BACKGROUND: The clinical trials emerged centromere protein E inhibitor GSK923295 as a promising anticancer drug, but its function in hepatocellular carcinoma (HCC) remain needs to be fully elucidated, especially as chemotherapy after hepatectomy for liver tumors. We aimed to describe anti-HCC activities of GSK923295 and compare its antiproliferative effects on liver regeneration after partial hepatectomy (PH). METHODS: All subjects were randomized to treatment with either vehicle or GSK923295. Antitumor activity of GSK923295 was assessed by xenograft growth assays. The C57BL/6 mice were subjected to 70% PH and the proliferation was calculated by liver coefficient, further confirmed by immunohistochemistry. The proliferation and cell cycle analysis of liver cell AML12 and HCC cells LM3, HUH7, and HepG2 were investigated using the cell counting kit-8 assay and Flow Cytometry. The chromosome misalignment and segregation in AML12 cells were visualized by immunofluorescence. RESULTS: Treatment with GSK923295 induced antiproliferation in HCC cell lines. It also caused delay on HCC tumor growth instead of regression both in a HCC cell line xenograft model and patient-derived tumor xenograft model. With microarray analysis, CENtromere Protein E was gradually increased in mouse liver after PH. Exposure of liver cells to GSK923295 resulted in delay on a cell cycle in mitosis with a phenotype of misaligned chromosomes and chromosomes clustered. In 70% PH mouse model, GSK923295 treatment also remarkably reduced liver regeneration in later stage, in parallel with the mitotic marker phospho-histone H3 elevation. CONCLUSION The anticancer drug GSK923295 causes a significant delay on HCC tumor growth and liver regeneration after PH in later stage.
Animals ; Antineoplastic Agents ; therapeutic use ; Blotting, Western ; Bridged Bicyclo Compounds, Heterocyclic ; therapeutic use ; Carcinoma, Hepatocellular ; drug therapy ; surgery ; Cell Cycle ; drug effects ; Cell Proliferation ; drug effects ; Chromosomal Proteins, Non-Histone ; antagonists & inhibitors ; Electrophoresis, Polyacrylamide Gel ; Female ; Fluorescent Antibody Technique ; Humans ; Immunohistochemistry ; Liver Neoplasms ; drug therapy ; surgery ; Liver Regeneration ; physiology ; Mice ; Mice, Inbred C57BL ; Real-Time Polymerase Chain Reaction ; Sarcosine ; analogs & derivatives ; therapeutic use ; Xenograft Model Antitumor Assays

OBJECTIVETo explore the value of nutrition management in obese patients with type 2 diabetes mellitus(T2DM) after laparoscopic sleeve gastrectomy(LSG).

METHODSClinical data of 22 obese T2DM patients undergoing LSG from March 2013 to July 2015 in Fudan University Pudong Medical Center were collected. All the patients strictly followed the specialized instruction by nutritionists: diabetic and low calorie diet 3347.2 to 5020.8 kJ (800 to 1200 kcal) per day before the operation; low calorie liquid diet 2510.4 kJ(600 kcal) per day before operation for promoting gastric emptying; fasting diet before postoperative ventilation; clear liquid diet 1673.6 to 2510.4 kJ (400 to 600 kcal) per day after postoperative ventilation (liquid intake >2000 ml); low fat liquid diet 2928.8 to 3765.6 kJ (700 to 900 kcal) per day (protein 60 g per day at least, 2000 ml liquid) 2 weeks after the operation; semi-liquid diet 1 month after operation and gradually normal diet. All the 22 patients were followed up at 1 week, 1, 3, 6 months after operation on time. Changes of body weight, waist circumference, hip circumference, body mass index(BMI), blood glucose indexes induding fasting blood glucose(FBG), 2-hour postparandial blood glucose(PBG), fasting C-peptide, 2-hour postprandial C-peptide, fasting serum inculin(FINS), 2-hour postprandial inculin(INS), HbAlc, blood pressure and blood lipid indexes were observed and analyzed before and 1 week, 1, 3, 6 months after operation.

RESULTSThe average age of 22 patients (10 men and 12 women) was 38.6 years (18 to 66 years). The duration of diabetes varied from 1 month to 15 years. Comorbidity included 12 patients of high blood pressure, 14 of fatty liver, 1 of coronary heart disease, 1 of gout, 1 of chronic thyroiditis and 1 of menstrual disorder. LSG was performed successfully in all the patients and no severe complications and transference to laparotomy occurred. As compared to pre-operation, at 6 months after operation, the average body weight decreased from (103.9±20.2) kg to (80.9±12.6) kg (t=6.294, P=0.000), waist circumference from (118.6±13.8) cm to (96.4±8.0) cm (t=6.331, P=0.000), hip circumference from (116.9±12.6) cm to (104.0±7.7) cm (t=3.854, P=0.000), BMI from (36.2±5.9) kg/mto (27.9±3.5) kg/m(t=5.630, P=0.000), showing a decreasing trend over time. There was no underweight patient after 6 months follow-up. As compared to pre-operation, at 6 months after operation, the average FBG reduced from (7.4±1.4) mmol/L to (6.0±0.9) mmol/L (t=3.172, P=0.003), 2 h PBG from (14.1±4.9) mmol/L to (7.5±2.2) mmol/L (t=7.026, P=0.000), FINS from (160.0±71.9) mIU/L to (43.8±20.8) mIU/L (t=7.259, P=0.000), 2-hour postprandial INS from (437.6±261.4) mIU/L to (140.5±104.6) mIU/L (t=5.858, P=0.000), fasting C-peptide from (1.1±0.6) μg/L to (0.7±0.3) μg/L (t=3.560, P=0.000), 2-hour postprandial C-peptide from (2.5±0.9) μg/L to (1.5±0.7) μg/L (t=3.865, P=0.000), HbAlc from (8.0±1.6)% to (5.9±0.6)% (t=5.953, P=0.000), showing a decreasing trend over time except FBG, 2h postprandial C-peptide and HbAlc(all P<0.05). FBG and 2-hour PBG of 16 patients returned to normal 3 months after the operation. Blood pressure and trigly ceride decreased obviously 6 months after operation compared to pre-operation with significant difference(P<0.05). At 6 months after operation, blood pressure of 8 comorbidity patients with high blood pressure became normal (8/12, 66.7%) and of 4 patients improved(4/12, 33.3%); B ultrasound examination revealed normal in 11 comorbidity patients with fatty liver(11/14,78.6%) and improvement in 3 patients (3/14,15.4%). Blood uric acid of the gout patient and the menstruation of the menstrual disorder patient returned to normal 3 months and 1 month after the operation respectively.

CONCLUSIONAs for obese patients with T2DM undergoing LSG, reasonable nutrition management is helpful to decrease body weight, and to obtain an ideal improvement of blood glucose and blood lipid levels.

Adolescent ; Adult ; Aged ; Bariatric Surgery ; Blood Glucose ; physiology ; Body Weights and Measures ; C-Peptide ; blood ; physiology ; Caloric Restriction ; Combined Modality Therapy ; Comorbidity ; Coronary Disease ; complications ; Diabetes Mellitus, Type 2 ; complications ; therapy ; Diet Therapy ; methods ; Diet, Diabetic ; Endoscopy ; Fatty Liver ; complications ; surgery ; Female ; Food, Formulated ; Gastrectomy ; Glycated Hemoglobin A ; physiology ; Gout ; complications ; surgery ; Hashimoto Disease ; complications ; Humans ; Hypertension ; complications ; surgery ; Insulin ; blood ; physiology ; Lipids ; blood ; physiology ; Male ; Menstruation Disturbances ; complications ; surgery ; Middle Aged ; Obesity ; complications ; therapy ; Perioperative Care ; methods ; Thyroiditis ; complications ; Treatment Outcome ; Triglycerides ; blood ; physiology

BACKGROUND/AIMS: We experimented with different ablation methods and two types of microwave antennas to determine whether microwave ablation (MWA) increases intrahepatic pressure and to identify an MWA protocol that avoids increasing intrahepatic pressure. METHODS: MWA was performed using either a single-step standard ablation or a stepwise increment ablation paired with either a 16-gauge (G) 2-cm antenna or a 14G 4-cm antenna. We compared the maximum pressures and total ablation volumes. RESULTS: The mean maximum intrahepatic pressures and ablation volumes were as follows: 16G single-step: 37+/-33.4 mm Hg and 4.63 cm3; 16G multistep: 31+/-18.7 mm Hg and 3.75 cm3; 14G single-step: 114+/-45.4 mm Hg and 15.33 cm3; and 14G multistep: 106+/-43.8 mm Hg and 10.98 cm3. The intrahepatic pressure rose during MWA, but there were no statistically significant differences between the single and multistep methods when the same gauge antennae were used. The total ablation volume was different only in the 14G groups (p<0.05). CONCLUSIONS: We demonstrated an increase in intrahepatic pressure during MWA. The multistep method may be used to prevent increased intrahepatic pressure after applying the proper power.
Ablation Techniques/instrumentation/*methods ; Animals ; Cattle ; Liver/*physiology/surgery ; Medical Illustration ; *Microwaves ; Models, Animal ; *Pressure

OBJECTIVETo explore the impact of microwave dealing with cutting surface on perioperative liver function recovery and recurrence and metastasis after hepatectomy for HCC.

METHODSClinical data of 133 patients with HCC from March 2009 to November 2010 were retrospectively analyzed. They were divided into the conventional surgery group (66 cases) and microwave treatment group (67 cases). A domestic ECO-100 microwave knife was inserted into the liver cutting surface 0.5 cm from the cutting edge, and repeated multi-point burning with an average time of 25 minutes in the microwave treatment group. Then the perioperative liver function recovery and recurrence and metastasis in the two groups were compared.

RESULTSThe operation time of conventional surgery group was (158.0 ± 31.0) minutes, and that of microwave treatment group was significantly longer (181.0 ± 28.0) minutes (P=0.027). There were no significant differences in the liver function recovery between the two groups (P>0.05). There were 6 cases of recurrence and metastasis after 6 months and 9 cases after 12 months in the microwave treatment group, while there were 15 cases of recurrence and metastasis after 6 months and 20 cases after 12 months in the conventional surgery group, showing a significant difference (P=0.034 and 0.022, respectively).

CONCLUSIONSMicrowave dealing with the cutting surface has no significant effect on perioperative liver function recovery in hepatectomy. However, microwave treatment can reduce the in situ recurrence in HCC patients within the first year after surgery, indicating a good clinical application value.

Carcinoma, Hepatocellular ; surgery ; therapy ; Hepatectomy ; Humans ; Liver ; physiology ; Liver Neoplasms ; surgery ; therapy ; Microwaves ; therapeutic use ; Neoplasm Recurrence, Local ; prevention & control ; Operative Time ; Recovery of Function ; Retrospective Studies

Living donor liver transplantation (LDLT) is a curative treatment for end stage liver disease. It is advantageous due to the shortage of deceased donors. However, in LDLT, whether the middle hepatic vein (MHV) should be preserved in donors remains controversial. We conducted searches in Pubmed, Embase, Cochrane Library, Web of Science, Ovid, and Google Scholar using the key words "living donor liver transplantation" and "middle hepatic vein". Due to ethical issues, there were no randomized control trails focusing on MHV in LDLT. The majority of reports were retrospective studies. We examined the reference lists to identify related investigations. Google Scholar was then used to obtain full texts. Nine observational studies were analyzed. There were no significant differences in liver function (WMD, -5.51; P=0.12) and complications (RR, 0.98; P=0.89) in donors with or without MHV. However, the liver function in recipients was greatly improved after LDLT with MHV (WMD, -78.32; P=0.01). No definite conclusion was obtained in terms of the liver regeneration indices between LDLT with or without MHV. It was conclude that grafts with MHV in LDLT favor recipient outcomes and do not harm the living donor if a careful preoperative evaluation is performed.
Adult ; Databases, Bibliographic ; Female ; Graft Survival ; Hepatic Veins ; surgery ; Humans ; Liver ; blood supply ; physiology ; Liver Transplantation ; Living Donors ; Male ; Middle Aged ; Observational Studies as Topic ; Prognosis

Based on their ability to differentiate into multiple cell types including hepatocytes, the transplantation of mesenchymal stem cells (MSCs) has been suggested as an effective therapy for chronic liver diseases. The aim of this study was to evaluate the safety, efficacy and therapeutic effects of MSCs in patients with chronic liver disease through a literature-based examination. We performed a systematic review (SR) and meta-analysis (MA) of the literature using the Ovid-MEDLINE, EMBASE and Cochrane Library databases (up to November 2014) to identify clinical studies in which patients with liver diseases were treated with MSC therapy. Of the 568 studies identified by the initial literature search, we analyzed 14 studies and 448 patients based on our selection criteria. None of the studies reported the occurrence of statistically significant adverse events, side effects or complications. The majority of the analyzed studies showed improvements in liver function, ascites and encephalopathy. In particular, an MA showed that MSC therapy improved the total bilirubin level, the serum albumin level and the Model for End-stage Liver Disease (MELD) score after MSC treatment. Based on these results, MSC transplantation is considered to be safe for the treatment of chronic liver disease. However, although MSCs are potential therapeutic agents that may improve liver function, in order to obtain meaningful insights into their clinical efficacy, further robust clinical studies must be conducted to evaluate the clinical outcomes, such as histological improvement, increased survival and reduced liver-related complications, in patients with chronic liver disease.
Cell Differentiation/physiology ; Cell- and Tissue-Based Therapy/adverse effects/*methods ; Hepatocytes/cytology ; Humans ; Liver/physiopathology/surgery ; Liver Diseases/*therapy ; Liver Function Tests ; Mesenchymal Stem Cell Transplantation/adverse effects/*methods ; Mesenchymal Stromal Cells/*cytology

OBJECTIVETo investigate whether RNA interference (RNAi) of LXRα gene in donor rats with fatty liver improves liver graft function after transplantation.

METHODSFifty donor SD rats were fed a high-fat diet and 56% alcohol to induce macrovesicular steatosis exceeding 60% in the liver. The donor rats were injected via the portal veins with 7 × 10⁷ TU LXRα-RNAi-LV mixture (n=25) or negative control-LV (NC-LV) vector (n=25) 72 h before orthotopic liver transplantation. At 2, 24, and 72 h after the transplantation, the recipient rats were sacrificed to examine liver transaminases, liver graft histology, immunostaining (TUNEL), and protein and mRNA levels of LXRα.

RESULTSLentivirus-LXRα RNAi inhibited LXRα gene expression at both the mRNA and protein levels in the liver graft and reduced the expressions of SREBP-1c and CD36 as compared with the controls, resulting also in reduced fatty acid accumulation in the hepatocytes. The recipient rats receiving RNAi-treated grafts showed more obvious reduction in serum ALT, AST, IL-1β and TNF-α levels, and exhibited milder hepatic pathologies than the control rats after the transplantation. TUNEL assay demonstrated a significant reduction in cell apoptosis in LXRα-RNAi-LV-treated liver grafts, and the rats receiving treated liver grafts had a prolonged mean overall survival time.

CONCLUSIONLXRα-RNAi-LV treatment of the donor rats with fatty liver can significantly down-regulate LXRα gene expression in the liver graft and improve the graft function and recipient rat survival after liver transplantation.

Animals ; Fatty Liver ; genetics ; surgery ; Gene Expression Regulation ; Hepatocytes ; cytology ; Lentivirus ; Liver ; physiology ; Liver Transplantation ; Liver X Receptors ; Orphan Nuclear Receptors ; genetics ; RNA Interference ; RNA, Messenger ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo perform a meta-analysis of randomized controlled trials (RCTs) assessing the benefit of providing branched chain amino acid (BCAA)-enriched nutrition to improve hepatic function in patients undergoing hepatic operation.

METHODSThe electronic databases of PubMed, Springerlink, the Chinese Biomedical Database (CBM), the Cochrane Library, and the China National Knowledge Infrastructure (CNKI) were searched for relevant RCTs using the following search terms: nutritional support, enteral nutrition, parenteral nutrition, hepatic/liver surgery, liver cirrhosis, cancer, hepatectomy, and liver transplantation. The quality of the retrieved RCTs was assessed according to the scale developed by the Cochrane Collaboration. The meta-analysis was conducted using RevMan software, version 5.2.

RESULTSA total of 11 relevant RCTs, representing 510 patients, were included in the meta-analysis. Compared to patients in the control (normal nutrition) group, the patients in the BCAA group experienced an effective improvement in hepatic function, as evidenced by significant decreases in total bilirubin (by 0.07 mumol/L; 95% confidence interval (CI): -0.18 to 0.05, P more than 0.05]. In addition, the BCAA group showed improvements in plasma levels of albumin (weighted mean difference (WMD) = 0.07; 95% CI: 0.06, 0.24, P less than 0.05) and alanine aminotransferase (WMD = +5.61; 95% CI: -8.63 to 19.86, P more than 0.05] but neither of the changes reached the threshold of a statistically significant improvement. The BCAA group did however show significantly lower complication rate after operation (65%, 95% CI: 0.48, 0.87, P less than 0.01] and mean duration of hospital stay (4.61 days; 95% CI: -6.61, -2.61, P less than 0.01].

CONCLUSIONBCAA-enriched nutrition improves hepatic function in patients undergoing hepatic operation, thereby helping to reduce the complication risk, duration of hospital stay, and financial burden. BCAA-enriched nutrition is a safe and effective therapy and further clinical application may be beneficial.

Amino Acids, Branched-Chain ; therapeutic use ; Hepatectomy ; methods ; Humans ; Intraoperative Period ; Liver ; physiology ; surgery ; Liver Transplantation ; methods ; Nutritional Support ; methods ; Randomized Controlled Trials as Topic

OBJECTIVETo perform a comparative analysis of the reactivation rate of hepatitis B virus (HBV) infection and related risk factors after treatment of HBV-related hepatocellular carcinoma (HCC) by radiofrequency ablation (RFA) or hepatic resection.

METHODSWe retrospectively analyzed the HBV reactivation rate and related risk factors of a cohort of 218 patients treated for HBV-related HCC between August 2008 and August 2011; the study population consisted of 125 patients who received RFA and 93 patients who received hepatic resection. Comparisons were made using the unpaired Student's t-test for continuous variables and the x2-test and Fisher's exact test for categorical variables. Univariate and multivariate logistic regression analysis was used to assess risk factors.

RESULTSTwenty patients showed HBV reactivation following treatment, but the incidence was significantly lower in the RFA group than in the hepatic resection group (5.6% vs. 14.0%, 7/125 vs. 13/93, x2 = 4.492, P = 0.034). The univariate and multivariate analysis indicated that no antiviral therapy (OR = 11.7; 95% CI: 1.52-90.8, P = 0.018) and the treatment type (i.e. RFA or hepatic resection) (OR = 3.36; 95% CI: 1.26-8.97, P = 0.016) were significant risk factors of HBV reactivation. Subgroup analysis showed that the incidence of HBV reactivation was lower in patients who received antiviral therapy than in those who did not for both the RFA group and the hepatic resection group but the difference was not significant in the former group (1/68 vs. 19/150, x2=7.039, P = 0.008 and 0/33 vs. 7/92, x2 = 2.660, P = 0.188, respectively). However, the incidence of HBV reactivation in patients who did not receive antiviral therapy was higher than in those who did receive antiviral therapy in the hepatic resection group (12/58 vs. 1/35, x2 = 5.773, P = 0.027).

CONCLUSIONThe incidence of HBV reactivation was lower in patients who received RFA than in those who received hepatic resection to treat HBV-related HCC. Antiviral therapy prior to the hepatic resection treatment may be beneficial for reducing the incidence of HBV reactivation.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Hepatocellular ; surgery ; virology ; Catheter Ablation ; adverse effects ; Female ; Hepatectomy ; adverse effects ; Hepatitis B virus ; physiology ; Humans ; Incidence ; Liver Neoplasms ; surgery ; virology ; Male ; Middle Aged ; Retrospective Studies ; Virus Activation ; Young Adult

BACKGROUNDHepatic artery variations are frequent clinical occurrences. The aim of this study was to investigate the characteristic course of variant hepatic arteries originating from the superior mesenteric artery for the purpose of providing instructions for abdominal tumor surgery.

METHODSThe course of variant hepatic arteries originating from the superior mesenteric artery was studied in 400 patients with liver cancer confirmed by digital subtraction angiography (DSA) and multi-slice spiral computed tomography angiography (MSCTA), and 86 patients with gastric cancer confirmed by preoperative MSCTA between June 2008 and June 2010 in the First Affiliated Hospital of Guangxi Medical University.

RESULTSHepatic artery variations originating from the superior mesenteric artery were noticed in 49 liver cancer patients and 14 gastric cancer patients (total 63 cases), with a variation rate of 12.96%, including two cases (3.17%) where the hepatic arteries ran along the anterior pancreas, and 61 cases (96.83%) where the hepatic arteries ran along the posterior pancreas.

CONCLUSIONSHepatic artery variations originating from the superior mesenteric artery present as two types: the pre-pancreas type and the post-pancreas type with the latter predominating. This finding is of clinical significance in abdominal tumor surgeries where clearance of portal lymph nodes is needed.

Hepatic Artery ; physiology ; Humans ; Liver Neoplasms ; surgery ; Mesenteric Artery, Superior ; physiology ; Middle Aged ; Stomach Neoplasms ; surgery