Background: The presence of microvascular invasion (MVI) is a significant malignant pathological feature related to recurrence and survival after liver resection for hepatocellular carcinoma (HCC). This study aimed to investigate the relationship between the severity in the grading of MVI and long-term oncological outcomes in patients with early-stage HCC. Methods: A retrospective study was conducted on a prospectively maintained multicenter database on patients who underwent curative resection for Barcelona Clinic Liver Cancer stage 0/A HCC between 2017 and 2020. Patients were classified into three groups according to the severity in the grading of MVI: M0 (no MVI), M1 (1–5 sites of MVI occurring ≤1 cm away from the tumor), and M2 (>5 sites occurring ≤1 cm and/or any site occurring >1 cm away from the tumor). Recurrence-free survival (RFS) and overall survival (OS) were compared among the groups. Results: Of 388 patients, M0, M1, and M2 of the MVI gradings were present in 223 (57.5%), 118 (30.4%), and 47 (12.1%) patients, respectively. The median OS and RFS in patients with M0, M1, and M2 were 61.1, 52.7, and 27.4 months; and 43.0, 29.1, and 13.1 months (both P<0.001), respectively. Multivariable analyses identified both M1 and M2 to be independent risk factors for OS [hazard ratio (HR): 1.682, P=0.003; and HR: 3.570, P<0.001] and RFS (HR: 1.550, P=0.037; and HR: 2.256, P<0.001). Conclusion: The severity in the grading of MVI was independently associated with recurrence and survival after HCC resection. Patients with the presence of MVI, especially those with a more severe MVI grading (M2), require more stringent recurrence surveillance and/or active adjuvant therapy against recurrence.

Background: The high incidence of early recurrence after liver resection (LR) for hepatocellular carcinoma (HCC) is the main obstacle in achieving good long-term survival outcomes. The aim of the present study is to develop a prognostic model in predicting the risk of very early (1-year) recurrence. Material and methods: Consecutive patients who underwent LR for HCC with curative intent at multicenters in China were enrolled in this study. The VERM-pre (the Preoperative Very Early Recurrence Model of HCC) with good performance was derived and validated by internal and external cohorts retrospectively and by another two-center cohort prospectively. Results: Seven thousand four hundred one patients were enrolled and divided randomly into three cohorts. Eight variables (tumor diameter, tumor number, macrovascular invasion, satellite nodule, alpha-fetoprotein, level of HBV-DNA, γ-GT, and prothrombin time) were identified as independent risk factors for recurrence-free survival on univariate and multivariate analyses. The VERM-pre model was developed which showed a high capacity of discrimination (C-index: 0.722; AUROC at 1-year: 0.722)) and was validated comprehensively by the internal, external, and prospective cohorts, retrospectively. Calibration plots showed satisfactory fitting of probability of early HCC recurrence in the cohorts. Three risk strata were derived to have significantly different recurrence-free survival rates (low-risk: 80.4–85.4%; intermediate-risk: 59.7–64.8%; high-risk: 32.6–42.6%). In the prospective validation cohort, the swimming plot illustrated consistent outcomes with the beginning predictive score. Conclusion: The VERM-pre model accurately predicted the 1-year recurrence rates of HCC after LR with curative intent. The model was retrospectively and prospectively validated and then developed as the online tool.

Background The clinical value of alpha-fetoprotein (AFP) in patients with AFP-negative (< 20 ng/ml) hepatocellular carcinoma (HCC) who underwent curative resection remained controversial. Aims To investigate clinical relevance and prognostic effect of preoperative serum AFP level in this subgroup. Methods A total of 1879 patients with AFP-negative HCC who underwent curative resection were included in the study. Overall survival (OS) and disease-free survival (DFS) rate were displayed by Kaplan–Meier method and compared by log-rank test. Multivariate cox proportional hazard regression analysis was used to identify the independent prognostic factors. The prognostic predictive performance was analyzed by time-dependent areas under receiver operating characteristic curve (AUC). Results Even in AFP-negative HCC, patients with high preoperative serum AFP level tended to have multiple tumor (P < 0.001), poorer differentiation of tumor cell (P < 0.001), presence of satellite nodules (P < 0.001), and MVI (P = 0.002). Kaplan–Meier analysis showed the adverse impact of AFP level on prognosis, especially for DFS. Multivariate analysis identified AFP as the independent unfavorable factor for OS and DFS (P < 0.001 for both). Time-dependent AUC analysis showed that the combination with AFP could improve the prognostic predictive performance of 8th AJCC and BCLC staging system. Conclusions AFP was still the surrogate of aggressive behavior of HCC and independent prognostic factor for patients with AFP-negative HCC underwent curative resection. Even combining with such a low level of AFP could significantly improve the predictive performance of conventional staging system.

Background: Patients with Barcelona Clinic Liver Cancer (BCLC) stage 0/A hepatocellular carcinoma (HCC) represent the guideline-recommended population for liver resection; however, treatment strategies for early recurrence after resection remain debated. This study aimed to analyze prognostic factors for survival after recurrence (SAR) in patients with early recurrence following R0 resection of BCLC stage 0/A HCC and to develop evidence-based treatment recommendations integrating time to recurrence (TTR) and BCLC stage at recurrence.Methods: We conducted a retrospective review of 544 patients with early recurrence after R0 resection of BCLC stage 0/A HCC at a tertiary hepatopancreatobiliary academic hospital. Curative treatments included repeat liver resection and ablation, while non-curative treatments comprised transarterial chemoembolization and systemic therapy. Kaplan–Meier methods were applied to estimate SAR, and independent prognostic factors were identified with multivariable Cox regression analysis.Results: The median SAR was 39.4 months, with 1-year, 3-year, and 5-year SAR rates of 81.8%, 52.6%, and 39.0%, respectively. Patients receiving curative treatments demonstrated significantly improved SAR compared with those undergoing non-curative therapies (P < 0.001). Multivariable analysis identified TTR, alpha-fetoprotein level, albumin level, BCLC stage at recurrence, treatment modality, and microvascular invasion in initial tumors as independent prognostic factors for SAR. Subgroup analysis showed that integrating TTR and BCLC stage effectively guided treatment allocation: for BCLC stage A or C disease, treatment should follow current BCLC guidelines, whereas for stage B disease, curative therapy conferred survival benefit when TTR was >6 months but offered no benefit when TTR was ≤6 months.Conclusions: Curative treatments remain an effective option for selected patients with early-recurrent HCC. Treatment allocation based on TTR and BCLC stage at recurrence may optimize outcomes for this population.

Objectives: The purpose of this study was to develop and validate a radiomics nomogram for predicting thymidylate synthase (TYMS) status in hepatocellular carcinoma (HCC) by using Gd-DTPA contrast enhanced MRI. Methods: We retrospectively enrolled 147 consecutive patients with surgically confirmed HCC and randomly allocated to training and validation set (7:3). The TYMS status was immunohistochemical determined and classified into low TYMS (positive cells ≤ 25%) and high TYMS (positive cells > 25%) groups. Radiomics features were extracted from the arterial phases and portal venous phase of Gd-DTPA contrast enhanced MRI. Least absolute shrinkage and selection operator (LASSO) were applied for generating the Rad score. Clinical data and MRI findings were assessed to build a clinical model. Rad score combined with clinical features was used to construct radiomics nomogram. Results: A total of 2260 features were extracted and reduced to 7 features as the most important discriminators to build the Rad score. InAFP was identified as the only independent clinical factors for TYMS status. The radiomics nomogram showed good discrimination in training (AUC, 0.759; 95% CI 0.665–0.838) and validation set (AUC, 0.739; 95% CI 0.585–0.860), and showed better discrimination capability (P < 0.05) compared with clinical model in training (AUC, 0.656; 95% CI 0.555–0.746) and validation set (AUC, 0.622; 95% CI 0.463–0.764). Conclusions: The radiomics nomogram shows favorable predictive efficacy for TYMS status in HCC, which might be helpful for the personalized treatment of HCC.