In June 2017,National Health Commission of the People's Republic of China released Guidelines for the diagnosis and treatment of primary liver cancer(2017 edition),which provided important recommendations for the diagnosis,staging,and treatment of liver cancer.Since then,high-level evidence in line with the principles of evidence-based medicine has been continuously obtained from the research on primary liver cancer in China and globally.Therefore,National Health Commission released Guidelines for the diagnosis and treatment of primary liver cancer(2024 edition).This article gives an interpretation of the updated key points in the guidelines,in order to better guide clinical practice.

The result of liver transplantation (LT) for the treatment of hepatocellular carcinoma (HCC) is constrained by the high rates of tumor recurrence and metastasis. To remove this bottleneck, precise patient selection is crucial for individuals with HCC, and the goal of down-staging therapy is to transform patients exceeding transplantation criteria into suitable candidates. The difficulty in treating tumor recurrence and metastasis post-transplantation calls for more breakthroughs. Immunotherapy, as an emerging treatment modality, requires further exploration to enhance its safety and efficacy. The immunosuppression strategy is also a key factor in reducing tumor recurrence, requiring precise assessment and balanced control.

Objective:To investigate the influence of COX-2 expression in hepatocellular carcinoma (HCC) on the infiltration and immune response of conventional type 1 dendritic cells (cDC1).Methods:Clinicopathological data from 111 HCC patients undergoing radical hepatectomy at Peking University People's Hospital from Jan 2016 to Jun 2017 were retrospectively analyzed. Immunofluorescence staining was employed to evaluate the cDC1 infiltration and COX-2 expression in tumor tissues. Patients were divided into two groups based on cDC1 infiltration: cDC1 enrichment and cDC1 depletion, and the correlation between COX-2 expression and cDC1 infiltration was analyzed. Single-cell sequencing of HCC tumor tissues was used to further investigate the correlation between PTGS2, the encoding gene of COX-2, and cDC1 infiltration. Hematopoietic stem cells (HSC) were utilized for in vitro generation of cDC1. HSC-derived cDC1s were sorted by FACS and cocultured with HCC cell line SNU423. Celecoxib, a selective COX-2 inhibitor, was used to suppress the COX-2 expression in HCC cell line SNU423. The functions of cDC1 were explored by FITC-dextran uptake assay, flow cytometry, and Luminex multiplex cytokine assay. Results:COX-2 expression was significantly higher in the cDC1 depletion group ( n=73) compared to the cDC1 enrichment group ( n=38) ( P=0.004 2). Patients with higher PTGS2 expression had significantly lower proportion of cDC1. Increased cDC1 infiltration in the HCC tumor microenvironment correlated with improved patient overall survival rates ( P=0.037) and disease-free survival rates ( P=0.048). Results from FITC-dextran uptake assay, flow cytometry, and Luminex assay indicated that cDC1 co-cultured with HCC showed significantly reduced antigen uptake function, co-stimulatory molecule expression, and cytokine secretion, but partially abrogated with celecoxib treatment. Conclusions:The intratumoral infiltration of cDC1 is positively correlated with favorable prognosis in HCC patients. Elevated COX-2 expression in HCC impedes the intratumoral accumulation of cDC1 and compromises their immune response capabilities. COX-2 inhibitors hold promise for enhancing cDC1 function in HCC.

Humans ; Consensus ; Liver Neoplasms/therapy* ; China

Objective:To investigate the expression level between AT-Rich Interaction Domain 1A(ARID1A) in intrahepatic cholangiocarcinoma (ICC) and the correlation with tumor microenvironment.Methods:The clinicopathological and survival data of 110 ICC patients undergoing radical hepatectomy in Peking University People's Hospital from Jan 2015 to May 2021 were retrospectively analyzed. Immunohistochemical staining was used to detect the expressions of ARID1A , programmed cell death 1 ligand 1( PD-L1) in tumor tissues , programmed cell death protein 1(PD-1) and cluster of differentiation 8(CD8) in the microenvironment. The relationship between ARID1A expression and PD-L1, PD-1, CD8 protein expression was analyzed.Results:Twenty seven patients did not express ARID1A, absence of ARID1A was associated with high PD-L1, PD-1 and CD8 expression ( P<0.05). Multivariate analysis showed ARID1A expression, preoperative CEA level,preoperative CA19-9 level, lymph node metastasis and tumor number were independent risk factors. Conclusion:Absent expression of ARID1A suggests poor prognosis of ICC patients, high expression of PD-L1,PD-1 and CD8 protein in ICC tumor microenvironment with ARID1A-deficient expression suggests a possible prognosis benefit by using anti-PD-1, anti-PD-L1 and other immunotherapy regimens.

Most patients with liver cancer in China cannot get radical surgical treatment at the time of diagnosis, and the breakthrough of immunotherapy for liver cancer in recent years has brought new hope to the patients with advanced liver cancer. In the field of liver transplantation for liver cancer, immunotherapy has attracted much attention because of its dual role in tumor immunity and transplantation immunity. There are also innovative applications of immunotherapy in preoperative down-staging treatment and the treatment of tumor recurrence after transplantation. In the era of immunotherapy, how to apply the thinking of transplant oncology to benefit liver cancer patients undergoing liver transplantation is a brand-new topic, and this requires multidisciplinary collaboration in clinical practice to explore the best treatment strategies for liver cancer patients undergoing liver transplantation and finally improve the prognosis of patients with advanced liver cancer.

Objective To investigate the clinical manifestations,imaging features and prognosis of mixed liver cancer.Methods The clinical and pathological data of 26 patients with combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) pathologically diagnosed after liver resection were retrospectively analyzed,and the relevant factors affecting the prognosis were statistically analyzed.Results Of the 26 cHCC-CC patients,19 were on background of chronic viral hepatitis,including 17 chronic viral hepatitis B and 2 chronic viral hepatitis C.There were 18 cases having AFP≥20ng/ml,9 cases were with carbohydrate antigen 199 (CA199) ≥ 37U/ml,and 5 cases with carcinoembryonic antigen (CEA) ≥5ng/ml.The 1-,3-,and 5-year postoperative survival rates were 68.8％,34.4％,and 17.4％.Multivariate analysis showed that serum CA199≥37U/ ml(x2 =5.687,P =0.019) was an independent risk factor for patients' survival.Conclusion Most cHCC-CC is found in association with chronic viral hepatitis.Serum CA199 ≥37U/ml is an independent risk factor affecting patients survival.

Objective To assess the efficacy and side effects of intravesical instillation of BCG after transurethral resection of the bladder tumor (TURBT) in non-muscle invasive bladder cancer (NMIBC) patients.Methods The clinical data of patients treated with BCG 120 mg per course induced perfusion or more after TURBT from December 2013 to October 2016 in 18 hospitals of northeast China region,were analyzed retrospectively.The first part,data of 106 patients with moderate,high-risk NMIBC were collected.A total of 83 patients were male,while the other 23 patients were female.The average age was 66.7 years old.The clinical staging were T1 in 86(81.1％) cases,Ta in 20(18.9％) cases and carcinoma in situ in 6 (5.7％) patients.Intravesical instillation of BCG was executed after transurethral resection of the bladder tumor.The incidence rate of recurrence and progression during more than 6 months' follow-up time were observed.Multivariate analyses were done by using logistic analysis and Cox proportional hazards regression model with Kaplan-Meier method.The second part,treatment compliance of 276 patients with bladder cancer,including moderate/high-risk NMIBC in 263 cases,moderate/high-risk NMIBC followed with renal pelvis/ureteral carcinoma in 8 cases were and moderate/high-risk NMIBC with renal pelvis/ureteral carcinoma in 5 cases who treated with BCG after the surgeries,were observed.Patients consisted of 211 males and 65 females with average age of 68.3 years.Results With a median follow-up of 12 months,9 (8.5％) patients experienced tumor recurrence and 2 (1.9％) patients were found progression in the first part.The one-year cancer free recurrence rate of the patients was 91.5％.Statistically significant prognostic factors for recurrence identified by multivariable analyses were prior recurrence of the tumors (OR =3.214,95％CI0.804-12.845,P =0.099).In the second port,an incidence rate of adverse effects was 64.1％ (177/276).The Ⅲ/Ⅳ degree complications were occurred in 11 patients and satisfactory outcomes achieved with active treatment.A total of 36 patients withdrawal with the major causes were recurrence and progression of bladder tumor in 12 cases (4.4 ％),9 cases (3.3 ％) with economic reasons and 11 cases (4.0％) with serious complications.Conclusions NMIBC patients treated with intravesical BCG therapy have approving cancer free recurrence rates and acceptable adverse effects.Prior recurrence may be prognostic factor of recurrence after intravesical BCG therapy.

Objective: To explore the characteristics of tumor recurrence after liver transplantation in patients with hepatocellular carcinoma (HCC) associated with hepatitis B and to analyze the risk factors that influence the recurrence and prognosis. Methods: The clinicopathological and survival data of 162 patients with hepatitis B –associated liver cancer who underwent liver transplantation in Peking University People’s Hospital from January 2002 to December 2016 were retrospectively analyzed. The postoperative survival rate (OS) and tumor free survival rate (DFS) was statistically analyzed by using the log-rank test. Univariate analysis was performed for various clinicopathological indicators, and the Cox proportional risk regression model was used for multivariate analysis. Results: Univariate analysis showed that the age of the recipients (P_OS = 0.047, P_DFS = 0.045), the maximum tumor size (P < 0.001, P_DFS < 0.001), preoperative AFP levels (P_OS < 0.001, P_DFS < 0.001), preoperative HBV-DNA levels (P_OS = 0.035, P_DFS = 0.029), vein tumor thrombosis (P_OS < 0.001, P_DFS < 0.001), and tumor differentiation degree (P_OS <0.001, P_DFS < 0.001) were associated with overall prognosis and tumor recurrence. Multivariate analysis revealed that preoperative AFP levels (P_OS = 0.014, P_DFS = 0.013), the maximum tumor size (P_OS < 0.001, P_DFS = 0.001), vein tumor thrombosis (P_OS = 0.012, P_DFS < 0.004), and tumor differentiation degree (P_OS = 0.004, P_DFS = 0.009) were independent risk factors affecting overall prognosis and tumor recurrence. Conclusion The major prognostic factors linked to tumor biological characteristics after liver transplantation in HBV-related HCC patients are preoperative AFP levels, the largest tumor size, and vein tumor thrombosis and tumor differentiation degree.