scholarly journals A Novel Correlation of Preoperative Gd-EOB-DTPA-contrast-enhanced MRI with FGFR4 Expression and Its Value in Targeted Therapy for Hepatocellular Carcinoma

Author(s):  
Zhiqing Mo ◽  
Liling Long ◽  
Hao Ding ◽  
Xiaojiao Zhou

Abstract Purpose: To assess the relationship between preoperative gadolinium ethoxy-benzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) features and fibroblast growth factor receptor 4 (FGFR4) gene expression in hepatocellular carcinoma (HCC).Materials and methods: Fifty-nine HCC patients (54 males, 5 females) who underwent preoperative enhanced MRI were retrospectively enrolled in this study. Quantitative and qualitative features of Gd-EOB-DTPA-enhanced MRI were analyzed in these pathologically confirmed HCC patients. Immunohistochemistry (IHC) and reverse transcription-polymerase chain reaction (RT-PCR) were performed to determine the mRNA and protein levels of FGFR4 in HCC. The relationship between these image features and the level of FGFR4 gene expression in HCC was evaluated by correlation analysis.Results: The FGFR4 mRNA and protein expression has significant correlation with the change of signal intensity in the phase of hepatobiliary, IHC analysis revealed significant correlation between the protein expression of FGFR4 and the qualitative enhanced MRI feature, mainly the manifestation of the intratumoral vessels at the arterial phase. Furthermore, the presence of intratumoral vessels (P =0.034, OR=4.71) and heterogeneous 3 signal performance in the hepatobiliary phase (P =0.008, OR=4.2) were identified as independent indicators for high FGFR4 expression in HCC. Conclusions: The findings demonstrate novel correlation between enhanced MRI features and FGFR4 gene expression, suggesting the heterogeneous signal intensity at the phase of hepatobiliary and the present of intratumoral vessels in the arterial phase as indicators for high FGFR4 expression in HCC. Our study may have clinical implication that enhanced MRI holds promise as useful modality in treatment selection of targeted therapies to HCC patients.

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Mengqi Huang ◽  
Bing Liao ◽  
Ping Xu ◽  
Huasong Cai ◽  
Kun Huang ◽  
...  

Objective. To investigate the imaging features observed in preoperative Gd-EOB-DTPA-dynamic enhanced MRI and correlated with the presence of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) patients. Methods. 66 HCCs in 60 patients with preoperative Gd-EOB-DTPA-dynamic enhanced MRI were retrospectively analyzed. Features including tumor size, signal homogeneity, tumor capsule, tumor margin, peritumor enhancement during mid-arterial phase, peritumor hypointensity during hepatobiliary phase, signal intensity ratio on DWI and apparent diffusion coefficients (ADC), T1 relaxation times, and the reduction rate between pre- and postcontrast enhancement images were assessed. Correlation between these features and histopathological presence of MVI was analyzed to establish a prediction model. Results. Histopathology confirmed that MVI were observed in 17 of 66 HCCs. Univariate analysis showed tumor size (p=0.003), margin (p=0.013), peritumor enhancement (p=0.001), and hypointensity during hepatobiliary phase (p=0.004) were associated with MVI. A multiple logistic regression model was established, which showed tumor size, margin, and peritumor enhancement were combined predictors for the presence of MVI (α=0.1). R2 of this prediction model was 0.353, and the sensitivity and specificity were 52.9% and 93.0%, respectively. Conclusion. Large tumor size, irregular tumor margin, and peritumor enhancement in preoperative Gd-EOB-DTPA-dynamic enhanced MRI can predict the presence of MVI in HCC.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jeong Yeop Lee ◽  
Byung Chan Lee ◽  
Hyoung Ook Kim ◽  
Suk Hee Heo ◽  
Sang Soo Shin ◽  
...  

AbstractTo identify the gadoxetic acid (GA)-enhanced magnetic resonance imaging (MRI) and laboratory findings that enable prediction of treatment response and disease-free survival (DFS) after the first session of drug eluting bead transarterial chemoembolization (DEB-TACE) in patients with hepatocellular carcinoma (HCC). A total of 55 patients who underwent GA-enhanced MRI and DEB-TACE from January 2014 to December 2018 were included. All MRI features were reviewed by two radiologists. Treatment response was evaluated according to the modified Response Evaluation Criteria in Solid Tumors. Univariate and multivariate logistic regression analyses were used to determine predictive factors of treatment response and DFS, respectively. A total of 27 patients (49.1%) achieved complete response (CR) after one session of treatment. There were no significant differences between the two groups in terms of clinical and laboratory characteristics. Heterogeneous signal intensity in the hepatobiliary phase (HBP) was the only independent predictor of non-CR (odds ratio, 4.807; p = 0.048). Recurrent HCC was detected in 19 patients (70.4%) after CR. In the multivariate analysis, elevated serum alpha-fetoprotein (AFP) level (≥ 30 ng/mL) was the only significant parameter associated with DFS (hazard ratio, 2.916; p = 0.040). This preliminary study demonstrated that heterogeneous signal intensity in the HBP and high serum AFP were useful predictive factors for poor treatment response and short DFS after DEB-TACE, respectively.


2021 ◽  
pp. 028418512110141
Author(s):  
San-Yuan Dong ◽  
Yu-Tao Yang ◽  
Wen-Tao Wang ◽  
Shuo Zhu ◽  
Wei Sun ◽  
...  

Background Gadoxetic acid-enhanced magnetic resonance imaging (MRI) has been widely used in clinical practice. However, scientific evidence is lacking for recommending a particular sequence for measuring tumor size. Purpose To retrospectively compare the size of hepatocellular carcinoma (HCC) measured on different gadoxetic acid-enhanced MRI sequences using pathology as a reference. Material and Methods A total of 217 patients with single HCC who underwent gadoxetic acid-enhanced MRI before surgery were included. The size of the HCC was measured by two abdominal radiologists independently on the following sequences: T1-weighted; T2-weighted; b-500 diffusion-weighted imaging (DWI); and arterial, portal venous, transitional, and hepatobiliary phases. Tumor size measured on MRI was compared with pathological size by using Pearson correlation coefficient, independent-sample t test, and Bland–Altman plot. Agreement between two readers was evaluated with intraclass correlation coefficient (ICC). Results Correlation between the MR images and pathology was high for both readers (0.899–0.955). Absolute error between MRI and pathologic assessment was lowest on hepatobiliary phase images for both readers (reader 1, 2.8±4.2 mm; reader 2, 3.2±3.4 mm) and highest on arterial phase images for reader 1 (4.9±4.4 mm) and DWI phase images for reader 2 (5.1±4.9 mm). Absolute errors were significantly different for hepatobiliary phase compared with other sequences for both readers (reader 1, P≤0.012; reader 2, P≤0.037). Inter-reader agreements for all sequence measurements were strong (0.971–0.997). Conclusion The performance of gadoxetic acid-enhanced MRI sequences varied with HCC size, and the hepatobiliary phase may be optimal among these sequences.


2019 ◽  
Vol 145 (12) ◽  
pp. 2995-3003 ◽  
Author(s):  
Xialing Huang ◽  
Liling Long ◽  
Jieqin Wei ◽  
Yajuan Li ◽  
Yuwei Xia ◽  
...  

Abstract Purpose To describe the clinical characteristics and outcomes of patients with dual-phenotype hepatocellular carcinoma (DPHCC) and investigate the use of radiomics to establish an image-based signature for preoperative differential diagnosis. Methods This study included 50 patients with a postoperative pathological diagnosis of DPHCC (observation group) and 50 patients with CK7- and CK19-negative HCC (control group) who attended our hospital between January 2015 and December 2018. All patients underwent Gd-EOB-DTPA-enhanced MRI within 1 month before surgery. Arterial phase (AP), portal venous phase (PVP), delayed phase (DP) and hepatobiliary phase (HBP) images were transferred into a radiomics platform. Volumes of interest covered the whole tumor. The dimensionality of the radiomics features were reduced using LASSO. Four classifiers, including multi-layer perceptron (MLP), support vector machines (SVM), logistic regression (LR) and K-nearest neighbor (KNN) were used to distinguish DPHCC from CK7- and CK19-negative HCC. Kaplan–Meier survival analysis was used to assess 1-year disease-free survival (DFS) and overall survival (OS) in the observation and control groups. Results The best preoperative diagnostic power for DPHCC will likely be derived from a combination of different phases and classifiers. The sensitivity, specificity and accuracy of LR in PVP (0.740, 0.780, 0.766), DP (0.893, 0.700, 0.798), HBP (0.800, 0.720, 0.756) and MLP in PVP (0.880, 0.720, 0.798) were better performance. The 1-year DFS and OS of the patients in the observation group were 69% and 78%, respectively. The 1-year DFS and OS of the patients in the control group were 83% and 85%, respectively. Kaplan–Meier survival analysis showed no statistical difference in DFS and OS between groups (P = 0.231 and 0.326), but DFS and OS were numerically lower in patients with DPHCC. Conclusion The radiomics features extracted from Gd-EOB-DTPA-enhanced MR images can be used to diagnose preoperative DPHCC. DPHCC is more likely to recur and cause death than HCC, suggesting that active postoperative management of patients with DPHCC is required.


2017 ◽  
Vol 59 (6) ◽  
pp. 639-648 ◽  
Author(s):  
Yo Na Kim ◽  
Ji Soo Song ◽  
Woo Sung Moon ◽  
Hong Pil Hwang ◽  
Young Kon Kim

Background Gadoxetic acid is being widely used for detection and characterization of hepatic nodules. However, there are no data regarding intra-individual comparison of imaging features of hepatocellular carcinoma (HCC) on dynamic computed tomography (CT), gadopentetate dimeglumine-enhanced magnetic resonance imaging (Gd-DTPA-MRI), and gadoxetic acid-enhanced MRI (Gd-EOB-MRI). Purpose To evaluate typical imaging features of HCC and capsule appearance with dynamic CT, Gd-DTPA-MRI, and Gd-EOB-MRI. Material and Methods We retrospectively reviewed 56 HCCs in 49 patients. Lesion attenuation/signal intensity was graded using a five-point scale based on dynamic phase and hepatobiliary phase (HBP) imaging. Subjective washout and capsule appearance were evaluated on portal venous phase (PVP) or delayed/transitional phase (DP/TP) imaging. The tumor-to-liver contrast ratio (TLCR) was calculated. Results Gd-DTPA-MRI and Gd-EOB-MRI was graded higher than CT on arterial phase ( P < 0.001). Gd-EOB-MRI was graded lower than Gd-DTPA-MRI on PVP and DP/TP ( P < 0.05). The detection rate of subjective washout and capsule appearance did not differ among the three imaging studies on either PVP or DP/TP. TLCR of Gd-EOB-MRI was lower than CT on PVP ( P = 0.004) and was lower than Gd-DTPA-MRI on DP/TP ( P = 0.001). Conclusion Arterial phase hyperenhancement and washout appearance of HCC were well demonstrated in Gd-EOB-MRI. The detection of capsule appearance using Gd-EOB-MRI was not inferior to Gd-DTPA-MRI or CT.


2017 ◽  
Vol 35 (6) ◽  
pp. 574-582 ◽  
Author(s):  
Takayuki Iwamoto ◽  
Yasuharu Imai ◽  
Takumi Igura ◽  
Sachiyo Kogita ◽  
Yoshiyuki Sawai ◽  
...  

Background: Non-hypervascular hypointense hepatic nodules during the hepatobiliary phase of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI have been reported to be associated with intrahepatic distant recurrence (IDR) after hepatectomy or radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). IDR is categorized into hypervascular transformation of non-hypervascular hypointense hepatic nodules and new intrahepatic recurrence. The aim of this study was to evaluate the relationship between non-hypervascular hypointense hepatic nodules on Gd-EOB-DTPA-enhanced MRI and IDR after RFA, focusing on new intrahepatic recurrence. Methods: Ninety-one consecutive patients with 115 HCCs undergoing pretreatment Gd-EOB-DTPA-enhanced MRI and RFA for treatment of HCC were enrolled. Results: Of the 91 patients who underwent RFA for HCC, 24 had non-hypervascular hypointense hepatic nodules on pretreatment Gd-EOB-DTPA-enhanced MRI. Recurrences were observed in 15 and 19 patients with and without non-hypervascular hypointense hepatic nodules, respectively. Of the 15 recurrences in patients with non-hypervascular hypointense hepatic nodules, 10 patients had new intrahepatic recurrences. The cumulative incidence of new intrahepatic recurrence was significantly higher in patients with non-hypervascular hypointense hepatic nodules than in those without non-hypervascular hypointense hepatic nodules (p < 0.0001). Multivariate analysis revealed that the presence of non-hypervascular hypointense hepatic nodules and Child-Pugh score were independent risk factors for new intrahepatic recurrence. Conclusions: Non-hypervascular hypointense hepatic nodules during the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI were a useful predictive factor for IDR, particularly for new intrahepatic recurrence, after RFA.


Liver Cancer ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 94-106
Author(s):  
Seung Baek Hong ◽  
Sang Hyun Choi ◽  
So Yeon Kim ◽  
Ju Hyun Shim ◽  
Seung Soo Lee ◽  
...  

<b><i>Purpose:</i></b> Microvascular invasion (MVI) is an important prognostic factor in patients with hepatocellular carcinoma (HCC). However, the reported results of magnetic resonance imaging (MRI) features for predicting MVI of HCC are variable and conflicting. Therefore, this meta-analysis aimed to identify the significant MRI features for MVI of HCC and to determine their diagnostic value. <b><i>Methods:</i></b> Original studies reporting the diagnostic performance of MRI for predicting MVI of HCC were identified in MEDLINE and EMBASE up until January 15, 2020. Study quality was assessed using QUADAS-2. A bivariate random-effects model was used to calculate the meta-analytic pooled diagnostic odds ratio (DOR) and 95% confidence interval (CI) for each MRI feature for diagnosing MVI in HCC. The meta-analytic pooled sensitivity and specificity were calculated for the significant MRI features. <b><i>Results:</i></b> Among 235 screened articles, we found 36 studies including 4,274 HCCs. Of the 15 available MRI features, 7 were significantly associated with MVI: larger tumor size (&#x3e;5 cm) (DOR = 5.2, 95% CI [3.0–9.0]), rim arterial enhancement (4.2, 95% CI [1.7–10.6]), arterial peritumoral enhancement (4.4, 95% CI [2.8–6.9]), peritumoral hypointensity on hepatobiliary phase imaging (HBP) (8.2, 95% CI [4.4–15.2]), nonsmooth tumor margin (3.2, 95% CI [2.2–4.4]), multifocality (7.1, 95% CI [2.6–19.5]), and hypointensity on T1-weighted imaging (T1WI) (4.9, 95% CI [2.5–9.6]). Both peritumoral hypointensity on HBP and multifocality showed very high meta-analytic pooled specificities for diagnosing MVI (91.1% [85.4–94.8%] and 93.3% [74.5–98.5%], respectively). <b><i>Conclusions:</i></b> Seven MRI features including larger tumor size, rim arterial enhancement, arterial peritumoral enhancement, peritumoral hypointensity on HBP, nonsmooth margin, multifocality, and hypointensity on T1WI were significant predictors for MVI of HCC. These MRI features predictive of MVI can be useful in the management of HCC.


2020 ◽  
Author(s):  
xuyang ma ◽  
Ying Ding ◽  
Li Zeng

Abstract Background: The potential correlation between H2AFY (also known as MacroH2A1) and the clinical characteristics of hepatocellular carcinoma (HCC) patients was analysed through gene expression profiles and clinical data in The Cancer Genome Atlas (TCGA) database, and the diagnostic and prognostic value of H2AFY in HCC was discussed. Methods: The gene expression data of HCC and the corresponding clinical characteristics of HCC patients were downloaded from the TCGA database. The differences in H2AFY in normal liver tissues and HCC were analysed. The relationship between H2AFY and clinical characteristics was analysed by Wilcoxon signed-rank test, logistic regression and Kruskal-Wallis test. The Kaplan-Meier method and the Cox regression method were used to analyse the relationship between overall survival and clinical characteristics of the patients. An ROC curve was used to predict the diagnostic value of H2AFY in HCC. Gene set enrichment analysis (GSEA) was used to analyse the pathway enrichment of H2AFY. Result: Compared with normal liver tissues, H2AFY was significantly highly expressed in HCC. H2AFY was positively correlated with the age, clinical stage, G stage (grade) and T stage (tumor stage) of liver cancer patients. Higher H2AFY expression predicted a poor prognosis in HCC patients. Cox regression analysis suggested that H2AFY was an independent risk factor for the prognosis of HCC patients. The ROC curve suggested that H2AFY had certain diagnostic value in HCC. GSEA suggested that H2AFY was correlated with lipid metabolism and a variety of tumour pathways. Conclusion: Our study showed that H2AFY was significantly overexpressed in HCC. H2AFY may be a potential diagnostic and prognostic marker for HCC, and high expression of H2AFY predicts a poor prognosis in patients with HCC.


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