Stratification of portal vein-invaded hepatocellular carcinoma treated with transarterial chemoembolization monotherapy

Purpose:The study aimed to establish a prognostic prediction model and an artificial neural network(ANN)model to determine who will benefit from transarterial chemoembolization(TACE)monotherapy for patients with hepatocellular carcinoma(HCC)invading portal vein.Methods:Treatment-naive patients with HCC and portal vein invasion who were treated with TACE monotherapy at hospital A as training cohort and hospital B as validation cohort were included.The primary endpoint was overall survival(OS).In training cohort,independent risk factors associated with OS were identified by univariate and multivariate analysis.The prognostic prediction(PP)and ANN models based on the independent risk factors were established to find out who will benefit most from TACE monotherapy.The type of portal vein tumor thrombosis was classified based on the Cheng’s Classification.The accuracy of the models was validated in validation cohort.Results:Totally,242 patients(training cohort:n=159;validation cohort:n=83)were included.The median OS was 7.1 and 8.5 months in training and validation cohort,respectively.In training cohort,the PP model was established based on the following five independent risk factors:Cheng’s Classification,Eastern Cooperative Oncology Group score,maximum tumor size,number of HCC nodules,and Child-Pugh stage.PP score of 17.5 was identified as cut-off point and patients were divided into two groups by PP score<17.5 and>17.5 in survival benefit and prognostication(8.8 vs.5.5 months;P<0.001).These five factors were included and ranked based on the importance associated with OS in the ANN model.Both of the two models received high accuracy after validation.Conclusions:Portal vein invaded HCC patients with PP score<17.5 may benefit most from TACE monotherapy.For these patients,TACE monotherapy should be considered.

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.

Comparison of embolic agents for varices during transjugular intrahepatic portosystemic shunt for variceal bleeding: Tissue gel or coil?

Purpose:We aimed to compare treatment efficacy,safety and material cost between tissue gel and coil regarding variceal embolization during transjugular intrahepatic portosystemic shunt(TIPS).Materials&Methods:This retrospective study including cirrhotic patients with variceal bleeding treated with TIPS combined with variceal embolization between January 2016 and August 2017.Patients were divided into three groups according to embolic agents used in variceal embolization:tissue gel group(Group A),combination group(Group B),and coil group(Group C).The primary endpoint was 1-year rebleeding rate after TIPS creation.The secondary endpoints included shunt dysfunction,overt hepatic encephalopathy,liver function,and embolic agents-related expense.Results:A total of 60 patients(30,10,and 20 in Group A,B,and C)were included.Variceal rebleeding occurred in3(10%),0(0%),and 4(20%)patients within one year after TIPS creation in Group A,B,and C,respectively.Stent dysfunction occurred in 2(3.3%)patients and 9(15.0%)patients experienced overt hepatic encephalopathy.No significant differences were observed between three groups regarding primary and secondary endpoints except embolic agents-related expense,with a significantly lower cost in Group A when compared to the other two groups.Stent dysfunction occurred in two patients,with one patient in Group A developed acute occlusion caused by thrombus and another patient in Group C underwent stent stenosis during follow-up.Conclusions:Compares to coil alone or combines with coil,tissue gel has similar treatment efficacy and safety,but with significantly lower cost for variceal bleeding during TIPS.

Percutaneous transhepatic intrahepatic portosystemic shunt for variceal bleeding: A series of six cases and literature review

Objectives:To present a case series of modified transjugular intrahepatic portosystemic shunts(TIPS) and percutaneous transhepatic intrahepatic portosystemic shunts(PTIPS) in cirrhotic patients with variceal bleeding(VB).In addition,the scientific literature pertaining to PTIPS was reviewed.Methods:This retrospective clinical case series included six cirrhotic patients with VB who were treated with PTIPS after the failure of endoscopic band ligation or endoscopic injection sclerotherapy combined with vasoactive drugs.The treatment was conducted between January 2017 and June 2019 at a single institution.Three patients suffered from severe atrophy of the right or left lobar of the liver as well as the main right or left branch of the portal vein.The remaining three patients showed severe atrophy of the whole liver and portal vein,resulting in widening of the liver fissure.A paired t-test was used to compare the changes in portal pressure gradient between before and after the PTIPS operation.The rebleeding rate,treatment efficacy,complications,and technical success rate were all assessed during follow-up.Results:All six PTIPS procedures were performed successfully,with no severe procedural-related complications observed.None of the patients experienced VB during a mean follow-up of 22.8(range,18.0-28.0) months.The mean portosystemic pressure gradient decreased from 28.3 ± 4.3 mmHg pre-procedure to 12.3 ± 2.6 mmHg immediately post-procedure(P <0.001).At follow-up,one patient was found to have developed grade 2 hepatic encephalopathy thrice during the first year,according to the West Haven criteria.However,this was resolved following medical treatment.Conclusions:When the patient’s portal venous anatomy is unconducive to the performance of TIPS using the transjugular approach,PTIPS can be considered as a safe,effective complementary surgical approach for patients with VB.

Application of radiomics in hepatocellular carcinoma:A review

Hepatocellular carcinoma(HCC)is the most common form of primary liver cancer with low 5-year survival rate.The high molecular heterogeneity in HCC poses huge challenges for clinical practice or trial design and has become a major barrier to improving the management of HCC.However,current clinical practice based on single bioptic or archived tumor tissue has been deficient in identifying useful biomarkers.The concept of radiomics was first proposed in 2012 and is different from the traditional imaging analysis based on the qualitative or semiquantitative analysis by radiologists.Radiomics refers to high-throughput extraction of large amounts number of high-dimensional quantitative features from medical images through machine learning or deep learning algorithms.Using the radiomics method could quantify tumoral phenotypes and heterogeneity,which may provide benefits in clinical decision-making at a lower cost.Here,we review the workflow and application of radiomics in HCC.

Role of Transarterial Chemoembolization in the Treatment of Hepatocellular Carcinoma

Hepatocellular carcinoma(HCC)is one of the most common cancers worldwide.According to the Barcelona Clinic Liver Cancer(BCLC)staging system,transarterial chemoembolization(TACE)is the first-line recommendation for intermediate-stage HCC.In real-world clinical practice,TACE also plays an important role in early-and advanced-stage HCC.This review article by the experts from Chinese Liver Cancer Clinical Study Alliance(CHANCE)summarizes the available clinical evidence pertaining to the current application of TACE in patients with early-,intermediate-,and advanced-stage HCC.In addition,combination of TACE with other treatment modalities,especially immunotherapy,is reviewed.

Prognostic Performance of the China Liver Cancer Staging System in Hepatocellular Carcinoma Following Transarterial Chemoembolization

Background and Aims:To validate prognostic performance of the China liver cancer(CNLC)staging system as well as to compare these parameters with those of the Barcelona Clinic Liver Cancer(BCLC)staging system for Chinese hepatocellular carcinoma(HCC)treated with transarterial chemoembolization(TACE).Methods:This multicenter retrospective study included 1,124 patients with HCC between January 2012 and December 2020 from six Chinese hospitals.Based on overall survival(OS),the prognostic performance outcomes for the CNLC and BCLC staging systems were compared by model discrimination[C statistic and Akaike information criterion(AIC)],monotonicity of the gradient(linear trend chi-square test),homogeneity(likelihood ratio chisquare test),and calibration(calibration plots).A prospective cohort of 44 patients receiving TACE-based therapy included between January 2021 and December 2022 was used to prospectively validate the outcomes.Results:Median OS was 19.1(18.2–20.0)months,with significant differences in OS between stages defined by the CNLC and BCLC observed(p<0.001).The CNLC performed better than the BCLC regarding model discrimination(C-index:0.661 vs.0.644;AIC:10,583.28 vs.10,583.72),model monotonicity of the gradient(linear trend chi-square test:66.107 vs.57.418;p<0.001),model homogeneity(159.2 vs.158.7;p<0.001).Both staging systems had good model calibration.Similar results were observed in the prospective cohort.Conclusions:Combining model discrimination,gradient monotonicity,homogeneity,and calibration,the CNLC performed better than the BCLC for Chinese HCC patients receiving TACE.

Re-evaluating Transarterial Chemoembolization Failure/Refractoriness:A Survey by Chinese College of Interventionalists

Background and Aims:The recognition of transarterial chemoembolization(TACE)failure/refractoriness among Chinese clinicians remains unclear.Using an online survey conducted by the Chinese College of Interventionalists(CCI),the aim of this study was to explore the recognition of TACE failure/refractoriness and review TACE application for hepatocellular carcinoma(HCC)treatment in clinical practice.Methods:From 27 August 2020 to 30 August 2020 during the CCI 2020 annual meeting,a survey with 34 questions was sent by email to 264 CCI clinicians in China with more than 10 years of experience using TACE for HCC treatment.Results:A total of 257 clinicians participated and responded to the survey.Most participants agreed that the concept of“TACE failure/refractoriness”has scientific and clinical significance(n=191,74.3%).Nearly half of these participants chose TACE-based combination treatment as subsequent therapy after so-called TACE failure/refractoriness(n=88,46.1%).None of the existing TACE failure/refractoriness definitions were widely accepted by the participants;thus,it is necessary to re-define this concept for the treatment of HCC in China(n=235,91.4%).Most participants agreed that continuing TACE should be performed for patients with preserved liver function,presenting portal vein tumor thrombosis(n=242,94.2%)or extrahepatic spread(n=253,98.4%),after the previous TACE treatment to control intrahepatic lesion(s).Conclusions:There is an obvious difference in the recognition of TACE failure/refractoriness among Chinese clinicians based on existing definitions.Further work should be carried out to re-define TACE failure/refractoriness.

Kyphoplasty versus vertebroplasty for the treatment of malignant vertebral compression fractures caused by metastases： a retrospective study

Background There are few comparative studies regarding kyphoplasty （KP） and vertebroplasty （VP） for the treatment of painful vertebral compression fractures （VCF） in patients with cancer. The purpose of this study is to retrospectively compare KP with VP in pain improvement, cement leakage incidence, and the cost of treatment of malignant VCE Methods We performed a retrospective study of clinical data for 80 patients with multiple spinal metastases, treated with KP in 42 cases and VP in 38. Visual analog scale （VAS） scores were collected pre-operatively, post-operatively, at 1 month, 6 months, and 1 year after treatment. Cement leakage was identified using fluoroscopy and CT scan. Total cost per patient was also collected. Results There was a significant difference between the pre- and post-operative VAS scores （7.4＋2.0 to 3.8＋1.6, P 〈0.001 in the KP group; 6.7＋2.4 to 3.7＋1.4, P 〈0.001 in the VP group）, and was maintained at 1-year follow-up （3.2＋1.4 in the KP group, 3.1＋1.3 in the VP group）. However, the difference in VAS score between these two groups was insignificant at baseline and every follow-up assessment post-operatively （P 〉0.05）. The incidence of cement leakage in the KP group was lower than that of the VP group （16.9% （14/83） vs 30.3% （23/76）, P 〈0.05）. However, none of the patients developed any symptoms. The length of postoperative hospital stay in the VP group was shorter than that of the KP group （（2.4＋1.3） vs （5.3＋1.9） days, P 〈0.05）. Total hospital cost in the KP group was much higher than that of the VP group （RMB Yuan 8 492_＋3 332 vs RMB Yuan 3 173~1 341, P〈0.01）. Conclusions VP and KP are both effective in providing pain relief for patients with cancer-related VCF. KP provides no greater degree of pain improvement. KP is associated with a lower rate of cement leakage compared with VP. VP is associated with lower cost and shorter postoperative hospital stay in China.

Clinical practice of transarterial chemoembolization for hepatocellular carcinoma:consensus statement from an international expert panel of International Society of Multidisciplinary Interventional Oncology(ISMIO)

Importance:Transarterial chemoembolization(TACE)has been associated with a wide range of practice variations for hepatocellular carcinoma(HCC)between the East and the West.This considerable ambiguity may lead to the heterogeneous quality in treatment and have a negative impact on the role of TACE in the overall multidisciplinary HCC treatment system.Objective:It may be a good start to establish a guideline worldwide to have this consensus from experts who represent east and west,although it does not cover all aspects of TACE.Evidence Review:An international expert panel on TACE is convened to cluster the expert’s opinions and summary a standard consensus.This panel committee consist of leading physicians in TACE on HCC from USA,France,Japan,Singapore,Korea,China,and so on.The first-round face-to-face consensus meeting was held during in Nanjing,China in October 2019.The second-round conference for revision of the consensus was held during the Annual Meeting of Chinese College of Interventionalists in August 2020 by a hybrid format of a Webinar and roundtable meeting.After several on-line revisions,the final manuscript was approved by all members of the panel in June 2021.Findings:The consensus statements were organized into the following categories:patients’selection,performing the procedure,TACE outcomes,repeat TACE,TACE failure/refractory,and TACE-based combination treatments.Conclusions and Relevance for Reviews:More and more evidences have showed the better outcomes with strategy of combined TACE with other local therapies such as ablations.The most-recently developing strategy of combined TACE with PD-1/PD-L1 plus tyrosine kinase inhibitor(TKI)agents has shined a light to the HCC patients,especially to those with high risk of tumor recurrence after treatment or TACE failure/refractory.

Transarterial chemoembolization failure/refractoriness: A scientific concept or pseudo-proposition

Multi-session transarterial chemoembolization(TACE)is usually needed for the treatment of intermediate-stage hepatocellular carcinoma(HCC),but it may not always have a positive influence on prognosis due to high heterogeneity of HCC.To avoid ineffective repeated TACE,the concept of TACE failure/refractoriness has been proposed by several organizations and is being addressed using tyrosine kinase inhibitors.The concept of TACE failure/refractoriness is controversial due to ambiguous definitions and low evidence-based data.To date,only a few studies have examined the rationality concerning the definition of TACE failure/refractoriness,although the concept has been introduced and applied in many TACE-related clinical trials.This review focuses on some of the issues related to different versions of TACE failure/refractoriness,the rationality of related definitions,and the feasibility of continuing TACE after so-called failure/refractoriness based on published evidence.A suggestion to re-define TAEC failure/refractoriness is also put forward.

Research progress of bariatric embolization for treatment of obesity

To the Editor:The prevalence of obesity,defined as body mass index(BMI)≥30 kg/m^2,is increasing worldwide and has been identified that obesity is a risk factor for several kinds of chronic diseases.[1]According to the severity of obesity,associated coexisting chronic diseases,and functional limitations,therapies for obesity include lifestyle intervention(eg,diet and exercise),pharmacotherapy,endoscopic bariatric therapies,bariatric surgery,and bariatric embolization(BAE).

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.

Subsequent Treatment after Transarterial Chemoembolization Failure/Refractoriness: A Review Based on Published Evidence

Transarterial chemoembolization(TACE)is widely applied for the treatment of hepatocellular carcinoma.Repeat TACE is often required in clinical practice because a satisfactory tumor response may not be achieved with a single session.However,repeated TACE procedures can impair liver function and increase treatment-related adverse events,all of which prompted the introduction of the concept of“TACE failure/refractoriness”.Mainly based on evidence from two retrospective studies conducted in Japan,sorafenib is recommended as the first choice for subsequent treatment after TACE failure/refractoriness.Several studies have investigated the outcomes of other subsequent treatments,including locoregional,other molecular targeted,anti-programmed death-1/anti-programed death ligand-1 therapies,and combination therapies after TACE failure/refractoriness.In this review,we summarize the up-to-date information about the outcomes of several subsequent treatment modalities after TACE failure/refractoriness.

索拉菲尼耐药肝癌细胞株PD-L1表达上调促进上皮-间质转化

背景:在多种癌症中均可观察到上皮-间质转化(EMT)与程序性死亡配体1(PD-L1)表达之间的相关性。然而,PD-L1在索拉非尼耐药的肝癌细胞EMT中的作用及分子机制尚不清楚。本研究旨在探讨PD-L1对索拉非尼耐药肝癌细胞EMT的调控。方法:首先建立索拉非尼耐药的肝癌细胞株HepG2 SR和Huh7 SR。Western blot法检测PD-L1、E-cadherin和N-cadherin的表达。通过对PD-L1的干预和过表达,探讨PD-L1在HepG2 SR和Huh7 SR肝癌细胞中对EMT的调控。Transwell法检测细胞迁移和侵袭能力。通过过表达和敲除PD-L1或SREBP-1来研究PD-L1在索拉非尼耐药肝癌细胞中的作用机制。结果:HepG2 SR和Huh7 SR细胞株中PD-L1表达上调,E-cadherin表达下调,N-cadherin表达上调。HepG2和Huh7细胞株存活率低于HepG2 SR和Huh7 SR细胞株。PD-L1过表达可使E-cadherin表达下调和N-cadherin表达上调,而PD-L1敲除则上调E-cadherin表达和下调N-cadherin表达。PD-L1的表达促进了HepG2 SR和Huh7 SR细胞株的EMT和侵袭能力。PD-L1促进索拉非尼耐药肝癌细胞(HepG2 SR和Huh7 SR)EMT是通过激活SREBP-1表达从而启动PI3K/Akt通路实现的。结论:本实验结果显示PD-L1可促进索拉非尼耐药肝癌细胞的EMT。

Prognostic nomogram on admission predicting progression for patients with nonsevere COVID-19

The present study aimed to establish a prognostic nomogram to stratify high-risk patients with Coronavirus Disease 2019(COVID-19)who progressed from the nonsevere condition on admission to severe during hospitalization.This multicenter retrospective study included patients with nonsevere COVID-19 on admission from Jan 10,2020 to Feb 7,2020.In the training cohort,independent risk factors associated with disease progression were identified by univariate and multivariate analyses.The prognostic nomogram was established and then validated externally using C-index.The study included 351 patients(293 and 58 in the training and validation cohorts,respectively),with 27(9.2%)and 5(8.6%)patients progressed,respectively.In the training cohort,older age(OR 1.036,95%Cl 1.000-1.073),more lobes involved on chest CT(OR 1.841,95%Cl 1.117-3.035),comorbidity present(OR 2.478,95%Cl 1.020-6.018),and lower lymphocyte count(OR 0.081,95%Cl 0.019-0.349)were identified as independent risk factors.The prognostic nomogram was established in the training cohort with satisfied external prognostic performance(C-index 0.906,95%Cl 0.806-1.000).In conclusion,older age,comorbidity present,more lobes involved on chest CT,and lower lymphocyte count are independent risk factors associated with disease progression during hospitalization for patients with nonsevere COVID-19.