BACKGROUND: A safe and effective preservation solution is a precondition for liver transplantation, which is accepted as the radical treatment for patients with end-stage liver disease. The increasing use of marginal donors and non-heart beating donors as well as the establishment of a national organ allocation network call for better preservation. New preservation solutions like histidine-tryptophan-ketoglutarate (HTK) solution and Celsior solution have been introduced to liver preservation, and protective gene intervention and other modifications have also been investigated. In this article, we review recent advances in liver preservation solutions.
DATA SOURCES: An English-language literature search was conducted using MEDLINE (1990-2005) on liver preservation solution, biliary complication, protective gene and other related subjects.
RESULTS: Although the high viscosity of the University of Wisconsin (UW) solution proved harmful to the hepatic microcirculation, three solutions showed equivalent preservation effects. When the cold ischemia time was short, there were no significant differences among the three solutions in the incidence of biliary complications. So far, modifications of preservation solutions have achieved great success. Several types of protective genes like A20, Bcl-2, Bcl-XL and HO-1 were reported to have definite liver protective effects. The addition of other substrates like TNF-α antibody, tacrolimus (FK506) and fructose-1, 6-bisphosphate (FBP) can also improve the preservation effect. However, addition of insulin to UW solution is harmful to the graft.
CONCLUSIONS:  In centers with highly-developed transplantation techniques, HTK and Celsior solutions are acceptable in liver preservation. Protective gene modification and addition of substrates like TNF-α antibody, FK506 and FBP are prominent approaches to improve liver preservation.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most frequent primary malignant tumors in the world. Hepatic resection and liver transplantation are considered optimal for potential treatment of HCC. However, only 20% of HCCs can be surgically treated. And most of surgically-noneligible patients have to receive interventional managements including local ablation and transarterial chemoembolization (TACE). In this paper, we review the interventional treatments of HCC.
DATA SOURCES: A literature search of PubMed database was conducted and research articles were reviewed.
RESULTS: Percutaneous ethanol injection (PEI) is usually applied to small HCC for a complete necrosis. Radiofrequency ablation, an alternative to PEI, also causes tumor necrosis and needs fewer times of ablation. Other methods such as acetic acid injection, laser, microwave, etc have enriched local ablation for HCC. High intensity focus ultrasound (HIFU) is thought to be promising. TACE, another common modality, can improve the survival rate of patients with HCC. The newly developed embolic agents and adjuvant rAd-p53 gene therapy are well reported.
CONCLUSIONS: Surgically-noneligible HCC can be treated with interventional procedures. Each method has its advantages and disadvantages. However, it is still pressing to develop ablative methods as well as new embolic agents for a better prognosis of HCC.

BACKGROUND: Acute pancreatitis (AP) is a common acute abdomen with high mortality, multiple complications and complicated causes. There is no effective therapy for AP. Radix salviae miltiorrhizae (Danshen), a traditional herbal medicine, has a low price and a wide range of clinical applications. It is effective to promote blood flow, eliminate stagnancy, and relieve pain. It is also found to be effective in treating AP. We reviewed the progress in research into the mechanism of Radix salviae miltiorrhizae in treatment of AP.
DATA SOURCES: An english-language literature search was conducted using MEDLINE (1988-2005) on Radix salviae miltiorrhizae (Danshen) and acute pancreatitis.
RESULTS: The mechanisms of Danshen in the treatment of AP include improvement of microcirculatory disturbances; elimination of oxygen free radicals; modulation of the metabolism of lipid inflammatory mediator; and blocking of calcium inflow and prevention of calcium overload. 
CONCLUSION: Danshen can effectively reduce the mortality and complications of AP.

BACKGROUND: Expression of Fas ligand (FasL) on the graft by gene transduction is expected to introduce apoptosis to lymphocytes to protect rejection, but the FasL-expressing graft cells may also induce apoptosis as the graft usually expresses Fas antigens. In this study, a strong antiapoptotic gene, bcl-2, was cotransfected with the FasL gene in rat liver graft to protect against Fas-mediated cell death and to prolong recipient survival.
METHODS: Orthotopic liver transplantation was done in a strain combination of DA to LEW rats. After donor vascular isolation, adenovirus-mediated FasL and bcl-2 genes were cotransfected in the liver graft.
RESULTS: Intragraft expression of FasL mRNA was constitutively expressed after adenovirus-mediated transduction, although expression of FasL increased mildly in control grafts. Bcl-2 mRNA was highly expressed at 2 days after reperfusion. In contrast, lower expression of bcl-2 was observed in the control group. The average survival of the gene transferred allografts increased from (9.8+1.3) days to (18.5+8.7) days compared with the control group.
CONCLUSION: Our results indicate that rat liver allografts can be protected against host immune responses by adenovirus-mediated FasL and bcl-2 transfection, and that bcl-2 expression prevents the graft from Fas-mediated apoptosis.

BACKGROUND: The clearance of propofol is very rapid, and its transformation takes place mainly in the liver. Some reports indicated extrahepatic clearance of the drug and that the lungs are the likely place where the process occurs. This study was undertaken to compare the plasma concentrations of propofol both in the pulmonary and radial arteries after constant infusion during the dissection, anhepatic and reperfusion phases of orthotopic liver transplantation (OLT) without veno-venous bypass, attempting to investigate extrahepatic clearance and to determine whether the human lungs take part in the elimination of propofol.
METHODS: Fifteen patients undergoing OLT without veno-venous bypass were enrolled in the study, and propofol was infused via a forearm vein at a rate  of  2  mg•kg-1•h-1. Blood samples were simultaneously collected from pulmonary and radial arteries at the end of the first hepatic portal dissection (T0), at the clamping of the portal vein (T1), 30, and 60 minutes after the beginning of the anhepatic phase (T2, T3), and 30, 60, and 120 minutes after the unclamping of the new liver (T4, T5, T6). Plasma propofol concentrations were measured using a reversed-phase, high-performance liquid chromatographic method with fluorescence detection.
RESULTS: The concentrations of plasma propofol in the pulmonary and radial arteries at T2 and T3 rose significantly compared with T0 and T1 (P<0.01) respectively.
After reperfusion, the drug concentrations at T4, T5 and T6 decreased significantly compared with T2, T3 (P<0.01) respectively. There were no significant differences in plasma propofol concentrations between the pulmonary and radial arteries at any time points.
CONCLUSIONS: Propofol is eliminated mainly by the liver, and also by extrahepatic organs. The lungs seem to be not a major site contributing to the extrahepatic metabolism of propofol in humans.

BACKGROUND: The critical shortage of transplantable organs necessitates utilization of unconventional donors. But the safe time limits of cold preservation of liver grafts subjected to warm ischemia (WI) for up to 30 minutes from non-heart-beating-donors (NHBDs) has not been delineated. In this study, we investigated how the limits of cold ischemia (CI) in University of Wisconsin (UW) solution are changed in liver grafts subjected to WI from 10 to 30 minutes.
METHODS: A simple porcine NHBD liver transplantation (LT) model was developed. In donors, livers were subjected to 10, 20 or 30 minutes of WI and subsequent different times of CI in UW solution. Animals were divided into three groups (WI 10 min, WI 20 min, WI 30 min, n=13 in each group) and nine subgroups (from CI 6 h to CI 28 h). One-week survival rates of recipients, hepatic function, liver energy metabolism, grafted liver microcirculation and pathological observations of the liver were compared.
RESULTS: In the WI 10 min group, the one-week survival rate of the CI 20 h subgroup was significantly higher than in the other two subgroups (CI 24 h and CI 28 h) (P<0.05). Furthermore, the CI 20 h subgroup had a lower level of alanine aminotransferase (ALT), less pathological damage, a higher concentration of adenosine triphosphate (ATP) and microcirculatory blood flow in the grafted livers at 1 hour after reperfusion than the other two subgroups. The same trends were also found in the other two groups (WI 20 min and WI 30 min) and their subgroups.
CONCLUSIONS:  The cold preservation limits of the liver grafts shortened from 20 to 12 to 6 hours when WI time was prolonged from 10 to 20 to 30 minutes. Only the liver grafts within these time limits could be safely transplanted.

BACKGROUND: The shortage of donor livers is a critical limiting factor for the use of liver transplantation in treatment of end-stage liver diseases. Organs from non-heart-beating donors seem to be an effective option to alleviate this problem. Warm ischemia injury, however, directly influences the grafts' activity and functional recovery after operation. We investigated the energy metabolism and post-transplant survival of liver grafts after different warm ischemia times (WITs) in rats and determined the maximum limit for liver grafts with warm ischemia.
METHODS: Rats were randomized into 7 groups with WITs of 0 (control), 10, 15, 20, 30, 45 or 60 minutes. The indices of energy metabolism were measured by reversed-phase high performance liquid chromatograpy and all liver graft specimens were subjected to ultrastructural observation. After orthotopic liver transplantation (OLT), the recovery of energy metabolism in liver grafts after 24 and 48 hours and the survival of the rats were assessed.
RESULTS: The levels of adenosine triphosphate (ATP) and energy charge (EC) decreased gradually after different WITs in a time-dependent manner, and this was especially significant within 30 minutes. The levels of ATP and EC in liver grafts with 30 minutes of warm ischemia largely recovered 24 hours after OLT, with 45 minutes of warm ischemia partially recovered 48 hours after OLT, and with 60 minutes of warm ischemia, hardly recovered even 48 hours after OLT. The survival time after OLT did not significantly change with up to 30 minutes of WIT, while long-term survival was reduced with 45 and 60 minutes of WIT.
CONCLUSIONS: The levels of ATP and EC after OLT may be important criteria for evaluating the quality of a liver graft. The WIT of a liver graft is closely related to the recovery of hepatic energy metabolism and the graft survival.

BACKGROUND: In spite of accurate selection of patients eligible for resection, and although advances in surgical techniques and perioperative management have greatly contributed to reducing the rate of perioperative deaths, stress must be placed on reducing the postoperative complication rates reported to be still as high as 50%. This study was designed to analyze the causes and foreseeable risk factors linked to postoperative morbidity on the grounds of data derived from a single-center surgical population. 
METHODS: From September 1989 to March 2005, 287 consecutive patients, affected either with HCC or liver metastasis, had liver resection at our department. Among the HCC series we recorded 98 patients (73.2%) in Child-Pugh class A, 32 (23.8%) in class B and 4 in class C (3%). In 104 colorectal metastases, 71% were due to colon cancer, 25% rectal, 3% sigmoid, and 1% anorectal. In 49 non-colorectal metastases, 22.4% were derived from breast cancer, 63.2% gastrointestinal tumors (excluding colon) and 14.4% other cancers. We performed 80 wedge resections, 77 bisegmentectomies and/or left lobectomies, 74 segmentectomies, 22 major hepatectomies, 20 left hepatectomies, and 14 trisegmentectomies. 
RESULTS: The in-hospital mortality rate in this series was 4.5%, and the morbidity rate was 47.7%, because of pleural effusion (30%), hepatic abscess (25%), hepatic insufficiency (19%), ascites (10%), hemoperitoneum (10%), or biliary fistula (6%). The variables associated with the technical aspects of the surgical procedure that were responsible for the complications were: a Pringle maneuver length more than 20 minutes (P=0.001); the type of liver resection procedure, including major hepatectomy (P=0.02), left hepatectomy (P=0.04), trisegmentectomy (P=0.04), bisegmentectomy and/or left lobectomy (P=0,04); and a blood transfusion of more than 600 ml (P=0.04). 
CONCLUSION: The evaluation of causes and foreseeable risk factors linked to postoperative morbidity during the planning of surgical treatment should play the same role as other factors weighed in the selection of patients eligible for liver resection.

BACKGROUND: Altered small-intestine motility, lengthening of orocecal transit time (OCTT), and small-intestinal bacterial overgrowth (SIBO) have been detected in patients with nonalcoholic steatohepatitis (NASH). These changes might be related to the progressive course and poor prognosis of the disease. This study was undertaken to investigate the effect of 4-week treatment with cisapride on OCTT.
METHODS: Ten NASH patients without diabetes were included. Ten healthy individuals served as controls. OCTT was measured by lactulose breath test (LBT). Anti-endotoxin core antibodies (EndoCAb) IgG were also examined. The effect of cisapride (10 mg TID during 4 weeks) on LBT and serum EndoCAb IgG levels in NASH patients was investigated.
RESULTS: The NASH patients had more significantly prolonged OCTT (95±17 min) than the controls (59±18 min, P=0.00032). Cisapride administration decreased OCTT (from 95±17 min to 83±19 min, P=0.037), basal breathed H2 (from 9.87±1.60 ppm to 8.61±1.63 ppm, P=0.046) and EndoCAb IgG titers (from 5.24±0.68 GMU/ml to 4.20±0.72 GMU/ml, P=0.013) in NASH patients.
CONCLUSIONS: The present data suggest the existence of deranged intestinal motility and endotoxemia in NASH patients. Cisapride administration during 4 weeks possibly restore intestinal motility and ameliorate endotoxemia in NASH patients.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, its prognosis is poor, and early detection is of utmost importance. Although alpha-fetoprotein (AFP) is a useful marker for detecting and monitoring HCC development, the false-negative or false-positive rates with AFP alone may be as high as 30%-40% for patients with small HCCs. To enhance the specificity and accuracy of AFP measurements for HCC, we analyzed AFP expression states in livers, detected the hepatoma-specific AFP (HS-AFP) fraction and AFP-mRNA from peripheral blood mononuclear cells, and explored their clinical implications for HCC diagnosis.
METHODS: AFP expression and hepatocyte distributions in liver specimens were investigated by an immunohistoche-mical assay. Total RNAs were extracted from circulating blood, synthesized to cDNA through random primers and reverse transcriptase, and fragments of the AFP gene were amplified by a nested-PCR assay. The HS-AFP fraction was separated by lectin-affinity chromatography and its level was detected by radioimmunoassay.
RESULTS: The incidence of AFP was 73.3% in HCC tissues and its expression in HCCs with moderate or low differentiation was significantly stronger than that of HCCs with high differentiation (P<0.05). The incidence of AFP gene fragments was 100% in HCCs, and 60% in paracancerous tissues (P<0.01). In the HCC and liver cirrhosis groups, the incidence of HS-AFP was 91.7% and 18% (P<0.01), and of AFP-mRNA was 56.7% and 16% (P<0.01), respectively, and neither was found in controls. HS-AFP or AFP-mRNA was not significantly related to size or number of HCC, but to its differentiation, metastasis, and relapse (P<0.05).
CONCLUSIONS: Different AFP expression is present in different parts of HCC tissues. HS-AFP and AFP-mRNA fragments improve sensitivity and specificity, and both are useful markers to diagnose HCC or monitor metastasis and relapse.

BACKGROUND: Malignant tumors are common diseases threatening to the health and life of human being. Clinically, the multidrug resistance of tumor cells and bone marrow depression caused by chemotherapeutic agents are the main obstacles to the treatment of tumors, and both are related to the mdr1 gene. The over expression of the mdr1 gene in tumor cells contributes to the multidrug resistance of malignant tumor cells. With little expression of the mdr1 gene, bone marrow cells particularly susceptible to multidrug resistance-sensitive agents, which cause serious toxicity in bone marrow. This study was undertaken to assess therapeutic efficacy of transplantation of bone marrow mononuclear cells transferred with the mdr1 gene and over-dose chemotherapy with doxorubicin for VX2 hepatocarcinoma of rabbits.
METHODS: The mdr1 gene was transferred into the bone marrow mononuclear cells of rabbits, which was co-cultured with retroviral vector-containing supernatant, and the cells were autotransplanted into a rabbit model with VX2 hepatocarcinoma. After chemotherapy with doxorubicin, the protective effects of the mdr1 gene and therapeutic efficacy of over-dose chemotherapy were observed.
RESULTS: The mdr1 gene was transferred successfully into the bone marrow mononuclear cells, with a transduction efficiency of 35%. After autotransplantation, the mdr1 gene was expressed functionally in bone marrow with a positive rate of 8%, indicating that the gene played an important role in bone marrow protection. The rabbits with VX2 hepatocarcinoma, which had received the mdr1 gene-transduced cells, survived after chemotherapy with a 3-fold dose of adriamycin, and their white blood cell counts were (4.26±1.03)×104/L. Since hepatocarcinoma cells were eradicated, the survival time (97.00±46.75 d) of the rabbits was extended (P<0.05) and the healing rate of the tumor was increased (P<0.05).
CONCLUSIONS: The transferring of the mdr1 gene into bone marrow mononuclear cells could confer chemoprotection to bone marrow, and over-dose chemotherapy could be prescribed for the treatment of malignant tumors.

BACKGROUND: Multidrug resistance is a major obstacle in cancer chemotherapy. We examined whether the antisense RNA of multidrug resistance gene 1 (mdr1) could reverse multidrug resistance in the human hepatocellular carcinoma (HCC) cell line SMMC7721/ADM.
METHODS: The recombinant adenoviruses pAdEasy-GFP-ASmdr1 product was produced by the adenoviral vector AdEasy system, which can express antisense RNA against the mdr1 gene. Following that, the recombinant adenovirus was transfected into the P-glycoprotein-producing multidrug resistance cell line, SMMC7721/ADM human HCC cells resistant to adriamycin (ADM) and daunorubicin (DNR). In order to investigate the reversal of multidrug resistance phenotype, we measured the expression of mdr1 mRNA by RT-PCR and the production of P-glycoprotein by flow cytometry. The sensitivities for ADM and DNR SMMC7721/ADM cells were examined by [3-(4, 5-dimethylthi-azol-2-yl)-2,5 diphenyl-terazolium bromide] (MTT) analysis.
RESULTS: The low-level expression of mdr1 mRNA and P-glycoprotein production were observed in parental sensitive cells SMMC/7721 in addition to the overexpression of mdr1 mRNA and P-glycoprotein in SMMC7721/ADM cells. The transfection of antisense-RNA into SMMC7721/ADM cells resulted in decreases of mdr1 mRNA and P-glycoprotein, but increase of drug sensitivities. The sensitivities of transfected SMMC7721/ADM cells to ADM and DNR in IC50 reduced by 31.25% and 62.96% respectively.
CONCLUSIONS: Mdr1 antisense RNA can increase the sensitivities of SMMC7721/ADM cells to anticancer drug by decreasing the expression of the mdr1 gene and inhibiting P-glycoprotein expression. This strategy may be applicable to cancer patients with P-glycoportein mediated multidrug resistance.

BACKGROUND: Excessive alcohol consumption can result in multiple organ injury, of which alcoholic liver disease (ALD) is the most common. With economic development and improvement of living standards, the incidence of diseases caused by alcohol abuse has been increasing in China, although its pathogenesis remains obscure. The aim of this study was to investigate the role of hypoxia in chronic ALD.
METHODS:  Twenty-eight male Sprague-Dawley rats were randomized into a control group (n=12) with a normal history and an experimental group (n=16) fed with 10 ml/kg of 56% (vol/vol) ethanol once per day by gastric lavage for 24 weeks. At 24 weeks, blood samples were collected and then the rats were killed. Liver samples were frozen at -80 ℃ and used for RT-PCR; other liver samples were obtained for immunohistochemical staining.
RESULTS: When the period of alcohol consumption increased, the positive rate of expression of hypoxia-inducible factor-1 alpha (HIF-1α) mRNA was more significantly elevated in the liver of the alcohol group than in the control group (P≤0.05).  The HIF-1α protein located in the cytoplasm was seldom expressed in the control group, but significantly in the alcohol group (P≤0.01).
CONCLUSION: HIF-1α mRNA expression was activated by ethanol-induced injury in this study, suggesting that hypoxia is involved in the underlying mechanism of ALD.

BACKGROUND:  The importance of nitric oxide (NO) in the pathogenesis of portal hypertension (PHT) has been extensively studied, but whether or not prostacyclin (PGI2) plays a role in formation and development of hyperdynamic circutatory state in PHT has not been verified. The present study was undertaken to investigate the possible interaction between prostacyclin (PGI2) and nitric oxide (NO) in the hyperdynamic circulatory state of rats with chronic portal hypertension (PHT), by measuring the hemodynamic changes and expression of cyclooxygenase (COX) mRNA in vessels and small intestine after administration of Nω-nitro-L-arginine (L-NNA) or indomethacin (INDO) either in the short-term (7 days) or long-term (15 days).
METHODS: Ninety-seven  male Sprague-Dawley rats were divided into three groups: intrahepatic portal hypertension (IHPH) induced by injection of CCl4, prehepatic portal hypertension (PHPH) induced by partial stenosis of the portal vein, and sham-operated controls (SO). Animals of each group received L-NNA or INDO either for 7 or 15 days, with saline as control. Splanchnic hemodynamics was measured by the radioactive microsphere technique. The concentration of NO in serum was determined as the nitrate; nitrite ratio (NO2-/NO3-, µmol/L) by a colorometric method, and that of PGI2 was measured by specific radioimmunoassay for its stable hydrolysis product 6-keto-PGF1α (pg/ml). The reverse transcription-polymerase chain reaction measured the levels of COX-1 mRNA in the superior mesenteric artery, thoracic aorta, and small intestine of these rats.
RESULTS: Compared with SO rats, COX-1 mRNA expression and the concentrations of plasma 6-keto-PGF1α and serum NO2-/NO3- were enhanced in both IHPH and PHPH rats; splanchnic vascular resistance (SVR) decreased, but portal venous inflow (PVI) markedly increased (P<0.05).  Seven or 15 days of L-NNA treatment reduced COX-1 mRNA expression in these vessels and the small intestine, concomitant with a significant decrease in the concentration of plasma PGI2 and serum NO in IHPH and PHPH rats (P<0.05). At the same time, PVI decreased but SVR increased significantly (P<0.05). In both IHPH and PHPH rats, the COX-1 mRNA expression and the concentration of plasma PGI2 after No synthase (NOS) blockade for 15 days were higher than those for 7 days, whereas the hyperdynamic circulatory state was improved after NOS blockade for 15 days compared with 7 days. The concentration of PGI2 treated by INDO for 15 days was not significantly different from that after 7-day COX blockade, and hemodynamics restored hyperdynamic circulatory state.
CONCLUSIONS: The hyperdynamic circulatory state in rats with PHT is correlated with the concentration of serum NO. There is a possible interaction between PGI2 and NO in the hyperhemodynamics of PHT. PGI2 is probably not the mediator in the formation and development of the hyperdynamic circulatory state in rats with chronic PHT.

BACKGROUND: The high operative risk of hepatectomy for specially located intrahepatic stones is still a problem to be solved. This study was undertaken to investigate the feasibility and effectiveness of chemical bile duct embolization for chemical hepatectomy.
METHODS: Oxybenzene or absolute ethanol plus N-butyl-cyanoacrylate was employed for embolization.The feasibility, effectiveness and mechanism of chemical hepatectomy were preliminarily analyzed histologically or by Fas, TIMP-1, TGF-β1, and collagen I.
RESULTS: Oxybenzene plus cyanonacrylate can preferably destroy and embolize the intrahepatic biliary duct, leading to the disappearance of hepatocytes in the periphery of embolized lobe and the achievement of effective chemical hepatectomy. The expressions of Fas, TIMP-1 and TGF-β1 in oxybenzene embolism group (88.90±38.10, 619.43±183.42, 185.22±70.39) and ethanol embolism group (72.39±29.51, 407.55±134.74, 163.56±51.75) were higher than those of biliary duct-ligated group (26.31±12.07, 195.31±107.67, 74.84±40.73) (P<0.05). The collagen Ⅰ-positive percentage in the oxybenzene embolism group was also greater than that of the ethanol embolism group (33.97±12.51% vs. 20.67±8.09%, P<0.05).
CONCLUSION: The effect of chemical hepatectomy may be achieved by chemical bile duct embolization.

BACKGROUND: Melatonin exerts complex physiological and pharmacological effects on multiple systems and organs. We hypothesized that melatonin might abate ischemia/reperfusion (I/R) injury in the liver by inhibiting excessive oxidative stress and keeping nitric oxide (NO) from being scavenged by free radicals. The aim of the present study was to investigate whether melatonin protects the liver from I/R injury and, if so, by what underlying mechanism.
METHODS: Under anesthesia, Wistar rats were intraperi-toneally injected with 20 mg/kg melatonin (dissolved in physiological saline containing 4% ethanol, Mel group), 4% alcohol (Alc group), or physiological saline (NS group). The artery, portal vein and bile duct of the left lobe of the liver were clamped for 60 minutes and then released. At different time points after I/R, the rats were sacrificed and blood samples were collected to measure the levels of serum alanine aminotransferase (ALT), lactic dehydrogenase (LDH), and NO. Hepatic tissue samples were collected for measuring endothelin expression by immunohistochemical staining and for routine morphological and histological examination.
RESULTS: The levels of both ALT and LDH in the Mel group were significantly reduced for up to 24 hours after I/R compared with the Alc and NS groups (P<0.05). The levels of NO in the Mel group were significantly elevated for up to 12 hours after I/R relative to the NS group (P<0.05). The NO levels were also elevated at 0.5 and 6 hours after I/R in the Alc group (P<0.05). The immunohistochemical staining of hepatic tissue showed that endothelin-positive cells were significantly fewer in the Mel group than in the Alc and NS groups at 6 hours after I/R (P<0.01). The necrosis of hepatocytes and the destruction of hepatic cords in the Alc and NS groups were greatly improved in Mel-treated rats, which is in concert with our functional data.
CONCLUSIONS: Pretreatment with melatonin increased NO bioavailability and decreased endothelin expression, and consequently played a protective role in preserving both liver function and structure during ischemia and reperfusion injury.

BACKGROUND: The second mitochondria-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low pI (Smac/DIABLO) was recently identified as a protein that is released from mitochondria in response to apoptotic stimuli and promotes apoptosis by antagonizing inhibitor of apoptosis proteins. Furthermore, Smac/DIABLO plays an important regulatory role in the sensitization of cancer cells to both immune- and drug-induced apoptosis. However, little is known about the clinical significance of Smac/DIABLO in various cancers including hepatocellular carcinoma (HCC). This study was undertaken to investigate the expression of Smac and Survivin and their relationship with the apoptosis in primary HCC.
METHODS: The expression of Smac and Survivin proteins was evaluated by immunohistochemistry. The mRNA expression of Smac and Survivin was evaluated by reverse transcription-polymerase chain reaction (RT-PCR) in HCC tissues of 50 patients, para-carcinoma tissues of 20 patients, and normal liver tissues of 15 patients.
RESULTS: Smac mRNA was detected by RT-PCR in HCC tissues of 21 (42.0%) of the 50 patients, para-carcinoma tissues of 19 (95.0%) of the 20 patients, and normal liver tissues of 15 (100%) of the 15 patients. Survivin mRNA was found in HCC tissues of 46 of the 50 patients, para-carcinoma tissues of 2 of the 20 patients, and normal liver tissues of 0 of 15 patients. Immunohistochemistry revealed Smac protein in HCC tissues of 20 patients (40.0%), in para-carcinoma tissues of 18 patients (90.0%), and normal liver tissues of 15 patients (100.0%). The expression of Smac was significantly different in HCC tissues and non-HCC tissues. Survivin protein was found in HCC tissues in 45 patients, para-carcinoma tissues in 2 patients, and  normal liver tissues in none of the patients. The expression of Survivin was significantly different in HCC tissues and non-HCC tissues.
CONCLUSION: Smac inhibits apoptosis of HCC cells by suppression of Survivin, and the two genes probably form an important link in the signal pathway of HCC cells.

BACKGROUND: Laparoscopic cholecystectomy (LC) has become the "gold standard" in treating benign gallbladder diseases. Increasing laparoscopic experience and techniques have made laparoscopic subtotal cholecystectomy (LSC) a feasible option in more complex procedures. In recent years, few studies with a few cases of LSC have reported good results in patients with various types of cholecystitis. This study was designed to evaluate the feasibility, indications, characteristics and benefits of LSC in patients with complicated cholecystitis.
METHODS: Altogether, 3485 patients were scheduled to receive LC during the past 4 years at our institute. Among them, 168 patients with various complicated forms of cholecystitis were treated by LSC. Meanwhile, the other 3317 patients who received standard LC were enrolled as the control group. Perioperative data from the two groups were collected and retrospectively analyzed.
RESULTS: In the LSC group, 135 patients suffered from acute calculic cholecystitis, 18 from chronic calculic cholecystitis with cirrhotic portal hypertention, and 15 from chronic calculic atrophy cholecystitis with severe fibrosis. These patients constituted 4.8% of the total patients who underwent LC (168/3485) in the same period at our institute. In 122 patients, the cystic duct and artery were clipped before division. In another 46 patients, the gallbladder was initially incised at Hartmann's pouch. Five patients (3.0%) were converted to open subtotal cholecystectomy. The median operation time for LSC was 65.5±15.2 minutes, estimated operative blood loss was 71.5±15.5 ml, and the time to resume diet was 20.4±6.3 hours. Thirteen patients (7.7%) had local complications. The mean postoperative hospital stay was 4.2±2.6 days. In the LC group, 2887 had chronic calculic cholecystitis, 312 had acute calculic cholecystitis, 47 had chronic calculic atrophy cholecystitis, and 71 had polypus. Seventeen patients (0.5%) were converted to open cholecystectomy. The median operation time was 32.6±10.2 minutes, the estimated operative blood loss was 24.5±8.5 ml, and the time to resume diet was 18.3±4.5 hours. Thirty-nine patients (1.2%) had local complications. Mean postoperative hospital stay was 3.8±1.4 days. There was no bile duct injury or mortality in either group.
CONCLUSIONS: LSC for patients with complicated cholecystitis is difficult, with a longer operation time, more operative blood loss and higher conversion and complication rates than LC. However, it is feasible and relatively safe. LSC is advantageous over open surgery, but it remains a non-routine choice. It is important to know the technical characteristics of LSC, and pay attention to perioperative bleeding and bile leak.

BACKGROUND: Getting directly into the common bile duct (CBD) is the most important step for successful therapeutic biliary endoscopy. In 5%-10% of cases, the CBD remains inaccessible, necessitating pre-cut papillotomy or fistulotomy with a needle-knife. The aim of this study was to assess the value of early application of the needle-knife in difficult biliary cannulation for endoscopic retrograde cholangiopancreatography (ERCP).
METHODS: Patients with failed biliary cannulation after 10 minutes or guide wire entering the pancreatic tube 3 times were randomly divided into group of needle-knife cut and group of persistent cannulation by standard techniques. The cannulation times, success rates and complication rates were compared between the two groups.
RESULTS: A total of 948 therapeutic biliary ERCP procedures were performed between October 2004 and February 2006. Of 91 patients with difficult biliary cannulation, 43 patients underwent needle-knife cut: the cannulation success rate was 90.7%, the mean cannulation time was 5.6 minutes, and the complication rate was 9.3%. The other 48 patients underwent persistent cannulation by standard techniques: the cannulation success rate was 75%, the mean cannulation time was 10.2 minutes, and the complication rate was 14.6%. Significant differences were observed in cannulation success rate and cannulation time but in complication rate between the two groups.
CONCLUSION: The early application of the needle-knife in difficult biliary cannulation is time-saving, safe and effective, with no increase in complication rate.

BACKGROUND: This study was designed to assess the expression of smooth muscle actin (SMA) in the healing process after implanting a ¹⁰³Pd radioactive stent in the biliary duct, and to discuss the function and significance of this stent in preventing biliary stricture formation.
METHODS: A model of biliary injury in dogs was made and then a ¹⁰³Pd radioactive stent was positioned in the biliary duct. The expression and distribution of SMA were assessed in the anastomotic tissue 30 days after implantation of the stent.
RESULTS: SMA expression was less in the ¹⁰³Pd stent group than in the ordinary stent group. The ¹⁰³Pd stent inhibited scar contracture and anastomotic stenosis.
CONCLUSION: The ¹⁰³Pd stent can reduce the expression of SMA in the healing process and inhibit scar contracture and anastomotic stenosis in the dog biliary duct.

BACKGROUND: Infected pancreatic necrosis is associated with high morbidity and mortality and is mandatory for surgical or radiological intervention. A selected group of patients with CT evidence of infected pancreatic necrosis and a comparatively lower APACHE score may be clinically stable throughout the course of their illness.
METHODS: Case records of 52 patients with severe acute pancreatitis admitted from October 2000 to September 2005 were retrospectively analysed to assess the feasibility of conservative management of infected pancreatic necrosis. CT evidence of retroperitoneal air pockets, deteriorated clinical condition, sepsis and positive blood culture were used to diagnose infected pancreatic necrosis.
RESULTS: In the 52 male patients reviewed, 24 patients had infected pancreatic necrosis. Eighteen patients who had progressively deteriorated clinical conditions required surgical intervention; five patients of whom (27.8%) died. Six patients with transient end organ dysfunction and stable clinical conditions were treated with prolonged administration of antibiotics and ICU support. All these patients recovered and discharged from the hospital, and no symptoms or readmission happened during follow-up of 6-44 months.
CONCLUSIONS: Selected patients with infected pancreatic necrosis who are clinically stable with transient end organ dysfunction can be treated conservatively with a favourable outcome. Necrosectomy associated with high morbidity and mortality in these patients can be avoided. The need for intervention should be individualized and based on clinical conditions of the patients.

BACKGROUND: Acute necrotizing pancreatitis leads to a systemic inflammatory response characterized by widespread leukocyte activation and, as a consequence, distant lung injury. The aim of this study was to evaluate the effect of ligustrazine, extracted from Ligusticum wallichii a traditional Chinese medicine, on lung injury in a rat model of acute necrotizing pancreatitis (ANP).
METHODS: A total of 192 rats were randomly divided into three groups: control (C group); ANP without treatment (P group); and ANP treated with ligustrazine (T group). Each group was further divided into 0.5, 2, 6 and 12 hours subgroups. All rats were anesthetized with an intraperitoneal injection of sodium pentobarbital. Sodium taurocholate was infused through the pancreatic membrane to induce ANP. For the T group, sodium taurocholate was infused as above, then 0.6% ligustrazine was administered via the femoral vein. The effects of ligustrazine on the severity of lung injury were assessed by lung wet/dry weight ratio, myeloperoxidase (MPO) activity and histopathological changes. Pulmonary blood flow was determined by the radioactive microsphere technique (RMT).
RESULTS: The blood flow in the P group was significantly lower than that of the C group, while the blood flow in the T group was significantly higher than that of the P group but showed no significant difference from the C group. Compared with C group, the lung wet/dry ratios in both the P and T groups were significantly increased, but there was no significant difference between them. The MPO activity in the P group was greatly increased over that of the C group. In the T group, although the MPO activity was also higher than in the C group, it much less increased than in the P group. Moreover, the difference between P and T groups was significant after 0.5 to 12 hours. After induction of the ANP model, the pancreas showed mild edema and congestion; the longer the time, the more severe this became. The pulmonary pathological changes were aggravated significantly in the P group. Histopathological scores were higher in the P group than in the C group throughout the experimental course. Histopathological scores in the T group were lower than those in the P group at 6 and 12 hours.
CONCLUSIONS: Microcirculatory disorder is an important factor of lung injury in ANP. Ligustrazine can ameliorate microcirculatory disorder and alleviate the damage to the lung.

BACKGROUND: Nasopharyngeal carcinoma (NPC) has a propensity to develop distant metastases at a high rate and with poor prognosis. Metastatic sites are usually multifocal and involve bones, lungs, liver and distant lymph nodes. Management of metastatic disease is essentially palliative and is based on chemotherapy.
METHODS: A 50-year-old man with a solitary liver metastasis from a newly diagnosed NPC was treated by segmentectomy. Prior to surgery, neoadjuvant chemo-therapy followed by concurrent chemoradiotherapy was administered.
RESULTS: Complete remission of the primary disease was achieved, although the size of the hepatic lesion was increased. After resection of the liver metastasis, no signs of local or distant recurrence was noted during the 6-month follow up.
CONCLUSION: Although surgical treatment has a limited role in metastatic NPC, there are rare cases of localized disease with a reasonable outcome after resection.

BACKGROUND: Patients with short bowel syndrome may require combined liver and intestinal transplantation due to total parenteral nutrition(TPN)-related liver damage. We report combined liver and intestinal allotransplantation as a non-composite technique in a patient in China.
METHODS: During the operation, a 380 cm long intestine was transplanted with systemic drainage and aortic inflow, while the liver graft was placed in a piggyback fashion. Warm ischemic time of the donor graft was 2 minutes and 30 seconds, and cold ischemic time for intestinal and the liver graft was 6 hours and 40 minutes and 8 hours and 7 minutes, respectively. Immunosuppressants used after operation included tacrolimus, methylprednisolone, mycophenolate mofetil and Zenapax.
RESULTS: The recipient recovered with no evidence of rejection and was kept well on tube feeding. Eventually, he died of massive hemorrhage of the thoracic cavity on day 210 after transplantation.
CONCLUSION: The non-composite combined liver and intestinal allotransplantation is superior to composite technique in adult patients, particularly those who have had abdominal infection or repeated abdominal operations.

BACKGROUND: Dubin-Johnson syndrome (DJS) is a rare clinical entity. We describe a case of DJS complicated by systemic lupus erythematosus (SLE).
METHODS: A case of congenital hyperbilirubinemia with SLE was evaluated systematically including review of history, physical examination for the stigmata of chronic liver disease, and other investigations.
RESULT: Liver biopsy revealed a black liver with preserved architecture suggestive of DJS.
CONCLUSIONS: SLE may develop in DJS. The relationship between DJS and SLE in this case is most likely a chance occurrence.

BACKGROUND: Malignant fibrous histiocytoma is the most common sarcoma of soft tissue, which occurs usually in the extremities, but less common in the retroperitoneal space, abdominal cavity or other sites. Primary malignant fibrous histiocytoma of the liver is extremely rare; only 28 cases have been reported to date in the English literature.
METHODS: In this report, a case of primary malignant fibrous histiocytoma of the liver was described in terms of clinical presentations, diagnosis and treatment and outcome.
RESULTS: A 50-year-old man had a large multicystic-mass lesion in the left lobe of the liver, which was inoperable by laparotomy. Pathological examination of biopsy specimen after operation confirmed a malignant fibrous histiocytoma of storiform-pleomorphic type. The tumor developed rapidly, and the patient died of hepatic failure 2 months after the surgery.
CONCLUSIONS: Primary malignant fibrous histiocytoma of the liver is diagnosed in late stage because of its rarity and non-specific presentations. Surgical resection, if feasible, is the first step treatment. The prognosis of primary malignant fibrous histiocytoma of the liver is grim with a median survival of 3 months as reported. Surgeons should be alert to the existence of this type of soft tissue tumor in the liver.

BACKGROUND: Biliary leakage after removal of a T-tube has significant morbidity and mortality. Its etiology is multifactorial. The treatment and outcome of this complication vary. In the present study we evaluated the procedures and efficacy of combined use of choledochoscope and duodenoscope in the treatment of bile peritonitis after T-tube removal.
METHODS: The procedures and results of 11 cases of biliary leakage after removal of T-tube who had been treated from January 1998 to June 2004 by combined use of choledochoscope and duodenoscope were analyzed retrospectively.
RESULT: After the treatment, 9 patients were cured, and 2 were reoperated on and cured.
CONCLUSIONS: Biliary leakage after removal of T-tube can be cured successfully by combined use of choledochoscope and duodenoscope. Importantly, the method is simple, effective and safe, and mostly reoperation can be avoided.