BACKGROUND: The immunosuppressive drugs used worldwide have a narrow therapeutic index, which results in a need to individualize the dose regimen for different recipients. The oxidative enzymes cytochrome P450 (CYP)3A and the drug efflux pump P-glycoprotein (P-gp) are two potential factors in the processes of metabolism. Pharmacogenetic study of immunosuppressive drugs has focused on these two enzymes. This review was undertaken to assess the role of single nuclear polymorphisms (SNPs) of these two enzymes in the individual administration of immunosuppressive drugs.
DATA SOURCES: An English-language literature search was made using MEDLINE for articles on CYP3A and P-gp in organ transplantation.
RESULTS: The SNPs of CYP3A and P-gp are closely correlated to the large variations of cyclosporine and tacrolimus dosage between different patients, although conflicting results were obtained by some authors.
CONCLUSIONS: More studies should be conducted to elucidate further the pharmacogenetics of immunosuppressive drugs in organ transplantation, a deep understanding of which would provide an important step toward drug regimen individualization in the posttransplant therapy.

BACKGROUND: Adult living donor liver transplantation (LDLT) is now widely applied to patients, children or adults, and the graft extends from the left hepatic lobe to the right hepatic lobe. Harvesting the right hepatic lobe would mean putting the donor at high risk. The congestion of a graft may cause small-for-size syndrome. The safety of the donor and its evaluation, which are related to the outcome for the recipient, play an important role in LDLT. How to decrease the congestion of the graft is another challenge to transplant experts.
DATA SOURCES: A literature search from MEDLINE about adult LDLT in recent years was made to analyze the safety of the living donor and the innovation of surgical techniques for preventing small-for-size syndrome.
RESULTS: The top priority for adult LDLT is donor safety. Preoperative donor evaluation consists of three stages: phase 1 for general evaluation, phase 2 for laboratory tests, and phase 3 for radiological evaluation of graft volume and vessel anatomy. The potential pathogenic mechanisms of small-for-size syndrome seem to be related to persistent portal hypertension and portal overperfusion. Improved surgical techniques for decreasing portal hypertension and preventing congestion of a graft may reduce the incidence of small-for-size syndrome. The improved techniques include reconstruction of the tributaries of the middle hepatic vein, end-to-side portocaval shunting, ligation of the splenic artery, dual-graft transplantation, and modified reconstruction of hepatic veins.
CONCLUSION: With the careful preoperative assessment and the safety of the living donor, as well as improved surgical techniques, adult LDLT using the right lobe is safe.

BACKGROUND: Currently, more and more nucleos(t)ide analogs are appearing as therapeutic options in the treatment of chronic hepatitis B (CHB). Their efficacy and safety profile in hepatitis B virus (HBV) infection have already been studied in detail worldwide. This review summarizes the efficacy of lamivudine, adefovir, entecavir and newer antiviral agents such as emtricitabine, telbivudine and clevudine in the treatment of hepatitis B in different clinical situations.
DATA SOURCES: An English-language literature search using OVID and MEDLINE was performed and a total of 40 articles on the treatment of chronic hepatitis with nucleos(t)ide analogues were selected.
RESULTS: Nucleos(t)ide analogs such as lamivudine, adefovir and entecavir are well tolerated and induce a decrease in serum HBV-DNA levels associated with normalization of serum alanine aminotransferase (ALT) levels. But their sustained response with HBeAg to anti-HBe seroconversion is rarely obtained and HBsAg loss is exceptional. The response is maintained during therapy which needs to be continued indefinitely in the majority of patients since withdrawal of treatment is generally followed by a rapid reactivation of hepatitis B. However, drug resistant mutations can be induced in long-term treatment. Other newer antiviral agents such as emtricitabine, telbivudine and clevudine in the treatment of hepatitis B are still under phase Ⅱ or Ⅲ clinical trials.
CONCLUSIONS: Nucleos(t)ide analogs play an important role in the therapy of hepatitis B now and in the future. Lamivudine is limited by the frequent emergence of drug-resistant (HBV) mutants (YMDD). Adefovir and entecavir appear to be effective against both YMDD mutation and wild type. Therapeutic options against hepatitis B virus remain a major clinical challenge.

BACKGROUND: Combined hepatitis B immune globulin (HBIg) and lamivudine in prophylaxis of the recurrence of hepatitis B after liver transplantation has significantly improved the survival of HBsAg positive patients. This study was undertaken to evaluate the outcomes of liver transplantation for patients with hepatitis B virus (HBV).
METHODS: A retrospective chart analysis and a review of the organ transplant database identified 51 patients (43 men and 8 women) transplanted for benign HBV-related cirrhotic diseases between June 2002 and December 2004 who had survived more than 3 months. HBIg was administered intravenously during the first week and intramuscularly thereafter.
RESULTS: At a median follow-up of 14.1 months, the overall recurrence rate in the 51 patients was 3.9% (2/51). The overall patient survival was 88.3%, and 82.4% after 1 and 2 years, respectively. A daily oral dose of 100 mg lamivudine for 2 weeks before transplantation for 10 patients enabled 57.1% (4/7) and 62.5% (5/8) of HBV-DNA and HBeAg positive patients respectively to convert to be negative. Intramuscular HBIg was well tolerated in all patients.
CONCLUSION: Lamivudine combined with intramuscular HBIg can effectively prevent allograft from the recurrence of HBV after liver transplantation.

BACKGROUND: Because of the complicated pathological features after liver transplantation, severe sepsis is difficult to treat and often leads to death. This study was undertaken to analyze the role of orthotopic liver transplantation (OLT) in patients with severe sepsis and to evaluate the effect of the scoring system.
METHODS: Fifty-six patients conformed to the inclusion criteria. They were divided into two groups: non-OLT group (group A) and OLT group (group B). Besides the general data of the patients, the surveillance of blood lactate, the number of failed organs, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) and mutiple organ dysfunction score (MODS) were evaluated at the 1st, 3rd and 7th day after OLT.
RESULTS: The mortality during hospitalization was 30% in the non-OLT group and 57.6% in the other group. The level of blood lactate at the 1st day of OLT increased more significantly in the OLT group than in the non-OLT group (P<0.01). It was decreased but higher than that in the non-OLT group in the seven days after OLT. The number of failed organs in the OLT group was greater than that in the non-OLT group (P<0.01). The continuous score of APACHE Ⅱwas not significantly different in the two groups. But the continuous MODS in the OLT group was higher than that in the non-OLT group (P<0.01), which was consistent with the number of failed organs.
CONCLUSIONS: The persistently higher level of blood lactate during 7 days may be a dependent risk factor. Immunosuppression may be another risk factor for OLT patients. The mortality of OLT in patients with severe sepsis in 28 days is almost double that in non-OLT patients. The MODS score is better than the APACHE Ⅱscore in the assessment of organ failure in OLT patients with severe sepsis. The standard scoring system could be improved or a new scoring system that includes the blood lactate score should be established for liver transplantation.

BACKGROUND: Little information is available about anesthesia management of nontransplant organ surgery of recipients after adult liver transplantation. The aim of this study was to discuss the anesthesia management of recipients for different stages after liver transplantation.
METHODS: The medical records of 16 patients were reviewed after OLT scheduled for elective nontransplant organ surgery at our institution from September 2002 to October 2005. The patients were divided into perioperative stage (group A) and mid-term and long-term stage (group B) groups according to post-OLT time. The data of 16 patients preoperation, intraoperation and postoperation were analyzed.
RESULTS: The measurements of alanine transaminase (ALT), total bilirubin (TB), prothrombin time (PT), and lung infection were significantly higher in group A than in group B (P<0.05). The incidence of hyperglycaemia was significantly higher in group B than in group A (P<0.05). During operation the incidence of hypotension was significantly higher in group A than in group B (P<0.05). After operation, the number of patients in ICU was significantly larger and the extubation time was longer in group A than in group B. General anesthesia was induced in 14 patients, and regional anesthesia in 2 patients.
CONCLUSIONS: Regional or general anesthesia can be safely delivered to adult OLT recipients except for contraindications. Special considerations include protection of the function of important organs, correction of hemodynamic instability in perioperative stage patients after OLT, and measurement of the side-effects of immunosuppression in mid-term and long-term stage patients.

BACKGROUND: Postoperative regional chemotherapy is one of the most effective methods to decrease the recurrent rate and improve the prognosis of primary hepatocarcinoma (PHC). This study was undertaken to assess the optimal pathway to implant the drug delivery system (DDS) in the different ways of resecting PHC so as to offer a valuable reference to clinical implantation of the DDS.
METHODS: One hundred and ninety cases were divided into two groups according to whether the tumors were resected completely (A) or not (B). Groups A and B were subdivided into three groups a, b and c according to the pathway selected for DDS implantation. The patients in subgroup a received DDS implantation through both the hepatic artery and portal vein (A+P-implanted group), the patients in subgroup b received DDS implantation through the portal vein (P-implanted group), and the patients in subgroup c received DDS implantation through the hepatic artery (A-implanted group).
RESULTS: The 1- and 3-year recurrent rates of subgroup c in group A were higher than those of subgroup b, and there was no significant difference between subgroups a and b. Compared with subgroups a and c, the 1- and 3-year survival rates of subgroup b were similar to those of group a but higher than those of group c. The 1- and 3-year survival rates between subgroups a and b in group B were significantly different. The prognosis of subgroup c was lower than that of subgroup a and no significant difference was observed between subgroups b and c.
CONCLUSIONS: The DDS should be implanted into the portal vein when PHC is resected completely. It may be better to implant it into both portal vein and hepatic artery if the tumor cannot be completely resected.

BACKGROUND:  Treatment of chronic hepatitis B (CHB) alone with interferon or lamivudine alone or in combination is effective in only a small proportion of patients. Treatment of patients in whom antiviral therapy fails is challenging. This study was made to determine the efficacy of combined pegylated interferon alpha (peg-IFN) and lamivudine in patients with CHB who had failed to respond to antiviral treatment.
METHODS: Twenty patients with CHB proven by liver biopsy, with ALT levels >1.5×ULN, HBV DNA levels>141 500 copies/ml, and previous treatment failure with an adequate regimen were treated with a combination of peg-IFN 1.5 µg/kg and lamivudine 100 mg/day for 52 weeks and followed up for a further 24 weeks. Biochemical response was defined as normalization of ALT and DNA response as HBV DNA<141 500 copies/ml. Secondary efficacy measures included HBsAg loss, HBeAg loss and appearance of anti-HBe (in cases of HBeAg-positive patients).
RESULTS: Twenty patients were treated, of whom 16 were HBeAg positive. At 52 weeks, normal ALT was seen in 10 (50%) (8 of 16 HBeAg+ and 2 of 4 HBeAg-), HBV DNA response in 5 (25%) (5 of 16 in HBeAg+ and none in HBeAg-), and HBeAg loss with appearance of anti-HBe in 5 (31.3%) of the 16 HBeAg positive patients. At 76 weeks, 8 (80%) of the 10 patients with normal ALT at 52 weeks relapsed, with normal ALT only in 2 (10%) (1 of 16  HBeAg+ and 1 of 4 HBeAg-), and all 5 patients who had a DNA response at 52 weeks relapsed at 76 weeks and had no DNA response. HBeAg loss with appearance of anti-HBe was seen in 1 (6.3%) of 16 HBeAg-positive patients. None of the patients lost HBsAg.
CONCLUSIONS: The combination of peg-IFN and lamivudine for 52 weeks is not effective for treatment of CHB patients with a failed treatment. New treatment strategies need to be developed.

BACKGROUND: Heat shock protein (HSP) gp96 is a member of the HSP90 family and presumably overexpresses as a result of stimulation by mutated or abnormal proteins. Its abnormal expression correlates with carcinogenesis, progression and prognosis of hepatocellular carcinoma (HCC). In this study, we investigated the pathological characteristics of liver gp96 expression and its relationship with hepatitis B virus (HBV) replication in HCC patients.
METHODS: Tumor specimens were prospectively collected from 30 HCC patients undergoing liver resection. Total RNAs were extracted from HCC or their non-cancerous tissues. The distribution of gp96 expression in hepatocytes was investigated by streptavidin peroxidase (S-P) immunohistochemistry and tissue HBV-DNA was detected by the in situ molecular hybridization technique. The association of gp96 expression with HBV replication, and the histopathological characteristics of HCC were analyzed.  
RESULTS: The gp96 was strongly expressed in HCC (73.3%, 22 of 30) and weakly (46.7%, 14 of 30) in non-cancerous tissues. The gp96 expression in HCC tissues was correlated with degree of tumor differentiation and tumor size, but not with tumor number (P>0.05). Immunohistochemical analysis showed that 17 of 19 HCC patients with HBV-DNA-positive were strongly expressed for gp96, whereas only 5 of 11 patients with HBV-DNA-negative were positive for gp96. A significant difference was found between the two groups (89.5% vs. 45.5%, P<0.05).
CONCLUSIONS: The abnormal expressions of HSP gp96 in HCC tissues are associated with HBV replication. This finding indicates that HBV infection plays an important role in the development of HCC.

BACKGROUND: The treatment for primary tumor in the caudate lobe of the liver is difficult because of its unique anatomical location. This study was undertaken to improve operative techniques and results by a new anatomical method of caudate lobectomy.
METHODS:  Clinical data of 16 patients who had had caudate lobectomy for the liver from January 1996 to November 2004 were retrospectively analyzed. The third porta hepatis anatomical method was performed in all 16 patients. Operative time, intraoperative blood loss, postoperative complications were recorded. The 1-, 3-, and 5-year survival rates of 13 patients with caudate lobe carcinoma were followed up. Anatomical status, operative routes, operative procedures, liver blood supply were evaluated.
RESULTS: The operation was successful in the 16 patients. The operative time was 255±70 minutes and blood loss 740±402 ml. None of the patients died from massive bleeding during the operation, nor did complications such as biliary fistula and liver failure occurred. In 13 patients with malignant tumor, 7 died from recurrence and metastasis of the tumor and the other 6 are still alive at the end of follow-up. One patient has survived for 6 years. The 1-, 3-, and 5-year survival rates in the 13 patients were 83.9%, 58.7% and 39.2%, respectively.
CONCLUSION: Caudate lobectomy by the third porta hepatis anatomical method can improve operative effect and increase the resection probability for solitary tumor in the caudate lobe.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common disease with high mortality and serious effect on the life quality of patients. Operation is still the most effective treatment. Currently, in China, patients with HCC are often complicated by hepatitis B related liver cirrhosis and secondary hypersplenism. This study was undertaken to evaluate the effect and indications of synchronous hepatectomy and splenectomy for HCC patients with hypersplenism.
METHODS: The clinical records and treating processes of 24 patients with HCC and hypersplenism during the period of January 1991 to July 2004 were analyzed retrospectively.
RESULTS: Sixteen patients underwent hepatectomy and splenectomy, including extensive devascularizasion around the cardia (9 patients). Seven patients were treated with microwave ablation and splenectomy plus extensive esophagogastric devascularization. One patient underwent hepatectomy combined with microwave ablation and splenectomy plus extensive esophagogastric devascularization. There were no deaths during the operation. During the first week after operation, the symptoms of hypersplenism disappeared and the platelet (Plt) and white blood cell (WBC) counts were significantly elevated (Plt: 247×109/L vs. 45.9×109/L, WBC: 13.0×109/L vs. 3.3×109/L, P<0.01).
CONCLUSIONS: Synchronous splenectomy can increase the safety of hepatectomy in selected patients with HCC and secondary hypersplenism by reducing bleeding complications. Splenectomy enhances patients' immunity against tumor in a long period as well.

BACKGROUND: Since hepatectomy has been widely performed, different operative manner, operating areas, and material in the residual cavity may be found ultrasonographi-cally near the resected area after the operation. In this study, we investigated the changes of focal ultrasonography at the resected area post hepatectomy and recognized the characteristic ultrasonographic images.
METHODS: 176 patients whose ultrasonographic findings were studied in the residual area during the early and later periods after hepatectomy were retrospectively analyzed in terms of  operative manner, operative area, and material in the residual cavity.
RESULTS: There were absence of partial hepatic lobe or hepatic segment, focal anechoic area with thin wall or mixed mass at the resected area, and conformation of irregular high-echoic conglomeration at the resected area, cystic non-anechoic area, and mixed mass with irregularly thickened wall at the resected area, inconsistent internal echoes, and color Doppler twinking artifacts around the material and the residual cavity after curettage and aspiration.
CONCLUSIONS: Focal ultrasonographic findings at the resected area after hepatectomy vary with different operative procedures, operative area, resection size, absence or existence of material, and kinds of material in the residual cavity.

BACKGROUND: Hepatic veno-occlusive disease (VOD) or sinusoidal obstruction syndrome is associated with a high mortality because of its severity. Gymura segetum, a Chinese herbal medicine, is always used to cure injury and bleeding in rural areas in China. This study was undertaken to better understand VOD and its relations to the effect of Gymura segetum.
METHODS: Between 2000 and 2002, two patients were admitted to our department because of VOD. Before admission, both of them had been injured and taken oral decoction of patent drug Gymura segetum. We analyzed the clinical manifestations, diagnosis and therapy of the two patients.
RESULTS: Pyrrolizidine in Panax notginseng was proved to induce VOD. The diagnosis of VOD depended on hepatic biopsy.
CONCLUSION: Gymura segetum can induce VOD. More attention should be paid to its unsuscepted side effects.

BACKGROUND: Matrix metalloproteinases (MMPs) and its natural tissue inhibitors of metalloproteinases (TIMPs) are involved in cancer progression. This study was undertaken to determine the effects of overexpression of TIMP-1 on human hepatocellular carcinoma (HCC) cell growth, proliferation, and invasion.
METHODS: Employing the efficient AdEasyTM system, recombinant adenovirus AdTIMP-1 containing full-length cDNA of TIMP-1 was generated by homologous recombination and amplified in 293 cells. Then, human HCC cell line (HepG2) underwent gene transfection to overexpress TIMP-1 (so-called HepG-T cells). The mRNA and protein expressions of TIMP-1 were detected with RT-PCR and Western blotting, respectively. The ultrastructure was observed with a transmission electron microscope and the proliferation of HepG-T cells was determined by MTT assay and growth curve. The potential of in vitro invasion was measured with Millicell Chamber.
RESULTS: The resulting AdTIMP-1 and HepG-T cells were generated and the expression of TIMP-1 was detected in vitro. The cell proliferation curves and MTT assay showed HepG-T cells' growth, and proliferation were obviously inhibited. The invasion across Matrigel-coated filters was significantly decreased compared with controls. The suppression rate of HepG-2 cells with AdhTIMP-1 transfection was 50%, and AdhTIMP-1 transfection inhibited by more than 91.6% of the invasion into the Matrigel-coated filter (P<0.01).
CONCLUSIONS: TIMP-1 overexpression results in the suppression of proliferative and invasive potential of HepG2 cells in vitro. This study demonstrates the potential role of TIMP-1 as a target for liver cancer gene therapy and has laid a foundation for further study on its anticancer function.

BACKGROUND: Hypoxic preconditioning can protect hepatocytes against hypoxic injury, but its mechanism has not been elucidated. The aim of this study was to profile gene expression patterns involved in hypoxic preconditioning and probable mechanism at the level of gene expression.
METHODS: Hepatocytes were divided into 2 groups: control group and hypoxic preconditioning group. Biotin-labeled cRNA from the control group and the hypoxic preconditioning group was hybridized by oligonucleotide microarray. Genes that were significantly associated with hypoxic preconditioning were filtered, and validated at the level of transcript expression.
RESULTS: Forty-three genes with significantly altered expression patterns were discovered and most of them had not been previously reported. Among these genes, genes encoding superoxide dismutase 2 (SOD2) and interleukin 10 (IL-10) in the hypoxic preconditioning group were confirmed to be up-regulated with real-time quantitative PCR.
CONCLUSIONS: Many cytokines are involved in hypoxic preconditioning and protect hepatocytes from hypoxia-reoxygenation injury, and the increase of oxygen free-radical scavengers and anti-inflammatory factors may play a key role in this phenomenon. Diverse signal pathways are probably involved.

BACKGROUND: Dendritic cells (DCs) loaded with complex antigen are always used to induce cytotoxic T lymphocytes (CTLs) which have a specific anti-tumor activity. However, CTLs can assault autologous cells induced by DCs loaded with autologous antigen. This study aimed to explore how to weaken the autoimmune reaction induced by DC vaccine by combining mature DC (mDC) activating immunity and immature DC (imDC) leading to immune tolerance to make hepatocellular carcinoma (HCC) vaccine in vitro.
METHODS: DC progenitors derived from human peripheral blood were assigned to two groups. One was cultured to mDC and pulsed with frozen-thawed antigen (FTA) of human HCC cell line SMMC-7721 cells (mDC group), and the other was cultured to imDC and pulsed with FTA of human liver cell line L-02 cells (imDC group). The morphology of DCs was monitored and cells phenotypes including HLA-DR, CD80, CD1α, CD83 were assayed by flowcytometry (FCM). The concentrations of interleukin-12 (IL-12) in the supernatant were assayed by ELISA. Methyl thiazolyl tetrazolium (MTT) was used to evaluate T cell proliferation induced by mDC and imDC and the killing rate of CTL induced by mDC and imDC respectively/together on SMMC-7721 and L-02 cells.
RESULTS: Compared with the imDC group, the mDC group was characterized by the following: increased secretion of IL-12 (P<0.05); higher expression of HLA-DR, CD1α, CD80, CD83; and stronger activity in stimulating proliferation of isogenic T cells (P<0.05). CTL induced by the mDC group had a significant killing response to SMMC-7721 as well as a higher killing rate for L-02 (P>0.05). CTL induced by mDC and imDC together had a higher killing response to SMMC-7721, but a lower killing rate for L-02 (P<0.01).
CONCLUSIONS: CTL induced by mDC and imDC together has a higher antigen-specific killing response in vitro than that induced by mDC alone. This may be of greater clinical value.

BACKGROUND: Brain-dead donors have been the main sources in organ transplantation. But many studies show that brain-death affects the organ's function after transplantation. This study was undertaken to investigate liver injury after brain-death in rats and the protective effects of N-acetyleysteine (NAC) on liver injury.
METHODS: A total of 30 Wistar rats were randomized into 3 groups: normal control group (C), brain-dead group (B), and NAC pretreatment group (N). At 4 hours after the establishment of a brain-dead model, serum was collected to determine the levels of ALT, AST, TNF-α and hyaluronic acid (HA). Hepatic tissue was obtained for electron microscopic examination.
RESULTS: At 4 hours, the levels of ALT, AST, TNF-α, and HA in group N were significantly higher than those in group C, but these parameters were significantly lower than those in group B. Electron microscopy showed activated Kupffer cells, denuded sinusoidal endothelial cells (SECs), and widened fenestration in group B, but eliminated activation of Kupffer cells and intact SECs in group N.
CONCLUSION: Brain death can cause liver injury, and N-acetyleysteine can protect the liver from the injury.

BACKGROUND: There is much debate over the regulation of mitochondrial calcium overload and reducing the impairment of energy metabolism in hepatic cells. It has not been reported whether L-arginine (L-Arg) can affect hepatic mitochondrial calcium overload. This study was undertaken to investigate the protective effect of L-Arg on Ca2+ handling of hepatic mitochondrion in rats with obstructive jaundice and to clarify its possible mechanism.
METHODS: Seventy-two male SD rats were randomly divided into 3 groups: sham operation+normal saline group (SO group), common bile duct ligation+normal saline group (BDL group), and common bile duct ligation+ L-Arg group (L-Arg group). The levels of malondialdehyde (MDA), superoxide dismutase (SOD) and Ca2+ in rat hepatic mitochondrion were examined at the 7th, 14th and 21st day after operation.
RESULTS: The Ca2+ and MDA levels of hepatic mitochondrion increased significantly but their SOD content decreased markedly at each time point in the BDL group. Except at the 21st day, the Ca2+ and MDA, contents of hepatic mitochondrion were significantly lower, and SOD concentrations were higher in the L-Arg group than those in the BDL group at the 7th and 14th day (P<0.01).
CONCLUSION: L-Arg has a protective effect on mitochondrion in the early and mid stages of obstructive jaundice.

BACKGROUND: Neutrophil plays an important role in hepatic ischemia-reperfusion injury. We investigated neutrophil infiltration in liver tissue, Kupffer cells' role in neutrophil accumulation, and apoptosis and regeneration of hepatocytes in liver ischemia-reperfusion injury.
METHODS: Vascular microclamps were placed across the pedicles of the median and left lateral lobes for 90 minutes after 30% hepatectomy with the resection of caudate, right lateral and quadrate lobes and papillary process. Gadolinium chloride (GdCl3) was used to destroy Kupffer cells. Neutrophil activity was inhibited with Urge-8, a monoclonal antibody against neutrophil produced in our laboratory. GdCl3 (10 mg/kg) and Urge-8 (50 mg/kg) were given intravenously in respective groups. Ischemia control, GdCl3 and Urge-8 groups were compared.
RESULTS: Following hepatic reperfusion, serum interleukin-8 (IL-8) levels and hepatic neutrophil counts peaked at 3 hours, and peak concentrations of alanine aminotransferase (ALT) occurred at 6 hours. Animals of the control group showed increases in neutrophil infiltration in liver tissue, liver enzyme levels, and apoptosis index of hepatocytes and decreases in overall survival rate and proliferating cell nuclear antigen (PCNA) expression of hepatocytes. The survival rates and PCNA proportion of hepatocytes were higher and the levels of hepatic neutrophil infiltration, liver enzymes, and hepatocyte apoptosis after reperfusion were lower in the GdCl3 and Urge-8 groups than those in the ischemia control group.
CONCLUSIONS: Blockades of Kupffer cells' activity and neutrophil infiltration by GdCl3 and Urge-8 eliminate neutrophil-mediated hepatic injury and enhance subsequent hepatic regeneration during liver ischemia-reperfusion.

BACKGROUND: The function of the intestinal barrier has drawn more and more attention from researchers in recent years for its important role in many diseases such as burns, wounds, and pancreatitis. In our experimental studies on pigment gallstone, we found potential relationships between the function of the intestinal barrier and pigment gallstone formation. This study was undertaken to investigate the possible action and mechanism of the function of the intestinal barrier in the pathogenesis of pigment gallstone.
METHODS: Eighty guinea pigs were divided into a normal group (CON), a pigment gallstone group (PS) and an intestinal mucosa protection group (GLN). Normal forage, pigment gallstone-forming forage and pigment gallstone-forming forage with supplemental intestinal mucosa protector (glutamine) were given to each group. In the gallstone-forming rate, morphology of intestinal mucosa, intestinal permeability, serum endotoxin and biliary β-glucuronidase were assessed after 8 weeks.
RESULTS: The rate of gallstone-formation was 73.9% in the PS group. Damage of intestinal mucosa, endotoxemia (from 77±43×10-6 EU/L to 1367±525×10-6 EU/L, P<0.01) and increased activity of biliary β-glucuronidase (endogenous β-glucuronidase from 122.1±39.5 to 209.8±47.5 Fishman Unit, P<0.01, and exogenous β-glucuronidase from 573.5±476.9 to 2206.6±983.9 Fishman Unit, P<0.01) were observed in the PS group compared with the CON group. The rate gallstone-formation decreased significantly to 44.4% and the other indices except β-glucuronidase were lower in the GLN group than in the PS group.
CONCLUSIONS: The function of the intestinal barrier is correlated with pigment gallstone formation. Dysfunction of the intestinal barrier function may promote pigment gallstone formation through bacterial translocation, endotoxemia, and biliary β-glucuronidase.

BACKGROUND: TMS1/ASC is a bipartite protein comprising two protein-protein interactive domains: pyrin (PYD) and caspase recruitment domain (CARD). Proteins containing these domains play pivotal roles in regulating apoptosis and immune response pathways. The absence of TMS1/ASC expression in some tumors is because methylation of the TMS1/ASC gene contributes to carcinogenesis and cancer development. We studied the methylation status of the TMS1/ASC gene and its clinical significance in cholangiocarcinoma.
METHODS: Target DNA was modified by sodium bisulfite, coverting all unmethylated, but not methylated, cytosines to uracil, and subsequently by a nested amplification with primers specific for methylated versus unmethylated DNA. The PCR product was detected by gel electrophoresis and combined with the clinical records of patients.
RESULTS: Aberrant methylation of the TMS1/ASC gene was detected in specimens of colorectal cancer tissues from 13 (36.1%) of 36 patients, and specimens of adjacent normal tissues from 3 patients (8.3%). No statistical differences were seen in the extent of differentiation and invasion, lymph node metastasis, and pathologic type between the methylated and unmethylated tissues (P>0.05).
CONCLUSIONS: The frequency of TMS1/ASC gene methylation in cholangiocarcinoma is high, but it is not related to pathologic changes. The TMS1/ASC gene is probably suppressed by methylation, and is resistant to apoptosis and immunological surveillance. The gene epigenetically affected in methylated tissues could be associated with carcinogenesis of cholangiocarcinoma.

BACKGROUND: Solid-pseudopapillary tumor (SPT) of the pancreas is a rare exocrine pancreatic tumor. Despite the increasing recognition of the tumor in recent years, its pathogenesis and apparent therapeutic algorithm remain unclear. This study was designed to define the clinical, imaging, and pathologic features and to improve the diagnosis and treatment of this rare disease.
METHOD: The clinical, imaging, and pathologic findings of 9 SPT patients managed in our hospital between 2001 and 2005 were retrospectively analyzed, and related literatures were reviewed.
RESULTS: In the 9 patients aged from 14 to 68 years, 8 were female and 1 male. The mean age of these patients at diagnosis was 30 years. Initially, 8 patients complained of vague abdominal pain and one patient had pancreatic mass detected incidentally by abdominal CT. The levels of blood and urine amylase and tumor markers were all within the normal range.  B-US, CT and MRI demonstrated that tumors were well encapsulated and contained some degree of internal hemorrhage or cystic degeneration. The mean transverse diameter of these tumors was 5.4 cm (range, 2-10.5 cm). The tumors were located at the head (2 patients), body (2), body and tail junction (4), and tail (1) of the pancreas. Surgical procedures included pancreaticoduodenectomy, distal pancreatectomy, distal pancreatectomy with splenectomy, and enucleation. Histological examination showed solidified cystic areas and papillary protrusions. Two malignant tumors demonstrated retroperitoneal metastases and vascular invasion. Follow-up for 2.5 years on average showed that one patient died of tumor recurrence at 10 months and the rest were alive.
CONCLUSIONS: SPT exhibits unique clinical and pathologic features and is readily diagnosed by its characteristic imaging and histological appearance. Surgical resection of the primary tumor and metastases is the treatment of choice.

BACKGROUND:  Because of the critical worldwide shortage of cadaveric organ donors, transplant professionals have increasingly turned to living donors. Partial hepatectomy for adult living donor liver transplantation has been performed since the late 1990s.  Most often, the complications of living donor hepatectomy have been related to the biliary tract, specifically biliary leaks.
METHODS: A 54-year-old man underwent donor right hepatectomy for living donor liver transplantation. Three years after liver donation he presented with upper abdominal pain and fullness. Radiographic workup revealed a diaphragmatic hernia of the right hemithorax.
RESULTS: After thoracoscopic evaluation of the right hemithorax, diaphragmatic hernia was repaired. Currently the patient remains well several months after the repair with complete resolution of abdominal pain, normal chest X-ray examination demonstrating no recurrence of diaphragmatic hernia, and normal liver functions tests.
CONCLUSIONS: Multiple complications of living donor liver transplantation have been described the transplant literature. Diaphragmatic hernia is a formerly-undescribed complication of right donor hepatectomy for transplantation.

BACKGROUND: Cholecystocolocutaneous fistula (CCCF) is a rare complication of gallstone disease resulting from spillage of gallstones from perforation of an empyema of the gallbladder, which can pose diagnostic dilemmas. We describe a patient, who presented initially with a swelling followed by discharging sinuses on her right flank where a diagnosis of CCCF was made and was treated surgically with satisfactory outcome.
METHODS: A computed tomography (CT) scan showed an ill-defined soft tissue mass in the right subhepatic space and a fistulogram demonstrated passage of contrast into the gallbladder fossa and hepatic flexure of colon. At laparotomy, a cutaneous fistula containing two pigment stones led to the gallbladder fossa and hepatic flexure of colon.
RESULTS: Debridement of infected granulation tissues which had replaced the gallbladder, closure of the cystic duct stump and colonic fistula followed by excision of the fistula tract led to complete resolution.
CONCLUSIONS: CCCF is a rare complication of perforated gallbladder with spillage of calculi, and a fistulogram is helpful in establishing the diagnosis. This case highlights the importance of retrieving spilled stones following interventions in the gallbladder to prevent the complication.

BACKGROUND: Neuroendocrine tumors of the ampulla of Vater are extremely rare, and few cases of large cell neuroendocrine carcinoma (LCNEC) of the ampulla have been reported.
METHODS: A 48-year-old male with obstructive jaundice was admitted to our hospital. On examination the patient was found to have a periampullary growth and subsequently underwent the Whipple's procedure.
RESULTS: Histopathological examination and immunohistochemistry revealed features of LCNEC of the ampulla of Vater. The patient developed multiple liver metastases 6 months after Whipple's procedure.
CONCLUSION: LCNEC of the ampulla of Vater is rare and highly aggressive, with a dismal prognosis.

BACKGROUND: There is no report on case of severe acute hyperlipidemic pancreatitis after treatment of Sheehan's syndrome.
METHODS: A 32-year-old female patient was diagnosed as having acute hyperlipidemic pancreatitis after treatment of Sheehan's syndrome, and treated with diet and lipid-lowering agents in early stage.
RESULTS: Abdominal pain and fever of the patient resolved within a few days. She was subjected to diet and oral lipid-lowering therapy on the 4th day after admission. The disease did not recur during the follow-up for more than one year.
CONCLUSIONS: Estrogen replacement therapy should be prescribed for Sheehan's syndrome. The serum level of triglyceride should be monitored and treatment should be given to prevent severe acute pancreatitis. Lipid-lowering therapy in early stage is the key step towards a complete recovery.

BACKGROUND: We reported a case of malignant nonfunction islet cell tumor (10.0 cm in diameter) of the pancreas, with malignant histological features and splenic infiltration. The case is rare, and few reports have been published.
METHODS: A 46-year-old woman with a vague pain in the left upper quadrant for 3 months was found to have a tumor in the spleen. Ultrasonography and computed tomography demonstrated a well-defined pancreatic tumor of 8.2×10.0 cm in size, her serum levels of pancreatic hormones were within normal limits.
RESULTS: Splenectomy combined with pancreatectomy was performed for the tail of the pancreas. Resected specimens showed a malignant nonfunctioning islet cell tumor invading the spleen.
CONCLUSIONS: The growth pattern of the tumor causes malignant features. Resection of the tumor should be performed by enucleation, pancreaticoduodenectomy or distal pancreatectomy.