BACKGROUND: The proportion of alcoholic liver disease among all kinds of liver diseases in China is increasing. Recent research has elucidated the mechanisms of alcohol-induced liver injury and offered the prospect of advances in the management of alcoholic liver disease.
DATA RESOURCES: Searching MEDLINE (1982-July 2004) for papers on alcoholic liver disease, especially those on the treatment of alcoholic liver disease.
RESULTS: Abstinence remains the cornerstone of management of all forms of alcoholic liver disease. Nutritional support therapy is also a basal treatment. Corticosteroids may be benefitial for some severe alcoholic hepatitis. None of other measures including anti-inflammatory agents, antioxidants or colchicine has been shown consistently to improve the course of alcoholic liver damage. Ultimately, liver transplantation remains an option for selected patients with liver failure due to chronic alcoholic liver disease.
CONCLUSIONS: Abstinence and nutritional support remain the base management of alcoholic liver disease. Corticosteroid is efficient for some severe alcoholic hepatitis. Anti-inflammatory agents and antioxidants may be of benefit but need further studies. The efficacy of other measures including the use of colchicine and propylthiouracil is controversial. Liver transplantation remains an option for selected patients with liver failure.

BACKGROUND: Hepatitis B related end-stage liver disease is recently acknowledged as one of the main indications for orthotopic liver transplantation (OLT).  However, the high recurrence rate of hepatitis B virus infection following transplantation is regarded as a major factor affecting the long-term survival of transplant recipients especially in China. Cyclosporine A (CsA), which is routinely used to prevent the allograft rejection, is reported to have the inhibitory activity on hepatitis B virus (HBV) replication in vitro. In this paper, we review the inhibitory effect and its possible mechanisms of CsA on HBV replication in vitro.
DATA RESOURCES: An English-language literature search was conducted using MEDLINE (1990-2004) on cyclosporine A, hepatitis B virus, mitochondria, calcium and other related reports and review articles.
RESULTS: Hepatitis B x protein (HBx) is essential to HBV replication. The cytosolic calcium signaling mediated by mitochondria and the Src kinase pathway were involved during HBx activation of HBV replication. CsA inhibits the HBV replication in vitro by its binding to mitochondrial cyclophilin D, then blocking the mitochondria-mediated cytosolic calcium signaling. The derivates of CsA also have the HBV replication inhibitory effect in vitro.
CONCLUSIONS: By interacting with mitochondria, preventing the release of intramitochondrial calcium, and then blocking the cytosolic calcium signaling, CsA inhibits the HBV replication in vitro. The derivates of CsA also have this activity.

BACKGROUND: The prophylactic use of antibiotics in patients with severe acute pancreatitis remains contentious. This study was undertaken to review the current studies on antibiotic prophylaxis in patients with severe acute pancreatitis. 
DATA RESOURCES: All papers found by a Medline search were relevant to human trials of antibiotic prophylaxis in patients with severe acute pancreatitis. 
RESULTS: In the 1970s, three small randomized studies of prophylactic ampicillin in the treatment of acute pancreatitis showed no effect on mortality or morbidity, but the inclusion of patients at low risk for infection and the use of an ineffective antibiotic were insufficient to detect any differences. From 1993 to 2001, eight prospective clinical trials of antibiotic prophylaxis were conducted in patients with severe acute pancreatitis (SAP). Seven of the 8 trials showed significant effect of the prophylaxis in prevention of pancreatic infections, and one showed significant improvement of clinical course documented by the Acute Physiology and Chronic Health Evaluation II (APACHE II) scores. Only two trials did demonstrate the significance of the prophylaxis in lowering the mortality rate. Despite variations in drug agents, study size and patient selection, duration of treatment, and methodology (None of the studies was double-blinded), a meta-analysis showed the positive effect of antibiotics in reducing the mortality. We suggested that antibiotic prophylaxis with proven efficacy in necrotic pancreatic tissues should be given to all patients with acute necrotizing pancreatitis. In recent years, however, the first double-blind, placebo-controlled multicenter study from Germany detected no benefit of antibiotic prophylaxis with respect to the risk of developing infected pancreatic necrosis. 
CONCLUSION: Prophylactic antibiotics for severe acute pancreatitis is still a matter of discussion and further studies are required to provide adequate data to answer many questions and to define the role of antibiotic prophylaxis in patients with severe acute pancreatitis.

BACKGROUND: It is not certain whether Klatskin tumor should be a routine indication for orthotopic liver transplantation (OLT). This study was to summarize the indication and value of orthotopic liver transplantation for patients with Klatskin tumor.
METHODS: Forty patients with Klatskin tumors including 5 patients who had had liver transplantation (LTx) and 35 patients who had not undergone LTx (WLTx) from January 1992 to December 2003 were analyzed retrospectively. Their TNM stages were comparable in both groups. In the LTx group, 4 patients had Klatskin tumor including recurrent tumor after resection(1), and 1 cancerization from Carolis disease. Biliary duct anastomosis was made by Roux-en-Y choledochojejunostomy in 2, and end-to-end choledochocholedochostomy (C-C) in 3.
RESULTS: In the LTx group, the total resection rate and radical resection rate were both 100%. Four patients have been surviving for 48, 38, 21 and 5 months, respectively, except one died from bile leakage at day 40 after transplantation. All 4 survivors enjoyed good life without tumors at local and distant sites， even though 2 of these patients developed biliary stricture, which was soon resolved by radiological intervention. The 1-,3-year survival rates were both 80% in this group. The total resection rate and radical resection rate in the WLTx group were 63.0% (17/27) and 40.7% (11/27) and, the 1-, 3-, 5-year survival rates were 32.2%, 8.0%, 0%, respectively. There were significant differences between the two groups in radical resection rates and survival rates (P=0.016).
CONCLUSIONS: OLT is a good choice for patients with unresectable Klatskin tumor by routine modalities. The prognosis of patients undergoing OLT is encouraging.

BACKGROUND: Orthotopic liver transplantation has become the treatment of choice for patients with end-stage liver disease. This study was designed to study whether multislice spiral CT angiography (MSCTA) could be used for preoperative evaluation for orthotopic liver transplantation candidates.
METHODS: Eighty consecutive potential candidates for liver transplantation were evaluated with dual-phase three-dimensional CT angiography (3DCTA).The arterial-phase was used to create vascular maps of the celiac axis (including the origin of the hepatic common artery, left gastric artery and splenic artery) and origin of the superior mesenteric artery. The portal venous-phase was used to analyze portal vein thrombosis and collateral vascularization of the portal vein. Statistical analyses were made using the chi-square test for differences between hepatic arterial anatomy of 80 patients and Michel’s type I anatomy of 200 patients. Appearance of MSCTA and operative results of 16 patients were analyzed.
RESULTS: Sixty-two patients (77.5%) showed conventional and 18 (22.5%) nonconventional hepatic arterial anatomy. A significant difference was found between the two groups in anatomy of the hepatic artery (P<0.05). Celiac axis stenosis was observed in 6 patients, SA aneurysm in 2, small-caliber hepatic arterial vessels in 2, and portal vein thrombosis in 15. Vascular structures of 16 operative patients were well defined.
CONCLUSION: As a noninvasive examination, MSCTA can provide a comprehensive preoperative vascular evaluation for liver transplantation candidates.

BACKGROUND: Morphological and functional changes commonly occur in livers of brain-death donors. Prevention of liver injury from brain-death will benefit the results of transplantation. This study was conducted to evaluate the protection effects of glycine on the liver of brain-death donor.
METHODS: Fourty-two male Wistar rats were randomly divided into brain-death donor (BDD) group (B), glycine pretreatment group with BDD (G), and strychnine pretreatment group with BDD(S).  For these groups, brain death model was established in donor rats and liver transplantation was performed subsequently utilizing microsurgical techniques.  After the establishment of the model and during cold rinsing of liver donors or liver reperfusion of recipients, glycine was given at a dose of 0.6 mmol, 25 μmol and 25 μmol in the group G, and a same dose of glycine and strychnine (1000:1) was prescribed for the group S, but nothing for the group B.  Before cold rinsing at 2 and 6 hours after portal vein(PV) reperfusion, blood samples were taken from infrahepatic vena cava (IHVC) to determine the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor alpha (TNF-α) and hyaluronic acid (HA).  At 6 hours after PV reperfusion, graft samples were fixed for morphological observation and apoptosis of hepatocytes was detected using the TUNEL method.
RESULTS: Before liver cold rinsing and at 2 and 6 hours after PV reperfusion, the serum levels of ALT, AST, TNF-α, HA and apoptosis index (AI) in the groups B and S were significantly higher than those in the group G (P<0.05). There was no significant difference between the groups B and S (P>0.05). Electron microscopy showed that Kupffer cells were activated and hepatic cells injured more obviously in the groups B and S than in the group G.
CONCLUSION: Glycine pretreatment can improve the viability of the liver of the brain-death donor rat.

BACKGROUND: Interleukin-1 receptor antagonist (IL-1ra) can inhibit the pro-inflammatory effects of IL-1, which recently has been thought to involve the pathogenesis of alcoholic liver disease (ALD). This study was undertaken to determine whether there is any association between IL-1ra gene polymorphism and ALD in a Chinese population.
METHODS: The polymorphism of IL-1ra gene intron 2 (VNTR) was assessed in 165 alcoholics (43 alcohol-dependent subjects without liver diseases, 30 patients with alcoholic fatty liver, 61 patients with alcoholic hepatitis and 31 patients with alcoholic cirrhosis) and 65 healthy control subjects by PCR with DNA of peripheral blood mononuclear cells.
RESULTS: The rate of IL-1RN*1 carriage was statistically higher in the alcoholics than in the control group (98.79% vs 93.85%, χ2=4.48, P<0.050). And the IL-1RN*1 allele frequency was more common in the alcoholics than in the control group (86.67% vs 76.92%, χ2=6.56, P<0.025). IL-1RN*1 heterozygote was significantly more frequent in the patients with alcoholic hepatitis or those with cirrhosis than in the alcohol-dependent subjects without liver diseases (32.79%, 29.03% vs 9.30%; χ2=7.84, χ2=4.84; P<0.010, P<0.050). The IL-1RN*2 allele frequency in the patients with alcoholic hepatitis and the patients with cirrhosis was also significantly higher than in those alcoholics without liver diseases (13.93%, 17.74% vs 4.65%; χ2=4.79, χ2=6.78; P<0.050, P<0.010). But the frequencies of IL-1RN*1 heterozygote and IL-1RN*2 allele appear to be not different between the patients with alcoholic fatty liver and the alcoholics without liver diseases.
CONCLUSIONS: IL-1ra gene polymorphism is closely associated with race. IL-1RN*2 allele doesn’t influence the susceptibility to ALD, but the gene carriers with ALD have additional risk for aggravation of the illness.

BACKGROUND: Hepatocellular carcinoma (HCC) is the second most common cancer in China. Hepatitis B and C viruses (HBV and HCV) and aflatoxins are known risk factors for HCC, but the etiological status of these factors in HCC development is not clear. This study was undertaken to define the absolute importance of HBV in hepatocarcinogenesis of North China.
METHODS: A consecutive series of 119 patients with pathologically proven HCC were collected from North China during January 1998 to December 2000 by the Cancer Hospital of the Chinese Academy of Medical Sciences, Beijing. Serum HBsAg, anti-HBc and anti-HCV were negative HBV sero-markers. The HBV X gene was analyzed for its expression by PCR, DNA sequencing, and immunohistochemistry.
RESULTS: In the 119 HCC patients, 82.4% (98/119) were HBsAg seropositive. When a comprehensive set of HBV markers were detected, the HBV infection rate in these HCC patients was 99.2% (118/119). Of the patients, 11.8%(14/119) were found to be anti-HCV positive. But all the anti-HCV positive HCC patients were co-infected with HBV.
CONCLUSIONS: HBV infection is virtually ubiquitous in HCC patients in North China. The tight association of HBV with HCC strongly suggests the dominant role of HBV infection in causing hepatocellular carcinoma. About 11.8% of HCC patients being HCV-related are co-infected with HBV.

BACKGROUND: With the progress in early clinical treatment of hepatocellular carcinoma (HCC), early detection and diagnosis of HCC have been increasingly pressing. Combined alpha-fetoprotein(AFP) determination and ultrasonography has become the main method for the detection of small HCC; but the relationship between low elevation of AFP and pathologic findings of small HCC has not been well defined. The aim of this study was to assess the value of ultrasound-guided fine needle biopsy of intrahepatic nodules and low elevation of serum AFP in the early diagnosis of HCC.
METHODS: Fifty-nine patients with serum AFP exceeding 20 ng/ml and intrahepatic nodules varying from 0.8 cm to 5.0 cm in diameter who had been detected by ultrasonography underwent ultrasound-guided percutaneous fine needle biopsy, and cytological staining and histological sectioning were performed at the same time.
RESULTS: Among the 59 patients, 11 patients (18.6%) showed AFP level above 400 ng/ml, 5 (8.5%) from 200 ng/ml to 400 ng/ml, 18 (30.5%) from 50 ng/ml to 200 ng/ml and 25 (42.4%) from 20 ng/ml to 50 ng/ml. Follow-up demonstrated that 53 patients (89.8%) had a progressive increase of AFP level. In 58 patients (98.3%) cancer cells were found by cytological staining and/or histological sectioning.
CONCLUSIONS: In those patients with slightly increased or continuously positive AFP, hepatic carcinoma should be highly suspected when AFP increases gradually and intrahepatic nodules are detected by ultrasonography in follow-up. Once intrahepatic carcinoma nodules are suspected, ultrasound-guided fine needle biopsy should be performed as early as possible for early diagnosis and treatment.

BACKGROUND: The abnormal metabolism caused by cirrhosis always results in a complex problem about nutritional support, which will be more intricate while patients with portal hypertension are treated with pericardial devascularization. Comparing the effects of early enteral and parenteral nutritional support in patients with cirrhotic portal hypertension after pericardial devascularization, we try to realize the advantages and disadvantages of the two nutritional therapies and to guide our clinical practice.
METHODS: After pericardial devascularization, 40 patients with cirrhotic portal hypertension were divided randomly into 2 groups: enteral and  parenteral nutritional support, respectively. The general nutritional condition, capability of producing protein，liver function, blood velocity of the portal vein, gut function, bowel bacterial translocation, mortality, complication rate, stay in ICU, duration of hospitalization and costs of treatment were determined in all the patients and compared between the 2 groups.
RESULTS: Both enteral and parenteral nutritional supports could improve the general nutrition condition of the patients; but patients receiving enteral nutritional support had fewer complications. Enteral nutrition was more effective than parenteral nutrition in increasing the blood velocity of the portal vein, stimulating gut motion, preventing bowel bacterial translocation, shortening the stay in ICU and the duration of hospitalization, and saving costs of treatment.
CONCLUSION: After pericardial devascularization, patients with cirrhotic portal hypertension should be treated with enteral nutritional support as early as possible.

BACKGROUND: Abnormal liver function was found in patients with severe acute respiratory syndrome (SARS). This study was undertaken to explore the clinical characteristics and mechanisms of liver damage.
METHODS: The serial laboratory data of liver function test and hepatic histological examination from 168 patients with SARS were retrospectively analyzed.
RESULTS: The abnormalities of serum alanine aminotransferase (ALT) were 52.5%, 71.8%, 85.7% and 85.2%. The average levels of ALT of the patients were 56.07±51.57 U/L, 86.46±69.93 U/L, 106.69±102.50 U/L and 111.32±160.24 U/L, and the average levels of serum albumin were 37.25±5.37 g/L, 35.82±4.74 g/L, 34.49±5.04 g/L, and 34.26±4.70 g/L, at the day of admission, the first week, second week, and third week after hospitalization, respectively. Significant correlation was not shown among liver damage, blood oxygen saturation (SaO2), degree of fever, and immune functional disorder in this study. Hepatic histological examination of 4 patients demonstrated that non-specific inflammation existed in the liver. 
CONCLUSIONS: Liver damage of patients with SARS usually occurs in the early stage of the disease with a high occurrence rate and a prolonged profile, which can be characterized by early, obvious decrease of albumin levels and slightly abnormal levels of ALT. The liver damage induced by SARS seems to be caused by SARS virus directly rather than by low SaO2 or high fever. Hepatotoxic drugs may play a role in increasing the severity of liver damage or prolonging the time of liver function recovery.

BACKGROUND: Hepatocholangioplasty combined with choledochostomy was designed through an isolated jejunum passage in 1988. This study was undertaken to evaluate its long-term curative effects in 163 patients.
METHODS: The 163 patients with hepatolithiasis complicated by stricture were treated with this procedure from 1988 to 2003.
RESULTS: Among these patients, 19 patients with postoperative hepatolithiasis complicated by acute cholangitis were treated successfully with percutaneous paracentesis drainage through the isolated jejunum passage and without operation, 36 patients had postoperative residual or recurrent stones (35 patients had stones removed through the stoma and one underwent relaparotomy because of stenosis of the common bile duct along with stone in canceration). The clearance rate of stones after the isolated jejunum passage was 97%; 35 patients (21%) complicated with stricture due to hepatolith were treated with combined hepatocholangioplasty and choledochostomy. Follow-up for 1 to 15 years showed no recurrent stricture of the biliary tract. The operation also successfully prevented reflux cholangitis and other serious complications after Roux-en-Y cholangio-jejunostomy.
CONCLUSION: Hepatocholangioplasty combined with choledochostomy through an isolated jejunum passage may significantly improve the long-term curative effects of hepatolithiasis with stricture.

BACKGROUND: Budd-Chiari syndrome (B-CS) is a disease with a poor prognosis, and the results of medication are not satisfactory. Surgical treatments are widely used to depress portal hypertension and hypertension of the inferior vena cava. Splenocaval shunt is usually applied to treat intrahepatic portal hypertension, but we used this method to treat patients with B-CS successfully.
METHODS: The clinical data of 72 B-CS patients (type II), including 26 patients treated with splenocaval shunt (splenocaval group) and 46 patients with mesocaval C-shape shunt (mesocaval group) were analyzed retrospectively.
RESULTS: The platelet count of the splenocaval group increased significantly after operation (P<0.05). Free portal pressure (FPP) significantly decreased in both groups after operation (P<0.05), but no significant difference was seen between the two groups (P>0.05). Twenty patients in the splenocaval group and 36 in the mesocaval group were followed up for 6 months to 3.5 years, showing the effective rates of 90.0% and 91.7% respectively in the two groups. The occurrence of hepatic encephalopathy was 5.0% and 5.6% respectively in both groups, but there was no recurrent hemorrhage.
CONCLUSIONS: Splenocaval shunt can effectively control B-CS, decrease FPP, prevent upper gastrointestinal hemorrhage, and eradicate hypersplenia. Its efficacy is similar to that of mesocaval shunt in treatment of B-CS.

BACKGROUND: Hepatitis C virus (HCV) is believed to be an important human pathogen causing carcinoma. But the effect of HCV infection on the alteration of cellular proliferation and apoptosis and the relationship between the effect and the development of hilar cholangiocarcinoma are largely unknown. The aim of this study was to assess the effect of HCV core protein on proliferation and apoptosis of hilar cholangiocarcinoma.
METHODS: HCV core protein (HCV C protein) was detected by peroxidase-antiperoxidase assay in surgical specimens from 48 patients with hilar cholangiocarcinoma. The apoptosis index (AI) and PCNA index (PI) in hilar cholangiocarcinoma were detected by in situ end labeling assay and streptavidin-biotin assay respectively.
RESULTS: The expression of HCV C protein was observed in 32 (67.7%) of the 48 specimens of hilar cholangiocarcinoma. The mean±standard deviation for AI and PI was 3.52%±0.64% and 46.24%±11.46% respectively. The AI of hilar cholangiocarcinoma specimens with HCV C protein expression was significantly lower than that of HCV C protein negative specimens (P<0.01), whereas the PI of HCV C protein positive specimens was significantly higher than that of HCV C protein negative specimens (P<0.01).
CONCLUSION: HCV C protein may promote the cellular proliferation of hilar cholangiocarcinoma and inhibit its cellular apoptosis.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignancies in China. The long-term survival rate of patients with HCC after prevention and management remains unsatisfactory. In order to provide a novel strategy to cure HCC, we investigated the effects of antisense oligonucleotides of PKC-α on proliferation and apoptosis of human hepatoma cell line HepG2 in vitro.
METHODS: The human hepatocellular carcinoma cell line HepG2 was cultured and subcultured in RPMI1640 medium in vitro. PKC-α antisense oligonucleotides(asODN) of different concentrations with a random sequence as a control were transfected into HepG2 cells by lipofectin(LP). The cell growth index (GI) and the clone formation rate of HepG2 were detected by MTT colorimetric assay and soft agar assay, respectively. The apoptosis rate of HepG2 treated with PKC-α asODN was assayed by flow cytometry(FCM). The results were analyzed by SPSS 10.0 software.
RESULTS: The GI of HepG2 transfected by PKC-α asODN with concentrations ranging from 0.10 μmol to 1.00 μmol were lower significantly than those of control groups (P<0.05). The clone formation rates of HepG2 transfected by PKC-α asODN from 0.05 μmol to 1.00 μmol were lower significantly than those of the control groups (P<0.01), and there was a dose-dependent relationship among them. The apoptosis rates of HepG2 treated with PKC-α asODN from 0.50 μmol to 1.00 μmol were significantly higher than those of the control groups.
CONCLUSION: PKC-α asODN could inhibit the growth and proliferation of HepG2 and induce its apoptosis by blocking the cell signal transduction related to PKC-α in vitro, and may be potentially used in the prevention and management of recurrent and metastatic HCC.

BACKGROUND: Hepatitis C virus (HCV) is a worldwide common disease. Some predictive factors influencing the response to interferon alpha (IFN-α) therapy have been identified, but the conclusions differ in various counties and areas. The aim of this study was to study the associations between HCV genotypes, HLA-DRB alleles and their response to IFN-α and ribavirin in Chinese patients with chronic hepatitis C in Northeast China.
METHODS: HCV genotypes of 113 patients with HCV were investigated. Gene chips were used to analyze the frequency of HLA-DRB in 25 of these patients and their response to IFN-α and ribavirin. The associations of HCV genotypes, HLA-DRB alleles and their response to IFN-α and ribavirin were also studied.
RESULTS: The response rates differed in several types of HCV, with HCV 2b being the highest (57.78%), HCV 1a and 2a lower (46.15% and 47.62%) and HCV 1b the lowest (11.76%). The response rates to IFN-α and ribavirin in patients with DRB1*07 were higher than those with DRB1*04. Sex, HCV type and HLA-DRB were all related to the response. Most female patients with HCV 2b and HLA-DRB1*07 presented complete response, whereas male patients with HCV 1b and HLA-DRB1*04 usually demonstrated no response. DRB1*07 allele and HCV 2b were the factors closely related to the response. 
CONCLUSIONS: The response rate of HCV 1b may be the lowest even IFN-α and ribavirin are combined in treatment. Not only virus but also the host plays an important role in anti-virus therapy. Thus, it is necessary to adjust the host’s  immune status to accelerate the clearance of HCV.

BACKGROUND: CD14 was first described as a differentiation antigen on the surface of myeloid lineage cells. It acts as a glycosylphosphatidylinositol (GPI)-anchored receptor for the complex of lipopolysaccharide (LPS) and plays a key role in the activation of LPS-induced monocytes. The purpose of this study was to observe the expression of CD14 protein and its gene in the human U937 promonocytic cell line when these cells were exposed to 1,25-dihydroxyvitamin D3(VitD3) and investigate their sensitivity to endotoxin stimulation. 
METHODS: U937 cells were exposed to (0.1 μmol) VitD3 for 24 hours and were induced to express the CD14 mRNA gene and CD14 protein, then their responses were observed when they were stimulated with different concentrations of LPS for different time.
RESULTS: The U937 cells induced by VitD3 were found to stably express CD14 mRNA and CD14 protein. And CD14 protein enhanced the sensitivity of U937/CD14 cells to lipopolysaccharide (LPS) stimulation. NF-κB in U937/CD14 cells can be activated with low concentration of LPS (1 ng/ml-10 ng/ml), the TNF-α mRNA gene was induced, and then TNF-α was produced and released into the supernatant of culture.
CONCLUSION: VitD3 can induce U937 cell to express the CD14 gene and CD14 protein and enhance the response of this type of cells to LPS stimulation.

BACKGROUND: The development of a harmless and efficient nonviral gene delivery system that can facilitate the penetration of nucleic acids through the plasma membrane is a key to successful gene therapy. The aim of this study was to test a nonviral gene transferring vector’s function of delivering DNA into liver cells to provide an important clue for gene transfer in liver gene therapy.
METHODS: The complex of DNA and DNA delivering protein was injected into mice through their tail veins. Then the mice were killed and their liver tissue was sectioned. The gene transferring results were detected using a confocal laser scanning microscope. RESULTS: Fluorescence analysis indicated that both DNA-membrane penetrating peptide (MPP) complex and DNA- hepatocyte specific receptor binding domain (HSRBD)-MPP complex could go into liver cells. The fluorescence value of liver cells in the DNA- HSRBD-MPP group was higher than that in the DNA-MPP group.
CONCLUSIONS: MPP can successfully deliver DNA and protein into cells, and MPP with a HSRBD can specifically deliver DNA into liver cells. These have laid a foundation for further study on the nonviral liver cell gene delivering system.

BACKGROUND: In recent years, extracorporeal liver perfusion (ECLP) has been regarded as a treatment of acute liver failure (ALF); but the system of ECLP has many problems. The purpose of this experiment was to detect the factors affecting the system of ECLP and to establish a stable and effective system of ECLP.
METHODS: Livers were harvested from health pigs, according to the different styles of perfusion and oxygenation, which were randomly divided into 3 groups. The livers in group A (n=4) were subjected to single portal vein perfusion, oxygenating perfusion blood; the livers in group B (n=4) to dual (portal vein and hepatic artery) vessel perfusion, oxygenating blood, together; and the livers in group C (n=4) to dual (portal vein and hepatic artery) vessel perfusion, but oxygenating blood, separately. The perfusion time, the data of bile production, and hemodynamic parameters of extracorporeal livers in each group were tested. The histological examination of liver tissues from each group was performed at the end of perfusion.
RESULTS: The perfusion time of the liver in group A is significantly shorter than in groups B and C (P<0.05). At 1, 3, 6 hours after perfusion, the data of bile production and hemodynamic parameters of livers in group A were statistically different from those of livers in groups B and C (P<0.05). At 1, 3, 6 hours after perfusion, the data of group B were not statistically different from those of livers in group C (P>0.05). But at 12 hours after perfusion, the data of group B were statistically different from those of livers in group C (P<0.01).
CONCLUSION: The system of ECLP, which is performed by dual (portal vein and hepatic artery) vessel perfusion and oxygenating blood separately, is more stable and effective to keep the function of extracorporeal liver.

BACKGROUND: Nonsurgical pathologic diagnosis of malignant bile duct stricture with a high sensitivity and specificity is desirable for therapeutic scheme. Percutaneous transhepatic endobiliary brush cytology in detecting obstructive jaundice is evaluated.
METHODS: Fifty-eight consecutive patients with obstructive jaundice underwent percutaneous transhepatic cholangiodrainage (PTCD). During the process, a brush was inserted into the bile duct through the preexisted percutaneous transhepatic 8-F sheath, then exfoliated cells were collected from the bile duct stenosis and sent for cytologic diagnosis. The suspicious results were considered of negative diagnosis. All patients had relevant clinical data and follow-up results (15 months to 3 years). Statistical analysis was performed with the chi-square test and Fisher’s exact test of probabilities, and a P value≤0.05 was considered significantly different.
RESULTS: Of all patients, 42 were diagnosed as having malignant stenosis according to brush cytology. Atypical hyperplasia was found in 9 patients and was suspicious of cholangiocarcinoma. Seven patients were found to have benign strictures.The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of brush cytology were 75%(42/56), 100%(2/2), 100%(42/42), 12.5%(2/16), and 75.9%(44/58), respectively. No complications were related to the procedures. In all patients with malignant stenosis, the sensitivity of brushing in diagnosis of cholangiocarcinoma was greater than that in those with non-cholangiocarcinoma (P<0.05). The site of stenosis did not influence the sensitivity and technical success (P>0.05).
CONCLUSION: The results of this study indicate that cytological brushing of biliary stricture during PTCD is a useful method to establish a diagnosis of malignant biliary stenosis with a high sensitivity, but the negative predictive value is not satisfied.

BACKGROUND: Choledocholith is prevalent in some Asian countries and may lead to liver fibrosis and portal vein hypertension. Biliary drainage is an effective treatment for choledocholith. The aim of this study was to assess the impact of biliary drainage on liver fibrosis due to choledocholith.
METHODS: Eight patients with liver fibrosis caused by choledocholith were followed up by biochemical tests (aspartate aminotransferase, alanine aminotransferase) and liver biopsy before and after biliary drainage, respectively. The severity of the fibrosis was scored on a scale from 0 to 3 (0: denoting none; 1: portal and periportal fibrosis; 2: the presence of numerous fiber septa; and 3: cirrhosis). The results were analyzed statistically.
RESULTS: The severity scores of liver fibrosis in the 8 patients were 2, 1; 2, 1; 1, 0; 1, 1; 2, 1; 1, 1; 2, 1; 1, 0 before and after biliary drainage, respectively. The results showed that the average severity of liver fibrosis decreased significantly after biliary drainage (n=8, t=4.573 P=0.003).
CONCLUSION: Liver fibrosis due to choledocholith may regress after biliary drainage.

BACKGROUND: Biliary atresia (BA) is the end results of an inflammatory process, which affect the intrahepatic and extrahepatic bile ducts, leading to fibrosis and obliteration of the biliary tract with the development of biliary cirrhosis. Early diagnosis of BA is difficult, and there is no speci-fic therapy for BA at present. The purpose of this study was to investigate the diagnosis, treatment and postoperative outcome of BA and to explore new diagnostic and therapeutic strategies.
METHODS: Thirty-one children with biliary atresia from our hospital and 201 children with such disease from other hospitals in China were reviewed retrospectively in terms of diagnostic modalities, operative age, operative methods and long-term survival rates after operation.
RESULTS: The operative age of the 31 patients varied from 13 to 270 days. It was <60 days in 6 children (19%), 61-90 days in 14 (45%), 91-120 days in 8 (26%), and >120 days in 3 (10%). No children underwent transplantation for BA. Their 1-6 year survival rate on average was 32.3% (10/31). The early operative rate in China was 12.9% (30/232). One child received liver transplantation with a long-term survival rate of 31.9%.
CONCLUSIONS: Early recognition of babies with BA is critical for optimal intervention for preventing progressive fibrosis. Clinical presentation, imaging and laparoscopy are helpful in enhancing the early diagnostic rate of BA patients. The long-term survival rates can be obtained after the improvement of operative methods, liver transplantation for children with advanced BA, and development of other medical strategies.

BACKGROUND: The short-term results of repair of laparoscopic bile duct injuries have been well discussed, but the long-term results have been rarely reported. This study was undertaken to evaluate the factors influencing the outcome of repair of bile duct injuries caused by laparoscopic cholecystectomy.
METHODS: The outcomes of repair of bile duct injuries caused by laparoscopic cholecystectomy in 31 patients were reviewed retrospectively, and the effects of injury recognition, cholangiography, repair modality and techniques on the long-term results were analyzed.
RESULTS: Bile duct injuries were repaired successfully in 19 (95%) of 20 patients with injuries who had been recognized intraoperatively, and in 10 (90%) of 11 patients with injuries who had been recognized postoperatively. Repair was successful in 29 (93%) of the 31 patients after complete cholangiography. Closure of partial division, laceration, or small perforation of the bile duct with or without T tube drainage was satisfactory in the 23 patients. End to end repair over T tube was successful in 2 transection patients, who were detected intraoperatively. Roux-en-Y hepaticojejunostomy was used successfully to repair transection, excision or stricture of the bile duct in 4 of 5 patients (80%).
CONCLUSION: Early detection of bile duct injuries caused by laparoscopy, complete evaluation of the biliary duct, and appropriate surgical modality and techniques are helpful to improve the results of repair for laparoscopic bile duct injuries.

BACKGROUND: Hypersecretion of biliary cholesterol is believed to be one of the important causes of lithogenic bile. Sterol carrier protein-2(SCP2) participates in cholesterol trafficking and metabolism and may play a key role in cholesterol gallstone formation. This study was undertaken to investigate the expression of liver SCP2 mRNA in patients with cholesterol gallstone and those patients with non-cholesterol gallstone.
METHODS: The expression of liver SCP2mRNA was studied in 36 patients with cholesterol gallstone and 30 patients with non-cholesterol gallstone by reverse transcription-polymerase chain reaction (RT-PCR).
RESULT: The expression of SCP2 mRNA was increased more significantly in patients with cholesterol gallstone than in patients with non-cholesterol gallstone.
CONCLUSION: The SCP2 gene was overexpressed in patients with cholesterol gallstone, indicating that SCP2 may be one of the important causes of cholesterol gallstone.

BACKGROUND: Dendritic cells (DCs) are the most potent antigen-presenting cells and are actively used in cancer immunotherapy. Wild-type p53 can be recognized as an antigen and can induce specific cytotoxic T lymphocytes (CTLs) in the host body. The aim of this study was to investigate the effects of DCs transfected with full length wild-type p53 and modified by bile duct lysates on immune response.
METHODS: The wild-type p53 was transducted to DCs with adenovirus, which were modified by bile duct lysates (Lywtp53DC). The concentration  of the  surface molecules (B7-1, B7-2, MHC-Ⅰ, MHC-Ⅱ) of all DCs was detected with fluorescence activated cell sorter (FACS), and the ability of the DCs to induce efficient and specific immunological response in anti51Cr-labeled target cells was studied. BALB/c mice infected with the DCs and QBC939 were used. CTL response in mice immunized with Lywtp53DC and treatment of tumor-bearing mice with Lywtp53DC and CTL response in these mice were studied.
RESULTS: The surface molecules of Lywtp53DC had a high expression  B7-1 (86.70%±0.07%), B7-2 (18.77%±0.08%), MHC-Ⅰ(87.20%±0.05%), MHC-Ⅱ(56.70%±0.07%) with FACS. The T lymphocytes had a specific CTL lysing ability induced by Lywtp53DC, with a CTL lysis rate of 81%. The immune protection of Lywtp53DC group was obvious, and the tumor diameter of the Lywtp53DC group was 3.10±0.31 mm, 2.73±0.23 mm, 3.70±0.07 mm on days 13, 16 and 19, smaller than those of any control groups (P<0.05), DC, wtp53DC and LyDC. On the other hand, the growth rate of tumor of the Lywtp53DC group was slower than that of any other groups (P<0.05).
CONCLUSION: Dendritic cells transfected with wild-type p53 and modified by bile duct lysates have specific CTL killing capability.

BACKGROUND: The exact mechanism by which cyclooxygenase-2 (COX-2) promotes inflammation in pancreatitis in obscure. This study was undertaken to investigate the role of COX-2 inhibition in an animal model of pancreatitis, a disease process characterized by a systemic inflammatory response and ensuing neutrophil-mediated lung injury.
METHODS: Pancreatitis was induced in 24 Sprague-Dawley rats by intraperitoneal injection of 20% L-arginine (500 mg/100 g body weight). The animals were randomized into 3 groups (8 rats in each group): controls and rats with pancreatitis intravenously resuscitated with either normal saline (0.9% NaCl 3 ml/kg)at 24 and 48 hours or COX-2 inhibitor (parecoxib 1 mg/kg). Pancreatic and lung injuries were assessed histologically. Lung injury was assessed utilizing wet:dry ratio and myeloperoxidase activity to indicate pulmonary neutrophil infiltration. A Western blot was used to determine COX-2 protein expression in pancreatic tissue.
RESULTS: The animals treated with COX-2 inhibitors displayed significantly less pancreatic and lung injuries than their normal saline counterparts. Histological pancreatic and lung injury scores were significantly reduced (P<0.05) in the COX-2 treated group. Lung wet:dry ratios were significantly improved and pulmonary neutrophil infiltration was attenuated in the COX-2 group (P<0.05). Western blot analysis confirmed attenuated COX-2 protein expression.
CONCLUSION: This study shows, for the first time in a rat model, that adjuvant COX-2 inhibition significantly attenuates the severity of both pancreatitis and its associated systemic inflammatory response and end-organ injury.

BACKGROUND: Resection of the superior mesenteric-portal vein (SMPV) during pancreatoduodenectomy is disputed. Although the morbidity and mortality of patients after this operation are acceptable, survival is limited. In this study, we evaluated the morbidity, mortality and survival of patients with ductal adenocarcinoma of the pancreas who had undergone pancreatectomy with en bloc portal vein resection.
METHODS: A total of 32 patients with ductal adenocarcinoma of the pancreas who had undergone pancreatectomy with  SMPV resection between 1999 and 2003 were retrospectively analyzed. In addition, they were categorized into two groups according to the invasion of the wall of the portal vein: group A (n=12),extended compression of the wall of the portal vein by surrounding carcinoma without true invasion and group B (n=20), true invasion including intramural and transmural invasion.
RESULTS: The morbidity of the 32 patients was 31.25%. There was no operative death, and the overall 1-, 3-year survival rates were 59% and 16%, respectively. The mean survival time of patients with microscopically positive margin was only 5.6 months as compared with 20 months in patients with microscopically negative margin. No differences in tumor size, margin positivity, nodal positivity, and 1-, 3-year survival rates were observed between the two groups.
CONCLUSIONS: If selected carefully, pancreatectomy combined with SMPV resection can be performed safely, without increase in the morbidity and mortality. SMPV resection should be performed only when a margin-negative resection is expected to be achieved. SMPV invasion is not associated with histologic parameters suggesting a poor prognosis.

BACKGROUND: Pancreatolithiasis is rarely recognized clinically. This study was undertaken to assess the value of ultrasonography in the diagnosis of 16 patients with pancreatolithiasis and its treatment with pancreatolithotomy plus side-to-side pancreaticojejunostomy. Extracorporeal shock wave lithotripsy was also used in some patients.
METHODS: In the 16 patients with pancreatolithiasis treated at our hospital from 1977 to June 2002, 3 patients were complicated by pancreatic cancer, 2 pancreatic head cyst, and 1 choledochal cyst. Ten patients underwent operation, 3 received endoscopic sphincterotomy (EST), and 3 refused operation and left the hospital.
RESULTS: Epigastric pain was the major symptom of the disease. Ultrasonography was the best choice for the diagnosis of the disease in addition to CT for determining characteristics and location of pancreatolithiasis associated with pancreatic cancer, ERCP for showing pancreatic stone, and EST for detecting stone in the pancreatic head. Pancreatolithotomy plus side-to-side pancreaticojejunostomy was used for the treatment of pancreatolithiasis.
CONCLUSIONS: Ultrasonography is the first choice for the diagnosis of pancreatolithiasis. Pancreatolithotomy plus side-to-side pancreaticojejunostomy is the best choice for the treatment of pancreatolithiasis. CT is of great value in determining characteristics and locations of pancreatolithiasis associated with pancreatic cancer. For patients with pancreatolithiasis associated with pancreatic cancer, surgical treatment should follow the principles of individualized therapy.

BACKGROUND: The efficacy of clinical islet transplantation has been demonstrated with autografts, and although islet allografts have established insulin independence in a small number of IDDM patients, the treatment is confounded by the necessity of central cell damage immunosuppression, the lack of donor tissue, and recurring islet immunogenicity. These limitations underscore a need to develop therapies to serve the large population of diabetic patients. This study was designed to document central cell damage to isolated islets of Langerhans in hamsters and its prevention.
METHODS: Islets were cultured at 37 ℃ for 7-14 days after isolation, and then at 26 ℃ for 2,4 and 7 days before additional culture at 37 ℃ for an additional 7 days. Central cell damage in the isolated islets was monitored by video-microscopy and analyzed quantitatively by a computer-assisted image analysis system. The analysis included daily measurement of the diameter and the area of the isolated islets and the area of the central cell damage that developed in those islets over time during culture. Histological examination and TdT-mediated dUTP-biotin nick end labeling (TUNEL) assay were used to characterize cell damage and to monitor islet function.
RESULTS: Microscopic analysis showed that during the 7 to 14 days of culture at 37 ℃, central cell damage appeared in the larger islets with diameters greater than 200 μm, which included both necrotic and apoptotic cell death. Low temperature (26 ℃) culture prevented central cell damage of isolated islets. The 7-day culture procedure at 26 ℃ could inhibit most of the central cell (excluding diameters greater than 300 μm) damage when the islets were rewarmed to 37 ℃.
CONCLUSIONS: Our results indicate that central cell damage to isolated islets of Langerhans correlates with the size of the islets. Low temperature (26 ℃) culture can prevent central cell damage to the isolated islets, and is capable to successfully precondition these islets for 37 ℃ culture. These novel findings may help to understand the pathophysiology of early loss of islet tissue after transplantation, and may provide a new strategy to improve graft function in the clinical setting of islet transplantation.

BACKGROUND: Neuroendocrine carcinoma of the gallbladder is rare. Its best treatment is not known.
METHODS: Two patients underwent surgery earlier: one for suspected cholecystitis and the other for cholelithiasis. Magnetic resonance cholangiopancreatography (MRCP) showed residual lesions in the livers. The two patients underwent revision surgery followed by chemotherapy.
RESULTS: Both patients tolerated the second stage surgery well, which was followed by chemotherapy with paclitaxel, ifosphamide and cisplatin for 6 cycles. They were treated this way for 8 months and 12 months  post treatment, respectively.
CONCLUSIONS: A proper diagnosis of neuroendocrine carcinoma is made often after surgery. As it is a slow growing tumor and not very chemotherapeutically, sensitive surgery offers the best local control.

BACKGROUND: Operative complications after laparoscopic cholecystectomy (LC) vary. Abdominal pain and other symptoms caused by fluid accumulation in the operative area are not uncommon. Cystic duct (CD) leakage is one of the main sources of the fluid. This study was to evaluate the procedures used in the diagnosis and management of CD leakage after LC.
METHOD: The clinical materials of 3 patients with CD leakage after LC were studied retrospectively.
RESULTS: Three female patients underwent LC for chronic cholecystitis associated with stones. Their clinical symptoms were worsened of pre-existed cardiac arrhythmia, bile draining out from drainage tube, and biliary spillage from umbilical incision, respectively. Final diagnosis was made at the 1st, 2nd and 20th post-operative day. Two of the 3 patients were treated laparoscopically. Their opened CD stumps were closed with an endo-loop, with the abdomen irrigated and drained. The other patient was drained with the percutaneous technique, and a biliary stent was inserted under endoscopy. All patients recovered well.
CONCLUSIONS: The clinical manifestations of CD leakage are different. Ascites can be found by B-ultrasound. Final diagnosis is dependent on magnetic resonance cholangiography and/or endoscopic retrograde cholangiopancreatography. Minimally invasive techniques can be applied to this complication safely and effectively. Reoperation for closure of the opened CD stump can be fulfilled under laparoscopy. Endoscopic drainage must be accompanied with effective abdominal drainage.

BACKGROUND: Hepatic angiomyolipoma (HAML) is a rare tumor containing a variable amount of fat, vessels and smooth muscle. We report the image findings on ultrasonography and computed tomography (CT) of huge HAML.
METHOD: The clinical, imaging and pathological data of a case of HAML were retrospectively collected and analyzed.
RESULTS: A huge heterogeneous hyperecho mass with anecho and hypoecho areas inside was found in the left hepatic lobe on ultrasonography. Color Doppler showed blood flow and arterial spectrum in it. CT scan showed a huge heterogeneous solid mass in the left lobe of the liver, with a low density and hypervascular area in arterial phase. The serum tumor marks were all negative. Ultrasound-guided biopsy was taken twice before resection and both showed necrosis tissue and reaction of inflammatory cells. Postoperative pathological results showed that the tumor was composed of epithelioid smooth muscle cells, thick-walled blood vessels and a few adipose cells with necrosis. The immunohistochemistry results showed appearance of typical HAML, with HMB-45 positive and alpha fetoprotein (AFP) negative.    
CONCLUSIONS: Preoperative diagnosis of HAML relies on combination of CT, MRI and ultrasonography. Our case of HAML showed heterogeneous hyperecho image on ultrasonography. Ultrasound-guided biopsy combined with morphological manifestation and specimen examination for HMB-45 may be helpful in the diagnosis of HAML.