ObjectiveTo establish a model for predicting microvascular invasion (MVI) of hepatocellular carcinoma based on magnetic resonance imaging (MRI) radiomics features.MethodsThe clinical and pathological datas of 190 patients with hepatocellular carcinoma who received surgical treatment in our hospital from September 2017 to May 2020 were prospectively collected. The patients were randomly divided into training group (n=158) and test group (n=32) with a ratio of 5∶1. Gadoxetate disodium (Gd-EOB-DTPA) -enhanced MR images of arterial phase and hepatobiliary phase were used to select radiomics features through the region of interest (ROI). The ROI included the tumor lesions and the area dilating to 2 cm from the margin of the tumor. Based on a machine learning algorithm logistic, a radiomics model for predicting MVI of hepatocellular carcinoma was established in the training group, and the model was evaluated in the test group.ResultsSeven radiomics features were obtained. The area under the receiver operating characteristic curve (AUC) of the training group and the test group were 0.830 [95%CI (0.669, 0.811)] and 0.734 [95%CI (0.600, 0.936)], respectively.ConclusionThe model based on MRI radiomics features seems to be a promising approach for predicting the microvascular invasion of hepatocellular carcinoma, which is of clinical significance for the management of hepatocellular carcinoma treatment.
Objective To compare therapeutic effects of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) and transcatheter arterial chemoembolization (TACE) on patients with advanced hepatocellular carcinoma. Methods Thirty-five patients with advanced hepatocellular carcinoma admitted in the Department of Hepatobiliary and Pancreatic Surgery of Shiyan Taihe Hospital Affiliated to Hubei University of Medicine from August 1, 2014 to August 1, 2015 were randomly divided into ALPPS group and TACE group, in which 17 cases treated by the ALPPS and 18 cases treated by the TACE. The survival, changes of liver function and life quality, postoperative complications and mortality were compared in these two groups. The follow-up was performed by the telephone and the outpatient. Results ① The baselines such as the age, gender, diameter of tumor, complications had no significant differences in these two groups (P>0.05). ② The changes of liver function and life quality after operation in the ALPPS group were significantly better than those in the TACE group (P<0.05). ③ The complications after operation were observed in 5 cases (there were 2 cases of bile leakage, 1 case of intraabdominal bleeding, 1 case of peritoneal effusion, and 1 case of pulmonary infection) in the ALPPS group, which in 13 cases (there were 6 cases of nausea and vomiting, 4 cases of liver function damage, 2 cases of granulocytopenia, 1 case of fever) in the TACE group. The rate of the overall complications in the ALPPS group was significantly lower than that in the TACE group (5/17versus 13/18, P=0.018). ④ The overall survival in the the ALPPS group was significantly better than that in the TACE group (P=0.024). During follow-up period, the deaths happened in 3 cases duo to hepatocellular carcinoma and 1 case duo to traffic accident, 1 case was lost on month 8, 12 cases were still alive in the ALPPS group; the deaths happened in 10 cases duo to hepatocellular carcinoma, 1 case duo to coronary disease, and 1 case duo to cerebral infarction, 6 cases were still alive in the TACE group. Conclusion Preliminary results of limited cases in this study show that ALPPS has a better effect than TACE on patients with advanced hepatocellular carcinoma.
Objective To systematically evaluate the diagnostic efficacy of circulating tumor DNA (ctDNA) in hepatitis B viral hepatocellular carcinoma (HBV-HCC), and to study the clinical value of ctDNA. Methods The databases of PubMed, Embase, Web of Science, and Cochrane Library database were retrieved systematically from the establishment of the database to April 26, 2021. The characteristic information of literatures and the original data such as the sensitivity, specificity, and area under curve (AUC) of the receiver operating characteristic (ROC) curve were extracted. A meta-analysis was conducted by applying RevMan 5.3 and Stata 15.0 software. The combined sensitivity, combined specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio (OR) were calculated, ROC curve was plotted and the AUC was calculated, Deck’s funnel chart to assess publication bias, the Fagan diagram to test the diagnostic efficiency. Results Finally, 16 studies involving 3 744 patients were enrolled in this study, of which 1 852 were HBV-HCC patients, and 1 892 were HBV-infected patients without HCC. The meta-analysis results showed that ctDNA had a pooled sensitivity of 0.85 [95%CI (0.78, 0.90)], a specificity of 0.74 [95%CI (0.63, 0.83)], a diagnostic OR of 15.98 [95%CI (10.65, 23.99)], and the AUC of ROC was 0.87 [95%CI (0.84, 0.90)] in the diagnosis of HBV-HCC. The pooled sensitivity, specificity, diagnostic OR, and the AUC of ROC for ctDNA combined with AFP in the diagnosis of HBV-HCC were 0.86 [95%CI (0.80, 0.90)], 0.79 [95%CI (0.68, 0.87)], 22.69 [95%CI (13.64, 37.76)], and 0.90 [95%CI (0.87, 0.92)]. Meta-regression analysis found that the heterogeneity came from other non-covariate factors. The Fagan chart showed that while HBV-HCC was diagnosed by liquid biopsy-based on ctDNA, the probability of being diagnosed with hepatocellular carcinoma was 77%, if HBV-HCC was excluded, the probability of having the corresponding disease was 17%. Deek’s test showed no obvious publication bias (P>0.05). ConclusionsThe ctDNA can diagnose HBV-HCC with high sensitivity, specificity and accuracy, and can be used as a promising circulating biomarker in the early diagnosis of HBV-related HCC. The combination of ctDNA in serum and AFP is beneficial to improve the diagnostic accuracy of HBV-HCC.
Objective To summarize the mechanism of microRNA in the recurrence and metastasis of hepatocellular carcinoma (HCC) and its possible clinical application. Methods The relevant literatures at home and abroad were reviewed to summarize the results of various scholars. Results microRNA played an important role in cell proliferation and apoptosis of HCC. microRNA of different types promoted or inhibited the recurrence and metastasis of HCC through different action targets and molecular pathways. Conclusions microRNA has a regulation role in the recurrence and metastasis of HCC, and the depth mechanisms study of microRNA in the recurrence and metastasis of HCC provides great significance to clinical therapy. The miRNA is expected to be one of the new target on the prediction and treatment of recurrence and metastasis in HCC.
Objective To introduce the inflammatory microenvironment and epithelial-mesenchymal transition process of hepatocellular carcinoma, and review the relationship between them. Methods Domestic and international literatures were collected to summary the relationship between epithelial-mesenchymal transition and the inflammatory microenvironment of hepatocellular carcinoma. Result Many inflammatory factors and viral gene encoding proteins in the inflammatory microenvironment play an important role in the process of epithelial-mesenchymal transition in hepatocellular carcinoma. Conclusions The inflammatory microenvironment of hepatocellular carcinoma is an indispensable role in the process of epithelial-mesenchymal transition. The inhibition and treatment of inflammatory microenvironment may play a more active role in the control of tumor invasion and metastasis.
ObjectiveTo study the differential expression of minichromosome maintenance protein (MCM) gene family in hepatocellular carcinoma (HCC) and to explore its survival predictive value.MethodsTranscriptome data, clinical data, and survival information of patients with HCC were extracted from The Cancer Genome Atlas (TCGA), and the differential expression of MCM gene was analyzed. The prognostic value of differentially expressed of MCM gene was studied by Cox proportional hazards regression model, the prognostic model and risk score system were constructed. On the basis of risk score, a number of indicators were included to construct a nomogram to predict the3- and 5-year survival probability of HCC patients, and to verify and evaluate their predictive ability and accuracy.ResultsThe expressions of MCM2, MCM3, MCM4, MCM5, MCM6, MCM7, MCM8, and MCM10 in HCC tissues were higher than those of normal liver tissues (P<0.05), and univariate analysis showed that they were all related to prognosis (P<0.05). Multivariate analysis showed that MCM6 and MCM10 were independent factors affecting survival of HCC patients (P<0.05). Through multivariate analysis, a prognostic model consisting of MCM6, MCM8, and MCM10 was constructed, and a risk scoring system was established. It had been verified that this risk score was an independent risk factor affecting the prognosis of patients with HCC, and the prognosis of patients with high scores were worse than those of patients with low scores (P<0.001). We used TNM stage, T stage, and risk score to construct a nomogram with a consistency index (C index) of 0.723 and draw a time-dependent receiver operating characteristic curve, the results showed that area under the curve of 3- and 5-year were 0.731 and 0.704, respectively.ConclusionsMCM6,MCM8, and MCM10 in the MCM gene family have important prognostic value in HCC. The nomogram constructed in this study can better predict the survival probability of HCC patients.
ObjectiveTo investigate the expression change characteristic of stemness-related markers for recurrent hepatocellular carcinoma (HCC), and to discuss the relationship between stemness-related markers and clinicopathologic characteristics of HCC.MethodsWe collected 25 recurrent HCC patients who also had the first liver resection for HCC in Sichuan Cancer Hospital from Jan. 2010 to Oct. 2018. Immunohistochemistry was used to compare expressions of CD133, CD90, CD117, and epithelial cell adhesion molecule (EpCAM) in HCC tissues. Fluorescence in situ hybridization was used to detect telomere length.ResultsThe primary HCC had higher platelet count, larger tumor, less microvascular invasion (MVI), and less multiple HCC than the recurrent HCC (P<0.05), but the expressions of CD90, CD133, CD117, and EpCAM were not significantly differed after recurrence (P>0.05). The expressions of CD90, CD133, CD117, and EpCAM were not associated with tumor size, tumor number, Barcelona Clinic Liver Cancer Staging (BCLC staging), satellite nodules, and differentiation (P>0.05). The MVI-positive group had a significantly higher expression level of EpCAM (P=0.016) and longer telomere length (P=0.001). The telomere length was longer for tumors diameter less than 5 cm (P=0.038) and poor differentiation (P=0.046). Correlation analysis found that there was no relationship between telomere length and expression levels of EpCAM (r=–0.092, P=0.513), CD90 (r=–0.235, P=0.100), CD133 (r=0.024, P=0.867), and CD117 (r=–0.277, P=0.052), but an apparent positive correlation between expression levels of EpCAM and CD133 was found (r=0.358, P=0.011). Survival analysis found that poor differentiation (P=0.003) and BCLC B–C staging (P=0.040) were the risk factors of disease-free survival for patients after first HCC resection, and BCLC B–C staging (P=0.017) and tumor diameter more than 5 cm (P=0.035) were the risk factors for recurrent HCC.ConclusionsRecurrent HCC had similar stemness-related markers expression and longer telomere length. Expression level of EpCAM and telomere length were associated with MVI.
ObjectiveTo study clinical practical value of multimode imaging technique in precise hepatectomy for huge hepatocellular carcinoma (HCC). MethodsThe clinicopathologic data of patients with huge HCC who underwent precise hepatectomy in Yuebei People’s Hospital from Jan. 2018 to Dec. 2020 were collected. The three-dimensional (3D) reconstruction, 3D visualization, 3D printing, and augmented reality (AR) were used to guide preoperative evaluation, surgical planning, and surgical navigation. The liver function indexes, surgical mode, operative time, intraoperative bleeding, volume of resected liver, postoperative hospitalization, and complications were analyzed. ResultsThere were 23 patients in this study, including 18 males and 5 females, with (56.8±8.1) years old. The virtual tumor volume assessed by multimodal imaging technology was (865.2±165.6) mL and the virtual resected liver volume was (1 628.8±144.4) mL. The planned operations were anatomical hepatectomy in 19 patients and non-anatomical hepatectomy in 4 patients. The actual operation included 17 cases of anatomical hepatectomy and 6 cases of non-anatomical hepatectomy, which was basically consistent with the results of AR. The operative time was (298.4±74.5) min, the median hepatic blood flow blocking time was 20 min, and the intraoperative bleeding was (330.4±152.8) mL. Compared with preoperative levels, the levels of hemoglobin and albumin decreased temporarily on the first day after operation (P<0.05), and then which began to rise on the third day and basically rose to the normal range; prothrombintime, total bilirubin, alanine aminotransferase, and aspartate aminotransferase increased transiently on the first day after operation (P<0.05), then which began to decline to the normal levels. There were no serious operative complications and no perioperative death. The median follow-up time was 18 months, the tumor recurrence and metastasis occurred in 3 cases. ConclusionFrom preliminary results of this study, it could improve surgical safety and precision of hepatectomy for huge HCC by preoperative precise assessment and operation navigation in good time of multimode imaging technology.
Objective To evaluate application of anterior approach combined with selective hepatic vein(s) occlusion in associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) for giant hepatocellular carcinoma (HCC) in right lobe. Method The clinical data of 9 patients underwent the ALPPS in the First Affiliated Hospital of Guangxi Medical University from January 2017 to September 2017 were retrospectively analyzed. Results Six cases underwent the complete ALPPS, 3 cases lost because it couldn’t match the standard for the second step. After the first step, The average increased volume of the future liver remnant (FLR) was 139.1 cm3 (46.4–291.6 cm3), and the average increased volume rate of FLR was 37.8% (15.1%–76.2%). The average blood loss was 356 mL (200–600 mL). In the second step, 4 cases underwent the right hemihepatectomy and 2 cases underwent the extend right hemihepatectomy, the average blood loss was 617 mL (300–1 400 mL). There was no bile fistula, liver failure, and death. Conclusions Preliminary results of limited cases in this study show that application of anterior approach combined with selective hepatic vein(s) occlusion is a safe and feasible strategy in ALPPS for giant HCC in right lobe. This strategy is conformity with the " no touch” principle of oncology surgery, and reduces blood loss and decreases complications. Long-term oncological result of ALPPS in HCC patients with cirrhosis is unknown.
ObjectiveTo explore the expression of genes related to hepatocellular carcinoma (HCC) stem cells and their prognostic correlation by using weighted gene co-expression network analysis (WGCNA).MethodsFirstly, the transcriptome sequencing (RNA-seq) and clinical data of HCC were downloaded from the public database the Cancer Genome Atlas (TCGA), and the mRNA expression-based stiffness index (mRNAsi) table of cancer stem cells was downloaded and sorted out to analyze the relationship between mRNAsi and pathological grade and prognosis of HCC. The mRNAsi of HCC was downloaded and the prognostic value of mRNAsi was discussed. Then we used WGCNA to screen the key modules related to liver cancer stem cells (LSCS). Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes were used for the functional and pathway enrichment analysis. The online database STRING was used to construct hub genes coding proteins interaction (PPI) network and screen key genes. Finally, the key genes were analyzed for expression differences and expression correlations. The online database Kaplan-Meier plotter was used for survival analysis and verified.ResultsmRNAsi was significantly upregulated in cancer tissues (P<0.001), and increased with the increase of pathological grade of HCC (P=0.001). The mortality rate of the higher mRNAsi group was higher than that of the lower mRNAsi group (P=0.006). GO analysis found that hub genes were mainly involved in biological processes, such as mitosis and DNA replication, and KEGG showed that hub genes were enriched in cell cycle, DNA mismatch repair, oocyte meiosis, and other signaling pathways. We screened 10?key genes (included CCNB1, CDC20, CDCA8, NDC80, KIF20A, TTK, CDC45, KIF15, MCM2, and NCAPG) related to mRNAsi of HCC based on WGCNA. The key genes were highly expressed in the tumor samples compared to the normal samples. In addition, there was a strong interaction between proteins of these key genes (P<0.05), a strong co-expression relationship at the transcriptional level, and all related to prognosis of HCC.ConclusionsmRNAsi plays an important role in the occurrence and development of HCC. Ten key genes related to LSCS were screened, which may act as therapeutic targets for inhibiting the stem cell characteristics of HCC.