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Background Noninvasive diagnostic guidelines for hepatocellular carcinoma (HCC) vary across different global geographic areas, especially regarding criteria about gadoxetic acid-enhanced MRI. Purpose To compare the diagnostic performance of four different international HCC diagnosis guidelines and readers' judgment in diagnosing HCC using gadoxetic acid-enhanced MRI in patients at high risk for HCC. Materials and Methods This retrospective study included patients who had not undergone treatment, were at risk for HCC, and who underwent gadoxetic acid-enhanced MRI from January 2015 to June 2018 from 11 tertiary hospitals in South Korea. Four radiologists independently reviewed focal liver lesions (FLLs) according to four guidelines: American Association for the Study of Liver Diseases (AASLD)/Liver Imaging Reporting and Data System (LI-RADS), Korean Liver Cancer Association-National Cancer Center (KLCA-NCC), European Association for the Study of the Liver (EASL), and Asian Pacific Association for the Study of the Liver (APASL). Reader judgment (HCC or not HCC) was also recorded. Malignant FLLs were confirmed at pathology, and histologic and clinical follow-up data were used for benign FLLs. The guidelines' diagnostic performance was compared using generalized estimating equations. Additionally, the diagnostic odds ratio was assessed. Results A total of 2445 FLLs (median size, 27.4 mm) were analyzed in 2237 patients (mean age, 59 years ± 11 [SD]; 1666 male patients); 69.3% (1694 of 2445) were HCCs. KLCA-NCC showed the highest accuracy (80.0%; 95% CI: 78.7, 81.2; P = .001), with high sensitivity in Eastern guidelines (APASL, 89.1% [95% CI: 87.8, 90.3]; KLCA-NCC, 78.2% [95% CI: 76.6, 79.7]) and high specificity in Western guidelines (AASLD/LI-RADS, 89.6% [95% CI: 87.8, 91.2]; EASL, 88.1% [95% CI: 86.2, 89.9]) ( P = .001). The diagnostic odds ratios were 20.7 (95% CI: 17.0, 25.3) for AASLD/LI-RADS, 18.9 (95% CI: 15.8, 22.6) for KLCA-NCC, 16.8 (95% CI: 13.8, 20.4) for EASL, and 8.9 (95% CI: 7.4, 10.7) for APASL. The readers' judgment demonstrated higher accuracy than that of the guidelines (accuracy, 86.0%; 95% CI: 84.9, 86.9; P = .001). Conclusion Among four different international HCC diagnosis guidelines, Eastern guidelines demonstrated higher sensitivity, whereas Western guidelines displayed higher specificity. KLCA-NCC achieved the highest accuracy, and AASLD/LI-RADS exhibited the highest diagnostic odds ratio. © RSNA, 2024 Supplemental material is available for this article.

Objectives: This study aimed to elucidate the relationship between gadoxetic acid-enhanced magnetic resonance imaging (MRI) features-enhancing capsule, corona enhancement or hypointense rim-observed in hepatocellular carcinomas (HCCs)., Methods: Of the HCCs surgically confirmed during a 5-year period (2013-2017), ≤ 3-cm lesions (n = 83) in 78 patients were evaluated. Presence of corona enhancement and enhancing capsule on multiphasic dynamic imaging and presence of hypointense rim on hepatobiliary phase imaging were determined retrospectively by two independent observers. The relationship among the three imaging features was statistically analysed and correlated with the presence of histologic fibrous capsules, tumour differentiation and gross morphologic type., Results: There was substantial overall interobserver agreement in determining the presence of the three imaging features. Sixty (72.3%) lesions had histologic fibrous capsule positively correlated with all three imaging features (p < 0.05). Corona enhancement was the most common (66.3%) feature followed by enhancing capsule (61.4%) and hypointense rim (33.7%), and the correspondence rate of enhancing capsule to corona enhancement was 68.6% (p = 0.004). Corona enhancement was more frequently observed in moderately differentiated HCCs than other lesions (p = 0.012) and not dependent (p = 0.465) on the tumour size, while enhancing capsule was significantly dependent on tumour size, as indicated by univariate (p < 0.001) and multivariate analyses (odds ratio, 4.241; p = 0.002)., Conclusions: Among the capsular features, corona enhancement might closely relate to enhancing capsule in HCCs. Corona enhancement was not dependent on tumour size and had the highest incidence of appearance on gadoxetic acid-enhanced multiphasic dynamic MRI., Key Points: • Enhancing capsule has a limited role in the LI-RADS categorisation during gadoxetic acid-enhanced MRI. • Appearance of corona enhancement is closely related to enhancing capsule and is not dependent on size of HCCs. • Corona enhancement can substitute enhancing capsule in the diagnosis of HCCs during multiple arterial and portal venous phase gadoxetic acid-enhanced MRI., (© 2021. European Society of Radiology.)

Purpose: To determine the intra- and extralesional factors that predict sclerotic degeneration of hepatic hemangiomas in the cirrhotic liver on long-term follow-up computed tomography (CT) examinations., Materials and Methods: Fifty-seven hepatic hemangiomas (> 5 mm in diameter) in 41 cirrhotic patients, recruited over a 5-year period (January 2005-December 2009), were subjected to CT to determine which factors predict sclerotic contraction or degeneration in hemangiomas. Prior and follow-up CT examinations (from 2000 to 2018) were included to observe time-related changes. The patients' gender, age, cause of cirrhosis, progression of background liver cirrhosis, lesion size/location/contrast enhancement pattern, and serum aspartate transaminase to platelet ratio index were correlated with sclerotic changes of each lesion., Results: According to the dynamic CT features, 36 of 57 (63%) hemangiomas were determined to have sclerotic changes during the follow-up period (1.1-14.4 years, median: 7.8 years), including 28 lesions (49%) reduced by ≥ 20% in diameter. In univariate analysis, age (p = 0.047) and morphological progression of background cirrhosis (p = 0.013) were significantly related to sclerotic change of hemangiomas. In the logistic regression analysis, only morphological progression of background liver cirrhosis independently predicted sclerotic change (odds ratio: 4.88, p = 0.007). With the exception of exophytic location free from size reduction (p = 0.023 in multivariate analysis), no other analyzed factors were significantly correlated with sclerotic changes., Conclusion: Overall, sclerotic changes of hepatic cavernous hemangioma followed the morphological progression of background liver cirrhosis, while exophytic lesions tended to be free of size reduction.

Objective: The aim of the study was to evaluate the performance of texture analysis for discriminating the histopathological grade of hepatocellular carcinoma (HCC) on magnetic resonance imaging., Methods: Preoperative magnetic resonance imaging data from 101 patients with HCC, including T2-weighted imaging, arterial phase, and apparent diffusion coefficient mapping, were analyzed using texture analysis software (TexRAD). Differences among the histological groups were analyzed using the Mann-Whitney U test. The performance of texture features was evaluated using receiver operating characteristic analysis., Results: Entropy was the most significantly relevant texture feature for distinguishing each histological grade group of HCC (P < 0.05). In ROC analysis, entropy with spatial scale filter 3 (area under curve the receiver operating characteristic curve [AUC], 0.778), mean with coarse filter (spatial scale filter 5; AUC, 0.670), and skewness without filtration (AUC, 0.760) had the highest AUC value on T2-weighted imaging, arterial phase, and apparent diffusion coefficient maps, respectively., Conclusions: Magnetic resonance imaging texture analysis demonstrated potential for predicting the histopathological grade of HCCs.

OBJECTIVE. The purpose of this study is to validate the use of subtraction images derived from gadoxetic acid-enhanced MRI for observation of washout and enhancing capsule in the diagnosis of hepatocellular carcinoma (HCC). MATERIALS AND METHODS. For 120 histologically verified HCCs in 115 high-risk patients, the presence of washout and enhancing capsule in the portal venous phase (PVP) on conventional MR images with and without corresponding subtraction images was determined by two independent observers. The incremental value of subtraction imaging in upgrading the categories outlined in the Liver Imaging Reporting and Data System (LI-RADS) version 2018 for the diagnosis of HCC was analyzed for different subgroups of patients classified on the basis of lesion size (< 10 mm, 10-19 mm, ≥ 20 mm), unenhanced T1-weighted signal intensity, and arterial phase hyperenhancement (APHE) of the lesions. RESULTS. When conventional PVP images were compared with the combination of conventional and subtraction PVP images, only T1-weighted isointensity or hyperintensity significantly increased the detection of washout (eight vs 15 of 18 lesions; p = 0.0233). Detection of enhancing capsule was significantly increased ( p < 0.05) regardless of various factors, except for a lesion size of less than 2 cm (five vs nine of 36 lesions; p = 0.1336). Two lesions (one LI-RADS category 3 lesion and one LI-RADS category 4 lesion) with APHE were upgraded to category 5 on the basis of a review of PVP subtraction images. CONCLUSION. PVP subtraction imaging during gadoxetic acid-enhanced MRI can upgrade LI-RADS categories for the diagnosis of HCC because of its superior ability in depicting enhancing capsule and the incremental benefit of showing washout.

Hepatocellular carcinoma (HCC) has high incidence and mortality in patients with chronic liver diseases worldwide. However, there are limited chemotherapeutic agents for HCC in clinic. Xanthatin, a natural sesquiterpene lactone, has significant antitumor activity against a variety of cancers, but little is known about its effects on HCC and the underlying mechanism. Here, we evaluated the antitumor effects of xanthatin on human hepatoma cells. We found that xanthatin caused morphological changes and reduced cell viability in three HCC cell lines in concentration- and time-dependent manners. Xanthatin at 10 μM significantly arrested cell cycle at the G2/M checkpoint, and at 40 μM significantly arrested cell cycle at the S phase in hepatoma cells. Additionally, xanthatin induced apoptosis associated with activation of caspase-3 in hepatoma cells, but did not apparently induce apoptosis in human normal LO2 hepatocytes. We also demonstrated that the three primary signaling pathways of unfolded protein response (UPR) were activated by xanthatin to different extents. Notably, the PERK/eIF-2α/ATF4 axis was most significantly activated by xanthatin. More importantly, both xanthatin and tunicamycin, an endoplasmic reticulum stress (ERS) inducing compound, increased the levels of CHOP and cleaved-caspase-3 in HepG2 cells, but their effects were significantly abolished by siRNA-mediated knockdown of CHOP. Further experiments validated that xanthatin more potently activated ATF4 by promoting its nuclear translocation in hepatoma cells. Taken together, we discovered that xanthatin induced apoptosis in human hepatoma cells by activating ERS. Our current data revealed a novel mechanism for xanthatin as a promising anti-tumor candidate for HCC therapy., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Heat shock protein 60 (HSP60) overexpresses in various types of cancer, but its expression levels and functions in hepatocellular carcinoma (HCC) are still in dispute. We aim to clarify this issue and examine whether HSP60 could be a therapeutic target for HCC. We found drastically enhanced cell apoptosis and suppressed cell proliferation in two HCC cell lines with HSP60-silencing, and also indicated survivin was involved in this regulatory process in vitro and in vivo. However, HSP60-silencing in normal human hepatocytes only resulted in a minimal reduction of cell proliferation but without effects on cell apoptosis. We also showed HSP60 interacted with cytosolic but not mitochondrial survivin by immunoprecipitation assay. A rigorous method was used to standardize quantification from immunoblot assay to obtain more precise expression levels of HSP60 and survivin. The expression of HSP60 and survivin positively correlated in both cancerous and non-cancerous liver tissues (P < 0.001) after analyzing 145 surgically removed HCC tissues. A total of 56.6% of HCC patients overexpressed HSP60 in cancerous tissues, and 40.0% under-expressed HSP60. Higher expression of HSP60 and survivin in non-cancerous tissues both correlated with shorter overall survival (P = 0.029 and P < 0.001, respectively). Finally, we evaluated the therapeutic potential of HSP60 using extraneous delivery of jetPEI/shHSP60 complexes. The treatment results showed significant reduction of tumor weight by 44.3% (P < 0.05), accompanied by under-expression of survivin. These studies suggested that HSP60 not only served as a prognostic marker but also served as a novel therapeutic target for HCC., (© 2018 Wiley Periodicals, Inc.)

Objectives: Apparent diffusion coefficient (ADC) has been suggested to reflect the tumor grades of hepatocellular carcinomas (HCCs); i.e., it can be used as a biomarker to predict the patients' prognosis. To verify its feasibility as a biomarker, the present study sought to determine how the ADC values of HCC are affected by a tumor's histopathologic grade and arterial vascularity., Materials and Methods: From 131 consecutive patients, 141 surgically resected HCCs (16 well-differentiated [wd-HCCs], 83 moderately-differentiated [md-HCCs], and 42 poorly-differentiated HCCs [pd-HCCs]) were subjected to a comparison of the tumors' arterial vascularity (non-, slightly-, or markedly-hypervascular) determined on dynamic magnetic resonance imaging (MRI) and the ADC was measured retrospectively., Results: The pd-HCCs (1.05±0.16 × 10-3 mm2/s) had a significantly lower ADC than md-HCCs (1.16±0.21 × 10-3 mm2/s; p = 0.010), but there was no significant difference compared to wd-HCCs (1.11±0.18 × 10-3 mm2/s; p = 0.968). The mean ADC was significantly higher in markedly hypervascular lesions (1.20±0.20 × 10-3 mm2/s) than in nonhypervascular lesions (0.95±0.14 × 10-3mm2/s; p<0.001) or slightly hypervascular lesions (1.04±0.15 × 10-3mm2/s; p<0.001). The ADC values and arterial vascularity were significantly correlated in wd-HCCs (p = 0.005) and md-HCCs (p<0.001). The mean ADC of pd-HCCs was significantly lower than those of other lesions, even in the markedly hypervascular lesion subgroup (p = 0.020)., Conclusion: Although pd-HCC constantly shows low ADCs regardless of arterial vascularities, ADCs cannot stably stratify histopathologic tumor grades due to the variable features of wd-HCCs; and the ADC should be used with caution as a tumor biomarker of HCC.

Purpose: To investigate the very long-term (> 5 years) follow-up changes of hepatic cavernous hemangiomas and to evaluate possible determinant factors for the changes., Materials and Methods: Among 1115 consecutive patients suspected of having hepatic hemangiomas based on imaging features, 101 patients with comparable computed tomography or magnetic resonance imaging data during a 5-year follow-up interval in the Picture Archiving and Communication System were analyzed. Two radiologists independently determined the largest dimension of each lesion on axial images. In addition to background liver fibrosis or steatosis on imaging, histories of use of chemotherapeutic agents were checked from the patients' records. The final size change of the hemangioma was categorized into three groups compared with the initial diameter (increased, > 120%; no change, 80-120%; decreased, < 80%)., Results: Among the 101 hemangiomas, 32 lesions (31.7%) were enlarged and 21 lesions (20.8%) were shrunken during intervals of 60-157 (median, 81) months. Younger patients showed a higher prevalence of lesion enlargement (mean age: enlarged, 47.3 years; no change, 52.8 years; shrunken, 57.1 years; p = 0.003). In 15 patients with cirrhosis, the lesions (shrunken, n = 7; enlarged, n = 1) showed a higher tendency of size decrease (p = 0.009), whereas other factors did not show statistical significance (p > 0.05). Only a minor proportion (1%, n = 1) of the lesions showed size fluctuation during follow-up., Conclusion: During the long-term (5-13 years) follow-up, about 50% of the hepatic hemangiomas were enlarged or shrunken to > 20% of the initial diameter. Aside from the cirrhosis and aging factors, the size changes seemed sporadic.

Background: Concurrent chemoradiation therapy (CCRT) followed by hepatic arterial infusional chemotherapy (HAIC) was reported to be effective for advanced hepatocellular carcinoma (HCC) with portal vein thrombosis. However, transarterial chemoembolization (TACE) is not preferred in this setting. The aim of this study was to assess the factors affecting survival after CCRT, including additional TACE during repeated HAIC., Methods: Thirty-eight patients who underwent CCRT as the initial treatment for Barcelona Clinic Liver Cancer stage C HCC with vascular invasion between 2009 and 2016 were reviewed retrospectively. During CCRT, 5-fluorouracil (5-FU) was infused via chemoport during the first and last five days of five weeks of external beam radiation therapy. After CCRT, repeated HAIC with cisplatin and 5-FU was performed monthly. Nineteen patients (50%) underwent additional TACE between repeated HAICs. Factors related to overall survival and progression free survival (PFS) were analyzed., Results: The mean age of patients was 55 years (male:female, 33:5). Underlying liver diseases were hepatitis B, hepatitis C and non-B/C in 29, 1 and 8 patients, respectively. The median radiation dose was 4500 cGy. The objective response (OR) rate at one months after CCRT was 36.8%. The median PFS was 7.4 (range, 1.8 - 32.1) months. The median overall survival was 11.6 (range 2.8-65.7) months. Achieving an OR after CCRT (hazard ratio [HR], 0.028; P < 0.001), additional TACE (HR, 0.134, P < 0.001), and further rounds of HAIC (HR, 0.742, P = 0.001) were independent significant factors related to overall survival. The overall survival duration of patients with an OR after CCRT (median 44.2 vs. 6.6 months, P < 0.001) and additional TACE (median 19.8 vs. 9.1 months, P = 0.001) were significantly greater than those without an OR after CCRT or additional TACE., Conclusion: Patients who achieved an OR after CCRT, underwent additional TACE, and were subjected to repeated rounds of HAIC following CCRT showed better survival after CCRT for advanced stage of HCC with vascular invasion. A further prospective study is needed to confirm the positive effect of additional TACE after CCRT.

Plentiful studies have established a close association between aberrant phosphorylation and hepatocellular carcinoma (HCC). Here, we applied a quantitative phosphoproteomics platform combining dimethylation labeling and online 3D strong cation exchange chromatography (SCX)-titanium oxide (TiO 2 )/RP-LTQ-Orbitrap to compare phosphoproteomes between three pairs of HCC tissues and non-tumor counterparts. This analysis yielded 7868 quantifiable phosphopeptides and numerous up- or down-regulated candidates. Increased phosphorylation of LMNA and NIPA was confirmed using specific antibodies. To expand our verification capability, we evaluated the use of LTQ-Orbitrap run in SIM/Accurate inclusion mass screening (AIMS) mode with a super-SILAC mixture as an internal standard to quantify a subset of phosphopeptide candidates in HCC tissue samples. In sample I used for discovery experiment, we successfully quantified 32 (in SIM mode) and 30 (in AIMS mode) phosphopeptides with median coefficients of variation (CVs) of 7.5% and 8.3%, respectively. When the assay was applied to other three pairs of HCC specimens for verification experiment, 40 target phosphopeptides were quantified reliably (~7.5% CV), and more than half of them were differentially expressed between tumor and adjacent non-tumor tissues. Collectively, these results indicate the feasibility of using super-SILAC mix-SIM/AIMS assays for targeted verification of phosphopeptides discovered by large-scale phosphoproteome analyses of HCC specimens., Significance: In this study, we developed a strategy for conducting both discovery and targeted verification of deregulated phosphoproteins in HCC tissue specimens on LTQ-Orbitrap. This strategy allowed us to generate a quantitative HCC tissue phosphoproteome dataset containing significantly deregulated phosphoproteins that represents a valuable resource for the identification of potential HCC biomarkers and/or therapeutic targets. Furthermore, our proof-of-concept experiments demonstrated the feasibility of applying LTQ-Orbitrap, operated in SIM/AIMS mode, to multiplex and targeted verification of phosphopeptides in individual tissue specimens using a super-SILAC mix as an internal phosphopeptide standard. This method could be readily applied to verify dozens of phosphopeptide candidates in a larger HCC sample set., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Aim: To validate the usefulness of diffusion-weighted imaging (DWI) in the differentiation of high-flow haemangiomas showing pseudo-washout appearance on gadoxetic acid-enhanced hepatic MRI from small hypervascular hepatocellular carcinomas (HCCs)., Materials and Methods: DWI (b=50, 800 s/mm 2 ) with apparent diffusion coefficient (ADC) maps for 50 haemangiomas (6.4±2.9 mm) showing intense enhancement on arterial dominant phase imaging and hypointensity on transitional and/or hepatobiliary phase imaging during gadoxetic acid-enhanced MRI were retrospectively analysed and compared with that of 113 hypervascular HCCs (12.8±3.7 mm). In addition to measurement of mean ADC values on DWI and contrast-to-noise ratio (CNR) on corresponding T2-weighted imaging, qualitative analysis of DWI was performed for each lesion by two independent observers using a five-point scale., Results: Both of mean ADC value (1.902 versus 0.997×10 -3  mm 2 /s) and mean CNR (119.2 versus 36.9) for haemangioma were significantly larger than for HCC (p<0.001). On receiver operating characteristic (ROC) analysis, an area under the curve (AUC) of 0.995 for ADC values was significantly larger than 0.915 for CNRs (p=0.002). When the ADC value of 1.327×10 -3  mm 2 /s was used as the threshold for the diagnosis of haemangioma, the sensitivity and specificity were 98% and 97.3%, respectively. The mean sensitivity and specificity of qualitative analysis for the differentiation of haemangioma from HCC were 92% and 99.1%, respectively., Conclusion: For high-flow small haemangiomas showing pseudo-washout appearance during gadoxetic acid-enhanced hepatic MRI, high b-factor DWI including an ADC map may provide additional information to enhance the confidence to exclude small hypervascular HCCs., (Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Objectives: To compare 10-minute (min) delayed hepatocyte phase imaging (HPI) using a 30° flip angle (FA) (10m-FA30) and 20-min delayed HPI using a 10° FA (20m-FA10) or 30° FA (20m-FA30) in Gd-EOB-DTPA-enhanced MRI in patients with chronic hepatitis or cirrhosis, in terms of lesion-to-liver contrast-to-noise ratio (CNR) for hepatocellular carcinoma (HCC) and detection sensitivity for focal hepatic lesions (FHLs)., Materials and Methods: One hundred and four patients with 168 HCCs and 55 benign FHLs who underwent Gd-EOB-DTPA-enhanced MRI with 10m-FA30, 20m-FA10, and 20m-FA30 were enrolled. Patients were divided into two groups according to the Child-Pugh classification: group A with chronic hepatitis or Child-Pugh A cirrhosis and group B with Child-Pugh B or C cirrhosis. Lesion-to-liver CNR for HCCs was compared between 10m-FA30 and 20m-FA10 or 20m-FA30 for each group. The presence of FHLs was evaluated using a four-point scale by two independent reviewers, and the detection sensitivity was analyzed., Results: In group A, the CNR for HCCs (n = 86) on 10m-FA30 (165.8 ± 99.7) was significantly higher than that on 20m-FA10 (113.4 ± 71.4) and lower than that of 20m-FA30 (210.2 ± 129.3). However, there was no significant difference in the sensitivity of FHL detection between 10m-FA30 (mean 95.0% for two reviewers) and 20m-FA10 (94.7%) or 20m-FA30 (94.7%). In group B, the CNR (54.0 ± 36.4) for HCCs (n = 57) and the sensitivity (94.2%) of FHL detection for 10m-FA30 were significantly higher than those for 20m-FA10 (41.8 ± 36.4 and 80.8%, respectively) and were not different from those for 20m-FA30 (62.7 ± 44.4 and 93.3%, respectively)., Conclusion: The diagnostic performance of 10m-FA30 was similar to or higher than 20m-FA10 or 20m-FA30 in both groups A and B. This finding indicates that 10m-FA30 could replace 20-min delayed HPI regardless of patient liver function and reduce the delay time by 10 minutes., Competing Interests: The authors have declared that no competing interests exist.

Objective: To validate the diffusion-weighted MRI (DWI) for differentiation of benign from malignant portal vein thrombosis., Materials and Methods: The Institutional Review Board approved this retrospective study and waived informed consent. A total of 59 consecutive patients (52 men and 7 women, aged 40-85 years) with grossly defined portal vein thrombus (PVT) on hepatic MRI were retrospectively analyzed. Among them, liver cirrhosis was found in 45 patients, and hepatocellular carcinoma in 47 patients. DWI was performed using b values of 50 and 800 sec/mm(2) at 1.5-T unit. A thrombus was considered malignant if it enhanced on dynamic CT or MRI; otherwise, it was considered bland. There were 18 bland thrombi and 49 malignant thrombi in 59 patients, including 8 patients with simultaneous benign and malignant PVT. Mean apparent diffusion coefficients (ADCs) of benign and malignant PVTs were compared by using Mann-Whitney U test. Diagnostic accuracy was evaluated using receiver operating characteristic (ROC) curve analysis., Results: The mean ADC ± standard deviation of bland and malignant PVT were 1.00 ± 0.39 × 10(-3) mm(2)/sec and 0.92 ± 0.25 × 10(-3) mm(2)/sec, respectively; without significant difference (p = 0.799). The area under ROC curve for ADC was 0.520. An ADC value of > 1.35 × 10(-3) mm(2)/sec predicted bland PVT with a specificity of 94.6% (95% confidence interval [CI]: 84.9-98.9%) and a sensitivity of 22.2% (95% CI: 6.4-47.6%), respectively., Conclusion: Due to the wide range and considerable overlap of the ADCs, DWI cannot differentiate the benign from malignant thrombi efficiently.

Objectives: To compare 10-minute delayed hepatocyte phase imaging using a 30° flip angle (10 min-FA30) and 20-minute hepatocyte phase imaging using a 10° FA (20 min-FA10) in gadoxetic acid-enhanced MRI of patients with possible liver metastases, regarding lesion-to-liver contrast-to-noise ratio (CNR) and focal hepatic lesion (FHL) detection to evaluate whether 10 min-FA30 would be superior to 20 min-FA10., Materials and Methods: Eighty-three patients with 248 liver metastases and 78 benign FHLs who underwent gadoxetic acid-enhanced MRI with 10 min-FA30 and 20 min-FA10 were enrolled. Lesion-to-liver CNRs were compared between the two image groups. Two radiologists independently assessed the presence of FHLs using a four-point scale and detection sensitivity was calculated., Results: The mean CNR for liver metastases on the 10 min-FA30 (248.5 ± 101.6) were significantly higher than that of the 20 min-FA10 (187.4 ± 77.4) (p < 0.001). The mean CNR difference between the two image groups was 61.2 ± 56.8. There was no significant difference in detection sensitivity of FHLs for two readers between 10 min-FA30 (mean 97.7%) and 20 min-FA10 (mean 97.9%), irrespective of the lesion size or malignancy., Conclusion: 10 min-FA30 yielded higher CNR with similar sensitivity compared to 20 min-FA10. This finding indicates that 10 min-FA30 can potentially replace 20 min-FA10 with higher diagnostic performance and save 10 minutes of time.

The role of the unfolded protein response (UPR) in tissue homeostasis remains largely unknown. Here we find that loss of Mst1/2, the mammalian Hippo orthologues, or their regulator WW45, leads to a remarkably enlarged endoplasmic reticulum (ER) size-associated UPR. Intriguingly, attenuation of the UPR by tauroursodeoxycholic acid (TUDCA) diminishes Mst1/2 mutant-driven liver overgrowth and tumorigenesis by promoting nuclear exit and degradation of Hippo downstream effector Yap. Yap is required for UPR activity and ER expansion to alleviate ER stress. During the adaptive stage of the UPR, PERK kinase-eIF2α axis activates Yap, while prolonged ER stress-induced Hippo signalling triggers assembly of the GADD34/PP1 complex in a negative feedback loop to inhibit Yap and promote apoptosis. Significantly, the deregulation of UPR signals associated with Yap activation is found in a substantial fraction of human hepatocellular carcinoma (HCC). Thus, we conclude Yap integrates Hippo and UPR signalling to control liver size and tumorigenesis.

Background/aims: To assess the perfusion parameters and angiogenesis of HCC using dynamic contrast enhanced(DCE) MR and to correlate it with histopathologic findings in an experimental rat model., Methodology: Twenty rats were continuously infused with diethylnitrosamine (DEN) for tumor induction. After 32 to 36 weeks of DEN treatment, the rats underwent MRI of the liver with a 3-T MR imaging system. Perfusion parametric maps and perfusion parameters such as, time to peak (TTP) and peak enhancement (PE) were obtained by using a commercially available software package. The nodules were correlated precisely to DCE MR images., Results: A total of 13 nodules were found in 12 rats; 5 dysplastic nodule (DN)s were identified in 5 rats and 8 HCCs (3 Edmonson grade I, 2 Edmonson grade I-II, 3 Edmonson grade II) were found in 7 rats. There were significant differences in mean values of PE and HPH (histogram peak height) of PE between DN and HCC. Mean value and HPH of PE showed statistically significant correlation with tumor grade., Conclusions: There were significant differences in perfusion parameters between DN and HCC. DCE MR imaging can be used in the differential diagnosis and management of liver disease in hepatocarcinogenesis.

Objective: To investigate the relationships between the apparent diffusion coefficients (ADCs) on diffusion-weighted imaging (DWI) and the speed of contrast-enhancement in hepatic hemangiomas., Materials and Methods: Sixty-nine hepatic hemangiomas (≥ 1 cm) were evaluated with DWI, by using multiple b values (b = 50, 400, 800 s/mm(2)), followed by a gadolinium-enhanced dynamic MRI. The lesions were classified into three groups, according to the speed of contrast-enhancement on the portal phase. ADCs were measured on the ADC map automatically, and were calculated by using the two different b values (mADC(50-400) with b values = 50 and 400; mADC(400-800) with b values = 400 and 800 s/mm(2))., Results: The mean ADCs (× 10(-3) mm(2)/s) were significantly higher in the rapid group (1.9 ± 0.44) than in the intermediate (1.7 ± 0.35, p = 0.046) or the slow groups (1.4 ± 0.34, p = 0.002). There were significant differences between the rapid and the slow groups in mADC(50-400) (2.12 vs. 1.48; p = 0.008) and mADC(400-800) (1.68 vs. 1.22, p = 0.010), and between the rapid and the intermediate groups in mADC(50-400) (2.12 vs. 1.79, p = 0.049). Comparing mADC(50-400) with mADC(400-800), there was a significant difference only in the rapid group (p = 0.001)., Conclusion: Higher ADCs of rapidly-enhancing hemangiomas may be related to richer intralesional vascular perfusion. Also, the restricted diffusion may be attributed to the difference of structural characteristics of hemangioma.

Objective: To compare the value of diffusion-weighted MRI (DWI) with the venous "washout" appearance during dynamic MRI for the assessment of small arterial hypervascular lesions in cirrhotic liver., Methods: After exclusion of benign hypervascular lesions, including haemangiomas and subcapsular non-tumorous arterioportal shunts, indicated by typical imaging features, a total of 109 small arterial hypervascular lesions (0.5-3.0 cm in the longest diameter) in 65 patients with cirrhosis who underwent gadopentetate dimeglumine-enhanced dynamic MRI and DWI (b=50, 400, 800 s mm(-2)) at 1.5 T during a 16-month period were retrospectively analysed to determine the presence of venous washout during dynamic imaging or sustained hyperintensity upon increasing the b factor size on DWI., Results: Among the 99 hypervascular hepatocellular carcinomas (HCCs), sustained hyperintensity on DWI (92/99, 93%) was more prevalent than the washout appearance (72/99, 72%) on dynamic MRI (p<0.001). Depending on the lesion size, subcentimetre-sized HCCs had a significantly lower prevalence of venous washout (13/30, 43%) than the sustained hyperintensity on DWI (27/30, 90%) (p=0.001). In all 10 hypervascular benign conditions, there was no venous washout on dynamic MRI and no sustained hyperintensity on DWI. Sensitivity and specificity for diagnosis of hypervascular HCCs were 92.9% and 100% in DWI and 72% and 100% in dynamic MRI, respectively., Conclusion: Compared with the venous washout during dynamic imaging, DWI provides more reliable information in the MRI assessment of small hypervascular HCCs, distinguishing them from atypical hypervascular benign or pseudolesions. DWI could complement the early diagnosis of small hypervascular HCCs that do not display venous washout during dynamic imaging.

Purpose: The purpose of our study was to validate diffusion-weighted MRI (DWI) before and after superparamagnetic iron oxide (SPIO) injection for assessment of hepatic metastases., Materials and Methods: Eighty-six hepatic metastases (size range, 0.3-4.7 cm; mean, 1.5 cm) verified pathologically or by follow-up imaging studies in 22 consecutive patients (17 men and 5 women; 44-83 years; mean age, 60 years) during a 13-month period were enrolled. Hepatic MRI, including DWI (b-factors=50, 400, 800 s/mm²) with breath-holding technique of single-shot spin-echo echo-planar imaging (TR/TE=1000/69 ms, average=2) before and after SPIO administration, were retrospectively reviewed by two independent radiologists with a 5-point scale confidence score for each hepatic lesion on pre-contrast DWI (pre-DWI), SPIO-enhanced DWI (SPIO-DWI), and SPIO-enhanced T2*-weighted imaging (SPIO-T2*wI)., Results: For all lesions, SPIO-T2*wI showed significantly higher confidence score in the diagnosis of hepatic metastases than pre-contrast or SPIO-DWI regardless of the size of b-factors (p<0.05) with only one exception; using b-factor=50 s/mm², the score of SPIO-T2*wI was still higher than SPIO-DWI but there was no statistical significance given by observer 1 (p=0.730). For the subcentimeter lesions (n=37), SPIO-T2*wI showed the highest score, and using b-factor= 50 or 400 s/mm² SPIO-DWI showed similar confidence scores to SPIO-T2*wI by both observers (p>0.05). Pre-DWI using b-factor=50 sec/mm² was also comparable with SPIO-T2*wI by observer 1 (p=0.060)., Conclusion: Pre-DWI has a limited value for the assessment of hepatic metastases, however, the repetition of DWI after SPIO injection using small b-factors could complement SPIO-T2*wI, especially for subcentimeter lesions.

Purpose: The purpose was to validate diffusion-weighted imaging (DWI) in the assessment of hepatic metastases compared with superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance imaging., Materials and Methods: For 21 consecutive patients with 160 metastases from extrahepatic malignancy and 25 benign focal lesions, two radiologists evaluated four separate review sessions (I, SPIO-enhanced T2-weighted images; II, precontrast DWI; III, SPIO-enhanced T2-weighted images and precontrast DWI; IV, SPIO-enhanced T2-weighted images plus precontrast and SPIO-enhanced DWI) and assigned confidence levels using a five-grade scale for each hepatic lesion., Results: The A(z) values after receiver operating characteristic curve analysis for Reader 1 and Reader 2 were 0.80 and 0.75 on session I, 0.91 and 0.91 on session II, 0.97 and 0.96 on session III and 0.96 and 0.96 on session IV, respectively. The A(z) value of session II was significantly higher than that of session I (Reader 1, P=.004; Reader 2, P<.001), and that of session III was significantly higher than that of session I (P<.001 for each reader) or session II (Reader 1, P=.004; Reader 2, P=.003). Although there was no significant difference of A(z) value between session III and session IV (Reader 1, P=.231; Reader 2, P=.878), the sensitivity improved for session IV compared with that for session III (Reader 1, P=.031; Reader 2, P=.039)., Conclusion: In the assessment of hepatic metastases, DWI can provide more accurate information than can SPIO-enhanced images. Diagnostic accuracy can be increased even more through the combination of both techniques., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: The purpose of the study was to validate diffusion-weighted imaging (DWI) in the assessment of hypervascular hepatocellular carcinoma (HCC) compared with superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance imaging (MRI) in the cirrhotic liver., Material and Methods: Forty-six consecutive patients with 106 hypervascular focal lesions in the cirrhotic liver who underwent DWI using three b factors and gadopentetate dimeglumine-enhanced dynamic MRI followed by SPIO-enhanced MRI were enrolled. Two independent radiologists evaluated two separated image sets (SPIO set, dynamic MRI and SPIO-enhanced T2*-weighted images; DWI set, DWI and dynamic MRI) and assigned confidence levels for diagnosis of HCC using a five-point scale for each lesion. Area under the receiver operating characteristic curve (A(z)) was calculated for each image set., Results: The A(z) value of the DWI set was larger than the SPIO set by both readers (reader 1, 0.936 vs. 0.900, P=.050; reader 2, 0.938 vs. 0.905, P=.110). For the sensitivity (reader 1, 93.1% vs. 86.2%, P=.146; reader 2, 95.4% vs. 88.5%, P=.070) and specificity (reader 1, 89.5% vs. 73.7%, P=.250; reader 2, 79.0% vs. 73.7%, P=1.000) of HCC diagnosis, DWI sets were superior to SPIO sets without statistically significant differences., Conclusion: For assessment of hypervascular HCC, DWI in combination with dynamic MRI provides comparable or slightly better information compared with the combination of dynamic and SPIO-enhanced MRI., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: The purpose of our study was to compare diffusion-weighted MR imaging (DWI) with conventional dynamic MRI in terms of the assessment of small intrahepatic metastases from hepatocellular carcinoma (HCC)., Materials and Methods: In 24 patients with multifocal, small (≤2 cm) intrahepatic metastatic foci of advanced HCC, a total of 134 lesions (≤1 cm, n=81; >1 cm, n=53) were subjected to a comparative analysis of hepatic MRI including static and gadopentetate dimeglumine-enhanced dynamic imaging, and DWI using a single-shot spin-echo echo-planar MRI (b values=50, 400 and 800 s/mm(2)), by two independent reviewers., Results: A larger number of the lesions were detected and diagnosed as intrahepatic metastases on DWI [Reviewer 1, 121 (90%); Reviewer 2, 117 (87%)] than on dynamic imaging [Reviewer 1, 107 (80%); Reviewer 2, 105 (78%)] (P<.05). For the 81 smaller lesions (≤1 cm), DWI was able to detect more lesions than dynamic imaging [Reviewer 1, 68 (84%) vs. 56 (69%), P=.008; Reviewer 2, 65 (80%) vs. 55 (68%), P=.031], but there was no statistically significant difference between the two image sets for larger (>1 cm) lesions., Conclusion: Due to its higher detection rate of subcentimeter lesions, DWI could be considered complementary to dynamic MRI in the diagnosis of intrahepatic metastases of HCCs., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: The purpose of our study was to evaluate the usefulness of superparamagnetic iron oxide (SPIO)-enhanced MRI for distinguishing focal eosinophilic necrosis (FEN) from hepatic metastasis., Materials and Methods: Forty-one cases of FEN in 41 patients and 40 hepatic metastases in 40 patients were analyzed on unenhanced and SPIO-enhanced T2-weighted MRI retrospectively. Depending on the extent of the remaining hyperintense area on SPIO-enhanced T2-weighted images compared with the unenhanced images, the lesions were classified into four categories--category 1, less than 25%; category 2, 25-49%; category 3, 50-75%; and category 4, more than 75%--by two independent readers. Contrast-to-noise ratio (CNR) was measured using the same region of interest on unenhanced and SPIO-enhanced T2-weighted images. In three pathologic specimens of FEN, the number of Kupffer cells was compared with that of background hepatic parenchyma., Results: All metastases were classified as category 4, whereas FEN showed various distributions overall (category 1, 45.2%; category 2, 24.6%; category 3, 13.4%; category 4, 17.1%). FEN showed a decrease in CNR (from 7.9 +/- 5.8 to 6.1 +/- 5.6, p < 0.05), and metastases showed an increase in CNR (from 33.7 +/- 27.0 to 55.0 +/- 44.3, p < 0.05) after SPIO administration. In biopsy specimens, FEN had many more Kupffer cells (174.7 +/- 120.3 cells/high-power field [hpf]) than background hepatic parenchyma (23.7 +/- 9.8 cells/hpf). When using signal loss categories 1, 2, or 3 or CNR decrease, the accuracy of SPIO enhancement was 88.3%., Conclusion: Unlike hepatic metastases, most of the cases of FEN showed a reduction in the extent of hyperintense area or a decrease in CNR after SPIO administration on the T2-weighted images. Therefore, SPIO-enhanced T2-weighted MRI can help to differentially diagnose FEN from metastases.

Following transcatheter arterial chemoembolisation (TACE), the appearances on CT or MR images are largely related to the chemical and ischaemic insults to the portal tract. Understanding the mechanism of TACE-induced changes is essential for radiologists in order to determine the therapeutic effect as well as to distinguish these changes from recurrent tumours. This pictorial review illustrates the haemodynamic and substantial parenchymal changes related to TACE for hepatic malignancy.

The aim of this study was to retrospectively compare the value of "washout" on dynamic MR imaging with superparamagnetic iron oxide (SPIO)-enhanced imaging features of small hepatocellular carcinoma (HCC). A total of 74 small (5-30 mm) hypervascular HCCs in 42 cirrhotic patients who underwent double contrast material-enhanced MR imaging were evaluated to determine the presence of washout in the portal or equilibrium phase of gadolinium-enhanced dynamic imaging and decreased uptake of SPIO on T2*-weighted imaging. HCCs were verified histologically (n = 13) or by serial follow-up imaging studies (n = 61). According to the size of the lesions, 27 vs. 73% (<10 mm, n = 15; P = 0.016 on McNemar test), 39 vs. 79% (10-14 mm, n = 28; P = 0.002), 50 vs. 93% (15-20 mm, n = 14; P = 0.031), and 82 vs. 100% (>20 mm, n = 17; P = 0.250) of the lesions showed washout vs. decreased SPIO accumulation respectively. The larger the lesion, the higher the prevalence of washout or decreased SPIO uptake (P = 0.004 or P = 0.036, respectively, on Mantel-Haenszel test). In many small hypervascular HCCs up to 2 cm, SPIO-enhanced MR imaging offers essential information for early diagnosis in the absence of washout on dynamic imaging.

Background: To demonstrate the characteristic feature of hepatic cavernous hemangiomas on ferucarbotran-enhanced T2-weighted MR imaging as a new diagnostic finding., Methods: In 201 hepatic lesions (61 hemangiomas, 61 cysts, 41 hepatocellular carcinomas, 31 metastatic carcinomas, and 7 cholangiocarcinomas), lesion-to-liver contrast on ferucarbotran-enhanced T2-weighted images was qualitatively compared with pre-contrast images by three independent readers using a four-grade scale (group 1, marked increase; group 2, mild increase; group 3, no change; group 4, decrease). The change in the contrast-to-noise ratio (CNR) for each lesion was quantitatively measured., Results: Only hemangiomas showed a significant decrease in CNR; 10% and 90% of the hemangiomas were categorized as group 3 and 4 lesions, respectively. Besides the hemangiomas, there was no other lesion categorized into group 4 except for one cyst. When group 4 lesions were considered hemangiomas, the accuracy of identification was 96.4%., Conclusion: Hemangiomas show a significant decrease in lesion-to-liver contrast on T2-weighted images after ferucarbotran injection, which might be another typical diagnostic imaging finding of hemangiomas distinguished from solid malignant lesions.

Purpose: To investigate the additional value of diffusion-weighted imaging (DWI) in the MRI assessment of perilesionally recurrent hepatocellular carcinomas (HCCs) after transcatheter arterial chemoembolization (TACE)., Materials and Methods: For gadopentetate dimeglumine-enhanced multiphasic dynamic images with precontrast T1- and T2-weighted images of 23 patients treated with TACE, two radiologists independently sorted the confidence levels for the presence of a viable tumor in the vicinity of the treated lesions into five grades. In another session, images from DWI (b factor = 50, 400, and 800 s/mm(2)) were added to the previously reviewed images and the same radiologists sorted the confidence levels., Results: A total of 26 lesions (0.7-3.5 cm) from 16 patients were confirmed to be perilesional recurrences of HCC. The area under the receiver operating characteristic curve (A(z)) for the second interpretation session (0.826) was not significantly different (P = 0.299) from that of the first session (0.859). The overall sensitivity was increased from 85% to 92%, but the specificity decreased from 65% to 50% after adding DWI., Conclusion: The addition of DWI has the potential to improve sensitivity, but not the overall diagnostic accuracy, in the assessment of perilesional recurrence of HCCs after chemoembolization., ((c) 2009 Wiley-Liss, Inc.)

Objective: The purpose of this article is to show the imaging findings of variant types of hepatocellular carcinoma (HCC) with pathologic correlations., Conclusion: The variant types of HCC may not share its typical imaging characteristics. An understanding of the radiologic findings for variant types of HCC can be helpful in the differential diagnosis of hepatic tumors.

Objective: The purpose of this study was to investigate the early manifestation of hypervascular hepatocellular carcinomas by means of evaluating the "nodule-in-nodule" hepatic lesions depicted on dynamic computed tomography., Methods: For 26 lesions with hypervascular foci in nonhypervascular nodules in 23 patients with cirrhotic liver, the size of the lesions was measured during the initial and follow-up studies in patients who had a comparable follow-up computed tomography or magnetic resonance imaging studies (ranging from 46 to 399 days)., Results: The mean volume doubling time of the total 26 inner nodules was 36 days, which was significantly shorter than the doubling time for the outer nodules (mean, 257 days for 18 enlarged lesions) (P < 0.001)., Conclusions: Because of the rapid progression of the inner hypervascular hepatocellular carcinomas, recognition of nodule-in-nodule lesions is essential for considering short-term follow-up or immediate treatment when managing patients with cirrhosis.

Aim: To determine the fate and clinical implication of large (>or=2 cm), non-hypervascular nodules depicted on magnetic resonance imaging (MRI) in the cirrhotic liver., Materials and Methods: In 21 patients with cirrhosis (14 hepatitis B, two ethanol abuse, four cryptogenic, one Wilson's disease), 25 large (>or=2 cm in the longest dimension) non-hypervascular nodules were identified on dynamic MRI. The implications for diagnosis of the initial size, contour, and signal characteristics on MRI in addition to patients' age and cause of cirrhosis were assessed in our analysis., Results: Twelve (75%) out of 16 lesions were malignant or potentially-malignant from 14 hepatitis B patients, while seven (78%) of the nine lesions from other patients were benign (p=0.016). The mean age of the patients who had malignant or potentially malignant lesions (57 years) was older than that for the other patients (47 years; p=0.039). The ratio of the short-to-long diameter was higher in malignant or potentially malignant lesions (mean 0.86) than in benign lesions (mean 0.69; p=0.008). There was no discriminative signal intensity characteristic (p>0.2 for all factors) that indicated the malignant potential for each non-hypervascular nodule. For all 10 lesions in the hepatitis B patients who were older than 52 years with a short-to-long diameter ratio of more than 0.75, the positive predictive value for malignant potential based on these three combined factors was 100%., Conclusion: In older patients with cirrhosis from hepatitis B, large (>or=2 cm), non-hypervascular nodules with a spherical contour have a high malignant potential.

Objective: To evaluate the imaging and clinical findings of pathologically proven sarcomatoid hepatocellular carcinoma (HCC) in 11 cases., Methods: We retrospectively reviewed the imaging findings and clinical features of 11 patients with pathologically proven sarcomatoid HCC at 2 university-based tertiary institutions from July 1997 to June 2006., Results: The most common gross morphologies of sarcomatoid HCC were massive expanding pattern (n = 6 [54%]) or multinodular confluent (n = 5 [46%]) with partial encapsulation (n = 9 [82%]). The most common enhancement pattern was peripheral enhancement with central necrosis (n = 8 [72%]) without a dominant dynamic pattern of enhancement. Six (54%) of 11 patients were positive for hepatitis B surface antigen or hepatitis C virus antibody. Only 1 patient (9%) had more than 500 ng/mL of preoperative serum alpha-fetoprotein., Conclusions: In a patient with low-level alpha-fetoprotein and no history of viral hepatitis, sarcomatoid HCC usually presents as a large mass with peripheral enhancement, central necrosis, variable enhancement of the solid portion with or without tumor capsule, and intrahepatic metastasis.

Aim: To describe the computed tomography (CT) and magnetic resonance imaging (MRI) findings that differentiate solid pseudopapillary carcinomas (SPC) from benign solid pseudopapillary tumours (SPT) of the pancreas., Materials and Methods: Preoperative CT or MRI images for 26 patients (eight patients with SPC and 18 patients with SPT) were retrospectively reviewed. In addition to the general morphological features, the presence of pancreatic duct dilation, vascular invasion, and extrapancreatic metastases were comparatively assessed., Results: There were no significant differences between pancreatic SPC and benign SPT with respect to tumour size, location, capsule thickness, internal composition, and pattern of calcification, nor was there any correlation with the age and gender of the patients. Pancreatic duct dilation was present in four of the eight (50%) SPC patients, and was absent in all benign SPT patients (p=0.005). Vascular encasement by the tumour (n=2) and hepatic metastases (n=2) were also exclusively demonstrated in SPC patients. Multivariate logistic regression analysis showed that pancreatic duct dilation (p=0.001), vessel encasement (p=0.027), and metastasis (p=0.027) were the variables that can be used to differentiate SPC from benign SPT., Conclusion: SPC of the pancreas may help to differentiate from benign SPT using the imaging features of aggressive behaviour of pancreatic duct dilation and vessel encasement with or without extrapancreatic metastases.

Background: Characterization of small nodules in the cirrhotic liver is always challenging in clinical practice. In the differential diagnosis of small hypervascular lesions, it has been reported that portal venous or delayed hypointensity is a useful sign to characterize hepatocellular carcinomas (HCCs) during dynamic magnetic resonance (MR) imaging. However, few studies have assessed the diagnostic value of this sign., Purpose: To determine the diagnostic value of portal-phase (PP) and delayed-phase (DP) images for the diagnosis of small hypervascular HCCs during intravenous (IV) contrast-enhanced dynamic MR imaging of cirrhotic liver., Material and Methods: A total of 69 small (6-20 mm) hypervascular HCCs in 53 cirrhotic patients were subjected to a retrospective analysis of the signal intensities (hypo-, iso-, or hyperintense) and rim enhancement on PP and 5-min DP images from three-phased dynamic MR imaging according to the pre-contrast T1- and T2-weighted imaging features. After exclusion of 33 subcapsular wedge-shaped pseudolesions and three hemangiomas by typical imaging features, 74 centrally located small hypervascular benign or pseudolesions were used as a control group for comparative analyses., Results: The sensitivities of PP hypointensity, DP hypointensity, and rim enhancement in the diagnosis were 11%, 29%, and 18%, respectively, for 6-10-mm hypervascular HCCs, and 42%, 63%, and 58%, respectively, for 16-20-mm lesions. After exclusion of the 48 lesions showing T2-weighted hyperintensity (HCCs, n = 39; benign lesions, n = 9), the overall sensitivity for diagnosis of small hypervascular HCCs decreased (8.3%, 25.0%, and 8.3%, respectively)., Conclusion: Although DP provides a better sensitivity than PP, both PP and DP have very limited diagnostic value for diagnosis of small hypervascular HCCs during dynamic MR imaging of the cirrhotic liver.

The purpose of this study was to investigate the natural history of transcatheter arterial chemoembolization (TACE)-induced, transient hepatic attenuation difference (THAD). Among the patients who underwent TACE for treatment of hepatocellular carcinomas during a 32-month period, 32 patients with 40 newly developed THADs defined as localized, transient, peripheral hepatic parenchymal enhancement during the hepatic arterial phase of dynamic CT (axial dimension, 1.9-8.8 cm; mean, 4.9 cm) in the vicinity of iodized-oil accumulation were subjected to a retrospective analysis of serial follow-up CT examinations. Among the 40 TACE-induced THADs, 18 (45%) and 9 (23%) were accompanied with arterial-portal venous fistula (APF) and portal venous stenosis (PVS), respectively, while 2 (5%) THADs showed both APF and PVS simultaneously. Thirty-eight (95%) THADs disappeared spontaneously during the follow-up period (range, 4-26 months; mean, 9 months), and 11 (29%) of them showed progressive atrophy of the corresponding hepatic parenchyma. Regardless of the presence of APF, 10 (91%) of 11 THADs of following parenchymal atrophy had shown PVSs (P<0.001). During the long-term follow-up period after TACE, almost all of the TACE-induced THADs spontaneously disappeared and either had or did not have corresponding parenchymal atrophy, which is strongly related to the presence of PVS. Understanding the nature of these CT features would be helpful for radiologists in determining the prognosis of the TACE-induced hepatic injuries as well as in distinguishing them from the recurrent tumour.

Objective: The objective of this study was to investigate the outcome and clinical implications of nonhypervascular hypoattenuating nodules observed on portal or equilibrium phase CT images of cirrhotic livers., Materials and Methods: One hundred one cirrhotic patients (male:female = 69:32) with hypoattenuating nodules observed on initial portal or equilibrium phase CT images were retrospectively evaluated by follow-up CT performed 6-66 months after the initial CT examination. Depending on the background nodularity, patients were separated into macronodular (n = 33, 288 nodules) and micronodular (n = 68, 346 nodules) cirrhotic groups. Each nodule was categorized as category I (enlarged) or category II (stable). Nodule categories were correlated with the initial lesion size and the pattern of background cirrhosis., Results: The frequency of category I nodules was higher in patients with micronodular cirrhosis (40%) than in those with macronodular cirrhosis (27%) (p = 0.001). Category I nodules were significantly larger than category II nodules in patients with micronodular cirrhosis (p < 0.001). The doubling times of category I nodules had no statistical difference between patients with micronodular or macronodular cirrhosis (p = 0.954). Of the category I nodules in patients with micronodular cirrhosis, 8.6% showed malignant changes., Conclusion: More careful attention should be paid to large nodules in patients with micronodular cirrhosis because of the potentially greater risk of malignancy, and small hypoattenuating nodules should be more often followed up in shorter intervals than large nodules.

Objective: Our purpose was to determine the significance of small hypervascular enhancing lesions exclusively on the arterial phase images of dynamic computed tomography in cirrhotic liver., Methods: One hundred sixty-nine enhancing lesions (>5 and <30 mm) on the arterial phase images of dynamic computed tomography in 67 patients with cirrhotic liver, not distinguished from background hepatic parenchyma on equilibrium phase images without hypoattenuation density on portal phase images, were subjected to a retrospective assessment in terms of the lesion growth in addition to the location, size, and contour of the lesions, depending on the final diagnoses of the individual lesions., Results: Twenty-eight (17%) of the 169 enhancing lesions were hepatocellular carcinomas (HCCs). All of the 43 wedge-shaped, subcapsular lesions were benign, and 126 nodular or irregular lesions were subcapsularly (benign, n = 59; HCC, n = 11) or centrally (benign, n = 39; HCC, n = 17) located. Significant differences were found between HCCs and benign lesions in terms of their shape (P = 0.002) and location (P = 0.041), and the positive and negative predictive values of centrally located lesions for diagnosing HCCs were 21% and 85%, respectively. The positive and negative predictive values for the diagnosis of HCC based on the lesion growth were 90% and 93%, respectively., Conclusions: Because of the low positive predictive value of non-wedge-shaped, centrally located, early enhancing lesions in the diagnosis of HCC, the serial follow-up for examining lesion growth is essential to the correct diagnosis of small arterial hypervascular lesions in cirrhotic liver.

In immunohistochemically-proven hepatic inflammatory myofibroblastic tumors, MRI revealed layered patterns of contrast enhancement during dynamic imaging, consisting of outer hypovascular rind and inner hypervascular stroma and mimicking the imaging features of pyogenic organized abscess with deficient central necrosis in four lesions in two patients. For the outer hypovascular rind, T2-weighted images showed hyperintensity, suggesting immature fibrosis corresponding to the area of arterial hypovascularity and delayed contrast enhancement. The patients' favorable clinical course and imaging findings reflected the benign nature of these lesions, from an infectious origin, despite the phenotypic expression of myofibroblastic proliferation in the hypervascular stroma containing chronic inflammatory cells., ((c) 2007 Wiley-Liss, Inc.)

Objective: The purpose of this study was to determine the ability of MRI to predict malignancy in fat-containing nodules in the cirrhotic liver., Materials and Methods: In 38 patients with cirrhotic livers, focal lesions > or = 5 mm containing fatty components were identified on chemical shift gradient-echo MRI. Positive predictive values (PPVs) for benignity and malignancy were calculated on the basis of lesion size, T1-weighted hypointensity, T2-weighted hyperintensity, and arterial hypervascularity on the initial MR images. The number of the fatty nodules (group A, up to 4; group B, numerous) in individual patients was also correlated with the malignant potential of the lesions that were verified pathologically or by follow-up imaging studies., Results: In 31 group A patients, 21 (47%) of the 45 lesions showed a malignant course, and their mean diameter (18.8 mm) was larger (p = 0.007) than that (10.5 mm) of benign lesions. In seven group B patients, all 35 lesions (the five largest lesions in each patient; mean diameter, 7.8 mm) proved to be benign. The PPV of larger (> or = 15 mm) fat-containing nodules for malignancy was 85% (11/13 lesions). Six (55%) of 11 immediately diagnosed hepatocellular carcinomas were entirely hypointense on unenhanced in-phase T1-weighted images. The PPV of T2-weighted hyperintensity and arterial hypervascularity for the diagnosis of malignancy was 100% in group A patients., Conclusion: In the cirrhotic liver, large size (> or = 15 mm) and T1-weighted hypointensity on in-phase images strongly suggest malignancy of the fat-containing nodules. The presence of numerous nodules < 1 cm suggests that the lesions are benign.

Purpose: The purpose of this work was to describe the initial magnetic resonance (MR) imaging findings obtained before an imaging diagnosis of overt hepatocellular carcinoma (HCC) in the chronically damaged liver., Methods: One hundred fifty-two newly diagnosed HCCs diagnosed by dynamic computed tomography (n = 111) or by MR imaging (n = 41), in addition to digital subtraction hepatic arteriography, in 96 patients were subjected to analysis of their MR imaging features within the previous 2 years., Results: Ninety-seven (64%) HCC cases showed no focal lesions distinguishable from background hepatic parenchyma in MR images taken before the indication of typical HCC. The remaining 55 (36%) lesions were readily identified in earlier images and were categorized into 3 groups: nonhypervascular lesions (category I, n = 6), lesions with partially hypervascular foci of "nodule-within-nodule" appearance (category II, n = 12), and homogeneously hypervascular and/or T2-weighted hyperintense lesions (category III, n = 37). The size and doubling time of category III lesions (0.7 cm, 154 days) were smaller and shorter than those of the other lesions (1.2 cm, 377 days)., Conclusions: Before the imaging diagnosis of HCCs, the premalignant or early malignant lesions can be found on the prior MR images just in the minority of the lesions in the cirrhotic liver.

Objective: Our purpose was to determine whether the perilesional parenchymal enhancement of hepatic metastases could be correlated with tumoral enhancement on arterial phase images or tumor size on dynamic MRI., Materials and Methods: One hundred thirty-four lesions of hepatic metastases in 44 patients were subjected to a retrospective analysis of the dynamic MR images obtained with 3D spoiled gradient-echo sequences. The thickness of the enhancing rim on arterial phase images was regarded as a summation of the enhancing component of tumor periphery and perilesional enhancement, which were estimated by the tumor size on precontrast T1-weighted images. The presence of wedge-shaped perilesional enhancement was also correlated with the lesion size., Results: Except for 17 diffusely enhanced lesions, lesion size was comparable between the lesions with (n = 87; 26 +/- 19 [SD] mm) and without rim enhancement (n = 30; 27 +/- 23 mm) on the arterial phase dynamic MR images (p > 0.05). The degree of peripheral tumoral enhancement showed an inverse correlation (r = -0.389) with the thickness of the circumferential perilesional enhancement (p < 0.001). The mean size of the lesions with wedge-shaped perilesional enhancement (n = 44; 33 +/- 20 mm) was larger than that of the other lesions (n = 90; 25 +/- 19 mm) (p = 0.016)., Conclusion: The degree of circumferential perilesional enhancement of hepatic metastases on arterial phase dynamic MR images would be independent of the lesion size but inversely correlated with the degree of peripheral tumoral vascularity. An understanding of these features may help tumor characterization and should prompt hypotheses and studies of microvascular phenomena in tumoral and epitumoral environments.

Objective: To compare the findings of magnetic resonance (MR) imaging with those of computed tomography (CT) of focal liver lesions related to peripheral eosinophilia., Methods: For 12 patients with peripheral eosinophilia (>7%) examined with hepatic MR imaging and CT, 52 focal hepatic lesions larger than 0.5 cm, including 31 lesions simultaneously found on the 2 imaging modalities, were subjected to a comparative analysis of their imaging features., Results: The total number of lesions distinguished from background liver was 39 (75%) on MR imaging and 44 (85%) on CT scans. On arterial phase images of 10 patients with comparable data, homogeneously hyperintense lesions were demonstrated more frequently (P = 0.006) on MR imaging (16 [50%] of 32 lesions) than on CT scans (4 [13%] of 32 lesions). Only 7 (22%) of the 32 hypoattenuating lesions on portal phase CT were depicted as hypointense lesions on portal phase MR images in 12 patients. On delayed phase images in 8 patients, the number of hyperintense lesions on MR images (9 [56%] of 16) was greater (P = 0.077) than that seen on the CT scans (4 [25%] of 16)., Conclusions: For many focal hepatic lesions related to peripheral eosinophilia, dynamic MR imaging more easily demonstrates lesional enhancement on arterial and delayed phases than CT scans. Because of the higher degree of lesional enhancement of MR imaging compared with CT, the lesion-to-liver contrast may not be sufficient to distinguish the lesion from the background liver, resulting in decreased sensitivity of portal phase dynamic MR imaging.

Objective: To determine the relative value of qualitative (reader opinion) and quantitative (values derived from dual echo T2 fast spin echo [FSE]) measures in distinguishing hepatic metastases from hemangiomas., Methods: Forty-nine patients with hemangiomas and 23 with metastases were studied with dual echo respiratory-triggered FSE and dynamic 2-dimensional spoiled gradient echo (GRE) imaging. Lesion T2 was estimated from signal intensity ratios on the first and second echoes. Two experienced radiologists independently evaluated groups of images based on 5 separate qualitative measures: first echo FSE, second echo FSE, first and second echo FSE, dynamic GRE, and all images together., Results: The mean calculated T2s were 226 +/- 74 milliseconds for hemangiomas and 105 +/- 22 milliseconds for metastases (P < 0.001). A T2 cutoff of 130 milliseconds distinguished metastases from hemangiomas with a sensitivity of 94%, specificity of 91%, and accuracy of nearly 94%. There was no significant difference between the best quantitative measure and the best qualitative measure for either reader., Conclusion: Liver lesion T2 relaxation times calculated from dual echo FSE images provide information useful in discriminating metastases from hemangiomas, as does reader opinion.

Objective: The purpose of our study was to evaluate the usefulness of dual-phase dynamic CT in the differentiation of focal eosinophilic necrosis of the liver and metastasis., Conclusion: Undetected isoattenuating lesions on arterial phase images that have an indistinct margin, a nonspherical shape, and a homogenous enhancement pattern on portal venous phase images suggest focal eosinophilic necrosis rather than metastasis. Two-phase dynamic CT was found to be useful at differentiating focal eosinophilic necrosis from metastasis.

Imaging findings of secondary hepatic lymphoma have been reported as variable, ranging from single or multiple small nodules to diffuse infiltrative tumor patterns. We hear present a rare case report concerning aggressive B cells, secondary Burkitt's lymphoma in non-AIDS demonstrating a surprising periportal lymphoma infiltration, without upper abdominal lymphadenopathy or splenomegaly on the sonography and CT scans. Clinically, the case was characterized by atypical and highly aggressive course, with the patient presenting an abruptly developed obstructive jaundice with rapidly deteriorating hepatic function that could be indicative of cholestatic hepatitis, which differs in its clinical manifestations from hepatic lymphoma without functional deterioration in respect of its non-tissue destructive growth pattern. We suggest that hepatic lymphoma can sometimes be consistent with periportal infiltrating homogeneous mass, with no lymphadenopathy or splenomegaly on the imaging examination, with a predictable aggressive clinical course of the disease and poor prognosis.