Current status of liver transplantation for adult patients with acute-on-chronic liver failure / 中华外科杂志

Acute-on-chronic liver failure(ACLF) is the most severe form of acute decompensation that develops in patients with chronic liver disease or liver cirrhosis,and is always accompanied by one or more extrahepatic organ failure, and has an extremely poor short-term prognosis. The causes triggering ACLF are complex and diverse,and the clinical stage and the type and the definition of organ failure differ greatly from one another. Therefore, a universally accepted diagnostic criteria for ACLF is not to be defined, and the epidemiological data and patient outcomes on ACLF are not easy to predict and compare among different regions. Accumulating evidence has shown that liver transplantation(LT) plays a significant role in the surgical treatment of patients with ACLF,but its clinical value is still controversial. The specific management and treatment strategy after the admission of patients with ACLF has not yet formed a unified and standardized process or opinions, which includes the monitoring in the ICU,the support and maintenance of organ functions, the selection of the surgical indication and the timing for LT and so on. Moreover, there still exists many controversies concerning, for example, whether patients with ACLF should receive greater priority for organ allocation compared to other potential candidates on the waiting list. Besides, more prospective controlled studies are urgently needed to investigate the role of the artificial liver support system in the bridging therapy to LT. The aim of this article is to review the indication selection of patients with ACLF suitable for LT,the survival outcomes and prognostic factors after LT, the selection of timing, the organ allocation policy and the bridging therapy to LT, which intends to provide new direction for designing the future clinical studies on LT in patients with ACLF.

Sodium aescinate inhibits proliferation of hepatocellular carcinoma through CARMA3/NF-κB signaling pathway / 中国药理学通报

Aim To investigate the expression of CAR-MA3, NF-κB in hepatocellular carcinoma tissues and the underlying mechanism of sodium aescinate in inhib-iting the proliferation of human hepatocellular carcino-ma cells. Methods The expression of CARMA3 and NF-κB in HCC tissues were detected by tissue microar-ray immunohistochemistry. MTT was used to determine the effect of sodium aescinate on the proliferation of HCC cells. Cell apoptosis was detected by flow cytom-etry. The expression of CARMA3, NF-κB protein in HepG2 and Hep3B cells treated with sodium aescinate was detected by Western blot and cell immunofluores-cence. Results Tissue microarray analysis showed that the expression of CARMA3 in HCC was up-regulated compared with the adjacent adjacent liver tissues, and the histopathological differentiation, TNM stage, tumor volume and prognosis were correlated. Sodium aesci-nate in 40 μmol·L-1concentration ( IC50) inhibited the growth of HCC cell lines, promoting its apoptosis, but without toxic effects on normal liver cells. Western blot and cell immunofluorescence detection of sodium aescinate could significantly inhibit the expression of CARMA3 and NF-κB. Conclusion Sodium aescinate can effectively inhibit the proliferation of HCC cells by inhibiting the activation of CARMA3/NF-κB signaling in HCC.

HSP90 and SIRT3 expression in hepatocellular carcinoma and their effect on invasive capability of human hepatocellular carcinoma cells

OBJECTIVE@#To vexplore expression of HSP90, SIRT3 in liver cancer tissue and its effect on liver cancer cell invasion ability.@*METHODS@#Moderate expression of HSP90 in SMMC-7721, HepG2, LO2 and Hep-3B cell lines were screened, which was validated by RT-PCR. Over-expression of HSP90 cell line and lentivirus packaging HSP90-RNAi were established, which was validated by RT-PCR and western blot. The level of epithelial-mesenchymal transition (EMT) related gene was detected by western blot. The percentage of cancer stem cells was assayed by flow cytometry.@*RESULTS@#RT-PCR demonstrated the highest expression of HSP90 mRNA in SMMC-7721 cells, the lowest expression of HSP90 mRNA in Hep3B and LO2 and the moderate expression of HSP90 mRNA in Hep-G2. Therefore, HepG2 was selected as a follow-up experiment cell lines. Compared with the blank control group, expression of HSP90 in HSP overexpression group was increased obviously, and expression of HSP90 in HSP90 shRNA group was significantly decreased, which indicated successful establishment of HSP overexpression and shRNA group. The apoptotic cell in hsp-siRNA group was higher than the blank control group, while the HSP overexpression group showed opposite results. Western blot results showed transfection HSP promoted cells EMT transformation, up-regulated the level of E-cadherin, and down-regulated the level of Vimentin; meanwhile, shRNA group showed opposite results.@*CONCLUSIONS@#Carcinoma HepG2 cell transfected high expression of HSP can promote the transformation of EMT, improve the expression of Vimentin, reduce the expression of E-cadherin, and inhibit apoptosis of cancer stem cells, which improve the invasive ability of cancer of the liver cells. While hsp-siRNA group presents opposite results. In summary, the expression of HSP is closely related to the occurrence, development and invasion of cancer of the liver tissue.

HSP90 and SIRT3 expression in hepatocellular carcinoma and their effect on invasive capability of human hepatocellular carcinoma cells

Objective: To vexplore expression of HSP90, SIRT3 in liver cancer tissue and its effect on liver cancer cell invasion ability. Methods: Moderate expression of HSP90 in SMMC-7721, HepG2, LO2 and Hep-3B cell lines were screened, which was validated by RT-PCR. Over-expression of HSP90 cell line and lentivirus packaging HSP90-RNAi were established, which was validated by RT-PCR and western blot. The level of epithelial-mesenchymal transition (EMT) related gene was detected by western blot. The percentage of cancer stem cells was assayed by flow cytometry. Results: RT-PCR demonstrated the highest expression of HSP90 mRNA in SMMC-7721 cells, the lowest expression of HSP90 mRNA in Hep3B and LO2 and the moderate expression of HSP90 mRNA in Hep-G2. Therefore, HepG2 was selected as a follow-up experiment cell lines. Compared with the blank control group, expression of HSP90 in HSP overexpression group was increased obviously, and expression of HSP90 in HSP90 shRNA group was significantly decreased, which indicated successful establishment of HSP overexpression and shRNA group. The apoptotic cell in hsp-siRNA group was higher than the blank control group, while the HSP overexpression group showed opposite results. Western blot results showed transfection HSP promoted cells EMT transformation, up-regulated the level of E-cadherin, and down-regulated the level of Vimentin; meanwhile, shRNA group showed opposite results. Conclusions: Carcinoma HepG2 cell transfected high expression of HSP can promote the transformation of EMT, improve the expression of Vimentin, reduce the expression of E-cadherin, and inhibit apoptosis of cancer stem cells, which improve the invasive ability of cancer of the liver cells. While hsp-siRNA group presents opposite results. In summary, the expression of HSP is closely related to the occurrence, development and invasion of cancer of the liver tissue.

Endoscopic papillary balloon dilatation vs. endoscopic sphincteropapillotomy for common bile duct stones: a meta analysis / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the safety and efficacy between endoscopic papillary balloon dilatation (EPBD) and endoscopic sphincteropapillotomy ( EST) for common bile duct stones using meta-analysis method.</p><p><b>METHODS</b>Randomizd controlled trials comparing EPBD with EST for common bile duct stones and published from January 1990 to July 2012 were recruited. This meta-analysis was conducted to estimate short-term and long-term complications. Fixed random effect model or random effect model was established to analyze the data.</p><p><b>RESULTS</b>Twelve randomizd controlled trials were included in this analysis. These studies included 1865 patients, 925 of them were treated with EPBD and 940 were treated with EST. The analysis of basic characteristics of these included studies showed that: compared to EST, patients in the EPBD group were younger (OR = -1.16, 95% CI: -1.49 to -0.84, P = 0.00), while in two groups, there were no significant difference (P > 0.05) in gender proportion, average size of stones, number of gallstones, previous cholecystectomy, the number of merged duodenal diverticulum, common bile duct diameter, the total follow-up time. Also, compared to EST, the overall stone clearance in the EPBD group was lower (OR = 0.64, 95% CI: 0.42 to 0.96, P = 0.03), pancreatitis incidence was higher (OR = 2.67, 95% CI: 1.61 to 4.43, P = 0.00), incidence of bleeding (OR = 0.12, 95% CI: 0.04 to 0.34, P = 0.00), acute cholecystitis (OR= 0.39, 95% CI: 0.18 to 0.84, P = 0.02), total long-term complication rate (OR = 0.53, 95% CI: 0.36 to 0.77, P = 0.01), stone recurrence rate more than a year were lower (OR= 0.48, 95% CI: 0.26 to 0.90, P = 0.02). While in two groups, there were no significant difference (P > 0.05) in the stone removal on 1 '' attempt, the total near-term complications and acute cholangitis.</p><p><b>CONCLUSIONS</b>On the basis of lower rates of bleeding, EPBD seems to be preferred strategy over EST for endoscopic remove of common bile duct stones in patients who have coagulopathy. Although stone recurrence rate more than a year of EPBD is lower, but the overall stone clearance rate is lower and the risk of pancreatitis is higher than that of EST.</p>

Family survey and clinical analysis of von Hippel-Lindau syndrome / 中华外科杂志

<p><b>OBJECTIVE</b>To study the clinical characteristics and summary diagnostic and therapeutical experience of von Hippel-Lindau syndrome.</p><p><b>METHODS</b>von Hippel-Lindau syndrome genealogy and clinical characteristics was investigated. Then a dendrogram was drawn and a genetic analysis was performed. Last the diagnostic and therapeutical experience of von Hippel-Lindau syndrome was investigated according to literatures.</p><p><b>RESULTS</b>There are 6 members attacked by the von Hippel-Lindau syndrome of 5 generations which includes 42 members. Three patients underwent operation. Two of the three patients who suffered operation had been removed of right lobe of liver tumor and one cerebellar hemangioblastomas independently. The third patient sustained three operations for removal of three cerebellar hemangioblastomas and left renal clear cell carcinoma. Three patients died of this syndrome.</p><p><b>CONCLUSIONS</b>The characteristic of this kindred is according with that of autosomal dominant inheritance disease. Until now, von Hippel-Lindau syndrome involves in multisystem, the prognosis of this syndrome is not very well. However, patients and their family members may get much benefit from genetic testing, periodic surveillance, early diagnosis and prompt treatment.</p>

Percutaneous radiofrequency ablation versus hepatic resection for small hepatocellular carcinoma: a meta analysis / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the curative effect of percutaneous radiofrequency ablation (RFA) and hepatic resection (RES) for small hepatocarcinoma eligible for Milan criterion using meta analysis method.</p><p><b>METHODS</b>Retrieved clinical trials comparing percutaneous radiofrequency ablation with RES for small hepatocarcinoma published from 1990 to 2010. A meta-analysis was conducted to estimate overall survival and disease free survival. A fixed random effect model or random effect model was established to collect the data.</p><p><b>RESULTS</b>Four randomized controlled trials were included in this analysis. These studies included a total of 539 patients: 252 treated with percutaneous RFA and 287 treated with RES. The differences in overall survival were not statistically significant between RFA and RES (P > 0.05). In the patients treated with RES group, the 2-, 3- and 4-years disease free survival rates were significantly better than that in the patients treated with percutaneous RFA (P < 0.05). The postoperative morbidity rate was significant lower in patients treated with percutaneous RFA (OR: 0.14, 95%CI: 0.09 - 0.22, P = 0.000). But percutaneous RFA had a higher rate of tumor recurrence compared to RES (OR: 2.63, 95%CI: 1.67 - 4.15, P = 0.000).</p><p><b>CONCLUSIONS</b>For small hepatocarcinoma eligible for Milan criterion, percutaneous RFA had a similar overall survival to RES. Percutaneous RFA was the invasive lesser and had a lower postoperative morbidity rate than RES, but RES may had a better prevention of the tumor recurrence than percutaneous RFA. For those patients who don't want to be treated by RES, percutaneous RFA may be a recommendable choice.</p>

The value of hepatic ischemic preconditioning in hepatectomy with a prospective randomized controlled study / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the value of ischemic preconditioning in clinical hepatectomy.</p><p><b>METHODS</b>A total of 48 unselected patients undergoing liver resection were analyzed by randomized controlled trial from December 2004 to June 2006. Forty-eight unselected patients were randomized into two groups: IP group (5 minutes of ischemia followed by 5 minutes of reperfusion) and control group (received Pringle's maneuver no and no IP was given). Postoperative days 1, 3 and 7, the liver function were checked. Perioperative mortality, morbidity and hospitalized days were compared.</p><p><b>RESULTS</b>In IP group, ischemic times were 5 - 80 min, mean 31 min, hospitalized days were 13 - 50 days, mean 20 days. In control group, ischemic times were 10 - 60 min, mean 27 min, hospitalized days were 10 - 33 days, mean 17 days. Forty-seven patients were satisfactory with postoperative recovery, except one patient died of chronic liver dysfunction after 3 months postoperatively. Postoperative days 1, 3 and 7, the ALT, AST, TBIL, ALB levels in two groups were not statistically significant (P > 0.05).</p><p><b>CONCLUSIONS</b>The clinical use of IP through 5 minutes of warm ischemia in this technique of hepatectomy does not protect the liver from hepatic injury induced by the IRI.</p>

Anatomy problems in the radical resection for hilar cholangiocarcinoma / 中华外科杂志

<p><b>OBJECTIVE</b>To analyze the clinical data, surgical strategies and results from the patients with hilar cholangiocarcinoma (HCCA), and to explore the anatomic factors related to the radical resection.</p><p><b>METHODS</b>The data from 52 patients with HCCA who underwent radical resection between January 1984 to December 2008 were investigated retrospectively, which included clinical diagnosis, Bismuth-Corlette classification, pathologic features, surgical procedures and follow-up results.</p><p><b>RESULTS</b>According to the Bismuth-Corlette classification, 5, 12, 6, 16 and 13 patients belonged to type I, II, IIIa, IIIb and IV respectively. There were 24 cases underwent combined hepatic lobectomy. The 1-, 3- and 5-year survival rates were 78.8%, 36.4% and 12.1% respectively. Postoperative complications rate was 30.8% with the 3.8% mortality rate. The frequency of surgical complications was significantly higher in patients with higher level of serum total bilirubin (> 340 micromol/L) than that in patients with a relatively lower one (170 micromol/L) before operation (P < 0.05).</p><p><b>CONCLUSIONS</b>Some anatomical factors should be considered during the radical resection of hilar cholangiocarcinoma, especially evaluation of potential hepatectomy, resection of caudate lobe, hepatic artery resection and/or reconstruction. The prognosis of the patients underwent R(0) radial resection could be significantly improved.</p>

Clinicopathological significance of aberrant methylation of the fragile histidine triad gene in patients with hepatocellular carcinoma / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the aberrant methylation of fragile histidine triad (FHIT) gene and to explore possible relationship between the aberrant methylation of FHIT and clinicopathological features in hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>The hypermethylation of FHIT was detected by the methylation specific PCR (MSP) method in 45 patients with HCC (tumoral and nontumoral tissue), 14 cases of normal livers and 4 HCC cell lines (SK-Hep-1, Hep-G2, Hep-3B and Huh7). The correlation of FHIT methylation and clinicopathological features was analyzed.</p><p><b>RESULTS</b>The frequencies of hypermethylation of FHIT in tumoral and nontumoral tissue, normal liver and cell lines were 71.1%, 64.4%, 14.3% and 75.0%, respectively. A significant relation between hypermethylation of FHIT and poor survival was present (P = 0.0430).</p><p><b>CONCLUSIONS</b>Hypermethylation of FHIT is a frequent and early event in HCC, it might relate to a poor prognosis for patients with HCC.</p>

Ultrastructure study on patients with spontaneous rupture of hepatocellular carcinoma / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the ultrastructure of small artery wall in patients with spontaneous rupture of hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>Transmission electron microscopy was used to study 11 specimens from ruptured HCC and 11 cases with non-ruptured HCC.</p><p><b>RESULTS</b>The phenomenon of activated phagocytosis in macrophage could be found in 3 cases with ruptured HCC and 10 cases with non-ruptured HCC, respectively (P < 0.05). In 9 specimens with ruptured HCC, the evidence of vascular injury characterized as less cell junctions and larger fenestrae in endothelial cells, broken elastic lamina, proliferated and fragmented elastin and damaged structure of collagen was found in small arteries. The phenomenon of electron-dense deposit in the elastic lamina, and signs of more protein synthesis in endothelial cells were also present in these specimens. In the patients with non-ruptured HCC, the evidence of vascular injury can be found only in 2 cases (P < 0.01). Less cell junctions and larger fenestrae could increase the permeability of vascular wall. The electron-dense deposition in elastic lamina may represent the deposition of antigen-antibody complex in elastic membrane which had been found in our previous study. The vascular injury was postulated to be caused by the deposition of antigen-antibody complex in vascular wall which was identified by our previous study. The vascular wall in the patient with ruptured HCC could become stiff and weak due to the proliferated fragment elastin and damaged collagen which would make the blood vessels more prone to splitting and result in hemorrhage and the rupture of HCC.</p><p><b>CONCLUSIONS</b>The vascular injury caused by antigen-antibody complex deposition might related to the spontaneous rupture of HCC.</p>

Hypermethylation of Ras association domain family protein 1A, hypermethylated in cancer 1 and p73 genes in hepatocellular carcinoma / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the status of promoter hypermethylation of Ras association domain family protein 1A (RASSF1A), hypermethylated in cancer 1 (HIC1) and p73 genes in hepatocellular carcinoma (HCC) and to explore the correlation with clinicopathological features.</p><p><b>METHODS</b>Forty cases of HCC and their corresponding non-tumor liver tissues, other 2 cases of healthy donor livers were detected using methylation specific polymorphism chain reaction (MSP) method.</p><p><b>RESULTS</b>The frequency of promoter hypermethylation of RASSF1A showed 90.0% and 72.5% in tumor and corresponding non-tumor tissues respectively, and there was significant difference between them (P < 0.05). The frequency of promoter hypermethylation of HIC1 showed 77.5% and 70.0% in tumor and corresponding non-tumor tissues respectively. The frequency of hypermethylation of HIC1 in non-tumor liver tissues showed significant correlation between younger and older patients. The frequency of promoter hypermethylation of p73 showed 5.0% in tumor tissues. However, none of hypermethylation of the gene was detected in corresponding non-tumor liver tissues. There was none of hypermethylation of the three genes showed in two cases of healthy donor livers.</p><p><b>CONCLUSION</b>Promoter hypermethylation of RASSF1A and HIC1 genes are common event in HCC and play an important role in the pathogenesis and may be used to develop novel diagnostic and therapeutic approaches for HCC in the future.</p>

Mechanism of spontaneous rupture of hepatocellular carcinoma / 中华外科杂志

<p><b>OBJECTIVE</b>To study the mechanism of spontaneous rupture of hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>The specimens of 30 patients with ruptured HCC and 30 patients with non-ruptured HCC were collected. Immunofluorescence, immunohistochemical and flow cytometry techniques were used to detect the phagocytosis of macrophages and the deposition of immune complex (IC) on vascular wall.</p><p><b>RESULTS</b>In this study, the poor function of macrophage phagocytosis was found in patients with ruptured HCC, which could results in the cumulating of IC and deposition on vascular wall. The IC, which composed of hepatitis B virus e1 antigen (HBeAg/1), complement C1q and immunoglobulins, was found deposited in the elastic membrane of arteries. Likely as a result of IC deposition, vascular injury occurs mainly in the small arteries where the deposition of IC was present. As the small arteries were the blood vessels with predominant injury, they would likely to be the ones to split and cause hemorrhage and rupture of HCC during vascular load increase.</p><p><b>CONCLUSIONS</b>We would conclude that the poor function of macrophage phagocytosis, which lead to the IC deposition and vascular injury may be the factors involved in the pathogenesis of ruptured HCC.</p>