Recommended 10-Year Follow-Up Strategy for Small Hepatocellular Carcinoma After Radiofrequency Ablation: A Cost-Effectiveness Evaluation.

INTRODUCTION: An optimal follow-up schedule for small (≤3-cm) hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA) remains unclear in clinical guidelines. We aimed to assess the cost-effectiveness of follow-up strategies in patients with small HCC after RFA. METHODS: In total, 11,243 patients were collected from global institutions to calculate recurrence rates. Subsequently, a Markov model covering a 10-year period was developed to compare 25 surveillance strategies involving different surveillance techniques (computed tomography [CT], magnetic resonance imaging or ultrasonography [US], and α-fetoprotein [AFP]) and intervals (3 or 6 months). The study endpoint was incremental cost-effectiveness ratio (ICER), which represented additional cost per incremental quality-adjusted life year. Sensitivity analysis was conducted by varying the values of input parameters to observe the ICER. RESULTS: In a base case analysis, the dominant strategy was CT every 3 months during an initial 2 years, followed by semiannual CT, and then switch to biannual the combination of US screening and AFP testing after 5 years (m3_CT-m6_CT-m6_USAFP), with an ICER of $68,570.92 compared with the "not followed" strategy. One-way sensitivity analysis showed the ICER consistently remained below the willingness-to-pay threshold of $100,000.00. In a probabilistic sensitivity analysis, m3_CT-m6_CT-m6_USAFP was the most cost-effective approach in 95.6% of simulated scenarios at a willingness-to-pay threshold. DISCUSSION: For small HCC after RFA, the recommended follow-up strategy is CT, with scans scheduled every 3 months for the first 2 years, every 6 months thereafter, and transition to biannual the combination of US screening and AFP testing after 5 years.

Hepatic arterial infusion therapy for advanced hepatocellular carcinoma after systemic treatment failure: Multicenter, real-world study.

AIM: The study was conducted to evaluate the feasibility and safety profile of hepatic arterial infusion chemotherapy with oxaliplatin, 5-fluorouracil, and leucovorin (HAIC-FOLFOX) as an alternative therapeutic choice for patients with advanced hepatocellular carcinoma (HCC) that is refractory to systemic treatment including immune checkpoint blockades or molecular targeting agents. METHODS: Two hundred and forty five consecutive patients with advanced HCC who received HAIC-FOLFOX treatment after systemic treatment failure were retrospectively reviewed in six institutions and their survival, tumor response, and tolerance were assessed. RESULTS: The median overall survival (OS) and progression-free survival of the 209 included participants were 10.5 months (95% confidence interval [CI], 8.1-12.9) and 6.0 months (95% CI, 5.1-6.9), respectively. According to Response Evaluation Criteria in Solid Tumors 1.1 criteria, the objective response rate was 21.1%, and the disease control rate was 64.6%. Multivariate analysis of risk factors of OS were albumin-bilirubin grade (2 and 3 vs. 1, hazard ratio [HR] 1.57; 95% CI, 1.05-2.34; p = 0.028), tumor number (>3 vs. 1-3, HR 2.18; 95% CI, 1.10-4.34; p = 0.026), extrahepatic spread (present vs. absent, HR 1.61, 95% CI, 1.06-2.45; p = 0.027), synchronous systemic treatment (present vs. absent, HR 0.55, 95% CI, 0.37-0.83; p = 0.004) and treatment response (responder vs. nonresponder, HR 0.30, 95% CI, 0.17-0.53; p < 0.001). Grade 3-4 adverse events (AEs) occurred in 59 (28.2%) HCC patients. All AEs were manageable, and deaths related to hepatic artery infusion chemotherapy treatment were not observed. CONCLUSIONS: Our findings support the effectiveness and safety of HAIC-FOLFOX treatment for patients with advanced HCC who have failed systemic treatment.

Ab initio determination of melting and sound velocity of neon up to the deep interior of the Earth.

The thermophysical properties and elemental abundances of the noble gases in terrestrial materials can provide unique insights into the Earth's evolution and mantle dynamics. Here, we perform extensive ab initio molecular dynamics simulations to determine the melting temperature and sound velocity of neon up to 370 GPa and 7500 K to constrain its physical state and storage capacity, together with to reveal its implications for the deep interior of the Earth. It is found that solid neon can exist stably under the lower mantle and inner core conditions, and the abnormal melting of neon is not observed under the entire temperature (T) and pressure (P) region inside the Earth owing to its peculiar electronic structure, which is substantially distinct from other heavier noble gases. An inspection of the reduction for sound velocity along the Earth's geotherm evidences that neon can be used as a light element to account for the low-velocity anomaly and density deficit in the deep Earth. A comparison of the pair distribution functions and mean square displacements of MgSiO3-Ne and Fe-Ne alloys further reveals that MgSiO3 has a larger neon storage capacity than the liquid iron under the deep Earth condition, indicating that the lower mantle may be a natural deep noble gas storage reservoir. Our results provide valuable information for studying the fundamental behavior and phase transition of neon in a higher T-P regime, and further enhance our understanding for the interior structure and evolution processes inside the Earth.

An integrated pan-cancer analysis of TFAP4 aberrations and the potential clinical implications for cancer immunity.

Studies have shown that transcription factor activating enhancer binding protein 4 (TFAP4) plays a vital role in multiple types of cancer; however, the TFAP4 expression profile is still unknown, as is its value within the human pan-cancer analysis. The present study comprehensively analysed TFAP4 expression patterns from 33 types of malignancies, along with the significance of TFAP4 for prognosis prediction and cancer immunity. TFAP4 displayed inconsistent levels of gene expression across the diverse cancer cell lines, and displayed abnormal expression within most malignant tumours, which closely corresponded to overall survival. More importantly, the TFAP4 level was also significantly related to the degree of tumour infiltration. TFAP4 was correlated using gene markers in tumour-infiltrating immune cells and immune scores. TFAP4 expression was correlated with tumour mutation burden and microsatellite instability in different cancer types, and enrichment analyses identified TFAP4-associated terms and pathways. The present study comprehensively analysed the expression of TFAP4 across 33 distinct types of cancers, which revealed that TFAP4 may possibly play a vital role during cancer formation and development. TFAP4 is related to differing degrees of immune infiltration within cancers, which suggests the potential of TFAP4 as an immunotherapy target in cancers. Our study demonstrated that TFAP4 plays an important role in tumorigenesis as a prognostic biomarker, which highlights the possibility of developing new targeted treatments.

Multishock to Quasi-Isentropic Compression of Dense Gaseous Deuterium-Helium Mixtures up to 120 GPa: Probing the Sound Velocities Relevant to Planetary Interiors.

Shock reverberation compression experiments on dense gaseous deuterium-helium mixtures are carried out to provide thermodynamic parameters relevant to the conditions in planetary interiors. The multishock pressures are determined up to 120 GPa and reshock temperatures to 7400 K. Furthermore, the unique compression path from shock-adiabatic to quasi-isentropic compressions enables a direct estimation of the high-pressure sound velocities in the unexplored range of 50-120 GPa. The equation of state and sound velocity provide particular dual perspectives to validate the theoretical models. Our experimental data are found to agree with several equation of state models widely used in astrophysics within the probed pressure range. The current data improve the experimental constraints on sound velocities in the Jovian insulating-to-metallic transition layer.

Surveillance Strategy after Complete Ablation of Initial Recurrent Hepatocellular Carcinoma: A Risk-Based Machine Learning Study.

PURPOSE: To investigate surveillance strategies for initial recurrent hepatocellular carcinoma (irHCC) after ablation to support clinical decision making, as there is no consensus regarding the monitoring strategy for irHCC after ablation. MATERIALS AND METHODS: Data from patients with irHCC who received ablation were retrospectively collected at 2 medical centers. The risk of tumor relapse in each month was calculated through random survival forest methodology, and follow-up schedules were arranged thereafter to maximize the capability of relapse detection at each visit. RESULTS: The cumulative 0.5-, 1-, 1.5-, and 2-year risk-adjusted probabilities in the training/validation cohorts were 26.2%/21.5%, 42.3%/39.4%, 55.5%/52.6%, and 61.3%/63.2%, respectively, with the highest recurrence rate occurring in the second month (maximum, 7.9%/7.4%). The surveillance regime primarily concentrated on the first year after treatment, especially the initial 6 months. The delay in detecting tumor recurrence gradually decreased when the total number of follow-up visits increased from 4 to 8. Compared with the control strategies, this schedule (follow-up visits at 2, 4, 6, 9, 12, and 18 months) reduced the delay in detection. The benefits of this surveillance regime were evident when the patients were followed up 6 times. The proposed 6-visit surveillance strategy significantly decreased the delay in detection compared with the control 7-visit approach (1.32 months vs 1.82 months, respectively; P < .001). CONCLUSIONS: The proposed new surveillance schedule minimized the delay in detecting recurrence in patients with irHCC after ablation. The risk-related machine learning method described in this study could be applied to develop follow-up strategies for other patients with hepatocellular carcinoma.

The enhanced mechanisms of Hansschlegelia zhihuaiae S113 degrading bensulfuron-methyl in maize rhizosphere by three organic acids in root exudates.

The residues of bensulfuron-methyl (BSM), a sulfonylurea herbicide, in soil have caused serious damage to the rotation of susceptible crops. Many studies have reported that the removal of BSM in soil was achieved by adding degrading bacteria. However, the mechanisms used by bacteria to degrade BSM in the crop rhizosphere remain unclear. In this study, a BSM-degrading bacterium, Hansschlegelia zhihuaiae S113, was applied to investigate the enhancement of effects mediated by organic acids during the bioremediation of BSM-contaminated maize rhizosphere soil. Organic acids, such as L-malic acid, tartaric acid, and fumaric acid, identified in maize root exudates, significantly stimulated the expression of cheA, which encoded the histidine kinase in strain S113 and contributed to the chemotactic response. This process accelerated the accumulation of strain S113 around the maize roots and promoted the colonization process on maize roots. The growth of strain S113 was significantly increased by L-malic acid but not tartaric acid or fumaric acid. After the S113 suspension was root-irrigated to BSM-contaminated soil, the density of strain S113 colonizing root surfaces and in rhizosphere soil reached 1.1 × 104 cells/g for roots and 4.9 × 104 cells/g in dry soil at 15 d, leading to 80.9% BSM degradation efficiency. The treatment with the addition of a mixture of S113 and L-malic acid completely degraded BSM in rhizosphere soil due to the strong attraction and growth promotion of strain S113 by L-malic acid, with a higher efficiency than that with the extra addition of fumaric acid (89.7%) or tartaric acid (87.0%). This paper revealed the enhancement effects of organic acids identified in root exudates for the in situ bioremediation of BSM-contaminated rhizosphere soil.

Analysis of competing endogenous RNA network identifies a poorly differentiated cancer-specific RNA signature for hepatocellular carcinoma.

Plenty of evidence has suggested that long noncoding RNAs (lncRNAs) play a vital role in competing endogenous RNA (ceRNA) networks. Poorly differentiated hepatocellular carcinoma (PDHCC) is a malignant phenotype. This paper aimed to explore the effect and the underlying regulatory mechanism of lncRNAs on PDHCC as a kind of ceRNA. Additionally, prognosis prediction was assessed. A total of 943 messenger RNAs (mRNAs), 86 miRNAs, and 468 lncRNAs that were differentially expressed between 137 PDHCCs and 235 well-differentiated HCCs were identified. Thereafter, a ceRNA network related to the dysregulated lncRNAs was established according to bioinformatic analysis and included 29 lncRNAs, 9 miRNAs, and 96 mRNAs. RNA-related overall survival (OS) curves were determined using the Kaplan-Meier method. The lncRNA ARHGEF7-AS2 was markedly correlated with OS in HCC (P = .041). Moreover, Cox regression analysis revealed that patients with low ARHGEF7-AS2 expression were associated with notably shorter survival time (P = .038). In addition, the area under the curve values of the lncRNA signature for 1-, 3-, and 5-year survival were 0.806, 0.741, and 0.701, respectively. Furthermore, a lncRNA nomogram was established, and the C-index of the internal validation was 0.717. In vitro experiments were performed to demonstrate that silencing ARHGEF7-AS2 expression significantly promoted HCC cell proliferation and migration. Taken together, our findings shed more light on the ceRNA network related to lncRNAs in PDHCC, and ARHGEF7-AS2 may be used as an independent biomarker to predict the prognosis of HCC.

Oxygen-functionalized TlTe buckled honeycomb from first-principles study.

A sizable band gap is crucial for the applications of topological insulators at room temperature. By first-principles calculations, we found that oxygen-functionalized TlTe buckled honeycomb, namely TlTeO, possessed quantum spin Hall (QSH) state with a sizable band gap of 0.17 eV, which owns potential applications at the room temperature. The QSH phase of TlTeO arose from the SOC-induced p-p band gap opening. In addition, the QSH phase was further confirmed by the topological invariant Z2 and gapless edge state in the bulk gap. Significantly, the QSH phase is robustly against the external strain and possesses more than 75% oxygen coverage, making the QSH effect of TlTeO easy to be achieved experimentally. Thus, the oxygen-functionalized TlTeO film is a fine candidate material for the topological device design and fabrication.

New C20-diterpenoid alkaloids from Aconitum vilmorrianum and structural revision of 2-O-acetylorochrine and orochrine.

Three new C20-diterpenoid alkaloids vilmorrianines E (1), F (2), and G (3) were isolated from the whole plants of Aconitum vilmorrianum, along with one artifact N-chloromethyl vilmorrianine E hydrochloride (4), as well as two known alkaloids hemsleyaconitines F (5) and G (6). The structures of 1-4 were established by HR-ESI-MS, 1D-, 2D-NMR (HMQC, HMBC, and NOESY), and single-crystal X-ray diffraction analysis. In addition, the structures of naturally occurring 2-O-acetylorochrine (7) and orochrine (8) were revised to be the known alkaloids heterophylloidine (9) and deacetyl heterophylloidine (10), respectively, on the basis of consideration of transannular effect and chemical correlations.

Generating skeletal diversity from the C19 -diterpenoid alkaloid deltaline: a ring-distortion approach.

The development of new drugs calls for large collections of diverse molecules with considerable complexity. Ring distortion of natural products provides an efficient and facile approach to access new architectures with intriguing biological activities, by harnessing their inherent complexity. In this study, such a strategy has been explored on an abundant C19 -diterpenoid alkaloid, deltaline, enabling the synthesis of 32 new derivatives bearing a broad spectrum of unique scaffolds. Extensive spectroscopic studies including X-ray crystallographic analyses strongly supported the structures of the obtained novel skeletons, which present comparable opportunities with the great contributions made by nature for discovery of new lead compounds.

Improving the Conversion Success Rate of Hepatocellular Carcinoma: Focus on the Use of Combination Therapy with a High Objective Response Rate.

The high mortality rate in hepatocellular carcinoma (HCC) is partially due to the fact that a significant number of patients are diagnosed at an intermediate or advanced stage, with surgical treatment options unavailable. Conversion therapy, which involves both locoregional and systemic treatments, has the potential to downstage tumors in selected patients with initially unresectable HCC, thereby making surgical treatment a possibility and potentially increasing long-term survival. To optimize the conversion rate, it is necessary to maximize successful conversions and clearly define the target population for conversion treatment through a collaborative effort. In this review article, we summarize the clinical experience and evidence for conversion therapy in patients with 'potentially resectable' HCC from four perspectives: 1) defining the target population for conversion therapy, 2) selecting the appropriate conversion strategy, placing emphasis on the utilization of combination therapy that exhibits a significant objective response rate, 3) determining the timing and urgency of surgical resection, 4) promoting the adoption of a multidisciplinary team model. The authors are optimistic that with the continuous progress in treatment and a deeper understanding of HCC, the success rate of HCC conversion therapy will increase, and the overall survival of HCC patients will be prolonged.

Noninvasive imaging-based machine learning algorithm to identify progressive disease in advanced hepatocellular carcinoma receiving second-line systemic therapy.

The aim of this study was to predict tyrosine kinase inhibitors (TKI) plus anti-PD-1 antibodies (TKI-PD-1) efficacy as second-line treatment in advanced hepatocellular carcinoma (HCC) using radiomics analysis. From November 2018 to November 2019, a total of 55 patients were included. Radiomic features were obtained from the CT images before treatment and filtered using intraclass correlation coefficients (ICCs) and least absolute shrinkage and selection operator (LASSO) methods. Subsequently, ten prediction algorithms were developed and validated based on radiomic characteristics. The accuracy of the constructed model was measured through area under the receiver operating characteristic curve (AUC) analysis; survival analysis was performed via Kaplan-Meier and Cox regression analyses. Overall, 18 (32.7%) out of 55 patients had progressive disease. Through ICCs and LASSO, ten radiomic features were entered into the algorithm construction and validation. Ten machine learning algorithms showed different accuracies, with the support vector machine (SVM) model having the highest AUC value of 0.933 in the training cohort and 0.792 in the testing cohort. The radiomic features were associated with overall survival. In conclsion, the SVM algorithm is a useful method to predict TKI-PD-1 efficacy in patients with advanced HCC using images taken prior to treatment.

Cost-effectiveness and prognostic model of hepatic arterial infusion chemotherapy for hepatocellular carcinoma with high tumor burden and/or Vp4 tumor thrombus compared with sorafenib: a post-hoc analysis of the FOHAIC-1 trial.

OBJECTIVES: The phase III FOHAIC-1 trial revealed that hepatic arterial infusion of chemotherapy (HAIC) improved overall survival compared to sorafenib in the high-risk hepatocellular carcinoma (HCC). This study therefore set out to evaluate the cost-effectiveness and establish a prognostic clinico-radiological score of HAIC. MATERIALS AND METHODS: A total of 409 patients with high-risk HCC who received HAIC between 2014 and 2020 were included. A Markov model was applied in the cost-effectiveness analysis using data from the FOHAIC-1 trial. In prognosis analysis, a clinico-radiological score was developed using a Cox-regression model and subsequently confirmed in the internal validation and test cohorts. The area under the curve from receiver operator characteristic analysis was used to assess the performance of the clinico-radiological score. RESULTS: HAIC resulted in an incremental cost-effectiveness ratio of $10190.41/quality-adjusted life years compared to sorafenib, which was lower than the willingness-to-pay threshold. Probabilistic sensitivity analysis predicted a ≥99.9% probability that the incremental cost-effectiveness ratio was below the willingness-to-pay. The Cox analysis identified five factors, namely extrahepatic metastasis (m), arterial enhancing type (a), tumor number (nu), albumin-bilirubin index (a), and involved lobe (l), which together comprise the clinico-radiological score (HAIC-manual). Patients were classified into three groups based on the number of factors present, with cutoffs at 2 and 4 factors. The stratified median overall survival for these groups were 21.6, 10.0, and 5.9 months, respectively ( P <0.001). These findings were verified through internal validation and test cohorts with a significance level of P ≤0.01. The time-dependent area under the curve from receiver operator characteristic for the ability of the HAIC-manual to predict survival in 1, 2, and 3 years were 0.71, 0.76, and 0.78, which significantly outperformed existing staging systems. CONCLUSION: HAIC is a promising and cost-effective strategy for patients with high-risk HCC. The clinico-radiological score may be a simple prognostic tool for predicting HAIC treatment.

An O-to-N intramolecular acyl migration in C19-diterpenoid alkaloids.

The O-acyl group at C-1 of two C19-diterpenoid alkaloids 2 and 5 was transferred to the secondary amine nitrogen to form amides 3 and 6 in the basic condition. This kind of O-to-N intramolecular acyl migration could be caused by the near distance between the nucleophilic nitrogen atom and the carbonyl group of the ester at C-1 in the C19-diterpenoid alkaloids, which is consistent with the conformation of rings A and E in the C19-diterpenoid alkaloids.

Transport properties of a quasisymmetric binary nitrogen-oxygen mixture in the warm dense regime.

Transport properties of mixtures in the warm dense matter (WDM) regime play an important role in natural astrophysics. However, a physical understanding of ionic transport properties in quasisymmetric liquid mixtures has remained elusive. Here, we present extensive ab initio molecular dynamics (AIMD) simulations on the ionic diffusion and viscosity of a quasisymmetric binary nitrogen-oxygen (N-O) mixture in a wide warm dense regime of 8-120 kK and 4.5-8.0 g/cm^{3}. Diffusion and viscosity of N-O mixtures with different compositions are obtained by using the Green-Kubo formula. Unlike asymmetric mixtures, the change of proportions in N-O mixtures slightly affects the viscosity and diffusion in the strong-coupling region. Furthermore, the AIMD results are used to build and verify a global pseudo-ion in jellium (PIJ) model for ionic transport calculations. The PIJ model succeeds in reproducing the transport properties of N-O mixtures where ionization has occurred, and provides a promising alternative approach to obtaining comparable results to AIMD simulations with relatively small computational costs. Our current results highlight the characteristic features of the quasisymmetric binary mixtures and demonstrate the applicability of the PIJ model in the WDM regime.

Arterial Chemotherapy of Oxaliplatin Plus Fluorouracil Versus Sorafenib in Advanced Hepatocellular Carcinoma: A Biomolecular Exploratory, Randomized, Phase III Trial (FOHAIC-1).

PURPOSE: Interventional hepatic arterial infusion chemotherapy of infusional fluorouracil, leucovorin, and oxaliplatin (HAIC-FO) displayed an encouraging safety profile and antitumor activity in a previous phase II trial and a propensity-score-matching study involving patients with locally advanced hepatocellular carcinoma (HCC). METHODS: In this open-label, phase III trial, patients with advanced HCC, previously untreated with systemic therapy, were randomly assigned in a 1:1 ratio to receive HAIC-FO or sorafenib. The primary end point was overall survival (OS) in the intention-to-treat population. An exploratory model for predicting the efficacy of HAIC-FO on the basis of genomic sequencing was developed. RESULTS: Between May 2017 and May 2020, 262 patients were randomly assigned. The median tumor size was 11.2 cm (interquartile range, 8.5-13.7 cm). Macrovascular invasion was present in 65.6%, and the percentage of patients with > 50% tumor volume involvement of the liver and/or Vp-4 portal vein tumor thrombosis was 49.2%. At data cutoff (October 31, 2020), median OS was 13.9 months for HAIC-FO and 8.2 for sorafenib (hazard ratio [HR] 0.408; 95% CI, 0.301 to 0.552; P < .001). Tumor downstaging occurred in 16 (12.3% of 130) patients receiving HAIC-FO, including 15 receiving curative surgery or ablation, and finally achieving a median OS of 20.8 months, with a 1-year OS rate of 93.8%. In high-risk subpopulations, OS was significantly longer with HAIC-FO than with sorafenib (10.8 months v 5.7 months; HR 0.343; 95% CI, 0.219 to 0.538; P < .001). A newly developed 15-mutant-gene prediction model identified 83% of patients with response to HAIC-FO. HAIC-FO responders had longer OS than HAIC-FO nonresponders (19.3 months v 10.6 months; HR 0.323; 95% CI, 0.186 to 0.560; P = .002). CONCLUSION: HAIC-FO achieved better survival outcomes than sorafenib in advanced HCC, even in association with a high intrahepatic disease burden.

Surveillance Strategy for Barcelona Clinic Liver Cancer B Hepatocellular Carcinoma Achieving Complete Response: An Individualized Risk-Based Machine Learning Study.

Background: For patients with complete response (CR) of Barcelona Clinical Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC), there is no consensus regarding the monitoring strategy. Optimal surveillance strategies that can detect early progression of HCC within a limited visit after treatment have not yet been investigated. A retrospective, real-world study was conducted to investigate surveillance strategies for BCLC stage B HCC (BBHCC) patients with CR after curative treatment to support clinical decision making. Methods: From January 2007 to December 2019, 546 BBHCC patients with CR after radical treatment were collected at Sun Yat-sen University Cancer Center. Seventy percent of patients were subjected to the train cohort randomly; the remaining patients comprised the validation cohort to verify the proposed arrangements. The random survival forest method was applied to calculate the disease progression hazard per month, and follow-up schedules were arranged to maximize the capability of progression detection at each visit. The primary endpoint of the study was the delayed-detection months for disease progression. Results: The cumulative 1, 2, and 3-years risk-adjusted probabilities for the train/validation cohorts were 32.8%/33.7%, 54.0%/56.3%, and 64.0%/67.4%, respectively, with peaks around approximately the 9th month. The surveillance regime was primarily concentrated in the first year posttreatment. The delayed-detection months gradually decreased when the total follow-up times increased from 6 to 11. Compared with controls, our schedule reduced delayed detection. Typically, the benefits of our surveillance regimes were obvious when the patients were followed seven times according to our schedule. The optional schedules were 5, 7, 9, 11, 17, 23, and 30 months. Conclusion: The proposed new surveillance schedule may provide a new perspective concerning follow-up for BBHCC patients with CR.

Consensus of Minimally Invasive and Multidisciplinary Comprehensive Treatment for Hepatocellular Carcinoma - 2020 Guangzhou Recommendations.

In China, the majority of patients with hepatocellular carcinoma (HCC) result from long-term infection of hepatitis B. Pathologically, HCC is characterized by rich blood supply, multicentric origins, early vascular invasion and intrahepatic metastasis. Therefore, HCC is not a local disease but a systemic disease at the beginning of its occurrence. For this reason, a comprehensive treatment strategy should be adopted in the management of HCC, including local treatments (such as surgical resection, radiofrequency ablation, microwave ablation, chemical ablation and cryoablation, etc.), organ-level treatments [such as transcatheter arterial infusion of chemotherapy and transcatheter arterial chemoembolization (TACE)], and systemic treatments (such as immunotherapy, antiviral therapy and molecular targeted therapy, etc.). This consensus sets forth the minimally-invasive and multidisciplinary comprehensive guideline of HCC, focusing on the following eight aspects (1) using hepaticarteriography, CT hepatic arteriography (CTHA), CT arterial portography (CTAP), lipiodol CT (Lp-CT), TACE-CT to find the intrahepatic lesion and make precise staging (2) TACE combined with ablation or ablation as the first choice of treatment for early stage or small HCC, while other therapies are considered only when ablation is not applicable (3) infiltrating HCC should be regarded as an independent subtype of HCC (4) minimally-invasive comprehensive treatment could be adopted in treating metastatic lymph nodes (5) multi-level subdivision of M-staging should be used for individualized treatment and predicting prognosis (6) HCC with severe hepatic decompensation is the only candidate criterion for liver transplantation (7) bio-immunotherapy, traditional Chinese medicine therapy, antiviral therapy, and psychosocial and psychopharmacological interventions should be advocated through the whole course of HCC treatment (8) implementation of multicenter randomized controlled trials of minimally-invasive therapy versus surgery for early and intermediate stage HCC is recommended.

Bioinformatic analysis and in vitro validation of a five-microRNA signature as a prognostic biomarker of hepatocellular carcinoma.

BACKGROUND: Existing research has identified correlations between numerous microRNAs (miRNAs) and the prognosis of hepatocellular carcinoma (HCC). However, the role of a combination of miRNAs in predicting HCC survival requires further elucidation. METHODS: miRNA expression profiles and clinical data from HCC patients were downloaded from The Cancer Genome Atlas (TCGA). Differentially expressed (DE) miRNAs in tumor versus normal samples were identified. All HCC patients were randomly assigned to a training cohort or a validation cohort at a ratio of 1 to 1. A least absolute shrinkage and selection operator (LASSO) Cox regression model was subsequently employed to establish the miRNA signature. The constructed miRNA signature was then developed and validated. RESULTS: In total, 127 DE miRNAs were detected between HCC and paracancerous tissue using HCC RNA sequencing (RNA-Seq) data extracted from TCGA database. LASSO Cox regression generated a five-miRNA signature consisting of has-mir-105-2, has-mir-9-3, has-mir-137, has-mir-548f-1, and has-mir-561 in the training cohort. This risk model was significantly related to survival (P=5.682e-6). Log-rank tests and multivariate Cox regression analyses revealed the five-miRNA signature as an independent prognostic indicator [HR =3.285, 95% confidence interval (CI): 1.737-6.213], with the area under curve (AUC) of the miRNA signature being 0.728. The effects of the miRNA signature were further confirmed in the validation cohort and in the OncomiR Cancer Database and Gene Expression Omnibus (GEO) dataset. Functional enrichment analysis revealed the potential effects of the five-miRNA signature in tumor-related biological pathways and processes. Cell Counting Kit-8, Transwell, and wound healing assays, were used to evaluate the role of has-mir-137 in HCC cell proliferation and migration in vitro. CONCLUSIONS: We established a novel five-miRNA signature which reliably predicted prognosis in HCC patients and which could be used to assist in both strategic counseling and personalized management in HCC.