Role of contrast-enhanced ultrasound in follow-up assessment after ablation for hepatocellular carcinoma

AIM:To assess the usefulness of contrast-enhanced ultrasound (CEUS) during follow-up after percutaneous ablation therapy for hepatocellular carcinoma (HCC).METHODS:A total of 141 patients with HCCs who received percutaneous ablation therapy were assessed by paired follow-up CEUS and contrast-enhanced computed tomography (CECT).The follow-up scheme was designed prospectively and the intervals between CEUS and CECT examinations were less than 14 d.Both im-ages of follow-up CEUS and CECT were reviewed by radiologists.The ablated lesions were evaluated and classified as local tumor progression (LTP) and LTPfree.LTP was defined as regrowth of tumor inside or adjacent to the successfully treated nodule.The detected new intrahepatic recurrences were also evaluated and defined as presence of intrahepatic new foci.On CEUS and CECT,LTP and new intrahepatic recurrence both were displayed as typical enhancement pattern of HCC (i.e.,hyper-enhancing during the arterial phase and washout in the late phase).With CECT as the reference standard,the ability of CEUS in detecting LTP or new intrahepatic recurrence during follow-up was evaluated.RESULTS:During a follow-up period of 1-31 mo (median,4 mo),169 paired CEUS and CECT examinations were carried out for the 141 patients.For a total of 221 ablated lesions,266 comparisons between CEUS and CECT findings were performed.Thirty-three LTPs were detected on CEUS whereas 40 LTPs were detected on CECT,there was significant difference (P < 0.001).In comparison with CECT,the numbers of false positive and false negative LTPs detected on CEUS were 6 and 13,respectively;the sensitivity,specificity,positive predictive value (PPV),negative predictive value (NPV) and overall accuracy of CEUS in detecting LTPs were 67.5%,97.4%,81.8%,94.4% and 92.3%,respectively.Meanwhile,131 new intrahepatic recurrent foci were detected on CEUS whereas 183 were detected on CECT,there was also significant difference (P < 0.05).In comparison with CECT,the numbers of false positive and false negative intrahepatic recurrences detected on CEUS were 13 and 65,respectively;the sensitivity,specificity,PPV,NPV and overall accuracy of CEUS in detecting new intrahepatic recurrent foci were 77.7%,92.0%,92.4%,76.7% and 84.0%,respectively.CONCLUSION:The sensitivity of CEUS in detecting LTP and new intrahepatic recurrence after percutaneous ablation therapy is relatively low in comparisonwith CECT.

Differentiation of intrahepatic cholangiocarcinoma from hepatocellular carcinoma in high-risk patients: a predictive model using contrast-enhanced ultrasound

AIM To develop a contrast-enhanced ultrasound(CEUS)predictive model for distinguishing intrahepatic cholangiocarcinoma(ICC) from hepatocellular carcinoma(HCC) in high-risk patients.METHODS This retrospective study consisted of 88 consecutive high-risk patients with ICC and 88 high-risk patients with HCC selected by propensity score matching between May 2004 and July 2016. Patients were assigned to two groups, namely, a training set and validation set, at a 1:1 ratio. A CEUS score for diagnosing ICC was generated based on significant CEUS features. Then, a nomogram based on the CEUS score was developed, integrating the clinical data. The performance of the nomogram was then validated and compared with that of the LR-M of the CEUS Liver Imaging Reporting and Data System(LI-RADS).RESULTS The most useful CEUS features for ICC were as follows: rim enhancement(64.5%), early washout(91.9%), intratumoral vein(58.1%), obscure boundary of intratumoral non-enhanced area(64.5%), and marked washout(61.3%, all P < 0.05). In the validation set, the area under the curve(AUC) of the CEUS score(AUC = 0.953) for differentiation between ICC and HCC was improved compared to the LI-RADS(AUC = 0.742)(P < 0.001). When clinical data were added, the CEUS score nomogram was superior to the LI-RADS nomogram(AUC: 0.973 vs 0.916, P = 0.036, Net Reclassification Improvement: 0.077, Integrated Discrimination Index: 0.152). Subgroup analysis demonstrated that the CEUS score model was notably improved compared to the LIRADS in tumors smaller than 5.0 cm(P < 0.05) but not improved in tumors smaller than 3.0 cm(P > 0.05).CONCLUSION The CEUS predictive model for differentiation between ICC and HCC in high-risk patients had improved discrimination and clinical usefulness compared to the CEUS LIRADS.

Practice guidelines for ultrasound-guided percutaneous microwave ablation for hepatic malignancy

Primary liver cancer and liver metastases are among the most frequent malignancies worldwide,with an increasing number of new cases and deaths every year.Traditional surgery is only suitable for a limited proportion of patients and imaging-guided percutaneous thermal ablation has achieved optimistic results for management of hepatic malignancy.This synopsis outlines the first clinical practice guidelines for ultrasoundguided percutaneous microwave ablation therapy for hepatic malignancy,which was created by a joint task force of the Society of Chinese Interventional Ultrasound.The guidelines aim at standardizing the microwave ablation procedure and therapeutic efficacy assessment,as well as proposing the criteria for the treatment candidates.

Microbubble-enhanced ultrasound exposure improves gene transfer in vascular endothelial cells

AIM: To explore the effects of ultrasound exposure combined with microbubble contrast agent (SonoVue) on the permeability of the cellular membrane and on the expression of plasmid DNA encoding enhanced green fluorescent protein (pEGFP) transfer into human umbilical vein endothelial cells (HUVECs). METHODS: HUVECs with fluorescein isothiocyanate- dextran (FD500) and HUVECs with pEGFP were exposed to continuous wave (1.9 MHz, 80.0 mW/cm2) for 5 min, with or without a SonoVue. The percentage of FD500 taken by the HUVECs and the transient expression rate of pEGFP in the HUVECs were examined by fluorescence microscopy and flow cytometry, respectively. RESULTS: The percentage of FD500-positive HUVECs in the group of ultrasound exposure combined with SonoVue was significantly higher than that of the group of ultrasound exposure alone (24.0% ± 5.5% vs 66.6% ± 4.1%, P < 0.001). Compared with the group of ultrasound exposure alone, the transfection expression rate of pEGFP in HUVECs was markedly increased with the addition of SonoVue (16.1% ± 1.9% vs 1.5% ± 0.2%, P < 0.001). No statistical significant difference was observed in the HUVECs survival rates between the ultrasound group with and without the addition of SonoVue (94.1% ± 2.3% vs 91.1% ± 4.1%).CONCLUSION: The cell membrane permeability of HUVECs and the transfection efficiency of pEGFP into HUVECs exposed to ultrasound are significantly increased after addition of an ultrasound contrast agent withoutobvious damage to the survival of HUVECs. This non- invasive gene transfer method may be a useful tool for clinical gene therapy of hepatic tumors.

Percutaneous ultrasound-guided thermal ablation for liver tumor with artificial pleural effusion or ascites

Background and Objective:Percutaneous ultrasound-guided thermal ablation is one of the major treatment methods for liver cancer.Tumor location close to the diaphragm or gastrointestinal tract was regarded as the treatment contraindication before due to poor visibility of the tumor or increased risk of thermal injury to the adjacent organs.This study used artificial pleural effusion or ascites to extend the indications of thermal ablation for liver cancer.Methods:Artificial pleural effusion (20 cases) or ascites (36 cases) was performed in 56 difficult cases of percutaneous thermal ablation for liver tumors.The technical success rates, the rate of approaching the procedure goal, complications, and local treatment response were assessed.Results:The technical success rates were 95%(19/20) for artificial pleural effusion and 100% (36/36) for artificial ascites, the achieve purpose rates were 100%(19/19) and 91.7% (33/36), the complete ablation rates were 84.2% (16/19) and 93.9% (31/33), respectively.Coughing, transient hematuria, and subcutaneous effusion were observed in 3 patients after the procedure of artificial pleural effusion, and hydrothorax in the right chest occurred in 1 patient during the artificial ascites process.Conclusions:Thermal ablation with the use of artificial pleural effusion or ascites is a safe and effective treatment for liver tumors, and the technique can widen the indications of thermal ablation for liver tumors.

Expression of thymidine kinase mediated by a novel non-viral delivery system under the control of vascular endothelial growth factor receptor 2 promoter selectively kills human umbilical vein endothelial cells

AIM: To investigate the killing efficiency of a recombinant plasmid containing a thymidine kinase (TK) domain insert driven by the vascular endothelial growth factor receptor 2 (VEGFR2) promoter (KDR) on vascular endothelial cells.METHODS: The KDR-TK fragment was extracted from pBluescript Ⅱ KDR-TK plasmid by enzymatic digestion with Xho I and Sal I. The enhanced green fluorescence protein (EGFP) carrier was extracted from pEGFP by the same procedure. The KDR-TK was inserted into the pEGFP carrier to construct pEGFP-KDR-TK. Using ultrasound irradiation and microbubble, pEGFP-KDR-TK was transferred into human umbilical vein endothelial cells (HUVECs). The transient infection rate was estimated by green fluorescent protein (GFP) expression. Transfected HUVECs, non-transfected HUVECs, and HepG2 cells were cultured in the presence of different concentrations of ganciclovir (GCV), and the killing efficacy of HSV-TK/GCV was analyzed by 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide (MTT) assay. RESULTS: The recombinant pEGFP-KDR-TK was successfully constructed by inserting the KDR-TK fragment into the pEGFP carrier. Transfected HUVECs showed cytoplasmic green fluorescence, and the transient transfection rate was about 20.3%. Pools of G418-resistant cells exhibited a higher sensitivity to theprodrug/GCV compared to non-transfected HUVECs or non-transfected HepG2 cells, respectively. CONCLUSION: KDR promoter and the suicide gene/prodrug system mediated by diagnostic ultrasound combined with microbubble can significantly kill HUVECs. Such therapy may present a novel and attractive approach to target gene therapy on tumor vessels.

Ultrasound virtual endoscopy: Polyp detection and reliability of measurement in an in vitro study with pig intestine specimens

AIM: To present our initial experience regarding the feasibility of ultrasound virtual endoscopy(USVE) and its measurement reliability for polyp detection in an in vitro study using pig intestine specimens.METHODS: Six porcine intestine specimens containing 30 synthetic polyps underwent USVE, computed tomography colonography(CTC) and optical colonoscopy(OC) for polyp detection. The polyp measurement defined as the maximum polyp diameter on twodimensional(2D) multiplanar reformatted(MPR) planes was obtained by USVE, and the absolute measurement error was analyzed using the direct measurement as the reference standard.RESULTS: USVE detected 29(96.7%) of 30 polyps, remaining a 7-mm one missed. There was one falsepositive finding. Twenty-six(89.7%) of 29 reconstructedimages were clearly depicted, while 29(96.7%) of 30 polyps were displayed on CTC with one false-negative finding. In OC, all the polyps were detected. The intraclass correlation coefficient was 0.876(95%CI: 0.745-0.940) for measurements obtained with USVE. The pooled absolute measurement errors ± the standard deviations of the depicted polyps with actual sizes ≤ 5 mm, 6-9 mm, and ≥ 10 mm were 1.9 ± 0.8 mm, 0.9 ± 1.2 mm, and 1.0 ± 1.4 mm, respectively.CONCLUSION: USVE is reliable for polyp detection and measurement in in vitro study.