BACKGROUND: The ultimate goal of transplantation is the donor specific immune tolerance, but at least in the first 15 to 20 years of this century, immunosuppressive agents are still the determinant of clinical outcome of transplant recipients. Individualizing patient’s immunosuppression to optimize the balance between therapeutic efficacy and the occurrence of adverse events poses a great challenge to physicians.
DATA SOURCES: The data in this article were taken mostly from MEDLINE (2000-2004), part of which were from the research of the authors.
RESULTS: Individualized immunosuppression remains a problem because of the narrow therapeutic index and wide inter- and intra-patient variation of commonly used immunosuppressants. Recent progress in study of pharmacokinetics and pharmacodynamics improved the clinical outcome of transplant recipients. More importantly, the emergence of pharmacogenomics might provide a promising and complementary tool for traditional therapeutic drug monitoring (TDM).
CONCLUSIONS: Individualizing organ recipient’s immunosuppression to balance the therapeutic efficacy and the adverse events represents a great challenge to transplant clinicians. Pharmacogenomics shows great promise for an interesting and hopefully better future.

BACKGROUND: Orthotopic liver transplantation as a successful treatment of end-stage liver disease is hampered by a persistent lack of cadaveric organs. Split liver transplantation, which was first successfully performed by Medical School of Hannover in 1988, has become a mature surgical technique to expand the donor pool. Between 1993 and 1999, split liver transplantation activities have increased in Europe from 1.2% to 10.4% in all performed liver transplantations. Current data have strongly supported that the survival rate of patients after split liver transplantation is not significantly different from that of patients after whole-size orthotopic liver transplantation. The most important step of donor graft selection is surgeon’s observation judged by the experience of individual transplant center. The paper aims to provide the guideline of donor selection, hepatic graft splitting, and recipient management as well.
DATA SOURCES: Medical School of Hannover has accumulated plentiful experience of split liver transplantation for more than 10 cases ever since 1998. Besides that, we also reviewed a variety of literatures from other famous European and American centers specialized in this field for many years.
RESULTS: According to our experience combined with the view points of others, the donor should meet the following criteria as well: (1) age less than 50 years; (2) hemodynamics stable; (3) ICU less than 5 days; (4) Na less than 170 mmol/L or better if less than 150 mmol/L. In 1996 and 1997, the Hamburg group and the UCLA group separately introduced a breakthrough technique performing split liver transplantation in situ Evidently, the in situ technique has been limited by prolonged time of donor organ procurement, coordination with other organ procurement teams, and even extra burden on donor hospital. Some groups, therefore, have restored the ex situ or bench splitting technique, and fortunately the transplant outcomes of the ex situ technique are equivalent to those of the in situ one. Recently some new techniques have been introduced to split the liver for two adult patients, including the split-cava technique.
CONCLUSIONS: It is clear that the most important factor for determining the prognosis of the patient is the time of receiving liver transplantation, not the type of liver transplantation. We still need to pay close attention to the graft to recipient weight ratio (GRWR) and the UNOS classification or MELD score before the patient is subjected to split liver transplantation.

BACKGROUND: Nonalcoholic fatty liver disease（NAFLD）is a common chronic liver disease in China, of which diabetic fatty liver（DFL）accounts for a large proportion in clinic. DFL is a disease without specific clinical features and lacking of confirmatory laboratory tests, and the etiology of hepatic steatosis remains poorly understood. The aim of this paper was to explore the clinical characteristics and to determine associated risk factors in type 2 diabetes patients with fatty liver.
METHODS: A total of 166 patients, 53 in DFL group and 113 in NDFL（diabetes without fatty liver）group participated in this study. Serum fasting blood glucose（FBG）, alanine aminotransferase（ALT）, aspartate aminotransferase（AST）, alkaline phosphate（AKP）, gamma glutamyl transpeptidase（GGT）, total cholesterol（TC）, triglyceride（TG）, high density lipoprotein-cholesterol（HDL-C）were measured in both groups. And these variables were analyzed by using Student’s t test and logistic regression model.
RESULTS:A progressive increase in the level of FBG, ALT, AST, AKP, GGT, TG (P＜0.05) and a decrease of HDL-C（P＜0.01）were observed from DFL group to NDFL group. And there was no statistical difference in the level of TC between the two groups.
CONCLUSIONS: Dyslipidemia, dysglycemia and elevation of liver enzyme can be seen more frequently in the DFL patients than in the NDFL patients. The successive escalation of serum ALT and TG levels and the lower HDL-C level are the independent risk factors of DFL.

BACKGROUND: Because of its complicated pathological features such as repeated cholangitis and multiple operations, hepatolithiasis is difficult to treat and often lead to portal hypertension, and liver failure. The aim of this study was to investigate the indications of orthotopic liver transplantation (OLT)for patients with hepatolithiasis and the improvement of operative techniques and the treatment of postoperative complications.
METHODS: The data of 4 patients with hepatolithiasis who had undergone OLT at our department in recent years were reviewed retrospectively.
RESULTS: The 4 patients with hepatolithiasis complicated with secondary biliary cirrhosis in end-stage liver disease included 1 woman and 3 men. One patient underwent OLT using veno-venous bypass prior to the mobilization of the liver. Two patients were subjected to liver transplantation with improved piggyback technique without bypass. One patient received OLT without bypass. All patients were operated on successfully and recovered uneventfully. Patient 1 had bleeding from the digestive tract on the postoperative day 6. Patient 2 had hemorrhage from the digestive tract and a leakage of end-to-side intestinal anastomosis on the postoperative day 44. Patient 4 was reoperated on because of hemorrhage from the anastomotic stoma of the hepatic artery on the postoperative days 8 and 10. In the 4 patients the mean operative time was 7.9 hours and blood loss was 910 ml. Postoperative pathological analysis revealed biliary liver cirrhosis. Follow-up of all patients showed good conditions.
CONCLUSIONS: Hepatolithiasis with secondary biliary liver cirrhosis in patients with end-stage liver disease is indicated for liver transplantation. Veno-venous bypass prior to the mobilization of the liver and improved piggyback technique can lower the incidence of intraoperative bleeding, the duration of surgery and postoperative complications.

BACKGROUND: It was demonstrated that xanthine oxidoreductase (XOR), during ischemia, catalyzes the formation of nitric oxide (NO) from nitrite (NO2-) and this NO2--derived NO protects the isolated perfused rat heart against thedamaging effects of ischemia-reperfusion (I/R) when conventional nitric oxide synthase (NOS)-dependent NO production is impaired. Liver is one of the organs with the highest XOR concentration. This study was designed to determine whether NO2--derived NO by XOR protects liver against I/R injury in vivo. For its minute amounts and active reactivity, NO cannot be detected directly in real time in vivo by this time. We have to prove the above hypothesis indirectly.
METHODS: Wistar rats were pretreated with saline, NOS inhibitor L-NAME (10 mg/kg intravenously), XOR inhibitor allopurinol (1.5 mg/kg orally), L-NAME+allopurinol and NO scavenger carboxy-PTIO (0.6 mg/kg intravenously) respectively (12 animals per group). And then, they were subjected to total liver ischemia for 40 minutes followed by reperfusion. Blood samples and liver tissues were obtained for analysis after 3 hours of reperfusion. Survival was also investigated.
RESULTS: Allopurinol-treated animals exhibited further increased serum alanine aminotransferase(ALT) levels and liver myeloperoxidase(MPO) activities, but further decreased liver adenosine triphosphate (ATP) stores after I/R compared to saline-treated counterparts (830.5±108.3 U/L, 56.5±11.0U/mg protein and 1.93±0.47μmol/g vs. 505.8±184.2 U/L, 41.5±10.2 U/mg protein and 3.05±0.55μmol/g respectively, P＜0.01, P＜0.05 and P＜0.01 respectively). The hepatocyte injury was further exacerbated and the overall survival rate was significantly decreased after I/R in animals given by allopurinol compared to those pretreated by saline (P＜0.05). L-NAME and allopurinol co-treated animals exhibited more severe liver injury (P＜0.05 and P＜0.01) and a further decreased overall survival rate (P＜0.05)compared to L-NAME or allopurinol alone-treated counterparts, but they were not different from carboxy-PTIO treated animals (P>0.05).
CONCLUSION: NO2--derived NO by XOR in the hypoxic and acidic environment induced by hepatic I/R protects the liver against I/R injury in vivo.

BACKGROUND: With the great development of liver transplantation in China, long survival and quality of life after liver transplantation have been matters of growing interest. This study was designed to investigate the impact of personality and coping skills on the quality of life after liver transplantation.
METHODS: Fifty-five outpatients who had been followed up after liver transplantation at our center were assessed by general quality of life inventory (GQOLI-74), a medical coping modes questionnaire (MCMQ), an eysenck personality questionnaire (EPQ), and a general condition questionnaire (GCQ).
RESULTS: The score for material well-being was the lowest (63.22±12.67) and for psychological well-being the highest (73.43±12.60) in 4 dimensions of  the GQOLI in post transplantation patients. Their main coping method was confrontation (21.40±3.70). The main characteristics of their personality were extraversation (E score 12.96±4.13) and neuroticism (N score 8.20±4.90). The total score of the GQOLI was positively correlated with confrontation and E score, and it was negatively correlated with acceptance and N score. The physical well-being positively associated with the E score. The psychological well-being was positively correlated with confrontation and L score, and was negatively correlated with acceptance, P and N score. Social well-being was positively correlated with confrontation and E score, and was negatively correlated with acceptance and N score. Material well-being was not correlated with coping methods and personality.
CONCLUSION: The quality of life in post liver transplantation patients is associated with their psychological characteristics.

BACKGROUND: It is reported that inducible nitric oxide synthase (iNOS) plays an important role in rejection. This study was designed to observe the expression of iNOS in the transplanted liver tissues and the effect of aminoguanidine (an inhibitor of iNOS) and (immunosuppression) on acute rejection after liver transplantation.
METHODS: All rats were divided into four groups: homogeneous (LEW-LEW), acute rejection (BN-LEW), aminoguanidine (BN-LEW), and FK506 (BN-LEW). In the last two groups the drugs were used in heterogeneous rats after liver transplantation. The expression of iNOS in liver tissues of all groups was investigated immunohistochemically.
RESULTS: In the acute rejection group, the expression of iNOS was extremely positive compared to the other three groups. The difference was statistically significant.
CONCLUSIONS: During the process of acute rejection in rat orthotopic liver transplantation, the enhanced expression of iNOS correlates to the severity of rejection. Aminoguanidine and FK506 can inhibit the expression of iNOS and palliate acute rejection.

BACKGROUND: After organ transplantation, rapid repair of injured vascular endothelial cell (VEC) is a key to prevent graft chronic dysfunction besides control of immunological rejection. Many studies have confirmed that vascular endothelial growth factor 165 (VEGF165) could accelerate the repair of VEC injury, decrease thrombosis and thrombotic occlusion, and inhibit hyperplasia of the intima. This study was designed to construct eukaryotic expression plasmid pBudCE4.1/VEGF165, and observe its effect on the proliferation of VEC.
METHODS: The VEGF165 gene cloned from human heart tissue by RT-PCR was cloned into eukaryotic expression plasmid pBudCE4.1. The recombinant expression plasmid pBudCE4.1/VEGF165 was identified by restriction enzyme (Hind III and BamH I) digestion analysis, and was sequenced. The pBudCE4.1/VEGF165 was introduced into VEC through lipofection transfection. The VEGF165 mRNA expression by Northern blot and VEGF165 protein expression was detected by immunocytochemical staining. The effect of expression protein on VEC proliferation was detected by flow cytometry.
RESULTS: The RT-PCR product of the VEGF165 gene was about 576bp. Sequencing analysis revealed that the sequence of the amplified VEGF165 gene was identical with that in GenBank. Restrictive enzyme digestion analysis showed that recombinant expression plasmid pBudCE4.1/tVEGF165 had been constructed successfully. The expression of VEGF165 at mRNA and protein levels in the transformed VSMCs had been demonstrated by Northern blot and immunocytochemical staining respectively. The expressed product of VEGF165 could notably accelerate the proliferation of VECs.
CONCLUSIONS: pBudCE4.1/VEGF165 is successfully constructed and is expressed in VECs. Expressed VEGF165 can accelerate the VEC proliferation. The present study has laid a foundation for potential use of VEGF165 gene transfection to prevent and treat vascular stenosis in the transplanted organ.

BACKGROUND: Liver resection is still a complicated operation with a high risk of postoperative morbidity. This study was undertaken to analyze the risk factors for postoperative complications after liver resection.
METHODS: From 2001 to 2004, a total of 146 patients underwent liver resection for malignant or benign lesions. Postoperative complications after the resection were classified as surgical and medical, their incidences were analyzed retrospectively. The risk factors for both surgical and medical complications were analyzed. To increase the safety of liver resection, surgical techniques were modified after April 2003, including control of inflow or outflow and intra-operative test with methylene blue.
RESULTS: Before April 2003, a series of 58 patients received liver resection. Modified surgical techniques were used in liver resections for 88 patients after April 2003. A total of 36 patients (24.7%) had postoperative complications. Surgical and medical complications occurred in 24 and 13 patients respectively (One patient had both surgical and medical complications). Perioperative blood transfusion was related to a higher risk of surgical complications (P<0.05). Patients with diabetes mellitus were associated with a higher risk of medical complications (P<0.05). Surgical complications and postoperative hospitalization were decreased after the use of modified surgical techniques (P<0.05).
CONCLUSION: Postoperative surgical complications can be decreased by modified surgical techniques, and careful selection of patients for liver resection may help to decrease postoperative medical complications also.

BACKGROUND: Postoperative pleural effusion occurs frequently after hepatectomy. The risk factors, prevention and management of postoperative pleural effusion in patients with primary liver cancer (PLC) who have undergone hepatectomy and the value of the argon beam coagulator (ABC) for the prevention of pleural effusion are studied.
METHODS: A total of 523 patients with PLC at our institution who had had right hepatectomy from July 2000 to June 2004 were studied retrospectively. Comparative analysis was made to identify the factors contributing to postoperative pleural effusion and the efficacy of various managements.
RESULTS: Of the 523 patients whose livers were dissociated using argon beam cutting and/or coagulation, 20(3.8%) developed pleural effusions; whereas in the other 467 patients underwent hepatectomy with suture ligation of the diaphragmatic secondary wound surface during the same period, 49(10.5%) had pleural effusion (P<0.01). The factors contributing to postoperative pleural effusion included subphrenic collection, postoperative hepatic insufficiency with ascites, duration of hepatic occlusion and underlying cirrhosis.
CONCLUSIONS: Dissociation of the liver by argon beam cutting and/or coagulation can save suture ligation of the diaphragmatic secondary wound surface and may also prevent postoperative pleural effusion. Pleural drainage using an indwelling central-venous-catheter (CVC) in the pleural cavity is safe and efficacious.

BACKGROUND: Early resection of hepatocellular carcinoma is a key measure to prolong the survival of patients. This study was designed to summarize our experience in surgical resection of small hepatocellular carcinoma (HCC), and to analyze the factors influencing the postoperative survival of patients.
METHODS: The clinicopathologic data of 105 patients with small HCC after resection from 1986 through 2003 were analyzed; the patients had been followed up for more than half a year (median 33 months). Nine clinicopathologic factors, preoperative α-fetoprotein (AFP) level, liver cirrhosis, Child-Pugh score, tumor size (>2 cm vs. ≤2 cm) and number (single vs. multiple), capsule formation, portal vein tumor thrombi (PVTT), Edmondson tumor grade and surgical method, were analyzed by the log-rank test and the Cox proportional harzards model analysis.
RESULTS: The cumulative 1-, 3- and 5-year survival rates after the operation were 86.5%, 70.3% and 55.2%, respectively, and the 1-, 3- and 5-year disease-free survival rates were 78%, 58.9% and 45.6%, respectively. One patient died from esophagogastric varices hemorrhage in 2 weeks after reoperation. Thirty-six patients had intrahepatic recurrence or metastasis postoperatively and 34 patients died. The Kaplan-Meier method and the Cox proportional harzards model analysis indicated that poor Child-Pugh score, tumor more than 2 cm in diameter, PVTT and multiple lesions (including satellitic lesions) were adverse factors affecting postoperative survival. The Cox proportional harzards model analysis indicated that tumor size, PVTT and multiple lesions were the factors influencing postoperative disease-free survival.
CONCLUSIONS: Limited hepatectomy with a margin more than 1 cm is an appropriate surgical approach. Adverse preoperative Child-Pugh score and postoperative intrahepatic recurrences are the main factors leading to the death of patients with small HCC.

BACKGROUND: Shunt and devascularization have totally different effects on hemodynamics of the portal venous system, and the actual results of combined shunt and devascularization should be determined by more clinical observations. This study aimed to evaluate effects on hemodynamics of the portal venous system after conventional splenorenal shunt combined with pericardial devascularization and pericardial devascularization only.
METHODS: In 20 patients who had received conventional splenorenal shunt combined with pericardial devascularization (CP) and 18 who had received pericardial devasculariation andsplenectomy (PCDV), hemodynamic parameters of the portal venous system were studied by magnetic resonance angiography 1 week before and 2 weeks after operation. Free portal pressure was detected continuously by a transducer during the operation.
RESULTS: Compared to the preoperative data, a decreased flow of the portal vein (PVF) (563.12±206.42 ml/min vs. 1080.63±352.85 ml/min, P＜0.05＝, a decreased diameter of the portal vein (PVD) (1.20±0.11 cm vs. 1.30±0.16 cm, P＜0.01＝, a decreased free portal pressure (FPP) (21.50±2.67 mmHg vs. 29.88±2.30 mmHg, P＜0.01＝ and an increased flow of the superior mesenteric vein (SMVF) (1105.45±309.03 ml/min vs. 569.13±178.46 ml/min, P＜0.05＝ were found in the CP group after operation; a decreased PVD (1.27±0.16 cm vs. 1.40±0.23 cm, P＜0.05＝, a decreased PVF(684.60±165.73 ml/min vs. 1175.64±415.09 ml/min, P＜0.05＝, a decreased FPP (24.40±3.78 mmHg vs. 28.80±3.56 mmHg, P＜0.05＝ and an increased SMVF (697.91±121.83 ml/min vs. 521.30±115.82 ml/min, P＜0.05＝ were found in the PCDV group. After operation, the PVF of CP group (563.12±206.42 ml/min vs. 684.60±165.73 ml/min, P＞0.05) was not decreased significantly while FPP (21.50±2.67 mmHg vs. 24.40±3.78 mmHg, P＜0.01＝ was decreased significantly as compared with that of the PCDV group.
CONCLUSIONS: PVF and FPP could be decreased by both surgical procedures, but the effect of decreasing FPP is much better in the combined procedures than in PCDV. Since there is no significant difference in PVF between the two groups, the combined procedures could integrate advantages of shunt with those of the devascularization, maintaining the normal anatomy structure of the hepatic portal vein, and should be one of the best choices for patients with PHT when surgical interventions are considered.

BACKGROUND: Viral variation may change pathogenicity, escape immunity, lead to persistence infection, and cause drug resistance against antiviral therapy. This study was undertaken to investigate the effects of HBV gene variation on the progression of disease and on the efficacy of antiviral therapy for patients with chronic hepatitis B (CHB).
METHODS: Hepatitis B virus (HBV) gene mutational sites were detected using gene chip in selected hepatitis B patients.
RESULTS: In the patients HBeAg did not show serologic conversion or HBeAg（-）/anti-Hbe (+), but their HBV DNA remained positive 24 weeks afterα-interferon therapy, which was associated with mutations of nt1896, nt1814, nt1762 and nt1764. In the patients, that HBV DNA levels decreased or were undetectable, but rebounded later after antiviral therapy by lamivudine was associated with mutations of aa528 and (or) aa552 (i.e. YMDD mutation), which resulted in lamivudine-resistance. YMDD mutation was prone to occur 52 weeks after lamivudine therapy in some chronic hepatitis B patients (26.4%). Nt1896 mutation was common in most chronic hepatitis B patients (68.5%). Chronic severe hepatitis, cirrhosis, and primary liver carcinoma were related to the mutations of nt1896, nt1762 and nt1764.
CONCLUSIONS: HBV gene mutations could aggravate patient’s condition and affect the efficacy of antiviral therapy. The regular detection of HBV gene mutatio

BACKGROUND: The understanding of cSNPs of cancer-related genes harboring in high frequency loss regions of tumor chromosomes can advance the disclosure of genetic and variant mechanisms of tumorigenesis, and the investigation of cancer susceptibility. In preparing a gene chip for detecting polymorphisms on coding region of genes in hepatocellular carcinoma tissues, some cSNPs are of interest for their potential links with phenotype. METHODS: The genes harboring in loss regions with high frequency of hepatocellular carcinoma (HCC) were selected, the related information of cSNP sequences was obtained from the SNP database (dbSNP) of the National Center for Biotechnology Information (NCBI). Then appropriate primers and oligonucleotide probes were designed according to the SNP sites, and a gene chip for the detection of SNPs was constructed. The chip included 48 cSNPs of 25 hepatocellular carcinoma-related genes. The PCR products labeled by Dig-dUTP were hybridized with the cSNP chip.
RESULTS: The sensitivity, influence by probe concentration, and reiteration of the chip were detected, with a high sensitivity of 6×10-3ng/μl. The signal of hybridization was reduced with a lower concentration of probe. Seven  polymorphisms of  caspase 9 (rs2308941)C→T and DOK2(rs2242241) T→G, 6 of polymorphisms of EGFL3（rs947345）A →G, caspase 9 ( rs2308938) C→G and PHGDH(rs1801955)T→A, 5 of polymorphisms of E2F2(rs3218170) G→A,4 of polymorphisms of MUTYH(rs1140507)T→C and BNIP3L(rs1055806)G→T, and 1 of polymorphism of TNFRSF1B (rs1061622)T→G were detected  by the chip in the tissues of 10 HCC. Samples of caspase 9 (rs2308941G) and (rs2308941A) were verified by PCR-SSCP and sequencing.
CONCLUSION: The cSNP chip of hepatocellular carcinoma-related genes can accelerate the discovery of polymorphic markers on hepatocellular carcinoma.

BACKGROUND: Interferon (IFN) with antiviral and immunomodulatory activities is one of the most important therapeutic agents for the treatment of chronic hepatitis. The apoptotic effect of IFN is influenced by cell type and the types of IFN, which suppresses proliferation and induces apoptosis in some cell types while inhibiting apoptosis in others. The aim of this study was to explore the effect of IFNα-2a on Fas expression and the apoptosis rate of peripheral blood cytotoxic T cells (CTLs) in patients with hepatitis B.
METHODS: Peripheral blood mononuclear cells were isolated from 26 patients with hepatitis B including 16 patients with chronic hepatitis B and 10 patients with chronic severe hepatitis B. Fas expression and apoptosis rate of CTLs were analyzed with flow cytometry before and after IFNα-2a treatment.
RESULTS:Before IFNα-2a treatment, Fas expression and apoptosis rate of CTLs from patients with chronic hepatitis B were significantly higher than those from patients with chronic severe hepatitis B and healthy controls respectively. No significant difference was observed between Fas expression and apoptosis rate of CTLs from patients with chronic severe hepatitis B and healthy controls. After IFNα-2a treatment, Fas expression and apoptosis rate of CTLs from different groups were compared with those before IFNα-2a treatment, showing no significant difference despite alternation of different degree.
CONCLUSIONS: Activation induced cell death（AICD）exists in peripheral blood CTLs from patients with hepatitis B. No effect of IFNα-2a exerts on Fas expression and apoptosis rate of Fas in patients with hepatitis B.

BACKGROUND: Diffusion-weighted imaging (DWI) as a new technique of magnetic resonance imaging (MRI) is used to detect focal hepatic lesions. This study was designed to evaluate the significance of DWI to differentiate focal hepatic lesions less than 3 cm in diameter by the quantitation of apparent diffusion coefficient (ADC) values.
METHODS: DWI using 1.5T MRI scanner unit was performed with a spin-echo single-shot echo planar imaging (EPI) in 56 cases of small focal hepatic lesions, including hepatocellular carcinoma (11), hepatic metastatic tumor (15), hepatic cavernous hemangioma (14), and hepatic cyst (16). The ADC values of these lesions were calculated respectively. The ratios of the ADC values of lesion/liver in hepatocellular carcinomas and hepatic metastatic tumors were also estimated.
RESULTS: The mean ADC values (mm2/s) were (0.93±0.06)×10-3 in hepatocellular carcinomas, (1.09±0.18)×10-3 in hepatic metastatic tumors, (1.95±0.38)×10-3 in hepatic cavernous hemangiomas, and (3.18±0.33)×10-3 in hepatic cysts. The ratios of ADC values of lesion/liver were 0.90±0.06 and 1.15±0.14 in hepatocellular carcinoma and hepatic metastatic tumors respectively, which were significantly different (P<0.05).
CONCLUSION: The measurement of ADC values and the ratios of ADC values of lesion/liver are helpful in MR diagnosis and differentiation of focal hepatic lesions.

BACKGROUND：The relations of the severity of hypoalbuminemia to morbidity and mortality of patients with critical illness illustrate the need for better understanding of molecular mechanism of hypoalbuminemia. This study was undertaken to investigate the response of albumin synthesis to lipopolysaccharide（LPS）in rat hepatocytes in vitro in early acute phase of sepsis.
METHODS： Hepatocytes were cultured at an initial cell density of 1.5×106 cells/well in 3 ml culture medium. There were two groups of samples which received either normal saline or 1μg/L LPS randomly. Albumin mRNA in hepatocytes was assessed by reverse transcription-polymerase chain reaction（RT-PCR）and albumin level in the supernatant was measured by ELISA at 0， 2， 8， 12， 24 hours after exposure. Meanwhile， the albumin precursor was evaluated at the same time points by flow cytometry.
RESULTS： The quantitative changes of mRNA，albumin precursor and its protein were analogous. All of them tended to decline at 12 hours post-treatment and did not decrease significantly until 24 hours after LPS exposure. Meanwhile， albumin mRNA decreased about 30% and the levels of albumin precursor and albumin reduced approximately 50%.
CONCLUSIONS： LPS can inhibit albumin synthesis in rat hepatocytes by prevention of albumin transcription. Moreover， the response of hepatic albumin synthesis to LPS changes with the stage of sepsis process. The results show that albumin metabolism in sepsis is a complicated process and further studies are required to understand the molecular mechanism of LPS-induced hypoalbuminemia in sepsis.

BACKGROUND: Hepatic cryosurgery, a safe and effective approach for an unresectable hepatoma, has been extensively applied in clinical setting. But whether direct deep freezing to the tumor involving special location, i.e., Glisson’s system of certain hepatic lobe could cause the impairment of the duct system or post impairment effect remains a mystery. Consequently, the aim of the study was to investigate the effect of freezing on the secondary branches enclosed in the Glisson’ s system of certain hepatic lobes.
METHODS: Twenty pigs were divided into 2 groups randomly. The treated group: the area of secondary branches of the Glisson’s system in the left lateral lobe was frozen by a cryoprobe at deep low temperature for 3 minutes, with the blockage of blood flow from the porta hepatis. The control group: only the blockage of the porta hepatis was performed for 3 minutes. Serologic examinations, color Doppler examination and pathological observation were used for evaluation of this procedure postoperatively.
RESULTS: The frozen hepatic parenchyma, the wall of the frozen secondary bile duct and portal vein showed necrosis. However,  the frozen hepatic artery ramification did not show any obvious changes postoperatively. Eight weeks after cryosurgery,  the lumen of the hepatic artery and portal vein maintained unobstructed. Meanwhile,  atrophy and fibroplasia occurred in the related hepatic lobe. All the animals recovered well.
CONCLUSIONS: Animals could tolerate the direct deep-freezing of the area of secondary branches enclosed in the Glisson’s system. The therapeutic effect could be attained by the necrosis of the frozen hepatic parenchyma.

BACKGROUND: Important advances have been made in research into the mechanism of alcoholic liver disease (ALD) over the past few years, but the role of liver sinusoidal endothelial cell (LSEC) in ALD has not been elucidated adequately. This study was undertaken to investigate the effect of ethanol on fenestrae of LSECs in rats.
METHODS: A rat model of alcoholic liver disease was established by means of direct intragastric instillation of ethanol. Fifty-five rats of experimental (35 rats) and control (20) groups were sacrificed at the end of 4, 8, 12 weeks respectively, and also at the end of 12-week abstinence. After heart perfusion, the liver tissue was fixed and stained with hematoxylin and eosin for observation of serial changes of LSEC-fenestrae under a transmission electron microscope.
RESULTS: Normal LESC was flat with a nucleus and organelles arranged regularly. The distal cytoplasm displayed as a lamina with many fenestrae, lacking the basement membrane (BM) underneath the endothelium. At the end of 4-week alcohol feeding, the number of fenestrae decreased at the distal cytoplasm in some LSECs, without the formation of the BM underneath the endothelium. At the end of 8 weeks, the number of fenestrae decreased significantly or even disappeared. The BM began to develop incompletely underneath the endothelium, while the active fibroblast appeared. At the end of 12 weeks, the number of fenestrae decreased more significantly and the complete BM could even be seen. But the changes were mostly limited in the single or adjoining sinus, and fibrosis was scarcely formed. At the end of 12-week abstinence, defenestration and formation of the endothelial BM lightened significantly.
CONCLUSIONS: Defenestration and formation of the BM in LSECs develop gradually with the chronic stimulation of ethanol. Hepatic sinusoidal capillarization and fibrosis will be seen if their state is more serious. These early changes, i.e., limited and regional defenestration and capillarization may be the basis of alcoholic peri-fibrosis. This kind of hepatic fibrosis is reversible after removal of etiological factors.

BACKGROUND: Diethylnitrosamine (DENA) is able to induce various benign and malignant liver lesions in rats with a high success rate and a low mortality rate. It provides a more appropriate model that better simulates the various lesions occurring in humans than the usual model of tumor implantations. The aim of the present study was to evaluate MRI liver examination in Sprague-Dawley (SD) rats as a routine method to detect hepatocellular carcinoma (HCC) nodules induced by DENA and to follow up their growth.
METHODS: Hepatic carcinogenesis was induced in 80 male SD rats using oral DENA solution. All animals were imaged for liver tumor detection with a 1.5 Tesla magnet (Siemens Sonata, Erlangen, Germany) using correspondence scan parameters and a radio-frequency knee coil. Macroscopic examinations were performed along the axial MRI sections to evaluate magnetic resonance imaging (MRI) findings, and histopathological assessment was also performed.
RESULTS: No false negative results were obtained on MR images. Hepatic tumors in 72 rats were confirmed macroscopically and 68 rats were detected by MRI till the 20th week. The smallest and the largest nodules detected by MRI were 2 mm and 37 mm in diameter respectively. The agreement rate of MRI with macroscopic observation was 39.1% and 97.4% respectively for 2 mm to 5 mm and more than 5 mm nodules.
CONCLUSIONS: The hepatic tumor induced by DENA provides a more representative range of tumors for imaging diagnosis and interventional treatment. MRI is the best approach for scrutinizing pathological changes of rat livers in the period of observation.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancer-related causes of death worldwide. The epidermal growth factor receptor (EGFR) is highly expressed in many human tumors and provides a new target for anticancer drug development. The aim of the present study was to explore the effect of EGFR antisense oligodeoxynucleotide on human HCC.
METHODS: SMMC-7721 cells in culture were treated with 10μmol/L antisense-odn for 24, 48, 72 hours respectively and MTT assay was adopted to determine the proliferation of tumor cells in vitro. About 2×106 SMMC-7721 cells with or without pretreatment(30μmol/L oligodeoxynucleotide) were inoculated into subcutaneous flap of 21 nude mice, of which 7 were treated with EGFR antisense-odn, 7 with scrambled oligodeoxynucleotide (scrambled-odn), and 7 not treated in vivo.
RESULTS: In vitro, after 24, 48, 72 hours the inhibitory rate of proliferation of SMMC-7721 cells treated with EGFR antisense-odn was 8%, 32%, and 34% respectively. In vivo after 8 weeks, no palpable tumor was found in 1/7 mice receiving cells pretreated with antisense-odn, whereas 7/7 untreated mice and 6/7 mice treated with scrambled-odn developed palpable tumors. Tumor growth in antisense-odn treated mice was significantly inhibited in comparison with that of those untreated (P<0.01) or treated with scrambled-odn (P<0.05).
CONCLUSIONS: Antisense oligodeoxynucleotide acts as a specific growth inhibitor on SMMC-7721 in a sequence specific and time-dependent manner. EGFR antisense-odn can significantly inhibit the proliferation of human hepatoma cell in vitro as well as in vivo, indicating that EGFR may play an important role in the development of hepatoma and will be a new target for its treatment.

BACKGROUND： Endoscopic retrograde cholangiopancreatography（ERCP） is the most complex gastrointestinal procedure, which needs patients’ cooperation. The aim of this study was to observe the quality and safey of sedation with propofol in patients undergoing therapeutic ERCP.
METHODS：Seventy patients who had undergone therapeutic ERCP were randomly divided into two groups.One group, given intravenously propofol, and the other sedated with routine method, served as  the control. Blood pressure, heart rate,oxygen saturation were monitored and cardiorespiratory event was observed.Patient cooperation, performance, recovery time and amnesia served as variables postoperation.
RESULTS： Blood pressure elevated in four patients in the propofol group,less than in the control group（P＜0.01＝. Seven patients showed decreased blood pressure after administration of propofol, but none in the control group(P＜0.01). Twelve patients in the control group showed mild or significant resistance, but none in the propofol group（P＜0.01＝.The time for performance in the propofol group（P＜0.05＝ was shorter than in the control group. Patient recovery was quicker in the propofol group than in the control group（P＜0.01＝. The degree of amnesia better in the propofol group than in the control group（P＜0.01＝. The degree of anmesia was also better in the propofol group than in the control group（P＜0.01）.
CONCLUSIONS： Propofol proves to be an excellent sedative for therapeutic ERCP. Being effective and safe, it shows a shorter ERCP duration but  quick recovery and better amnesia. It is better than other routine sedatives.

BACKGROUND: Bile leakage remains a serious complication after biliary surgery. The aim of this study was to assess the etiology, diagnosis and treatment of postoperative biliary leakage.
METHODS: Thirty-eight patients with biliary leakage we treated in recent 8 years were analyzed retrospectively. Among them, 8 patients had bilioenterostomy leakage, 7 accessory bile duct leakage, 7 cholecyst bed leakage, 6 leakage after removal of T-tube, 5 leakage after laparoscopic cholecystectomy, 3 leakage around T-tube, and 2 leakage caused by choledochal damage. Drainage was performed in 17 patients, reoperation in 13, drainage plus percutaneous transhepatic cholangio drainage (PTCD), endoscopic retrograde cholangiography (ERCP), endoscopic nasobiliary drainage (ENBD) and endostenting in 5, and drainage plus growth hormone in 3.
RESULTS: In this series, 37 patients were cured, and 1 died of multiple organ dysfunction syndrome (MODS). These patients were hospitalized for 2 weeks to 8 weeks. The drainage group was hospitalized shorter than the undrainage group.
CONCLUSIONS: A piece of white gauze can be used to touch surgical area in detecting biliary leakage intraoperatively. Mucous to mucous suture of the bile duct and appropriate time for removal of T-tube are recommended to prevent biliary leakage. Reoperation is essential to acute peritonitis. Drainage can be used if leakage don’t diffuse or it occurs after pulling out T-tube. Drainage plus ERCP, ENBD, PTCD and drainage are effective.

BACKGROUND: Extrahepatic biliary obstruction promotes intestinal translocation of bacteria and endotoxin and this process is an important cause of morbidity and mortality in patients with jaundice. This study was undertaken to investigate the effect and mechanism of recombinant human growth hormone (rhGH) and to alleviate intestinal translocation of bacteria and endotoxin in murine obstructive jaundice.
METHODS: A group of 42 Wistar rats were divided into 3 groups:sham operation(SO), bile duct ligation (BDL), and BDL and rhGH treatment(rhGH). By the end of the experiment, on day 7,the animals were killed, and their liver function and serum endotoxin were measured, bacterial cultures of the liver, kidney and mesenchymal lymph were made. Terminal ileum mucosa was observed under an electron microscope.
RESULTS: Liver function was improved more significantly in the rhGH group than in the BDL group. The value of endotoxin in the rhGH group was 0.38±0.03 EU/ml，significantly lower than that in the BDL group (0.65±0.04 EU/ml, P<0.01), and similar to that in the SO group (0.30±0.02 EU/ml, P>0.05). The rate of bacteria translocation in the liver, kidney and mesenteric lymph was much higher in the BDL group than in other two groups. The rate of bacteria translocation in mesenteric lymph was 64.29%，significantly higher than that in the SO group and the rhGH group（P<0.05）. There was no significant difference in bacteria translocation rate between the SO group and the rhGH group（P>0.05）. Under an electron microscope, ileum mucosa epithelial cells in the BDL group were necrotic, and organelle were markedly metamorphic. In the rhGH group, ultrastructural changes were less evident or similar to those in the SO group.
CONCLUSION: rhGH has significant protective effects on intestinal mucosa barrier in obstructive jaundice, and reduces intestinal translocation of bacteria and endotoxin.

BACKGROUND: Pancreato-enteric reconstruction after pancreatoduodenectomy (PD) is still a source of debate because of the high incidence of complications. Among the various types of pancreato-jejunostomies we don’t know yet which is the best in terms of anastomotic failure and related complications rates. Wirsung-jejunal duct-to-mucosa anastomosis (WJ) and “dunking” pancreato-jejunal anastomosis (DPJ) are the two most used ones worldwide but conflicting results are reported. To determine which is the safer anastomosis and to define when an anastomosis should be preferred, we retrospectively reviewed two groups of patients who underwent WJ or DPJ.
METHODS: Twenty-three patients underwent PD with WJ (n=17) with dilated (WJD) (n= 9) or not-dilated Wirsung’s duct (WJND) (n=8) or with a DPJ (n=6) over a 3-year period at a single institution.
RESULTS: The complications rate was high in all groups of patients (33.3% in WJD, 37.5% in WJND and 66.7% in DPJ). A pancreatic fistula developed in one patient in each group (11.1% in WJD, 12.5% in WJND and 16.7% in DPJ). All these patients were managed conservatively. Anastomotic disruption took place in the WJ patients especially in the WJND group (n=2) compared to the WJD (n=1) (25% vs. 11.1%) or DPJ groups (0%): these three patients required a re-operation. Overall, the anastomotic defects were higher in patients who underwent WJND (37.5%), compared to WJD (22.2%) and to DPJ (16.7%). However, no statistical differences were found among the groups. Delayed gastric emptying (DGE) and total parenteral nutrition (TPN) along with anastomotic defects were responsible for a prolonged hospital stay.
CONCLUSIONS: Our results were not able to demonstrate any statistical difference between the two different techniques in preventing anastomotic failure. WJ can represent a valid choice in case of a dilated duct and a firm, fibrotic enlarged gland that could not be properly invaginated in a small jejunal loop. DGE may occur in those patients who experienced an anastomotic failure and required a TPN regimen with a prolonged hospital stay.

BACKGROUND: Solid-pseudopapillary tumors (SPTs) of the pancreas have been reported as rare lesions with“low malignant potential”occurring mainly in young women. This study was designed to define the clinicopathological characteristics and the effect of surgical intervention.
METHODS: A retrospective clinical analysis was made of 21 patients with solid-pseudopapillary tumor of the pancreas admitted from June 1994 to December 2004.
RESULTS: Abdominal pain as the major complaint was found in 13 patients, and palpable abdominal mass in 7. Imaging examination showed the abdominal mass clearly, but diagnosis was not defined. In 12 patients, tumors were located in the pancreatic head and in 9 patients, in the pancreatic tail. The average diameter of the tumor was 9.5 cm (range, 3-20 cm). One patient had liver metastasis. The diagnosis of the tumor was proved pathologically during operation in 14 patients, and other 3 patients who had been diagnosed as having insulinoma and other malignant tumors were confirmed by paraffin section and enzyme labeling after operation. Eighteen patients (85.7%) were followed up with a median period of 24 months, 1-60 months without tumor recurrence.
CONCLUSION: Huge pancreatic masses of the pancreas in young women are suggestive of solid-pseudopapillary tumors. Aggressive surgical therapy can result in good prognosis in these patients.

BACKGROUND: Vascular endothelial growth factor (VEGF, namely VEGF-A) is an angiogenic polypeptide and VEGF-C is a lymphangiogenic polypeptide that has been implicated in cancer growth, invasion and metastasis. Several cytokines and growth factors play an important part in cancer progression. These cytokines and growth factors are the principal mediators of cancer cells—stromal cell interaction, which is critical for invasion of cancer cells to the surrounding tissues and metastatic dissemination to distant organs. In this study, we studied VEGF-A, C expression in cultured human pancreatic cancer cell lines and whether the presence of VEGF-A, C in the cell lines is regulated by cytokines interleukin-1α(IL-1α), and interleukin-6 (IL-6).
METHODS: We used Northern blot and Western blot methods to analyze expression of the gene and protein of VEGF-A, C in all 6 tested cell lines (ASPC-1, CAPAN-1, MIA-PaCa-2, PANC-1, COLO-357 and T3M4) respectively. To analyze what is the regulator for this VEGF-A, C expression in pancreatic cancer, we used the  reverse transcription-polymerase chain reaction (RT-PCR) method to analyze VEGF-A, C expression in cultured human pancreatic cancer cell lines (CAPAN-1 and COLO-357) under the stimulation with IL-1α(10μg/L) or IL-6 (100μg/L).
RESULTS: Northern blot analysis revealed the presence of the 4.1-kb VEGF-A mRNA transcript and 2.4-kb VEGF-C mRNA transcript in all 6 tested cell lines. Immunoblotting with highly specific anti-VEGF-A, anti-VEGF-C antibody revealed the presence of a molecular weight of 43-kDa VEGF-A protein and 55-kDa VEGF-C protein in all the cell lines. RT-PCR analysis revealed the levels of the VEGF-A and VEGF-C gene were 1-2 fold and a 1-fold increase in the COLO-357 cell line by stimulation with IL-1α, however, no effect was found in the CAPAN-1 cell line. The levels of the VEGF-A and VEGF-C gene were 2-5 fold and a 1-fold increase in the CAPAN-1 cell line by stimulation with IL-6, but no effect was found in the COLO-357 cell line.
CONCLUSION: These findings suggested that the expression of VEGF-A, C and their regulation by IL-1α, IL-6 in pancreatic cancer contributes to the lymphatic and distant metastasis and the disease progression.

BACKGROUND: Biliary cystadenocarcinoma as a very rare hepatic neoplasm may be difficult to distinguish from simple hepatic cysts, especially in the unilocular form. Although diagnosis of cystadenocarcinoma during open hepatic surgery demands a complete surgical resection, few reports described the correct approach to such lesions revealed by laparoscopic approach. Five cases of incidental cystadenocarcinoma after laparoscopic surgery for hepatic cystic lesions were presented with discussion of diagnostic and management implications.
METHODS: Clinical records of 5 patients who had undergone operation and histological examination at our hospital from 1993 to 2002 were analyzed retrospectively.
RESULTS: In all patients who received liver lobectomy, primary hepatic cystadenocarcinoma was diagnosed. Primary biliary cystic neoplasm was difficult to diagnose and the management of both benign and malignant tumors was similar in the 5 patients.
CONCLUSIONS: Cystadenocarcinoma is often difficult to diagnose because its clinical manifestations are similar to those of hepatic cysts and other cystic lesions. Imagining examination is helpful in evaluating the disease. Complete excision of cystadenocarcinoma with a wide margin is the best treatment.

BACKGROUND: Annular pancreas in adults is a rare embryologic abnormality detected after development of complications. Embryology, diagnosis and treatment strategies for symptomatic adult annular pancreas remain controversial. In this paper we reevaluated these problems in view of the technological and theoretical advances.
METHODS: In 2 patients with annular pancreas, one (36-year-old male patient) presenting with duodenal obstruction and duodenal ulcer associated with duodenocolic fistula underwent Billroth II gastrectomy and fistula ectomy and the other (17-year-old male patient) presenting with duodenal obstruction and duodenal ulcer underwent Billroth II gastrectomy. English language literature about annular pancreas etiology, diagnosis and treatment was reviewed.
RESULTS: Both of the patients had uneventfully recovered. Abdominal computed tomography, endoscopic retrograde cholangiopancreatography and magnetic resonance cholangiopancreatography showed typical images of annular pancreas. Duodenal bypass procedure, choledochojejunostomy, endoscopic sphincterotomy or biliary stenting, and pancreatic resection were alternative to treat this sort of anomaly.
CONCLUSIONS: Annular pancreas in adults is a rare congenital abnormality, while newer imaging modalities and an index of suspicion may assist in finding more cases. The management of this congenital anomaly should be individualized according to the associated complications.

BACKGROUND: Celiomesenteric trunk is a rare vascular anomaly, which has significant clinical implications. 3-dimensional contrast-enhanced magnetic resonance angiography (3D CE MRA) is a new imaging modality, non-invasive, fast and easy to perform. We describe a patient with a common celiomesenteric trunk demonstrated by 3D CE MRA.
METHODS: A 45-year-old man was subjected to 3D CE MRA before transarterial chemoembolization (TACE) for hepatocellular carcinoma. The examination was performed on a 1.5T MR imager with a body coil. The contrast medium was gadopentetate dimeglumine. Source images from the hepatic arterial phase acquisition were reconstructed into MRA images. Intra-arterial digital subtraction angiography (DSA) during TACE was carried out 3 days after 3D CE MRA.
RESULTS: On 3D CE MRA, a common trunk of the celiac and superior mesenteric artery was clearly depicted. The origin and course of the hepatic, splenic and superior mesenteric arteries were also visualized. These findings were confirmed by intra-arterial DSA.
CONCLUSIONS: Celiomesenteric trunk can be well delineated by 3D CE MRA. The image is correlated precisely with that from DSA.