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Background: Combined therapy with tyrosine kinase inhibitors (TKIs) and anti-PD-1 antibodies has shown high tumor response rates for patients with unresectable hepatocellular carcinoma (HCC). However, using this treatment strategy to convert initially unresectable HCC to resectable HCC was not reported. Methods: Consecutive patients with unresectable HCC who received first-line therapy with combined TKI/anti-PD-1 antibodies were analyzed. Tumor response and resectability were evaluated via imaging every 2 months (±2 weeks) using RECIST v1.1. Resectability criteria were (1) R0 resection could be achieved with sufficient remnant liver volume and function; (2) intrahepatic lesions were evaluated as partial responses or stable disease for at least 2 months; (3) no severe or persistent adverse effects occurred; and (4) hepatectomy was not contraindicated. Results: Sixty-three consecutive patients were enrolled. Of them, 10 (15.9%) underwent R0 resection in 3.2 months (range: 2.4–8.3 months) after the initiation of combination therapy. At baseline, these 10 patients had a median largest tumor diameter of 9.3 cm, 7 had Barcelona Clinic Liver Cancer stage C (vascular invasion) disease, 2 had stage B, and 1 had stage A. Before surgery, 6 patients were evaluated as a partial response, 3 stable disease, and 1 partial response in the intrahepatic lesion but a new metastatic lesion in the right adrenal gland. Six patients (60%) achieved a pathological complete response. One patient died from immune-related adverse effects 2.4 months after hepatectomy. After a median follow-up of 11.2 months (range: 7.8–15.9 months) for other 9 patients, 8 survived without disease recurrence, and 1 experienced tumor recurrence. Conclusions: Combination of TKI/anti-PD-1 antibodies is a feasible conversion therapy for patients with unresectable HCC to become resectable. This study represents the largest patient cohort on downstaging role of combinational systemic therapy on TKI and PD-1 antibody for HCC.

Extracting implicit anomaly information through deformation monitoring data mining is highly significant to determining dam safety status. As an intelligent singular value diagnostic method for concrete dam deformation monitoring, shallow neural network models result in local optima and overfitting, and require manual feature extraction. To obtain an intelligent singular value diagnosis model that can be used for dam safety monitoring, a convolutional neural network (CNN) model that has advantages of deep learning (DL), such as automatic feature extraction, good model fitting, and strong generalizability, was trained in this study. An engineering example shows that the predicted result of the intelligent singular value diagnostic method based on CNN is highly compatible with the confusion matrix, with a precision of 92.41%, receiver operating characteristic (ROC) coordinates of (0.03, 0.97), an area-under-curve (AUC) value of 0.99, and an F1-score of 0.91. Moreover, the performance of the CNN model is better than those of models based on decision tree (DT) and k-nearest neighbor (KNN) methods. Therefore, the intelligent singular value diagnostic method based on CNN is simple to operate, highly intelligent, and highly reliable, and it has a high potential for application in engineering. Keywords: Singular value diagnosis, Convolutional neural network, Artificial intelligence, Deformation monitoring, Concrete dam

We aim to investigate the safety and efficacy of microwave ablation (MWA) combined with attenuated Salmonella typhimurium strain VNP20009 in treating hepatocellular carcinoma. Portions of tumor tissues were orthotopically implanted in the livers of 40 male rats weighed 150~200 g to establish tumor models. Three weeks later, the rats were randomly divided into four groups: (A) MWA plus VNP20009 group; (B) MWA group; (C) VNP20009 group; and (D) control group. Incomplete MWA was performed (20~30 W, 1~2 min) after the hepatic carcinoma was properly exposed. VNP20009 (about 1×107 cfu) was directly injected into the tumor immediately. MRI scans were performed to assess the tumor responses 7 and 14 days later, respectively. Micro CT was used to observe the lung metastases. After the animals were sacrificed or died, the tumors were cut off for the purpose of pathological and immunohistochemical analyses. The results showed that the mean tumor volumes of MWA plus VNP20009 group on the 7th and 14th day post treatment were obviously smaller than those of other groups (P < 0.05). Lung metastases rates were 20%, 60%, 30% and 100% in MWA plus VNP20009 group, MWA group, VNP20009 group and control group, respectively. The median survival of the rats in MWA plus VNP20009 group was distinctly longer than those in other groups (P < 0.05). In summary, MWA combined with VNP20009 produced better effects than MWA or VNP20009 alone in treating hepatic carcinoma. This strategy might have potential ability to decrease lung metastases and prolong the overall survival.

The present study aimed to determine the prognostic significance of soluble Programmed Death-ligand 1 (sPD-L1) in hepatocellular carcinoma (HCC) patients undergoing transcatheter arterial chemoembolization (TACE).We treated 114 HCC patients with TACE from 2012 to 2013 and determined their sPD-L1 levels by enzyme-linked immunosorbent assay. We evaluated prognosis according to mRESIST criteria and analyzed prognostic values by Cox regression and Kaplan-Meier analysis. We further evaluated correlations between sPD-L1 level and inflammatory status, as well as immunosuppressive environment.sPD-L1 levels were significantly increased in patients who developed HCC progression (P = 0.002) and death (P 0.001). Patients with higher pre-treatment sPD-L1 levels had a significantly shorter time to progression (10.50 vs. 18.25 months, P = 0.001) and decreased overall survival (16.50 vs. 28.50 months, P = 0.003). Importantly, sPD-L1 levels positively correlated with SII (r = 0.284, P = 0.002), sIL-2R (r = 0.239, P = 0.010), IL-10 (r = 0.283, P = 0.002), HBV-DNA loads (r = 0.229, P = 0.014), and CRP (r = 0.237, P = 0.011). Moreover, high sPD-L1 levels had increased numbers of Treg cells (FOXP3+; P = 0.026), Macrophage cells (CD68+; P = 0.014), and M2-Macrophage cells (CD163+; P = 0.026) CONCLUSIONS: sPD-L1 level is a prognostic indicator of poor outcomes after TACE. High sPD-L1 might reflect increased immune activation in an immunosuppressive environment that hindered anti-tumor response activity.

e16152 Background: We reviewed real-world outcomes for patients with uHCC and PVTT receiving TACE with 125I seed and stent implantation combined with lenvatinib plus anti-PD-1 antibodies. Methods: We retrospectively reviewed medical records from 62 consecutive adult (≥18 to ≤75 years) patients with HBV-related HCC and type III and IV PVTT with Child-Pugh class A or B liver function and ECOG performance status of 0-2 who received 125I seed strand and stent implantation combined with TACE at our center between November 2018 and May 2020. Patients were divided into two groups; those who had received adjuvant lenvatinib plus anti-PD-1 inhibitors, initiated 3 days after the first interventional procedure (Group A; n=18), and those who only received locoregional therapy (Group B; n=44). Propensity score matching (PSM) with a 1:1 ratio was used to reduce selection bias. Tumor response, progression-free survival (PFS, time from the first interventional procedure to progression or death for both Group A and Group B) and time-to-progression (TTP) were assessed using the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Time to untreatable progression (TTUP) and overall survival (OS) were also assessed. Adverse events (AEs) were graded according to the Common Toxicity Criteria for Adverse Events (CTCAE) v4.0. Results: PSM resulted in 15 matched pairs of patients, and baseline demographic parameters were comparable between the two groups. The median follow-up time was 12.4 ± 4.6 and 9.4 ± 4.8 months for patients in Groups A (n=15) and B (n=15) after PSM, respectively. Compared with patients in Group B, those in Group A had a higher overall response rate (66.7 vs. 18.2%; p=0.001) and disease control rate (72.2 vs. 43.2%; p=.038) and a longer median PFS, TTP, TTUP and OS (Table). No serious complications related to locoregional procedures were reported in either group. In Group A, 13% (n=2) of patients experienced ≥1 AE but the majority were Grade

Highlights • The arterial supply of the future liver remnant (FLR) may be important for the FLR growth. • Huge hepatocellular carcinoma (HCC) can cause blood-stream steal from the FLR, which can result in ALPPS failure. • Transarterial embolization (TAE) of HCC can salvage failed Stage I ALPPS. • TAE can induce significant hypertrophy of FLR. • TAE-salvaged ALPPS may be suitable for huge HCC with chronic liver disease., Introduction The degree of hypertrophy of the future liver remnant (FLR) induced by associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) in patients with HCC and chronic liver disease is often limited as compared with patients with a healthy liver. Presentation of case We reported a 53-year-old male who had a huge HCC (14.8 × 12 × 9.4 cm) arising from a background of hepatitis B liver fibrosis (METAVIR score F3). The ratio of the FLR/standard liver volume (SLV) was 23.8%. After stage I ALPPS, volumetric assessment on postoperative day (POD) 7 and 13 showed insufficient FLR hypertrophy (FLR/SLV: 28.7% and 30.7%, respectively). A postoperative computed tomographic 3D reconstruction and hepatic angiography showed steal of arterial blood from the FLR to the huge tumour in the right liver. Salvage transhepatic arterial embolization (TAE) was performed to block the major arterial blood supply to the tumour on POD 13. The FLR/SLV increased to 42.5% in 7 days. Stage II ALPPS consisting of right trisectionectomy was successfully performed. Discussion Salvage TAE which blocked the main arterial blood supply to the huge HCC improved the arterial supply with subsequent adequate and fast hypertrophy of the FLR to allow trisectionectomy in stage II ALPPS to be carried out. Conclusion Salvage TAE after failed stage I ALPPS with inadequate hypertrophy of the FLR allowed trisectionectomy in stage II ALPPS to be carried out in a patient with a huge HCC with chronic liver disease.

Deformation is a comprehensive reflection of the structural state of a concrete dam, and research on prediction models for concrete dam deformation provides the basis for safety monitoring and early warning strategies. This paper focuses on practical problems such as multicollinearity among factors; the subjectivity of factor selection; robustness, externality, generalization, and integrity deficiencies; and the unsoundness of evaluation systems for prediction models. Based on rough set (RS) theory and a long short-term memory (LSTM) network, single-point and multipoint concrete dam deformation prediction models for health monitoring based on RS-LSTM are studied. Moreover, a new prediction model evaluation system is proposed, and the model accuracy, robustness, externality, and generalization are defined as quantitative evaluation indexes. An engineering project shows that the concrete dam deformation prediction models based on RS-LSTM can quantitatively obtain the representative factors that affect dam deformation and the importance of each factor relative to the effect. The accuracy evaluation index (AVI), robustness evaluation index (RVI), externality evaluation index (EVI), and generalization evaluation index (GVI) of the model are superior to the evaluation indexes of existing shallow neural network models and statistical models according to the new evaluation system, which can estimate the comprehensive performance of prediction models. The prediction model for concrete dam deformation based on RS-LSTM optimizes the factors that influence the model, quantitatively determines the importance of each factor, and provides high-performance, synchronous, and dynamic predictions for concrete dam behaviours; therefore, the model has strong engineering practicality.

Background Soluble programmed death-ligand 1 (sPD-L1) is associated with hepatocellular carcinoma (HCC) prognosis after resection or radiotherapy. However, its value in patients who received transcatheter arterial chemoembolization (TACE) remains unclear. The present study aimed to determine the prognostic significance of sPD-L1 in TACE subgroup. Methods 114 HCC patients with hepatitis B virus (HBV)-background who received TACE from 2012 to 2013 were recruited. sPD-L1 levels were determined by enzyme-linked immunosorbent assay. We evaluated prognoses according to mRESIST criteria and analyzed prognostic values by Cox regression and Kaplan-Meier analysis. We further evaluated correlations between sPD-L1 and systemic inflammation index (SII), soluble interleukin-2 receptor (sIL-2R), IL-10, hepatitis B virus (HBV)-DNA loads, and C-reactive protein. Results Significantly elevated sPD-L1 levels were found in patients who developed HCC progression (P = 0.002) and death (P Conclusions sPD-L1 level is a prognostic indicator of poor outcomes after TACE. High sPD-L1 indicated increased immune activation in an immunosuppressive environment that hindered anti-tumor response activity. Lowering sPD-L1 levels may provide a novel avenue for preventing HCC progression post-TACE. Legal entity responsible for the study The authors. Funding The National Natural Science Foundation of China (87172263 and 81572064) and Key Developing Disciplines of Shanghai Municipal Commission of Health and Family Planning (2015ZB0201). Disclosure All authors have declared no conflicts of interest.

Arsenic trioxide (ATO) has been found effective in several types of cancer cells, including acute promyelocytic leukemia, and recently in hepatocellular carcinoma (HCC). In this study, we investigated the role of ATO in regulating the invasive activity of HCC after transarterial embolization (TAE). Cell migration and invasion were observed using Transwell and wound-healing assay. The molecular changes in E-cadherin, N-cadherin, and Vimentin of surviving tumor cells were determined by Western blotting. The effects of ATO on Twist activity of the tumor cells were further analyzed. In animal study, 40 male buffalo rats implanted with McA-RH7777 tumor in the liver were randomly divided into four groups: control, TAE, ATO, and TAE + ATO. TAE procedures were performed on the 14th day after implantation. Lung metastases were observed using fluorescence imaging, and the molecular changes in residual tumor cells were evaluated by Western blotting or immunohistochemistry. Tumor growth and survival analysis were also evaluated. Arsenic trioxide markedly reduced cell migration and invasiveness, which were enhanced by hypoxia after TAE. Western blot analysis revealed ATO inhibited the expression of epithelial–mesenchymal transition (EMT) markers by suppressing Twist. The marked suppression effect of ATO on invasiveness and metastatic potential related to EMT was also shown in tissue. The results of this study demonstrated that ATO is an effective anticancer agent in combination with TAE in the treatment of HCC, by suppressing tumor progression and metastasis via selectively inducing tumor cell apoptosis and arresting EMT by inhibiting the Twist activation.

Transarterial chemoembolization represents a first-line non-curative therapy for hepatocellular carcinoma (HCC), although the biological changes in the remaining cancer after embolization are not completely understood. In the present study, we examined whether transarterial embolization (TAE) enhances the metastatic potential of residual HCC and investigated the mechanisms underlying embolization. The hepatoma cell line McA-RH7777, which is marked by green fluorescent protein (GFP), was used in the study. The invasion of cells cultured under hypoxia and normoxia was observed using the Transwell assay. Twenty male buffalo rats were implanted with GFP transfected McA-RH7777 tumors in the left lateral lobe of the liver. After laparotomy and retrograde placement of a catheter into the gastroduodenal artery (on the 14th day after implantation), TAE using lipiodol (0.2 ml/kg) was performed. Tumor volumes were measured before and after treatment using magnetic resonance imaging (MRI). Lung metastases were observed using fluorescence imaging, and the molecular changes of residual tumor cells were evaluated by western blotting or immunohistochemistry. The invasion assays indicated that the number of invading hypoxic cells was significantly higher than that of normoxic cells (30.2 ± 2.46 vs. 20.4 ± 1.89, P=0.013). Accompanying an increase in hypoxia-inducible factor-1α (HIF-1α) expression, the metastatic potential of tumor cells following hypoxia or TAE was enhanced. This enhanced metastatic potential was indicated by a significant reduction in the expression of E-cadherin and an upregulation of N-cadherin and vimentin expression. The number of lung metastases in the TAE group was 19.20 ± 1.76, whereas this number was 11.30 ± 1.54 in the control group, which represented a statistically significant difference (P=0.003). In conclusion, hypoxia in the residual tumor after TAE can increase the invasiveness and metastatic potential of HCC and may be responsible for the failure of TAE.

The purpose of this study was to establish an animal model of implanted inferior vena cava tumor thrombus (IVCTT) and to evaluate the effect of linear iodine-125 seeds strand in treating implanted IVCTT. Tumor cell line VX2 was inoculated subcutaneously into New Zealand rabbit to develop the parent tumor. The tumor strip was inoculated into inferior vena cava (IVC) to establish the IVCTT model. The IVCTT was confirmed by multidetector computed tomography (MDCT) after 2 weeks. Twelve rabbits with IVCTT were randomly divided into two groups. Treatment group (group T; n = 6) underwent Iodine-125 seeds brachytherapy, and the control group (group C; n = 6) underwent blank seeds strand. The blood laboratory examination (including blood routine examination, hepatic and renal function), body weight, survival time, and IVCTT volume by MDCT were monitored. All rabbits were dissected postmortem, and the therapeutic effects were evaluated on the basis of histopathology. The proliferating cell nuclear antigen index (PI) and apoptosis index (AI) of IVCTT were compared between two groups. T test, Wilcoxon rank test, and Kaplan–Meier survival curve analysis were used. The success rate of establishing IVCTT was 100 %. The body weight loss and cachexia of rabbits in group C appeared earlier than in group T. Body weight in the third week, the mean survival time, PI, AI in groups T and C were 2.23 ± 0.12 kg, 57.83 ± 8.68 days, (16.73 ± 5.18 %), (29.47 ± 7.18 %), and 2.03 ± 0.13 kg, 43.67 ± 5.28 days, (63.01 ± 2.01 %), (6.02 ± 2.93 %), respectively. There were statistically significant differences between group T and group C (P

Zeng-Bao Wu,1,* Zeng-Mei Si,1,* Sheng Qian,1 Ling-Xiao Liu,1 Xu-Dong Qu,1 Bo Zhou,1 Wei Zhang,1 Guang-Zhi Wang,2 Rong Liu,1 Jian-Hua Wang1 1Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Intervention Radiology, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China *These authors contributed equally to this work Background: The purpose of this study was to retrospectively evaluate the therapeutic efficacy and safety of ultrasound-guided percutaneous microwave ablation (MWA) combined with synchronous transcatheter arterial chemoembolization (TACE) in patients with colorectal liver metastases (CRLM).Patients and methods: A retrospective analysis was performed in 30 patients who were treated with ultrasound-guided percutaneous MWA combined with synchronous TACE for colorectal cancer liver metastases from November 2011 to December 2014 in Zhongshan Hospital, Fudan University. The response of the tumor to treatment was evaluated by follow-up computed tomography and/or magnetic resonance imaging. Local tumor control, procedure-related complications, and long-term survival data were analyzed.Results: A total of 30 patients with 43 tumors ranging in size from 1.4cm to 10.0cm were analyzed. The patients’ mean age was 61.6±10.3years (range, 44.0–78.0years). The median follow-up time was 26.5±10.4months (range, 13.3–50.6months). The complete ablation rate was 81.4% (35/43 lesions) for CRLM. Complete response was achieved in eight cases (26.7%), and partial response was achieved in 17 cases (56.7%) 1month after the procedure. The objective response rate (complete response + partial response) was 83.4%. Progression-free survival and overall survival were 5.0months and 11.0months, respectively. The 12-month and 24-month survival rates were 46.7% and 25.4%, respectively. A total of 22 patients succumbed during follow-up due to tumor progression. No major complications or perioperative mortalities were recorded.Conclusion: Ultrasound-guided percutaneous MWA combined with synchronous TACE therapy is a safe and effective modality for patients with CRLM. Keywords: colorectal liver metastases, microwave ablation, transcatheter arterial chemoem­bolization

Purpose To conduct a single-center, open-label, randomized, controlled trial to compare the effectiveness and safety of (a) ginsenoside Rg3 combined with transcatheter arterial chemoembolization (TACE) and (b) TACE alone in patients with advanced hepatocellular carcinoma (HCC). Materials and Methods This trial was approved by the Fudan University Zhongshan Hospital ethics committee and was registered with the Chinese Clinical Trial Registry (ChiCTR-TRC-11001643). After informed consent was obtained, 228 patients with advanced HCC (Barcelona Clinic Liver Cancer stage C) were randomly assigned to receive an Rg3 capsule and undergo TACE (n = 152; mean age ± standard deviation, 52.4 years ± 11.8; 84.2% men) or undergo TACE alone (n = 76; mean age, 52.4 years ± 10.4; 82.9% men). TACE was performed by using iodized oil with epirubicin and gelatin sponge after oxaliplatin and 5-fluorouracil were infused. The primary end point was overall survival. Secondary end points included time to progression, time to untreatable progression, disease control rate, and safety. Data were compared with the log-rank test, and survival curves were generated with the Kaplan-Meier method. Results Median overall survival was 13.2 months (95% confidence interval [CI]: 11.15, 15.26) in the TACE with Rg3 group and 10.1 months (95% CI: 9.14, 11.06) in the control group (hazard ratio, 0.63 [95% CI: 0.46, 0.85]; P = .002). Median time to progression (4.3 vs 3.2 months, respectively; P = .151) and median time to untreatable progression (8.3 vs 7.3 months, respectively; P = .063) were similar in the two groups. Disease control rate was 69.7% in the TACE with Rg3 group versus 51.3% in the control group (P = .012). Constipation and epistaxis were more frequent in the Rg3 with TACE group (P < .05). Importantly, Rg3 alleviated some TACE-related adverse syndromes and blood anomalies. Conclusion In patients with advanced HCC and adequate liver function, the combination of TACE and ginsenoside Rg3 may prolong overall survival when compared with TACE alone. (©) RSNA, 2016.

Guo-Wei Yang,* Qing Zhao,* Sheng Qian, Liang Zhu, Xu-Dong Qu, Wei Zhang, Zhi-Ping Yan, Jie-Min Cheng, Qing-Xin Liu, Rong Liu, Jian-Hua Wang Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China *These authors contributed equally tothis work Aim: To retrospectively evaluate the safety and efficacy of ultrasound-guided percutaneous microwave ablation (MWA) combined with simultaneous transarterial chemoembolization (TACE) in the treatment of patients with advanced intrahepatic cholangiocarcinoma (ICC).Methods: All patients treated with ultrasound-guided percutaneous MWA combined with simultaneous TACE for advanced ICC at our institution were included. Posttreatment contrast-enhanced computed tomography and/or magnetic resonance imaging were retrieved and reviewed for tumor response to the treatment. Routine laboratory studies, including hematology and liver function tests were collected and analyzed. Procedure-related complications were reviewed and survival rates were analyzed.Results: From January 2011to December 2014, a total of 26advanced ICC patients were treated at our single institute with ultrasound-guided percutaneous MWA combined with simultaneous TACE. There were 15males and eleven females with an average age of 57.9±10.4years (range, 43–75years). Of 26patients, 20(76.9%) patients were newly diagnosed advanced ICC without any treatment, and six (23.1%) were recurrent and treated with surgical resection of the original tumor. The complete ablation rate was 92.3% (36/39lesions) for advanced ICC. There were no major complications observed. There was no death directly from the treatment. Median progression-free survival and overall survival were 6.2and 19.5months, respectively. The 6-, 12-, and 24-month survival rates were 88.5%, 69.2%, and 61.5%, respectively.Conclusion: The study suggests that ultrasound-guided percutaneous MWA combined with simultaneous TACE therapy can be performed safely in all patients with advanced ICC. The complete ablation rate was high and there was no major complication. The overall 24-month survival was 61.5%.Keywords: intrahepatic cholangiocarcinoma, interventional radiology, microwave ablation, transarterial chemoembolization&nbsp

Qing Zhao,* Sheng Qian,* Liang Zhu, Xu-Dong Qu, Wei Zhang, Zhi-Ping Yan, Jie-Min Cheng, Qing-Xin Liu, Rong Liu, Jian-Hua Wang Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China *These authors contributed equally to this work Background: The aim of this study was to determine the therapeutic efficacy and safety of transarterial chemoembolization (TACE) with gemcitabine and oxaliplatin in patients with advanced biliary tract cancer (BTC). Methods: We retrospectively analyzed the outcomes for 65 patients with advanced BTC treated by TACE with gemcitabine 1,000 mg/m2 and oxaliplatin 100 mg/m2. Follow-up laboratory tests and computed tomography or magnetic resonance imaging were performed routinely to evaluate the response of the tumor to treatment. All patients were assessed for adverse effects. Results: Of the 65 patients, 19 (29.2%) achieved a partial response, 36 (55.4%) showed stable disease, and ten (15.4%) showed progressive disease. The overall response rate was 29.2%. At the end of this study, five patients were still alive. The median overall survival was 12.0 months (95% confidence interval 8.5–15.5). There were no serious complications after TACE. Conclusion: The disease control rate and overall survival in this retrospective study were consistent with those in previous reports. TACE with gemcitabine and oxaliplatin was well tolerated and highly effective in patients with advanced BTC. Keywords: gemcitabine, oxaliplatin, transcatheter arterial chemoembolization, biliary tract cancer&nbsp

Objective: To investigate the safety and efficacy of radiofrequency ablation combined with transarterial chemoembolization in patients with specially located small hepatocellular carcinoma. Materials and Methods: Between March 2014 and March 2017, a total of 26 patients with 26 lesions (10 perivascular, 6 subdiaphragmatic, 5 subcapsular, 5 perivascular, and subdiaphragmatic location; mean diameter 2.12 (0.62) cm), who received radiofrequency ablation–transarterial chemoembolization treatment, were retrospectively analyzed. Local tumor response was assessed by computed tomography/magnetic resonance imaging 1 month after the procedure. Tumor-free survival was also assessed according to the modified Response Evaluation Criteria in Solid Tumors. Complications were evaluated according to the National Cancer Institute’s Common Terminology Criteria for Adverse Events (version 4.0). Results: Complete response was achieved in all patients 1 month after the procedure. During a median follow-up duration of 16.76 months (95% confidence interval: 7.78-25.73 months), local tumor recurrence occurred in 2 patients and new intrahepatic lesions developed in 7 patients. The 1-, 2-, and 3-year cumulative local tumor progression rates were 3.84%, 7.69%, and 7.69%, respectively. The median tumor-free survival duration was 21.96 months (95% confidence interval: 17.58-26.34 months). The 1-, 2-, and 3-year tumor-free survival rates were 67.4%, 46.1%, and 39.3%, respectively. Conclusion: The radiofrequency ablation–transarterial chemoembolization combination therapy appears to be safe and effective and might be a treatment option for specially located small hepatocellular carcinoma lesions that have a risk of incomplete ablation or major complications.

Intrahepatic arterioportal fistula (IAPF) can be caused by many secondary factors. We report four cases of portal hypertension that were eventually determined to be caused by congenital hepatic arterioportal fistula. The clinical manifestations included ascites, variceal hemorrhage and hepatic encephalopathy. Computed tomography scans from all of the patients revealed the early enhancement of the portal branches in the hepatic arterial phase. All patients were diagnosed using digital subtraction angiography (DSA). DSA before embolization revealed an arteriovenous fistula with immediate filling of the portal venous radicles. All four patients were treated with interventional embolization. The four patients remained in good condition throughout follow-up and at the time of publication. IAPF is frequently misdiagnosed due to its rarity; therefore, clinicians should consider IAPF as a potential cause of non-cirrhotic portal hypertension.

Background Three-dimensional (3D) whole-liver perfusion magnetic resonance(MR) imaging with parallel imaging, a novel imaging method to characterize tumor vascularization in vivo, has recently been applied to comprehensively image perfusion changes in large tumors. Coupled with new perfusion software, this technique enables motion correction, registration, and evaluation of perfusion MR parameters. The purpose of this study was to assess the feasibility of 3D whole-liver perfusion MR, for imaging hepatocellular carcinoma (HCC) and colorectal hepatic metastases (CRHM). Methods 26 patients with hepatic tumors (10 HCC; 16 CRHM) were subjected to 3D whole-liver perfusion MR with a temporal resolution of 3.7 seconds. The following estimated perfusion parameters were measured: the volume transfer constant Ktrans (min-1); the volume (Ve) of extravascular extracellular space (EES) per volume unit of tissue; and the flux rate constant between EES and plasma Kep (min-1). Statistical analysis was conducted to investigate inter-observer characteristics and significance of the measured parameters. Results Inter-observer agreement analysis (95% limits of agreement) yielded a mean difference of −0.0048 min-1 (−0.0598 ~ 0.0502) for Ktrans , -0.0630 ml (−0.5405 ~ 0.4145) for Ve, and −0.0031 min-1 (−0.0771 ~ 0.0709) for Kep respectively. When comparing images from patients with HCC vs. CRHM, significant differences were seen for the mean Ktrans (p = 0.017), but not for Ve(p = 0.117) or Kep(p = 0.595). Conclusion Herein we show that 3D whole-liver MR perfusion imaging with semi-automatic data analysis is feasible and enables the reliable quantitative evaluation of the perfusion parameters for HCCs and CRHMs.

Background The long-term survival in hepatocellullar carcinoma (HCC) patients after transarterial chemoembolization (TACE) remains dismal due to local and/or regional recurrence as well as distant metastasis. The efficacy of sorafenib in advanced HCC has been demonstrated and brought great hope. Recently, the use of sorafenib in combination with TACE for BCLC stage B and C HCC patients was recommended. However, data on this dual-modality treatment is little, and its advantage over TACE alone has not been addressed. The present study sought to understand the efficacy of the combination of TACE and sorafenib in the treatment of advanced HCC. Methods Between June 2008 and Feb 2011, 45 patients with advanced HCC were enrolled and treated with sorafenib in combination with TACE according to an institutional protocol of the Zhongshan hospital, Fudan University. The control group of 45 other HCC patients with similar characteristics treated with TACE alone in the same period of time in our institute were selected for retrospective comparison of the treatment outcomes especially overall survival time. Adverse reactions induced by sorafenib were observed and recorded. Results The median overall survival time of the combined treatment group was 27 (95% Confidence Interval: 21.9–32.1) months, and that of TACE alone group was 17 months (95% Confidence Interval: 8.9–25.0) months (P = 0.001). Patients required significantly less frequent TACE for their symptomatic treatment after the initiation of sorafenib therapy. The most common adverse events associated with sorafenib were hand-foot skin reaction, rash and diarrhea. Of CTCAE grade IV or V toxicity was observed. Conclusion TACE combined sorafenib significantly prolonged median overall survival time of patients with advanced HCC.

Background Ginsenoside Rg3 is a low toxic inhibitor of vascular endothelial growth factor (VEGF), which is implicated in angiogenesis in hepatocellular carcinoma (HCC). This single-centre, open-label, randomised, controlled trial evaluated the efficacy and safety of ginsenoside Rg3 plus transarterial chemoembolisation (TACE) in patients with advanced HCC. Methods Advanced HCC patients (Child-Pugh A) who had no prior systemic therapy were randomly assigned (2:1 ratio) to receive 20 mg twice daily orally (n = 152) combined with TACE or TACE alone (n = 76). The primary endpoint was overall survival (OS). Secondary endpoints included time to progression (TTP), time to untreatable progression (TTUP), disease control rate (DCR) based on modified Response Evaluation Criteria in Solid Tumors, and safety. Results Median overall survival was 13.2 months (95% confidence interval (CI) 11.15–15.26) in the TACE + Rg3 group compared with 10.1 months (95% CI 9.14–11.06) for those receiving TACE alone (hazard ratio (HR) 0.63 [95% CI 0.46–0.85], p = 0.002). Median TTP was 4.3 months (95% CI 3.32–5.28) in the TACE + Rg3 group compared with 3.2 months (95% CI 2.51–3.89) in the TACE group (HR 0.82 [95% CI 0.62–1.08], p = 0.151). Patients in the TACE + Rg3 group had longer median TTUP (8.3 months [95% CI 7.05–9.55]) than in the TACE group (7.3 months [95% CI 6.40–8.20]; HR 0.76 [95% CI 0.57–1.02], p = 0.063). The most frequently reported Rg3-related grade 3–4 adverse events in 152 patients were constipation (two [1.3%]) and hypertension (six [3.9%]). The incidence of ascites was lower in the TACE + Rg3 group than in the TACE group (23.7% versus 48.7%, p = 0.002), as was the incidence of anorexia [12.5% versus 44.7%, p = 0.000], fatigue (9.9% versus 50.0% p = 0.000), anaemia (36.8% versus 51.3%, p = 0.037), leukopenia (46.7% versus 76.3%, p = 0.000), thrombocytopenia (32.9% versus 50.0%, p = 0.012), and hyperbilirubinaemia (17.8% versus 34.2%, p = 0.028). Interpretation In patients with advanced HCC and sufficient liver function, median survival was nearly 3 months longer for patients treated with TACE and ginsenoside Rg3 than for those who received TACE only.

Zhu-Ting Fang,1,2,† Wei Zhang,1,† Guang-Zhi Wang,1 Bo Zhou,1 Guo-Wei Yang,1 Xu-Dong Qu,1 Rong Liu,1 Sheng Qian,1 Liang Zhu,1 Ling-Xiao Liu,1 Jian-Hua Wang1 1Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, 2Department of Interventional Radiology, Fujian Provincial Hospital, Provincial Clinic College of Fujian Medical University, Fuzhou, People's Republic of China†These authors contributed equally to this work Abstract: The aims of this study were to assess the effect of transarterial chemoembolization (TACE) on circulating tumor cells (CTCs) in the peripheral blood and right atrium of patients with HCC and to evaluate whether perioperative shedding of CTCs affects time to progression of HCC. Before and after TACE, peripheral and right atrial blood samples (7.5 mL) were collected from 42 patients with HCC. CTCs were enriched using EpCAM antibody-conjugated magnetic beads. The number of CTCs was 0–30 and 0–54 in peripheral blood before and after TACE, respectively (P=0.166), and 0–65 and 0–98 in the right atrium before and after TACE, respectively (P=0.102). The number of CTCs was significantly different between the two samples both before (P=0.007) and after (P=0.021) TACE. There was no difference in time to progression between patients with and without an increase in the number of CTCs after TACE in either sample (P>0.05 for both). There were more CTCs in right atrial blood than in peripheral blood. The numbers of CTCs in both samples remained unchanged after TACE. Shedding of tumor cells did not affect time to progression of disease in patients with HCC. Keywords: hepatocellular carcinoma, transcatheter arterial chemoembolization, circulating tumor cells, metastasis, positive screening

Zhu-Ting Fang,1,2,* Guang-Zhi Wang,1,* Wei Zhang,1 Xu-Dong Qu,1 Rong Liu,1 Sheng Qian,1 Liang Zhu,1 Bo Zhou,1 Jian-Hua Wang1 1Department of Intervention Radiology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China; 2Department of Intervention Radiology, Provincial Hospital of Fujian Province, Teaching Hospital of Fujian Medical University, Fuzhou, People's Republic of China *Authors who have contributed equally to this article Abstract: Transcatheter arterial embolization (TAE) is widely used as an effective palliative treatment for hepatocellular carcinoma (HCC), and can prolong survival time. However, the high incidence of tumor recurrence and metastasis after TAE is still a major problem. Recent studies demonstrated that circulating tumor cells (CTCs) contribute to tumor metastasis. In this study, we tried to clarify whether the residual HCC after TAE can increase metastasis by increasing the number of CTCs. An orthotopic liver tumor model in the Buffalo rat was established using green fluorescent protein (GFP)-transfected HCC cell line, McA-RH7777. Two weeks after orthotopic liver tumor implantation, the rats underwent TAE treatment from the gastroduodenal artery. Iodized oil or saline was injected intra-arterially. Blood samples were taken on day 0, 1, 3, 7, 14, and 21 for detection of CTCs after TAE treatment. We analyzed the number of CTCs and assessed the metastatic potential of surviving tumor cells in rats between TAE and control groups. Our results demonstrated that the metastatic colonies in the lung were significantly increased by TAE treatment. The number of CTCs was also significantly increased by TAE treatment from day 7 to day 21. The expression of hypoxia-inducible factor (HIF)-1α and epithelial–mesenchymal transition (EMT) marker proteins (N-cadherin and vimentin) was upregulated, but E-cadherin was downregulated after TAE treatment. In conclusion, the metastatic potential of residual HCC can be induced by TAE treatment in a rat liver tumor model, which involves the acquisition of EMT features and an increased number of CTCs. Keywords: transcatheter arterial embolization, hepatocellular carcinoma, circulating tumor cells, epithelial–mesenchymal transition

279 Background: The purpose of this prospective trial is to evaluate the efficacy and safety of the concurrent use of TACE and sorafenib in a group of patients with unresectable HCC.The treatment outcomes of this group of patients were also compared in a retrospective fashion with a group of HCC patients with similar characteristics of patient and disease in a case controlled setting. Methods: A total of 45 patients (BCLC stage B/C: 16/29) with unresectable HCC were enrolled between June 2008 and Feb 2011 as experimental group and were treated with combination of sorafenib and TACE according to an institutional protocol. To evaluate the efficacy of the combination therapy, a group of 45 HCC patients (n=45, BCLC stage B/C: 17/28) with comparable baseline characteristics who had been treated with TACE alone in our institute were retrospectively selected as control group to compare the treatment outcomes. Median overall survival was compared between the two groups. Adverse events related to sorafenib were assessed according to CTCAE3.0 to observe safety endpoints. The study was approved by the Institutional Ethics Committee at Zhongshan Hospital, Fudan University, China. Results: The median follow-up time for the entire group of patients was 21 months (12.66 - 29.33). The median survival time for the TACE/sorafenib group was 27 months (21.89 - 32.10), and that for TACE alone group was 17 months (8.9 - 25.04) (P Conclusions: The combination treatment of TACE and sorafenib significantly prolonged median survival in Chinese patients with unresectable HCC, with well tolerated safety profile.

AIM: To explore the diffusion gradient b-factor that optimizes both apparent diffusion coefficient (ADC) measurement and contrast-to-noise (CNR) for assessing tumor response to transarterial chemoembolization (TACE) in a rabbit model. METHODS: Twelve New Zealand white rabbits bearing VX2 tumors in the liver were treated with TACE. Diffusion-weighted imaging (DWI) with various b values was performed using the same protocol before and 3 d after treatment with TACE. ADC values and CNR of each tumor pre- and post-treatment with different b factors were analyzed. Correlation between ADC values and extent of necrosis in histological specimens was analyzed by a Pearson’s correlation test. RESULTS: The quality of diffusion-weighted images diminished as the b value increased. A substantial decrease in the mean lesion-to-liver CNR was observed on both pre- and post-treatment DW images, the largest difference in CNR pre- and post-treatment was manifested at a b value of 1000 s/mm2 (P = 0.036 ). The effect of therapy on diffusion early after treatment was shown by a significant increase in ADCs (P = 0.007), especially with large b factors (≥ 600 s/mm2). The mean percentage of necrotic cells present within the tumor was 76.3%-97.5%. A significant positive correlation was found between ADC values and the extent of necrosis with all b values except for b200, a higher relative coefficient between ADC values and percentage of necrosis was found on DWI with b1000 and b2000 (P = 0.002 and 0.006, respectively). CONCLUSION: An increasing b value of up to 600 s/mm2 would increase ADC contrast pre- and post-treatment, but decrease image quality. Taking into account both CNR and ADC measurement, diffusion-weighted imaging obtained with a b value of 1000 s/mm2 is recommended for monitoring early hepatic tumor response to TACE.