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Table of Content

    30 September 2020, Volume 7 Issue 3
    Experts reviews
    New progress of interventional therapy for liver cancer
    Xu Ke, Shao Haibo
    2020, 7(3):  2-6. 
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    As one of the most common malignant tumors, interventional therapy has become an important treatment for liver cancer. The interventional therapy of liver cancer has developed from TACE (transcatheter arterial chemoembolization) to a variety of interventional therapy through different stages of liver cancer. Especially with the rapid development of interventional therapy equipment, and materials in recent years, the development of interventional therapy for liver cancer is changing rapidly. This paper reviews the latest progress in TACE, transcutaneous ablation of liver cancer (radiofrequency ablation, microwave ablation, cryoablation, irreversible electroporation), brachytherapy with radioactive particles, interventional therapy combined with molecular targeting and immunotherapy, and looks forward to new drugs, materials and equipment related to interventional therapy of liver cancer.
    Original article
    Radiotherapy compared with palliative care for advanced hepatocellular carcinoma with portal vein tumor thrombus: using a new classification
    Yang Liu, Zhu Xiling, Jin Shuai, Chang Na, Zhao Yufei, Li Gong
    2020, 7(3):  7-11. 
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    Objective: To evaluate the efficiency of radiotherapy (RT) for unresectable hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) and the significance of Cheng's classification for the prognosis. Methods: A retrospective analysis was performed on 105 patients with HCC with PVTT in the Third Medical Center of PLA General Hospital from January 2010 to October 2016, among whom 67 underwent RT and 38 received palliative care. Survival analysis of the two treatment groups was performed with Kaplan-Meier and then stratified by Cheng’s classification of PVTT. And the prognostic factors were analyzed. Results: The median survival,1-year, 2-year and 5-year survival rate of RT group and palliative group was 9 vs. 3 months, 41.8% vs. 2.6%, 20.1% vs. 0, 4.5% vs. 0. On subgroup analysis of PVTT, the median survival in the RT group for type Ⅱ, Ⅲ, and Ⅳ PVTT was 13, 8, and 5 months, respectively. In RT group, the survival of type III was better than type IV (P = 0.044), but inferior to type II (P = 0.011). PVTT type, tumor number and RT dose were independent prognostic factors for survival (P = 0.041, P = 0.028, P = 0.015). Conclusions: Radiotherapy is an effective treatment compared with palliative care for HCC and PVTT, and Cheng's classification can initially provide a better prognosis evaluation for HCC with PVTT who underwent radiotherapy.
    Effects of stroke volume variation guided goal-directed fluid therapy on liver and renal function of patients after liver cancer surgery
    Liu Chao, Zou Liang, Zheng Hui
    2020, 7(3):  12-16. 
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    Objective: To investigate the effect of stroke volume variation (SVV) guided goal-directed fluid therapy (GDFT) on liver and renal function of patients after liver cancer surgeries. Methods: Sixty patients undergoing liver cancer surgeries in cancer hospital of Chinese academy of medical sciences were randomly divided into a low SVV group (1<SVV≤5) and a high SVV group (5<SVV≤9). In both groups, doses of ringer lactate were infused slowly at a steady speed. If SVV was higher than the threshold (SVV>5 in the low SVV group and SVV>9 in the high SVV group), a dose of 250ml hydroxyethyl starch 130/0.4 was given within 15 minutes to observe the changes of SVV. If SVV is still higher than the threshold, such dose was repeatedly given until SVV readings fall below the threshold. Records of fluid intake and output during operation, as well as operation time are done and kept, besides AST, ALT, APTT, Cr, BUN and other liver and renal function indicators within 3 days post-surgery. Results: The amount of fluid input was significantly reduced in the high SVV group, and there was no statistical difference in postoperative liver and kidney function compared with the low SVV group. Conclusion: Goal-directed fluid therapy based on SVV guidance will facilitate intraoperative fluid input limitation and intraoperative fluid management in liver cancer surgery .
    Prognostic value of four prognostic tools in end-stage primary liver cancer
    Yang Min, Wang Chao, Han Binbin, Sun Rui, Yu Lei, Xu Haiyan
    2020, 7(3):  17-21. 
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    Objective: To evaluate the prognostic value of glasgow prognostic score(GPS), prognostic nutritional index (PNI), model for end-stage liver disease(MELD) score and WPCBAL score in end-stage primary liver cancer(PLC) patients. Methods: Clinical data of 50 end-stage PLC patients discharged dead from the Cancer Hospital of the Chinese Academy of Medical Sciences between January 2010 to April 2020 were retrospectively analyzed. The general information and scores of four prognostic tools on last admission were collected. Differences of survival time among prognostic tools were compared by the log-rank test. Predictive values of various prognostic tools for 3-week mortality were evaluated by the receiver operating characteristic curve(ROC) analysis. Results: The median survival time was 9.5 days (95% CI: 6 ~15 days), and the 3-week mortality rate was 80.0%. Log-rank test showed that the survival time of MELD score≥ 15 group was shorter than MELD score < 15 group (7d vs. 16d, P = 0.002), and WPCBAL score≥ 5 group had a shorter survival time than WPCBAL score < 5 group (7d vs. 10d, P = 0.029). ROC analysis showed that the area under the ROC (AUC) of MELD score and WPCBAL score in predicting 3 week survival of patients with end-stage liver cancer were 0.7325 (95% CI: 0.5571~0.9079) and 0.6838 (95% CI: 0.5188~0.8487), respectively. Conclusion: MELD score and WPCBAL score are valuable in predicting the short-term survival status of end-stage PLC patients with low sensitivity.
    Nomogram model of prognosis of hepatocellular carcinoma patients was constructed based on NRS-2002
    Wang Chao, Han Shanshan, Chen Shu, Ding Shengyi, Feng Zhiqiang
    2020, 7(3):  22-29. 
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    Objective: The nutritional risk Assessment Form (NRS-2002) was used to assess the nutritional status of patients with hepatocellular carcinoma (HCC) and to construct a Nomogram model to predict the recurrence of HCC patients in combination with other risk factors. Methods: The clinical data of 241 patients with HCC underwent hepatectomy in Suixi County People's Hospital, Beijing Chaoyang Emergency Rescue Center and Air Force Characteristic Medical Center from July 2015 to January 2019 were retrospectively analyzed. Univariate and multivariate Cox proportional risk models were used to analyze the independent risk factors for recurrence and death of HCC patients. Nomogram model was constructed according to independent risk factors.Internal data were used to verify the effectiveness of the Nomogram model. Results: ROC curve was used to analyze the correlation variables according to the mortality of HCC patients.The AUC of age, AFP, TBIL, ALT and ALB were 0.783, 0.715, 0.758, 0.729 and 0.822, respectively.The optimal truncation values were 65years、400μg/L、34.67μmol/L、40.54U/L、35g/L, respectively.The proportion of cirrhosis(yes), TBIL (>34.67μmol/L) and ALB(≤35g/L)in patients with malnutrition was higher than that in patients with normal nutrition (P<0.05).At the end of follow-up, 127 of the 241 HCC patients relapsed, with a median relapse-free survival of 14 months and 101 deaths of 19 months.The relapse-free survival rate and overall survival rate of nutritionally normal patients were higher than that of malnutrition patients (P<0.05).Multiariable Cox risk proportion model analysis results showed that liver cirrhosis (YES), tumor diameter (>5cm), TNM staging(Ⅲ+Ⅳ), TBIL (>34.67 μmol) and NRS-2002 (malnutrition) are independent risk factors for recurrence of HCC patients (P<0.05);Cirrhosis of the liver (YES), tumor diameter (>5cm), TNM staging(Ⅲ+Ⅳ)are the independent risk factors of death in patients with HCC (P<0.05).The results of internal validation showed that the 6 month, 12 month and 24 month recurrence free survival rates were 0.716(95%CI: 0.671-0.866), 0.710(95%CI: 0.624-0.838) and 0.699 (95%CI: 0.611-0.796), respectively. Conclusion: In this study, the Nomogram model was effective in predicting the recurrence free survival rate of HCC patients at 6, 12, and 24 months after surgery, which could be used to improve the perioperative treatment plan .
    Effect of miRNA-149 expression on the prognosis of patients with hepatocellular carcinoma and its potential mechanism
    Jin Xiaoxin, He Shilin, Gao Yanyan, Yu Xiaoshuang, Wang Zhenguo, Hou Shike
    2020, 7(3):  30-35. 
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    Objective: To explore the effect of miRNA-149 expression on the prognosis of patients with hepatocellular carcinoma (HCC) and its potential mechanism. Methods: Clinical and genomic data of 344 patients with hepatocellular carcinoma was selected from TCGA database. According to the level of miRNA-149 expression, the patients were divided into two groups: high expression group (n = 172) and low expression group (n = 172). The survival curves of the two groups were drawn, and the relative expression levels of miRNA-149 in patients with different tumor stages were compared. The top 50 genes with the highest positive and negative correlation coefficients with miRNA-149 were selected for biological annotation, classification and interaction analysis of encoded proteins. The expression levels of miRNA-149, glutamate dehydrogenase 1 (GLUD1) and hydroxysteroid 17-β dehydrogenase 4 (HSD17B4) were detected by RT-PCR in 32 patients with hepatocellular carcinoma. The differences of miRNA-149 expression in patients with different stages were compared. 32 patients were divided into high miRNA-149 expression group (group H) and low expression group (group L). The clinical data of the two groups were compared. Results: The median survival time of patients with low expression of miRNA-149 was longer than that of patients with high expression of miRNA-149, and the difference was statistically significant (2532 d vs.1271 d P<0.001). According to the pathological stage, the expression level of miRNA-149 in stage I was significantly lower than that in stageⅡ andⅢ (P<0. 05). According to T stage, the expression level of miRNA-149 in T1 stage was significantly lower than that in T2 and T3 stage (P<0. 05). The main biological processes involved in miRNA-149-related genes are biological regulation. The main molecular functions involved are protein binding. The main cell components involved are cell membrane. The main signal pathways involved are extracellular matrix metabolic pathway. GLUD1 and HSD17B4 are proteins at the core of the interaction network between related genes. Compared with group H, the expression of GLUD1 and HSD17B4 genes in group L was significantly higher than that in group H (P<0.05). There was significant difference in the expression level of miRNA-149 among different stages of clinical samples (P = 0.019). The expression level of miRNA-149 in patients with stage Ⅲ was significantly higher than that in patients with stage Ⅰ or Ⅱ (P<0.05). Conclusion: The high expression of miRNA-149 is related to the poor long-term prognosis of HCC, which may be related to its targeted regulation of glutamate and estradiol metabolic pathway.
    Review
    Application and progression of ablation combined with targeted therapies in the treatment of liver cancer
    Yan Xue, Han Yue
    2020, 7(3):  36-38. 
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    Liver cancer is one of the most common malignant tumors worldwide.Furthermore,China has the world's highest incidence rate and the largest number of deaths.At present,the most commonly used radical treatment for liver cancer is surgical resection and local ablation.However,due to its insidious onset,rapid progression,early recurrence and poor prognosis,many patients have reached advanced stage when diagnosed.In recent years,with the application of targeted drugs,the curative effect of liver cancer patients has been significantly improved.This article will review the effect of ablation combined with targeted therapy for liver cancer.
    Advances of biomarker for efficacy prediction in targeted therapy and immunotherapy of hepatocellular carcinoma
    He Jian, Chen Xiaoming
    2020, 7(3):  39-42. 
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    Hepatocellular carcinoma (HCC) is the most common malignant liver tumor in China, which is seriously threating the life and health of our people. At present, molecular targeted therapy and immunotherapy are the mainly systematic treatment for advanced HCC. How to choose multi-targeted inhibitor and appropriate immunotherapy has become a research hotspot nowadays. With the continuous development of various sequencing technology, exploring the biomarkers of molecular targeted therapy and immunotherapy can precise select the beneficial population as well as predict drugs efficacy and disease prognosis. In this paper, we will review the advances of biomarker for efficacy prediction in targeted therapy and immunotherapy of hepatocellular carcinoma.