Background: The treatment response to radiotherapy of hepatocellular carcinoma (HCC) primary tumors and different types of tumor thrombus under identical radiation doses remains uncertain. Objectives: This multicenter study aimed to evaluate and compare the radiotherapy responses of primary tumors (PT), portal vein tumor thrombus (PVTT), and hepatic vein tumor thrombus (HVTT) in HCC patients and to establish a prediction model for treatment response. Design: This multicenter retrospective cohort study analyzed the treatment response of 242 HCC patients with macrovascular tumor thrombus who received radiotherapy combined with systemic therapy from five hospitals. Methods: The objective response rate (ORR) was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) V1.1 and modified RECIST (mRECIST) criteria. Independent factors of treatment response were identified by logistic regression analysis and used to create a nomogram. Model performance was evaluated through the area under the receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis (DCA). Results: Among the entire cohort, the ORRs evaluated by RECIST were 51.65% for PT, 56.32% for PVTT, and 81.93% for HVTT; the ORRs evaluated by mRECIST were 55.79% for PT, 62.63% for PVTT, and 87.95% for HVTT. Both criteria demonstrated that HVTT exhibited significantly higher response rates than PT and PVTT ( p < 0.001). Multivariate logistic regression analysis identified irradiated primary tumor size, biologically effective dose, and tumor thrombus type as independent predictors of response in the radiation-field lesions. The developed nomogram showed good discriminative ability with an AUC of 0.788 in the training cohort and 0.736 in the external validation cohort. Calibration and DCA indicated that the model provided reliable predictions and substantial clinical benefit. Conclusion: Under identical radiation doses, macrovascular tumor thrombus, especially HVTT, is associated with a higher response rate to radiotherapy compared to HCC primary tumors. The nomogram demonstrated good predictive performance, but prospective validation in larger cohorts is still warranted.

External beam radiotherapy (EBRT)-based combination therapy yields heterogeneous survival outcomes in unresectable hepatocellular carcinoma (uHCC), underscoring the need for precise prognostic stratification. We conducted a multicenter retrospective study across six institutions, enrolling 875 uHCC patients treated with either EBRT combined with systemic therapy (ES cohort, n = 383) or EBRT combined with transarterial chemoembolization (TACE) and systemic therapy (ETS cohort, n = 492). After propensity score matching, median overall survival was significantly prolonged in the ETS cohort compared to the ES cohort (24.0 vs. 19.0 months; HR = 0.73, P < 0.0001). The multimodal deep learning model, TRIM-uHCC (transformer-based risk-stratification integrated multimodal model for uHCC), was developed to stratify patients into high-, intermediate-, and low-risk groups. Prognostic performance was compared with current guideline-based staging systems (BCLC/CNLC/AJCC-TNM) and deep learning models (Swin-Transformer/ViT/ResNet50/ResNeXt50) using the C-index and time-dependent AUC. TRIM-uHCC model showed significantly superior prognostic prediction performance compared to current guideline standards (C-indices: 0.71-0.79 vs. 0.51-0.61, all P < 0.0001) and deep learning models (C-indices: vs. 0.62-0.75, P < 0.0001-0.106) in the ETS and ES cohorts. Based on TRIM-uHCC, 8.8 % (29/331) of patients in the ES cohort could potentially achieve improved survival by adjusting to ETS, whereas 7.9 % (26/331) of patients in the ETS cohort were recommended to switch to ES treatment. Collectively, the TRIM-uHCC model offers more accurate individualized prognostic stratification than current guideline standards and other deep learning models, providing valuable decision-making support for EBRT-based combination therapies.

The development of the immune system (ISD) plays a pivotal role in both the genesis and progression of tumors, yet its specific functions in hepatocellular carcinoma (HCC) and the mechanisms behind sorafenib resistance remain elusive. In our investigation, we initially created 167 algorithms by amalgamating 10 distinct machine learning algorithms to identify an optimal and potent ISD-related signature (ISDRS), which proved to be superior to 73 previously published signatures. Moreover, we found that resistance to sorafenib was associated with both ISD levels and ISDRS. These, in turn, exhibited a positive correlation with the infiltration of T regulatory cells (Tregs) and a negative correlation with the levels of IL-6/IL-6R. Furthermore, through single-cell analysis, we uncovered a novel Tregs subgroup that contributes to sorafenib resistance and identified BATF as a potential biomarker for this subgroup.

The combination of immune checkpoint inhibitors (ICIs) with anti-angiogenic agents has demonstrated efficacy in the clinical treatment of advanced hepatocellular carcinoma (HCC). This study seeks to elucidate the underlying mechanisms that contribute to the enhanced therapeutic effects of apatinib when administered in conjunction with ICIs for the treatment of advanced HCC. The effects of apatinib on the viability, clonal formation, and apoptosis of HCC cells were evaluated through in vitro experiments. Meanwhile, in vivo experiments were conducted to substantiate these findings and further investigate the synergistic effects of apatinib with PD-1 inhibitors on the immune microenvironment, particularly by activating the signal transducer and activator of transcription 1 (STAT1)/natural killer (NK) cell axis. In vitro experiments demonstrated that apatinib significantly suppressed HCC cell viability, colony formation capacity, and induced apoptosis. In tumor-bearing mouse models, the combination of apatinib with PD-1 inhibitors showed superior tumor growth inhibition compared to monotherapy (combination group exhibited the smallest tumor volume and 100% survival rate vs. 0% in PBS group, p < 0.001). Western blot and immunohistochemical analyses revealed STAT1/NK axis activation through combination therapy (upregulated STAT1 expression with increased CD8+T cell and NK cell infiltration, p < 0.001). In the mechanism discussion, STAT1-overexpressing Hepa1-6 cells confirmed the antitumor effect of STAT1 in the combination therapy. Subsequently, we validated our findings using the STAT1 inhibitor fludarabine or the NK cell-depleting agent Asialo GM1. Furthermore, combination therapy remodeled the tumor microenvironment by reducing CA IX (hypoxia marker), CD31 (angiogenesis marker), and α-SMA (stromal activation marker) expression (p < 0.05). Apatinib enhances the efficacy and responsiveness of PD-1 inhibition via the STAT1/NK axis, while the combination therapy remodels the tumor microenvironment to potentiate anti-tumor effects.

Hepatocellular carcinoma (HCC) treatment remains challenging, particularly for immune checkpoint inhibitors (ICIs) non-response patients. Spatial transcriptome (ST) data and machine learning algorithms offer new insights into understanding HCC heterogeneity and ICIs resistance mechanisms. Utilizing ST data from HCC patients on ICIs treatment, we analyzed pathway activity and immune infiltration. We combined 167 machine learning models to develop a G2M-checkpoint related signature (G2MRS) based on differential gene expression. The four cohorts and in-house cohort was used to validate G2MRS, and KPNA2’s role was further examined through in vitro experiments in two different liver cancer cell lines. Our analysis revealed a distinct suppressive immune barrier structure (SIBS) in ICIs non-response patients, associated with upregulated G2M-checkpoint levels. G2MRS, consisting of KPNA2, CENPA, and UCK2, accurately predicted HCC prognosis and ICIs response. Further in vitro experiments demonstrated KPNA2’s role in regulating migration, proliferation, and apoptosis in liver cancer. This study highlights the importance of spatial heterogeneity and machine learning in refining HCC prognosis and ICIs response prediction. G2MRS and KPNA2 emerge as promising biomarkers for personalized HCC management.

Cancer cachexia is a debilitating syndrome that profoundly impacts survival, yet its systemic metabolic characteristics and prognostic drivers in locally advanced rectal cancer (LARC) remain poorly defined. This study aimed to comprehensively profile the host’s metabolic response in LARC-associated cachexia using [18 F]FDG PET-CT and to evaluate its prognostic implications. In this retrospective analysis, 131 LARC patients were stratified by cachexia status. Receiver operating characteristic (ROC) analysis was used to identify the most discriminative metabolic parameters. Structural equation modeling was applied to assess the mediating role of systemic metabolism between primary tumor metabolic tumor volume (MTV) and cachexia. Survival analysis was conducted using Kaplan–Meier curves and Cox proportional hazards models, with overall survival (OS) as the primary endpoint. Cachectic patients displayed a distinct systemic metabolic profile. First, a coordinated reduction in aortic, hepatic, and pancreatic FDG uptake emerged as a hallmark of systemic metabolic suppression. Conversely, adipose tissue exhibited a paradoxical hypermetabolism that was not only preserved but markedly accentuated across all depots after normalization to aortic uptake, revealing a consistent and systemic shift in metabolic partitioning. Path analysis within our model revealed significant direct paths from hypometabolism in the aorta and pancreas to cachexia. The effect of primary tumor MTV was channeled through both direct and indirect routes, with subcutaneous fat metabolism exhibiting the most substantial mediating effect. Critically, survival analysis pinpointed subcutaneous fat glucose uptake (SubFat SUVmax) from this metabolic network, validating it in multivariate analysis as a powerful independent prognostic factor that surpassed the clinical diagnosis of cachexia. This study delineates a comprehensive metabolic landscape of cachexia in LARC, revealing a systemic energy imbalance in which adipose tissue hypermetabolism acts as both a key pathophysiological mediator and a superior prognostic biomarker compared to clinical cachexia diagnosis. These findings support a shift from phenotypic to metabolic stratification in the management of cancer cachexia.

To identify tumor size could be taken as a decision-making factor in the management of preoperative radiotherapy (RT) for patients with locally advanced rectal cancer (LARC). In this study, patients diagnosed with rectal adenocarcinoma and staged at II/III from the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2014 were included. Kaplan-Meier curve was conducted to investigate the overall survival (OS) between subgroups with different tumor sizes and the relationship between the tumor size and the efficacy of preoperative RT. There were 1402 patients eligible for this study, of whom 1105 (78.8

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.

This study aims to compare the efficacy and safety of radiotherapy (RT) and transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) with inferior vena cava/right atrium tumor thrombus (IVC/RATT) treated with lenvatinib and camrelizumab. HCC with IVC/RATT from four hospitals were enrolled in this retrospective study. The patients were divided into RT group and TACE group. Stabilized inverse probability of treatment weighting (sIPTW) was used to minimize bias. The primary endpoints were overall survival (OS) and progression free survival (PFS). The second endpoints were objective response rate (ORR) and disease control rate (DCR). In addition, safety was assessed by treatment-related adverse events (TRAEs) between the two groups. Among 108 patients included in this study, 48 patients in TACE group and 60 patients in RT group. The median follow-up time was 24.8 months. After the application of sIPTW, baseline characteristics were well-balanced between the two groups. Before and after sITPW, the median OS and median PFS in the RT group were significantly longer than in the TACE group. Multivariate Cox analysis showed that RT was an independent prognosis factor of both OS and PFS. There was no significant difference between two groups in overall response, while IVC/RATT response rate of RT group was significantly higher than TACE group. Incidence rate of TRAEs in two groups were similar. In combination with lenvatinib and camrelizumab, RT significantly improves the prognosis of HCC with IVC/RATT compared to TACE, with a comparable safety profile.

Radiotherapy (RT) has been reported to induce abscopal effect in advanced hepatocellular carcinoma (HCC), but such phenomenon was only observed in sporadic cases. Here, we demonstrated that subcutaneous administration of Toll-like receptor 3 (TLR3) agonist poly(I:C) could strengthen the abscopal effect during RT through activating tumor cell ferroptosis signals in bilateral HCC subcutaneous tumor mouse models, which could be significantly abolished by TLR3 knock-out or ferroptosis inhibitor ferrostatin-1. Moreover, poly(I:C) could promote the presentation of tumor neoantigens by dendritic cells to enhance the recruitment of activated CD8+ T cells into distant tumor tissues for inducing tumor cell ferroptosis during RT treatment. Finally, the safety and feasibility of combining poly(I:C) with RT for treating advanced HCC patients were further verified in a prospective clinical trial. Thus, enhancing TLR3 signaling activation during RT could provide a novel strategy for strengthening abscopal effect to improve the clinical benefits of advanced HCC patients.

BackgroundHepatocellular carcinoma (HCC) poses a significant global health challenge due to its poor prognosis and limited therapeutic modalities. Anoikis and ErbB signaling pathways are pivotal in cancer cell proliferation and metastasis, but their relevance in HCC remains insufficiently explored.MethodsThis study evaluates the prognostic significance of anoikis and ErbB signaling pathways in HCC by utilizing data from The Cancer Genome Atlas (TCGA), the International Cancer Genome Consortium (ICGC), three additional independent validation cohorts, and an in-house cohort. Advanced bioinformatics analyses and 167 machine learning models based on leave-one-out cross-validation (LOOCV) were used to predict HCC prognosis and assess outcomes of immune-targeted therapies. Additionally, key biological processes of the anoikis and ErbB signaling pathways in HCC were further investigated.ResultsThe single sample Gene Set Enrichment Analysis revealed a strong correlation between upregulated ErbB signaling in high anoikis-expressing tumors and poor clinical outcomes. The development of the Anoikis-ErbB Related Signature (AERS) using the LASSO + RSF model demonstrated robust predictive capabilities, as validated across multiple patient cohorts, and proved effective in predicting responses to immune-targeted therapies. Further investigation highlighted activated NOTCH signaling pathways and decreased macrophage infiltration was associated with resistance to sorafenib and immune checkpoint inhibitors, as evidenced by bulk and single-cell RNA sequencing (scRNA-seq).ConclusionAERS provides a novel tool for clinical prognosis and paves the way for immune-targeted therapeutic approaches, underscoring the potential of integrated molecular profiling in enhancing treatment strategies for HCC.

Abstract Objective To evaluate the prognostic significance of microscopic bile duct invasion (MiBDI) in hepatocellular carcinoma (HCC) following R0 resection. Patients and Methods Patients who underwent R0 resection for HCC at nine medical centers were stratified into five groups: neither bile duct nor vascular invasion (MiBDI−MVI−), microscopic bile duct invasion alone (MiBDI+MVI−), both microscopic bile duct and vascular invasion (MiBDI+MVI+), microscopic vascular invasion alone (MiBDI−MVI+), and macroscopic bile duct invasion (MaBDI). Overall survival (OS) was assessed using Kaplan–Meier analysis, and independent risk factors of OS were determined using Cox proportional hazards models. Results A total of 377 HCC cases were analyzed. The OS for MiBDI+MVI‐ was similar to that of MiBDI−MVI− (p > 0.05) but better than MiBDI+MVI+, MiBDI−MVI+, and MaBDI (all p < 0.05). Multivariate analysis indicated that MiBDI was not an independent risk factor for OS, while MVI and MaBDI were. Conclusions Overall survival (OS) in patients with MiBDI was superior to those with MVI and MaBDI. Isolated MiBDI did not influence OS in patients with HCC after R0 resection.

Objective:To analyze and predict the clinical efficacy of rigid choledochoscopic percutaneous transhepatic biliary fistulation (PTBF) lithotripsy for the treatment of hepatolithiasis.Methods:Databases including PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang were searched for literatures from January 1, 1990 to March 1, 2022 on rigid choledochoscopic PTBF lithotripsy for hepatolithiasis studies. The primary outcomes including the final clearance rate, recurrence rate and overall postoperative complication rate, were analyzed by the random effects model in meta analysis and Bayesian network. The Markov Chain Monte Carlo was used for evaluation and prediction.Results:Fifteen articles were ultimately included, involving 1 296 patients, of which 1 008 patients were clearly shown to have complex intrahepatic bile duct stones in the literature [divided into two groups, the percutaneous transhepatic one-step biliary fistulation (PTOBF) stone removal group ( n=568) and the percutaneous transhepatic two-step biliary fistulation (PTTBF) stone removal group ( n=440)]. The results of Bayesian single-arm meta-analysis showed that the final clearance rate, recurrence rate and overall postoperative complication rate of PTOBF for hepatolithiasis were 84.19% (95% HPD: 79.08%-88.93%), 15.79% (95% HPD: 11.01%-21.07%) and 10.85% (95% HPD: 7.93%-14.21%). For complex hepatolithiasis, the final clearance rate, recurrence rate and overall postoperative complication rate of PTOBF were 82.58% (95% HPD: 75.46%-88.83%), 17.99% (95% HPD: 11.51%-25.45%), 10.34% (95% HPD: 6.42%-15.40%). For PTTBF, they were respectively 73.56% (95% HPD: 65.67%-80.30%), 29.48% (95% HPD: 23.13%-36.01%), 11.42% (95% HPD: 6.18%-17.67%). In comparison to PTTBF, the patients treated with PTOBF has a higher clearance rate ( OR=1.74, 95% CI: 1.17-2.60) and a lower recurrence rate ( OR=0.56, 95% CI: 0.37-0.84)but the overall complication rate did not improve ( OR=1.03, 95% CI: 0.66-1.62). Conclusions:Rigid choledochoscopic PTBF lithotripsy for hepatolithiasis is safe, effective and feasible. For complex hepatolithiasis, PTOBF has a higher clearance rate and a lower recurrence rate.

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.

Background: The efficacy and safety of tyrosine kinase inhibitors (TKIs) combined with anti-PD-1 antibodies (alpha-PD-1) in advanced hepatocellular carcinoma (HCC) with high hepatitis B virus (HBV) DNA levels (>500 IU/ mL) remain unclear.Methods: We retrospectively assessed patients from seven medical institutions diagnosed with HBV-related HCC, undergoing treatment with TKIs and alpha-PD-1 in conjunction with antiviral therapies. Based on HBV-DNA levels, patients were categorized into either high (HHBV-DNA, >500 IU/mL) or low HBV-DNA (LHBV-DNA, <500 IU/ mL) cohorts Propensity score matching (PSM) was used to minimize baseline imbalance between groups.Results: 149 patients were included, with 66 patients exhibiting HBV-DNA > 500 IU/mL and 83 patients presenting HBV-DNA < 500 IU/mL. Compared with the LHBV-DNA cohort, the HHBV-DNA cohort had a greater incidence of serum HBeAg positivity, tumor diameter >= 10 cm, and vascular invasion. Following PSM, 57 individuals were enrolled in each group. Oncological outcomes were comparable between HHBV-DNA and LHBVDNA cohorts before and after PSM. Before PSM, the median PFS and OS were 6.1 months and 17.5 months in the HHBV-DNA cohort and 6.7 months and 19.3 months in the LHBV-DNA cohort (all P > 0.05). After PSM, the median PFS and OS were 6.0 months and 19.5 months in the HHBV-DNA cohort and 6.0 months and 17.1 months in the LHBV-DNA cohort, respectively (all P > 0.05). Safety profiles were equivalent across cohorts with no fatal incidents reported. Seven patients (4.7 %) had HBV reactivation.1 (0.7 %) from HHBV-DNA and 6 (4.0 %) from LHBV-DNA (P = 0.134). Only one patient developed HBV-related hepatitis.Conclusions: The effectiveness and safety of TKIs plus alpha-PD-1 in advanced HCC with HBV-DNA > 500 IU/mL were not compromised in the context of concomitant antiviral therapy.

Purpose This study aimed to assess the efficacy and safety of adjuvant transarterial chemoembolization (TACE) plus tyrosine kinase inhibitor (TKI) treatment in patients with hepatocellular carcinoma (HCC) with a high risk of early recurrence after curative resection. Patients and Methods Patients from multiple centres were divided into postoperative adjuvant TACE with (n=57) or without (n=142) TKI administration groups. The disease-free survival (DFS) curve was depicted by the Kaplan–Meier method, and the difference between the two groups was tested using the log rank test. Univariate and multivariate Cox analyses were performed to identify independent risk factors for DFS. Additionally, three propensity score analyses were performed to minimise the potential confounding factors to facilitate a more reliable conclusion. Adverse events (AEs) were assessed according to the Common Terminology Criteria for Adverse Events, version 4.0. Results The 1-and 2-year DFS rates of the TACE plus TKI treatment group were 45.5% and 34.9%, respectively, which were significantly better than those of the TACE alone group (26.8% and 18.3%, respectively). Multivariate analysis identified adjuvant TACE plus TKI treatment as an independent prognostic factor for DFS (hazard ratio: 0.611, 95% confidence interval: 0.408–0.915, P=0.017). Further analysis based on the various propensity score methods yielded similar results. Subgroup analysis showed that patients with tumour diameter ≥5 cm, tumour number <3, absence of hepatic vein tumour thrombus and bile duct tumour thrombus, ruptured tumours, and stage IIIB could benefit more from TACE plus TKI treatment (all P<0.05). Some patients (33.33%) experienced grade ≥3 AEs in the TACE plus TKI group. Conclusion TACE plus TKI treatment can reduce the incidence of early recurrence with tolerable adverse events in HCC patients at high risk of recurrence after hepatectomy and may be an appropriate option in postoperative anti-recurrence treatment.

Abstract Background and Objectives Previous studies have reported that the microvascular invasion three‐tiered grading (MiVI‐TTG) scheme is a better prognostic predictor than the two‐tiered microvascular invasion (MiVI) grading scheme in hepatocellular carcinoma. This study aims to explore the prognostic significance of MiVI‐TTG in patients undergoing liver resection for combined hepatocellular‐cholangiocarcinoma (cHCC) and to explore the risk factors for MiVI in cHCC. Methods This research included 208 patients graded as M0, M1, or M2 using the MiVI‐TTG scheme. Predictive performance was assessed by Cox regression analysis, Kaplan–Meier curve with Log rank test, Harrell's c‐index, and time‐dependent areas under the receiver operating characteristic curve (tdAUC). The clinical utility of the two schemes was evaluated by decision cure analysis (DCA). The risk factors for MiVI were evaluated using logistic regression analysis. Results Among 208 cHCC patients, the proportions of M0, M1 and M2 were 38.9%, 36.5%, and 24.5%, respectively. Patients with severe MiVI status had worse recurrence‐free survival and overall survival (OS) based on Kaplan–Meier analysis. M1, M2, and MiVI‐positive were independent risk factors for early recurrence, while M2 and MiVI‐positive were associated with overall survival (OS). MiVI‐TTG had a larger c‐index, tdAUC, and net benefit rate than the two‐tiered MiVI grading scheme for predicting recurrence free survival and OS. AFP≥400 ng/ml was the independent risk factor for MiVI, and satellite nodules were independent risk factors for M2. Conclusions MiVI‐TTG has a greater prognostic value than the two‐tiered MiVI grading scheme in patients undergoing hepatic resection for cHCC.

Background Prophylactic transarterial chemoembolization (p-TACE) is frequently conducted for patients with hepatocellular carcinoma (HCC) in China, but the question of who could benefit from it remains controversial. Hence, we wanted to establish a nomogram model to identify patients eligible for p-TACE. Methods Data from HCC patients receiving R0 resection with or without p-TACE between January 2013 and December 2014 were identified, using primary liver cancer big data, to establish a nomogram model to predict overall survival (OS). Based on the model, Patients receiving R0 resection between January 2015 and December 2015 were divided into three subgroups, and survival curves were constructed using the Kaplan–Meier method and analyzed by the log-rank test among patients in each subgroup. Results A nomogram integrating the neutrophil to lymphocyte ratio, AFP, tumor diameter, and microvascular invasion was developed to predict the OS of patients with HCC receiving R0 resection, and significant differences were observed in the median OS of the subgroups of low-risk (≤20), intermediate-risk (20~120), and high-risk (>120) identified by the current model. This model showed good calibration and discriminatory power in the validation cohort and the external cohort (c-index of 0.669 and 0.676, respectively). In the external cohort, the Kaplan–Meier curves showed that p-TACE could only significantly prolong the median OS of high-risk patients (25.6 vs. 33.7 months, P<0.05), but no differences were observed in any subgroups stratified by the current staging systems (all P>0.05). Conclusion This readily available nomogram model could help guide decisions about p-TACE, but it needs further validation.

PurposeDigestive system carcinoma is one of the most devastating diseases worldwide. Lack of valid clinicopathological parameters as prognostic factors needs more accurate and effective biomarkers for high-confidence prognosis that guide decision-making for optimal treatment of digestive system carcinoma. The aim of the present study was to establish a novel model to improve prognosis prediction of digestive system carcinoma, with a particular interest in transcription factors (TFs).Materials and MethodsA TF-related prognosis model of digestive system carcinoma with data from TCGA database successively were processed by univariate and multivariate Cox regression analyses. Then, for evaluating the prognostic prediction value of the model, ROC curve and survival analysis were performed by external data from GEO database. Furthermore, we verified the expression of TFs expression by qPCR in digestive system carcinoma tissue. Finally, we constructed a TF clinical characteristics nomogram to furtherly predict digestive system carcinoma patient survival probability with TCGA database.ResultsBy Cox regression analysis, a panel of 17 TFs (NFIC, YBX2, ZBTB47, ZNF367, CREB3L3, HEYL, FOXD1, TIGD1, SNAI1, HSF4, CENPA, ETS2, FOXM1, ETV4, MYBL2, FOXQ1, ZNF589) was identified to present with powerful predictive performance for overall survival of digestive system carcinoma patients based on TCGA database. A nomogram that integrates TFs was established, allowing efficient prediction of survival probabilities and displaying higher clinical utility.ConclusionThe 17-TF panel is an independent prognostic factor for digestive system carcinoma, and 17 TFs based nomogram might provide implication an effective approach for digestive system carcinoma patient management and treatment.