DNA N6-methyladenine involvement and regulation of hepatocellular carcinoma development.

DNA N6-methyladenine (6 mA) is a new type of DNA methylation identified in various eukaryotic cells. However, its alteration and genomic distribution features in hepatocellular carcinoma (HCC) remain elusive. In this study, we found that N6AMT1 overexpression increased HCC cell viability, suppressed apoptosis, and enhanced migration and invasion, whereas ALKBH1 overexpression induced the opposite effects. Further, 23,779 gain-of-6 mA regions and 11,240 loss-of-6 mA regions were differentially identified in HCC tissues. The differential gain and loss of 6 mA regions were considerably enriched in intergenic regions. Moreover, 7% of the differential 6 mA modifications were associated with tumors, with 60 associated with oncogenes and 57 with tumor suppressor genes (TSGs), and 17 were common to oncogenes and TSGs. The candidate genes affected by 6 mA were filtered by gene ontology (GO) and RNA-seq. Using quantitative polymerase chain reaction (qPCR), BCL2 and PARTICL were found to be correlated with DNA 6 mA in certain HCC processes.

Exosome-mediated miRNA delivery promotes liver cancer EMT and metastasis.

The deregulation of exosomal microRNAs (miRNAs) plays an important role in the progression of hepatocarcinogenesis. In this study, we highlight exosomes as mediators involved in modulating miRNA profiles in liver cancer cells after induction of the epithelial-mesenchymal transition (EMT) and metastasis. Initially, we induced EMT in a hepatocellular carcinoma cell (HCC) line (Hep3B) by stimulation with transforming growth factor-ß (TGF-ß) and confirmed by western blot detection of EMT markers such as vimentin and E-cadherin. Exosomes were then isolated from the cells and identified by nanoparticle tracking analysis (NTA). The isolated exosomal particles from unstimulated Hep3B cells (Hep3B exo) or TGF-ß-stimulated EMT Hep3B cells (EMT-Hep3B exo) contained higher levels of exosome marker proteins, CD63 and TSG101. After incubation with EMT-Hep3B exo, Hep3B cell proliferation increased. EMT-Hep3B exo promoted the migration and invasion of Hep3B and 7721 cells. High-throughput sequencing of miRNAs and mRNA within the exosomes showed 119 upregulated and 186 downregulated miRNAs and 156 upregulated and 166 downregulated mRNA sequences in the EMT-Hep3B exo compared with the control Hep3B exo. The most differentially expressed miRNAs and target mRNA sequences were validated by RT-qPCR. Based on the known miRNA targets for specific mRNA sequences, we hypothesized that GADD45A was regulated by miR-374a-5p. Inhibition of miR-374a-5p in Hep3B cells resulted in exosomes that inhibited the proliferation, migration, and invasion of HCC cells. These results enhance our understanding of metastatic progression of liver cancer and provide a foundation for the future development of potential biomarkers for diagnosis and prognosis of hepatic cancer.

Stent placement with iodine-125 seeds strand effectively extends the duration of stent patency and survival in patients with unresectable malignant obstructive jaundice.

Background: This study aimed to compare the treatment outcomes and safety between stent placement with or without Iodine-125 (125I) seeds strand for patients with unresectable malignant obstructive jaundice (MOJ).Methods: A total of 84 patients with unresectable MOJ treated in our hospital were retrospectively included and divided into the stent group (n = 54) undergoing biliary stent placement and the stent + seeds group (n = 30) receiving stent placement with 125I seeds strand. The therapeutic outcome, postoperative complications, duration of patient survival and stent patency were compared between groups. Kaplan-Meier survival analysis was performed to compare the duration of patient survival and stent patency between groups. Cox-regression analysis was performed to investigate predictive factors for disease-free survival and overall survival.Results: The stent + seeds group had significantly longer duration of patency (231.57 ± 256.54 vs. 110.37 ± 120.52) and overall survival (310.57 ± 330.54 vs. 173.15 ± 219.40) than the stent group (both p < .05). In addition, Kaplan-Meier survival analysis confirmed that the stent + seeds group had longer duration of patency (log-rank test, p = .001) and higher overall survival rate (log-rank test, p = .020) than the stent group. Furthermore, Cox-regression analysis demonstrated that treatment methods was an independent factor associated with disease-free survival (HR: 0.36, 95% CI: 0.19-0.70; p = .003) and overall survival (HR: 1.01, 95% CI: 1.00-1.01; p < .001).Conclusion: The stent placement with 125I seeds strand can significantly improve the primary patency rate and overall survival time in MOJ patients.

Large mode area microstructured fiber supporting 56 super-OAM modes.

In this paper, a kind of super-mode orbital angular momentum microstructured fiber (SM-OAM-MSF) is proposed. By introducing 20 Ge-doped equiangular cylindrical inclusions in the ring-core region, mode coupling mechanism is employed in the formation of super-OAM (SOAM) modes. Specifically, the double degenerated out-of-phase SMs are first generated by the coupling of individual core mode, then the quadruple degenerated SOAM modes are formed by combining two components of the out-of-phase SMs with a phase difference of ±π/2. Theoretical analysis and numerical results reveal that the effective index difference (Δneff) between adjacent out-of-phase SM groups are strongly influenced by the parameters of the individual core except the ring-core's width. Therefore, large mode area and SOAM modes' index separation larger than 1.0×10-4 can be achieved simultaneously in our proposed SM-OAM-MSF. Through careful fiber design, HE1,1 and HE2,1 are used in the formation of SMs and SOAM modes. Simulations show that all the nine SOAM groups originating from HE1,1 mode and the first five SOAM groups stemming from normal coupling of HE2,1 mode can be supported above 1.0µm, that are 56 SOAM modes in total. The highest purity is 99.86% for SOAM±2,1±,5 mode. And the maximum mode area (Aeff) value reaches up to 638.88µm2 at 1.55µm, which is nearly eight times larger compared to that of conventional ring-core MSFs.

In Vivo Bioluminescence Imaging of Transplanted Mesenchymal Stromal Cells and Their Rejection Mediated by Intrahepatic NK Cells.

PURPOSE: Mesenchymal stromal cells (MSCs) hold promise in the treatment of liver disease. However, short survival time of MSCs after intrahepatic transplantation limits their value; therefore, understanding the basis of MSCs survival and rejection may increase their utility. This study was aimed at determining the role of intrahepatic natural killer (NK) cells on MSCs survival and their retention in the liver shortly after transplant. PROCEDURES: Human MSCs were labeled with the Luc2-mKate2 dual-fusion reporter gene (MSCs-R), and the residence time and survival of MSCs-R xenografts after intrahepatic transplantation were evaluated by in vivo bioluminescence imaging (BLI). Coculture of MSCs and NK cells was performed to assess cytotoxicity. To evaluate the role of NK cells in rejection of the xenografted cells, the fates of transplanted MSCs-R were then assessed in vivo by BLI after activation of intrahepatic NK cells. RESULTS: We observed a linear correlation between luciferase activity from live MSCs-R and cell number in vitro (R 2 = 0.9956). In vivo, we observed a gradual decline in bioluminescent signals from transplanted MSCs-R over a region corresponding to the liver in both the control group and the NK-activated group. However, the survival time and retention of intrahepatic MSCs-R decreased more rapidly in the NK-activated group of mice compared to the control group. This indicated that activated NK cells accelerate the elimination of transplanted MSCs. Also, we found that the number of hepatic NK cells and the expression of NK activation markers significantly increased after intrahepatic delivery of MSCs. This suggested that resident NK cells, in a resting state, were activated by intrahepatic transplantation of human MSCs. Taken together, the data suggests that activated hepatic NK cells mediate, in part, rejection of the MSCs xenografts. Cytotoxicity assays showed that activated NK cells may inhibit the proliferation of MSCs and, to a certain extent, induce MSCs death. CONCLUSION: Human MSCs could be followed dynamically in vivo by BLI, and the role of murine hepatic NK cells, especially activated NK cells, could be inferred from the loss of signals from MSCs. This finding may have practical clinical implications in MSCs transplantation in treating liver disease.

[Diagnosis and treatment of carotid-cavernous fistula: analysis of 28 patients].

OBJECTIVE: To evaluate the feasibility and efficacy of endovascular treatment for different types of carotid cavernous fistula (CCF) via the approach of internal carotid artery (ICA) or inferior petrosal sinus (IPS). METHODS: From April 2005 to June 2010, 28 CCF patients underwent endovascular treatment at our institution. There were 13 males and 15 females with a mean age of 39 years (range: 21 - 71). According to the Barrow's classification, they were classified into type A (n = 21), type B (n = 2) and type D (n = 5). Patients of type A underwent detachable balloon embolization of ipsilateral cavernous sinus or stent-graft placement via the ICA approach. Patients of types B and D received detachable coil plus n-BCA (n-butyl-2-cyanoacrylate) embolization of ipsilateral cavernous sinus via the IPS approach. The technical results, complications and therapeutic outcomes were reviewed. RESULTS: Detachable balloons (number: 1 - 4) were used in 16 patients of type A. Angiography at immediate postembolization showed a complete occlusion of fistula in 15 patients and a small residual fistula (< 20%) in 1 patient. Five patients of type A received stent-graft placement. One stent was placed in 4 patients and 2 stents in 1 patient. Complete fistula closures with preserved ICA were documented on immediate angiogram in 3 patients whereas a large residual flow (> 50%) persisted in 1. The fistula was completely occluded after 3 detachable balloons were deployed in affected cavernous sinus through a gap between stent and vascular wall. Both fistula and ICA were occluded in 1 patient after stenting. No cerebral infarction was observed due to the adequate collateral blood flow from contralateral ICA. Complete closures of affected cavernous sinus were achieved in 6 patients of types B and D while residual flow (< 50%) persisted in 1. The number of detachable coils for each embolization ranged from 3 to 8 (mean: 6.0). The volume of n-BCA mixture varied from 1.0 to 2.1 ml (mean: 1.3). The mean duration of n-BCA injection was 65 s (range: 45 - 90). Clinical symptoms were completely relieved in 26 patients. During the mean follow-up period of 30 months (range: 12 - 60), no recurrence of clinical symptoms was observed. No thrombosis or stenosis was found in the lumina of stents. CONCLUSION: Detachable balloon embolization is the preferential treatment for direct CCF. Detachable coil plus n-BCA embolization of cavernous sinus via the IPS approach is an efficient and safe treatment for indirect CCF.

The inhibitory effect of MSCs expressing TRAIL as a cellular delivery vehicle in combination with cisplatin on hepatocellular carcinoma.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been demonstrated to induce cell apoptosis in many types of tumors, while many hepatocellular carcinoma (HCC) cells display high resistance to TRAIL. Another outstanding limitation of TRAIL is the short half-life in vivo. Stem cell-based therapies provide a promising approach for the treatment of many types of tumors because of the ability of tropism. Therefore, as a new therapeutic strategy, the combination of chemotherapeutic agents and TRAIL gene modified MSCs (TRAIL-MSCs) would improve the therapeutic efficacy of HCC in vivo. This is the first time to show the potential of combination of chemotherapeutic agents and MSCs as a gene vector in the therapy of HCC.

Different methods of detaching adherent cells significantly affect the detection of TRAIL receptors.

AIMS AND BACKGROUND: As a powerful technique allowing analysis of large numbers of cells, fluorescence-activated cell sorting (FACS) is used more and more widely. For FACS analysis, adherent cells are usually detached by trypsinization, followed by centrifugation and resuspension. However, trypsinization can cut off some receptors from the cell surface like fine scissors, which will affect the accuracy of FACS results. Though non-enzymatic methods such as citric saline buffer have been used to determine cell surface receptors, how much of the receptors is cut off by trypsinization has been rarely studied. This work aimed to investigate whether different methods of detaching adherent cells could affect the detection of cell surface receptors. METHODS: Human hepatocellular carcinoma cell lines (HepG2, Huh7 and Hep3B) were detached enzymatically with trypsin-EDTA solution or non-enzymatically with citric saline buffer, and then the receptors of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) were detected by FACS analysis. Cell viability, cell cycle and apoptosis (sub-G1 fraction detected by FACS) of the trypsin-EDTA group and citric saline buffer group were also studied. RESULTS: Different methods of detaching adherent cells could significantly affect the detection of TRAIL receptors. Compared to the conventional trypsin-EDTA group, the non-enzymatic group showed a 3.42-fold increase in the mean fluorescence intensity index of DcR HepG2 and a 1.25-fold increase in DR Huh 7 (P <0.05). However, the viability, cell cycle and apoptosis of these cells were not affected. CONCLUSIONS: Citric saline buffer might be recommended as the first choice to detach adherent cells for FACS analysis of cell surface receptors.

[Labeling of liver cancer cell for fluorescence imaging study by far-red fluorescence protein reporter gene mKate2].

OBJECTIVE: To create far-red fluorescence protein reporter gene mKate2 lentivirus, label human liver cancer cell line HepG2 with lentivirus and explore the feasibility of in vitro fluorescence imaging of labeled tumor cells so as to provide experimental rationales for in vivo fluorescence tumor imaging. METHODS: mKate2 gene was amplified from pmKate2-N plasmid. Then the fragment was inserted into the lentivirus expression vector pLenti6.3/V5-DEST. The expression plasmids pLenti6.3-mKate2 and the packaging plasmids were cotransfected into 293T cells. The biological titer of lentivirus was determined. HepG2 cells were infected with mKate2 lentivirus at a MOI (virus multiplicity of infection) of 6 for 96 hours. The infection efficiency was assayed through fluorescence microscope and fluorescent-activated cell scanning (FACS). And 2 × 10(6) mKate2-HepG2 cells were collected for fluorescence imaging through an optical imaging system. And the optimal imaging parameters were determined. RESULTS: DNA sequencing analysis confirmed that mKate2 gene sequence was correct and there was no mutation or deletion. The biological titer of produced mKate2 lentivirus was 1.6 × 10(6) TU/ml. At 96 hours after mKate2 lentivirus infection, fluorescence microscope showed that mKate2 was expressed in a large percentage of cells. FACS assay showed that the mKate2 positive rate was 93.8% ± 0.4%. Excitation light 530 ± 15 nm and emission light 710 ± 28 nm were the optimal imaging parameters for mKate2-HepG2 cells. CONCLUSION: Lentivirus can mediate efficiently the mKate2 reporter gene labeling of human liver cancer cell line HepG2. The mKate2-labeled HepG2 cells can be detected through in vitro fluorescence imaging. Further tracing studies of in vivo tumor fluorescence imaging are technically feasible.

Cisplatin sensitizes human hepatocellular carcinoma cells, but not hepatocytes and mesenchymal stem cells, to TRAIL within a therapeutic window partially depending on the upregulation of DR5.

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF family of cytokines and has been shown to induce cell apoptosis in many types of tumors, but not in normal cells. This tumor-selective property has made TRAIL a promising approach for the development of cancer therapy. However, hepatocellular carcinoma (HCC) cells display a striking resistance to TRAIL. Although some chemotherapeutic agents can overcome this resistance, safety issues remain a concern because the combination of these agents and TRAIL has been reported to induce toxicity in normal hepatocytes. In this study, we examined whether cisplatin could reverse TRAIL resistance in HCC cells with different p53 status and evaluated the toxicity of combination TRAIL and cisplatin to normal hepatocytes and mesenchymal stem cells (MSCs). We observed that cisplatin could efficiently sensitize HCC cells, but not hepatocytes and MSCs to TRAIL-induced apoptosis within a wide therapeutic window. The apoptosis of HCC cells only partially depended on the upregulation of DR5 and the status of p53. In addition, we provide favorable evidence supporting the feasibility of the combination of chemotherapy and MSCs transduced with TRAIL.

Transvenous embolization of cavernous sinus dural arteriovenous fistulas using detachable coils and Glubran 2 acrylic glue via the inferior petrosal sinus approach.

OBJECTIVES: To describe the technique, efficacy, and safety of transvenous embolisation (TVE) of cavernous sinus arteriovenous fistulas (CSDAVFs) via the inferior petrosal sinus (IPS) with detachable coils and acrylic glue. METHODS: Spontaneous unilateral CSDAVFs were confirmed by cerebral angiography in eight patients, with angiographic patency of the ipsilateral IPS in three and angiographic non-visualisation of the ipsilateral IPS in five. There were two patients with complete occlusion of the ipsilateral internal jugular vein (IJV). TVE with detachable coils and acrylic glue were performed through a femoral vein and an IPS approach. RESULTS: TVE viaipsilateral IPS was successfully performed in all eight patients in our group. The number of detachable coils for each patient ranged from 2 to 8 (mean, 5.0). Angiography immediately after TVE showed complete occlusion of the CSCAVFs in seven patients and nearly complete occlusion in one. Complete recovery of clinical symptoms was achieved in all eight patients. No recurrence of clinical symptoms was observed at follow-up. CONCLUSIONS: Transvenous embolisation via an IPS approach is a highly efficient and safe treatment for CSDAVFs. Embolisation with a combination of coils and acrylic glue may help to achieve complete occlusion of fistulas with fewer coils.

[Enhanced green fluorescence protein reporter gene labeling of mesenchymal stem cells mediated by lentivirus].

OBJECTIVE: To explore the effect of enhanced green fluorescence protein (EGFP) labeling mediated by lentivirus on the biophysical properties of mesenchymal stem cells (MSC), and whether the EGFP gene expression is permanent and stable. METHODS: MSC were infected with EGFP lentivirus at different virus multiplicity of infection (MOI). EGFP positive rate was measured with fluorescent-activated cell scanning (FACS) analysis, and EGFP expression in MSC was investigated under a fluorescence microscope. Cell viability, proliferation, apoptosis and cell cycle were detected with trypan blue stain, MTT colorimetric assay, Hoechst stain and FACS analysis respectively. To evaluate the stability of EGFP expression, EGFP lentivirus infected MSC were harvested after cultured continuously in vitro for 2, 4, 8 or 16 weeks, and EGFP positive rate and fluorescence strength were detected with FACS analysis. RESULTS: After infected with EGFP lentivirus (MOI = 20) for 96 h, EGFP positive rate of MSC was 97.39% +/- 0.68%. Cell viability, proliferation, apoptosis and cell cycle of MSC infected with EGFP lentivirus were unaffected, as compared with control MSC (P > 0.05). When cultured in vitro continuously for 2, 4, 8 or 16 weeks, EGFP positive rates of EGFP-MSC were 97.50% +/- 0.54%, 97.32% +/- 0.51%, 97.39% +/- 0.11%, and 97.48% +/- 0.13% respectively, while EGFP fluorescence strength were 440 +/- 13, 445 +/- 12, 458 +/- 13 and 456 +/- 16 respectively. Both EGFP positive rate and fluorescence strength kept in a stable level. CONCLUSION: EGFP lentivirus can efficiently label MSC and has no significant effect on the biophysical properties of MSC. EGFP gene expression in MSC is permanent and stable. EGFP-MSC can be used for further cell tracing research.

[The role of early hepatic artery ischemia on biliary complications after liver transplantation and hepatic arterial interventional therapy].

OBJECTIVE: To explore the influence of early hepatic artery ischemia on the occurrence and prognosis of biliary complications after orthotopic liver transplantation (OLT), and the value of early hepatic arterial interventional therapy. METHODS: In the 720 recipients who received OLT in our hospital from October 2003 to June 2007, 32 cases were detected hepatic artery stenosis (HAS, 30 cases) or hepatic artery thrombosis (HAT, 2 cases) by color Doppler Ultrasound from 4 to 65 days (mean, 25 +/- 15) after OLT. All of them were confirmed by DSA and/or CT angiography. Of the 32 patients, 20 were treated by hepatic arterial interventional therapy. The end-point of follow-up was the time of patient's death and retransplantation. RESULTS: In this study, 20 cases developed biliary complications, including the common bile duct stenosis in 2 cases, intra- and extra hepatic bile duct stenosis in 13 cases and multiple intrahepatic bile duct stenosis in 5 cases. Among them, 2 patients complicated with bile leakage, 4 with biloma and 3 with liver abscess. Of the 20 patients, 8 with HAS received successful hepatic arterial interventional therapy which was performed two weeks after HAS detected; 10 with HAS didn't receive hepatic arterial interventional therapy; 1 with HAT received successful thrombolysis; 1 with HAS received failed hepatic artery stent implantation. During a median follow-up of 262 days (range, 22 -517 days), 10 patients died, 6 underwent retransplantation, and the other 4 survived; cumulated survival rates at 6, 12 and 24 months were 60.0%, 34.9% and 0, respectively. 12 cases didn't develop biliary complications. Nine of them received successful hepatic arterial interventional therapy within 2 weeks HAS detected, 2 with acute rejection received flushing anti-rejection therapy, 1 with HAT received retransplantation because of unsuccessful thrombolysis. During a median follow-up of 952 days (range, 14 - 1398 days), 3 patients died, 1 underwent retransplantation, and the other 8 survived; cumulated survival rates at 6, 12 and 24 months were 75%, 66.7% and 66.7%, respectively. CONCLUSION: Early hepatic artery ischemia after OLT is an important agent for biliary complications. Early and successful hepatic arterial interventional therapy helped to reduce the incidence of biliary complications and improve the patients' prognosis.

[Multimodality interventional treatments for biliary complications after orthotopic liver transplantation: a preliminary study].

OBJECTIVE: To describe the technique, efficacy, and safety of multimodality interventional treatments for biliary complications after orthotopic liver transplantation (OLT). The core of multimodality interventional treatments is percutaneous transhepatic biliary drainage (PTBD). METHODS: From January 2006 to May 2008, seventy-two patients with biliary complications afte OLT were closed in our study. On the basis of the cholangiographic appearance, patients were classified into 4 groups: anastomotic biliary strictures (n = 19), hilar biliary strictures (n = 16), multifocal/diffuse biliary strictures (n = 31), and anastomotic biliary fistulae (n = 6). All patients were treated in our hospital, including PTBD only in 6 patients, PTBD combined with balloon dilation in 50 patients, balloon dilation and plastic stent implantation in 10 patients, balloon dilation and metallic stent implantation in 6 patients. Their data were analyzed retrospectively, including serum hemobilirubin, cholangiographic appearance and complications. RESULTS: PTBD were successful in all cases. The clinical symptoms improved or eliminated were observed in 66 cases, the effective rate was 91.7% (66/72). Among 72 patients, 26 patients were free of drainage tube, 8 patients underwent second PTBD for the obstruction of biliary stents, and 38 patients maintained drainage tube for long-term. In 66 patients with biliary obstruction, the direct bilirubin was (145 +/- 106) micromol/L before treatments and 76 micromol/L +/- 59 micromol/L one month after PTBD (t = 3.78, P < 0.001). The rate of biliary tract infection was 14.3% and 43.8% respectively with the tip of drainage tube placed in biliary duct and in duodenum. There was a significantly statistical difference between these two items (chi(2) = 4.886, P = 0.027). CONCLUSION: PTBD combined with balloon dilation and biliary stent implantation is a effective therapeutic modality for biliary complications after OLT, which can improve patients' clinical symptoms, elevate patients' quality of life. The tip of drainage tube being placed in biliary duct can decrease the rate of biliary tract infection significantly.

[Transportal variceal sclerotherapy with n-butyl-2-cyanoacrylate for gastric fundal varices].

OBJECTIVE: To evaluate the technique, safety and clinical efficacy of transportal variceal sclerotherapy with n-butyl-2-cyanoacrylate (NBCA) for gastric fundal varices. METHODS: Twenty-one patients with gastric fundal varices confirmed by endoscopy were enrolled in this study. The causes of the gastric varices were cirrhosis caused by hepatitis virus B or C (n = 16) and hepatocellular carcinoma with portal venous obstruction (n = 5). Percutaneous transhepatic or transplenic portography were performed on all 21 patients. The gastric varices were treated with NBCA-lipiodol mixture injected via a microcatheter introduced into the varices. For 8 patients who had large gastrorenal shunts (GRS), a balloon-occluded catheter was introduced into the GRS via the right femoral and left renal veins before injecting the NBCA-lipiodol. During the NBCA-lipiodol injection, the balloon was inflated to block the flow of GRS. Follow-up evaluations included findings of the laboratory liver function tests, upper intestinal endoscopies, and the occurrences of rebleeding. RESULTS: In 20 patients (95.2%), the gastric varices were successfully obliterated with 2-8 ml of NBCA-lipiodol. In one patient with a large GRS, sclerotherapy was not successfully performed because a balloon-occluded catheter was not available during the procedure. In five patients, small amounts of NBCA-lipiodol entered into the distal pulmonary artery branches. Two of them suffered from transient irritable coughs; no patient developed severe pulmonary embolism. Embolization of portal venous branches occurred in two patients, which were not treated specifically. In comparison with the findings before the treatments, the serum alanine aminotransferase levels decreased at both 3 and 6 months after treatments (P less than 0.05); serum albumin levels increased at 6 months (P less than 0.05); the prothrombin times decreased at 6 months (P less than 0.05); but no significant changes were seen in the serum bilirubin levels. Fifteen patients were followed-up endoscopically for 3 months after the treatment. Gastric varices were completely resolved in 10 patients (66.7%) and were markedly smaller in 4 patients (26.6%). Worsening of the esophageal varices occurred in 3 patients (20%). All the patients were followed-up from 1 to 30 months [(16.7+/-8.8) months]. Rebleeding was observed in 4 patients, and the cumulative rebleeding rate at 1 year was 9.52%. CONCLUSION: Transportal variceal sclerotherapy with NBCA is a safe and effective method for treating gastric varices. Microcatheter technique and occlusion of the large gastrorenal shunt with a balloon-occluded catheter are necessary to ensure obliteration of gastric varices and prevent pulmonary embolism.

[Radiofrequency ablation with or without transcather arterial chemoembolization for management of hepatocellular carcinoma].

OBJECTIVE: To evaluate the efficacy and complications of radiofrequency ablation (RFA) with or without transcatheter arterial chemoembolization (TACE) for management of hepatocellular carcinoma (HCC). METHODS: A retrospective analysis was conducted for 62 small HCC cases undergoing RFA with or without TACE, and in each case, the tumors were not more than 3 with a diameter below 5 cm. Nineteen cases were managed with RFA alone (RFA group) while the other 27 underwent RFA combined with TACE (TACE+RFA group). Percutaneous RFA (RITA 1500) procedure was performed under CT guidance 1-3 weeks after TACE in TACE+RFA group. RESULTS: The complete tumor necrosis rate was 77.8% (21/27) in TACE+RFA group, significantly higher than that in RFA group [57.9% (11/19), P<0.01], and the former group had a significantly lower local recurrence rate than the latter [22.2% (6/27) vs 42.1% (8/19), P<0.01]. Postoperative fever, local pain and temporary hepatic function abnormality were the common complications that were relieved after proper interventions, and mortality did not occur in these cases. CONCLUSION: The combination of TACE and RFA significantly increases the complete tumor necrosis rate and decreases the recurrence rate of small HCC. CT-guided percutaneous RFA can be a safe and effective therapy for small HCC.

Role of interventional therapy in hepatic artery stenosis and non-anastomosis bile duct stricture after orthotopic liver transplantation.

AIM: To analyze the clinical manifestations and the effectiveness of therapy in patients with orthotopic liver transplantation (OLT)-associated hepatic artery stenosis (HAS) and non-anastomosis bile duct stricture. METHODS: Nine cases were diagnosed as HAS and non-anastomosis bile duct stricture. Percutaneous transluminal angioplasty (PTA) was performed in four HAS cases, and expectant treatment in other five HAS cases; percutaneous transhepatic bile drainage, balloon dilation, stent placement were performed in all nine cases. RESULTS: Diffuse intra- and extra-bile duct stricture was observed in nine cases, which was associated with bile mud siltation and biliary infection. Obstruction of the bile duct was improved obviously or removed. Life span/follow-up period was 13-30 mo after PTA of four HAS cases, 6-23 mo without PTA of other five cases. CONCLUSION: Progressive, non-anastomosis, and diffuse bile duct stricture are the characteristic manifestations of HAS and non-anastomosis bile duct stricture after OLT. These are often associated with bile mud siltation, biliary infection, and ultimate liver failure. Interventional therapy is significantly beneficial.

[The role of multi-detector row CT in the diagnosis and hemodynamic studies of gastric varices in portal hypertension].

OBJECTIVE: To evaluate the value of multi-detector row CT (MDCT) in the diagnosis and hemodynamic studies of gastric varices (GV) in portal hypertension by comparison with endoscopy and DSA direct portography. METHODS: Thirty-six consecutive cirrhotic patients with GV confirmed by endoscopy underwent tri-phase contrast-enhanced CT scans and CT portography (CTP) within 2 weeks after endoscopy examination. Three independent experienced radiologists, who were blinded to the patients' clinical data, analyzed the CT images, including the size and location of GV as well as afferent and efferent veins of GV, separately. Interobserver agreement among the 3 radiologists with regard to the diagnosis of submucosal and perigastric GV was determined by Kappa (k) values. The findings of endoscopy were used as standards. RESULTS: Sub mucosal GV was diagnosed in 34 of the 36 patients (94.4%) and perigastric GV in all 36 patients (100%) by the observation of the 3 radiologists. MDCT showed an excellent interobserver reliability with regard to the diagnosis of submucosal GV (kappa = 0.85) and perigastric GV (kappa = 1.0). Agreement between MDCT and endoscopy with regard to the opacification of variceal size and location were 86.1% and 88.9% respectively. The sensitivity, specificity, accuracy, and positive predictive value of CTP in the opacification of afferent and efferent veins of GV were all more than 80%. The frequencies of participation of posterior gastric vein and short gastric vein in blood supply to gastric fundal varices in the isolated gastric varices and gastroesophageal varices type 2 (GEV2) were 94.1% and 70.6% respectively, both significantly higher than those in the gastroesophageal varices type 1 (GEV1, 52.6% and 31.6%, respectively, both P < 0.05). The main blood drainage route of GEV1 was via azygous system into the super vena cava (100%), whereas in the gastric fundal varices the main blood drainage route was via the gastrorenal shunts into the inferior vena cava (82.4%). CONCLUSION: MDCT can be used as an important tool for detecting submucosal and perigastric GV, and can clearly reveal the size, location, and hemodynamics of GV.

[Stent placement in treating hepatic artery stenosis after liver transplantation].

OBJECTIVES: To evaluate the feasibility and effectiveness of stent placement in treating hepatic artery stenosis after orthotopic liver transplantation (OLT). METHODS: From November 2003 to September 2005, 14 patients who had hepatic artery stenosis after OLT underwent stent placement in their narrowed hepatic arteries. This included early interventional treatment in 10 patients and delayed interventional treatment in 4 patients. The technical results, clinical outcomes, and the hepatic artery patencies were reviewed. RESULTS: Technical and immediate success was 100%. After a mean follow-up of 146 days (range, 9-345 days), all patients' hepatic arteries were patent, except that hepatic arterious restenosis occurred in 2 patients at 26 and 45 days after the stent placement. Of the 10 patients who received early treatment, 8 survived with normal results of liver function test and 2 patients died of septic multiple-organ failure at 9 and 30 days after the stent procedure. One patient received a retransplantation because of refractory biliary infection. Of the 4 patients who received a delayed interventional treatment, 1 patient survived for 345 days but with abnormal liver functional test results, the other 3 patients died of septic multiple-organ failure resulting from liver abscesses biliary infection. CONCLUSION: Hepatic artery stenosis after OLT can successfully be treated with stent placement and an early interventional treatment is the key for a good clinical outcome.

[Budd-Chiari syndrome with occlusion of hepatic vein: multi-slice spiral CT diagnosis and its clinical significance in the treatment].

OBJECTIVE: To evaluate the multi-slice spiral CT dynamic enhancement features and the diagnostic value of CT angiography in Budd-Chiari syndrome with occlusion of hepatic vein (HVBCS), and to assess the CT clinical significance in the treatment of HVBCS. METHODS: Twenty-one patients with HVBCS confirmed by digital subtraction angiography (DSA) were retrospectively analyzed. All patients received multi-slice spiral dynamic enhancement scans within 2 weeks before DSA. The relevant vein vessels were reconstructed respectively with Maximum Intensity Projection (MIP), Volume Rendering (VR) and Oblique Reformat techniques. The course of disease was less than three months in four patients, more than three months in seventeen patients. RESULTS: In the four patients with the course of disease of less than three months, CT showed global liver enlargement with diffuse hypodensity on plain scans and patchy enhancement in caudate lobe and perihilar areas on post-contrast CT scans, and the enhancement field spread to larger area as the time of scans delayed. In the seventeen patients with the course of disease of more than three months, plain CT scans showed abnormalities of liver morphology and hypodensity either in atrophic areas or in the periphery of the liver. On post-contrast CT scans, the hypodensity areas showed poor and heterogeneous enhancement, and hepatic drainage veins in these areas obstructed, whereas in hepatic veins drainage normal areas hepatic parenchymal showed homogeneous enhancement, their drainage veins had at least one patent hepatic vein or a dilated accessory hepatic vein that can provide adequate collaterals. Hepatic CT enhancement features were closely related to the occlusion location of hepatic vein and collateral drainage veins. In twenty-one patients, a total of 42 hepatic veins were occluded. Among them, 9 left hepatic veins, 12 middle hepatic veins, 16 right hepatic veins, and 6 accessory hepatic veins were occluded. The accuracy rate of hepatic veins occlusion showed on transverse scans and CT angiography were 61.9% and 100% respectively. CONCLUSION: Multi-slice spiral dynamic enhancement scans can accurately reflect the changes of intrahepatic hymodynamics. Transverse scans combined with CT angiography can explicitly show the location of hepatic veins occlusion and collateral circulation in HVBCS, which is of important clinical significance in the treatment of HVBCS.