A novel liver-function-indicators-based prognosis signature for patients with hepatocellular carcinoma treated with anti-programmed cell death-1 therapy.

BACKGROUND: The liver function reserve has a significant impact on the therapeutic effects of anti-programmed cell death-1 (PD-1) for hepatocellular carcinoma (HCC). This study aimed to comprehensively evaluate the ability of liver-function-based indicators to predict prognosis and construct a novel prognostic score for HCC patients with anti-PD-1 immunotherapy. METHODS: Between July 2018 and January 2020, patients diagnosed with HCC who received anti-PD-1 treatment were screened for inclusion in the study. The valuable prognostic liver-function-based indicators were selected using Cox proportional hazards regression analysis to build a novel liver-function-indicators-based signature (LFIS). Concordance index (C-index), the area under the receiver operating characteristic (ROC) curve (AUC), and Kaplan-Meier survival curves were utilized to access the predictive performance of LFIS. RESULTS: A total of 434 HCC patients who received anti-PD-1 treatment were included in the study. The LFIS, based on alkaline phosphatase-to-albumin ratio index, Child-Pugh score, platelet-albumin score, aspartate aminotransferase-to-lymphocyte ratio index, and gamma-glutamyl transpeptidase-to-lymphocyte ratio index, was constructed and identified as an independent risk factor for patient survival. The C-index of LFIS for overall survival (OS) was 0.692, which was higher than the other single liver-function-based indicator. The AUC of LFIS at 6-, 12-, 18-, and 24-month were 0.74, 0.714, 0.747, and 0.865 for OS, respectively. Patients in the higher-risk LFIS group were associated with both worse OS and PFS. An online and easy-to-use calculator was further constructed for better application of the LFIS signature. CONCLUSION: The LFIS score had an excellent prognosis prediction ability superior to every single liver-function-based indicator for anti-PD-1 treatment in HCC patients. It is a reliable, easy-to-use tool to stratify risk for OS and PFS in HCC patients who received anti-PD-1 treatment.

The pyroptosis-related gene signature predicts prognosis and indicates immune activity in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) remains one of the most common malignant tumors with poor survival. Pyroptosis is a kind of programmed cell death that can regulate the proliferation, invasion, and metastasis of tumor cells. However, the expression levels of pyroptosis-related genes (PRGs) in HCC and their relationship with prognosis are still unclear. METHODS: Our study identified 35 PRGs through bioinformatics analysis that were differentially expressed between tumor samples and nontumor samples. According to these differentially expressed genes, HCC patients could be divided into two groups, cluster 1 and cluster 2. The least absolute shrinkage and selection operator (LASSO) Cox regression method was performed to construct a 10-gene signature that classified HCC patients in the cancer genome atlas (TCGA) database into low-risk and high-risk groups. RESULTS: The results showed that the survival rate of HCC patients in the low-risk group was significantly higher than that in the high-risk group (p < 0.001). The validation cohort, the Gene Expression Omnibus (GEO) cohort, was divided into two risk groups based on the median risk score calculated by the TCGA cohort. The overall survival (OS) of the low-risk group was significantly better than that of the high-risk group (p = 0.007). Univariate and multivariate Cox regression analyses revealed that the risk score was an independent factor in predicting OS in HCC patients. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that immune-related high-risk groups were rich in genes and had reduced immune status. CONCLUSIONS: PRGs play a significant role in tumor immunity and have the potential capability to predict the prognosis of HCC patients.

Four-gene signature predicting overall survival and immune infiltration in hepatocellular carcinoma by bioinformatics analysis with RT‒qPCR validation.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most lethal cancers, with a poor prognosis. Prognostic biomarkers for HCC patients are urgently needed. We aimed to establish a nomogram prediction system that combines a gene signature to predict HCC prognosis. METHODS: Differentially expressed genes (DEGs) were identified from publicly available Gene Expression Omnibus (GEO) datasets. The Cancer Genome Atlas (TCGA) cohort and International Cancer Genomics Consortium (ICGC) cohort were regarded as the training cohort and testing cohort, respectively. First, univariate and multivariate Cox analyses and least absolute shrinkage and selection operator (LASSO) regression Cox analysis were performed to construct a predictive risk score signature. Furthermore, a nomogram system containing a risk score and other prognostic factors was developed. In addition, a correlation analysis of risk group and immune infiltration was performed. Finally, we validated the expression levels using real-time PCR. RESULTS: Ninety-five overlapping DEGs were identified from four GEO datasets, and we constructed a four-gene-based risk score predictive model (risk score = EZH2 * 0.075 + FLVCR1 * 0.086 + PTTG1 * 0.015 + TRIP13 * 0.020). Moreover, this signature was an independent prognostic factor. Next, the nomogram system containing risk score, sex and TNM stage indicated better predictive performance than independent prognostic factors alone. Moreover, this signature was significantly associated with immune cells, such as regulatory T cells, resting NK cells and M2 macrophages. Finally, RT‒PCR confirmed that the mRNA expressions of four genes were upregulated in most HCC cell lines. CONCLUSION: We developed and validated a nomogram system containing the four-gene risk score, sex, and TNM stage to predict prognosis.

Development and Validation of a Novel Nomogram for Predicting Vessels that Encapsulate Tumor Cluster in Hepatocellular Carcinoma.

BACKGROUND: Vessels that encapsulate tumor cluster (VETC) is associated with poor prognosis in hepatocellular carcinoma (HCC). Vessels that encapsulate tumor cluster estimation before initial treatment is helpful for clinical doctors. We aimed to construct a novel predictive model for VETC, using preoperatively accessible clinical parameters and imagine features. METHODS: Totally, 365 HCC patients who received curative hepatectomy in the Sun Yat-Sen University Cancer Center from 2013 to 2014 were enrolled in this study. Vessels that encapsulate tumor cluster pattern was confirmed by immunochemistry staining. 243 were randomly assigned to the training cohort while the rest was assigned to the validation cohort. Independent predictive factors for VETC estimation were determined by univariate and multivariate logistic analysis. We further constructed a predictive nomogram for VETC in HCC. The performance of the nomogram was evaluated by C-index, receiver operating characteristic (ROC) curve, and calibration curve. Besides, the decision curve was plotted to evaluate the clinical usefulness. Ultimately, Kaplan-Meier survival curves were utilized to confirm the association between the nomogram and survival. RESULTS: Immunochemistry staining revealed VETC in 87 patients (23.8%). lymphocyte to monocyte ratio (>7.75, OR = 4.06), neutrophil (>7, OR = 4.48), AST to ALT ratio (AAR > .86, OR = 2.16), ALT to lymphocyte ratio index (BLRI > 21.73, OR = 2.57), alpha-fetoprotein (OR = 1.1), and tumor diameter (OR = 2.65) were independent predictive factors. The nomogram incorporating these predictive factors performed well with an area under the curve (AUC) of .746 and .707 in training and validation cohorts, respectively. Calibration curves indicated the predicted probabilities closely corresponded with the actual VETC status. Moreover, the decision curve proved our nomogram could provide clinical benefits with patients. Finally, low probability of VETC group had significantly longer recurrence free survival (RFS) and overall survival (OS) than the high probability of the VETC group (all P < .001). CONCLUSION: A novel predictive nomogram integrating clinical indicators and image characteristics shows strong predictive VETC performance and might provide standardized net clinical benefits.

Pan-cancer analysis of the CASP gene family in relation to survival, tumor-infiltrating immune cells and therapeutic targets.

The cysteinyl aspartate protease (caspase, or CASP) gene family plays a significant role in programmed cell death, inflammation and immunity. However, the correlation between CASP family members and prognosis and tumor-infiltrating lymphocytes in different tumors has not been determined. We investigated the role of CASP genes in cancer prognosis and their relationship with clinicopathological parameters. We also evaluated the correlation between the expression of CASP family members and cancer immune infiltration and evaluated whether these molecules can be used as targets for immunotherapy. The CASP1/2/4/5/7/9 genes may represent prognostic factors and therapeutic targets for breast cancer, hepatocellular carcinoma and pancreatic cancer. Another finding is that the CASP1/4/5 genes help to regulate innate immunity and T cell immunity and may also have an important effect on tumor checkpoint inhibition. These findings may elucidate the roles played by CASP family members in cancer progression and identify strategies to promote collaborative activities in the context of immunotherapy.

The microstructure and property of Al-Si alloy improved by the Sc-microalloying and Y2O3 nano-particles.

The effect of Sc-microalloying and Y2O3 nano-particles on the microstructure and mechanical properties of as-cast Al-5.5Si alloy is studied by means of optical microscopy, transmission electron microscopy, hardness test and tensile test. The influence of annealing treatment on the microstructure and properties of the Al-Si alloys is also investigated as well. The results show that the addition of Sc and Y2O3 nano-particles could significantly improve the mechanical property of the Al-Si alloy. The ultimate tensile strength and yield strength of Al-Si-Sc/Y2O3 alloy are improved by around 45 and 71%, respectively, when compared to that of the Al-Si alloy. The effect of the nanosized particles (precipitated and added) on strengthening and deformation of Al-Si alloy is analyzed and discussed in detail. The results of annealing treatment indicate that the change in mechanical property of the Al-Si-Sc alloy during annealing treatment is mainly associated with the precipitation of the secondary Si phase.

Assessment of the expression of the immune checkpoint molecules PD-1, CTLA4, TIM-3 and LAG-3 across different cancers in relation to treatment response, tumor-infiltrating immune cells and survival.

Immune checkpoint molecules have been identified as crucial regulators of the immune response, which motivated the emergence of immune checkpoint-targeting therapeutic strategies. However, the prognostic significance of the immune checkpoint molecules PD-1, CTLA4, TIM-3 and LAG-3 remains controversial. The aim of our study was to conduct a systematic assessment of the expression of these immune checkpoint molecules across different cancers in relation to treatment response, tumor-infiltrating immune cells and survival. Oncomine and PrognoScan database analyses were used to investigate the expression levels and prognostic values of these immune checkpoint molecule genes across various cancers. Then, we used Kaplan-Meier plotter to validate the associations between the checkpoint molecules and cancer survival identified in the PrognoScan analysis. TIMER analysis was used to evaluate immune cell infiltration data from The Cancer Genome Atlas. Finally, we used Gene Expression Profiling Interactive Analysis to investigate the prognostic value of these four checkpoint molecules and assess the correlations between these four checkpoint molecules and genetic markers. These immune checkpoint molecules may potentially serve as prognostic factors and therapeutic targets in breast cancer, ovarian cancer and lung cancer. The prognostic roles of these checkpoint molecules varied greatly across cancers, which implied a noteworthy amount of heterogeneity among tumors, even within the same molecular subtype. In addition, the expression patterns of these checkpoint molecules were closely associated with treatment response and provided some useful direction when choosing chemotherapeutic drugs. These findings enhance our understanding of these checkpoints in cancer treatment and identify strategies to promote synergistic activities in the context of other immunotherapies.

Risk of hepatitis B virus reactivation and its effect on survival in advanced hepatocellular carcinoma patients treated with hepatic arterial infusion chemotherapy and lenvatinib plus programmed death receptor-1 inhibitors.

Background: Hepatitis B virus (HBV) reactivation is a common complication in hepatocellular carcinoma (HCC) patients treated with chemotherapy or immunotherapy. This study aimed to evaluate the risk of HBV reactivation and its effect on survival in HCC patients treated with HAIC and lenvatinib plus PD1s. Methods: We retrospectively collected the data of 213 HBV-related HCC patients who underwent HAIC and lenvatinib plus PD1s treatment between June 2019 to June 2022 at Sun Yat-sen University, China. The primary outcome was the risk of HBV reactivation. The secondary outcomes were overall survival (OS), progression-free survival (PFS), and treatment-related adverse events. Results: Sixteen patients (7.5%) occurred HBV reactivation in our study. The incidence of HBV reactivation was 5% in patients with antiviral prophylaxis and 21.9% in patients without antiviral prophylaxis, respectively. The logistic regression model indicated that for HBV reactivation, lack of antiviral prophylaxis (P=0.003) and tumor diameter (P=0.036) were independent risk factors. The OS and PFS were significantly shorter in the HBV reactivation group than the non-reactivation group (P=0.0023 and P=0.00073, respectively). The number of AEs was more in HBV reactivation group than the non-reactivation group, especially hepatic AEs. Conclusion: HBV reactivation may occur in HCC patients treated with HAIC and lenvatinib plus PD1s. Patients with HBV reactivation had shorter survival time compared with non-reactivation. Therefore, HBV-related HCC patients should undergo antiviral therapy and HBV-DNA monitoring before and during the combination treatment.

The ARH score, a practical guide to decision-making for retreatment with hepatic arterial infusion chemotherapy in hepatocellular carcinoma patients.

BACKGROUND: Hepatic arterial infusionchemotherapy (HAIC) is a promising option for large unresectable hepatocellular carcinoma (HCC). Identifying patients who could benefit from continuous HAIC remains a challenge. We aimed to establish an objective model to guide the decision for retreatment with HAIC. METHODS: Between 2015 and 2020, the data of patients with large unresectable HCC without macrovascular invasion or extrahepatic spread undergoing multiple HAIC cycles from 3 different centers were retrieved. We investigated the basic tumor parameters and the effect of HAIC on liver function and tumor response, and their impact on overall survival (OS). A point score (ARH, Assessment for Retreatment with HAIC) was built by using a stepwise Cox regression model in the training cohort (n = 112) and was validated in an independent validation cohort (n = 71). RESULTS: The high α-fetoprotein before the second cycle of HAIC, an increase in Child-Pugh score, and undesirable radiologic tumor responses remained independent negative prognostic factors and were used to create the ARH score. The prognosis of HCC patients deteriorated significantly with the increase in ARH score. The median OS of patients with ARH score 0-2 points and ≥ 2.5 points were 19.37 months and 11.60 months (P < 0.001). All of these results had been confirmed in the external validation cohort and demonstrated significance across multiple subgroups. CONCLUSIONS: The ARH score makes an excellent prediction of the prognosis of HCC patients who received retreatment of HAIC. Patients with an ARH score ≥ 2.5 prior to the second cycle of HAIC may not profit from further sessions.

Hepatic Arterial Infusion Chemotherapy vs Transcatheter Arterial Chemoembolization as Adjuvant Therapy Following Surgery for MVI-Positive Hepatocellular Carcinoma: A Multicenter Propensity Score Matching Analysis.

Background: Microvascular invasion (MVI) is a significant pathological feature in hepatocellular carcinoma (HCC), adjuvant hepatic arterial infusion chemotherapy (a-HAIC) and adjuvant transcatheter arterial chemoembolization (a-TACE), are commonly used for HCC patients with MVI. This study aims to evaluate the efficacies of two adjuvant therapies after surgical treatment for HCC, compare them, and identify the significant factors. Methods: Clinical data from two randomized controlled trials involving HCC patients with MVI after surgical treatment were retrospectively reviewed. Propensity score matching (PSM) analysis was performed to balance baseline differences between patients who received a-HAIC or a-TACE, and control groups who underwent hepatectomy alone. Disease-free survival (DFS) and overall survival (OS) rates were compared. Results: In total of 549 patients were collected from two randomized controlled trials. Using the PSM and Kaplan-Meier method, the median DFS of the a-HAIC, a-TACE, and control groups was 63.2, 21.7, and 11.2 months (P<0.05). The a-HAIC group show significantly better 1-, 3-, and 5-year OS rates compared to the a-TACE and control groups (96.3%, 80.0%, 72.8% vs 84.4%, 57.0%, 29.8% vs 84.5%, 62.8%, 53.4%, P<0.05). But the OS rates of a-TACE and control groups showed no significant difference (P=0.279). Multivariate analysis identified a-HAIC (HR=0.449, P=0.000) and a-TACE (HR=0.633, P=0.007) as independent protective factors. For OS, a-HAIC (HR=0.388, P=0.003) was identified as an independent protective factor, too. Conclusion: Compared to a-TACE and the control group, a-HAIC demonstrated greater benefits in preventing tumor recurrence and improving survival in HCC patients with MVI.

Patients with hepatocellular carcinoma extrahepatic metastases can benefit from hepatic arterial infusion chemotherapy combined with lenvatinib plus programmed Death-1 inhibitors.

BACKGROUND: Lenvatinib plus Programmed Death-1 (PD-1) inhibitors (LEN-P) have been recommended in China for patients with advanced hepatocellular carcinoma (HCC). However, they provide limited survival benefits to patients with extrahepatic metastases. We aimed to investigate whether combining hepatic arterial infusion chemotherapy (HAIC) with LEN-P could improve its efficacy. MATERIALS AND METHODS: This multi-center cohort study included patients with HCC extrahepatic metastases who received HAIC combined with LEN-P (HAIC-LEN-P group, n=127) or LEN-P alone (n=103) as the primary systemic treatment between January 2019 and December 2022. Baseline data were balanced using a one-to-one propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). RESULTS: After PSM, the HAIC-LEN-P group significantly extended the median overall survival (mOS) and median progression-free survival (mPFS), compared with the LEN-P group (mOS: 27.0 months vs. 9.0 months, P<0.001; mPFS: 8.0 months vs. 3.0 months, P=0.001). After IPTW, the mOS (hazard ratio (HR)=0.384, P<0.001) and mPFS (HR=0.507, P<0.001) were significantly higher in the HAIC-LEN-P group than in the LEN-P group. The HAIC-LEN-P group's objective response rate was twice as high as that of the LEN-P group (PSM cohort: 67.3% vs. 29.1%, P<0.001; IPTW cohort: 66.1% vs. 27.8%, P<0.001). Moreover, the HAIC-LEN-P group exhibited no noticeable increase in the percentages of grade 3 and 4 adverse events compared with the LEN-P group (P>0.05). CONCLUSION: HAIC can improve the efficacy of LEN-P in patients with HCC extrahepatic metastases and may be an alternative treatment for advanced HCC management.

In vitro degradation of four magnesium-zinc-strontium alloys and their cytocompatibility with human embryonic stem cells.

Magnesium alloys have attracted great interest for medical applications due to their unique biodegradable capability and desirable mechanical properties. When designed for medical applications, these alloys must have suitable degradation properties, i.e., their degradation rate should not exceed the rate at which the degradation products can be excreted from the body. Cellular responses and tissue integration around the Mg-based implants are critical for clinical success. Four magnesium-zinc-strontium (ZSr41) alloys were developed in this study. The degradation properties of the ZSr41 alloys and their cytocompatibility were studied using an in vitro human embryonic stem cell (hESC) model due to the greater sensitivity of hESCs to known toxicants which allows to potentially detect toxicological effects of new biomaterials at an early stage. Four distinct ZSr41 alloys with 4 wt% zinc and a series of strontium compositions (0.15, 0.5, 1, and 1.5 wt% Sr) were produced through metallurgical processing. Their degradation was characterized by measuring total mass loss of samples and pH change in the cell culture media. The concentration of Mg ions released from ZSr41 alloy into the cell culture media was analyzed using inductively coupled plasma atomic emission spectroscopy. Surface microstructure and composition before and after culturing with hESCs were characterized using field emission scanning electron microscopy and energy dispersive X-ray spectroscopy. Pure Mg was used as a control during cell culture studies. Results indicated that the Mg-Zn-Sr alloy with 0.15 wt% Sr provided slower degradation and improved cytocompatibility as compared with pure Mg control.

Analysis of the Prognosis Prediction Ability of a Necroptosis-Related Gene Signature and its Relationship With the Hepatocellular Carcinoma Immune Microenvironment Using Bioinformatics Analysis and Experimental Validation.

Background: Hepatocellular carcinoma (HCC) is one of the most malignant cancers and has a poor prognosis. The immune microenvironment is closely related to the drug sensitivity of a tumor. Necroptosis was reported to be a key factor for HCC. The prognostic value of necroptosis-related genes and their association with the tumor immune microenvironment are still unknown. Methods: Necroptosis-related genes that could comprise a signature for predicting the prognosis of HCC cases were identified using univariate analysis and least absolute shrinkage and selection operator Cox regression analysis. The association between this prognosis prediction signature and HCC immune microenvironment was analyzed. The immunological activities and drug sensitivities were compared between different risk score groups identified using the prognosis prediction signature. The expression levels of the five genes comprising the signature were validated using RT-qPCR. Results: A prognosis prediction signature consisting of five necroptosis-related genes was constructed and validated. Its risk score was = (0.1634 × PGAM5 expression) + (0.0134 × CXCL1 expression) - (0.1007 × ALDH2 expression) + (0.2351 × EZH2 expression) - (0.0564 × NDRG2 expression). The signature was found to be significantly associated with the infiltration of B cells, CD4+ T cells, neutrophils, macrophages, and myeloid dendritic cells into the HCC immune microenvironment. The number of infiltrating immune cells and the expression levels of immune checkpoints in the immune microenvironment of high-risk score patients were higher. Sorafenib and immune checkpoint blockade were determined to be ideally suited for treating high-risk score patients and low-risk score patients, respectively. Finally, RT-qPCR results confirmed that the expression levels of EZH2, NDRG2, and ALDH2 were significantly down-regulated in HuH7 and HepG2 cells compared to those in LO2 cells. Conclusion: The necroptosis-related gene signature developed herein can classify patients with HCC according to prognosis risk well and is associated with infiltration of immune cells into the tumor immune microenvironment.

Is the CRAFITY score a superior predictor of prognosis and adverse events in hepatocellular carcinoma patients treated with locoregional-immunotherapy?

BACKGROUND: The level of C­reactive protein (CRP) and alpha­fetoprotein (AFP) in immunotherapy (CRAFITY) score was associated with the prognosis of hepatocellular carcinoma (HCC) patients treated with immunotherapy. Based on the CRAFITY score, this study aimed to investigate the efficacy and safety of locoregional-immunotherapy for treating HCC patients. METHODS: HCC patients who received locoregional-immunotherapy were consecutively recruited at Sun Yat-sen University Cancer Center in 2019. CRAFITY 0 score was defined as the AFP level below 100 ng/ml and a CRP level of less than 1 mg/dl, CRAFITY 1 score was defined as the AFP level of at least 100 ng/ml or the CRP level of at least 1 mg/dl, and CRAFITY 2 score was defined as both the AFP level over 100 ng/ml and the CRP level of more than 1 mg/dl. The primary outcomes were progression-free survival (PFS) and overall survival (OS). The second outcomes were tumor response rate and treatment-related adverse events (AEs). RESULTS: The median PFS for HCC patients with the CRAFITY 0 score was not estimable. The PFS was 11.0 months [95% confidence interval (CI) 7.2-14.9] and 6.0 months (95% CI 4.2-7.8) for patients with CRAFITY 1 and 2 scores, respectively, with a significant difference between the two groups (p < 0.001). HCC patients with CRAFITY 0, 1, and 2 scores had 3 years OS rates of 63.8%, 60.8%, and 32.1%, respectively, with statistical differences among the three groups (p < 0.001). Patients with the CRAFITY 2 score were more likely to experience fever than those with other scores (p < 0.05). A greater CRAFITY score was correlated with a higher incidence of grade 3 and above liver injury (p < 0.01). CONCLUSIONS: The CRAFITY score is a superior predictor of prognosis and treatment-related AEs in HCC patients treated with locoregional-immunotherapy.

Hepatic arterial infusion chemotherapy versus transarterial chemoembolization, potential conversion therapies for single huge hepatocellular carcinoma: a retrospective comparison study.

BACKGROUND: The treatment efficacy of transarterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) for huge single hepatocellular carcinoma (HCC) has not been fully documented. The aim of this study was to compare TACE and HAIC for patients with solitary nodular HCCs greater than or equal to 10 cm without vascular invasion and metastasis. METHODS: From July 2015 to June 2020, a total of 147 patients with single nodular HCC greater than or equal to 10 cm without vascular invasion and metastasis receiving TACE ( n =77) or HAIC ( n =70) were retrospectively enrolled. The tumor response, overall survival (OS), and progression-free survival (PFS) were investigated and compared. The treatment outcome of two transarterial interventional therapies was explored. RESULTS: The objective response rate and PFS were higher in patients who received HAIC than in those who received TACE (44.3 vs. 10.4% and 8.9 vs. 4.2 months, respectively; P =0.001 and P =0.030), whereas the disease control rate and OS were not significantly different (92.9 vs. 84.4% and 21.3 vs. 26.6 months, respectively; P =0.798 and P =0.749). The decreased levels of alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II (PIVKA-II) in patients treated with HAIC were significantly higher than those treated with TACE ( P =0.038 and P <0.001). Multivariable analysis showed that the aspartate aminotransferase/platelet ratio index was associated with OS, whereas albumin-bilirubin grade and PIVKA-II were associated with PFS. CONCLUSIONS: HAIC has better potential than TACE to control local tumors for huge single HCC without vascular invasion and metastasis and thus may be the preferred conversion therapy for these tumors.

A Comparison between Porous to Fully Dense Electrodeposited CuNi Films: Insights on Electrochemical Performance.

Nanostructuring of metals is nowadays considered as a promising strategy towards the development of materials with enhanced electrochemical performance. Porous and fully dense CuNi films were electrodeposited on a Cu plate by electrodeposition in view of their application as electrocatalytic materials for the hydrogen evolution reaction (HER). Porous CuNi film were synthesized using the hydrogen bubble template electrodeposition method in an acidic electrolyte, while fully dense CuNi were electrodeposited from a citrate-sulphate bath with the addition of saccharine as a grain refiner. The prepared films were characterized chemically and morphologically by scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), and X-ray diffraction (XRD). The Rietveld analysis of the XRD data illustrates that both CuNi films have a nanosized crystallite size. Contact angle measurements reveal that the porous CuNi film exhibits remarkable superhydrophobic behavior, and fully dense CuNi film shows hydrophilicity. This is predominately ascribed to the surface roughness of the two films. The HER activity of the two prepared CuNi films were investigated in 1 M KOH solution at room temperature by polarization measurements and electrochemical impedance spectroscopy (EIS) technique. Porous CuNi exhibits an enhanced catalysis for HER with respect to fully dense CuNi. The HER kinetics for porous film is processed by the Volmer-Heyrovsky reaction, whereas the fully dense counterpart is Volmer-limited. This study presents a clear comparison of HER behavior between porous and fully dense CuNi films.

Development of nomograms to predict recurrence after conversion hepatectomy for hepatocellular carcinoma previously treated with transarterial interventional therapy.

BACKGROUND: Lack of opportunity for radical surgery and postoperative tumor recurrence are challenges for surgeons and hepatocellular carcinoma (HCC) patients. This study aimed to develop nomograms to predict recurrence risk and recurrence-free survival (RFS) probability after conversion hepatectomy for patients previously receiving transarterial interventional therapy. METHODS: In total, 261 HCC patients who underwent conversion liver resection and previously received transarterial interventional therapy were retrospectively enrolled. Nomograms to predict recurrence risk and RFS were developed, with discriminative ability and calibration evaluated by C-statistics, calibration plots, and the Area under the Receiver Operator Characteristic (AUROC) curves. RESULTS: Univariate/multivariable logistic regression and Cox regression analyses were used to identify predictive factors for recurrence risk and RFS, respectively. The following factors were selected as predictive of recurrence: age, tumor number, microvascular invasion (MVI) grade, preoperative alpha-fetoprotein (AFP), preoperative carbohydrate antigen 19-9 (CA19-9), and Eastern Cooperative Oncology Group performance score (ECOG PS). Similarly, age, tumor number, postoperative AFP, postoperative protein induced by vitamin K absence or antagonist-II (PIVKA-II), and ECOG PS were incorporated for the prediction of RFS. The discriminative ability and calibration of the nomograms revealed good predictive ability. Calibration plots showed good agreement between the nomogram predictions of recurrence and RFS and the actual observations. CONCLUSIONS: A pair of reliable nomograms was developed to predict recurrence and RFS in HCC patients after conversion resection who previously received transarterial interventional therapy. These predictive models can be used as guidance for clinicians to help with treatment strategies.

Nomograms for predicting the recurrence probability and recurrence-free survival in patients with hepatocellular carcinoma after conversion hepatectomy based on hepatic arterial infusion chemotherapy: a multicenter, retrospective study.

BACKGROUND: This study aimed to establish and validate nomograms to predict the probability of recurrence and recurrence-free survival (RFS) in patients with hepatocellular carcinoma (HCC) after conversion hepatectomy based on hepatic arterial infusion chemotherapy (HAIC). METHODS: Nomograms were constructed using data from a retrospective study of 214 consecutive patients treated with HAIC-based conversion liver resection between January 2016 and July 2020. Nomograms predicting the probability of tumor recurrence and RFS were established based on predictors selected by multivariate regression analysis. Predictive accuracy and discriminative ability of the nomogram were examined. Bootstrap method was used for internal validation. External validation was performed using cohorts ( n =128) from three other centers. RESULTS: Recurrence rates in the primary and external validation cohorts were 63.6 and 45.3%, respectively. Nomograms incorporating clinicopathological features of tumor recurrence and RFS were generated. Concordance index (C-index) scores of the nomograms for predicting recurrence probability and RFS were 0.822 (95% CI, 0.703-0.858) and 0.769 (95% CI, 0.731-0.814) in the primary cohort, and 0.802 (95% CI, 0.726-0.878) and 0.777 (95% CI, 0.719-0.835) in the external validation cohort, respectively. Calibration curves indicated good agreement between the nomograms and actual observations. Moreover, the nomograms outperformed the commonly used staging systems. Patients with low risk, stratified by the median nomogram scores had better RFS (low risk vs. high risk, 36.5 vs. 5.2 months, P <0.001). The external validation cohort supported these findings. CONCLUSIONS: The presented nomograms showed favorable accuracy for predicting recurrence probability and RFS in HCC patients treated with HAIC-based conversion hepatectomy. Identifying risk factors and estimating tumor recurrence may help clinicians in the decision-making process regarding adjuvant therapies for patients with HCC, which eventually achieves better oncological outcomes.

Postoperative Adjuvant Hepatic Arterial Infusion Chemotherapy With FOLFOX in Hepatocellular Carcinoma With Microvascular Invasion: A Multicenter, Phase III, Randomized Study.

PURPOSE: To report the efficacy and safety of postoperative adjuvant hepatic arterial infusion chemotherapy (HAIC) with 5-fluorouracil and oxaliplatin (FOLFOX) in hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI). PATIENTS AND METHODS: In this randomized, open-label, multicenter trial, histologically confirmed HCC patients with MVI were randomly assigned (1:1) to receive adjuvant FOLFOX-HAIC (treatment group) or routine follow-up (control group). The primary end point was disease-free survival (DFS) by intention-to-treat (ITT) analysis while secondary end points were overall survival, recurrence rate, and safety. RESULTS: Between June 2016 and August 2021, a total of 315 patients (ITT population) at five centers were randomly assigned to the treatment group (n = 157) or the control group (n = 158). In the ITT population, the median DFS was 20.3 months (95% CI, 10.4 to 30.3) in the treatment group versus 10.0 months (95% CI, 6.8 to 13.2) in the control group (hazard ratio, 0.59; 95% CI, 0.43 to 0.81; P = .001). The overall survival rates at 1 year, 2 years, and 3 years were 93.8% (95% CI, 89.8 to 98.1), 86.4% (95% CI, 80.0 to 93.2), and 80.4% (95% CI, 71.9 to 89.9) for the treatment group and 92.0% (95% CI, 87.6 to 96.7), 86.0% (95% CI, 79.9 to 92.6), and 74.9% (95% CI, 65.5 to 85.7) for the control group (hazard ratio, 0.64; 95% CI, 0.36 to 1.14; P = .130), respectively. The recurrence rates were 40.1% (63/157) in the treatment group and 55.7% (88/158) in the control group. Majority of the adverse events were grade 0-1 (83.8%), with no treatment-related death in both groups. CONCLUSION: Postoperative adjuvant HAIC with FOLFOX significantly improved the DFS benefits with acceptable toxicities in HCC patients with MVI.

A CuNi-Loaded Porous Magnetic Soft Material: Preparation, Characterization and Magnetic Field-Controlled Modulus.

Novel porous magnetic soft materials (pMSMs) based on a poly (vinyl alcohol) (PVA) porous matrix filled with CuNi nanoparticles (NPs) of around 70 nm were synthesized. Initially, magnetic CuNi NPs were fabricated by the reduction of Ni and Cu ions with hydrazine hydrate in ethylene glycol medium in the absence of other capping agents. The pMSMs are subsequently fabricated by mixing CuNi NPs and PVA through freezing-drying process. The as-obtained pMSMs can respond to a magnetic field, i.e., the compressive modulus increase under a magnetic field of 0.23 T. The experimental results indicate that CuNi NPs can easily move to form chain-like structures under the application of a magnetic field. A combination of direct observation and finite element modeling has shown that under the influence of a magnetic field, chain-like aggregates of CuNi NPs lead to self-reinforcement of the pMSMs and, thus, to the increased compressive modulus. From a technological point of view, these materials with good magnetic responsiveness and moderate mechanical strength have potential applications in artificial muscle, soft actuators and drug release, to name a few.