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.

Existence and Nonlinear Stability of Stationary Solutions to the Viscous Two-Phase Flow Model in a Half Line

The outflow problem for the viscous two-phase flow model in a half line is investigated in the present paper.The existence and uniqueness of the stationary solution is shown for both supersonic state and sonic state at spatial far field,and the nonlinear time stability of the stationary solution is also established in the weighted Sobolev space with either the exponential time decay rate for supersonic flow or the algebraic time decay rate for sonic flow.

Recent Progress on Outflow/Inflow Problem for Viscous Multi-phase Flow

According to the boundary condition with the zero,negative,or positive velocity,the initial boundary problem for compressible multi-phase flow with the Dirichlet-type boundary condition can be classified into three cases:impermeable problem,inflow problem,or outflow problem.In this paper,we review the recent progress on the existence and nonlinear stability of the stationary solution to the outflow/inflow problems for viscous multi-phase flow.

TIME ASYMPTOTIC BEHAVIOR OF THE BIPOLAR NAVIER-STOKES-POISSON SYSTEM

The bipolar Navier-Stokes-Poisson system （BNSP） has been used to simulate the transport of charged particles （ions and electrons for instance） under the influence of electrostatic force governed by the self-consistent Poisson equation. The optimal L^2 time convergence rate for the global classical solution is obtained for a small initial perturbation of the constant equilibrium state. It is shown that due to the electric field, the difference of the charge densities tend to the equilibrium states at the optimal rate （1 ＋ t）^-3/4 in L^2-norm, while the individual momentum of the charged particles converges at the optimal rate （1 ＋ t）^-1/4 which is slower than the rate （1 ＋ t）^-3/4 for the compressible Navier-Stokes equations （NS）. In addition, a new phenomenon on the charge transport is observed regarding the interplay between the two carriers that almost counteracts the influence of the electric field so that the total density and momentum of the two carriers converges at a faster rate （1 ＋ t）^-3/4＋ε for any small constant ε 〉 0. The above estimates reveal the essential difference between the unipolar and the bipolar Navier-Stokes-Poisson systems.

Influence of lactulose on interventional therapy for HCC patients with hepatocirrhosis and hypersplenism

Objective: To investigate the influence of lactulose on immunity of hepatocellular carcinoma(HCC) patients with hepatocirrhosis and hypersplenism after double-interventional therapies. Methods: A total of 40 HCC patients with hepatocirrhosis and hypersplenism, hospitalized during January 2013 to June 2014, were enrolled and randomized into control group and observation group. Both groups received partial splenic embolization combined with transcatheter arterial chemoembolization. Besides, observation group orally took lactulose 30 m L/d. Four days before interventional therapies and at day 1, 3, 7 and 14 after therapies, fasting venous blood was collected to detect white blood cell count, red blood cell count(RBC), and platelet count(PLT). Four days before therapies and at day 7 and 14 after therapies, the levels of alanine aminotransferase, aspartate transaminase, total bilirubin, malondialdehyde, super-oxide dismutase(SOD), IFN-α, and IL-4 as well as the distribution of T cell subsets in peripheral blood were tested. Complications were observed after interventional therapies. Results: Before interventional therapies the levels of white blood cell count, PLT and RBC in both groups showed no difference, while after interventional therapies the levels of PLT and RBC in both groups showed an increasing tendency(P<0.05). At day 14 after interventional therapies, the level of blood cell as well as that of SOD, IFN-α and IL-4 in serum were significantly higher than that before therapies; meanwhile, the levels of alanine aminotransferase and total bilirubin of observation group after therapies were significantly lower than before and control group(P<0.05), the levels of CD4+/CD8+, SOD and IFN-α were all higher than before and control group(P<0.05). Conclusions: Oral administration of lactulose could adjust the imbalance of oxidation system/antioxidant system in HCC patients with hepatocirrhosis and hypersplenism after interventional therapies, and improve the antitumor immunity and prognosis.

Transarterial chemoembolization with PD-(L)1 inhibitors plus molecular targeted therapies for hepatocellular carcinoma(CHANCE001)

There is considerable potential for integrating transarterial chemoembolization(TACE),programmed death-(ligand)1(PD-[L]1)inhibitors,and molecular targeted treatments(MTT)in hepatocellular carcinoma(HCC).It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations.In this nationwide,retrospective,cohort study,826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT(combination group,n=376)or TACE monotherapy(monotherapy group,n=450)were included from January 2018 to May 2021.The primary endpoint was progression-free survival(PFS)according to modified RECIST.The secondary outcomes included overall survival(OS),objective response rate(ORR),and safety.We performed propensity score matching approaches to reduce bias between two groups.After matching,228 pairs were included with a predominantly advanced disease population.Median PFS in combination group was 9.5 months(95%confidence interval[CI],8.4-11.0)versus 8.0 months(95%CI,6.6-9.5)(adjusted hazard ratio[HR],0.70,P=0.002).OS and ORR were also significantly higher in combination group(median OS,19.2[16.1-27.3]vs.15.7 months[13.0-20.2];adjusted HR,0.63,P=0.001;ORR,60.1%vs.32.0%;P<0.001).Grade 3/4 adverse events were observed at a rate of 15.8%and 7.5%in combination and monotherapy groups,respectively.Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS,OS,and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice,with an acceptable safety profile.

Global Weak Solutions for Compressible Navier-Stokes-Vlasov-Fokker-Planck System

The one-dimensional compressible Navier-Stokes-Vlasov-Fokker-Planck system with density-dependent viscosity and drag force coefficients is investigated in the present paper.The existence,uniqueness,and regularity of global weak solution to the initial value problem for general initial data are established in spatial periodic domain.Moreover,the iong time behavior of the weak solution is analyzed.It is shown that as the time grows,the distri-bution function of the particles converges to the global Maxwellian,and both the fluid velocity and the macroscopic velocity of the particles converge to the same speed.

Long Time Behavior of the Fokker-Planck-Boltzmann Equation

This paper is devoted to the existence and long time behavior of the global classical solution to Fokker-Planck-Boltzmann equation with initial data near the absolute Maxwellian.

Global Weak Solutions for Compressible Navier-Stokes-Vlasov-Fokker-Planck System

The one-dimensional compressible Navier-Stokes-Vlasov-Fokker-Planck system with density-dependent viscosity and drag force coefficients is investigated in the present paper.The existence,uniqueness,and regularity of global weak solution to the initial value problem for general initial data are established in spatial periodic domain.Moreover,the long time behavior of the weak solution is analyzed.It is shown that as the time grows,the distribution function of the particles converges to the global Maxwellian,and both the fluid velocity and the macroscopic velocity of the particles converge to the same speed.

Partial Regularity of Suitable Weak Solutions to the System of the Incompressible Shear-thinning Flow

This paper is devoted to the partial regularity of suitable weak solutions to the system of the incompressible shear-thinning flow in a bounded domainΩ■R^(n),n≥2.It is proved that there exists a suitable weak solution of the shear-thinning fluid in the n-D smooth bounded domain(for n≥2).For 3 D model,it is proved that the singular points are concentrated on a closed set whose 1 dimensional Hausdorff measure is zero.