Hypoxic Hepatocellular Carcinoma Cells Acquire Arsenic Trioxide Resistance by Upregulating HIF-1α Expression.

BACKGROUND: Although arsenic trioxide (ATO) is used in the treatment of advanced hepatocellular carcinoma (HCC) in clinical trials, it is not satisfactory in terms of improving HCC patients' overall survival. Intratumoral hypoxia and overexpression of hypoxia-inducible factor-1α (HIF-1α) may result in ATO resistance and tumor progression. AIMS: We investigated the mechanisms involving HIF-1α expression and acquired ATO chemoresistance in HCC cells and mice. METHODS: The therapeutic effects of ATO in normoxic and hypoxic HCC cells were assessed using cell viability and apoptosis assays in vitro and a xenograft model in vivo. mRNA and protein expression of HIF-1α, P-glycoprotein, and VEGF were measured by qRT-PCR and western blotting. HIF-1α inhibition was performed to investigate the mechanism of ATO resistance. VEGF secretion was tested using ELISA and tube formation assays. RESULTS: Compared to normoxic cells, hypoxic HCC cells were more resistant to ATO, with higher IC50 values and less apoptosis, and upregulated HIF-1α protein expression, accompanied with the enhancement of P-glycoprotein and VEGF synthesis after ATO treatment. VEGF secretion was elevated in the supernatant of ATO-treated HCC cells, and this change can potentiate angiogenesis in vitro. HIF-1α inhibition attenuated ATO resistance and angiogenesis and promoted the anticancer effects of ATO both in vitro and in vivo by downregulating therapy-induced P-glycoprotein and VEGF overexpression. CONCLUSIONS: Hypoxic HCC cells acquire ATO resistance by upregulating HIF-1α levels; thus, combining ATO with a HIF-1α-targeting agent may lead to enhanced antitumor effects in HCC.

A nomogram to predict survival of patients with intermediate-stage hepatocellular carcinoma after transarterial chemoembolization combined with microwave ablation.

OBJECTIVES: To develop a prognostic nomogram based on the albumin-bilirubin (ALBI) grade for prediction of the long-term survival of patients with intermediate-stage hepatocellular carcinoma (HCC) after transarterial chemoembolization combined with microwave ablation (TACE-MWA). METHODS: We retrospectively studied 546 consecutive patients with intermediate-stage HCC according to the Barcelona Clinic Liver Cancer guidelines who underwent TACE-MWA between January 2000 and December 2016. Overall survival (OS) and progression-free survival (PFS) were analyzed. The predictive value of the ALBI grade was investigated. The prognostic nomogram was constructed using the independent predictors assessed by the multivariate Cox proportional hazards model. RESULTS: After a median follow-up of 35.0 months (range, 4.0-221.0 months), 380 patients had died. The median OS was 35.0 months (95% confidence interval (CI), 30.84-39.16 months), and the median PFS was 6.5 months (95% CI, 6.13-6.87 months). The ALBI grade was validated as an independent predictor of OS (p < 0.001). Multivariate analyses showed that Eastern Cooperative Oncology Group performance status score more than 0, presence of liver cirrhosis, a-fetoprotein level above 400 ng/mL, tumor size greater than 5 cm, tumor number more than 3, advanced ALBI grade, and treatment sessions of TACE or MWA fewer than 3 were independently associated with overall mortality. The prognostic nomogram incorporating these eight predictors achieved good calibration and discriminatory abilities with a concordance index of 0.770 (95% CI, 0.746-0.795). CONCLUSIONS: The prognostic nomogram based on the ALBI grade resulted in reliable efficacy for prediction of individualized OS in patients with intermediate-stage HCC after TACE-MWA. KEY POINTS: • TACE-MWA was associated with a median overall survival of 35.0 months for patients with intermediate-stage HCC. • A prognostic nomogram was built to predict individualized survival of patients with intermediate-stage HCC after TACE-MWA. • The prognostic nomogram incorporating eight predictors achieved good calibration and discriminatory abilities with a concordance index of 0.770.

Clinical management of vascular lake during transarterial chemoembolization with CalliSpheres drug-eluting beads (DEBs) for the treatment of hepatocellular carcinoma.

BACKGROUND: To summarize the incidence and management strategy of vascular lake (VL) during the treatment of hepatocellular carcinoma (HCC) using transarterial chemoembolization (TACE) with CalliSpheres drug-eluting beads (DEBs), and to analyze its relationship with tumor response rate (RR). The etiology and clinical significance of VL were also analyzed based on the available literature. METHODS: The clinical data of 92 HCC patients who were treated with chemoembolization using CalliSpheres DEBs (DEB-TACE) in two centers were retrospectively analyzed. All 92 patients were treatment-naïve and treated by DEB-TACE. The incidence of VL and its clinical treatment during the first embolization session were summarized. The lesions were divided into a VL group and a non-VL group to analyze the relationship between VL and tumor RR. RESULTS: The embolization was successful in 98.9% of patients (91/92). A total of 33 VLs (18.4%; including 15 stable and 18 unstable VLs) were found among the 179 nodules treated. The unstable VLs were further embolized with embolic agent. One patient with unstable VL developed bleeding due to hepatic rupture and died. During the follow-up, residual tumors were found around 2 stable VLs, 2 lesions in 2 patients were treated with CT-guided radiofrequency ablation. The tumor RR was 84.4% in VL group, which was significantly higher than that (58.9%) in the non-VL group (P=0.007). CONCLUSIONS: VL is a unique phenomenon during DEB-TACE. It may be accompanied by residual tumors and bleeding due to rupture. Therefore, VL should be cautiously managed in clinical practice.

Effectiveness and safety of irreversible electroporation for recurrent hepatocellular carcinoma ineligible for thermal ablation after surgery.

OBJECTIVES: To preliminarily evaluate the clinical effectiveness and safety of computed tomography (CT) image-guided irreversible electroporation (IRE) for the treatment of recurrent hepatocellular carcinoma (HCC) after surgical resection. METHODS: From January 2016 to February 2018, 18 patients diagnosed with recurrent HCC after surgical resection received IRE under CT image guidance for 22 tumors. Patients were enrolled for IRE when ineligible for thermal ablation due to tumor location. Clinical records and imaging data were reviewed to assess complete ablation rate, local tumor progression free rate (LTPFR), local tumor progression free survival (LTPFS) and complications after a median follow-up time of 14 months. RESULTS: Successful complete ablations were achieved in 20/22 (90.1%) tumors. Mean LTPFS was 10.5 â€‹± â€‹9.4 months. Overall 3-, 6- and 12-months LTPFR in 22 tumors following IRE were 68.2% (95% confidence interval [CI]: 45%-83%), 59.1% (95% CI: 33%-76%) and 36.4% (95% CI: 17%-56%), respectively. Complications included pneumothorax (2/18, 11.1%), localized pain (3/18, 16.7%), bile duct dilation (1/18, 5.6%) and transient hypertension (1/18, 5.6%). No major complications or treatment-related deaths were observed. The alpha-fetoprotein levels of two patients decreased to the normal range at 3 and 4 months, respectively. CONCLUSIONS: This study showed that percutaneous CT image-guided IRE can serve as a safe and effective treatment for recurrent HCC not suitable for thermal ablation.

Comparison of albumin-bilirubin grade, platelet-albumin-bilirubin grade and Child-Turcotte-Pugh class for prediction of survival in patients with large hepatocellular carcinoma after transarterial chemoembolization combined with microwave ablation.

Purpose: To compare the predictive value of albumin-bilirubin (ALBI) grade, platelet-ALBI (PALBI) grade and Child-Turcotte-Pugh (CTP) class in patients with large hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE) combined with microwave ablation (TACE-MWA). Methods: A total of 349 consecutive HCC patients (89.1% male; mean [± SD] age 53.4 ± 12.27 years) from three medical centers, who underwent TACE-MWA for up to 3 HCCs with maximum diameters of 5.1-8.0 cm between January 2000 and June 2018, were investigated. Overall survival (OS) and progression-free survival (PFS) were analyzed. The prognostic performances of ALBI grade, PALBI grade and CTP class were compared. Results: TACE procedures were performed using lobaplatin (20-50 mg), epirubicin (30-60 mg), lipiodol (5-25 mL) and gelatin sponge particles (350-560 µm). The end point of the TACE procedure was stasis of blood flow in the feeder artery. The median follow-up duration was 28.0 months, the median OS was 28.0 months (95% confidence interval [CI] 23.55-32.45 months), and the median PFS was 4.8 months (95% CI 4.26-5.34 months). Patients with a ablation margin size of 11-15 mm experienced better PFS than those with a margin size of 6-10 or 0-5 mm (median, 6.5 versus [vs] 4.0 vs 2.3 months; p < .001). PALBI grade demonstrated significantly greater area under the curve values than ALBI grade or CTP class in predicting 1-, 3- and 5-year OS. Conclusions: PALBI grade provided better predictive value than ALBI grade or CTP class in patients with large HCCs after TACE-MWA.

Transarterial Chemoembolization and Sorafenib Combined with Microwave Ablation for Advanced Primary Hepatocellular Carcinoma: A Preliminary Investigation of Safety and Efficacy.

PURPOSE: The aim of this study was to investigate the safety and efficacy of transarterial chemoembolization and sorafenib (TACE-S) combined with microwave ablation (TACE-S-MWA) for the treatment of patients with advanced primary hepatocellular carcinoma (HCC). METHODS: Between January 2015 and December 2018, 152 consecutive advanced HCC patients, who underwent TACE-S-MWA (MWA group, n=77) or TACE-S (Non-MWA group, n=75), were investigated. Overall survival (OS), time to progression (TTP) and safety were compared between the two groups. Prognostic factors were analyzed using the Cox proportional hazard regression model. RESULTS: Baseline patient characteristics were balanced between the two groups. MWA group was associated with a higher OS (median, 19.0 vs 13.0 months; P<0.001) and a longer TTP (median, 6.0 vs 3.0 months; P<0.001) compared with non-MWA group. Multivariate analyses showed that portal vein tumor thrombosis (PVTT) (P=0.002), duration of sorafenib (P<0.001), and MWA treatment (P=0.011) were independently associated with OS. MWA treatment strategy (P<0.001) was a significant predictor of TTP. There were no treatment-related mortalities in either group. The rates of minor complications (42.9% vs 38.7%, P=0.599) and major complications (1.29% vs 1.33%, P=0.985) in the MWA group were similar to those in the non-MWA group. CONCLUSION: TACE-S-MWA was safe and effective for advanced primary HCC. TACE-S-MWA resulted in better OS and TTP than did TACE-S for treatment of patients with advanced primary HCC.

Transcatheter hepatic arterial infusion chemotherapy vs sorafenib in the treatment of patients with hepatocellular carcinoma of Barcelona Clinic Liver Cancer stage C: a meta-analysis of Asian population.

OBJECTIVE: To compare the clinical efficacy and safety of transcatheter hepatic arterial infusion chemotherapy (HAIC) with those of sorafenib in the treatment of patients with hepatocellular carcinoma (HCC) of Barcelona Clinic Liver Cancer (BCLC) stage C. METHODS: Potentially relevant studies comparing the clinical efficacy and safety of HAIC with those of sorafenib were searched using Medline, PubMed, Embase, Cochrane Library, and Chinese databases (Wanfang Data and China National Knowledge Infrastructure). Overall survival rate (OSR), tumor response rate, disease control rate (DCR), and serious adverse events (SAEs) were compared and analyzed. Pooled ORs with 95% CIs were calculated using either the fixed-effects model or the random-effects model. All statistical analyses were conducted using Review Manager (version 5.3) from the Cochrane Collaboration. RESULTS: A total of 1,264 patients were included in this meta-analysis. The results of this study showed that HAIC was associated with significantly higher 1-, 2-, and 3-year OSRs than sorafenib (OR 1.88, 95% CI1-year: [1.27-2.78], P1-year=0.002; OR 2.15, 95% CI2-year: [1.06-4.37], P2-year=0.03; OR 7.90, 95% CI3-year: [2.12-29.42], P3-year=0.002). Compared to sorafenib, HAIC was associated with superior complete response (CR), partial response (PR), and objective response rate (ORR) (OR 3.90, 95% CICR: [1.89-8.03], P CR =0.0002; OR 3.47, 95% CIPR: [2.31-5.24], P PR <0.00001; OR 3.02, 95% CIOR: [2.05-4.45], P OR <0.0001). There was no statistically significant difference between HAIC and sorafenib in stable disease (SD), progressive disease (PD), DCR, and SAEs (OR 0.86, 95% CISD: [0.51-1.45], P SD =0.56; OR 0.62, 95% CIPD: [0.35-1.11], P PD =0.11; OR 0.53, 95% CISAE: [0.14-1.92], P SAE =0.33). CONCLUSION: This study showed that HAIC was associated with better efficacy than sorafenib in terms of OSR and tumor response. Therefore, HAIC can be considered as an alternative treatment option for patients with HCCs of BCLC stage C.

Radiofrequency Ablation Combined with Transcatheter Arterial Chemoembolization Therapy Versus Surgical Resection for Hepatocellular Carcinoma within the Milan Criteria: A Meta-Analysis.

Objective: To meta-analytically compare combined transarterial chemoembolization (TACE) plus radiofrequency ablation (RFA) and surgical resection (SR) for the treatment of hepatocellular carcinoma (HCC) within the Milan criteria. Materials and Methods: PubMed, Medline, Embase, and Cochrane Library were searched for studies comparing these two therapies that were published between January 2006 and August 2017. Overall survival rate (OS), recurrence-free survival rate (RFS), major complications and the average length of hospital stay were compared between these two therapies. Meta-analytic pooled odds ratio (OR) was calculated using TACE plus RFA as the base category. Results: Seven case-control studies and one randomized trial were identified. Meta-analytic results revealed that, compared with SR, TACE plus RFA had significantly higher 1-year OS (OR for survival = 0.50, p = 0.009) and lower major complications (OR = 1.88, p = 0.02) after therapy. Three studies reported on the length of hospital stay. The average length ± standard deviation reported in individual studies for SR and TACE plus RFA groups was 19.8 ± 8.4 days and 7.4 ± 2.2 days, respectively; 18.7 ± 4.9 days and 11.5 ± 6.9 days, respectively; and 16.6 ± 6.7 days and 8.5 ± 4.1 days, respectively (p < 0.0001 for all studies). Three or 5-year OS and 1-, 3-, or 5-year RFS did not significantly differ between the two therapies. Conclusion: Combined TACE plus RFA may be an alternative to SR for the treatment of patients with HCC within Milan the criteria. Non-randomized design in most of the original studies was a limitation.

Prognostic Factors for Survival After Transarterial Chemoembolization Combined with Sorafenib in the Treatment of BCLC Stage B and C Hepatocellular Carcinomas.

RATIONALE AND OBJECTIVE: The objective of this study was to analyze prognostic factors for survival after transarterial chemoembolization (TACE) combined with sorafenib for hepatocellular carcinoma (HCC) of Barcelona Clinic Liver Cancer (BCLC) stages B and C. MATERIALS AND METHODS: Clinical data of 198 patients with BCLC stage B and C HCCs who underwent TACE combined with sorafenib between June 2012 and January 2017 were retrospectively collected and analyzed. Survival curves were detected using log-rank test. Univariate analysis was performed using log-rank test with respect to 11 prognostic factors potentially affecting survival. All statistically significant prognostic factors identified by univariate analysis were entered into a Cox proportion hazards regression model to identify independent predictors of survival. P values were two-sided and P < 0.05 was considered statistically significant. RESULTS: By the end of this study, the median follow-up duration was 43.6 months. The median overall survival (OS) of the patients was 21.0 months (95% confidence interval [CI]: 16.94-25.05), and the 1-, 2-, 3- and 5-year OS rates were 72%, 43%, 28%, and 4%, respectively. Tumor size (χ2 = 33.607, P < 0.0001), tumor number (χ2 = 4.084, P = 0.043), Child-Pugh class (χ2 = 33.187, P < 0.0001), BCLC stage (χ2 = 50.224, P < 0.0001), portal vein tumor thrombus (χ2 = 88.905, P < 0.0001), Eastern Cooperative Oncology Group (ECOG) performance status (χ2 = 98.007, P < 0.0001), extrahepatic spread (χ2 = 34.980, P < 0.0001), TACE times (χ2 = 8.350, P = 0.015), and sorafenib treatment strategy (χ2 = 81.593, P < 0.0001) were found to be significantly associated with OS by univariate analysis. Multivariate analysis showed that BCLC stage (95% CI: 1.133-3.982, P = 0.019), extrahepatic spread (95% CI: 1.136-2.774, P = 0.012), and sorafenib treatment duration (95% CI: 0.352-0.574, P = 0.000) were independent prognostic factors associated with OS. There were no serious treatment-related adverse events. CONCLUSIONS: This study showed that extrahepatic spread was a risk factor, and sorafenib treatment and superior BCLC stage were protective factors. Therefore, the study indicated that TACE combined with sorafenib was an effective and safe treatment for patients with BCLC stage B HCC without extrahepatic spread.

Drug-eluting bead transarterial chemoembolization in the treatment for unresectable soft tissue sarcoma refractory to systemic chemotherapy: a preliminary evaluation of efficacy and safety.

PURPOSE: To preliminarily evaluate the clinical efficacy and safety of drug-eluting bead transarterial chemoembolization (DEB-TACE) for unresectable soft tissue sarcoma refractory to systemic chemotherapy. METHODS: Ten patients with refractory sarcoma who underwent DEB-TACE therapy between January 2015 and January 2017 were identified. Clinical information and radiological data were retrospectively collected to analyze tumor response, overall survival (OS), progression-free survival and adverse events (AEs). Tumor response to DEB-TACE was assessed with modified Response Evaluation Criteria in Solid Tumors (mRECIST) guidelines applied to computed tomography or magnetic resonance imaging. RESULTS: All DEB-TACE procedures were successfully performed for ten patients with 15 tumor lesions. The median follow-up duration was 19 months and the median survival time was 21 months (range 11-30 months). The 1- and 2-year OS rate was 90 and 30%, respectively. According to the guidance of mRECIST, complete response, partial response, stable disease and progressive disease were noted in zero (0%), three (30%), four (40%) and three (30%) patients, respectively. The disease control rate and objective response rate was 70 and 30%, respectively. There were no serious AEs in patients after DEB-TACE. CONCLUSIONS: Our data showed that DEB-TACE was effective and safe for patients with soft tissue sarcoma. Therefore, DEB-TACE can be considered as an alternative treatment option for unresectable soft tissue sarcoma refractory to conventionally systemic chemotherapy.

Radiofrequency ablation combined with transcatheter arterial chemoembolization therapy versus surgical resection for Barcelona-Clinic Liver Cancer (BCLC) A hepatocellular carcinoma: a meta-analysis.

Purpose: The objective of our study was to compare the effectiveness of the combination of transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA) with that of surgical resection (SR) in Barcelona-Clinic Liver Cancer (BCLC) A hepatocellular carcinoma. Materials and Methods: PubMed, Medline, Embase, and Cochrane Library were searched for comparisons of the two therapies from January 2006 to December 2017. Overall survival rate (OS), recurrence-free survival rate (RFS), complications, and the average length of hospital stay were compared and analyzed. Review Manager v. 5.2 from the Cochrane Collaboration was used for statistical analyses. Results: Seven case-control studies and one randomized controlled trial were identified, of which 717 were treated with a combination of TACE and RFA and 785 were treated with SR. Meta-analysis data revealed that TACE plus RFA had significantly better effectiveness on 1.0-y OS (OR = 0.50, p = .009). The major complications (ORcomplications = 1.88, p = .02) after the combined therapy were significantly lower than those after SR. There were three studies that reported the average length of hospital stay. The hospital stay for the SR group vs the combined therapy group was 19.8 ± 8.4 d vs 7.4 ± 2.2 d, respectively (p < .0001); 18.7 ± 4.9 d vs 11.5 ± 6.9 d, respectively (p < .0001); and 16.6 ± 6.7 d vs 8.5 ± 4.1 d, respectively (p < .0001). There was no significant difference in 3.0- or 5.0-y OS and 1.0-, 3.0-, or 5.0-y RFS. Conclusion: The combination of TACE and RFA has advantages in improving 1.0-y OS, reducing complications, and shortening the length of hospital stay over that of SR in the treatment of patients with BCLC A HCC.

The effect of lipiodol deposition in HCC after TACE on the necrosis range of PMCT.

OBJECTIVE: To study the impact of lipiodol deposition in the lesion of hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE) on the necrosis area of percutaneous microwave coagulation therapy (PMCT). MATERIALS AND METHODS: A total of 44 patients with HCC with 56 nodules, with a size ranging from 1.5 to 3.5 cm, was selected in our study. About 23 patients (26 nodules) underwent PMCT treatment only as Group A and 21 patients (30 nodules) were treated by PMCT-combined TACE as Group B. All patients underwent PMCT with single-electrode and one-point ablation. Paired t-test was used to analyze pre- and postoperatively the volume of tumor and the necrosis volume after PMCT. Independent t-test was used to compare the difference in the necrosis area between two groups (α=0.05). RESULTS: All patients underwent PMCT or PMCT combined with TACE successfully. The tumor and necrosis size of Group A was 16.29±19.23 cm3 and 17.98±18.49 cm3 (P=0.650), and 11.95±12.78 cm3 and 16.60±11.70 cm3 of Group B (P=0.017). There was no significant difference on necrosis volume between the two groups (P=0.581). The necrosis area of Group B was larger than the size of the tumor (P=0.017), but the ablation area of the two groups was smaller than the theoretic area (P=0.001). (The theoretic area means that the necrosis area of ablation should be 1.0 cm larger than the tumor in diameter.). CONCLUSION: PMCT combined with TACE could enlarge the ablation area, but will not lead to an ideal necrosis area than the PMCT alone. The lipiodol deposition in the tumor lesion may hinder the expansion of the heating field. Therefore, further research was needed.

Transarterial embolization combined with RNA interference targeting hypoxia-inducible factor-1α for hepatocellular carcinoma: a preliminary study of rat model.

PURPOSE: To study whether transarterial embolization (TAE) with RNA interference (RNAi) targeting hypoxia-inducible factor-1α (HIF-1α) can improve efficacy of TAE in treating hepatocellular carcinoma (HCC). MATERIALS AND METHODS: CBRH-7919 rat hepatoma cell line was used and HCC models of rats were constructed. The siRNA transfection compound was made by mixing specific siRNA and Lipofectamine 2000™. Delivery and transfection of siRNA were administered by injecting iodized oil emulsion (diluted lipiodol and siRNA) via hepatic artery. The expression levels of mRNA and protein were detected using the real-time reverse transcription polymerase chain reaction (RT-PCR), immunohistochemistry and western blotting assays, respectively. RESULTS: In vitro experiment, the specific HIF-1α-siRNA was proved to inhibit expression levels of HIF-1α and vascular endothelial growth factor (VEGF) effectively. In animal study, real-time RT-PCR assay showed the average relative mRNA expressions of HIF-1α were 0.31 ± 0.01, 0.65 ± 0.03, 0.46 ± 0.005, and 1.00 ± 0.00 in TAE + siRNA, siRNA, TAE, and control groups, respectively. Western blotting assay showed the average relative protein expressions of HIF-1α were 0.13 ± 0.02, 0.87 ± 0.02, 0.39 ± 0.02, and 1.02 ± 0.01 in TAE + siRNA, siRNA, TAE, and control groups, respectively. Compared with control, TAE, and siRNA groups, TAE + siRNA can significantly inhibit protein expressions of HIF-1α and VEGF (P HIF-1α < 0.001; P VEGF < 0.001). Overall survival of rats underwent TAE + siRNA was significantly longer than that of rats treated with TAE monotherapy (P = 0.001). CONCLUSION: This animal study showed TAE combined with HIF-1α-RNAi could significantly improve efficacy of TAE in treating HCC by inhibiting expressions of HIF-1α and VEGF after TAE treatment.

Treatment of the recanalization of maxillary and mandibular arteriovenous malformations in children.

OBJECTIVE: This study reviewed our experience in treating the recanalization of maxillary and mandibular arteriovenous malformations in children. STUDY DESIGN: Four patients with maxillary or mandibular arteriovenous malformations (AVMs) were included in this study. All the patients had undergone multidisciplinary treatment of AVM at least 26 months before our review, including superselective intra-arterial embolization combined with bone wax packing. Computed tomographic angiography and digital subtraction angiography were performed to confirm the presence of recanalization. Superselective intra-arterial embolization combined with bone wax packing and tooth extractions were performed in the patients with recanalization. RESULTS: After confirmation of the recanalization of AVM by digital subtraction angiography, the patients were treated with superselective intra-arterial embolization combined with bone wax packing and tooth extractions (if necessary). All the patients were followed up for 5 to 14 months, with an average of 9.5 months. The outcome for all patients was good, and no patient complained of pulsatile sensation or hemorrhage after treatment. CONCLUSIONS: In the treatment for recanalization of maxillary and mandibular AVMs, reapplication of the superselective intra-arterial embolization, combined with bone wax packing, remains necessary.

Regional thermochemotherapy versus hepatic arterial infusion chemotherapy for palliative treatment of advanced hilar cholangiocarcinoma: a retrospective controlled study.

OBJECTIVES: To retrospectively assess the efficacy of regional thermochemotherapy (TCT) compared with hepatic arterial infusion chemotherapy (HAIC)-alone for palliative treatment of advanced hilar cholangiocarcinoma (HC) and to determine the prognostic factors associated with survival. METHODS: Forty-three consecutive patients with advanced HC underwent regional TCT (TCT group) and HAIC (HAIC group). We analyzed baseline characteristics, overall survival (OS), progression-free survival (PFS), stent patency time (SPT), adverse events (AEs), and prognostic factors for OS between the two groups. RESULTS: OS of patients treated with regional TCT was significantly longer compared to that of patients treated with HAIC (median OS: 20.3 vs. 13.2 months, P = 0.004), and SPT and PFS were significantly increased in the TCT group compared with the HAIC group (median SPT: 26.5 vs. 10.5 months, P < 0.001; median PFS: 16.5 vs. 10.2 months, P = 0.001). TCT and metal stent insertion were two independent prognostic factors associated with survival. The treatment-related AEs were tolerable and similar in the two groups, except for hilar pain (34.6 %) and skin rashes (24.6 %) in the TCT group. CONCLUSIONS: Our results show that regional TCT is safe and more effective than HAIC-alone and may be a promising option for palliative treatment of advanced HC. Metal stenting before TCT appears to improve patients' OS. KEY POINTS: • Regional TCT is a novel combination for palliative treatment of advanced HC • Our data showed significantly promising outcomes in the TCT group • HC patients with metal stenting appeared to derive greater benefit from TCT.

Prognostic factors for survival after transarterial chemoembolization combined with microwave ablation for hepatocellular carcinoma.

AIM: To analyze prognostic factors for survival after transarterial chemoembolization (TACE) combined with microwave ablation (MWA) for hepatocellular carcinoma (HCC). METHODS: Clinical data of 86 patients who underwent TACE combined with MWA between January 2006 and December 2013 were retrospectively analyzed in this study. Survival curves were detected using log-rank test. Univariate analysis was performed using log-rank test with respect to 13 prognostic factors affecting survival. All statistically significant prognostic factors identified by univariate analysis were entered into a Cox proportion hazards regression model to identify independent predictors of survival. P values were two-sided and P < 0.05 was considered statistically significant. RESULTS: Median follow-up time was 47.6 mo, and median survival time of enrolled patients was 21.5 mo. The 1-, 2-, 3- and 5-year overall survival rates were 72.1%, 44.1%, 31.4% and 13.9%, respectively. Tumor size(χ(2) = 14.999, P = 0.000), Barcelona Clinic Liver Cancer (BCLC) stage (χ(2) = 29.765, P = 0.000), Child-Pugh class (χ(2) = 51.820, P = 0.000), portal vein tumor thrombus (PVTT) (χ(2) = 43.086, P = 0.000), arterio-venous fistula (χ(2) = 29.791, P = 0.000), MWA therapy times (χ(2) = 12.920, P = 0.002), Eastern Cooperative Oncology Group (ECOG) score (χ(2) = 28.660, P = 0.000) and targeted drug usage (χ(2) = 10.901, P = 0.001) were found to be significantly associated with overall survival by univariate analysis. Multivariate analysis identified that tumor size (95%CI: 1.608-4.962, P = 0.000), BCLC stage (95%CI: 1.016-2.208, P = 0.020), PVTT (95%CI: 2.062-9.068, P = 0.000), MWA therapy times (95%CI: 0.402-0.745, P = 0.000), ECOG score (95%CI: 1.012-3.053, P = 0.045) and targeted drug usage (95%CI: 1.335-3.143, P = 0.001) were independent prognostic factors associated with overall survival. CONCLUSION: Superior performance status, MWA treatment and targeted drug were favorable factors, and large HCC, PVTT and advanced BCLC stage were risk factors for survival after TACE-MWA for HCC.

Interventional digital subtraction angiography for small bowel gastrointestinal stromal tumors with bleeding.

AIM: To retrospectively evaluate the diagnostic efficacy of interventional digital subtraction angiography (DSA) for bleeding small bowel gastrointestinal stromal tumors (GISTs). METHODS: Between January 2006 and December 2013, small bowel tumors in 25 consecutive patients undergoing emergency interventional DSA were histopathologically confirmed as GIST after surgical resection. The medical records of these patients and the effects of interventional DSA and the presentation and management of the condition were retrospectively reviewed. RESULTS: Of the 25 patients with an age range from 34- to 70-year-old (mean: 54 ± 12 years), 8 were male and 17 were female. Obscure gastrointestinal bleeding, including tarry or bloody stool and intermittent melena, was observed in all cases, and one case also involved hematemesis. Nineteen patients required acute blood transfusion. There were a total of 28 small bowel tumors detected by DSA. Among these, 20 were located in the jejunum and 8 were located in the ileum. The DSA characteristics of the GISTs included a hypervascular mass of well-defined, homogeneous enhancement and early developed draining veins. One case involved a complication of intussusception of the small intestine that was discovered during surgery. No pseudoaneurysms, arteriovenous malformations or fistulae, or arterial rupture were observed. The completely excised size was approximately 1.20 to 5.50 cm (mean: 3.05 ± 1.25 cm) in maximum diameter based on measurements after the resection. There were ulcerations (n = 8), erosions (n = 10), hyperemia and edema (n = 10) on the intra-luminal side of the tumors. Eight tumors in patients with a large amount of blood loss were treated with transcatheter arterial embolization with gelfoam particles during interventional DSA. CONCLUSION: Emergency interventional DSA is a useful imaging option for locating and diagnosing small bowel GISTs in patients with bleeding, and is an effective treatment modality.

Conventional transarterial chemoembolization vs microsphere embolization in hepatocellular carcinoma: a meta-analysis.

AIM: To compare conventional transarterial chemoembolization (c-TACE) with microsphere embolization in hepatocellular carcinoma (HCC). METHODS: We searched PubMed, Medline, Embase and the Cochrane Library for trials assessing the efficacy and safety of c-TACE in comparison with those of yttrium-90 microsphere or drug-eluting bead embolization from January 2004 to December 2013. Overall survival rate (OSR), tumor response [complete response, partial response (PR), stable disease (SD), progressive disease (PD)], α-fetoprotein (AFP) response, progression rate and complications were compared and analyzed. Pooled ORs with 95%CI were calculated using either the fixed-effects model or random-effects model. All statistical analyses were conducted using the Review Manager (version 5.1.) from the Cochrane collaboration. RESULTS: Thirteen trials were identified, including a total of 1834 patients; 1233 were treated with c-TACE, 377 underwent yttrium-90 microsphere embolization and 224 underwent drug-eluting bead embolization. The meta-analysis with either the random-effects model or fixed-effects model indicated that microsphere embolization was associated with significantly higher OSRs compared with those of c-TACE (OR(1-year) = 1.38, 95%CI(1-year): 1.05-1.82; OR(2-year) = 2.88, 95%CI(2-year): 1.18-7.05; OR(3-year) = 2.15, 95%CI(3-year): 1.18-3.91). The complete tumor response rates of patients who underwent microspheres embolization were significantly higher than those of patients treated with c-TACE (OR = 2.19, 95%CI: 1.31-3.64). The tumor progression rate after microsphere embolization was markedly lower than that after c-TACE (OR = 0.56, 95%CI: 0.39-0.81). There was no significant difference between microsphere embolization and c-TACE in PR (OR = 0.73, 95%CI: 0.47-1.15), SD (OR = 1.07, 95%CI: 0.79-1.44), PD (OR = 0.75, 95%CI: 0.33-1.68), AFP response (OR = 1.38, 95%CI: 0.64-2.94) and complications (OR = 0.68, 95%CI: 0.46-1.00). CONCLUSION: Our analysis indicated that microsphere embolization was associated with superior survival and treatment response in comparison with c-TACE in the treatment of patients with HCC.

Hepatic arterial infusion chemotherapy combined with endogenetic hyperthermia treatment of hilar cholangiocarcinoma.

BACKGROUND/AIMS: To evaluate the curative effect and clinical application of hepatic arterial infusion (HAI) chemotherapy combined with endogenetic field tumor hyperthermia (EFTH) in patients with hilar cholangiocarcinoma. METHODOLOGY: Nine patients with unresectable hilar cholangiocarcinoma were enrolled. They were first treated with HAI using gemcitabine, and then carboplatin was continuously infused intra-arterially whereas EFTH was applied to the hilar region for 60 min. After hyperthermia, 5-fluorouracil was administered intra-arterially for three days. The same dose of gemcitabine was administered intravenously on Day 8. The side effects, tumor markers, tumor response and overall survival (OS) were observed and assessed. RESULTS: Nine patients underwent 27 cycles of the combination therapy. Of the nine patients, five patients achieved complete remission and they are still alive, and four died. Of the four patients who died, two achieved partial remission, one had stable disease, and one had progressive disease. The tumor markers decreased at varied degrees among the seven patients. The overall response rate was 77.78% (7/9), and the disease control rate was 88.89% (8/9). The treatment had no severe side effects and complications, including grade 3/4 hematological toxicities. CONCLUSIONS: HAI chemotherapy combined with EFTH is safe, minimally invasive, and well tolerated.

Percutaneous ablation therapy versus surgical resection in the treatment for early-stage hepatocellular carcinoma: a meta-analysis of 21,494 patients.

PURPOSE: To compare comprehensively the benefits of radiofrequency ablation (RFA) and percutaneous ethanol injection (PEI) with those of surgical resection (SR) in early-stage hepatocellular carcinoma (HCC). METHODS: The potentially relevant studies comparing the efficacy and safety of RFA and/or PEI with those of SR were searched using the databases such as PubMed, MEDLINE, Embase and Chinese databases (CNKI and Wanfang data). Overall survival rate, recurrence-free survival rate and complications were compared and analyzed. Pooled odds ratios with 95 % confidence intervals (95 % CIs) were calculated using either the fixed-effects model or random-effects model. All statistic analyses were conducted using the Review Manager (version 5.1.) from the Cochrane Collaboration. RESULTS: Our analysis showed that the overall survival rate in patients treated with SR was significantly higher than that of percutaneous ablation therapy (PAT) [SR vs. PAT: 95 % confidence interval (95 % CI)2-year 0.46-0.89, P = 0.009; 95 % CI3-year 0.57-0.83, P < 0.0001; 95 % CI5-year 0.45-0.46, P < 0.0001]. SR was associated with significantly higher recurrence-free survival rate compared with PAT (SR vs. PAT: 95 % CI1-year 0.51-0.90, P = 0.008; 95 % CI2-year 0.41-0.78, P = 0.0004; 95 % CI3-year 0.38-0.77, P = 0.0006; 95 % CI5-year 0.33-0.61, P < 0.0001). SR resulted in longer survival than PAT in HCCs no larger than 3 cm. PAT was associated with less complications compared with SR (PAT vs. SR: 95 % CI 0.14-0.76, P = 0.01). CONCLUSIONS: Although SR was associated with more complications, SR was superior to RFA and PEI for treatment of patients with early-stage HCC.