Objective A random survival forest algorithm was applied to explore the prognostic factors and develop the prognosis model for patients with unresectable hepatocellular carcinoma(HCC)after transcatheter arterial chemoembolization(TACE).Methods Retrospective selection of 636 HCC patients treated with TACE as first-line treatment in the Department of Hepatology,Zhongshan Hospital,Fudan University from January 2014 to December 2017.The patients were divided into a training set(n=445)and a validation set(n=191)in a 7∶3 ratio.Based on the clinical data,laboratory indicators and follow-up survival of patients,the Cox proportional-hazards regression model and the random survival forest model based on machine learning algorithm was developed,and the predictive ability of the two models was evaluated.Results The tumor burden,age,baseline gamma-glutamyl transpeptidase(GGT)level,baseline alpha-fetoprotein(AFP)level and albumin-bilirubin grade(ALBI)were independent factors affecting the prognosis of unresectable HCC patients treated with TACE.In the Cox model,the 1-year,3-year and 5-year AUC of the training set was 0.782,0.796 and 0.791,respectively,and the validation set was 0.750,0.766 and 0.766,respectively.The 1-year,3-year and 5-year AUC of the training set in the random survival forest model was 0.896,0.894 and 0.875,respectively,and validation set was 0.743,0.763 and 0.770,respectively.Random survival forest model could distinguish patients into good prognosis group and poor prognosis group,and the overall survival of these two groups was significantly different(P＜0.05).The decision curve analysis showed that the net benefit of the random survival forest model was better than that of the Cox proportional-hazards model.Conclusions The random survival forest model is a reliable tool for predicting the prognosis of unresectable HCC patients treated with TACE.

Objective To explore whether liver cirrhosis markers aspartate aminotransferase-to-platelet ratio index(APRI)and fibrosis-4 index(FIB-4)based on blood biochemical indicators can predict disease free survival(DFS)and overall survival(OS)in patients with hepatocellular carcinoma(HCC)after resection.Methods 300 patients with HCC who underwent radical resection in Zhongshan Hospital,Fudan University from February 2005 to July 2017 were enrolled and the clinicopathological characteristics,recurrence and survival of these patients were retrospectively collected.The relationships between APRI,FIB-4 and postoperative recurrence and survival were evaluated.The ROC curve was used to evaluate the predictive values of APRI,FIB-4.Results The median follow-up of 300 patients was 61 months.Univariate Cox regression analysis showed that APRI,FIB-4,vascular invasion were risk factors affecting postoperative DFS and OS.The multivariate Cox regression analysis showed that vascular invasion was the independent risk factor for postoperative DFS(HR=1.518,95%CI 1.024-2.252,P=0.038)and OS(HR=2.301,95%CI 1.270-4.167,P=0.006).The time dependent ROC(time-ROC)curve showed that AUCs of APRI and FIB-4 predicting 1-year,3-year,and 5-year DFS were 0.555-0.596,which were 0.600-0.679 when predicting 1-year,3-year,and 5-year OS.Conclusions The predictive value of APRI and FIB-4 based on blood biochemical indicators alone for postoperative DFS and OS in HCC patients is limited.

The pandemic of Corona Virus Disease 2019 (COVID-19) continues, which shows the concentrated or sporadic cases in multiple places. Current COVID situation is still complex. During the COVID-19, routine diagnosis and treatment of liver cancer patients has been affected in different degrees. Under the premise of following the treatment guidelines, how to reduce the risk of infection of patients and medical staff, utilize limited medical resources to maximally ensure anti-tumor treatment and related emergency treatment, and help patients get through the epidemic period is a problem for liver oncologists. Thus, experts of liver cancer treatment related disciplines of Zhongshan Hospital, Fudan University have written the Expert guidance on overall management of liver cancer during the COVID-19, which aims to provide references for liver oncolo-gists to conduct clinical work safely and effectively under the epidemic prevention and control, and to help patients fight against the epidemic smoothly.

The application of immune checkpoint inhibitors has significantly improved the immunotherapy effect of a variety of solid tumors. With the US Food and Drug Administration's approval of nivolumab and pembrolizumab as second-line treatments for hepatocellular carcinoma, the application of immune checkpoint inhibitors, especially in combination with other treatment methods, has become more and more widely used in hepatocellular carcinoma. Notably, these drugs play a therapeutic role in tumor immunosuppression; however, they can also stimulate related side effects caused by autoimmunity, so their side effects are very different from traditional chemotherapy and targeted drugs. Therefore, effective monitoring, detection and intervention of immune-related side effects are obligatory assurances for patients to attain clinical benefits.

The clinical application of immune checkpoint inhibitors (ICIs) has significantly improved the prognosis of hepatocellular carcinoma (HCC) patients. With the widespread applica-tion of ICIs in HCC, the management of immune-related adverse events (irAE) gained more and more attention. However, the complicated disease characteristics and various combination therapies in HCC throw out challenges to irAE management. Therefore, the editorial board of the 'Chinese expert consensus on the management of immune-related adverse events of hepatocellular carcinoma treated with immune checkpoint inhibitors (2021 edition)' organizes multidisciplinary experts to discuss and formulate this consensus. The consensus focuses on issues related to HCC irAE manage-ment, and puts forward suggestions, in order to improve standardized and safety clinical medication, so as to maximize the benefits of immunotherapy for patients.

Objective: To investigate the association between expression of phosphoglycerate kinase 1 (PGK1) in liver cancer tissue and prognosis, as well as its influence on metastasis and invasion of hepatocellular carcinoma (HCC) cells. Methods: Overexpression and downregulated expression of PGK1 in HCC cells were mediated by lentivirus to establish hepatoma cell lines with different expression levels of PGK1. The Transwell chamber invasion assay, wound healing assay, and colony-forming assay were used to investigate the influence of PGK1 on metastasis, invasion, and proliferation of HCC cells. Immunohistochemistry was used to measure the expression of PGK1 in liver cancer tissue samples from 116 patients with hepatocellular carcinoma who underwent radical surgery, and the Kaplan-Meier method and the log-rank test were used to determine the association between PGK1 expression and prognosis of patients with liver cancer. Results: HCCLM3 and MHCC97H HCC cells with high metastatic potential had significantly higher expression of PGK1 than Hep3B and Huh7 HCC cells with low metastatic potential. Downregulation of PGK1 expression significantly inhibited the migration (31.2% ± 2.4% vs 12.0% ± 1.3%, t = 21.57, P < 0.01), invasion (58 ± 11 vs 21 ± 8, t = 4.687, P < 0.05), and colony-forming ability (168.6 ± 15.1 vs 118.4 ± 8.1, t = 6.650, P < 0.05) of MHCC97H cells, while overexpression of PGK1 enhanced the migration (62.8% ± 4.4% vs 83.6% ± 6.1%, t = 20.56, P < 0.01), invasion (80 ± 12 vs 121 ± 15, t = 4.603, P < 0.05), and colony-forming ability (52.3 ± 8.6 vs 84.7 ± 9.0, t = 27.18, P < 0.01) of Hep3B cells. The high PGK1 expression group had significantly shorter median disease-free survival time and mean survival time than the low PGK1 expression group (22.00 ± 8.51 vs not reached, P < 0.05; 46.00 ± 16.87 vs not reached, P < 0.01). Conclusions PGK1 is involved in the regulation of metastasis and invasion of HCC cells and can promote the migration and invasion of HCC cells. Therefore, PGK1 may be an important predictor of prognosis and postoperative recurrence in patients with liver cancer.

Aurora A plays a key role in cellular mitosis. It is located in the centrosome and spindle, and is mainly involved in the processes of centrosome maturation and separation, bipolar spindle assembly, and the regulation of mitotic progression. Recent studies have suggested that Aurora A is involved in tumorigenesis and tumor development through multiple mechanisms. Overexpression of Aurora A could cause abnormal centrosome amplification, aneuploidy formation, and G2/M checkpoint defects, which result in chromosome instability and imbalance between cell division and apoptosis, and eventually leads to abnormal cell proliferation. Aurora A also participates in the regulation of the p53 and BRCA1 pathways, leading to suppressor gene dysfunction and changes in cell viability, and it induces telomerase activity by upregulating c-Myc, resulting in tumorigenesis. In addition, Aurora A also induces drug resistance in liver cancer cells. Thus, Aurora A has gradually become a new target for cancer therapy in recent years. This paper has summarized the recent studies on Aurora A, and reviewed its biological functions in cell mitosis and roles in liver tumorigenesis.

Chemotherapy remains the main treatment for many cancer patients. However, P-glycoprotein (P-gp) mediated multidrug resistance poses severe challenges to current chemotherapies. As ideal vectors to overcome drug resistance, nanovehicles are extensively explored for cancer treatment by diverting P-gp mediated drug efflux mechanisms. Surface engineering of nanocarriers has attracted great attention for targeted therapeutic delivery. The folate receptors, one of the most researched targets in cancer therapeutics, are over-expressed in several carcinomas. And folate has become one of the most investigated ligands in cancer therapeutic direction due to its small size, easy conjugation to nanocarriers, nontoxic, nonimmunogenic nature, and well stability in storage or in circulation. This review discussed the current status of folate functionalized nanoparticles in diverting P-gp mediated drug efflux mechanisms.

OBJECTIVETo investigate the correlation between magnetic resonance imaging (MRI) characteristics and intrahepatic recurrence of small hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA).

METHODSA total of 34 patients with 39 small HCC who underwent RFA were included in our study.MRI characteristics were compared between the recurrence group and the non-recurrence group; and a subgroup comparison was also made between the solitary recurrence group and the multiple recurrence group.Kaplan-Meier test,t-test/Mann-Whitney U test,Fisher's exact test and F-test were used for statistical analyses.

RESULTSThe median follow-up period was 25 (4-45) months and recurrence was observed in 19 (55.9%) of the patients.The 12-and 24-month cumulative recurrence-free survival rates were 71.3% and 51.8%,respectively.The recurrence group had a higher prevalence of lack of tumour capsule before RFA (P =0.017),no or disrupted periablational enhancement within 24 hours after RFA (P =0.012),and a smaller ablative margin (P=0.037).Meanwhile,the average apparent diffusion coefficient value within 24 hours after RFA was higher in the multiple recurrence group (1.57 * 10-3mm2/s) than in the solitary recurrence group (1.34 * 10(-3) mm2/s) (P =0.04).

CONCLUSIONMRI can provide early noninvasive findings useful for advanced warning ofintrahepatic recurrence after RFA.

Carcinoma, Hepatocellular ; pathology ; Catheter Ablation ; Humans ; Kaplan-Meier Estimate ; Liver Neoplasms ; pathology ; Magnetic Resonance Imaging ; Recurrence ; Retrospective Studies ; Survival Rate ; Treatment Outcome

Sorafenib is a novel oral multikinase inhibitor that inhibits Raf kinase because of its anti-proliferative property. Sorafenib also inhibits receptor tyrosine kinases of multiple proangiogenic factors, such as VEGFR-1/2/3 and PDGFR-β. The combina-tion of both its anti-proliferative and anti-angiogenic properties makes sorafenib an attractive agent in cancer treatment. To date, sorafenib is the only approved systemic treatment for patients with hepatocellular carcinoma. The most common adverse events of this inhibitor included hand-foot skin reactions, nausea, diarrhea, weight loss, and hypertension. These adverse events can severely affect patient compliance, which may negate the effect of therapy. Correct understanding and treatment of these adverse events can improve clinical outcome. This paper discusses the clinical aspect of sorafenib-induced adverse events and the molecular basis behind their toxic-ity. Recommendations for the management of the adverse effects are also provided.