Inflammation-related nomogram for predicting survival of patients with unresectable hepatocellular carcinoma received conversion therapy

BACKGROUND The efficacy of conversion therapy for patients with unresectable hepatocellular carcinoma(HCC)is a common clinical concern.AIM To analyse the prognostic factors of overall survival(OS)in patients with unresectable HCC who received conversion therapy.METHODS One hundred and fifty patients who met the inclusion criteria were enrolled and divided into a training cohort(n=120)and a validation cohort(n=30).Using the independent risk factors in the training cohort,a nomogram model was constructed to predict OS for patients treated with transarterial chemoembolization following hepatic resection.The nomogram was internally validated with the bootstrapping method.The predictive performance of nomogram was assessed by Harrell’s concordance index(C-index),calibration plot and timedependent receiver operating characteristic curves and compared with six other conventional HCC staging systems.RESULTS Multivariate Cox analysis identified that albumin,blood urea nitrogen,gamma-glutamyl transpeptidase to platelet ratio,platelet to lymphocyte ratio,macrovascular invasion and tumour number were the six independent prognostic factors correlated with OS in nomogram model.The C-index in the training cohort and validation cohort were 0.752 and 0.807 for predicting OS,which were higher than those of the six conventional HCC staging systems(0.563 to 0.715 for the training cohort and 0.458 to 0.571 for the validation cohort).The calibration plots showed good consistency between the nomogram prediction of OS and the actual observations of OS.Decision curve analyses indicated satisfactory clinical utility.With a total nomogram score of 196,patients were accurately classified into low-risk and high-risk groups.Furthermore,we have deployed the model into online calculators that can be accessed for free at https://ctmodelforunresectablehcc.shinyapps.io/DynNomapp/.CONCLUSION The nomogram achieved optimal individualized prognostication of OS in HCC patients who received conversion therapy,which could be a useful clinical tool to help guide postoperative personalized interventions and prognosis judgement.

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 bansplantation （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.

Aspirin-induced long-term tumor remission in hepatocellular carcinoma with adenomatous polyposis coli stop-gain mutation:A case report

BACKGROUND Targeted therapy based on pathway analysis of hepatitis B-related hepatocellular carcinoma(HCC)may be a promising remedy.CASE SUMMARY The present case involved an advanced hepatocellular carcinoma(HCC)patient who did not receive local regional therapy and was intolerant to sorafenib.Total RNA extracted from the patient’s tumor tissue was used to obtain the gene mutation profile.The c.3676A>T and c.4402A>T stop-gain mutations in adenomatous polyposis coli(APC)were the most prevalent(42.2%and 35.1%,respectively).MutationMapper analysis indicated that the functional domain of APC was lost in the two APC mutant genes.APC is a major suppressor of the Wnt signaling pathway.Thus,the Wnt pathway was exclusively activated due to APC dysfunction,as other elements of this pathway were not found to be mutated.Aspirin has been reported to suppress the Wnt pathway by inducingβ-catenin phosphorylation through the activation of glycogen synthase kinase 3 beta via cyclooxygenase-2 pathway inhibition.Therefore,aspirin was administered to the patient,which achieved four years of disease control.CONCLUSION Exclusive mutations of APC of all the Wnt pathway elements could be a therapeutic target in HCC,with aspirin as an effective treatment option.

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.