A Radiomics-based Approach for Predicting Early Recurrence in Intrahepatic Cholangiocarcinoma after Surgical Resection: A Multicenter Study.

This work aimed to develop a noninvasive and reliable computed tomography (CT)-based imaging biomarker to predict early recurrence (ER) of intrahepatic cholangiocarcinoma (ICC) via radiomics analysis. In this retrospective study, a total of 177 ICC patients were enrolled from three independent hospitals. Radiomic features were extracted on CT images, then 11 feature selection algorithms and 4 classifiers were to conduct a multi-strategy radiomics modeling. Six established radiomics models were selected as stable ones by robustness-based rule. Among those models, Max-Relevance Min-Redundancy (MRMR) combined with Gradient Boosting Machine (GBM) yielded the highest areas under the receiver operating characteristics curve (AUCs) of 0.802 (95% confidence interval [CI]: 0.727-0.876) and 0.781 (95% CI: 0.655-0.907) in the training and test cohorts, respectively. To evaluate the generalization of the developed radiomics model, stratification analysis was performed regarding different centers. The MRMR-GBM-based model manifested good generalization with comparable AUCs in each hospital (p > 0.05 for paired comparison). Thus, the MRMR-GBM-based model could offer a potential imaging biomarker to assist the prediction of ER in ICC in a noninvasive manner.Clinical Relevance-The proposed radiomics model achieved satisfactory accuracy and good generalization ability in predicting ER in ICC, which might assist personalized surveillance and clinical treatment strategy making.

Co-Administration of iRGD with Sorafenib-Loaded Iron-Based Metal-Organic Framework as a Targeted Ferroptosis Agent for Liver Cancer Therapy.

PURPOSE: Hepatocellular carcinoma (HCC) is one of the most common fatal cancers, with no curative therapy available. The concept of ferroptosis is attracting increasing attention in cancer research. Herein, we describe the use of a nanodevice as an effective strategy for inducing ferroptosis to manage HCC. METHODS: To improve ferroptosis-induced treatment of HCC, we constructed sorafenib (sor)-loaded MIL-101(Fe) nanoparticles (NPs) [MIL-101(Fe)@sor] and evaluated the efficacy of ferroptosis-based HCC therapy after co-administration with the iRGD peptide both in vitro and in vivo. RESULTS: The prepared MIL-101(Fe) NPs have several promising characteristics including drug-loading, controllable release, peroxidase activity, biocompatibility, and T2 magnetic resonance imaging ability. MIL-101(Fe)@sor NPs significantly induced ferroptosis in HepG2 cells, increased the levels of lipid peroxidation and malondialdehyde, and reduced those of glutathione and glutathione peroxidase 4 (GPX-4). The in vivo results showed that the MIL-101(Fe)@sor NPs significantly inhibited tumor progression and decreased GPX-4 expression levels, with negligible long-term toxicity. Meanwhile, co-administration of MIL-101(Fe)@sor NPs with iRGD significantly accelerated ferroptosis. CONCLUSION: Our findings suggest that MIL-101(Fe)@sor NPs co-administered with iRGD are a promising strategy for inducing HCC ferroptosis.

Impact of low serum hemoglobin on development of contrast-induced nephropathy (CIN) in patients with hepatocellular carcinoma (HCC) following transarterial chemoembolisation (TACE).

OBJECTIVES: To assess the association between low hemoglobin (Hb) level and development of contrast-induced nephropathy (CIN) for hepatocellular carcinoma (HCC) patients after transarterial chemoembolization (TACE). METHODS: A retrospective analysis was performed on 284 patients undergoing 503 consecutive sessions of TACE. Propensity score matching (PSM) analysis was used to reduce the influence of the difference in variables in normal and low hemoglobin groups. Risk factors of CIN were assessed by univariate and multivariate logistic regression analysis. The relation between Hb level and CIN development was analyzed by receiver operating characteristic (ROC) curve. RESULTS: CIN developed in 5.6% patients after TACE. Multivariate logistic regression analysis showed that hypertension, Hb and serum creatinine (Scr) were independent risk factors for the development of post-TACE CIN. Grouped by normal or low Hb, the incidence of CIN was 14.6% (16/110) in the low Hb group and 3.4% (4/116) in the normal Hb group after PSM. Multivariate logistic regression analysis revealed that Hb, lymphocyte count, and neutrophil to lymphocyte ratio (NLR) were independent risk factors for the development of post-TACE CIN. The optimal cut-off point at which the Hb concentration resulted in a high probability of developing CIN was 105.5 g/L in males. CONCLUSIONS: Low Hb is an independent risk factor for post-TACE CIN. Therefore, HCC patients with low Hb levels should be closely monitored before and during TACE.

Transcatheter arterial chemoembolization (TACE) with iRGD peptide in rabbit VX2 liver tumor.

PURPOSE: Transcatheter arterial chemoembolization (TACE) is the first-line therapy for unresectable hepatocellular carcinoma (HCC). However, its therapeutic effects are hampered by the poor distribution of anticancer drugs in tumors. iRGD, a novel tumor-penetrating peptide, enhances the penetration distance and therapeutic efficacy of anticancer drugs. Herein, we evaluated the therapeutic effects of iRGD coupled with TACE in the rabbit VX2 liver tumor model. SUBJECTS AND METHODS: This study had two stages: tumor permeability assay and anticancer efficacy evaluation. In the tumor permeability assay, we coadministered TACE with either iRGD + lipiodol-doxorubicin emulsion (LDE) or LDE in the rabbit VX2 liver tumor model. We evaluated the doxorubicin (DOX) distribution at predetermined times by immunofluorescence microscopy. To evaluate anticancer efficacy, we administered saline, LDE, or iRGD + LDE to tumor-grafted rabbits. We measured tumor volume using magnetic resonance scanning. We quantified the expression levels of Bax, Bcl-2, and cleaved caspase-3 using Western blot (WB) analysis and determined the apoptosis rate in tumor cells using transferase-mediated dUTP nick-end labeling assay. RESULTS: The iRGD + LDE infusion significantly increased the DOX concentration and DOX penetration in tumors compared with the LDE infusion (P < 0.05). The antitumor efficacy of the iRGD + LDE in tumor inhibition was higher than that of the other treatments (P < 0.05). Besides, iRGD + LDE induced more apoptosis (P < 0.05). CONCLUSIONS: We demonstrated that iRGD coadministered with TACE is effective against HCC.