Xihui Ying

OBJECTIVES: To develop and validate a pre-transcatheter arterial chemoembolization (TACE) MRI-based radiomics model for predicting tumor response in intermediate-advanced hepatocellular carcinoma (HCC) patients. MATERIALS: Ninety-nine intermediate-advanced HCC patients (69 for training, 30 for validation) treated with TACE were enrolled. MRI examinations were performed before TACE, and the efficacy was evaluated according to the mRECIST criterion 3 months after TACE. A total of 396 radiomics features were extracted from T2-weighted pre-TACE images, and least absolute shrinkage and selection operator (LASSO) regression was applied to feature selection and model construction. The performance of the model was evaluated by receiver operating characteristic (ROC) curves, calibration curves, and decision curves. RESULTS: The AFP value, Child-Pugh score, and BCLC stage showed a significant difference between the TACE response (TR) and non-TACE response (nTR) patients. Six radiomics features were selected by LASSO and the radiomics score (Rad-score) was calculated as the sum of each feature multiplied by the non-zero coefficient from LASSO. The AUCs of the ROC curve based on Rad-score were 0.812 and 0.866 in the training and validation cohorts, respectively. To improve the diagnostic efficiency, the Rad-score was further integrated with the above clinical indicators to form a novel predictive nomogram. Results suggested that the AUC increased to 0.861 and 0.884 in the training and validation cohorts, respectively. Decision curve analysis showed that the radiomics nomogram was clinically useful. CONCLUSION: The radiomics and clinical indicator-based predictive nomogram can well predict TR in intermediate-advanced HCC and can further be applied for auxiliary diagnosis of clinical prognosis. KEY POINTS: • The therapeutic outcome of TACE varies greatly even for patients with the same clinicopathologic features. • Radiomics showed excellent performance in predicting the TACE response. • Decision curves demonstrated that the novel predictive model based on the radiomics signature and clinical indicators has great clinical utility.

Abstract Hepatocellular carcinoma (HCC) is a common malignant tumour, especially in Asia. Its prognosis is poor, and there are limited methods for predicting patient survival. This study was carried out to analyse the prognostic value of tumour-infiltrating lymphocytes (TILs), especially regulatory T cells (Tregs), in HCC patients. TILs were analysed in 57 randomly selected HCC patients. The prognostic effects of groups with high and low numbers were evaluated by the Kaplan-Meier and Cox model analyses. Although higher densities of CD3 + , CD4 + , and CD8 + cytotoxic lymphocytes (CTLs) as well as CD56 + NK cells and CD68 + macrophages were observed in peritumoural tissue, increased numbers of forkhead/winged helix transcription factor P3 + (FOXP3 + ) Tregs were found in intratumoural tissue. Additionally, regarding ICOS + FOXP3 + Tregs, an increased prevalence in carcinoma was not only associated with the absolute number but also with the percentage of FOXP3 + cells. Higher Treg levels in tumour tissues indicated a worse prognosis, and the FOXP3 + Tregs/CD4 + T cells ratio was an independent prognostic factor for OS. Therefore, FOXP3 + Tregs, especially ICOS + FOXP3 + Tregs, contribute to the immunosuppressive HCC microenvironment. High tumour-infiltrating Tregs are thought to be an unfavourable prognostic indicator of HCC.

To investigate the incidence and outcome of major complication following conventional transarterial embolization/chemoembolization (TAE/TACE) therapy for hepatocellular carcinoma (HCC).From May 2010 to May 2016, all patients with major complication following conventional TAE/TACE for HCC were included. Major complication was defined as admission to a hospital for therapy, an unplanned increase in the level of care, prolonged hospitalization, permanent adverse sequelae, or death after conventional TAE/TACE therapy by Society of Interventional Radiology.During the study period, a total of 2863 TAE/TACE procedures were performed among 1120 patients, and a total of 24 patients (21 male and 3 female) developed major complication with the incidence of 2.1% (24/1120) per patient and 0.84% (24/2863) per TAE/TACE procedure. The major complications were liver rupture (n = 6), liver abscess (n = 5), femoral artery pseudoaneurysm (n = 3), cholecystitis (n = 2), biloma (n = 2), pulmonary embolism (n = 2), and 1 each of the following: cerebral lipiodol embolism, tumor lysis syndrome, partial intestinal obstruction, gallbladder perforation. The mean interval from last TAE/TACE procedure to the diagnosis of major complication was 11.1 ± 7.7 days. The treatments of the complications were conservative treatment (n = 12), conservative treatment plus percutaneous drainage (n = 3), ultrasound-guided thrombin injection (n = 3), conservative treatment plus TAE (n = 2), and conservative treatment plus surgery (n = 2). Of the 24 patients, 20 patients were recovered, and remaining 4 patients were died of major complications; therefore, the mortality rate of major complication was 16.7% (4/24).Major complication following conventional TAE/TACE therapy is uncommon; the outcomes are benign of most major complications, but some are mortality.

LncRNAs can act crucial roles in multiple tumors including cholangiocarcinoma (CCA). M2 polarization of macrophages is crucial for their biological roles in immunologic tolerance, which is able to induce tumorigenesis. Given that increasing evidence have suggested that lncRNAs could participate in modulating immune cell differentiation and function. Our current study was aimed to identify the underlying mechanism of lncRNA prostate cancer-associated transcript 6 (PCAT6) in CCA progression via regulating M2 macrophage polarization. PCAT6 has been reported as an oncogene in many cancers. In our work, we observed increased expression of PCAT6 in CCA patients. PCAT6 expression in various types of immune cells derived from CCA patients was tested by quantitative real-time PCR (qRT-PCR). It was revealed that PCAT6 was highly expressed in macrophages, which indicated that PCAT6 might regulate the function of macrophages to promote CCA progression. Then, via establishing CCA xenograft mouse model, we found loss of PCAT6 obviously triggered the immune response and reduced the in vivo tumor growth. In addition, overexpression of PCAT6 led to the M2 polarization of THP-1-differentiated macrophages. Moreover, miR-326 was predicted and proved as a target for PCAT6. In addition, down-regulation of PCAT6 repressed M2 polarization of macrophages, which was reversed by miR-326 inhibitors. The increase of PCAT6 induced the accumulation of ROS, mitochondrial and metabolic dysfunction in macrophages and mimics of miR-326 exhibited an opposite process. RohA has been recognized as a significant regulator of immune cell function. In our current work, we observed that RohA function as a downstream target for miR-326. In conclusion, our study highlighted a significant role of PCAT6/miR-326/RohA in immune response of macrophages in CCA and indicated PCAT6 as a potential target of immunotherapy in CCA.

BACKGROUND: The aim of this study was to investigate the prognostic value of radiofrequency ablation (RFA) plus transcatheter arterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) patients with tumor size ranging from 3.0 to 10.0 cm. MATERIAL/METHODS: We retrospectively analyzed data on 201 patients with medium-to-large HCC. According to treatment procedure, the patients were divided into the TACE group (n=124) and the TACE+RFA group (n=77). We recorded data on patient safety, subcapsular hepatic hematoma, large amount of ascites, liver abscess, gallbladder injury, and local skin infection. The overall survival (OS) and progression-free survival (PFS) in the 2 groups were analyzed and compared between groups. RESULTS: The median PFS was 4.00 months (3.00–5.00 months) in the TACE group and 9.13 months (6.64–11.62 months) in the TACE+RFA group (P<0.001). Median OS was 12.00 months (8.88–15.13 months) in the TACE group and 27.57 months (20.06–35.08 months) in the TACE+RFA group (P<0.001). In the TACE+RFA group, multivariate Cox regression analysis showed that tumor size ≤5 cm) (HR: 1.952, 95% CI: 1.213–3.143, P=0.006), hepatitis B (HR: 2.323, 95% CI: 1.096–4.923, P=0.028), TACE times (1 or >1) (HR: 1.867, 95% CI: 1.156–3.013, P=0.011), alpha-fetoprotein (AFP) level >200 ng/ml (HR: 2.426, 95% CI: 1.533–3.839, P<0.001), and AST level >40 U/L (HR: 1.946, 95% CI: 1.196–3.166, P=0.007) were independent prognostic factors for overall survival. CONCLUSIONS: Combination therapy of TACE with RFA is a safe and effective treatment for patients with medium-to-large HCC, with the long-term beneficial effect of retarding tumor progression and improving PFS and OS.