TIPS improves liver transplantation-free survival in cirrhotic patients with refractory ascites:An updated meta-analysis

AIM: To compare the liver transplantation-free (LTF) survival rates between patients who underwent transjugular intrahepatic portosystemic shunts (TIPS) and those who underwent paracentesis by an updated meta-analysis that pools the effects of both number of deaths and time to death.

Shunting branch of portal vein and stent position predict survival after transjugular intrahepatic portosystemic shunt

AIM: To evaluate the effect of the shunting branch of the portal vein (PV) (left or right) and the initial stent position (optimal or suboptimal) of a transjugular intrahepatic portosystemic shunt (TIPS).

Expression and function of classical protein kinase C isoenzymes in gastric cancer cell line and its drugresistant sublines

AIM: To investigate the expression and function of classicalprotein kinase C (PKC) isoenzymes in inducing MDRphenotype in gastric cancer cells.METHODS: Two cell lines were used in the study: gastriccancer cell SGC7901 and its drug-resistant cell SGC7901/VCRstepwise-selected by vincristine 0.3, 0. 7 and 1.0 mg@ L-1 ,respectively. The expression of classical PKC (cPKC)isoenzymes in SGC7901 cells and SGC7901/VCR cells weredetected using immunofluorescent cytochemistry, laserconfocal scanning microscope and Wsstern blot. The effectsof anti-PKC isoenzymes antibody of adriamycinaccumulation in SGC7901/VCR cells were determined usingflow cytometric analysis.RESULTS: (1) SGC7901 cells exhibited positive staining ofPKC-α. SGC7901/VCR cells exhibited stronger staining ofPKC-α than SGC7901 cells. The higher dosage vincristineselected, the much stronger staining of PKC-α was observedon SGC7901/VCR cells. (2) Both SGC7901 and SGC7901/VCRcells exhibited positive staining of PKC-βⅠ and PKC-βⅡ withno significant difference. ( 3 ) Compared with SGC7901,SGC7901/VCR cells had decreased adriamycin accumulationand retention. Accumulation of adriamycin in SGC7901 was5.21 + 2.56 mg@ L-1, in SGC7901/VCR 0.3 was 0.85 + 0.29 mg@L-1 , in SGC7901/VCR 0.7 was 0.81 + 0.32 og@ L-1 , and inSGC7901NCR 1.0 was 0.80 + 0.33 mg @ L-1; Retention ofadriamycin in SGC 7901 was 2.51 + 1.23 mg@L-1, in SGC7901/VCR 0.3 was 0.47 + 0.14 mg@ L-1 , in SGC7901/VCR 0.7 was 0.44 + 0.15 mg@ L-1, and in SGC 7901/VCR 1.0 was 0.41 + 0.1 1mg @ L-1 . (4) Fluorescence intensity presented adriamycinaccumulation in SGC7901/VCR cells was increased from 1.14+0.36 to 2.71 +0.94 when cells were co-incubated with anti-PKC-αbut not with anti-PKC-βⅠ, PKC-βⅡ and PKCγ antibodies.CONCLUSION: PKC-α, but not PKC-βⅠ, PKC-βⅡ or PKCγ,may play a role in multidrug resistance of gastric cancercells SGC7901/VCR.

Selection of treatment modalities for Budd-Chiari Syndrome in China:A preliminary survey of published literature

AIM: To evaluate the frequency of use of various treatment modalities for Budd-Chiari syndrome (BCS) in China by conducting a preliminary survey of relevant literature.

Selection of a TIPS stent for management of portal hypertension in liver cirrhosis: An evidence-based review

Nowadays,transjugular intrahepatic portosystemic shunt(TIPS)has become a mainstay treatment option for the management of portal hypertension-related complications in liver cirrhosis.Accumulated evidence has shown that its indications are being gradually expanded.Notwithstanding,less attention has been paid for the selection of an appropriate stent during a TIPS procedure.Herein,we attempt to review the current evidence regarding the diameter,type,brand,and position of TIPS stents.Several following recommendations may be considered in the clinical practice:(1)a 10-mm stent may be more effective than an 8-mm stent for the management of portal hypertension,and may be superior to a 12-mm stent for the improvement of survival and shunt patency;(2)covered stents are superior to bare stents for reducing the development of shunt dysfunction;(3)if available,Viatorr stent-grafts may be recommended due to a higher rate of shunt patency;and(4)the placement of a TIPS stent in the left portal vein branch may be more reasonable for decreasingthe development of hepatic encephalopathy.However,given relatively low quality of evidence,prospective well-designed studies should be warranted to further confirm these recommendations.

Hepatic venous pressure gradient measurement before TIPS for acute variceal bleeding

Hepatic venous pressure gradient(HVPG)is an independent predictor of variceal rebleeding in patients with cirrhosis.After pharmacological and/or endoscopic therapy,the use of a transjugular intrahepatic portosystemic shunt(TIPS)may be necessary in HVPG non-responders,but not in responders.Thus,HVPG measurement may be incorporated into the treatment algorithm for acute variceal bleeding,which further identifies the candidates that should undergo early insertion of TIPS or maintain the traditional pharmacological and/or endoscopic therapy.The potential benefits are to reduce the cost and prevent TIPS-related complications.

Nonselective β-blockers may induce development of portal vein thrombosis in cirrhosis

Currently, nonselective β-blockers (NSBBs) are commonly used for the prevention of variceal bleeding in liver cirrhosis. The beneficial effects of NSBBs are primarily attributed to the reduction in cardiac output by blockade of β1 receptors and vasoconstriction of the splanchnic circulation by the blockade of β2 receptors. The prognostic value of occlusive portal vein thrombosis (PVT) in cirrhotic patients has been increasingly recognized. The most important risk factor for the development of PVT in liver cirrhosis is the decreased portal vein inflow velocity. Collectively, we propose that the use of NSBBs potentially increases the development of portal vein thrombosis by reducing portal vein inflow velocity. The hypothesis should be confirmed by prospective cohort studies, in which cirrhotic patients without prior PVT treated with and without NSBBs are enrolled, and the development of PVT during follow-up is compared between the two groups. Additionally, subgroup analyses should be performed according to the dosage of NSBBs and the reduction of portal inflow velocity after use of NSBBs.

EVS vs TIPS shunt for gastric variceal bleeding in patients with cirrhosis:A meta-analysis

AIM: To evaluate the clinical effects of transjugular intrahepatic portosystemic shunt (TIPS) vs endoscopic variceal sclerotherapy (EVS) in the management of gastric variceal (GV) bleeding in terms of variceal rebleeding, hepatic encephalopathy (HE), and survival by meta-analysis.METHODS: Medline, Embase, and CNKI were searched. Studies compared TIPS with EVS in treating GV bleeding were identified and included according to our predefined inclusion criteria. Data were extracted independently by two of our authors. Studies with prospective randomized design were considered to be of high quality. Hazard ratios (HRs) or odd ratios(ORs) were calculated using a fixed-effects model when there was no inter-trial heterogeneity. Oppositely, a random-effects model was employed.RESULTS: Three studies with 220 patients who had at least one episode of GV bleeding were included in the present meta-analysis. The proportions of patients with viral cirrhosis and alcoholic cirrhosis were 39% (range 0%-78%) and 36% (range 12% to 41%), respectively. The pooled incidence of variceal rebleeding in the TIPS group was significantly lower than that in the EVS group (HR = 0.3, 0.35, 95% CI: 0.17-0.71, P = 0.004). However, the risk of the development of any degree of HE was significantly increased in the TIPS group (OR = 15.97, 95% CI: 3.61-70.68). The pooled HR of survival was 1.26(95% CI: 0.76-2.09, P = 0.36). No inter-trial heterogeneity was observed among these analyses. CONCLUSION: The improved effect of TIPS in the prevention of GV rebleeding is associated with an increased risk of HE. There is no survival difference between the TIPS and EVS groups. Further studies are needed to evaluate the survival benefit of TIPS in cirrhotic patients with GV bleeding.

Validation of the six-and-twelve criteria among patients with hepatocellular carcinoma and performance score 1 receiving transarterial chemoembolization

BACKGROUND Transarterial chemoembolization(TACE)is recommended for patients with intermediate hepatocellular carcinoma(HCC)according to treatment guidelines.However,a large number of patients with advanced HCC also receive TACE in clinical practice,especially for those with liver-confined HCC and Eastern Cooperative Oncology Group score(ECOG)1.In view of previous studies,such patients have different prognoses from advanced HCC patients with macrovascular invasion or extrahepatic spread;therefore,patients with ECOG 1 alone might be classified into the intermediate stage and benefit from TACE treatment,but a study particularly focusing on such patients and exploring the effectiveness of TACE therapy is lacking.AIM To investigate treatment outcomes of TACE in HCC patients with ECOG 1 alone and propose a specific prognostic model.METHODS Patients from 24 Chinese tertiary hospitals were selected in this nationwide multicenter observational study from January 2010 to May 2016.Overall survival(OS)was estimated using Kaplan–Meier curves and compared by the log-rank test.Multivariate Cox regression was used to develop the potential prognostic models.The discriminatory ability of the models was compared and validated in various patient subgroups.The individual survival prediction for six-and-twelve(6&12)criteria,defined as the algebraic sum of tumor size(cm)and tumor number,was illustrated by contour plot of 3-year survival probability and nomogram.RESULTS A total of 792 eligible patients were included.During follow-up,median OS reached 18.9 mo[95%confidence interval(CI):16.9-21.0].Three independent multivariate analyses demonstrated that tumor size,tumor number,α-fetoprotein level,albumin–bilirubin grade and total bilirubin were prognostic factors of OS(P<0.05).The previously proposed 6&12 criteria was comparable or even better than currently proposed with the highest predictive ability.In addition,the 6&12 criteria was correlated with OS in various subgroups of patients.The patients were stratified into three strata with score≤6,>6 but≤12,and>12 with different median OS of 39.8 mo(95%CI:23.9-55.7),21.1 mo(95%CI:18.4-23.8)and 9.8 mo(95%CI:8.3-11.3),respectively(P<0.001).CONCLUSION TACE is effective for advanced HCC patients with ECOG 1 alone,and the 6&12 criteria may help with clinical decision-making.

Validation and evaluation of clinical prediction systems for first and repeated transarterial chemoembolization in unresectable hepatocellular carcinoma: A Chinese multicenter retrospective study

BACKGROUND The treatment outcome of transarterial chemoembolization(TACE)in unresectable hepatocellular carcinoma(HCC)varies greatly due to the clinical heterogeneity of the patients.Therefore,several prognostic systems have been proposed for risk stratification and candidate identification for first TACE and repeated TACE(re-TACE).AIM To investigate the correlations between prognostic systems and radiological response,compare the predictive abilities,and integrate them in sequence for outcome prediction.METHODS This nationwide multicenter retrospective cohort consisted of 1107 unresectable HCC patients in 15 Chinese tertiary hospitals from January 2010 to May 2016.The Hepatoma Arterial-embolization Prognostic(HAP)score system and its modified versions(mHAP,mHAP2 and mHAP3),as well as the six-and-twelve criteria were compared in terms of their correlations with radiological response and overall survival(OS)prediction for first TACE.The same analyses were conducted in 912 patients receiving re-TACE to evaluate the ART(assessment for re-treatment with TACE)and ABCR(alpha-fetoprotein,Barcelona Clinic Liver Cancer,Child-Pugh and Response)systems for post re-TACE survival(PRTS).RESULTS All the prognostic systems were correlated with radiological response achieved by first TACE,and the six-and-twelve criteria exhibited the highest correlation(Spearman R=0.39,P=0.026)and consistency(Kappa=0.14,P=0.019),with optimal performance by area under the receiver operating characteristic curve of 0.71[95%confidence interval(CI):0.68-0.74].With regard to the prediction of OS,the mHAP3 system identified patients with a favorable outcome with the highest concordance(C)-index of 0.60(95%CI:0.57-0.62)and the best area under the receiver operating characteristic curve at any time point during follow-up;whereas,PRTS was well-predicted by the ABCR system with a C-index of 0.61(95%CI:0.59-0.63),rather than ART.Finally,combining the mHAP3 and ABCR systems identified candidates suitable for TACE with an improved median PRTS of 36.6 mo,compared with non-candidates with a median PRTS of 20.0 mo(logrank test P<0.001).CONCLUSION Radiological response to TACE is closely associated with tumor burden,but superior prognostic prediction could be achieved with the combination of mHAP3 and ABCR in patients with unresectable liver-confined HCC.

Holistic integrative medicine declaration

Holistic integrative medicine,abbreviated as HIM,has been officially proposed since 2012.Its theoretical system has been continuously improved,and its practical methods have become increasingly diverse,becoming an inevitable choice and path for the medical development in the new era.This article demonstrates ten major propositions for HIM,elaborating on the connotation and extension of HIM from the perspectives of epistemology and methodology,in order to achieve the transformation and adaptive evolution of modernmedicine.