BACKGROUND: Inflammatory mediators are not only initiation factors of acute pancreatitis (AP) but also key factors causing pancreatic hemorrhage and necrosis, which damage important organs such as the heart, brain, liver, kidney and lung. Microcirculatory disturbance in AP has attracted widespread attention. In order to provide a theoretical basis for clinical therapy of AP, it is very important to explore the effect of inflammatory mediators on microcirculatory disturbance in this disease.
DATA SOURCES: In this review, the impact of inflammatory mediators on microcirculatory disturbance in AP was reviewed according to the literature, especially the articles indexed in PubMed and books published in China and reports from websites.
RESULTS: At present, inflammatory mediation and microcirculatory disturbance are the two major hypotheses to explain the development of AP. Although experimental studies have shown that inflammatory mediators induce or aggravate microcirculatory disturbance, the clinical application of these findings is still difficult because the inflammatory mediators are diverse and their research is not comprehensive and thorough.
CONCLUSION: It is very important to explore the influence of inflammatory mediators on microcirculatory disturbance in AP.

BACKGROUND: Liver transplantation currently represents the ultimate therapy for bleeding esophageal varices in patients with liver cirrhosis. It is the only therapy that cures both portal hypertension and the underlying liver disease. The outcome of liver transplantation is thought to be correlated with several factors. In this study, the clinical outcome of living-related liver transplantation (LRLT) was evaluated in patients with variceal bleeding, and the prognostic indicators of short-term survival in these patients were identified. =
METHODS: We reviewed retrospectively 121 patients with a history of variceal bleeding who had received LRLT from 1998 to 2006. The clinical outcomes were analyzed, and the risk factors for short-term survival were defined.
RESULTS: The 3-month survival rate of patients with variceal bleeding was 83.4%, while that of non-bleeders was 87%. Sepsis was the commonest cause of death in both groups. Portal vein diameter and blood transfusion were the only independent prognostic factors for short-term survival among variceal bleeders.
CONCLUSION: The outcome of LRLT in recipients with variceal bleeding is based on the improvement of portal hemodynamics, by minimizing intraoperative blood loss and subsequent blood transfusion.

BACKGROUND: A simultaneously transplanted liver shields a bowel graft from immunologic attack in small animals, while the possible immuno-tolerance induced by the liver in liver and small bowel transplantation (LSBT) is uncertain in large animal models. To investigate the clinically suspected beneficial effect of the liver on small bowel allograft, we developed a new model of composite LSBT in the pig.
METHODS: Seventy outbred long-white pigs were randomized into four groups. LSBT without immuno-suppressive treatment (n=10, group A); LSBT with routine immunosuppressive treatment (n=10, group B); LSBT with a lower dose of immunosuppressive treatment (n=10, group C); and small bowel segment allotransplantation without immunosuppressive treatment (n=10, group D).
RESULTS: There was no remarkable difference in survival time between groups A and D (10.33 vs. 12.89 days, P>0.05), but the initial time of acute rejection of the intestinal graft in group A was clearly delayed when compared to group D (8.22 vs. 4.33 days, P<0.05), and the rejection scores in group A were remarkably lower than those in group D at each postoperative time point (0 vs. 0.44 on day 3, P<0.05; 0.22 vs. 1.78 on day 5, P<0.05; 1.11 vs. 2.56 on day 7, P<0.05). There were evident differences in postoperative survival time, initial time of acute rejection and postoperative rejection scores between groups A, B and C. Postoperative survival time (30.00 vs. 28.13 days, P>0.05), initial acute rejection time (25.40 vs. 22.13 days, P>0.05) or rejection score did not differ between groups B and C within one postoperative month.
CONCLUSIONS: Compared to isolated segment small bowel allotransplantation, the intestinal graft in LSBT (group A) had a delayed initial time of acute rejection and a lower postoperative acute rejection score, and a lower dose of immunosuppressive treatment led to persistent graft immuno-tolerance in LSBT. Thus the simultaneously transplanted liver graft may reduce the risk of intestinal rejection and protect the bowel graft from severe acute rejection.

BACKGROUND: Contrast-enhanced ultrasonography (CEUS) is increasingly accepted in clinical settings for diagnostic imaging of focal liver lesions (FLLs). This study aimed to assess the efficacy of CEUS in the characterization of FLLs in comparison with final diagnosis based on gold standard assessment.
METHODS: The study was approved by the local ethics committee and participating patients provided written informed consent. A total of 148 patients with 164 FLLs were studied. Unenhanced ultrasonography (US) and CEUS were performed using fundamental and harmonic imaging, respectively. Contrast enhancement was assessed during the arterial, portal and late vascular phases after intravenous administration of contrast (SonoVue®, Bracco, Italy). Sensitivity, specificity and diagnostic accuracy of US and CEUS were compared in identifying the lesion as benign, malignant or indeterminate and its actual tumor type. Final diagnosis was established by biopsy (129/164), MR imaging (11/164) or medical history (24/164).
RESULTS: When compared to the gold standard, the number of indeterminate diagnoses was reduced from 56.7% (93/164) as assessed by fundamental imaging to 6.1% (10/164) after SonoVue® enhanced US examination. Sensitivity and specificity improved from 49% and 25% at baseline US to 93% and 75% with CEUS, respectively (P<0.01). Diagnostic accuracy of CEUS was 88% in contrast to 41% of baseline US.
CONCLUSION: SonoVue® enhanced US improves the characterization of FLLs and may limit the need for further investigations.

BACKGROUND: Fatty liver disease (FLD) is increasingly recognized as one of the most common chronic liver diseases in China. This study aimed to investigate the prevalence and risk factors of FLD in Chengdu, Southwest China, and to provide a relevant basis for the prevention and intervention of FLD.
METHODS: Altogether 9094 subjects (4721 men and 4373 women) of over 18 years old who had received a medical checkup in the West China Hospital of Sichuan University between January and December 2007 were evaluated for FLD. FLD was diagnosed by ultrasonography. Body mass index (BMI), height, body weight, blood pressure, fasting plasma glucose (FPG), triglycerides (TG), total cholesterol (TCh), alanine aminotransferase (ALT), hepatitis B surface antigen (HBsAg), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were measured using routine laboratory methods.
RESULTS: The overall prevalence of FLD was 12.5%, which was more than 3-fold higher in males than in females (18.9% vs. 5.7%, χ2=359.624, P<0.001). The prevalence increased with age in females and males of less than 50 years. The prevalence of alcoholic, suspected alcoholic, and non-alcoholic FLD was 2.6%, 3.6%, and 6.3%, respectively. Multiple logistic regression analyses showed that 10 factors (male sex, age, BMI, FPG, hypertension, TG, TCh, HDL-C, LDL-C, and ALT abnormalities) were closely related to FLD. In heavy drinkers, obesity increased the risk of FLD by 23.78-fold (95% CI, 10.22-55.33), but heavy drinking was only associated with a 2-fold (95% CI, 1.50-2.66) increased risk in obese subjects.
CONCLUSIONS: The prevalence of FLD among a health-checkup population in Chengdu, Southwest China was lower than the published for other areas of China. FLD in Chengdu adults was found to be closely associated with sex, age, BMI, and other metabolic syndrome features.

BACKGROUND: There are more than 100 million asymptomatic HBV carriers (ASCs) in China and they are at a high risk of developing liver disease, which creates a serious health problem. But more than 90% of normal adults clear virus from primary HBV infection, so the difference of gene expression between ASCs and normal adults determines the differential outcomes. To identify differentially expressed genes in ASCs compared to normal adults, we used suppression subtractive hybridization to compare gene expression.
METHODS: cDNA subtracted libraries were constructed by suppression subtracted hybridization from peripheral blood monocytes of ASCs and normal adults, the subtracted clones were prescreened by dot blot hybridization, and the levels of genes of interest were confirmed by real-time reverse transcriptase-polymerase chain reaction(RT-PCR).
RESULTS: One hundred and two and 96 positive clones were acquired from the A-N and N-A libraries, respectively, and 14 and 11 clones were identified by dot blot hybridization in the A-N and N-A libraries. Two genes were confirmed as differentially expressed between a set of ASC and normal adult samples by real-time RT-PCR.
CONCLUSIONS: Differentially expressed genes in peripheral blood mononuclear cells between ASCs and normal adults were isolated by suppression subtractive hybridization, and included some new genes. Of the upregulated genes in ASCs, checkpoint suppressor 1 is associated with DNA damage-induced cell cycle arrest. Perforin 1 is associated with inflammation. The information about such alterations in gene expression could be useful for elucidating the mechanisms of ASC pathogenesis.

BACKGROUND: The mechanism of regulation of KAI1, a specific tumor metastasis suppression gene, is controversial. A recent study showed that the synergism of wild-type p53 and JunB has the function of regulating the expression of KAI1, a metastasis inhibiting factor in prostate cancer cells. The wild-type p53 gene is an activator of apoptosis and is closely related to malignant tumor cell multiplication. JunB, a member of the fos/jun family, is a key component of activator protein transcription factor and a major target element in the transmission pathway of mitosis. This study aimed to evaluate the relationship between the expression of KAI1 and p53 combined with JunB in tumor tissues and clinical outcomes in hepatocellular carcinoma (HCC) patients.
METHODS: Quantitative real-time RT-PCR, Western blotting techniques and immunohistochemistry were used to evaluate the expression of KAI1 mRNA, KAI1/CD82, p53 and JunB in HCC patients, and the relationship between their expression and the clinicopathological prognostic parameters was analyzed.
RESULTS: In cancer tissues, the values for positive expression of KAI1 mRNA, KAI1/CD82, p53 and JunB were 31.25%, 26.25%, 48.75%, and 20.00%, respectively, while in adjacent non-tumor tissues, they were 100%, 94.74%, 2.63%, and 76.32%, respectively. There was no correlation between the expression levels of p53 or JunB and KAI1 mRNA or KAI1/CD82. However, there were significant correlations between the expression levels of p53 combined with JunB and not only KAI1 mRNA but also KAI1/CD82 proteins.
CONCLUSIONS: When p53 dysfunction and low expression of JunB are simultaneous, they may play an important role in down-regulating the expression of KAI1 by synergism in HCC. But further studies in vivo and in vitro are needed to verify these results.

BACKGROUND: Based on differences in the virus nucleotide sequence, hepatitis B virus (HBV) genotypes are presently divided into genotypes A-H. The geographic distributions of HBV genotypes differ in countries and regions. To determine the general characteristics of their distributions in the mainland of China, we reviewed articles on HBV genotypes published in China.
METHODS: The Wanfang Database and the CNKI Database were searched for original articles involving HBV in China, and then the data from the articles were classified according to genotype and latitude and analyzed using SPSS 11.0.
RESULTS: The main HBV genotypes were C, B and BC, and their rates were 50.99%, 35.58%, 6.07%, respectively; other genotypes were rare. There was a negative correlation between latitude and the rate of genotype B (r=-0.782, P<0.01), while a positive correlation existed between latitude and the rate of genotype C (r=0.646, P<0.01). No correlation was observed between latitude and the rates of other genotypes (r=0.294, P>0.05).
CONCLUSIONS: In China, HBV genotype C predominates, followed by genotype C and mixed genotype BC; genotypes A, D and others are rare. With an increasing latitude, the distribution of genotype B decreases gradually, while that of genotype C tends to increase. The other genotypes do not show any changes.

BACKGROUND: The mda-7/IL-24 receptor belongs to the type Ⅱ cytokine receptor family, and its two heterodimeric receptors are IL-22R1/IL-20R2 and IL-20R1/IL-20R2. Mda-7/IL-24 receptor expression in liver cancer cell lines has not yet been described. This information may be helpful for further clinical gene therapy.
METHODS: With normal skin total RNA as template, the cDNA sequences of IL-20R1, IL-20R2 and IL-22R were amplified by RT-PCR. Total RNA was extracted from cultured liver cancer cell lines and a normal liver cell line, then detected by northern blotting, and the expression of mda-7/IL-24 receptors was analyzed.
RESULTS: PLC/PRF/5 and SMMC-7721 expressed IL-20R1; BEL-7402, Hep3B, HepG2, and PLC/PRF/5 expressed IL-20R2; and HepG2 and PLC/PRF/5 expressed IL-22R. Only HepG2 expressed the IL-22R/IL-20R2 receptor complex. PLC/PRF/5 completely expressed both heterodimeric receptors. Huh-7, QGY-7701 and WRL-68 did not express the IL-24 receptor.
CONCLUSION: Complete mda-7/IL-24 receptors are seldom expressed in liver cancer cell lines.

BACKGROUND: Hepatic hypoxia-inducible factor-1 (HIF-1) is activated in the progression of hepatocellular carcinoma (HCC). This study aimed to investigate the dynamic alterations of HIF-1α and its gene expression so as to explore the relationship between HIF-1α expression and hepatocarcinogenesis at the early stage of HCC.
METHODS: A hepatoma model was made with 2-fluorenyl-acetamide (2-FAA) in male Sprague-Dawley rats. Morpho-logical changes of rat hepatocytes were assessed pathologically (HE staining). The dynamic expression of hepatic and circulating HIF-1α was quantitatively analyzed by ELISA. The gene fragments of hepatic HIF-1α mRNA were amplified by RT-PCR and confirmed by sequencing. The cellular distribution of hepatic HIF-1α expression was confirmed by immunohistochemistry.
RESULTS: Histological examination confirmed granule-like degeneration to atypical hyperplasia and HCC development in rat hepatocytes and progressive increases in the levels of hepatic and circulating HIF-1α and its gene expression during the course. The levels of HIF-1α expression in the liver and blood of rats with hepatoma were significantly higher than those in normal rats and those with degeneration. Immunohistochemical analysis confirmed the positive expression and hepatocyte distribution of HIF-1α in the development of rat hepatoma. A positive relationship was found between HIF-1α expression in the liver and blood (P<0.01).
CONCLUSIONS: The above observations support the hypothesis that the overexpression of HIF-1α and its gene are closely associated with the malignant transformation of hepatocytes and play an important role at the stage of hepatocarcinogenesis.

BACKGROUND: Since the widespread adoption of laparoscopic cholecystectomy (LC) in the late 1980s, a rise in common bile duct (CBD) injury has been reported. We analyzed the factors contributing to a record of zero CBD injuries in 10 000 consecutive LCs.
METHODS: The retrospective investigation included 10 000 patients who underwent LC from July 1992 to June 2007. LC was performed by 4 teams of surgeons. The chief main surgeon of each team has had over 10 years of experience in hepatobiliary surgery. Calot s triangle was carefully dissected, and the relationship of the cystic duct to the CBD and common hepatic duct was clearly identified. A clip was applied to the cystic duct at the neck of the gallbladder and the duct was incised with scissors proximal to the clip. The cystic artery was dissected by the same method. Then, the gallbladder was dissected from its liver bed. A drain was routinely left at the gallbladder bed for 1-2 days postoperatively.
RESULTS: No CBD injuries occurred in 10 000 consecutive LCs, and there were 16 duct leaks (0.16%). Among these, there were 10 Luschka duct leaks (0.1%) and 6 cystic duct leaks (0.06%). Four hundred thirty cases were converted to open cholecystectomy (OC), giving a conversion rate of 4.3%. After a mean follow-up of 17.5 months (range 6-24 months), no postoperative death due to LC occurred, and good results were observed in 95% of the patients.
CONCLUSIONS: In our 10 000 LCs with zero CBD injuries, the techniques used and practices at our department have been successful. Surgeon s expertise in biliary surgery, preoperative imaging, precise operative procedures, and conversion from LC to OC when needed are important measures to prevent CBD injuries.

BACKGROUND: Pancreatic cancer is one of the most aggressive malignancies, and has a poor prognosis. Despite efforts made in multiple fields, there has been little success in improving the disease-free survival rate of patients. This study was undertaken to investigate the effectiveness and feasibility of using intra-tumoral injection of ricin-loaded thermosensitive hydrogel for treatment of pancreatic cancer xenografts, attempting to develop a new treatment for human pancreatic cancer.
METHODS: BALB/c-(nu/nu) nude mice were inoculated subcutaneously in the right flank with the human pancreatic cancer cells, SW1990. Fourteen days after inoculation, 32 mice, bearing tumors of volume 1.5-2.0 cm3, were randomly assigned to one of four groups, and given an intra-tumoral injection of: (1) saline; (2) 23% w/w thermosensitive hydrogel alone; (3) ricin, 10 µg/kg; or (4) 10 µg/kg ricin loaded in thermosensitive hydrogel. On day 14 after administration, the tumors were excised to calculate the inhibition rate of tumor growth and perform histopathological examination. Tumor cell apoptosis was detected by flow cytometry, and RT-PCR was performed to evaluate the mRNA expression levels of Bcl2 and Bax.
RESULTS: Intra-tumoral injection of ricin-loaded thermo-sensitive hydrogel resulted in remarkable control of tumor growth. The tumor became necrotic by day 14 after administration. The histological results clearly confirmed that the tumor cells were lysed. The percentage of apoptotic cells detected by flow cytometry was higher in the ricin hydrogel group than in the other groups. Semi-quantitative RT-PCR revealed that the mRNA expression level of Bcl2 was down-regulated whereas Bax was upregulated.
CONCLUSIONS: Intra-tumoral injection of ricin-loaded thermosensitive hydrogel may provide an effective approach for interstitial chemotherapy in pancreatic cancer. Inducing apoptosis by downregulating Bcl2 expression and upregulating Bax expression may be a key molecular mechanism.

BACKGROUND: Hepatic venous outflow stenosis is an uncommon but serious complication after right lobe living donor liver transplantation (LDLT). Failure to recognize and treat this complication early can result in graft failure and even death. The early diagnosis and management of hepatic venous outflow stenosis has become an important issue.
METHOD: We report a case with this complication treated by endovascular stent placement in the early period after right lobe LDLT and review related reports to explore the possible mechanism.
RESULTS: A 44-year-old man with end-stage hepatitis B liver cirrhosis underwent right lobe LDLT. On postoperative day 13, his liver function deteriorated and he developed refractory ascites for maximal diuretic therapy. Hepatic venography showed a stenosis with an element of torsion of the venous drainage proximal to the anastomosis of the right hepatic venous orifice and inferior vena cava. The stenosis was successfully treated by insertion of an expandable metallic stent.
CONCLUSIONS: The result demonstrates that stent placement for stenosis is safe and effective. We suspect that rapid hypertrophy of an asymmetric right lobe graft may result in hepatic venous outflow stenosis caused by twisting or external compression of the hepatic veins.

BACKGROUND: Recurrence of inflammation in the extrahepatic bile duct can lead to bile duct stenosis, obstructive jaundice and cavernous transformation of the portal vein. The latter can develop into extrahepatic portal hypertension (PHT). It is difficult to establish the correct method for treating these conditions.
METHODS: At another hospital, a 51-year-old man developed PHT as a result of endoscopic retrograde cholangiopancreatography and endoscopic nasobiliary drainage to relieve cholelithiasis and obstructive jaundice. We dealt with the biliary tract obstruction through percutaneous transhepatic cholangial drainage (PTCD), followed by selective devascularization and a shunt operation 2 weeks after the disappearance of jaundice. Three months after cholecystojejunostomy, there were no obvious changes around the bile duct.
RESULT: The patient recovered uneventfully and was discharged 14 days after operation.
CONCLUSION: For this patient, surgery in stages was the best choice. The most suitable method to decrease jaundice is PTCD.

BACKGROUND: Upper gastrointestinal (GI) bleeding is a common complication of portal hypertension in cirrhotic patients, and hepatocellular carcinoma (HCC) is the most common tumor in cirrhotic livers. Bleeding from tumor erosion into the GI tract is very rare. A patient with HCC and gastric tumor invasion was described and the previously reported cases were reviewed.
METHOD: A patient with upper GI bleeding was treated in a tertiary hospital.
RESULTS: A cirrhotic patient with a HCC invading the stomach leading to upper GI bleeding was treated by left lateral segmentectomy and sub-total gastrectomy. The bleeding was controlled and a good surgical outcome was achieved.
CONCLUSIONS: HCC with gastric invasion should be differentially diagnosed from upper GI bleeding in cirrhotic patients. Bleeding can be controlled and symptomatic relief marked in selected cases.

BACKGROUND: Choledochal cysts are classified into five types based on the location of the cyst. Mixed types of choledochal cysts are extremely rare. Only five cases of mixed type Ⅰ and Ⅱ choledochal cysts have been reported, of which one was an adult case. We report a mixed type Ⅰ and Ⅱ choledochal cyst in a 25-year-old man.
METHODS: The unusual nature of the choledochal cyst, suspected on magnetic resonance cholangiopancreatography RCP to be type Ⅰ initially, was confirmed by laparotomy to be a mixed type Ⅰ+Ⅱ cyst. Excision of the cyst and hepaticojejunostomy were performed.
RESULT: The operation was uneventful, and the patient recovered well.
CONCLUSIONS: Mixed type choledochal cysts are rare, and may be missed on imaging, unless careful evaluation is done. The operative method may not need to be modified significantly, as in the management of our case.

To the Editor:
    I read the paper by Chen et al^[1] with great interest. The authors performed a retrospective study to evaluate the short-term efficacy of antiviral therapy with entecavir for patients with severe chronic hepatitis B (CHB), and found that the survival at 3 months, the improvement of the model for end-stage liver disease (MELD) score and liver function tests in the entecavir group were not significantly different from those of the control group without antiviral therapy, although entecavir therapy could inhibit hepatitis B virus (HBV) replication rapidly.
      Included in this study were the patients with severe CHB whose serum bilirubin levels were more than ten times the upper limit of normal value (>171 µmol/L). The mean baseline bilirubin levels in the entecavir group and control group were 418.83±174.51 and 316.91±154.43 µmol/L, respectively and MELD scores were 21.76±4.68 and 17.33±6.61, respectively. It seemed that the bilirubin levels and MELD scores in the entecavir group were much higher although the differences were not statistically significant (P=0.50 and 0.13, respectively). Univariate analysis showed that the patients who survived less than 3 months had significantly higher baseline bilirubin levels, prothrombin time and MELD scores. The paper by Tseng et al^[2] also reported the value of these factors to predict early mortality in patients with decompensated HBV cirrhosis. Baseline HBV DNA level wasn't a predictive factor of early mortality in both studies. However, another study found that elevated bilirubin and creatinine levels as well as the presence of detectable HBV DNA (by the bDNA assay) pretreatment were significantly associated with the 6-month mortality in patients with decompensated CHB treated with lamivudine.^[3]
    Several studies have shown that inhibition of viral replication with nucleos(t)ide analogues such as lamivudine could potentially decrease hepatic necroinflammation and result in a significant improvement of liver function in patients with decompensated HBV cirrhosis.^[3-5] However, clinical efficacy was not obvious until 3-6 months later. So, antiviral therapy should be started promptly without the need of emphasis on high HBV DNA or elevated ALT levels.[3] The results of this study didn't show the efficacy of entecavir on the survival at 3 months. We couldn't deny the efficacy of entecavir by this short-term follow-up study and further longer studies are needed to evaluate whether antiviral therapy is efficient to improve the long-term survivals.