BACKGROUND: Many treatments have been proposed for non-resectable primary or secondary hepatic cancer but the results have been disappointing. Isolated hepatic perfusion (IHP) was attempted five decades ago but it has been accepted recently after spectacular tumour responses were obtained by several phase Ⅰ-Ⅱ trials.
DATA SOURCES: An English-language literature search using MEDLINE (2003), Index Medicus (2003) and bibliographic reviews of books and review articles. IHP and its history and recent clinical application.
RESULTS: IHP offers unique pharmacokinetic advantages for locoregional chemotherapy and biotherapy. Surgical isolation of the liver and percutaneous techniques using balloon occlusion catheters are reliable and safe. They appear to have significant efficacy even in patients with advanced tumor burden or those with tumors refractory to other types of therapy.
CONCLUSION: IHP which has been developed in recent years is becoming a promising strategy for the treatment of unresectable liver cancer.

BACKGROUND: Few comprehensive reviews on the pathogenesis of hepatitis C virus (HCV)-related liver diseases have been presented to the present. This article was to review the pathogenesis and treatment of HCV-related liver diseases.
DATA SOURCES: Data presented here are mostly taken from Japanese studies.
RESULTS: HCV infection is characterized by persistent inflammation of the liver and frequent development of hepatocellular carcinoma (HCC) in most cases. These characteristic evidences could be explained by immunological alterations and oxidative stress in the hepatocyte caused by HCV infection. Interferon (IFN) treatment is carried out, at present, not only for the elimination of infected HCV for the treatment of chronic liver diseases, but also for both the prevention of HCC and the treatment of advanced HCC with chemotherapy. The treatment for oxidative stress is also important for non-responders to IFN.
CONCLUSION: It is important to understand the pathogenesis of HCV-related liver diseases for a successful treatment.

BACKGROUND: Hepatic artery thrombosis (HAT) which is a serious complication after orthotopic liver transplantation (OLT) remains a significant cause of graft loss. The purpose of this study was to sum up our experiences in the prevention, diagnosis and management of HAT after liver transplantation.
METHODS: From April 1993 to September 2003, a total of 198 patients underwent OLT at our hospital. The hepatic artery was anastomosed using 7/0 prolane with running continuous suture in 96 patients (group 1) and with interrupted suture in 102 (group 2). Ultrasonography was performed every day in two weeks after operation and selectively afterwards.
RESULTS: HAT occurred in 6 patients (6.3%, 6/96) of group 1, and in 1 (1%, 1/102) of group 2 (χ2=4.027, P=0.045). Six patients received emergency thrombectomy, and 1 conservative therapy but died from tumor recurrence eventually. Biliary complication developed in 3 patients after thrombectomy of whom 2 died of liver failure and one waited for retransplantation. In the other 3 patients after thrombectomy, 1 died of renal failure, and 2 survived. The mortality of patients with HAT was 57.1% (4/7).
CONCLUSIONS: The technique of hepatic arterial anastomosis is the key factor for the prevention of HAT. Routine ultrasonography is very important in early detection of HAT after OLT. Biliary complication is a severe outcome secondary to HAT.

BACKGROUND: The first orthotopic liver transplantation in rat (ROLT) was reported by Lee in 1973. Kamada innovatively applied cuff technique to ROLT in 1979. However, the operative procedures were highly demanding and the operative mortality was relatively high. The purpose of this study was to improve the model of ROLT, simplify operative procedures, and enhance the successful rate of operation.
METHODS: Orthotopic liver transplantation was performed in 160 Wistar rats by improved two-cuff technique. The portal vein between donor and recipient was anastomosed with the cuff technique. The same method was used to anastomose the infrahepatic vena cava. The suprahepatic vena cava and the hepatic artery were anastomosed by microvascular suturing and the bile duct was anastomosed end to end by a Teflon catheter.
RESULTS: The average time for donor operation, graft preparation and anhepatic phase was 31 minutes, 14 minutes and 13 minutes, respectively. The anastomosis time for the suprahepatic vena cava, portal vein, infrahepatic vena cava, hepatic artery and bile duct was 7 minutes, 2 minutes, 2 minutes, 8 minutes and 1 minute, respectively. The main causes for operative mortality were pneumothorax, anesthesia, air embolism and massive bleeding, and the successful rate of operation was 92.5%. The causes for death after operation were stoma bleeding, infection, biliary obstruction and graft failure.
CONCLUSION: The improved two-cuff technique can reduce operative mortality, enhance survival rate, and serve as an ideal method for the establishment of animal model of ROLT.

BACKGROUND: Pulmonary complications after orthotopic liver transplantation (OLT) include high morbidity and mortality. Experimental data have suggested hepatic ischemia and reperfusion are induced by pro-inflammatory cytokines. The high level of inflammatory cytokines might additionally influence pulmonary cappillary fluid filtration. The objectives of this study were to measure the concentrations of tumor necrotic factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-8 (IL-8) during OLT and to investigate the relationship between these cytokines and postoperative pulmonary complications.
METHODS: Twenty-two patients undergoing OLT were divided into two groups according to whether they had postoperative pulmonary complications: group A consisting of 8 patients with postoperative pulmonary complications, and group B consisting of 14 patients without postoperative pulmonary complications. Enzyme-linked immunoassay (ELISA) was used to determine serum TNF-α, IL-6 and IL-8. Blood samples were taken at the beginning of operation (T0), clamping and cross-clamping of the inferior cava and portal vein (T1, T2), 90 minutes and 3 hours after reperfusion (T3, T4) and 24 hours after operation (T5).
RESULTS: The level of PaO2/FiO2 in group A was lower than that in group B (P<0.05). The concentrations of TNF-α, IL-6 and IL-8 in the two groups increased rapidly at T2, peaked at T3, decreased rapidly after T3 until 24 hours after operation. The concentrations of TNF-α, IL-6 and IL-8 in group A were higher than those in group B at T2, T3, and T4 (P<0.05).
CONCLUSION: After un-clamping of the inferior cava and portal vein, the serum concentrations of TNF-α, IL-6 and IL-8 increased may be related to pulmonary injury after hepatic ischemic reperfusion.

BACKGROUND: Standard combination-therapy of ribavirin with alternate day interferon (IFN) in patients with chronic hepatitis C (CHC) has been reported to achieve 30%-55% sustained viral response. Early reduction of viral load by daily dosage of IFN could enhance viral clearance. However, the duration of daily dosage protocol and the likely side-effects have not been well studied. We compared the efficacy and safety of a 4 vs 12-week daily IFN dosage in patients with CHC.
METHODS: Fifty-nine, histologically proven CHC patients having ALT levels >1.5×ULN were divided randomly into 2 groups, group I was given IFN 3 MIU daily for 4 weeks, followed by tiw up to 12 months and group II was given IFN 3 MIU daily for 12 weeks, followed by tiw up to 12 months. Ribavirin was given in a dose of 800-1200 mg/d for 12 months.
RESULTS: Fifty-two of the 59 patients (group I=28; group II=24) completed the study. The pretreatment variables and the prevalence of HCV genotype 1 were comparable between the groups. Nine patients (29%) in group I and 6 (25%) in group II had stage 3, 4 fibrosis. At the end of 4, 12, 24 and 52 weeks, HCV RNA negativity was observed in 27%, 54%, 65% and 71% in group I and 38%, 54%, 71% and 75% in group II, respectively (P=ns). Four of the eight (50%) patients with genotype 1 and 30 (69.8%) of 43 patients with genotype non-1 responded to therapy (P=ns). Sustained viral response was achieved in 61% and 71% in groups I and II, respectively. None of the variables predicted non-response precisely. No serious adverse effects were observed and they were comparable between the two groups.
CONCLUSION: Daily IFN dosage with ribavirin is safe and can achieve response in up to 65% patients. Since the efficacy of a 4-week daily dosage of IFN is comparable to a 12-week schedule, we recommend the former regimen.

BACKGROUND: Unresectable hepatocellular carcinoma (HCC) lacks effective therapy and entails very poor progress. In 1991, we found that Chinese herbal compound Star-99 has potentially effect on HCC. The purpose of this study was to probe the anti-cancer effect and the mechanism of focal injection of Chinese herbal compound Star-99 into HCC of mice.
METHODS: In 32 nude mice transplanted with human hepatocellular carcinoma SMMC-7721, 16 received hypodermic implant and the other 16 orthotopic liver transplant. They were randomly divided into three groups: Star-99 group (Chinese herbal compound, 16 mice), alcohol group (8) and saline group (8), respectively. Intratumoral injection of Star-99, alcohol and saline was carried out 10 days after transplantation of HCC. Twenty days after the first injection, the nude mice were killed after being injected every 5 days with a total of 4 injections in each mouse. Tumor tissues were examined pathologically or via an electron microscope and flow cytometrical (FCM) DNA analysis. The three diameters of the tumor were measured with high-frequency ultrasound before and after injection, and the growth index was calculated with the following formula: volume of tumor (after treatment-before treatment)/volume of tumor (before treatment). Double-blind method was applied in the experiment.
RESULTS: The growth index of the Star-99 group (0.068±0.022) and the alcohol group (0.079±0.024) was markedly lower than that of the saline group (4.345±1.453, P<0.01), but there was no significant difference between the Star-99 and alcohol groups. Coagulation (8/8) was the major pathological change in the alcohol group. In the Star-99 group, however, the phenomenon of lymphocytes attacking cancer cells could even be seen under the electron microscope. The typical apoptosis cells and apoptosis bodies as well as the collagen fibrae lined in mass could also be seen in the group (14/16). FCM DNA analysis showed that the rate of apoptosis in the Star-99 group (93.8%) was significantly higher than that in the alcohol (12.5%) and saline groups (12.5%) (P<0.01).
CONCLUSIONS: This study shows that Star-99 markedly inhibits and destructs hepatocellular cancer cells. Star-99 is effective to directly destroy the membrane, cytoplasm and nuclei of tumor cells, causing their crumbling, activate the immune function and inflammatory reaction of nude mice, and induce the apoptosis of cancer cells. The effect of Star99 is significantly different from that of alcohol that mainly causes coagulation of cancer cells. Star-99 is feasible in the treatment of HCC.

BACKGROUND: The resection rate of primary liver tumor in China is only about 20%. A lot of patients with moderate and advanced liver tumor may lose the chance of operation. The objective of present research was to study the efficacy of transcatheter arterial chemoembolization (TACE) combined with percutaneous injection of chemical agents and acetic acids in the treatment of patients with primary liver cancer (PLC).
METHODS: Thirty-three patients with middle and advanced stage of PLC were divided into two groups: percutaneous injection of chemical agents and acetic acids (15 patients, group A) and TACE (18 patients, group B).
RESULTS: Tumor diameter and serum AFP level reduced to 86.6% and 83.3% in group A, and 55.5% and 40% in group B, respectively. There was significant difference between the two groups (P<0.01). The 1, 2, 3, 4-year survival rates of group A were 96.7%, 86.6%, 51.3%, 33.3%, respectively and in group B were 66.7%, 44.4%, 16.7%, 0%, respectively (P<0.01).
CONCLUSION: TACE combined with percutaneous injection of chemical agents and acetic acids is efficacious to increase the survival rate of patients with PLC.

BACKGROUND: Plasma D(-)-lactate and diamine oxidase (DAO) can reflect patients’ intestinal mucosal condition. We evaluated the changes of plasma D(-)-lactate, DAO and endotoxin activities and their significance in patients with liver cirrhosis.
METHODS: Fifty liver cirrhosis patients were enrolled into experimental group and 30 healthy people into control group. The plasma levels of D(-)-lactate, DAO and endotoxin were detected spectrophotographically.
RESULTS: The level of D(-)-lactate was significantly higher in the experimental group than that in the control group (P<0.01). Significant differences of D(-)-lactate levels were observed in Child-Pugh subgroups of the experimental group (P<0.01). The level of DAO was significantly higher in the experimental group than that in the control group (P<0.01), but the level of DAO in Child-Pugh subgroup C was significantly lower than that in Child-Pugh subgroup B (P<0.01). The level of endotoxin was significantly increased in the experimental group except Child-Pugh subgroup A (P<0.01). The plasma levels of D(-)-lactate, DAO and endotoxin were positively correlated with each other (P<0.01).
CONCLUSIONS: The data suggest that both plasma D(-)-lactate and DAO activity are sensitive markers for early diagnosis of gut failure and endotoxemia in patients with liver cirrhosis. The impairment of intestinal barrier function may be one of the critical reasons for deterioration of liver cirrhosis.

BACKGROUND: Molecular cytogenetics of oncogene HER-2 amplification in primary hepatocellular carcinoma (HCC) is still unknown. The aim of this study was to investigate the frequency of HER-2 oncogene amplification in primary HCC and its relations to clinicopathological parameters and prognosis.
METHODS: Forty-two surgical samples from patients with primary HCC were detected for their HER-2 oncogene amplification. The number of chromosome 17 and their ratio were tested by dual fluorescence in situ hybridization (FISH) technique, and then the correlations between HER-2 amplification, clinicopathological characteristics and prognosis were analyzed statistically.
RESULTS: HER-2 oncogene amplification was detected in 9 (21.4%) of the 42 primary HCCs, including 4 patients with high copy (HC) (9.5%) and 5 patients with low copy (LC) (11.9%). HER-2 amplification was associated significantly with tumor size and postoperative survival time of HCC patients (P<0.05), and the presence of HER-2 gene amplification was correlated with postoperative relapse (P=0.257), but not related to sex, age, AFP level, HBV infection, histopathological grading and clinical staging of HCC patients (P>0.05). The HER-2 oncogene copy was examined in 31 (73.8%) of the 42 primary HCCs, consisting of 9 patients with HER-2 amplification (21.4%) and 22 patients with aneuploidy (52.4%). No significant relations were observed between the HER-2 oncogene copy, patient sex, tumor size, histopathological grading, clinical staging, postoperative relapse and survival time (P>0.05); but the HER-2 oncogene copy was correlated significantly to age, AFP level and HBV infection (P<0.05).
CONCLUSIONS: There are a lower frequency of HER-2 oncogene amplification and a higher frequency of chromosome 17 aneuploidy in primary HCC. HER-2 oncogene amplification may be involved in the development and progression of large HCC in some patients, and seems to be a valuably independent prognostic factor predicting the recurrence and poor survival in patients with large HCC.

BACKGROUND: Hepatitis B virus (HBV) infection, a global public health problem, is the leading cause of cirrhosis and hepatocellular carcinoma (HCC) worldwide. There are more than 350 million HBV carriers in the world and up to one million die annually due to hepatitis B associated liver disease. So far no optimal treatment is available for patients with chronic hepatitis B. In the paper we investigated the efficacy of intramuscular matrine in the treatment of chronic hepatitis B.
METHODS: One hundred and twenty patients with chronic hepatitis B were randomly divided into matrine treatment group (n=60) and control group (n=60). The patients of the matrine group were given intramuscularly with matrine (an alkaloid extracted from a traditional Chinese herb Radix Sophorae Flavescentis by Guangzhou Ming Xing Pharmaceutical Factory, Guangzhou, China) of 100 mg daily for 90 days in addition to conventional liver-protective drugs including glucurone, inosine, compound vitamin B and caryophyllin. The control group received conventional liver-protective drugs alone. Clinical manifestations and laboratory parameters including liver biochemistry and serum hepatitis B virus markers were monitored before and after treatment in the two groups.
RESULTS: Significant differences were seen between the two groups in terms of improvement of clinical symptoms and signs, recovery of liver functions, and serum conversion from hepatitis Be antigen to HBe antibody and from positive to negative serum HBV DNA (P<0.05-0.01). The result of the matrine group was more marked than that of the control group. Serious side-effects were not observed except mild pain at the site of injection of matrine in a few patients.
CONCLUSION: These results indicate that intramuscular matrine may be an economical, efficacious, safe drug for the treatment of chronic hepatitis B.

BACKGROUND: Budd-Chiari syndrome (BCS) presents a kind of disease resulted from the occlusion of hepatic vein and/or the intrahepatic inferior vena cava. Its different pathological types were proposed. According to our experience, the membranous type takes a large part of it, and we tried to explore the best treatment of membranous BCS through the analysis of 480 cases retrospectively.
METHOD: The operative results of 480 patients with membranous BCS were analysed retrospectively.
RESULTS: Patients after Kimura’s finger rupture, interventional treatment and membrane resection were followed up with rates of 84.62%, 86.55%, and 87.37%, respectively. The effective rates of the three methods were 61.4%, 91.7%, and 90.4%, respectively, and the recurrence rates of the disease after the 3 procedures were 38.6%, 8.3% and 9.6%, respectively. The long-term effects of interventional treatment and resection were significantly better than those of Kimura’s finger rupture (P<0.05).
CONCLUSION: Balloon dilatation is the choice for membranous BCS. Patients with extensive lesion, thick membrane or recurrence after percutaneous transhepatic angiography should undergo membrane resection.

BACKGROUND: A single-chain antibody (ScFv) phage display library was created by cloning antigen-binding regions of VH (variable domain) and VL gene repertoires as fusion proteins with a minor coat protein of filamentous phage, from which high affinity completely humanized ScFv against PreS1 of hepatitis B virus could be screened and characterized.
METHODS: A combinatorial library of phage-display human ScFv genes, which were derived from peripheral blood lymphocytes immunized by peptide PreS1 in vitro, was constructed. The library contained 7×108 clones.
RESULTS: After 3 rounds panning, a high affinity (K=10-7-10-8 mol/L) ScFv specific to PreS1 was obtained. Sequence analysis showed that the VH belonged to the VH4 family and Vλ to Vλ4.
CONCLUSIONS: The described ScFv may provide a more satisfactory therapy. This application further illustrates that the method of in vitro antigen stimulation is expeditious for the source of human immune antibody library.

BACKGROUND: Convenient way to clarify liver volume or tumor volume in the liver is eagerly demanded by hepatobiliary surgeons, for so many aspects of clinical work need to know the liver volumetry. At present, some methods have been used to measure the liver volumetry, such as computed tomography (CT) scans, three-dimensional ultrasound volumetric system[1] and 3-dimensional sonography[2,3] et al. But enough volumetric information was failed to obtain by surgeons and a new way of measuring the liver volumetry that can be operated by themselves is exigent. Whereas we devise a new method of using PhotoShop in personal computer to measure the liver volumetry.
METHODS: A piece of whole CT film was transformed to a high quality digitized image by digital camera or scanner and then the digitized image was conducted as JPEG file into personal computer. The JPEG image file of CT film was opened by PhotoShop. Determining the edge of interested areas, and the data of pixel values of the interested areas divided by 1 cm2 pixel value will produce the actual area with the unit of square centimeter. If section thickness of CT scan is 1 cm, the sum of the areas of the liver or tumor in all sections naturally is the volume of the liver or tumor.
RESULTS: Comparison of 10 hepatic volumes gained by this method and those gained by the GE Prospeed CT set showed a good relativity between the two groups. The volumes of three right lobes were calculated by this method before lobectomy and their real volumes were obtained postoperatively by a volumenometer. Their variation was limited to 5%.
CONCLUSIONS: Hepatic volume obtained by PhotoShop is reliable. This method can be used to measure hepatic volume perfectly to meet clinical demand, and many parameters such as liver resection rate, graft volume can be achieved. The disadvantage of this method is the step of copying the pixel value from PhotoShop to Microsoft Excel.

BACKGROUND: Recent research found abnormal expression of the c-fms oncogene, which encodes the macrophage colony-stimulating factor receptor (CSF-1R), in several human carcinomas including hepatocellular carcinoma (HCC). But the relationship between the point mutation and abnormal expressing of c-fms oncogene in HCC was not clear. This study is to investigate the relationship between point mutation and abnormal expression of c-fms oncogene in hepatocellular carcinoma (HCC) and to clarify the mechanism of HCC.
METHODS: The expression of c-fms oncogene at different levels of cell, protein and transcription was observed using immune histological ABC, Western blot and Northern blot. PCR-single strand conformation polymorphism and gene sequencing were used to detect the mutation of c-fms in HCC tissues and their surrounding tissues of 30 patients.
RESULTS: The expression of c-fms was significantly higher in HCC tissues than in their surrounding tissues (P<0.01). Point mutation of Leu (TTG)→Ser (TCG) at codon 301 of c-fms amino acids was observed in 21.4% (3/14) HCC tissues. No mutation of c-fms oncogene was detected in the surrounding cancerous tissues.
CONCLUSION: Point mutation at codon 301 of c-fms oncogene is one of the mechanisms of abnormal over-expression in HCC.

BACKGROUND: Fine needle aspiration cytology (FNAC) is a less invasive, inexpensive and rapid method for pathologic evaluation of hepatic masses. This study was to investigate the role of fine needle aspiration cytology in the early diagnosis of liver disease.
METHODS: Fourty-six patients received fine needle (1 mm diameter or 18G) aspiration for the diagnosis of liver disease under ultrasonography or computed tomography guidance. The diagnosis was verified by using hematoxylin and eosin (HE) staining and immunohistochemistry.
RESULTS: Of the 46 patients, 19 had hepatocellular carcinoma (HCC), 2 cholangiocarcinoma, 1 lymphoma, 1 carcinoid tumor, 1 squamous cell carcinoma, 1 tuberculosis, 14 no abnormality, and 6 red blood cells. Cytological diagnosis of 3 patients was inconsistent with histological diagnosis after surgery: incorrect diagnosis (2), and false-negative for failure of aspiration (1).
CONCLUSIONS: Cytological diagnosis should mostly depend on cellular morphology. In addition, immunohistochemistry and special staining are helpful for diagnosis if cytologic preparation is available. Fine needle aspiration cytology of the liver is a diagnostic method that can be used to identify the vast majority of neoplasms of primary or metastatic nature.

BACKGROUND: Epidemiology investigation showed that no worker drunk Maotai liquor for nearly 30 years died of hepatic diseases, and no obvious hepatic fibrosis and cirrhosis were found in 99 workers who had drunk Maotai liquor for a long period by epidemiology investigation and needle biopsy. The same finding was detected in rats that were drunk by Maotai liquor continued for 56 days. This study was to investigate the effects of Maotai liquor on the liver and its mechanism of preventing hepatic fibrosis.
METHODS: After ingestion of Maotai for 56 consecutive days, male SD rats were killed for detecting the levels of metallothionein and malondialdehyde (MDA) in liver tissues. Rat hepatic stellate cells (HSCs) and human HSCs were cultured in vitro to observe the effect of Maotai on HSCs proliferation and collagen synthesis. After ingestion of Maotai for 14 consecutive weeks, the livers of male SD rats were harvested for pathohistological examination.
RESULTS: The level of metallothionein in the liver of Maotai-induced rats increased by 22 folds, whereas the levels of hepatic lipid peroxide and MDA was decreased significantly (P<0.05) in Maotai-induced animals suffering from CCl4. Maotai demonstrated obvious inhibitory effect on proliferation of HSCs and the inhibition was concentration-dependent. Gene expression and protein secretion of collagens could also be inhibited by Maotai. In alcoholic group, typical liver cirrhosis was observed. In Maotai group, however, though fatty degeneration of hepatocytes and mild fibrosis of the interstitium were observed, no obvious hepatic fibrosis and cirrhosis were found.
CONCLUSION: It might be an important mechanism of interfering the progress of hepatic fibrosis that Maotai increases the level of metallothionein in the liver and inhibits the activation of HSCs and the synthesis of collagen proteins.

BACKGROUND: Cordeceps sinensis (CS) is a herb which can inhibit the liver fibrosis. Hyperinsulinemia is common in liver cirrhosis patients. The activity of insulin degrading enzyme could reflect the metabolism of insulin. This study was to detect the dynamical effects and mechanisms of CS on the activity of hepatic insulinase in CCl4 induced liver cirrhosis in rats.
METHODS: Rats were randomly allocated into three groups: normal group, model group and CS group. The rats in the normal group were sacrificed at the beginning of experiment, and the other two groups were sacrificed randomly at the end of the third, sixth and ninth weeks. Blood and tissue specimens were taken. Biochemical assays were used to determine the changes of alanine transaminase (ALT), albumin levels in serum. And radioimmunological assays were used to determine the changes of hyaluronic acid (HA), insulin levels in serum and the activity of hepatic insulinase.
RESULTS: No significant differences were seen in the serum levels of ALT, albumin, HA between the CS group and the model group at the third and sixth weeks (P>0.05). The serum levels of ALT, HA in the CS group were lower than those in the model group at the ninth week (P<0.05), but the serum level of albumin in the CS group was higher than that in the model group at the ninth week (P<0.05). No significant differences were observed in the serum levels of insulin and the activity of hepatic insulinase between the CS and model groups at the third week and the normal group (P>0.05). The serum levels of insulin in the CS and model groups at the sixth and ninth weeks were higher than those in the normal group (P<0.05). But the activity of hepatic insulinase was lower than that in the normal group (P<0.05 or P<0.01). No significant differences were found in the serum levels of insulin and the activity of hepatic insulinase between the CS and model groups at the third, sixth and ninth weeks (P>0.05).
CONCLUSIONS: CS may decrease the damage to hepatocyte by CCl4, and inhibit hepatic fibrogenesis. Six weeks after CCl4 administration, the activity of hepatic insulinase began decreasing. CS could not inhibit the decrease of the activity of hepatic insulinase.

BACKGROUND: Salvianolic acid B (SA-B), one of water soluble compounds derived from Radix salviae miltiorrhizae, had good action against liver fibrosis of patients with chronic hepatitis. Hepatic stellate cells (HSCs) is the cellular resource for liver fibrogenesis, while transforming growth factor-β1 (TGF-β1) is most potent fibrogenic factor. In this study we investigated the mechanism of SA-B action against liver fibrosis relating to the interference with TGF-β1 signaling at HSC.
METHODS: Hepatic stellate cells (HSCs) were isolated, cultured, and incubated with SA-B. The TGF-β1 content in the supernatant of subcultured HSCs was assayed with ELISA. Type I collagen and Smad3 protein in TGF-β1-stimulated primarily cultured HSCs for 4 days were detected by Western blot.
RESULTS: TGF-β1 secreted in activated HSCs was more than in primary HSCs, and SA-B significantly decreased TGF-β1 secretion in activated HSCs. TGF-β1 increased the expression of type I collagen and Smad3 protein in d4 primary HSCs, while SA-B inhibited their expression.
CONCLUSIONS: SA-B inhibits TGF-β1 secretion in activated HSCs and counteracts the expression of TGF-β1 stimulated type I collagen and Smad3. These actions are associated with the effect of SA-B on liver fibrosis.

BACKGROUND: Hepatic fibrosis, a common response to chronic liver injury, is characterized by increased production of extracellular matrix components, whose major part is produced by hepatic stellate cells (HSCs). Taurine is a sulfur containing beta-amino acid rich in human body, and our previous experiments showed that it can inhibit the deposition of the extracellular matrix in the damaged liver. This work was to investigate the effects of taurine on proliferation and apoptosis of HSC and its possible mechanism.
METHODS: Cell proliferation was detected by the thiazole blue (MTT) colorimetric assay. Cell apoptosis and cell cycle were assessed via flow cytometry. The morphology of apoptotic cells was observed by phase-contrast fluorescent micrography after orange acridine staining, and the cAMP content was measured by radioimmunoassay. The expression of c-jun and c-fos was determined by the combination of immunocytochemistry and image analysis software.
RESULTS: Taurine dose-dependently inhibited the proliferation of HSCs at the concentration of 5-50 mmol/L, resulting in more cells in the G0/G1 phase and fewer in the S phase. Taurine markedly increased the synthesis of cAMP and suppressed the gene expression of c-jun and c-fos (P<0.01) in addition to the inhibition of the proliferative effect of platelet-derived growth factor BB on HSC. However, taurine had no effect on induction of cell apoptosis.
CONCLUSIONS: Taurine can significantly inhibit the proliferation of HSC, causing a G0/G1-phase arrest. This effect on HSC proliferation is associated with the enhancement of the synthesis of cAMP and inhibition of the gene expression of c-jun and c-fos. However it can not induce the apoptosis of HSC.

BACKGROUND: A diverse range of cytogenetic alterations of autosomal chromosomes has been reported to date. However, few studies have addressed the abnormalities of X chromosome in hepatocellular carcinoma (HCC) except sporadic reports on the deletion of band F1 in X chromosome, and the clonal analysis of methylation pattern of the X chromosome-linked human androgen receptor gene. Identification of specific X chromosome alterations during the course of neoplastic development would be essential to defining the genetic basis of HCC. Therefore, we studied the regularity of aberration of X chromosome in liver cancer.
METHODS: Hepatocarcinoma cellular lines and tumor tissues were detected respectively through DNA probes of X chromosome after fluorescence in situ hybridization (FISH).
RESULTS: Increased copies of X chromosome were observed in all samples, and four signals of hybridization were of the major type.
CONCLUSIONS: Increased copy number of X chromosome frequently occur in liver cancer. The relationship between copy number of X chromosome and liver cancer genesis needs further investigation. This study is the first of its kind determining the copy number of X chromosome in liver cancer by using FISH.

BACKGROUND: The inhibitory effect of antisense oligodeoxynucleotide (asODN) on the replication and expression of hepatitis C virus (HCV) in vitro is not well elucidated. This study was to assess the effect of asODN on HCV in cholangiocarcinoma.
METHODS: The QBC939 cells transfected by a recombinant HCV containing HCV core gene cloned in vector of PBK-CMV (PBK-HCVC) were treated by 14-mers phosphorothioate ODN complementary to the HCV core genomic region. The variation of HCVmRNA level was detected by RT-PCR. Moreover, the inhibitory effect of asODN was observed in nude mice.
RESULTS: HCVmRNA was detected in transfected-QBC939 cells. The 14-mers complementary phosphorothioate ODN showed effective inhibition on HCVmRNA and unexpression HCVmRNA at 6 μmol/L. The tumorigenicity of the transfected-QBC939 cells incubated with asODN in nude mice was greatly inhibited.
CONCLUSION: The results suggest a potential therapy of asODN for HCV infected cholangiocarcinoma.

BACKGROUND: Intraductal ultrasonography (IDUS) is highly accurate in detection of extrahepatic bile duct stones. This study was to compare the accuracy of IDUS and endoscopic retrograde cholangiography (ERC) in the diagnosis of extrahepatic bile duct stones.
METHODS: Thirty patients suspected of extrahepatic bile duct stones on B ultrasonography, CT, or MRI were enrolled for study. ERC was performed using a Fujinon duodenoscope (ED-410XT, ED-410Xu), then IDUS was done by inserting a Fujinon microprobe (PL2220-15) through the endoscopic biopsy channel to detect the extrahepatic bile duct. Finally stones in the extrahepatic bile duct were detected and extracted by endoscopic sphincterotomy (EST).
RESULTS: Among the 30 patients, 26 were diagnosed as having cholelithiasis accurately through ERC. In one patient the stone detected by ERC was really floccule. Misdiagnosis happened in 2 patients with extrahepatic bile duct stones. So the overall accuracy and sensitivity of ERC in the diagnosis of extrahepatic bile duct stones were 86.7% (26/30) and 92.9% (26/28) respectively. In contrast, IDUS showed the results of diagnosis were in consistent with those of EST stone extraction. Its accuracy and sensitivity in the diagnosis of extrahepatic bile duct stones were 100% (30/30) and 100% (28/28) respectively.
CONCLUSION: IDUS which is superior to ERC in diagnosing extrahepatic bile duct stones can avoid the visual error of ERC.

BACKGROUND: Choledochal cyst, an isolated defect unrestricted to the bile duct, is more appropriately regarded as the sentinel feature of a constellation of anomalies affecting the pancreatobiliary system. This study was to assess the relationship between the expression of inducible nitric oxide synthase (iNOS) and the p53 gene as well as the pathogenesis of choledochal cysts.
METHODS: iNOS and p53 were detected by immunohistochemistry staining in 26 patients with congenital choledochal cysts. Histopathologically, hyperplasia of the mucosa of the cysts and the amylase level in the bile were also investigated.
RESULTS: Patients with a high level of amylase in the bile had higher expression of iNOS than those with a low level of amylase. p53 protein was expressed neither in fusiform type nor in cystic type. The incidence of mucosal hyperplasia was significantly higher in the fusiform type than that in the cystic type.
CONCLUSIONS: Higher expression of iNOS may participate in hyperplasia and carcinogenesis of the mucosa of choledochal cysts. The regurgitation of pancreatic juice into the biliary system might induce mucosal hyperplasia of the biliary tract and inflammatory reaction. In preventing regurgitation-caused hyperplasia and malignancy of the biliary tract, early surgery is important for children with congenital choledochal cysts.

BACKGROUND: Since the resection rate is low for bile duct cancer and the drugs used for chemotherapy are less effective, we studied the inhibitory effects of 5-aza-2-deoxycytidine (ZdCyd) on bile duct cancer cell line QBC939 in vivo and in vitro and its possibility in clinical treatment.
METHODS: The survival and apoptosis rates of QBC939 after treatment with different dose of ZdCyd were detected by methyl thiazoy tetrazolium (MTT) and flow cytometry. The cooperative effect of ZdCyd with other chemotherapeutic drugs was also studied with MTT. The cancer cells were transplanted into nude mice, which were pre-treated with ZdCyd after tumor occurrence.
RESULTS: ZdCyd decreased the cell survival rate, blocked the cell cycle at G1 phase, and increased the apoptosis rate. These effects were dose and time-dependent. ZdCyd also increased the anti-tumor effects of other chemotherapeutic drugs when used in combination. The tumor occurrence rate was lower in the ZdCyd pre-treated cells than in the untreated cells in nude mice, and ZdCyd was found to inhibit tumor growth.
CONCLUSION: ZdCyd can inhibit the growth of QBC939 in vivo and in vitro through induction of cell apoptosis and has the cooperative effect on bile duct cancer cell when it is used with other chemotherapeutic drugs.

BACKGROUND: The major causive factors of gallbladder carcinoma are very complex. Cholecystitis with gallstone was reported one of the most important factors. Many research revealed that cholecystitis or gallstone can give rise to epithelial hyperplasia of gallbladder mucusa or canceration secondarily. In this study, 46 patients were detected in order to find the relationship between infection of different bacteria and formation of gallbladder carcinoma.
METHODS: Using the common gene primer of bacteria 16S ribosomal RNA (rRNA), we detected bacterial gene fragments of gallbladder carcinoma tissues in 46 patients by polymerase chain reaction (PCR). Relative bile was also detected by PCR in 18 patients who underwent operations, including U-tube drainage (1), right or left biliary tube drainage (4), radical cholecystectomy (9), and cholecystorrhaphy (4). The tissue fragments of gallbladder carcinoma from the remaining 28 patients were paraffin slices.
RESULTS: The positive rate of bacterial DNA in gallbladder carcinoma tissue was 78.3% (36/46). The sequence of 16S ribosomal RNA gene fragments amplified by PCR was approximately 371 base pairs (bp). Multiple kinds of standard bacterial gene fragments obtained from 36 patients included Colibacillus, B.fragilis, Klebsiella, C.perfringens and Clostridium, with a positive rate of 78.3% (36/46). Among the 36 patients, 14 patients with gallbladder carcinoma received operation and their relative bile at operation was detected bacterial gene fragments with a positive rate of 77.8% (14/18). This result was close to that in gallbladder carcinoma tissues.
CONCLUSIONS: Our results suggested that there might be a relationship between occurrence of gallbladder carcinoma and infection of different kinds of bacteria, especially anaerobic bacteria—C.perfringers. This reminds us that the gallbladder mucosa stimulated by anaerobic and aerobic bacteria might be the principal cause for the development of carcinoma.

BACKGROUND: Anomalous pancreaticobiliary junction is often associated with biliary tract carcinoma and acute pancreatitis. We assessed the value of image analysis in the diagnosis of patients with anomalous pancreaticobiliary junction (APBJ) and the principles for the treatment of APBJ.
METHODS: Sixty-four patients with APBJ were subjected to ultrasound imaging, endoscopic retrograde cholangiopancreatography (ERCP) and magnetic resonance cholangiopancreatography (MRCP) before surgery. The diagnostic accuracy of image analysis and their surgical outcomes were evaluated retrospectively.
RESULTS: On ERCP and MRCP, the length of the common channel was calculated to be 15 mm or longer in all patients, and the angle of the junction was more than 75° in 49 (76.6%) of the 64 patients. Of the 64 patients, 28 were defined of pancreatic duct type (P-C) (28/64, 43.75%), 32 bile duct type (C-P) (32/64, 50%), and 4 common channel type (4/64, 6.25%).
CONCLUSIONS: Patients with APBJ are often associated with biliary tract and pancreatic diseases, and early detection and correct surgical treatment could avoid serious complications. ERCP and MRCP are accurate in the diagnosis of APBJ.

BACKGROUND: Anastomotic leakage at the pancreaticojejunostomy remains a common and dreaded complication after pancreaticoduodenectomy. This study was to introduce a method for lowering the mortality, morbidity, and other postoperative complications after pancreaticoduodenectomy.
METHODS: From January 1991 to December 2001, twenty-six patients were treated using one-layer pancreaticojejunostomy. The mean age of these patients was 52.3 years. Some of these patients were complicated by hypoproteinemia, anemia and jaundice. All patients were subjected to pancreaticoduodenectomy, reconstruction of the digestive tract by Child’s method, and one-layer or Braun’s anastomosis after pancreaticojejunostomy, choledochojejunostomy, and gastrojejunostomy.
RESULT: No death and pancreatic fistula were observed after operation.
CONCLUSION: One-layer pancreaticojejunostomy is simple and safe.

BACKGROUND: Type 1 diabets is an autoimmune disease caused by the destruction of pancreatic β-cell with an increased incidence worldwide in the closing decades of the 20th century. This study was to investigate the effects of human umbilical cord serum (UCS) on the proliferation and function of human fetal islet-like cell clusters (ICCs) in vitro.
METHODS: Eight fresh pancreatic glands obtained after induction of labor with water bag were mildly exposed to collagenase V, and the digested cells were cultured in a RPMI-1640 medium plus 10% pooled UCS or fetal calf serum (FCS) to permit cells attachment and outgrowth of ICCs.
RESULTS: In 8 consecutively explanted glands, development and proliferation of ICCs were observed. In the presence of FCS, the outgrowth of ICC took place on the top of a fibroblast monocellular layer. UCS affected less growth of fibroblasts and increased the formation of ICCs about four-fold compared with explants from the same glands maintained in FCS. In both UCS and FCS, the insulin content of the medium was variable to a certain extent and progressively declined from day 2 to day 6. Dithizone-stained ICCs in UCS suggested that most cell clusters were islet cells (β-cells), and the purity of islets was estimated 80%-90%. The ultrastructure of the cultured cells showed a large number of granule-containing cells, most of which were identified as β-cells.
CONCLUSION: We conclude that in comparison with explants with FCS, the yield of ICCs and purification of islet cells are markedly increased by UCS and may facilitate the proliferation of pancreatic β-cells intended for islet transplantation.

BACKGROUND: Hepatic artery thrombosis is one of the serious complications after liver transplantation. It will mostly cause a failure of the transplantation. This case of hepatic artery thrombosis showed a stable clinical course and minimal histological change, and now has been surviving for 4 years with normal liver function. We investigated the possible causes for asymptomatic hepatic artery thrombosis in one patient after orthotopic liver transplantation (OLT) and discussed the diagnosis of ischemia of OLT pathologically and clinically.
METHODS: Liver function test, color Doppler ultrasonography, and hepatic arteriography were performed during the development of hepatic arteriothrombosis. Possible factors for the asymptomatic process of the thrombosis were analyzed.
RESULTS: On the 4th postoperative day, thrombosis formed at the anastomotic stoma of the hepatic artery, and on the 11th postoperative day, the artery was completely occluded. Serial liver biopsies revealed intrahepatic cholestasis, hydropic degeneration of hepatocytes, atrophy of the biliary epithelium, and fibrosis in the portal area. Monitoring of liver function showed nothing abnormal except elevation of γ-GT and ALP levels. On the 71st day after OLT, arteriography demonstrated that the hepatic artery remained completely occluded in addition to the establishment of collateral circulation and compensation of the portal vein. The patient didn’t show any symptoms of arterial thrombosis.
CONCLUSION: Collateral circulation and compensation of the portal vein are beneficial to allograft survival and avoidence of retransplantation after thrombosis of the hepatic artery. Color Doppler ultrasonography within 2 weeks after OLT is helpful to the early diagnosis of hepatic arteriothrombosis.

BACKGROUND: A 27-year-old woman in her 20th week of pregnancy was hospitalized because of food poisoning caused by Amanita phalloides.
METHODS: Previously extracorporeal purification treatments with 2 times of hemodialysis plus hemoperfusion and a high volume therapeutic plasma exchange (PE) in addition to intensive medication during the first 8 days failed to improve hepatic encephalopathy (HE) and liver function but developed deep coma with severe blood chemistry and signs of threatened abortion.
RESULTS: Treatments with intermittent molecular adsorbent recirculating system (MARS) for 3 times resulted in an immediate improvement of liver function and clinical symptoms including HE and threatened abortion until her fully recovery. When the life-threatening maternal illness was cured gestation went on until premature birth at the 36th week of pregnancy, and the infant underwent an undisturbed development.
CONCLUSION: MARS method appears to be an optimal therapy for patients with acute liver failure secondary to cytoxic mushroom poisoning during pregnancy.

BACKGROUND: Lymphoepithelial cyst of the pancreas is a rare lesion of undetermined pathogenesis that had been documented almost exclusively in males. The literature on this entity is limited to reports of single or a small number of cases.
METHODS: The case we described herein was compared with a total of 36 cases reported elsewhere.
RESULTS: The 37 cases of lymphoepithelial cyst of the pancreas including our case were reviewed. Lymphoepithelial cysts have uniform and distinctive clinicopathologic features. Approximately 46% of the reported cases were asymptomatic with the lesions found incidentally, and their symptoms were non-specific.
CONCLUSIONS: Lymphoepithelial cyst is a rare benign lesion of the pancreas. Fine-needle aspiration biopsy (FNAB) is a rapid and reliable technique that can be used as the first diagnostic step in cases of cystic lesions of the pancreas.