Prognosis stratification of cancer patients treated with immune checkpoint inhibitors through lung immune prognostic index: a meta-analysis and systematic review.

BACKGROUND: Although numerous studies have reported the prognostic value of the lung immune prognostic index (LIPI) in non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs), the prognostic value of the LIPI in a pancancer setting remains unclear. METHODS: A comprehensive search was conducted until July 2023 across the PubMed, Embase, Web of Science, and Cochrane Library databases to identify relevant studies evaluating the prognostic value of the LIPI in cancer patients treated with ICIs. The outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). We described and compared the pooled outcomes by stratifying the patients based on different groupings of LIPI (good vs. intermediate [0 vs. 1], good vs. poor [0 vs. 2], and good vs. intermediate / poor [0 vs. 1 + 2]). RESULTS: A total of 9959 patients in 35 studies were included. A higher score of LIPI was associated with impaired OS. The pooled HRs were 1.69 (95% CI: 1.55-1.85, p < 0.001; 0 vs. 1), 3.03 (95% CI: 2.53-3.63, p < 0.001; 0 vs. 2), and 2.38 (95% CI: 1.97-2.88, p < 0.001; 0 vs. 1 + 2). A higher LIPI score was associated with shorter PFS. The pooled HRs were 1.41 (95% CI: 1.31-1.52, p < 0.001; 0 vs. 1), 2.23 (95% CI: 1.87-2.66, p < 0.001; 0 vs. 2), and 1.65 (95% CI: 1.46-1.86, p < 0.001; 0 vs. 1 + 2). Similarly, a higher LIPI score was associated with a lower ORR. The pooled ORs were 0.63 (95% CI: 0.54-0.75, p < 0.001; 0 vs. 1) and 0.38 (95% CI: 0.29-0.50, p < 0.001; 0 vs. 2). A higher LIPI score was associated with a lower DCR. The pooled ORs were 0.47 (95% CI: 0.35-0.61, p < 0.001; 0 vs. 1) and 0.19 (95% CI: 0.12-0.30, p < 0.001; 0 vs. 2). CONCLUSION: In patients with NSCLC or other solid tumours, the lung immune prognostic index could robustly stratify the clinical outcomes into three groups among the patients who receive ICIs. LIPI is a low-cost, simple, accessible, and accurate prognostic tool in a pancancer setting and it may contribute to the evaluation of risk stratification in patients treated with ICIs.

Longitudinal investigation of undergraduates' radiation anxiety, interest, and career intention in interventional radiology.

PURPOSE: To evaluate the effect of the school curriculum and on-site observation of interventional radiology (IR) operations in clinics on undergraduates' radiation anxiety, interest, and career intention. METHODS: Between the academic years 2021 and 2023, all of the fourth-year undergraduates were surveyed by questionnaires, which covered their pre-curriculum, post-curriculum in-school, and post-on-site view of IR surgeries in clinic. The survey included categories of gender, fear of X-ray and IR operation, interest in IR surgery, and career-pursuing intention. RESULTS: A total of 333 (91.0%) respondents (111 students for three times) were included in analyses. The fear of X-ray and radiation exposure during IR procedures was reduced after taking school courses (p < 0.001), and it was further decreased after on-site viewing (p < 0.001). The association values among the three groups were 33.8% and 41.9%, respectively. The interest in IR was improved both after applying for the curriculum and after clinical exposure to IR surgery (p < 0.001). In addition, 4 (3.6%) and 12 (10.8%) students showed a sense of achievement after taking courses and on-site viewing, respectively. The association value was 49.4%. Regarding career intention, it was both significantly increased after taking courses and on-site observation (p < 0.001). Besides, 8 (7.2%), 17 (15.3%), and 36 (32.4%) students in the three groups considered IR as the preferred career choice, respectively. CONCLUSIONS: Applying for IR curriculum could reduce undergraduates' radiation anxiety, and activate their professional interest and career pursuing intention. Clinical exposure to IR surgeries further boosted this effect. CLINICAL RELEVANCE STATEMENT: Educational interventions of curriculum and on-site view of IR surgery improve the undergraduates' interest in IR and stimulate their career intention, which is crucial for the advancement of IR. KEY POINTS: Increasing interest in interventional radiology (IR) as a career is urgent, given rising demand of services. Education and on-site viewing of IR surgery reduced radiation anxiety and increased interest in IR. Early exposure to IR is effective at encouraging undergraduates to consider IR as their career.

Interventional real-time optical imaging guidance for complete tumor ablation.

The aim of this study was to develop an interventional optical imaging (OI) technique for intraprocedural guidance of complete tumor ablation. Our study employed four strategies: 1) optimizing experimental protocol of various indocyanine green (ICG) concentrations/detection time windows for ICG-based OI of tumor cells (ICG cells); 2) using the optimized OI to evaluate ablation-heat effect on ICG cells; 3) building the interventional OI system and investigating its sensitivity for differentiating residual viable tumors from nonviable tumors; and 4) preclinically validating its technical feasibility for intraprocedural monitoring of radiofrequency ablations (RFAs) using animal models with orthotopic hepatic tumors. OI signal-to-background ratios (SBRs) among preablation tumors, residual, and ablated tumors were statistically compared and confirmed by subsequent pathology. The optimal dose and detection time window for ICG-based OI were 100 µg/mL at 24 h. Interventional OI displayed significantly higher fluorescence signals of viable ICG cells compared with nonviable ICG cells (189.3 ± 7.6 versus 63.7 ± 5.7 au, P < 0.001). The interventional OI could differentiate three definitive zones of tumor, tumor margin, and normal surrounding liver, demonstrating significantly higher average SBR of residual viable tumors compared to ablated nonviable tumors (2.54 ± 0.31 versus 0.57 ± 0.05, P < 0.001). The innovative interventional OI technique permitted operators to instantly detect residual tumors and thereby guide repeated RFAs, ensuring complete tumor eradication, which was confirmed by ex vivo OI and pathology. In conclusion, we present an interventional oncologic technique, which should revolutionize the current ablation technology, leading to a significant advancement in complete treatment of larger or irregular malignancies.

Transarterial viroembolization improves the therapeutic efficacy of immune-excluded liver cancer: Three birds with one stone.

OBJECTIVE: To investigate the mechanism and efficacy of transarterial viroembolization (TAVE) with an oncolytic virus (OH2) for the treatment of liver cancer in rabbit VX2 tumor models. MATERIALS AND METHODS: Subcutaneous tumor and liver cancer models were established to determine the optimal viral titer and administration modality of OH2. Different liver cancer models were established to evaluate the locoregional tumor response, synergistic and standby effects, survival benefit, and specific antitumor immune memory after TAVE treatment. The immune cell densities in tumor tissues were measured. RESULTS: The optimal viral titer of OH2 was 1 × 107 CCID50. TAVE was the most effective modality with greater homogeneous OH2 distribution and therapeutic efficacy compared to other administration routes of transarterial virus infusion (TAVI), commonly adopted intratumor injection (TI), and intravenous injection (IV). Additionally, TAVE treatment significantly improved the locoregional tumor response, standby effect, and survival benefit compared to the TAVI, transarterial embolization (TAE), and control groups. TAVE modified the immune cell densities for immune-excluded liver cancer, partially destroyed vessel metastases, and established antitumor immune memory. The synergistic treatment efficacy of TAVE was superior to the simple addition of two independent monotherapies. CONCLUSION: TAVE was the optimal and a safe modality for treating immune-excluded liver cancer, and its synergistic effect achieved a remarkable tumor response, standby effect, survival benefit, and antitumor immune memory, which providing an innovative therapeutic modality for clinical practice. DATA AVAILABILITY: Data is available from the corresponding author upon requirement.

Injectable hydrogel loaded with lysed OK-432 and doxorubicin for residual liver cancer after incomplete radiofrequency ablation.

OBJECTIVE: To investigate the efficacy of an injectable hydrogel loaded with lysed OK-432 (lyOK-432) and doxorubicin (DOX) for residual liver cancer after incomplete radiofrequency ablation (iRFA) of hepatocellular carcinoma (HCC), and explore the underlying mechanism. MATERIALS AND METHODS: The effect of OK-432 and lyOK-432 was compared in activating dendritic cells (DCs). RADA16-I (R) peptide was dissolved in a mixture of lyOK-432 (O) and DOX (D) to develop an ROD hydrogel. The characteristics of ROD hydrogel were evaluated. Tumor response and mice survival were measured after different treatments. The number of immune cells and cytokine levels were measured, and the activation of cGAS/STING/IFN-I signaling pathway in DC was evaluated both in vitro and in vivo. RESULTS: LyOK-432 was more effective than OK-432 in promoting DC maturation and activating the IFN-I pathway. ROD was an injectable hydrogel for effectively loading lyOK-432 and DOX, and presented the controlled-release property. ROD treatment achieved the highest tumor necrosis rate (p < 0.001) and the longest survival time (p < 0.001) compared with the other therapies. The ROD group also displayed the highest percentages of DCs, CD4+ T cells and CD8+ T cells (p < 0.001), the lowest level of Treg cells (p < 0.001), and the highest expression levels of IFN-γ and TNF-α (p < 0.001) compared with the other groups. The expression levels of pSTING, pIRF3, and IFN-ß in DCs were obviously higher after treatment of lyOK-432 in combination with DOX than the other therapies. The surviving mice in the ROD group showed a growth inhibition of rechallenged subcutaneous tumor. CONCLUSION: The novel ROD peptide hydrogel induced an antitumor immunity by activating the STING pathway, which was effective for treating residual liver cancer after iRFA of HCC.

Multimodal Imaging Response after the Singular or Combination Treatments of Vascular Endothelial Growth Factor Inhibitor and Immune Checkpoint Inhibitor.

This study aims to dynamically assess tumor changes after variable treatments with vascular endothelial growth factor (VEGF) inhibitor and/or immune checkpoint inhibitor (ICI) using multimodal imaging of MRI and 18F-FDG PET/CT in a hepatocellular carcinoma (HCC) mice model. Based on different treatments, 24 mice were randomly divided into four groups: control (isotype-matched IgG antibody 10 mg/kg), VEGF inhibitor (sorafenib 50 mg/kg), ICI (anti-PD-L1 antibody 10 mg/kg), and combination groups (sorafenib 50 mg/kg + anti-PD-L1 antibody 10 mg/kg). Quantitative imaging assessments, including volume transfer constant (Ktrans), apparent diffusion coefficient (ADC), lactate/choline ratio, and the maximum standardized 18F-FDG uptake value ratio of tumor to muscle (SUVtumor/SUVmuscle ratio), were acquired at different time points (before treatment and 7, 14, and 21 days after treatment). Quantitative data were presented as the mean ± standard errors and two-way repeated-measure ANOVA tests were performed for intergroup and intertime point comparisons. After 21 days from the initiation of therapies, combination group showed the lowest tumor volume and weight, followed by ICI, VEGF inhibitor, and control group, with no significance between the VEGF inhibitor and control groups. In addition, Ktrans values significantly decreased, and the lactate/choline ratio and SUVtumor/SUVmuscle ratio were significantly elevated in the VEGF inhibitor group. ADC significantly increased in the ICI and combination groups, with no significant differences in ADC observed between the control and VEGF inhibitor groups, which showed a similar dynamic change to the tumor volume. Furthermore, Ktrans, lactate/choline ratio, and ADC were significantly correlated with CD31+ area, hypoxyprobe+ area, and apoptosis, respectively. Our results suggest that the singular treatment and combination of the VEGF inhibitor and ICI treatments for HCC present different multimodal imaging changes in accordance with the specific histopathological features. These findings might facilitate the formulation of better treatment response criteria; besides, we find ADC is probably an indicator easily to obtain for treatment response evaluation.

Value of 18F-FDG PET/MR Imaging in the Early Evaluation of Treatment Response following Radiofrequency Ablation of Liver Cancer in a Rabbit Model.

PURPOSE: To test the hypothesis that 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) and magnetic resonance (MR) imaging can detect early residual tumor following radiofrequency (RF) ablation of liver cancer using a VX2 tumor model. MATERIALS AND METHODS: Twenty-four rabbits with VX2 liver tumors were randomly divided into 3 groups (n = 8/group): Group 1 without RF ablation treatment, Group 2 with complete ablation, and Group 3 with partial ablation. An 18F-FDG PET/MR imaging scan was obtained within 2 hours after RF ablation. The maximum standardized uptake values (SUV) of the nontreated liver tumor, benign periablational enhancement (BPE), residual tumor, ablated tumor, and adjacent liver parenchyma and mean SUV of the normal liver were measured. The ratios of maximum SUV for these targets to the mean SUV of the normal liver (TNR) were calculated and compared. RESULTS: The mean TNR of the nontreated liver tumors in Group 1 was significantly greater than that of the adjacent liver parenchyma (8.68 ± 0.71 vs 1.89 ± 0.26, P < .001). In Group 2, the mean TNR of BPE was significantly greater than that of the adjacent liver parenchyma (2.85 ± 0.20 vs 1.86 ± 0.25, P < .001). In Group 3, the mean TNR of the residual tumor was significantly greater than that of BPE (8.64 ± 0.59 vs 2.78 ± 0.23, P < .001), which was significantly greater than that of completely ablated tumor (2.78 ± 0.23 vs 0.50 ± 0.06, P < .001). CONCLUSIONS: 18F-FDG PET/MR imaging may serve as a promising imaging tool for the early detection of viable residual tumors due to incomplete tumor ablation.

Tumor feeding artery contraction and metastasis inhibition after transarterial chemoembolization combined with apatinib for hepatocellular carcinoma: A propensity score matching study.

AIM: To investigate the change of tumor feeding artery diameter and the efficacy of metastasis inhibition after transarterial chemoembolization (TACE) combined with apatinib or TACE monotherapy for patients with advanced hepatocellular carcinoma who without metastasis. MATERIALS AND METHODS: A total of 616 consecutive patients who received the treatment of TACE-apatinib or TACE in our center was enrolled. Propensity score matching (PSM) analysis was used to reduce bias. The overall survival (OS), OS-after-metastasis (OSM), time to progression (TTP), time to metastasis (TTM), time to vessel or organ metastasis (TVOM), time to lymph node metastasis, and tumor feeding artery diameter between the two treatment groups were compared. RESULTS: A total of 113 pairs of patients were eligible after the PSM. Time to lymph node metastasis between the two groups was not significantly different (P > 0.05). The tumor feeding artery diameter was significantly smaller after TACE-apatinib management (P < 0.001). Median OS (P < 0.001) and OSM (P < 0.001) were significantly longer in the TACE-apatinib group compared with the TACE group. Median TTP (P < 0.001), TTM (P < 0.001), and TVOM (P < 0.001) were significantly prolonged in TACE-apatinib group. CONCLUSION: TACE-apatinib treatment could improve the prognosis compared with TACE alone, and inhibit metastasis after TACE procedure with contracted tumor feeding artery for advanced HCCs without metastasis.

Sequential transarterial chemoembolization and early radiofrequency ablation improves clinical outcomes for early-intermediate hepatocellular carcinoma in a 10-year single-center comparative study.

BACKGROUND: Transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) are effective treatment methods for unresectable hepatocellular carcinoma (HCC). However, there is still a lack of clinical research on whether early sequential RFA, compared with late combination therapy, can improve the long-term efficacy of initial TACE treatment. METHODS: This retrospective study investigated a cohort of patients who underwent combination therapy using TACE and RFA (TACE followed by RFA) from January 2010 to January 2020 at our medical centre. A total of 96 patients underwent TACE combined with early RFA (usually during the first hospitalization), which was called TACE + eRFA. Thirty-four patients received 1-2 palliative TACE treatments first and then underwent TACE treatment combined with late RFA (TACE + lRFA). All patients continued to receive palliative TACE treatments after intrahepatic lesion progression until reaching intolerance. The overall survival (OS) rate, time to tumour progression (TTP), tumour response rate and major complication rates were compared between the two groups. RESULTS: There were significant differences in the median OS (46 months vs 33 months; P = 0.013), median TTP (28 months vs 14 months; P < 0.00), objective response rate (ORR) (89.6% vs 61.8%, P = 0.000) and disease control rate (DCR) (94.8% vs 73.5% P = 0.002) between the two groups. Multivariable analysis revealed that the Barcelona Clinic Liver Cancer stage was an independent risk factor for OS. Meanwhile, multivariable analysis revealed that TACE + eRFA was associated with an enhanced TTP. CONCLUSION: Early sequential RFA treatment in patients with early-intermediate HCC can improve local tumour control and clinical outcomes while reducing the frequency of TACE treatment. In clinical practice, in HCC patients initially treated with TACE, it is recommended to combine RFA as soon as possible to obtain long-term survival.

Radiomics Signature: A potential biomarker for the prediction of survival in Advanced Hepatocellular Carcinoma.

Objectives: To develop and validate radiomics nomograms for the pretreatment predictions of overall survival (OS) and time to progression (TTP) in the patients with advanced hepatocellular carcinoma (HCC) treated with apatinib plus transarterial chemoembolization (TACE), and to assess the incremental value of the clinical-radiomics nomograms for estimating individual OS and TTP. Methods: A total of 60 patients with advanced HCC (BCLC stage C) treated with apatinib plus TACE were divided into a training set (n=48) and a validation set (n=12). The predictors identified from the clinical variables and the radiomics signature constructed from the computed tomography images, such as ɑ-fetoprotein level (AFP), formfactor, the grey level co-occurrence matrix, the gray level size zone matrix, and the gray level run-length matrix, were used to build the clinical-radiomics nomograms and the radiomics nomograms for the prediction of OS and TTP. Results: Apatinib plus TACE benefited the patients with advanced HCC, with a 579-day median OS and a 270-day median TTP. The nomograms were built with the radiomics signature and AFP, and achieved favorable prediction efficacy with acceptable calibration curves. Decision curve analyses demonstrated that the clinical-radiomics nomograms outperformed the radiomics nomograms for the predictions of OS and TTP. Conclusions: Apatinib plus TACE may improve OS and prolonged TTP in the patients with advanced HCC. The clinical-radiomics nomograms, a noninvasive pretreatment prediction tool that incorporate radiomics signature and AFP, demonstrated good prediction accuracy for OS and TTP in these patients. These results indicate that the clinical-radiomics nomograms may provide novel insight for precise personalized medicine approaches in the patients with advanced HCC.

Endovascular management of transplant renal artery stenosis: A single-center retrospective study.

OBJECTIVES: The aim is to evaluate the efficacy and complications of percutaneous transluminal angioplasty (PTA)/stenting in the treatment of transplant renal artery stenosis (TRAS). BACKGROUND: TRAS is a relatively rare condition, and currently, there is not enough study about interventional therapy for TRAS. METHODS: Between April 2011 and July 2018, 33 patients with TRAS underwent interventional therapy. Analysis of parameters was as follows: technical success, pretreatment and posttreatment serum creatinine, and blood pressure, and vessel patency via ultrasound at 1, 6, and 12 months posttreatment and once a year thereafter. RESULTS: One procedure failed. The success rate of PTA/stenting placement was 97.0%. Fourteen PTAs with 16 stents were primary interventions, with 2 stent procedures performed subsequently due to restenosis; the restenosis rate was 6.3%. During the follow-up period, two patients progressed to graft renal failure and three patients were lost to follow-up. The rest of the patients still had stable graft function and blood pressure. Compared with preoperative conditions, blood pressure and serum creatinine significantly decreased (p < .05). No treatment-related deaths or serious complications occurred. CONCLUSIONS: PTA/stenting is a safe and effective treatment for TRAS. For selected TRAS patients, PTA or PTA with stent may achieve good therapeutic outcomes. Selecting appropriate puncture pathways may help improve the success rate and affect the operation results, and open surgery may be avoided.

Platelet-to-lymphocyte ratio predicts therapy outcomes of transarterial chemoembolization plus apatinib in the treatment of advanced hepatocellular carcinoma.

To evaluate the predictive value of preoperative biochemical marker [platelet-to-lymphocyte ratio (PLR)] in patients with advanced hepatocellular cancer receiving transarterial chemoembolization (TACE) plus targeted molecular therapy (apatinib) treatment. Clinical records of 134 patients receiving the treatment of TACE + apatinib (TACE-A) and the treatment of TACE alone were compared in a single-center study. Time to progression (TTP) and overall survival (OS) were compared between TACE-A and TACE alone groups in patients with PLR > 150 and PLR ≤ 150, respectively. The area under the receiver operating characteristic (ROC) curve was used to determine the prediction power of PLR. The median TTP and OS in the TACE-A group were significantly longer than those in the TACE alone group (P < 0.001). The median TTP and OS in the TACE-A (PLR ≤ 150) group were longer than those in the TACE-A (PLR > 150) group (P < 0.05). There was no significant difference between TACE-A (PLR > 150) and TACE alone (P = 0.232) groups in OS, but the median TTP in the TACE-A (PLR > 150) group was longer than that in the TACE alone group (P = 0.001). ROC analysis showed that the area under the curve was 0.643 and 0.623 for 6- and 12-month survival, respectively. PLR might predict the results of patients with advanced hepatocellular carcinoma received TACE-A treatment.

Clinical characteristics, CT signs, and pathological findings of Pyrrolizidine alkaloids-induced sinusoidal obstructive syndrome: a retrospective study.

BACKGROUND: One major etiology of hepatic sinusoidal obstruction syndrome (HSOS) in China is the intake of pyrrolizidine alkaloids (PAs). Since PAs-induced HSOS is a rare disease that has not been clearly characterized until now, the aim of this study was to investigate clinical characteristics, CT features, and pathological findings of PA-induced HSOS. METHODS: This retrospective cohort study included 116 patients with PAs-induced HSOS and 68 patients with Budd-Chiari syndrome from Jan 2006 to Sep 2016. We collected medical records of the patients, and reviewed image features of CT, and analyzed pathological findings. RESULTS: Common clinical manifestations of PAs-induced HSOS were abdominal distention (98.26%), ascites (100%), jaundice (52.94%), abdominal pain (36.36%). Abnormal liver function was observed in most of PAs-induced HSOS. On CT scan, common findings included: ascites, hepatomegaly, the thickening of gallbladder wall, pleural effusion, patchy liver enhancement, and heterogeneous hypoattenuation. Most of the patients had a low ascitic total protein (< 25 g/L) and a high SAAG (≥ 11.0 g/L). In acute stage, pathologic features were massive sinusoidal dilatation, sinusoidal congestion, the extravasation of erythrocytes, hepatocellular necrosis, the accumulation of macrophages, the deposition of hemosiderin. In subacute stage, complete loss of pericentral hepatocytes, sinusoidal dilatation, the deposition of pigment granules were observed. CONCLUSIONS: The PAs-induced HSOS patients displayed distinct clinical characteristics, imaging features, and pathological findings, which provided some evidences for the diagnosis of PAs-induced HSOS. TRIAL REGISTRATION: ChiCTR-DRD-17010709.

Transarterial chemoembolization combined with iodine 125 seeds versus transarterial chemoembolization combined with radiofrequency ablation in the treatment of early- and intermediate-stage hepatocellular carcinoma.

BACKGROUND: Transarterial chemoembolization (TACE), radiofrequency ablation (RFA), and iodine 125 seeds implantation are optional treatments for hepatocellular carcinoma (HCC). The aim of this study is to compare the efficacy of the combined treatment of TACE with iodine 125 seeds implantation (TACE-iodine 125) with TACE with RFA (TACE-RFA) in patients with early- and intermediate-stage HCC. METHODS: The study included 112 patients who were diagnosed with early- and intermediate-stage HCC from January 1, 2014, to May 31, 2018. Among them, 38 patients were treated with TACE-Iodine 125, and 74 with TACE-RFA. The efficacy of the two treatment groups was retrospectively analyzed. To reduced the selective bias, a propensity score matching (PSM) analysis and inverse probability of treatment weighting (IPTW) method were used to compare the outcomes between the two groups. RESULTS: In the absence of PSM and IPTW, the median overall survival (OS) and progression-free survival (PFS) of the TACE-RFA group were slightly longer than those of the TACE-Iodine 125 group (OS: 41 months vs. 36 months; PFS: 18 months vs. 15 months). However, there were no statistically significant differences in the median OS, PFS, and objective response rate (ORR) between the two groups (P > 0.05). After adjusting the age, gender, Child-Pugh class, Barcelona Clinic Liver Cancer (BCLC) stage, and Alpha-fetoprotein (AFP), TACE-Iodine 125 treatment was not associated with a significant increasing the risks of death (HR: 0.763; 95%CI: 0.403,1.345, P = 0.320) and recurrence (HR: 1.020; 95%CI: 0.645,1.611, P = 0.934). After PSM, 35 matched pairs of patients were obtained, and there were no statistically significant differences in the median OS and PFS between the two groups. After IPTW, similar results presented. CONCLUSIONS: The combination of TACE with iodine 125 seeds implantation may represent an effective treatment for patients with early- and intermediate-stage HCC.

Improved clinical outcome using transarterial chemoembolization combined with radiofrequency ablation for patients in Barcelona clinic liver cancer stage A or B hepatocellular carcinoma regardless of tumor size: results of a single-center retrospective case control study.

BACKGROUND: To determine the safety and efficacy of transarterial chemoembolization (TACE) combined with radiofrequency ablation (hereafter, TACE-RFA) in treating Barcelona Clinic Liver Cancer (BCLC) Stage A or B (hereafter, BCLC A/B) hepatocellular carcinoma (HCC) patients, and to explore the range of tumor sizes suitable for combination therapy. METHODS: This retrospective study assessed the consecutive medical records of HCC patients with BCLC A/B who received TACE-RFA or TACE from September 2009 to September 2018. Progression-free survival (PFS), overall survival (OS), therapeutic response, and complications were compared between the two groups. RESULTS: Among 2447 patients who received TACE-RFA or TACE, 399 eligible patients were enrolled in our study, including 128 patients in the TACE-RFA group and 271 patients in the TACE group. Compared with the TACE group, the PFS and OS rates of 1,3,5,8 years in the TACE-RFA group were significantly better, with higher objective tumor regression rate and better disease control rate. RFA treatment did not increase the risk of death in patients with HCC, and both liver subcapsular hematoma and bile duct injury were improved by symptomatic treatment. Serum α-fetoprotein level and treatment method were important independent prognostic factors for OS, whereas albumin, hepatitis B and treatment method were important independent prognostic factors for PFS. Subgroup analysis showed that patients in the TACE-RFA group always showed better OS and PFS. CONCLUSIONS: TACE-RFA had an advantage over TACE alone in prolonging PFS and improving OS in HCC patients with BCLC A/B, and can benefit patients regardless of tumor size.

GPX2 overexpression indicates poor prognosis in patients with hepatocellular carcinoma.

Glutathione peroxidase 2 has important role of tumor progression in lots of carcinomas, yet little is known about the prognosis of glutathione peroxidase 2 in hepatocellular carcinoma. Glutathione peroxidase 2 expression was assessed by immunohistochemistry in hepatocellular carcinoma tissues. The association between glutathione peroxidase 2 expression with clinicopathological/prognostic value was examined. Glutathione peroxidase 2 overexpression was correlated with alpha-fetoprotein level, larger tumor, BCLC stage, and tumor recurrence. Kaplan-Meier analysis showed that glutathione peroxidase 2 was an independent predictor for overall survival and time to recurrence. glutathione peroxidase 2 overexpression was correlated with poor prognosis in patient subgroups stratified by tumor size, differentiation, tumor-node-metastasis, and BCLC stage. Moreover, stratified analysis showed that tumor-node-metastasis stage-I patients with high glutathione peroxidase 2 expression had poor prognosis than those with low glutathione peroxidase 2 expression. Additionally, combination of glutathione peroxidase 2 and serum alpha-fetoprotein was correlated with prognosis in hepatocellular carcinoma. In conclusion, glutathione peroxidase 2 overexpression contributes to poor prognosis of hepatocellular carcinoma patients and helps to identify the high-risk hepatocellular carcinoma patients.

Scutellaria barbata D. Don extract inhibits the tumor growth through down-regulating of Treg cells and manipulating Th1/Th17 immune response in hepatoma H22-bearing mice.

BACKGROUND: Previous studies showed Scutellaria barbata D. Don extract (SBE) is a potent inhibitor in hepatoma and could improve immune function of hepatoma H22-bearing mice. However, the immunomodulatory function of SBE on the tumor growth of hepatoma remains unclear. This study aimed to investigate the anti-tumor effects of SBE on hepatoma H22-bearing mice and explore the underlying immunomodulatory function. METHODS: The hepatoma H22-bearing mice were treated by SBE for 30 days. The effect of SBE on the proliferation of HepG2 cells in vitro, the growth of transplanted tumor, the cytotoxicity of natural killer (NK) cells in spleen, the amount of CD4+CD25+Foxp3+ Treg cells and Th17 cells in tumor tissue, and the levels of IL-10, TGF-ß, IL-17A, IL-2, and IFN-γ in serum of the hepatoma H22-bearing mice was observered. IL-17A was injected to the SBE treated mice from day 9 post H22 inoculation to examine its effect on tumor growth. RESULTS: SBE treatment inhibited the proliferation of HepG2 cells in vitro with a dose-dependent manner and significantly suppressed the tumor growth of hepatoma H22-bearing mice. Meanwhile, it increased NK cells' cytotoxicity in spleen, down-regulated the amount of CD4+CD25+Foxp3+ Treg cells and Th17 cells in tumor tissue, and decreased IL-10, TGF-ß, and IL-17A levels (P < 0.01) whereas increased IL-2 and IFN-γ levels (P < 0.01) in the serum of hepatoma H22-bearing mice. Moreover, administration of recombinant mouse IL-17A reversed the anti-tumor effects of SBE. CONCLUSION: SBE could inhibit the proliferation of HepG2 cells in vitro. Meanwhile, SBE also could inhibit the growth of H22 implanted tumor in hepatoma H22-bearing mice, and this function might be associated with immunomodulatory activity through down-regulating of Treg cells and manipulating Th1/Th17 immune response.

Stress Test of Contrast-Enhanced US with Phenylephrine in a Rabbit VX2 Liver Tumor Model: Differentiating Benign Periablational Enhancement from Residual Tumor after Radiofrequency Ablation.

PURPOSE: To differentiate benign periablational enhancement (BPE) from residual tumor after radiofrequency (RF) ablation by using a stress contrast-enhanced ultrasonography (US) test with phenylephrine in a rabbit VX2 liver tumor model. MATERIALS AND METHODS: VX2 tumors were implanted in the livers of 40 rabbits for two experiments. In experiment one, liver tumors from 32 animals were completely ablated. On days 2, 7, 14, and 21 after RF ablation, eight animals were randomly chosen for contrast-enhanced US before and after phenylephrine administration, and the microvessel density (MVD) of BPE at these four time points was assessed. In experiment two, liver tumors from eight animals were partly ablated, and each animal underwent contrast-enhanced US before and after phenylephrine administration on day 7 after RF ablation. Perfusion parameters were observed, including maximum intensity (IMAX), rise time (ie, time between 10% and 90% of IMAX), time to peak, mean transit time, and area under the curve (AUC), along with the profile of time-intensity curves (TICs) in BPE and residual tumor in response to phenylephrine. RESULTS: Among the four time points after ablation, the IMAX and AUC before phenylephrine administration and the MVD of BPE were greatest on day 7 (P < .05). The profile of TICs and the corresponding perfusion parameters in residual tumor did not change significantly in response to phenylephrine. However, those from BPE changed significantly (P < .05). CONCLUSIONS: Contrast-enhanced US with phenylephrine stress may be helpful in differentiating BPE from residual tumor after RF ablation in hepatocellular carcinoma.