Ming Kuang

Ethanol ablation of hepatocellular carcinoma up to 5.0 cm by using a multipronged injection needle with high-dose strategy

PURPOSE To investigate whether ethanol ablation by using a multipronged needle delivery system (multipronged ethanol ablation) could eradicate hepatocellular carcinoma (HCC) up to 5.0 cm in diameter with a single-session high-dose strategy. MATERIALS AND METHODS The hospital ethics committee approved the prospective study, and each patient provided written informed consent. One hundred forty-one patients (125 men, 16 women; mean age, 53 years; range, 27-76 years) with 164 primary or recurrent HCC ranging from 1.3 to 5.0 cm in diameter (mean, 2.9 cm +/- 0.9) were treated with high-dose multipronged ethanol ablation. Patients were unsuitable for surgery, declined surgery and radiofrequency ablation, or had tumors located at unfavorable sites. Primary technique effectiveness (PTE) (complete ablation within two sessions), local tumor progression (LTP), and complications after the treatment were observed. Twenty risk factors of local effectiveness and complications were analyzed by means of univariate and multivariate analysis. RESULTS Mean number of treatment sessions was 1.1. The mean volume of ethanol per tumor was 31 mL (range, 8-68 mL). PTE was achieved in 134 (95%) of 141 patients and was significantly associated with tumor pattern (capsulated vs noncapsulated, P = .018). After a mean follow-up period of 25 months, LTP was observed in 16 (12%) of 134 patients, and in nine (56%) patients, LTP occurred in tumors 3.1-5.0 cm in diameter. Alanine aminotransferase level (P = .023) was the independent risk factor for LTP. Three (2%) of 141 patients had major complications. CONCLUSION Multipronged ethanol ablation with a high-dose strategy can be used to treat HCC up to 5.0 cm in diameter effectively and safely, often in a single session.

Treatment response evaluation with three-dimensional contrast-enhanced ultrasound for liver cancer after local therapies

OBJECTIVE To investigate the potential usefulness of three-dimensional contrast-enhanced ultrasound (3D-CEUS) in evaluating the treatment response for liver cancer after local therapies. METHODS A total of 107 lesions in 95 consecutive patients with liver cancer underwent local therapies and thereafter received low acoustic power 3D-CEUS examination. The LOGIQ 9 ultrasound scanner and a volume transducer were used and the ultrasound contrast agent was SonoVue. The image quality of 3D-CEUS images was evaluated and the influence of 3D-CEUS to clinical outcome was investigated. RESULTS The image quality of 3D-CEUS was defined as high in 102 (102/107, 95.3%) lesions and common in 5 (5/107, 4.7%) lesions. 3D-CEUS did not change the diagnosis in any patient compared with 2D-CEUS. However, 3D-CEUS changed the management in 3 (2.8%) of 107 lesions, increased confidence but made no change in diagnosis in 85 (79.5%) lesions, added some information but did not change management or diagnosis in 15 (14.0%), and made no change in 4 (3.7%), respectively, in comparison with 2D-CEUS. CONCLUSION 3D-CEUS enhances the diagnostic confidence in the majority of the patients and even changes the management in some patients. 3D-CEUS has potential usefulness in evaluating treatment response for liver cancer after local therapies.

Apatinib inhibits VEGF signaling and promotes apoptosis in intrahepatic cholangiocarcinoma

Tumor cells co-express vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFRs) that interact each other to support a self-sustainable cell growth. So far, this autocrine VEGF loop is not reported in human intrahepatic cholangiocarcinoma (ICC). Apatinib is a highly selective VEGFR2 inhibitor, but its effects on ICC have not been investigated. In this study, we reported that VEGF and phosphorylated VEGFR2 were expressed at a significantly high level in ICC patient tissues (P<0.05). In vitro, treating ICC cell lines RBE and SSP25 with recombinant human VEGF (rhVEGF) induced phosphorylation of VEGFR1 (pVEGFR1) and VEGFR2 (pVEGFR2); however, only the VEGFR2 played a role in the anti-apoptotic cell growth through activating a PI3K-AKT-mTOR anti-apoptotic signaling pathway which generated more VEGF to enter this autocrine loop. Apatinib inhibited the anti-apoptosis induced by VEGF signaling, and promoted cell death in vitro. In addition, Apatinib treatment delayed xenograft tumor growth in vivo. In conclusion, the autocrine VEGF/VEGFR2 signaling promotes ICC cell survival. Apatinib inhibits anti-apoptotic cell growth through suppressing the autocrine VEGF signaling, supporting a potential role for using Apatinib in the treatment of ICC.

Intracellular autocrine VEGF signaling promotes EBDC cell proliferation, which can be inhibited by Apatinib

Tumor cells produce vascular endothelial growth factor (VEGF) which can interact with membrane or cytoplasmic VEGF receptors (VEGFRs) to promote cell growth. We aimed to investigate the role of extracellular/intracellular autocrine VEGF signaling and Apatinib, a highly selective VEGFR2 inhibitor, in extrahepatic bile duct cancer (EBDC). We found conditioned medium or recombinant human VEGF treatment promoted EBDC cell proliferation through a phospholipase C-γ1-dependent pathway. This pro-proliferative effect was diminished by VEGF, VEGFR1 or VEGFR2 neutralizing antibodies, but more significantly suppressed by intracellular VEGFR inhibitor. The rhVEGF induced intracellular VEGF signaling by promoting nuclear accumulation of pVEGFR1/2 and enhancing VEGF promoter activity, mRNA and protein expression. Internal VEGFR2 inhibitor Apatinib significantly inhibited intracellular VEGF signaling, suppressed cell proliferation in vitro and delayed xenograft tumor growth in vivo, while anti-VEGF antibody Bevacizumab showed no effect. Clinically, overexpression of pVEGFR1 and pVEGFR2 was significantly correlated with poorer overall survival (P = .007 and P = .020, respectively). In conclusion, the intracellular autocrine VEGF loop plays a predominant role in VEGF-induced cell proliferation. Apatinib is an effective intracellular VEGF pathway blocker that presents a great therapeutic potential in EBDC.

Preinjected Fluids do not Benefit Microwave Ablation as Those in Radiofrequency Ablation

RATIONALE AND OBJECTIVES To detect whether the efficacy of microwave ablation (MWA) could be improved by preinjected fluids in an ex vivo porcine liver model. MATERIALS AND METHODS Ablations were performed for 12 minutes using energy output of impedance-based (power output gradually rose to 200W, maintained until increases in tissue impedance of 20 Ω, reduced to 10W, and switched on again 15 seconds later) in radiofrequency ablation (RFA) or 80 W in MWA. Before ablation, 5 mL of ethanol, distilled water, 0.9% NaCl solution, or 10% NaCl solution (n = 6 each) was injected into the targeted liver tissue. Ablations without fluid injection served as control. The ablation diameter, volume, shape index, and temperature were recorded and compared. RESULTS Preinjection of 0.9% or 10% NaCl solution resulted in larger coagulation volumes than that of the control group in RFA experiments (28.1 ± 2.9 cm(3), 45.3 ± 6.3 cm(3), 20.0 ± 2.5 cm(3), respectively; P < .05). Ethanol and distilled water had no impact on coagulation volumes in RFA. Preinjection of ethanol or 10% NaCl solution created smaller coagulation volumes than that of the control group in MWA experiments (34.3 ± 2.0 cm(3), 33.9 ± 4.1 cm(3), 58.0 ± 6.6 cm(3), respectively; P < .001). 0.9% NaCl solution and distilled water had no impact on coagulation volumes in MWA. CONCLUSION In an ex vivo porcine liver, preinjected fluids do not benefit microwave ablation as those in radiofrequency ablation.

Role of Portal Vein Tumor Thrombosis in Quantitative Perfusion Analysis of Contrast-Enhanced Ultrasound of Hepatocellular Carcinoma

The goal of our study was to evaluate the differences between quantitative parameters of hepatocellular carcinoma (HCC) with or without portal vein tumor thrombosis (PVTT) on contrast-enhanced ultrasound (CEUS). Twenty-four patients with HCC with PVTT and 48 without PVTT underwent CEUS using sulfur hexafluoride microbubbles. Dynamic images were analyzed with quantification software. Time-intensity curves were obtained for HCC and surrounding liver parenchyma, and parameters including the intensity maximum (IMAX), rising time (RT), mean transit time and time to peak (TTP) were compared within and between the PVTT and control groups, respectively. RT and TTP of HCC were significantly faster than those of surrounding liver parenchyma in both the PVTT and control groups. IMAX of HCC was significantly stronger than that of surrounding liver in the control group, but not significantly different from that of liver parenchyma in the PVTT group. RT and TTP of HCC and surrounding liver were significantly faster in the PVTT group compared with the control group, whereas IMAX values of HCC in the PVTT group were lower than those in the control group. HCC with PVTT presents different hemodynamic parameters, with faster RT and TTP and lower IMAX than those for HCC without PVTT. Quantitative perfusion analysis of CEUS may be a potential method for predicting PVTT.

Percutaneous radiofrequency ablation of malignant liver tumors with ultrasound and CT fusion imaging guidance

To evaluate the feasibility, accuracy, and utility of sonography (US) and CT fusion imaging guidance for radiofrequency ablation (RFA) of malignant liver tumors not visualized on conventional US.

LINC01410-miR-532-NCF2-NF-kB feedback loop promotes gastric cancer angiogenesis and metastasis

Dysregulation of non-coding RNAs, including miRNAs and lncRNAs has been reported to play vital roles in gastric cancer (GC) carcinogenesis, but the mechanism involved is largely unknown. Using the cancer genome atlas (TCGA) data set and bioinformatics analyses, we identified miR-532-5p as a potential tumor suppressor in GC, and found that lncRNA LINC01410 might be a negative regulator of miR-532-5p. We then conducted a series of in vivo and in vitro assays to explore the effect of LINC01410 on miR-532-5p-mediated GC malignancy and the underlying mechanism involved. MiR-532-5p overexpression inhibited GC metastasis and angiogenesis in vitro and in vivo, whereas miR-532-5p silencing had the opposite effect. Further study showed that miR-532-5p attenuated NF-κB signaling by directly inhibiting NCF2 expression, while miR-532-5p silencing in GC enhanced NF-κB activity. Furthermore, we demonstrated miR-532-5p down-regulation was caused by aberrantly high expression of LINC01410 in GC. Mechanistically, overexpression of LINC01410 promoted GC angiogenesis and metastasis by binding to and suppressing miR-532-5p, which resulted in up-regulation of NCF2 and sustained NF-κB pathway activation. Interestingly, NCF2 could in turn increase the promoter activity and expression of LINC01410 via NF-κB, thus forming a positive feedback loop that drives the malignant behavior of GC. Finally, high expression of LINC01410, along with low expression of miR-532-5p, was associated with poor survival outcome in GC patients. Our studies uncover a mechanism for constitutive LINC1410-miR-532-5p-NCF2-NF-κB feedback loop activation in GC, and consequently, as a potential therapeutic target in GC treatment.

Contrast-Enhanced Sonographically Guided Thermal Ablation for Treatment of Solid-Organ Hemorrhage Preliminary Clinical Results

The purpose of this series was to preliminarily evaluate the use of contrast‐enhanced sonographically guided percutaneous thermal ablation in the evaluation and treatment of solid‐organ bleeding by retrospectively analyzing 6 cases observed in clinical practice. Six patients who underwent contrast‐enhanced sonographically guided thermal ablation for treatment of solid‐organ bleeding (5 in liver and 1 in spleen) from December 2005 to August 2012 were included in this series. Clinical information, contrast‐enhanced sonograms before and after ablation, and the ablation method were retrospectively collected and analyzed. In 5 of the 6 patients, the location of the bleeding lesion was clearly seen. Hemostasis was successfully achieved in 4 of these 5 patients: 1 by radiofrequency ablation and 3 by microwave ablation. Ablation failed to achieve hemostasis in 1 patient who had postbiopsy splenic arterial bleeding because the bleeding vessel was a thick branch of the splenic artery. In the sixth remaining patient, who had bleeding after liver biopsy, hemostasis failed because contrast‐enhanced sonography did not precisely locate the bleeding lesion; hence, the ablation zone did not cover the whole lesion. Contrast‐enhanced sonographically guided ablation can be an alternative choice for treating solid‐organ bleeding because of its effectiveness and minimal invasiveness. However, it should be carefully investigated for those in whom the bleeding lesion cannot be located by contrast‐enhanced sonography and in those who have bleeding in a large vessel.

Combined radiofrequency ablation and ethanol injection versus repeat hepatectomy for elderly patients with recurrent hepatocellular carcinoma after initial hepatic surgery

Abstract Purpose: To retrospectively compare the efficacy and safety of combined radiofrequency ablation and percutaneous ethanol injection (RFA–PEI) with repeat hepatectomy for elderly patients with initial recurrent hepatocellular carcinoma (HCC) after hepatic surgery. Methods: From January 2009 to June 2015, 105 elderly patients (≥70 years) who underwent RFA–PEI (n = 57) or repeated hepatectomy (n = 48) for recurrent HCC ≤ 5.0 cm were included in the study. The overall survival (OS) and recurrence-free survival (RFS) were analysed with the Kaplan–Meier method and compared by the log-rank test. Non-tumour-related death, complications and hospital stays were assessed. Univariate and multivariate analyses were performed to identify the prognostic significance of the variables in predicting the OS and RFS. Results: OS rates were 78.2%, 40.8% and 36.7% at 1, 3 and 5 years after RFA–PEI and 76.3%, 52.5% and 42.6% after repeat hepatectomy, respectively (p = 0.413). Correspondingly, the 1-, 3- and 5-year RFS rates after RFA–PEI and repeat hepatectomy were 69.5%, 37.8%, 33.1% and 73.1%, 49.7%, 40.7%, respectively (p = 0.465). Non-tumour-related deaths in the RFA–PEI group (2/57) were significantly fewer than those in the repeat hepatectomy group (10/48) (p = 0.016). RFA–PEI was superior to repeat hepatectomy regarding the major complication rates and length of in-hospital stay (both p < 0.001). Multivariate analysis showed that the tumour number was the significant prognostic factor for the OS (hazard ratio (HR) = 1.961, 95% CI = 1.043–3.686, p = 0.037) and RFS (HR = 1.866, 95% CI = 1.064–3.274, p = 0.030). Conclusion: RFA–PEI provides comparable OS and RFS to repeat hepatectomy for elderly patients with small recurrent HCC after hepatectomy but with fewer non-tumour-related deaths, major complications and shorter hospital stays.