Liver transplantation and BCLC classification:Limitations impede optimum treatment

Background:The Barcelona Clinic Liver Cancer(BCLC)system has been endorsed by international guidelines as a staging algorithm of hepatocellular carcinoma.This analysis was performed to assess the outcome of liver transplantation in patients treated against the BCLC recommendations.Methods:The data of 198 patients who underwent liver transplantation for hepatocellular carcinoma were extracted from a prospectively maintained database to classify the patients according to the BCLC system.Results:BCLC staging was as follows:0,n=5;A,n=77;B,n=41;C,n=53;and D,n=22.Accordingly,liver transplantation was performed in the majority of patients against BCLC recommendations.Surgery(n=16),radiofrequency ablation(n=15)and transarterial chemoembolization(n=151)preceded liver transplantation in 182 patients.Sixteen patients were transplanted without pretreatment.The 1-,5-and 10-year survival rates were 83.8%,62.4%and 45.9%,and 1-,5-,and 10-year recurrence rates were 7.7%,22.7%and 26.7%.The BCLC classification did neither impact survival(P=0.796)nor recurrence(P=0.693).In the Cox analysis,RECIST tumor progression and initial alpha fetoprotein were independent predictors of outcome.Conclusions:Neither the oncological nor the functional stratification imposed by the BCLC system was of importance for outcome.Lack of flexibility and disregard of biological parameters hamper its clinical applicability in liver transplantation.

Hepatocellular carcinoma recurrence after acute liver allograft rejection treatment: A multicenter European experience

Background:During the last decades,several risk factors for the recurrence of hepatocellular carcinoma(HCC)after liver transplantation(LT)have been investigated.However,the impact of two important drivers of oncogenesis,namely the immunosuppression and the treatment of acute cellular rejection(ACR)have been marginally addressed.This study aimed at investigating the impact of ACR treatment on the incidence of tumor recurrence in a large European HCC-LT population.Methods:Seven hundred and eighty-one adult patients transplanted between February 1,1985 and June 30,2016 were retrospectively analyzed.After propensity score match,116 patients treated for ACR using steroid boluses were compared with 115 patients who did not present any ACR or a histologic but clinical irrelevant ACR.Results:Steroid boluses treated patients had a 18-fold higher overall incidence of HCC recurrence than those non-treated patients(16.4%vs.0.9%;P<0.0001).At multivariate Cox regression analysis,steroid boluses used to treat ACR were an independent risk factor for HCC recurrence(HR=14.2;95%CI:1.8–110.4;P=0.010).Conclusions:The decision to treat ACR as well as to reinforce immunosuppression load should be cautiously taken in view of the presented results.Prospective studies are needed to further elucidate the clinical impact of immunosuppression on HCC recurrence after transplantation.

Intrahepatic cholangiocarcinoma: Introducing the preoperative prediction score based on preoperative imaging

Background: Intrahepatic cholangiocarcinoma(ICC) still has a poor long-term outcome, even after complete resection. We investigated different parameters gathered in preoperative imaging and analyzed their influence on resectability, recurrence, and survival. Methods: All patients who underwent exploration due to ICC between January 2008 and June 2018 were analyzed retrospectively. Kaplan-Meier model, log-rank test and Cox regression were used. Results: Out of 184 patients, 135(73.4%) underwent curative intended resection. Median overall survival(OS) was 22.2 months with a consecutive 1-, 3-and 5-year OS of 73%, 29%, and 17%. Median recurrencefree survival(RFS) was 9.3 months with a consecutive 1-, 3-and 5-year RFS of 36%, 15%, and 11%. Site of tumor, parenchymal localization, tumor configuration/dissemination, and estimated tumor volume had significant influence on resectability. Univariate analyses showed that site of tumor, tumor configuration/dissemination, number of nodules, and estimated tumor volume had predictive values for OS and RFS. Together with tumor size the preoperative prediction(POP) score was created showing significance for OS and RFS(all P<0.001). In multivariate analysis, POP score(HR=1.779;95% CI: 1.26 8-2.4 95;P=0.001), T stage(HR=1.255;95% CI: 1.040-1.514;P=0.018) and N stage(HR=1.334;95% CI: 1.081-1.645;P=0.007) were the independent predictors for OS. For RFS, POP score(HR=1.733;95% CI: 1.30 0-2.311;P<0.0 01) and M stage(HR=3.036;95% CI: 1.376-6.697;P=0.006) were the independent predictors. Conclusions: The POP score showed to have a highly significant influence on OS and RFS. The score is easy to assess through preoperative imaging. For patients in the high risk group at least staging laparoscopy or preoperative chemotherapy should be evaluated, because they showed equal outcome compared to the irresectable group.

Development and validation of an artificial intelligence model for predicting post-transplant hepatocellular cancer recurrence

Dear Editor,In recent years,criteria based on the combinationof morphology and biology have been proposed forimproving the selection of hepatocellular cancer(HCC)patients waiting for liver transplantation(LT)[1,2].Since all the proposed models showed suboptimalresults in predicting the risk of postLT recurrence,aprediction model constructed using artificial intelligence(Al)could be an attractive way to surpass this limit[3,4].Therefore,the Time_Radiological-response_Alpha-fetoproteIN_Artificial-Intelligence(TRAIN-AI)modelwas developed,combining morphology and biology tumorvariables.