OBJECTIVE: We wanted to determine whether combined radiofrequency ablation (RFA) and acetic acid-hypertonic saline solution (AHS) instillation can increase the extent of thermally mediated coagulation in in vivo rabbit liver tissue. We also wished to determine the optimal concentration of the solution in order to maximize its effect on extent of the RFA-induced coagulation. MAERIALS AND METHODS: Forty thermal ablation zones were produced in 40 rabbits by using a 17-gauge internally cooled electrode with a 1-cm active tip under ultrasound guidance. The rabbits were assigned to one of four groups: group A: RFA alone (n=10) ; group B: RFA with 50% AHS instillation (n=10) ; group C: RFA with 25% AHS instillation (n=10) ; group D: RFA with 15% AHS instillation (n=10). A range of acetic acid concentrations diluted in 36% NaCl to a total volume of 1 mL were instilled into the liver before RFA. The RF energy (30 W) was applied for three minutes. After RFA, in each group, the maximum diameters of the thermal ablation zones in the gross specimens were compared. Technical success and the complications that arose were evaluated by CT and on the basis of autopsy findings. RESULTS: All procedures are technically successful. There were six procedure-related complications (6/40; 15%) : two localized perihepatic hematomas and four chemical peritonitis. The incidence of chemical peritonitis was highest for group B with the 50% AHS solution instillation (30%). With instillation of 15% AHS solution, a marked decrease of tissue impedance (24.5+/-15.6 omega) and an increase of current (250 mA) occurred as compared to RFA alone. With instillation of the solutions before RFA (group B, C and D), this produced a greater mean diameter of coagulation necrosis than the diameters for rabbits not instilled with the solution (group A) (p < 0.05). However, there was no significant difference between group B, C, and D. CONCLUSION: Combined AHS instillation and RFA can increase the dimension of coagulation necrosis in the liver with a single application. A low concentration of AHS (15%) showed similar effects in increasing the extent of RF-induced coagulation, but there were less side effects as compared to the high concentration of AHS.
Acetic Acid/*administration & dosage ; Animals ; *Catheter Ablation ; Combined Modality Therapy ; Instillation, Drug ; Liver/*drug effects/pathology/*surgery ; Liver Neoplasms/drug therapy/surgery ; Necrosis ; Rabbits ; Saline Solution, Hypertonic/*administration & dosage

BACKGROUNDPortacaval shunt (PCS) prevent hepatotrophic factors from flowing into the liver, but they enter directly the systemic circulation and worsen liver injury. This study was designed to investigate the effects of hepatotrophic factors through the portal vein on the liver in rats with portal hypertension after portacaval shunt.

METHODSIntrahepatic portal hypertension (IHPH) was induced by intragastric administration of carbon tetrachloride, and end-to-side PCS was performed. Eight normal rats served as controls, and eight rats with IHPH served as IHPH model (IHPH group). Another 32 rats with IHPH-PCS were randomly subdivided into 4 groups: normal saline (NS) given to 8 rats, hepatocyte growth factor (HGF) 8, insulin (INS) 8, hepatocyte growth factor and insulin (HGF + INS) 8. Hepatotrophic factors were infused into the portal vein through an intravenous catheter. Portal venous pressure (PVP) was measured. The levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were tested biochemically and those of hyaluronic acid (HA) and laminin (LN) were measured by radioimmunoassay. Hepatic fibrosis was assessed histologically and the expression of collagens type I and III were detected immunohistochemically. Ultrastructural change of hepatocytes and the number of mitochondria were observed under an electron microscope. The data were compared between groups and subgroups by Student-Newman-Keuls procedure with SPSS10.0.

RESULTSPVP was significantly higher in the IHPH rats than in the control rats (P < 0.05). The levels of serum ALT, AST, HA, and LN, hepatic fibrosis score, the amount of collagen deposition, collagens type I and III increased more significantly in the IHPH group than in the control rats (P < 0.05). The number of mitochondria decreased more significantly in the IHPH rats than in the control rats (P < 0.05). The levels of serum ALT, AST, HA and LN as well as hepatic fibrosis score, the amount of collagen deposition, and the amount of collagens type I and III in the HGF and HGF + INS rats were significantly lower than those in the NS rats (P < 0.05). The damage to hepatocyte ultrastructure was markedly alleviated and the number of mitochondria was increased more significantly in the HGF and HGF + INS rats than in the NS rats under an electron microscope.

CONCLUSIONSPerfusion of exogenous hepatotrophic factors through the portal vein can alleviate liver injury, minimize the damage to the ultrastructure of hepatocyte, protect liver function, and lessen hepatic fibrosis in rats with portal hypertension after PCS.

Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Extracellular Matrix ; metabolism ; Hepatocyte Growth Factor ; pharmacology ; Hypertension, Portal ; metabolism ; pathology ; surgery ; Insulin ; pharmacology ; Liver ; drug effects ; pathology ; ultrastructure ; Liver Cirrhosis, Experimental ; drug therapy ; Male ; Portacaval Shunt, Surgical ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the expression of Toll-like receptor 4 (TLR4) in the liver tissue of rats with bile duct ligation (BDL)-induced hepatic fibrosis and evaluate the inhibitory effects of perindopril and losartan on TLR4 expression.

METHODSMale Wistar Rats were randomly divided into sham-operated group (n=6), BDL group, perindopril treatment group (2 mg/kg) and losartan treatment group (50 mg/kg) (n=12). Perindopril and losartan groups were further divided into two subgroups for corresponding treatments by gastric lavage once daily for 14 and 30 days. The protein level of TLR4 in the liver tissue was examined by Western blotting.

RESULTSIn 14-day BDL group, the protein level of TLR4 significantly increased to 6.53∓1.11 folds of that in the sham group (P<0.05), and was lowered significantly to 1.71∓0.41 folds and 0.95∓0.38 folds following perindopril and losartan treatments for 14 days. TLR4 expression significantly increased to 6.51∓0.87 folds and 5.64∓0.87 folds of that of the sham group in perindopril and losartan groups after the 30-day treatments (P<0.05).

CONCLUSIONTLR4 expression is up-regulated in the liver of rats with BDL-induced hepatic fibrosis, and can be lowered by perindopril and losartan treatmemts for 14 days.

Animals ; Bile Ducts ; surgery ; Down-Regulation ; drug effects ; Ligation ; Liver Cirrhosis, Experimental ; metabolism ; pathology ; Losartan ; pharmacology ; Male ; Perindopril ; pharmacology ; Rats ; Rats, Wistar ; Toll-Like Receptor 4 ; genetics ; metabolism

Vertical sleeve gastrectomy (VSG) is becoming more and more popular among the world. Despite its dramatic efficacy, however, the mechanism of VSG remains largely undetermined. This study aimed to test interferon (IFN)-γ secretion n of mesenteric lymph nodes in obese mice (ob/ob mice), a model of VSG, and its relationship with farnesoid X receptor (FXR) expression in the liver and small intestine, and to investigate the weight loss mechanism of VSG. The wild type (WT) mice and ob/ob mice were divided into four groups: A (WT+Sham), B (WT+VSG), C (ob/ob+Sham), and D (ob/ob+VSG). Body weight values were monitored. The IFN-γ expression in mesenteric lymph nodes of ob/ob mice pre- and post-operation was detected by flow cytometry (FCM). The FXR expression in the liver and small intestine was detected by Western blotting. The mouse AML-12 liver cells were stimulated with IFN-γ at different concentrations in vitro. The changes of FXR expression were also examined. The results showed that the body weight of ob/ob mice was significantly declined from (40.6±2.7) g to (27.5±3.8) g on the 30th day after VSG (P<0.05). At the same time, VSG induced a higher level secretion of IFN-γ in mesenteric lymph nodes of ob/ob mice than that pre-operation (P<0.05). The FXR expression levels in the liver and small intestine after VSG were respectively 0.97±0.07 and 0.84±0.07 fold of GAPDH, which were significantly higher than pre-operative levels of 0.50±0.06 and 0.48±0.06 respectively (P<0.05). After the stimulation of AML-12 liver cells in vitro by different concentrations of IFN-γ (0, 10, 25, 50, 100, and 200 ng/mL), the relative FXR expression levels were 0.22±0.04, 0.31±0.04, 0.39±0.05, 0.38±0.05, 0.56±0.06, and 0.35±0.05, respectively, suggesting IFN-γ could distinctly promote the FXR expression in a dose-dependent manner in comparison to those cells without IFN-γ stimulation (P<0.05). It was concluded that VSG induces a weight loss in ob/ob mice by increasing IFN-γ secretion of mesenteric lymph nodes, which then increases the FXR expression of the liver and small intestine.
Animals ; Body Weight ; Cell Line ; Gastrectomy ; methods ; Gene Expression ; Hepatocytes ; cytology ; drug effects ; metabolism ; Interferon-gamma ; biosynthesis ; pharmacology ; secretion ; Intestine, Small ; drug effects ; metabolism ; Liver ; drug effects ; metabolism ; Lymph Nodes ; drug effects ; metabolism ; Mesentery ; drug effects ; metabolism ; Mice ; Mice, Obese ; Obesity ; metabolism ; pathology ; surgery ; Receptors, Cytoplasmic and Nuclear ; agonists ; genetics ; metabolism ; Weight Loss

Fontan surgery is a widely used palliative procedure that significantly improves the survival period of patients with complex congenital heart disease (CHD). However, it does not decrease postoperative complication rate. Previous studies suggested that elevated mean pulmonary artery pressure (mPAP) and vascular resistance lead to decreased exercise tolerance and myocardial dysfunction. Therapy with endothelial receptor antagonists (Bosentan) has been demonstrated to improve the patients' prognosis. A double-blind, randomized controlled trial was performed to explore the efficacy of Bosentan in treating patients who underwent the Fontan procedure. Eligible participants were randomly divided into Bosentan group and control group. Liver function was tested at a local hospital and the results were reported to the phone inspector every month. If the results suggested abnormal liver function, treatment would be adjusted or terminated. All the participants finished the follow-up study, with no patients lost to follow-up. Unblinding after 2-year follow-up, no mortality was observed in either group. However, secondary end-points were found to be significantly different in the comparable groups. The cardiac function and 6-min walking distance in the Bosentan group were significantly superior to those in the control group (P=0.018 and P=0.027). Bosentan could improve New York Heart Association (NYHA) functional status and improve the results of the 6-min walking test (6MWT) in Fontan patients post-surgery, and no other benefits were observed. Furthermore, a primary meta-analysis study systematically reviewed all the similar clinical trails worldwide and concluded an overall NYHA class improvement in Fontan patients who received Bosentan treatments.
Adolescent ; Child ; Double-Blind Method ; Female ; Follow-Up Studies ; Fontan Procedure ; Heart Defects, Congenital ; drug therapy ; pathology ; surgery ; Humans ; Liver ; drug effects ; pathology ; Male ; Palliative Care ; Prognosis ; Sulfonamides ; administration & dosage ; Treatment Outcome

BACKGROUNDRegional intra-arterial infusion chemotherapy (RIAC) has been more valuable to improve prognosis and quality of life of patients with inoperable pancreatic adenocarcinomas, and adjuvant RIAC plays an important role in prolonging survival and reducing risk of liver metastasis after radical resection of pancreatic cancer, but the effect of preoperative or multiple-phase RIAC (preoperative combined with postoperative RIAC) for resectable pancreatic cancers has not been investigated. In this prospective study, the effect of multiple-phase RIAC for patients with resectable pancreatic head adenocarcinoma was evaluated, and its safety and validity comparing with postoperative RIAC were also assessed.

METHODSPatients with resectable pancreatic head cancer were randomly assigned to two groups. Patients in group A (n=50) were treated with new therapeutic mode of extended pancreaticoduodenectomy combined with multiple-phase RIAC, and those in group B (n=50) were treated with extended pancreaticoduodenectomy combined with postoperative RIAC in the same period. The feasibility, compliance and efficiency of the new therapeutic mode were evaluated by tumor size, serum tumor markers, clinical benefit response (CBR), surgical complications, mortality and toxicity of RIAC. The disease-free survival time, median survival time, incidence of liver metastasis, survival rate at 1, 2, 3 and 5 years were also observed. Life curves were generated by the Kaplan-Meier method.

RESULTSThe pain relief rate and CBR in group A was 80% and 84% respectively. Serum tumor markers decreased obviously and tumors size decreased in 26% of patients after preoperative RIAC in group A. No more surgical complications, mortality or severe systemic side effects were observed in group A compared with group B. The incidence of liver metastasis in group A was 34% which was lower than 50% in group B. The disease-free survival time and median survival time in group A were 15.5 months and 18 months respectively. The 1-, 2-, 3- and 5-year survival rates were 54.87%, 34.94%, 24.51% and 12.25% respectively. There was no significant difference of survival time or survival rates between two groups.

CONCLUSIONSMultiple-phase RIAC is effective in combined therapy of resectable pancreatic head carcinomas by enhancing inhibition of tumor growth and reduction of liver metastasis, without negative effect on patients' safety or surgical procedure.

Adenocarcinoma ; drug therapy ; mortality ; pathology ; surgery ; Adult ; Aged ; Deoxycytidine ; analogs & derivatives ; therapeutic use ; Disease-Free Survival ; Female ; Fluorouracil ; therapeutic use ; Humans ; Infusions, Intra-Arterial ; methods ; Liver Neoplasms ; secondary ; Male ; Middle Aged ; Mitomycin ; therapeutic use ; Neoplasm Metastasis ; Pancreas ; drug effects ; pathology ; surgery ; Pancreatic Neoplasms ; drug therapy ; mortality ; pathology ; surgery ; Pancreaticoduodenectomy

Adenocarcinoma ; drug therapy ; secondary ; surgery ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents ; adverse effects ; therapeutic use ; Benzenesulfonates ; adverse effects ; therapeutic use ; Carcinoma, Renal Cell ; drug therapy ; secondary ; surgery ; Diarrhea ; chemically induced ; Female ; Follow-Up Studies ; Humans ; Kidney Neoplasms ; drug therapy ; pathology ; surgery ; Liver Neoplasms ; drug therapy ; secondary ; Lung Neoplasms ; drug therapy ; secondary ; Male ; Middle Aged ; Niacinamide ; analogs & derivatives ; Phenylurea Compounds ; Pyridines ; adverse effects ; therapeutic use ; Remission Induction

OBJECTIVETo observe the evolution and differentiation of hepatic oval cells after transplanted into the spleens of homogenous rats, providing experimental data for treating hepatic failure with hepatic stem cells.

METHODSA two-step perfusion procedure was used to separate hepatic parenchymal cells from nonparenchymal cells. Then the suspension of nonparenchymal cells was centrifuged in Percoll gradients. The isolated cells were cultured, identified, and then transplanted into the spleens of homogenous rats undergone 2/3 hepatectomy.

RESULTSThe obtained cells were various in size with ovoid nuclei and inadequate cytoplasm. After 12 hours' culture, they revealed the characteristics of epithelial cells. Both the freshly isolated and cultured cells showed positive staining for cytokeratin 19 (CK19), OV6, alpha fetal protein (AFP), but negative for leucocyte common antigen (LCA). After intraspleenic transplantation into homogenous rats undergone partial hepatectomy, hepatic oval cells were differentiated into liver tissue-like structure including hepatocyte cords and bile ducts, and formed hepaticized spleen. But this kind of structure was not observed in the controls.

CONCLUSIONThe isolated rat hepatic oval cells show the biological characteristics of hepatic stem cells and can differentiate into hepatocytes and biliary epithelial cells under appropriate circumstances.

Animals ; Antigens, Differentiation ; analysis ; Cell Differentiation ; Cell Separation ; Cell Transplantation ; pathology ; Cells, Cultured ; Hepatectomy ; methods ; Hepatocytes ; drug effects ; physiology ; ultrastructure ; Liver ; cytology ; growth & development ; Liver Transplantation ; methods ; Male ; RNA, Messenger ; metabolism ; Rats ; Rats, Wistar ; Spleen ; surgery ; Stem Cells ; drug effects ; physiology ; ultrastructure

BACKGROUNDS AND AIMS: Angiotensin receptors are found on hepatic stellate cells, which participate in hepatic fibrosis. Therefore, it is presumed that angiotensin has a role in hepatic fibrosis. The aim of this study was to evaluate the effects of angiotensin blockade on inhibition of hepatic fibrosis in cirrhotic rat model. Material and METHODS: Cirrhosis with portal hypertension was produced by common bile duct ligation (BDL) in the adult Sprague-Dawley rats. They were classified into 4 groups (each group n=6) as follows; G1: BDL without drug, G2: BDL+captopril 100 mg/kg/day beginning 2 weeks after BDL, G3: BDL+captopril 100 mg/kg/day, starting just after BDL, G4: BDL+losartan 10 mg/kg/day, starting just after BDL. After 4 weeks following BDL, hepatic fibrosis was histomorphologically analyzed by Batts & Ludwig score. Alpha smooth muscle actin by immunohistochemical stain, hydroxyproline contents of liver tissue by spectrophotometry and expression of collagen, procollagen, and TGF-beta by real-time PCR were measured. RESULTS: Batts & Ludwig score were 3.8, 3.0, 2.6,and 2.6 in G1, G2, G3, and G4, respectively. The expression of alpha-SMA was significantly lower in G3 and G4 than in G1; 11.9%, 10.9%, 2.6%, and 1.1% in G1, G2, G3, and G4, respectively (p<0.05). The concentration of hydroxyproline (microgram/g liver tissue) was lower in G3 and G4 compared with G1 (p<0.05). Also, the administration of angiotensin blockade just after BDL significantly reduced the expression of collagen, procollagen, and TGF-beta mRNA. CONCLUSIONS: Angiotensin blockades are effective in the prevention of hepatic fibrosis in BDL rats.
Actins/metabolism ; Angiotensin II Type 1 Receptor Blockers/administration & dosage/*therapeutic use ; Animals ; Bile Ducts/pathology/surgery ; Captopril/administration & dosage/*therapeutic use ; Fibrosis ; Hydroxyproline/metabolism ; Ligation ; Liver/drug effects/metabolism/pathology ; Liver Cirrhosis, Experimental/*drug therapy/etiology/metabolism ; Losartan/administration & dosage/*therapeutic use ; Male ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor beta/metabolism

OBJECTIVEThe aim of this study is to investigate the efficiency and toxicity of the FOLFOX regimen, the combination of oxaliplatin (L-OHP), 5-fluorouracil (5-Fu) and calcium folinate (CF), for patients with locally advanced or metastatic gastric cancer.

METHODSNinety-six patients with locally advanced or metastatic gastric adenocarcinoma, including 72 males and 24 females, were treated with FOLFOX regimen: L-OHP 85 mg/m(2) iv in 2 hours on D1, CF 200 mg/m(2) iv in 2 hours on D1 and D2, 5-Fu 400 mg/m(2) iv on D1 and D2, and then continuous infusion of it at a dose of 600 mg/m(2) for 44 hours. This regimen was repeated every 2 weeks. The first evaluation was done after four cycles. The median cycle of the chemotherapy was 6 (range: 1 to 12 cycles).

RESULTSOf the 96 patients with gastric cancers, 21 underwent R0 resection and afterward received adjuvant FOLFOX chemotherapy. Ten of those were still alive, while the other 11 died of the disease, with a median disease free survival time of 24.0 months and 3-year survival rate of 51.8%. The other 75 received only palliative chemotherapy due to non-operable advanced disease. Thirty of those achieved partial response (PR), the other 20 had a stable disease (SD), but the remaining 25 experienced disease progression (PD), with an overall response rate of 40.0%. The median TTP and overall survival in those 75 patients was 5.9 and 12.0 months, respectively. All 96 patients were evaluable for toxicity according to NCI criteria. The patients of grade 3 vomiting and neural toxicity were 6 and 4, respectively.

CONCLUSIONIn terms of efficacy and safety, the FOLFOX regimen is effective and well tolerable for patients with locally advanced or metastatic gastric cancers either as adjuvant or palliative chemotherapy.

Adenocarcinoma ; drug therapy ; pathology ; secondary ; surgery ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Carcinoma, Signet Ring Cell ; drug therapy ; pathology ; secondary ; surgery ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; Fluorouracil ; administration & dosage ; adverse effects ; therapeutic use ; Follow-Up Studies ; Humans ; Leucovorin ; administration & dosage ; adverse effects ; therapeutic use ; Liver Neoplasms ; drug therapy ; secondary ; Lymphatic Metastasis ; Male ; Middle Aged ; Neutropenia ; chemically induced ; Organoplatinum Compounds ; administration & dosage ; adverse effects ; therapeutic use ; Palliative Care ; Remission Induction ; Stomach Neoplasms ; drug therapy ; pathology ; surgery ; Survival Rate ; Vomiting ; chemically induced