Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in some areas of the world with an extremely poor prognosis. The major etiologic risk factors for HCC development include hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, toxins (alcohol, aflatoxin B1) and various inherited metabolic liver diseases, such as hemochromatosis and alpha-1-antitrypsin deficiency.
Central to the molecular pathogenesis of HCC are mutations of various genes and genetic/chromosomal instability that result from chronic liver disease and the associated enhanced liver cell regeneration and mitotic activity. Alterations in the structure or expression of several tumor suppressor genes and oncogenes have been described. In addition, mechanisms leading to genetic instability due to mismatch repair deficiency or chromosomal instability and aneuploidy due to defective chromosomal segregation appear to be involved.
The prognosis of HCC patients is generally very poor. Most studies have shown a five-year survival rate of less than 5% in symptomatic patients. HCC has been found to be quite resistant to radio- or chemotherapy. Investigations of the natural history and clinical course of HCC revealed a long-term survival of patients only with small asymptomatic HCC that could be treated surgically or nonsurgically. For patients with advanced symptomatic HCC, novel therapeutic strategies such as gene therapy are urgently needed.
Apart from exploring and refining new HCC treatment strategies, the implementation of the existing measures or the development of novel measures to prevent HCC is most important. Primary HCC prevention could have a major impact on the incidence of HCC. Further, secondary prevention of a local recurrence or of new HCC lesions in patients after successful surgical or nonsurgical HCC treatment is of paramount importance and is expected to significantly improve disease-free and overall survival rates of patients.
Based on rapid scientific advances, molecular diagnosis, gene therapy and molecular prevention are becoming increasingly part of our patient management and will eventually complement or in part replace the existing diagnostic, therapeutic and preventive strategies. Overall, this should result in a reduced HCC incidence and an improved clinical outcome for patients with HCC, one of the most devastating malignancies worldwide.

As a benign liver disease, end-stage viral hepatitis has been acknowledged as a main indication for liver transplantation. However, the recurrence of viral hepatitis is the major factor affecting the survival of transplant recipients. The recurrence of hepatitis B is defined as a return of positive HBsAg, while in case of hepatitis C, it is the return of positive HCV-RNA in serum. Several factors are believed as the hazardous factors of hepatitis recurrence, including the types and course of hepatitis, ethnical background, usage of antiviral drugs and immunosuppressive protocol. High dose, long term and combinative therapy of HBIg and novel drugs such as lamivudine and ribavirin offers the promising result of preventing hepatitis recurrence.

A possible link is suggested between hepatic diseases and rheumatic disease. Polyarthralgia and polyarthritis may be seen during the prodromal period of acute viral hepatitis, especially in hepatitis B virus (HBV). The symptoms of arthritis, mild, localized or generalized, mostly involve the small joints of hands. Joint symptoms frequently precede the onset of jaundice, no residual joint deformities. Circulating immune complexes are believed to play a causative role in the development of vasculitis and arthritis. Hemochromatosis is an antosomal recessive disorder of iron. About 43%-81% of patients with hemochromatosis have arthritis. The common extrahepatic manifestations of autoimmune hepatitis are arthralgia and skin rash. The reported prevalence of symptomatic inflammatory arthropathy in patients with primary biliary cirrhosis ranges from 4% to 50%. Skeletal involvement with Wilson’s disease is common. Such patients may complain of pain and stiffness, mainly in the knee, wrist, or other large joints. Shwachman’s syndrome is a disorder of pancreatic exocrine. Symmetric bone lesions have been reported in 10% to 15% of patients. They are involved predominantly at the femoral neck. Rheumatic symptoms are seen in one third of adult patients with cystic fibrosis and arthritis in 2.5% to 12% of patients. The arthritis caused by pancreatic panniculitis is usually symmetrical and involves the small joints of the hand, wrist, and feet, but may involve such larger joints as the elbow, ankle, and knee.

OBJECTIVE: To investigate the gene expression of 4-1BB in peripheral blood mononuclear cells (PBMCs) and its possible significance in clinical liver transplantation.
METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the gene expression of 4-1BB in PBMCs from 22 patients receiving liver transplantation, 13 patients with primary liver carcinoma (PLC), and 12 healthy controls. To determine whether 4-1BB molecule is also expressed on the surface of CD4+ and CD8+ T cell, flow cytometry was used to analyse the phenotype of T cell subsets from the blood of liver transplantation patients.
RESULTS: 4-1BB mRNA was detected in PBMCs from stable survivors after liver transplantation, but almost not detected in PBMCs from PLC patients and healthy controls. Meanwhile, 4-1BB was almost not expressed on the surface of CD4+ and CD8+ T cells in healthy controls and PLC patients. A low level of 4-1BB expression, however, was found on the surface of CD4+ and CD8+ T cells from the stable survivors after liver transplantation.
CONCLUSIONS: This study demonstrates that although patients are stable after liver transplantation, effector T-cells can also be activated through the signal of 4-1BB molecule and persistent immune response to grafts. Blockage of 4-1BB/4-1BBL pathway may benefitially reduce the clinical dosage of immunosuppressive agents and prolong the survival of grafts.

BACKGROUND: To evaluate feasibility and safety of venovenous bypass prior to mobilization of the liver during orthotopic liver transplantation (OLT).
METHODS: Fifty-four patients were classified into two groups. Group A consisted of 23 patients receiving OLT with classical venovenous bypass. Group B consisted of 31 patients who received a modified-procedure: venovenous bypass ahead of the mobilization of the liver during OLT. The blood loss, duration of venovenous bypass, cold ischemia time, anhepatic phase, and transfusion during operation in the two groups were compared. Complications after the operation were also compared between the two groups.
RESULTS: The duration of venovenous bypass and cold ischemia time in group A were longer than those in group B [(99.78±21.36 min) vs (96.32±22.25 min) and (484.78±134.01 min) vs (443.15± 85.27 min)]. The anhepatic phase lasted for about 100 min averagely in the two groups. The volumes of blood loss and transfusion during the operation were larger in group A than in group B [(5096±4243 ml) vs (1726±1125 ml) and (3676±2938.74 ml) vs (1217.69±829.72 ml)]. Postoperative complications occurred in 26 patients of group A and in 19 patients of group B.
CONCLUSION: This modified-procedure or venovenous bypass ahead of mobilization of the liver in OLT can reduce the blood loss during OLT and the incidence of postoperative complications without prolongation of the anhepatic phase and duration of venovenous bypass.

OBJECTIVE: To investigate the prevention and treatment of biliary complications after ortho topic liver transplantation (OLT).
METHODS: OLT was performed in 18 patients with end-stage liver disease, including 6 patients with primary liver cancer. Except 1 patient was infused only through the portal vein, others were infused through the portal vein and hepatic artery of the donor. The biliary tract was reconstructed using choledochocholedostomic anastomosis in 17 patients, and using Roux-en-Y choledochojejunostomic anastomosis in 1 patient.
RESULTS: Four patients with biliary complication were found. In one patient, biliary leakage was found around the T-tube on day 14 postoperatively, and disappeared after re-opening of the tube. In one patient undergoing Roux-en-Y choledochojejunostomic anastomosis, biliary leakage was found on day 12 postoperatively and reoperation was performed. The T-tube was removed from the anastomosis after reoperation, and abdominal infection was controlled, but high fever recurred on day 49 postoperatively. The patient died on day 52 postoperatively. Autopsy revealed biliary leakage and biliary tract necrosis. In another patient, biliary leakage was found on day 3 after operation, and was treated by adequate drainage. Four months after operation, biliary sludge in the common tract was found and treated successfully with oral chemolysis. But biliary sludge or stone recur on one and half year after OLT. Spincterotomy and basket extraction were performed via endoscopic retrograde cholangiopancreatography, and the biliary sludge or stone was cleared out. In case 4, biliary drainage tube cholangiogram showed anastomotic stenosis one month after operation. Three months later, biliary sludge or stone was found beyond anastomotic stenosis. After oral chemolysis (ursodeoxycholic acid) and irrigation with heparinized saline solution via the biliary drainage tube, the biliary sludge disappeared.
CONCLUSIONS: To reduce the incidence of biliary complications, adequate infusion of the hepatic artery, complete slushing of the biliary tract, and reduction of injury to the blood supply of the donor biliary tract are essential. Most biliary complications can be treated successfully by non-operative treatment or minimally invasive operation.

OBJECTIVE: To assess the value of color Doppler ultrasonography in monitoring normal orthot opic liver transplantation and postoperative complications.
METHODS: Forty-one patients after orthotopic liver transplantation were examined by using color Doppler flow imaging to observe the hepatic blood flow and change of ultrasonography of the hepatic parenchyma and bile duct. The measured indexes included maximum blood flow velocity, time-average blood flow velocity (TAV), resistance index (RI) and diameter of the bile duct.
RESULTS: Among 41 patients, 17 (41.5%) suffered from liver transplant rejection. Of the 17 patients, 13 (76.4%) showed decrease of TAV of the portal vein, 15 (88.25%) low-amplitude single-phase serrated wave or negative biphasic wave of the hepatic vein, 9 (52.9%) increased hepatic arterial RI, and 5 (29.4%) slightly dilated bile duct. Sonography showed disappearance of the hepatic artery blood flow around the portal vein in 5 (12.2%) of the 41 patients with hepatic artery thrombosis in the postoperative period. Slight dilatation of the intrahepatic bile duct was found in 3 (7.3%) of the 41 patients in the early postoperational period and it normalized within 2 weeks. Ultrasonography of 20 patients (48.8%) revealed a visible dilatation of the intrahepatic bile duct, which was worsening gradually. The causes of bile duct dilatation included biliary stricture in 2 patients (10%), stone in 15 patients (75%) and others in 3 patients (15%).
CONCLUSIONS: Color Doppler ultrasonography is valuable for monitoring normal liver transplanta- tion and postoperative complications.

OBJECTIVES: To understand the characteristics of primary liver cancer (PLC) in the elderly and summarize the experience in treatment of such patients.
METHODS: The clinical data of PLC in the elderly group (≥60 years, 125 patients) and the young group (≤59 years, 295 patients) were analyzed retrospectively.
RESULTS: In the elderly group, 64 patients were found HBsAg positive, 39 patients small PLC, 24 large PLC, 15 tumor emboli in the portal vein, 86 AFP positive, and 34 hepatectomy performed. In the young group, 205 patients were found HBsAg positive, 79 patients small PLC, 97 large PLC, 96 tumor emboli in the portal vein, 200 AFP positive, and 126 hepatectomy performed. The median survival was 44 and 25 months respectively, and no significant difference was observed in the mortality between the two groups (P>0.05).
CONCLUSIONS: Hepatectomy is a choice of treatment for PLC in the elderly based on their liver function. AFP and B-ultrasonography are important methods for the diagnosis of PLC in the elderly.

OBJECTIVE: To summarize the experience in diagnosis and surgical treatment of hepatic cholangiocarcinoma.
METHODS: Clinical features, diagnosis, surgical treatment and prognosis of 52 patients with hepatic cholangiocarcinoma treated at our hospital from 1993 to 2001 were retrospectively reviewed.
RESULTS: The patients with hepatic cholangiocarcinoma accounted for 4.1% (52/1261) of the total patients with primary liver carcinoma encountered at this hospital. The ratio of male to female was 1.36∶1 in this group. Some patients were complicated by hepatitis B (32.7%), hepatolith (34.6%), liver abscess (13.5%), cirrhosis (53.8%), and serum positivity for alpha-fetaprotein (21.2%). No typical clinical manifestations were present in all patients. The diagnostic rates of ultrasound examination and CT were 80.8% and 94.2%, respectively. The resection rate of hepatic cholangiocarcinoma was 48.1%; and the 1-, 3-, 5-year survival rates were 48.1% (25/52), 30.8% (16/52), and 19.2% (10/52) respectively in this group. In resectable cases, the 1-, 3-, 5-year survival rates were 80.0% (20/25), 48.0% (12/25), 28.0% (7/25) respectively. Seven patients without cirrhosis who had received radical resection and intra-arterial chemotherapy survived for more than 5 years. In unresectable 27 cases, only 5 survived over one year even if selective hepatic arterial embolism and perfusion chemotherapy were employed.
CONCLUSIONS: No specific serum marker is found for hepatic cholangiocarcinoma. CT diagnosis is superior to ultrasonography. When a patient has already diagnosed as having hepatolith or liver abscess before operation and occupying lesion is seen intraoperatively, rapid pathological examination should be done for a fair judgement of the nature of the mass and a decision-making of operative protocol. The patient can survive well after curative resection. No matter whether hepatic cholangiocarcinoma is resectable or not, both selective hepatic arterial embolism and perfusion chemotherapy are valuable.

OBJECTIVE: To investigate the effect of pericardial devascularization combined with preservation of Latarjet’s innervation on portal hypertension.
METHODS: Sixty-two patients (57 men and 5 women) have been undergone pericardial devascularization combined with Latarjet’s innervation since 1984. Clinical results and postoperative complications were evaluated.
RESULTS: The incidence of upper-digestive tract bleeding was 3.2% (2 patients) within 1 month after operation. Four patients (6.5%) died within 1 month after operation (3 patients received emergency operation and 1 selective operation). Among them, 3 patients died from hepatic failure, and one patient from sepsis due to subphrentic infection. Among these deaths, 3 were evaluated Child’s C. After operation, the number of patients with abdominal distension, sudden diarrhea and gastric retension was 7 (11.3%), 3 (4.8%) and 0, respectively.
CONCLUSION: Pericardial devascularization combined with Latarjet’s innervation can preserve the normal function of gastric emptying, prevent acute lesion of the gastric mucosa, and reduce the incidence of esophageal varices rebleeding after operation.

OBJECTIVE: To assess the significance of serum hyaluronic acid (HA), procollagen type Ⅲ (PCⅢ), collagen type Ⅳ (CⅣ) in the histological diagnosis of liver fibrosis.
METHODS: The concentrations of serum HA, PCⅢ, CⅣ in 253 patients with chronic liver diseases were measured by radioimmunoassay. Liver biopsies were performed in all patients at the same time. The liver was pathologically evaluated by a pathologist according to a scoring system. Combined with the results of liver pathological diagnosis, the accuracy of serum HA, PCⅢ, CⅣ in diagnosing patients with hepatic fibrosis (staging ≥S2) or cirrhosis (S4) was assessed using the receiver operating curve (ROC).
RESULTS: The cutoff values of serum HA, PCⅢ and CⅣ for identifying patients with hepatic fibrosis (≥S2) or cirrhosis (S4) were determined. The cutoff values of serum HA, PCⅢ and CⅣ for detecting patients with fibrosis (stage ≥S2) were 90 μg/L, 90 μg/L, 75 μg/L, respectively; their sensitivity (Se) was 80.4%, 82%, 63.1%; their specificity (Spe) was 70.2%, 60.8%, 83.8%; their positive predictive values (PPV) were 86.7%, 83.5%, 90.4%; their negative predictive values (NPV) were 59.8%, 58.4%, 48.4%, respectively. The cutoff values for detecting patients with liver cirrhosis were 210 μg/L for HA, 96.2% for Se, 85.3% for Spe, 65.4% for PPV, 98.8% for NPV; 150 μg/L for PCⅢ, 76.4% for Se, 68.7% for Spe, 40.4% for PPV, 91.3% for NPV; 90 μg/L for CⅣ, 80% for Se, 75.8% for Spe, 47.8% for PPV, 93.2% for NPV, respectively.
CONCLUSIONS: Serum HA, PCⅢ and CⅣ can be determined for an accurate diagnosis of hepatic fibrosis in various stages. HA is the best for screening liver cirrhosis.

OBJECTIVES: To analyze the characteristics of early hepatocellular carcinoma by using multi- phase helical CT and assess the value of this method.
METHODS: Multi-phase helical CT findings were reviewed double-blindly by radiologists.
RESULTS: Altogether 24 lesions were found in 21 patients. In plain CT, the lesions were seen as hypodense or isodense areas. After contrast enhancement, 87.5% of the lesions showed regular or irregular hyperdense enhancement, whereas 12.5% demonstrated tumor vessels in arterial phase, which became hypodensed or isodensed nodules in portal phase or the hypodensed in delayed phase. The prevalence of density changes showed a hypo-hyper-hypo and hypo-hypo pattern.
CONCLUSIONS: Multi-phase helical CT could reflect the blood supply of early hepatocelluar carcinoma, and is also convenient for the differential diagnosis of hepatic cavernous angioma, metastatic tumor, hepatic nodulous hyperplasia, and hepatic inflammatory granuloma.

OBJECTIVE: To detect the mode of yearly biological cycle of malignant biological behavior of hepatocellular carcinoma (HCC).
METHODS: Twenty-one kinds of CT signs reflecting various degrees of malignant biological behavior were determined. A total of 360 patients were collected by random sampling of 30 patients each month. CT signs of each patient were fitted in corresponding group of yearly cyclic data respectively by cosine curves and analysed in terms of sequence characteristics (cosinor).
RESULTS: With a 95% confidence, 10 CT signs showed biological rhythm (P <0.05). The acrophase of CT features for highly-invasive growth concentrated between -60° and -120° from March to April. For low-invasive growth, however, the CT features were relatively low and concentrated between -180° and -270° from July to September. No acrophase was shown between -120°and -180°from May to June, and between
-270°and -330° from October to November.
CONCLUSION: Between CT signs of the highly-invasive and those of low-invasive growth of HCC, a sequential difference in biological cycles can be observed.

OBJECTIVE: To investigate the biological function of augmenter of liver regeneration (ALR), we used yeast-two hybrid technique to detect proteins in hepatocytes interacting with ALR.
METHODS: ALR bait plasmid was constructed by using yeast-two hybrid system 3, then transformed into yeast AH109. The transformed yeast was mated with yeast Y187 containing liver cDNA library plasmid in a 2×YPDA medium. Diploid yeast was plated on a synthetic dropout nutrient medium (SD/-Trp-Leu-His-Ade) containing x-α-gal for selection and screening. After extracting and sequencing of the plasmid from blue colonies. Analysis was performed by bioinformatics.
RESULTS: Of 36 colonies sequenced, 14 are metallothionein, 12 albumin, and 3 selenoprotein P. One colony is a new gene with unknown function.
CONCLUSION: The successful cloning of gene of ALR interacting protein has paved the way for studying the physiological function of ALR and associated proteins.

OBJECTIVE: To investigate the relationship between HBV lamivudine resistance and HBV genotypes or basic core promoter (BCP) mutations.
METHODS: The common coated probes were synthesized according to the conserved regions of the preC gene of hepatitis B virus (HBV). Different colorized probes were chosen from the sequences of different genotypes of HBV (A to F), BCP and YMDD wild types and mutants, respectively. HBV DNA levels, HBV genotypes, BCP and YMDD resistants were analyzed by PCR microplate hybridization ELISA at the zero and 6th month after the patients were treated with lamivudine.
RESULTS: HBV genotyping results showed that HBV types B, C, D accounted for about 30%, 36% and 23% patients respectively. Thirteen BCP mutations (type B in 1 patient, type C in 8 and type D in 4) were found before treatment with lamivudine. HBV DNA levels were lower than 100 pg/ml in 2 patients and higher than 100 pg/ml in 11. 9.4% of the HBV patients (5/43; type C in 3 and type D in 2) showed YMDD resistants and 4 BCP mutations at the same time.
CONCLUSION: Oral treatment of lamivudine decreases the level of serum HBV DNA. The appearance of HBV YMDD resistants is related to certain HBV genotypes, and most of them are BCP mutations.

OBJECTIVE: To identify the influence of transfusion transmitted virus (TTV) co-infection in other virus infected patients and its genotypes.
METHODS: A conservative sequence of ORF1 in the TTV genome was selected as primers and TTV DNA was measured in students and other hepatitis patients by using microplate nucleic acid hybridization and ELISA. The results were statistically analyzed. Nucleotide sequence of divergence >50% was used as color probe for distinguishing TTV genotypes I or II.
RESULTS: TTV DNA was detected in the sera from 2 (3.3%) of 60 students, 2 (14.3%) of 14 patients with non A-non E hepatitis, 6 (12%) of 50 patients with chronic hepatitis B, and 4 (16%) of 25 patients with liver cirrhosis, respectively. Statistical difference was observed between the patient group and the student group (P <0.05), but no significant difference in age, gender, serum ALT levels and TBiL between TTV DNA positive and negative patients (P >0.05). TTV genotype type I was by far the most frequent viral genotype (66.7%), followed by type II (25%), and mixed infection (8.3%).
CONCLUSIONS: These results suggest that the routes of TTV infection may be similar to those of HBV and HCV, and concurrent infection with HBV, HCV are common. TTV co-infection could not affect the clinical features of patients with liver diseases and the pathological process. TTV is not a main causative factor for patients with non A-non E hepatitis. Further study is needed to clarify the role of TTV in patients with non A-non E hepatitis.

OBJECTIVES: To observe the biological effect of ectopic expression of angiopoietin-1 and -2 cDNA on SMMC7721 hepatocellular carcinoma cell line and study the possible role of the angiopoietin gene in the growth or metastasis of implantation carcinoma.
METHODS: Angiopoietin-1 and -2 cDNA were subcloned into the pcDNA3 vector and subsequently transfected into a human SMMC7721 hepatocellular carcinoma (HCC) cell line without detectable angiopoietin gene expression before transfection. Then HCC cells were injected subcutaneously into 30 nude mice and the tumor growth speed and amount of newborn vasculature in the HE stained tissue were observed every 2 days till 3 weeks or the death of animals.
RESULTS: The tumor grew faster with angiopoietin-2 expression; much more blood vessels were seen in the tumor tissue than that without angiopoietin-2 expression. Angiopoietin-1 gene expression seems to have no obvious effect on the increase of vasculature and tumor growth.
CONCLUSIONS: The angiopoietin gene may play a role in the growth and progression of HCC and angiopoietin-2 seems to promote the angiogenesis of the tumor.

OBJECTIVE: To explore the relationship between the changes in the activity of caspase-8 and apoptosis of HepG2 cells induced by 5-fluorouracil (5-Fu).
METHODS: Human hepatoma HepG2 cells were treated with 5-Fu at the concentrations of 1×10-1, 1×10-2, 1×10-3, 1×10-4, 1×10-5 mol/L and for 1, 2, 4, 8, 16, 24 hours, respectively. The caspase-8 activity was detected using caspase-8 fluorescent assay kit. The apoptotic rate of HepG2 cells induced by 5-Fu with or without the caspase-8 inhibitor IETD-FMK was measured by flow cytometry.
RESULTS: After the HepG2 cells were treated with 10-2 mol/L 5-Fu, the caspase-8 activity increased gradually and reached the peak level (313.9±6.9) at 16 hours, then fell down. Compared with the control group, the activity was still significantly higher (274.2±3.9 vs 68.3±3.6, P <0.01). With the increasing concentration of 5-Fu, the caspase-8 activity was also increased; the activity in high concentration 5-Fu was significantly higher than that in low concentration 5-Fu (370.5±4.7 vs 313.7±6.9; 225.7±5.4 vs 183.3±4.8; 183.3±4.8 vs 124.0±6.2, P <0.01). The caspase-8 activity was the highest at 1×10-1 mol/L 5-Fu (370.5±4.7). The caspase-8 activity in low concentration 5-Fu was higher than in the blank control group and inhibitor group (124.0±6.2 vs 68.5±3.4; 124.0±6.2 vs 41.0±2.1, P <0.01). IETD-FMK could block the activation of caspase-8 and reduce the apoptosis of HepG2 cells induced by 5-Fu. The apoptotic rate of HepG2 cells in the 5-Fu group was significantly different from that in the inhibitor group (P <0.01).
CONCLUSIONS: 5-Fu can induce apoptosis of HepG2 cells via caspase-8 signal transduction pathway, which can be blocked by IETD-FMK. 5-Fu promotes the increase of caspase-8 activity in a time- or concentration-dependent manner.

OBJECTIVE: To investigate whether hepatocyte apoptosis in hepatic ischemia-reperfusion (I/R) injury is mediated by Fas pathway.
METHODS: Fas-mRNA expression detected by in situ hybridization assay, caspase-3 activity measured by fluorescence spectrophotometer, and hepatocyte apoptosis detected by TUNEL assay were compared in different I/R conditions between cirrhotic and normal rats. The relationship was analyzed between hepatocyte apoptosis, Fas-mRNA expression, and caspase-3 activity.
RESULTS: In cirrhotic rats, Fas-mRNA expression and caspase-3 activity were significantly increased when the ischemic time prolonged, and subsequently, hepatocyte apoptosis was increased (P <0.01). Under the same I/R condition, the Fas-mRNA expression, caspase-3 activity and hepatocyte apoptosis in cirrhotic liver were significantly higher than those in normal liver (P <0.01).
CONCLUSIONS: Hepatocyte apoptosis in hepatic I/R injury might be mediated by Fas pathway. The possible underlying mechanism that cirrhotic liver is more sensitive to ischemic injury than normal liver is alteration of Fas expression level.

OBJECTIVE: To better understand mucobilia as well as its diagnosis and treatment.
METHODS: The etiological factors, diagnosis, and treatment of 8 patients with mucobilia were discussed.
RESULTS: Mucobilia characterized by copious mucin secretion in the extrahepatic bile duct resulted in obstructive jaundice and cholangitis. Four patients receiving curative resection of primary lesions were free from jaundice and cholangitis while the other 4 who had had palliative biliary drainage showed persistent symptoms.
CONCLUSIONS: Mucobilia is attributable to biliary mucous metaplasia, and benign or malignant biliary tumors. Cholangioscopy and biopsy can offer precise information about the location and extension of the primary lesion. The best choice of treatment is curative resection of the primary lesion.

OBJECTIVE: To evaluate the results of palliative surgical treatment of hilar cholangiocarcinoma in terms of quality of life, survival period and cholangitis rate.
METHODS: The clinical data on 232 patients with hilar cholangiocarcinoma in the last 22 years were analyzed retrospectively. Palliative operations included extrahepatic or intrahepatic choledochojejunostomy (123 patients), bridge internal drainage (15), endoscopic biliary drainage (49), percutaneous transhepatic biliary drainage or celiotomy biliary drainage (29), and exploratory celiotomy external drainage (16).
RESULTS: In this series, the operative mortality rate was 9.1%, and no significant difference was observed between groups. The rate of cholangitis after operation was significantly lower in Roux-en-Y choledochojejunostomy group (16.2%) and bridge internal drainage group (15.4%) than in internal drainage group (35.5%, P <0.01), including percutaneous transhepatic biliary drainage (PTBD), endoscopic retrograde biliary drainage (ERBD), and celiotomy (or PTBD) external biliary drainage group (39.1%, P <0.01). No significant difference in survival was observed between the Roux-en-Y choledochojejunostomy group (9.3±1.8 months) and PTBD (or ERBD) internal drainage group (8.7± 2.2 months), but the survivals of the above groups were significantly longer than those of the bridge internal drainage group (6.5±1.7 months, P <0.05) and celiotomy (or PTBD) external biliary drainage group (4.4±2.1 months, P <0.01).
CONCLUSIONS: In unresectable cholangiocarcinomas, either operative bilioenteric bypass or percutaneous transhepatic biliary drainage can achieve significant palliation. Roux-en-Y choledochojejunostomy is the best choice for palliative operation. The use of U-tube is recommended for internal radiation therapy.

OBJECTIVE: To avoid the pitfalls of choledochotomy with T-tube drainage in the treatment of choledocholith.
METHODS: A novel operation was designed as cholecysto-choledochostomy plus construction of subcutaneous cholecystic tunnel. After the common bile duct was cut open and stones were removed, the gallbladder was appropriately dissociated and the cholecystic ampulla was incised. Then, the incision of the cholecystic ampulla was anastomosed to the opened common bile duct, and the cholecystic fundus was fixed out of the abdominal muscular stratum.
RESULTS: Twenty-one patients with choledocholith underwent this operation successfully and recovered well without postoperative complications. One of them was diagnosed as having recurrent stones in 2 years and 3 months after operation. Consequently, the subcutaneous cholecystic tunnel was opened under local anesthesia to remove successfully the stones with choledochoscope.
CONCLUSION: This operation provides a convenient way to remove postoperative recurrent stones with choledochoscope and avoid receliotomy.

OBJECTIVE: To assess the value of endoscopy in the etiological diagnosis and treatment of post- cholecystectomy syndrome (PCS).
METHODS: 386 patients with PCS were given endoscopic retrograde cholangiopancreatography (ERCP). Having been made the etiology clear, patients with choledocholithiasis were subjected to endoscopic sphincterotomy (EST) or endoscopic papillary balloon dilatation (EPBD) to extract stones, those with papillary inflammatory stricture to EST or EPBD, those with papillary diverticulum and sphincter of Oddi dysfunction (SOD) to EPBD, those with papillary tumor and hepatobiliary tumor to endoscopic metal biliary endoprosthese (EMBE), and those with biliary stricture in the mid bile duct, purulent cholangitis, choledocholithiasis (stones not extracted one time) and bile leakage to endoscopic nose-biliary drainage (ENBD).
RESULTS: ERCP was performed successfully in 371 patients (96.1%). No abnormalities were found endoscopically in 30 patients. In 243 patients with choledocholithiasis, 235 had stones removed after one to three times. Thirty-nine patients with papillary inflammatory stricture were successfully treated with EST or EPBD. Nine patients with papillary diverticulum which oppressed the papillary opening and 7 patients with SOD were also successfully treated with EPBD. In 16 patients with stricture in the mid bile duct, 11 showed improvement after ENBD. Six patients with papillary tumor and 5 patients with hepatobiliary stricture after EMBE showed significant alleviation of jaundice. Six patients with bile leakage caused by cholecystectomy received ENBD successfully, avoiding re-operation. Six patients developed gastroduodenal ulcer and 4 residual stones in the cholecystic duct. Complications occurred in 21 patients (5.7%).
CONCLUSIONS: ERCP may detect the etiology of post-cholecystectomy syndrome at early stage, and therapeutic measures can be taken accordingly in clinical practice.

OBJECTIVE: To evaluate the effects of morphine on the human sphincter of Oddi pressure and the antagonism of anticholinergic agents against morphine.
METHODS: The action of these drugs on the sphincter of Oddi (SO) was evaluated by means of choledochofiberscopy manometry in 40 operated patients with T-tube. The patients were divided randomly into 4 groups: anisodamine, atropine, buscopan, and control. The following data were recorded: duodenal pressure (DP), basal pressure of the sphincter of Oddi (BPSO), contractive amplitude of the sphincter of Oddi (CASO), contractive frequency of the sphincter of Oddi (CFSO), contractive duration of the sphincter of Oddi (CDSO), and pressure of the common bile duct (PCBD). Both morphine and anticholinergic agents were given intramuscularly.
RESULTS: After injection of 10 mg morphine, BPSO, CASO, CFSO, and PCBD increased significantly. After injection of 15 mg anisodamine or 0.75 mg atropine, CASO, BPSO declined obviously, and after injection of 20 mg buscopan, CASO, BPSO, CFSO declined obviously, but in anisodamine, atropine and buscopan groups, they differed insignificantly.
CONCLUSIONS: The results illustrate that SO manometry via choledochofiberscopy is a new method for SO dynamic study. Morphine can increase DP, BPSO, CASO, PCBD, but anisodamine atropine and buscopan can antagonize the effect of morphine.

OBJECTIVE: To investigate the causes of hemorrhage from the gallbladder bed during laparoscopic cholecystectomy.
METHODS: 617 patients who had received laparoscopic cholecystectomy from September, 2000 to March, 2001 at this hospital were reviewed retrospectively. Ninety-one of these patients were selected randomly for prospective observation. Color Doppler ultrasound was used to examine the cause of venous hemorrhage from the gallbladder bed during laparoscopic cholecystectomy and to examine the anatomic relationship between the gallbladder bed and the branches of the middle hepatic vein in 91 patients preoperatively.
RESULTS: A large branch of the middle hepatic vein extended closely behind the gallbladder bed in all 91 patients. The mean distance between the closest point (C point) of this branch to the gallbladder bed was 5.0±4.6 mm. The branch of the middle hepatic vein was completely adherent to the gallbladder bed in 14 (15.38%) of the 91 patients. The distance between this branch and the gallbladder bed was within 1 mm in 10 (10.99%) of the 91 patients. The inside diameter at C point of this branch was 3.2±1.1 mm. The C point was found on the left side of the longitudinal axis of the gallbladder in 31 (34.66%) of the 91 patients, on the right side in 39 patients (42.86%), just on the axis in 21 patients (23.08%). The venous blood flow rate at the C point was 9.9±3.3 cm/s.
CONCLUSIONS: A large branch of the middle hepatic vein passes behind the gallbladder. The inside diameter of this branch is relatively larger. The bleeding of this branch during operation can only be stopped by transfixion. The closest point of this vein to the gallbladder is mostly situated on the right side of the longitudinal axis of the gallbladder. Patients with large branches of the middle hepatic vein close to the gallbladder bed are at risk of hemorrhage during laparoscopic cholecystectomy and should be identified preoperatively with ultrasound.

OBJECTIVE: To introduce a new reconstructional procedure to decrease the complications after pancreaticoduodenectomy.
METHODS: Separate internal drainage of bile and pancreatic fluid in pancreaticoduodenectomy was performed in 256 patients. The digestive tract was reconstructed with Child method, with invaginated pancreaticojejunostomy using a long silastic tube to drain pancreatic fluid internally, an end-to-side choledochojejunostomy and an end-to-side duodenojejunostomy or gastrojejunostomy. Gastrostomy drainage was also performed.
RESULTS: No complications of pancreatic leakage were found.
CONCLUSION: The separate internal drainage of bile and pancreatic fluid plays an important role in preventing pancreaticojejunal anastomotic leakage.

OBJECTIVES: To evaluate the behavior of serum interleukin 10 (IL-10) in patients with acute pancreatitis and to explore the relationship between this cytokine and the severity of the disease.
METHODS: In 45 patients with acute pancreatitis, the serum concentrations of IL-10 was determined on days 1, 2, 3, 4, 5 after admission. Twelve healthy subjects were also studied as controls. These subjects were tested using a commercial ELISA kit. The severity of pancreatitis was determined according to APACHE Ⅱ score and Balthazar CT criteria.
RESULTS: Healthy subjects had no detectable serum levels of IL-10. In acute pancreatitis patients, the serum IL-10 levels were increased on the first day after the onset of the disease and then progressively decreased in the following days. On the first day after the onset of acute pancreatitis, the serum levels of IL-10 in patients with mild acute pancreatitis were significantly higher than in those with severe acute pancreatitis. In the following days, however, no statistically significant difference was observed between the two groups.
CONCLUSIONS: Serum IL-10 concentration reflects the severity of acute pancreatitis. IL-10 is a useful variable for early prediction of the prognosis of acute pancreatitis. The low values of serum IL-10 in patients with severe acute pancreatitis suggests that there may be altered down-regulation of immune system response. An enhanced release of IL-10 may be a method for early treatment of acute pancreatitis.

OBJECTIVE: To evaluate the surgical treatment of pancreatic carcinoma.
METHODS: 101 patients with pancreatic carcinoma admitted from 1995 to 2002 were studied retrospectively. Of 83 patients undergoing surgery, 56 (64.5%) were subjected to tumor resection. Whipple’s procedure was performed in 48 patients, extended regional pancreatectomy and autograft intestinal transplantation in 2, combined resection of pancreatic body or tail carcinoma in 6, and 27 patients with unresectable pancreatic carcinoma were given inner drainage.
RESULTS: Wound dehiscence and digestive bleeding were found in one patient respectively. Pancreatic fistula was found in one patient undergoing extended regional pancreatectomy and autograft intestinal transplantation. Other patients recovered uneventfully.
CONCLUSIONS: Most patients with pancreatic carcinoma could undergo tumor resection. Blood vessel repair or transplantation can be used if the tumor adherent to the superior mesenteric-portal vein. Extended regional pancreatectomy and autograft intestinal transplantation are feasible. Simple inner drainage should be used in the patient whose neoplasm is unresectable.

OBJECTIVE: To investigate the effect of inhibiting factor of cell cycle regulation p27^kip1, retinoblastinoma protein (Rb protein), and proliferating cell nuclear antigen (PCNA) on the genesis and progression of human pancreatic cancer.
METHODS: The expression of p27^kip1, Rb protein and PCNA in the tumor tissue and adjacent tissue of 32 patients with pancreatic cancer was detected by SP immunohistochemical technique.
RESULTS: The p27^kip1 protein positive-expression rate in the tumor tissue of pancreatic cancer was 56.25%, which was lower than that in the adjacent pancreatic tissue (P<0.05). p27^kip1 protein positive-expression was correlated significantly with tumor cell differentiation and lymph node metastasis (P<0.05). The Rb gene protein positive-expression rate in the tumor tissue was 50%, which was also lower than that in the adjacent pancreatic tissue (P<0.05). The PCNA positive-expression rate was 71.87%, which was higher than that in the adjacent pancreatic tissue (P<0.05). PCNA positive-expression was also correlated significantly with tumor cell differentia- tion and lymph node metastasis (P<0.05).
CONCLUSION: The decreased expression of p27^kip1, Rb protein and over-expression of PCNA may play an important role in the genesis and progression of pancreatic cancer.

OBJECTIVE: To evaluate the killing effects of the cytosine deaminase (CD) gene mediated by adenovirus vector on human pancreatic cancer cell lines in vitro.
METHODS: The CD gene was cloned into pAdTrack-CMV-CD, and pAdTrack-CMV-CD and pAdEasy-1 were recombinated in bacteria. The newly recombinated Ad-CD containing green fluorescent protein (GFP) was propagated in 293 cells and purified by cesium chloride gradient centrifugation. Human pancreatic cancer cell lines Patu8988 and SW1990 were infected with this virus, then 5-FC was added. XTT assay was used to estimate relative numbers of viable cells.
RESULTS: The positive clones were selected by using endonuclease to digest the combinatants and the concentration of viral liquids containing the CD gene was 2×1011 pfu/ml. It was found that significant cytotoxic activities were possessed by 5-FC for the CD gene transduced pancreatic cell lines, but little effects exerted on the nontransduced pancreatic carcinoma cells.
CONCLUSIONS: The CD gene mediated by adenovirus with a high infectivity is efficient for gene therapy of pancreatic carcinoma cell lines. These data demonstrate the therapeutic efficacy of an enzyme prodrug strategy in experimental pancreatic cancer.