Comparison of modified percutaneous transhepatic variceal embolization and endoscopic cyanoacrylate injection for gastric variceal rebleeding

AIM:To compare the efficacy of modified percutaneous transhepatic variceal embolization(PTVE)with 2-octyl-cyanoacrylate(2-OCA)and endoscopic variceal obturation(EVO)with an injection of 2-OCA for prophylaxis of gastric variceal rebleeding. METHODS:In this retrospective study,the medical records of liver cirrhosis patients with gastric variceal bleeding who underwent either endoscopic 2-OCA(EVO) or modified PTVE using 2-OCA at Shandong Provincial Hospital from January 2006 to December 2008 were reviewed.Patient demographics,rebleeding rate,survival rate,and complications were compared between the two groups(PTVE and EVO).All results were expressed as mean±SD,or as a percentage.Quantitative variables were compared by two sample Student t tests, and qualitative variables were compared by the Fisher exact test or theχ 2 test(with Yates correction)where appropriate.A P value less than 0.05 was considered significant.Statistical computation was performed using SPSS 13.0 software. RESULTS:A total of 77 patients were included;45 patients who underwent EVO and 32 patients who received PTVE.During the follow-up(19.78±7.70 mo in the EVO group,vs 21.53±8.56 mo in the PTVE group) rebleeding occurred in 17 patients in the EVO group and in 4 patients in the PTVE group(37.78%vs 12.5%, P=0.028).The cumulative rebleeding-free rate was 75%,59%,and 49%in 1,2,and 3 years respectively for EVO,and 93%,84%,and 84%for PTVE(P=0.011). Cox analysis was used to identify independent factors that predicted rebleeding after treatment.Variables including age,gender,cause,Child-Pugh classification, size of gastric varices(GV),location of GV,and treatment methods were analyzed.It was revealed that Child-Pugh classification[risk ratio(RR)2.10,95%CI:1.03-4.28,P=0.040],choice of treatment(RR 0.25, 95%CI:0.08-0.80,P=0.019),and size of GV(RR 2.14, 95%CI:1.07-4.28,P=0.032)were the independent factors for predicting rebleeding.Follow-up computed tomography revealed that cyanoacrylate was retained in the varices and in the feeding veins of PTVE patients. During the follow-up,eight patients in the EVO group and four patients in the PTVE group died.The cumulative survival rates at 1,2,and 3 years were 93%,84%, and 67%respectively in the EVO group,and 97%, 88%,and 74%respectively in the PTVE group.The survival rates were not significantly different between the two groups(P=0.432).Cox analysis showed that the Child-Pugh classification was the most significant prognostic factor of survival(RR 2.77,95%CI:1.12-6.80,P=0.027).The incidence of complications was similar in both groups. CONCLUSION:With extensive and permanent obliteration of gastric varices and its feeding veins,PTVE with 2-OCA is superior to endoscopic 2-OCA injection for preventing gastric variceal rebleeding.

MDCT angiography to evaluate the therapeutic effect of PTVE for esophageal varices

Abstract AIM:To evaluate the role of multi-detector row computed tomography(MDCT) angiography for assessing the therapeutic effects of percutaneous transhepatic variceal embolization(PTVE) for esophageal varices(EVs).METHODS:The subjects of this prospective study were 156 patients who underwent PTVE with cyanoacrylate for EVs.Patients were divided into three groups according to the filling range of cyanoacrylate in EVs and their feeding vessels:(1) group A,complete obliteration,with at least 3 cm of the lower EVs and peri-/EVs,as well as the adventitial plexus of the gastric cardia and fundus filled with cyanoacrylate;(2) group B,partial obliteration of varices surrounding the gastric cardia and fundus,with their feeding vessels being obliterated with cyanoacrylate,but without reaching lower EVs;and(3) group C,trunk obliteration,with the main branch of the left gastric vein being filled with cyanoacrylate,but without reaching varices surrounding the gastric cardia or fundus.We performed chart reviews and a prospective follow-up using MDCT images,angiography,and gastrointestinal endoscopy.RESULTS:The median follow-up period was 34 mo.The rate of eradication of varices for all patients was 56.4%(88/156) and the rate of relapse was 31.3%(41/131).The rates of variceal eradication at 1,3,and 5 years after PTVE were 90.2%,84.1% and 81.7%,respectively,for the complete group;61.2%,49% and 42.9%,respectively,for the partial group;with no varices disappearing in the trunk group.The relapsefree rates at 1,3 and 5 years after PTVE were 91.5%,86.6% and 81.7%,respectively,for the complete group;71.1%,55.6% and 51.1%,respectively,for the partial group;and all EVs recurred in the trunk group.Kaplan-Meier analysis showed P values of 0.000 and 0.000,and odds ratios of 3.824 and 3.603 for the rates of variceal eradication and relapse free rates,respectively.Cyanoacrylate in EVs disappeared with time,but those in the EVs and other feeding vessels remained permanently in the vessels without a decrease with time,which is important for the continued obliteration of the feeding vessels and prevention of EV relapse.CONCLUSION:MDCT provides excellent visualization of cyanoacrylate obliteration in EV and their feeding veins after PTVE.It confirms that PTVE is effective for treating EVs.

Carvedilol may attenuate liver cirrhosis by inhibiting angiogenesis through the VEGF-Src-ERK signaling pathway

AIM: To investigate the effect of carvedilol on angiogenesis and the underlying signaling pathways.METHODS: The effect of carvedilol on angiogenesis was examined using a human umbilical vascular endothelial cell(HUVEC) model. The effect of carvedilol on cell viability was measured by CCK8 assay. Flow cytometry was used to assess the effect of carvedilol on cell cycle progression. Cell migration, transwell migration and tube formation assays were performed to analyze the effect of carvedilol on HUVEC function. Vascular endothelial growth factor(VEGF) induced activation of HUVECs, which were pretreated with different carvedilol concentrations or none. Western blot analysis detected the phosphorylation levels of three cell signaling pathway proteins, VEGFR-2, Src, and extracellular signal-regulated kinase(ERK). The specific Src inhibitor PP2 was used to assess the role of Src in the VEGF-induced angiogenic pathway.RESULTS: Carvedilol inhibited HUVEC proliferation in a dose-dependent manner(IC50 = 38.5 mmol/L). The distribution of cells in the S phase decreased from 43.6% to 37.2%, 35.6% and 17.8% by 1, 5 and 10 μmol/L carvedilol for 24 h, respectively. Carvedilol(10 μmol/L) reduced VEGF-induced HUVEC migration from 67.54 ± 7.83 to 37.11 ± 3.533(P < 0.001). Carvedilol concentrations of 5 μmol/L and 10 μmol/L reduced cell invasion from 196.3% ± 18.76% to 114.0% ± 12.20% and 51.68% ± 8.28%, respectively. VEGFinduced tube formation was also reduced significantly by 5 μmol/L and 10 μmol/L carvedilol from 286.0 ± 36.72 to 135.7 ± 18.13(P < 0.05) and 80.27 ± 11.16(P < 0.01) respectively. We investigated several intracellular protein levels to determine the reason for these reductions. Treatment with 10 μmol/L carvedilol reduced VEGF-induced tyrosine phosphorylation of VEGFR-2 from 175.5% ± 8.54% to 52.67% ± 5.33%(P < 0.01). Additionally, 10 μmol/L carvedilol reduced VEGF-induced ERK 1/2 phosphorylation from 181.9% ± 18.61% to 56.45% ± 7.64%(P < 0.01). The VEGFinduced increase in Src kinase activity was alleviated by carvedilol [decreased from 141.8% ± 15.37% to 53.57 ± 7.18%(P < 0.01) and 47.04% ± 9.74%(P < 0.01) at concentrations of 5 and 10 μmol/L, respectively]. Pretreatment of HUVECs with Src kinase inhibitor almost completely prevented the VEGF-induced ERK upregulation [decreased from 213.2% ± 27.68% to 90.96% ± 17.16%(P < 0.01)].CONCLUSION: Carvedilol has an anti-angiogenic effect on HUVECs. This inhibitory effect is mediated by VEGF-induced Src-ERK signaling pathways.