Baoxian Liu

Shear wave elastography versus real-time elastography on evaluation thyroid nodules: A preliminary study

OBJECTIVE To comparatively evaluate shear wave elastography (SWE) and real-time elastography (RTE) in distinguishing malignant from benign thyroid nodules. METHODS 49 patients with 64 focal thyroid nodules were enrolled and underwent SWE and RTE before surgery. SWE elasticity indices (mean, minimum and maximum value of 2-mm region of interest) of nodules were measured. For RTE, elastograms were assessed by Rago criteria and nodules with scores of 4 or 5 were classified as suspicious for malignancy. Surgery histopathologic results were adopted as diagnostic standard. RESULTS Of the 64 nodules, 19 were papillary thyroid carcinomas and 45 were benign. SWE indices were significantly higher in malignant than benign nodules (P<0.05). Areas under the ROC curves (AUC) of SWE parameters were 0.840, 0.831 and 0.788, which were not significantly different from that of RTE showed as 0.880 (P=0.148-0.482). When the most accurate cut-off, 38.3kPa for mean value was applied to predict malignancy, the diagnostic specificity, sensitivity, accuracy, positive predictive value and negative predictive value of SWE and RTE were 68.4% versus 79.0%, 86.7% versus 84.4%, 81.3% versus 78.1%, 68.4% versus 64.7% and 86.7% versus 83.3%, respectively (P=0.683-1.000). CONCLUSION SWE as a promising tool can be performed in differentiating thyroid nodules with comparable results to RTE.

Optimizing the US Diagnosis of Biliary Atresia with a Modified Triangular Cord Thickness and Gallbladder Classification.

Purpose To evaluate the diagnostic performance of ultrasonography (US) in the identification and exclusion of biliary atresia with a modified triangular cord thickness metric together with a gallbladder classification scheme, as well as hepatic artery (HA) diameter and liver and spleen size, in a large sample of jaundiced infants. Materials and Methods The ethics committee approved this study, and written informed parental consent was obtained. In 273 infants with conjugated hyperbilirubinemia (total bilirubin level ≥ 31.2 μmol/L, with direct bilirubin level > indirect bilirubin level), detailed abdominal US was performed to exclude biliary atresia. Biliary atresia was found in 129 infants and ruled out in 144. A modified triangular cord thickness was measured at the anterior branch of the right portal vein, and a gallbladder classification scheme was identified that incorporated the appearance of the gallbladder and a gallbladder length-to-width ratio of up to 5.2 when the lumen was visualized, as well as HA diameter and liver and spleen size. Reference standard diagnosis was based on results of one or more of the following: surgery, liver biopsy, cholangiography, and clinical follow-up. Area under the receiver operating characteristic curve (AUC) analysis, binary logistic regression analysis, Fisher exact test, and unpaired t test were performed. Results Triangular cord thickness, HA diameter, ratio of gallbladder length to gallbladder width, liver size, and spleen size exhibited statistically significant differences (all P < .05) between the group with biliary atresia and the group without. AUCs of triangular cord thickness, ratio of gallbladder length to width, and HA diameter were 0.952, 0.844, and 0.838, respectively. Logistic regression analysis demonstrated that these three US parameters were significantly associated (all P < .05) with biliary atresia. The combination of triangular cord thickness and gallbladder classification could yield comparable AUCs (0.915 vs 0.933, P = .400) and a higher sensitivity (96.9% vs 92.2%), compared with triangular cord thickness alone. Conclusion By using the combination of modified triangular cord thickness and gallbladder classification scheme, most infants with biliary atresia could be identified. (©) RSNA, 2015.

Mcl-1 Is a Novel Target of miR-26b That Is Associated with the Apoptosis Induced by TRAIL in HCC Cells

Aim. To investigate the role of miR-26b and Mcl-1 in TRAIL-inducing cell death in hepatocellular carcinoma. Methods. The expression of miR-26b and Mcl-1 in HCC was detected by RT-qPCR and western blot. The regulation of Mcl-1 by miR-26b was determined by luciferase reporter assay. MTT and flow cytometry were employed to detect the cell viability and apoptosis. Results. miR-26b is commonly downregulated in HCC cell lines compared with the LO2 cell line. In contrast, the Mcl-1 expression is upregulated in HCC cell lines. Bioinformatic analysis identified a putative target site in the Mcl-1 mRNA for miR-26b and luciferase reporter assay showed that miR-26b directly targeted the 3′-UTR (3′-Untranslated Regions) of Mcl-1 mRNA. Transfection of miR-26b mimics suppressed Mcl-1 expression in HCC cells and sensitized the cancer cells to TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) cytotoxicity. In addition, transfection of HCC cells with Mcl-1 expression plasmid abolished the sensitization effect of miR-26b to TRAIL-inducing apoptosis. Conclusions. Our study showed that miR-26b was a negative regulator of Mcl-1 gene and sensitized TRAIL-inducing apoptosis in HCC cells, suggesting that the miR-26b-Mcl-1 pathway might be a novel target for the treatment of HCC.

Shear Wave Elastography in the Diagnosis of Thyroid Nodules with Coexistent Chronic Autoimmune Hashimoto's Thyroiditis.

Objective To evaluate the diagnostic performance of shear wave elastography (SWE) in the differentiation of malignant and benign thyroid nodules with coexistent Hashimoto’s thyroiditis (HT). Study Design Case series with chart review. Setting Tertiary general hospital. Subjects and Methods From September 2012 to January 2014, conventional ultrasound and SWE were performed on 243 patients with 286 thyroid nodules with histologic results. The HT group consisted of 93 patients with 117 nodules. The non-HT group consisted of 140 patients with 169 nodules. Results In the benign and malignant nodules, there were no significant differences of the mean, minimum, or maximum SWE values between HT and non-HT groups (P = .158-.945). However, SWE values of extranodular tissue were significantly higher in the HT group (P = .000-.011). In the HT group, the maximum SWE value showed the highest area under the receiver operating characteristic curve (0.817; 95% confidence interval, .735-.900), and there were no significant differences when compared with other SWE parameters (P = .669-.848). In the multivariate analysis, hypoechogenicity (odds ratio = 9.855, P = .002), microcalcification (odds ratio = 3.977, P = .046), and maximum SWE value (odds ratio = 40.712, P < .001) were independent predictors of thyroid malignancy. Conclusions SWE could be performed to obtain a differential diagnosis between malignant and benign thyroid nodules, including nodules with coexistent HT. Although all the SWE parameters within a 2-mm region of interest that was placed on the stiffest region could be applied, we suggest that the maximum value of nodules harbored within a Hashimoto’s gland be used.

miR-500a-3p promotes cancer stem cells properties via STAT3 pathway in human hepatocellular carcinoma

BackgroundmiR-500a-3p has been demonstrated to be involved in the development, progression and metastasis in several human cancers. Constitutive activation of JAK/STAT3 signaling pathway has been reported to play an important role in the development and progression of hepatocellular carcinoma (HCC).The purpose of this study was to determine the biological roles and clinical significance of miR-500a-3p in HCC and to identify whether miR-500a-3p has an effect on the activity of JAK/STAT3 signaling in HCC.MethodsmiR-500a-3p expression was examined by real-time PCR in 8 paired HCC tissues and individual 120 HCC tissues respectively. Statistical analysis was performed to explore the clinical correlation between miR-500a-3p expression and clinicopathological features and overall and relapse-free survival in HCC patients. In vitro and in vivo assays were performed to investigate the biological roles of miR-500a-3p in HCC. The bioinformatics analysis, real-time PCR, western blot and luciferase reporter assay were performed to discern and examine the relationship between miR-500a-3p and its potential targets. Clinical correlation of miR-500a-3p with its targets was examined in HCC tissues.ResultsmiR-500a-3p is dramatically elevated in HCC tissues and cells and high expression of miR-500a-3p correlates with poor overall and relapse-free survival in HCC patients. Upregulating miR-500a-3p enhances, while silencing miR-500a-3p suppresses, the spheroid formation ability, fraction of side population and expression of cancer stem cell factors in vitro and tumorigenicity in vivo in HCC cells. Our findings further reveal miR-500a-3p promotes the cancer stem cell characteristics via targeting multiple negative regulators of JAK/STAT3 signaling pathway, including SOCS2, SOCS4 and PTPN11, leading to constitutive activation of STAT3 signaling. Moreover, the inhibitory effects of anti-miR-500a-3p on cancer stem cell phenotypes and activity of STAT3 signaling were reversed by silencing SOCS2, SOCS4 and PTPN11 in miR-500a-3p-downexpressing cells, respectively. Clinical correlation of miR-500a-3p with the targets was examined in human HCC tissues.Conclusionour results uncover a novel mechanism by which miR-500a-3p promotes the stemness maintenance of cancer stem cell in HCC, suggesting that silencing miR-500a-3p may serve as a new therapeutic strategy in the treatment of hepatocellular carcinoma.

MicroRNA-15a-5p suppresses cancer proliferation and division in human hepatocellular carcinoma by targeting BDNF

We examined the expression pattern and functional roles of microRNA 15a-5p (miR-15a-5p) in human hepatocellular carcinoma (HCC). Possible miR-15a-5p aberrant expression in HCC cell lines or clinical HCC specimens was examined by quantitative real-time PCR (qRT-PCR). In HCC HepG2 and SNU-182 cells, miR-15a-5p was ectopically overexpressed by lentiviral transduction. Its effect on HCC proliferation, cancer division, and in vivo tumor growth were examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, cell cycle assay, and tumorigenicity assay, respectively. The targeting of miR-15a-5p on its downstream gene, brain-derived neurotrophic factor (BDNF), was examined by dual-luciferase assay, qRT-PCR, and Western blot, respectively. BDNF was then overexpressed in HepG2 and SNU-182 cells to evaluate its selective effect on miR-15a-5p in HCC modulation. MiR-15a-5p is aberrantly downregulated in in vitro HCC cell lines and in vivo HCC clinical specimens. Ectopic overexpression of miR-15a-5p suppressed cancer proliferation, induced cell cycle arrest in HepG2 or SNU-182 cells in vitro, and inhibited HCC tumor growth in vivo. MiR-15a-5p selectively and negatively regulated BDNF at both gene and protein levels in HCC cells. Forced overexpression of BDNF effectively reversed the tumor suppressive functions of miR-15a-5p on HCC proliferation and cell division in vitro. Our study demonstrated that miR-15a-5p is a tumor suppressor in HCC and its regulation is through BDNF in HCC.

Supersonic shearwave elastography in the assessment of liver fibrosis for postoperative patients with biliary atresia.

To explore an effective noninvasive tool for monitoring liver fibrosis of children with biliary atresia (BA) is important but evidences are limited. This study is to investigate the predictive accuracy of supersonic shearwave elastography (SSWE) in liver fibrosis for postoperative patients with BA and to compare it with aspartate aminotransferase to platelet ratio index (APRI) and fibrosis-4 (FIB-4). 24 patients with BA received SSWE and laboratory tests before scheduled for liver biopsy. Spearman rank coefficient and receiver operating characteristic (ROC) were used to analyze data. Metavir scores were F0 in 3, F1 in 2, F2 in 4, F3 in 7 and F4 in 8 patients. FIB-4 failed to correlate with fibrosis stage. The areas under the ROC curves of SSWE, APRI and their combination were 0.79, 0.65 and 0.78 for significant fibrosis, 0.81, 0.64 and 0.76 for advanced fibrosis, 0.82, 0.56 and 0.84 for cirrhosis. SSWE values at biopsy was correlated with platelet count (r = −0.426, P = 0.038), serum albumin (r = −0.670, P < 0.001), total bilirubin (r = 0.419, P = 0.041) and direct bilirubin levels (r = 0.518, P = 0.010) measured at 6 months after liver biopsy. Our results indicate that SSWE is a more promising tool to assess liver fibrosis than APRI and FIB-4 in children with BA.

Liver stiffness measurements with supersonic shear wave elastography in the diagnosis of biliary atresia: a comparative study with grey-scale US

ObjectivesTo prospectively assess the diagnostic performance of supersonic shear wave elastography (SSWE) in identifying biliary atresia (BA) among infants with conjugated hyperbilirubinaemia by comparing this approach with grey-scale ultrasonography (US).MethodsForty infants were analysed as the control group to determine normal liver stiffness values. The use of SSWE values for identifying BA was investigated in 172 infants suspected of having BA, and results were compared with the results obtained by grey-scale US. The Mann-Whitney U test, unpaired t-test, Spearman correlation and linear regression were also performed.ResultsThe success rates of SSWE measurements in the control and study group were 100% (40/40) and 96.4% (244/253), respectively. Age, direct bilirubin, and indirect bilirubin all significantly correlated with SSWE in the liver (all P < 0.001). Linear regression showed that age had a greater effect on SSWE values than direct or indirect bilirubin. The diagnostic performance of liver stiffness values in identifying BA was lower than that of grey-scale US (area under the receiver operating characteristic curve [AUC], 0.790 vs 0.893, P < 0.001).ConclusionsSSWE is feasible and valuable in differentiating BA from non-BA. However, its diagnostic performance does not exceed that of grey-scale US.Key points• SSWE could be successfully performed in an infant population.• For infants, the liver stiffness will increase as age increases.• SSWE is potentially useful in assessing infants suspected of biliary atresia.• SSWE is inferior to grey-scale US in identifying biliary atresia.

Elastography of shear wave speed imaging for the evaluation of liver fibrosis: a meta-analysis.

A meta‐analysis was carried out to assess the accuracies of shear wave speed imaging (SWSI) in predicting significant fibrosis (stages F2–4) and cirrhosis (stage F4).

Real-Time Shear Wave Ultrasound Elastography Differentiates Fibrotic from Inflammatory Strictures in Patients with Crohn’s Disease

Background and aim The distinction of intestinal fibrosis from inflammation in Crohns disease (CD) associated strictures has important therapeutic implications. Ultrasound elastography is useful in evaluating the degree of fibrosis in liver, but there is little evidence whether it can assess fibrosis in the bowel. We determined whether shear-wave elastography (SWE), a novel modification of elastography, quantifying tissue stiffness, could differentiate between inflammatory and fibrotic components in strictures of patients with CD. Methods Consecutive CD patients with ileal/ileocolonic strictures who underwent SWE within 1 week to surgical resection were enrolled. The SWE value of the stenotic bowel wall was compared to the grade and severity of fibrosis and inflammation, respectively, in the resected bowel specimen. Results Thirty-five patients were enrolled. The mean SWE value of stenotic bowel wall was significantly higher in severe fibrosis (23.0 ± 6.3 Kpa) than that in moderate (17.4 ± 3.8 Kpa) and mild fibrosis (14.4 ± 2.1 Kpa)(P = 0.008). Using 22.55 KPa as the cutoff value in discriminating between mild/moderate and severe fibrosis, the sensitivity and specificity was 69.6 % and 91.7% with an area under the curve (AUC) of 0.822 (P = 0.002). However, no significant difference regarding mean SWE existed among different grades of inflammation. The sensitivity and specificity of bowel vascularization score on conventional ultrasound in differentiating severe inflammation from mild/moderate was 87.5 % and 57.9% with AUC of 0.811 (P = 0.002). Combining SWE and conventional ultrasound (bowel vascularization score), we propose a bowel ultrasound classification of intestinal strictures. A moderate agreement between ultrasound and pathological classification was observed (κ = 0.536, P＜0.001). Conclusions This pilot study suggests that SWE is feasible and accurate in detecting intestinal fibrosis in patients with CD. After validation, combing SWE and bowel vascularization on conventional ultrasound might be applied to guide a management strategy in CD patients through defining the type of intestinal stricture. 10.1093/ibd/izy115_video1izy115.video15777734754001.