Primary Hepatocellular Carcinoma Patients Research Articles

Analysis of Survival Rate and Influencing Factors in Surgical Treatment of Primary Hepatocellular Carcinoma

Objective: To study the survival rate of patients with primary hepatocellular carcinoma (HCC) undergoing clinical surgical treatment and various influencing factors, with the aim of further improving the survival rate of primary HCC patients. Methods: Sixty patients with primary hepatocellular carcinoma who underwent liver cancer resection surgery between January 2020 and December 2022 in our hospital were selected. A retrospective analysis was conducted on the patients' clinical characteristics (family medical history, alpha-fetoprotein levels, degree of liver cirrhosis, vascular invasion), treatment methods (surgical techniques, adjunctive therapies), and prognosis. The survival rate of patients and the influencing factors on the postoperative survival rate were analyzed. Results: There was a statistically significant difference in the five-year survival rate comparisons between different liver cirrhosis statuses, tumor sizes, preoperative alpha-fetoprotein levels, vascular invasion statuses, adjunctive treatment methods, and family medical histories (P < 0.05). Comparisons between different genders, ages, tumor locations, tumor pathological types, hepatitis B surface antigens, Child-Pugh classifications of liver function, tumor numbers, and methods of liver cancer resection showed no statistically significant differences (P > 0.05). Liver cirrhosis, tumor size ≥ 5cm, preoperative alpha-fetoprotein level > 400ng/ml, change in alpha-fetoprotein levels pre-and post-surgery, vascular invasion, adjunctive treatment methods, and PLC family medical history are independent factors influencing the survival rate of surgical treatment in primary HCC patients. Conclusion: There are several factors affecting the postoperative survival rate of primary HCC patients. Clinicians need to take a comprehensive approach. For high-risk patients, regular follow-ups are necessary, coupled with early diagnosis and treatment, to improve the prognosis. This approach is worth promoting. 

Impact of Sarcopenia on Prognosis in Primary Hepatocellular Carcinoma Patients Treated with Transcatheter Arterial Chemoembolization: A Single Center Retrospective Study.

Objective: This study aimed to investigate the prognostic effect of sarcopenia on primary hepatocellular carcinoma (HCC) patients after transcatheter arterial chemoembolization (TACE). Methods: This retrospective study enrolled 265 patients diagnosed with HCC who underwent TACE between April 2014 and February 2021. The patients were divided into two groups: the sarcopenia group (n=133) and the non-sarcopenia group (n=132). The study analyzed the differences in overall survival (OS) and progression-free survival (PFS) using Kaplan-Meier curves. The independent risk factors for OS and PFS were determined using univariate and multivariate Cox regression analysis. Based on these factors, the study constructed a prognostic risk grading system. Results: At 3 and 6 months post-TACE, the prognoses of the sarcopenia group were worse than that of the non-sarcopenia group according to the mRECIST criteria. Kaplan-Meier curves showed that the cumulative OS and PFS rate in the non-sarcopenia group were significantly higher compared to the sarcopenia group (HR=3.319, 95%CI: 2.283-4.824, Log-rank P < 0.001; HR=0.631, 95%CI: 0.486-0.820, Log-rank P < 0.001). Sarcopenia, maximal tumor diameter, and AFP ≥ 200 ng/mL were independent risk factors for OS and PFS. The prognostic risk grading system based on sarcopenia, AFP ≥ 200 ng/mL, and maximal tumor diameter≥8.9 cm showed significant differences in prognosis between risk groups. Conclusion: Sarcopenia had excellent predictive value for OS and PFS in patients after TACE, and AFP ≥ 200 ng/mL and maximal tumor diameter were also independent risk factors for a poor prognosis. The prognostic risk grading system based on sarcopenia, AFP, and maximal tumor diameter had good guiding value for the prognosis of patients.

Sorafenib as first-line treatment for patients with primary hepatocellular carcinoma: an outcome evaluation.

To evaluate the clinical outcomes following first-line treatment with sorafenib in patients with primary hepatocellular carcinoma (HCC). This retrospective cohort study enrolled patients with primary HCC that had been treated with sorafenib. Their data were collected from the hospital medical records database at three time-points: after three cycles, after six cycles and at the end of the sorafenib treatment regimen. The starting dose was 800 mg/day sorafenib but this could be reduced to 600 mg/day or 400 mg/day if patients developed adverse events (AEs). A total of 98 patients participated in the study. Of these, nine (9.2%) had a partial response, 47 patients (48.0%) had stable disease and 42 patients (42.9%) had progressive disease. The overall disease control rate was 57.1% (56 of 98 patients). Median progression-free survival for the overall cohort was 4.7 months. The most common AEs were hand-foot skin reaction (49 of 98 patients; 50.0%), fatigue (41 of 98 patients; 41.8%), appetite loss (39 of 98 patients; 39.8%) and hepatotoxicity/transaminitis (24 of 98 patients; 24.5%). The majority of the AEs were toxicity grades 1 and 2. Sorafenib as a first-line treatment for primary HCC patients provided survival benefits and the AEs were well tolerated by patients.

A retrospective study of the efficacy and safety of donafenib combined with TACE as adjuvant therapy in patients with high-risk recurrence factors after hepatocellular carcinoma surgery.

e16121 Background: Surgical resection is the most important treatment for patients with hepatocellular carcinoma (HCC) to obtain long-term survival. However, the 5-year recurrence rate after hepatectomy is as high as 40%-60% and above. Reducing the postoperative recurrence rate is the key to improve the overall efficacy of HCC. This study aimed to evaluate the efficacy and safety of donafenib combined with TACE as adjuvant therapy in HCC patients with high-risk recurrence factors after surgical resection. Methods: This single-center retrospective study enrolled primary HCC patients with high-risk recurrence factors who underwent surgical resection at Shanghai Eastern Hepatobiliary Surgery Hospital from April 2021 to October 2022. High-risk recurrence factors included: the number of tumors ≥ 3, tumor diameter ≥ 5 cm, portal vein tumor thrombus, microvascular invasion (MVI) and satellite lesions. Patients received adjuvant therapy of donafenib combined with TACE after surgery. Patients’ demographic characteristics, etiological characteristics, 1-year recurrence-free survival rate (RFSR), recurrence-free survival (RFS), overall survival (OS), and treatment-related safety were analyzed. Results: A total of 40 patients were enrolled with a median age of 55.5 years (21-78), 39 patients (97.5%) in BCLC stage B and 1 patient (2.5%) in BCLC stage C. 33 patients (82.5%) were co-infected with HBV. All 40 patients had ECOG PS scores of 0 and Child-Pugh scores of A. A total of 34 patients (85%) with MVI were pathologically reported after surgery, 23 patients (57.5%) with tumor diameter ≥5cm, 9 patients (22.5%) with portal vein cancer thrombus, and 6 patients (15%) with satellite lesions. All patients received at least one TACE treatment after surgery, 31 patients (77.5%) received the TACE treatment one month after surgery, and 9 patients (22.5%) received the TACE treatment within one month after surgery. The initial dose of donafenib was 200mg/day. As of the cut-off date of data collection, the median follow-up time was 9 months (95%CI: 7.73-10.27), 4 patients relapsed and 2 patients died. The median RFS was 18 months (95% CI: 13.673-22.327), the one-year RFSR was 83.3% (95% CI: 61.9%-93.8%), and the one-year OS rate was 95.8% (95% CI: 75.2%-99.6%). 21 patients (52.5%) had combined treatment-related adverse events (TRAE), of which 4 patients (10%) had Grade 3 TRAE and no grade 4 or 5 TRAE were reported. Common adverse events included hand-foot skin reaction (9 patients, 22.5%), diarrhea (9 patients, 22.5%), rash (5 patients, 12.5%), hypertension, and gastrointestinal reactions (2 patients each, 5%). Conclusions: Donafenib combined with TACE was used for adjuvant therapy in patients with high-risk recurrence of HCC, which has a high one-year recurrence-free survival rate and was well tolerated.

Combination of neutrophil/lymphocyte ratio and albumin/bilirubin grade as a prognostic predictor for hepatocellular carcinoma patients undergoing curative hepatectomy

Background and aimPrognosis determination is essential for hepatocellular carcinoma (HCC) patient management and treatment planning. The current study aimed to evaluate the prognosis performance of NLR, ALBI, and the combination of NLR-ALBI in determining the overall survival (OS) of HCC patients under curative hepatectomy.Methods144 primary HCC patients with curative hepatectomy were recruited in the retrospective study. The clinicopathologic characteristics and OS were compared between stratified groups. The predictive performance of NLR, ALBI, and the combination of NLR-ALBI was explored by the area under the receiver operating characteristic curve (AUC). Univariate and multivariate analyses were used to determine the risk factors of OS.ResultsAUC determined NLR cutoff > 2.60 for predicting prognosis. The univariate analysis indicated pathological differentiation, tumor size, AFP, TNM stage, NLR score, and ALBI grade were significant indicators of OS. However, only TMN grade, AFP, NLR score, and NLR-ALBI score were identified as independent predictors of OS in the multivariable analysis. The AUC of NLR, ALBI and the combination of NLR-ALBI was 0.618(95%CI 0.56–0.710), 0.533 (95%CI 0.437–0.629), 0.679 (95%CI 0.592–0.767) respectively. Patients with higher NLR-ALBI scores presented worse outcomes than those with lower NLR-ALBI scores.ConclusionNLR is an independent prognostic factor of HCC and a reliable biomarker in predicting the OS of HCC patients. The combination of NLR-ALBI showed a better prognostic performance than using NLR or ALBI alone, implicating the effectiveness and feasibility of combining multiple risk factors for postoperative prognosis assessment.

Body mass index and serum alpha-fetoprotein level associated with PD1 expression and prognosis in patients with hepatocellular carcinoma

BackgroundMany factors affect the outcome of treatment with programmed death 1 (PD1) inhibitors for hepatocellular carcinoma (HCC). The objective of this study was to investigate the associations of clinicopathological parameters with PD1 expression and HCC prognosis. MethodsA total of 372 HCC patients (Western population) from The Cancer Genome Atlas (TCGA), and 115 primary HCC tissues and 52 adjacent tissues (Dataset GSE76427, Eastern population) from Gene Expression Omnibus (GEO) database were enrolled in this study. The primary outcome was 2-year relapse-free survival. Kaplan-Meier survival curves with the log-rank test were used to analyze the differences in prognosis between the two groups. X-tile software was used to confirm the optimal cut-off for clinicopathological parameters while assessing the outcome. Immunofluorescence was performed on HCC tissues to evaluate PD1 expression. ResultsExpression of PD1 was up-regulated in tumor tissue from both TCGA and GSE76427 patients, which positively correlated with body mass index (BMI), serum alpha-fetoprotein (AFP) level, and prognosis. Patients with higher PD1, lower AFP, or lower BMI had longer overall survival than those with lower PD1, higher AFP, or higher BMI, respectively. AFP and PD1 expression were validated in 17 primary HCC patients from the first affiliated hospital, Zhejiang University School of Medicine. Finally, we confirmed longer relapse-free survival with higher PD1 or lower AFP. ConclusionThe findings indicate that BMI and AFP are associated with PD1 expression and HCC prognosis, offering insight for clinical management and personalized immunotherapy for HCC.

Construction of a lipid metabolism-related risk model for hepatocellular carcinoma by single cell and machine learning analysis.

One of the most common cancers is hepatocellular carcinoma (HCC). Numerous studies have shown the relationship between abnormal lipid metabolism-related genes (LMRGs) and malignancies. In most studies, the single LMRG was studied and has limited clinical application value. This study aims to develop a novel LMRG prognostic model for HCC patients and to study its utility for predictive, preventive, and personalized medicine. We used the single-cell RNA sequencing (scRNA-seq) dataset and TCGA dataset of HCC samples and discovered differentially expressed LMRGs between primary and metastatic HCC patients. By using the least absolute selection and shrinkage operator (LASSO) regression machine learning algorithm, we constructed a risk prognosis model with six LMRGs (AKR1C1, CYP27A1, CYP2C9, GLB1, HMGCS2, and PLPP1). The risk prognosis model was further validated in an external cohort of ICGC. We also constructed a nomogram that could accurately predict overall survival in HCC patients based on cancer status and LMRGs. Further investigation of the association between the LMRG model and somatic tumor mutational burden (TMB), tumor immune infiltration, and biological function was performed. We found that the most frequent somatic mutations in the LMRG high-risk group were CTNNB1, TTN, TP53, ALB, MUC16, and PCLO. Moreover, naïve CD8+ T cells, common myeloid progenitors, endothelial cells, granulocyte-monocyte progenitors, hematopoietic stem cells, M2 macrophages, and plasmacytoid dendritic cells were significantly correlated with the LMRG high-risk group. Finally, gene set enrichment analysis showed that RNA degradation, spliceosome, and lysosome pathways were associated with the LMRG high-risk group. For the first time, we used scRNA-seq and bulk RNA-seq to construct an LMRG-related risk score model, which may provide insights into more effective treatment strategies for predictive, preventive, and personalized medicine of HCC patients.

NFYAv1 is a Tumor-Promoting Transcript Associated with Poor Prognosis of Hepatocellular Carcinoma.

BACKGROUND Nuclear Transcription Factor Y Subunit Alpha (NFYA), together with NFYB and NFYC, form a sequence-specific heterotrimeric nuclear transcription factor (NFY), but their functional role in hepatocellular carcinoma (HCC) is still unclear. In this study, we explored the association between the NFY subunit genes and the survival of primary hepatocellular carcinoma (HCC) patients in The Cancer Genome Atlas (TCGA). The transcript-specific effect on HCC cell growth was studied. MATERIAL AND METHODS RNA-seq data from the Genotype-Tissue Expression Project (GTEx) and TCGA were analyzed in combination. In vitro cellular and molecular studies were conducted using SK-Hep-1 and Hep3B cells. Pearson's correlation coefficients were calculated to assess correlations. Welch's unpaired t test and one-way ANOVA with post hoc Tukey's multiple comparisons were performed. Kaplan-Meier (K-M) survival curves were assessed by conducting log-rank (Mantel-Cox) test. RESULTS NFYA was the only prognosis-related gene. Among the 2 splicing transcripts of NFYA, the long isoform (NFYAv1, NM_002505.5) but not the short-form (NFYAv2, NM_021705.4) was significantly associated with worse progression-free survival (PFS) (high [n=179] vs low [n=179], HR: 1.657, 95% CI: 1.228-2.235, P<0.001) and disease-specific survival (DSS) (high [n=175] vs low [n=175], HR: 1.986, 95% CI: 1.269-3.108, P<0.001) in HCC patients. GO/KEGG analysis in TCGA confirmed that NFYAv1 and NFYAv2 co-expressed (|Pearson's r|≥0.6) genes in primary HCC patients were enriched in quite different GO/KEGG terms. NFYAv1 knockdown significantly decreased cell viability and increased G0/G1 cell cycle arrest. The shRNA only targeting NFYAv1 had a significantly stronger growth-inhibiting effect than the shRNA targeting both NFYAv1 and NFYAv2. CONCLUSIONS This study showed that NFYAv1 is a tumor-promoting transcript associated with poor prognosis of HCC.

18F-FDG PET/CT-based radiomics nomogram for preoperative prediction of macrotrabecular-massive hepatocellular carcinoma: a two-center study.

To explore the potential of β-2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) in the evaluation of macrotrabecular-massive (MTM) hepatocellular carcinoma (HCC) and to apply radiomics approach to build a radiomics nomogram for predicting MTM-HCC. This study included 140 (training cohort:101; validation cohort:39) HCC patients who underwent preoperative 18F-FDG PET/CT at two institutions. The clinical features and tumor FDG metabolism measured by the tumor-to-liver ratio (TLR) via 18F-FDG PET/CT were retrospectively collected. Radiomics features were extracted from 18F-FDG PET/CT images and a radiomics score (Rad-score) was calculated. A radiomics nomogram was then constructed by combining Rad-score and independent clinical features and was assessed with a calibration curve. The performance of the radiomics nomogram, Rad-score and TLR was evaluated by receiver operating characteristic (ROC) curves and decision curve analysis (DCA). A total of six top weighted radiomics features were selected from PET/CT images by the least absolute shrinkage and selection operator (LASSO) regression algorithm and were used to construct a Rad-score. Multivariate analysis identified Rad-score (OR = 2.183, P = 0.004), age ≤ 50years (OR = 3.136, P = 0.036), AST > 40U/L (OR = 0.270, P = 0.017) and TLR (OR = 1.641, P = 0.049) as independent predictors of MTM-HCC. The radiomics nomogram had a higher area under the curves (AUCs) than the Rad-score and TLR for predicting MTM-HCC in both training (0.849 [95% CI 0.774-0.924] vs. 0.764 [95% CI 0.669-0.843], 0.763 [95% CI 0.668-0.842]) and validation (0.749 [95% CI 0.584-0.873] vs. 0.690 [95% CI 0.522-0.828], 0.541 [95% CI 0.374-0.701]) cohorts. DCA showed the radiomics nomogram to be more clinically useful than Rad-score and TLR. Tumor FDG metabolism is significantly associated with MTM-HCC. A 18F-FDG PET/CT-based radiomics nomogram may be useful for preoperatively predicting the MTM subtype in primary HCC patients, contributing to pretreatment decision-making.

Health Disparities in Liver Cancer: An Analysis of the Ohio Cancer Incidence Surveillance System

Background: We explored associations between neighborhood deprivation and tumor characteristics, treatment, and 5-year survival among primary hepatocellular carcinoma (HCC) patients in Ohio diagnosed between 2008 and 2016. Methods: We used data from the Ohio Cancer Incidence Surveillance System and limited our analysis to adult (&gt;18 years of age) HCC patients with known census tract information based on address at diagnosis. Using principal components analysis, we created a neighborhood deprivation index (NDI) using 9 census tract-level variables. We examined associations between tumor characteristics (stage and tumor size) and NDI quintile using chi-square tests and analysis of variance (ANOVA). Associations between guideline-concordant care and NDI using log-binomial regression adjusted for sex, race, age at diagnosis, metropolitan status, cancer stage, and year of diagnosis were conducted. For 5-year survival, we utilized Cox proportional hazards models with a similar adjustment set. Results: Neighborhood deprivation index was not associated with stage or tumor size. Individuals living in the most deprived neighborhoods were 16% less likely to receive guideline-concordant care as compared to individuals living in the least deprived neighborhoods (adjusted prevalence ratio [PR]: 0.84; 95% confidence interval [CI]: 0.74-0.94). Similarly, individuals living in the most deprived neighborhoods were 15% less likely to survive 5 years compared to individuals living in the least deprived neighborhoods (adjusted Hazard Ratio: 1.15; 95% CI: 1.01-1.29). Conclusion: Our results suggest a negative association between neighborhood deprivation on guideline-concordant care and survival among HCC patients. Interventions targeting disparities of HCC should focus not only on individual-level factors but address larger neighborhood level factors as well.

Multiradiographic Diagnosis of Primary Hepatocellular Carcinoma and Evaluation of Its Postoperative Observation after Interventional Treatment.

Objective To investigate the focal imaging performance of MRI and CT multiphase dynamic enhancement scan examination in primary liver cancer patients, analyze its clinical diagnostic value, and provide a basis for early diagnosis of the disease. Methods 236 patients with primary liver cancer admitted to our hospital from May 2019 to November 2021 were randomly divided into two groups, the control group was given MRI multiphase dynamic enhancement scan diagnostic method, and the observation group was given CT scan combined with the MRI diagnostic method. The patients' examination results and pathological examination results were compared and analyzed, and the therapeutic effects of patients in the two groups after interventional treatment were compared. Results After the imaging and pathological examinations of patients in both groups, it was found that the diagnostic accuracy of patients in the observation group and the therapeutic effect after interventional treatment were significantly better than those in the control group. Conclusions Compared with CT multiphase dynamic enhancement scan, MRI multiphase dynamic enhancement scan can show multidirectional and multiangle lesions in primary hepatocellular carcinoma patients, with better characteristics of blood supply to hepatocellular carcinoma and a higher accuracy rate.

Abstract 5140: Evaluation of multiple serological biomarkers for treatment response in HCC patients

Abstract Background: Although there have been some scientific advances in the diagnosis and treatment of hepatocellular carcinoma (HCC), there still remains challenges due to late presentation, therapeutic resistance, and recurrence. Because not all patients respond to therapeutic treatments, it is urgently needed to more precisely identify the patients who fail to achieve complete response and only have a partial response or no response to treatments. No biomarker(s) or assay(s) are currently available to predict the treatment response in HCC patients. Aim: To evaluate serological biomarkers in BCLC Stage B &amp; C HCC patients undergoing treatment(s) including trans-arterial doxorubicin-eluting beads (DEB), trans-arterial radioembolization (Y-90 beads), and targeted molecular therapy (sorafenib). Methods: Fifty newly diagnosed primary HCC patients without any treatment were recruited between January 2014 and December 2018. Patients received, DEB, Y-90 beads, and Nexavar throughout their treatment course. The serum samples were collated before treatment (Pre-tx) and post treatment (Post-tx) at month 3, month 6 and month 9. A U-PLEX assay (Meso Scale Diagnostics) was performed to detect multiple serological biomarkers in serum, including growth factors (FGF19, HGF, insulin and FGF21) and inflammatory cytokines (IFN-γ, IL-17, IL-6, and TNF-α). The U-PLEX data were further validated by enzyme-linked immunosorbent assay. All patients were followed 3-5 years for survival with or without further surgical operations including tumor resection/ablation and orthotopic liver transplantation. Results: Based on the treatment outcome, patients were divided into 3 groups: a. overall survival (OS) &amp;lt; 1 year was defined as poor response; b. progression-free survival 3-5 years was defined as moderate response; and c. OS &amp;gt; 5 years was defined as good response. In the patients with moderate response and good response, the serum levels of FGF21 showed an increasing trend, with significant increases Post-tx at month 3, month 6 and month 9 (p &amp;lt; 0.05 vs Pre-tx). The serum levels of IFN-γ also showed an increasing trend, with significant increases at Post-tx-month 9 (p &amp;lt; 0.05 vs Pre-tx). In the patients with poor response, the serum levels of HGF and IL-6 were increased Post-tx, with statistically significance at Post-tx-month 6 (p &amp;lt; 0.05 vs Pre-tx). Increased serum levels of IL-17, TNF-α, FGF19, and insulin were found in the patients with poor response but no statistically significance reached (p &amp;gt; 0.05 versus Pre-tx). Conclusion: 1) Combination of growth factors and cytokines are applicable to find serological biomarkers in cancer patients for treatment response; 2) FGF21 and IFN-γ for good response and HGF and IL-6 for poor response may be used as biomarkers to monitor the HCC patients with adjuvant treatment(s); 3) Further study is needed to recruit more patients to correlate the serological biomarkers with their clinical outcome. Citation Format: Yan Li. Evaluation of multiple serological biomarkers for treatment response in HCC patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5140.

Evaluation of Therapeutic Effects of Computed Tomography Imaging Classification Algorithm-Based Transcatheter Arterial Chemoembolization on Primary Hepatocellular Carcinoma.

To investigate the evaluation of therapeutic effects of computerized tomography (CT) imaging machine learning classification algorithm-based transcatheter arterial chemoembolization (TACE) on primary hepatocellular carcinoma (PHC), machine learning algorithm was optimized to propose the feature extraction of soft margin, analyze CT images, and acquire relevant texture features to assess if it can predict the multistage features of PHC for the application of the therapeutic effects of TACE on PHC. Besides, PHC patients receiving surgical excision were retrospectively collected, and then 483 patients with hepatocellular carcinoma (HCC) were determined from cases. After that, a total of 162 cases meeting the standards were selected. Besides, the features of images were classified and analyzed by machine learning algorithm, and volume of interest (VOI) images of patients in each group were acquired by image segmentation layer by layer. In addition, the texture features of images were extracted. The results showed that 5 CT image-based texture features, including 2 histogram features and 3 matrix-based features, all described the specificity and heterogeneity of tumors. The analysis of the diagnostic effectiveness of the evaluation of response group by each texture parameter demonstrated that its sensitivity, specificity, and area under curve (AUC) were 83.63%, 90.91%, and 0.08%, respectively. Based on CT prediction, machine learning algorithm was fused to realize excellent classification effects on multistage and multiphase features and offer imaging support to the clinical selection of reasonable therapeutic plans. In addition, multiphase and multifeature-based medical tumor classification method was put forward.

Efficacy and Safety of Central Memory T Cells Combined With Adjuvant Therapy to Prevent Recurrence of Hepatocellular Carcinoma With Microvascular Invasion: A Pilot Study.

BackgroundPostoperative adjuvant transcatheter arterial chemoembolization (TACE) following curative hepatectomy has been reported to improve the clinical outcomes of hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI), but more endeavors are required to achieve greater clinical benefit. Central memory T-cell (Tcm) self-transfusion has shown superior antitumor activity in several preclinical studies; however, clinical studies are rare. The aim of this study was to evaluate the clinical benefit and safety of combination treatment with Tcm self-transfusion and TACE as adjuvant treatment in HCC patients with MVI after curative hepatectomy.MethodsFrom October 2016 to September 2018, primary HCC patients with histologically confirmed MVI who underwent curative hepatectomy at the Cancer Hospital of the Chinese Academy of Medical Sciences were recruited for this study. The patients were divided into a Tcm group (combined Tcm self-transfusion with TACE treatment) or a control group (TACE treatment alone) according to their willingness. The recurrence-free survival (RFS), quality-of-life (QOL) score, and adverse events of each patient were recorded within 2 years.ResultsA total of 52 patients were enrolled, and 48 were eligible for the final data analysis. The median follow-up time was 20.5 months (95% CI: 17.05–22.55 months). The median RFS time was 9.5 months in the control group; the cutoff date was not reached in the Tcm group (when the follow-up duration was 12 months, p = 0.049, HR = 0.40; 95% CI: 0.16–0.99). Compared with the control group, 1- and 2-year RFS rates were higher in the Tcm group (72.0% vs. 46.4% and 58.18% vs. 39.14%, respectively). Multivariate analysis did not indicate that Tcm treatment was an independent prognostic factor associated with HCC recurrence (p = 0.107, HR = 2.312; 95% CI: 0.835–6.400), which might be due to the small sample size of this study. Nevertheless, Tcm treatment effectively improved a reduced QOL due to HCC and liver function injury. Finally, the safety profile of Tcm treatment in this study was good, without any serious adverse events.ConclusionsThis pilot study showed that Tcm self-transfusion combined with TACE treatment might be a beneficial adjuvant therapy with good safety for primary HCC patients with MVI after curative hepatectomy.Trial registration numberNCT03575806

The Influence of ICAM1 3'UTR Gene Polymorphism on the Occurrence and Metastasis of Primary Liver Cancer.

Objective In this study, we explored the influence of single nucleotide polymorphism (SNP) in the noncoding region of intercellular adhesion molecule 1 (ICAM1) gene on the occurrence and metastasis of primary hepatocellular carcinoma (PHC). Methods Sanger sequencing was used to analyze the genotypes of rs3093032, rs923366, and rs281437 locus in the 3′untranslated region (UTR) of the ICAM1 gene. The level of plasma ICAM1 was analyzed by enzyme-linked immunosorbent assay (ELISA). Results After adjusting for risk factors such as BMI, smoking, drinking, family history of tumors, and hepatitis B virus test results, the CT genotype at rs3093032 of the ICAM1 gene (OR = 0.19, 95% CI: 0.08-0.44, P < 0.01), dominance model (OR = 0.23, 95% CI: 0.11-0.48, P < 0.01), and T allele (OR = 0.27, 95% CI: 0.14-0.53, P < 0.01) were related to the reduced risk of PHC susceptibility. rs923366 locus CT genotype (OR = 0.63, 95% CI: 0.44-0.90, P = 0.01), TT genotype (OR = 0.23, 95% CI: 0.10-0.53, P < 0.01), dominant model (OR = 0.55, 95% CI: 0.39-0.77, P < 0.01), recessive model (OR = 0.28, 95% CI: 0.12-0.62, P < 0.01), and T allele (OR = 0.55, 95% CI: 0.42-0.73, P < 0.01) were related to a reduction in the risk of PHC susceptibility. rs281437 locus CT genotype (OR = 2.08, 95% CI: 1.40-3.09, P < 0.01), TT genotype (OR = 5.20, 95% CI: 2.22-12.17, P < 0.01), dominant model (OR = 2.45, 95% CI: 1.69-3.54, P < 0.01), recessive model (OR = 4.32, 95% CI: 1.86-10.06, P < 0.01), and T allele (OR = 2.46, 95% CI: 1.79-3.38, P < 0.01) were significantly related to the increased risk of PHC susceptibility. SNPs at rs3093032, rs923366, and rs281437 of the ICAM1 gene were significantly correlated with TNM stage and tumor metastasis of PHC patients (P < 0.05). Conclusion SNPs at rs3093032, rs923366, and rs281437 in the 3′UTR region of the ICAM1 gene are related to the occurrence and metastasis of PHC.

Effects of Serum From Radiofrequency Ablation Patients Receiving General Anesthesia or Local Anesthesia on Hepatocellular Carcinoma Cancer Cell Malignancy: A Prospective Randomized Controlled Trial.

BackgroundWhether anesthesia methods affect malignant biological behavior of cancer remains unresolved. In this study, we aim to compare the effects of general anesthesia (GA) and local anesthesia (LA) on serum collected from primary hepatocellular carcinoma (HCC) patients presenting for radiofrequency ablation (RFA).MethodsFrom August 2020 to December 2020, a prospective, randomized, and controlled study was conducted at Renji Hospital, which is affiliated with Shanghai Jiaotong University School of Medicine. 25 qualified patients from 18 to 65 years of age undergoing RFA were enrolled in the study and randomly assigned into two groups: the GA group (n = 14) and the LA group (n = 11). Venous blood was drawn from all patients preoperatively and 1 hour postoperatively. The serum collected was then used for the culturing of HepG2 cells. The malignant biological behaviors of HepG2 cells, including invasion, migration and proliferation, were observed after 24 hours of exposure to patients’ serum. ELISA was used to compare expression levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and lymphokines (IFN-γ, IL-2) in patients’ serum from both groups.ResultsHepG2 cells cultured with postoperative serum obtained from patients who received GA, but not LA, were associated with significantly increased cell invasion, migration and proliferation, compared to preoperative serum from the same patient group. Expression levels of pro-inflammatory cytokines were significantly higher, and lymphokines significantly lower in postoperative serum from GA patients compared to the corresponding preoperative serum.ConclusionGA affects the serum milieu of patients with HCC, promoting the malignant biological behavior of a human HCC cell line.

Local anesthetic bupivacaine inhibits proliferation and metastasis of hepatocellular carcinoma cells via suppressing PI3K/Akt and MAPK signaling.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Retrospective studies suggest that using local/regional anesthetic (LA/RA) is associated with better outcomes in primary HCC patients. In this study, we evaluated the effects of LA/RA bupivacaine in HCC cells and the underlying molecular mechanisms. The biological functions of bupivacaine in HCC cells were evaluated by transcriptome RNA sequencing, cell viability assay, bromodeoxyuridine incorporation assay, colony formation assay, flow cytometry, western blot, wound healing assay, transwell cell migration assay, tumor xenograft formation, and lung metastasis assay. Bupivacaine suppressed proliferation and induced apoptosis of HepG2 and SNU-449 cells in a time- and dose-dependent manner. Bupivacaine treatment also decreased colony formation, migration, and invasion of HepG2 and SNU-449 cells. In mouse models, bupivacaine repressed tumor xenograft growth and lung metastasis of HepG2 cells. Transcriptome sequencing of HepG2 cells suggested that PI3K/Akt and MAPK signaling pathways were suppressed by bupivacaine treatment. In western blot analysis, bupivacaine reduced the expression of total and phosphorylated Akt, mTOR, and MAPK. Furthermore, reactivated PI3K/Akt and MAPK signaling by EGF or NRG1 partially reversed the effects of bupivacaine on cell growth, colony formation, and invasion of HCC cells. Local anesthetic bupivacaine suppressed proliferation, migration and invasion, and induced apoptosis of HCC cells. Our results provided novel insights into the local anesthetic bupivacaine in the therapy of HCC patients.

Occurrence, Related Factors and Prognostic Value of Vascular Lake in Hepatocellular Carcinoma Patients Treated with Drug-Eluting Bead Transarterial Chemoembolization.

PurposeThe present study aimed to assess the prevalence of vascular lake (VL), its associated factors and correlation with prognosis in hepatocellular carcinoma (HCC) patients treated with drug-eluting bead transarterial chemoembolization (DEB-TACE). Patients and Methods A total of 286 primary HCC patients (with 384 treated nodules) receiving DEB-TACE treatment were recruited, and their clinical characteristics were documented. The occurrence of VL was recorded, and treatment responses were assessed according to the modified response evaluation criteria in solid tumor (mRECIST).In terms of treatment response, the total response status (including CR, PR, SD and PD), objective response rate (ORR) and disease control rate (DCR) were elevated in VL patients compared to non-VL patients as well as in VL nodules compared to non-VL nodules. Liver function indexes and adverse events were assessed. Progression-free survival (PFS) and overall survival (OS) were evaluated with the last follow-up date of March 2020. ResultsThe patient-based and nodule-based VL occurrence rates were 17.1% and 16.4%, respectively. Larger tumor size, pseudocapsules and smaller bead size were independently associated with VL occurrence. PFS and OS were more prolonged in VL patients than in non-VL patients, and VL independently correlated with better PFS and OS. For liver function, the liver function indexes before and after DEB-TACE were of no difference between VL patients and non-VL patients. Additionally, the incidences of adverse events were similar between VL patients and non-VL patients.Conclusion VL occurs in 17.1% of HCC patients treated with DEB-TACE, and it is correlated with larger tumor size, pseudocapsule, smaller bead size, more favorable treatment response and better survival.

Erzhu Qinggan Jiedu Recipe improves the clinical outcome of hepatocellular cancer after surgical resection: a case-control retrospective study.

This study retrospectively reviewed the recurrence rate and survival time of primary hepatocellular carcinoma (HCC) patients after treatment with Erzhu Qinggan Jiedu Recipe (ESQJR), explored the impact of Chinese medicine in reducing tumour recurrence and prolonging survival time, and explored an effective prevention treatment for the recurrence of HCC. To explore the impact of Chinese medicine in reducing tumor recurrence and prolonging survival time, and explore an effective prevention treatment for the recurrence of HCC. A total of 137 patients who underwent HCC resection from May 2004 to January 2018 was included in this retrospective study. The patients were divided into two groups, with 68 patients in the Western medicine group and 69 patients in the Western medicine plus ESQJR group. The relapse rate, overall survival period, and disease-free survival period before and after treatment were analysed. Indices including alpha-fetoprotein, alanine aminotransferase, aspartate aminotransferase and Karnofsky performance score were obtained for analysis and comparison. There was no significant difference among patient clinical parameters between the two groups. Compared with the Western medicine group, the Western medicine plus ESQJR group had a reduced cumulative recurrence rate, prolonged overall survival time and disease-free survival time and improved clinical symptoms, including quality of life and liver function. ESQJR effectively improved long-term survival in resected HCC patients. ESQJR has the potential to be used as an adjuvant therapy with significant beneficial effects for treating HCC.

Laparoscopic Liver Resection Should Be a Standard Procedure for Hepatocellular Carcinoma with Low or Intermediate Difficulty.

Background: To investigate the feasibility of laparoscopic liver resection (LLR) for hepatocellular carcinoma (HCC), we compared the outcome between LLR and conventional open liver resection (OLR) in patient groups with different IWATE criteria difficulty scores (DS). Methods: We retrospectively reviewed 607 primary HCC patients (LLR: 81, OLR: 526) who underwent liver resection in Linkou Chang Gung Memorial hospital from 2012 to 2019. By using 1:1 propensity score-matched (PSM) analysis, their baseline characteristics and the DS stratified by the IWATE criteria were matched between the LLR and OLR. Their perioperative and oncologic outcomes were compared. Results: After 1:1 PSM, 146 patients (73 in LLR, 73 in OLR) were analyzed. Among them, 13, 41, 13 and 6 patients were classified as low, intermediate, advanced and expert DS group, respectively. Compared to OLR, the LLR had shorter hospital stay (9.4 vs. 11.5 days, p = 0.071), less occurrence of surgical complications (16.4% vs. 30.1%, p = 0.049), lower rate of hepatic inflow control (42.5% vs. 65.8%, p = 0.005), and longer time of inflow control (70 vs. 51 min, p = 0.022). The disease-free survival (DFS) and overall survivals were comparable between the two groups. While stratified by the DS groups, the LLR tended to have lower complication rate and shorter hospital stay than OLR. The DFS of LLR in the intermediate DS group was superior to that of the OLR (p = 0.020). In the advanced and expert DS groups, there were no significant differences regarding outcomes between the two groups. Conclusion: We have demonstrated that with sufficient experience and technique, LLR for HCC is feasible and the perioperative outcome is favorable. Based on the current study, we suggest LLR should be a standard procedure for HCC with low or intermediate difficulty. It can provide satisfactory postoperative recovery and comparable oncological outcomes. Further larger scale prospective studies are warranted to validate our findings.