BACKGROUND: Reports on the relationship between pancreaticobiliary maljunction (PBM) and gallbladder carcinoma (GBC) are conflicting. The frequency of PBM in GBC patients and the clinical features of GBC patients with PBM vary in different studies.
DATA SOURCES: English-language articles describing the association between PBM and GBC were searched in the PubMed and Web of Science databases. Nine case-control studies fulfilled the inclusion criteria and addressed the relevant clinical questions of this analysis. Data were extracted independently by two reviewers using a predefined spreadsheet.
RESULTS: The incidence of PBM was higher in GBC patients than in controls (10.60% vs 1.76%, OR: 7.41, 95% CI: 5.03 to 10.87, P<0.00001). The proportion of female patients with PBM was 1.96-fold higher than in GBC patients without PBM (80.5% vs 62.9%, OR: 1.96, 95% CI: 1.09 to 3.52, P=0.12). GBC patients with PBM were 10 years younger than those without PBM (SMD: -9.90, 95% CI: -11.70 to -8.10, P<0.00001). And a difference in the incidence of associated gallstone was found between GBC patients with and without PBM (10.8% vs 54.3%, OR: 0.09, 95% CI: 0.05 to 0.17, P<0.00001). Among the GBC patients with PBM, associated congenital dilatation of the common bile duct was present with a higher incidence ranging from 52.2% to 85.7%, and 70.0%-85.7% of them belonged to the P-C type of PBM (the main pancreatic duct enters the common bile duct). No substantial heterogeneity was found and no evidence of publication bias was observed.
CONCLUSIONS: PBM is a high-risk factor for developing GBC, especially the P-C type of PBM without congenital dilatation of the common bile duct. To prevent GBC, laparoscopic cholecystectomy is highly recommended for PBM patients without congenital dilatation of the common bile duct, especially relatively young female patients without gallstones.

BACKGROUND: In adult-to-adult living donor liver transplantation (LDLT), the use of a right lobe graft without the middle hepatic vein (MHV) can cause hepatic congestion and disturbance of venous drainage. To solve this problem, we successfully used cadaveric venous allografts preserved in 4 ℃ University of Wisconsin (UW) solution within 10 days as interposition veins for drainage of the paramedian portion of the right lobe in adult LDLT.
METHODS: From June 2007 to January 2008, 11 adult LDLT patients received modified right liver grafts. The major MHV tributaries (greater than 5 mm in diameter) of 9 cases were preserved and reconstructed using cadaveric interposition vein allografts that had been stored for 1 to 10 days in 4 ℃ UW solution. The regeneration of the paramedian sector of the grafts and the patency of the interposition vein allografts were examined by Doppler ultrasonography after the operation.
RESULTS: MHV tributaries were reconstructed in 9 recipients. Only 1 recipient died of renal failure and severe pulmonary infection on day 9 after transplantation without any hemiliver venous outflow obstruction. The other 8 recipients achieved long-term survival with a median follow-up of 30 months. The cumulative patency rates of the 8 recipients were 63.63% (7/11), 45.45% (5/11), 45.45% (5/11) and 36.36% (4/11) at 3, 6, 12 and 24 months, respectively. Regeneration of the paramedian sectors was equivalent.
CONCLUSION: The cadaveric venous allograft preserved in 4 ℃ UW solution within 10 days serves as a useful alternative for interposition veins in facilitating implantation of a right lobe graft and guarantees outflow of the MHV.

BACKGROUND: Initial poor graft function (IPGF) following orthotopic liver transplantation is a major determinant of postoperative survival and morbidity. Lactate clearance is a good marker of liver function. In this study, we investigated the clinical utility of early lactate clearance as an early and accurate predictor for IPGF following liver transplantation.
METHODS: This was a prospective observational study of 222 patients referred to the surgical intensive care unit (SICU) after orthotopic liver transplantation. The IPGF group consisted of patients with alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >1500 IU/L within 72 hours after orthotopic liver transplantation. Early lactate clearance was defined as lactate at SICU presentation (hour 0) minus lactate at hour 6, divided by lactate at SICU presentation. The model for end-stage liver disease (MELD) score, Child-Pugh score and laboratory data including AST, ALT, total bilirubin (TB) and prothrombin time (PT) were recorded at SICU presentation and compared between the non-IPGF and IPGF groups. Receiver operating characteristic (ROC) curves were plotted to measure the performance of early lactate clearance, MELD score, Child-Pugh score, TB and PT.
RESULTS: IPGF occurred in 45 of the 222 patients (20.3%). The early lactate clearance in the non-IPGF group was markedly higher than that in the IPGF group (43.2±13.8% vs 13.4±13.7% P<0.001). The optimum cut-off value for early lactate clearance predicting IPGF was 24.8% (sensitivity 95.5%, specificity 88.9%). The area under the curve of the ROC was 0.961, which was significantly superior to MELD score, Child-Pugh score, TB and PT. Patients with early lactate clearance ≤24.8% had a higher IPGF rate (OR=169) and a higher risk of in-hospital mortality (OR=3.625).
CONCLUSIONS: Early lactate clearance can serve as a prompt and accurate bedside predictor of IPGF. Patients with early lactate clearance less than 24.8% are associated with a higher incidence of IPGF.

BACKGROUND: The genetic diversity of chemokines and chemokine receptors has been associated with the outcome of hepatitis B virus infection. The aim of this study was to evaluate whether the copy number variation in the CCL3L1 gene and the polymorphisms of CCR5Δ32 and CCR5-2459A→G (rs1799987) are associated with recurrent hepatitis B in liver transplantation for hepatitis B virus infection-related end- stage liver disease.
METHODS: A total of 185 transplant recipients were enrolled in this study. The genomic DNA was extracted from whole blood, the copy number of the CCL3L1 gene was determined by a quantitative real-time PCR based assay, CCR5Δ32 was detected by a sizing PCR method, and a single-nucleotide polymorphism in CCR5-2459 was detected by restriction fragment length polymorphism PCR.
RESULTS: No CCR5Δ32 mutation was detected in any of the individuals from China. Neither copy number variation nor polymorphism in CCR5-2459 was associated with post-transplant re-infection with hepatitis B virus. However, patients with fewer copies (<4) of the CCL3L1 gene compared with the population median in combination with the CCR5G allele had a significantly higher risk for recurrent hepatitis B (odds ratio=1.93, 95% CI: 1.00-3.69; P=0.047).
CONCLUSION: Patients possessing the compound decreased functional genotype of both CCL3L1 and CCR5 genes might be more likely to have recurrence of hepatitis B after transplantation.

BACKGROUND: Harmine has antitumor and antinociceptive effects, and inhibits human DNA topoisomerase. However, no detailed data are available on the mechanisms of action of harmine in hepatocellular carcinoma. This study aimed to investigate the effects of harmine on proliferation and apoptosis, and the underlying mechanisms in the human hepatocellular carcinoma cell line HepG2.
METHODS: The proliferation of HepG2 cells was determined by the cell counting kit-8 (CCK-8) assay and the clone formation test. The morphology of HepG2 cells was examined using fluorescence microscopy after Hoechst 33258 staining. Annexin V/propidium iodide (PI) was used to analyze apoptosis and PI to analyze the cell cycle. Western blotting was used to assess expression of the apoptosis-regulated genes Bcl-2, Bax, Bcl-xl, Mcl-1, caspase-3, and caspase-9. Mitochondrial transmembrane potential (Ψm) was determined using JC-1.
RESULTS: Harmine inhibited the proliferation of HepG2 cells in a dose-dependent manner. Hoechst 33258 staining revealed nuclear fragmentation and chromosomal condensation, cell shrinkage, and attachment loss in HepG2 cells treated with harmine. The percentage of the sub/G1 fraction was increased in a concentration-dependent manner, indicating apoptotic cell death. PI staining showed that harmine changed the cell cycle distribution, by decreasing the proportion of cells in G0/G1 and increasing the proportion in S and G2/M. Harmine induced apoptosis in a concentration-dependent manner, with rates of 20.0%, 32.7% and 64.9%, respectively. JC-1 revealed a decrease in Ψm. Apoptosis of HepG2 cells was associated with caspase-3 and caspase-9 activation, down-regulation of Bcl-2, Mcl-1, and Bcl-xl, and no change in Bax.
CONCLUSIONS: Harmine had an anti-proliferative effect in HepG2 cells by inducing apoptosis. Mitochondrial signal pathways were involved in the apoptosis. The cancer-specific selectivity shown in this study suggested that harmine is a promising novel drug for human hepatocellular carcinoma.

BACKGROUND: YKL-40 is a new biomarker with diagnostic value in many different cancers. Whether it may serve as a biomarker for hepatocellular carcinoma (HCC) is still unclear. This study aimed to examine the expression of YKL-40 in the serum and liver tissues of HCC patients and in HCC cell lines, in comparison with that in non-HCC liver disease patients and non-tumor hepatic cell lines, respectively.
METHODS: Immunohistochemical staining was used to detect YKL-40 protein expression in liver biopsy specimens from 8 HCC patients. ELISA was used to assess the serum YKL-40 level in 90 HCC patients, 90 inactive HBsAg carrier (IHC) patients with normal liver functions, and 90 liver cirrhosis patients. Real-time PCR was used to determine the YKL-40 mRNA expression in three HCC cell lines and two non-tumor hepatic cell lines.
RESULTS: Immunohistochemical staining of liver biopsy specimens from HCC patients showed that the YKL-40 protein expression in tumor tissue was higher than that in adjacent normal tissues. ELISA revealed that the YKL-40 serum level in the HCC group was significantly higher than that in the IHC group, but not significantly different from that in the cirrhosis group. Real-time PCR showed that YKL-40 mRNA levels in HCC cell lines were significantly higher than those in non-tumor hepatic cells.
CONCLUSIONS: YKL-40 is highly expressed in HCC at the molecular, cellular and tissue levels. However, it may not serve as a serum biomarker for HCC because measurement of the serum YKL-40 level cannot distinguish HCC from cirrhosis.

Retraction in Hepatobiliary Pancreat Dis Int. 2012 Apr;11(2):202.    
BACKGROUND: A reliable model of fulminant liver failure (FLF) is urgently required in this research field. This study aimed to develop a murine FLF model.
METHODS: We used three groups of male C57BL/6 mice: control, with azoxymethane treatment (AOM group), and with galactosamine and tumor necrosis factor-alpha treatment (Gal+TNF-α group). The effects of body temperature (BT) control on survival in all three groups were investigated. Using BT control, we compared the survival, histopathological findings and biochemical/coagulation profiles between the two experimental groups. The effects of hydration on international normalized ratios of prothrombin time (PT-INRs) were also checked. Dose-dependent survival curves were constructed for both experimental groups. Neurological behavior was assessed using a coma scale.
RESULTS: No unexpected BT effects were seen in the control group. The AOM group, but not the Gal+TNF-α group, showed a significant difference in survival curves between those with and without BT care. Histopathological assessment showed consistent FLF findings in both experimental groups with BT care. There were significant differences between the experimental groups in aspartate aminotransferase levels and PT-INRs, and significant differences in PT-INRs between the sufficiently and insufficiently hydrated groups. There were significant differences between FLF models in the duration of each coma stage, with significant differences in stages 1 and 3 as percentages of the disease state (stages 1-4). The two FLF models with BT care showed different survival curves in the dose-dependent survival study.
CONCLUSIONS: AOM provides a good FLF model, but requires a specialized environment and careful BT control. Other FLF models may also be useful, depending on the research purpose. Thoughtful attention to caregiving and close observation are indispensable for successful FLF models.

BACKGROUND: Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) is an uncommon subtype of primary hepatic carcinoma, and its prognosis is poor. This study was undertaken to investigate the prognosis and the clinicopathological characteristics of cHCC-CC, including their possible cellular origin.
METHODS: Among 852 patients with a primary hepatic carcinoma who underwent hepatectomy from January 1998 to April 2008 at our hospital, cHCC-CC was identified in 14 patients. The clinicopathological characteristics of the 14 patients were analyzed retrospectively. The expression of the liver stem cell markers (c-kit, CD90, CD133 and CK19) in the tumor tissue was detected by immunohistochemistry, and the Kaplan-Meier method was used to evaluate survival.
RESULTS: Among the 14 patients, 9 presented with abdominal pain, 3 with anorexia and debilitation, and the remaining two patients were asymptomatic. The mean age was 53.6±3.0 (range 38-74) years. Among the included patients, 11 had an elevated serum alpha-fetoprotein level, 13 were infected with hepatitis B virus, 9 had vascular invasion and 1 had lymph node metastasis. The average diameter of the tumors was 9.9±1.1 (range 5.0-16.0) cm. The median overall survival time was 7.9±1.0 months. In addition, the presence of the liver stem cell markers, c-kit, CD90, CD133 and CK19 was 71.4%, 85.7%, 92.9% and 78.6%, respectively. All four markers were simultaneously expressed in eight cases.
CONCLUSIONS: cHCC-CC has aggressive characteristics and the prognosis is extremely dismal. The high expression of liver stem cell markers in the tumor tissue suggests that these tumors may derive from liver stem cells.

BACKGROUND: Why 3.3% to 10% of all patients with hepatolithiasis develop intrahepatic cholangiocarcinoma (ICC) remains unknown. We carried out a hospital-based case-control study to identify risk factors for the development of ICC in patients with hepatolithiasis in China.
METHODS: Eighty-seven patients with pathologically diagnosed hepatolithiasis associated with ICC and 228 with hepatolithiasis alone matched by sex, age (±2 years), hospital admittance and place of residence were interviewed during the period of 2000-2008. Odds ratios (OR) and 95% confidence intervals (CI) were calculated for each risk factor.
RESULTS: Among the patients with hepatolithiasis associated with ICC, the mean age was 57.7 years and 61.0% were female. Univariate analysis showed that the significant risk factors for ICC development in hepatolithiasis were smoking, family history of cancer, appendectomy during childhood (under age 20), and duration of symptoms >10 years. In multivariate stepwise logistic regression analysis, smoking (OR=1.931, 95% CI: 1.000-3.731), family history of cancer (OR=5.175, 95% CI: 1.216-22.022), and duration of symptoms >10 years (OR=2.348, 95% CI: 1.394-3.952) were independent factors.
CONCLUSION: Smoking, family history of cancer and duration of symptoms >10 years may be risk factors for ICC in patients with hepatolithiasis.

BACKGROUND: Severe acute pancreatitis (SAP) is characterized by fatal pathogenic conditions and a high mortality. It is important to study SAP complicated with multiple organ injury. In this study we compared the protective effects of three traditional Chinese medicines (Ligustrazine, Kakonein and Panax Notoginsenoside) on the small intestine and immune organs (thymus, spleen and lymph nodes) of rats with SAP and explored their mechanism of action.
METHODS: One hundred forty-four rats with SAP were randomly divided into model control, Ligustrazine-treated, Kakonein-treated, and Panax Notoginsenoside-treated groups (n=36 per group). Another 36 normal rats comprised the sham-operated group. According to the different time points after operation, the experimental rats in each group were subdivided into 3-, 6- and 12-hour subgroups (n=12). At various time points after operation, the mortality rate of rats and pathological changes in the small intestine and immune organs were recorded and the serum amylase levels were measured.
RESULTS: Compared to the model control groups, the mortality rates in all treated groups declined and the pathological changes in the small intestine and immune tissues were relieved to different degrees. The serum amylase levels in the three treated groups were significantly lower than those in the model control group at 12 hours. The pathological severity scores for the small intestinal mucosa, thymus and spleen (at 3 and 12 hours) in the Ligustrazine-treated group, for the thymus (at 3 and 12 hours) and spleen (at 3 and 6 hours) in the Kakonein-treated group, and for the thymus (at 3 hours) and spleen (at 3 hours) in the Panax Notoginsenoside-treated group were significantly lower than those in the model control group. The pathological severity scores of the small intestinal mucosa (at 6 and 12 hours) and thymus (at 6 hours) in the Ligustrazine-treated group were significantly lower than those in the Kakonein- and Panax Notoginsenoside-treated groups.
CONCLUSIONS: All the three traditional Chinese drugs significantly alleviated the pathological changes in the small intestine and immune organs of SAP rats. Ligustrazine was the most effective one among them.

BACKGROUND: Pancreaticoduodenectomy is the treatment of choice for periampullary and pancreatic head tumors. In case of hepatic artery abnormalities, early pancreatic transection during pancreaticoduodenectomy may prove inappropriate. Early retroportal lamina dissection improves exposure of the superior mesenteric vessels and anatomic variants of the hepatic artery, where safeguarding is mandatory.
METHOD: We describe our early retroportal lamina approach in patients with anatomic variants of the hepatic artery before pancreatic transection.
RESULTS: This approach was used during 42 pancreaticoduodenectomies with a hepatic artery anatomic variant which was spared in 40 patients. Arterial reconstruction was performed in 2 patients. Five patients with a hepatic artery variant and adenocarcinoma involving the portomesenteric junction required venous resection and reconstruction.
CONCLUSIONS: Early retroportal lamina dissection during pancreaticoduodenectomy in patients with hepatic artery anatomic variants enables easier exposure, avoiding injuries that might compromise the liver arterial supply. When the portomesenteric vein is involved, this approach facilitates en bloc "no touch" venous resection and reconstruction.

BACKGROUND: Hemoperitoneum is associated with several emergency conditions and is especially evident when it occurs in patients with liver cirrhosis. This study aimed to assess the clinical characteristics of cirrhotic patients who did not have abdominal trauma or tumor but who developed hemoperitoneum.
METHODS: We reviewed the clinical records of 1276 consecutive cirrhotic patients with hemoperitoneum at our center between January 2007 and December 2009. Hemoperitoneum was confirmed by abdominal paracentesis.
RESULTS: Of the 1276 cirrhotic patients, 19 were found to have hemoperitoneum, but only 6 did not have abdominal trauma or tumor. The occurrence of spontaneous hemoperitoneum in the cirrhotic patients was therefore 0.5%. Hemoperitoneum can occur spontaneously in severely decompensated cirrhotic patients with intra-abdominal collateral vessels and high scores on the model for end-stage liver disease and Child-Pugh-Turcotte test. Most patients presented with abdominal distension, abdominal pain, increased abdominal girth and hemodynamic instability with a significant drop in the hemoglobin level. Three patients died of hemorrhagic shock within 24 hours, and the other 3 died of hepatic encephalopathy or spontaneous bacterial peritonitis after 5 to 10 days because of further decompensation of the liver.
CONCLUSIONS: Hemoperitoneum can occur in cirrhotic patients who do not have abdominal trauma or tumor. It mainly occurs in severely decompensated end-stage cirrhotic patients. Cirrhotic patients with hemoperitoneum have a poor prognosis.

BACKGROUND: Survival of the partial graft after living donor liver transplantation owes much to its tremendous regenerative ability. With excellent venous outflow capacity, a graft within a wide range of graft-to-standard-liver-volume ratios can cope with portal hypertension that is common in liver transplant recipients. However, when the ratio range is exceeded, modulation of graft vascular inflow becomes necessary for graft survival. The interplay between graft-to-standard-liver-volume ratio and portal pressure, in the presence of portosystemic shunt or otherwise, requires individualized modulation of graft portal and arterial inflows. Boosting of portal inflow by shunt ligation can be guided by transonic flowmetry, whereas muting of portal inflow by splenic artery ligation can be monitored by portal electronic manometry.
METHOD: We describe four cases to illustrate the above.
RESULTS: One patient had hepatic artery thrombosis resulting from splenic artery steal syndrome which was the sequela of small-for-size syndrome. Emergency splenic artery ligation and re-anastomosis of the hepatic artery successfully muted the portal inflow and boosted the hepatic arterial inflow. Another patient with portal vein thrombosis underwent thrombendvenectomy. Portal inflow was boosted with ligation of portosystemic shunt, which is often present in these patients with portal hypertension. The coexistence of splenic aneurysm and splenorenal shunt required ligation of both in the third patient. The fourth patient, with portal pressure and flow monitoring, avoided ligation of a coronary vein which became a main portal inflow after portal thrombendvenectomy.
CONCLUSION: Management of graft inflow modulation guided selectively by transonic flowmetry or portal manometry was described.

BACKGROUND: Undifferentiated embryonal sarcoma (UES) of the liver is a rare, highly malignant neoplasm with a poor prognosis occurring almost exclusively in late childhood (6-10 years of age). Only a few cases have been reported in adults, accounting for less than 1% of all primary liver neoplasms.
METHODS: A 47-year-old woman presented with a palpable mass in the left upper abdomen. Magnetic resonance imaging revealed a 12×10 cm cystic mass with hemorrhage in the left lateral segment of the liver. The initial impression was a hemorrhagic cystic tumor of the liver. The patient underwent a left lateral sectionectomy of the liver. Histopathology and immunohistochemistry helped make a diagnosis of UES.
RESULTS: The patient recovered uneventfully and received systemic chemotherapy. Radiologic examination for follow-up revealed a metastatic lesion in the lumbar spine (L5). She was subjected to radiotherapy at the lumbar spine. She survived 48 months.
CONCLUSION: Although hepatic cyst as UES of the liver is difficult to diagnose because of its rarity in adults and lack of specific findings, it should be considered in a differential diagnosis.

Recently the Liver Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine announced the successful performance of 1021 liver transplants by October 17, 2011. At a gathering celebrating this event, experts from the USA and China highly appreciated this achievement made by the center headed by Professor Shu-Sen Zheng. The noted guests at the gathering included Sheung Tat Fan from Queen Mary Hospital, University of Hong Kong, Ronald W. Busuttil from the Pfleger Liver Institute at UCLA, USA and others. The center once issued the Hangzhou criteria on the basis of the Milan criteria. Briefly, the Hangzhou criteria include: 1) no macrovascular invasion; 2) either a total tumor diameter <8 cm, or a total tumor diameter >8 cm plus histopathological grade I or II and alpha-fetoprotein level <400 ng/mL.