cells, the cell proliferation was inhibited and apoptosis rate was increased significantly in HepG2/ADM cells treated with ADM along or combination with GNP, and these effects were more remarkable in the latter than in the former (all P<0.05). The intracellular ADM concentration in HepG2/ADM cells exposed to GNP plus ADM was significantly higher than in those exposed to ADM alone [(2.92±0.13) μg/L vs. (1.68±0.74) μg/L, P<0.05]. Conclusion: GNP can enhance the sensitivity of HepG2/ADM cells to ADM, and this effect may be related to its increasing the intracellular ADM accumulation in HepG2/ADM cells.

Abstract:Objective: The investigate the inhibitory effect of the adenovirus-mediated CD/TK double suicide gene system driven by KDR promoter (Ad-KDRP-CD/TK) combined with survivin gene interference on the growth of hepatocellular carcinoma (HCC) cells in nude mice. Methods: Twenty nude mice were equally randomized into model group (subcutaneous implantation of HCC BEL-7402 cells to establish xenograft tumor without other additional treatment), double suicide gene transfection group (subcutaneous implantation of BEL-7402 cells transfected with Ad-KDRP-CD/TK, followed by intratumor injection with the prodrug gancilovir and 5-fluorocytosine after tumor formation), survivin siRNA transfection group (subcutaneous implantation of BEL-7402 cells, followed by intratumor injection with survivin siRNA/Lip-DMEM transfection complex after tumor formation), and combination transfection group (double suicide gene transfection plus survivin siRNA transfection). Two weeks after transfection treatment, mice in each group were sacrificed, tumor weight and tumor inhibition rate were measured, the microvessel density (MVD), and survivin mRNA and protein expressions in the tumor tissues were determined. Results: In each treatment group compared with model group, the tumor weight was significantly reduced, with the maximum tumor inhibition in combination transfection group (all P<0.05); the MVD, and the expression levels of survivin mRNA and protein were significantly decreased, with the maximum decreasing amplitude in combination transfection group (all P<0.05). Conclusion: Double suicide gene combined with survivin gene interference is an effective method to inhibit the growth of HCC cells in vivo.

Abstract:Objective: To investigate the expressions of TGF-β1 and Smad7 and change of dendritic cells (DCs) in colorectal cancer liver metastases (CRLM) tissue and the clinical significance. Methods: The expressions of TGF-β1, Smad7, CD1α (marker of immature DCs) and CD83 (marker of mature DCs) in resection specimens of CRLM tissue and normal liver tissue around the CRLM with negative margin were determined by immunohistochemical staining. The mutual relations among these expressions in CRLM tissue and their relations with the characteristics of the primary tumor were analyzed. Results: The expressions of TGF-β1, Smad7, and CD1α in CRLM tissue were significantly higher than those in normal liver tissue (all P<0.05), and their expressions showed mutual positive correlations in CRLM tissue (r=0.455, r=0.623, r=0.448, all P<0.05); CD83 expression was negative in almost all the studied CRLM tissue specimens, and only two cases of weak positive expression were found in the normal liver tissue specimens. All expressions of TGF-β1, Smad7 and CD1α were significantly related to the depth of invasion of the primary tumor and lymph node metastasis (all P<0.05), but irrelevant to differentiation of the primary tumor (P>0.05) in CRLM patients. Conclusion: The high TGF-β1 and Smad7 expressions and increased immature DCs number may together promote the occurrence and development of CRLM.

Abstract:Objective: To investigate the alleviation effect of ischemic preconditioning (IP) on hepatic ischemia-reperfusion (I/R) injury in rats and the mechanism. Methods: Fifteen male SD rats were equally randomized into sham operation group, I/R group and IP plus I/R group, respectively. I/R injury model was created by Pringle maneuver (30-min hepatic ischemia followed by 3-h reperfusion), and IP was induced by 10-min hepatic ischemia followed by 10-min reperfusion prior to I/R. Rats in each group were sacrificed and samples were collected after 3-h reperfusion, liver specimen pathological examination and measurement of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were performed, and meanwhile, the NF-κB protein expression, and the levels of inflammatory cytokines (IL-1β and TNF-α) as well as oxidative stress indexes that included malondialdehyde (MDA) and myeloperoxidase (MPO) in the liver tissues were determined. Results: Except in sham operation group, the liver tissues from either I/R group or IP plus I/R group showed pathological changes of liver injury, but the injury was milder in IP plus I/R group than that in I/R group. In both I/R group and IP plus I/R group compared with sham operation group, the serum AST and ALT levels, and liver tissue levels of NF-κB protein expression, IL-1β, TNF-α, MDA and MPO were all significantly increased (all P<0.05), but the increasing amplitudes of all these parameters in IP plus I/R group were significantly less than those in I/R group (all P<0.05). Conclusion: IP lessens hepatic I/R through inhibiting NF-κB activity, and thereby reduces inflammatory and oxidative stress responses.

Abstract:Objective: To assess the application value and efficacy of interventional therapy for hepatic artery complications after liver transplantation. Methods: The diagnosis and treatment as well as the follow-up data of 49 patients with suspicious hepatic artery complications after liver transplantation during January 2006 to January 2012 were retrospectively analyzed. Results: Hepatic artery complications were detected in 26 patients by hepatic arteriography. Hepatic artery stenosis was found in 21 patients, of whom 6 cases with mild and moderate stenosis underwent no treatment; 15 cases with severe stenosis underwent hepatic artery stent placement and intra-stent restenosis developed in 3 of them during follow-up. Pseudoaneurysm formation was found in 2 patients, of whom one case underwent covered stent placement and the aneurysm was completely occluded; one case developed hepatic artery occlusion after undergoing stent-assisted coil embolization, and extensive biliary necrosis occurred at 1.5 months of follow-up, and then underwent percutaneous transhepatic biliary drainage. Hepatic artery thrombosis was found in 3 patients, of whom one case received transcatheter thrombolysis and no thrombosis formation was observed during 23 months of follow-up; one case with ineffective thrombolysis underwent a second liver transplantation 3 d after interventional treatment; one case with hepatic artery occlusion did not undergo treatment because the collateral circulation was established. Conclusion: Interventional therapy can effectively deal with various hepatic artery complications after liver transplantation and has certain application value in ensuring the success of liver transplantation and improving the survival of the patients.

Abstract:Objective: To investigate the clinical efficacy and value of using radiofrequency coagulation device in liver resection. Methods: The clinical data of 108 patients undergoing hepatectomy from July 2011 to July 2013 were retrospective analyzed. Of the patients, 41 cases underwent radiofrequency-assisted liver transection (observational group), and 67 cases underwent liver transection using conventional clamp technique (control group). The clinical variables between the two groups were compared. Results: In observational group compared with control group, the operative time, intraoperative blood loss, and the percentage of cases requiring blood transfusion and hepatic portal occlusion were reduced, the values of postoperative transaminase and bilirubin were decreased, the volume of postoperative peritoneal drainage and length of hospital stay were decreased, and all the differences reached statistical significance (all P<0.05). There was no statistical difference in incidence of postoperative complications and hospitalization costs between the two group (both P>0.05). Conclusion: The use of radiofrequency coagulation in liver resection can effectively control blood loss and decrease liver damage and length of hospital stay, and does not increase medical expenses, so it can valuably be applied in hepatectomy.

Abstract:

Objective: To evaluate the application value of microwave hemostatic device in laparoscopic hepatectomy. Methods: The clinical data of 28 patients undergoing laparoscopic hepatectomy with microwave hemostatic device (HeSetor) from July 2009 to June 2013 were retrospectively analyzed. Results: Laparoscopic hepatectomy was successfully completed in all the 28 patients and no conversion or surgical death occurred. The average operative time was (124±45) min and average intraoperative blood loss was (140±110) mL. No postoperative hemorrhage, bile leakage or liver function failure occurred in the entire group of patients. The mean length of postoperative hospital stay was (6.9±2.7) d. Follow-up was conducted for 6 to 53 months in the 28 patients, and intrahepatic recurrence occurred in 6 cases with hepatocellular carcinoma in postoperative 5–16 months, but no port site tumor implantation was observed. Conclusion: Laparoscopic hepatectomy with microwave hemostatic device can provide excellent hemostatic effect without severe postoperative complications, so it is a safe and feasible technique for liver resection.

Abstract:Objective: To systematically assess the safety and efficacy of using fast track surgery (FTS) technique in liver resection. Methods: The randomized controlled trials (RCTs) or clinical controlled trials (CCTs) concerning using fast-track surgery in hepatectomy were collected by searching several national and international databases. Data collection ended in October 2014. After screening for inclusion and data extraction, Meta-analysis was performed by the RevMan 5.2.3 software. Results: Five RCTs and 11 CCTs were finally included involving 1 529 patients, of whom 766 cases underwent hepatectomy with FTS protocol (FTS group) and 763 cases underwent hepatectomy with traditional perioperative management (control group). Meta-analysis results showed that in FTS group compared with the control group, the time to first postoperative flatus and food intake, as well as length of hospital stay were significantly shorter, hospitalization cost was significantly reduced, times for recovery of each of the liver function parameters and overall incidence of postoperative complications were all significantly decreased (all P<0.05). Conclusion: Application of FTS in hepatectomy is safe and effective, and it also can accelerate the postoperative recovery of patients.

Abstract:Objective: To compare different perioperative nutritional support methods for patients undergoing liver resection under fast track (FT) scheme. Methods: One hundred and four patients scheduled for liver resection were equally randomized into two groups to receive enteral nutrition support (EN group) and parenteral nutrition support (PN group), respectively. All patients underwent FT perioperative management. Comparison was made between the two groups in pre- and postoperative changes in body weight (WT) and hemoglobin (HB), total protein (TP), albumin (ALB) and total lymphocyte count (TLC), and postoperative time to first flatus and defecation, length of postoperative hospital stay, and incidence of gastrointestinal adverse reactions and postoperative complications. Results: The nutrition indicators on postoperative 7 d were all decreased significantly compared with preoperative 3 d values in PN group, among which only TP and ALB levels were significantly decreased in EN group, but the decreasing amplitudes were significantly less than those in PN group (all P<0.05). In EN group, compared to PN group, the time to either flatus or defecation was shortened, and the incidence of adverse reactions was reduced (all P<0.05). There was no significant difference in length of postoperative hospital stay and incidence of postoperative complications between the two groups (all P<0.05). Conclusion: For hepatectomy patients receiving fast track protocol, perioperative EN support is beneficial for improving nutritional status and immune function, and accelerating postoperative recovery.

Abstract:Hypoxia inducible factor 2 (HIF-2) is a member of the basic helix-loop-helix/Per Arnt-Sim (bHLH-PAS) family, which can regulate the expressions of a variety of genes in response to intracellular hypoxia, and also closely related to tumor occurrence and development. Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China, with limited therapeutic options and high mortality. So, investigation of the role of HIF-2 in HCC may provide insights into improving treatment access and outcomes of the patients.

Abstract:MicroRNAs (miRNAs) are endogenous non-coding RNAs, participating in diverse pathways that regulate tumor occurrence and progression. Hepatocellular carcinoma (HCC) is one of the most common malignancies, with poor prognosis due to lack of effective treatment modalities at present. Studies have showed that miR-122 plays an important suppressive role in genesis and progression of HCC, so it may probably become a novel biomarker for diagnosis and prognosis as well as therapeutic target of HCC. Here, the authors present the research progress in relationship between miR-122 and HCC.

Abstract:Liver cancer is a common malignancy, and its treatment strategy is mainly surgery-based comprehensive therapy, but the prognosis is still poor because of high frequency of postoperative recurrence and metastasis. According to the cancer stem cell theory, liver cancer can be radically cured only by eradication of the liver cancer stem cells, which leads to the isolation and identification of the liver cancer stem cells to become a hot area of research. This article overviews the research progress in surface markers of liver stem cells.

Abstract:Transcatheter arterial chemoembolization (TACE) has now been widely used in unresectable liver cancer, and also used in liver cancer complicated with portal vein tumor thrombus (PVTT). Here, the authors address the issues of application of TACE in liver cancer with PVTT, and the complications as well as the aspects that need to be improved.